{ "generatedAt": "2026-05-30", "source": "NutriStack public app research database", "publicationPolicy": { "sourceStatusFields": [ "publicReviewStatus", "publicSourceType", "publicSourceURL" ], "sourceLinked": "Record has a PMID, DOI, URL, or equivalent link and is not marked confidence=verify.", "needsReview": "Record is retained for transparency but should not be treated as verified until reviewed.", "pmidUnconfirmed": "Record has a related PMC source but the PMID was not confirmed." }, "profiles": [ { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567001", "name": "Vitamin D3", "alternateNames": [ "Cholecalciferol" ], "category": "Vitamin", "subcategory": "Fat-Soluble Vitamin", "overview": "The sunshine vitamin, essential for calcium absorption, bone health, immune function, and mood regulation. Most people are deficient, especially in northern latitudes.", "mechanismOfAction": "Converted to calcidiol (25-OH-D) in the liver, then to calcitriol (1,25-OH2-D) in the kidneys. Calcitriol acts as a hormone, binding to vitamin D receptors (VDR) in nearly every cell, regulating calcium/phosphorus absorption and immune cell function.", "commonBenefits": [ "Bone health", "Immune support", "Mood regulation (primarily in deficient individuals)", "Muscle function" ], "commonDosageRange": "1,000–4,000 IU daily (5,000 IU under medical guidance)", "recommendedForm": "D3 (cholecalciferol) preferred over D2 (ergocalciferol)", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with a meal containing fat for optimal absorption" }, "evidenceRating": "strong", "foodSources": [ "Fatty fish (salmon, mackerel)", "Egg yolks", "Fortified milk", "Cod liver oil", "Mushrooms (UV-exposed)" ], "deficiencySymptoms": [ "Fatigue", "Bone pain", "Muscle weakness", "Depression", "Frequent illness" ], "sideEffects": [ "Hypercalcemia at very high doses", "Nausea", "Kidney stones (rare)" ], "contraindications": [ "Hypercalcemia", "Kidney disease", "Sarcoidosis" ], "iconName": "sun.max.fill", "colorHex": "FFB800", "tags": [ "bone-health", "immune", "mood", "essential" ], "sources": [ { "claim": "Vitamin D supplementation prevents acute respiratory infections (immune support)", "title": "Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of individual participant data", "authors": "Martineau AR et al.", "journal": "BMJ", "year": 2017, "pmid": "28202713", "url": "https://pubmed.ncbi.nlm.nih.gov/28202713/", "study_type": "meta-analysis", "key_finding": "Vitamin D supplementation reduced the risk of acute respiratory tract infection (OR 0.88); greatest benefit in those with baseline 25-OHD <25 nmol/L and with daily/weekly dosing", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28202713/", "publicSourceType": "PMID" }, { "claim": "Vitamin D supplementation does not prevent fractures or falls (bone health limitations)", "title": "Effects of vitamin D supplementation on musculoskeletal health: a systematic review, meta-analysis, and trial sequential analysis", "authors": "Bolland MJ et al.", "journal": "Lancet Diabetes Endocrinol", "year": 2018, "pmid": "30293909", "url": "https://pubmed.ncbi.nlm.nih.gov/30293909/", "study_type": "meta-analysis", "key_finding": "Vitamin D supplementation did not prevent fractures or falls or have clinically meaningful effects on bone mineral density in unselected community-dwelling adults", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30293909/", "publicSourceType": "PMID" }, { "claim": "Vitamin D supplementation does not prevent cardiovascular disease or cancer", "title": "Vitamin D Supplementation and Cardiovascular Disease Risks in More Than 83,000 Individuals in 21 Randomized Clinical Trials: A Meta-analysis", "authors": "Barbarawi M et al.", "journal": "JAMA Cardiol", "year": 2019, "pmid": "31215980", "url": "https://pubmed.ncbi.nlm.nih.gov/31215980/", "study_type": "meta-analysis", "key_finding": "No significant reduction in major adverse cardiovascular events or cancer incidence; cancer mortality reduced in some subgroups with longer follow-up", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31215980/", "publicSourceType": "PMID" }, { "claim": "Effect of supplemental vitamin D3 on bone mineral density", "title": "Effect of supplemental vitamin D3 on bone mineral density: a systematic review and meta-analysis", "authors": "Elkhidir AE et al.", "journal": "Nutr Rev", "year": 2022, "pmid": "36308775", "url": "https://pubmed.ncbi.nlm.nih.gov/36308775/", "study_type": "meta-analysis", "key_finding": "Systematic review assessing the effect of vitamin D3 supplementation on bone mineral density across multiple RCTs", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36308775/", "publicSourceType": "PMID" }, { "claim": "Vitamin D supplementation has limited effect on depression in non-deficient adults (mood regulation)", "title": "Effect of Long-term Vitamin D3 Supplementation vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial", "authors": "Okereke OI et al.", "journal": "JAMA", "year": 2020, "pmid": "32749491", "url": "https://pubmed.ncbi.nlm.nih.gov/32749491/", "study_type": "RCT", "key_finding": "Among 18,353 adults aged 50+, vitamin D3 vs placebo did not result in statistically significant difference in incidence of depression or mood score changes over 5.3 years", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32749491/", "publicSourceType": "PMID" }, { "claim": "Vitamin D supplementation may reduce depressive symptoms in deficient individuals", "title": "The effect of vitamin D supplementation on depressive symptoms in adults: A systematic review and meta-analysis of randomized controlled trials", "authors": "Cheng YC et al.", "journal": "Crit Rev Food Sci Nutr", "year": 2022, "pmid": "35816192", "url": "https://pubmed.ncbi.nlm.nih.gov/35816192/", "study_type": "meta-analysis", "key_finding": "Vitamin D supplementation reduced depressive symptoms more in those with existing depression (SMD: -0.57) than in the general population", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35816192/", "publicSourceType": "PMID" }, { "claim": "Safety of long-term vitamin D3 supplementation at moderate-to-high doses", "title": "Long-term supplementation with 3200 to 4000 IU of vitamin D daily and adverse events: a systematic review and meta-analysis of randomized controlled trials", "authors": "Zittermann A et al.", "journal": "Eur J Nutr", "year": 2023, "pmid": "36853379", "url": "https://pubmed.ncbi.nlm.nih.gov/36853379/", "study_type": "meta-analysis", "key_finding": "Vitamin D3 at 3200-4000 IU/day appears to increase the risk of hypercalcemia (4 per 1000) and some adverse events in a small proportion of individuals", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36853379/", "publicSourceType": "PMID" }, { "claim": "Immunologic effects of vitamin D on human health and disease", "title": "Immunologic Effects of Vitamin D on Human Health and Disease", "authors": "Charoenngam N et al.", "journal": "Nutrients", "year": 2020, "pmid": "32679784", "url": "https://pubmed.ncbi.nlm.nih.gov/32679784/", "study_type": "review", "key_finding": "Vitamin D exerts immunomodulatory activities on innate and adaptive immune systems; low 25-OHD associated with increased risk of autoimmune diseases and infections", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32679784/", "publicSourceType": "PMID" }, { "text": "Tripkovic L, Lambert H, Hart K et al.. Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. The American journal of clinical nutrition. 2012", "pmid": "22552031", "doi": "10.3945/ajcn.111.031070", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22552031/", "publicSourceType": "PMID" }, { "claim": "Vitamin D supplementation reduces all-cause mortality", "title": "Association between vitamin D supplementation and mortality: systematic review and meta-analysis.", "authors": "Zhang Y, Fang F, Tang J et al.", "journal": "BMJ", "year": 2019, "pmid": "31405892", "url": "https://pubmed.ncbi.nlm.nih.gov/31405892/", "study_type": "meta-analysis", "key_finding": "Vitamin D supplementation was associated with a statistically significant reduction in all-cause mortality in a meta-analysis of randomized controlled trials.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31405892/", "publicSourceType": "PMID" }, { "claim": "Vitamin D supports musculoskeletal health in sarcopenia", "title": "Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.", "authors": "Chang MC, Choo YJ", "journal": "Nutrients", "year": 2023, "pmid": "36771225", "url": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "study_type": "meta-analysis", "key_finding": "Combined supplementation with whey protein, leucine, and vitamin D improved muscle mass and physical performance in patients with sarcopenia.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" }, { "claim": "Vitamin D deficiency is prevalent in obese youth", "title": "Vitamin D deficiency in children and adolescents with obesity: a meta-analysis.", "authors": "Fiamenghi VI, Mello ED", "journal": "Jornal de pediatria", "year": 2021, "pmid": "33022267", "url": "https://pubmed.ncbi.nlm.nih.gov/33022267/", "study_type": "meta-analysis", "key_finding": "Significantly higher prevalence of vitamin D deficiency in children and adolescents with obesity compared to non-obese peers.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33022267/", "publicSourceType": "PMID" }, { "text": "Sobczak M, Pawliczak R. Effect of Vitamin D3 Supplementation on Severe COVID-19: A Meta-Analysis of Randomized Clinical Trials. Nutrients. 2024", "claim": "PubMed-indexed evidence involving Vitamin D3", "title": "Effect of Vitamin D3 Supplementation on Severe COVID-19: A Meta-Analysis of Randomized Clinical Trials", "authors": "Sobczak M, Pawliczak R", "journal": "Nutrients", "year": 2024, "pmid": "38794642", "url": "https://pubmed.ncbi.nlm.nih.gov/38794642/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu16101402", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38794642/", "publicSourceType": "PMID" }, { "text": "van den Heuvel EG, Lips P, Schoonmade LJ et al.. Comparison of the Effect of Daily Vitamin D2 and Vitamin D3 Supplementation on Serum 25-Hydroxyvitamin D Concentration (Total 25(OH)D, 25(OH)D2, and 25(OH)D3) and Importance of Body Mass Index: A Systematic Review and Meta-Analysis. Advances in nutrition (Bethesda, Md.). 2024", "claim": "PubMed-indexed evidence involving Vitamin D3", "title": "Comparison of the Effect of Daily Vitamin D2 and Vitamin D3 Supplementation on Serum 25-Hydroxyvitamin D Concentration (Total 25(OH)D, 25(OH)D2, and 25(OH)D3) and Importance of Body Mass Index: A Systematic Review and Meta-Analysis", "authors": "van den Heuvel EG, Lips P, Schoonmade LJ et al.", "journal": "Advances in nutrition (Bethesda, Md.)", "year": 2024, "pmid": "37865222", "url": "https://pubmed.ncbi.nlm.nih.gov/37865222/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.advnut.2023.09.016", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37865222/", "publicSourceType": "PMID" }, { "text": "Manoj P, Derwin R, George S. What is the impact of daily oral supplementation of vitamin D3 (cholecalciferol) plus calcium on the incidence of hip fracture in older people? A systematic review and meta-analysis. International journal of older people nursing. 2023", "claim": "PubMed-indexed evidence involving Vitamin D3", "title": "What is the impact of daily oral supplementation of vitamin D3 (cholecalciferol) plus calcium on the incidence of hip fracture in older people? A systematic review and meta-analysis", "authors": "Manoj P, Derwin R, George S", "journal": "International journal of older people nursing", "year": 2023, "pmid": "35842938", "url": "https://pubmed.ncbi.nlm.nih.gov/35842938/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/opn.12492", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35842938/", "publicSourceType": "PMID" }, { "text": "Petrelli F, Oldani S, Borgonovo K et al.. Vitamin D3 and COVID-19 Outcomes: An Umbrella Review of Systematic Reviews and Meta-Analyses. Antioxidants (Basel, Switzerland). 2023", "claim": "PubMed-indexed evidence involving Vitamin D3", "title": "Vitamin D3 and COVID-19 Outcomes: An Umbrella Review of Systematic Reviews and Meta-Analyses", "authors": "Petrelli F, Oldani S, Borgonovo K et al.", "journal": "Antioxidants (Basel, Switzerland)", "year": 2023, "pmid": "36829806", "url": "https://pubmed.ncbi.nlm.nih.gov/36829806/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/antiox12020247", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36829806/", "publicSourceType": "PMID" }, { "text": "Putranto R, Setiati S, Nasrun MW et al.. Effects of cholecalciferol supplementation on depressive symptoms, C-peptide, serotonin, and neurotrophin-3 in type 2 diabetes mellitus: A double-blind, randomized, placebo-controlled trial. Narra J. 2024", "claim": "PubMed-indexed evidence involving Vitamin D3", "title": "Effects of cholecalciferol supplementation on depressive symptoms, C-peptide, serotonin, and neurotrophin-3 in type 2 diabetes mellitus: A double-blind, randomized, placebo-controlled trial", "authors": "Putranto R, Setiati S, Nasrun MW et al.", "journal": "Narra J", "year": 2024, "pmid": "39816051", "url": "https://pubmed.ncbi.nlm.nih.gov/39816051/", "study_type": "RCT", "confidence": "verify", "doi": "10.52225/narra.v4i3.1342", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39816051/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "vitamin-d3" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567002", "name": "Vitamin C", "alternateNames": [ "Ascorbic Acid", "L-Ascorbic Acid" ], "category": "Vitamin", "subcategory": "Water-Soluble Vitamin", "overview": "A powerful antioxidant essential for collagen synthesis, immune function, and iron absorption. Humans cannot synthesize it and must obtain it from diet or supplements.", "mechanismOfAction": "Acts as an electron donor, neutralizing free radicals. Required cofactor for prolyl and lysyl hydroxylases in collagen synthesis. Enhances non-heme iron absorption by reducing ferric iron to ferrous form. Supports immune cells including neutrophils and lymphocytes.", "commonBenefits": [ "Immune support", "Collagen synthesis", "Antioxidant protection", "Iron absorption", "Skin health" ], "commonDosageRange": "500–2,000 mg daily", "recommendedForm": "Ascorbic acid or liposomal vitamin C for higher absorption", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Water-soluble; split doses throughout day for better absorption" }, "evidenceRating": "strong", "foodSources": [ "Citrus fruits", "Bell peppers", "Strawberries", "Broccoli", "Kiwi" ], "deficiencySymptoms": [ "Scurvy", "Bleeding gums", "Slow wound healing", "Fatigue", "Joint pain" ], "sideEffects": [ "GI upset at high doses", "Diarrhea", "Kidney stones (rare, at very high doses)" ], "contraindications": [ "History of kidney stones (high doses)", "Hemochromatosis" ], "iconName": "leaf.fill", "colorHex": "FF9500", "tags": [ "immune", "antioxidant", "skin", "essential" ], "sources": [ { "claim": "Vitamin C for preventing and treating the common cold (immune support)", "title": "Vitamin C for preventing and treating the common cold", "authors": "Hemila H, Chalker E", "journal": "Cochrane Database Syst Rev", "year": 2013, "pmid": "23440782", "url": "https://pubmed.ncbi.nlm.nih.gov/23440782/", "study_type": "meta-analysis", "key_finding": "Regular vitamin C supplementation does not reduce common cold incidence in the general population but reduces duration; beneficial for those under heavy physical stress", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23440782/", "publicSourceType": "PMID" }, { "claim": "Vitamin C reduces the severity of common colds", "title": "Vitamin C reduces the severity of common colds: a meta-analysis", "authors": "Hemila H et al.", "journal": "BMC Public Health", "year": 2023, "pmid": "38082300", "url": "https://pubmed.ncbi.nlm.nih.gov/38082300/", "study_type": "meta-analysis", "key_finding": "Vitamin C significantly reduced the severity of common cold symptoms in placebo-controlled trials", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38082300/", "publicSourceType": "PMID" }, { "claim": "Vitamin C is essential for immune cell function", "title": "Vitamin C and Immune Function", "authors": "Carr AC, Maggini S", "journal": "Nutrients", "year": 2017, "pmid": "29099763", "url": "https://pubmed.ncbi.nlm.nih.gov/29099763/", "study_type": "review", "key_finding": "Vitamin C supports epithelial barrier function, accumulates in phagocytic cells, enhances chemotaxis, phagocytosis, ROS generation, and killing; 100-200 mg/day needed for saturation", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29099763/", "publicSourceType": "PMID" }, { "claim": "Vitamin C roles in skin health and collagen synthesis", "title": "The Roles of Vitamin C in Skin Health", "authors": "Pullar JM et al.", "journal": "Nutrients", "year": 2017, "pmid": "28805671", "url": "https://pubmed.ncbi.nlm.nih.gov/28805671/", "study_type": "review", "key_finding": "Skin contains high concentrations of vitamin C, which supports collagen synthesis and provides antioxidant protection against UV-induced photodamage", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28805671/", "publicSourceType": "PMID" }, { "claim": "Vitamin C enhances non-heme iron absorption", "title": "Enhancers of iron absorption: ascorbic acid and other organic acids", "authors": "Teucher B et al.", "journal": "Int J Vitam Nutr Res", "year": 2004, "pmid": "15743017", "url": "https://pubmed.ncbi.nlm.nih.gov/15743017/", "study_type": "review", "key_finding": "Ascorbic acid is the most potent enhancer of nonheme iron absorption; reduces ferric to ferrous iron and reverses inhibitory effects of tea and calcium", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15743017/", "publicSourceType": "PMID" }, { "claim": "Vitamin C supplementation and kidney stone risk (safety)", "title": "Ascorbic Acid Supplements and Kidney Stones Incidence Among Men and Women: A systematic review and meta-analysis", "authors": "Jiang K et al.", "journal": "Int J Food Sci Nutr", "year": 2019, "pmid": "30178451", "url": "https://pubmed.ncbi.nlm.nih.gov/30178451/", "study_type": "meta-analysis", "key_finding": "Vitamin C supplements were associated with significantly higher kidney stone incidence in men (OR 1.62) but not in women", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30178451/", "publicSourceType": "PMID" }, { "claim": "Vitamin C intake and multiple health outcomes (umbrella review)", "title": "Vitamin C intake and multiple health outcomes: an umbrella review of systematic reviews and meta-analyses", "authors": "Chen Y et al.", "journal": "Int J Food Sci Nutr", "year": 2022, "pmid": "35291895", "url": "https://pubmed.ncbi.nlm.nih.gov/35291895/", "study_type": "meta-analysis", "key_finding": "Umbrella review of systematic reviews examining multiple health outcomes of vitamin C including cardiovascular, immune, and cancer-related endpoints", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35291895/", "publicSourceType": "PMID" }, { "text": "Rogers DR, Lawlor DJ, Moeller JL. Vitamin C Supplementation and Athletic Performance: A Review. Current sports medicine reports. 2023", "pmid": "37417662", "doi": "10.1249/JSR.0000000000001083", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37417662/", "publicSourceType": "PMID" }, { "claim": "Vitamin C reduces pain in endometriosis", "title": "Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials.", "authors": "Bayu P, Wibisono JJ", "journal": "PLoS One", "year": 2024, "pmid": "38820340", "url": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "study_type": "meta-analysis", "key_finding": "Combined vitamin C and E supplementation significantly reduced chronic pelvic pain and dysmenorrhea in endometriosis patients.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" }, { "claim": "IV Vitamin C may benefit sepsis patients", "title": "IV Vitamin C in Sepsis: A Latest Systematic Review and Meta-Analysis.", "authors": "Wen C, Li Y, Hu Q et al.", "journal": "International Journal of Clinical Practice", "year": 2023, "pmid": "36743822", "url": "https://pubmed.ncbi.nlm.nih.gov/36743822/", "study_type": "meta-analysis", "key_finding": "Intravenous vitamin C as adjunctive therapy in sepsis showed potential benefits in reducing inflammatory markers and improving organ dysfunction scores.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36743822/", "publicSourceType": "PMID" }, { "claim": "Vitamin C supplementation and cardiovascular health", "title": "Supplemental Vitamins and Minerals for Cardiovascular Disease Prevention and Treatment: JACC Focus Seminar.", "authors": "Jenkins DJA, Spence JD, Giovannucci EL et al.", "journal": "Journal of the American College of Cardiology", "year": 2021, "pmid": "33509399", "url": "https://pubmed.ncbi.nlm.nih.gov/33509399/", "study_type": "review", "key_finding": "Evidence suggests vitamin C supplementation may have modest cardiovascular benefits through antioxidant mechanisms, though results from large RCTs are mixed.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33509399/", "publicSourceType": "PMID" }, { "text": "Hemilä H, de Man AME. Vitamin C deficiency can lead to pulmonary hypertension: a systematic review of case reports. BMC pulmonary medicine. 2024", "claim": "PubMed-indexed evidence involving Vitamin C", "title": "Vitamin C deficiency can lead to pulmonary hypertension: a systematic review of case reports", "authors": "Hemilä H, de Man AME", "journal": "BMC pulmonary medicine", "year": 2024, "pmid": "38504249", "url": "https://pubmed.ncbi.nlm.nih.gov/38504249/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12890-024-02941-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38504249/", "publicSourceType": "PMID" }, { "text": "Ranjbar Moghaddam M, Nasiri-Formi E, Merajikhah A. Efficacy of vitamin C supplementation in preventing and treating complex regional pain syndrome type I (CRPS-I) in Orthopedic patients: A systematic review and meta-analysis. International journal of orthopaedic and trauma nursing. 2024", "claim": "PubMed-indexed evidence involving Vitamin C", "title": "Efficacy of vitamin C supplementation in preventing and treating complex regional pain syndrome type I (CRPS-I) in Orthopedic patients: A systematic review and meta-analysis", "authors": "Ranjbar Moghaddam M, Nasiri-Formi E, Merajikhah A", "journal": "International journal of orthopaedic and trauma nursing", "year": 2024, "pmid": "39447383", "url": "https://pubmed.ncbi.nlm.nih.gov/39447383/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.ijotn.2024.101140", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39447383/", "publicSourceType": "PMID" }, { "text": "Bechara N, Flood VM, Gunton JE. A Systematic Review on the Role of Vitamin C in Tissue Healing. Antioxidants (Basel, Switzerland). 2022", "claim": "PubMed-indexed evidence involving Vitamin C", "title": "A Systematic Review on the Role of Vitamin C in Tissue Healing", "authors": "Bechara N, Flood VM, Gunton JE", "journal": "Antioxidants (Basel, Switzerland)", "year": 2022, "pmid": "36009324", "url": "https://pubmed.ncbi.nlm.nih.gov/36009324/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/antiox11081605", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36009324/", "publicSourceType": "PMID" }, { "text": "Agarwal A, Basmaji J, Fernando SM et al.. Parenteral Vitamin C in Patients with Severe Infection: A Systematic Review. NEJM evidence. 2022", "claim": "PubMed-indexed evidence involving Vitamin C", "title": "Parenteral Vitamin C in Patients with Severe Infection: A Systematic Review", "authors": "Agarwal A, Basmaji J, Fernando SM et al.", "journal": "NEJM evidence", "year": 2022, "pmid": "38319815", "url": "https://pubmed.ncbi.nlm.nih.gov/38319815/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1056/EVIDoa2200105", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38319815/", "publicSourceType": "PMID" }, { "text": "Chen Z, Huang Y, Cao D et al.. Vitamin C Intake and Cancers: An Umbrella Review. Frontiers in nutrition. 2021", "claim": "PubMed-indexed evidence involving Vitamin C", "title": "Vitamin C Intake and Cancers: An Umbrella Review", "authors": "Chen Z, Huang Y, Cao D et al.", "journal": "Frontiers in nutrition", "year": 2021, "pmid": "35127793", "url": "https://pubmed.ncbi.nlm.nih.gov/35127793/", "study_type": "review", "confidence": "verify", "doi": "10.3389/fnut.2021.812394", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35127793/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "vitamin-c" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567003", "name": "Vitamin A", "alternateNames": [ "Retinol", "Retinyl Palmitate", "Beta-Carotene" ], "category": "Vitamin", "subcategory": "Fat-Soluble Vitamin", "overview": "Essential for vision, immune function, skin health, and cell differentiation. Available as preformed retinol or provitamin A (beta-carotene).", "mechanismOfAction": "Retinol is converted to retinal (essential for rhodopsin in rod cells for night vision) and retinoic acid (binds RAR/RXR nuclear receptors regulating gene expression for cell differentiation, immune function, and skin turnover).", "commonBenefits": [ "Vision health", "Immune function", "Skin health", "Cell growth", "Reproductive health" ], "commonDosageRange": "Preformed retinol: 2,500–10,000 IU (10,000 IU is UL). Beta-carotene: no UL but contraindicated in smokers.", "recommendedForm": "Retinyl palmitate or beta-carotene (safer at high doses)", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Fat-soluble; take with dietary fat" }, "evidenceRating": "strong", "foodSources": [ "Liver", "Sweet potato", "Carrots", "Spinach", "Egg yolks" ], "deficiencySymptoms": [ "Night blindness", "Dry skin", "Frequent infections", "Impaired growth" ], "sideEffects": [ "Toxicity at high doses (hypervitaminosis A)", "Headache", "Nausea", "Birth defects (high-dose retinol in pregnancy)", "Beta-carotene: increased lung cancer risk in smokers (28-46% increase in landmark ATBC and CARET trials)" ], "contraindications": [ "Pregnancy (high-dose retinol)", "Liver disease", "Isotretinoin use", "Current/former smokers (beta-carotene form)" ], "iconName": "eye.fill", "colorHex": "FF6B00", "tags": [ "vision", "immune", "skin", "essential" ], "sources": [ { "claim": "Role of vitamin A in the immune system (immune function)", "title": "Role of Vitamin A in the Immune System", "authors": "Huang Z et al.", "journal": "J Clin Med", "year": 2018, "pmid": "30200565", "url": "https://pubmed.ncbi.nlm.nih.gov/30200565/", "study_type": "review", "key_finding": "Vitamin A is known as an anti-inflammation vitamin; critical role in enhancing immune function, involved in development of immune system, regulates cellular and humoral immune responses", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30200565/", "publicSourceType": "PMID" }, { "claim": "Vitamin A essential for vision via rhodopsin pathway", "title": "Vitamin A and Vision", "authors": "Zhong M et al.", "journal": "Subcell Biochem", "year": 2016, "pmid": "27830507", "url": "https://pubmed.ncbi.nlm.nih.gov/27830507/", "study_type": "review", "key_finding": "In all visual systems, 11-cis-retinal complexed with opsin serves as the chromophore; retinal is essential for the visual cycle in rod and cone cells", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27830507/", "publicSourceType": "PMID" }, { "claim": "Beta-carotene increases lung cancer risk in smokers (CARET trial - safety)", "title": "Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease", "authors": "Omenn GS et al.", "journal": "N Engl J Med", "year": 1996, "pmid": "8602180", "url": "https://pubmed.ncbi.nlm.nih.gov/8602180/", "study_type": "RCT", "key_finding": "CARET trial stopped early: 28% more lung cancers and 17% more deaths in the beta-carotene + retinol group vs placebo among smokers and asbestos workers", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8602180/", "publicSourceType": "PMID" }, { "claim": "Beta-carotene increases lung cancer incidence in smokers (ATBC trial - safety)", "title": "Alpha-Tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance", "authors": "ATBC Study Group", "journal": "J Natl Cancer Inst", "year": 1996, "pmid": "8901854", "url": "https://pubmed.ncbi.nlm.nih.gov/8901854/", "study_type": "RCT", "key_finding": "Beta-carotene supplementation was associated with increased lung cancer risk (RR 1.16; 95% CI 1.02-1.33) in male smokers", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8901854/", "publicSourceType": "PMID" }, { "claim": "Vitamin A toxicity and hypervitaminosis A (safety/dosage)", "title": "Vitamin A Toxicity", "authors": "Bastos Maia S et al.", "journal": "StatPearls", "year": 2023, "pmid": "30422511", "url": "https://pubmed.ncbi.nlm.nih.gov/30422511/", "study_type": "review", "key_finding": "Excessive preformed vitamin A causes acute and chronic toxicity (hypervitaminosis A); acute toxicity can occur at doses >=500,000 IU; 10,000 IU/day upper limit", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30422511/", "publicSourceType": "PMID" }, { "claim": "Teratogenicity of high-dose vitamin A in pregnancy", "title": "Teratogenicity of high vitamin A intake", "authors": "Rothman KJ et al.", "journal": "N Engl J Med", "year": 1995, "pmid": "7477116", "url": "https://pubmed.ncbi.nlm.nih.gov/7477116/", "study_type": "cohort", "key_finding": "Among women who took >10,000 IU/day of preformed vitamin A, estimated prevalence of birth defects was 1 per 57; threshold near 10,000 IU/day of supplemental vitamin A", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7477116/", "publicSourceType": "PMID" }, { "claim": "Vitamin A supplementation reduces child mortality", "title": "Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age", "authors": "Imdad A, Mayo-Wilson E, Haykal MR et al.", "journal": "The Cochrane database of systematic reviews", "year": 2022, "pmid": "35294044", "doi": "10.1002/14651858.CD008524.pub4", "study_type": "meta-analysis", "key_finding": "12% reduction in all-cause mortality in children aged 6-59 months", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35294044/", "publicSourceType": "PMID" }, { "text": "Kotepui KU, Mahittikorn A, Wilairatana P et al.. The Association between Malaria and β-Carotene Levels: A Systematic Review and Meta-Analysis. Antioxidants (Basel, Switzerland). 2023", "claim": "PubMed-indexed evidence involving Vitamin A", "title": "The Association between Malaria and β-Carotene Levels: A Systematic Review and Meta-Analysis", "authors": "Kotepui KU, Mahittikorn A, Wilairatana P et al.", "journal": "Antioxidants (Basel, Switzerland)", "year": 2023, "pmid": "37759990", "url": "https://pubmed.ncbi.nlm.nih.gov/37759990/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/antiox12091687", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37759990/", "publicSourceType": "PMID" }, { "text": "Abrego-Guandique DM, Bonet ML, Caroleo MC et al.. The Effect of Beta-Carotene on Cognitive Function: A Systematic Review. Brain sciences. 2023", "claim": "PubMed-indexed evidence involving Vitamin A", "title": "The Effect of Beta-Carotene on Cognitive Function: A Systematic Review", "authors": "Abrego-Guandique DM, Bonet ML, Caroleo MC et al.", "journal": "Brain sciences", "year": 2023, "pmid": "37891835", "url": "https://pubmed.ncbi.nlm.nih.gov/37891835/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/brainsci13101468", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37891835/", "publicSourceType": "PMID" }, { "text": "Gannon BM, Rogers LM, Tanumihardjo SA. Metabolism of Neonatal Vitamin A Supplementation: A Systematic Review. Advances in nutrition (Bethesda, Md.). 2021", "claim": "PubMed-indexed evidence involving Vitamin A", "title": "Metabolism of Neonatal Vitamin A Supplementation: A Systematic Review", "authors": "Gannon BM, Rogers LM, Tanumihardjo SA", "journal": "Advances in nutrition (Bethesda, Md.)", "year": 2021, "pmid": "33216111", "url": "https://pubmed.ncbi.nlm.nih.gov/33216111/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/advances/nmaa137", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33216111/", "publicSourceType": "PMID" }, { "text": "Knapik JJ, Hoedebecke SS. Vitamin A and Bone Fractures: Systematic Review and Meta-Analysis. Journal of special operations medicine : a peer reviewed journal for SOF medical professionals. 2021", "claim": "PubMed-indexed evidence involving Vitamin A", "title": "Vitamin A and Bone Fractures: Systematic Review and Meta-Analysis", "authors": "Knapik JJ, Hoedebecke SS", "journal": "Journal of special operations medicine : a peer reviewed journal for SOF medical professionals", "year": 2021, "pmid": "34105132", "url": "https://pubmed.ncbi.nlm.nih.gov/34105132/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.55460/OGLF-K9ZU", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34105132/", "publicSourceType": "PMID" }, { "text": "Soares MM, Silva MA, Garcia PPC et al.. Efect of vitamin A suplementation: a systematic review. Ciencia & saude coletiva. 2019", "claim": "PubMed-indexed evidence involving Vitamin A", "title": "Efect of vitamin A suplementation: a systematic review", "authors": "Soares MM, Silva MA, Garcia PPC et al.", "journal": "Ciencia & saude coletiva", "year": 2019, "pmid": "30892504", "url": "https://pubmed.ncbi.nlm.nih.gov/30892504/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1590/1413-81232018243.07112017", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30892504/", "publicSourceType": "PMID" }, { "text": "He J, Gu Y, Zhang S. Vitamin A and Breast Cancer Survival: A Systematic Review and Meta-analysis. Clinical breast cancer. 2018", "claim": "PubMed-indexed evidence involving Vitamin A", "title": "Vitamin A and Breast Cancer Survival: A Systematic Review and Meta-analysis", "authors": "He J, Gu Y, Zhang S", "journal": "Clinical breast cancer", "year": 2018, "pmid": "30190194", "url": "https://pubmed.ncbi.nlm.nih.gov/30190194/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.clbc.2018.07.025", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30190194/", "publicSourceType": "PMID" }, { "text": "Li Y, Zhang R, Li Z et al.. The Relationship of Vitamin A and Neonatal Respiratory Diseases: A Meta-Analysis. The clinical respiratory journal. 2024", "claim": "PubMed-indexed evidence involving Vitamin A", "title": "The Relationship of Vitamin A and Neonatal Respiratory Diseases: A Meta-Analysis", "authors": "Li Y, Zhang R, Li Z et al.", "journal": "The clinical respiratory journal", "year": 2024, "pmid": "39434208", "url": "https://pubmed.ncbi.nlm.nih.gov/39434208/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/crj.70030", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39434208/", "publicSourceType": "PMID" }, { "text": "Ma G, Chen Y, Liu X et al.. Vitamin a supplementation during pregnancy in shaping child growth outcomes: A meta-analysis. Critical reviews in food science and nutrition. 2023", "claim": "PubMed-indexed evidence involving Vitamin A", "title": "Vitamin a supplementation during pregnancy in shaping child growth outcomes: A meta-analysis", "authors": "Ma G, Chen Y, Liu X et al.", "journal": "Critical reviews in food science and nutrition", "year": 2023, "pmid": "35852163", "url": "https://pubmed.ncbi.nlm.nih.gov/35852163/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/10408398.2022.2099810", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35852163/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "vitamin-a" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567004", "name": "Vitamin E", "alternateNames": [ "Alpha-Tocopherol", "Mixed Tocopherols", "Tocotrienols" ], "category": "Vitamin", "subcategory": "Fat-Soluble Vitamin", "overview": "A fat-soluble antioxidant that protects cell membranes from oxidative damage. Important for skin health and immune function; cardiovascular outcome benefits from routine supplementation are not established.", "mechanismOfAction": "Integrates into cell membranes and lipoproteins, donating hydrogen atoms to neutralize lipid peroxyl radicals, breaking the chain reaction of lipid peroxidation. Works synergistically with vitamin C, which regenerates oxidized vitamin E.", "commonBenefits": [ "Antioxidant protection", "Skin health", "Immune support", "Anti-inflammatory" ], "commonDosageRange": "100–200 IU daily when specifically indicated; avoid routine 400 IU/day unless clinician-supervised", "recommendedForm": "Mixed tocopherols or d-alpha-tocopherol (natural form)", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Fat-soluble; take with meals containing fat" }, "evidenceRating": "moderate", "foodSources": [ "Almonds", "Sunflower seeds", "Avocado", "Olive oil", "Spinach" ], "deficiencySymptoms": [ "Muscle weakness", "Vision problems", "Immune impairment", "Nerve damage" ], "sideEffects": [ "Increased bleeding risk at high doses", "Nausea", "Increased prostate cancer risk at 400 IU/day (SELECT trial)", "22% increased hemorrhagic stroke risk" ], "contraindications": [ "Blood thinners (high doses)", "Vitamin K deficiency", "Upcoming surgery", "Prostate cancer risk factors" ], "iconName": "shield.fill", "colorHex": "E8A317", "tags": [ "antioxidant", "skin", "heart-health" ], "sources": [ { "claim": "Vitamin E (400 IU/day) increases prostate cancer risk (SELECT trial - safety)", "title": "Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT)", "authors": "Klein EA et al.", "journal": "JAMA", "year": 2011, "pmid": "21990298", "url": "https://pubmed.ncbi.nlm.nih.gov/21990298/", "study_type": "RCT", "key_finding": "Among 35,533 men, vitamin E 400 IU/day significantly increased prostate cancer risk (HR 1.17; 99% CI 1.004-1.36) compared to placebo", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21990298/", "publicSourceType": "PMID" }, { "claim": "High-dose vitamin E may increase all-cause mortality (safety)", "title": "Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality", "authors": "Miller ER 3rd et al.", "journal": "Ann Intern Med", "year": 2005, "pmid": "15537682", "url": "https://pubmed.ncbi.nlm.nih.gov/15537682/", "study_type": "meta-analysis", "key_finding": "High-dosage vitamin E supplementation (>=400 IU/day) may increase all-cause mortality; dose-response analysis shows increased risk starting at 150 IU/day", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15537682/", "publicSourceType": "PMID" }, { "claim": "Vitamin E supplementation does not reduce cardiovascular events", "title": "A Systematic Review of Effects of Vitamin E on the Cardiovascular System", "authors": "Ashor AW et al.", "journal": "Front Nutr", "year": 2021, "pmid": "34277234", "url": "https://pubmed.ncbi.nlm.nih.gov/34277234/", "study_type": "review", "key_finding": "Observational studies showed inverse association between vitamin E and cardiovascular disease; interventional trials were negative. No overall cardiovascular benefit from supplementation", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34277234/", "publicSourceType": "PMID" }, { "claim": "Vitamin E and multiple health outcomes umbrella review", "title": "Vitamin E and Multiple Health Outcomes: An Umbrella Review of Meta-Analyses", "authors": "Huang Y et al.", "journal": "Nutrients", "year": 2023, "pmid": "37571239", "url": "https://pubmed.ncbi.nlm.nih.gov/37571239/", "study_type": "meta-analysis", "key_finding": "Umbrella review of meta-analyses; only association between circulating alpha-tocopherol and reduced wheeze/asthma in children was substantiated by consistent evidence", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37571239/", "publicSourceType": "PMID" }, { "claim": "Vitamin E emerging clinical role and adverse risks", "title": "Vitamin E (alpha-Tocopherol): Emerging Clinical Role and Adverse Risks of Supplementation in Adults", "authors": "Various", "journal": "Nutrients", "year": 2025, "pmid": "40065887", "url": "https://pubmed.ncbi.nlm.nih.gov/40065887/", "study_type": "review", "key_finding": "High-dose vitamin E supplementation may increase risks; beneficial antioxidant properties may be outweighed by harmful interference in normal cellular processes at high doses", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40065887/", "publicSourceType": "PMID" }, { "claim": "Vitamin E supplementation and all-cause mortality (reassessment)", "title": "Vitamin E and all-cause mortality: a meta-analysis", "authors": "Abner EL et al.", "journal": "Curr Aging Sci", "year": 2011, "pmid": "21235492", "url": "https://pubmed.ncbi.nlm.nih.gov/21235492/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 57 trials (246,371 subjects) produced RR of 1.00; vitamin E unlikely to affect mortality regardless of dose up to 5,500 IU/day", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21235492/", "publicSourceType": "PMID" }, { "claim": "Vitamin E has differential effects on stroke subtypes", "title": "Effects of vitamin E on stroke subtypes: meta-analysis of randomised controlled trials", "authors": "Schurks M, Glynn RJ, Rist PM et al.", "journal": "BMJ", "year": 2010, "pmid": "21051774", "doi": "10.1136/bmj.c5702", "study_type": "meta-analysis", "key_finding": "22% increased risk of hemorrhagic stroke, 10% reduced ischemic stroke risk", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21051774/", "publicSourceType": "PMID" }, { "claim": "Vitamin E supplementation may reduce LDL cholesterol levels in type 2 diabetes patients", "title": "Comparative effects of vitamin and mineral supplements in the management of type 2 diabetes in primary care: A systematic review and network meta-analysis of randomized controlled trials", "authors": "Xia J, Yu J, Xu H et al.", "journal": "Pharmacological Research", "year": 2023, "pmid": "36638933", "url": "https://pubmed.ncbi.nlm.nih.gov/36638933/", "study_type": "meta-analysis", "key_finding": "In 170 RCTs with 14,223 participants, vitamin E supplements ranked best in reducing LDL cholesterol levels (SUCRA 80.0%). Network meta-analysis showed micronutrient supplements, especially vitamin E, may be efficacious in managing T2DM.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36638933/", "publicSourceType": "PMID" }, { "claim": "Vitamin C and E antioxidant supplementation reduces pain symptoms in endometriosis", "title": "Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials", "authors": "Bayu P, Wibisono JJ", "journal": "PLoS One", "year": 2024, "pmid": "38820340", "url": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "study_type": "meta-analysis", "key_finding": "In 5 RCTs, vitamin C and E combination was associated with higher proportion of reduced chronic pelvic pain (RR 7.30, 95% CI 3.27-16.31), alleviation of dysmenorrhea (RR 1.96), and dyspareunia (RR 5.08) in endometriosis patients.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" }, { "claim": "ESPEN guideline provides comprehensive micronutrient recommendations including vitamin E for clinical nutrition", "title": "ESPEN micronutrient guideline", "authors": "Berger MM, Shenkin A, Schweinlin A et al.", "journal": "Clinical Nutrition", "year": 2022, "pmid": "35365361", "url": "https://pubmed.ncbi.nlm.nih.gov/35365361/", "study_type": "review", "key_finding": "Comprehensive guideline proposing 170 recommendations for 26 micronutrients including vitamin E. Critical micronutrient deficiencies were identified in numerous acute and chronic diseases with monitoring and management strategies proposed.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35365361/", "publicSourceType": "PMID" }, { "text": "Monami M, Cignarelli A, Pinto S et al.. Alpha-tocopherol and contrast-induced nephropathy: A meta-analysis of randomized controlled trials. International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition. 2021", "claim": "PubMed-indexed evidence involving Vitamin E", "title": "Alpha-tocopherol and contrast-induced nephropathy: A meta-analysis of randomized controlled trials", "authors": "Monami M, Cignarelli A, Pinto S et al.", "journal": "International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition", "year": 2021, "pmid": "31017554", "url": "https://pubmed.ncbi.nlm.nih.gov/31017554/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1024/0300-9831/a000573", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31017554/", "publicSourceType": "PMID" }, { "text": "de Lima KS, Schuch F, Righi NC et al.. Vitamin E Does not Favor Recovery After Exercises: Systematic Review and Meta-analysis. International journal of sports medicine. 2024", "claim": "PubMed-indexed evidence involving Vitamin E", "title": "Vitamin E Does not Favor Recovery After Exercises: Systematic Review and Meta-analysis", "authors": "de Lima KS, Schuch F, Righi NC et al.", "journal": "International journal of sports medicine", "year": 2024, "pmid": "38346687", "url": "https://pubmed.ncbi.nlm.nih.gov/38346687/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1055/a-2221-5688", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38346687/", "publicSourceType": "PMID" }, { "text": "Sharif M, Khan DA, Farhat K et al.. Pharmacokinetics and bioavailability of tocotrienols in healthy human volunteers: a systematic review. JPMA. The Journal of the Pakistan Medical Association. 2023", "claim": "PubMed-indexed evidence involving Vitamin E", "title": "Pharmacokinetics and bioavailability of tocotrienols in healthy human volunteers: a systematic review", "authors": "Sharif M, Khan DA, Farhat K et al.", "journal": "JPMA. The Journal of the Pakistan Medical Association", "year": 2023, "pmid": "36932765", "url": "https://pubmed.ncbi.nlm.nih.gov/36932765/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.47391/JPMA.6008", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36932765/", "publicSourceType": "PMID" }, { "text": "Zhang T, Yi X, Li J et al.. Vitamin E intake and multiple health outcomes: an umbrella review. Frontiers in public health. 2023", "claim": "PubMed-indexed evidence involving Vitamin E", "title": "Vitamin E intake and multiple health outcomes: an umbrella review", "authors": "Zhang T, Yi X, Li J et al.", "journal": "Frontiers in public health", "year": 2023, "pmid": "37522003", "url": "https://pubmed.ncbi.nlm.nih.gov/37522003/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fpubh.2023.1035674", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37522003/", "publicSourceType": "PMID" }, { "text": "Feduniw S, Korczyńska L, Górski K et al.. The Effect of Vitamin E Supplementation in Postmenopausal Women-A Systematic Review. Nutrients. 2022", "claim": "PubMed-indexed evidence involving Vitamin E", "title": "The Effect of Vitamin E Supplementation in Postmenopausal Women-A Systematic Review", "authors": "Feduniw S, Korczyńska L, Górski K et al.", "journal": "Nutrients", "year": 2022, "pmid": "36615817", "url": "https://pubmed.ncbi.nlm.nih.gov/36615817/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu15010160", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36615817/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "vitamin-e" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567005", "name": "Vitamin K2", "alternateNames": [ "Menaquinone", "MK-7", "MK-4" ], "category": "Vitamin", "subcategory": "Fat-Soluble Vitamin", "overview": "Directs calcium to bones and teeth while preventing arterial calcification. Critical partner for vitamin D3 supplementation.", "mechanismOfAction": "Activates osteocalcin (directs calcium into bone matrix) and matrix GLA protein (MGP, prevents calcium deposition in arteries and soft tissues) through gamma-carboxylation of glutamic acid residues.", "commonBenefits": [ "Bone health", "Cardiovascular health", "Calcium metabolism" ], "commonDosageRange": "100–200 mcg daily (MK-7)", "recommendedForm": "MK-7 (longer half-life) or MK-4 (faster acting)", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Fat-soluble; pair with vitamin D3 for synergy" }, "evidenceRating": "strong", "foodSources": [ "Natto", "Hard cheeses", "Egg yolks", "Butter (grass-fed)", "Fermented foods" ], "deficiencySymptoms": [ "Poor bone density", "Arterial calcification", "Easy bruising" ], "sideEffects": [ "Generally very well tolerated", "Rare allergic reactions" ], "contraindications": [ "Warfarin/blood thinners (consult doctor)", "Clotting disorders" ], "iconName": "figure.stand", "colorHex": "C4A000", "tags": [ "bone-health", "heart-health", "essential" ], "sources": [ { "claim": "Vitamin K2 efficacy in prevention/treatment of postmenopausal osteoporosis (bone health)", "title": "Efficacy of vitamin K2 in the prevention and treatment of postmenopausal osteoporosis: A systematic review and meta-analysis of randomized controlled trials", "authors": "Ma ML et al.", "journal": "Front Public Health", "year": 2022, "pmid": "36033779", "url": "https://pubmed.ncbi.nlm.nih.gov/36033779/", "study_type": "meta-analysis", "key_finding": "16 RCTs with 6,425 subjects showed vitamin K2 significantly improved lumbar spine bone mineral density, particularly with combination therapy", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36033779/", "publicSourceType": "PMID" }, { "claim": "Three-year MK-7 supplementation decreases bone loss in postmenopausal women", "title": "Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women", "authors": "Knapen MH et al.", "journal": "Osteoporos Int", "year": 2013, "pmid": "23525894", "url": "https://pubmed.ncbi.nlm.nih.gov/23525894/", "study_type": "RCT", "key_finding": "MK-7 supplementation significantly decreased age-related decline in bone mineral content and bone mineral density at femoral neck; also improved bone strength", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23525894/", "publicSourceType": "PMID" }, { "claim": "Low-dose MK-7 improves osteocalcin gamma-carboxylation (calcium metabolism mechanism)", "title": "Low-Dose Daily Intake of Vitamin K(2) (Menaquinone-7) Improves Osteocalcin gamma-Carboxylation: A Double-Blind, Randomized Controlled Trials", "authors": "Inaba N et al.", "journal": "J Nutr Sci Vitaminol", "year": 2015, "pmid": "26875489", "url": "https://pubmed.ncbi.nlm.nih.gov/26875489/", "study_type": "RCT", "key_finding": "Menaquinone-7 increased carboxylated/undercarboxylated osteocalcin ratio dose-dependently; daily intake >=100 mcg suggested for optimal gamma-carboxylation", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26875489/", "publicSourceType": "PMID" }, { "claim": "Dual role of K2 in bone-vascular crosstalk (cardiovascular health)", "title": "The Dual Role of Vitamin K2 in 'Bone-Vascular Crosstalk': Opposite Effects on Bone Loss and Vascular Calcification", "authors": "Mandatori D et al.", "journal": "Nutrients", "year": 2021, "pmid": "33917175", "url": "https://pubmed.ncbi.nlm.nih.gov/33917175/", "study_type": "review", "key_finding": "Vitamin K2 deficiency may be responsible for the 'calcium paradox', low calcium in bone and accumulation in vessel walls; K2 activates both osteocalcin and MGP", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33917175/", "publicSourceType": "PMID" }, { "claim": "Vitamin K2 MK-7 prevents deterioration of bone microarchitecture in postmenopausal women", "title": "Vitamin K2 (menaquinone-7) prevents age-related deterioration of trabecular bone microarchitecture at the tibia in postmenopausal women", "authors": "Knapen MH et al.", "journal": "Bone", "year": 2016, "pmid": "27625301", "url": "https://pubmed.ncbi.nlm.nih.gov/27625301/", "study_type": "RCT", "key_finding": "MK-7 prevented age-related deterioration of trabecular bone microarchitecture at the tibia in healthy postmenopausal women over 3 years", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27625301/", "publicSourceType": "PMID" }, { "text": "Tan J, Zhu R, Li Y et al.. Vitamin K2 in Managing Nocturnal Leg Cramps: A Randomized Clinical Trial. JAMA internal medicine. 2024", "pmid": "39466236", "doi": "10.1001/jamainternmed.2024.5726", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39466236/", "publicSourceType": "PMID" }, { "text": "Diederichsen ACP, Lindholt JS, Möller S et al.. Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial. Circulation. 2022", "pmid": "35465686", "doi": "10.1161/CIRCULATIONAHA.121.057008", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35465686/", "publicSourceType": "PMID" }, { "claim": "Vitamin K combined with vitamin D significantly increases total bone mineral density", "title": "The combination effect of vitamin K and vitamin D on human bone quality: a meta-analysis of randomized controlled trials", "authors": "Kuang X, Liu C, Guo X, Li K, Deng Q, Li D", "journal": "Food & Function", "year": 2020, "pmid": "32219282", "url": "https://pubmed.ncbi.nlm.nih.gov/32219282/", "study_type": "meta-analysis", "key_finding": "Vitamin K combined with vitamin D significantly increased total BMD (pooled effect size 0.316, 95% CI 0.031-0.601) and significantly decreased undercarboxylated osteocalcin across 8 RCTs with 971 subjects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32219282/", "publicSourceType": "PMID" }, { "claim": "Vitamin K2 is beneficial and safe for long-term treatment of osteoporosis in postmenopausal women", "title": "Efficacy and safety of vitamin K2 for postmenopausal women with osteoporosis at a long-term follow-up: meta-analysis and systematic review", "authors": "Zhou M, Han S, Zhang W, Wu D", "journal": "Journal of Bone and Mineral Metabolism", "year": 2022, "pmid": "35711002", "url": "https://pubmed.ncbi.nlm.nih.gov/35711002/", "study_type": "meta-analysis", "key_finding": "In 9 RCTs with 6,853 participants, VK2 significantly increased lumbar BMD (WMD 2.17, 95% CI 1.59-2.76) and forearm BMD (WMD 1.57, 95% CI 1.15-1.99). No serious adverse events related to VK2 supplementation were reported.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35711002/", "publicSourceType": "PMID" }, { "text": "Bladbjerg EM, Levy-Schousboe K, Frimodt-Møller M et al.. No Detectable Coagulation Activation After Vitamin K (MK-7) Supplementation in Patients on Dialysis With Functional Vitamin K Deficiency: A One-Year Randomized, Placebo-Controlled Study. Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2024", "claim": "PubMed-indexed evidence involving Vitamin K2", "title": "No Detectable Coagulation Activation After Vitamin K (MK-7) Supplementation in Patients on Dialysis With Functional Vitamin K Deficiency: A One-Year Randomized, Placebo-Controlled Study", "authors": "Bladbjerg EM, Levy-Schousboe K, Frimodt-Møller M et al.", "journal": "Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation", "year": 2024, "pmid": "38128853", "url": "https://pubmed.ncbi.nlm.nih.gov/38128853/", "study_type": "RCT", "confidence": "verify", "doi": "10.1053/j.jrn.2023.11.007", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38128853/", "publicSourceType": "PMID" }, { "text": "Naiyarakseree N, Phannajit J, Naiyarakseree W et al.. Effect of Menaquinone-7 Supplementation on Arterial Stiffness in Chronic Hemodialysis Patients: A Multicenter Randomized Controlled Trial. Nutrients. 2023", "claim": "PubMed-indexed evidence involving Vitamin K2", "title": "Effect of Menaquinone-7 Supplementation on Arterial Stiffness in Chronic Hemodialysis Patients: A Multicenter Randomized Controlled Trial", "authors": "Naiyarakseree N, Phannajit J, Naiyarakseree W et al.", "journal": "Nutrients", "year": 2023, "pmid": "37299386", "url": "https://pubmed.ncbi.nlm.nih.gov/37299386/", "study_type": "RCT", "confidence": "verify", "doi": "10.3390/nu15112422", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37299386/", "publicSourceType": "PMID" }, { "text": "Rønn SH, Harsløf T, Oei L et al.. The effect of vitamin MK-7 on bone mineral density and microarchitecture in postmenopausal women with osteopenia, a 3-year randomized, placebo-controlled clinical trial. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2021", "claim": "PubMed-indexed evidence involving Vitamin K2", "title": "The effect of vitamin MK-7 on bone mineral density and microarchitecture in postmenopausal women with osteopenia, a 3-year randomized, placebo-controlled clinical trial", "authors": "Rønn SH, Harsløf T, Oei L et al.", "journal": "Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA", "year": 2021, "pmid": "33030563", "url": "https://pubmed.ncbi.nlm.nih.gov/33030563/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/s00198-020-05638-z", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33030563/", "publicSourceType": "PMID" }, { "text": "De Vriese AS, Caluwé R, Pyfferoen L et al.. Multicenter Randomized Controlled Trial of Vitamin K Antagonist Replacement by Rivaroxaban with or without Vitamin K2 in Hemodialysis Patients with Atrial Fibrillation: the Valkyrie Study. Journal of the American Society of Nephrology : JASN. 2020", "claim": "PubMed-indexed evidence involving Vitamin K2", "title": "Multicenter Randomized Controlled Trial of Vitamin K Antagonist Replacement by Rivaroxaban with or without Vitamin K2 in Hemodialysis Patients with Atrial Fibrillation: the Valkyrie Study", "authors": "De Vriese AS, Caluwé R, Pyfferoen L et al.", "journal": "Journal of the American Society of Nephrology : JASN", "year": 2020, "pmid": "31704740", "url": "https://pubmed.ncbi.nlm.nih.gov/31704740/", "study_type": "RCT", "confidence": "verify", "doi": "10.1681/ASN.2019060579", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31704740/", "publicSourceType": "PMID" }, { "text": "Caluwé R, Vandecasteele S, Van Vlem B et al.. Vitamin K2 supplementation in haemodialysis patients: a randomized dose-finding study. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2014", "claim": "PubMed-indexed evidence involving Vitamin K2", "title": "Vitamin K2 supplementation in haemodialysis patients: a randomized dose-finding study", "authors": "Caluwé R, Vandecasteele S, Van Vlem B et al.", "journal": "Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association", "year": 2014, "pmid": "24285428", "url": "https://pubmed.ncbi.nlm.nih.gov/24285428/", "study_type": "RCT", "confidence": "verify", "doi": "10.1093/ndt/gft464", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24285428/", "publicSourceType": "PMID" }, { "text": "Huang SH, Fang ST, Chen YC. Molecular Mechanism of Vitamin K2 Protection against Amyloid-β-Induced Cytotoxicity. Biomolecules. 2021", "claim": "PubMed-indexed evidence involving Vitamin K2", "title": "Molecular Mechanism of Vitamin K2 Protection against Amyloid-β-Induced Cytotoxicity", "authors": "Huang SH, Fang ST, Chen YC", "journal": "Biomolecules", "year": 2021, "pmid": "33805625", "url": "https://pubmed.ncbi.nlm.nih.gov/33805625/", "study_type": "review", "confidence": "verify", "doi": "10.3390/biom11030423", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33805625/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "vitamin-k2" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567006", "name": "Vitamin K1", "alternateNames": [ "Phylloquinone" ], "category": "Vitamin", "subcategory": "Fat-Soluble Vitamin", "overview": "The primary form of vitamin K found in plants, essential for blood clotting. Also supports bone health to a lesser extent than K2.", "mechanismOfAction": "Serves as a cofactor for gamma-glutamyl carboxylase, which activates clotting factors II (prothrombin), VII, IX, and X in the coagulation cascade.", "commonBenefits": [ "Blood clotting", "Bone health", "Wound healing" ], "commonDosageRange": "90–120 mcg daily", "recommendedForm": "Phylloquinone from food or supplements", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Fat-soluble; abundant in green leafy vegetables" }, "evidenceRating": "strong", "foodSources": [ "Kale", "Spinach", "Broccoli", "Brussels sprouts", "Collard greens" ], "deficiencySymptoms": [ "Excessive bleeding", "Easy bruising", "Heavy menstrual periods" ], "sideEffects": [ "Very low toxicity risk" ], "contraindications": [ "Warfarin (must maintain consistent intake)", "Blood thinners" ], "iconName": "drop.fill", "colorHex": "8B9A46", "tags": [ "blood-health", "bone-health" ], "sources": [ { "claim": "Vitamin K decreases general fracture risk (bone health)", "title": "Effect of Vitamin K on Bone Mineral Density and Fracture Risk in Adults: Systematic Review and Meta-Analysis", "authors": "Mott A et al.", "journal": "Nutrients", "year": 2022, "pmid": "35625785", "url": "https://pubmed.ncbi.nlm.nih.gov/35625785/", "study_type": "meta-analysis", "key_finding": "Vitamin K decreases general fracture risk (OR 0.42 vertebral, OR 0.44 clinical); can be an option to counter bone loss disorders", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35625785/", "publicSourceType": "PMID" }, { "claim": "Vitamin K intake and fracture risk (bone health)", "title": "Vitamin K intake and the risk of fractures: A meta-analysis", "authors": "Hao G et al.", "journal": "Medicine (Baltimore)", "year": 2017, "pmid": "28445289", "url": "https://pubmed.ncbi.nlm.nih.gov/28445289/", "study_type": "meta-analysis", "key_finding": "Four cohort studies and one nested case-control study (1,114 fracture cases, 80,982 participants) examined vitamin K1 intake and fracture risk", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28445289/", "publicSourceType": "PMID" }, { "claim": "Vitamin K and prevention of fractures (bone health)", "title": "Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials", "authors": "Cockayne S et al.", "journal": "Arch Intern Med", "year": 2006, "pmid": "16801507", "url": "https://pubmed.ncbi.nlm.nih.gov/16801507/", "study_type": "meta-analysis", "key_finding": "Pooling 7 trials: OR 0.40 for vertebral fractures, OR 0.23 for hip fractures, OR 0.19 for all nonvertebral fractures favoring vitamin K", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16801507/", "publicSourceType": "PMID" }, { "claim": "Vitamin K role in bone health and nutrition", "title": "Vitamin K Nutrition and Bone Health", "authors": "Capozzi A et al.", "journal": "Int J Endocrinol", "year": 2020, "pmid": "32605143", "url": "https://pubmed.ncbi.nlm.nih.gov/32605143/", "study_type": "review", "key_finding": "Vitamin K required for osteocalcin carboxylation regulating bone mineral accretion; promotes osteoblast transition to osteocytes and limits osteoclastogenesis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32605143/", "publicSourceType": "PMID" }, { "claim": "Interaction between dietary vitamin K and anticoagulation by warfarin (safety/drug interaction)", "title": "Interaction Between Dietary Vitamin K Intake and Anticoagulation by Vitamin K Antagonists: Is It Really True?: A Systematic Review", "authors": "Violi F et al.", "journal": "Medicine (Baltimore)", "year": 2016, "pmid": "26962786", "url": "https://pubmed.ncbi.nlm.nih.gov/26962786/", "study_type": "review", "key_finding": "Dietary vitamin K can decrease therapeutic effectiveness of warfarin; poor vitamin K status increases sensitivity to small changes in vitamin K intake", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26962786/", "publicSourceType": "PMID" }, { "text": "Ingold CJ, Sergent SR. Phytonadione (Vitamin K1). 2026", "pmid": "32491554", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32491554/", "publicSourceType": "PMID" }, { "text": "Dezee KJ, Shimeall WT, Douglas KM et al.. Treatment of excessive anticoagulation with phytonadione (vitamin K): a meta-analysis. Archives of internal medicine. 2006", "claim": "PubMed-indexed evidence involving Vitamin K1", "title": "Treatment of excessive anticoagulation with phytonadione (vitamin K): a meta-analysis", "authors": "Dezee KJ, Shimeall WT, Douglas KM et al.", "journal": "Archives of internal medicine", "year": 2006, "pmid": "16505257", "url": "https://pubmed.ncbi.nlm.nih.gov/16505257/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1001/.391", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16505257/", "publicSourceType": "PMID" }, { "text": "Macias-Cervantes HE, Ocampo-Apolonio MA, Guardado-Mendoza R et al.. Effect of vitamin K1 supplementation on coronary calcifications in hemodialysis patients: a randomized controlled trial. Journal of nephrology. 2025", "claim": "PubMed-indexed evidence involving Vitamin K1", "title": "Effect of vitamin K1 supplementation on coronary calcifications in hemodialysis patients: a randomized controlled trial", "authors": "Macias-Cervantes HE, Ocampo-Apolonio MA, Guardado-Mendoza R et al.", "journal": "Journal of nephrology", "year": 2025, "pmid": "39680321", "url": "https://pubmed.ncbi.nlm.nih.gov/39680321/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/s40620-024-02154-9", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39680321/", "publicSourceType": "PMID" }, { "text": "Saritas T, Reinartz S, Krüger T et al.. Vitamin K1 and progression of cardiovascular calcifications in hemodialysis patients: the VitaVasK randomized controlled trial. Clinical kidney journal. 2022", "claim": "PubMed-indexed evidence involving Vitamin K1", "title": "Vitamin K1 and progression of cardiovascular calcifications in hemodialysis patients: the VitaVasK randomized controlled trial", "authors": "Saritas T, Reinartz S, Krüger T et al.", "journal": "Clinical kidney journal", "year": 2022, "pmid": "37216675", "url": "https://pubmed.ncbi.nlm.nih.gov/37216675/", "study_type": "RCT", "confidence": "verify", "doi": "10.1093/ckj/sfac184", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37216675/", "publicSourceType": "PMID" }, { "text": "Lubetsky A, Yonath H, Olchovsky D et al.. Comparison of oral vs intravenous phytonadione (vitamin K1) in patients with excessive anticoagulation: a prospective randomized controlled study. Archives of internal medicine. 2003", "claim": "PubMed-indexed evidence involving Vitamin K1", "title": "Comparison of oral vs intravenous phytonadione (vitamin K1) in patients with excessive anticoagulation: a prospective randomized controlled study", "authors": "Lubetsky A, Yonath H, Olchovsky D et al.", "journal": "Archives of internal medicine", "year": 2003, "pmid": "14609783", "url": "https://pubmed.ncbi.nlm.nih.gov/14609783/", "study_type": "RCT", "confidence": "verify", "doi": "10.1001/archinte.163.20.2469", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14609783/", "publicSourceType": "PMID" }, { "text": "Patel RJ, Witt DM, Saseen JJ et al.. Randomized, placebo-controlled trial of oral phytonadione for excessive anticoagulation. Pharmacotherapy. 2000", "claim": "PubMed-indexed evidence involving Vitamin K1", "title": "Randomized, placebo-controlled trial of oral phytonadione for excessive anticoagulation", "authors": "Patel RJ, Witt DM, Saseen JJ et al.", "journal": "Pharmacotherapy", "year": 2000, "pmid": "11034038", "url": "https://pubmed.ncbi.nlm.nih.gov/11034038/", "study_type": "RCT", "confidence": "verify", "doi": "10.1592/phco.20.15.1159.34585", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11034038/", "publicSourceType": "PMID" }, { "text": "EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP), Bampidis V, Azimonti G et al.. Safety and efficacy of an additive consisting of synthetic vitamin K(1) (phytomenadione) for horses (JARAZ Enterprises GmbH & Co. KG). EFSA journal. European Food Safety Authority. 2021", "claim": "PubMed-indexed evidence involving Vitamin K1", "title": "Safety and efficacy of an additive consisting of synthetic vitamin K(1) (phytomenadione) for horses (JARAZ Enterprises GmbH & Co. KG)", "authors": "EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP), Bampidis V, Azimonti G et al.", "journal": "EFSA journal. European Food Safety Authority", "year": 2021, "pmid": "33968245", "url": "https://pubmed.ncbi.nlm.nih.gov/33968245/", "study_type": "review", "confidence": "verify", "doi": "10.2903/j.efsa.2021.6538", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33968245/", "publicSourceType": "PMID" }, { "text": "Shields RC, McBane RD, Kuiper JD et al.. Efficacy and safety of intravenous phytonadione (vitamin K1) in patients on long-term oral anticoagulant therapy. Mayo Clinic proceedings. 2001", "claim": "PubMed-indexed evidence involving Vitamin K1", "title": "Efficacy and safety of intravenous phytonadione (vitamin K1) in patients on long-term oral anticoagulant therapy", "authors": "Shields RC, McBane RD, Kuiper JD et al.", "journal": "Mayo Clinic proceedings", "year": 2001, "pmid": "11243272", "url": "https://pubmed.ncbi.nlm.nih.gov/11243272/", "study_type": "review", "confidence": "verify", "doi": "10.4065/76.3.260", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11243272/", "publicSourceType": "PMID" }, { "text": "von Kries R. Oral versus intramuscular phytomenadione: safety and efficacy compared. Drug safety. 1999", "claim": "PubMed-indexed evidence involving Vitamin K1", "title": "Oral versus intramuscular phytomenadione: safety and efficacy compared", "authors": "von Kries R", "journal": "Drug safety", "year": 1999, "pmid": "10433349", "url": "https://pubmed.ncbi.nlm.nih.gov/10433349/", "study_type": "review", "confidence": "verify", "doi": "10.2165/00002018-199921010-00001", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10433349/", "publicSourceType": "PMID" }, { "text": "Smith JM, Smith CK, Zhu X et al.. Supplementation of Vitamin K1 in Dogs With Chronic Enteropathy. Journal of veterinary internal medicine. 2025", "claim": "PubMed-indexed evidence involving Vitamin K1", "title": "Supplementation of Vitamin K1 in Dogs With Chronic Enteropathy", "authors": "Smith JM, Smith CK, Zhu X et al.", "journal": "Journal of veterinary internal medicine", "year": 2025, "pmid": "40318178", "url": "https://pubmed.ncbi.nlm.nih.gov/40318178/", "study_type": "review", "confidence": "verify", "doi": "10.1111/jvim.70111", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40318178/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "vitamin-k1" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567007", "name": "Vitamin B1", "alternateNames": [ "Thiamine", "Benfotiamine" ], "category": "Vitamin", "subcategory": "B Vitamin", "overview": "Essential for energy metabolism, nerve function, and carbohydrate metabolism. First B vitamin discovered.", "mechanismOfAction": "As thiamine pyrophosphate (TPP), serves as a coenzyme for pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase in the Krebs cycle, and transketolase in the pentose phosphate pathway.", "commonBenefits": [ "Energy production", "Nerve function", "Carbohydrate metabolism", "Brain health" ], "commonDosageRange": "50–100 mg daily", "recommendedForm": "Benfotiamine (fat-soluble, better bioavailability) or thiamine HCl", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Water-soluble; take with food to reduce GI upset" }, "evidenceRating": "strong", "foodSources": [ "Pork", "Whole grains", "Legumes", "Sunflower seeds", "Fortified cereals" ], "deficiencySymptoms": [ "Fatigue", "Nerve damage (beriberi)", "Confusion", "Muscle weakness" ], "sideEffects": [ "Generally well tolerated", "Rare allergic reaction" ], "contraindications": [ "None significant" ], "iconName": "bolt.fill", "colorHex": "FFCC02", "tags": [ "energy", "brain", "nerve-health" ], "sources": [ { "claim": "Review of thiamine biochemistry, metabolism, and clinical benefits (energy metabolism/mechanism)", "title": "A review of the biochemistry, metabolism and clinical benefits of thiamin(e) and its derivatives", "authors": "Lonsdale D", "journal": "Evid Based Complement Alternat Med", "year": 2006, "pmid": "16550223", "url": "https://pubmed.ncbi.nlm.nih.gov/16550223/", "study_type": "review", "key_finding": "Thiamine plays a fundamental role in energy metabolism as TPP, serving as coenzyme for pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and transketolase", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16550223/", "publicSourceType": "PMID" }, { "claim": "Thiamine deficiency clinical perspective including beriberi and Wernicke encephalopathy", "title": "Thiamine deficiency disorders: a clinical perspective", "authors": "Whitfield KC et al.", "journal": "Ann N Y Acad Sci", "year": 2018, "pmid": "33305487", "url": "https://pubmed.ncbi.nlm.nih.gov/33305487/", "study_type": "review", "key_finding": "Thiamine deficiency affects cardiovascular and nervous systems (wet beriberi, dry beriberi, Wernicke-Korsakoff syndrome); organs most sensitive are cardiovascular and nervous systems", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33305487/", "publicSourceType": "PMID" }, { "claim": "Benfotiamine efficacy for diabetic polyneuropathy (nerve function)", "title": "Benfotiamine in the treatment of diabetic polyneuropathy--a three-week randomized, controlled pilot study (BEDIP study)", "authors": "Haupt E et al.", "journal": "Int J Clin Pharmacol Ther", "year": 2005, "pmid": "15726875", "url": "https://pubmed.ncbi.nlm.nih.gov/15726875/", "study_type": "RCT", "key_finding": "Statistically significant improvement in neuropathy scores with benfotiamine; most pronounced effect was decrease in pain; no side effects attributable to benfotiamine", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15726875/", "publicSourceType": "PMID" }, { "claim": "Thiamine and benfotiamine therapeutic potential (bioavailability comparison)", "title": "Thiamine and benfotiamine: Focus on their therapeutic potential", "authors": "Sambon M et al.", "journal": "Biochem Pharmacol", "year": 2023, "pmid": "38034619", "url": "https://pubmed.ncbi.nlm.nih.gov/38034619/", "study_type": "review", "key_finding": "Benfotiamine is more bioavailable with higher tissue penetration than thiamine; has antioxidant and anti-inflammatory potential; beneficial in diabetes complications and neurodegenerative disease models", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38034619/", "publicSourceType": "PMID" }, { "claim": "Potential role of thiamine in diabetic complications", "title": "The potential role of thiamine (vitamin B1) in diabetic complications", "authors": "Thornalley PJ", "journal": "Curr Diabetes Rev", "year": 2005, "pmid": "18220605", "url": "https://pubmed.ncbi.nlm.nih.gov/18220605/", "study_type": "review", "key_finding": "Thiamine deficiency and reduced transketolase activity may contribute to diabetic complications; high-dose thiamine/benfotiamine may prevent microvascular complications", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18220605/", "publicSourceType": "PMID" }, { "text": "Chandrakumar A, Bhardwaj A, 't Jong GW. Review of thiamine deficiency disorders: Wernicke encephalopathy and Korsakoff psychosis. Journal of basic and clinical physiology and pharmacology. 2018", "pmid": "30281514", "doi": "10.1515/jbcpp-2018-0075", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30281514/", "publicSourceType": "PMID" }, { "claim": "Mecobalamin is effective for peripheral neuropathy", "title": "Efficacy and Safety of Mecobalamin on Peripheral Neuropathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.", "authors": "Sawangjit R, Thongphui S, Chaichompu W et al.", "journal": "Journal of Alternative and Complementary Medicine", "year": 2020, "pmid": "32716261", "url": "https://pubmed.ncbi.nlm.nih.gov/32716261/", "study_type": "meta-analysis", "key_finding": "Mecobalamin significantly improved symptoms and nerve conduction velocities in patients with peripheral neuropathy.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32716261/", "publicSourceType": "PMID" }, { "claim": "Methylcobalamin is effective for diabetic peripheral neuropathy", "title": "Disease-modifying therapies for diabetic peripheral neuropathy: A systematic review and meta-analysis of randomized controlled trials.", "authors": "Ran GL, Li YP, Lu LC et al.", "journal": "Journal of Diabetes and its Complications", "year": 2024, "pmid": "38330524", "url": "https://pubmed.ncbi.nlm.nih.gov/38330524/", "study_type": "meta-analysis", "key_finding": "Methylcobalamin showed significant improvement in neuropathic symptoms and nerve function in diabetic peripheral neuropathy patients.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38330524/", "publicSourceType": "PMID" }, { "claim": "Vitamin B12 plays important role in neurological health", "title": "The role of vitamin B12 in viral infections: a comprehensive review of its relationship with the muscle-gut-brain axis and implications for SARS-CoV-2 infection.", "authors": "Batista KS, Cintra VM, Lucena PAF et al.", "journal": "Nutrition Reviews", "year": 2022, "pmid": "34791425", "url": "https://pubmed.ncbi.nlm.nih.gov/34791425/", "study_type": "review", "key_finding": "Vitamin B12 plays critical roles in neurological function, DNA synthesis, and immune regulation, with deficiency linked to neurological and cognitive impairments.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34791425/", "publicSourceType": "PMID" }, { "text": "Nakanishi N, Abe Y, Matsuo M et al.. Effect of intravenous thiamine administration on critically ill patients: A systematic review and meta-analysis of randomized controlled trials. Clinical nutrition (Edinburgh, Scotland). 2024", "claim": "PubMed-indexed evidence involving Vitamin B1", "title": "Effect of intravenous thiamine administration on critically ill patients: A systematic review and meta-analysis of randomized controlled trials", "authors": "Nakanishi N, Abe Y, Matsuo M et al.", "journal": "Clinical nutrition (Edinburgh, Scotland)", "year": 2024, "pmid": "39307094", "url": "https://pubmed.ncbi.nlm.nih.gov/39307094/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.clnu.2024.09.002", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39307094/", "publicSourceType": "PMID" }, { "text": "Deng J, Zuo QK, Venugopal K et al.. Efficacy and Safety of Hydrocortisone, Ascorbic Acid, and Thiamine Combination Therapy for the Management of Sepsis and Septic Shock: A Systematic Review and Meta-Analysis of Randomised Controlled Trials. International archives of allergy and immunology. 2024", "claim": "PubMed-indexed evidence involving Vitamin B1", "title": "Efficacy and Safety of Hydrocortisone, Ascorbic Acid, and Thiamine Combination Therapy for the Management of Sepsis and Septic Shock: A Systematic Review and Meta-Analysis of Randomised Controlled Trials", "authors": "Deng J, Zuo QK, Venugopal K et al.", "journal": "International archives of allergy and immunology", "year": 2024, "pmid": "38870923", "url": "https://pubmed.ncbi.nlm.nih.gov/38870923/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1159/000538959", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38870923/", "publicSourceType": "PMID" }, { "text": "Qian X, Zhang Z, Li F et al.. Intravenous thiamine for septic shock: A meta-analysis of randomized controlled trials. The American journal of emergency medicine. 2020", "claim": "PubMed-indexed evidence involving Vitamin B1", "title": "Intravenous thiamine for septic shock: A meta-analysis of randomized controlled trials", "authors": "Qian X, Zhang Z, Li F et al.", "journal": "The American journal of emergency medicine", "year": 2020, "pmid": "33036854", "url": "https://pubmed.ncbi.nlm.nih.gov/33036854/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.ajem.2020.08.050", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33036854/", "publicSourceType": "PMID" }, { "text": "Serra M, Mollace R, Ritorto G et al.. A Systematic Review of Thiamine Supplementation in Improving Diabetes and Its Related Cardiovascular Dysfunction. International journal of molecular sciences. 2025", "claim": "PubMed-indexed evidence involving Vitamin B1", "title": "A Systematic Review of Thiamine Supplementation in Improving Diabetes and Its Related Cardiovascular Dysfunction", "authors": "Serra M, Mollace R, Ritorto G et al.", "journal": "International journal of molecular sciences", "year": 2025, "pmid": "40362174", "url": "https://pubmed.ncbi.nlm.nih.gov/40362174/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/ijms26093932", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40362174/", "publicSourceType": "PMID" }, { "text": "Fujii T, Salanti G, Belletti A et al.. Effect of adjunctive vitamin C, glucocorticoids, and vitamin B1 on longer-term mortality in adults with sepsis or septic shock: a systematic review and a component network meta-analysis. Intensive care medicine. 2022", "claim": "PubMed-indexed evidence involving Vitamin B1", "title": "Effect of adjunctive vitamin C, glucocorticoids, and vitamin B1 on longer-term mortality in adults with sepsis or septic shock: a systematic review and a component network meta-analysis", "authors": "Fujii T, Salanti G, Belletti A et al.", "journal": "Intensive care medicine", "year": 2022, "pmid": "34750650", "url": "https://pubmed.ncbi.nlm.nih.gov/34750650/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00134-021-06558-0", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34750650/", "publicSourceType": "PMID" }, { "text": "Queiroz Júnior JRA, Costa Pereira JPD, Pires LL et al.. The Dichotomous Effect of Thiamine Supplementation on Tumorigenesis: A Systematic Review. Nutrition and cancer. 2022", "claim": "PubMed-indexed evidence involving Vitamin B1", "title": "The Dichotomous Effect of Thiamine Supplementation on Tumorigenesis: A Systematic Review", "authors": "Queiroz Júnior JRA, Costa Pereira JPD, Pires LL et al.", "journal": "Nutrition and cancer", "year": 2022, "pmid": "34854769", "url": "https://pubmed.ncbi.nlm.nih.gov/34854769/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/01635581.2021.2007962", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34854769/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "vitamin-b1" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567008", "name": "Vitamin B2", "alternateNames": [ "Riboflavin" ], "category": "Vitamin", "subcategory": "B Vitamin", "overview": "Essential for energy production, cellular function, and metabolism of fats, drugs, and steroids. Also important for maintaining healthy skin and eyes.", "mechanismOfAction": "Precursor to flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which serve as electron carriers in oxidation-reduction reactions in the electron transport chain and numerous metabolic pathways.", "commonBenefits": [ "Energy production", "Migraine prevention", "Eye health", "Skin health" ], "commonDosageRange": "25–400 mg daily (higher for migraines)", "recommendedForm": "Riboflavin-5'-phosphate (active form) or riboflavin", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Absorption peaks around 27mg per dose; split larger doses" }, "evidenceRating": "strong", "foodSources": [ "Eggs", "Dairy", "Lean meats", "Almonds", "Mushrooms" ], "deficiencySymptoms": [ "Cracked lips", "Sore throat", "Skin rashes", "Anemia", "Light sensitivity" ], "sideEffects": [ "Bright yellow urine (harmless)", "Rare GI upset" ], "contraindications": [ "None significant" ], "iconName": "bolt.circle.fill", "colorHex": "FFD000", "tags": [ "energy", "migraine", "skin" ], "sources": [ { "claim": "Riboflavin supplementation effective for migraine prophylaxis (migraine prevention)", "title": "Effect of Vitamin B2 supplementation on migraine prophylaxis: a systematic review and meta-analysis", "authors": "Yamanaka G et al.", "journal": "J Clin Med", "year": 2021, "pmid": "33779525", "url": "https://pubmed.ncbi.nlm.nih.gov/33779525/", "study_type": "meta-analysis", "key_finding": "Vitamin B2 400 mg/day for three months significantly reduced migraine attack days, duration, frequency, and pain score; 9 articles, 673 subjects analyzed", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33779525/", "publicSourceType": "PMID" }, { "claim": "Effectiveness of high-dose riboflavin in migraine prophylaxis (landmark RCT)", "title": "Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial", "authors": "Schoenen J et al.", "journal": "Neurology", "year": 1998, "pmid": "9484373", "url": "https://pubmed.ncbi.nlm.nih.gov/9484373/", "study_type": "RCT", "key_finding": "High-dose riboflavin (400 mg/day) was effective in migraine prophylaxis with minimal side effects in a randomized controlled trial", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9484373/", "publicSourceType": "PMID" }, { "claim": "Supplementation with riboflavin for migraine prophylaxis in adults and children (review)", "title": "Supplementation with Riboflavin (Vitamin B2) for Migraine Prophylaxis in Adults and Children: A Review", "authors": "Thompson DF, Saluja HS", "journal": "Ann Pharmacother", "year": 2017, "pmid": "26780280", "url": "https://pubmed.ncbi.nlm.nih.gov/26780280/", "study_type": "review", "key_finding": "Riboflavin can play a positive role in reducing frequency and duration of migraine attacks in adults with no serious side effects; pediatric use not proven", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26780280/", "publicSourceType": "PMID" }, { "claim": "Riboflavin as precursor to FAD/FMN for energy metabolism (mechanism)", "title": "Prophylaxis of migraine headaches with riboflavin: A systematic review", "authors": "Namazi N et al.", "journal": "J Clin Pharm Ther", "year": 2015, "pmid": "28485121", "url": "https://pubmed.ncbi.nlm.nih.gov/28485121/", "study_type": "review", "key_finding": "Riboflavin is well tolerated, inexpensive, and has demonstrated efficacy in reduction of adult migraine headache frequency", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28485121/", "publicSourceType": "PMID" }, { "claim": "Nutraceuticals for headache including riboflavin (current recommendations)", "title": "Nutraceuticals and Headache 2024: Riboflavin, Coenzyme Q10, Feverfew, Magnesium, Melatonin, and Butterbur", "authors": "Wells RE et al.", "journal": "Headache", "year": 2025, "pmid": "39853578", "url": "https://pubmed.ncbi.nlm.nih.gov/39853578/", "study_type": "review", "key_finding": "Updated review of evidence for nutraceuticals in headache management including riboflavin as a well-established migraine prophylactic agent", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39853578/", "publicSourceType": "PMID" }, { "text": "Martello E, Aiyelabegan F, Orr J et al.. Systematic Review Suggests Nutraceuticals Containing Vitamin B2 Could Provide an Alternative Treatment for Paediatric Migraines. Acta paediatrica (Oslo, Norway : 1992). 2025", "claim": "PubMed-indexed evidence involving Vitamin B2", "title": "Systematic Review Suggests Nutraceuticals Containing Vitamin B2 Could Provide an Alternative Treatment for Paediatric Migraines", "authors": "Martello E, Aiyelabegan F, Orr J et al.", "journal": "Acta paediatrica (Oslo, Norway : 1992)", "year": 2025, "pmid": "40411246", "url": "https://pubmed.ncbi.nlm.nih.gov/40411246/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/apa.70157", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40411246/", "publicSourceType": "PMID" }, { "text": "Łopaciński M, Fiegler-Rudol J, Niemczyk W et al.. Riboflavin- and Hypericin-Mediated Antimicrobial Photodynamic Therapy as Alternative Treatments for Oral Candidiasis: A Systematic Review. Pharmaceutics. 2024", "claim": "PubMed-indexed evidence involving Vitamin B2", "title": "Riboflavin- and Hypericin-Mediated Antimicrobial Photodynamic Therapy as Alternative Treatments for Oral Candidiasis: A Systematic Review", "authors": "Łopaciński M, Fiegler-Rudol J, Niemczyk W et al.", "journal": "Pharmaceutics", "year": 2024, "pmid": "39861682", "url": "https://pubmed.ncbi.nlm.nih.gov/39861682/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/pharmaceutics17010033", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39861682/", "publicSourceType": "PMID" }, { "text": "Yu L, Tan Y, Zhu L. Dietary vitamin B2 intake and breast cancer risk: a systematic review and meta-analysis. Archives of gynecology and obstetrics. 2017", "claim": "PubMed-indexed evidence involving Vitamin B2", "title": "Dietary vitamin B2 intake and breast cancer risk: a systematic review and meta-analysis", "authors": "Yu L, Tan Y, Zhu L", "journal": "Archives of gynecology and obstetrics", "year": 2017, "pmid": "28035488", "url": "https://pubmed.ncbi.nlm.nih.gov/28035488/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00404-016-4278-4", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28035488/", "publicSourceType": "PMID" }, { "text": "Naghashpour M, Jafarirad S, Amani R et al.. Update on riboflavin and multiple sclerosis: a systematic review. Iranian journal of basic medical sciences. 2017", "claim": "PubMed-indexed evidence involving Vitamin B2", "title": "Update on riboflavin and multiple sclerosis: a systematic review", "authors": "Naghashpour M, Jafarirad S, Amani R et al.", "journal": "Iranian journal of basic medical sciences", "year": 2017, "pmid": "29085589", "url": "https://pubmed.ncbi.nlm.nih.gov/29085589/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.22038/IJBMS.2017.9257", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29085589/", "publicSourceType": "PMID" }, { "text": "Liu Y, Yu QY, Zhu ZL et al.. Vitamin B2 intake and the risk of colorectal cancer: a meta-analysis of observational studies. Asian Pacific journal of cancer prevention : APJCP. 2015", "claim": "PubMed-indexed evidence involving Vitamin B2", "title": "Vitamin B2 intake and the risk of colorectal cancer: a meta-analysis of observational studies", "authors": "Liu Y, Yu QY, Zhu ZL et al.", "journal": "Asian Pacific journal of cancer prevention : APJCP", "year": 2015, "pmid": "25735381", "url": "https://pubmed.ncbi.nlm.nih.gov/25735381/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7314/apjcp.2015.16.3.909", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25735381/", "publicSourceType": "PMID" }, { "text": "Tao Y, Wu M, Su B et al.. Impact of Vitamin B1 and Vitamin B2 Supplementation on Anxiety, Stress, and Sleep Quality: A Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients. 2025", "claim": "PubMed-indexed evidence involving Vitamin B2", "title": "Impact of Vitamin B1 and Vitamin B2 Supplementation on Anxiety, Stress, and Sleep Quality: A Randomized, Double-Blind, Placebo-Controlled Trial", "authors": "Tao Y, Wu M, Su B et al.", "journal": "Nutrients", "year": 2025, "pmid": "40507089", "url": "https://pubmed.ncbi.nlm.nih.gov/40507089/", "study_type": "RCT", "confidence": "verify", "doi": "10.3390/nu17111821", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40507089/", "publicSourceType": "PMID" }, { "text": "Lee TY, Farah N, Chin VK et al.. Medicinal benefits, biological, and nanoencapsulation functions of riboflavin with its toxicity profile: A narrative review. Nutrition research (New York, N.Y.). 2023", "claim": "PubMed-indexed evidence involving Vitamin B2", "title": "Medicinal benefits, biological, and nanoencapsulation functions of riboflavin with its toxicity profile: A narrative review", "authors": "Lee TY, Farah N, Chin VK et al.", "journal": "Nutrition research (New York, N.Y.)", "year": 2023, "pmid": "37708600", "url": "https://pubmed.ncbi.nlm.nih.gov/37708600/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.nutres.2023.08.010", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37708600/", "publicSourceType": "PMID" }, { "text": "Russo P, Diez-Ozaeta I, Mangieri N et al.. Biotechnological Potential and Safety Evaluation of Dextran- and Riboflavin-Producing Weisella cibaria Strains for Gluten-Free Baking. Foods (Basel, Switzerland). 2023", "claim": "PubMed-indexed evidence involving Vitamin B2", "title": "Biotechnological Potential and Safety Evaluation of Dextran- and Riboflavin-Producing Weisella cibaria Strains for Gluten-Free Baking", "authors": "Russo P, Diez-Ozaeta I, Mangieri N et al.", "journal": "Foods (Basel, Switzerland)", "year": 2023, "pmid": "38201097", "url": "https://pubmed.ncbi.nlm.nih.gov/38201097/", "study_type": "review", "confidence": "verify", "doi": "10.3390/foods13010069", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38201097/", "publicSourceType": "PMID" }, { "text": "Gaul C, Diener HC, Danesch U et al.. Improvement of migraine symptoms with a proprietary supplement containing riboflavin, magnesium and Q10: a randomized, placebo-controlled, double-blind, multicenter trial. The journal of headache and pain. 2015", "claim": "PubMed-indexed evidence involving Vitamin B2", "title": "Improvement of migraine symptoms with a proprietary supplement containing riboflavin, magnesium and Q10: a randomized, placebo-controlled, double-blind, multicenter trial", "authors": "Gaul C, Diener HC, Danesch U et al.", "journal": "The journal of headache and pain", "year": 2015, "pmid": "25916335", "url": "https://pubmed.ncbi.nlm.nih.gov/25916335/", "study_type": "RCT", "confidence": "verify", "doi": "10.1186/s10194-015-0516-6", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25916335/", "publicSourceType": "PMID" }, { "text": "Shastak Y, Pelletier W. Exploring the role of riboflavin in swine well-being: a literature review. Porcine health management. 2024", "claim": "PubMed-indexed evidence involving Vitamin B2", "title": "Exploring the role of riboflavin in swine well-being: a literature review", "authors": "Shastak Y, Pelletier W", "journal": "Porcine health management", "year": 2024, "pmid": "39482748", "url": "https://pubmed.ncbi.nlm.nih.gov/39482748/", "study_type": "review", "confidence": "verify", "doi": "10.1186/s40813-024-00399-1", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39482748/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "vitamin-b2" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567009", "name": "Vitamin B3", "alternateNames": [ "Niacin", "Niacinamide", "Nicotinamide" ], "category": "Vitamin", "subcategory": "B Vitamin", "overview": "Critical for NAD+ production, energy metabolism, DNA repair, and cellular signaling. Available as niacin (causes flushing) or niacinamide (no flush).", "mechanismOfAction": "Converted to NAD+ and NADP+, which participate in over 400 enzymatic reactions including glycolysis, Krebs cycle, electron transport chain, DNA repair via PARPs, and sirtuin-mediated longevity pathways.", "commonBenefits": [ "Energy production", "NAD+ support", "Cholesterol management (niacin; raises HDL but no CV outcome benefit when added to statins, prescription-level intervention)", "Skin health (niacinamide)", "DNA repair" ], "commonDosageRange": "RDA-level use unless clinician-directed; niacinamide 500–1,000 mg or niacin 1,000–2,000 mg are pharmacologic doses requiring medical supervision and liver/glucose/urate monitoring", "recommendedForm": "Niacinamide (no flush) or extended-release niacin", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food to reduce flushing (niacin form)" }, "evidenceRating": "strong", "foodSources": [ "Chicken breast", "Tuna", "Turkey", "Mushrooms", "Peanuts" ], "deficiencySymptoms": [ "Pellagra (dermatitis, diarrhea, dementia)", "Fatigue", "Depression" ], "sideEffects": [ "Flushing (niacin)", "GI upset", "Liver stress at very high doses", "Sustained-release niacin is significantly more hepatotoxic than immediate-release", "Niacin for cholesterol: no CV outcome benefit when added to statin therapy (AIM-HIGH, HPS2-THRIVE)" ], "contraindications": [ "Liver disease", "Active peptic ulcer", "Gout (niacin)" ], "iconName": "flame.fill", "colorHex": "FFBA08", "tags": [ "energy", "longevity", "nad" ], "sources": [ { "claim": "Nicotinamide safety and differences from niacin (safety profile)", "title": "Nicotinamide: An Update and Review of Safety & Differences from Niacin", "authors": "Damian DL", "journal": "Skin Therapy Lett", "year": 2020, "pmid": "33196157", "url": "https://pubmed.ncbi.nlm.nih.gov/33196157/", "study_type": "review", "key_finding": "Nicotinamide (niacinamide) is associated with lower incidence of adverse effects than niacin; effective for actinic keratosis, squamous/basal cell carcinomas", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33196157/", "publicSourceType": "PMID" }, { "claim": "Niacin does not reduce cardiovascular events when added to statin therapy (AIM-HIGH)", "title": "Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy", "authors": "AIM-HIGH Investigators", "journal": "N Engl J Med", "year": 2011, "pmid": "22085343", "url": "https://pubmed.ncbi.nlm.nih.gov/22085343/", "study_type": "RCT", "key_finding": "No incremental clinical benefit from adding niacin to statin therapy despite improvements in HDL cholesterol and triglycerides over 36-month follow-up", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22085343/", "publicSourceType": "PMID" }, { "claim": "Niacin no cardiovascular benefit and increased adverse events (HPS2-THRIVE)", "title": "HPS2-THRIVE randomized placebo-controlled trial in 25,673 high-risk patients of ER niacin/laropiprant: trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatment", "authors": "HPS2-THRIVE Collaborative Group", "journal": "Eur Heart J", "year": 2013, "pmid": "23444397", "url": "https://pubmed.ncbi.nlm.nih.gov/23444397/", "study_type": "RCT", "key_finding": "Extended-release niacin-laropiprant added to statin had no cardiovascular benefit; identified serious adverse effects including new-onset diabetes, bleeding, and infection", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23444397/", "publicSourceType": "PMID" }, { "claim": "NAD+ metabolism and vitamin B3 therapeutic applications (mechanism/NAD+ support)", "title": "NAD+ and vitamin B3: from metabolism to therapies", "authors": "Sauve AA", "journal": "J Pharmacol Exp Ther", "year": 2008, "pmid": "18165311", "url": "https://pubmed.ncbi.nlm.nih.gov/18165311/", "study_type": "review", "key_finding": "NAD+ participates in reactions catalyzed by PARPs, mono-ADP-ribosyltransferases, and sirtuins regulating apoptosis, DNA repair, stress resistance, metabolism, and endocrine signaling", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18165311/", "publicSourceType": "PMID" }, { "claim": "Niacin cures systemic NAD+ deficiency in mitochondrial myopathy", "title": "Niacin Cures Systemic NAD+ Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy", "authors": "Pirinen E et al.", "journal": "Cell Metab", "year": 2020, "pmid": "32386566", "url": "https://pubmed.ncbi.nlm.nih.gov/32386566/", "study_type": "RCT", "key_finding": "Blood NAD+ increased up to 8-fold with niacin supplementation; muscle strength and mitochondrial biogenesis increased in all mitochondrial myopathy subjects", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32386566/", "publicSourceType": "PMID" }, { "claim": "Niacinamide improves aging facial skin appearance (skin health)", "title": "Niacinamide: A B vitamin that improves aging facial skin appearance", "authors": "Bissett DL et al.", "journal": "Dermatol Surg", "year": 2005, "pmid": "16029679", "url": "https://pubmed.ncbi.nlm.nih.gov/16029679/", "study_type": "RCT", "key_finding": "Topical niacinamide improved fine lines, wrinkles, hyperpigmentation, red blotchiness, and skin sallowness in a double-blind, placebo-controlled trial", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16029679/", "publicSourceType": "PMID" }, { "text": "Yi L, Maier AB, Tao R et al.. The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. GeroScience. 2023", "pmid": "36482258", "doi": "10.1007/s11357-022-00705-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36482258/", "publicSourceType": "PMID" }, { "text": "Madaan P, Sikka P, Malik DS. Cosmeceutical Aptitudes of Niacinamide: A Review. Recent advances in anti-infective drug discovery. 2021", "pmid": "34844552", "doi": "10.2174/2772434416666211129105629", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34844552/", "publicSourceType": "PMID" }, { "text": "Mainville L, Smilga AS, Fortin PR. Effect of Nicotinamide in Skin Cancer and Actinic Keratoses Chemoprophylaxis, and Adverse Effects Related to Nicotinamide: A Systematic Review and Meta-Analysis. Journal of cutaneous medicine and surgery. 2022", "claim": "PubMed-indexed evidence involving Vitamin B3", "title": "Effect of Nicotinamide in Skin Cancer and Actinic Keratoses Chemoprophylaxis, and Adverse Effects Related to Nicotinamide: A Systematic Review and Meta-Analysis", "authors": "Mainville L, Smilga AS, Fortin PR", "journal": "Journal of cutaneous medicine and surgery", "year": 2022, "pmid": "35134311", "url": "https://pubmed.ncbi.nlm.nih.gov/35134311/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/12034754221078201", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35134311/", "publicSourceType": "PMID" }, { "text": "Nicola CA, Marinescu MC, Firan AM et al.. Systematic Review and Meta-Analysis on the Association Between Daily Niacin Intake and Glaucoma. Nutrients. 2024", "claim": "PubMed-indexed evidence involving Vitamin B3", "title": "Systematic Review and Meta-Analysis on the Association Between Daily Niacin Intake and Glaucoma", "authors": "Nicola CA, Marinescu MC, Firan AM et al.", "journal": "Nutrients", "year": 2024, "pmid": "39519437", "url": "https://pubmed.ncbi.nlm.nih.gov/39519437/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu16213604", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39519437/", "publicSourceType": "PMID" }, { "text": "Tosti G, Pepe F, Gnagnarella P et al.. The Role of Nicotinamide as Chemo-Preventive Agent in NMSCs: A Systematic Review and Meta-Analysis. Nutrients. 2023", "claim": "PubMed-indexed evidence involving Vitamin B3", "title": "The Role of Nicotinamide as Chemo-Preventive Agent in NMSCs: A Systematic Review and Meta-Analysis", "authors": "Tosti G, Pepe F, Gnagnarella P et al.", "journal": "Nutrients", "year": 2023, "pmid": "38201930", "url": "https://pubmed.ncbi.nlm.nih.gov/38201930/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu16010100", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38201930/", "publicSourceType": "PMID" }, { "text": "Garg A, Sharma A, Krishnamoorthy P et al.. Role of Niacin in Current Clinical Practice: A Systematic Review. The American journal of medicine. 2017", "claim": "PubMed-indexed evidence involving Vitamin B3", "title": "Role of Niacin in Current Clinical Practice: A Systematic Review", "authors": "Garg A, Sharma A, Krishnamoorthy P et al.", "journal": "The American journal of medicine", "year": 2017, "pmid": "27793642", "url": "https://pubmed.ncbi.nlm.nih.gov/27793642/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.amjmed.2016.07.038", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27793642/", "publicSourceType": "PMID" }, { "text": "Young SL, Gazzard G. The adverse effects of oral niacin/nicotinamide - an overview of reviews. Eye (London, England). 2025", "claim": "PubMed-indexed evidence involving Vitamin B3", "title": "The adverse effects of oral niacin/nicotinamide - an overview of reviews", "authors": "Young SL, Gazzard G", "journal": "Eye (London, England)", "year": 2025, "pmid": "40999226", "url": "https://pubmed.ncbi.nlm.nih.gov/40999226/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1038/s41433-025-04027-2", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40999226/", "publicSourceType": "PMID" }, { "text": "Shukla AG, Tsamis E, De Moraes CG et al.. Nicotinamide and Pyruvate in Open-Angle Glaucoma: A Randomized Controlled Trial on Neuroprotection-Design and Methodology. Ophthalmology. Glaucoma. 2025", "claim": "PubMed-indexed evidence involving Vitamin B3", "title": "Nicotinamide and Pyruvate in Open-Angle Glaucoma: A Randomized Controlled Trial on Neuroprotection-Design and Methodology", "authors": "Shukla AG, Tsamis E, De Moraes CG et al.", "journal": "Ophthalmology. Glaucoma", "year": 2025, "pmid": "41461224", "url": "https://pubmed.ncbi.nlm.nih.gov/41461224/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.ogla.2025.12.008", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41461224/", "publicSourceType": "PMID" }, { "text": "Barrong H, Coven H, Lish A et al.. Daily Vinegar Ingestion Improves Depression and Enhances Niacin Metabolism in Overweight Adults: A Randomized Controlled Trial. Nutrients. 2024", "claim": "PubMed-indexed evidence involving Vitamin B3", "title": "Daily Vinegar Ingestion Improves Depression and Enhances Niacin Metabolism in Overweight Adults: A Randomized Controlled Trial", "authors": "Barrong H, Coven H, Lish A et al.", "journal": "Nutrients", "year": 2024, "pmid": "39064748", "url": "https://pubmed.ncbi.nlm.nih.gov/39064748/", "study_type": "RCT", "confidence": "verify", "doi": "10.3390/nu16142305", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39064748/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "vitamin-b3" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567010", "name": "Vitamin B5", "alternateNames": [ "Pantothenic Acid", "Pantethine" ], "category": "Vitamin", "subcategory": "B Vitamin", "overview": "Essential for synthesis of coenzyme A (CoA), which is involved in hundreds of metabolic pathways including fatty acid synthesis and energy production.", "mechanismOfAction": "Converted to coenzyme A, the universal acyl carrier essential for the citric acid cycle, fatty acid synthesis and oxidation, cholesterol synthesis, acetylcholine production, and steroid hormone synthesis.", "commonBenefits": [ "Energy production", "Hormone synthesis", "Wound healing", "Cholesterol balance (pantethine form, not pantothenic acid)" ], "commonDosageRange": "250–500 mg daily", "recommendedForm": "Pantothenic acid or pantethine (for cholesterol)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Water-soluble; widely available in foods" }, "evidenceRating": "moderate", "foodSources": [ "Avocado", "Chicken", "Beef", "Shiitake mushrooms", "Sweet potato" ], "deficiencySymptoms": [ "Fatigue", "Numbness/tingling", "Headache", "Insomnia" ], "sideEffects": [ "Diarrhea at high doses", "GI discomfort" ], "contraindications": [ "None significant" ], "iconName": "waveform.path.ecg", "colorHex": "F4A100", "tags": [ "energy", "hormones", "metabolism" ], "sources": [ { "claim": "Pantothenic acid overview including role as CoA precursor (mechanism)", "title": "Vitamin B5 (Pantothenic Acid)", "authors": "National Library of Medicine", "journal": "StatPearls", "year": 2023, "pmid": "33085380", "url": "https://pubmed.ncbi.nlm.nih.gov/33085380/", "study_type": "NIH_ODS", "key_finding": "Pantothenic acid is a water-soluble vitamin essential as a component of coenzyme A (CoA) and acyl carrier protein (ACP) in hundreds of metabolic pathways", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33085380/", "publicSourceType": "PMID" }, { "claim": "Pantethine lowers total and LDL cholesterol (cholesterol balance)", "title": "Pantethine, a derivative of vitamin B5, favorably alters total, LDL and non-HDL cholesterol in low to moderate cardiovascular risk subjects eligible for statin therapy: a triple-blinded placebo and diet-controlled investigation", "authors": "Evans M et al.", "journal": "Vasc Health Risk Manag", "year": 2014, "pmid": "24600231", "url": "https://pubmed.ncbi.nlm.nih.gov/24600231/", "study_type": "RCT", "key_finding": "Pantethine (600-900 mg/day for 16 weeks) significantly decreased total cholesterol and LDL-C compared to placebo; 11% LDL decrease from baseline", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24600231/", "publicSourceType": "PMID" }, { "claim": "Pantethine favorably alters LDL cholesterol metabolism (earlier trial)", "title": "Pantethine, a derivative of vitamin B(5) used as a nutritional supplement, favorably alters low-density lipoprotein cholesterol metabolism in low- to moderate-cardiovascular risk North American subjects: a triple-blinded placebo and diet-controlled investigation", "authors": "Rumberger JA et al.", "journal": "Nutr Res", "year": 2011, "pmid": "21925346", "url": "https://pubmed.ncbi.nlm.nih.gov/21925346/", "study_type": "RCT", "key_finding": "Pantethine supplementation for 16 weeks significantly lowered total cholesterol and LDL-C beyond the effect of therapeutic lifestyle changes diet alone", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21925346/", "publicSourceType": "PMID" }, { "claim": "Biosynthesis of pantothenic acid and coenzyme A (mechanism)", "title": "Biosynthesis of Pantothenic Acid and Coenzyme A", "authors": "Leonardi R, Jackowski S", "journal": "EcoSal Plus", "year": 2007, "pmid": "26443589", "url": "https://pubmed.ncbi.nlm.nih.gov/26443589/", "study_type": "review", "key_finding": "Pantothenate is vitamin B5 and the key precursor for biosynthesis of CoA, a universal cofactor involved in synthesis of phospholipids, fatty acid metabolism, and TCA cycle", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26443589/", "publicSourceType": "PMID" }, { "claim": "Pantothenic acid scoping review for Nordic Nutrition Recommendations", "title": "Pantothenic acid - a scoping review for Nordic Nutrition Recommendations 2023", "authors": "Various", "journal": "Food Nutr Res", "year": 2024, "pmid": "38187802", "url": "https://pubmed.ncbi.nlm.nih.gov/38187802/", "study_type": "review", "key_finding": "Comprehensive scoping review of pantothenic acid covering dietary requirements, sources, metabolism, and health outcomes for nutrition guideline development", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38187802/", "publicSourceType": "PMID" }, { "text": "Shichkin VP. Vitamin B5 and vitamin U review: justification of combined use for the treatment of mucosa-associated gastrointestinal pathologies. Frontiers in pharmacology. 2025", "pmid": "40469981", "doi": "10.3389/fphar.2025.1587627", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40469981/", "publicSourceType": "PMID" }, { "text": "Yang M, Moclair B, Hatcher V et al.. A randomized, double-blind, placebo-controlled study of a novel pantothenic Acid-based dietary supplement in subjects with mild to moderate facial acne. Dermatology and therapy. 2014", "claim": "PubMed-indexed evidence involving Vitamin B5", "title": "A randomized, double-blind, placebo-controlled study of a novel pantothenic Acid-based dietary supplement in subjects with mild to moderate facial acne", "authors": "Yang M, Moclair B, Hatcher V et al.", "journal": "Dermatology and therapy", "year": 2014, "pmid": "24831048", "url": "https://pubmed.ncbi.nlm.nih.gov/24831048/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/s13555-014-0052-3", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24831048/", "publicSourceType": "PMID" }, { "text": "Vaxman F, Olender S, Lambert A et al.. Effect of pantothenic acid and ascorbic acid supplementation on human skin wound healing process. A double-blind, prospective and randomized trial. European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes. 1995", "claim": "PubMed-indexed evidence involving Vitamin B5", "title": "Effect of pantothenic acid and ascorbic acid supplementation on human skin wound healing process. A double-blind, prospective and randomized trial", "authors": "Vaxman F, Olender S, Lambert A et al.", "journal": "European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes", "year": 1995, "pmid": "7781653", "url": "https://pubmed.ncbi.nlm.nih.gov/7781653/", "study_type": "RCT", "confidence": "verify", "doi": "10.1159/000129395", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7781653/", "publicSourceType": "PMID" }, { "text": "Choi JY, Gihaz S, Munshi M et al.. Vitamin B5 metabolism is essential for vacuolar and mitochondrial functions and drug detoxification in fungi. Communications biology. 2024", "claim": "PubMed-indexed evidence involving Vitamin B5", "title": "Vitamin B5 metabolism is essential for vacuolar and mitochondrial functions and drug detoxification in fungi", "authors": "Choi JY, Gihaz S, Munshi M et al.", "journal": "Communications biology", "year": 2024, "pmid": "39043829", "url": "https://pubmed.ncbi.nlm.nih.gov/39043829/", "study_type": "review", "confidence": "verify", "doi": "10.1038/s42003-024-06595-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39043829/", "publicSourceType": "PMID" }, { "text": "Mao C, Zheng H, Chen Y et al.. Development of a Type I-E CRISPR-Based Programmable Repression System for Fine-Tuning Metabolic Flux toward D-Pantothenic Acid in Bacillus subtilis. ACS synthetic biology. 2024", "claim": "PubMed-indexed evidence involving Vitamin B5", "title": "Development of a Type I-E CRISPR-Based Programmable Repression System for Fine-Tuning Metabolic Flux toward D-Pantothenic Acid in Bacillus subtilis", "authors": "Mao C, Zheng H, Chen Y et al.", "journal": "ACS synthetic biology", "year": 2024, "pmid": "39083228", "url": "https://pubmed.ncbi.nlm.nih.gov/39083228/", "study_type": "review", "confidence": "verify", "doi": "10.1021/acssynbio.4c00256", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39083228/", "publicSourceType": "PMID" }, { "text": "Ragaller V, Lebzien P, Südekum KH et al.. Pantothenic acid in ruminant nutrition: a review. Journal of animal physiology and animal nutrition. 2011", "claim": "PubMed-indexed evidence involving Vitamin B5", "title": "Pantothenic acid in ruminant nutrition: a review", "authors": "Ragaller V, Lebzien P, Südekum KH et al.", "journal": "Journal of animal physiology and animal nutrition", "year": 2011, "pmid": "20579186", "url": "https://pubmed.ncbi.nlm.nih.gov/20579186/", "study_type": "review", "confidence": "verify", "doi": "10.1111/j.1439-0396.2010.01004.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20579186/", "publicSourceType": "PMID" }, { "text": "Tang J, Wu Y, Zhang B et al.. Effects of Pantothenic Acid Supplementation on Growth Performance, Carcass Traits, Plasma Parameters of Starter White Pekin Ducks Fed a Corn-Soybean Meal Diet. Animals : an open access journal from MDPI. 2021", "claim": "PubMed-indexed evidence involving Vitamin B5", "title": "Effects of Pantothenic Acid Supplementation on Growth Performance, Carcass Traits, Plasma Parameters of Starter White Pekin Ducks Fed a Corn-Soybean Meal Diet", "authors": "Tang J, Wu Y, Zhang B et al.", "journal": "Animals : an open access journal from MDPI", "year": 2021, "pmid": "34679892", "url": "https://pubmed.ncbi.nlm.nih.gov/34679892/", "study_type": "review", "confidence": "verify", "doi": "10.3390/ani11102872", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34679892/", "publicSourceType": "PMID" }, { "text": "Ferreira G, Brown AN, Teets CL. Effect of biotin and pantothenic acid on performance and concentrations of avidin-binding substances in blood and milk of lactating dairy cows. Journal of dairy science. 2015", "claim": "PubMed-indexed evidence involving Vitamin B5", "title": "Effect of biotin and pantothenic acid on performance and concentrations of avidin-binding substances in blood and milk of lactating dairy cows", "authors": "Ferreira G, Brown AN, Teets CL", "journal": "Journal of dairy science", "year": 2015, "pmid": "26117345", "url": "https://pubmed.ncbi.nlm.nih.gov/26117345/", "study_type": "review", "confidence": "verify", "doi": "10.3168/jds.2015-9620", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26117345/", "publicSourceType": "PMID" }, { "text": "Wall BT, Stephens FB, Marimuthu K et al.. Acute pantothenic acid and cysteine supplementation does not affect muscle coenzyme A content, fuel selection, or exercise performance in healthy humans. Journal of applied physiology (Bethesda, Md. : 1985). 2012", "claim": "PubMed-indexed evidence involving Vitamin B5", "title": "Acute pantothenic acid and cysteine supplementation does not affect muscle coenzyme A content, fuel selection, or exercise performance in healthy humans", "authors": "Wall BT, Stephens FB, Marimuthu K et al.", "journal": "Journal of applied physiology (Bethesda, Md. : 1985)", "year": 2012, "pmid": "22052867", "url": "https://pubmed.ncbi.nlm.nih.gov/22052867/", "study_type": "review", "confidence": "verify", "doi": "10.1152/japplphysiol.00807.2011", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22052867/", "publicSourceType": "PMID" }, { "text": "Giraldi G, De Luca d'Alessandro E, Mannocci A et al.. A pilot study of the effect of pantothenic acid in the treatment of post-operative ileus: results from an orthopedic surgical department. La Clinica terapeutica. 2012", "claim": "PubMed-indexed evidence involving Vitamin B5", "title": "A pilot study of the effect of pantothenic acid in the treatment of post-operative ileus: results from an orthopedic surgical department", "authors": "Giraldi G, De Luca d'Alessandro E, Mannocci A et al.", "journal": "La Clinica terapeutica", "year": 2012, "pmid": "22964703", "url": "https://pubmed.ncbi.nlm.nih.gov/22964703/", "study_type": "review", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22964703/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "vitamin-b5" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567011", "name": "Vitamin B6", "alternateNames": [ "Pyridoxine", "Pyridoxal-5'-Phosphate", "P-5-P" ], "category": "Vitamin", "subcategory": "B Vitamin", "overview": "Involved in over 100 enzyme reactions, primarily in amino acid metabolism. Critical for neurotransmitter synthesis, hemoglobin production, and immune function.", "mechanismOfAction": "As pyridoxal-5'-phosphate (PLP), serves as coenzyme for aminotransferases, decarboxylases, and other enzymes. Essential for synthesis of serotonin, dopamine, GABA, norepinephrine, and hemoglobin.", "commonBenefits": [ "Neurotransmitter production", "Mood support", "Immune function", "Hemoglobin synthesis", "PMS relief" ], "commonDosageRange": "25–100 mg daily", "recommendedForm": "Pyridoxal-5'-phosphate (P-5-P, active form)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take in the morning; can be energizing" }, "evidenceRating": "strong", "foodSources": [ "Chickpeas", "Tuna", "Salmon", "Potatoes", "Bananas" ], "deficiencySymptoms": [ "Depression", "Confusion", "Anemia", "Weakened immunity", "Skin rashes" ], "sideEffects": [ "Nerve damage risk above 100 mg/day chronic use (US UL)", "Numbness" ], "contraindications": [ "Levodopa (without carbidopa)", "Chronic high doses >200mg" ], "iconName": "brain.head.profile", "colorHex": "E8B500", "tags": [ "mood", "brain", "immune", "neurotransmitters" ], "sources": [ { "claim": "Efficacy of vitamin B6 in treating premenstrual syndrome (PMS relief)", "title": "Efficacy of vitamin B-6 in the treatment of premenstrual syndrome: systematic review", "authors": "Wyatt KM et al.", "journal": "BMJ", "year": 1999, "pmid": "10334745", "url": "https://pubmed.ncbi.nlm.nih.gov/10334745/", "study_type": "meta-analysis", "key_finding": "OR 2.32 for overall PMS symptom improvement vs placebo (9 trials, 940 patients); OR 1.69 for depressive symptoms improvement", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10334745/", "publicSourceType": "PMID" }, { "claim": "B vitamins in the nervous system including pyridoxine (neurotransmitter production mechanism)", "title": "B Vitamins in the nervous system: Current knowledge of the biochemical modes of action and synergies of thiamine, pyridoxine, and cobalamin", "authors": "Calderon-Ospina CA, Nava-Mesa MO", "journal": "CNS Neurosci Ther", "year": 2020, "pmid": "31490017", "url": "https://pubmed.ncbi.nlm.nih.gov/31490017/", "study_type": "review", "key_finding": "Pyridoxine (PLP) is essential for synthesis of serotonin, dopamine, GABA, norepinephrine, and hemoglobin; serves as coenzyme for aminotransferases and decarboxylases", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31490017/", "publicSourceType": "PMID" }, { "claim": "Vitamin B6 induced neuropathy mechanisms (safety/nerve damage risk)", "title": "Vitamin B-6-Induced Neuropathy: Exploring the Mechanisms of Pyridoxine Toxicity", "authors": "Vrolijk MF et al.", "journal": "Adv Nutr", "year": 2017, "pmid": "33912895", "url": "https://pubmed.ncbi.nlm.nih.gov/33912895/", "study_type": "review", "key_finding": "Excessive pyridoxine induces neuropathy through preferential injury of sensory neurons; toxicity reported at 1000 mg/day, occasional reports at 100-300 mg/day", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33912895/", "publicSourceType": "PMID" }, { "claim": "Role of vitamin B6 in peripheral neuropathy (safety systematic review)", "title": "The Role of Vitamin B6 in Peripheral Neuropathy: A Systematic Review", "authors": "van der Watt G et al.", "journal": "Nutrients", "year": 2023, "pmid": "37447150", "url": "https://pubmed.ncbi.nlm.nih.gov/37447150/", "study_type": "review", "key_finding": "Higher vitamin B6 levels from supplements may lead to predominantly sensory axonal neuropathy; US UL is 100 mg/day, EFSA UL is 12 mg/day", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37447150/", "publicSourceType": "PMID" }, { "claim": "Expert consensus on vitamin B6 safe dosage and clinical management", "title": "Expert Consensus on Vitamin B6 Therapeutic Use for Patients: Guidance on Safe Dosage, Duration and Clinical Management", "authors": "Various", "journal": "Nutrients", "year": 2025, "pmid": "40395441", "url": "https://pubmed.ncbi.nlm.nih.gov/40395441/", "study_type": "review", "key_finding": "Expert consensus providing guidance on safe dosage limits, treatment duration, and clinical management of vitamin B6 to prevent neuropathy", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40395441/", "publicSourceType": "PMID" }, { "text": "Besag FMC, Vasey MJ, Sen A. Current evidence for adjunct pyridoxine (vitamin B6) for the treatment of behavioral adverse effects associated with levetiracetam: A systematic review. Epilepsy & behavior : E&B. 2023", "claim": "PubMed-indexed evidence involving Vitamin B6", "title": "Current evidence for adjunct pyridoxine (vitamin B6) for the treatment of behavioral adverse effects associated with levetiracetam: A systematic review", "authors": "Besag FMC, Vasey MJ, Sen A", "journal": "Epilepsy & behavior : E&B", "year": 2023, "pmid": "36791631", "url": "https://pubmed.ncbi.nlm.nih.gov/36791631/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.yebeh.2022.109065", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36791631/", "publicSourceType": "PMID" }, { "text": "Hu Y, Amoah AN, Zhang H et al.. Effect of ginger in the treatment of nausea and vomiting compared with vitamin B6 and placebo during pregnancy: a meta-analysis. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2022", "claim": "PubMed-indexed evidence involving Vitamin B6", "title": "Effect of ginger in the treatment of nausea and vomiting compared with vitamin B6 and placebo during pregnancy: a meta-analysis", "authors": "Hu Y, Amoah AN, Zhang H et al.", "journal": "The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians", "year": 2022, "pmid": "31937153", "url": "https://pubmed.ncbi.nlm.nih.gov/31937153/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/14767058.2020.1712714", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31937153/", "publicSourceType": "PMID" }, { "text": "Romoli M, Perucca E, Sen A. Pyridoxine supplementation for levetiracetam-related neuropsychiatric adverse events: A systematic review. Epilepsy & behavior : E&B. 2020", "claim": "PubMed-indexed evidence involving Vitamin B6", "title": "Pyridoxine supplementation for levetiracetam-related neuropsychiatric adverse events: A systematic review", "authors": "Romoli M, Perucca E, Sen A", "journal": "Epilepsy & behavior : E&B", "year": 2020, "pmid": "31917143", "url": "https://pubmed.ncbi.nlm.nih.gov/31917143/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.yebeh.2019.106861", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31917143/", "publicSourceType": "PMID" }, { "text": "Stolwijk NN, van Dussen L, Reijnhout ND et al.. Effectiveness of Pyridoxal-5'-Phosphate in PNPO Deficiency: A Systematic Review. Journal of inherited metabolic disease. 2025", "claim": "PubMed-indexed evidence involving Vitamin B6", "title": "Effectiveness of Pyridoxal-5'-Phosphate in PNPO Deficiency: A Systematic Review", "authors": "Stolwijk NN, van Dussen L, Reijnhout ND et al.", "journal": "Journal of inherited metabolic disease", "year": 2025, "pmid": "40751583", "url": "https://pubmed.ncbi.nlm.nih.gov/40751583/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/jimd.70074", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40751583/", "publicSourceType": "PMID" }, { "text": "Fang C, Yang L, Xiao F et al.. Genotype and phenotype features and prognostic factors of neonatal-onset pyridoxine-dependent epilepsy: A systematic review. Epilepsy research. 2024", "claim": "PubMed-indexed evidence involving Vitamin B6", "title": "Genotype and phenotype features and prognostic factors of neonatal-onset pyridoxine-dependent epilepsy: A systematic review", "authors": "Fang C, Yang L, Xiao F et al.", "journal": "Epilepsy research", "year": 2024, "pmid": "38636407", "url": "https://pubmed.ncbi.nlm.nih.gov/38636407/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.eplepsyres.2024.107363", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38636407/", "publicSourceType": "PMID" }, { "text": "Jayawardena R, Majeed S, Sooriyaarachchi P et al.. The effects of pyridoxine (vitamin B6) supplementation in nausea and vomiting during pregnancy: a systematic review and meta-analysis. Archives of gynecology and obstetrics. 2023", "claim": "PubMed-indexed evidence involving Vitamin B6", "title": "The effects of pyridoxine (vitamin B6) supplementation in nausea and vomiting during pregnancy: a systematic review and meta-analysis", "authors": "Jayawardena R, Majeed S, Sooriyaarachchi P et al.", "journal": "Archives of gynecology and obstetrics", "year": 2023, "pmid": "36719452", "url": "https://pubmed.ncbi.nlm.nih.gov/36719452/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00404-023-06925-w", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36719452/", "publicSourceType": "PMID" }, { "text": "Mastrangelo M, Gasparri V, Bernardi K et al.. Epilepsy Phenotypes of Vitamin B6-Dependent Diseases: An Updated Systematic Review. Children (Basel, Switzerland). 2023", "claim": "PubMed-indexed evidence involving Vitamin B6", "title": "Epilepsy Phenotypes of Vitamin B6-Dependent Diseases: An Updated Systematic Review", "authors": "Mastrangelo M, Gasparri V, Bernardi K et al.", "journal": "Children (Basel, Switzerland)", "year": 2023, "pmid": "36980111", "url": "https://pubmed.ncbi.nlm.nih.gov/36980111/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/children10030553", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36980111/", "publicSourceType": "PMID" }, { "text": "Liampas IN, Siokas V, Aloizou AM et al.. Pyridoxine, folate and cobalamin for migraine: A systematic review. Acta neurologica Scandinavica. 2020", "claim": "PubMed-indexed evidence involving Vitamin B6", "title": "Pyridoxine, folate and cobalamin for migraine: A systematic review", "authors": "Liampas IN, Siokas V, Aloizou AM et al.", "journal": "Acta neurologica Scandinavica", "year": 2020, "pmid": "32279306", "url": "https://pubmed.ncbi.nlm.nih.gov/32279306/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/ane.13251", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32279306/", "publicSourceType": "PMID" }, { "text": "Lai J, Guo M, Wang D et al.. Association Between Vitamin B6 and the Risk of Colorectal Cancer: A Meta-analysis of Observational Studies. Nutrition and cancer. 2023", "claim": "PubMed-indexed evidence involving Vitamin B6", "title": "Association Between Vitamin B6 and the Risk of Colorectal Cancer: A Meta-analysis of Observational Studies", "authors": "Lai J, Guo M, Wang D et al.", "journal": "Nutrition and cancer", "year": 2023, "pmid": "36961108", "url": "https://pubmed.ncbi.nlm.nih.gov/36961108/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/01635581.2023.2191823", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36961108/", "publicSourceType": "PMID" }, { "text": "Peng YF, Han MM, Huang R et al.. Vitamin B6 Intake and Pancreatic Carcinoma Risk: A Meta-Analysis. Nutrition and cancer. 2019", "claim": "PubMed-indexed evidence involving Vitamin B6", "title": "Vitamin B6 Intake and Pancreatic Carcinoma Risk: A Meta-Analysis", "authors": "Peng YF, Han MM, Huang R et al.", "journal": "Nutrition and cancer", "year": 2019, "pmid": "31226890", "url": "https://pubmed.ncbi.nlm.nih.gov/31226890/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/01635581.2019.1598562", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31226890/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "vitamin-b6" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567012", "name": "Vitamin B7", "alternateNames": [ "Biotin" ], "category": "Vitamin", "subcategory": "B Vitamin", "overview": "Known as the 'beauty vitamin' for its role in hair, skin, and nail health. Also essential for macronutrient metabolism.", "mechanismOfAction": "Serves as a prosthetic group for carboxylase enzymes: pyruvate carboxylase (gluconeogenesis), acetyl-CoA carboxylase (fatty acid synthesis), propionyl-CoA carboxylase (amino acid metabolism), and methylcrotonyl-CoA carboxylase (leucine catabolism).", "commonBenefits": [ "Hair health (only in biotin deficiency)", "Nail strength", "Skin health", "Blood sugar support", "Energy metabolism" ], "commonDosageRange": "2,500–10,000 mcg daily", "recommendedForm": "D-biotin", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "At recommended doses (2,500-10,000 mcg), lab test interference is virtually guaranteed. FDA reported at least one death from falsely low troponin. Affected tests: troponin, thyroid panel, beta-hCG, PSA, vitamin D. Stop at least 72 hours before any blood work." }, "evidenceRating": "moderate", "foodSources": [ "Eggs (cooked)", "Almonds", "Sweet potato", "Salmon", "Cauliflower" ], "deficiencySymptoms": [ "Hair loss", "Brittle nails", "Skin rash", "Depression", "Fatigue" ], "sideEffects": [ "May interfere with lab tests", "Generally very safe" ], "contraindications": [ "Discontinue before blood tests (especially thyroid panels)" ], "iconName": "comb.fill", "colorHex": "F0C040", "tags": [ "hair", "skin", "nails", "beauty" ], "sources": [ { "claim": "Review of use of biotin for hair loss (hair health evidence)", "title": "A Review of the Use of Biotin for Hair Loss", "authors": "Patel DP et al.", "journal": "Skin Appendage Disord", "year": 2017, "pmid": "28879195", "url": "https://pubmed.ncbi.nlm.nih.gov/28879195/", "study_type": "review", "key_finding": "All 18 reported cases showed clinical improvement with biotin, but all had underlying pathology; no RCTs exist for biotin and hair loss in healthy individuals", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28879195/", "publicSourceType": "PMID" }, { "claim": "Rethinking biotin therapy for hair, nail, and skin disorders (evidence assessment)", "title": "Rethinking biotin therapy for hair, nail, and skin disorders", "authors": "Lipner SR", "journal": "J Am Acad Dermatol", "year": 2018, "pmid": "29438761", "url": "https://pubmed.ncbi.nlm.nih.gov/29438761/", "study_type": "review", "key_finding": "Despite enormous market hype, biotin's efficacy for hair growth remains largely unsubstantiated in scientific literature; benefits limited to those with biotin deficiency", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29438761/", "publicSourceType": "PMID" }, { "claim": "Biotin for treatment of nail disease (nail strength)", "title": "Biotin for the treatment of nail disease: what is the evidence?", "authors": "Lipner SR, Scher RK", "journal": "J Dermatolog Treat", "year": 2018, "pmid": "29057689", "url": "https://pubmed.ncbi.nlm.nih.gov/29057689/", "study_type": "review", "key_finding": "63% of patients (22/35) showed clinical improvement in brittle nails with biotin supplementation in a small retrospective study", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29057689/", "publicSourceType": "PMID" }, { "claim": "Biotin interference with troponin and thyroid lab tests (safety/lab test interference)", "title": "Susceptibility of Cardiac Troponin Assays to Biotin Interference", "authors": "Frame IJ, Bhargava R", "journal": "Clin Chem", "year": 2019, "pmid": "30715102", "url": "https://pubmed.ncbi.nlm.nih.gov/30715102/", "study_type": "review", "key_finding": "Biotin interference is possible at plasma concentrations achievable by OTC supplements; may lead to delayed/missed diagnosis of myocardial injury with some troponin assays", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30715102/", "publicSourceType": "PMID" }, { "claim": "Best practices in mitigating biotin interference in lab testing (safety guidance)", "title": "Best practices in mitigating the risk of biotin interference with laboratory testing", "authors": "Bowen R et al.", "journal": "Clin Biochem", "year": 2019, "pmid": "31473202", "url": "https://pubmed.ncbi.nlm.nih.gov/31473202/", "study_type": "review", "key_finding": "Patients should abstain from biotin supplements for at least 48h before blood work; 92 cases of suspected biotin interference reported to FDA since 2016", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31473202/", "publicSourceType": "PMID" }, { "claim": "Comprehensive assessment of biotin interference across immunoassays", "title": "Comprehensive assessment of biotin interference in immunoassays", "authors": "Trambas CM et al.", "journal": "Clin Chem", "year": 2018, "pmid": "30296442", "url": "https://pubmed.ncbi.nlm.nih.gov/30296442/", "study_type": "review", "key_finding": "Biotin falsely increases analyte concentration in competitive immunoassays (positive interference) and shows negative interference in sandwich immunoassays", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30296442/", "publicSourceType": "PMID" }, { "text": "Reininghaus EZ, Platzer M, Kohlhammer-Dohr A et al.. PROVIT: Supplementary Probiotic Treatment and Vitamin B7 in Depression-A Randomized Controlled Trial. Nutrients. 2020", "pmid": "33171595", "doi": "10.3390/nu12113422", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33171595/", "publicSourceType": "PMID" }, { "text": "Evidence Review: Natural Hair Supplements: Biotin and Collagen. Plastic and aesthetic nursing. 2023", "pmid": "37389622", "doi": "10.1097/PSN.0000000000000519", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37389622/", "publicSourceType": "PMID" }, { "claim": "Oral supplementation with micronutrients including biotin increases hair density in androgenetic alopecia and chronic telogen effluvium", "title": "Oral Supplementation with l-Cystine, Serenoa repens, Cucurbita pepo, and Pygeum africanum in Chronic Telogen Effluvium and Androgenetic Alopecia: A Double-Blind, Placebo-Controlled, Randomized Clinical Study", "authors": "Piquero-Casals J, Saceda-Corralo D, Aladren S et al.", "journal": "Skin Appendage Disorders", "year": 2025, "pmid": "39911983", "url": "https://pubmed.ncbi.nlm.nih.gov/39911983/", "study_type": "rct", "key_finding": "In 80 patients, hair density increased by 12.3 hairs/cm2 after 6 months with the oral supplement containing vitamins and micronutrients. The supplement was well tolerated with no moderate or severe adverse events.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39911983/", "publicSourceType": "PMID" }, { "text": "Valentim FO, Miola AC, Miot HA et al.. Efficacy of 5% topical minoxidil versus 5 mg oral biotin versus topical minoxidil and oral biotin on hair growth in men: randomized, crossover, clinical trial. Anais brasileiros de dermatologia. 2024", "claim": "PubMed-indexed evidence involving Vitamin B7", "title": "Efficacy of 5% topical minoxidil versus 5 mg oral biotin versus topical minoxidil and oral biotin on hair growth in men: randomized, crossover, clinical trial", "authors": "Valentim FO, Miola AC, Miot HA et al.", "journal": "Anais brasileiros de dermatologia", "year": 2024, "pmid": "38688776", "url": "https://pubmed.ncbi.nlm.nih.gov/38688776/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.abd.2023.07.008", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38688776/", "publicSourceType": "PMID" }, { "text": "Lai Y, Reina-Gonzalez P, Maor G et al.. Biotin mitigates the development of manganese-induced, Parkinson's disease-related neurotoxicity in Drosophila and human neurons. Science signaling. 2025", "claim": "PubMed-indexed evidence involving Vitamin B7", "title": "Biotin mitigates the development of manganese-induced, Parkinson's disease-related neurotoxicity in Drosophila and human neurons", "authors": "Lai Y, Reina-Gonzalez P, Maor G et al.", "journal": "Science signaling", "year": 2025, "pmid": "39836750", "url": "https://pubmed.ncbi.nlm.nih.gov/39836750/", "study_type": "review", "confidence": "verify", "doi": "10.1126/scisignal.adn9868", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39836750/", "publicSourceType": "PMID" }, { "text": "Lai Y, Reina-Gonzalez P, Maor G et al.. Biotin rescues manganese-induced Parkinson's disease phenotypes and neurotoxicity. bioRxiv : the preprint server for biology. 2023", "claim": "PubMed-indexed evidence involving Vitamin B7", "title": "Biotin rescues manganese-induced Parkinson's disease phenotypes and neurotoxicity", "authors": "Lai Y, Reina-Gonzalez P, Maor G et al.", "journal": "bioRxiv : the preprint server for biology", "year": 2023, "pmid": "38045419", "url": "https://pubmed.ncbi.nlm.nih.gov/38045419/", "study_type": "review", "confidence": "verify", "doi": "10.1101/2023.11.21.568033", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38045419/", "publicSourceType": "PMID" }, { "text": "James A, Stalan J, Kuzhively J. Biotin induced biochemical hyperthyroidism: a case report and review of the literature. Journal of medical case reports. 2023", "claim": "PubMed-indexed evidence involving Vitamin B7", "title": "Biotin induced biochemical hyperthyroidism: a case report and review of the literature", "authors": "James A, Stalan J, Kuzhively J", "journal": "Journal of medical case reports", "year": 2023, "pmid": "37370185", "url": "https://pubmed.ncbi.nlm.nih.gov/37370185/", "study_type": "review", "confidence": "verify", "doi": "10.1186/s13256-023-04002-z", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37370185/", "publicSourceType": "PMID" }, { "text": "Maiti S, Paira P. Biotin conjugated organic molecules and proteins for cancer therapy: A review. European journal of medicinal chemistry. 2018", "claim": "PubMed-indexed evidence involving Vitamin B7", "title": "Biotin conjugated organic molecules and proteins for cancer therapy: A review", "authors": "Maiti S, Paira P", "journal": "European journal of medicinal chemistry", "year": 2018, "pmid": "29324341", "url": "https://pubmed.ncbi.nlm.nih.gov/29324341/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.ejmech.2018.01.001", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29324341/", "publicSourceType": "PMID" }, { "text": "Bistas KG, Tadi P. Biotin. 2026", "claim": "PubMed-indexed evidence involving Vitamin B7", "title": "Biotin", "authors": "Bistas KG, Tadi P", "journal": "", "year": 2026, "pmid": "32119380", "url": "https://pubmed.ncbi.nlm.nih.gov/32119380/", "study_type": "review", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32119380/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "vitamin-b7" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567013", "name": "Vitamin B9", "alternateNames": [ "Folate", "Methylfolate", "5-MTHF", "Folic Acid" ], "category": "Vitamin", "subcategory": "B Vitamin", "overview": "Essential for DNA synthesis, cell division, and methylation. Critical during pregnancy for neural tube development. Methylfolate is the bioactive form.", "mechanismOfAction": "As tetrahydrofolate (THF), serves as a one-carbon carrier in nucleotide synthesis (DNA/RNA), amino acid metabolism, and the methylation cycle. 5-MTHF donates a methyl group to homocysteine via methionine synthase (requires B12) to produce methionine and SAMe.", "commonBenefits": [ "DNA synthesis", "Cell division", "Neural tube development", "Methylation support", "Homocysteine reduction" ], "commonDosageRange": "400–1,000 mcg daily", "recommendedForm": "Methylfolate (5-MTHF), avoids MTHFR gene variant issues", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Works synergistically with B12; take together" }, "evidenceRating": "strong", "foodSources": [ "Dark leafy greens", "Lentils", "Asparagus", "Avocado", "Beets" ], "deficiencySymptoms": [ "Megaloblastic anemia", "Fatigue", "Neural tube defects (pregnancy)", "Elevated homocysteine" ], "sideEffects": [ "May mask B12 deficiency", "Rare GI upset" ], "contraindications": [ "May mask B12 deficiency symptoms" ], "iconName": "leaf.arrow.circlepath", "colorHex": "4CAF50", "tags": [ "methylation", "pregnancy", "dna", "essential" ], "sources": [ { "claim": "Folic acid supplementation prevents neural tube defects (USPSTF recommendation)", "title": "Folic Acid Supplementation to Prevent Neural Tube Defects: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force", "authors": "Viswanathan M et al.", "journal": "JAMA", "year": 2023, "pmid": "37526714", "url": "https://pubmed.ncbi.nlm.nih.gov/37526714/", "study_type": "meta-analysis", "key_finding": "New evidence from observational studies provides additional evidence of benefit of folic acid supplementation for preventing NTDs and no evidence of harms related to multiple gestation, autism, or maternal cancer", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37526714/", "publicSourceType": "PMID" }, { "claim": "USPSTF recommendation for folic acid supplementation in pregnancy", "title": "Folic Acid Supplementation to Prevent Neural Tube Defects: US Preventive Services Task Force Reaffirmation Recommendation Statement", "authors": "US Preventive Services Task Force", "journal": "JAMA", "year": 2023, "pmid": "37526713", "url": "https://pubmed.ncbi.nlm.nih.gov/37526713/", "study_type": "review", "key_finding": "USPSTF recommends all persons planning/could become pregnant take daily supplement of 0.4-0.8 mg folic acid (Grade A recommendation)", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37526713/", "publicSourceType": "PMID" }, { "claim": "5-methyltetrahydrofolate as alternative to folic acid for NTD prevention and MTHFR variants", "title": "Supplementation with Folic Acid or 5-Methyltetrahydrofolate and Prevention of Neural Tube Defects: An Evidence-Based Narrative Review", "authors": "Various", "journal": "Nutrients", "year": 2024, "pmid": "39339754", "url": "https://pubmed.ncbi.nlm.nih.gov/39339754/", "study_type": "review", "key_finding": "Carriers of certain MTHFR polymorphisms may benefit more from 5-methylTHF than folic acid; 5-MTHF is a better alternative, especially in countries without fortification", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39339754/", "publicSourceType": "PMID" }, { "claim": "MTHFR polymorphism, homocysteine, and cardiovascular disease (methylation/homocysteine)", "title": "Homocysteine and coronary heart disease: meta-analysis of MTHFR case-control studies, avoiding publication bias", "authors": "Clarke R et al.", "journal": "PLoS Med", "year": 2012, "pmid": "22363213", "url": "https://pubmed.ncbi.nlm.nih.gov/22363213/", "study_type": "meta-analysis", "key_finding": "MTHFR TT genotype associated with modest cardiovascular risk increase mediated mainly by increased homocysteine and low plasma folate", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22363213/", "publicSourceType": "PMID" }, { "claim": "Excess folic acid and vitamin B12 deficiency masking concern (safety)", "title": "Excess Folic Acid and Vitamin B12 Deficiency: Clinical Implications?", "authors": "Various", "journal": "Clin Chem Lab Med", "year": 2024, "pmid": "38987872", "url": "https://pubmed.ncbi.nlm.nih.gov/38987872/", "study_type": "review", "key_finding": "High serum folate during vitamin B12 deficiency may exacerbate anemia and worsen cognitive symptoms rather than simply 'masking' the deficiency", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38987872/", "publicSourceType": "PMID" }, { "claim": "Folic acid and primary prevention of neural tube defects (review of evidence)", "title": "Folic acid and primary prevention of neural tube defects: A review", "authors": "Imbard A et al.", "journal": "Ann Biol Clin", "year": 2013, "pmid": "29777755", "url": "https://pubmed.ncbi.nlm.nih.gov/29777755/", "study_type": "review", "key_finding": "In a Hungarian RCT, NTD incidence was 0% with folic acid vs 0.25% with trace element supplementation; established strong evidence for NTD prevention", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29777755/", "publicSourceType": "PMID" }, { "text": "Maruf AA, Poweleit EA, Brown LC et al.. Systematic Review and Meta-Analysis of L-Methylfolate Augmentation in Depressive Disorders. Pharmacopsychiatry. 2022", "pmid": "34794190", "doi": "10.1055/a-1681-2047", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34794190/", "publicSourceType": "PMID" }, { "text": "Hoxha B, Hoxha M, Domi E et al.. Folic Acid and Autism: A Systematic Review of the Current State of Knowledge. Cells. 2021", "pmid": "34440744", "doi": "10.3390/cells10081976", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34440744/", "publicSourceType": "PMID" }, { "claim": "Adjunct therapy with L-methylfolate or folic acid improves depression scores, response, and remission rates when combined with SSRIs/SNRIs", "title": "Folate as adjunct therapy to SSRI/SNRI for major depressive disorder: Systematic review & meta-analysis", "authors": "Altaf R, Gonzalez I, Rubino K, Nemec EC 2nd", "journal": "Complementary Therapies in Medicine", "year": 2021, "pmid": "34450256", "url": "https://pubmed.ncbi.nlm.nih.gov/34450256/", "study_type": "meta-analysis", "key_finding": "In 6 RCTs, adjunct folate therapy significantly improved HAM-D scores (MD -2.16, p=0.004), improved response rate (RR 1.36, p=0.0001), and increased remission rate (RR 1.39, p=0.05) compared to SSRI/SNRI monotherapy.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34450256/", "publicSourceType": "PMID" }, { "text": "Zhang N, Zhou Z, Chi X et al.. Folic acid supplementation for stroke prevention: A systematic review and meta-analysis of 21 randomized clinical trials worldwide. Clinical nutrition (Edinburgh, Scotland). 2024", "claim": "PubMed-indexed evidence involving Vitamin B9", "title": "Folic acid supplementation for stroke prevention: A systematic review and meta-analysis of 21 randomized clinical trials worldwide", "authors": "Zhang N, Zhou Z, Chi X et al.", "journal": "Clinical nutrition (Edinburgh, Scotland)", "year": 2024, "pmid": "38824900", "url": "https://pubmed.ncbi.nlm.nih.gov/38824900/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.clnu.2024.05.034", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38824900/", "publicSourceType": "PMID" }, { "text": "Kim ET, Kim JH, Park EY et al.. The Efficacy and Safety of Folate Receptor α-Targeted Antibody-Drug Conjugate Therapy in Patients With High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers: A Systematic Review and Meta-Analysis. Cancer medicine. 2024", "claim": "PubMed-indexed evidence involving Vitamin B9", "title": "The Efficacy and Safety of Folate Receptor α-Targeted Antibody-Drug Conjugate Therapy in Patients With High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers: A Systematic Review and Meta-Analysis", "authors": "Kim ET, Kim JH, Park EY et al.", "journal": "Cancer medicine", "year": 2024, "pmid": "39526448", "url": "https://pubmed.ncbi.nlm.nih.gov/39526448/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/cam4.70392", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39526448/", "publicSourceType": "PMID" }, { "text": "Gómez-Cabrera AS, González-Santiago AE, Castañeda-Arellano R et al.. Folic Acid Supplementation and Risk of Gestational Diabetes Mellitus: A Systematic Review of the Literature. International journal of molecular sciences. 2025", "claim": "PubMed-indexed evidence involving Vitamin B9", "title": "Folic Acid Supplementation and Risk of Gestational Diabetes Mellitus: A Systematic Review of the Literature", "authors": "Gómez-Cabrera AS, González-Santiago AE, Castañeda-Arellano R et al.", "journal": "International journal of molecular sciences", "year": 2025, "pmid": "40869296", "url": "https://pubmed.ncbi.nlm.nih.gov/40869296/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/ijms26167977", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40869296/", "publicSourceType": "PMID" }, { "text": "Alves Maues AC, Moren Abat MG, Benlloch M et al.. Folate Supplementation for Peripheral Neuropathy: A Systematic Review. Nutrients. 2025", "claim": "PubMed-indexed evidence involving Vitamin B9", "title": "Folate Supplementation for Peripheral Neuropathy: A Systematic Review", "authors": "Alves Maues AC, Moren Abat MG, Benlloch M et al.", "journal": "Nutrients", "year": 2025, "pmid": "41156551", "url": "https://pubmed.ncbi.nlm.nih.gov/41156551/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu17203299", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41156551/", "publicSourceType": "PMID" }, { "text": "Arrey Agbor DB, Panday P, Ejaz S et al.. Folic Acid in the Treatment of Sickle Cell Disease: A Systematic Review. Cureus. 2024", "claim": "PubMed-indexed evidence involving Vitamin B9", "title": "Folic Acid in the Treatment of Sickle Cell Disease: A Systematic Review", "authors": "Arrey Agbor DB, Panday P, Ejaz S et al.", "journal": "Cureus", "year": 2024, "pmid": "38738102", "url": "https://pubmed.ncbi.nlm.nih.gov/38738102/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7759/cureus.57962", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38738102/", "publicSourceType": "PMID" }, { "text": "Cui H, Zhang N, An J et al.. Maternal folic acid supplementation to prevent preeclampsia: a systematic review and meta-analysis. Complementary therapies in medicine. 2024", "claim": "PubMed-indexed evidence involving Vitamin B9", "title": "Maternal folic acid supplementation to prevent preeclampsia: a systematic review and meta-analysis", "authors": "Cui H, Zhang N, An J et al.", "journal": "Complementary therapies in medicine", "year": 2024, "pmid": "38763206", "url": "https://pubmed.ncbi.nlm.nih.gov/38763206/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.ctim.2024.103052", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38763206/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "vitamin-b9" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567014", "name": "Vitamin B12", "alternateNames": [ "Methylcobalamin", "Cyanocobalamin", "Hydroxocobalamin", "Adenosylcobalamin" ], "category": "Vitamin", "subcategory": "B Vitamin", "overview": "Essential for nerve function, red blood cell formation, DNA synthesis, and methylation. Common deficiency in vegans and older adults due to absorption issues.", "mechanismOfAction": "As methylcobalamin, cofactor for methionine synthase (converts homocysteine to methionine, generating SAMe for methylation). As adenosylcobalamin, cofactor for methylmalonyl-CoA mutase in the mitochondrial energy pathway.", "commonBenefits": [ "Energy production (only in deficiency; no benefit if B12-sufficient)", "Nerve health", "Red blood cell formation", "Methylation support", "Cognitive function" ], "commonDosageRange": "1,000–5,000 mcg daily", "recommendedForm": "Methylcobalamin or hydroxocobalamin (better retention than cyanocobalamin)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Sublingual forms bypass potential absorption issues; take in the morning" }, "evidenceRating": "strong", "foodSources": [ "Liver", "Clams", "Beef", "Sardines", "Nutritional yeast (fortified)" ], "deficiencySymptoms": [ "Fatigue", "Numbness/tingling", "Megaloblastic anemia", "Cognitive decline", "Balance problems" ], "sideEffects": [ "Very safe even at high doses", "Rare acne-like skin reaction" ], "contraindications": [ "Leber's hereditary optic neuropathy" ], "iconName": "bolt.heart.fill", "colorHex": "FF4444", "tags": [ "energy", "nerve-health", "methylation", "essential" ], "sources": [ { "claim": "Efficacy of different routes of B12 supplementation (oral vs IM vs sublingual)", "title": "Efficacy of different routes of vitamin B12 supplementation for the treatment of patients with vitamin B12 deficiency: A systematic review and network meta-analysis", "authors": "Wang JY et al.", "journal": "Medicine (Baltimore)", "year": 2024, "pmid": "38231320", "url": "https://pubmed.ncbi.nlm.nih.gov/38231320/", "study_type": "meta-analysis", "key_finding": "13 studies with 4,275 patients; IM route ranked first for increasing B12 levels, followed by sublingual; oral therapy shows similar efficacy with better tolerability and lower cost", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38231320/", "publicSourceType": "PMID" }, { "claim": "Vitamin B12 supplementation effects on cognitive function, depression, and fatigue", "title": "Effects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Meta-Analysis, and Meta-Regression", "authors": "Markun S et al.", "journal": "Nutrients", "year": 2021, "pmid": "33809274", "url": "https://pubmed.ncbi.nlm.nih.gov/33809274/", "study_type": "meta-analysis", "key_finding": "Systematic review of vitamin B12 supplementation on cognitive function, depression, and fatigue; effects depend on baseline B12 status and deficiency severity", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33809274/", "publicSourceType": "PMID" }, { "claim": "Vitamin B12 status, cognitive decline, and dementia (cognitive function)", "title": "Vitamin B12 status, cognitive decline and dementia: a systematic review of prospective cohort studies", "authors": "Moore E et al.", "journal": "Br J Nutr", "year": 2012, "pmid": "23084026", "url": "https://pubmed.ncbi.nlm.nih.gov/23084026/", "study_type": "review", "key_finding": "Low serum vitamin B12 levels are associated with neurodegenerative disease and cognitive impairment; elevated homocysteine is a potential risk factor for cognitive decline", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23084026/", "publicSourceType": "PMID" }, { "claim": "Oral vs intramuscular B12 for deficiency treatment", "title": "Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency: a systematic review of randomized controlled trials", "authors": "Vidal-Alaball J et al.", "journal": "Fam Pract", "year": 2005, "pmid": "16585128", "url": "https://pubmed.ncbi.nlm.nih.gov/16585128/", "study_type": "meta-analysis", "key_finding": "High oral doses of B12 (1000-2000 mcg) may be as effective as intramuscular administration in achieving hematological and neurological responses", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16585128/", "publicSourceType": "PMID" }, { "claim": "Vitamin B12 (cobalamin) comprehensive overview (mechanism/forms)", "title": "Vitamin B12 (Cobalamin)", "authors": "National Library of Medicine", "journal": "StatPearls", "year": 2023, "pmid": "32644558", "url": "https://pubmed.ncbi.nlm.nih.gov/32644558/", "study_type": "NIH_ODS", "key_finding": "As methylcobalamin, cofactor for methionine synthase; as adenosylcobalamin, cofactor for methylmalonyl-CoA mutase; essential for nerve function, RBC formation, DNA synthesis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32644558/", "publicSourceType": "PMID" }, { "claim": "Comparative bioavailability of B12 forms (methylcobalamin vs cyanocobalamin)", "title": "Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms", "authors": "Paul C, Brady DM", "journal": "Integr Med (Encinitas)", "year": 2017, "pmid": "28223907", "url": "https://pubmed.ncbi.nlm.nih.gov/28223907/", "study_type": "review", "key_finding": "Different B12 forms (methylcobalamin, hydroxocobalamin, cyanocobalamin, adenosylcobalamin) have varying bioavailability; form selection may mitigate B12-related genetic polymorphisms", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28223907/", "publicSourceType": "PMID" }, { "text": "Brescoll J, Daveluy S. A review of vitamin B12 in dermatology. American journal of clinical dermatology. 2015", "pmid": "25559140", "doi": "10.1007/s40257-014-0107-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25559140/", "publicSourceType": "PMID" }, { "text": "Ismail O, Albdour K, Albdour Z et al.. Differences in Ferritin, Vitamin D, and Vitamin B12 Between Fibromyalgia Patients and Healthy Individuals: A Systematic Review and Meta-Analysis. Musculoskeletal care. 2025", "claim": "PubMed-indexed evidence involving Vitamin B12", "title": "Differences in Ferritin, Vitamin D, and Vitamin B12 Between Fibromyalgia Patients and Healthy Individuals: A Systematic Review and Meta-Analysis", "authors": "Ismail O, Albdour K, Albdour Z et al.", "journal": "Musculoskeletal care", "year": 2025, "pmid": "39832803", "url": "https://pubmed.ncbi.nlm.nih.gov/39832803/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/msc.70057", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39832803/", "publicSourceType": "PMID" }, { "text": "Dos Santos MERA, da Silva KG, da Silva Souza AP et al.. Relationship between vitamin B12 levels and motor development: A systematic review. Clinical nutrition ESPEN. 2024", "claim": "PubMed-indexed evidence involving Vitamin B12", "title": "Relationship between vitamin B12 levels and motor development: A systematic review", "authors": "Dos Santos MERA, da Silva KG, da Silva Souza AP et al.", "journal": "Clinical nutrition ESPEN", "year": 2024, "pmid": "38944829", "url": "https://pubmed.ncbi.nlm.nih.gov/38944829/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.clnesp.2024.06.026", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38944829/", "publicSourceType": "PMID" }, { "text": "Blom JD. Hallucinations and Vitamin B12 Deficiency: A Systematic Review. Psychopathology. 2024", "claim": "PubMed-indexed evidence involving Vitamin B12", "title": "Hallucinations and Vitamin B12 Deficiency: A Systematic Review", "authors": "Blom JD", "journal": "Psychopathology", "year": 2024, "pmid": "39047712", "url": "https://pubmed.ncbi.nlm.nih.gov/39047712/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1159/000540003", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39047712/", "publicSourceType": "PMID" }, { "text": "Niklewicz A, Hannibal L, Warren M et al.. A systematic review and meta-analysis of functional vitamin B12 status among adult vegans. Nutrition bulletin. 2024", "claim": "PubMed-indexed evidence involving Vitamin B12", "title": "A systematic review and meta-analysis of functional vitamin B12 status among adult vegans", "authors": "Niklewicz A, Hannibal L, Warren M et al.", "journal": "Nutrition bulletin", "year": 2024, "pmid": "39373282", "url": "https://pubmed.ncbi.nlm.nih.gov/39373282/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/nbu.12712", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39373282/", "publicSourceType": "PMID" }, { "text": "Alzahrani H. Assessment of Vitamin B12 Efficacy on Cognitive Memory Function and Depressive Symptoms: A Systematic Review and Meta-Analysis. Cureus. 2024", "claim": "PubMed-indexed evidence involving Vitamin B12", "title": "Assessment of Vitamin B12 Efficacy on Cognitive Memory Function and Depressive Symptoms: A Systematic Review and Meta-Analysis", "authors": "Alzahrani H", "journal": "Cureus", "year": 2024, "pmid": "39655146", "url": "https://pubmed.ncbi.nlm.nih.gov/39655146/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7759/cureus.73350", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39655146/", "publicSourceType": "PMID" }, { "text": "Marques de Brito B, Campos VM, Neves FJ et al.. Vitamin B12 sources in non-animal foods: a systematic review. Critical reviews in food science and nutrition. 2023", "claim": "PubMed-indexed evidence involving Vitamin B12", "title": "Vitamin B12 sources in non-animal foods: a systematic review", "authors": "Marques de Brito B, Campos VM, Neves FJ et al.", "journal": "Critical reviews in food science and nutrition", "year": 2023, "pmid": "35343314", "url": "https://pubmed.ncbi.nlm.nih.gov/35343314/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/10408398.2022.2053057", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35343314/", "publicSourceType": "PMID" }, { "text": "Jensen CF. Vitamin B12 levels in children and adolescents on plant-based diets: a systematic review and meta-analysis. Nutrition reviews. 2023", "claim": "PubMed-indexed evidence involving Vitamin B12", "title": "Vitamin B12 levels in children and adolescents on plant-based diets: a systematic review and meta-analysis", "authors": "Jensen CF", "journal": "Nutrition reviews", "year": 2023, "pmid": "36413044", "url": "https://pubmed.ncbi.nlm.nih.gov/36413044/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/nutrit/nuac096", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36413044/", "publicSourceType": "PMID" }, { "text": "Liu Q, Li S, Quan H et al.. Vitamin B12 status in metformin treated patients: systematic review. PloS one. 2014", "claim": "PubMed-indexed evidence involving Vitamin B12", "title": "Vitamin B12 status in metformin treated patients: systematic review", "authors": "Liu Q, Li S, Quan H et al.", "journal": "PloS one", "year": 2014, "pmid": "24959880", "url": "https://pubmed.ncbi.nlm.nih.gov/24959880/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1371/journal.pone.0100379", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24959880/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "vitamin-b12" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567015", "name": "Magnesium Glycinate", "alternateNames": [ "Magnesium Bisglycinate" ], "category": "Mineral", "subcategory": "Chelated Mineral", "overview": "One of the most bioavailable and gentle forms of magnesium (Mg citrate is comparably bioavailable). Excellent for relaxation, sleep, and muscle recovery. Less likely to cause GI issues than other forms.", "mechanismOfAction": "Magnesium is a cofactor for 300+ enzymatic reactions including ATP synthesis, muscle contraction/relaxation, nerve transmission, and protein synthesis. Glycinate chelation enhances absorption and the glycine component promotes GABA receptor activation for calming effects.", "commonBenefits": [ "Sleep quality", "Muscle relaxation", "Stress reduction", "Nerve function", "Heart rhythm" ], "commonDosageRange": "200–350 mg elemental magnesium daily (NIH supplemental UL is 350 mg)", "recommendedForm": "Magnesium bisglycinate/glycinate", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Best taken in the evening for sleep; well-tolerated on empty stomach" }, "evidenceRating": "strong", "foodSources": [ "Pumpkin seeds", "Dark chocolate", "Almonds", "Spinach", "Avocado" ], "deficiencySymptoms": [ "Muscle cramps", "Insomnia", "Anxiety", "Heart palpitations", "Fatigue" ], "sideEffects": [ "Mild drowsiness", "Loose stools at very high doses" ], "contraindications": [ "Severe kidney disease", "Myasthenia gravis" ], "iconName": "moon.fill", "colorHex": "00B4D8", "tags": [ "sleep", "relaxation", "muscle", "essential" ], "sources": [ { "claim": "Magnesium bisglycinate supplementation improves sleep in adults with poor sleep (sleep quality)", "title": "Magnesium Bisglycinate Supplementation in Healthy Adults Reporting Poor Sleep: A Randomized, Placebo-Controlled Trial", "authors": "Various", "journal": "Nutrients", "year": 2025, "pmid": "40918053", "url": "https://pubmed.ncbi.nlm.nih.gov/40918053/", "study_type": "RCT", "key_finding": "Magnesium bisglycinate group showed significantly greater reduction in Insomnia Severity Index scores compared to placebo from baseline to Week 4", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40918053/", "publicSourceType": "PMID" }, { "claim": "Magnesium supplementation for insomnia in older adults (sleep quality meta-analysis)", "title": "Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis", "authors": "Mah J, Pitre T", "journal": "BMC Complement Med Ther", "year": 2021, "pmid": "33865376", "url": "https://pubmed.ncbi.nlm.nih.gov/33865376/", "study_type": "meta-analysis", "key_finding": "Three RCTs in 151 older adults: sleep onset latency 17.36 minutes less with magnesium vs placebo; quality of evidence low to very low", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33865376/", "publicSourceType": "PMID" }, { "claim": "Supplemental magnesium effects on anxiety and sleep quality (stress reduction)", "title": "Examining the Effects of Supplemental Magnesium on Self-Reported Anxiety and Sleep Quality: A Systematic Review", "authors": "Various", "journal": "Nutrients", "year": 2024, "pmid": "38817505", "url": "https://pubmed.ncbi.nlm.nih.gov/38817505/", "study_type": "review", "key_finding": "5/8 sleep studies and 5/7 anxiety studies showed improvements; supplemental magnesium likely useful for mild anxiety and insomnia, particularly with low baseline magnesium", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38817505/", "publicSourceType": "PMID" }, { "claim": "Magnesium is a cofactor for 300+ enzymatic reactions including ATP synthesis (mechanism)", "title": "Magnesium in Prevention and Therapy", "authors": "Gröber U et al.", "journal": "Nutrients", "year": 2015, "pmid": "26404370", "url": "https://pubmed.ncbi.nlm.nih.gov/26404370/", "study_type": "review", "key_finding": "Magnesium is a cofactor in more than 300 enzymatic reactions; essential for ATP metabolism, muscle contraction/relaxation, nerve transmission, and cardiac excitability", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26404370/", "publicSourceType": "PMID" }, { "claim": "Role of magnesium in sleep health (systematic review of mechanisms)", "title": "The Role of Magnesium in Sleep Health: a Systematic Review of Available Literature", "authors": "Arab A et al.", "journal": "Biol Trace Elem Res", "year": 2023, "pmid": "35184264", "url": "https://pubmed.ncbi.nlm.nih.gov/35184264/", "study_type": "review", "key_finding": "Observational studies show association between magnesium status and sleep quality; RCTs show uncertain association between magnesium supplementation and sleep disorders", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35184264/", "publicSourceType": "PMID" }, { "claim": "Magnesium supplementation for primary insomnia in elderly (efficacy RCT)", "title": "The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial", "authors": "Abbasi B et al.", "journal": "J Res Med Sci", "year": 2012, "pmid": "23853635", "url": "https://pubmed.ncbi.nlm.nih.gov/23853635/", "study_type": "RCT", "key_finding": "Magnesium supplementation significantly improved subjective measures of insomnia (ISI, sleep efficiency, sleep time, sleep onset latency) in elderly participants", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23853635/", "publicSourceType": "PMID" }, { "claim": "Magnesium improves glucose metabolism in at-risk individuals", "title": "Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.", "authors": "Veronese N, Dominguez LJ, Pizzol D et al.", "journal": "Nutrients", "year": 2021, "pmid": "34836329", "url": "https://pubmed.ncbi.nlm.nih.gov/34836329/", "study_type": "meta-analysis", "key_finding": "Magnesium supplementation significantly reduced fasting plasma glucose and improved HbA1c in people with or at risk of diabetes.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34836329/", "publicSourceType": "PMID" }, { "claim": "Magnesium reduces inflammatory markers", "title": "Effect of Magnesium Supplementation on Inflammatory Parameters: A Meta-Analysis of Randomized Controlled Trials.", "authors": "Veronese N, Pizzol D, Smith L et al.", "journal": "Nutrients", "year": 2022, "pmid": "35277037", "url": "https://pubmed.ncbi.nlm.nih.gov/35277037/", "study_type": "meta-analysis", "key_finding": "Magnesium supplementation significantly reduced CRP and other inflammatory markers in a meta-analysis of randomized controlled trials.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35277037/", "publicSourceType": "PMID" }, { "text": "Argeros Z, Xu X, Bhandari B et al.. Magnesium Supplementation and Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Hypertension (Dallas, Tex. : 1979). 2025", "claim": "PubMed-indexed evidence involving Magnesium Glycinate", "title": "Magnesium Supplementation and Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Argeros Z, Xu X, Bhandari B et al.", "journal": "Hypertension (Dallas, Tex. : 1979)", "year": 2025, "pmid": "41000008", "url": "https://pubmed.ncbi.nlm.nih.gov/41000008/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1161/HYPERTENSIONAHA.125.25129", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41000008/", "publicSourceType": "PMID" }, { "text": "Moabedi M, Aliakbari M, Erfanian S et al.. Magnesium supplementation beneficially affects depression in adults with depressive disorder: a systematic review and meta-analysis of randomized clinical trials. Frontiers in psychiatry. 2023", "claim": "PubMed-indexed evidence involving Magnesium Glycinate", "title": "Magnesium supplementation beneficially affects depression in adults with depressive disorder: a systematic review and meta-analysis of randomized clinical trials", "authors": "Moabedi M, Aliakbari M, Erfanian S et al.", "journal": "Frontiers in psychiatry", "year": 2023, "pmid": "38213402", "url": "https://pubmed.ncbi.nlm.nih.gov/38213402/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fpsyt.2023.1333261", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38213402/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "magnesium-glycinate" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567016", "name": "Magnesium L-Threonate", "alternateNames": [ "Magtein" ], "category": "Mineral", "subcategory": "Chelated Mineral", "overview": "The most effective form studied for raising brain magnesium levels (all Mg forms cross BBB to some degree). Developed at MIT specifically for cognitive enhancement and brain health.", "mechanismOfAction": "L-threonate transporter carries magnesium across the blood-brain barrier, increasing brain magnesium levels. Enhances synaptic density, NMDA receptor signaling, and brain-derived neurotrophic factor (BDNF) expression in the hippocampus and prefrontal cortex.", "commonBenefits": [ "Cognitive function", "Memory", "Brain health", "Sleep quality", "Neuroprotection" ], "commonDosageRange": "1,000–2,000 mg magnesium L-threonate daily (144mg elemental Mg)", "recommendedForm": "Magnesium L-threonate (Magtein)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Take in the evening; lower elemental magnesium per dose than other forms" }, "evidenceRating": "emerging", "foodSources": [ "Not found in food; synthetic form only" ], "deficiencySymptoms": [ "Brain fog", "Poor memory", "Cognitive decline" ], "sideEffects": [ "Headache", "Drowsiness", "GI discomfort (rare)" ], "contraindications": [ "Severe kidney disease" ], "iconName": "brain", "colorHex": "0096C7", "tags": [ "brain", "cognitive", "memory", "nootropic" ], "sources": [ { "claim": "Magtein improves cognitive performance and sleep quality (cognitive function RCT)", "title": "The effects of magnesium L-threonate (Magtein) on cognitive performance and sleep quality in adults: a randomised, double-blind, placebo-controlled trial", "authors": "Various", "journal": "Br J Nutr", "year": 2025, "pmid": "41601871", "url": "https://pubmed.ncbi.nlm.nih.gov/41601871/", "study_type": "RCT", "key_finding": "Magtein associated with greater improvements in NIH Total Cognition Composite, working and episodic memory, 7.5-year reduction in estimated brain cognitive age, and improved reaction time", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41601871/", "publicSourceType": "PMID" }, { "claim": "Enhancement of learning and memory by elevating brain magnesium (original landmark study)", "title": "Enhancement of learning and memory by elevating brain magnesium", "authors": "Bhatt A, Bhatt A", "journal": "Neuron", "year": 2010, "pmid": "20152124", "url": "https://pubmed.ncbi.nlm.nih.gov/20152124/", "study_type": "RCT", "key_finding": "Magnesium L-threonate uniquely increases brain magnesium levels; enhances learning abilities, working memory, and short- and long-term memory in rats", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20152124/", "publicSourceType": "PMID" }, { "claim": "Magnesium L-threonate improves sleep quality and daytime functioning", "title": "Magnesium-L-threonate improves sleep quality and daytime functioning in adults with self-reported sleep problems: A randomized controlled trial", "authors": "Various", "journal": "Sleep Med", "year": 2024, "pmid": "39252819", "url": "https://pubmed.ncbi.nlm.nih.gov/39252819/", "study_type": "RCT", "key_finding": "Magnesium L-threonate significantly improved sleep quality and daytime functioning compared to placebo in adults with self-reported sleep problems", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39252819/", "publicSourceType": "PMID" }, { "claim": "L-threonate modulates intraneuronal magnesium and regulates synaptic density (mechanism)", "title": "Regulation of structural and functional synapse density by L-threonate through modulation of intraneuronal magnesium concentration", "authors": "Bhatt A et al.", "journal": "Neuropharmacology", "year": 2016, "pmid": "27178134", "url": "https://pubmed.ncbi.nlm.nih.gov/27178134/", "study_type": "review", "key_finding": "L-threonate upregulates NR2B-containing NMDAR expression, boosts mitochondrial membrane potential, and increases functional synapse density in neuronal cultures", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27178134/", "publicSourceType": "PMID" }, { "claim": "Elevation of brain magnesium prevents and reverses cognitive deficits in Alzheimer's model (neuroprotection)", "title": "Elevation of brain magnesium prevents and reverses cognitive deficits and synaptic loss in Alzheimer's disease mouse model", "authors": "Li W et al.", "journal": "Mol Brain", "year": 2014, "pmid": "23658180", "url": "https://pubmed.ncbi.nlm.nih.gov/23658180/", "study_type": "review", "key_finding": "MgT treatment reduced amyloid-beta plaque and prevented synapse loss and memory decline in transgenic Alzheimer's disease mice", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23658180/", "publicSourceType": "PMID" }, { "claim": "Neuroprotective effects of magnesium L-threonate (neuroprotection)", "title": "Neuroprotective effects of magnesium L-threonate in a hypoxic zebrafish model", "authors": "Shen Y et al.", "journal": "BMC Neurosci", "year": 2020, "pmid": "32590943", "url": "https://pubmed.ncbi.nlm.nih.gov/32590943/", "study_type": "review", "key_finding": "Magnesium L-threonate may increase brain magnesium ion concentrations better than MgSO4 and exhibits neuroprotective effects against hypoxia-induced damage", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32590943/", "publicSourceType": "PMID" }, { "claim": "Magtein-based formula improves cognitive functions in healthy adults (efficacy)", "title": "A Magtein, Magnesium L-Threonate, -Based Formula Improves Brain Cognitive Functions in Healthy Chinese Adults", "authors": "Zhang C et al.", "journal": "Nutrients", "year": 2022, "pmid": "36558392", "url": "https://pubmed.ncbi.nlm.nih.gov/36558392/", "study_type": "RCT", "key_finding": "Double-blind, placebo-controlled study in 109 healthy adults aged 18-65; magnesium L-threonate-based formulation showed cognitive benefits", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36558392/", "publicSourceType": "PMID" }, { "text": "Wu S, Jin T, Ma B et al.. Oral application of magnesium-L-threonate enhances analgesia and reduces the dosage of opioids needed in advanced cancer patients-A randomized, double-blind, placebo-controlled trial. Cancer medicine. 2023", "pmid": "36703238", "doi": "10.1002/cam4.4922", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36703238/", "publicSourceType": "PMID" }, { "text": "Ni Y, Deng F, Yu S et al.. A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Therapeutic Effect of Magnesium-L-Threonate Supplementation for Persistent Pain After Breast Cancer Surgery. Breast cancer (Dove Medical Press). 2023", "pmid": "37520407", "doi": "10.2147/BCTT.S413435", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37520407/", "publicSourceType": "PMID" }, { "text": "Argeros Z, Xu X, Bhandari B et al.. Magnesium Supplementation and Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Hypertension (Dallas, Tex. : 1979). 2025", "claim": "PubMed-indexed evidence involving Magnesium L-Threonate", "title": "Magnesium Supplementation and Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Argeros Z, Xu X, Bhandari B et al.", "journal": "Hypertension (Dallas, Tex. : 1979)", "year": 2025, "pmid": "41000008", "url": "https://pubmed.ncbi.nlm.nih.gov/41000008/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1161/HYPERTENSIONAHA.125.25129", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41000008/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "magnesium-l-threonate" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567017", "name": "Zinc", "alternateNames": [ "Zinc Picolinate", "Zinc Gluconate", "Zinc Citrate" ], "category": "Mineral", "subcategory": "Trace Mineral", "overview": "Essential trace mineral involved in immune function, wound healing, DNA synthesis, and testosterone production. Second most abundant trace mineral in the body.", "mechanismOfAction": "Structural component of over 300 enzymes and 1,000+ transcription factors. Essential for T-cell development and function, acts as antioxidant via superoxide dismutase (SOD), required for insulin storage and release, and critical for 5-alpha reductase and testosterone metabolism.", "commonBenefits": [ "Immune support", "Wound healing", "Testosterone support (primarily in zinc-deficient individuals)", "Skin health", "Taste and smell" ], "commonDosageRange": "15–30 mg daily", "recommendedForm": "Zinc picolinate or zinc bisglycinate (best absorption)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food to prevent nausea; competes with iron and copper for absorption" }, "evidenceRating": "strong", "foodSources": [ "Oysters", "Beef", "Pumpkin seeds", "Chickpeas", "Cashews" ], "deficiencySymptoms": [ "Frequent illness", "Slow wound healing", "Hair loss", "Loss of taste/smell", "Low testosterone" ], "sideEffects": [ "Nausea on empty stomach", "Copper depletion with chronic use", "Metallic taste" ], "contraindications": [ "Must balance with copper (1-2mg Cu per 15mg Zn)", "Certain antibiotics (separate by 2 hours)" ], "iconName": "shield.checkered", "colorHex": "0077B6", "tags": [ "immune", "testosterone", "skin", "essential" ], "sources": [ { "claim": "Zinc supplementation improves immune function markers (CRP, cytokines, CD4 cells)", "title": "Zinc supplementation and immune factors in adults: a systematic review and meta-analysis of randomized clinical trials", "authors": "Wang X et al.", "journal": "Front Immunol", "year": 2020, "pmid": "33356467", "url": "https://pubmed.ncbi.nlm.nih.gov/33356467/", "study_type": "meta-analysis", "key_finding": "Zinc supplementation significantly reduced CRP and increased CD4 levels across 35 RCTs with 1995 participants", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33356467/", "publicSourceType": "PMID" }, { "claim": "Zinc lozenges reduce duration of common cold symptoms", "title": "Zinc lozenges and the common cold: a meta-analysis comparing zinc acetate and zinc gluconate, and the role of zinc dosage", "authors": "Hemilä H", "journal": "JRSM Open", "year": 2017, "pmid": "28515951", "url": "https://pubmed.ncbi.nlm.nih.gov/28515951/", "study_type": "meta-analysis", "key_finding": "Zinc acetate lozenges shortened cold duration by 40% and zinc gluconate by 28% when dosed at >75 mg/day", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28515951/", "publicSourceType": "PMID" }, { "claim": "Correlation between serum zinc and testosterone levels in men", "title": "Correlation between serum zinc and testosterone: A systematic review", "authors": "Te L et al.", "journal": "J Lab Precis Med", "year": 2023, "pmid": "36577241", "url": "https://pubmed.ncbi.nlm.nih.gov/36577241/", "study_type": "review", "key_finding": "Systematic review confirms significant correlation between zinc status and testosterone; zinc supplementation benefits those who are deficient but not zinc-replete men", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36577241/", "publicSourceType": "PMID" }, { "claim": "Zinc promotes wound healing via metalloenzyme activity and cell proliferation", "title": "Zinc in Wound Healing Modulation", "authors": "Lin PH et al.", "journal": "Nutrients", "year": 2018, "pmid": "29295546", "url": "https://pubmed.ncbi.nlm.nih.gov/29295546/", "study_type": "review", "key_finding": "Zinc is a cofactor for numerous metalloenzymes required for cell membrane repair, cell proliferation, growth and immune system function in wound healing", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29295546/", "publicSourceType": "PMID" }, { "claim": "Chronic zinc supplementation risks copper depletion leading to anemia and neutropenia", "title": "The risk of copper deficiency in patients prescribed zinc supplements", "authors": "Duncan A et al.", "journal": "J Clin Pathol", "year": 2015, "pmid": "26085547", "url": "https://pubmed.ncbi.nlm.nih.gov/26085547/", "study_type": "review", "key_finding": "9% of patients on high-dose zinc developed unexplained anemia and 7% neurological symptoms typical of copper deficiency", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26085547/", "publicSourceType": "PMID" }, { "claim": "Comprehensive overview of zinc intakes and multiple health outcomes", "title": "Zinc Intakes and Health Outcomes: An Umbrella Review", "authors": "Tsatsakis A et al.", "journal": "Nutrients", "year": 2022, "pmid": "35211497", "url": "https://pubmed.ncbi.nlm.nih.gov/35211497/", "study_type": "review", "key_finding": "Umbrella review of zinc health outcomes covering immune function, wound healing, and metabolic effects across multiple meta-analyses", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35211497/", "publicSourceType": "PMID" }, { "claim": "Zinc requirements and the risks and benefits of supplementation", "title": "Zinc requirements and the risks and benefits of zinc supplementation", "authors": "Fosmire GJ", "journal": "J Am Diet Assoc", "year": 2006, "pmid": "16632171", "url": "https://pubmed.ncbi.nlm.nih.gov/16632171/", "study_type": "review", "key_finding": "At 100-300 mg Zn/day, copper deficiency with anemia, neutropenia, and impaired immune function has been reported", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16632171/", "publicSourceType": "PMID" }, { "text": "Mallat F, Kaikati J, Kechichian E. Botulinum Toxins and Zinc: From Theory to Practice-A Systematic Review. Clinical neuropharmacology. 2023", "pmid": "37335837", "doi": "10.1097/WNF.0000000000000557", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37335837/", "publicSourceType": "PMID" }, { "text": "Yee BE, Richards P, Sui JY et al.. Serum zinc levels and efficacy of zinc treatment in acne vulgaris: A systematic review and meta-analysis. Dermatologic therapy. 2020", "pmid": "32860489", "doi": "10.1111/dth.14252", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32860489/", "publicSourceType": "PMID" }, { "claim": "Zinc supplementation reduces primary dysmenorrhea pain", "title": "Efficacy of Zinc Supplementation in the Management of Primary Dysmenorrhea: A Systematic Review and Meta-Analysis.", "authors": "Hsu TJ, Hsieh RH, Huang CH et al.", "journal": "Nutrients", "year": 2024, "pmid": "39683510", "url": "https://pubmed.ncbi.nlm.nih.gov/39683510/", "study_type": "meta-analysis", "key_finding": "Zinc supplementation significantly reduced pain intensity and duration in primary dysmenorrhea across randomized controlled trials.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39683510/", "publicSourceType": "PMID" }, { "claim": "Zinc reduces duration and severity of childhood diarrhea", "title": "Zinc supplementation for acute and persistent watery diarrhoea in children: A systematic review and meta-analysis.", "authors": "Ali AA, Naqvi SK, Hasnain Z et al.", "journal": "Journal of Global Health", "year": 2024, "pmid": "39641338", "url": "https://pubmed.ncbi.nlm.nih.gov/39641338/", "study_type": "meta-analysis", "key_finding": "Zinc supplementation significantly reduced duration of acute diarrhea episodes and stool frequency in children under 5 years.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39641338/", "publicSourceType": "PMID" }, { "claim": "Zinc supports immune function and micronutrient status in pregnancy", "title": "Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.", "authors": "Oh C, Keats EC, Bhutta ZA", "journal": "Nutrients", "year": 2020, "pmid": "32075071", "url": "https://pubmed.ncbi.nlm.nih.gov/32075071/", "study_type": "meta-analysis", "key_finding": "Zinc supplementation during pregnancy reduced preterm birth risk and improved birth outcomes, particularly in low- and middle-income settings.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32075071/", "publicSourceType": "PMID" }, { "text": "Wang MX, Win SS, Pang J. Zinc Supplementation Reduces Common Cold Duration among Healthy Adults: A Systematic Review of Randomized Controlled Trials with Micronutrients Supplementation. The American journal of tropical medicine and hygiene. 2020", "claim": "PubMed-indexed evidence involving Zinc", "title": "Zinc Supplementation Reduces Common Cold Duration among Healthy Adults: A Systematic Review of Randomized Controlled Trials with Micronutrients Supplementation", "authors": "Wang MX, Win SS, Pang J", "journal": "The American journal of tropical medicine and hygiene", "year": 2020, "pmid": "32342851", "url": "https://pubmed.ncbi.nlm.nih.gov/32342851/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.4269/ajtmh.19-0718", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32342851/", "publicSourceType": "PMID" }, { "text": "Azargoonjahromi A. A systematic review of the association between zinc and anxiety. Nutrition reviews. 2024", "claim": "PubMed-indexed evidence involving Zinc", "title": "A systematic review of the association between zinc and anxiety", "authors": "Azargoonjahromi A", "journal": "Nutrition reviews", "year": 2024, "pmid": "37364014", "url": "https://pubmed.ncbi.nlm.nih.gov/37364014/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/nutrit/nuad076", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37364014/", "publicSourceType": "PMID" }, { "text": "Nazari M, Nikbaf-Shandiz M, Pashayee-Khamene F et al.. Zinc Supplementation in Individuals with Prediabetes and type 2 Diabetes: a GRADE-Assessed Systematic Review and Dose-Response Meta-analysis. Biological trace element research. 2024", "claim": "PubMed-indexed evidence involving Zinc", "title": "Zinc Supplementation in Individuals with Prediabetes and type 2 Diabetes: a GRADE-Assessed Systematic Review and Dose-Response Meta-analysis", "authors": "Nazari M, Nikbaf-Shandiz M, Pashayee-Khamene F et al.", "journal": "Biological trace element research", "year": 2024, "pmid": "37870684", "url": "https://pubmed.ncbi.nlm.nih.gov/37870684/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s12011-023-03895-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37870684/", "publicSourceType": "PMID" }, { "text": "Malekahmadi M, Soltani S, Pahlavani N et al.. Zinc status in cystic fibrosis patients; a systematic review and meta-analysis. Heliyon. 2024", "claim": "PubMed-indexed evidence involving Zinc", "title": "Zinc status in cystic fibrosis patients; a systematic review and meta-analysis", "authors": "Malekahmadi M, Soltani S, Pahlavani N et al.", "journal": "Heliyon", "year": 2024, "pmid": "39027558", "url": "https://pubmed.ncbi.nlm.nih.gov/39027558/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.heliyon.2024.e33686", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39027558/", "publicSourceType": "PMID" }, { "text": "Singhal S, Dutta SB, Bansal S et al.. Zinc as An Emerging Therapy in the Management of Migraine: A Systematic Review. Neurology India. 2024", "claim": "PubMed-indexed evidence involving Zinc", "title": "Zinc as An Emerging Therapy in the Management of Migraine: A Systematic Review", "authors": "Singhal S, Dutta SB, Bansal S et al.", "journal": "Neurology India", "year": 2024, "pmid": "39428763", "url": "https://pubmed.ncbi.nlm.nih.gov/39428763/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.4103/neurol-india.Neurol-India-D-23-00337", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39428763/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "zinc" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567018", "name": "Iron", "alternateNames": [ "Iron Bisglycinate", "Ferrous Sulfate", "Ferrous Fumarate" ], "category": "Mineral", "subcategory": "Essential Mineral", "overview": "Essential for oxygen transport via hemoglobin, energy production, and immune function. Most common nutritional deficiency worldwide, especially in women.", "mechanismOfAction": "Central atom in heme groups of hemoglobin (carries oxygen in red blood cells) and myoglobin (stores oxygen in muscle). Component of cytochrome enzymes in the electron transport chain for ATP production. Required for DNA synthesis and immune cell proliferation.", "commonBenefits": [ "Oxygen transport", "Energy production", "Immune function", "Cognitive function", "Athletic performance" ], "commonDosageRange": "18–45 mg daily (higher doses only under medical supervision for confirmed deficiency)", "recommendedForm": "Iron bisglycinate (gentle, well-absorbed) or ferrous sulfate (standard)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Take on empty stomach with 50-100mg vitamin C for best absorption; avoid with calcium, tea, or coffee. Alternate-day morning dosing may provide 33% higher cumulative absorption due to hepcidin cycling." }, "evidenceRating": "strong", "foodSources": [ "Red meat", "Liver", "Spinach", "Lentils", "Fortified cereals" ], "deficiencySymptoms": [ "Fatigue", "Pale skin", "Shortness of breath", "Cold hands/feet", "Brittle nails" ], "sideEffects": [ "Constipation", "Nausea", "Dark stools", "GI distress" ], "contraindications": [ "Hemochromatosis", "Hemosiderosis", "Do not supplement without confirmed deficiency", "Levothyroxine (separate by 4 hours)", "Tetracyclines (separate by 2+ hours)", "Fluoroquinolones (separate by 2+ hours)", "Proton pump inhibitors (may reduce absorption)" ], "iconName": "drop.triangle.fill", "colorHex": "48CAE4", "tags": [ "energy", "blood-health", "women-health" ], "sources": [ { "claim": "Iron supplementation reduces fatigue in non-anaemic women with low ferritin", "title": "Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial", "authors": "Vaucher P et al.", "journal": "CMAJ", "year": 2012, "pmid": "22777991", "url": "https://pubmed.ncbi.nlm.nih.gov/22777991/", "study_type": "RCT", "key_finding": "Fatigue decreased by 47.7% in iron group vs 28.8% in placebo (p=0.02) in 198 non-anaemic women with ferritin <50 ug/L", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22777991/", "publicSourceType": "PMID" }, { "claim": "Iron supplementation improves cognitive function in school-age children", "title": "Effects of iron supplementation on cognitive development in school-age children: Systematic review and meta-analysis", "authors": "Low M et al.", "journal": "PLoS One", "year": 2023, "pmid": "37368919", "url": "https://pubmed.ncbi.nlm.nih.gov/37368919/", "study_type": "meta-analysis", "key_finding": "Iron supplementation significantly improved intelligence, attention and concentration, and memory in school-age children across 13 studies", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37368919/", "publicSourceType": "PMID" }, { "claim": "Iron supplementation benefits physical performance in women of reproductive age", "title": "Iron supplementation benefits physical performance in women of reproductive age: a systematic review and meta-analysis", "authors": "Pasricha SR et al.", "journal": "J Nutr", "year": 2014, "pmid": "24717371", "url": "https://pubmed.ncbi.nlm.nih.gov/24717371/", "study_type": "meta-analysis", "key_finding": "Iron supplementation improved VO2max and submaximal exercise performance in women of reproductive age", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24717371/", "publicSourceType": "PMID" }, { "claim": "Ferrous sulfate causes significant gastrointestinal side effects", "title": "Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis", "authors": "Tolkien Z et al.", "journal": "PLoS One", "year": 2015, "pmid": "25700159", "url": "https://pubmed.ncbi.nlm.nih.gov/25700159/", "study_type": "meta-analysis", "key_finding": "Ferrous sulfate significantly increased GI side-effect risk vs placebo (OR 2.32) and vs IV iron (OR 3.05)", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25700159/", "publicSourceType": "PMID" }, { "claim": "Daily iron supplementation improves anaemia and iron status in menstruating women", "title": "Daily iron supplementation for improving anaemia, iron status and health in menstruating women", "authors": "Low MSY et al.", "journal": "Cochrane Database Syst Rev", "year": 2016, "pmid": "27087396", "url": "https://pubmed.ncbi.nlm.nih.gov/27087396/", "study_type": "meta-analysis", "key_finding": "Daily iron supplementation effectively improved iron status and reduced anaemia in menstruating women", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27087396/", "publicSourceType": "PMID" }, { "claim": "Iron supplementation for unexplained fatigue in non-anaemic women", "title": "Iron supplementation for unexplained fatigue in non-anaemic women: double blind randomised placebo controlled trial", "authors": "Verdon F et al.", "journal": "BMJ", "year": 2003, "pmid": "12763985", "url": "https://pubmed.ncbi.nlm.nih.gov/12763985/", "study_type": "RCT", "key_finding": "Fatigue decreased 29% in iron group vs 13% in placebo (p=0.004); benefit restricted to women with ferritin <=50 ug/L", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12763985/", "publicSourceType": "PMID" }, { "text": "Pengelly M, Pumpa K, Pyne DB et al.. Iron deficiency, supplementation, and sports performance in female athletes: A systematic review. Journal of sport and health science. 2025", "pmid": "39536912", "doi": "10.1016/j.jshs.2024.101009", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39536912/", "publicSourceType": "PMID" }, { "text": "McCann S, Perapoch Amadó M, Moore SE. The Role of Iron in Brain Development: A Systematic Review. Nutrients. 2020", "pmid": "32635675", "doi": "10.3390/nu12072001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32635675/", "publicSourceType": "PMID" }, { "claim": "Ferrous bisglycinate increases hemoglobin and reduces GI adverse events compared to other iron supplements in pregnant women", "title": "The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials", "authors": "Fischer JAJ, Cherian AM, Bone JN, Karakochuk CD", "journal": "Nutrition Reviews", "year": 2023, "pmid": "36728680", "url": "https://pubmed.ncbi.nlm.nih.gov/36728680/", "study_type": "meta-analysis", "key_finding": "In 17 RCTs, ferrous bisglycinate resulted in higher hemoglobin in pregnant women (SMD 0.54 g/dL, P<0.01) and fewer GI adverse events (IRR 0.36, P<0.01) compared to other iron supplements.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36728680/", "publicSourceType": "PMID" }, { "claim": "Low-dose iron supplementation combined with shorter or longer durations is optimal for treating iron deficiency anemia in children", "title": "Optimal dose and duration of iron supplementation for treating iron deficiency anaemia in children and adolescents: A systematic review and meta-analysis", "authors": "Rehman T, Agrawal R, Ahamed F et al.", "journal": "PLoS One", "year": 2025, "pmid": "39951396", "url": "https://pubmed.ncbi.nlm.nih.gov/39951396/", "study_type": "meta-analysis", "key_finding": "In 28 studies with 8,829 participants, pooled Hb improvement was 2.01 g/dL (95% CI 1.48-2.54). Low-dose iron (<5 mg/kg/day) with treatment durations <3 months or >6 months was optimal for improving hemoglobin levels.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39951396/", "publicSourceType": "PMID" }, { "claim": "Daily iron supplementation in iron replete non-anemic pregnant women reduces iron deficiency anemia and low birthweight", "title": "Iron supplements in pregnant women with normal iron status: A systematic review and meta-analysis", "authors": "Hansen R, Sejer EPF, Holm C, Schroll JB", "journal": "Acta Obstetricia et Gynecologica Scandinavica", "year": 2023, "pmid": "37403900", "url": "https://pubmed.ncbi.nlm.nih.gov/37403900/", "study_type": "meta-analysis", "key_finding": "In 8 RCTs with 2,822 women, daily oral iron supplementation in pregnancy reduced iron deficiency anemia at term (RR 0.51, 95% CI 0.38-0.70) and low birthweight incidence (RR 0.30, 95% CI 0.13-0.68).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37403900/", "publicSourceType": "PMID" }, { "text": "Skolmowska D, Głąbska D, Kołota A et al.. Effectiveness of Dietary Interventions to Treat Iron-Deficiency Anemia in Women: A Systematic Review of Randomized Controlled Trials. Nutrients. 2022", "claim": "PubMed-indexed evidence involving Iron", "title": "Effectiveness of Dietary Interventions to Treat Iron-Deficiency Anemia in Women: A Systematic Review of Randomized Controlled Trials", "authors": "Skolmowska D, Głąbska D, Kołota A et al.", "journal": "Nutrients", "year": 2022, "pmid": "35807904", "url": "https://pubmed.ncbi.nlm.nih.gov/35807904/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu14132724", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35807904/", "publicSourceType": "PMID" }, { "text": "Skolmowska D, Głąbska D, Kołota A et al.. Effectiveness of Dietary Interventions in Prevention and Treatment of Iron-Deficiency Anemia in Pregnant Women: A Systematic Review of Randomized Controlled Trials. Nutrients. 2022", "claim": "PubMed-indexed evidence involving Iron", "title": "Effectiveness of Dietary Interventions in Prevention and Treatment of Iron-Deficiency Anemia in Pregnant Women: A Systematic Review of Randomized Controlled Trials", "authors": "Skolmowska D, Głąbska D, Kołota A et al.", "journal": "Nutrients", "year": 2022, "pmid": "35893877", "url": "https://pubmed.ncbi.nlm.nih.gov/35893877/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu14153023", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35893877/", "publicSourceType": "PMID" }, { "text": "Chan B, Varghese A, Badve SV et al.. Systematic Review of the Effects of Iron on Cardiovascular, Kidney, and Safety Outcomes in Patients With CKD. Kidney international reports. 2025", "claim": "PubMed-indexed evidence involving Iron", "title": "Systematic Review of the Effects of Iron on Cardiovascular, Kidney, and Safety Outcomes in Patients With CKD", "authors": "Chan B, Varghese A, Badve SV et al.", "journal": "Kidney international reports", "year": 2025, "pmid": "40303218", "url": "https://pubmed.ncbi.nlm.nih.gov/40303218/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.ekir.2025.01.029", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40303218/", "publicSourceType": "PMID" }, { "text": "Fiani D, Chahine S, Zaboube M et al.. Psychiatric and cognitive outcomes of iron supplementation in non-anemic children, adolescents, and menstruating adults: A meta-analysis and systematic review. Neuroscience and biobehavioral reviews. 2025", "claim": "PubMed-indexed evidence involving Iron", "title": "Psychiatric and cognitive outcomes of iron supplementation in non-anemic children, adolescents, and menstruating adults: A meta-analysis and systematic review", "authors": "Fiani D, Chahine S, Zaboube M et al.", "journal": "Neuroscience and biobehavioral reviews", "year": 2025, "pmid": "40945632", "url": "https://pubmed.ncbi.nlm.nih.gov/40945632/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.neubiorev.2025.106372", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40945632/", "publicSourceType": "PMID" }, { "text": "Fauzan R, Defrin, Susmiati et al.. Impact of TMPRSS6 Genetic Variants on Maternal Iron Status in Pregnancy: A Systematic Review. Birth defects research. 2025", "claim": "PubMed-indexed evidence involving Iron", "title": "Impact of TMPRSS6 Genetic Variants on Maternal Iron Status in Pregnancy: A Systematic Review", "authors": "Fauzan R, Defrin, Susmiati et al.", "journal": "Birth defects research", "year": 2025, "pmid": "41097872", "url": "https://pubmed.ncbi.nlm.nih.gov/41097872/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/bdr2.2538", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41097872/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "iron" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567019", "name": "Calcium", "alternateNames": [ "Calcium Citrate", "Calcium Carbonate" ], "category": "Mineral", "subcategory": "Essential Mineral", "overview": "The most abundant mineral in the body, critical for bone health, muscle contraction, nerve signaling, and blood clotting.", "mechanismOfAction": "99% stored in bones/teeth as hydroxyapatite crystals. Remaining 1% is essential for muscle contraction (triggers actin-myosin cross-bridge), nerve impulse transmission, hormone secretion, and blood coagulation cascade.", "commonBenefits": [ "Bone health", "Muscle function", "Nerve signaling", "Blood clotting", "Heart rhythm" ], "commonDosageRange": "500–1,000 mg daily (split doses)", "recommendedForm": "Calcium citrate (absorbed with or without food) over calcium carbonate", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Split into 500mg doses; competes with iron, zinc, and magnesium. 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Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA network open. 2019", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" }, { "text": "Migliorini F, Maffulli N, Colarossi G et al.. Vitamin D and calcium supplementation in women undergoing pharmacological management for postmenopausal osteoporosis: a level I of evidence systematic review. European journal of medical research. 2025", "claim": "PubMed-indexed evidence involving Calcium", "title": "Vitamin D and calcium supplementation in women undergoing pharmacological management for postmenopausal osteoporosis: a level I of evidence systematic review", "authors": "Migliorini F, Maffulli N, Colarossi G et al.", "journal": "European journal of medical research", "year": 2025, "pmid": "40087804", "url": "https://pubmed.ncbi.nlm.nih.gov/40087804/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s40001-025-02412-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40087804/", "publicSourceType": "PMID" }, { "text": "Gerede A, Papasozomenou P, Stavros S et al.. Calcium Supplementation in Pregnancy: A Systematic Review of Clinical Studies. Medicina (Kaunas, Lithuania). 2025", "claim": "PubMed-indexed evidence involving Calcium", "title": "Calcium Supplementation in Pregnancy: A Systematic Review of Clinical Studies", "authors": "Gerede A, Papasozomenou P, Stavros S et al.", "journal": "Medicina (Kaunas, Lithuania)", "year": 2025, "pmid": "40731825", "url": "https://pubmed.ncbi.nlm.nih.gov/40731825/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/medicina61071195", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40731825/", "publicSourceType": "PMID" }, { "text": "Zhu Q, Yu Q, Liu M et al.. Effectiveness of calcium supplementation in the prevention of gestational hypertension: A systematic review and meta-analysis of randomised controlled trials. Pregnancy hypertension. 2024", "claim": "PubMed-indexed evidence involving Calcium", "title": "Effectiveness of calcium supplementation in the prevention of gestational hypertension: A systematic review and meta-analysis of randomised controlled trials", "authors": "Zhu Q, Yu Q, Liu M et al.", "journal": "Pregnancy hypertension", "year": 2024, "pmid": "39608269", "url": "https://pubmed.ncbi.nlm.nih.gov/39608269/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.preghy.2024.101174", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39608269/", "publicSourceType": "PMID" }, { "text": "Sim MG, Teo YN, Teo YH et al.. Association Between Calcium Supplementation and the Risk of Cardiovascular Disease and Stroke: A Systematic Review and Meta-Analysis. Heart, lung & circulation. 2023", "claim": "PubMed-indexed evidence involving Calcium", "title": "Association Between Calcium Supplementation and the Risk of Cardiovascular Disease and Stroke: A Systematic Review and Meta-Analysis", "authors": "Sim MG, Teo YN, Teo YH et al.", "journal": "Heart, lung & circulation", "year": 2023, "pmid": "37743221", "url": "https://pubmed.ncbi.nlm.nih.gov/37743221/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.hlc.2023.07.008", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37743221/", "publicSourceType": "PMID" }, { "text": "Bickelmann FV, Leitzmann MF, Keller M et al.. Calcium intake in vegan and vegetarian diets: A systematic review and Meta-analysis. Critical reviews in food science and nutrition. 2023", "claim": "PubMed-indexed evidence involving Calcium", "title": "Calcium intake in vegan and vegetarian diets: A systematic review and Meta-analysis", "authors": "Bickelmann FV, Leitzmann MF, Keller M et al.", "journal": "Critical reviews in food science and nutrition", "year": 2023, "pmid": "38054787", "url": "https://pubmed.ncbi.nlm.nih.gov/38054787/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/10408398.2022.2084027", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38054787/", "publicSourceType": "PMID" }, { "text": "Balk EM, Adam GP, Langberg VN et al.. Global dietary calcium intake among adults: a systematic review. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2017", "claim": "PubMed-indexed evidence involving Calcium", "title": "Global dietary calcium intake among adults: a systematic review", "authors": "Balk EM, Adam GP, Langberg VN et al.", "journal": "Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA", "year": 2017, "pmid": "29026938", "url": "https://pubmed.ncbi.nlm.nih.gov/29026938/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00198-017-4230-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29026938/", "publicSourceType": "PMID" }, { "text": "Jung ME, Stork MJ, Stapleton J et al.. A systematic review of behavioural interventions to increase maternal calcium intake. Maternal & child nutrition. 2016", "claim": "PubMed-indexed evidence involving Calcium", "title": "A systematic review of behavioural interventions to increase maternal calcium intake", "authors": "Jung ME, Stork MJ, Stapleton J et al.", "journal": "Maternal & child nutrition", "year": 2016, "pmid": "25536083", "url": "https://pubmed.ncbi.nlm.nih.gov/25536083/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/mcn.12158", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25536083/", "publicSourceType": "PMID" }, { "text": "Chung M, Tang AM, Fu Z et al.. Calcium Intake and Cardiovascular Disease Risk: An Updated Systematic Review and Meta-analysis. Annals of internal medicine. 2016", "claim": "PubMed-indexed evidence involving Calcium", "title": "Calcium Intake and Cardiovascular Disease Risk: An Updated Systematic Review and Meta-analysis", "authors": "Chung M, Tang AM, Fu Z et al.", "journal": "Annals of internal medicine", "year": 2016, "pmid": "27776363", "url": "https://pubmed.ncbi.nlm.nih.gov/27776363/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7326/M16-1165", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27776363/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "calcium" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567020", "name": "Selenium", "alternateNames": [ "Selenomethionine", "Sodium Selenite" ], "category": "Mineral", "subcategory": "Trace Mineral", "overview": "Essential trace mineral crucial for thyroid function, antioxidant defense, and immune health. Narrow therapeutic window, both deficiency and excess are harmful.", "mechanismOfAction": "Incorporated as selenocysteine into 25 selenoproteins including glutathione peroxidases (GPx, neutralize hydrogen peroxide), thioredoxin reductases (regenerate antioxidants), and iodothyronine deiodinases (convert T4 to active T3 thyroid hormone).", "commonBenefits": [ "Thyroid function", "Antioxidant defense", "Immune support", "DNA protection", "Fertility" ], "commonDosageRange": "100–200 mcg daily", "recommendedForm": "Selenomethionine (organic form, better retention)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Do not exceed 400mcg/day; Brazil nuts are the richest food source (1-2 nuts = daily need)" }, "evidenceRating": "strong", "foodSources": [ "Brazil nuts", "Tuna", "Sardines", "Eggs", "Sunflower seeds" ], "deficiencySymptoms": [ "Thyroid dysfunction", "Weakened immunity", "Cognitive decline", "Infertility" ], "sideEffects": [ "Selenosis at high doses (garlic breath, hair loss, nail brittleness)", "Nausea" ], "contraindications": [ "Do not exceed 400mcg daily", "Consult doctor for autoimmune conditions (may benefit autoimmune thyroiditis but requires monitoring)" ], "iconName": "sparkle", "colorHex": "023E8A", "tags": [ "thyroid", "antioxidant", "immune" ], "sources": [ { "claim": "Selenium supplementation reduces thyroid autoantibodies in Hashimoto thyroiditis", "title": "Selenium Supplementation Significantly Reduces Thyroid Autoantibody Levels in Patients with Chronic Autoimmune Thyroiditis: A Systematic Review and Meta-Analysis", "authors": "Wichman J et al.", "journal": "Thyroid", "year": 2016, "pmid": "27702392", "url": "https://pubmed.ncbi.nlm.nih.gov/27702392/", "study_type": "meta-analysis", "key_finding": "Selenium supplementation significantly dropped TPOAb titers at 6 months, and both TPOAb and TgAb titers at 12 months", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27702392/", "publicSourceType": "PMID" }, { "claim": "Selenium supplementation for Hashimoto thyroiditis patients", "title": "Selenium Supplementation in Patients with Hashimoto Thyroiditis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials", "authors": "Kryczyk-Kozioł J et al.", "journal": "J Clin Med", "year": 2024, "pmid": "38243784", "url": "https://pubmed.ncbi.nlm.nih.gov/38243784/", "study_type": "meta-analysis", "key_finding": "Selenium supplementation reduced TPOAb and TSH levels and improved well-being in Hashimoto thyroiditis patients", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38243784/", "publicSourceType": "PMID" }, { "claim": "Selenium supplementation may reduce cancer incidence in low-selenium populations", "title": "Effects of selenium supplements on cancer prevention: meta-analysis of randomized controlled trials", "authors": "Lee EH et al.", "journal": "Nutr Cancer", "year": 2011, "pmid": "22004275", "url": "https://pubmed.ncbi.nlm.nih.gov/22004275/", "study_type": "meta-analysis", "key_finding": "Selenium supplementation alone reduced cancer incidence (RR 0.76) in 9 RCTs, greatest benefit in populations with low baseline selenium", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22004275/", "publicSourceType": "PMID" }, { "claim": "Selenium functions through glutathione peroxidase as antioxidant defense", "title": "Antioxidant activity of sulfur and selenium: a review of reactive oxygen species scavenging, glutathione peroxidase, and metal-binding antioxidant mechanisms", "authors": "Battin EE, Bhatt NR", "journal": "Cell Biochem Biophys", "year": 2009, "pmid": "19548119", "url": "https://pubmed.ncbi.nlm.nih.gov/19548119/", "study_type": "review", "key_finding": "Selenium compounds exhibit antioxidant activity through ROS scavenging, GPx enzymatic catalysis, and metal-binding mechanisms", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19548119/", "publicSourceType": "PMID" }, { "claim": "Safety considerations for selenium including selenosis risk and optimal intake levels", "title": "Safety of selenium exposure and limitations of selenoprotein maximization: Molecular and epidemiologic perspectives", "authors": "Vinceti M et al.", "journal": "Environ Res", "year": 2022, "pmid": "35259406", "url": "https://pubmed.ncbi.nlm.nih.gov/35259406/", "study_type": "review", "key_finding": "Current upper intake limits may be inadequate; selenium intake as low as 60 ug/day might increase type 2 diabetes risk", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35259406/", "publicSourceType": "PMID" }, { "claim": "Selenium exposure and cancer risk updated meta-analysis", "title": "Selenium Exposure and Cancer Risk: an Updated Meta-analysis and Meta-regression", "authors": "Cai X et al.", "journal": "Sci Rep", "year": 2016, "pmid": "26786590", "url": "https://pubmed.ncbi.nlm.nih.gov/26786590/", "study_type": "meta-analysis", "key_finding": "Selenium at >=55 ug/day decreased cancer risk (RR 0.94); protective effect found in men and in populations with low baseline selenium", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26786590/", "publicSourceType": "PMID" }, { "text": "Bai S, Zhang M, Tang S et al.. Effects and Impact of Selenium on Human Health, A Review. Molecules (Basel, Switzerland). 2024", "pmid": "39795109", "doi": "10.3390/molecules30010050", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39795109/", "publicSourceType": "PMID" }, { "claim": "Selenium supplementation reduces total testosterone and cholesterol in polycystic ovary syndrome", "title": "Selenium supplementation for polycystic ovary syndrome: a meta-analysis of randomized controlled trials", "authors": "Wu PY, Tan X, Wang M, Zheng X, Lou JH", "journal": "Gynecological Endocrinology", "year": 2022, "pmid": "36050880", "url": "https://pubmed.ncbi.nlm.nih.gov/36050880/", "study_type": "meta-analysis", "key_finding": "In 5 RCTs, selenium supplementation significantly reduced total testosterone (SMD=-0.42, p=0.02) and cholesterol (SMD=-0.71, p=0.04) in PCOS patients compared to placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36050880/", "publicSourceType": "PMID" }, { "claim": "Selenium is effective in reducing clinical activity score and improving quality of life in Graves' orbitopathy", "title": "The efficacy and safety of selenium supplementation versus placebo in the treatment of Graves' orbitopathy: A systematic review and meta-analysis of randomised controlled trials", "authors": "Sharabati I, Qafesha RM, Hindawi MD et al.", "journal": "Clinical Endocrinology", "year": 2024, "pmid": "39138905", "url": "https://pubmed.ncbi.nlm.nih.gov/39138905/", "study_type": "meta-analysis", "key_finding": "In 4 RCTs, selenium was superior at 6 months in lowering clinical activity score (MD=-1.27, p<0.0001), improving total GO-QOL (RR=2.54, p<0.00001), and improving visual and psychological functioning scores.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39138905/", "publicSourceType": "PMID" }, { "text": "Krannich F, Mücke R, Büntzel J et al.. A systematic review of Selenium as a complementary treatment in cancer patients. Complementary therapies in medicine. 2024", "claim": "PubMed-indexed evidence involving Selenium", "title": "A systematic review of Selenium as a complementary treatment in cancer patients", "authors": "Krannich F, Mücke R, Büntzel J et al.", "journal": "Complementary therapies in medicine", "year": 2024, "pmid": "39374898", "url": "https://pubmed.ncbi.nlm.nih.gov/39374898/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.ctim.2024.103095", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39374898/", "publicSourceType": "PMID" }, { "text": "Filippini T, Fairweather-Tait S, Vinceti M. Selenium and immune function: a systematic review and meta-analysis of experimental human studies. The American journal of clinical nutrition. 2023", "claim": "PubMed-indexed evidence involving Selenium", "title": "Selenium and immune function: a systematic review and meta-analysis of experimental human studies", "authors": "Filippini T, Fairweather-Tait S, Vinceti M", "journal": "The American journal of clinical nutrition", "year": 2023, "pmid": "36789948", "url": "https://pubmed.ncbi.nlm.nih.gov/36789948/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.ajcnut.2022.11.007", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36789948/", "publicSourceType": "PMID" }, { "text": "Zhou J, Zhang W, Cao Z et al.. Association of Selenium Levels with Neurodegenerative Disease: A Systemic Review and Meta-Analysis. Nutrients. 2023", "claim": "PubMed-indexed evidence involving Selenium", "title": "Association of Selenium Levels with Neurodegenerative Disease: A Systemic Review and Meta-Analysis", "authors": "Zhou J, Zhang W, Cao Z et al.", "journal": "Nutrients", "year": 2023, "pmid": "37686737", "url": "https://pubmed.ncbi.nlm.nih.gov/37686737/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu15173706", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37686737/", "publicSourceType": "PMID" }, { "text": "Wang P, Chen B, Huang Y et al.. Selenium intake and multiple health-related outcomes: an umbrella review of meta-analyses. Frontiers in nutrition. 2023", "claim": "PubMed-indexed evidence involving Selenium", "title": "Selenium intake and multiple health-related outcomes: an umbrella review of meta-analyses", "authors": "Wang P, Chen B, Huang Y et al.", "journal": "Frontiers in nutrition", "year": 2023, "pmid": "37781125", "url": "https://pubmed.ncbi.nlm.nih.gov/37781125/", "study_type": "review", "confidence": "verify", "doi": "10.3389/fnut.2023.1263853", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37781125/", "publicSourceType": "PMID" }, { "text": "Fakhrolmobasheri M, Mazaheri-Tehrani S, Kieliszek M et al.. COVID-19 and Selenium Deficiency: a Systematic Review. Biological trace element research. 2022", "claim": "PubMed-indexed evidence involving Selenium", "title": "COVID-19 and Selenium Deficiency: a Systematic Review", "authors": "Fakhrolmobasheri M, Mazaheri-Tehrani S, Kieliszek M et al.", "journal": "Biological trace element research", "year": 2022, "pmid": "34739678", "url": "https://pubmed.ncbi.nlm.nih.gov/34739678/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s12011-021-02997-4", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34739678/", "publicSourceType": "PMID" }, { "text": "Lima LG, Santos AAMD, Gueiber TD et al.. Relation between Selenium and Female Fertility: A Systematic Review. Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia. 2022", "claim": "PubMed-indexed evidence involving Selenium", "title": "Relation between Selenium and Female Fertility: A Systematic Review", "authors": "Lima LG, Santos AAMD, Gueiber TD et al.", "journal": "Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia", "year": 2022, "pmid": "35668679", "url": "https://pubmed.ncbi.nlm.nih.gov/35668679/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1055/s-0042-1744288", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35668679/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "selenium" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567021", "name": "Chromium", "alternateNames": [ "Chromium Picolinate", "Chromium GTF" ], "category": "Mineral", "subcategory": "Trace Mineral", "overview": "Trace mineral that enhances insulin sensitivity and supports healthy blood sugar metabolism. Popular supplement for glucose management and body composition.", "mechanismOfAction": "Potentiates insulin action by enhancing insulin receptor signaling via chromodulin (low-molecular-weight chromium-binding substance). Increases GLUT4 transporter translocation to cell membranes, facilitating glucose uptake.", "commonBenefits": [ "Blood sugar support", "Insulin sensitivity", "Appetite control", "Body composition" ], "commonDosageRange": "200–1,000 mcg daily", "recommendedForm": "Chromium picolinate (most studied form)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with meals; picolinate form has best bioavailability" }, "evidenceRating": "emerging", "foodSources": [ "Broccoli", "Grape juice", "Turkey", "Whole grains", "Green beans" ], "deficiencySymptoms": [ "Blood sugar dysregulation", "Insulin resistance", "Weight gain" ], "sideEffects": [ "GI discomfort", "Headache", "Rare kidney issues at very high doses" ], "contraindications": [ "Kidney disease", "Liver disease", "Diabetes medications (may potentiate)" ], "iconName": "gauge.with.dots.needle.33percent", "colorHex": "0353A4", "tags": [ "blood-sugar", "metabolism", "insulin" ], "sources": [ { "claim": "Chromium supplementation improves glycemic control in type 2 diabetes", "title": "Effects of chromium supplementation on glycemic control in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials", "authors": "Asbaghi O et al.", "journal": "Pharmacol Res", "year": 2020, "pmid": "32730903", "url": "https://pubmed.ncbi.nlm.nih.gov/32730903/", "study_type": "meta-analysis", "key_finding": "Chromium supplementation significantly reduced FPG (-19 mg/dl), insulin (-12.35 pmol/l), HbA1C (-0.71%), and HOMA-IR (-1.53) in T2D patients", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32730903/", "publicSourceType": "PMID" }, { "claim": "Systematic review of chromium supplementation efficacy and safety in diabetes", "title": "Systematic review and meta-analysis of the efficacy and safety of chromium supplementation in diabetes", "authors": "Suksomboon N et al.", "journal": "J Clin Pharm Ther", "year": 2014, "pmid": "24635480", "url": "https://pubmed.ncbi.nlm.nih.gov/24635480/", "study_type": "meta-analysis", "key_finding": "Chromium supplementation significantly improved glycemic control with HbA1c reduction of -0.55% and FPG reduction of -1.15 mmol/L, especially with chromium picolinate", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24635480/", "publicSourceType": "PMID" }, { "claim": "Chromium supplementation may reduce body weight in overweight/obese individuals", "title": "Chromium supplementation in overweight and obesity: a systematic review and meta-analysis of randomized clinical trials", "authors": "Onakpoya I et al.", "journal": "Obes Rev", "year": 2013, "pmid": "23495911", "url": "https://pubmed.ncbi.nlm.nih.gov/23495911/", "study_type": "meta-analysis", "key_finding": "Chromium supplementation produced statistically significant but small reductions in body weight; clinical relevance is uncertain", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23495911/", "publicSourceType": "PMID" }, { "claim": "Chromium anthropometric effects in overweight/obesity meta-analysis", "title": "A meta-analysis of the effect of chromium supplementation on anthropometric indices of subjects with overweight or obesity", "authors": "Tsang C et al.", "journal": "Clin Obes", "year": 2019, "pmid": "31115179", "url": "https://pubmed.ncbi.nlm.nih.gov/31115179/", "study_type": "meta-analysis", "key_finding": "Significant reductions in weight (-0.75 kg), BMI, and body fat percentage, particularly for durations <=12 weeks and doses <=400 ug/d", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31115179/", "publicSourceType": "PMID" }, { "claim": "Scientific review of chromium's role in insulin resistance mechanism", "title": "A scientific review: the role of chromium in insulin resistance", "authors": "Cefalu WT, Hu FB", "journal": "Diabetes Educ", "year": 2004, "pmid": "15208835", "url": "https://pubmed.ncbi.nlm.nih.gov/15208835/", "study_type": "review", "key_finding": "Chromium potentiates insulin action by enhancing insulin receptor signaling and GLUT4 transporter activity via chromodulin", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15208835/", "publicSourceType": "PMID" }, { "text": "Georgaki MN, Tsokkou S, Keramas A et al.. Chromium supplementation and type 2 diabetes mellitus: an extensive systematic review. Environmental geochemistry and health. 2024", "pmid": "39541030", "doi": "10.1007/s10653-024-02297-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39541030/", "publicSourceType": "PMID" }, { "text": "Maret W. Chromium Supplementation in Human Health, Metabolic Syndrome, and Diabetes. Metal ions in life sciences. 2019", "pmid": "30855110", "doi": "10.1515/9783110527872-015", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30855110/", "publicSourceType": "PMID" }, { "claim": "Chromium supplementation reduces HbA1c in type 2 diabetes patients but does not significantly improve fasting blood glucose or lipid levels", "title": "Effect of Chromium Supplementation on Blood Glucose and Lipid Levels in Patients with Type 2 Diabetes Mellitus: a Systematic Review and Meta-analysis", "authors": "Zhao F, Pan D, Wang N, Xia H, Zhang H, Wang S, Sun G", "journal": "Biological Trace Element Research", "year": 2022, "pmid": "33783683", "url": "https://pubmed.ncbi.nlm.nih.gov/33783683/", "study_type": "meta-analysis", "key_finding": "In 10 RCTs with 509 patients, chromium supplementation significantly reduced HbA1c but did not significantly improve fasting plasma glucose, triglycerides, total cholesterol, LDL, or HDL in type 2 diabetes patients.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33783683/", "publicSourceType": "PMID" }, { "claim": "Chromium supplementation at doses >500 µg/day may decrease triglycerides but overall shows no beneficial effects on blood lipids", "title": "Effects of Chromium Supplementation on Lipid Profile: an Umbrella of Systematic Review and Meta-analysis", "authors": "Vajdi M, Musazadeh V, Karimi A et al.", "journal": "Biological Trace Element Research", "year": 2023, "pmid": "36376714", "url": "https://pubmed.ncbi.nlm.nih.gov/36376714/", "study_type": "meta-analysis", "key_finding": "Umbrella review of 8 meta-analyses found no significant effect of chromium on TG, TC, LDL-c, or HDL-c. Subgroup analysis suggested chromium at doses >500 µg/day could significantly decrease triglycerides.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36376714/", "publicSourceType": "PMID" }, { "text": "Vajdi M, Khajeh M, Safaei E et al.. Effects of chromium supplementation on body composition in patients with type 2 diabetes: A dose-response systematic review and meta-analysis of randomized controlled trials. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2024", "claim": "PubMed-indexed evidence involving Chromium", "title": "Effects of chromium supplementation on body composition in patients with type 2 diabetes: A dose-response systematic review and meta-analysis of randomized controlled trials", "authors": "Vajdi M, Khajeh M, Safaei E et al.", "journal": "Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)", "year": 2024, "pmid": "37952433", "url": "https://pubmed.ncbi.nlm.nih.gov/37952433/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jtemb.2023.127338", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37952433/", "publicSourceType": "PMID" }, { "text": "Morvaridzadeh M, Estêvão MD, Qorbani M et al.. The effect of chromium intake on oxidative stress parameters: A systematic review and meta-analysis. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2022", "claim": "PubMed-indexed evidence involving Chromium", "title": "The effect of chromium intake on oxidative stress parameters: A systematic review and meta-analysis", "authors": "Morvaridzadeh M, Estêvão MD, Qorbani M et al.", "journal": "Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)", "year": 2022, "pmid": "34710707", "url": "https://pubmed.ncbi.nlm.nih.gov/34710707/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jtemb.2021.126879", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34710707/", "publicSourceType": "PMID" }, { "text": "White PE, Vincent JB. Systematic Review of the Effects of Chromium(III) on Chickens. Biological trace element research. 2019", "claim": "PubMed-indexed evidence involving Chromium", "title": "Systematic Review of the Effects of Chromium(III) on Chickens", "authors": "White PE, Vincent JB", "journal": "Biological trace element research", "year": 2019, "pmid": "30430417", "url": "https://pubmed.ncbi.nlm.nih.gov/30430417/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s12011-018-1575-8", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30430417/", "publicSourceType": "PMID" }, { "text": "Tang XL, Sun Z, Gong L. Chromium supplementation in women with polycystic ovary syndrome: Systematic review and meta-analysis. The journal of obstetrics and gynaecology research. 2018", "claim": "PubMed-indexed evidence involving Chromium", "title": "Chromium supplementation in women with polycystic ovary syndrome: Systematic review and meta-analysis", "authors": "Tang XL, Sun Z, Gong L", "journal": "The journal of obstetrics and gynaecology research", "year": 2018, "pmid": "28929602", "url": "https://pubmed.ncbi.nlm.nih.gov/28929602/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/jog.13462", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28929602/", "publicSourceType": "PMID" }, { "text": "Fazelian S, Rouhani MH, Bank SS et al.. Chromium supplementation and polycystic ovary syndrome: A systematic review and meta-analysis. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2017", "claim": "PubMed-indexed evidence involving Chromium", "title": "Chromium supplementation and polycystic ovary syndrome: A systematic review and meta-analysis", "authors": "Fazelian S, Rouhani MH, Bank SS et al.", "journal": "Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)", "year": 2017, "pmid": "28595797", "url": "https://pubmed.ncbi.nlm.nih.gov/28595797/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jtemb.2017.04.008", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28595797/", "publicSourceType": "PMID" }, { "text": "Feng C, Wuren Q, Zhang X et al.. Effects of dietary chromium picolinate supplementation on broiler growth performance: A meta-analysis. PloS one. 2021", "claim": "PubMed-indexed evidence involving Chromium", "title": "Effects of dietary chromium picolinate supplementation on broiler growth performance: A meta-analysis", "authors": "Feng C, Wuren Q, Zhang X et al.", "journal": "PloS one", "year": 2021, "pmid": "33822801", "url": "https://pubmed.ncbi.nlm.nih.gov/33822801/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1371/journal.pone.0249527", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33822801/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "chromium" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567022", "name": "Potassium", "alternateNames": [ "Potassium Citrate", "Potassium Gluconate" ], "category": "Mineral", "subcategory": "Essential Mineral", "overview": "Crucial electrolyte for heart rhythm, muscle contraction, nerve signaling, and blood pressure regulation. Most people don't get enough from diet alone.", "mechanismOfAction": "Primary intracellular cation maintaining cell membrane potential via Na+/K+-ATPase pump. Essential for cardiac myocyte depolarization/repolarization, skeletal muscle contraction, nerve impulse conduction, and renal sodium excretion (lowering blood pressure).", "commonBenefits": [ "Blood pressure regulation", "Heart rhythm", "Muscle function", "Nerve signaling", "Electrolyte balance" ], "commonDosageRange": "99–500 mg supplemental (2,600 mg women / 3,400 mg men total daily need per 2019 NASEM, mostly from food)", "recommendedForm": "Potassium citrate or gluconate", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Supplements limited to 99mg per capsule by FDA; get most from food" }, "evidenceRating": "strong", "foodSources": [ "Bananas", "Sweet potatoes", "Avocado", "Coconut water", "White beans" ], "deficiencySymptoms": [ "Muscle cramps", "Weakness", "Heart palpitations", "Fatigue", "Constipation" ], "sideEffects": [ "GI upset", "Hyperkalemia risk (dangerous at high doses)" ], "contraindications": [ "Kidney disease", "ACE inhibitors", "Potassium-sparing diuretics" ], "iconName": "bolt.batteryblock.fill", "colorHex": "00A6FB", "tags": [ "electrolyte", "heart-health", "blood-pressure" ], "sources": [ { "claim": "Potassium supplementation significantly lowers blood pressure, especially in hypertensives", "title": "Potassium Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials", "authors": "Filippini T et al.", "journal": "J Am Heart Assoc", "year": 2020, "pmid": "32500831", "url": "https://pubmed.ncbi.nlm.nih.gov/32500831/", "study_type": "meta-analysis", "key_finding": "Potassium supplementation reduced SBP by 4.7 mmHg and DBP by 3.5 mmHg overall; in hypertensives SBP fell by 6.8 mmHg and DBP by 4.6 mmHg", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32500831/", "publicSourceType": "PMID" }, { "claim": "Higher potassium intake reduces stroke and cardiovascular disease risk", "title": "Potassium intake, stroke, and cardiovascular disease a meta-analysis of prospective studies", "authors": "D'Elia L et al.", "journal": "J Am Coll Cardiol", "year": 2011, "pmid": "21371638", "url": "https://pubmed.ncbi.nlm.nih.gov/21371638/", "study_type": "meta-analysis", "key_finding": "Higher potassium intake associated with 24% lower stroke risk across 333,250 participants in 14 cohort studies", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21371638/", "publicSourceType": "PMID" }, { "claim": "WHO review: increased potassium reduces blood pressure with no adverse effects on renal function", "title": "Effect of increased potassium intake on cardiovascular risk factors and disease: systematic review and meta-analyses", "authors": "Aburto NJ et al.", "journal": "BMJ", "year": 2013, "pmid": "23558164", "url": "https://pubmed.ncbi.nlm.nih.gov/23558164/", "study_type": "meta-analysis", "key_finding": "High quality evidence shows increased potassium reduces BP in hypertensives with no adverse effect on blood lipids, catecholamines, or renal function", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23558164/", "publicSourceType": "PMID" }, { "claim": "Oral potassium supplementation is safe and effective for essential hypertension", "title": "Oral potassium supplementation for management of essential hypertension: A meta-analysis of randomized controlled trials", "authors": "Poorolajal J et al.", "journal": "PLoS One", "year": 2017, "pmid": "28419159", "url": "https://pubmed.ncbi.nlm.nih.gov/28419159/", "study_type": "meta-analysis", "key_finding": "Potassium supplementation is safe with no important adverse effects and has modest but significant impact on blood pressure in essential hypertension", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28419159/", "publicSourceType": "PMID" }, { "claim": "Hyperkalemia risk from potassium supplementation, especially in renal impairment", "title": "Hyperkalemia", "authors": "Viera AJ, Wouk N", "journal": "Am Fam Physician", "year": 2015, "pmid": "29261936", "url": "https://pubmed.ncbi.nlm.nih.gov/29261936/", "study_type": "review", "key_finding": "Hyperkalemia manifests in cardiovascular, neuromuscular, and GI symptoms; risk greatest with renal impairment or concurrent use of potassium-sparing medications", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29261936/", "publicSourceType": "PMID" }, { "claim": "Potassium supplementation at doses ≤60 mmol/day for >1 month reduces systolic blood pressure in normotensive populations", "title": "Magnesium and Potassium Supplementation for Systolic Blood Pressure Reduction in the General Normotensive Population: A Systematic Review and Subgroup Meta-Analysis for Optimal Dosage and Treatment Length", "authors": "Behers BJ, Behers BM, Stephenson-Moe CA et al.", "journal": "Nutrients", "year": 2024, "pmid": "39519450", "url": "https://pubmed.ncbi.nlm.nih.gov/39519450/", "study_type": "meta-analysis", "key_finding": "Potassium at dosages ≤60 mmol/day reduced SBP by -2.34 mmHg, and durations >1 month reduced SBP by -2.80 mmHg in the general normotensive population. Greater reductions occurred at lower dosages and longer treatment durations.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39519450/", "publicSourceType": "PMID" }, { "claim": "Potassium supplementation improves endothelial function as measured by flow-mediated dilation", "title": "Effect of Potassium Supplementation on Endothelial Function: A Systematic Review and Meta-Analysis of Intervention Studies", "authors": "D'Elia L, Cappuccio FP, Masulli M et al.", "journal": "Nutrients", "year": 2023, "pmid": "36839211", "url": "https://pubmed.ncbi.nlm.nih.gov/36839211/", "study_type": "meta-analysis", "key_finding": "In 5 studies with 332 participants, potassium supplementation was associated with significant increase in FMD (MD 0.74%), with higher effect for urinary potassium excretion >90 mmol/day. This supports increasing dietary potassium to reduce cardiovascular risk.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36839211/", "publicSourceType": "PMID" }, { "text": "Rokkas T, Ekmektzoglou K, Niv Y et al.. Comparative Efficacy and Safety of Potassium-Competitive Acid Blocker-Based Dual, Triple, and Quadruple Regimens for First-Line Helicobacter pylori Infection Treatment: A Systematic Review and Network Meta-Analysis. The American journal of gastroenterology. 2025", "claim": "PubMed-indexed evidence involving Potassium", "title": "Comparative Efficacy and Safety of Potassium-Competitive Acid Blocker-Based Dual, Triple, and Quadruple Regimens for First-Line Helicobacter pylori Infection Treatment: A Systematic Review and Network Meta-Analysis", "authors": "Rokkas T, Ekmektzoglou K, Niv Y et al.", "journal": "The American journal of gastroenterology", "year": 2025, "pmid": "39298553", "url": "https://pubmed.ncbi.nlm.nih.gov/39298553/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.14309/ajg.0000000000003084", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39298553/", "publicSourceType": "PMID" }, { "text": "Ouyang M, Zou S, Cheng Q et al.. Comparative Efficacy and Safety of Potassium-Competitive Acid Blockers and Proton Pump Inhibitors for First-Line Helicobacter pylori Eradication Therapy: A Systematic Review and Network Meta-Analysis. Helicobacter. 2024", "claim": "PubMed-indexed evidence involving Potassium", "title": "Comparative Efficacy and Safety of Potassium-Competitive Acid Blockers and Proton Pump Inhibitors for First-Line Helicobacter pylori Eradication Therapy: A Systematic Review and Network Meta-Analysis", "authors": "Ouyang M, Zou S, Cheng Q et al.", "journal": "Helicobacter", "year": 2024, "pmid": "39508303", "url": "https://pubmed.ncbi.nlm.nih.gov/39508303/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/hel.13150", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39508303/", "publicSourceType": "PMID" }, { "text": "Baird-Heinz HE, Van Schoick AL, Pelsor FR et al.. A systematic review of the safety of potassium bromide in dogs. Journal of the American Veterinary Medical Association. 2012", "claim": "PubMed-indexed evidence involving Potassium", "title": "A systematic review of the safety of potassium bromide in dogs", "authors": "Baird-Heinz HE, Van Schoick AL, Pelsor FR et al.", "journal": "Journal of the American Veterinary Medical Association", "year": 2012, "pmid": "22380809", "url": "https://pubmed.ncbi.nlm.nih.gov/22380809/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2460/javma.240.6.705", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22380809/", "publicSourceType": "PMID" }, { "text": "Huang N, Xu Y, Liu C et al.. Novel Potassium Binders in Reduction of Hyperkalemia and Optimization of RAAS Inhibitors Treatment in Patients with Chronic Kidney Disease or Heart Failure: A Systematic Review and Meta-analysis. Drugs. 2025", "claim": "PubMed-indexed evidence involving Potassium", "title": "Novel Potassium Binders in Reduction of Hyperkalemia and Optimization of RAAS Inhibitors Treatment in Patients with Chronic Kidney Disease or Heart Failure: A Systematic Review and Meta-analysis", "authors": "Huang N, Xu Y, Liu C et al.", "journal": "Drugs", "year": 2025, "pmid": "40542996", "url": "https://pubmed.ncbi.nlm.nih.gov/40542996/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s40265-025-02198-6", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40542996/", "publicSourceType": "PMID" }, { "text": "Kanu JE, Soldera J. Treatment of Helicobacter pylori with potassium competitive acid blockers: A systematic review and meta-analysis. World journal of gastroenterology. 2024", "claim": "PubMed-indexed evidence involving Potassium", "title": "Treatment of Helicobacter pylori with potassium competitive acid blockers: A systematic review and meta-analysis", "authors": "Kanu JE, Soldera J", "journal": "World journal of gastroenterology", "year": 2024, "pmid": "38577188", "url": "https://pubmed.ncbi.nlm.nih.gov/38577188/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3748/wjg.v30.i9.1213", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38577188/", "publicSourceType": "PMID" }, { "text": "Reddin C, Ferguson J, Murphy R et al.. Global mean potassium intake: a systematic review and Bayesian meta-analysis. European journal of nutrition. 2023", "claim": "PubMed-indexed evidence involving Potassium", "title": "Global mean potassium intake: a systematic review and Bayesian meta-analysis", "authors": "Reddin C, Ferguson J, Murphy R et al.", "journal": "European journal of nutrition", "year": 2023, "pmid": "36882596", "url": "https://pubmed.ncbi.nlm.nih.gov/36882596/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00394-023-03128-6", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36882596/", "publicSourceType": "PMID" }, { "text": "Kessi M, Chen B, Peng J et al.. Intellectual Disability and Potassium Channelopathies: A Systematic Review. Frontiers in genetics. 2020", "claim": "PubMed-indexed evidence involving Potassium", "title": "Intellectual Disability and Potassium Channelopathies: A Systematic Review", "authors": "Kessi M, Chen B, Peng J et al.", "journal": "Frontiers in genetics", "year": 2020, "pmid": "32655623", "url": "https://pubmed.ncbi.nlm.nih.gov/32655623/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fgene.2020.00614", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32655623/", "publicSourceType": "PMID" }, { "text": "van Dronkelaar C, van Velzen A, Abdelrazek M et al.. Minerals and Sarcopenia; The Role of Calcium, Iron, Magnesium, Phosphorus, Potassium, Selenium, Sodium, and Zinc on Muscle Mass, Muscle Strength, and Physical Performance in Older Adults: A Systematic Review. Journal of the American Medical Directors Association. 2018", "claim": "PubMed-indexed evidence involving Potassium", "title": "Minerals and Sarcopenia; The Role of Calcium, Iron, Magnesium, Phosphorus, Potassium, Selenium, Sodium, and Zinc on Muscle Mass, Muscle Strength, and Physical Performance in Older Adults: A Systematic Review", "authors": "van Dronkelaar C, van Velzen A, Abdelrazek M et al.", "journal": "Journal of the American Medical Directors Association", "year": 2018, "pmid": "28711425", "url": "https://pubmed.ncbi.nlm.nih.gov/28711425/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jamda.2017.05.026", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28711425/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "potassium" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567023", "name": "Copper", "alternateNames": [ "Copper Bisglycinate", "Copper Gluconate" ], "category": "Mineral", "subcategory": "Trace Mineral", "overview": "Essential trace mineral for iron metabolism, connective tissue formation, and antioxidant defense. Must be balanced with zinc intake.", "mechanismOfAction": "Cofactor for ceruloplasmin (ferroxidase for iron metabolism), cytochrome c oxidase (electron transport chain), superoxide dismutase (SOD, antioxidant), lysyl oxidase (collagen/elastin cross-linking), and dopamine beta-hydroxylase (norepinephrine synthesis).", "commonBenefits": [ "Iron metabolism", "Connective tissue health", "Antioxidant defense", "Energy production", "Nerve function" ], "commonDosageRange": "1–2 mg daily", "recommendedForm": "Copper bisglycinate", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Balance with zinc (1-2mg copper per 15mg zinc); competes with zinc for absorption" }, "evidenceRating": "moderate", "foodSources": [ "Liver", "Oysters", "Dark chocolate", "Cashews", "Shiitake mushrooms" ], "deficiencySymptoms": [ "Anemia (unresponsive to iron)", "Neutropenia", "Osteoporosis", "Fatigue" ], "sideEffects": [ "Nausea", "Liver damage at high doses", "GI upset" ], "contraindications": [ "Wilson's disease", "Liver disease" ], "iconName": "link.circle.fill", "colorHex": "B87333", "tags": [ "iron-metabolism", "connective-tissue", "essential" ], "sources": [ { "claim": "Copper is essential for ceruloplasmin-mediated iron metabolism", "title": "Ceruloplasmin metabolism and function", "authors": "Hellman NE, Gitlin JD", "journal": "Annu Rev Nutr", "year": 2002, "pmid": "12055353", "url": "https://pubmed.ncbi.nlm.nih.gov/12055353/", "study_type": "review", "key_finding": "Ceruloplasmin, a multicopper ferroxidase, is essential for normal iron efflux from cells and links copper and iron homeostasis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12055353/", "publicSourceType": "PMID" }, { "claim": "Copper deficiency causes reversible anemia and neutropenia", "title": "Hematological manifestations of copper deficiency: a retrospective review", "authors": "Halfdanarson TR et al.", "journal": "Eur J Haematol", "year": 2008, "pmid": "18284630", "url": "https://pubmed.ncbi.nlm.nih.gov/18284630/", "study_type": "review", "key_finding": "Copper deficiency presents as anemia and neutropenia, often misdiagnosed as myelodysplastic syndrome; hematological but not neurological manifestations respond to copper replacement", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18284630/", "publicSourceType": "PMID" }, { "claim": "Copper supplementation and bone health effects", "title": "Copper as Dietary Supplement for Bone Metabolism: A Review", "authors": "Ledda C et al.", "journal": "Nutrients", "year": 2021, "pmid": "34210051", "url": "https://pubmed.ncbi.nlm.nih.gov/34210051/", "study_type": "review", "key_finding": "Copper supplementation at 2.5-3 mg/day showed good results in slowing bone mineral loss and reducing resorption markers", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34210051/", "publicSourceType": "PMID" }, { "claim": "Dietary copper and human health: current evidence", "title": "Dietary copper and human health: Current evidence and unresolved issues", "authors": "Bost M et al.", "journal": "J Trace Elem Med Biol", "year": 2016, "pmid": "27049134", "url": "https://pubmed.ncbi.nlm.nih.gov/27049134/", "study_type": "review", "key_finding": "Intakes below 0.8 mg/day lead to net copper losses; net gains consistently observed above 2.4 mg/day; 10 mg/day for 60 days elevated liver enzymes transiently", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27049134/", "publicSourceType": "PMID" }, { "claim": "Copper supplementation effects on blood lipid levels meta-analysis", "title": "Effects of Copper Supplementation on Blood Lipid Level: a Systematic Review and a Meta-Analysis on Randomized Clinical Trials", "authors": "Aslani S et al.", "journal": "Biol Trace Elem Res", "year": 2021, "pmid": "33030656", "url": "https://pubmed.ncbi.nlm.nih.gov/33030656/", "study_type": "meta-analysis", "key_finding": "Copper supplementation had no significant effect on total cholesterol, LDL, or HDL levels across 5 RCTs", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33030656/", "publicSourceType": "PMID" }, { "text": "Myint ZW, Oo TH, Thein KZ et al.. Copper deficiency anemia: review article. Annals of hematology. 2018", "pmid": "29959467", "doi": "10.1007/s00277-018-3407-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29959467/", "publicSourceType": "PMID" }, { "claim": "Heart failure patients have higher serum copper concentrations compared to healthy subjects", "title": "Association between biomarkers of zinc and copper status and heart failure: a meta-analysis", "authors": "Liu R, Yao J, Chen K, Peng W", "journal": "ESC Heart Failure", "year": 2024, "pmid": "38690587", "url": "https://pubmed.ncbi.nlm.nih.gov/38690587/", "study_type": "meta-analysis", "key_finding": "Meta-analysis showed increased serum copper levels in heart failure patients compared to healthy controls (SMD 0.66, 95% CI 0.09-1.23). Patients with HF also had lower zinc levels. The relationship warrants further investigation.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38690587/", "publicSourceType": "PMID" }, { "text": "Muñoz-Bravo C, Marín-Burdallo I, González-Herrera L et al.. Copper in colorectal cancer patients: a systematic review and meta-analysis. Carcinogenesis. 2025", "claim": "PubMed-indexed evidence involving Copper", "title": "Copper in colorectal cancer patients: a systematic review and meta-analysis", "authors": "Muñoz-Bravo C, Marín-Burdallo I, González-Herrera L et al.", "journal": "Carcinogenesis", "year": 2025, "pmid": "39847508", "url": "https://pubmed.ncbi.nlm.nih.gov/39847508/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/carcin/bgaf001", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39847508/", "publicSourceType": "PMID" }, { "text": "Gutiérrez-Guerra MA, Puerto-Parejo LM, Pastor-Ramón E et al.. Dietary Copper Intake and Bone Health: A Systematic Review and Meta-Analysis of Observational Studies. Calcified tissue international. 2025", "claim": "PubMed-indexed evidence involving Copper", "title": "Dietary Copper Intake and Bone Health: A Systematic Review and Meta-Analysis of Observational Studies", "authors": "Gutiérrez-Guerra MA, Puerto-Parejo LM, Pastor-Ramón E et al.", "journal": "Calcified tissue international", "year": 2025, "pmid": "41361655", "url": "https://pubmed.ncbi.nlm.nih.gov/41361655/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00223-025-01463-w", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41361655/", "publicSourceType": "PMID" }, { "text": "Kumar P, Hamza N, Madhok B et al.. Copper Deficiency after Gastric Bypass for Morbid Obesity: a Systematic Review. Obesity surgery. 2016", "claim": "PubMed-indexed evidence involving Copper", "title": "Copper Deficiency after Gastric Bypass for Morbid Obesity: a Systematic Review", "authors": "Kumar P, Hamza N, Madhok B et al.", "journal": "Obesity surgery", "year": 2016, "pmid": "27034062", "url": "https://pubmed.ncbi.nlm.nih.gov/27034062/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s11695-016-2162-8", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27034062/", "publicSourceType": "PMID" }, { "text": "Wang X, Sun H, Zheng Y et al.. Effects of Dietary Copper Supplementation on Fish Growth: A Meta-Analysis. Biological trace element research. 2025", "claim": "PubMed-indexed evidence involving Copper", "title": "Effects of Dietary Copper Supplementation on Fish Growth: A Meta-Analysis", "authors": "Wang X, Sun H, Zheng Y et al.", "journal": "Biological trace element research", "year": 2025, "pmid": "40178735", "url": "https://pubmed.ncbi.nlm.nih.gov/40178735/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s12011-025-04606-0", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40178735/", "publicSourceType": "PMID" }, { "text": "Ding J, Zhang Y. Associations of Dietary Copper, Selenium, and Manganese Intake With Depression: A Meta-Analysis of Observational Studies. Frontiers in nutrition. 2022", "claim": "PubMed-indexed evidence involving Copper", "title": "Associations of Dietary Copper, Selenium, and Manganese Intake With Depression: A Meta-Analysis of Observational Studies", "authors": "Ding J, Zhang Y", "journal": "Frontiers in nutrition", "year": 2022, "pmid": "35369103", "url": "https://pubmed.ncbi.nlm.nih.gov/35369103/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fnut.2022.854774", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35369103/", "publicSourceType": "PMID" }, { "text": "Feng C, Xie B, Wuren Q et al.. Meta-analysis of the correlation between dietary copper supply and broiler performance. PloS one. 2020", "claim": "PubMed-indexed evidence involving Copper", "title": "Meta-analysis of the correlation between dietary copper supply and broiler performance", "authors": "Feng C, Xie B, Wuren Q et al.", "journal": "PloS one", "year": 2020, "pmid": "32421726", "url": "https://pubmed.ncbi.nlm.nih.gov/32421726/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1371/journal.pone.0232876", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32421726/", "publicSourceType": "PMID" }, { "text": "Sachdev PK, Freeland-Graves J, Beretvas SN et al.. Zinc, Copper, and Iron in Oral Submucous Fibrosis: A Meta-Analysis. International journal of dentistry. 2018", "claim": "PubMed-indexed evidence involving Copper", "title": "Zinc, Copper, and Iron in Oral Submucous Fibrosis: A Meta-Analysis", "authors": "Sachdev PK, Freeland-Graves J, Beretvas SN et al.", "journal": "International journal of dentistry", "year": 2018, "pmid": "30046309", "url": "https://pubmed.ncbi.nlm.nih.gov/30046309/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1155/2018/3472087", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30046309/", "publicSourceType": "PMID" }, { "text": "Zeng Q, Yin J, Fan F et al.. Decreased copper and zinc in sera of Chinese vitiligo patients: a meta-analysis. The Journal of dermatology. 2014", "claim": "PubMed-indexed evidence involving Copper", "title": "Decreased copper and zinc in sera of Chinese vitiligo patients: a meta-analysis", "authors": "Zeng Q, Yin J, Fan F et al.", "journal": "The Journal of dermatology", "year": 2014, "pmid": "24517587", "url": "https://pubmed.ncbi.nlm.nih.gov/24517587/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/1346-8138.12392", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24517587/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "copper" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567024", "name": "Iodine", "alternateNames": [ "Potassium Iodide", "Kelp", "Lugol's" ], "category": "Mineral", "subcategory": "Trace Mineral", "overview": "Essential for thyroid hormone production. Deficiency is the leading cause of preventable intellectual disability worldwide. Many people are mildly deficient.", "mechanismOfAction": "Incorporated into thyroid hormones T3 (triiodothyronine) and T4 (thyroxine) by thyroid peroxidase. T3 is the active hormone that regulates metabolic rate, body temperature, growth, and development in virtually every cell.", "commonBenefits": [ "Thyroid function", "Metabolism", "Cognitive development", "Energy", "Hormone balance" ], "commonDosageRange": "150–300 mcg daily", "recommendedForm": "Potassium iodide or kelp-derived iodine", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Selenium is required for proper thyroid hormone conversion; take together" }, "evidenceRating": "strong", "foodSources": [ "Seaweed", "Iodized salt", "Cod", "Dairy", "Eggs" ], "deficiencySymptoms": [ "Goiter", "Hypothyroidism", "Fatigue", "Weight gain", "Cognitive impairment" ], "sideEffects": [ "Thyroid dysfunction (excess)", "Acne", "Metallic taste" ], "contraindications": [ "Hashimoto's thyroiditis (consult doctor)", "Hyperthyroidism" ], "iconName": "thermometer.medium", "colorHex": "5E60CE", "tags": [ "thyroid", "metabolism", "essential" ], "sources": [ { "claim": "Iodine supplementation improves thyroid function in mild-to-moderate deficiency", "title": "Therapy of endocrine disease: Impact of iodine supplementation in mild-to-moderate iodine deficiency: systematic review and meta-analysis", "authors": "Taylor PN et al.", "journal": "Eur J Endocrinol", "year": 2014, "pmid": "24088547", "url": "https://pubmed.ncbi.nlm.nih.gov/24088547/", "study_type": "meta-analysis", "key_finding": "Iodine supplementation improves some maternal thyroid indices and may benefit cognitive function in school-age children in marginally iodine-deficient areas", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24088547/", "publicSourceType": "PMID" }, { "claim": "Iodine supplementation during pregnancy and child neurodevelopment", "title": "Effect of iodine supplementation in pregnancy on child development and other clinical outcomes: a systematic review of randomized controlled trials", "authors": "Zhou SJ et al.", "journal": "Am J Clin Nutr", "year": 2013, "pmid": "24025628", "url": "https://pubmed.ncbi.nlm.nih.gov/24025628/", "study_type": "meta-analysis", "key_finding": "Iodine supplementation during pregnancy reduced cretinism risk in severe deficiency areas but insufficient evidence for benefits in mild-to-moderate deficiency", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24025628/", "publicSourceType": "PMID" }, { "claim": "Excess iodine can precipitate thyroid dysfunction (hyper/hypothyroidism)", "title": "Excess iodine intake: sources, assessment, and effects on thyroid function", "authors": "Farebrother J et al.", "journal": "Ann N Y Acad Sci", "year": 2019, "pmid": "30891786", "url": "https://pubmed.ncbi.nlm.nih.gov/30891786/", "study_type": "review", "key_finding": "High iodine tolerated by most healthy individuals, but may precipitate hyperthyroidism, hypothyroidism, goiter, or thyroid autoimmunity in susceptible persons", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30891786/", "publicSourceType": "PMID" }, { "claim": "Iodine deficiency and thyroid disorders overview", "title": "Iodine deficiency and thyroid disorders", "authors": "Zimmermann MB, Boelaert K", "journal": "Lancet Diabetes Endocrinol", "year": 2015, "pmid": "25591468", "url": "https://pubmed.ncbi.nlm.nih.gov/25591468/", "study_type": "review", "key_finding": "Iodine is essential for thyroid hormone synthesis; deficiency causes goiter, hypothyroidism, and is the most common cause of preventable brain damage worldwide", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25591468/", "publicSourceType": "PMID" }, { "claim": "Role of iodine and other micronutrients in thyroid function", "title": "Role of iodine, selenium and other micronutrients in thyroid function and disorders", "authors": "Triggiani V et al.", "journal": "Endocr Metab Immune Disord Drug Targets", "year": 2009, "pmid": "19594417", "url": "https://pubmed.ncbi.nlm.nih.gov/19594417/", "study_type": "review", "key_finding": "Iodine incorporated into T3 and T4 thyroid hormones via thyroid peroxidase; selenium, iron, and zinc also essential for proper thyroid function", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19594417/", "publicSourceType": "PMID" }, { "claim": "There is insufficient evidence to support iodine supplementation in pregnancy in areas of mild-to-moderate iodine deficiency", "title": "Systematic review and meta-analysis of the effects of iodine supplementation on thyroid function and child neurodevelopment in mildly-to-moderately iodine-deficient pregnant women", "authors": "Dineva M, Fishpool H, Rayman MP, Mendis J, Bath SC", "journal": "American Journal of Clinical Nutrition", "year": 2020, "pmid": "32320029", "url": "https://pubmed.ncbi.nlm.nih.gov/32320029/", "study_type": "meta-analysis", "key_finding": "In 37 publications (10 RCTs), most showed no effect of iodine supplementation on maternal or infant thyroid function. Meta-analyses of 2 RCTs showed no effect on child cognitive, language, or motor scores. Evidence is insufficient to support routine supplementation in mild-to-moderate deficiency.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32320029/", "publicSourceType": "PMID" }, { "text": "Spallek L, Krille L, Reiners C et al.. Adverse effects of iodine thyroid blocking: a systematic review. Radiation protection dosimetry. 2012", "claim": "PubMed-indexed evidence involving Iodine", "title": "Adverse effects of iodine thyroid blocking: a systematic review", "authors": "Spallek L, Krille L, Reiners C et al.", "journal": "Radiation protection dosimetry", "year": 2012, "pmid": "22021061", "url": "https://pubmed.ncbi.nlm.nih.gov/22021061/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/rpd/ncr400", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22021061/", "publicSourceType": "PMID" }, { "text": "He H, Xu Q, Yu C. The efficacy and safety of Iodine-131-metaiodobenzylguanidine therapy in patients with neuroblastoma: a meta-analysis. BMC cancer. 2022", "claim": "PubMed-indexed evidence involving Iodine", "title": "The efficacy and safety of Iodine-131-metaiodobenzylguanidine therapy in patients with neuroblastoma: a meta-analysis", "authors": "He H, Xu Q, Yu C", "journal": "BMC cancer", "year": 2022, "pmid": "35227236", "url": "https://pubmed.ncbi.nlm.nih.gov/35227236/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12885-022-09329-2", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35227236/", "publicSourceType": "PMID" }, { "text": "Azevedo FM, Machamba AAL, Candido AC et al.. Correlation Between Drinking Water and Iodine Status: a Systematic Review and Meta-analysis. Biological trace element research. 2023", "claim": "PubMed-indexed evidence involving Iodine", "title": "Correlation Between Drinking Water and Iodine Status: a Systematic Review and Meta-analysis", "authors": "Azevedo FM, Machamba AAL, Candido AC et al.", "journal": "Biological trace element research", "year": 2023, "pmid": "35075595", "url": "https://pubmed.ncbi.nlm.nih.gov/35075595/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s12011-022-03127-4", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35075595/", "publicSourceType": "PMID" }, { "text": "Dineva M, Hall A, Tan M et al.. Iodine status during child development and hearing ability: a systematic review. The British journal of nutrition. 2023", "claim": "PubMed-indexed evidence involving Iodine", "title": "Iodine status during child development and hearing ability: a systematic review", "authors": "Dineva M, Hall A, Tan M et al.", "journal": "The British journal of nutrition", "year": 2023, "pmid": "35535480", "url": "https://pubmed.ncbi.nlm.nih.gov/35535480/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1017/S0007114522001441", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35535480/", "publicSourceType": "PMID" }, { "text": "Greenwood DC, Webster J, Keeble C et al.. Maternal Iodine Status and Birth Outcomes: A Systematic Literature Review and Meta-Analysis. Nutrients. 2023", "claim": "PubMed-indexed evidence involving Iodine", "title": "Maternal Iodine Status and Birth Outcomes: A Systematic Literature Review and Meta-Analysis", "authors": "Greenwood DC, Webster J, Keeble C et al.", "journal": "Nutrients", "year": 2023, "pmid": "36678261", "url": "https://pubmed.ncbi.nlm.nih.gov/36678261/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu15020387", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36678261/", "publicSourceType": "PMID" }, { "text": "Eveleigh ER, Coneyworth L, Welham SJM. Systematic review and meta-analysis of iodine nutrition in modern vegan and vegetarian diets. The British journal of nutrition. 2023", "claim": "PubMed-indexed evidence involving Iodine", "title": "Systematic review and meta-analysis of iodine nutrition in modern vegan and vegetarian diets", "authors": "Eveleigh ER, Coneyworth L, Welham SJM", "journal": "The British journal of nutrition", "year": 2023, "pmid": "36912094", "url": "https://pubmed.ncbi.nlm.nih.gov/36912094/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1017/S000711452300051X", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36912094/", "publicSourceType": "PMID" }, { "text": "Candido AC, Azevedo FM, Silva DLF et al.. Effects of iodine supplementation on thyroid function parameter: Systematic review and meta-analysis. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2023", "claim": "PubMed-indexed evidence involving Iodine", "title": "Effects of iodine supplementation on thyroid function parameter: Systematic review and meta-analysis", "authors": "Candido AC, Azevedo FM, Silva DLF et al.", "journal": "Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)", "year": 2023, "pmid": "37562272", "url": "https://pubmed.ncbi.nlm.nih.gov/37562272/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jtemb.2023.127275", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37562272/", "publicSourceType": "PMID" }, { "text": "Mohammadi M, Azizi F, Hedayati M. Iodine deficiency status in the WHO Eastern Mediterranean Region: a systematic review. Environmental geochemistry and health. 2018", "claim": "PubMed-indexed evidence involving Iodine", "title": "Iodine deficiency status in the WHO Eastern Mediterranean Region: a systematic review", "authors": "Mohammadi M, Azizi F, Hedayati M", "journal": "Environmental geochemistry and health", "year": 2018, "pmid": "28224254", "url": "https://pubmed.ncbi.nlm.nih.gov/28224254/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s10653-017-9911-z", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28224254/", "publicSourceType": "PMID" }, { "text": "O'Kane SM, Mulhern MS, Pourshahidi LK et al.. Micronutrients, iodine status and concentrations of thyroid hormones: a systematic review. Nutrition reviews. 2018", "claim": "PubMed-indexed evidence involving Iodine", "title": "Micronutrients, iodine status and concentrations of thyroid hormones: a systematic review", "authors": "O'Kane SM, Mulhern MS, Pourshahidi LK et al.", "journal": "Nutrition reviews", "year": 2018, "pmid": "29596650", "url": "https://pubmed.ncbi.nlm.nih.gov/29596650/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/nutrit/nuy008", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29596650/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "iodine" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567025", "name": "Boron", "alternateNames": [ "Boron Citrate", "Boron Glycinate" ], "category": "Mineral", "subcategory": "Trace Mineral", "overview": "Trace mineral studied for bone-mineral, vitamin D, magnesium, and selected hormone-marker contexts.", "mechanismOfAction": "May influence mineral metabolism, vitamin D hydroxylation, cell-membrane biology, and steroid-hormone markers in small or context-specific studies; effects are not reliable testosterone claims.", "commonBenefits": [ "Bone-mineral support", "Vitamin D metabolism research", "Hormone-marker research", "Joint-health research" ], "commonDosageRange": "3–6 mg daily", "recommendedForm": "Boron citrate or boron glycinate", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Very well absorbed; enhances magnesium retention" }, "evidenceRating": "emerging", "foodSources": [ "Raisins", "Almonds", "Avocado", "Prunes", "Red wine" ], "deficiencySymptoms": [ "Not applicable" ], "sideEffects": [ "GI upset at high doses", "Nausea" ], "contraindications": [ "Kidney disease", "Hormone-sensitive conditions (high doses)" ], "iconName": "diamond.fill", "colorHex": "6930C3", "tags": [ "bone-health", "mineral-metabolism", "hormone-markers" ], "sources": [ { "claim": "Boron supplementation supports bone health and prevents calcium loss", "title": "Pivotal role of boron supplementation on bone health: A narrative review", "authors": "Pizzorno L", "journal": "J Trace Elem Med Biol", "year": 2020, "pmid": "32540741", "url": "https://pubmed.ncbi.nlm.nih.gov/32540741/", "study_type": "review", "key_finding": "Small/context-specific studies reported changes in hormone markers; do not present boron as a reliable testosterone-increasing supplement.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32540741/", "publicSourceType": "PMID" }, { "claim": "Boron supplementation has been studied for steroid-hormone markers in context-specific trials", "title": "Effect of dietary boron on mineral, estrogen, and testosterone metabolism in postmenopausal women", "authors": "Nielsen FH et al.", "journal": "FASEB J", "year": 1987, "pmid": "3678698", "url": "https://pubmed.ncbi.nlm.nih.gov/3678698/", "study_type": "RCT", "key_finding": "Small/context-specific studies reported changes in hormone markers; do not present boron as a reliable testosterone-increasing supplement.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3678698/", "publicSourceType": "PMID" }, { "claim": "Boron supplementation effects on plasma hormone and cytokine markers", "title": "Comparative effects of daily and weekly boron supplementation on plasma steroid hormones and proinflammatory cytokines", "authors": "Naghii MR et al.", "journal": "J Trace Elem Med Biol", "year": 2011, "pmid": "21129941", "url": "https://pubmed.ncbi.nlm.nih.gov/21129941/", "study_type": "RCT", "key_finding": "Small/context-specific studies reported changes in hormone markers; do not present boron as a reliable testosterone-increasing supplement.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21129941/", "publicSourceType": "PMID" }, { "claim": "Boron is essential for healthy bones and joints including arthritis benefit", "title": "Essentiality of boron for healthy bones and joints", "authors": "Newnham RE", "journal": "Environ Health Perspect", "year": 1994, "pmid": "7889887", "url": "https://pubmed.ncbi.nlm.nih.gov/7889887/", "study_type": "review", "key_finding": "50% of subjects on 6 mg boron/day improved vs 10% on placebo; arthritis incidence 0-10% in high boron areas vs 20-70% in low boron areas", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7889887/", "publicSourceType": "PMID" }, { "claim": "Boron may enhance vitamin D metabolism by inhibiting 24-hydroxylase", "title": "Up-regulatory impact of boron on vitamin D function -- does it reflect inhibition of 24-hydroxylase?", "authors": "Miljkovic D et al.", "journal": "Med Hypotheses", "year": 2004, "pmid": "15504575", "url": "https://pubmed.ncbi.nlm.nih.gov/15504575/", "study_type": "review", "key_finding": "Boron may potentiate vitamin D protection through inhibition of microsomal enzymes that catabolize 25-hydroxyvitamin D", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15504575/", "publicSourceType": "PMID" }, { "claim": "Comprehensive review of boron's biological roles", "title": "Nothing Boring About Boron", "authors": "Pizzorno L", "journal": "Integr Med (Encinitas)", "year": 2015, "pmid": "26770156", "url": "https://pubmed.ncbi.nlm.nih.gov/26770156/", "study_type": "review", "key_finding": "Small/context-specific studies reported changes in hormone markers; do not present boron as a reliable testosterone-increasing supplement.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26770156/", "publicSourceType": "PMID" }, { "text": "Das BC, Chokkalingam P, Masilamani P et al.. Stimuli-Responsive Boron-Based Materials in Drug Delivery. International journal of molecular sciences. 2023", "pmid": "36769081", "doi": "10.3390/ijms24032757", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36769081/", "publicSourceType": "PMID" }, { "claim": "Boron supplementation may be an effective strategy alongside calcium and vitamin D for osteoporosis prevention", "title": "Nutrition, Physical Activity, and Dietary Supplementation to Prevent Bone Mineral Density Loss: A Food Pyramid", "authors": "Rondanelli M, Faliva MA, Barrile GC et al.", "journal": "Nutrients", "year": 2021, "pmid": "35010952", "url": "https://pubmed.ncbi.nlm.nih.gov/35010952/", "study_type": "review", "key_finding": "Review recommends that when daily requirements cannot be satisfied through diet, calcium, vitamin D, boron, omega 3, and isoflavones supplementation could be an effective strategy for osteopenia/osteoporosis patients with a great benefit/cost ratio.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35010952/", "publicSourceType": "PMID" }, { "claim": "Evidence for boron supplementation to improve athletic performance is limited and of low quality", "title": "The Role of Mineral and Trace Element Supplementation in Exercise and Athletic Performance: A Systematic Review", "authors": "Heffernan SM, Horner K, De Vito G, Conway GE", "journal": "Nutrients", "year": 2019, "pmid": "30909645", "url": "https://pubmed.ncbi.nlm.nih.gov/30909645/", "study_type": "review", "key_finding": "Only 4 studies on boron supplementation and exercise were identified. Currently there is little evidence to support boron supplementation for improving physiological markers of athletic performance. More high quality research is required.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30909645/", "publicSourceType": "PMID" }, { "text": "Vousoughi G, Soleimanzadeh H, Radkhah N et al.. The Effect of Boron Supplementation on Kidney Stones in Patients With Nephrolithiasis: A Double-Blind Randomized Controlled Trial. Food science & nutrition. 2025", "claim": "PubMed-indexed evidence involving Boron", "title": "The Effect of Boron Supplementation on Kidney Stones in Patients With Nephrolithiasis: A Double-Blind Randomized Controlled Trial", "authors": "Vousoughi G, Soleimanzadeh H, Radkhah N et al.", "journal": "Food science & nutrition", "year": 2025, "pmid": "40792045", "url": "https://pubmed.ncbi.nlm.nih.gov/40792045/", "study_type": "RCT", "confidence": "verify", "doi": "10.1002/fsn3.70777", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40792045/", "publicSourceType": "PMID" }, { "text": "Akbari N, Ostadrahimi A, Tutunchi H et al.. Possible therapeutic effects of boron citrate and oleoylethanolamide supplementation in patients with COVID-19: A pilot randomized, double-blind, clinical trial. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2022", "claim": "PubMed-indexed evidence involving Boron", "title": "Possible therapeutic effects of boron citrate and oleoylethanolamide supplementation in patients with COVID-19: A pilot randomized, double-blind, clinical trial", "authors": "Akbari N, Ostadrahimi A, Tutunchi H et al.", "journal": "Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)", "year": 2022, "pmid": "35183882", "url": "https://pubmed.ncbi.nlm.nih.gov/35183882/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.jtemb.2022.126945", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35183882/", "publicSourceType": "PMID" }, { "text": "Naemi M, Naghshi S, Rostami S et al.. Effects of boron citrate supplementation on cardiometabolic factors, inflammatory biomarkers and anthropometric measures in obese patients: study protocol for a randomised, double-blind clinical trial. BMJ open. 2023", "claim": "PubMed-indexed evidence involving Boron", "title": "Effects of boron citrate supplementation on cardiometabolic factors, inflammatory biomarkers and anthropometric measures in obese patients: study protocol for a randomised, double-blind clinical trial", "authors": "Naemi M, Naghshi S, Rostami S et al.", "journal": "BMJ open", "year": 2023, "pmid": "38072490", "url": "https://pubmed.ncbi.nlm.nih.gov/38072490/", "study_type": "RCT", "confidence": "verify", "doi": "10.1136/bmjopen-2023-075941", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38072490/", "publicSourceType": "PMID" }, { "text": "Cho HM, Macelline SP, Wickramasuriya SS et al.. Moderate dietary boron supplementation improved growth performance, crude protein digestibility and diarrhea index in weaner pigs regardless of the sanitary condition. Animal bioscience. 2022", "claim": "PubMed-indexed evidence involving Boron", "title": "Moderate dietary boron supplementation improved growth performance, crude protein digestibility and diarrhea index in weaner pigs regardless of the sanitary condition", "authors": "Cho HM, Macelline SP, Wickramasuriya SS et al.", "journal": "Animal bioscience", "year": 2022, "pmid": "34293844", "url": "https://pubmed.ncbi.nlm.nih.gov/34293844/", "study_type": "review", "confidence": "verify", "doi": "10.5713/ab.21.0110", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34293844/", "publicSourceType": "PMID" }, { "text": "Bhasker TV, Gowda NKS, Pal DT et al.. Influence of boron supplementation on performance, immunity and antioxidant status of lambs fed diets with or without adequate level of calcium. PloS one. 2017", "claim": "PubMed-indexed evidence involving Boron", "title": "Influence of boron supplementation on performance, immunity and antioxidant status of lambs fed diets with or without adequate level of calcium", "authors": "Bhasker TV, Gowda NKS, Pal DT et al.", "journal": "PloS one", "year": 2017, "pmid": "29141035", "url": "https://pubmed.ncbi.nlm.nih.gov/29141035/", "study_type": "review", "confidence": "verify", "doi": "10.1371/journal.pone.0187203", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29141035/", "publicSourceType": "PMID" }, { "text": "Olgun O, Bahtiyarca Y. Effects of Dietary Cadmium and Boron Supplementation on Performance, Eggshell Quality and Mineral Concentrations of Bone in Laying Hens. Biological trace element research. 2015", "claim": "PubMed-indexed evidence involving Boron", "title": "Effects of Dietary Cadmium and Boron Supplementation on Performance, Eggshell Quality and Mineral Concentrations of Bone in Laying Hens", "authors": "Olgun O, Bahtiyarca Y", "journal": "Biological trace element research", "year": 2015, "pmid": "25749927", "url": "https://pubmed.ncbi.nlm.nih.gov/25749927/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s12011-015-0291-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25749927/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "boron" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567026", "name": "Ashwagandha", "alternateNames": [ "Withania Somnifera", "KSM-66", "Sensoril" ], "category": "Adaptogen", "subcategory": "Ayurvedic Adaptogen", "overview": "Ayurvedic adaptogenic herb studied for stress, cortisol-related wellness markers, sleep quality, strength/recovery, and thyroid-related markers in selected populations.", "mechanismOfAction": "Withanolides may influence HPA-axis signaling and GABAergic pathways. Effects on DHEA-S, testosterone, cognition, and thyroid markers are population- and study-specific and should not be treated as established outcomes for every user.", "commonBenefits": [ "Stress support", "Cortisol-related wellness markers", "Sleep quality support", "Strength and recovery support", "Thyroid marker support (limited)" ], "commonDosageRange": "300–600 mg daily (standardized extract)", "recommendedForm": "KSM-66 (root extract) or Sensoril (root + leaf)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Can take morning or evening; evening for sleep, morning for energy. Effects build over 4-8 weeks." }, "evidenceRating": "moderate", "foodSources": [ "Not a food source; herb supplement only" ], "deficiencySymptoms": [ "Not applicable" ], "sideEffects": [ "Drowsiness", "GI upset", "Thyroid elevation (monitor if thyroid condition)", "Hepatotoxicity (rare but potentially severe; cases of liver failure reported, monitor liver function)" ], "contraindications": [ "Hyperthyroidism", "Autoimmune conditions", "Pregnancy", "Surgery (stop 2 weeks before)", "Sedative medications (benzodiazepines, sleep medications, anesthesia)", "Diabetes medications (may lower blood sugar)", "Immunosuppressant drugs" ], "iconName": "leaf.fill", "colorHex": "2D6A4F", "tags": [ "stress", "cortisol", "adaptogen", "sleep", "strength" ], "sources": [ { "claim": "Ashwagandha reduces stress and anxiety vs placebo in meta-analysis", "title": "Does Ashwagandha supplementation have a beneficial effect on the management of anxiety and stress? A systematic review and meta-analysis of randomized controlled trials", "authors": "Akhgarjand C et al.", "journal": "Phytother Res", "year": 2022, "pmid": "36017529", "url": "https://pubmed.ncbi.nlm.nih.gov/36017529/", "study_type": "meta-analysis", "key_finding": "12 RCTs with 1,002 participants showed ashwagandha significantly reduced anxiety and stress at 300-600 mg/day", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36017529/", "publicSourceType": "PMID" }, { "claim": "Ashwagandha significantly reduces serum cortisol levels", "title": "A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults", "authors": "Chandrasekhar K et al.", "journal": "Indian J Psychol Med", "year": 2012, "pmid": "23439798", "url": "https://pubmed.ncbi.nlm.nih.gov/23439798/", "study_type": "RCT", "key_finding": "300 mg twice daily for 60 days significantly reduced serum cortisol levels compared to placebo", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23439798/", "publicSourceType": "PMID" }, { "claim": "Ashwagandha improves muscle strength and recovery during resistance training", "title": "Examining the effect of Withania somnifera supplementation on muscle strength and recovery: a randomized controlled trial", "authors": "Wankhede S et al.", "journal": "J Int Soc Sports Nutr", "year": 2015, "pmid": "26609282", "url": "https://pubmed.ncbi.nlm.nih.gov/26609282/", "study_type": "RCT", "key_finding": "Ashwagandha group had significantly greater increases in bench-press and leg-extension strength, muscle size, and testosterone levels vs placebo", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26609282/", "publicSourceType": "PMID" }, { "claim": "Ashwagandha improves sleep quality especially in those with insomnia", "title": "Effect of Ashwagandha (Withania somnifera) extract on sleep: A systematic review and meta-analysis", "authors": "Cheah KL et al.", "journal": "PLoS One", "year": 2021, "pmid": "34559859", "url": "https://pubmed.ncbi.nlm.nih.gov/34559859/", "study_type": "meta-analysis", "key_finding": "Small but significant effect on overall sleep (SMD -0.59) across 5 RCTs; more prominent benefit in adults with diagnosed insomnia", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34559859/", "publicSourceType": "PMID" }, { "claim": "Ashwagandha improves physical performance per Bayesian meta-analysis", "title": "Effects of Ashwagandha (Withania somnifera) on Physical Performance: Systematic Review and Bayesian Meta-Analysis", "authors": "Bonilla DA et al.", "journal": "J Funct Morphol Kinesiol", "year": 2021, "pmid": "33670194", "url": "https://pubmed.ncbi.nlm.nih.gov/33670194/", "study_type": "meta-analysis", "key_finding": "Ashwagandha supplementation more efficacious than placebo for improving variables related to physical performance in healthy men and women", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33670194/", "publicSourceType": "PMID" }, { "claim": "Ashwagandha-induced liver injury: rare but potentially severe hepatotoxicity", "title": "Ashwagandha-induced liver injury: A case series from Iceland and the US Drug-Induced Liver Injury Network", "authors": "Björnsson HK et al.", "journal": "J Hepatol", "year": 2020, "pmid": "31991029", "url": "https://pubmed.ncbi.nlm.nih.gov/31991029/", "study_type": "review", "key_finding": "Liver injury (cholestatic/mixed) with 2-12 week latency; 3 patients with pre-existing liver disease developed fatal acute-on-chronic liver failure", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31991029/", "publicSourceType": "PMID" }, { "text": "Arumugam V, Vijayakumar V, Balakrishnan A et al.. Effects of Ashwagandha (Withania Somnifera) on stress and anxiety: A systematic review and meta-analysis. Explore (New York, N.Y.). 2024", "pmid": "39348746", "doi": "10.1016/j.explore.2024.103062", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39348746/", "publicSourceType": "PMID" }, { "text": "Verma N, Gupta SK, Tiwari S et al.. Safety of Ashwagandha Root Extract: A Randomized, Placebo-Controlled, study in Healthy Volunteers. Complementary therapies in medicine. 2021", "pmid": "33338583", "doi": "10.1016/j.ctim.2020.102642", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33338583/", "publicSourceType": "PMID" }, { "claim": "Ashwagandha reduces stress hormones in healthy adults", "title": "A standardized Ashwagandha root extract alleviates stress, anxiety, and improves quality of life in healthy adults by modulating stress hormones: Results from a randomized, double-blind, placebo-controlled study.", "authors": "Majeed M, Nagabhushanam K, Mundkur L", "journal": "Medicine", "year": 2023, "pmid": "37832082", "url": "https://pubmed.ncbi.nlm.nih.gov/37832082/", "study_type": "rct", "key_finding": "Standardized ashwagandha root extract significantly reduced cortisol levels and perceived stress while improving quality of life scores in healthy adults.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37832082/", "publicSourceType": "PMID" }, { "text": "Ferreira JF, Ferreira RM, Maia F et al.. Biopsychological Effects of Ashwagandha (Withania somnifera) in Athletes and Healthy Individuals: A Systematic Review. Muscles (Basel, Switzerland). 2025", "claim": "PubMed-indexed evidence involving Ashwagandha", "title": "Biopsychological Effects of Ashwagandha (Withania somnifera) in Athletes and Healthy Individuals: A Systematic Review", "authors": "Ferreira JF, Ferreira RM, Maia F et al.", "journal": "Muscles (Basel, Switzerland)", "year": 2025, "pmid": "40843911", "url": "https://pubmed.ncbi.nlm.nih.gov/40843911/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/muscles4030024", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40843911/", "publicSourceType": "PMID" }, { "text": "Della Porta M, Maier JA, Cazzola R. Effects of Withania somnifera on Cortisol Levels in Stressed Human Subjects: A Systematic Review. Nutrients. 2023", "claim": "PubMed-indexed evidence involving Ashwagandha", "title": "Effects of Withania somnifera on Cortisol Levels in Stressed Human Subjects: A Systematic Review", "authors": "Della Porta M, Maier JA, Cazzola R", "journal": "Nutrients", "year": 2023, "pmid": "38140274", "url": "https://pubmed.ncbi.nlm.nih.gov/38140274/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu15245015", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38140274/", "publicSourceType": "PMID" }, { "text": "Ng QX, Loke W, Foo NX et al.. A systematic review of the clinical use of Withania somnifera (Ashwagandha) to ameliorate cognitive dysfunction. Phytotherapy research : PTR. 2020", "claim": "PubMed-indexed evidence involving Ashwagandha", "title": "A systematic review of the clinical use of Withania somnifera (Ashwagandha) to ameliorate cognitive dysfunction", "authors": "Ng QX, Loke W, Foo NX et al.", "journal": "Phytotherapy research : PTR", "year": 2020, "pmid": "31742775", "url": "https://pubmed.ncbi.nlm.nih.gov/31742775/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/ptr.6552", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31742775/", "publicSourceType": "PMID" }, { "text": "Pérez-Gómez J, Villafaina S, Adsuar JC et al.. Effects of Ashwagandha (Withania somnifera) on VO(2max): A Systematic Review and Meta-Analysis. Nutrients. 2020", "claim": "PubMed-indexed evidence involving Ashwagandha", "title": "Effects of Ashwagandha (Withania somnifera) on VO(2max): A Systematic Review and Meta-Analysis", "authors": "Pérez-Gómez J, Villafaina S, Adsuar JC et al.", "journal": "Nutrients", "year": 2020, "pmid": "32316411", "url": "https://pubmed.ncbi.nlm.nih.gov/32316411/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu12041119", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32316411/", "publicSourceType": "PMID" }, { "text": "Nasimi Doost Azgomi R, Zomorrodi A, Nazemyieh H et al.. Effects of Withania somnifera on Reproductive System: A Systematic Review of the Available Evidence. BioMed research international. 2018", "claim": "PubMed-indexed evidence involving Ashwagandha", "title": "Effects of Withania somnifera on Reproductive System: A Systematic Review of the Available Evidence", "authors": "Nasimi Doost Azgomi R, Zomorrodi A, Nazemyieh H et al.", "journal": "BioMed research international", "year": 2018, "pmid": "29670898", "url": "https://pubmed.ncbi.nlm.nih.gov/29670898/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1155/2018/4076430", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29670898/", "publicSourceType": "PMID" }, { "text": "Smith SJ, Lopresti AL, Fairchild TJ. Exploring the efficacy and safety of a novel standardized ashwagandha (Withania somnifera) root extract (Witholytin®) in adults experiencing high stress and fatigue in a randomized, double-blind, placebo-controlled trial. Journal of psychopharmacology (Oxford, England). 2023", "claim": "PubMed-indexed evidence involving Ashwagandha", "title": "Exploring the efficacy and safety of a novel standardized ashwagandha (Withania somnifera) root extract (Witholytin®) in adults experiencing high stress and fatigue in a randomized, double-blind, placebo-controlled trial", "authors": "Smith SJ, Lopresti AL, Fairchild TJ", "journal": "Journal of psychopharmacology (Oxford, England)", "year": 2023, "pmid": "37740662", "url": "https://pubmed.ncbi.nlm.nih.gov/37740662/", "study_type": "RCT", "confidence": "verify", "doi": "10.1177/02698811231200023", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37740662/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "ashwagandha" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567027", "name": "Rhodiola Rosea", "alternateNames": [ "Golden Root", "Arctic Root" ], "category": "Adaptogen", "subcategory": "Nordic Adaptogen", "overview": "Arctic adaptogen used for centuries in Scandinavian and Russian traditional medicine. Excels at combating fatigue, enhancing mental performance, and improving stress resilience.", "mechanismOfAction": "Active compounds such as rosavins and salidroside may influence stress-response and monoamine pathways. In-vitro MAO findings exist, but human relevance at typical supplement doses is uncertain.", "commonBenefits": [ "Mental performance", "Fatigue reduction", "Stress resilience", "Physical endurance", "Mood support" ], "commonDosageRange": "200–600 mg daily (3% rosavins, 1% salidroside)", "recommendedForm": "Standardized extract (3% rosavins, 1% salidroside)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Take in the morning on empty stomach; can be stimulating, avoid evening use" }, "evidenceRating": "moderate", "foodSources": [ "Not a food source; herb supplement only" ], "deficiencySymptoms": [ "Not applicable" ], "sideEffects": [ "Insomnia if taken late", "Dizziness", "Dry mouth", "Restlessness" ], "contraindications": [ "Bipolar disorder (may trigger mania)", "Autoimmune conditions", "Blood pressure medications", "SSRIs/antidepressants (discuss with prescriber; interaction evidence is limited)", "Warfarin", "Diabetes medications" ], "iconName": "mountain.2.fill", "colorHex": "40916C", "tags": [ "energy", "focus", "adaptogen", "endurance" ], "sources": [ { "claim": "Rhodiola rosea may be helpful for physical and mental fatigue", "title": "Rhodiola rosea for physical and mental fatigue: a systematic review", "authors": "Ishaque S et al.", "journal": "BMC Complement Altern Med", "year": 2012, "pmid": "22643043", "url": "https://pubmed.ncbi.nlm.nih.gov/22643043/", "study_type": "review", "key_finding": "11 RCTs reviewed; some evidence suggests R. rosea may be helpful for enhancing physical performance and alleviating mental fatigue, though methodological flaws limit conclusions", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22643043/", "publicSourceType": "PMID" }, { "claim": "Rhodiola rosea produced less antidepressant effect than sertraline but fewer adverse events in a small trial", "title": "Rhodiola rosea versus sertraline for major depressive disorder: A randomized placebo-controlled trial", "authors": "Mao JJ et al.", "journal": "Phytomedicine", "year": 2015, "pmid": "25837277", "url": "https://pubmed.ncbi.nlm.nih.gov/25837277/", "study_type": "RCT", "key_finding": "R. rosea produced less antidepressant effect than sertraline but fewer adverse events in a small phase II trial.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25837277/", "publicSourceType": "PMID" }, { "claim": "Rhodiola rosea is EMA-approved adaptogen for stress indication", "title": "The Effectiveness of Rhodiola rosea L. Preparations in Alleviating Various Aspects of Life-Stress Symptoms and Stress-Induced Conditions-Encouraging Clinical Evidence", "authors": "Anghelescu IG et al.", "journal": "Molecules", "year": 2022, "pmid": "35745023", "url": "https://pubmed.ncbi.nlm.nih.gov/35745023/", "study_type": "review", "key_finding": "Rhodiola rosea extract (RRE) is the main adaptogen approved by HMPC/EMA for the indication 'stress'; influences stress hormones and boosts energy metabolism", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35745023/", "publicSourceType": "PMID" }, { "claim": "Rhodiola rosea improves endurance exercise performance", "title": "Acute Rhodiola rosea intake can improve endurance exercise performance", "authors": "De Bock K et al.", "journal": "Int J Sport Nutr Exerc Metab", "year": 2004, "pmid": "15256690", "url": "https://pubmed.ncbi.nlm.nih.gov/15256690/", "study_type": "RCT", "key_finding": "Acute R. rosea intake improved endurance exercise capacity in young healthy volunteers by decreasing perception of effort", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15256690/", "publicSourceType": "PMID" }, { "claim": "Clinical trial of Rhodiola rosea in mild to moderate depression", "title": "Clinical trial of Rhodiola rosea L. extract SHR-5 in the treatment of mild to moderate depression", "authors": "Darbinyan V et al.", "journal": "Nord J Psychiatry", "year": 2007, "pmid": "17990195", "url": "https://pubmed.ncbi.nlm.nih.gov/17990195/", "study_type": "RCT", "key_finding": "SHR-5 extract improved depression symptom scores in one small trial; replication and comparative evidence remain limited.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17990195/", "publicSourceType": "PMID" }, { "claim": "Evidence-based efficacy of adaptogens in fatigue including molecular mechanisms", "title": "Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity", "authors": "Panossian A, Wikman G", "journal": "Curr Clin Pharmacol", "year": 2009, "pmid": "19500070", "url": "https://pubmed.ncbi.nlm.nih.gov/19500070/", "study_type": "review", "key_finding": "Strong scientific evidence for Rhodiola rosea SHR-5 extract improving attention, cognitive function and mental performance in fatigue and chronic fatigue syndrome", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19500070/", "publicSourceType": "PMID" }, { "text": "Lu Y, Deng B, Xu L et al.. Effects of Rhodiola Rosea Supplementation on Exercise and Sport: A Systematic Review. Frontiers in nutrition. 2022", "pmid": "35464040", "doi": "10.3389/fnut.2022.856287", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35464040/", "publicSourceType": "PMID" }, { "text": "Lara PM, Vera J, Marcos-Frutos D et al.. Can Rhodiola rosea supplementation mitigate digital eye strain? A triple-blinded placebo-controlled study. Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists). 2025", "pmid": "40873122", "doi": "10.1111/opo.70005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40873122/", "publicSourceType": "PMID" }, { "claim": "Salidroside (Rhodiola active compound) improves exercise performance", "title": "Salidroside and exercise performance in healthy active young adults - an exploratory, randomized, double-blind, placebo-controlled study.", "authors": "Schwarz NA, Stratton MT, Colquhoun RJ et al.", "journal": "Journal of the International Society of Sports Nutrition", "year": 2024, "pmid": "39601362", "url": "https://pubmed.ncbi.nlm.nih.gov/39601362/", "study_type": "rct", "key_finding": "Salidroside supplementation improved exercise performance and reduced perceived exertion in healthy active young adults.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39601362/", "publicSourceType": "PMID" }, { "claim": "Rhodiola may help prevent acute mountain sickness", "title": "The preventive effect of four drugs on acute mountain sickness: a Bayesian network meta-analysis.", "authors": "Yang HL, Deng MJ, Zhang W et al.", "journal": "Zhonghua Jie He He Hu Xi Za Zhi", "year": 2021, "pmid": "34758521", "url": "https://pubmed.ncbi.nlm.nih.gov/34758521/", "study_type": "meta-analysis", "key_finding": "Rhodiola (Hongjingtian) showed preventive effects against acute mountain sickness in a network meta-analysis comparing multiple pharmacological interventions.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34758521/", "publicSourceType": "PMID" }, { "claim": "Rhodiola is used as adaptogenic phytotherapy for stress and fatigue", "title": "From St. John's wort to tomato and from Rhodiola to cranberry: A review of phytotherapy and some examples.", "authors": "Weixlbaumer V, Draxler L, Zeitlinger M et al.", "journal": "Wiener klinische Wochenschrift", "year": 2020, "pmid": "32211986", "url": "https://pubmed.ncbi.nlm.nih.gov/32211986/", "study_type": "review", "key_finding": "Rhodiola rosea has established evidence as an adaptogen for reducing stress-related fatigue and improving mental performance under stressful conditions.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32211986/", "publicSourceType": "PMID" }, { "text": "Sanz-Barrio PM, Noreen EE, Gilsanz-Estebaranz L et al.. Rhodiola rosea supplementation on sports performance: A systematic review of randomized controlled trials. Phytotherapy research : PTR. 2023", "claim": "PubMed-indexed evidence involving Rhodiola Rosea", "title": "Rhodiola rosea supplementation on sports performance: A systematic review of randomized controlled trials", "authors": "Sanz-Barrio PM, Noreen EE, Gilsanz-Estebaranz L et al.", "journal": "Phytotherapy research : PTR", "year": 2023, "pmid": "37495266", "url": "https://pubmed.ncbi.nlm.nih.gov/37495266/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/ptr.7950", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37495266/", "publicSourceType": "PMID" }, { "text": "Wang X, Yang X, Gao Z et al.. The effect of Rhodiola rosea supplementation on endurance performance and related biomarkers: a systematic review and meta-analysis. Frontiers in nutrition. 2025", "claim": "PubMed-indexed evidence involving Rhodiola Rosea", "title": "The effect of Rhodiola rosea supplementation on endurance performance and related biomarkers: a systematic review and meta-analysis", "authors": "Wang X, Yang X, Gao Z et al.", "journal": "Frontiers in nutrition", "year": 2025, "pmid": "41080184", "url": "https://pubmed.ncbi.nlm.nih.gov/41080184/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fnut.2025.1645346", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41080184/", "publicSourceType": "PMID" }, { "text": "Lu Y, Deng B, Xu L et al.. Corrigendum: Effects of Rhodiola Rosea Supplementation on Exercise and Sport: A Systematic Review. Frontiers in nutrition. 2022", "claim": "PubMed-indexed evidence involving Rhodiola Rosea", "title": "Corrigendum: Effects of Rhodiola Rosea Supplementation on Exercise and Sport: A Systematic Review", "authors": "Lu Y, Deng B, Xu L et al.", "journal": "Frontiers in nutrition", "year": 2022, "pmid": "35799587", "url": "https://pubmed.ncbi.nlm.nih.gov/35799587/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fnut.2022.928909", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35799587/", "publicSourceType": "PMID" }, { "text": "Marcos-Frutos D, Leban Ž, Li Z et al.. The Impact of Rhodiola Rosea Extract on Strength Performance in Alternative Bench-Press and Bench-Pull Exercises Under Resting and Mental Fatigue Conditions: A Randomized, Triple-Blinded, Placebo-Controlled, Crossover Trial. Nutrients. 2025", "claim": "PubMed-indexed evidence involving Rhodiola Rosea", "title": "The Impact of Rhodiola Rosea Extract on Strength Performance in Alternative Bench-Press and Bench-Pull Exercises Under Resting and Mental Fatigue Conditions: A Randomized, Triple-Blinded, Placebo-Controlled, Crossover Trial", "authors": "Marcos-Frutos D, Leban Ž, Li Z et al.", "journal": "Nutrients", "year": 2025, "pmid": "40289957", "url": "https://pubmed.ncbi.nlm.nih.gov/40289957/", "study_type": "RCT", "confidence": "verify", "doi": "10.3390/nu17060940", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40289957/", "publicSourceType": "PMID" }, { "text": "Koozehchian MS, Newton AT, Mabrey G et al.. Dose-Response Effects of Short-Term Rhodiola rosea (Golden Root Extract) Supplementation on Anaerobic Exercise Performance and Cognitive Function in Resistance-Trained Athletes: A Randomized, Crossover, Double-Blind, and Placebo-Controlled Study. Nutrients. 2025", "claim": "PubMed-indexed evidence involving Rhodiola Rosea", "title": "Dose-Response Effects of Short-Term Rhodiola rosea (Golden Root Extract) Supplementation on Anaerobic Exercise Performance and Cognitive Function in Resistance-Trained Athletes: A Randomized, Crossover, Double-Blind, and Placebo-Controlled Study", "authors": "Koozehchian MS, Newton AT, Mabrey G et al.", "journal": "Nutrients", "year": 2025, "pmid": "41374026", "url": "https://pubmed.ncbi.nlm.nih.gov/41374026/", "study_type": "RCT", "confidence": "verify", "doi": "10.3390/nu17233736", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41374026/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "rhodiola-rosea" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567028", "name": "Lion's Mane", "alternateNames": [ "Hericium Erinaceus" ], "category": "Adaptogen", "subcategory": "Medicinal Mushroom", "overview": "Unique medicinal mushroom with preclinically demonstrated nerve growth factor (NGF) stimulating properties. The premier nootropic mushroom for cognitive enhancement and neuroprotection.", "mechanismOfAction": "Hericenones (in fruiting body) and erinacines (in mycelium) cross the blood-brain barrier and stimulate NGF and BDNF synthesis. This promotes neurogenesis, myelination, and synaptic plasticity. Also reduces neuroinflammation via inhibition of NF-κB pathway.", "commonBenefits": [ "Cognitive enhancement", "Nerve regeneration", "Neuroprotection", "Mood support", "Gut health" ], "commonDosageRange": "500–3,000 mg daily", "recommendedForm": "Dual extract (fruiting body + mycelium) for both hericenones and erinacines", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Effects build over 4-8 weeks; take with meals" }, "evidenceRating": "emerging", "foodSources": [ "Lion's mane mushroom (culinary)" ], "deficiencySymptoms": [ "Not applicable" ], "sideEffects": [ "Rare GI discomfort", "Rare skin rash (allergic)" ], "contraindications": [ "Mushroom allergies", "Blood thinners (theoretical)" ], "iconName": "brain.head.profile", "colorHex": "52B788", "tags": [ "brain", "nootropic", "nerve-health", "mushroom" ], "sources": [ { "claim": "Hericium erinaceus improves cognitive function in older adults", "title": "Improvement of cognitive functions by oral intake of Hericium erinaceus", "authors": "Saitsu Y et al.", "journal": "Biomed Res", "year": 2019, "pmid": "31413233", "url": "https://pubmed.ncbi.nlm.nih.gov/31413233/", "study_type": "RCT", "key_finding": "Oral H. erinaceus supplementation improved cognitive function scores in older adults with mild cognitive impairment", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31413233/", "publicSourceType": "PMID" }, { "claim": "Lion's Mane reduces depression and anxiety", "title": "Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake", "authors": "Nagano M et al.", "journal": "Biomed Res", "year": 2010, "pmid": "20834180", "url": "https://pubmed.ncbi.nlm.nih.gov/20834180/", "study_type": "RCT", "key_finding": "4 weeks of H. erinaceus cookie intake significantly reduced depression and anxiety scores vs placebo in 30 females", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20834180/", "publicSourceType": "PMID" }, { "claim": "Hericium erinaceus compounds stimulate nerve growth factor (NGF) synthesis", "title": "Neurotrophic properties of the Lion's mane medicinal mushroom, Hericium erinaceus (Higher Basidiomycetes) from Malaysia", "authors": "Lai PL et al.", "journal": "Int J Med Mushrooms", "year": 2013, "pmid": "24266378", "url": "https://pubmed.ncbi.nlm.nih.gov/24266378/", "study_type": "review", "key_finding": "H. erinaceus extracts induced NGF synthesis and promoted neurite outgrowth via JNK signaling pathway", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24266378/", "publicSourceType": "PMID" }, { "claim": "Erinacine A-enriched H. erinaceus mycelia may prevent early Alzheimer's disease", "title": "Prevention of Early Alzheimer's Disease by Erinacine A-Enriched Hericium erinaceus Mycelia Pilot Double-Blind Placebo-Controlled Study", "authors": "Li IC et al.", "journal": "Front Aging Neurosci", "year": 2020, "pmid": "32581767", "url": "https://pubmed.ncbi.nlm.nih.gov/32581767/", "study_type": "RCT", "key_finding": "After 49 weeks of erinacine A-enriched H. erinaceus intervention, significant improvement in MMSE scores in treatment group", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32581767/", "publicSourceType": "PMID" }, { "claim": "H. erinaceus improves mood, sleep and BDNF in overweight/obese patients", "title": "Hericium erinaceus Improves Mood and Sleep Disorders in Patients Affected by Overweight or Obesity: Could Circulating Pro-BDNF and BDNF Be Potential Biomarkers?", "authors": "Vigna L et al.", "journal": "Evid Based Complement Alternat Med", "year": 2019, "pmid": "31118969", "url": "https://pubmed.ncbi.nlm.nih.gov/31118969/", "study_type": "RCT", "key_finding": "8 weeks of H. erinaceus supplementation decreased depression, anxiety, and sleep disorders and enhanced pro-BDNF and BDNF production", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31118969/", "publicSourceType": "PMID" }, { "claim": "Systematic review of benefits, side effects, and uses of Hericium erinaceus", "title": "Benefits, side effects, and uses of Hericium erinaceus as a supplement: a systematic review", "authors": "Roda E et al.", "journal": "Nutrients", "year": 2025, "pmid": "40959699", "url": "https://pubmed.ncbi.nlm.nih.gov/40959699/", "study_type": "review", "key_finding": "HE is effective in enhancing cognitive function and improving symptoms of anxiety and depression; side effects include stomach discomfort and headache", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40959699/", "publicSourceType": "PMID" }, { "text": "Surendran G, Saye J, Binti Mohd Jalil S et al.. Acute effects of a standardised extract of Hericium erinaceus (Lion's Mane mushroom) on cognition and mood in healthy younger adults: a double-blind randomised placebo-controlled study. Frontiers in nutrition. 2025", "pmid": "40276537", "doi": "10.3389/fnut.2025.1405796", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40276537/", "publicSourceType": "PMID" }, { "text": "Mori K, Inatomi S, Ouchi K et al.. Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial. Phytotherapy research : PTR. 2009", "pmid": "18844328", "doi": "10.1002/ptr.2634", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18844328/", "publicSourceType": "PMID" }, { "claim": "Lion's Mane improves cognitive function and reduces stress", "title": "The Acute and Chronic Effects of Lion's Mane Mushroom Supplementation on Cognitive Function, Stress and Mood in Young Adults: A Double-Blind, Parallel Groups, Pilot Study.", "authors": "Docherty S, Doughty FL, Smith EF", "journal": "Nutrients", "year": 2023, "pmid": "38004235", "url": "https://pubmed.ncbi.nlm.nih.gov/38004235/", "study_type": "rct", "key_finding": "Lion's Mane supplementation improved cognitive performance on certain tasks and reduced self-reported stress levels in young adults over 28 days.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38004235/", "publicSourceType": "PMID" }, { "claim": "Lion's Mane has therapeutic potential for depression", "title": "Therapeutic Potential of Hericium erinaceus for Depressive Disorder.", "authors": "Chong PS, Fung ML, Wong KH et al.", "journal": "International Journal of Molecular Sciences", "year": 2019, "pmid": "31881712", "url": "https://pubmed.ncbi.nlm.nih.gov/31881712/", "study_type": "review", "key_finding": "Hericium erinaceus demonstrated neuroprotective properties and potential antidepressant effects through modulation of neurotrophic factors and reduction of neuroinflammation.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31881712/", "publicSourceType": "PMID" }, { "text": "Spangenberg ET, Moneypenny A, Bozzo GG et al.. Unveiling the role of erinacines in the neuroprotective effects of Hericium erinaceus: a systematic review in preclinical models. Frontiers in pharmacology. 2025", "claim": "PubMed-indexed evidence involving Lion's Mane", "title": "Unveiling the role of erinacines in the neuroprotective effects of Hericium erinaceus: a systematic review in preclinical models", "authors": "Spangenberg ET, Moneypenny A, Bozzo GG et al.", "journal": "Frontiers in pharmacology", "year": 2025, "pmid": "40626304", "url": "https://pubmed.ncbi.nlm.nih.gov/40626304/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fphar.2025.1582081", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40626304/", "publicSourceType": "PMID" }, { "text": "Othman A, Amen Y, Shimizu K. Hericenones From Hericium erinaceus (Bull.) Pers.: A Scoping Review of Structural Diversity and Health Benefits. Chemistry & biodiversity. 2026", "claim": "PubMed-indexed evidence involving Lion's Mane", "title": "Hericenones From Hericium erinaceus (Bull.) Pers.: A Scoping Review of Structural Diversity and Health Benefits", "authors": "Othman A, Amen Y, Shimizu K", "journal": "Chemistry & biodiversity", "year": 2026, "pmid": "41518660", "url": "https://pubmed.ncbi.nlm.nih.gov/41518660/", "study_type": "review", "confidence": "verify", "doi": "10.1002/cbdv.202502560", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41518660/", "publicSourceType": "PMID" }, { "text": "Cornford N, Charnley M. Hericium erinaceus: A possible future therapeutic treatment for the prevention and delayed progression of Alzheimer's disease? - A narrative review. Nutrition research reviews. 2025", "claim": "PubMed-indexed evidence involving Lion's Mane", "title": "Hericium erinaceus: A possible future therapeutic treatment for the prevention and delayed progression of Alzheimer's disease? - A narrative review", "authors": "Cornford N, Charnley M", "journal": "Nutrition research reviews", "year": 2025, "pmid": "39988819", "url": "https://pubmed.ncbi.nlm.nih.gov/39988819/", "study_type": "review", "confidence": "verify", "doi": "10.1017/S0954422425000058", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39988819/", "publicSourceType": "PMID" }, { "text": "Contato AG, Conte-Junior CA. Lion's Mane Mushroom (Hericium erinaceus): A Neuroprotective Fungus with Antioxidant, Anti-Inflammatory, and Antimicrobial Potential-A Narrative Review. Nutrients. 2025", "claim": "PubMed-indexed evidence involving Lion's Mane", "title": "Lion's Mane Mushroom (Hericium erinaceus): A Neuroprotective Fungus with Antioxidant, Anti-Inflammatory, and Antimicrobial Potential-A Narrative Review", "authors": "Contato AG, Conte-Junior CA", "journal": "Nutrients", "year": 2025, "pmid": "40284172", "url": "https://pubmed.ncbi.nlm.nih.gov/40284172/", "study_type": "review", "confidence": "verify", "doi": "10.3390/nu17081307", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40284172/", "publicSourceType": "PMID" }, { "text": "He X, Wang X, Fang J et al.. Structures, biological activities, and industrial applications of the polysaccharides from Hericium erinaceus (Lion's Mane) mushroom: A review. International journal of biological macromolecules. 2017", "claim": "PubMed-indexed evidence involving Lion's Mane", "title": "Structures, biological activities, and industrial applications of the polysaccharides from Hericium erinaceus (Lion's Mane) mushroom: A review", "authors": "He X, Wang X, Fang J et al.", "journal": "International journal of biological macromolecules", "year": 2017, "pmid": "28087447", "url": "https://pubmed.ncbi.nlm.nih.gov/28087447/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.ijbiomac.2017.01.040", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28087447/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "lion-s-mane" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567029", "name": "Cordyceps", "alternateNames": [ "Cordyceps Militaris", "Cordyceps Sinensis" ], "category": "Adaptogen", "subcategory": "Medicinal Mushroom", "overview": "Energy-boosting medicinal mushroom traditionally used in Tibetan and Chinese medicine. Enhances oxygen utilization, ATP production, and physical performance.", "mechanismOfAction": "Cordycepin (3'-deoxyadenosine) activates AMPK (signals low energy status, promotes catabolic pathways); net effect on ATP in humans is unclear. Shown to increase EPO under hypoxic conditions in vitro only; no human RCT confirms serum EPO increase. Adenosine receptor agonist providing anti-inflammatory effects.", "commonBenefits": [ "Athletic performance", "Energy and stamina", "Oxygen utilization", "Immune modulation" ], "commonDosageRange": "1,000–3,000 mg daily", "recommendedForm": "Cordyceps militaris fruiting body extract (standardized for cordycepin)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Take in the morning or pre-workout; may be too stimulating for evening" }, "evidenceRating": "emerging", "foodSources": [ "Not a common food source" ], "deficiencySymptoms": [ "Not applicable" ], "sideEffects": [ "GI upset", "Insomnia if taken late", "Dry mouth" ], "contraindications": [ "Autoimmune conditions", "Blood thinners", "Upcoming surgery" ], "iconName": "figure.run", "colorHex": "74C69D", "tags": [ "energy", "performance", "mushroom", "endurance" ], "sources": [ { "claim": "Cordyceps militaris improves high-intensity exercise tolerance and VO2max", "title": "Cordyceps militaris Improves Tolerance to High-Intensity Exercise After Acute and Chronic Supplementation", "authors": "Hirsch KR et al.", "journal": "J Diet Suppl", "year": 2017, "pmid": "27408987", "url": "https://pubmed.ncbi.nlm.nih.gov/27408987/", "study_type": "RCT", "key_finding": "After 3 weeks of supplementation VO2max improved by 4.8 ml/kg/min; time to exhaustion increased by 69.8 seconds", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27408987/", "publicSourceType": "PMID" }, { "claim": "Cordyceps sinensis (Cs-4) improves exercise performance in older adults", "title": "Effect of Cs-4 (Cordyceps sinensis) on exercise performance in healthy older subjects: a double-blind, placebo-controlled trial", "authors": "Chen S et al.", "journal": "J Altern Complement Med", "year": 2010, "pmid": "20804368", "url": "https://pubmed.ncbi.nlm.nih.gov/20804368/", "study_type": "RCT", "key_finding": "After 12 weeks of Cs-4, the metabolic threshold increased by 10.5% vs no change in placebo group", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20804368/", "publicSourceType": "PMID" }, { "claim": "Cordyceps promotes cellular energy production and ATP synthesis", "title": "Beneficial Effect of Cordyceps militaris on Exercise Performance via Promoting Cellular Energy Production", "authors": "Xiao H et al.", "journal": "Evid Based Complement Alternat Med", "year": 2020, "pmid": "33312018", "url": "https://pubmed.ncbi.nlm.nih.gov/33312018/", "study_type": "review", "key_finding": "Cordyceps militaris improves exercise performance associated with increased ATP production rather than decreased muscle fatigue", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33312018/", "publicSourceType": "PMID" }, { "claim": "Cordyceps has immune-stimulatory and anti-inflammatory properties via cordycepin", "title": "Anti-inflammatory effects of cordycepin: A review", "authors": "Tan L et al.", "journal": "Phytother Res", "year": 2020, "pmid": "33090621", "url": "https://pubmed.ncbi.nlm.nih.gov/33090621/", "study_type": "review", "key_finding": "Cordycepin exerts anti-inflammatory effects against ALI, asthma, rheumatoid arthritis, Parkinson's disease, hepatitis, and atherosclerosis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33090621/", "publicSourceType": "PMID" }, { "claim": "Cordyceps militaris immune modulation clinical trial", "title": "A randomized controlled clinical trial examining the effects of Cordyceps militaris beverage on the immune response in healthy adults", "authors": "Jung SJ et al.", "journal": "J Funct Foods", "year": 2024, "pmid": "38580687", "url": "https://pubmed.ncbi.nlm.nih.gov/38580687/", "study_type": "RCT", "key_finding": "NK cell activity markedly increased within 4 weeks in males; IL-1beta reduced in males and IL-6 decreased in females", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38580687/", "publicSourceType": "PMID" }, { "claim": "Safety evaluation of cultivated Chinese cordyceps", "title": "Toxicological safety evaluation of the cultivated Chinese cordyceps", "authors": "Li X et al.", "journal": "J Ethnopharmacol", "year": 2021, "pmid": "33220357", "url": "https://pubmed.ncbi.nlm.nih.gov/33220357/", "study_type": "review", "key_finding": "Acute toxicity LD50 >5 g/kg (non-toxic); no abnormal changes in tissues or organs at 20 g/kg; no-observed-adverse-effect level >1000 mg/kg", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33220357/", "publicSourceType": "PMID" }, { "text": "Chen B, Sun Y, Luo F et al.. Bioactive Metabolites and Potential Mycotoxins Produced by Cordyceps Fungi: A Review of Safety. Toxins. 2020", "pmid": "32575649", "doi": "10.3390/toxins12060410", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32575649/", "publicSourceType": "PMID" }, { "text": "Liu Y, Guo ZJ, Zhou XW. Chinese Cordyceps: Bioactive Components, Antitumor Effects and Underlying Mechanism-A Review. Molecules (Basel, Switzerland). 2022", "pmid": "36235111", "doi": "10.3390/molecules27196576", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36235111/", "publicSourceType": "PMID" }, { "claim": "Cordyceps sinensis improves outcomes in lung cancer adjuvant treatment", "title": "Adjuvant treatment with Cordyceps sinensis for lung cancer: A systematic review and meta-analysis of randomized controlled trials.", "authors": "Wang C, Wang J, Qi Y", "journal": "Journal of Ethnopharmacology", "year": 2024, "pmid": "38484953", "url": "https://pubmed.ncbi.nlm.nih.gov/38484953/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 12 RCTs (928 patients) showed CS as adjuvant for lung cancer improved tumor response rate (RR: 1.17), immune function (CD4, CD8, NK cells), quality of life (KPS MD: 8.20), and reduced adverse drug reactions including myelosuppression, leukopenia, and radiation pneumonitis.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38484953/", "publicSourceType": "PMID" }, { "claim": "Cordyceps-derived Bailing capsule improves COPD outcomes", "title": "Therapeutic efficacy and pharmacological mechanism of Bailing capsule on chronic obstructive pulmonary disease: a meta-analysis and network pharmacology.", "authors": "Ma G, Jin Y", "journal": "Pharmaceutical Biology", "year": 2024, "pmid": "39460586", "url": "https://pubmed.ncbi.nlm.nih.gov/39460586/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 27 RCTs showed Bailing capsule (derived from Cordyceps sinensis) significantly improved FEV1, FEV1/FVC ratio, 6-min walk test, reduced acute COPD exacerbations, and improved quality of life.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39460586/", "publicSourceType": "PMID" }, { "claim": "Cordyceps has anti-fatigue and exercise performance benefits", "title": "Effectiveness of Cordyceps sinensis as an adjunct to physical performance: A systematic review and meta-analysis.", "authors": "Hirsch KR, Smith-Ryan AE, Roelofs EJ et al.", "journal": "Journal of Dietary Supplements", "year": 2023, "pmid": "38645562", "url": "https://pubmed.ncbi.nlm.nih.gov/38645562/", "study_type": "meta-analysis", "key_finding": "Systematic review found limited but suggestive evidence that Cordyceps supplementation may improve VO2 max and exercise performance, though more high-quality RCTs are needed.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38645562/", "publicSourceType": "PMID" }, { "text": "Pu F, Li T, Shen C et al.. Fermented Ophiocordyceps sinensis mycelium products for preventing contrast-associated acute kidney injury: a systematic review of randomized controlled trials. Renal failure. 2024", "claim": "PubMed-indexed evidence involving Cordyceps", "title": "Fermented Ophiocordyceps sinensis mycelium products for preventing contrast-associated acute kidney injury: a systematic review of randomized controlled trials", "authors": "Pu F, Li T, Shen C et al.", "journal": "Renal failure", "year": 2024, "pmid": "38189088", "url": "https://pubmed.ncbi.nlm.nih.gov/38189088/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/0886022X.2023.2300302", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38189088/", "publicSourceType": "PMID" }, { "text": "Liu M, Cui C, Chang T et al.. Effects and safety of Ophiocordyceps sinensis preparation in the adjuvant treatment for dialysis patients: a systematic review and meta-analysis. Frontiers in pharmacology. 2024", "claim": "PubMed-indexed evidence involving Cordyceps", "title": "Effects and safety of Ophiocordyceps sinensis preparation in the adjuvant treatment for dialysis patients: a systematic review and meta-analysis", "authors": "Liu M, Cui C, Chang T et al.", "journal": "Frontiers in pharmacology", "year": 2024, "pmid": "39101133", "url": "https://pubmed.ncbi.nlm.nih.gov/39101133/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fphar.2024.1360997", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39101133/", "publicSourceType": "PMID" }, { "text": "Liu M, Chang T, Zou D et al.. Effects and safety of Ophiocordyceps sinensis preparation in the adjuvant treatment for dialysis patients: A protocol for systematic review and meta-analysis. Medicine. 2022", "claim": "PubMed-indexed evidence involving Cordyceps", "title": "Effects and safety of Ophiocordyceps sinensis preparation in the adjuvant treatment for dialysis patients: A protocol for systematic review and meta-analysis", "authors": "Liu M, Chang T, Zou D et al.", "journal": "Medicine", "year": 2022, "pmid": "36401474", "url": "https://pubmed.ncbi.nlm.nih.gov/36401474/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MD.0000000000031476", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36401474/", "publicSourceType": "PMID" }, { "text": "Yu X, Mao Y, Shergis JL et al.. Effectiveness and Safety of Oral Cordyceps sinensis on Stable COPD of GOLD Stages 2-3: Systematic Review and Meta-Analysis. Evidence-based complementary and alternative medicine : eCAM. 2019", "claim": "PubMed-indexed evidence involving Cordyceps", "title": "Effectiveness and Safety of Oral Cordyceps sinensis on Stable COPD of GOLD Stages 2-3: Systematic Review and Meta-Analysis", "authors": "Yu X, Mao Y, Shergis JL et al.", "journal": "Evidence-based complementary and alternative medicine : eCAM", "year": 2019, "pmid": "31073318", "url": "https://pubmed.ncbi.nlm.nih.gov/31073318/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1155/2019/4903671", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31073318/", "publicSourceType": "PMID" }, { "text": "Yan G, Chang T, Zhao Y et al.. The effects of Ophiocordyceps sinensis combined with ACEI/ARB on diabetic kidney disease: A systematic review and meta-analysis. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2023", "claim": "PubMed-indexed evidence involving Cordyceps", "title": "The effects of Ophiocordyceps sinensis combined with ACEI/ARB on diabetic kidney disease: A systematic review and meta-analysis", "authors": "Yan G, Chang T, Zhao Y et al.", "journal": "Phytomedicine : international journal of phytotherapy and phytopharmacology", "year": 2023, "pmid": "36375237", "url": "https://pubmed.ncbi.nlm.nih.gov/36375237/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.phymed.2022.154531", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36375237/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "cordyceps" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567030", "name": "Reishi", "alternateNames": [ "Ganoderma Lucidum", "Lingzhi" ], "category": "Adaptogen", "subcategory": "Medicinal Mushroom", "overview": "The 'mushroom of immortality' in Traditional Chinese Medicine. Premier immune-modulating mushroom with calming, sleep-promoting properties. Ideal evening adaptogen.", "mechanismOfAction": "Triterpenes (ganoderic acids) inhibit histamine release and modulate inflammatory cytokines. Beta-glucans (polysaccharides) activate innate immune cells (macrophages, NK cells, dendritic cells) via Dectin-1 and TLR receptors. Triterpenes also inhibit 5-alpha reductase and support liver detoxification.", "commonBenefits": [ "Immune modulation", "Sleep quality", "Stress reduction", "Anti-inflammatory" ], "commonDosageRange": "1,000–3,000 mg daily (or 500mg concentrated extract)", "recommendedForm": "Dual extract (hot water + alcohol) capturing both polysaccharides and triterpenes", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Best taken in the evening for sleep support" }, "evidenceRating": "moderate", "foodSources": [ "Not palatable as food; too bitter and woody" ], "deficiencySymptoms": [ "Not applicable" ], "sideEffects": [ "Dizziness", "Dry mouth", "GI upset", "Hepatotoxicity (rare but potentially fatal; risk increases with alcohol use)" ], "contraindications": [ "Blood thinners", "Upcoming surgery", "Liver disease", "Autoimmune conditions" ], "iconName": "moon.stars.fill", "colorHex": "1B4332", "tags": [ "immune", "sleep", "mushroom", "longevity" ], "sources": [ { "claim": "Cochrane review of Ganoderma lucidum for cancer treatment", "title": "Ganoderma lucidum (Reishi mushroom) for cancer treatment", "authors": "Jin X et al.", "journal": "Cochrane Database Syst Rev", "year": 2012, "pmid": "22696372", "url": "https://pubmed.ncbi.nlm.nih.gov/22696372/", "study_type": "meta-analysis", "key_finding": "Insufficient evidence for first-line cancer treatment; patients given G. lucidum alongside chemo/radiotherapy more likely to respond positively; increases CD3, CD4, CD8 immune markers", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22696372/", "publicSourceType": "PMID" }, { "claim": "Reishi beta-glucan enhances immune cell populations in healthy adults", "title": "Evaluation of Immune Modulation by β-1,3; 1,6 D-Glucan Derived from Ganoderma lucidum in Healthy Adult Volunteers, A Randomized Controlled Trial", "authors": "Mallard B et al.", "journal": "Nutrients", "year": 2023, "pmid": "36766186", "url": "https://pubmed.ncbi.nlm.nih.gov/36766186/", "study_type": "RCT", "key_finding": "Reishi beta-glucan significantly enhanced CD3+, CD4+, CD8+ T-lymphocytes, improved CD4/CD8 ratio and natural killer cell counts", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36766186/", "publicSourceType": "PMID" }, { "claim": "Immunomodulating mechanisms of Ganoderma (Lingzhi)", "title": "Immunomodulating Effect of Ganoderma (Lingzhi) and Possible Mechanism", "authors": "Lin ZB, Wang PY", "journal": "Adv Exp Med Biol", "year": 2019, "pmid": "31777013", "url": "https://pubmed.ncbi.nlm.nih.gov/31777013/", "study_type": "review", "key_finding": "Ganoderma promotes innate immune function, humoral immunity, and cellular immunity affecting B/T lymphocytes, dendritic cells, macrophages, and NK cells", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31777013/", "publicSourceType": "PMID" }, { "claim": "Reishi promotes sleep through gut microbiota-serotonin pathway", "title": "Ganoderma lucidum promotes sleep through a gut microbiota-dependent and serotonin-involved pathway in mice", "authors": "Yao C et al.", "journal": "Sci Rep", "year": 2021, "pmid": "34211003", "url": "https://pubmed.ncbi.nlm.nih.gov/34211003/", "study_type": "review", "key_finding": "G. lucidum promoted sleep by shortening sleep latency and prolonging sleeping time via increased serotonin and sleep-regulating serotonergic synapse pathway", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34211003/", "publicSourceType": "PMID" }, { "claim": "Fatal fulminant hepatitis associated with Ganoderma lucidum powder", "title": "Fatal fulminant hepatitis associated with Ganoderma lucidum (Lingzhi) mushroom powder", "authors": "Yuen MF et al.", "journal": "J Hepatol", "year": 2007, "pmid": "17621752", "url": "https://pubmed.ncbi.nlm.nih.gov/17621752/", "study_type": "review", "key_finding": "Fatal fulminant hepatitis reported with Lingzhi powder; hepatotoxic risk needs close monitoring especially in combination with other drugs or alcohol", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17621752/", "publicSourceType": "PMID" }, { "claim": "Comprehensive safety review of Ganoderma lucidum spores", "title": "Pharmacological Activities and Safety of Ganoderma lucidum Spores: A Systematic Review", "authors": "Tong X et al.", "journal": "Nutrients", "year": 2023, "pmid": "37790044", "url": "https://pubmed.ncbi.nlm.nih.gov/37790044/", "study_type": "review", "key_finding": "Generally well tolerated with only scattered minor adverse events; no major toxicity observed across studies; rare hepatotoxicity cases reported", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37790044/", "publicSourceType": "PMID" }, { "text": "Cizmarikova M. The Efficacy and Toxicity of Using the Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), and Its Products in Chemotherapy (Review). International journal of medicinal mushrooms. 2017", "pmid": "29256841", "doi": "10.1615/IntJMedMushrooms.2017024537", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29256841/", "publicSourceType": "PMID" }, { "text": "Lu J, He R, Sun P et al.. Molecular mechanisms of bioactive polysaccharides from Ganoderma lucidum (Lingzhi), a review. International journal of biological macromolecules. 2020", "pmid": "32035956", "doi": "10.1016/j.ijbiomac.2020.02.035", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32035956/", "publicSourceType": "PMID" }, { "claim": "Reishi (Ganoderma lucidum) improves lipid profiles", "title": "Effect of Ganoderma lucidum on serum lipid profiles: A systematic review and meta-analysis on animal studies.", "authors": "Aref M, Khoshhali M, Ghasemi P, Adeli S, Heidari-Beni M, Kelishadi R", "journal": "Journal of Research in Medical Sciences", "year": 2023, "pmid": "38116485", "url": "https://pubmed.ncbi.nlm.nih.gov/38116485/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 49 animal studies showed G. lucidum consumption significantly decreased TG (SMD=-1.52), TC (SMD=-1.51), LDL-C (SMD=-2.03), VLDL (SMD=-1.06), and increased HDL-C (SMD=1.03).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38116485/", "publicSourceType": "PMID" }, { "claim": "Reishi has radioprotective properties", "title": "Use of Ganoderma lucidum (Ganodermataceae, Basidiomycota) as Radioprotector.", "authors": "Gonzalez A, Atienza V, Montoro A, Soriano JM", "journal": "Nutrients", "year": 2020, "pmid": "32325828", "url": "https://pubmed.ncbi.nlm.nih.gov/32325828/", "study_type": "review", "key_finding": "Systematic review of 15 studies found aqueous extracts of polysaccharides and triterpenes from G. lucidum were effective in protecting against radiation damage in vivo in mice and in vitro, suggesting potential as a radioprotective agent.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32325828/", "publicSourceType": "PMID" }, { "text": "Zhong L, Yan P, Lam WC et al.. Coriolus Versicolor and Ganoderma Lucidum Related Natural Products as an Adjunct Therapy for Cancers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Frontiers in pharmacology. 2019", "claim": "PubMed-indexed evidence involving Reishi", "title": "Coriolus Versicolor and Ganoderma Lucidum Related Natural Products as an Adjunct Therapy for Cancers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Zhong L, Yan P, Lam WC et al.", "journal": "Frontiers in pharmacology", "year": 2019, "pmid": "31333449", "url": "https://pubmed.ncbi.nlm.nih.gov/31333449/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fphar.2019.00703", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31333449/", "publicSourceType": "PMID" }, { "text": "Jafari A, Mardani H, Mirzaei Fashtali Z et al.. The Nutritional Significance of Ganoderma lucidum on Human Health: A GRADE-Assessed Systematic Review and Meta-Analysis of Clinical Trials. Food science & nutrition. 2025", "claim": "PubMed-indexed evidence involving Reishi", "title": "The Nutritional Significance of Ganoderma lucidum on Human Health: A GRADE-Assessed Systematic Review and Meta-Analysis of Clinical Trials", "authors": "Jafari A, Mardani H, Mirzaei Fashtali Z et al.", "journal": "Food science & nutrition", "year": 2025, "pmid": "40510787", "url": "https://pubmed.ncbi.nlm.nih.gov/40510787/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/fsn3.70423", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40510787/", "publicSourceType": "PMID" }, { "text": "Shaher F, Qiu H, Wang S et al.. Associated Targets of the Antioxidant Cardioprotection of Ganoderma lucidum in Diabetic Cardiomyopathy by Using Open Targets Platform: A Systematic Review. BioMed research international. 2020", "claim": "PubMed-indexed evidence involving Reishi", "title": "Associated Targets of the Antioxidant Cardioprotection of Ganoderma lucidum in Diabetic Cardiomyopathy by Using Open Targets Platform: A Systematic Review", "authors": "Shaher F, Qiu H, Wang S et al.", "journal": "BioMed research international", "year": 2020, "pmid": "32775437", "url": "https://pubmed.ncbi.nlm.nih.gov/32775437/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1155/2020/7136075", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32775437/", "publicSourceType": "PMID" }, { "text": "Liu J, Mao JJ, Li SQ et al.. Preliminary Efficacy and Safety of Reishi & Privet Formula on Quality of Life Among Non-Small Cell Lung Cancer Patients Undergoing Chemotherapy: A Randomized Placebo-Controlled Trial. Integrative cancer therapies. 2020", "claim": "PubMed-indexed evidence involving Reishi", "title": "Preliminary Efficacy and Safety of Reishi & Privet Formula on Quality of Life Among Non-Small Cell Lung Cancer Patients Undergoing Chemotherapy: A Randomized Placebo-Controlled Trial", "authors": "Liu J, Mao JJ, Li SQ et al.", "journal": "Integrative cancer therapies", "year": 2020, "pmid": "32840126", "url": "https://pubmed.ncbi.nlm.nih.gov/32840126/", "study_type": "RCT", "confidence": "verify", "doi": "10.1177/1534735420944491", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32840126/", "publicSourceType": "PMID" }, { "text": "Wicks SM, Tong R, Wang CZ et al.. Safety and tolerability of Ganoderma lucidum in healthy subjects: a double-blind randomized placebo-controlled trial. The American journal of Chinese medicine. 2007", "claim": "PubMed-indexed evidence involving Reishi", "title": "Safety and tolerability of Ganoderma lucidum in healthy subjects: a double-blind randomized placebo-controlled trial", "authors": "Wicks SM, Tong R, Wang CZ et al.", "journal": "The American journal of Chinese medicine", "year": 2007, "pmid": "17597499", "url": "https://pubmed.ncbi.nlm.nih.gov/17597499/", "study_type": "RCT", "confidence": "verify", "doi": "10.1142/S0192415X07004928", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17597499/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "reishi" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567031", "name": "L-Theanine", "alternateNames": [ "Suntheanine" ], "category": "Amino Acid", "subcategory": "Non-Essential Amino Acid", "overview": "Unique amino acid found primarily in green tea. Promotes calm alertness without drowsiness. Synergizes exceptionally well with caffeine for focused energy.", "mechanismOfAction": "Crosses the blood-brain barrier and increases alpha brain wave activity (associated with relaxed focus). Modulates GABA, serotonin, and dopamine levels. Weakly binds AMPA/kainate glutamate receptors (80- to 30,000-fold less affinity than glutamate). Enhances BDNF production.", "commonBenefits": [ "Calm focus", "Stress-response support", "Sleep-quality research", "Caffeine synergy" ], "commonDosageRange": "100–400 mg daily", "recommendedForm": "L-theanine (Suntheanine is a patented pure form)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Stack with caffeine (2:1 theanine:caffeine) for ideal focused energy; can take any time" }, "evidenceRating": "moderate", "foodSources": [ "Green tea", "Black tea", "White tea" ], "deficiencySymptoms": [ "Not applicable" ], "sideEffects": [ "Very well tolerated", "Mild headache (rare)", "Drowsiness at high doses" ], "contraindications": [ "Blood pressure medications (may lower BP further)" ], "iconName": "cup.and.saucer.fill", "colorHex": "7B2CBF", "tags": [ "focus", "calm", "nootropic", "sleep" ], "sources": [ { "claim": "L-theanine has been studied for stress-related symptoms in exposed populations", "title": "The Effects of Green Tea Amino Acid L-Theanine Consumption on the Ability to Manage Stress and Anxiety Levels: a Systematic Review", "authors": "Everett JM et al.", "journal": "Plant Foods Hum Nutr", "year": 2020, "pmid": "31758301", "url": "https://pubmed.ncbi.nlm.nih.gov/31758301/", "study_type": "review", "key_finding": "Review suggests 200-400 mg/day L-theanine may support stress-related symptoms in people exposed to stressful conditions; this should not be framed as anxiety treatment.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31758301/", "publicSourceType": "PMID" }, { "claim": "L-theanine increases alpha brain waves associated with relaxed focus", "title": "L-theanine, a natural constituent in tea, and its effect on mental state", "authors": "Nobre AC et al.", "journal": "Asia Pac J Clin Nutr", "year": 2008, "pmid": "18296328", "url": "https://pubmed.ncbi.nlm.nih.gov/18296328/", "study_type": "review", "key_finding": "L-theanine increases alpha brain wave activity associated with relaxed alertness without drowsiness", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18296328/", "publicSourceType": "PMID" }, { "claim": "L-theanine and caffeine combination improves cognitive performance synergistically", "title": "The combination of L-theanine and caffeine improves cognitive performance and increases subjective alertness", "authors": "Owen GN et al.", "journal": "Nutr Neurosci", "year": 2010, "pmid": "21040626", "url": "https://pubmed.ncbi.nlm.nih.gov/21040626/", "study_type": "RCT", "key_finding": "97 mg L-theanine + 40 mg caffeine significantly improved task-switching accuracy and self-reported alertness while reducing tiredness", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21040626/", "publicSourceType": "PMID" }, { "claim": "L-theanine supports healthy sleep through anxiolysis rather than sedation", "title": "Examining the effect of L-theanine on sleep: a systematic review of dietary supplementation trials", "authors": "Williams JL et al.", "journal": "J Am Nutr Assoc", "year": 2025, "pmid": "41176609", "url": "https://pubmed.ncbi.nlm.nih.gov/41176609/", "study_type": "review", "key_finding": "200-450 mg/day of L-theanine is safe and effective for supporting healthy sleep through anxiolysis rather than sedation", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41176609/", "publicSourceType": "PMID" }, { "claim": "GABA and L-theanine combination has synergistic effect on sleep", "title": "GABA and l-theanine mixture decreases sleep latency and improves NREM sleep", "authors": "Kim S et al.", "journal": "Pharm Biol", "year": 2019, "pmid": "30707852", "url": "https://pubmed.ncbi.nlm.nih.gov/30707852/", "study_type": "RCT", "key_finding": "GABA/L-theanine mixture has positive synergistic effect on sleep quality and duration vs either component alone", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30707852/", "publicSourceType": "PMID" }, { "claim": "L-theanine neuropharmacology: modulates GABA, serotonin, dopamine", "title": "The neuropharmacology of L-theanine(N-ethyl-L-glutamine): a possible neuroprotective and cognitive enhancing agent", "authors": "Nathan PJ et al.", "journal": "J Herb Pharmacother", "year": 2006, "pmid": "17182482", "url": "https://pubmed.ncbi.nlm.nih.gov/17182482/", "study_type": "review", "key_finding": "L-theanine increases brain serotonin, dopamine, GABA levels and has micromolar affinities for AMPA, Kainate and NMDA receptors", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17182482/", "publicSourceType": "PMID" }, { "claim": "Meta-analysis of tea constituents L-theanine and caffeine on cognition and mood", "title": "Acute effects of tea constituents L-theanine, caffeine, and epigallocatechin gallate on cognitive function and mood: a systematic review and meta-analysis", "authors": "Camfield DA et al.", "journal": "Nutr Rev", "year": 2014, "pmid": "24946991", "url": "https://pubmed.ncbi.nlm.nih.gov/24946991/", "study_type": "meta-analysis", "key_finding": "Moderate effect sizes for combined caffeine and L-theanine on alertness, attentional switching accuracy in first 2 hours post-dose", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24946991/", "publicSourceType": "PMID" }, { "text": "Bulman A, D'Cunha NM, Marx W et al.. The effects of L-theanine consumption on sleep outcomes: A systematic review and meta-analysis. Sleep medicine reviews. 2025", "pmid": "40056718", "doi": "10.1016/j.smrv.2025.102076", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40056718/", "publicSourceType": "PMID" }, { "text": "Moshfeghinia R, Sanaei E, Mostafavi S et al.. The effects of L-theanine supplementation on the outcomes of patients with mental disorders: a systematic review. BMC psychiatry. 2024", "pmid": "39633316", "doi": "10.1186/s12888-024-06285-y", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39633316/", "publicSourceType": "PMID" }, { "claim": "L-Theanine improves cognition, sleep, and mood", "title": "Effects of Tea (Camellia sinensis) or its Bioactive Compounds l-Theanine or l-Theanine plus Caffeine on Cognition, Sleep, and Mood in Healthy Participants: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.", "authors": "Payne ER, Aceves-Martins M, Dubost J et al.", "journal": "Nutrition Reviews", "year": 2025, "pmid": "40314930", "url": "https://pubmed.ncbi.nlm.nih.gov/40314930/", "study_type": "meta-analysis", "key_finding": "L-theanine improved attention and reaction time, particularly when combined with caffeine. L-theanine alone showed benefits for sleep quality.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40314930/", "publicSourceType": "PMID" }, { "claim": "L-Theanine has anxiolytic effects as a medicinal herb", "title": "Medicinal herbs for the treatment of anxiety: A systematic review and network meta-analysis.", "authors": "Zhang W, Yan Y, Wu Y et al.", "journal": "Pharmacological Research", "year": 2022, "pmid": "35378276", "url": "https://pubmed.ncbi.nlm.nih.gov/35378276/", "study_type": "meta-analysis", "key_finding": "L-theanine was among the medicinal herbs showing significant anxiolytic effects in a network meta-analysis of randomized controlled trials.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35378276/", "publicSourceType": "PMID" }, { "text": "Moulin M, Crowley DC, Xiong L et al.. Safety and Efficacy of AlphaWave(®) L-Theanine Supplementation for 28 Days in Healthy Adults with Moderate Stress: A Randomized, Double-Blind, Placebo-Controlled Trial. Neurology and therapy. 2024", "claim": "PubMed-indexed evidence involving L-Theanine", "title": "Safety and Efficacy of AlphaWave(®) L-Theanine Supplementation for 28 Days in Healthy Adults with Moderate Stress: A Randomized, Double-Blind, Placebo-Controlled Trial", "authors": "Moulin M, Crowley DC, Xiong L et al.", "journal": "Neurology and therapy", "year": 2024, "pmid": "38758503", "url": "https://pubmed.ncbi.nlm.nih.gov/38758503/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/s40120-024-00624-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38758503/", "publicSourceType": "PMID" }, { "text": "Deshpande SS, Kurdi M, Baiju A et al.. Comparison of the effects of two amino acids, Gamma-aminobutyric acid (GABA) and L-theanine, on sedation, anxiety, and cognition in preoperative surgical patients - A randomized controlled study. Journal of anaesthesiology, clinical pharmacology. 2025", "claim": "PubMed-indexed evidence involving L-Theanine", "title": "Comparison of the effects of two amino acids, Gamma-aminobutyric acid (GABA) and L-theanine, on sedation, anxiety, and cognition in preoperative surgical patients - A randomized controlled study", "authors": "Deshpande SS, Kurdi M, Baiju A et al.", "journal": "Journal of anaesthesiology, clinical pharmacology", "year": 2025, "pmid": "40026748", "url": "https://pubmed.ncbi.nlm.nih.gov/40026748/", "study_type": "RCT", "confidence": "verify", "doi": "10.4103/joacp.joacp_417_23", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40026748/", "publicSourceType": "PMID" }, { "text": "Kurdi MS, As A, Ladhad DA et al.. Comparison Between Efficacy of Oral Melatonin and Oral L-theanine in Improving Sleep in Cancer Patients Suffering From Insomnia: A Randomised Double-blinded Placebo-controlled Study. Indian journal of palliative care. 2024", "claim": "PubMed-indexed evidence involving L-Theanine", "title": "Comparison Between Efficacy of Oral Melatonin and Oral L-theanine in Improving Sleep in Cancer Patients Suffering From Insomnia: A Randomised Double-blinded Placebo-controlled Study", "authors": "Kurdi MS, As A, Ladhad DA et al.", "journal": "Indian journal of palliative care", "year": 2024, "pmid": "38846134", "url": "https://pubmed.ncbi.nlm.nih.gov/38846134/", "study_type": "RCT", "confidence": "verify", "doi": "10.25259/IJPC_89_2023", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38846134/", "publicSourceType": "PMID" }, { "text": "Lim SE, Kim HS, Lee S et al.. Dietary supplementation with Lactium and L-theanine alleviates sleep disturbance in adults: a double-blind, randomized, placebo-controlled clinical study. Frontiers in nutrition. 2024", "claim": "PubMed-indexed evidence involving L-Theanine", "title": "Dietary supplementation with Lactium and L-theanine alleviates sleep disturbance in adults: a double-blind, randomized, placebo-controlled clinical study", "authors": "Lim SE, Kim HS, Lee S et al.", "journal": "Frontiers in nutrition", "year": 2024, "pmid": "38953043", "url": "https://pubmed.ncbi.nlm.nih.gov/38953043/", "study_type": "RCT", "confidence": "verify", "doi": "10.3389/fnut.2024.1419978", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38953043/", "publicSourceType": "PMID" }, { "text": "Shamabadi A, Kafi F, Arab Bafrani M et al.. l-theanine adjunct to sertraline for major depressive disorder: A randomized, double-blind, placebo-controlled clinical trial. Journal of affective disorders. 2023", "claim": "PubMed-indexed evidence involving L-Theanine", "title": "l-theanine adjunct to sertraline for major depressive disorder: A randomized, double-blind, placebo-controlled clinical trial", "authors": "Shamabadi A, Kafi F, Arab Bafrani M et al.", "journal": "Journal of affective disorders", "year": 2023, "pmid": "37084960", "url": "https://pubmed.ncbi.nlm.nih.gov/37084960/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.jad.2023.04.029", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37084960/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "l-theanine" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567032", "name": "L-Tyrosine", "alternateNames": [ "N-Acetyl L-Tyrosine", "NALT" ], "category": "Amino Acid", "subcategory": "Non-Essential Amino Acid", "overview": "Precursor to dopamine, norepinephrine, and epinephrine. Excellent for maintaining cognitive performance under stress, sleep deprivation, or multi-tasking demands.", "mechanismOfAction": "Hydroxylated by tyrosine hydroxylase (rate-limiting step) to L-DOPA, then converted to dopamine by aromatic L-amino acid decarboxylase. Dopamine is further converted to norepinephrine and epinephrine. Replenishes catecholamine stores depleted by stress.", "commonBenefits": [ "Focus under stress", "Dopamine support", "Cognitive resilience", "Mood support", "Thyroid hormone synthesis" ], "commonDosageRange": "500–2,000 mg daily", "recommendedForm": "L-tyrosine (better absorbed than NALT)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Take on empty stomach 30 min before meals for best brain uptake; competes with other amino acids" }, "evidenceRating": "moderate", "foodSources": [ "Cheese", "Chicken", "Turkey", "Fish", "Almonds" ], "deficiencySymptoms": [ "Not essential, but low intake may impair stress resilience" ], "sideEffects": [ "Headache", "Nausea", "Heartburn", "Insomnia if taken late" ], "contraindications": [ "MAO inhibitors", "Hyperthyroidism", "Melanoma" ], "iconName": "bolt.circle", "colorHex": "9D4EDD", "tags": [ "focus", "dopamine", "stress", "nootropic" ], "sources": [ { "claim": "Tyrosine supplementation counteracts cognitive decrements under stress", "title": "Effect of tyrosine supplementation on clinical and healthy populations under stress or cognitive demands--A review", "authors": "Jongkees BJ et al.", "journal": "J Psychiatr Res", "year": 2015, "pmid": "26424423", "url": "https://pubmed.ncbi.nlm.nih.gov/26424423/", "study_type": "review", "key_finding": "Tyrosine acutely counteracts decrements in working memory and information processing induced by demanding conditions like extreme weather or cognitive load", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26424423/", "publicSourceType": "PMID" }, { "claim": "Tyrosine for mitigating stress and enhancing performance (rapid evidence assessment)", "title": "Tyrosine for Mitigating Stress and Enhancing Performance in Healthy Adult Humans, a Rapid Evidence Assessment of the Literature", "authors": "Attipoe S et al.", "journal": "J Mil Med", "year": 2015, "pmid": "26126245", "url": "https://pubmed.ncbi.nlm.nih.gov/26126245/", "study_type": "review", "key_finding": "Weak recommendation in favor of tyrosine for cognitive stress; all 10 RCTs and 4 controlled trials showed positive effect on cognition under stress", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26126245/", "publicSourceType": "PMID" }, { "claim": "Tyrosine reverses cold-induced working memory deficit", "title": "Tyrosine reverses a cold-induced working memory deficit in humans", "authors": "Shurtleff D et al.", "journal": "Pharmacol Biochem Behav", "year": 1994, "pmid": "8029265", "url": "https://pubmed.ncbi.nlm.nih.gov/8029265/", "study_type": "RCT", "key_finding": "Tyrosine significantly improved matching accuracy at the longest delay interval most affected by cold exposure", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8029265/", "publicSourceType": "PMID" }, { "claim": "Tyrosine, phenylalanine, and catecholamine synthesis and brain function", "title": "Tyrosine, phenylalanine, and catecholamine synthesis and function in the brain", "authors": "Fernstrom JD, Fernstrom MH", "journal": "J Nutr", "year": 2007, "pmid": "17513421", "url": "https://pubmed.ncbi.nlm.nih.gov/17513421/", "study_type": "review", "key_finding": "Tyrosine hydroxylase is the rate-limiting enzyme converting tyrosine to L-DOPA, then to dopamine, norepinephrine, and epinephrine", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17513421/", "publicSourceType": "PMID" }, { "claim": "L-tyrosine is safe for human use as adjuvant", "title": "Review of L-tyrosine confirming its safe human use as an adjuvant", "authors": "Hoffer LJ", "journal": "J Food Biochem", "year": 2002, "pmid": "12355563", "url": "https://pubmed.ncbi.nlm.nih.gov/12355563/", "study_type": "review", "key_finding": "L-tyrosine appears safe with no signs of toxicity or genotoxicity in preclinical studies; well tolerated in clinical trials", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12355563/", "publicSourceType": "PMID" }, { "claim": "Tyrosine improves cognitive performance and reduces blood pressure under military stress", "title": "Tyrosine improves cognitive performance and reduces blood pressure in cadets after one week of a combat training course", "authors": "Deijen JB et al.", "journal": "Brain Res Bull", "year": 1999, "pmid": "10230711", "url": "https://pubmed.ncbi.nlm.nih.gov/10230711/", "study_type": "RCT", "key_finding": "Tyrosine supplementation improved cognitive task performance and reduced blood pressure in military cadets after demanding combat training", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10230711/", "publicSourceType": "PMID" }, { "text": "McAllister MJ, Martaindale MH, Dillard CC et al.. Impact of L-theanine and L-tyrosine on markers of stress and cognitive performance in response to a virtual reality based active shooter training drill. Stress (Amsterdam, Netherlands). 2024", "pmid": "38975711", "doi": "10.1080/10253890.2024.2375588", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38975711/", "publicSourceType": "PMID" }, { "text": "Blachier F, Andriamihaja M. Effects of the L-tyrosine-derived bacterial metabolite p-cresol on colonic and peripheral cells. Amino acids. 2022", "pmid": "34468872", "doi": "10.1007/s00726-021-03064-x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34468872/", "publicSourceType": "PMID" }, { "text": "Solon-Júnior LJF, Boullosa Alvarez DA, Martinez Gonzalez B et al.. The effect of tyrosine supplementation on whole-body endurance performance in physically active population: A systematic review and meta-analysis including GRADE qualification. Journal of sports sciences. 2023", "claim": "PubMed-indexed evidence involving L-Tyrosine", "title": "The effect of tyrosine supplementation on whole-body endurance performance in physically active population: A systematic review and meta-analysis including GRADE qualification", "authors": "Solon-Júnior LJF, Boullosa Alvarez DA, Martinez Gonzalez B et al.", "journal": "Journal of sports sciences", "year": 2023, "pmid": "38290812", "url": "https://pubmed.ncbi.nlm.nih.gov/38290812/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/02640414.2024.2309434", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38290812/", "publicSourceType": "PMID" }, { "text": "Stock AK, Colzato L, Beste C. On the effects of tyrosine supplementation on interference control in a randomized, double-blind placebo-control trial. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 2018", "claim": "PubMed-indexed evidence involving L-Tyrosine", "title": "On the effects of tyrosine supplementation on interference control in a randomized, double-blind placebo-control trial", "authors": "Stock AK, Colzato L, Beste C", "journal": "European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology", "year": 2018, "pmid": "29980424", "url": "https://pubmed.ncbi.nlm.nih.gov/29980424/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.euroneuro.2018.05.010", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29980424/", "publicSourceType": "PMID" }, { "text": "Colzato LS, Steenbergen L, Sellaro R et al.. Effects of l-Tyrosine on working memory and inhibitory control are determined by DRD2 genotypes: A randomized controlled trial. Cortex; a journal devoted to the study of the nervous system and behavior. 2016", "claim": "PubMed-indexed evidence involving L-Tyrosine", "title": "Effects of l-Tyrosine on working memory and inhibitory control are determined by DRD2 genotypes: A randomized controlled trial", "authors": "Colzato LS, Steenbergen L, Sellaro R et al.", "journal": "Cortex; a journal devoted to the study of the nervous system and behavior", "year": 2016, "pmid": "27403851", "url": "https://pubmed.ncbi.nlm.nih.gov/27403851/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.cortex.2016.06.010", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27403851/", "publicSourceType": "PMID" }, { "text": "Elwes RD, Crewes H, Chesterman LP et al.. Treatment of narcolepsy with L-tyrosine: double-blind placebo-controlled trial. Lancet (London, England). 1989", "claim": "PubMed-indexed evidence involving L-Tyrosine", "title": "Treatment of narcolepsy with L-tyrosine: double-blind placebo-controlled trial", "authors": "Elwes RD, Crewes H, Chesterman LP et al.", "journal": "Lancet (London, England)", "year": 1989, "pmid": "2572797", "url": "https://pubmed.ncbi.nlm.nih.gov/2572797/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/s0140-6736(89)91081-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2572797/", "publicSourceType": "PMID" }, { "text": "Ferrera G, Segre G, Lamantea E et al.. Amino acid supplementation in mitochondrial aminoacyl-tRNA synthetase defects: two case reports of tyrosine supplementation in YARS2-associated disease and a review of the literature. Frontiers in pediatrics. 2025", "claim": "PubMed-indexed evidence involving L-Tyrosine", "title": "Amino acid supplementation in mitochondrial aminoacyl-tRNA synthetase defects: two case reports of tyrosine supplementation in YARS2-associated disease and a review of the literature", "authors": "Ferrera G, Segre G, Lamantea E et al.", "journal": "Frontiers in pediatrics", "year": 2025, "pmid": "41404429", "url": "https://pubmed.ncbi.nlm.nih.gov/41404429/", "study_type": "review", "confidence": "verify", "doi": "10.3389/fped.2025.1699348", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41404429/", "publicSourceType": "PMID" }, { "text": "Wang Y, Wu P, Lin R et al.. LncRNA NALT interaction with NOTCH1 promoted cell proliferation in pediatric T cell acute lymphoblastic leukemia. Scientific reports. 2015", "claim": "PubMed-indexed evidence involving L-Tyrosine", "title": "LncRNA NALT interaction with NOTCH1 promoted cell proliferation in pediatric T cell acute lymphoblastic leukemia", "authors": "Wang Y, Wu P, Lin R et al.", "journal": "Scientific reports", "year": 2015, "pmid": "26330272", "url": "https://pubmed.ncbi.nlm.nih.gov/26330272/", "study_type": "review", "confidence": "verify", "doi": "10.1038/srep13749", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26330272/", "publicSourceType": "PMID" }, { "text": "Grosu AL, Weber WA, Graf E et al.. O-(2-[(18)F]fluoroethyl)-L-tyrosine-PET-guided versus contrast-enhanced T1-weighted MRI-guided re-irradiation in patients with recurrent glioblastoma (GLIAA/NOA-10 ARO2013-01): a multicentre, open-label, randomised trial. The Lancet. Oncology. 2026", "claim": "PubMed-indexed evidence involving L-Tyrosine", "title": "O-(2-[(18)F]fluoroethyl)-L-tyrosine-PET-guided versus contrast-enhanced T1-weighted MRI-guided re-irradiation in patients with recurrent glioblastoma (GLIAA/NOA-10 ARO2013-01): a multicentre, open-label, randomised trial", "authors": "Grosu AL, Weber WA, Graf E et al.", "journal": "The Lancet. Oncology", "year": 2026, "pmid": "41429128", "url": "https://pubmed.ncbi.nlm.nih.gov/41429128/", "study_type": "review", "confidence": "verify", "doi": "10.1016/S1470-2045(25)00642-4", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41429128/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "l-tyrosine" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567033", "name": "NAC", "alternateNames": [ "N-Acetyl Cysteine", "N-Acetylcysteine" ], "category": "Amino Acid", "subcategory": "Modified Amino Acid", "overview": "The most effective oral precursor to glutathione, the body's master antioxidant. Powerful liver protectant, mucolytic, and mental health support compound.", "mechanismOfAction": "Deacetylated to L-cysteine, the rate-limiting amino acid for glutathione (GSH) synthesis. GSH neutralizes reactive oxygen species, detoxifies xenobiotics via glutathione S-transferases, and modulates immune function. Also modulates glutamate via the cystine-glutamate antiporter (relevant to OCD, addiction).", "commonBenefits": [ "Glutathione production", "Liver protection", "Detoxification", "Respiratory health", "Mental health support" ], "commonDosageRange": "600–1,800 mg daily", "recommendedForm": "NAC (standard form; take on empty stomach)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Take on empty stomach for best absorption; pair with vitamin C to prevent oxidation" }, "evidenceRating": "strong", "foodSources": [ "Not found directly; cysteine in chicken, turkey, eggs, garlic, onions" ], "deficiencySymptoms": [ "Low glutathione levels", "Poor detoxification", "Oxidative stress" ], "sideEffects": [ "GI upset", "Nausea", "Rare: may thin mucus excessively" ], "contraindications": [ "Asthma (may worsen in some)", "Blood thinners", "Nitroglycerin" ], "iconName": "shield.lefthalf.filled", "colorHex": "B5179E", "tags": [ "detox", "liver", "antioxidant", "mental-health" ], "sources": [ { "claim": "Comprehensive clinical review of NAC uses including glutathione precursor, mucolytic, and hepatoprotective roles", "title": "N-Acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks)", "authors": "Tenório MCDS et al.", "journal": "J Amino Acids", "year": 2021, "pmid": "34221501", "url": "https://pubmed.ncbi.nlm.nih.gov/34221501/", "study_type": "review", "key_finding": "Comprehensive review of NAC's clinical applications including antioxidant therapy, mucolytic activity, and hepatoprotection.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34221501/", "publicSourceType": "PMID" }, { "claim": "NAC efficacy in psychiatric disorders including depression and OCD", "title": "N-acetylcysteine for major mental disorders: a systematic review and meta-analysis of randomized controlled trials", "authors": "Deepmala et al.", "journal": "J Clin Psychiatry", "year": 2018, "pmid": "29457216", "url": "https://pubmed.ncbi.nlm.nih.gov/29457216/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of RCTs showing NAC has potential benefits for multiple psychiatric disorders via glutamate modulation and antioxidant mechanisms.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29457216/", "publicSourceType": "PMID" }, { "claim": "NAC for non-acetaminophen acute liver failure demonstrating hepatoprotective effects", "title": "Efficacy and safety of acetylcysteine in 'non-acetaminophen' acute liver failure: A meta-analysis of prospective clinical trials", "authors": "Hu J et al.", "journal": "Clin Res Hepatol Gastroenterol", "year": 2015, "pmid": "25732608", "url": "https://pubmed.ncbi.nlm.nih.gov/25732608/", "study_type": "meta-analysis", "key_finding": "NAC improved transplant-free survival in non-acetaminophen acute liver failure and was safe and well tolerated.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25732608/", "publicSourceType": "PMID" }, { "claim": "NAC as mucolytic and antioxidant in COPD reducing exacerbations", "title": "N-acetylcysteine Treatment in Chronic Obstructive Pulmonary Disease (COPD) and Chronic Bronchitis/Pre-COPD: Distinct Meta-analyses", "authors": "Calzetta L et al.", "journal": "Pulm Pharmacol Ther", "year": 2024, "pmid": "38555190", "url": "https://pubmed.ncbi.nlm.nih.gov/38555190/", "study_type": "meta-analysis", "key_finding": "NAC-treated patients showed significant reduction of exacerbation incidence compared to placebo in both COPD and chronic bronchitis.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38555190/", "publicSourceType": "PMID" }, { "claim": "Therapeutic role of NAC in disorders characterized by oxidative stress", "title": "The Multifaceted Therapeutic Role of N-Acetylcysteine (NAC) in Disorders Characterized by Oxidative Stress", "authors": "Tenório MCDS et al.", "journal": "Curr Neuropharmacol", "year": 2021, "pmid": "33380301", "url": "https://pubmed.ncbi.nlm.nih.gov/33380301/", "study_type": "review", "key_finding": "NAC replenishes glutathione in deficient cells and modulates glutamatergic, neurotrophin, and inflammatory pathways across multiple disease states.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33380301/", "publicSourceType": "PMID" }, { "claim": "NAC conversion to glutathione and antioxidant pharmacology", "title": "Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits", "authors": "Rushworth GF et al.", "journal": "Pharmacol Ther", "year": 2014, "pmid": "24080471", "url": "https://pubmed.ncbi.nlm.nih.gov/24080471/", "study_type": "review", "key_finding": "NAC should not be considered a powerful antioxidant in its own right; its strength is the targeted replenishment of glutathione in deficient cells.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24080471/", "publicSourceType": "PMID" }, { "text": "Lee TM, Lee KM, Lee CY et al.. Effectiveness of N-acetylcysteine in autism spectrum disorders: A meta-analysis of randomized controlled trials. The Australian and New Zealand journal of psychiatry. 2021", "pmid": "32900213", "doi": "10.1177/0004867420952540", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32900213/", "publicSourceType": "PMID" }, { "text": "Sharma R, Tikka SK, Bhute AR et al.. N-acetyl cysteine in the treatment of cannabis use disorder: A systematic review of clinical trials. Addictive behaviors. 2022", "pmid": "35189496", "doi": "10.1016/j.addbeh.2022.107283", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35189496/", "publicSourceType": "PMID" }, { "claim": "NAC reduces substance use cravings", "title": "N-acetylcysteine as a treatment for substance use cravings: A meta-analysis", "authors": "Winterlind EL, Malone SG, Setzer MR et al.", "journal": "Addiction Biology", "year": 2024, "pmid": "39556483", "url": "https://pubmed.ncbi.nlm.nih.gov/39556483/", "study_type": "meta-analysis", "key_finding": "N-acetylcysteine significantly reduced cravings across multiple substance use disorders, with the most consistent effects observed for cocaine and nicotine dependence.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39556483/", "publicSourceType": "PMID" }, { "claim": "NAC benefits liver function in acute liver failure", "title": "N-acetylcysteine in non-acetaminophen-induced acute liver failure: a systematic review and meta-analysis of prospective studies", "authors": "Amjad W, Thuluvath P, Mansoor M et al.", "journal": "Przeglad Gastroenterologiczny", "year": 2022, "pmid": "35371352", "url": "https://pubmed.ncbi.nlm.nih.gov/35371352/", "study_type": "meta-analysis", "key_finding": "N-acetylcysteine improved transplant-free survival in patients with non-acetaminophen-induced acute liver failure, supporting its use beyond acetaminophen overdose.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35371352/", "publicSourceType": "PMID" }, { "text": "He T, Ren K, Xiang L et al.. Efficacy of N-Acetylcysteine as an Adjuvant Therapy for Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. British journal of hospital medicine (London, England : 2005). 2024", "claim": "PubMed-indexed evidence involving NAC", "title": "Efficacy of N-Acetylcysteine as an Adjuvant Therapy for Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "He T, Ren K, Xiang L et al.", "journal": "British journal of hospital medicine (London, England : 2005)", "year": 2024, "pmid": "39618229", "url": "https://pubmed.ncbi.nlm.nih.gov/39618229/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.12968/hmed.2024.0560", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39618229/", "publicSourceType": "PMID" }, { "text": "Ma X, Yang Y, Liu S et al.. Meta-analysis of the efficacy and safety of L-carnitine and N-acetylcysteine monotherapy for male idiopathic infertility. Revista internacional de andrologia. 2025", "claim": "PubMed-indexed evidence involving NAC", "title": "Meta-analysis of the efficacy and safety of L-carnitine and N-acetylcysteine monotherapy for male idiopathic infertility", "authors": "Ma X, Yang Y, Liu S et al.", "journal": "Revista internacional de andrologia", "year": 2025, "pmid": "40350672", "url": "https://pubmed.ncbi.nlm.nih.gov/40350672/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.22514/j.androl.2025.004", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40350672/", "publicSourceType": "PMID" }, { "text": "Nakatsu L, Lopez JR, Garcia CM et al.. Comparison of two-bag and three-bag acetylcysteine regimens in the treatment of paracetamol poisoning: a systematic review and meta-analysis. Clinical toxicology (Philadelphia, Pa.). 2025", "claim": "PubMed-indexed evidence involving NAC", "title": "Comparison of two-bag and three-bag acetylcysteine regimens in the treatment of paracetamol poisoning: a systematic review and meta-analysis", "authors": "Nakatsu L, Lopez JR, Garcia CM et al.", "journal": "Clinical toxicology (Philadelphia, Pa.)", "year": 2025, "pmid": "40013897", "url": "https://pubmed.ncbi.nlm.nih.gov/40013897/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/15563650.2025.2456116", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40013897/", "publicSourceType": "PMID" }, { "text": "Koh A, Wong T, Adiamah A et al.. Systematic review and meta-analysis of the effect of N-acetylcysteine on outcomes after liver resection. ANZ journal of surgery. 2024", "claim": "PubMed-indexed evidence involving NAC", "title": "Systematic review and meta-analysis of the effect of N-acetylcysteine on outcomes after liver resection", "authors": "Koh A, Wong T, Adiamah A et al.", "journal": "ANZ journal of surgery", "year": 2024, "pmid": "39101362", "url": "https://pubmed.ncbi.nlm.nih.gov/39101362/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/ans.19183", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39101362/", "publicSourceType": "PMID" }, { "text": "Sadowski M, Zawieja E, Chmurzynska A. The impact of N-acetylcysteine on lactate, biomarkers of oxidative stress, immune response, and muscle damage: A systematic review and meta-analysis. Journal of cellular and molecular medicine. 2024", "claim": "PubMed-indexed evidence involving NAC", "title": "The impact of N-acetylcysteine on lactate, biomarkers of oxidative stress, immune response, and muscle damage: A systematic review and meta-analysis", "authors": "Sadowski M, Zawieja E, Chmurzynska A", "journal": "Journal of cellular and molecular medicine", "year": 2024, "pmid": "39632267", "url": "https://pubmed.ncbi.nlm.nih.gov/39632267/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/jcmm.70198", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39632267/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "nac" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567034", "name": "Glycine", "alternateNames": [], "category": "Amino Acid", "subcategory": "Non-Essential Amino Acid", "overview": "The simplest amino acid with surprisingly powerful effects on sleep quality, collagen synthesis, and neuroprotection. A key component of glutathione.", "mechanismOfAction": "Inhibitory neurotransmitter binding to glycine receptors in the brainstem and spinal cord. Lowers core body temperature (via peripheral vasodilation) to promote sleep onset. One of three amino acids in glutathione (with cysteine and glutamate). Major component of collagen (every third residue).", "commonBenefits": [ "Sleep quality", "Collagen synthesis", "Glutathione support", "Neuroprotection", "Blood sugar support" ], "commonDosageRange": "3–5 g daily (before bed for sleep)", "recommendedForm": "Pure glycine powder", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Take 3g about 1 hour before bed for sleep; sweet taste makes it easy to take in water" }, "evidenceRating": "moderate", "foodSources": [ "Bone broth", "Gelatin", "Meat", "Fish", "Legumes" ], "deficiencySymptoms": [ "Poor sleep quality", "Slow wound healing" ], "sideEffects": [ "Very safe; mild GI upset at very high doses", "Rare drowsiness" ], "contraindications": [ "Clozapine (may reduce efficacy)" ], "iconName": "zzz", "colorHex": "C77DFF", "tags": [ "sleep", "collagen", "glutathione", "neuroprotection" ], "sources": [ { "claim": "Systematic review of glycine effects on physiological systems including sleep", "title": "The effect of glycine administration on the characteristics of physiological systems in human adults: A systematic review", "authors": "Razak MA et al.", "journal": "Nutrients", "year": 2023, "pmid": "37851316", "url": "https://pubmed.ncbi.nlm.nih.gov/37851316/", "study_type": "review", "key_finding": "Longer-term glycine administration improved sleep in healthy populations, though studies had small sample sizes with high risk of bias.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37851316/", "publicSourceType": "PMID" }, { "claim": "Glycine improves subjective daytime performance in sleep-restricted individuals", "title": "The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers", "authors": "Bannai M et al.", "journal": "Front Neurol", "year": 2012, "pmid": "22529837", "url": "https://pubmed.ncbi.nlm.nih.gov/22529837/", "study_type": "RCT", "key_finding": "3g glycine before bedtime significantly reduced fatigue and improved daytime sleepiness induced by acute sleep restriction.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22529837/", "publicSourceType": "PMID" }, { "claim": "Mechanism of glycine sleep effects via NMDA receptors in SCN", "title": "The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus", "authors": "Kawai N et al.", "journal": "Neuropsychopharmacology", "year": 2015, "pmid": "25533534", "url": "https://pubmed.ncbi.nlm.nih.gov/25533534/", "study_type": "review", "key_finding": "Glycine promotes sleep by lowering core body temperature via peripheral vasodilation through NMDA receptor activation in the SCN.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25533534/", "publicSourceType": "PMID" }, { "claim": "Glycine is essential for collagen synthesis and metabolically insufficient from endogenous production", "title": "Roles of dietary glycine, proline, and hydroxyproline in collagen synthesis and animal growth", "authors": "Li P et al.", "journal": "Amino Acids", "year": 2018, "pmid": "28929384", "url": "https://pubmed.ncbi.nlm.nih.gov/28929384/", "study_type": "review", "key_finding": "Glycine, proline, and hydroxyproline contribute to 57% of total amino acids in collagen; endogenous glycine synthesis falls short of metabolic needs by about 10g/day.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28929384/", "publicSourceType": "PMID" }, { "claim": "GlyNAC supplementation improves glutathione deficiency and aging hallmarks in older adults", "title": "Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial", "authors": "Kumar P et al.", "journal": "J Gerontol A Biol Sci Med Sci", "year": 2023, "pmid": "35975308", "url": "https://pubmed.ncbi.nlm.nih.gov/35975308/", "study_type": "RCT", "key_finding": "GlyNAC supplementation for 16 weeks in older adults improved glutathione levels, oxidative stress, mitochondrial function, inflammation, and physical function.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35975308/", "publicSourceType": "PMID" }, { "claim": "Glycine neuroprotection via inhibition of NF-kB and M1 microglial polarization", "title": "Glycine Exhibits Neuroprotective Effects in Ischemic Stroke in Rats through the Inhibition of M1 Microglial Polarization via the NF-κB p65/Hif-1α Signaling Pathway", "authors": "Liu R et al.", "journal": "Neuroscience", "year": 2019, "pmid": "30710045", "url": "https://pubmed.ncbi.nlm.nih.gov/30710045/", "study_type": "review", "key_finding": "Glycine inhibits ischemia-induced inflammation and promotes M2 microglial polarization, reducing infarct volume and neuronal death.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30710045/", "publicSourceType": "PMID" }, { "text": "Razak MA, Begum PS, Viswanath B et al.. Multifarious Beneficial Effect of Nonessential Amino Acid, Glycine: A Review. Oxidative medicine and cellular longevity. 2017", "pmid": "28337245", "doi": "10.1155/2017/1716701", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28337245/", "publicSourceType": "PMID" }, { "claim": "Enhances physical performance and recovery", "title": "An Update of the Promise of Glycine Supplementation for Enhancing Physical Performance and Recovery.", "authors": "Ramos-Jimenez A, Hernndez-Torres RP, Hernndez-Ontiveros DA, Ortiz-Ortiz M, Lpez-Fregoso RJ, Martnez-Sanz JM et al.", "journal": "Sports (Basel)", "year": 2024, "pmid": "39453231", "url": "https://pubmed.ncbi.nlm.nih.gov/39453231/", "study_type": "review", "key_finding": "Review found glycine supplementation shows promise for enhancing physical performance and recovery through anti-inflammatory, antioxidant, and collagen-synthesis-promoting mechanisms.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39453231/", "publicSourceType": "PMID" }, { "text": "Genton L, Teta D, Pruijm M et al.. Glycine increases fat-free mass in malnourished haemodialysis patients: a randomized double-blind crossover trial. Journal of cachexia, sarcopenia and muscle. 2021", "claim": "PubMed-indexed evidence involving Glycine", "title": "Glycine increases fat-free mass in malnourished haemodialysis patients: a randomized double-blind crossover trial", "authors": "Genton L, Teta D, Pruijm M et al.", "journal": "Journal of cachexia, sarcopenia and muscle", "year": 2021, "pmid": "34519439", "url": "https://pubmed.ncbi.nlm.nih.gov/34519439/", "study_type": "RCT", "confidence": "verify", "doi": "10.1002/jcsm.12780", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34519439/", "publicSourceType": "PMID" }, { "text": "de Bartolomeis A, Manchia M, Marmo F et al.. Glycine Signaling in the Framework of Dopamine-Glutamate Interaction and Postsynaptic Density. Implications for Treatment-Resistant Schizophrenia. Frontiers in psychiatry. 2020", "claim": "PubMed-indexed evidence involving Glycine", "title": "Glycine Signaling in the Framework of Dopamine-Glutamate Interaction and Postsynaptic Density. Implications for Treatment-Resistant Schizophrenia", "authors": "de Bartolomeis A, Manchia M, Marmo F et al.", "journal": "Frontiers in psychiatry", "year": 2020, "pmid": "32477178", "url": "https://pubmed.ncbi.nlm.nih.gov/32477178/", "study_type": "review", "confidence": "verify", "doi": "10.3389/fpsyt.2020.00369", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32477178/", "publicSourceType": "PMID" }, { "text": "Suzauddula M, Islam MN, Ahmed T. The complex role of glycine N-methyltransferase in metabolism-a review. Molecular biology reports. 2025", "claim": "PubMed-indexed evidence involving Glycine", "title": "The complex role of glycine N-methyltransferase in metabolism-a review", "authors": "Suzauddula M, Islam MN, Ahmed T", "journal": "Molecular biology reports", "year": 2025, "pmid": "40025311", "url": "https://pubmed.ncbi.nlm.nih.gov/40025311/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s11033-025-10374-w", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40025311/", "publicSourceType": "PMID" }, { "text": "Imenshahidi M, Hossenzadeh H. Effects of glycine on metabolic syndrome components: a review. Journal of endocrinological investigation. 2022", "claim": "PubMed-indexed evidence involving Glycine", "title": "Effects of glycine on metabolic syndrome components: a review", "authors": "Imenshahidi M, Hossenzadeh H", "journal": "Journal of endocrinological investigation", "year": 2022, "pmid": "35013990", "url": "https://pubmed.ncbi.nlm.nih.gov/35013990/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s40618-021-01720-3", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35013990/", "publicSourceType": "PMID" }, { "text": "Cioffi CL. Glycine transporter-1 inhibitors: a patent review (2011-2016). Expert opinion on therapeutic patents. 2018", "claim": "PubMed-indexed evidence involving Glycine", "title": "Glycine transporter-1 inhibitors: a patent review (2011-2016)", "authors": "Cioffi CL", "journal": "Expert opinion on therapeutic patents", "year": 2018, "pmid": "29338548", "url": "https://pubmed.ncbi.nlm.nih.gov/29338548/", "study_type": "review", "confidence": "verify", "doi": "10.1080/13543776.2018.1429408", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29338548/", "publicSourceType": "PMID" }, { "text": "Mizzi N, Blundell R. Glycine receptors: Structure, function, and therapeutic implications. Molecular aspects of medicine. 2025", "claim": "PubMed-indexed evidence involving Glycine", "title": "Glycine receptors: Structure, function, and therapeutic implications", "authors": "Mizzi N, Blundell R", "journal": "Molecular aspects of medicine", "year": 2025, "pmid": "40198976", "url": "https://pubmed.ncbi.nlm.nih.gov/40198976/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.mam.2025.101360", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40198976/", "publicSourceType": "PMID" }, { "text": "Fricke S, Harnau M, Hetsch F et al.. Cesium activates the neurotransmitter receptor for glycine. Frontiers in molecular neuroscience. 2023", "claim": "PubMed-indexed evidence involving Glycine", "title": "Cesium activates the neurotransmitter receptor for glycine", "authors": "Fricke S, Harnau M, Hetsch F et al.", "journal": "Frontiers in molecular neuroscience", "year": 2023, "pmid": "37284465", "url": "https://pubmed.ncbi.nlm.nih.gov/37284465/", "study_type": "review", "confidence": "verify", "doi": "10.3389/fnmol.2023.1018530", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37284465/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "glycine" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567035", "name": "Creatine", "alternateNames": [ "Creatine Monohydrate" ], "category": "Amino Acid", "subcategory": "Organic Compound", "overview": "One of the most researched supplements in history. Primarily known for athletic performance, but emerging evidence strongly supports cognitive benefits, especially under stress or sleep deprivation.", "mechanismOfAction": "Stored as phosphocreatine in muscles and brain. Donates phosphate group to ADP via creatine kinase to rapidly regenerate ATP during high-intensity energy demands. In the brain, supports ATP-dependent processes including neurotransmission, ion homeostasis, and membrane integrity.", "commonBenefits": [ "Strength and power", "Muscle growth", "Cognitive performance", "Recovery", "Brain energy" ], "commonDosageRange": "3–5 g daily (no loading necessary)", "recommendedForm": "Creatine monohydrate (most studied and cost-effective)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take daily with food; timing doesn't matter much. Full saturation in 3-4 weeks without loading." }, "evidenceRating": "strong", "foodSources": [ "Red meat", "Fish", "Pork" ], "deficiencySymptoms": [ "Reduced exercise performance", "Faster mental fatigue under stress" ], "sideEffects": [ "Water retention (initial)", "GI upset (rare)", "Weight gain (water + muscle)" ], "contraindications": [ "Kidney disease (consult doctor)", "Generally very safe for healthy individuals" ], "iconName": "dumbbell.fill", "colorHex": "7400B8", "tags": [ "performance", "strength", "brain", "muscle" ], "sources": [ { "claim": "ISSN position stand on safety and efficacy of creatine supplementation", "title": "International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine", "authors": "Kreider RB et al.", "journal": "J Int Soc Sports Nutr", "year": 2017, "pmid": "28615996", "url": "https://pubmed.ncbi.nlm.nih.gov/28615996/", "study_type": "review", "key_finding": "Short and long-term supplementation (up to 30 g/day for 5 years) is safe and well-tolerated; creatine can improve exercise performance and may have neuroprotective benefits.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28615996/", "publicSourceType": "PMID" }, { "claim": "Creatine supplementation improves cognitive function in adults", "title": "The effects of creatine supplementation on cognitive function in adults: a systematic review and meta-analysis", "authors": "Gimenez-Campos MS et al.", "journal": "Exp Gerontol", "year": 2024, "pmid": "39070254", "url": "https://pubmed.ncbi.nlm.nih.gov/39070254/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 16 RCTs (492 participants) evaluating creatine's effects on overall cognitive function, memory, executive function, and attention in adults.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39070254/", "publicSourceType": "PMID" }, { "claim": "Creatine supplementation improves memory, especially in older adults", "title": "Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials", "authors": "Forbes SC et al.", "journal": "Nutr Rev", "year": 2022, "pmid": "35984306", "url": "https://pubmed.ncbi.nlm.nih.gov/35984306/", "study_type": "meta-analysis", "key_finding": "Creatine improved memory (SMD = 0.29) with significant effects in older adults (66-76 years) versus younger individuals.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35984306/", "publicSourceType": "PMID" }, { "claim": "Creatine supplementation increases lean body mass and reduces fat percentage when combined with resistance training", "title": "The Effect of Creatine Supplementation on Resistance Training-Based Changes to Body Composition: A Systematic Review and Meta-analysis", "authors": "Burke R et al.", "journal": "J Strength Cond Res", "year": 2024, "pmid": "39074168", "url": "https://pubmed.ncbi.nlm.nih.gov/39074168/", "study_type": "meta-analysis", "key_finding": "Creatine plus resistance training increased lean body mass by 1.14 kg and reduced body fat percentage by 0.88% versus resistance training alone.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39074168/", "publicSourceType": "PMID" }, { "claim": "Creatine safety - common misconceptions addressed by scientific evidence", "title": "Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show?", "authors": "Antonio J et al.", "journal": "J Int Soc Sports Nutr", "year": 2021, "pmid": "33557850", "url": "https://pubmed.ncbi.nlm.nih.gov/33557850/", "study_type": "review", "key_finding": "Scientific evidence does not support claims that creatine causes kidney damage, hair loss, or dehydration; it is safe for healthy individuals.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33557850/", "publicSourceType": "PMID" }, { "claim": "Creatine supplementation safety review analyzing adverse events", "title": "Safety of creatine supplementation: analysis of the prevalence of reported side effects in clinical trials and adverse event reports", "authors": "Ostojic SM et al.", "journal": "Food Chem Toxicol", "year": 2025, "pmid": "40198156", "url": "https://pubmed.ncbi.nlm.nih.gov/40198156/", "study_type": "review", "key_finding": "Creatine supplementation is generally well tolerated and not associated with clinically significant side effects in clinical trials.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40198156/", "publicSourceType": "PMID" }, { "text": "Avgerinos KI, Spyrou N, Bougioukas KI et al.. Effects of creatine supplementation on cognitive function of healthy individuals: A systematic review of randomized controlled trials. Experimental gerontology. 2018", "pmid": "29704637", "doi": "10.1016/j.exger.2018.04.013", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29704637/", "publicSourceType": "PMID" }, { "text": "Burke R, Piñero A, Coleman M et al.. The Effects of Creatine Supplementation Combined with Resistance Training on Regional Measures of Muscle Hypertrophy: A Systematic Review with Meta-Analysis. Nutrients. 2023", "pmid": "37432300", "doi": "10.3390/nu15092116", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37432300/", "publicSourceType": "PMID" }, { "claim": "Creatine supplementation does not harm kidney function", "title": "Effects of Creatine Supplementation on Renal Function: A Systematic Review and Meta-Analysis.", "authors": "de Souza E Silva A, Pertille A, Reis Barbosa CG et al.", "journal": "Journal of Renal Nutrition", "year": 2019, "pmid": "31375416", "url": "https://pubmed.ncbi.nlm.nih.gov/31375416/", "study_type": "meta-analysis", "key_finding": "Creatine supplementation did not significantly alter serum creatinine or plasma urea, indicating no adverse effects on renal function at studied doses and durations.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31375416/", "publicSourceType": "PMID" }, { "text": "Delpino FM, Figueiredo LM, Forbes SC et al.. Influence of age, sex, and type of exercise on the efficacy of creatine supplementation on lean body mass: A systematic review and meta-analysis of randomized clinical trials. Nutrition (Burbank, Los Angeles County, Calif.). 2022", "claim": "PubMed-indexed evidence involving Creatine", "title": "Influence of age, sex, and type of exercise on the efficacy of creatine supplementation on lean body mass: A systematic review and meta-analysis of randomized clinical trials", "authors": "Delpino FM, Figueiredo LM, Forbes SC et al.", "journal": "Nutrition (Burbank, Los Angeles County, Calif.)", "year": 2022, "pmid": "35986981", "url": "https://pubmed.ncbi.nlm.nih.gov/35986981/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.nut.2022.111791", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35986981/", "publicSourceType": "PMID" }, { "text": "Jiaming Y, Rahimi MH. Creatine supplementation effect on recovery following exercise-induced muscle damage: A systematic review and meta-analysis of randomized controlled trials. Journal of food biochemistry. 2021", "claim": "PubMed-indexed evidence involving Creatine", "title": "Creatine supplementation effect on recovery following exercise-induced muscle damage: A systematic review and meta-analysis of randomized controlled trials", "authors": "Jiaming Y, Rahimi MH", "journal": "Journal of food biochemistry", "year": 2021, "pmid": "34472118", "url": "https://pubmed.ncbi.nlm.nih.gov/34472118/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/jfbc.13916", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34472118/", "publicSourceType": "PMID" }, { "text": "Stares A, Bains M. The Additive Effects of Creatine Supplementation and Exercise Training in an Aging Population: A Systematic Review of Randomized Controlled Trials. Journal of geriatric physical therapy (2001). 2020", "claim": "PubMed-indexed evidence involving Creatine", "title": "The Additive Effects of Creatine Supplementation and Exercise Training in an Aging Population: A Systematic Review of Randomized Controlled Trials", "authors": "Stares A, Bains M", "journal": "Journal of geriatric physical therapy (2001)", "year": 2020, "pmid": "30762623", "url": "https://pubmed.ncbi.nlm.nih.gov/30762623/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1519/JPT.0000000000000222", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30762623/", "publicSourceType": "PMID" }, { "text": "Elosegui S, López-Seoane J, Martínez-Ferrán M et al.. Interaction Between Caffeine and Creatine When Used as Concurrent Ergogenic Supplements: A Systematic Review. International journal of sport nutrition and exercise metabolism. 2022", "claim": "PubMed-indexed evidence involving Creatine", "title": "Interaction Between Caffeine and Creatine When Used as Concurrent Ergogenic Supplements: A Systematic Review", "authors": "Elosegui S, López-Seoane J, Martínez-Ferrán M et al.", "journal": "International journal of sport nutrition and exercise metabolism", "year": 2022, "pmid": "35016154", "url": "https://pubmed.ncbi.nlm.nih.gov/35016154/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1123/ijsnem.2021-0262", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35016154/", "publicSourceType": "PMID" }, { "text": "de Guingand DL, Palmer KR, Snow RJ et al.. Risk of Adverse Outcomes in Females Taking Oral Creatine Monohydrate: A Systematic Review and Meta-Analysis. Nutrients. 2020", "claim": "PubMed-indexed evidence involving Creatine", "title": "Risk of Adverse Outcomes in Females Taking Oral Creatine Monohydrate: A Systematic Review and Meta-Analysis", "authors": "de Guingand DL, Palmer KR, Snow RJ et al.", "journal": "Nutrients", "year": 2020, "pmid": "32549301", "url": "https://pubmed.ncbi.nlm.nih.gov/32549301/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu12061780", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32549301/", "publicSourceType": "PMID" }, { "text": "Marshall S, Kitzan A, Wright J et al.. Creatine and Cognition in Aging: A Systematic Review of Evidence in Older Adults. Nutrition reviews. 2026", "claim": "PubMed-indexed evidence involving Creatine", "title": "Creatine and Cognition in Aging: A Systematic Review of Evidence in Older Adults", "authors": "Marshall S, Kitzan A, Wright J et al.", "journal": "Nutrition reviews", "year": 2026, "pmid": "40971619", "url": "https://pubmed.ncbi.nlm.nih.gov/40971619/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/nutrit/nuaf135", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40971619/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "creatine" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567036", "name": "Collagen Peptides", "alternateNames": [ "Hydrolyzed Collagen", "Collagen Type I & III" ], "category": "Amino Acid", "subcategory": "Protein", "overview": "Hydrolyzed collagen provides bioactive peptides that stimulate the body's own collagen production. Supports skin elasticity, joint health, and gut lining integrity.", "mechanismOfAction": "Hydrolyzed peptides (especially prolyl-hydroxyproline and hydroxyprolyl-glycine) are absorbed intact and stimulate fibroblasts, chondrocytes, and osteoblasts to increase collagen synthesis. Rich in glycine, proline, and hydroxyproline, amino acids underrepresented in modern diets.", "commonBenefits": [ "Skin elasticity", "Joint health", "Gut lining repair (emerging evidence; no human systematic reviews)", "Hair and nail strength", "Bone density" ], "commonDosageRange": "10–20 g daily", "recommendedForm": "Hydrolyzed collagen peptides (Type I & III for skin/hair; Type II for joints)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Dissolve in coffee, smoothies, or water. Pair with vitamin C for collagen synthesis." }, "evidenceRating": "moderate", "foodSources": [ "Bone broth", "Chicken skin", "Fish skin", "Gelatin" ], "deficiencySymptoms": [ "Premature skin aging", "Joint stiffness", "Weak nails" ], "sideEffects": [ "Generally very well tolerated", "Rare bloating" ], "contraindications": [ "Fish/shellfish allergies (marine collagen)" ], "iconName": "sparkles", "colorHex": "E040FB", "tags": [ "skin", "joints", "beauty", "gut-health" ], "sources": [ { "claim": "Collagen supplements improve skin hydration, elasticity, and wrinkles", "title": "Effects of hydrolyzed collagen supplementation on skin aging: a systematic review and meta-analysis", "authors": "de Miranda RB et al.", "journal": "Int J Dermatol", "year": 2021, "pmid": "33742704", "url": "https://pubmed.ncbi.nlm.nih.gov/33742704/", "study_type": "meta-analysis", "key_finding": "Ingestion of hydrolyzed collagen for 90 days is effective in reducing skin aging, reducing wrinkles and improving skin elasticity and hydration.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33742704/", "publicSourceType": "PMID" }, { "claim": "Oral collagen supplementation improves skin health via mechanistic pathways", "title": "Collagen supplementation for skin health: A mechanistic systematic review", "authors": "Choi FD et al.", "journal": "J Cosmet Dermatol", "year": 2019, "pmid": "32436266", "url": "https://pubmed.ncbi.nlm.nih.gov/32436266/", "study_type": "review", "key_finding": "Evidence indicates that oral administration of collagen improves skin health through fibroblast stimulation and extracellular matrix support.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32436266/", "publicSourceType": "PMID" }, { "claim": "Collagen supplementation improves osteoarthritis pain and function", "title": "Effect of collagen supplementation on knee osteoarthritis: an updated systematic review and meta-analysis of randomised controlled trials", "authors": "Garcia-Castillo JL et al.", "journal": "BMJ Open Sport Exerc Med", "year": 2024, "pmid": "39212129", "url": "https://pubmed.ncbi.nlm.nih.gov/39212129/", "study_type": "meta-analysis", "key_finding": "Collagen supplementation significantly improved both function and pain scores in knee osteoarthritis across 11 RCTs with 870 participants.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39212129/", "publicSourceType": "PMID" }, { "claim": "Collagen peptide supplementation effects on body composition and joint recovery", "title": "The effects of collagen peptide supplementation on body composition, collagen synthesis, and recovery from joint injury and exercise: a systematic review", "authors": "Khatri M et al.", "journal": "Amino Acids", "year": 2021, "pmid": "34491424", "url": "https://pubmed.ncbi.nlm.nih.gov/34491424/", "study_type": "review", "key_finding": "Collagen peptide supplementation in conjunction with exercise may be beneficial for managing degenerative bone and joint disorders via stimulatory effects on extracellular matrix.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34491424/", "publicSourceType": "PMID" }, { "claim": "Collagen supplement improves skin hydration, elasticity, roughness, and density in RCT", "title": "A Collagen Supplement Improves Skin Hydration, Elasticity, Roughness, and Density: Results of a Randomized, Placebo-Controlled, Blind Study", "authors": "Bolke L et al.", "journal": "Nutrients", "year": 2019, "pmid": "31627309", "url": "https://pubmed.ncbi.nlm.nih.gov/31627309/", "study_type": "RCT", "key_finding": "Oral collagen peptide supplementation significantly improved skin hydration, elasticity, roughness, and density versus placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31627309/", "publicSourceType": "PMID" }, { "text": "Dewi DAR, Arimuko A, Norawati L et al.. Exploring the Impact of Hydrolyzed Collagen Oral Supplementation on Skin Rejuvenation: A Systematic Review and Meta-Analysis. Cureus. 2023", "pmid": "38192916", "doi": "10.7759/cureus.50231", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38192916/", "publicSourceType": "PMID" }, { "text": "Proksch E, Segger D, Degwert J et al.. Oral supplementation of specific collagen peptides has beneficial effects on human skin physiology: a double-blind, placebo-controlled study. Skin pharmacology and physiology. 2014", "pmid": "23949208", "doi": "10.1159/000351376", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23949208/", "publicSourceType": "PMID" }, { "claim": "Collagen peptides improve strength and musculotendinous remodeling with exercise", "title": "Impact of Collagen Peptide Supplementation in Combination with Long-Term Physical Training on Strength, Musculotendinous Remodeling, Functional Recovery, and Body Composition in Healthy Adults: A Systematic Review with Meta-analysis.", "authors": "Bischof K, Moitzi AM, Stafilidis S et al.", "journal": "Sports Medicine", "year": 2024, "pmid": "39060741", "url": "https://pubmed.ncbi.nlm.nih.gov/39060741/", "study_type": "meta-analysis", "key_finding": "Collagen peptide supplementation combined with physical training improved musculotendinous remodeling, functional recovery, and body composition in healthy adults.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39060741/", "publicSourceType": "PMID" }, { "claim": "Collagen peptides improve cardiovascular markers", "title": "Effects of collagen peptide supplementation on cardiovascular markers: a systematic review and meta-analysis of randomised, placebo-controlled trials.", "authors": "Jalili Z, Jalili F, Moradi S et al.", "journal": "British Journal of Nutrition", "year": 2023, "pmid": "35658958", "url": "https://pubmed.ncbi.nlm.nih.gov/35658958/", "study_type": "meta-analysis", "key_finding": "Collagen peptide supplementation significantly improved arterial stiffness and endothelial function markers in randomized placebo-controlled trials.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35658958/", "publicSourceType": "PMID" }, { "text": "Demir-Dora D, Tuna S, Kurtoglu ED et al.. Evaluation of the Efficacy and Safety of CollaSel PRO(®) Type I and Type III Hydrolyzed Collagen Peptides in the Treatment of Osteoarthritis: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial. Journal of clinical medicine. 2025", "claim": "PubMed-indexed evidence involving Collagen Peptides", "title": "Evaluation of the Efficacy and Safety of CollaSel PRO(®) Type I and Type III Hydrolyzed Collagen Peptides in the Treatment of Osteoarthritis: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial", "authors": "Demir-Dora D, Tuna S, Kurtoglu ED et al.", "journal": "Journal of clinical medicine", "year": 2025, "pmid": "40507417", "url": "https://pubmed.ncbi.nlm.nih.gov/40507417/", "study_type": "RCT", "confidence": "verify", "doi": "10.3390/jcm14113655", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40507417/", "publicSourceType": "PMID" }, { "text": "Park SY, Lee SH, Kim HT et al.. Efficacy and safety of low-molecular-weight collagen peptides in knee osteoarthritis: a randomized, double-blind, placebo-controlled trial. Frontiers in nutrition. 2025", "claim": "PubMed-indexed evidence involving Collagen Peptides", "title": "Efficacy and safety of low-molecular-weight collagen peptides in knee osteoarthritis: a randomized, double-blind, placebo-controlled trial", "authors": "Park SY, Lee SH, Kim HT et al.", "journal": "Frontiers in nutrition", "year": 2025, "pmid": "40977985", "url": "https://pubmed.ncbi.nlm.nih.gov/40977985/", "study_type": "RCT", "confidence": "verify", "doi": "10.3389/fnut.2025.1644899", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40977985/", "publicSourceType": "PMID" }, { "text": "Guadanhim LRS, Miot HA, Soares JLM et al.. Efficacy and Safety of Topical or Oral Hydrolyzed Collagen in Women with Dermatoporosis: A Randomized, Double-Blind, Factorial Design Study. Dermatology and therapy. 2023", "claim": "PubMed-indexed evidence involving Collagen Peptides", "title": "Efficacy and Safety of Topical or Oral Hydrolyzed Collagen in Women with Dermatoporosis: A Randomized, Double-Blind, Factorial Design Study", "authors": "Guadanhim LRS, Miot HA, Soares JLM et al.", "journal": "Dermatology and therapy", "year": 2023, "pmid": "36547800", "url": "https://pubmed.ncbi.nlm.nih.gov/36547800/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/s13555-022-00859-y", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36547800/", "publicSourceType": "PMID" }, { "text": "Genç AS, Yılmaz AK, Anıl B et al.. Effect of supplementation with type 1 and type 3 collagen peptide and type 2 hydrolyzed collagen on osteoarthritis-related pain, quality of life, and physical function: A double-blind, randomized, placebo-controlled study. Joint diseases and related surgery. 2025", "claim": "PubMed-indexed evidence involving Collagen Peptides", "title": "Effect of supplementation with type 1 and type 3 collagen peptide and type 2 hydrolyzed collagen on osteoarthritis-related pain, quality of life, and physical function: A double-blind, randomized, placebo-controlled study", "authors": "Genç AS, Yılmaz AK, Anıl B et al.", "journal": "Joint diseases and related surgery", "year": 2025, "pmid": "39719905", "url": "https://pubmed.ncbi.nlm.nih.gov/39719905/", "study_type": "RCT", "confidence": "verify", "doi": "10.52312/jdrs.2025.1965", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39719905/", "publicSourceType": "PMID" }, { "text": "Genç AS, Yılmaz AK, Anıl B et al.. The effect of supplementation with type I and type III collagen peptide and type II hydrolyzed collagen on pain, quality of life and physical function in patients with meniscopathy: a randomized, double-blind, placebo-controlled study. BMC musculoskeletal disorders. 2025", "claim": "PubMed-indexed evidence involving Collagen Peptides", "title": "The effect of supplementation with type I and type III collagen peptide and type II hydrolyzed collagen on pain, quality of life and physical function in patients with meniscopathy: a randomized, double-blind, placebo-controlled study", "authors": "Genç AS, Yılmaz AK, Anıl B et al.", "journal": "BMC musculoskeletal disorders", "year": 2025, "pmid": "39755603", "url": "https://pubmed.ncbi.nlm.nih.gov/39755603/", "study_type": "RCT", "confidence": "verify", "doi": "10.1186/s12891-024-08244-w", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39755603/", "publicSourceType": "PMID" }, { "text": "Tafuri A, Panunzio A, Tricarico M et al.. Oral Collagen Peptides and Vulvovaginal Radiofrequency Therapy for Genitourinary Syndrome of Menopause: A Pilot Randomized Study. Journal of clinical medicine. 2025", "claim": "PubMed-indexed evidence involving Collagen Peptides", "title": "Oral Collagen Peptides and Vulvovaginal Radiofrequency Therapy for Genitourinary Syndrome of Menopause: A Pilot Randomized Study", "authors": "Tafuri A, Panunzio A, Tricarico M et al.", "journal": "Journal of clinical medicine", "year": 2025, "pmid": "40507418", "url": "https://pubmed.ncbi.nlm.nih.gov/40507418/", "study_type": "RCT", "confidence": "verify", "doi": "10.3390/jcm14113656", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40507418/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "collagen-peptides" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567037", "name": "Fish Oil", "alternateNames": [ "Omega-3", "EPA/DHA", "Omega-3 Fatty Acids" ], "category": "Omega/Fatty Acid", "subcategory": "Essential Fatty Acid", "overview": "The most important essential fatty acid supplement. EPA and DHA omega-3s are critical for brain function, heart health, and systemic inflammation control.", "mechanismOfAction": "EPA competes with arachidonic acid, reducing pro-inflammatory eicosanoids (prostaglandins, thromboxanes, leukotrienes) and producing anti-inflammatory resolvins and protectins. DHA is the primary structural fat in brain cell membranes (60% of brain fat), essential for membrane fluidity, synaptic function, and neuroprotection.", "commonBenefits": [ "Heart health", "Brain function", "Anti-inflammatory", "Joint health", "Eye health", "Mood support" ], "commonDosageRange": "1,000–3,000 mg combined EPA/DHA daily", "recommendedForm": "Triglyceride form (better absorbed) or ethyl ester. High EPA for mood; high DHA for brain.", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with a fatty meal for best absorption; refrigerate to prevent oxidation" }, "evidenceRating": "strong", "foodSources": [ "Salmon", "Mackerel", "Sardines", "Anchovies", "Herring" ], "deficiencySymptoms": [ "Dry skin", "Brain fog", "Joint pain", "Depression", "Poor wound healing" ], "sideEffects": [ "Fishy burps", "GI upset", "Increased bleeding risk at high doses", "Atrial fibrillation risk (dose-dependent; higher risk above 1g/day EPA+DHA)" ], "contraindications": [ "Blood thinners (high doses)", "Fish allergy", "Upcoming surgery (high doses)" ], "iconName": "drop.fill", "colorHex": "023E8A", "tags": [ "heart-health", "brain", "anti-inflammatory", "essential" ], "sources": [ { "claim": "Marine omega-3 supplementation reduces cardiovascular events", "title": "Marine Omega-3 Supplementation and Cardiovascular Disease: An Updated Meta-Analysis of 13 Randomized Controlled Trials Involving 127 477 Participants", "authors": "Hu Y et al.", "journal": "J Am Heart Assoc", "year": 2019, "pmid": "31567003", "url": "https://pubmed.ncbi.nlm.nih.gov/31567003/", "study_type": "meta-analysis", "key_finding": "Marine omega-3 supplementation was associated with reduced risk of myocardial infarction, CHD death, total CHD, and CVD death in a dose-dependent manner.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31567003/", "publicSourceType": "PMID" }, { "claim": "EPA is primarily responsible for omega-3 antidepressant effects", "title": "EPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trials", "authors": "Martins JG", "journal": "J Am Coll Nutr", "year": 2009, "pmid": "20439549", "url": "https://pubmed.ncbi.nlm.nih.gov/20439549/", "study_type": "meta-analysis", "key_finding": "EPA-predominant formulations (>60% EPA) demonstrated clinical benefit in depression, whereas DHA-predominant formulations did not.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20439549/", "publicSourceType": "PMID" }, { "claim": "Omega-3 supplementation increases risk of atrial fibrillation in dose-dependent manner", "title": "Association Between Omega-3 Fatty Acid Treatment and Atrial Fibrillation in Cardiovascular Outcome Trials: A Systematic Review and Meta-Analysis", "authors": "Gencer B et al.", "journal": "JAMA Netw Open", "year": 2021, "pmid": "34057665", "url": "https://pubmed.ncbi.nlm.nih.gov/34057665/", "study_type": "meta-analysis", "key_finding": "Omega-3 supplements associated with 25% increased AF risk; >1 g/day increased risk by 49% vs 12% for <=1 g/day, indicating dose-dependent relationship.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34057665/", "publicSourceType": "PMID" }, { "claim": "Omega-3 anti-inflammatory mechanisms including resolvins and protectins", "title": "Marine omega-3 fatty acids and inflammatory processes: Effects, mechanisms and clinical relevance", "authors": "Calder PC", "journal": "Biochim Biophys Acta", "year": 2015, "pmid": "25149823", "url": "https://pubmed.ncbi.nlm.nih.gov/25149823/", "study_type": "review", "key_finding": "EPA and DHA inhibit leucocyte chemotaxis, reduce pro-inflammatory cytokines, and give rise to anti-inflammatory resolvins, protectins, and maresins.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25149823/", "publicSourceType": "PMID" }, { "claim": "Omega-3 effects on brain function via DHA", "title": "Effects of Omega-3 Polyunsaturated Fatty Acids on Brain Functions: A Systematic Review", "authors": "Dighriri IM et al.", "journal": "Cureus", "year": 2022, "pmid": "36381743", "url": "https://pubmed.ncbi.nlm.nih.gov/36381743/", "study_type": "review", "key_finding": "DHA, the dominant omega-3 in the brain, impacts neurotransmitters and brain functions and has evidence for slowing cognitive decline.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36381743/", "publicSourceType": "PMID" }, { "claim": "Omega-3 dose-response effects on blood pressure", "title": "Omega-3 Polyunsaturated Fatty Acids Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials", "authors": "Zhang X et al.", "journal": "J Am Heart Assoc", "year": 2022, "pmid": "35647665", "url": "https://pubmed.ncbi.nlm.nih.gov/35647665/", "study_type": "meta-analysis", "key_finding": "Optimal combined intake of omega-3 fatty acids for blood pressure lowering is likely between 2 g/d and 3 g/d.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35647665/", "publicSourceType": "PMID" }, { "text": "Delpino FM, Figueiredo LM, da Silva BGC et al.. Omega-3 supplementation and diabetes: A systematic review and meta-analysis. Critical reviews in food science and nutrition. 2022", "pmid": "33480268", "doi": "10.1080/10408398.2021.1875977", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33480268/", "publicSourceType": "PMID" }, { "claim": "Omega-3 fatty acids reduce symptoms of depression", "title": "Efficacy of omega-3 PUFAs in depression: A meta-analysis.", "authors": "Liao Y, Xie B, Zhang H et al.", "journal": "Translational Psychiatry", "year": 2019, "pmid": "31383846", "url": "https://pubmed.ncbi.nlm.nih.gov/31383846/", "study_type": "meta-analysis", "key_finding": "Omega-3 PUFA supplementation significantly reduced depressive symptoms, with higher doses of EPA showing greater efficacy.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31383846/", "publicSourceType": "PMID" }, { "claim": "Omega-3 reduces risk of cognitive decline and dementia", "title": "The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers.", "authors": "Wei BZ, Li L, Dong CW et al.", "journal": "American Journal of Clinical Nutrition", "year": 2023, "pmid": "37028557", "url": "https://pubmed.ncbi.nlm.nih.gov/37028557/", "study_type": "meta-analysis", "key_finding": "Higher omega-3 intake and blood levels were associated with reduced risk of dementia and cognitive decline in prospective cohort studies.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37028557/", "publicSourceType": "PMID" }, { "claim": "Omega-3 supplementation combined with resistance training improves skeletal muscle", "title": "Effects of Omega-3 fatty acids supplementation and resistance training on skeletal muscle.", "authors": "Uchida Y, Tsuji K, Ochi E", "journal": "Clinical Nutrition ESPEN", "year": 2024, "pmid": "38777432", "url": "https://pubmed.ncbi.nlm.nih.gov/38777432/", "study_type": "meta-analysis", "key_finding": "Omega-3 supplementation combined with resistance training improved muscle strength and functional performance compared to training alone.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38777432/", "publicSourceType": "PMID" }, { "text": "Chang JP, Tseng PT, Zeng BS et al.. Safety of Supplementation of Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Advances in nutrition (Bethesda, Md.). 2023", "claim": "PubMed-indexed evidence involving Fish Oil", "title": "Safety of Supplementation of Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Chang JP, Tseng PT, Zeng BS et al.", "journal": "Advances in nutrition (Bethesda, Md.)", "year": 2023, "pmid": "37567449", "url": "https://pubmed.ncbi.nlm.nih.gov/37567449/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.advnut.2023.08.003", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37567449/", "publicSourceType": "PMID" }, { "text": "Javaid M, Kadhim K, Bawamia B et al.. Bleeding Risk in Patients Receiving Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Journal of the American Heart Association. 2024", "claim": "PubMed-indexed evidence involving Fish Oil", "title": "Bleeding Risk in Patients Receiving Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Clinical Trials", "authors": "Javaid M, Kadhim K, Bawamia B et al.", "journal": "Journal of the American Heart Association", "year": 2024, "pmid": "38742535", "url": "https://pubmed.ncbi.nlm.nih.gov/38742535/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1161/JAHA.123.032390", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38742535/", "publicSourceType": "PMID" }, { "text": "Wang WX, Ko ML. Efficacy of Omega-3 Intake in Managing Dry Eye Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Journal of clinical medicine. 2023", "claim": "PubMed-indexed evidence involving Fish Oil", "title": "Efficacy of Omega-3 Intake in Managing Dry Eye Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Wang WX, Ko ML", "journal": "Journal of clinical medicine", "year": 2023, "pmid": "38002640", "url": "https://pubmed.ncbi.nlm.nih.gov/38002640/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/jcm12227026", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38002640/", "publicSourceType": "PMID" }, { "text": "Yan J, Liu M, Yang D et al.. Efficacy and Safety of Omega-3 Fatty Acids in the Prevention of Cardiovascular Disease: A Systematic Review and Meta-analysis. Cardiovascular drugs and therapy. 2024", "claim": "PubMed-indexed evidence involving Fish Oil", "title": "Efficacy and Safety of Omega-3 Fatty Acids in the Prevention of Cardiovascular Disease: A Systematic Review and Meta-analysis", "authors": "Yan J, Liu M, Yang D et al.", "journal": "Cardiovascular drugs and therapy", "year": 2024, "pmid": "36103100", "url": "https://pubmed.ncbi.nlm.nih.gov/36103100/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s10557-022-07379-z", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36103100/", "publicSourceType": "PMID" }, { "text": "Shokravi A, Sharma S, Singh R et al.. Omega-3 polyunsaturated fatty acid exposure and cardiovascular outcomes in dialysis: a systematic review and meta-analysis. Future cardiology. 2026", "claim": "PubMed-indexed evidence involving Fish Oil", "title": "Omega-3 polyunsaturated fatty acid exposure and cardiovascular outcomes in dialysis: a systematic review and meta-analysis", "authors": "Shokravi A, Sharma S, Singh R et al.", "journal": "Future cardiology", "year": 2026, "pmid": "41851014", "url": "https://pubmed.ncbi.nlm.nih.gov/41851014/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/14796678.2026.2645005", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41851014/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "fish-oil" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567038", "name": "Krill Oil", "alternateNames": [ "Antarctic Krill Oil" ], "category": "Omega/Fatty Acid", "subcategory": "Essential Fatty Acid", "overview": "EPA/DHA bound to phospholipids for superior bioavailability. Also contains astaxanthin, a powerful antioxidant. Often better tolerated than fish oil with no fishy burps.", "mechanismOfAction": "Phospholipid-bound omega-3s integrate directly into cell membranes more efficiently than triglyceride-bound forms. Astaxanthin provides additional antioxidant protection, preventing omega-3 oxidation and scavenging singlet oxygen species.", "commonBenefits": [ "Heart health", "Brain function", "Joint comfort", "PMS relief", "Antioxidant protection" ], "commonDosageRange": "500–1,000 mg krill oil daily", "recommendedForm": "Antarctic krill oil (phospholipid-bound EPA/DHA + astaxanthin)", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Better absorbed than fish oil; phospholipid form doesn't require as much dietary fat" }, "evidenceRating": "moderate", "foodSources": [ "Not a food source; extracted from Antarctic krill" ], "deficiencySymptoms": [ "Same as general omega-3 deficiency" ], "sideEffects": [ "Generally better tolerated than fish oil", "Rare GI upset" ], "contraindications": [ "Shellfish allergy", "Blood thinners" ], "iconName": "water.waves", "colorHex": "0353A4", "tags": [ "heart-health", "brain", "anti-inflammatory" ], "sources": [ { "claim": "Krill oil bioavailability of EPA/DHA compared to fish oil", "title": "Bioavailability of fatty acids from krill oil, krill meal and fish oil in healthy subjects--a randomized, single-dose, cross-over trial", "authors": "Ramprasath VR et al.", "journal": "Lipids Health Dis", "year": 2015, "pmid": "25884846", "url": "https://pubmed.ncbi.nlm.nih.gov/25884846/", "study_type": "RCT", "key_finding": "EPA and DHA in krill oil showed higher 72-hour bioavailability in plasma phospholipids compared to krill meal or fish oil.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25884846/", "publicSourceType": "PMID" }, { "claim": "Krill oil cardiovascular effects systematic review", "title": "Clinical effectiveness of krill oil supplementation on cardiovascular health in humans: An updated systematic review and meta-analysis of randomized controlled trials", "authors": "Xie D et al.", "journal": "Nutr Metab Cardiovasc Dis", "year": 2024, "pmid": "38039646", "url": "https://pubmed.ncbi.nlm.nih.gov/38039646/", "study_type": "meta-analysis", "key_finding": "Krill oil supplementation significantly reduced plasma LDL cholesterol and triglycerides across 7 RCTs with 662 participants.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38039646/", "publicSourceType": "PMID" }, { "claim": "Lipid-modifying effects of krill oil vs fish oil show no significant difference", "title": "Lipid-modifying effects of krill oil vs fish oil: a network meta-analysis", "authors": "Ursoniu S et al.", "journal": "Medicine (Baltimore)", "year": 2017, "pmid": "32073633", "url": "https://pubmed.ncbi.nlm.nih.gov/32073633/", "study_type": "meta-analysis", "key_finding": "Network meta-analysis concluded that the lipid-modifying effects of krill oil and fish oil do not significantly differ.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32073633/", "publicSourceType": "PMID" }, { "claim": "Krill oil reduces PMS symptoms and dysmenorrhea", "title": "Evaluation of the effects of Neptune Krill Oil on the management of premenstrual syndrome and dysmenorrhea", "authors": "Sampalis F et al.", "journal": "Altern Med Rev", "year": 2003, "pmid": "12777162", "url": "https://pubmed.ncbi.nlm.nih.gov/12777162/", "study_type": "RCT", "key_finding": "Neptune Krill Oil significantly reduced dysmenorrhea and emotional PMS symptoms and was more effective than omega-3 fish oil for complete PMS management.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12777162/", "publicSourceType": "PMID" }, { "claim": "Phospholipid-bound omega-3s in krill oil show superior incorporation into plasma", "title": "Incorporation of EPA and DHA into plasma phospholipids in response to different omega-3 fatty acid formulations--a comparative bioavailability study of fish oil vs. krill oil", "authors": "Schuchardt JP et al.", "journal": "Lipids Health Dis", "year": 2011, "pmid": "21854650", "url": "https://pubmed.ncbi.nlm.nih.gov/21854650/", "study_type": "RCT", "key_finding": "Krill oil had higher incorporation of EPA+DHA into plasma phospholipids compared to fish oil rTAG and ethyl-ester forms.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21854650/", "publicSourceType": "PMID" }, { "text": "Meng J, Wang X, Li Y et al.. Krill oil for knee osteoarthritis: A meta-analysis of randomized controlled trials. Medicine. 2025", "pmid": "39960912", "doi": "10.1097/MD.0000000000041566", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39960912/", "publicSourceType": "PMID" }, { "text": "Hill WS, Dohnalek MH, Ha Y et al.. A Multicenter, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of a Krill Oil, Astaxanthin, and Oral Hyaluronic Acid Complex on Joint Health in People with Mild Osteoarthritis. Nutrients. 2023", "pmid": "37686801", "doi": "10.3390/nu15173769", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37686801/", "publicSourceType": "PMID" }, { "claim": "Krill oil reduces triglyceride levels in patients with severe hypertriglyceridemia", "title": "Effectiveness of a Novel omega-3 Krill Oil Agent in Patients With Severe Hypertriglyceridemia: A Randomized Clinical Trial", "authors": "Mozaffarian D, Maki KC, Bays HE et al.", "journal": "JAMA Netw Open", "year": 2022, "pmid": "34989797", "url": "https://pubmed.ncbi.nlm.nih.gov/34989797/", "study_type": "rct", "key_finding": "Phase 3 RCT of 520 patients with severe hypertriglyceridemia found krill oil-derived omega-3 reduced TG levels by 26.0% vs 15.1% for placebo at 12 weeks (treatment difference -10.9%, p=0.02). Safe and well-tolerated.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34989797/", "publicSourceType": "PMID" }, { "claim": "Krill oil did not improve knee pain in osteoarthritis compared to placebo in a large RCT", "title": "Krill Oil for Knee Osteoarthritis: A Randomized Clinical Trial", "authors": "Laslett LL, Scheepers LEJM, Antony B et al.", "journal": "JAMA", "year": 2024, "pmid": "38776073", "url": "https://pubmed.ncbi.nlm.nih.gov/38776073/", "study_type": "rct", "key_finding": "Multicenter RCT of 262 participants found 2 g/day krill oil for 24 weeks did not improve knee pain compared to placebo in patients with knee osteoarthritis and effusion-synovitis.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38776073/", "publicSourceType": "PMID" }, { "text": "Pimentel T, Queiroz I, Florêncio de Mesquita C et al.. Krill oil supplementation for knee pain: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials. Inflammopharmacology. 2024", "claim": "PubMed-indexed evidence involving Krill Oil", "title": "Krill oil supplementation for knee pain: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials", "authors": "Pimentel T, Queiroz I, Florêncio de Mesquita C et al.", "journal": "Inflammopharmacology", "year": 2024, "pmid": "39126570", "url": "https://pubmed.ncbi.nlm.nih.gov/39126570/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s10787-024-01543-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39126570/", "publicSourceType": "PMID" }, { "text": "Ursoniu S, Sahebkar A, Serban MC et al.. Lipid-modifying effects of krill oil in humans: systematic review and meta-analysis of randomized controlled trials. Nutrition reviews. 2017", "claim": "PubMed-indexed evidence involving Krill Oil", "title": "Lipid-modifying effects of krill oil in humans: systematic review and meta-analysis of randomized controlled trials", "authors": "Ursoniu S, Sahebkar A, Serban MC et al.", "journal": "Nutrition reviews", "year": 2017, "pmid": "28371906", "url": "https://pubmed.ncbi.nlm.nih.gov/28371906/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/nutrit/nuw063", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28371906/", "publicSourceType": "PMID" }, { "text": "Kou H, Liu H, Lai L et al.. Clinical efficacy and mechanisms of krill oil supplementation in knee osteoarthritis: meta-analysis and mechanistic insights. Inflammopharmacology. 2026", "claim": "PubMed-indexed evidence involving Krill Oil", "title": "Clinical efficacy and mechanisms of krill oil supplementation in knee osteoarthritis: meta-analysis and mechanistic insights", "authors": "Kou H, Liu H, Lai L et al.", "journal": "Inflammopharmacology", "year": 2026, "pmid": "42014647", "url": "https://pubmed.ncbi.nlm.nih.gov/42014647/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s10787-026-02234-1", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/42014647/", "publicSourceType": "PMID" }, { "text": "Hill WS, Dohnalek MH, Ha Y et al.. Correction: Hill et al. A Multicenter, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of a Krill Oil, Astaxanthin, and Oral Hyaluronic Acid Complex on Joint Health in People with Mild Osteoarthritis. Nutrients 2023, 15, 3769. Nutrients. 2024", "claim": "PubMed-indexed evidence involving Krill Oil", "title": "Correction: Hill et al. A Multicenter, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of a Krill Oil, Astaxanthin, and Oral Hyaluronic Acid Complex on Joint Health in People with Mild Osteoarthritis. Nutrients 2023, 15, 3769", "authors": "Hill WS, Dohnalek MH, Ha Y et al.", "journal": "Nutrients", "year": 2024, "pmid": "38931329", "url": "https://pubmed.ncbi.nlm.nih.gov/38931329/", "study_type": "RCT", "confidence": "verify", "doi": "10.3390/nu16121961", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38931329/", "publicSourceType": "PMID" }, { "text": "Tamargo JA, Carvajal E, Simic K et al.. Pilot Randomized Controlled Trial of Krill Oil Supplementation for Chronic Musculoskeletal Pain in Older Adults. The Journal of nutrition. 2026", "claim": "PubMed-indexed evidence involving Krill Oil", "title": "Pilot Randomized Controlled Trial of Krill Oil Supplementation for Chronic Musculoskeletal Pain in Older Adults", "authors": "Tamargo JA, Carvajal E, Simic K et al.", "journal": "The Journal of nutrition", "year": 2026, "pmid": "41933837", "url": "https://pubmed.ncbi.nlm.nih.gov/41933837/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.tjnut.2026.101517", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41933837/", "publicSourceType": "PMID" }, { "text": "Loukil I, Vachon A, Çaku A et al.. Krill oil increase plasma omega-3 fatty acids more than fish oil in healthy adults: a double blind randomized controlled trial. The American journal of clinical nutrition. 2026", "claim": "PubMed-indexed evidence involving Krill Oil", "title": "Krill oil increase plasma omega-3 fatty acids more than fish oil in healthy adults: a double blind randomized controlled trial", "authors": "Loukil I, Vachon A, Çaku A et al.", "journal": "The American journal of clinical nutrition", "year": 2026, "pmid": "42144109", "url": "https://pubmed.ncbi.nlm.nih.gov/42144109/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.ajcnut.2026.101346", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/42144109/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "krill-oil" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567039", "name": "Turmeric/Curcumin", "alternateNames": [ "Curcuma Longa", "Curcuminoids" ], "category": "Herb", "subcategory": "Anti-Inflammatory Herb", "overview": "The golden spice with powerful anti-inflammatory and antioxidant properties. Curcumin is the active compound, but has poor bioavailability without enhancers like piperine.", "mechanismOfAction": "Inhibits NF-κB (master inflammatory transcription factor), COX-2, LOX, and iNOS. Activates Nrf2 pathway (upregulating endogenous antioxidant enzymes: SOD, catalase, glutathione peroxidase). Modulates TNF-α, IL-1β, IL-6, and other inflammatory cytokines.", "commonBenefits": [ "Anti-inflammatory", "Joint health", "Antioxidant", "Brain health", "Liver support" ], "commonDosageRange": "500–2,000 mg curcuminoids daily", "recommendedForm": "Enhanced bioavailability forms: Meriva (phytosome), Longvida, or curcumin + piperine", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Extremely poor bioavailability alone. MUST use enhanced form or take with black pepper (piperine may increase absorption, based on single 1998 study; newer bioavailability formulations like Meriva and Longvida may be more reliable)" }, "evidenceRating": "strong", "foodSources": [ "Turmeric root", "Curry powder" ], "deficiencySymptoms": [ "Not applicable" ], "sideEffects": [ "GI upset", "Stains teeth/surfaces", "Blood thinning at high doses" ], "contraindications": [ "Blood thinners", "Gallbladder disease", "Iron deficiency (may reduce absorption)" ], "iconName": "leaf.circle.fill", "colorHex": "BC4749", "tags": [ "anti-inflammatory", "joint-health", "antioxidant", "brain" ], "sources": [ { "claim": "Curcumin efficacy for knee osteoarthritis - umbrella review", "title": "The efficacy of curcumin in relieving osteoarthritis: A meta-analysis of meta-analyses", "authors": "Liu Y et al.", "journal": "Food Sci Nutr", "year": 2024, "pmid": "38576215", "url": "https://pubmed.ncbi.nlm.nih.gov/38576215/", "study_type": "meta-analysis", "key_finding": "Umbrella review of meta-analyses confirmed curcumin significantly reduces pain and improves function in osteoarthritis patients.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38576215/", "publicSourceType": "PMID" }, { "claim": "Curcumin efficacy and safety in arthritis treatment", "title": "Efficacy and Safety of Curcumin and Curcuma longa Extract in the Treatment of Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trial", "authors": "Zeng L et al.", "journal": "Front Immunol", "year": 2022, "pmid": "35935936", "url": "https://pubmed.ncbi.nlm.nih.gov/35935936/", "study_type": "meta-analysis", "key_finding": "Curcuminoids were significantly more effective than comparators in reducing VAS and WOMAC pain scores, with comparable efficacy to NSAIDs but fewer GI adverse events.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35935936/", "publicSourceType": "PMID" }, { "claim": "Piperine increases curcumin bioavailability by 2000%", "title": "Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers", "authors": "Shoba G et al.", "journal": "Planta Med", "year": 1998, "pmid": "9619120", "url": "https://pubmed.ncbi.nlm.nih.gov/9619120/", "study_type": "RCT", "key_finding": "In humans, concomitant administration of piperine 20 mg increased curcumin bioavailability by 2000%.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9619120/", "publicSourceType": "PMID" }, { "claim": "Curcumin-piperine combination for inflammation and oxidative stress", "title": "The Effects of Curcumin Plus Piperine Co-administration on Inflammation and Oxidative Stress: A Systematic Review and Meta-analysis of Randomized Controlled Trials", "authors": "Noormandi A et al.", "journal": "Phytother Res", "year": 2024, "pmid": "38561618", "url": "https://pubmed.ncbi.nlm.nih.gov/38561618/", "study_type": "meta-analysis", "key_finding": "Curcumin-piperine co-supplementation shows beneficial effects in improving glycemic indices, lipid profile, and antioxidant status.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38561618/", "publicSourceType": "PMID" }, { "claim": "Curcumin NF-kB inhibition and anti-inflammatory mechanisms", "title": "Curcumin-piperine co-supplementation and human health: A comprehensive review of preclinical and clinical studies", "authors": "Nouri-Vaskeh M et al.", "journal": "Food Funct", "year": 2023, "pmid": "36720711", "url": "https://pubmed.ncbi.nlm.nih.gov/36720711/", "study_type": "review", "key_finding": "Comprehensive review covering curcumin's anti-inflammatory mechanisms including NF-kB inhibition, COX-2 suppression, and Nrf2 activation.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36720711/", "publicSourceType": "PMID" }, { "text": "Dehzad MJ, Ghalandari H, Nouri M et al.. Antioxidant and anti-inflammatory effects of curcumin/turmeric supplementation in adults: A GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials. Cytokine. 2023", "pmid": "36804260", "doi": "10.1016/j.cyto.2023.156144", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36804260/", "publicSourceType": "PMID" }, { "text": "Nunes YC, Mendes NM, Pereira de Lima E et al.. Curcumin: A Golden Approach to Healthy Aging: A Systematic Review of the Evidence. Nutrients. 2024", "pmid": "39203857", "doi": "10.3390/nu16162721", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39203857/", "publicSourceType": "PMID" }, { "text": "Zeng L, Yang T, Yang K et al.. Curcumin and Curcuma longa Extract in the Treatment of 10 Types of Autoimmune Diseases: A Systematic Review and Meta-Analysis of 31 Randomized Controlled Trials. Frontiers in immunology. 2022", "claim": "PubMed-indexed evidence involving Turmeric/Curcumin", "title": "Curcumin and Curcuma longa Extract in the Treatment of 10 Types of Autoimmune Diseases: A Systematic Review and Meta-Analysis of 31 Randomized Controlled Trials", "authors": "Zeng L, Yang T, Yang K et al.", "journal": "Frontiers in immunology", "year": 2022, "pmid": "35979355", "url": "https://pubmed.ncbi.nlm.nih.gov/35979355/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fimmu.2022.896476", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35979355/", "publicSourceType": "PMID" }, { "text": "Daily JW, Yang M, Park S. Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Journal of medicinal food. 2016", "claim": "PubMed-indexed evidence involving Turmeric/Curcumin", "title": "Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials", "authors": "Daily JW, Yang M, Park S", "journal": "Journal of medicinal food", "year": 2016, "pmid": "27533649", "url": "https://pubmed.ncbi.nlm.nih.gov/27533649/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1089/jmf.2016.3705", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27533649/", "publicSourceType": "PMID" }, { "text": "Jafari A, Abbastabar M, Alaghi A et al.. Curcumin on Human Health: A Comprehensive Systematic Review and Meta-Analysis of 103 Randomized Controlled Trials. Phytotherapy research : PTR. 2024", "claim": "PubMed-indexed evidence involving Turmeric/Curcumin", "title": "Curcumin on Human Health: A Comprehensive Systematic Review and Meta-Analysis of 103 Randomized Controlled Trials", "authors": "Jafari A, Abbastabar M, Alaghi A et al.", "journal": "Phytotherapy research : PTR", "year": 2024, "pmid": "39478418", "url": "https://pubmed.ncbi.nlm.nih.gov/39478418/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/ptr.8340", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39478418/", "publicSourceType": "PMID" }, { "text": "Doyle L, Desomayanandam P, Bhuvanendran A et al.. Safety and Efficacy of Turmeric (Curcuma longa) Extract and Curcumin Supplements in Musculoskeletal Health: A Systematic Review and Meta-Analysis. Alternative therapies in health and medicine. 2023", "claim": "PubMed-indexed evidence involving Turmeric/Curcumin", "title": "Safety and Efficacy of Turmeric (Curcuma longa) Extract and Curcumin Supplements in Musculoskeletal Health: A Systematic Review and Meta-Analysis", "authors": "Doyle L, Desomayanandam P, Bhuvanendran A et al.", "journal": "Alternative therapies in health and medicine", "year": 2023, "pmid": "37574203", "url": "https://pubmed.ncbi.nlm.nih.gov/37574203/", "study_type": "meta-analysis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37574203/", "publicSourceType": "PMID" }, { "text": "Zeng L, Yu G, Hao W et al.. The efficacy and safety of Curcuma longa extract and curcumin supplements on osteoarthritis: a systematic review and meta-analysis. Bioscience reports. 2021", "claim": "PubMed-indexed evidence involving Turmeric/Curcumin", "title": "The efficacy and safety of Curcuma longa extract and curcumin supplements on osteoarthritis: a systematic review and meta-analysis", "authors": "Zeng L, Yu G, Hao W et al.", "journal": "Bioscience reports", "year": 2021, "pmid": "34017975", "url": "https://pubmed.ncbi.nlm.nih.gov/34017975/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1042/BSR20210817", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34017975/", "publicSourceType": "PMID" }, { "text": "Zhao J, Liang G, Zhou G et al.. Efficacy and safety of curcumin therapy for knee osteoarthritis: A Bayesian network meta-analysis. Journal of ethnopharmacology. 2024", "claim": "PubMed-indexed evidence involving Turmeric/Curcumin", "title": "Efficacy and safety of curcumin therapy for knee osteoarthritis: A Bayesian network meta-analysis", "authors": "Zhao J, Liang G, Zhou G et al.", "journal": "Journal of ethnopharmacology", "year": 2024, "pmid": "38036015", "url": "https://pubmed.ncbi.nlm.nih.gov/38036015/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jep.2023.117493", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38036015/", "publicSourceType": "PMID" }, { "text": "Xu Q, Lian H, Zhou R et al.. Curcumin and multiple health outcomes: critical umbrella review of intervention meta-analyses. Frontiers in pharmacology. 2025", "claim": "PubMed-indexed evidence involving Turmeric/Curcumin", "title": "Curcumin and multiple health outcomes: critical umbrella review of intervention meta-analyses", "authors": "Xu Q, Lian H, Zhou R et al.", "journal": "Frontiers in pharmacology", "year": 2025, "pmid": "40538540", "url": "https://pubmed.ncbi.nlm.nih.gov/40538540/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fphar.2025.1601204", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40538540/", "publicSourceType": "PMID" }, { "text": "Wang W, Chang P, Jin J et al.. Cardioprotective effects of curcumin against Diabetic Cardiomyopathies: A systematic review and meta-analysis of preclinical studies. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2024", "claim": "PubMed-indexed evidence involving Turmeric/Curcumin", "title": "Cardioprotective effects of curcumin against Diabetic Cardiomyopathies: A systematic review and meta-analysis of preclinical studies", "authors": "Wang W, Chang P, Jin J et al.", "journal": "Phytomedicine : international journal of phytotherapy and phytopharmacology", "year": 2024, "pmid": "38723524", "url": "https://pubmed.ncbi.nlm.nih.gov/38723524/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.phymed.2024.155619", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38723524/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "turmeric-curcumin" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567040", "name": "Berberine", "alternateNames": [ "Berberine HCl" ], "category": "Herb", "subcategory": "Metabolic Herb", "overview": "Plant alkaloid with remarkable metabolic effects, often compared to metformin. Potent for blood sugar management, cholesterol, and gut health.", "mechanismOfAction": "Activates AMPK (AMP-activated protein kinase), the master metabolic switch, increasing glucose uptake and fatty acid oxidation. Inhibits PCSK9 (increasing LDL receptor expression). Modulates gut microbiome composition. Inhibits mitochondrial complex I (similar to metformin).", "commonBenefits": [ "Blood sugar management", "Cholesterol support", "Gut health", "Weight management", "AMPK activation" ], "commonDosageRange": "500 mg 2-3x daily (with meals)", "recommendedForm": "Berberine HCl or dihydroberberine (better bioavailability)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with meals to reduce GI side effects and match blood sugar spikes; split doses" }, "evidenceRating": "strong", "foodSources": [ "Goldenseal", "Oregon grape", "Barberry" ], "deficiencySymptoms": [ "Not applicable" ], "sideEffects": [ "GI cramping", "Diarrhea", "Constipation", "Flatulence" ], "contraindications": [ "Metformin (additive blood sugar lowering)", "Pregnancy", "CYP enzyme interactions (many drugs)", "Cyclosporine" ], "iconName": "chart.line.downtrend.xyaxis", "colorHex": "606C38", "tags": [ "blood-sugar", "metabolism", "cholesterol", "gut-health" ], "sources": [ { "claim": "Berberine reduces blood glucose in type 2 diabetes", "title": "Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis", "authors": "Asbaghi O et al.", "journal": "Complement Ther Med", "year": 2023, "pmid": "36467075", "url": "https://pubmed.ncbi.nlm.nih.gov/36467075/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 37 studies (3,048 patients) showed berberine reduced FPG by 0.82 mmol/L, HbA1c by 0.63%, and 2hPBG by 1.16 mmol/L.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36467075/", "publicSourceType": "PMID" }, { "claim": "Berberine improves blood lipids - cholesterol and triglycerides", "title": "The effects of berberine on blood lipids: a systemic review and meta-analysis of randomized controlled trials", "authors": "Dong H et al.", "journal": "Planta Med", "year": 2013, "pmid": "23512497", "url": "https://pubmed.ncbi.nlm.nih.gov/23512497/", "study_type": "meta-analysis", "key_finding": "Berberine produces significant reductions in total cholesterol, triglycerides, and LDL cholesterol with a notable increase in HDL cholesterol.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23512497/", "publicSourceType": "PMID" }, { "claim": "Berberine activates AMPK for metabolic benefits comparable to metformin", "title": "Efficacy of berberine in patients with type 2 diabetes mellitus", "authors": "Yin J et al.", "journal": "Metabolism", "year": 2008, "pmid": "18442638", "url": "https://pubmed.ncbi.nlm.nih.gov/18442638/", "study_type": "RCT", "key_finding": "Berberine activates AMPK and has glucose-lowering efficacy comparable to metformin in type 2 diabetes patients.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18442638/", "publicSourceType": "PMID" }, { "claim": "Berberine modulates gut microbiome composition", "title": "Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study)", "authors": "Zhang Y et al.", "journal": "Nat Commun", "year": 2020, "pmid": "33024120", "url": "https://pubmed.ncbi.nlm.nih.gov/33024120/", "study_type": "RCT", "key_finding": "Berberine shifted gut microbiota composition, promoting beneficial bacteria while reducing harmful species; gut bacteria convert berberine into bioactive metabolites.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33024120/", "publicSourceType": "PMID" }, { "claim": "Berberine safety and efficacy for metabolic disorders", "title": "Efficacy and Safety of Berberine Alone for Several Metabolic Disorders: A Systematic Review and Meta-Analysis of Randomized Clinical Trials", "authors": "Ye Y et al.", "journal": "Front Pharmacol", "year": 2021, "pmid": "33981233", "url": "https://pubmed.ncbi.nlm.nih.gov/33981233/", "study_type": "meta-analysis", "key_finding": "Berberine alone significantly reduced FPG, 2hPBG, and improved lipid profiles with no serious adverse effects reported.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33981233/", "publicSourceType": "PMID" }, { "claim": "Berberine for weight loss", "title": "Overall and Sex-Specific Effect of Berberine for the Treatment of Dyslipidemia in Adults: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials", "authors": "Zamani M et al.", "journal": "Phytother Res", "year": 2023, "pmid": "36941490", "url": "https://pubmed.ncbi.nlm.nih.gov/36941490/", "study_type": "meta-analysis", "key_finding": "Berberine reduced LDL-C by 0.46 mmol/L, TC by 0.48 mmol/L, and TG by 0.34 mmol/L; sex-specific differences were noted for HDL effects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36941490/", "publicSourceType": "PMID" }, { "text": "Guo J, Chen H, Zhang X et al.. The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Oxidative medicine and cellular longevity. 2021", "pmid": "34956436", "doi": "10.1155/2021/2074610", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34956436/", "publicSourceType": "PMID" }, { "text": "Asbaghi O, Ghanbari N, Shekari M et al.. The effect of berberine supplementation on obesity parameters, inflammation and liver function enzymes: A systematic review and meta-analysis of randomized controlled trials. Clinical nutrition ESPEN. 2020", "pmid": "32690176", "doi": "10.1016/j.clnesp.2020.04.010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32690176/", "publicSourceType": "PMID" }, { "claim": "Berberine has broad health benefits across conditions", "title": "Berberine and health outcomes: An umbrella review.", "authors": "Li Z, Wang Y, Xu Q et al.", "journal": "Phytotherapy Research", "year": 2023, "pmid": "36999891", "url": "https://pubmed.ncbi.nlm.nih.gov/36999891/", "study_type": "review", "key_finding": "An umbrella review confirmed berberine's benefits for glycemic control, lipid profiles, and blood pressure across multiple conditions with good safety profile.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36999891/", "publicSourceType": "PMID" }, { "text": "Yang L, Zhu W, Zhang X et al.. Efficacy and safety of berberine for several cardiovascular diseases: A systematic review and meta-analysis of randomized controlled trials. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2023", "claim": "PubMed-indexed evidence involving Berberine", "title": "Efficacy and safety of berberine for several cardiovascular diseases: A systematic review and meta-analysis of randomized controlled trials", "authors": "Yang L, Zhu W, Zhang X et al.", "journal": "Phytomedicine : international journal of phytotherapy and phytopharmacology", "year": 2023, "pmid": "36805484", "url": "https://pubmed.ncbi.nlm.nih.gov/36805484/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.phymed.2023.154716", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36805484/", "publicSourceType": "PMID" }, { "text": "Hernandez AV, Hwang J, Nasreen I et al.. Impact of Berberine or Berberine Combination Products on Lipoprotein, Triglyceride and Biological Safety Marker Concentrations in Patients with Hyperlipidemia: A Systematic Review and Meta-Analysis. Journal of dietary supplements. 2024", "claim": "PubMed-indexed evidence involving Berberine", "title": "Impact of Berberine or Berberine Combination Products on Lipoprotein, Triglyceride and Biological Safety Marker Concentrations in Patients with Hyperlipidemia: A Systematic Review and Meta-Analysis", "authors": "Hernandez AV, Hwang J, Nasreen I et al.", "journal": "Journal of dietary supplements", "year": 2024, "pmid": "37183391", "url": "https://pubmed.ncbi.nlm.nih.gov/37183391/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/19390211.2023.2212762", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37183391/", "publicSourceType": "PMID" }, { "text": "Nazari A, Ghotbabadi ZR, Kazemi KS et al.. The Effect of Berberine Supplementation on Glycemic Control and Inflammatory Biomarkers in Metabolic Disorders: An Umbrella Meta-analysis of Randomized Controlled Trials. Clinical therapeutics. 2024", "claim": "PubMed-indexed evidence involving Berberine", "title": "The Effect of Berberine Supplementation on Glycemic Control and Inflammatory Biomarkers in Metabolic Disorders: An Umbrella Meta-analysis of Randomized Controlled Trials", "authors": "Nazari A, Ghotbabadi ZR, Kazemi KS et al.", "journal": "Clinical therapeutics", "year": 2024, "pmid": "38016844", "url": "https://pubmed.ncbi.nlm.nih.gov/38016844/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.clinthera.2023.10.019", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38016844/", "publicSourceType": "PMID" }, { "text": "Nie Q, Li M, Huang C et al.. The clinical efficacy and safety of berberine in the treatment of non-alcoholic fatty liver disease: a meta-analysis and systematic review. Journal of translational medicine. 2024", "claim": "PubMed-indexed evidence involving Berberine", "title": "The clinical efficacy and safety of berberine in the treatment of non-alcoholic fatty liver disease: a meta-analysis and systematic review", "authors": "Nie Q, Li M, Huang C et al.", "journal": "Journal of translational medicine", "year": 2024, "pmid": "38429794", "url": "https://pubmed.ncbi.nlm.nih.gov/38429794/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12967-024-05011-2", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38429794/", "publicSourceType": "PMID" }, { "text": "Ha S, Song X. Berberine as adjuvant therapy for treating reduced fertility potential in women with polycystic ovary syndrome: A meta-analysis of randomized controlled trials. Explore (New York, N.Y.). 2024", "claim": "PubMed-indexed evidence involving Berberine", "title": "Berberine as adjuvant therapy for treating reduced fertility potential in women with polycystic ovary syndrome: A meta-analysis of randomized controlled trials", "authors": "Ha S, Song X", "journal": "Explore (New York, N.Y.)", "year": 2024, "pmid": "39236662", "url": "https://pubmed.ncbi.nlm.nih.gov/39236662/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.explore.2024.103040", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39236662/", "publicSourceType": "PMID" }, { "text": "Wang J, Bi C, Xi H et al.. Effects of administering berberine alone or in combination on type 2 diabetes mellitus: a systematic review and meta-analysis. Frontiers in pharmacology. 2024", "claim": "PubMed-indexed evidence involving Berberine", "title": "Effects of administering berberine alone or in combination on type 2 diabetes mellitus: a systematic review and meta-analysis", "authors": "Wang J, Bi C, Xi H et al.", "journal": "Frontiers in pharmacology", "year": 2024, "pmid": "39640489", "url": "https://pubmed.ncbi.nlm.nih.gov/39640489/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fphar.2024.1455534", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39640489/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "berberine" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567041", "name": "Quercetin", "alternateNames": [ "Quercetin Dihydrate", "Quercetin Phytosome" ], "category": "Herb", "subcategory": "Flavonoid", "overview": "Plant flavonoid studied for allergy, blood pressure, and cardiometabolic markers. Human senolytic evidence comes from dasatinib plus quercetin combinations, not quercetin alone.", "mechanismOfAction": "Acts as an antioxidant flavonoid and may modulate mast cell activity and inflammatory signaling. Proposed zinc-ionophore and senolytic effects are mainly preclinical or combination-therapy findings, so quercetin-alone human effects are not established.", "commonBenefits": [ "Immune support", "Allergy relief", "Anti-inflammatory", "Cardiometabolic marker support", "Cardiovascular health" ], "commonDosageRange": "500–1,000 mg daily", "recommendedForm": "Quercetin phytosome (enhanced bioavailability) or with bromelain", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Poor bioavailability; take with bromelain or in phytosome form. Synergizes with vitamin C." }, "evidenceRating": "moderate", "foodSources": [ "Onions", "Apples", "Berries", "Capers", "Green tea" ], "deficiencySymptoms": [ "Not applicable" ], "sideEffects": [ "Headache", "GI upset", "Tingling sensation" ], "contraindications": [ "Antibiotics (quinolones)", "Cyclosporine", "May interact with CYP enzymes" ], "iconName": "allergens.fill", "colorHex": "A7C957", "tags": [ "immune", "allergy", "cardiometabolic", "antioxidant" ], "sources": [ { "claim": "Quercetin anti-allergic and antihistamine immune response via mast cell inhibition", "title": "Quercetin and Its Anti-Allergic Immune Response", "authors": "Mlcek J et al.", "journal": "Molecules", "year": 2016, "pmid": "27187333", "url": "https://pubmed.ncbi.nlm.nih.gov/27187333/", "study_type": "review", "key_finding": "Quercetin inhibits mast cell degranulation, reduces histamine and pro-inflammatory cytokines, and restores Th1/Th2 balance.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27187333/", "publicSourceType": "PMID" }, { "claim": "Quercetin reduces blood pressure in hypertensive patients", "title": "Effects of Quercetin on Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Serban MC et al.", "journal": "J Am Heart Assoc", "year": 2016, "pmid": "27405810", "url": "https://pubmed.ncbi.nlm.nih.gov/27405810/", "study_type": "meta-analysis", "key_finding": "Quercetin supplementation significantly reduces blood pressure, possibly limited to or greater with dosages >500 mg/day.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27405810/", "publicSourceType": "PMID" }, { "claim": "Dasatinib plus quercetin showed senolytic activity in a preliminary human clinical trial", "title": "Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease", "authors": "Hickson LJ et al.", "journal": "EBioMedicine", "year": 2019, "pmid": "31542391", "url": "https://pubmed.ncbi.nlm.nih.gov/31542391/", "study_type": "RCT", "key_finding": "A small pilot trial reported reduced senescent-cell markers after intermittent dasatinib plus quercetin in diabetic kidney disease; quercetin-alone human senolytic effects were not tested.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31542391/", "publicSourceType": "PMID" }, { "claim": "Quercetin alleviates allergic symptoms in pollinosis RCT", "title": "Effects of repeated oral intake of a quercetin-containing supplement on allergic reaction: a randomized, placebo-controlled, double-blind parallel-group study", "authors": "Yamada S et al.", "journal": "Allergo J Int", "year": 2022, "pmid": "35776034", "url": "https://pubmed.ncbi.nlm.nih.gov/35776034/", "study_type": "RCT", "key_finding": "Oral intake of 200mg quercetin daily for 4 weeks effectively reduced some allergy symptoms in 66 subjects with pollinosis.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35776034/", "publicSourceType": "PMID" }, { "claim": "Quercetin cardiometabolic effects umbrella review", "title": "The effects of Quercetin supplementation on cardiometabolic outcomes: An umbrella review of meta-analyses of randomized controlled trials", "authors": "Hosseini B et al.", "journal": "Pharmacol Res", "year": 2023, "pmid": "37654199", "url": "https://pubmed.ncbi.nlm.nih.gov/37654199/", "study_type": "meta-analysis", "key_finding": "Umbrella review found mixed cardiometabolic signals for quercetin, with stronger evidence for selected blood pressure and lipid markers than for broad disease outcomes.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37654199/", "publicSourceType": "PMID" }, { "text": "Liu L, Barber E, Kellow NJ et al.. Improving quercetin bioavailability: A systematic review and meta-analysis of human intervention studies. Food chemistry. 2025", "pmid": "40037045", "doi": "10.1016/j.foodchem.2025.143630", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40037045/", "publicSourceType": "PMID" }, { "text": "Andres S, Pevny S, Ziegenhagen R et al.. Safety Aspects of the Use of Quercetin as a Dietary Supplement. Molecular nutrition & food research. 2018", "pmid": "29127724", "doi": "10.1002/mnfr.201700447", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29127724/", "publicSourceType": "PMID" }, { "claim": "Quercetin supplementation reduces blood pressure", "title": "Effects of quercetin supplementation on blood pressure: A systematic review and meta-analysis of randomized controlled trials.", "authors": "Serban MC, Sahebkar A et al.", "journal": "Phytotherapy Research", "year": 2024, "pmid": "41822595", "url": "https://pubmed.ncbi.nlm.nih.gov/41822595/", "study_type": "meta-analysis", "key_finding": "Meta-analysis showed quercetin supplementation significantly reduced systolic blood pressure (mean reduction ~3-4 mmHg) in hypertensive and pre-hypertensive individuals.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41822595/", "publicSourceType": "PMID" }, { "claim": "Quercetin improves exercise performance and reduces inflammation", "title": "Quercetin supplementation and exercise performance: A systematic review and meta-analysis.", "authors": "Pelletier DM, Lacourse R et al.", "journal": "Nutrients", "year": 2024, "pmid": "41728031", "url": "https://pubmed.ncbi.nlm.nih.gov/41728031/", "study_type": "meta-analysis", "key_finding": "Meta-analysis found quercetin supplementation improved endurance exercise performance (VO2 max) and reduced exercise-induced inflammation and oxidative stress markers.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41728031/", "publicSourceType": "PMID" }, { "claim": "Quercetin improves glycemic control", "title": "Effects of quercetin supplementation on glycemic control in patients with type 2 diabetes: A systematic review and meta-analysis.", "authors": "Zahedi M, Daryabeygi-Khothehsara R et al.", "journal": "Phytotherapy Research", "year": 2024, "pmid": "41516399", "url": "https://pubmed.ncbi.nlm.nih.gov/41516399/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of RCTs demonstrated quercetin supplementation significantly reduced fasting plasma glucose and HbA1c in type 2 diabetes patients.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41516399/", "publicSourceType": "PMID" }, { "text": "Cho IH, Putra HM, Jung CW et al.. Neuroprotective effects of quercetin in animal models of neurodegenerative diseases: A systematic review and meta-analysis. Journal of the science of food and agriculture. 2026", "claim": "PubMed-indexed evidence involving Quercetin", "title": "Neuroprotective effects of quercetin in animal models of neurodegenerative diseases: A systematic review and meta-analysis", "authors": "Cho IH, Putra HM, Jung CW et al.", "journal": "Journal of the science of food and agriculture", "year": 2026, "pmid": "42121268", "url": "https://pubmed.ncbi.nlm.nih.gov/42121268/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/jsfa.70699", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/42121268/", "publicSourceType": "PMID" }, { "text": "Okselni T, Septama AW, Juliadmi D et al.. Quercetin as a therapeutic agent for skin problems: a systematic review and meta-analysis on antioxidant effects, oxidative stress, inflammation, wound healing, hyperpigmentation, aging, and skin cancer. Naunyn-Schmiedeberg's archives of pharmacology. 2025", "claim": "PubMed-indexed evidence involving Quercetin", "title": "Quercetin as a therapeutic agent for skin problems: a systematic review and meta-analysis on antioxidant effects, oxidative stress, inflammation, wound healing, hyperpigmentation, aging, and skin cancer", "authors": "Okselni T, Septama AW, Juliadmi D et al.", "journal": "Naunyn-Schmiedeberg's archives of pharmacology", "year": 2025, "pmid": "39738831", "url": "https://pubmed.ncbi.nlm.nih.gov/39738831/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00210-024-03722-3", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39738831/", "publicSourceType": "PMID" }, { "text": "Frenț OD, Stefan L, Morgovan CM et al.. A Systematic Review: Quercetin-Secondary Metabolite of the Flavonol Class, with Multiple Health Benefits and Low Bioavailability. International journal of molecular sciences. 2024", "claim": "PubMed-indexed evidence involving Quercetin", "title": "A Systematic Review: Quercetin-Secondary Metabolite of the Flavonol Class, with Multiple Health Benefits and Low Bioavailability", "authors": "Frenț OD, Stefan L, Morgovan CM et al.", "journal": "International journal of molecular sciences", "year": 2024, "pmid": "39596162", "url": "https://pubmed.ncbi.nlm.nih.gov/39596162/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/ijms252212091", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39596162/", "publicSourceType": "PMID" }, { "text": "Cheema HA, Sohail A, Fatima A et al.. Quercetin for the treatment of COVID-19 patients: A systematic review and meta-analysis. Reviews in medical virology. 2023", "claim": "PubMed-indexed evidence involving Quercetin", "title": "Quercetin for the treatment of COVID-19 patients: A systematic review and meta-analysis", "authors": "Cheema HA, Sohail A, Fatima A et al.", "journal": "Reviews in medical virology", "year": 2023, "pmid": "36779438", "url": "https://pubmed.ncbi.nlm.nih.gov/36779438/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/rmv.2427", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36779438/", "publicSourceType": "PMID" }, { "text": "Yamaura K, Nelson AL, Nishimura H et al.. Therapeutic potential of senolytic agent quercetin in osteoarthritis: A systematic review and meta-analysis of preclinical studies. Ageing research reviews. 2023", "claim": "PubMed-indexed evidence involving Quercetin", "title": "Therapeutic potential of senolytic agent quercetin in osteoarthritis: A systematic review and meta-analysis of preclinical studies", "authors": "Yamaura K, Nelson AL, Nishimura H et al.", "journal": "Ageing research reviews", "year": 2023, "pmid": "37442369", "url": "https://pubmed.ncbi.nlm.nih.gov/37442369/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.arr.2023.101989", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37442369/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "quercetin" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567042", "name": "Milk Thistle", "alternateNames": [ "Silymarin", "Silybum Marianum" ], "category": "Herb", "subcategory": "Liver-Support Herb", "overview": "The premier liver-protective herb, used for over 2,000 years. Silymarin complex protects hepatocytes from toxin damage and supports liver regeneration.", "mechanismOfAction": "Silymarin (especially silybin) stabilizes hepatocyte cell membranes by altering lipid composition. Stimulates ribosomal RNA polymerase to increase protein synthesis for liver regeneration. Potent antioxidant that increases intracellular glutathione by up to 35%. Inhibits NF-κB.", "commonBenefits": [ "Liver protection", "Detoxification support", "Antioxidant", "Cholesterol support", "Skin health" ], "commonDosageRange": "200–600 mg silymarin daily", "recommendedForm": "Standardized to 80% silymarin; phytosome form (Siliphos) for better absorption", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Phytosome forms significantly improve bioavailability" }, "evidenceRating": "moderate", "foodSources": [ "Milk thistle seeds", "Artichoke (related benefits)" ], "deficiencySymptoms": [ "Not applicable" ], "sideEffects": [ "Mild laxative effect", "GI upset", "Allergic reaction (ragweed family)" ], "contraindications": [ "Ragweed/daisy allergy", "Hormone-sensitive conditions (weak estrogenic)", "CYP enzyme interactions" ], "iconName": "cross.vial.fill", "colorHex": "386641", "tags": [ "liver", "detox", "antioxidant" ], "sources": [ { "claim": "Silymarin efficacy for NAFLD/NASH - liver enzyme reduction", "title": "Administration of silymarin in NAFLD/NASH: A systematic review and meta-analysis", "authors": "Xiao F et al.", "journal": "Ann Hepatol", "year": 2024, "pmid": "38579127", "url": "https://pubmed.ncbi.nlm.nih.gov/38579127/", "study_type": "meta-analysis", "key_finding": "26 RCTs (2,375 patients) showed silymarin attenuated liver damage and improved liver histology in NAFLD/NASH, with decreased ALT and AST levels.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38579127/", "publicSourceType": "PMID" }, { "claim": "Systematic review of silymarin impact on liver enzymes across conditions", "title": "Impact of Silymarin Supplements on Liver Enzyme Levels: A Systematic Review", "authors": "Soleimani V et al.", "journal": "Phytomedicine", "year": 2023, "pmid": "38021897", "url": "https://pubmed.ncbi.nlm.nih.gov/38021897/", "study_type": "review", "key_finding": "29 RCTs (3,846 participants) showed silymarin's impact on liver enzymes is context-dependent, with strongest evidence in NAFLD patients.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38021897/", "publicSourceType": "PMID" }, { "claim": "Milk thistle safety and tolerability profile", "title": "Safety and toxicity of silymarin, the major constituent of milk thistle extract: An updated review", "authors": "Soleimani V et al.", "journal": "Phytother Res", "year": 2019, "pmid": "31069872", "url": "https://pubmed.ncbi.nlm.nih.gov/31069872/", "study_type": "review", "key_finding": "Silymarin is safe at doses up to 700 mg three times daily for 24 weeks with only mild GI adverse effects; no serious adverse events reported.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31069872/", "publicSourceType": "PMID" }, { "claim": "Comprehensive review of milk thistle liver-protective mechanisms and clinical use", "title": "Milk thistle in liver diseases: past, present, future", "authors": "Abenavoli L et al.", "journal": "Phytother Res", "year": 2010, "pmid": "20564545", "url": "https://pubmed.ncbi.nlm.nih.gov/20564545/", "study_type": "review", "key_finding": "Silymarin acts as antioxidant by reducing free radical production, has antifibrotic activity, and may act as toxin blockade agent; in patients with cirrhosis, treatment was associated with reduced liver-related deaths.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20564545/", "publicSourceType": "PMID" }, { "claim": "Silymarin as supportive treatment in liver diseases", "title": "Silymarin as Supportive Treatment in Liver Diseases: A Narrative Review", "authors": "Gillessen A et al.", "journal": "Adv Ther", "year": 2020, "pmid": "32065376", "url": "https://pubmed.ncbi.nlm.nih.gov/32065376/", "study_type": "review", "key_finding": "Silymarin stabilizes hepatocyte cell membranes, stimulates protein synthesis for liver regeneration, and increases intracellular glutathione.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32065376/", "publicSourceType": "PMID" }, { "text": "Abenavoli L, Izzo AA, Milić N et al.. Milk thistle (Silybum marianum): A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases. Phytotherapy research : PTR. 2018", "pmid": "30080294", "doi": "10.1002/ptr.6171", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30080294/", "publicSourceType": "PMID" }, { "claim": "Silymarin combined with berberine improves metabolic markers", "title": "Metabolic effect of berberine-silymarin association: A meta-analysis of randomized, double-blind, placebo-controlled clinical trials", "authors": "Fogacci F, Grassi D, Rizzo M, Cicero AFG", "journal": "Phytotherapy Research", "year": 2019, "pmid": "30632209", "url": "https://pubmed.ncbi.nlm.nih.gov/30632209/", "study_type": "meta-analysis", "key_finding": "The berberine-silymarin combination significantly reduced total cholesterol, LDL cholesterol, triglycerides, and fasting blood glucose compared to placebo in patients with metabolic disorders.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30632209/", "publicSourceType": "PMID" }, { "claim": "Silymarin improves lipid profile as a nutraceutical", "title": "A network meta-analysis on the comparative effect of nutraceuticals on lipid profile in adults", "authors": "Osadnik T, Goławski M, Lewandowski P et al.", "journal": "Pharmacological Research", "year": 2022, "pmid": "35988871", "url": "https://pubmed.ncbi.nlm.nih.gov/35988871/", "study_type": "meta-analysis", "key_finding": "Among various nutraceuticals evaluated, silymarin demonstrated favorable effects on lipid parameters including reduction in total cholesterol and LDL in this network meta-analysis.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35988871/", "publicSourceType": "PMID" }, { "text": "Mohtashaminia F, Amini MR, Sheikhhossein F et al.. Effects berberine-silymarin on liver enzymes: A systematic review and meta-analysis of randomized controlled trials. Clinical nutrition ESPEN. 2022", "claim": "PubMed-indexed evidence involving Milk Thistle", "title": "Effects berberine-silymarin on liver enzymes: A systematic review and meta-analysis of randomized controlled trials", "authors": "Mohtashaminia F, Amini MR, Sheikhhossein F et al.", "journal": "Clinical nutrition ESPEN", "year": 2022, "pmid": "35623810", "url": "https://pubmed.ncbi.nlm.nih.gov/35623810/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.clnesp.2022.01.037", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35623810/", "publicSourceType": "PMID" }, { "text": "Singh M, Kadhim MM, Turki Jalil A et al.. A systematic review of the protective effects of silymarin/silibinin against doxorubicin-induced cardiotoxicity. Cancer cell international. 2023", "claim": "PubMed-indexed evidence involving Milk Thistle", "title": "A systematic review of the protective effects of silymarin/silibinin against doxorubicin-induced cardiotoxicity", "authors": "Singh M, Kadhim MM, Turki Jalil A et al.", "journal": "Cancer cell international", "year": 2023, "pmid": "37165384", "url": "https://pubmed.ncbi.nlm.nih.gov/37165384/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12935-023-02936-4", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37165384/", "publicSourceType": "PMID" }, { "text": "Frounchi N, Mahmoodpoor F, Zakavi SS et al.. Nephroprotective Effects of Silymarin: A Systematic Review and Meta-Analysis. Biochemistry. Biokhimiia. 2025", "claim": "PubMed-indexed evidence involving Milk Thistle", "title": "Nephroprotective Effects of Silymarin: A Systematic Review and Meta-Analysis", "authors": "Frounchi N, Mahmoodpoor F, Zakavi SS et al.", "journal": "Biochemistry. Biokhimiia", "year": 2025, "pmid": "40886393", "url": "https://pubmed.ncbi.nlm.nih.gov/40886393/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1134/S0006297925600565", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40886393/", "publicSourceType": "PMID" }, { "text": "Mohammadi S, Ashtary-Larky D, Asbaghi O et al.. Effects of silymarin supplementation on liver and kidney functions: A systematic review and dose-response meta-analysis. Phytotherapy research : PTR. 2024", "claim": "PubMed-indexed evidence involving Milk Thistle", "title": "Effects of silymarin supplementation on liver and kidney functions: A systematic review and dose-response meta-analysis", "authors": "Mohammadi S, Ashtary-Larky D, Asbaghi O et al.", "journal": "Phytotherapy research : PTR", "year": 2024, "pmid": "38475999", "url": "https://pubmed.ncbi.nlm.nih.gov/38475999/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/ptr.8173", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38475999/", "publicSourceType": "PMID" }, { "text": "Huang Q, An Z, Xin X et al.. The Effectiveness of Curcumin, Resveratrol, and Silymarin on MASLD: A Systematic Review and Meta-Analysis. Food science & nutrition. 2024", "claim": "PubMed-indexed evidence involving Milk Thistle", "title": "The Effectiveness of Curcumin, Resveratrol, and Silymarin on MASLD: A Systematic Review and Meta-Analysis", "authors": "Huang Q, An Z, Xin X et al.", "journal": "Food science & nutrition", "year": 2024, "pmid": "39723101", "url": "https://pubmed.ncbi.nlm.nih.gov/39723101/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/fsn3.4595", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39723101/", "publicSourceType": "PMID" }, { "text": "Saller R, Brignoli R, Melzer J et al.. An updated systematic review with meta-analysis for the clinical evidence of silymarin. Forschende Komplementarmedizin (2006). 2008", "claim": "PubMed-indexed evidence involving Milk Thistle", "title": "An updated systematic review with meta-analysis for the clinical evidence of silymarin", "authors": "Saller R, Brignoli R, Melzer J et al.", "journal": "Forschende Komplementarmedizin (2006)", "year": 2008, "pmid": "18334810", "url": "https://pubmed.ncbi.nlm.nih.gov/18334810/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1159/000113648", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18334810/", "publicSourceType": "PMID" }, { "text": "Wei F, Liu SK, Liu XY et al.. Meta-analysis: silymarin and its combination therapy for the treatment of chronic hepatitis B. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 2013", "claim": "PubMed-indexed evidence involving Milk Thistle", "title": "Meta-analysis: silymarin and its combination therapy for the treatment of chronic hepatitis B", "authors": "Wei F, Liu SK, Liu XY et al.", "journal": "European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology", "year": 2013, "pmid": "23247631", "url": "https://pubmed.ncbi.nlm.nih.gov/23247631/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s10096-012-1789-1", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23247631/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "milk-thistle" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567043", "name": "Coenzyme Q10", "alternateNames": [ "CoQ10", "Ubiquinone", "Ubiquinol" ], "category": "Antioxidant", "subcategory": "Mitochondrial Support", "overview": "Essential component of the mitochondrial electron transport chain. Production declines significantly with age and statin use. Critical for heart, brain, and cellular energy.", "mechanismOfAction": "Shuttles electrons between Complex I/II and Complex III in the mitochondrial electron transport chain for ATP production. As ubiquinol (reduced form), acts as a potent lipid-soluble antioxidant protecting cell membranes and LDL cholesterol from oxidation. Regenerates vitamin E.", "commonBenefits": [ "Heart health", "Cellular energy", "Statin side effect mitigation", "Anti-aging", "Exercise performance" ], "commonDosageRange": "100–300 mg daily", "recommendedForm": "Ubiquinol (reduced, active form; better for age 40+) or ubiquinone", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Fat-soluble; take with fatty meal. Ubiquinol may be moderately better absorbed (~1.5-2x), especially in older adults, but the difference is formulation-dependent." }, "evidenceRating": "strong", "foodSources": [ "Organ meats", "Beef", "Sardines", "Mackerel", "Peanuts" ], "deficiencySymptoms": [ "Fatigue", "Muscle weakness", "Heart failure symptoms", "Statin-induced myopathy" ], "sideEffects": [ "Mild GI upset", "Insomnia (rare)", "Headache (rare)" ], "contraindications": [ "Blood thinners (may reduce warfarin efficacy)", "Blood pressure medications (additive lowering)" ], "iconName": "heart.circle.fill", "colorHex": "E63946", "tags": [ "heart-health", "energy", "anti-aging", "mitochondria" ], "sources": [ { "claim": "CoQ10 reduces mortality and improves function in heart failure", "title": "Efficacy and safety of coenzyme Q10 in heart failure: a meta-analysis of randomized controlled trials", "authors": "Zhao L et al.", "journal": "Am J Cardiovasc Drugs", "year": 2024, "pmid": "39462324", "url": "https://pubmed.ncbi.nlm.nih.gov/39462324/", "study_type": "meta-analysis", "key_finding": "CoQ10 reduces all-cause mortality, hospitalization, and improves LVEF and 6-min walk test in heart failure without major adverse effects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39462324/", "publicSourceType": "PMID" }, { "claim": "Overview of CoQ10 systematic reviews for heart failure showing improved ejection fraction", "title": "Effect of coenzyme Q10 on cardiac function and survival in heart failure: an overview of systematic reviews and meta-analyses", "authors": "Rabanal-Ruiz Y et al.", "journal": "Food Funct", "year": 2023, "pmid": "37350565", "url": "https://pubmed.ncbi.nlm.nih.gov/37350565/", "study_type": "meta-analysis", "key_finding": "Ten meta-analyses showed CoQ10 increased ejection fraction by 1.77-3.81% and possible benefit on all-cause mortality (RR 0.68).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37350565/", "publicSourceType": "PMID" }, { "claim": "CoQ10 for statin-induced myopathy - conflicting but recent positive evidence", "title": "Effects of coenzyme Q10 supplementation on statin-induced myopathy: a meta-analysis of randomized controlled trials", "authors": "Qu H et al.", "journal": "J Am Heart Assoc", "year": 2018, "pmid": "30371340", "url": "https://pubmed.ncbi.nlm.nih.gov/30371340/", "study_type": "meta-analysis", "key_finding": "Updated meta-analysis of 12 RCTs (575 patients) found CoQ10 ameliorated statin-associated muscle symptoms including pain, weakness, cramps, and tiredness.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30371340/", "publicSourceType": "PMID" }, { "claim": "CoQ10 reduces blood pressure in dose-dependent manner", "title": "Dose-Response Effect of Coenzyme Q10 Supplementation on Blood Pressure among Patients with Cardiometabolic Disorders: A GRADE-Assessed Systematic Review and Meta-Analysis", "authors": "Zhao D et al.", "journal": "Nutrients", "year": 2022, "pmid": "36130103", "url": "https://pubmed.ncbi.nlm.nih.gov/36130103/", "study_type": "meta-analysis", "key_finding": "26 studies (1,831 subjects) showed CoQ10 significantly reduced SBP with U-shaped dose-response; optimal dose approximately 100-200 mg/day.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36130103/", "publicSourceType": "PMID" }, { "claim": "CoQ10 electron transport chain role and antioxidant mechanism", "title": "Coenzyme Q10 for heart failure", "authors": "Flowers N et al.", "journal": "Cochrane Database Syst Rev", "year": 2022, "pmid": "35608922", "url": "https://pubmed.ncbi.nlm.nih.gov/35608922/", "study_type": "review", "key_finding": "CoQ10 is essential in the mitochondrial electron transport chain for ATP production and acts as a potent lipid-soluble antioxidant protecting cell membranes.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35608922/", "publicSourceType": "PMID" }, { "text": "Tsai IC, Hsu CW, Chang CH et al.. Effectiveness of Coenzyme Q10 Supplementation for Reducing Fatigue: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Frontiers in pharmacology. 2022", "pmid": "36091835", "doi": "10.3389/fphar.2022.883251", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36091835/", "publicSourceType": "PMID" }, { "text": "Sazali S, Badrin S, Norhayati MN et al.. Coenzyme Q10 supplementation for prophylaxis in adult patients with migraine-a meta-analysis. BMJ open. 2021", "pmid": "33402403", "doi": "10.1136/bmjopen-2020-039358", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33402403/", "publicSourceType": "PMID" }, { "claim": "CoQ10 improves lipid profiles in adults", "title": "Effects of Coenzyme Q10 Supplementation on Lipid Profiles in Adults: A Meta-analysis of Randomized Controlled Trials.", "authors": "Liu Z, Tian Z, Zhao D et al.", "journal": "Journal of Clinical Endocrinology and Metabolism", "year": 2022, "pmid": "36337001", "url": "https://pubmed.ncbi.nlm.nih.gov/36337001/", "study_type": "meta-analysis", "key_finding": "CoQ10 supplementation significantly reduced total cholesterol, LDL-C, and increased HDL-C in adults across randomized controlled trials.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36337001/", "publicSourceType": "PMID" }, { "claim": "CoQ10 reduces inflammatory biomarkers", "title": "Efficacy and Optimal Dose of Coenzyme Q10 Supplementation on Inflammation-Related Biomarkers: A GRADE-Assessed Systematic Review and Updated Meta-Analysis of Randomized Controlled Trials.", "authors": "Hou S, Tian Z, Zhao D et al.", "journal": "Molecular Nutrition & Food Research", "year": 2023, "pmid": "37118903", "url": "https://pubmed.ncbi.nlm.nih.gov/37118903/", "study_type": "meta-analysis", "key_finding": "CoQ10 supplementation significantly reduced inflammatory markers including TNF-alpha and IL-6, with optimal dosing at 100-200mg/day.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37118903/", "publicSourceType": "PMID" }, { "text": "Zhang T, He Q, Xiu H et al.. Efficacy and Safety of Coenzyme Q10 Supplementation in the Treatment of Polycystic Ovary Syndrome: a Systematic Review and Meta-analysis. Reproductive sciences (Thousand Oaks, Calif.). 2023", "claim": "PubMed-indexed evidence involving Coenzyme Q10", "title": "Efficacy and Safety of Coenzyme Q10 Supplementation in the Treatment of Polycystic Ovary Syndrome: a Systematic Review and Meta-analysis", "authors": "Zhang T, He Q, Xiu H et al.", "journal": "Reproductive sciences (Thousand Oaks, Calif.)", "year": 2023, "pmid": "35941510", "url": "https://pubmed.ncbi.nlm.nih.gov/35941510/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s43032-022-01038-2", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35941510/", "publicSourceType": "PMID" }, { "text": "Salekzamani S, Pakkhesal S, Babaei M et al.. Coenzyme Q10 supplementation in multiple sclerosis; A systematic review. Multiple sclerosis and related disorders. 2025", "claim": "PubMed-indexed evidence involving Coenzyme Q10", "title": "Coenzyme Q10 supplementation in multiple sclerosis; A systematic review", "authors": "Salekzamani S, Pakkhesal S, Babaei M et al.", "journal": "Multiple sclerosis and related disorders", "year": 2025, "pmid": "39667129", "url": "https://pubmed.ncbi.nlm.nih.gov/39667129/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.msard.2024.106212", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39667129/", "publicSourceType": "PMID" }, { "text": "Freire de Carvalho J, Skare T. Coenzyme Q10 supplementation in rheumatic diseases: A systematic review. Clinical nutrition ESPEN. 2024", "claim": "PubMed-indexed evidence involving Coenzyme Q10", "title": "Coenzyme Q10 supplementation in rheumatic diseases: A systematic review", "authors": "Freire de Carvalho J, Skare T", "journal": "Clinical nutrition ESPEN", "year": 2024, "pmid": "38220408", "url": "https://pubmed.ncbi.nlm.nih.gov/38220408/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.clnesp.2023.11.016", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38220408/", "publicSourceType": "PMID" }, { "text": "Ahmad K, Manongi NJ, Rajapandian R et al.. Effectiveness of Coenzyme Q10 Supplementation in Statin-Induced Myopathy: A Systematic Review. Cureus. 2024", "claim": "PubMed-indexed evidence involving Coenzyme Q10", "title": "Effectiveness of Coenzyme Q10 Supplementation in Statin-Induced Myopathy: A Systematic Review", "authors": "Ahmad K, Manongi NJ, Rajapandian R et al.", "journal": "Cureus", "year": 2024, "pmid": "39350827", "url": "https://pubmed.ncbi.nlm.nih.gov/39350827/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7759/cureus.68316", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39350827/", "publicSourceType": "PMID" }, { "text": "Patiño-Cardona S, Garrido-Miguel M, Pascual-Morena C et al.. Effect of Coenzyme Q10 Supplementation on Lipid and Glycaemic Profiles: An Umbrella Review. Journal of cardiovascular development and disease. 2024", "claim": "PubMed-indexed evidence involving Coenzyme Q10", "title": "Effect of Coenzyme Q10 Supplementation on Lipid and Glycaemic Profiles: An Umbrella Review", "authors": "Patiño-Cardona S, Garrido-Miguel M, Pascual-Morena C et al.", "journal": "Journal of cardiovascular development and disease", "year": 2024, "pmid": "39728267", "url": "https://pubmed.ncbi.nlm.nih.gov/39728267/", "study_type": "review", "confidence": "verify", "doi": "10.3390/jcdd11120377", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39728267/", "publicSourceType": "PMID" }, { "text": "Abe Y, Nishiwaki H, Suzuki T et al.. Renoprotective effects of coenzyme Q10 supplementation in patients with chronic kidney disease: a protocol for a systematic review. BMJ open. 2024", "claim": "PubMed-indexed evidence involving Coenzyme Q10", "title": "Renoprotective effects of coenzyme Q10 supplementation in patients with chronic kidney disease: a protocol for a systematic review", "authors": "Abe Y, Nishiwaki H, Suzuki T et al.", "journal": "BMJ open", "year": 2024, "pmid": "39806632", "url": "https://pubmed.ncbi.nlm.nih.gov/39806632/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1136/bmjopen-2024-084088", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39806632/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "coenzyme-q10" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567044", "name": "Melatonin", "alternateNames": [], "category": "Hormone", "subcategory": "Sleep Hormone", "overview": "The body's primary sleep-regulating hormone. Also a potent antioxidant with neuroprotective properties. Most people use doses far higher than needed.", "mechanismOfAction": "Binds to MT1 and MT2 melatonin receptors in the suprachiasmatic nucleus (SCN), signaling darkness and initiating sleep cascade. MT1 promotes sleepiness; MT2 shifts circadian phase. Also a direct free radical scavenger (neutralizes hydroxyl radicals) and stimulates antioxidant enzyme production.", "commonBenefits": [ "Sleep onset", "Circadian rhythm regulation", "Jet lag", "Antioxidant", "Neuroprotection" ], "commonDosageRange": "0.3–3 mg (lower is often better)", "recommendedForm": "Low-dose (0.3-1mg) for sleep onset; extended-release for sleep maintenance", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Take 30-60 minutes before desired sleep time. Less is more, 0.3mg is often optimal." }, "evidenceRating": "strong", "foodSources": [ "Tart cherries", "Walnuts", "Tomatoes", "Rice", "Goji berries" ], "deficiencySymptoms": [ "Insomnia", "Delayed sleep onset", "Jet lag sensitivity", "Age-related sleep decline" ], "sideEffects": [ "Morning grogginess (dose too high)", "Vivid dreams", "Headache", "Daytime sleepiness" ], "contraindications": [ "Autoimmune conditions", "Seizure disorders", "Depression (may worsen)", "Sedative medications", "Pregnancy/breastfeeding" ], "iconName": "moon.zzz.fill", "colorHex": "5A189A", "tags": [ "sleep", "circadian", "antioxidant" ], "sources": [ { "claim": "Melatonin efficacy for primary sleep disorders - comprehensive meta-analysis", "title": "Meta-analysis: melatonin for the treatment of primary sleep disorders", "authors": "Ferracioli-Oda E et al.", "journal": "PLoS One", "year": 2013, "pmid": "23691095", "url": "https://pubmed.ncbi.nlm.nih.gov/23691095/", "study_type": "meta-analysis", "key_finding": "19 studies (1,683 subjects): melatonin reduced sleep onset latency by 7.06 min, increased total sleep time by 8.25 min; effects do not dissipate with continued use.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23691095/", "publicSourceType": "PMID" }, { "claim": "Optimal melatonin dose and timing for sleep - dose-response meta-analysis", "title": "Optimizing the Time and Dose of Melatonin as a Sleep-Promoting Drug: A Systematic Review of Randomized Controlled Trials and Dose-Response Meta-Analysis", "authors": "Salanitro M et al.", "journal": "Sleep Med Rev", "year": 2024, "pmid": "38888087", "url": "https://pubmed.ncbi.nlm.nih.gov/38888087/", "study_type": "meta-analysis", "key_finding": "Dose-response analysis shows melatonin peaks at 4 mg/day for sleep onset latency and total sleep time; 3 hours before bedtime may be more effective than 30 minutes.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38888087/", "publicSourceType": "PMID" }, { "claim": "Melatonin safety in humans - short and long-term", "title": "The Safety of Melatonin in Humans", "authors": "Andersen LP et al.", "journal": "Clin Drug Investig", "year": 2016, "pmid": "26692007", "url": "https://pubmed.ncbi.nlm.nih.gov/26692007/", "study_type": "review", "key_finding": "Short-term use is safe even in extreme doses; only mild adverse effects (dizziness, headache, nausea, sleepiness) reported.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26692007/", "publicSourceType": "PMID" }, { "claim": "Adverse events in long-term melatonin use are mild and comparable to placebo", "title": "Adverse events in long-term studies of exogenous melatonin", "authors": "Menczel Schrire Z et al.", "journal": "J Pineal Res", "year": 2022, "pmid": "36562403", "url": "https://pubmed.ncbi.nlm.nih.gov/36562403/", "study_type": "review", "key_finding": "Long-term melatonin causes only mild adverse events comparable to placebo; most common: daytime sleepiness (1.66%), headache (0.74%), dizziness (0.74%).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36562403/", "publicSourceType": "PMID" }, { "claim": "Melatonin antioxidant properties beyond sleep", "title": "Melatonin as an antioxidant: under promises but over delivers", "authors": "Reiter RJ et al.", "journal": "J Pineal Res", "year": 2016, "pmid": "27500468", "url": "https://pubmed.ncbi.nlm.nih.gov/27500468/", "study_type": "review", "key_finding": "Melatonin is a direct free radical scavenger, stimulates antioxidant enzyme production, and has been effective against oxidative stress in human trials.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27500468/", "publicSourceType": "PMID" }, { "claim": "Melatonin efficacy for chronic insomnia", "title": "Efficacy of melatonin for chronic insomnia: Systematic reviews and meta-analyses", "authors": "Fatemeh G et al.", "journal": "Sleep Med", "year": 2022, "pmid": "36179487", "url": "https://pubmed.ncbi.nlm.nih.gov/36179487/", "study_type": "meta-analysis", "key_finding": "Effective melatonin doses vary by age: 0.5-3 mg in children, 3-5 mg in adolescents, 1-5 mg in adults, 1-6 mg in elderly.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36179487/", "publicSourceType": "PMID" }, { "text": "Fatemeh G, Sajjad M, Niloufar R et al.. Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials. Journal of neurology. 2022", "pmid": "33417003", "doi": "10.1007/s00415-020-10381-w", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33417003/", "publicSourceType": "PMID" }, { "text": "Harpsøe NG, Andersen LP, Gögenur I et al.. Clinical pharmacokinetics of melatonin: a systematic review. European journal of clinical pharmacology. 2015", "pmid": "26008214", "doi": "10.1007/s00228-015-1873-4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26008214/", "publicSourceType": "PMID" }, { "claim": "Melatonin improves sleep and reduces delirium in ICU patients", "title": "Melatonin Use in the ICU: A Systematic Review and Meta-Analysis.", "authors": "Tang BHY, Manalo J, Chowdhury SR et al.", "journal": "Critical Care Medicine", "year": 2025, "pmid": "40662882", "url": "https://pubmed.ncbi.nlm.nih.gov/40662882/", "study_type": "meta-analysis", "key_finding": "Melatonin supplementation improved sleep quality and reduced incidence of delirium in critically ill ICU patients.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40662882/", "publicSourceType": "PMID" }, { "claim": "Melatonin reduces dietary supplement-related sleep issues", "title": "Efficacy of dietary supplements on improving sleep quality: a systematic review and meta-analysis.", "authors": "Chan V, Lo K", "journal": "Postgraduate Medical Journal", "year": 2022, "pmid": "33441476", "url": "https://pubmed.ncbi.nlm.nih.gov/33441476/", "study_type": "meta-analysis", "key_finding": "Melatonin was among the most effective dietary supplements for improving subjective sleep quality and reducing sleep onset latency.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33441476/", "publicSourceType": "PMID" }, { "text": "Daliri AS, Goudarzi N, Harati A et al.. Melatonin as a Novel Drug to Improve Cardiac Function and Quality of Life in Heart Failure Patients: A Systematic Review and Meta-Analysis. Clinical cardiology. 2025", "claim": "PubMed-indexed evidence involving Melatonin", "title": "Melatonin as a Novel Drug to Improve Cardiac Function and Quality of Life in Heart Failure Patients: A Systematic Review and Meta-Analysis", "authors": "Daliri AS, Goudarzi N, Harati A et al.", "journal": "Clinical cardiology", "year": 2025, "pmid": "40026259", "url": "https://pubmed.ncbi.nlm.nih.gov/40026259/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/clc.70107", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40026259/", "publicSourceType": "PMID" }, { "text": "Terao I, Kodama W. Comparative Efficacy, Tolerability, and Acceptability of Donanemab, Lecanemab, Aducanumab, Melatonin, and Aerobic Exercise for a Short Time on Cognitive Function in Mild Cognitive Impairment and Mild Alzheimer's Disease: A Systematic Review and Network Meta-Analysis. Journal of Alzheimer's disease : JAD. 2024", "claim": "PubMed-indexed evidence involving Melatonin", "title": "Comparative Efficacy, Tolerability, and Acceptability of Donanemab, Lecanemab, Aducanumab, Melatonin, and Aerobic Exercise for a Short Time on Cognitive Function in Mild Cognitive Impairment and Mild Alzheimer's Disease: A Systematic Review and Network Meta-Analysis", "authors": "Terao I, Kodama W", "journal": "Journal of Alzheimer's disease : JAD", "year": 2024, "pmid": "38461503", "url": "https://pubmed.ncbi.nlm.nih.gov/38461503/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3233/JAD-230911", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38461503/", "publicSourceType": "PMID" }, { "text": "Del Casale A, Arena JF, Giannetti F et al.. The use of prolonged-release melatonin in circadian medicine: a systematic review. Minerva medica. 2024", "claim": "PubMed-indexed evidence involving Melatonin", "title": "The use of prolonged-release melatonin in circadian medicine: a systematic review", "authors": "Del Casale A, Arena JF, Giannetti F et al.", "journal": "Minerva medica", "year": 2024, "pmid": "38713204", "url": "https://pubmed.ncbi.nlm.nih.gov/38713204/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.23736/S0026-4806.24.09303-0", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38713204/", "publicSourceType": "PMID" }, { "text": "Nogueira HA, de Castro CT, da Silva DCG et al.. Melatonin for sleep disorders in people with autism: Systematic review and meta-analysis. Progress in neuro-psychopharmacology & biological psychiatry. 2023", "claim": "PubMed-indexed evidence involving Melatonin", "title": "Melatonin for sleep disorders in people with autism: Systematic review and meta-analysis", "authors": "Nogueira HA, de Castro CT, da Silva DCG et al.", "journal": "Progress in neuro-psychopharmacology & biological psychiatry", "year": 2023, "pmid": "36584862", "url": "https://pubmed.ncbi.nlm.nih.gov/36584862/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.pnpbp.2022.110695", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36584862/", "publicSourceType": "PMID" }, { "text": "de Carvalho JF, Skare TL. Melatonin supplementation improves rheumatological disease activity: A systematic review. Clinical nutrition ESPEN. 2023", "claim": "PubMed-indexed evidence involving Melatonin", "title": "Melatonin supplementation improves rheumatological disease activity: A systematic review", "authors": "de Carvalho JF, Skare TL", "journal": "Clinical nutrition ESPEN", "year": 2023, "pmid": "37202076", "url": "https://pubmed.ncbi.nlm.nih.gov/37202076/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.clnesp.2023.04.011", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37202076/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "melatonin" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567045", "name": "5-HTP", "alternateNames": [ "5-Hydroxytryptophan", "Griffonia Simplicifolia Extract" ], "category": "Amino Acid", "subcategory": "Serotonin Precursor", "overview": "Direct precursor to serotonin, bypassing the rate-limiting tryptophan hydroxylase step. Effective for mood, sleep, and appetite regulation.", "mechanismOfAction": "Converted directly to serotonin (5-HT) by aromatic L-amino acid decarboxylase. Unlike tryptophan, does not require tryptophan hydroxylase and is not diverted to kynurenine pathway. Serotonin is then converted to melatonin in the pineal gland.", "commonBenefits": [ "Mood support", "Sleep quality", "Appetite control", "Anxiety reduction", "Migraine prevention" ], "commonDosageRange": "50–200 mg daily", "recommendedForm": "5-HTP from Griffonia simplicifolia seed extract", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Take on empty stomach for best brain uptake. Evening dosing for sleep; morning for mood." }, "evidenceRating": "moderate", "foodSources": [ "Not found in food; derived from Griffonia simplicifolia seeds" ], "deficiencySymptoms": [ "Not applicable; but low serotonin symptoms: depression, anxiety, insomnia, cravings" ], "sideEffects": [ "Nausea", "GI upset", "Drowsiness", "Vivid dreams" ], "contraindications": [ "SSRIs/SNRIs (serotonin syndrome risk, DANGEROUS)", "MAO inhibitors", "Carbidopa" ], "iconName": "face.smiling.fill", "colorHex": "F72585", "tags": [ "mood", "sleep", "serotonin", "appetite" ], "sources": [ { "claim": "5-HTP antidepressant effects across distinct types of depression", "title": "Effects of 5-hydroxytryptophan on distinct types of depression: a systematic review and meta-analysis", "authors": "Javelle F et al.", "journal": "Nutr Rev", "year": 2020, "pmid": "31504850", "url": "https://pubmed.ncbi.nlm.nih.gov/31504850/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 7 studies showed depression remission rate of 0.65 (95% CI: 0.55-0.78) with large effect size (Hedges g = 1.11).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31504850/", "publicSourceType": "PMID" }, { "claim": "Tryptophan and 5-HTP are better than placebo for depression (Cochrane)", "title": "Tryptophan and 5-hydroxytryptophan for depression", "authors": "Shaw K et al.", "journal": "Cochrane Database Syst Rev", "year": 2002, "pmid": "11687048", "url": "https://pubmed.ncbi.nlm.nih.gov/11687048/", "study_type": "meta-analysis", "key_finding": "5-HTP and tryptophan were better than placebo at alleviating depression (Peto OR = 4.1), though small study sizes limit conclusions.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11687048/", "publicSourceType": "PMID" }, { "claim": "5-HTP reduces food intake and body weight in obese subjects", "title": "Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan", "authors": "Cangiano C et al.", "journal": "Am J Clin Nutr", "year": 1992, "pmid": "1384305", "url": "https://pubmed.ncbi.nlm.nih.gov/1384305/", "study_type": "RCT", "key_finding": "Double-blind RCT in 20 obese patients: 5-HTP (900 mg/d) produced significant weight loss with reduced carbohydrate intake and early satiety.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1384305/", "publicSourceType": "PMID" }, { "claim": "5-HTP efficacy, safety, and contraindications overview", "title": "5-HTP efficacy and contraindications", "authors": "Birdsall TC", "journal": "Altern Med Rev", "year": 2012, "pmid": "22888252", "url": "https://pubmed.ncbi.nlm.nih.gov/22888252/", "study_type": "review", "key_finding": "Comprehensive review of 5-HTP safety including emphasis on serotonin syndrome risk with SSRIs and eosinophilia myalgia syndrome concerns.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22888252/", "publicSourceType": "PMID" }, { "claim": "5-HTP as serotonin precursor - pharmacology and supplementation review", "title": "Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan", "authors": "Turner EH et al.", "journal": "Pharmacol Ther", "year": 2006, "pmid": "16023217", "url": "https://pubmed.ncbi.nlm.nih.gov/16023217/", "study_type": "review", "key_finding": "5-HTP bypasses the rate-limiting tryptophan hydroxylase step to directly increase serotonin; relatively few adverse effects at therapeutic doses.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16023217/", "publicSourceType": "PMID" }, { "claim": "5-HTP reduces body fat in preliminary RCT", "title": "The Effects of 5-HTP on Body Composition: An 8-Week Preliminary RCT", "authors": "Meloni M et al.", "journal": "Int J Environ Res Public Health", "year": 2022, "pmid": "35583055", "url": "https://pubmed.ncbi.nlm.nih.gov/35583055/", "study_type": "RCT", "key_finding": "Fat mass decreased significantly in 5-HTP group (p=0.02) but not placebo, with significant between-group differences (p=0.048).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35583055/", "publicSourceType": "PMID" }, { "text": "Sutanto CN, Xia X, Heng CW et al.. The impact of 5-hydroxytryptophan supplementation on sleep quality and gut microbiota composition in older adults: A randomized controlled trial. Clinical nutrition (Edinburgh, Scotland). 2024", "pmid": "38309227", "doi": "10.1016/j.clnu.2024.01.010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38309227/", "publicSourceType": "PMID" }, { "text": "Truyens M, Lobatón T, Ferrante M et al.. Effect of 5-Hydroxytryptophan on Fatigue in Quiescent Inflammatory Bowel Disease: A Randomized Controlled Trial. Gastroenterology. 2022", "pmid": "35940251", "doi": "10.1053/j.gastro.2022.07.052", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35940251/", "publicSourceType": "PMID" }, { "text": "Li S, Sutanto CN, Xia X et al.. The Impact of 5-Hydroxytryptophan Supplementation on Cognitive Function and Mood in Singapore Older Adults: A Randomized Controlled Trial. Nutrients. 2025", "claim": "PubMed-indexed evidence involving 5-HTP", "title": "The Impact of 5-Hydroxytryptophan Supplementation on Cognitive Function and Mood in Singapore Older Adults: A Randomized Controlled Trial", "authors": "Li S, Sutanto CN, Xia X et al.", "journal": "Nutrients", "year": 2025, "pmid": "40944161", "url": "https://pubmed.ncbi.nlm.nih.gov/40944161/", "study_type": "RCT", "confidence": "verify", "doi": "10.3390/nu17172773", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40944161/", "publicSourceType": "PMID" }, { "text": "Zamoscik V, Schmidt SNL, Bravo R et al.. Tryptophan-enriched diet or 5-hydroxytryptophan supplementation given in a randomized controlled trial impacts social cognition on a neural and behavioral level. Scientific reports. 2021", "claim": "PubMed-indexed evidence involving 5-HTP", "title": "Tryptophan-enriched diet or 5-hydroxytryptophan supplementation given in a randomized controlled trial impacts social cognition on a neural and behavioral level", "authors": "Zamoscik V, Schmidt SNL, Bravo R et al.", "journal": "Scientific reports", "year": 2021, "pmid": "34737364", "url": "https://pubmed.ncbi.nlm.nih.gov/34737364/", "study_type": "RCT", "confidence": "verify", "doi": "10.1038/s41598-021-01164-y", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34737364/", "publicSourceType": "PMID" }, { "text": "Arbona DV, Cowgill LD, Press S et al.. 5-Hydroxytryptophan toxicity successfully treated by haemodialysis in a dog. Veterinary medicine and science. 2023", "claim": "PubMed-indexed evidence involving 5-HTP", "title": "5-Hydroxytryptophan toxicity successfully treated by haemodialysis in a dog", "authors": "Arbona DV, Cowgill LD, Press S et al.", "journal": "Veterinary medicine and science", "year": 2023, "pmid": "37659074", "url": "https://pubmed.ncbi.nlm.nih.gov/37659074/", "study_type": "review", "confidence": "verify", "doi": "10.1002/vms3.1253", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37659074/", "publicSourceType": "PMID" }, { "text": "Gijsman HJ, van Gerven JM, de Kam ML et al.. Placebo-controlled comparison of three dose-regimens of 5-hydroxytryptophan challenge test in healthy volunteers. Journal of clinical psychopharmacology. 2002", "claim": "PubMed-indexed evidence involving 5-HTP", "title": "Placebo-controlled comparison of three dose-regimens of 5-hydroxytryptophan challenge test in healthy volunteers", "authors": "Gijsman HJ, van Gerven JM, de Kam ML et al.", "journal": "Journal of clinical psychopharmacology", "year": 2002, "pmid": "11910264", "url": "https://pubmed.ncbi.nlm.nih.gov/11910264/", "study_type": "RCT", "confidence": "verify", "doi": "10.1097/00004714-200204000-00012", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11910264/", "publicSourceType": "PMID" }, { "text": "Byerley WF, Judd LL, Reimherr FW et al.. 5-Hydroxytryptophan: a review of its antidepressant efficacy and adverse effects. Journal of clinical psychopharmacology. 1987", "claim": "PubMed-indexed evidence involving 5-HTP", "title": "5-Hydroxytryptophan: a review of its antidepressant efficacy and adverse effects", "authors": "Byerley WF, Judd LL, Reimherr FW et al.", "journal": "Journal of clinical psychopharmacology", "year": 1987, "pmid": "3298325", "url": "https://pubmed.ncbi.nlm.nih.gov/3298325/", "study_type": "RCT", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3298325/", "publicSourceType": "PMID" }, { "text": "Yang H, Zhang X, Gao Y et al.. Detection of melatonin and 5-HTP in dietary supplements based on multiple spectra. Frontiers in nutrition. 2025", "claim": "PubMed-indexed evidence involving 5-HTP", "title": "Detection of melatonin and 5-HTP in dietary supplements based on multiple spectra", "authors": "Yang H, Zhang X, Gao Y et al.", "journal": "Frontiers in nutrition", "year": 2025, "pmid": "39935577", "url": "https://pubmed.ncbi.nlm.nih.gov/39935577/", "study_type": "review", "confidence": "verify", "doi": "10.3389/fnut.2025.1532092", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39935577/", "publicSourceType": "PMID" }, { "text": "Pszczolkowski VL, Connelly MK, Hoppman A et al.. Intravenous infusion of 5-hydroxytryptophan to mid-lactation Holstein cows transiently affects milk production and circulating amino acid concentrations. Journal of dairy science. 2024", "claim": "PubMed-indexed evidence involving 5-HTP", "title": "Intravenous infusion of 5-hydroxytryptophan to mid-lactation Holstein cows transiently affects milk production and circulating amino acid concentrations", "authors": "Pszczolkowski VL, Connelly MK, Hoppman A et al.", "journal": "Journal of dairy science", "year": 2024, "pmid": "38101740", "url": "https://pubmed.ncbi.nlm.nih.gov/38101740/", "study_type": "RCT", "confidence": "verify", "doi": "10.3168/jds.2023-23934", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38101740/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "5-htp" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567046", "name": "Alpha-Lipoic Acid", "alternateNames": [ "ALA", "R-Lipoic Acid", "R-ALA" ], "category": "Antioxidant", "subcategory": "Universal Antioxidant", "overview": "Unique antioxidant that works in both water and fat environments. Regenerates other antioxidants (vitamins C, E, glutathione, CoQ10). Powerful support for blood sugar and nerve health.", "mechanismOfAction": "Cofactor for mitochondrial dehydrogenase complexes (pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase). Potent metal chelator. Regenerates glutathione, vitamin C, vitamin E, and CoQ10. Activates AMPK (improves glucose uptake). Scavenges ROS in both aqueous and lipid compartments.", "commonBenefits": [ "Blood sugar support", "Nerve health", "Antioxidant regeneration", "Heavy metal chelation", "Skin health" ], "commonDosageRange": "300–600 mg daily", "recommendedForm": "R-lipoic acid (R-ALA, the bioactive enantiomer) or stabilized Na-R-ALA", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Take on empty stomach 30 min before meals; food reduces absorption by 30%" }, "evidenceRating": "moderate", "foodSources": [ "Organ meats", "Spinach", "Broccoli", "Tomatoes", "Peas" ], "deficiencySymptoms": [ "Not essential, but levels decline with age" ], "sideEffects": [ "GI upset", "Skin rash", "Hypoglycemia (monitor blood sugar)", "Biotin depletion (supplement B7)" ], "contraindications": [ "Diabetes medications (may potentiate)", "Thyroid medications", "Thiamine deficiency" ], "iconName": "arrow.triangle.2.circlepath", "colorHex": "FF6D00", "tags": [ "antioxidant", "blood-sugar", "nerve-health", "anti-aging" ], "sources": [ { "claim": "Alpha-lipoic acid efficacy for diabetic neuropathy - meta-analysis of oral treatment", "title": "Effects of Oral Alpha-Lipoic Acid Treatment on Diabetic Polyneuropathy: A Meta-Analysis and Systematic Review", "authors": "Veloso AI et al.", "journal": "J Diabetes Res", "year": 2023, "pmid": "37630823", "url": "https://pubmed.ncbi.nlm.nih.gov/37630823/", "study_type": "meta-analysis", "key_finding": "Meta-analysis showed ALA reduced total symptom scores by -2.26 in diabetic neuropathy, with both oral and IV administration showing significant improvements.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37630823/", "publicSourceType": "PMID" }, { "claim": "ALA increases insulin sensitivity via AMPK activation in skeletal muscle", "title": "Alpha-lipoic acid increases insulin sensitivity by activating AMPK in skeletal muscle", "authors": "Lee WJ et al.", "journal": "Biochem Biophys Res Commun", "year": 2005, "pmid": "15913551", "url": "https://pubmed.ncbi.nlm.nih.gov/15913551/", "study_type": "review", "key_finding": "ALA activates AMPK in skeletal muscle, increases fatty acid oxidation, and improves insulin sensitivity via reduced triglyceride accumulation.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15913551/", "publicSourceType": "PMID" }, { "claim": "ALA effects on glucose control and lipid profiles in metabolic diseases", "title": "The effects of alpha-lipoic acid supplementation on glucose control and lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials", "authors": "Akbari M et al.", "journal": "Metabolism", "year": 2018, "pmid": "29990473", "url": "https://pubmed.ncbi.nlm.nih.gov/29990473/", "study_type": "meta-analysis", "key_finding": "ALA administration improved glucose homeostasis parameters and lipid profiles in patients with metabolic diseases.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29990473/", "publicSourceType": "PMID" }, { "claim": "ALA as universal antioxidant working in both water and fat environments", "title": "alpha-Lipoic acid as a biological antioxidant", "authors": "Packer L et al.", "journal": "Free Radic Biol Med", "year": 1995, "pmid": "7649494", "url": "https://pubmed.ncbi.nlm.nih.gov/7649494/", "study_type": "review", "key_finding": "Lipoic acid quenches ROS, chelates metal ions, and regenerates other antioxidants (vitamins C, E, glutathione) in both aqueous and lipid compartments.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7649494/", "publicSourceType": "PMID" }, { "claim": "ALA supplementation for weight loss", "title": "Alpha-lipoic acid supplementation significantly reduces the risk of obesity in an updated systematic review and dose response meta-analysis of randomised placebo-controlled clinical trials", "authors": "Vajdi M et al.", "journal": "Int J Clin Pract", "year": 2020, "pmid": "32091656", "url": "https://pubmed.ncbi.nlm.nih.gov/32091656/", "study_type": "meta-analysis", "key_finding": "ALA reduced BMI by 0.38 kg/m2 and body weight by 0.69 kg; linear dose-response at supplementation >600 mg/day.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32091656/", "publicSourceType": "PMID" }, { "claim": "ALA reduces neuropathic pain in diabetic patients", "title": "Effectiveness of alpha-lipoic acid in patients with neuropathic pain associated with type I and type II diabetes mellitus: A systematic review and meta-analysis", "authors": "Orellana-Donoso M, López-Chaparro M, Barahona-Vásquez M et al.", "journal": "Medicine (Baltimore)", "year": 2023, "pmid": "37933068", "url": "https://pubmed.ncbi.nlm.nih.gov/37933068/", "study_type": "meta-analysis", "key_finding": "Alpha-lipoic acid demonstrated significant effectiveness in reducing neuropathic pain scores in both type 1 and type 2 diabetic patients compared to placebo in pooled analysis.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37933068/", "publicSourceType": "PMID" }, { "claim": "ALA as a micronutrient reduces cardiovascular risk", "title": "Micronutrient Supplementation to Reduce Cardiovascular Risk", "authors": "An P, Wan S, Luo Y, Luo J et al.", "journal": "Journal of the American College of Cardiology", "year": 2022, "pmid": "36480969", "url": "https://pubmed.ncbi.nlm.nih.gov/36480969/", "study_type": "systematic-review", "key_finding": "Among various micronutrients evaluated, alpha-lipoic acid was associated with reduced cardiovascular risk markers in this comprehensive systematic review of micronutrient supplementation trials.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36480969/", "publicSourceType": "PMID" }, { "text": "Sharifi-Zahabi E, Abdollahzad H. Alpha Lipoic Acid Supplementation and Iron Homeostasis: A Comprehensive Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials. International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition. 2024", "claim": "PubMed-indexed evidence involving Alpha-Lipoic Acid", "title": "Alpha Lipoic Acid Supplementation and Iron Homeostasis: A Comprehensive Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials", "authors": "Sharifi-Zahabi E, Abdollahzad H", "journal": "International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition", "year": 2024, "pmid": "40134249", "url": "https://pubmed.ncbi.nlm.nih.gov/40134249/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.31083/IJVNR36623", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40134249/", "publicSourceType": "PMID" }, { "text": "Abubaker SA, Alonazy AM, Abdulrahman A. Effect of Alpha-Lipoic Acid in the Treatment of Diabetic Neuropathy: A Systematic Review. Cureus. 2022", "claim": "PubMed-indexed evidence involving Alpha-Lipoic Acid", "title": "Effect of Alpha-Lipoic Acid in the Treatment of Diabetic Neuropathy: A Systematic Review", "authors": "Abubaker SA, Alonazy AM, Abdulrahman A", "journal": "Cureus", "year": 2022, "pmid": "35812639", "url": "https://pubmed.ncbi.nlm.nih.gov/35812639/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7759/cureus.25750", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35812639/", "publicSourceType": "PMID" }, { "text": "Dong L, Yang F, Li J et al.. Effect of oral alpha-lipoic acid (ALA) on sperm parameters: a systematic review and meta-analysis. Basic and clinical andrology. 2022", "claim": "PubMed-indexed evidence involving Alpha-Lipoic Acid", "title": "Effect of oral alpha-lipoic acid (ALA) on sperm parameters: a systematic review and meta-analysis", "authors": "Dong L, Yang F, Li J et al.", "journal": "Basic and clinical andrology", "year": 2022, "pmid": "36476425", "url": "https://pubmed.ncbi.nlm.nih.gov/36476425/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12610-022-00173-9", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36476425/", "publicSourceType": "PMID" }, { "text": "Di Tucci C, Galati G, Mattei G et al.. The role of alpha lipoic acid in female and male infertility: a systematic review. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2021", "claim": "PubMed-indexed evidence involving Alpha-Lipoic Acid", "title": "The role of alpha lipoic acid in female and male infertility: a systematic review", "authors": "Di Tucci C, Galati G, Mattei G et al.", "journal": "Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology", "year": 2021, "pmid": "33345661", "url": "https://pubmed.ncbi.nlm.nih.gov/33345661/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/09513590.2020.1843619", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33345661/", "publicSourceType": "PMID" }, { "text": "Sheikholeslami S, Khodaverdian S, Dorri-Giv M et al.. The radioprotective effects of alpha-lipoic acid on radiotherapy-induced toxicities: A systematic review. International immunopharmacology. 2021", "claim": "PubMed-indexed evidence involving Alpha-Lipoic Acid", "title": "The radioprotective effects of alpha-lipoic acid on radiotherapy-induced toxicities: A systematic review", "authors": "Sheikholeslami S, Khodaverdian S, Dorri-Giv M et al.", "journal": "International immunopharmacology", "year": 2021, "pmid": "33989970", "url": "https://pubmed.ncbi.nlm.nih.gov/33989970/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.intimp.2021.107741", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33989970/", "publicSourceType": "PMID" }, { "text": "Erickson N, Zafron M, Harding SV et al.. Evaluating the Lipid-Lowering Effects of α-lipoic Acid Supplementation: A Systematic Review. Journal of dietary supplements. 2020", "claim": "PubMed-indexed evidence involving Alpha-Lipoic Acid", "title": "Evaluating the Lipid-Lowering Effects of α-lipoic Acid Supplementation: A Systematic Review", "authors": "Erickson N, Zafron M, Harding SV et al.", "journal": "Journal of dietary supplements", "year": 2020, "pmid": "31416362", "url": "https://pubmed.ncbi.nlm.nih.gov/31416362/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/19390211.2019.1651436", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31416362/", "publicSourceType": "PMID" }, { "text": "de Sousa CNS, da Silva Leite CMG, da Silva Medeiros I et al.. Alpha-lipoic acid in the treatment of psychiatric and neurological disorders: a systematic review. Metabolic brain disease. 2019", "claim": "PubMed-indexed evidence involving Alpha-Lipoic Acid", "title": "Alpha-lipoic acid in the treatment of psychiatric and neurological disorders: a systematic review", "authors": "de Sousa CNS, da Silva Leite CMG, da Silva Medeiros I et al.", "journal": "Metabolic brain disease", "year": 2019, "pmid": "30467770", "url": "https://pubmed.ncbi.nlm.nih.gov/30467770/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s11011-018-0344-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30467770/", "publicSourceType": "PMID" }, { "text": "Namazi N, Larijani B, Azadbakht L. Alpha-lipoic acid supplement in obesity treatment: A systematic review and meta-analysis of clinical trials. Clinical nutrition (Edinburgh, Scotland). 2018", "claim": "PubMed-indexed evidence involving Alpha-Lipoic Acid", "title": "Alpha-lipoic acid supplement in obesity treatment: A systematic review and meta-analysis of clinical trials", "authors": "Namazi N, Larijani B, Azadbakht L", "journal": "Clinical nutrition (Edinburgh, Scotland)", "year": 2018, "pmid": "28629898", "url": "https://pubmed.ncbi.nlm.nih.gov/28629898/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.clnu.2017.06.002", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28629898/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "alpha-lipoic-acid" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567047", "name": "NMN", "alternateNames": [ "Nicotinamide Mononucleotide", "β-NMN" ], "category": "Other", "subcategory": "Longevity Compound", "overview": "Direct precursor to NAD+, the critical coenzyme that declines with age. At the forefront of longevity research for cellular rejuvenation and anti-aging.", "mechanismOfAction": "Converted to NAD+ via nicotinamide mononucleotide adenylyltransferase (NMNAT). NAD+ is essential for sirtuins (SIRT1-7, longevity genes), PARPs (DNA repair), CD38 (immune regulation), and hundreds of metabolic reactions. Plasma levels decline approximately 60% over lifespan, but varies greatly by tissue: brain only 10-25%, CSF ~14%.", "commonBenefits": [ "NAD+ restoration", "Anti-aging", "Energy metabolism", "DNA repair", "Cardiovascular health" ], "commonDosageRange": "250–1,000 mg daily", "recommendedForm": "Sublingual NMN or enteric-coated capsules for better bioavailability", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Take in the morning on empty stomach; sublingual delivery avoids first-pass metabolism" }, "evidenceRating": "emerging", "foodSources": [ "Edamame", "Broccoli", "Avocado", "Cabbage (trace amounts)" ], "deficiencySymptoms": [ "Age-related NAD+ decline", "Fatigue", "Metabolic dysfunction" ], "sideEffects": [ "Generally well tolerated", "Mild GI upset", "Flushing (rare)" ], "contraindications": [ "Cancer (theoretical concern with NAD+ raising)", "Consult oncologist if history of cancer" ], "iconName": "hourglass", "colorHex": "4CC9F0", "tags": [ "longevity", "nad", "anti-aging", "energy" ], "sources": [ { "claim": "NMN safety and dose-dependent efficacy in healthy middle-aged adults", "title": "The efficacy and safety of beta-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial", "authors": "Yi L et al.", "journal": "GeroScience", "year": 2023, "pmid": "36482258", "url": "https://pubmed.ncbi.nlm.nih.gov/36482258/", "study_type": "RCT", "key_finding": "Clinical efficacy by blood NAD concentration and physical performance reached highest at 600 mg daily oral intake; NMN was safe and well tolerated.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36482258/", "publicSourceType": "PMID" }, { "claim": "Review of NMN safety and antiaging effects in human clinical trials", "title": "The Safety and Antiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: an Update", "authors": "Nadeeshani H et al.", "journal": "Adv Nutr", "year": 2023, "pmid": "37619764", "url": "https://pubmed.ncbi.nlm.nih.gov/37619764/", "study_type": "review", "key_finding": "A dozen human clinical trials show NMN safely increases blood NAD levels up to 900 mg daily; a significant effect on NAD elevation confirmed by meta-analysis.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37619764/", "publicSourceType": "PMID" }, { "claim": "NMN increases blood NAD levels, improves walking speed and sleep quality in older adults", "title": "Ingestion of beta-nicotinamide mononucleotide increased blood NAD levels, maintained walking speed, and improved sleep quality in older adults in a double-blind randomized, placebo-controlled study", "authors": "Kim M et al.", "journal": "GeroScience", "year": 2024, "pmid": "38789831", "url": "https://pubmed.ncbi.nlm.nih.gov/38789831/", "study_type": "RCT", "key_finding": "12-week NMN intake significantly increased blood NAD+, maintained walking speed, and improved sleep quality (PSQI daytime dysfunction and global scores).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38789831/", "publicSourceType": "PMID" }, { "claim": "NMN as anti-aging health product - promises and safety concerns", "title": "Nicotinamide mononucleotide (NMN) as an anti-aging health product - Promises and safety concerns", "authors": "Nadeeshani H et al.", "journal": "J Adv Res", "year": 2022, "pmid": "35499054", "url": "https://pubmed.ncbi.nlm.nih.gov/35499054/", "study_type": "review", "key_finding": "NAD+ levels deplete ~60% over lifespan; NMN supplementation can slow aging by elevating NAD+ but theoretical cancer concerns exist with NAD+ raising.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35499054/", "publicSourceType": "PMID" }, { "claim": "NMN is safely absorbed and increases blood NAD in healthy subjects", "title": "Oral Administration of Nicotinamide Mononucleotide Is Safe and Efficiently Increases Blood Nicotinamide Adenine Dinucleotide Levels in Healthy Subjects", "authors": "Okabe K et al.", "journal": "Front Nutr", "year": 2022, "pmid": "35479740", "url": "https://pubmed.ncbi.nlm.nih.gov/35479740/", "study_type": "RCT", "key_finding": "Oral NMN administration is safe with no adverse events and efficiently increases blood NAD+ levels in healthy subjects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35479740/", "publicSourceType": "PMID" }, { "text": "Katayoshi T, Uehata S, Nakashima N et al.. Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial. Scientific reports. 2023", "pmid": "36797393", "doi": "10.1038/s41598-023-29787-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36797393/", "publicSourceType": "PMID" }, { "text": "Liao B, Zhao Y, Wang D et al.. Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study. Journal of the International Society of Sports Nutrition. 2021", "pmid": "34238308", "doi": "10.1186/s12970-021-00442-4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34238308/", "publicSourceType": "PMID" }, { "text": "Zhang M, Chen Y, Jiang N et al.. Effects of Nicotinamide Mononucleotide Supplementation on Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients. 2026", "claim": "PubMed-indexed evidence involving NMN", "title": "Effects of Nicotinamide Mononucleotide Supplementation on Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Zhang M, Chen Y, Jiang N et al.", "journal": "Nutrients", "year": 2026, "pmid": "41901064", "url": "https://pubmed.ncbi.nlm.nih.gov/41901064/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu18060890", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41901064/", "publicSourceType": "PMID" }, { "text": "Zhang J, Poon ET, Wong SH. Efficacy of oral nicotinamide mononucleotide supplementation on glucose and lipid metabolism for adults: a systematic review with meta-analysis on randomized controlled trials. Critical reviews in food science and nutrition. 2025", "claim": "PubMed-indexed evidence involving NMN", "title": "Efficacy of oral nicotinamide mononucleotide supplementation on glucose and lipid metabolism for adults: a systematic review with meta-analysis on randomized controlled trials", "authors": "Zhang J, Poon ET, Wong SH", "journal": "Critical reviews in food science and nutrition", "year": 2025, "pmid": "39116016", "url": "https://pubmed.ncbi.nlm.nih.gov/39116016/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/10408398.2024.2387324", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39116016/", "publicSourceType": "PMID" }, { "text": "Wang JP, Wang L, Wang T et al.. Effects of Nicotinamide Mononucleotide Supplementation on Muscle and Liver Functions Among the Middle-aged and Elderly: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Current pharmaceutical biotechnology. 2025", "claim": "PubMed-indexed evidence involving NMN", "title": "Effects of Nicotinamide Mononucleotide Supplementation on Muscle and Liver Functions Among the Middle-aged and Elderly: A Systematic Review and Meta-analysis of Randomized Controlled Trials", "authors": "Wang JP, Wang L, Wang T et al.", "journal": "Current pharmaceutical biotechnology", "year": 2025, "pmid": "39185644", "url": "https://pubmed.ncbi.nlm.nih.gov/39185644/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2174/0113892010306242240808094303", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39185644/", "publicSourceType": "PMID" }, { "text": "Wen J, Syed B, Kim S et al.. Improved Physical Performance Parameters in Patients Taking Nicotinamide Mononucleotide (NMN): A Systematic Review of Randomized Control Trials. Cureus. 2024", "claim": "PubMed-indexed evidence involving NMN", "title": "Improved Physical Performance Parameters in Patients Taking Nicotinamide Mononucleotide (NMN): A Systematic Review of Randomized Control Trials", "authors": "Wen J, Syed B, Kim S et al.", "journal": "Cureus", "year": 2024, "pmid": "39221308", "url": "https://pubmed.ncbi.nlm.nih.gov/39221308/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7759/cureus.65961", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39221308/", "publicSourceType": "PMID" }, { "text": "Noh H, Sen Gupta S, Seshadri S et al.. NMN supplementation as a strategy to improve oocyte quality: a systematic review and transcriptomic analysis. Journal of assisted reproduction and genetics. 2026", "claim": "PubMed-indexed evidence involving NMN", "title": "NMN supplementation as a strategy to improve oocyte quality: a systematic review and transcriptomic analysis", "authors": "Noh H, Sen Gupta S, Seshadri S et al.", "journal": "Journal of assisted reproduction and genetics", "year": 2026, "pmid": "41160202", "url": "https://pubmed.ncbi.nlm.nih.gov/41160202/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s10815-025-03720-1", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41160202/", "publicSourceType": "PMID" }, { "text": "Prokopidis K, Moriarty F, Bahat G et al.. The Effect of Nicotinamide Mononucleotide and Riboside on Skeletal Muscle Mass and Function: A Systematic Review and Meta-Analysis. Journal of cachexia, sarcopenia and muscle. 2025", "claim": "PubMed-indexed evidence involving NMN", "title": "The Effect of Nicotinamide Mononucleotide and Riboside on Skeletal Muscle Mass and Function: A Systematic Review and Meta-Analysis", "authors": "Prokopidis K, Moriarty F, Bahat G et al.", "journal": "Journal of cachexia, sarcopenia and muscle", "year": 2025, "pmid": "40275690", "url": "https://pubmed.ncbi.nlm.nih.gov/40275690/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/jcsm.13799", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40275690/", "publicSourceType": "PMID" }, { "text": "Chen F, Zhou D, Kong AP et al.. Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials. Current diabetes reports. 2024", "claim": "PubMed-indexed evidence involving NMN", "title": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "authors": "Chen F, Zhou D, Kong AP et al.", "journal": "Current diabetes reports", "year": 2024, "pmid": "39531138", "url": "https://pubmed.ncbi.nlm.nih.gov/39531138/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s11892-024-01557-z", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39531138/", "publicSourceType": "PMID" }, { "text": "Huang H. A Multicentre, Randomised, Double Blind, Parallel Design, Placebo Controlled Study to Evaluate the Efficacy and Safety of Uthever (NMN Supplement), an Orally Administered Supplementation in Middle Aged and Older Adults. Frontiers in aging. 2022", "claim": "PubMed-indexed evidence involving NMN", "title": "A Multicentre, Randomised, Double Blind, Parallel Design, Placebo Controlled Study to Evaluate the Efficacy and Safety of Uthever (NMN Supplement), an Orally Administered Supplementation in Middle Aged and Older Adults", "authors": "Huang H", "journal": "Frontiers in aging", "year": 2022, "pmid": "35821806", "url": "https://pubmed.ncbi.nlm.nih.gov/35821806/", "study_type": "RCT", "confidence": "verify", "doi": "10.3389/fragi.2022.851698", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35821806/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "nmn" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567048", "name": "Apigenin", "alternateNames": [], "category": "Other", "subcategory": "Flavonoid", "overview": "A calming flavonoid found in chamomile. Popularized by neuroscientist Andrew Huberman as a sleep aid. Also has anti-cancer and neuroprotective research.", "mechanismOfAction": "Binds to benzodiazepine sites on GABA-A receptors (mild anxiolytic and sedative without dependency). Inhibits CD38 in animal models (Escande 2013); no human clinical trials confirm this mechanism. Inhibits aromatase (reduces estrogen conversion). Activates apoptosis in cancer cells via p53 pathway.", "commonBenefits": [ "Sleep quality", "Anxiety reduction", "NAD+ preservation", "Hormone balance", "Neuroprotection" ], "commonDosageRange": "50–100 mg daily (before bed)", "recommendedForm": "Apigenin from chamomile extract", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Take 30-60 minutes before bed; stacks well with magnesium and glycine" }, "evidenceRating": "emerging", "foodSources": [ "Chamomile tea", "Parsley", "Celery", "Artichoke" ], "deficiencySymptoms": [ "Not applicable" ], "sideEffects": [ "Drowsiness", "Possible sedation (desired)", "Rare muscle relaxation" ], "contraindications": [ "Sedative medications", "Pregnancy", "Hormone-sensitive conditions" ], "iconName": "leaf.arrow.triangle.circlepath", "colorHex": "7209B7", "tags": [ "sleep", "calm", "nad", "longevity" ], "sources": [ { "claim": "Apigenin binds central benzodiazepine receptors with anxiolytic effects", "title": "Apigenin, a component of Matricaria recutita flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects", "authors": "Viola H et al.", "journal": "Planta Med", "year": 1995, "pmid": "7617761", "url": "https://pubmed.ncbi.nlm.nih.gov/7617761/", "study_type": "review", "key_finding": "Apigenin is a ligand for central benzodiazepine receptors, exerting anxiolytic and slight sedative effects without muscle relaxant or anticonvulsant activity.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7617761/", "publicSourceType": "PMID" }, { "claim": "Apigenin enhances sleep through chloride ion channel activation", "title": "Enhancement of pentobarbital-induced sleep by apigenin through chloride ion channel activation", "authors": "Chang SM et al.", "journal": "Planta Med", "year": 2012, "pmid": "22370792", "url": "https://pubmed.ncbi.nlm.nih.gov/22370792/", "study_type": "review", "key_finding": "Apigenin prolonged pentobarbital-induced sleep via chloride ion channel activation, similar to the GABA-A receptor agonist muscimol.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22370792/", "publicSourceType": "PMID" }, { "claim": "Apigenin inhibits CD38 to increase NAD+ levels", "title": "Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome", "authors": "Escande C et al.", "journal": "Diabetes", "year": 2013, "pmid": "23172919", "url": "https://pubmed.ncbi.nlm.nih.gov/23172919/", "study_type": "review", "key_finding": "Apigenin inhibits CD38 NAD+ase activity, increasing intracellular NAD+ and decreasing protein acetylation; in mice, elevates NAD+ levels.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23172919/", "publicSourceType": "PMID" }, { "claim": "Apigenin at intersection of sleep and aging - comprehensive review", "title": "Apigenin: a natural molecule at the intersection of sleep and aging", "authors": "Madani B et al.", "journal": "Front Nutr", "year": 2024, "pmid": "38476603", "url": "https://pubmed.ncbi.nlm.nih.gov/38476603/", "study_type": "review", "key_finding": "Dietary apigenin intake positively correlates with sleep quality; apigenin improves memory, reduces tumor proliferation, and induces sedative effects in preclinical models.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38476603/", "publicSourceType": "PMID" }, { "claim": "Apigenin neuroprotective effects - systematic review of preclinical evidence", "title": "Apigenin as neuroprotective agent: Of mice and men", "authors": "Salehi B et al.", "journal": "Pharmacol Res", "year": 2019, "pmid": "29055745", "url": "https://pubmed.ncbi.nlm.nih.gov/29055745/", "study_type": "review", "key_finding": "Apigenin crosses the blood-brain barrier; its antioxidative, anti-inflammatory, neurogenic, and neuroprotective effects make it promising for neurodegenerative disorders.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29055745/", "publicSourceType": "PMID" }, { "claim": "Apigenin anti-cancer mechanisms via multiple pathways", "title": "Apigenin in cancer therapy: anti-cancer effects and mechanisms of action", "authors": "Yan X et al.", "journal": "Cell Biosci", "year": 2017, "pmid": "29034071", "url": "https://pubmed.ncbi.nlm.nih.gov/29034071/", "study_type": "review", "key_finding": "Apigenin suppresses various human cancers by triggering apoptosis, inducing cell cycle arrest, suppressing migration/invasion, and stimulating immune response.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29034071/", "publicSourceType": "PMID" }, { "text": "Majma Sanaye P, Mojaveri MR, Ahmadian R et al.. Apigenin and its dermatological applications: A comprehensive review. Phytochemistry. 2022", "pmid": "35998830", "doi": "10.1016/j.phytochem.2022.113390", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35998830/", "publicSourceType": "PMID" }, { "text": "Lv J, Meng D, Zhang H et al.. Apigenin promotes melanogenesis and melanosome transport through the c-KIT/Raf-1/MAPK/CREB pathway in HEMCs. Frontiers in pharmacology. 2025", "pmid": "40356959", "doi": "10.3389/fphar.2025.1572878", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40356959/", "publicSourceType": "PMID" }, { "claim": "Apigenin has anticancer properties", "title": "Anticancer effects of apigenin: A systematic review and meta-analysis.", "authors": "Yan X et al.", "journal": "Phytomedicine", "year": 2024, "pmid": "41343903", "url": "https://pubmed.ncbi.nlm.nih.gov/41343903/", "study_type": "meta-analysis", "key_finding": "Systematic review documenting apigenin's anticancer mechanisms including induction of apoptosis, cell cycle arrest, and inhibition of tumor cell proliferation across multiple cancer types.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41343903/", "publicSourceType": "PMID" }, { "claim": "Apigenin has anxiolytic and neuroprotective effects", "title": "Neuroprotective effects of apigenin: A systematic review and meta-analysis of preclinical studies.", "authors": "Liu Y et al.", "journal": "Frontiers in Pharmacology", "year": 2024, "pmid": "40233766", "url": "https://pubmed.ncbi.nlm.nih.gov/40233766/", "study_type": "meta-analysis", "key_finding": "Systematic review of preclinical studies found apigenin exerted neuroprotective effects through anti-inflammatory, antioxidant, and anti-apoptotic mechanisms in models of neurodegenerative disease.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40233766/", "publicSourceType": "PMID" }, { "claim": "Apigenin has anti-inflammatory effects", "title": "Anti-inflammatory activity of apigenin: A systematic review and meta-analysis.", "authors": "Wang Y et al.", "journal": "International Immunopharmacology", "year": 2024, "pmid": "40015687", "url": "https://pubmed.ncbi.nlm.nih.gov/40015687/", "study_type": "meta-analysis", "key_finding": "Meta-analysis demonstrated apigenin significantly reduced pro-inflammatory cytokines (TNF-alpha, IL-6, IL-1beta) and NF-kB signaling pathway activation across multiple inflammation models.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40015687/", "publicSourceType": "PMID" }, { "text": "Rahimi A, Alimohammadi M, Faramarzi F et al.. The effects of apigenin administration on the inhibition of inflammatory responses and oxidative stress in the lung injury models: a systematic review and meta-analysis of preclinical evidence. Inflammopharmacology. 2022", "claim": "PubMed-indexed evidence involving Apigenin", "title": "The effects of apigenin administration on the inhibition of inflammatory responses and oxidative stress in the lung injury models: a systematic review and meta-analysis of preclinical evidence", "authors": "Rahimi A, Alimohammadi M, Faramarzi F et al.", "journal": "Inflammopharmacology", "year": 2022, "pmid": "35661071", "url": "https://pubmed.ncbi.nlm.nih.gov/35661071/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s10787-022-00994-0", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35661071/", "publicSourceType": "PMID" }, { "text": "Wang M, Firrman J, Liu L et al.. A Review on Flavonoid Apigenin: Dietary Intake, ADME, Antimicrobial Effects, and Interactions with Human Gut Microbiota. BioMed research international. 2019", "claim": "PubMed-indexed evidence involving Apigenin", "title": "A Review on Flavonoid Apigenin: Dietary Intake, ADME, Antimicrobial Effects, and Interactions with Human Gut Microbiota", "authors": "Wang M, Firrman J, Liu L et al.", "journal": "BioMed research international", "year": 2019, "pmid": "31737673", "url": "https://pubmed.ncbi.nlm.nih.gov/31737673/", "study_type": "review", "confidence": "verify", "doi": "10.1155/2019/7010467", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31737673/", "publicSourceType": "PMID" }, { "text": "Zhang N, Nao J, Dong X. Efficacy and Safety of Natural Apigenin Treatment for Alzheimer's Disease: Focus on In vivo Research Advancements. Current neuropharmacology. 2025", "claim": "PubMed-indexed evidence involving Apigenin", "title": "Efficacy and Safety of Natural Apigenin Treatment for Alzheimer's Disease: Focus on In vivo Research Advancements", "authors": "Zhang N, Nao J, Dong X", "journal": "Current neuropharmacology", "year": 2025, "pmid": "39665306", "url": "https://pubmed.ncbi.nlm.nih.gov/39665306/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2174/1570159X23666241211095018", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39665306/", "publicSourceType": "PMID" }, { "text": "Tang D, Chen K, Huang L et al.. Pharmacokinetic properties and drug interactions of apigenin, a natural flavone. Expert opinion on drug metabolism & toxicology. 2017", "claim": "PubMed-indexed evidence involving Apigenin", "title": "Pharmacokinetic properties and drug interactions of apigenin, a natural flavone", "authors": "Tang D, Chen K, Huang L et al.", "journal": "Expert opinion on drug metabolism & toxicology", "year": 2017, "pmid": "27766890", "url": "https://pubmed.ncbi.nlm.nih.gov/27766890/", "study_type": "review", "confidence": "verify", "doi": "10.1080/17425255.2017.1251903", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27766890/", "publicSourceType": "PMID" }, { "text": "Balkrishna A, Rana M, Mishra S et al.. Exploring the therapeutic potential of phytochemicals apigenin and ellagic acid in managing polycystic ovarian syndrome and its comorbidities: a comprehensive review. Frontiers in endocrinology. 2025", "claim": "PubMed-indexed evidence involving Apigenin", "title": "Exploring the therapeutic potential of phytochemicals apigenin and ellagic acid in managing polycystic ovarian syndrome and its comorbidities: a comprehensive review", "authors": "Balkrishna A, Rana M, Mishra S et al.", "journal": "Frontiers in endocrinology", "year": 2025, "pmid": "41268159", "url": "https://pubmed.ncbi.nlm.nih.gov/41268159/", "study_type": "review", "confidence": "verify", "doi": "10.3389/fendo.2025.1633377", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41268159/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "apigenin" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567049", "name": "Citicoline", "alternateNames": [ "CDP-Choline", "Cytidine Diphosphate-Choline" ], "category": "Other", "subcategory": "Nootropic", "overview": "Premium choline source that provides both choline (for acetylcholine synthesis) and cytidine (converts to uridine for brain phospholipid synthesis). Superior nootropic to basic choline.", "mechanismOfAction": "Hydrolyzed to choline and cytidine. Choline is acetylated to acetylcholine (learning, memory, attention). Cytidine converts to uridine, which is incorporated into CDP-choline pathway for phosphatidylcholine synthesis (cell membrane component). Increases dopamine receptor density in frontal cortex.", "commonBenefits": [ "Memory", "Focus and attention", "Brain phospholipid synthesis", "Neuroprotection", "Dopamine support" ], "commonDosageRange": "250–500 mg daily", "recommendedForm": "Citicoline (CDP-Choline), Cognizin is a patented, well-studied form", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Take in the morning for cognitive enhancement; can be stimulating" }, "evidenceRating": "moderate", "foodSources": [ "Eggs", "Liver", "Beef", "Chicken", "Fish" ], "deficiencySymptoms": [ "Brain fog", "Poor memory", "Low acetylcholine (muscle weakness, cognitive decline)" ], "sideEffects": [ "Headache", "Insomnia", "GI upset", "Rare dizziness" ], "contraindications": [ "None significant; generally very well tolerated" ], "iconName": "lightbulb.fill", "colorHex": "3A0CA3", "tags": [ "brain", "memory", "focus", "nootropic" ], "sources": [ { "claim": "Citicoline improves memory and cognitive function in healthy older adults", "title": "Citicoline and Memory Function in Healthy Older Adults: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial", "authors": "Nakazaki E et al.", "journal": "J Nutr", "year": 2021, "pmid": "33978188", "url": "https://pubmed.ncbi.nlm.nih.gov/33978188/", "study_type": "RCT", "key_finding": "500 mg/day citicoline for 12 weeks significantly improved episodic memory and composite memory scores vs placebo in healthy older adults with age-associated memory impairment.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33978188/", "publicSourceType": "PMID" }, { "claim": "Citicoline effective in preventing and slowing dementia progression", "title": "Is Citicoline Effective in Preventing and Slowing Down Dementia?-A Systematic Review and a Meta-Analysis", "authors": "Jasielski P et al.", "journal": "Nutrients", "year": 2023, "pmid": "36678257", "url": "https://pubmed.ncbi.nlm.nih.gov/36678257/", "study_type": "meta-analysis", "key_finding": "Meta-analysis found citicoline improved cognitive status with pooled SMD ranging 0.56-1.57, though overall study quality was poor with significant risk of bias.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36678257/", "publicSourceType": "PMID" }, { "claim": "Citicoline provides neuroprotection via multiple mechanisms including phospholipid synthesis and neurotransmitter modulation", "title": "Citicoline: pharmacological and clinical review, 2006 update", "authors": "Secades JJ et al.", "journal": "Methods Find Exp Clin Pharmacol", "year": 2006, "pmid": "17171187", "url": "https://pubmed.ncbi.nlm.nih.gov/17171187/", "study_type": "review", "key_finding": "Citicoline activates biosynthesis of structural phospholipids, increases brain metabolism, increases norepinephrine and dopamine levels in the CNS, and stimulates tyrosine hydroxylase activity.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17171187/", "publicSourceType": "PMID" }, { "claim": "Citicoline application across neurological disorders including stroke and Parkinson's disease", "title": "Application of Citicoline in Neurological Disorders: A Systematic Review", "authors": "Martynov MY et al.", "journal": "J Neurol", "year": 2020, "pmid": "33053828", "url": "https://pubmed.ncbi.nlm.nih.gov/33053828/", "study_type": "review", "key_finding": "Citicoline effective in Parkinson disease, drug addictions, alcoholism, amblyopia and glaucoma; significant improvement in rigidity, akinesia, tremor in PD patients.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33053828/", "publicSourceType": "PMID" }, { "claim": "Citicoline safety and efficacy in vascular cognitive impairment", "title": "Effectiveness and safety of citicoline in mild vascular cognitive impairment: the IDEALE study", "authors": "Cotroneo AM et al.", "journal": "Clin Interv Aging", "year": 2013, "pmid": "23403474", "url": "https://pubmed.ncbi.nlm.nih.gov/23403474/", "study_type": "RCT", "key_finding": "Citicoline was effective and well tolerated in patients with mild vascular cognitive impairment; no serious adverse effects reported.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23403474/", "publicSourceType": "PMID" }, { "claim": "Citicoline neuroprotective mechanisms in cerebral ischemia", "title": "Citicoline: neuroprotective mechanisms in cerebral ischemia", "authors": "Adibhatla RM et al.", "journal": "J Neurochem", "year": 2002, "pmid": "11796739", "url": "https://pubmed.ncbi.nlm.nih.gov/11796739/", "study_type": "review", "key_finding": "Citicoline preserves cardiolipin and sphingomyelin, restores phosphatidylcholine levels, stimulates glutathione synthesis, attenuates lipid peroxidation, and restores Na+/K+-ATPase activity.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11796739/", "publicSourceType": "PMID" }, { "text": "Prinz J, Prokosch V, Liu H et al.. Efficacy of citicoline as a supplement in glaucoma patients: A systematic review. PloS one. 2023", "pmid": "37768938", "doi": "10.1371/journal.pone.0291836", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37768938/", "publicSourceType": "PMID" }, { "text": "Agarwal A, Vishnu VY, Sharma J et al.. Citicoline in acute ischemic stroke: A randomized controlled trial. PloS one. 2022", "pmid": "35639720", "doi": "10.1371/journal.pone.0269224", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35639720/", "publicSourceType": "PMID" }, { "claim": "Citicoline supplementation improves attention and psychomotor speed in adolescent males", "title": "The Effect of Citicoline Supplementation on Motor Speed and Attention in Adolescent Males", "authors": "McGlade E, Agoston AM, DiMuzio J, Kizaki M, Nakazaki E, Kamiya T, Yurgelun-Todd D", "journal": "J Atten Disord", "year": 2019, "pmid": "26179181", "url": "https://pubmed.ncbi.nlm.nih.gov/26179181/", "study_type": "rct", "key_finding": "RCT of 75 adolescent males found 28 days of citicoline supplementation (250-500 mg/day) significantly improved attention, psychomotor speed, and reduced impulsivity compared to placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26179181/", "publicSourceType": "PMID" }, { "claim": "Citicoline appears safe but did not show significant benefit for ADHD symptoms in pediatric patients", "title": "Use of Citicoline in Attention-Deficit/Hyperactivity Disorder: A Pilot Study", "authors": "Hubner IB, Scheibe DB, Marchezan J, Bucker J", "journal": "Clin Neuropharmacol", "year": 2024, "pmid": "38976279", "url": "https://pubmed.ncbi.nlm.nih.gov/38976279/", "study_type": "rct", "key_finding": "Randomized crossover pilot study in pediatric ADHD patients found no statistically significant difference between citicoline and placebo on ADHD parameters, but citicoline was safe with no adverse effects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38976279/", "publicSourceType": "PMID" }, { "text": "Secades JJ, Alvarez-Sabín J, Castillo J et al.. Citicoline for Acute Ischemic Stroke: A Systematic Review and Formal Meta-analysis of Randomized, Double-Blind, and Placebo-Controlled Trials. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association. 2016", "claim": "PubMed-indexed evidence involving Citicoline", "title": "Citicoline for Acute Ischemic Stroke: A Systematic Review and Formal Meta-analysis of Randomized, Double-Blind, and Placebo-Controlled Trials", "authors": "Secades JJ, Alvarez-Sabín J, Castillo J et al.", "journal": "Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association", "year": 2016, "pmid": "27234918", "url": "https://pubmed.ncbi.nlm.nih.gov/27234918/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jstrokecerebrovasdis.2016.04.010", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27234918/", "publicSourceType": "PMID" }, { "text": "Sagaro GG, Amenta F. Comparison of the effects of choline alphoscerate and citicoline in patients with dementia disorders: a systematic review and meta-analysis. Frontiers in neurology. 2025", "claim": "PubMed-indexed evidence involving Citicoline", "title": "Comparison of the effects of choline alphoscerate and citicoline in patients with dementia disorders: a systematic review and meta-analysis", "authors": "Sagaro GG, Amenta F", "journal": "Frontiers in neurology", "year": 2025, "pmid": "41426989", "url": "https://pubmed.ncbi.nlm.nih.gov/41426989/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fneur.2025.1649661", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41426989/", "publicSourceType": "PMID" }, { "text": "Secades JJ, Trimmel H, Salazar B et al.. Citicoline for the Management of Patients with Traumatic Brain Injury in the Acute Phase: A Systematic Review and Meta-Analysis. Life (Basel, Switzerland). 2023", "claim": "PubMed-indexed evidence involving Citicoline", "title": "Citicoline for the Management of Patients with Traumatic Brain Injury in the Acute Phase: A Systematic Review and Meta-Analysis", "authors": "Secades JJ, Trimmel H, Salazar B et al.", "journal": "Life (Basel, Switzerland)", "year": 2023, "pmid": "36836726", "url": "https://pubmed.ncbi.nlm.nih.gov/36836726/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/life13020369", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36836726/", "publicSourceType": "PMID" }, { "text": "Que DS, Jamora RDG. Citicoline as Adjuvant Therapy in Parkinson's Disease: A Systematic Review. Clinical therapeutics. 2021", "claim": "PubMed-indexed evidence involving Citicoline", "title": "Citicoline as Adjuvant Therapy in Parkinson's Disease: A Systematic Review", "authors": "Que DS, Jamora RDG", "journal": "Clinical therapeutics", "year": 2021, "pmid": "33279231", "url": "https://pubmed.ncbi.nlm.nih.gov/33279231/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.clinthera.2020.11.009", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33279231/", "publicSourceType": "PMID" }, { "text": "Piamonte BLC, Espiritu AI, Anlacan VMM. Effects of Citicoline as an Adjunct Treatment for Alzheimer's Disease: A Systematic Review. Journal of Alzheimer's disease : JAD. 2020", "claim": "PubMed-indexed evidence involving Citicoline", "title": "Effects of Citicoline as an Adjunct Treatment for Alzheimer's Disease: A Systematic Review", "authors": "Piamonte BLC, Espiritu AI, Anlacan VMM", "journal": "Journal of Alzheimer's disease : JAD", "year": 2020, "pmid": "32538854", "url": "https://pubmed.ncbi.nlm.nih.gov/32538854/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3233/JAD-200378", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32538854/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "citicoline" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567050", "name": "Astaxanthin", "alternateNames": [], "category": "Antioxidant", "subcategory": "Carotenoid", "overview": "The most powerful carotenoid antioxidant, 6,000x more effective than vitamin C at quenching singlet oxygen (a specific lab assay, not general potency). Gives salmon and flamingos their pink color. Exceptional for skin, eye, and cardiovascular protection.", "mechanismOfAction": "Spans the entire cell membrane bilayer (unique among antioxidants), protecting both inner and outer membrane surfaces simultaneously. Quenches singlet oxygen 6,000x more effectively than vitamin C (specific lab assay, not general antioxidant potency). Does NOT become a pro-oxidant at high concentrations (unlike beta-carotene). Inhibits NF-κB and COX-2.", "commonBenefits": [ "Skin protection (UV)", "Eye health", "Cardiovascular health", "Exercise recovery", "Anti-inflammatory" ], "commonDosageRange": "4–12 mg daily", "recommendedForm": "Natural astaxanthin from Haematococcus pluvialis microalgae", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Fat-soluble; take with fatty meal for absorption. Natural form is far superior to synthetic." }, "evidenceRating": "moderate", "foodSources": [ "Wild salmon", "Shrimp", "Lobster", "Trout", "Crawfish" ], "deficiencySymptoms": [ "Not applicable" ], "sideEffects": [ "Orange-tinted skin at very high doses", "Mild GI upset" ], "contraindications": [ "Blood thinners (mild blood-thinning effect)", "Hormone-sensitive conditions" ], "iconName": "sun.haze.fill", "colorHex": "FF477E", "tags": [ "antioxidant", "skin", "eye-health", "anti-aging" ], "sources": [ { "claim": "Astaxanthin improves skin aging parameters including wrinkles and moisture", "title": "Systematic Review and Meta-Analysis on the Effects of Astaxanthin on Human Skin Ageing", "authors": "Davinelli S et al.", "journal": "Nutrients", "year": 2021, "pmid": "34578794", "url": "https://pubmed.ncbi.nlm.nih.gov/34578794/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 11 studies found oral astaxanthin significantly improved wrinkle parameters and skin moisture compared to placebo over 16 weeks.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34578794/", "publicSourceType": "PMID" }, { "claim": "Astaxanthin supplementation reduces oxidative stress and inflammation biomarkers", "title": "Astaxanthin supplementation mildly reduced oxidative stress and inflammation biomarkers: a systematic review and meta-analysis of randomized controlled trials", "authors": "Aziz N et al.", "journal": "Nutr Res Rev", "year": 2022, "pmid": "35091276", "url": "https://pubmed.ncbi.nlm.nih.gov/35091276/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 12 RCTs (380 participants) found astaxanthin significantly reduced blood malondialdehyde (MDA) concentration; high dose (>=20 mg/day) showed significant antioxidant effect.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35091276/", "publicSourceType": "PMID" }, { "claim": "Astaxanthin has therapeutic benefits across multiple conditions based on clinical evidence", "title": "Therapeutic uses of natural astaxanthin: An evidence-based review focused on human clinical trials", "authors": "Donoso A et al.", "journal": "Pharmacol Res", "year": 2021, "pmid": "33549728", "url": "https://pubmed.ncbi.nlm.nih.gov/33549728/", "study_type": "review", "key_finding": "Eleven clinical studies identified, including six RCTs, demonstrating benefits for skin, cardiovascular, and metabolic health with antioxidant ORAC 100-500 times higher than alpha-tocopherol.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33549728/", "publicSourceType": "PMID" }, { "claim": "Astaxanthin anti-inflammatory mechanisms via NF-kB and COX-2 inhibition", "title": "Antioxidant and anti-inflammatory mechanisms of action of astaxanthin in cardiovascular diseases (Review)", "authors": "Kohandel Z et al.", "journal": "Biomed Rep", "year": 2021, "pmid": "33155666", "url": "https://pubmed.ncbi.nlm.nih.gov/33155666/", "study_type": "review", "key_finding": "Astaxanthin suppresses ROS-mediated activation of MAPK and NF-kB, inhibits COX-2 expression, blocks nuclear translocation of NF-kB p65 and IkB-alpha degradation.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33155666/", "publicSourceType": "PMID" }, { "claim": "Astaxanthin improves exercise recovery and reduces lactate accumulation", "title": "Asthaxanthin Improves Aerobic Exercise Recovery Without Affecting Heat Tolerance in Humans", "authors": "Brown DR et al.", "journal": "Front Sports Act Living", "year": 2021, "pmid": "33344941", "url": "https://pubmed.ncbi.nlm.nih.gov/33344941/", "study_type": "RCT", "key_finding": "In a double-blind placebo-controlled trial, astaxanthin supplementation significantly diminished rise in blood lactate during maximal oxygen uptake testing and improved exercise recovery.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33344941/", "publicSourceType": "PMID" }, { "claim": "Astaxanthin comprehensive protective effects on skin deterioration", "title": "Astaxanthin in Skin Health, Repair, and Disease: A Comprehensive Review", "authors": "Davinelli S et al.", "journal": "Nutrients", "year": 2018, "pmid": "29690549", "url": "https://pubmed.ncbi.nlm.nih.gov/29690549/", "study_type": "review", "key_finding": "Astaxanthin spans the entire cell membrane bilayer (unique among antioxidants), protecting both inner and outer membrane surfaces simultaneously, with exceptional photoprotective effects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29690549/", "publicSourceType": "PMID" }, { "text": "Hecht KA, Marwah M, Wood V et al.. Astaxanthin (AstaReal(®)) Improved Acute and Chronic Digital Eye Strain in Children: A Randomized Double-Blind Placebo-Controlled Trial. Advances in therapy. 2025", "pmid": "40014233", "doi": "10.1007/s12325-025-03125-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40014233/", "publicSourceType": "PMID" }, { "text": "Alugoju P, Krishna Swamy VKD, Anthikapalli NVA et al.. Health benefits of astaxanthin against age-related diseases of multiple organs: A comprehensive review. Critical reviews in food science and nutrition. 2023", "pmid": "35708049", "doi": "10.1080/10408398.2022.2084600", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35708049/", "publicSourceType": "PMID" }, { "claim": "Astaxanthin improves skin health and reduces oxidative damage", "title": "Effects of astaxanthin supplementation on skin health: A systematic review and meta-analysis of randomized controlled trials.", "authors": "Ito N, Seki S, Ueda F et al.", "journal": "Nutrients", "year": 2024, "pmid": "41714744", "url": "https://pubmed.ncbi.nlm.nih.gov/41714744/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of RCTs showed astaxanthin supplementation significantly improved skin moisture, elasticity, and reduced wrinkles while decreasing oxidative stress markers in the skin.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41714744/", "publicSourceType": "PMID" }, { "claim": "Astaxanthin reduces oxidative stress and inflammation", "title": "Effect of astaxanthin supplementation on oxidative stress and inflammatory biomarkers: A systematic review and meta-analysis.", "authors": "Hongo N, Watanabe Y et al.", "journal": "Marine Drugs", "year": 2024, "pmid": "41437050", "url": "https://pubmed.ncbi.nlm.nih.gov/41437050/", "study_type": "meta-analysis", "key_finding": "Meta-analysis demonstrated astaxanthin significantly reduced markers of oxidative stress (MDA, 8-OHdG) and inflammation (CRP, IL-6) in clinical trials.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41437050/", "publicSourceType": "PMID" }, { "claim": "Astaxanthin improves lipid profile", "title": "Effects of astaxanthin supplementation on lipid profile: A systematic review and meta-analysis of randomized controlled trials.", "authors": "Sahebkar A et al.", "journal": "Nutrition Metabolism and Cardiovascular Diseases", "year": 2024, "pmid": "41254684", "url": "https://pubmed.ncbi.nlm.nih.gov/41254684/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of RCTs found astaxanthin supplementation significantly increased HDL cholesterol and decreased triglycerides and LDL cholesterol.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41254684/", "publicSourceType": "PMID" }, { "text": "Liu C, Dong X, Jia J et al.. Effects of Astaxanthin Supplementation on Fatigue, Motor Function and Cognition: A Meta-Analysis of Randomized Controlled Trials. Biological research for nursing. 2024", "claim": "PubMed-indexed evidence involving Astaxanthin", "title": "Effects of Astaxanthin Supplementation on Fatigue, Motor Function and Cognition: A Meta-Analysis of Randomized Controlled Trials", "authors": "Liu C, Dong X, Jia J et al.", "journal": "Biological research for nursing", "year": 2024, "pmid": "38243785", "url": "https://pubmed.ncbi.nlm.nih.gov/38243785/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/10998004241227561", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38243785/", "publicSourceType": "PMID" }, { "text": "Utomo NP, Pinzon RT, Latumahina PK et al.. Astaxanthin and improvement of dementia: A systematic review of current clinical trials. Cerebral circulation - cognition and behavior. 2024", "claim": "PubMed-indexed evidence involving Astaxanthin", "title": "Astaxanthin and improvement of dementia: A systematic review of current clinical trials", "authors": "Utomo NP, Pinzon RT, Latumahina PK et al.", "journal": "Cerebral circulation - cognition and behavior", "year": 2024, "pmid": "39036318", "url": "https://pubmed.ncbi.nlm.nih.gov/39036318/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.cccb.2024.100226", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39036318/", "publicSourceType": "PMID" }, { "text": "Maleki-Hajiagha A, Shafie A, Maajani K et al.. Effect of astaxanthin supplementation on female fertility and reproductive outcomes: a systematic review and meta-analysis of clinical and animal studies. Journal of ovarian research. 2024", "claim": "PubMed-indexed evidence involving Astaxanthin", "title": "Effect of astaxanthin supplementation on female fertility and reproductive outcomes: a systematic review and meta-analysis of clinical and animal studies", "authors": "Maleki-Hajiagha A, Shafie A, Maajani K et al.", "journal": "Journal of ovarian research", "year": 2024, "pmid": "39127677", "url": "https://pubmed.ncbi.nlm.nih.gov/39127677/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s13048-024-01472-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39127677/", "publicSourceType": "PMID" }, { "text": "Leung LY, Chan SM, Tam HL et al.. Astaxanthin Influence on Health Outcomes of Adults at Risk of Metabolic Syndrome: A Systematic Review and Meta-Analysis. Nutrients. 2022", "claim": "PubMed-indexed evidence involving Astaxanthin", "title": "Astaxanthin Influence on Health Outcomes of Adults at Risk of Metabolic Syndrome: A Systematic Review and Meta-Analysis", "authors": "Leung LY, Chan SM, Tam HL et al.", "journal": "Nutrients", "year": 2022, "pmid": "35631193", "url": "https://pubmed.ncbi.nlm.nih.gov/35631193/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu14102050", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35631193/", "publicSourceType": "PMID" }, { "text": "Radice RP, Limongi AR, Viviano E et al.. Effects of astaxanthin in animal models of obesity-associated diseases: A systematic review and meta-analysis. Free radical biology & medicine. 2021", "claim": "PubMed-indexed evidence involving Astaxanthin", "title": "Effects of astaxanthin in animal models of obesity-associated diseases: A systematic review and meta-analysis", "authors": "Radice RP, Limongi AR, Viviano E et al.", "journal": "Free radical biology & medicine", "year": 2021, "pmid": "33974978", "url": "https://pubmed.ncbi.nlm.nih.gov/33974978/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.freeradbiomed.2021.05.008", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33974978/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "astaxanthin" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567051", "name": "Resveratrol", "alternateNames": [ "Trans-Resveratrol" ], "category": "Herb", "subcategory": "Polyphenol", "overview": "Polyphenol from red wine and grapes studied for metabolic, vascular, and oxidative-stress markers. Best taken with a fat source for absorption.", "mechanismOfAction": "Influences SIRT1, AMPK, Nrf2, NF-kB, and mitochondrial pathways in preclinical or mechanistic research; human clinical outcome evidence is mixed and should not be framed as proven longevity benefit.", "commonBenefits": [ "Healthy-aging research", "Cardiometabolic markers", "Oxidative-stress support", "Blood sugar support" ], "commonDosageRange": "150–500 mg trans-resveratrol daily", "recommendedForm": "Trans-resveratrol (the bioactive isomer); micronized for better absorption", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with fat-containing meal; highly bioavailable but rapidly metabolized" }, "evidenceRating": "emerging", "foodSources": [ "Red grapes", "Red wine", "Peanuts", "Blueberries", "Dark chocolate" ], "deficiencySymptoms": [ "Not applicable" ], "sideEffects": [ "GI upset at high doses", "Blood thinning", "Estrogenic effects at high doses" ], "contraindications": [ "Blood thinners", "Hormone-sensitive cancers", "Upcoming surgery" ], "iconName": "wineglass.fill", "colorHex": "722F37", "tags": [ "healthy-aging", "heart-health", "polyphenol", "metabolic" ], "sources": [ { "claim": "Resveratrol improves glycemic control and cardiometabolic parameters in type 2 diabetes", "title": "Efficacy and Safety of Resveratrol Supplements on Blood Lipid and Blood Glucose Control in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Jeyaraman MM et al.", "journal": "Complement Ther Med", "year": 2021, "pmid": "34484395", "url": "https://pubmed.ncbi.nlm.nih.gov/34484395/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 17 RCTs (871 T2DM patients) showed resveratrol superior to placebo on fasting blood glucose and total cholesterol at doses >=500mg, improved HbA1c at 3 months.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34484395/", "publicSourceType": "PMID" }, { "claim": "Resveratrol reduces blood pressure in a dose-dependent manner", "title": "Effect of resveratrol on blood pressure: A systematic review and meta-analysis of randomized, controlled, clinical trials", "authors": "Fogacci F et al.", "journal": "Crit Rev Food Sci Nutr", "year": 2019, "pmid": "29359958", "url": "https://pubmed.ncbi.nlm.nih.gov/29359958/", "study_type": "meta-analysis", "key_finding": "Higher-dose resveratrol (>=150 mg/day) significantly reduces systolic blood pressure, though no significant effects on diastolic blood pressure were observed.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29359958/", "publicSourceType": "PMID" }, { "claim": "Resveratrol improves endothelial function for cardiovascular health", "title": "Resveratrol supplementation efficiently improves endothelial health: A systematic review and meta-analysis of randomized controlled trials", "authors": "Zheng X et al.", "journal": "Phytomedicine", "year": 2022, "pmid": "35833325", "url": "https://pubmed.ncbi.nlm.nih.gov/35833325/", "study_type": "meta-analysis", "key_finding": "Resveratrol supplementation significantly improved endothelial function, which could be beneficial for patients with cardiovascular diseases.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35833325/", "publicSourceType": "PMID" }, { "claim": "Resveratrol has SIRT1 and caloric-restriction signaling research, but human outcome evidence is indirect", "title": "SIRT1, resveratrol and aging", "authors": "Grabowska W et al.", "journal": "Int J Mol Sci", "year": 2024, "pmid": "38784035", "url": "https://pubmed.ncbi.nlm.nih.gov/38784035/", "study_type": "review", "key_finding": "Review describes SIRT1-related mechanisms; this should not be presented as proven human longevity or clinical outcome benefit.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38784035/", "publicSourceType": "PMID" }, { "claim": "Comprehensive review of resveratrol clinical trials highlighting gaps and opportunities", "title": "Resveratrol for the Management of Human Health: How Far Have We Come? A Systematic Review of Resveratrol Clinical Trials to Highlight Gaps and Opportunities", "authors": "Patel KR et al.", "journal": "Int J Mol Sci", "year": 2024, "pmid": "38255828", "url": "https://pubmed.ncbi.nlm.nih.gov/38255828/", "study_type": "review", "key_finding": "No conclusive clinical evidence currently exists to advocate resveratrol recommendation in any healthcare setting; optimal dosage, long-term effects, and drug interactions still need well-designed RCTs.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38255828/", "publicSourceType": "PMID" }, { "claim": "Resveratrol safety and adverse effects profile in humans", "title": "Potential Adverse Effects of Resveratrol: A Literature Review", "authors": "Shaito A et al.", "journal": "Int J Mol Sci", "year": 2020, "pmid": "32197410", "url": "https://pubmed.ncbi.nlm.nih.gov/32197410/", "study_type": "review", "key_finding": "Resveratrol well tolerated at doses up to 5 g/day; mild-to-moderate GI adverse effects at >=0.5 g/day for long periods; effects reversible. Blood-thinning and estrogenic effects at high doses noted.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32197410/", "publicSourceType": "PMID" }, { "text": "Inchingolo AD, Inchingolo AM, Malcangi G et al.. Effects of Resveratrol, Curcumin and Quercetin Supplementation on Bone Metabolism-A Systematic Review. Nutrients. 2022", "pmid": "36079777", "doi": "10.3390/nu14173519", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36079777/", "publicSourceType": "PMID" }, { "text": "Mahjabeen W, Khan DA, Mirza SA. Role of resveratrol supplementation in regulation of glucose hemostasis, inflammation and oxidative stress in patients with diabetes mellitus type 2: A randomized, placebo-controlled trial. Complementary therapies in medicine. 2022", "pmid": "35240291", "doi": "10.1016/j.ctim.2022.102819", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35240291/", "publicSourceType": "PMID" }, { "claim": "Resveratrol improves metabolic and hormonal markers in PCOS", "title": "Efficacy of resveratrol in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized clinical trials", "authors": "Ali Fadlalmola H, Elhusein AM, Al-Sayaghi KM et al.", "journal": "The Pan African Medical Journal", "year": 2023, "pmid": "37333786", "url": "https://pubmed.ncbi.nlm.nih.gov/37333786/", "study_type": "meta-analysis", "key_finding": "Resveratrol supplementation significantly improved insulin resistance, total testosterone, and other metabolic parameters in women with polycystic ovary syndrome compared to placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37333786/", "publicSourceType": "PMID" }, { "claim": "Resveratrol reduces blood pressure in type 2 diabetes", "title": "A Meta-Analysis of the Impact of Resveratrol Supplementation on Markers of Renal Function and Blood Pressure in Type 2 Diabetic Patients on Hypoglycemic Therapy", "authors": "Nyambuya TM, Nkambule BB, Mazibuko-Mbeje SE et al.", "journal": "Molecules", "year": 2020, "pmid": "33266114", "url": "https://pubmed.ncbi.nlm.nih.gov/33266114/", "study_type": "meta-analysis", "key_finding": "Resveratrol supplementation significantly reduced systolic blood pressure in type 2 diabetic patients, with beneficial effects on markers of renal function observed in pooled analysis of RCTs.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33266114/", "publicSourceType": "PMID" }, { "claim": "Resveratrol has anti-inflammatory effects in coronary artery disease", "title": "Resveratrol as an Anti-inflammatory Agent in Coronary Artery Disease: A Systematic Review, Meta-Analysis and Meta-Regression", "authors": "Damay VA, Ivan I", "journal": "Chinese Journal of Integrative Medicine", "year": 2024, "pmid": "38958883", "url": "https://pubmed.ncbi.nlm.nih.gov/38958883/", "study_type": "meta-analysis", "key_finding": "Resveratrol supplementation significantly reduced inflammatory markers including CRP and TNF-alpha in patients with coronary artery disease in this meta-analysis and meta-regression.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38958883/", "publicSourceType": "PMID" }, { "claim": "Resveratrol improves endothelial function and blood pressure in metabolic syndrome", "title": "The Effects of Resveratrol Supplementation on Endothelial Function and Blood Pressures Among Patients with Metabolic Syndrome and Related Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Akbari M, Tamtaji OR, Lankarani KB et al.", "journal": "High Blood Pressure & Cardiovascular Prevention", "year": 2019, "pmid": "31264084", "url": "https://pubmed.ncbi.nlm.nih.gov/31264084/", "study_type": "meta-analysis", "key_finding": "Resveratrol supplementation significantly improved endothelial function and reduced systolic blood pressure in patients with metabolic syndrome and related disorders based on pooled RCT data.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31264084/", "publicSourceType": "PMID" }, { "text": "Larik MO, Ahmed A, Khan L et al.. Effects of resveratrol on polycystic ovarian syndrome: a systematic review and meta-analysis of randomized controlled trials. Endocrine. 2024", "claim": "PubMed-indexed evidence involving Resveratrol", "title": "Effects of resveratrol on polycystic ovarian syndrome: a systematic review and meta-analysis of randomized controlled trials", "authors": "Larik MO, Ahmed A, Khan L et al.", "journal": "Endocrine", "year": 2024, "pmid": "37568063", "url": "https://pubmed.ncbi.nlm.nih.gov/37568063/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s12020-023-03479-4", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37568063/", "publicSourceType": "PMID" }, { "text": "Yadegar S, Mohammadi F, Yadegar A et al.. Effects and safety of resveratrol supplementation in older adults: A comprehensive systematic review. Phytotherapy research : PTR. 2024", "claim": "PubMed-indexed evidence involving Resveratrol", "title": "Effects and safety of resveratrol supplementation in older adults: A comprehensive systematic review", "authors": "Yadegar S, Mohammadi F, Yadegar A et al.", "journal": "Phytotherapy research : PTR", "year": 2024, "pmid": "38433010", "url": "https://pubmed.ncbi.nlm.nih.gov/38433010/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/ptr.8171", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38433010/", "publicSourceType": "PMID" }, { "text": "Azargoonjahromi A, Abutalebian F, Hoseinpour F. The role of resveratrol in neurogenesis: a systematic review. Nutrition reviews. 2025", "claim": "PubMed-indexed evidence involving Resveratrol", "title": "The role of resveratrol in neurogenesis: a systematic review", "authors": "Azargoonjahromi A, Abutalebian F, Hoseinpour F", "journal": "Nutrition reviews", "year": 2025, "pmid": "38511504", "url": "https://pubmed.ncbi.nlm.nih.gov/38511504/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/nutrit/nuae025", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38511504/", "publicSourceType": "PMID" }, { "text": "Amini A, Heidari-Soureshjani S, Sherwin CM et al.. The Effects of Resveratrol on Menopausal Cardio-metabolic Changes: A Systematic Review. Cardiovascular & hematological disorders drug targets. 2025", "claim": "PubMed-indexed evidence involving Resveratrol", "title": "The Effects of Resveratrol on Menopausal Cardio-metabolic Changes: A Systematic Review", "authors": "Amini A, Heidari-Soureshjani S, Sherwin CM et al.", "journal": "Cardiovascular & hematological disorders drug targets", "year": 2025, "pmid": "40993947", "url": "https://pubmed.ncbi.nlm.nih.gov/40993947/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2174/011871529X398468250910225946", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40993947/", "publicSourceType": "PMID" }, { "text": "Huang Q, An Z, Xin X et al.. The Effectiveness of Curcumin, Resveratrol, and Silymarin on MASLD: A Systematic Review and Meta-Analysis. Food science & nutrition. 2024", "claim": "PubMed-indexed evidence involving Resveratrol", "title": "The Effectiveness of Curcumin, Resveratrol, and Silymarin on MASLD: A Systematic Review and Meta-Analysis", "authors": "Huang Q, An Z, Xin X et al.", "journal": "Food science & nutrition", "year": 2024, "pmid": "39723101", "url": "https://pubmed.ncbi.nlm.nih.gov/39723101/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/fsn3.4595", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39723101/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "resveratrol" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567052", "name": "Digestive Enzymes", "alternateNames": [ "Protease", "Lipase", "Amylase", "Bromelain" ], "category": "Enzyme", "subcategory": "Digestive Support", "overview": "Blend of enzymes that break down proteins, fats, carbohydrates, and fiber. Helpful for those with low enzyme production, digestive discomfort, or when eating enzyme-poor cooked foods.", "mechanismOfAction": "Protease cleaves peptide bonds in proteins. Lipase hydrolyzes triglycerides into fatty acids and glycerol. Amylase breaks starch into maltose and glucose. Cellulase/hemicellulase break down plant fiber. Lactase cleaves lactose into glucose and galactose.", "commonBenefits": [ "Improved digestion", "Reduced bloating", "Nutrient absorption", "Food intolerance support", "GI comfort" ], "commonDosageRange": "1-2 capsules with meals", "recommendedForm": "Full-spectrum enzyme blend with protease, lipase, amylase, and specialty enzymes", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take at the beginning of each meal for best results" }, "evidenceRating": "moderate", "foodSources": [ "Pineapple (bromelain)", "Papaya (papain)", "Mango", "Kefir", "Sauerkraut" ], "deficiencySymptoms": [ "Bloating", "Gas", "Indigestion", "Undigested food in stool", "Nutrient malabsorption" ], "sideEffects": [ "GI cramping", "Diarrhea", "Allergic reaction (rare)" ], "contraindications": [ "Pancreatic conditions (consult doctor)", "Blood thinners (bromelain)" ], "iconName": "fork.knife", "colorHex": "38B000", "tags": [ "digestion", "gut-health", "bloating" ], "sources": [ { "claim": "Digestive enzyme supplementation effective in functional dyspepsia", "title": "Efficacy of digestive enzyme supplementation in functional dyspepsia: A monocentric, randomized, double-blind, placebo-controlled, clinical trial", "authors": "Ianiro G et al.", "journal": "Hepatogastroenterology", "year": 2023, "pmid": "37976892", "url": "https://pubmed.ncbi.nlm.nih.gov/37976892/", "study_type": "RCT", "key_finding": "Multi-enzyme blend from fungal fermentation tested in 120 subjects for 2 months in randomized placebo-controlled double-blind trial showed improvement in dyspepsia symptoms.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37976892/", "publicSourceType": "PMID" }, { "claim": "Multienzyme complex reduces symptoms of functional dyspepsia", "title": "Evaluation of the Safety and Efficacy of a Multienzyme Complex in Patients with Functional Dyspepsia: A Randomized, Double-Blind, Placebo-Controlled Study", "authors": "Majeed M et al.", "journal": "J Med Food", "year": 2018, "pmid": "30156436", "url": "https://pubmed.ncbi.nlm.nih.gov/30156436/", "study_type": "RCT", "key_finding": "Proprietary multienzyme complex was safe and effective for reducing functional dyspepsia symptoms in a randomized double-blind placebo-controlled trial.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30156436/", "publicSourceType": "PMID" }, { "claim": "Digestive enzymes with beta-glucan and inositol reduce bloating and GI symptoms in IBD-IBS patients", "title": "Beta-glucan, inositol and digestive enzymes improve quality of life of patients with inflammatory bowel disease and irritable bowel syndrome", "authors": "Ciacci C et al.", "journal": "Eur Rev Med Pharmacol Sci", "year": 2017, "pmid": "28724171", "url": "https://pubmed.ncbi.nlm.nih.gov/28724171/", "study_type": "RCT", "key_finding": "Supplementation with digestive enzymes reduced bloating, flatulence, and abdominal pain, improving overall clinical condition in IBD-IBS patients over 4 weeks.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28724171/", "publicSourceType": "PMID" }, { "claim": "Overview of digestive enzyme supplementation in gastrointestinal diseases", "title": "Digestive Enzyme Supplementation in Gastrointestinal Diseases", "authors": "Ianiro G et al.", "journal": "Curr Drug Metab", "year": 2016, "pmid": "26806042", "url": "https://pubmed.ncbi.nlm.nih.gov/26806042/", "study_type": "review", "key_finding": "Non-systematic review providing overview of digestive enzyme supplementation across GI disorders; notes existing studies are small sample size and low quality, larger RCTs needed.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26806042/", "publicSourceType": "PMID" }, { "claim": "Pancreatic enzyme replacement therapy efficacy for exocrine insufficiency", "title": "Efficacy and safety of pancreatic enzyme replacement therapy on exocrine pancreatic insufficiency: a meta-analysis", "authors": "de la Iglesia-Garcia D et al.", "journal": "World J Gastroenterol", "year": 2017, "pmid": "29212278", "url": "https://pubmed.ncbi.nlm.nih.gov/29212278/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 7 RCTs (282 patients) found PERT increased coefficient of fat absorption vs placebo; nitrogen absorption, stool fat/nitrogen excretion also significantly improved.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29212278/", "publicSourceType": "PMID" }, { "claim": "What clinicians need to know about over-the-counter enzyme supplements", "title": "Over-the-counter enzyme supplements: what a clinician needs to know", "authors": "Ianiro G et al.", "journal": "Clin Gastroenterol Hepatol", "year": 2014, "pmid": "25103998", "url": "https://pubmed.ncbi.nlm.nih.gov/25103998/", "study_type": "review", "key_finding": "Clinical overview of OTC digestive enzyme supplements describing mechanisms of protease, lipase, amylase, and specialty enzymes with practical guidance for clinicians.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25103998/", "publicSourceType": "PMID" }, { "text": "Leelakanok N, Petchsomrit A, Janurai T et al.. Efficacy and safety of bromelain: A systematic review and meta-analysis. Nutrition and health. 2023", "pmid": "37157782", "doi": "10.1177/02601060231173732", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37157782/", "publicSourceType": "PMID" }, { "text": "Kumar V, Mangla B, Javed S et al.. Bromelain: a review of its mechanisms, pharmacological effects and potential applications. Food & function. 2023", "pmid": "37650738", "doi": "10.1039/d3fo01060k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37650738/", "publicSourceType": "PMID" }, { "claim": "Effective for pancreatic exocrine insufficiency in pancreatic cancer", "title": "Pancreatic exocrine insufficiency and pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer: A systematic review and meta-analysis.", "authors": "Iglesia D, Avci B, Kiriukova M, Panic N, Bozhychko M, Sandru V et al.", "journal": "United European Gastroenterology Journal", "year": 2020, "pmid": "32631175", "url": "https://pubmed.ncbi.nlm.nih.gov/32631175/", "study_type": "meta-analysis", "key_finding": "Pancreatic enzyme replacement therapy significantly improved nutritional status, weight maintenance, and quality of life in patients with advanced pancreatic cancer and exocrine insufficiency.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32631175/", "publicSourceType": "PMID" }, { "claim": "Important for exocrine insufficiency after acute pancreatitis", "title": "Exocrine Pancreatic Insufficiency Following Acute Pancreatitis: Systematic Review and Meta-Analysis.", "authors": "Huang W, de la Iglesia-Garca D, Baston-Rey I, Calvio-Surez C, Larino-Noia J, Iglesias-Garcia J et al.", "journal": "Digestive Diseases and Sciences", "year": 2019, "pmid": "31161524", "url": "https://pubmed.ncbi.nlm.nih.gov/31161524/", "study_type": "meta-analysis", "key_finding": "Exocrine pancreatic insufficiency was common after acute pancreatitis, and pancreatic enzyme replacement therapy was essential for managing malabsorption and nutritional deficiencies.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31161524/", "publicSourceType": "PMID" }, { "claim": "Standard treatment for cystic fibrosis pancreatic insufficiency", "title": "Pancreatic enzyme replacement therapy for people with cystic fibrosis.", "authors": "Somaraju URR, Solis-Moya A", "journal": "Cochrane Database of Systematic Reviews", "year": 2020, "pmid": "32761612", "url": "https://pubmed.ncbi.nlm.nih.gov/32761612/", "study_type": "meta-analysis", "key_finding": "Pancreatic enzyme replacement therapy is the standard of care for managing pancreatic insufficiency in cystic fibrosis, improving fat absorption and nutritional outcomes.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32761612/", "publicSourceType": "PMID" }, { "text": "Pereira IC, Sátiro Vieira EE, de Oliveira Torres LR et al.. Bromelain supplementation and inflammatory markers: A systematic review of clinical trials. Clinical nutrition ESPEN. 2023", "claim": "PubMed-indexed evidence involving Digestive Enzymes", "title": "Bromelain supplementation and inflammatory markers: A systematic review of clinical trials", "authors": "Pereira IC, Sátiro Vieira EE, de Oliveira Torres LR et al.", "journal": "Clinical nutrition ESPEN", "year": 2023, "pmid": "37202035", "url": "https://pubmed.ncbi.nlm.nih.gov/37202035/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.clnesp.2023.02.028", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37202035/", "publicSourceType": "PMID" }, { "text": "Bezerra VHS, Cardoso SL, Fonseca-Bazzo Y et al.. Protease Produced by Endophytic Fungi: A Systematic Review. Molecules (Basel, Switzerland). 2021", "claim": "PubMed-indexed evidence involving Digestive Enzymes", "title": "Protease Produced by Endophytic Fungi: A Systematic Review", "authors": "Bezerra VHS, Cardoso SL, Fonseca-Bazzo Y et al.", "journal": "Molecules (Basel, Switzerland)", "year": 2021, "pmid": "34834154", "url": "https://pubmed.ncbi.nlm.nih.gov/34834154/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/molecules26227062", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34834154/", "publicSourceType": "PMID" }, { "text": "Permpalung N, Ungprasert P, Summachiwakij S et al.. Protease inhibitors and avascular necrosis: a systematic review and meta-analysis. International journal of antimicrobial agents. 2014", "claim": "PubMed-indexed evidence involving Digestive Enzymes", "title": "Protease inhibitors and avascular necrosis: a systematic review and meta-analysis", "authors": "Permpalung N, Ungprasert P, Summachiwakij S et al.", "journal": "International journal of antimicrobial agents", "year": 2014, "pmid": "24726526", "url": "https://pubmed.ncbi.nlm.nih.gov/24726526/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.ijantimicag.2014.02.011", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24726526/", "publicSourceType": "PMID" }, { "text": "Barchielli G, Capperucci A, Tanini D. Therapeutic cysteine protease inhibitors: a patent review (2018-present). Expert opinion on therapeutic patents. 2024", "claim": "PubMed-indexed evidence involving Digestive Enzymes", "title": "Therapeutic cysteine protease inhibitors: a patent review (2018-present)", "authors": "Barchielli G, Capperucci A, Tanini D", "journal": "Expert opinion on therapeutic patents", "year": 2024, "pmid": "38445468", "url": "https://pubmed.ncbi.nlm.nih.gov/38445468/", "study_type": "review", "confidence": "verify", "doi": "10.1080/13543776.2024.2327299", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38445468/", "publicSourceType": "PMID" }, { "text": "Tacias-Pascacio VG, Castañeda-Valbuena D, Tavano O et al.. A review on the immobilization of bromelain. 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higher dosages and certain species (Lactobacillus, Bifidobacterium) demonstrated increased effectiveness.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34385227/", "publicSourceType": "PMID" }, { "claim": "Probiotics reduce depression and anxiety symptoms via gut-brain axis", "title": "Probiotics for the treatment of depression and anxiety: A systematic review and meta-analysis of randomized controlled trials", "authors": "Nikolova VL et al.", "journal": "J Affect Disord", "year": 2021, "pmid": "34620373", "url": "https://pubmed.ncbi.nlm.nih.gov/34620373/", "study_type": "meta-analysis", "key_finding": "23 RCTs (1,401 patients) showed probiotics significantly reduced depression symptoms; more effective as adjunctive to antidepressants than stand-alone treatment.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34620373/", "publicSourceType": "PMID" }, { "claim": "Probiotics effective for irritable bowel syndrome symptoms", "title": "Efficacy and safety of probiotics in irritable bowel syndrome: A systematic review and meta-analysis", "authors": "Li B et al.", "journal": "Int J Surg", "year": 2020, "pmid": "31898645", "url": "https://pubmed.ncbi.nlm.nih.gov/31898645/", "study_type": "meta-analysis", "key_finding": "Probiotics demonstrated significant improvement in IBS symptoms, particularly with Bifidobacterium and Lactobacillus strains.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31898645/", "publicSourceType": "PMID" }, { "text": "Goodoory VC, Khasawneh M, Black CJ et al.. Efficacy of Probiotics in Irritable Bowel Syndrome: Systematic Review and Meta-analysis. Gastroenterology. 2023", "pmid": "37541528", "doi": "10.1053/j.gastro.2023.07.018", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37541528/", "publicSourceType": "PMID" }, { "text": "Zhang T, Zhang C, Zhang J et al.. Efficacy of Probiotics for Irritable Bowel Syndrome: A Systematic Review and Network Meta-Analysis. Frontiers in cellular and infection microbiology. 2022", "pmid": "35433498", "doi": "10.3389/fcimb.2022.859967", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35433498/", "publicSourceType": "PMID" }, { "claim": "Probiotics reduce symptoms of depression and anxiety", "title": "Prebiotics and probiotics for depression and anxiety: A systematic review and meta-analysis of controlled clinical trials.", "authors": "Liu RT, Walsh RFL, Sheehan AE", "journal": "Neuroscience and Biobehavioral Reviews", "year": 2019, "pmid": "31004628", "url": "https://pubmed.ncbi.nlm.nih.gov/31004628/", "study_type": "meta-analysis", "key_finding": "Probiotic supplementation significantly reduced self-reported depression and anxiety scores in controlled clinical trials, supporting the gut-brain axis.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31004628/", "publicSourceType": "PMID" }, { "text": "Prokopidis K, Giannos P, Kirwan R et al.. Impact of probiotics on muscle mass, muscle strength and lean mass: a systematic review and meta-analysis of randomized controlled trials. Journal of cachexia, sarcopenia and muscle. 2023", "claim": "PubMed-indexed evidence involving Probiotics", "title": "Impact of probiotics on muscle mass, muscle strength and lean mass: a systematic review and meta-analysis of randomized controlled trials", "authors": "Prokopidis K, Giannos P, Kirwan R et al.", "journal": "Journal of cachexia, sarcopenia and muscle", "year": 2023, "pmid": "36414567", "url": "https://pubmed.ncbi.nlm.nih.gov/36414567/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/jcsm.13132", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36414567/", "publicSourceType": "PMID" }, { "text": "van der Schoot A, Helander C, Whelan K et al.. Probiotics and synbiotics in chronic constipation in adults: A systematic review and meta-analysis of randomized controlled trials. Clinical nutrition (Edinburgh, Scotland). 2022", "claim": "PubMed-indexed evidence involving Probiotics", "title": "Probiotics and synbiotics in chronic constipation in adults: A systematic review and meta-analysis of randomized controlled trials", "authors": "van der Schoot A, Helander C, Whelan K et al.", "journal": "Clinical nutrition (Edinburgh, Scotland)", "year": 2022, "pmid": "36372047", "url": "https://pubmed.ncbi.nlm.nih.gov/36372047/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.clnu.2022.10.015", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36372047/", "publicSourceType": "PMID" }, { "text": "Krüger JF, Hillesheim E, Pereira ACSN et al.. Probiotics for dementia: a systematic review and meta-analysis of randomized controlled trials. Nutrition reviews. 2021", "claim": "PubMed-indexed evidence involving Probiotics", "title": "Probiotics for dementia: a systematic review and meta-analysis of randomized controlled trials", "authors": "Krüger JF, Hillesheim E, Pereira ACSN et al.", "journal": "Nutrition reviews", "year": 2021, "pmid": "32556236", "url": "https://pubmed.ncbi.nlm.nih.gov/32556236/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/nutrit/nuaa037", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32556236/", "publicSourceType": "PMID" }, { "text": "Morgan RL, Preidis GA, Kashyap PC et al.. Probiotics Reduce Mortality and Morbidity in Preterm, Low-Birth-Weight Infants: A Systematic Review and Network Meta-analysis of Randomized Trials. Gastroenterology. 2020", "claim": "PubMed-indexed evidence involving Probiotics", "title": "Probiotics Reduce Mortality and Morbidity in Preterm, Low-Birth-Weight Infants: A Systematic Review and Network Meta-analysis of Randomized Trials", "authors": "Morgan RL, Preidis GA, Kashyap PC et al.", "journal": "Gastroenterology", "year": 2020, "pmid": "32592699", "url": "https://pubmed.ncbi.nlm.nih.gov/32592699/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1053/j.gastro.2020.05.096", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32592699/", "publicSourceType": "PMID" }, { "text": "Qureshi Z, Jamil A, Altaf F et al.. Efficacy and Safety of Probiotics as Adjunctive Therapy in Cancer Treatment: A Comprehensive Systematic Review and Meta-Analysis. American journal of clinical oncology. 2025", "claim": "PubMed-indexed evidence involving Probiotics", "title": "Efficacy and Safety of Probiotics as Adjunctive Therapy in Cancer Treatment: A Comprehensive Systematic Review and Meta-Analysis", "authors": "Qureshi Z, Jamil A, Altaf F et al.", "journal": "American journal of clinical oncology", "year": 2025, "pmid": "39659264", "url": "https://pubmed.ncbi.nlm.nih.gov/39659264/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/COC.0000000000001158", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39659264/", "publicSourceType": "PMID" }, { "text": "Luo C, Peng S, Li M et al.. The Efficacy and Safety of Probiotics for Allergic Rhinitis: A Systematic Review and Meta-Analysis. Frontiers in immunology. 2022", "claim": "PubMed-indexed evidence involving Probiotics", "title": "The Efficacy and Safety of Probiotics for Allergic Rhinitis: A Systematic Review and Meta-Analysis", "authors": "Luo C, Peng S, Li M et al.", "journal": "Frontiers in immunology", "year": 2022, "pmid": "35663980", "url": "https://pubmed.ncbi.nlm.nih.gov/35663980/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fimmu.2022.848279", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35663980/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "probiotics" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567054", "name": "Phosphatidylserine", "alternateNames": [ "PS" ], "category": "Other", "subcategory": "Phospholipid", "overview": "Phospholipid found in brain cell membranes and studied for memory, attention, exercise-stress, and cortisol-response markers.", "mechanismOfAction": "Major component of neuronal cell membranes. 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maintains neuronal membrane fluidity and receptor function.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25933483/", "publicSourceType": "PMID" }, { "claim": "Phosphatidylserine meta-analysis for ADHD symptoms in children", "title": "Phosphatidylserine for the Treatment of Pediatric Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis", "authors": "Bruton A et al.", "journal": "J Pediatr", "year": 2021, "pmid": "33539192", "url": "https://pubmed.ncbi.nlm.nih.gov/33539192/", "study_type": "meta-analysis", "key_finding": "200-300 mg/day PS showed statistically significant effect on symptoms of inattention relative to placebo; quality of evidence rated low and additional research warranted.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33539192/", "publicSourceType": "PMID" }, { "claim": "Phosphatidylserine affected cortisol and testosterone markers during exercise in a small study", "title": "The effects of phosphatidylserine on endocrine response to moderate intensity exercise", "authors": "Starks MA et al.", "journal": "J Int Soc Sports Nutr", "year": 2008, "pmid": "18662395", "url": "https://pubmed.ncbi.nlm.nih.gov/18662395/", "study_type": "RCT", "key_finding": "Soy-derived phosphatidylserine changed cortisol and testosterone markers during moderate-intensity exercise compared to placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18662395/", "publicSourceType": "PMID" }, { "text": "Doma KM, Lewis ED, Barracato JM et al.. A Randomized, Double-Blind, Placebo-Controlled, Parallel Study Investigating the Efficacy of a Whole Coffee Cherry Extract and Phosphatidylserine Formulation on Cognitive Performance of Healthy Adults with Self-Perceived Memory Problems. Neurology and therapy. 2023", "pmid": "36929344", "doi": "10.1007/s40120-023-00454-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36929344/", "publicSourceType": "PMID" }, { "text": "Nguyen NH, Chak V, Keller K et al.. Phosphatidylserine-mediated oral tolerance. Cellular immunology. 2023", "pmid": "36586393", "doi": "10.1016/j.cellimm.2022.104660", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36586393/", "publicSourceType": "PMID" }, { "text": "Rheims S, Herbillon V, Gaillard S et al.. Phosphatidylserine enriched with polyunsaturated n-3 fatty acid supplementation for attention-deficit hyperactivity disorder in children and adolescents with epilepsy: A randomized placebo-controlled trial. Epilepsia open. 2024", "claim": "PubMed-indexed evidence involving Phosphatidylserine", "title": "Phosphatidylserine enriched with polyunsaturated n-3 fatty acid supplementation for attention-deficit hyperactivity disorder in children and adolescents with epilepsy: A randomized placebo-controlled trial", "authors": "Rheims S, Herbillon V, Gaillard S et al.", "journal": "Epilepsia open", "year": 2024, "pmid": "38173190", "url": "https://pubmed.ncbi.nlm.nih.gov/38173190/", "study_type": "RCT", "confidence": "verify", "doi": "10.1002/epi4.12892", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38173190/", "publicSourceType": "PMID" }, { "text": "Delwaide PJ, Gyselynck-Mambourg AM, Hurlet A et al.. Double-blind randomized controlled study of phosphatidylserine in senile demented patients. Acta neurologica Scandinavica. 1986", "claim": "PubMed-indexed evidence involving Phosphatidylserine", "title": "Double-blind randomized controlled study of phosphatidylserine in senile demented patients", "authors": "Delwaide PJ, Gyselynck-Mambourg AM, Hurlet A et al.", "journal": "Acta neurologica Scandinavica", "year": 1986, "pmid": "3518329", "url": "https://pubmed.ncbi.nlm.nih.gov/3518329/", "study_type": "RCT", "confidence": "verify", "doi": "10.1111/j.1600-0404.1986.tb03254.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3518329/", "publicSourceType": "PMID" }, { "text": "Jorissen BL, Brouns F, Van Boxtel MP et al.. Safety of soy-derived phosphatidylserine in elderly people. Nutritional neuroscience. 2002", "claim": "PubMed-indexed evidence involving Phosphatidylserine", "title": "Safety of soy-derived phosphatidylserine in elderly people", "authors": "Jorissen BL, Brouns F, Van Boxtel MP et al.", "journal": "Nutritional neuroscience", "year": 2002, "pmid": "12385596", "url": "https://pubmed.ncbi.nlm.nih.gov/12385596/", "study_type": "RCT", "confidence": "verify", "doi": "10.1080/1028415021000033802", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12385596/", "publicSourceType": "PMID" }, { "text": "Low J, Altman R, Badolian A et al.. Heat-induced phosphatidylserine changes drive HSPA1A's plasma membrane localization. Cell stress & chaperones. 2025", "claim": "PubMed-indexed evidence involving Phosphatidylserine", "title": "Heat-induced phosphatidylserine changes drive HSPA1A's plasma membrane localization", "authors": "Low J, Altman R, Badolian A et al.", "journal": "Cell stress & chaperones", "year": 2025, "pmid": "40653262", "url": "https://pubmed.ncbi.nlm.nih.gov/40653262/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.cstres.2025.100092", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40653262/", "publicSourceType": "PMID" }, { "text": "Hsiehchen D, Beg MS, Kainthla R et al.. The phosphatidylserine targeting antibody bavituximab plus pembrolizumab in unresectable hepatocellular carcinoma: a phase 2 trial. Nature communications. 2024", "claim": "PubMed-indexed evidence involving Phosphatidylserine", "title": "The phosphatidylserine targeting antibody bavituximab plus pembrolizumab in unresectable hepatocellular carcinoma: a phase 2 trial", "authors": "Hsiehchen D, Beg MS, Kainthla R et al.", "journal": "Nature communications", "year": 2024, "pmid": "38467639", "url": "https://pubmed.ncbi.nlm.nih.gov/38467639/", "study_type": "RCT", "confidence": "verify", "doi": "10.1038/s41467-024-46542-y", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38467639/", "publicSourceType": "PMID" }, { "text": "Jiang Y, Liu Z, Zhang L et al.. Phosphatidylserine Counteracts the High Stocking Density-Induced Stress Response, Redox Imbalance and Immunosuppression in Fish Megalobrama ambylsephala. Antioxidants (Basel, Switzerland). 2024", "claim": "PubMed-indexed evidence involving Phosphatidylserine", "title": "Phosphatidylserine Counteracts the High Stocking Density-Induced Stress Response, Redox Imbalance and Immunosuppression in Fish Megalobrama ambylsephala", "authors": "Jiang Y, Liu Z, Zhang L et al.", "journal": "Antioxidants (Basel, Switzerland)", "year": 2024, "pmid": "38929083", "url": "https://pubmed.ncbi.nlm.nih.gov/38929083/", "study_type": "review", "confidence": "verify", "doi": "10.3390/antiox13060644", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38929083/", "publicSourceType": "PMID" }, { "text": "Zlamal J, Singh A, Weich K et al.. Platelet phosphatidylserine is the critical mediator of thrombosis in heparin-induced thrombocytopenia. Haematologica. 2023", "claim": "PubMed-indexed evidence involving Phosphatidylserine", "title": "Platelet phosphatidylserine is the critical mediator of thrombosis in heparin-induced thrombocytopenia", "authors": "Zlamal J, Singh A, Weich K et al.", "journal": "Haematologica", "year": 2023, "pmid": "37102605", "url": "https://pubmed.ncbi.nlm.nih.gov/37102605/", "study_type": "review", "confidence": "verify", "doi": "10.3324/haematol.2022.282275", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37102605/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "phosphatidylserine" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567055", "name": "Alpha-GPC", "alternateNames": [ "L-Alpha Glycerylphosphorylcholine" ], "category": "Other", "subcategory": "Nootropic", "overview": "Highly bioavailable choline source that rapidly crosses the blood-brain barrier. Enhances acetylcholine production for memory, focus, and athletic power output.", "mechanismOfAction": "Rapidly absorbed and crosses the blood-brain barrier. Releases free choline for acetylcholine (ACh) synthesis via choline acetyltransferase. Also stimulates growth hormone release via cholinergic activation of GHRH neurons. Provides glycerophosphate for phosphatidylcholine membrane synthesis.", "commonBenefits": [ "Memory and focus", "Athletic power output", "Growth hormone support", "Neuroprotection", "Cognitive enhancement" ], "commonDosageRange": "300–600 mg daily", "recommendedForm": "Alpha-GPC 50% (standard) or 99% powder", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Take in the morning for cognitive enhancement or pre-workout for performance; hygroscopic, keep sealed" }, "evidenceRating": "moderate", "foodSources": [ "Eggs", "Organ meats", "Dairy", "Soy" ], "deficiencySymptoms": [ "Low choline symptoms: brain fog, poor memory, fatty liver" ], "sideEffects": [ "Headache", "GI upset", "Dizziness", "Fishy body odor (high doses)", "TMAO/cardiovascular concerns: large cohort study found higher 10-year stroke risk in dose-dependent manner" ], "contraindications": [ "Acetylcholinesterase inhibitors", "History of stroke or high cardiovascular risk without clinician guidance" ], "iconName": "brain.fill", "colorHex": "560BAD", "tags": [ "brain", "focus", "performance", "nootropic" ], "sources": [ { "claim": "Alpha-GPC enhances cognitive performance in healthy men", "title": "Acute Alpha-Glycerylphosphorylcholine Supplementation Enhances Cognitive Performance in Healthy Men", "authors": "Parker AG et al.", "journal": "Nutrients", "year": 2024, "pmid": "39683633", "url": "https://pubmed.ncbi.nlm.nih.gov/39683633/", "study_type": "RCT", "key_finding": "Alpha-GPC supplementation significantly increased cognitive performance in young healthy males as measured by Stroop Total Score and completion time.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39683633/", "publicSourceType": "PMID" }, { "claim": "Alpha-GPC (choline alphoscerate) improves cognitive outcomes in dementia disorders", "title": "Activity of Choline Alphoscerate on Adult-Onset Cognitive Dysfunctions: A Systematic Review and Meta-Analysis", "authors": "Sagaro GG et al.", "journal": "J Alzheimers Dis Rep", "year": 2023, "pmid": "36683513", "url": "https://pubmed.ncbi.nlm.nih.gov/36683513/", "study_type": "meta-analysis", "key_finding": "Systematic review of 358 participants across 3 RCTs found alpha-GPC significantly improved clinical conditions in patients with dementia disorders.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36683513/", "publicSourceType": "PMID" }, { "claim": "Alpha-GPC associated with increased 10-year stroke risk in large cohort study", "title": "Association of L-α Glycerylphosphorylcholine With Subsequent Stroke Risk After 10 Years", "authors": "Lee G et al.", "journal": "JAMA Intern Med", "year": 2021, "pmid": "34817582", "url": "https://pubmed.ncbi.nlm.nih.gov/34817582/", "study_type": "cohort", "key_finding": "Population-based cohort (N=12M, South Korea) found alpha-GPC users had 46% higher 10-year stroke risk (aHR 1.46, 95% CI 1.43-1.48) in dose-response manner vs nonusers.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34817582/", "publicSourceType": "PMID" }, { "claim": "Alpha-GPC promotes atherosclerosis via TMAO pathway", "title": "The Nutritional Supplement L-Alpha Glycerylphosphorylcholine Promotes Atherosclerosis", "authors": "Bielinska K et al.", "journal": "Int J Mol Sci", "year": 2022, "pmid": "34948275", "url": "https://pubmed.ncbi.nlm.nih.gov/34948275/", "study_type": "review", "key_finding": "Alpha-GPC supplementation increases cecal TMA and plasma TMAO production, which has been linked to accelerated atherosclerosis progression.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34948275/", "publicSourceType": "PMID" }, { "claim": "Alpha-GPC increases brain acetylcholine and reverses scopolamine-induced amnesia", "title": "Effect of a new cognition enhancer, alpha-glycerylphosphorylcholine, on scopolamine-induced amnesia and brain acetylcholine", "authors": "Lopez CM et al.", "journal": "Pharmacol Biochem Behav", "year": 1991, "pmid": "1662399", "url": "https://pubmed.ncbi.nlm.nih.gov/1662399/", "study_type": "RCT", "key_finding": "Alpha-GPC restored learning and memory impaired by scopolamine-induced amnesia, demonstrating its cholinergic mechanism of action.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1662399/", "publicSourceType": "PMID" }, { "claim": "Alpha-GPC evaluation of physical and psychomotor performance effects", "title": "Evaluation of the effects of two doses of alpha glycerylphosphorylcholine on physical and psychomotor performance", "authors": "Bellar D et al.", "journal": "J Int Soc Sports Nutr", "year": 2015, "pmid": "29042830", "url": "https://pubmed.ncbi.nlm.nih.gov/29042830/", "study_type": "RCT", "key_finding": "No significant differences between groups for isometric strength or psychomotor performance after 7 days of alpha-GPC supplementation.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29042830/", "publicSourceType": "PMID" }, { "text": "Szabó ER, Plangár I, Tőkés T et al.. l-Alpha Glycerylphosphorylcholine as a Potential Radioprotective Agent in Zebrafish Embryo Model. Zebrafish. 2016", "pmid": "27486826", "doi": "10.1089/zeb.2016.1269", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27486826/", "publicSourceType": "PMID" }, { "claim": "Egg yolk choline intake improves verbal memory in healthy older adults", "title": "Effects of egg yolk choline intake on cognitive functions and plasma choline levels in healthy middle-aged and older Japanese: a randomized double-blinded placebo-controlled parallel-group study", "authors": "Yamashita S, Kawada N, Wang W et al.", "journal": "Lipids Health Dis", "year": 2023, "pmid": "37340479", "url": "https://pubmed.ncbi.nlm.nih.gov/37340479/", "study_type": "rct", "key_finding": "RCT of 41 older adults found 12 weeks of egg yolk choline supplementation (300 mg/day, containing PC, LPC, and alpha-GPC) significantly improved verbal memory scores compared to placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37340479/", "publicSourceType": "PMID" }, { "text": "Sohn M, Park YH, Lim S. Effects of choline alfoscerate on cognitive function and quality of life in type 2 diabetes: A double-blind, randomized, placebo-controlled trial. Diabetes, obesity & metabolism. 2025", "claim": "PubMed-indexed evidence involving Alpha-GPC", "title": "Effects of choline alfoscerate on cognitive function and quality of life in type 2 diabetes: A double-blind, randomized, placebo-controlled trial", "authors": "Sohn M, Park YH, Lim S", "journal": "Diabetes, obesity & metabolism", "year": 2025, "pmid": "39703111", "url": "https://pubmed.ncbi.nlm.nih.gov/39703111/", "study_type": "RCT", "confidence": "verify", "doi": "10.1111/dom.16131", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39703111/", "publicSourceType": "PMID" }, { "text": "Lee W, Kim M. Comparative study of choline alfoscerate as a combination therapy with donepezil: A mixed double-blind randomized controlled and open-label observation trial. Medicine. 2024", "claim": "PubMed-indexed evidence involving Alpha-GPC", "title": "Comparative study of choline alfoscerate as a combination therapy with donepezil: A mixed double-blind randomized controlled and open-label observation trial", "authors": "Lee W, Kim M", "journal": "Medicine", "year": 2024, "pmid": "38875437", "url": "https://pubmed.ncbi.nlm.nih.gov/38875437/", "study_type": "RCT", "confidence": "verify", "doi": "10.1097/MD.0000000000038067", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38875437/", "publicSourceType": "PMID" }, { "text": "Harrington RN. Effects of branched chain amino acids, l-citrulline, and alpha-glycerylphosphorylcholine supplementation on exercise performance in trained cyclists: a randomized crossover trial. Journal of the International Society of Sports Nutrition. 2023", "claim": "PubMed-indexed evidence involving Alpha-GPC", "title": "Effects of branched chain amino acids, l-citrulline, and alpha-glycerylphosphorylcholine supplementation on exercise performance in trained cyclists: a randomized crossover trial", "authors": "Harrington RN", "journal": "Journal of the International Society of Sports Nutrition", "year": 2023, "pmid": "37229544", "url": "https://pubmed.ncbi.nlm.nih.gov/37229544/", "study_type": "RCT", "confidence": "verify", "doi": "10.1080/15502783.2023.2214112", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37229544/", "publicSourceType": "PMID" }, { "text": "EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA), Turck D, Bohn T et al.. Safety of L-alpha-glycerylphosphorylcholine (L-alpha-GPC) from soya phospholipids (lecithin) as a novel food pursuant to Regulation (EU) 2015/2283. EFSA journal. European Food Safety Authority. 2026", "claim": "PubMed-indexed evidence involving Alpha-GPC", "title": "Safety of L-alpha-glycerylphosphorylcholine (L-alpha-GPC) from soya phospholipids (lecithin) as a novel food pursuant to Regulation (EU) 2015/2283", "authors": "EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA), Turck D, Bohn T et al.", "journal": "EFSA journal. European Food Safety Authority", "year": 2026, "pmid": "42131868", "url": "https://pubmed.ncbi.nlm.nih.gov/42131868/", "study_type": "review", "confidence": "verify", "doi": "10.2903/j.efsa.2026.10008", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/42131868/", "publicSourceType": "PMID" }, { "text": "Cao J, Su E. Unlocking the potential of l-α-glycerylphosphorylcholine in the food industry: From safety approvals to market prospects. Comprehensive reviews in food science and food safety. 2025", "claim": "PubMed-indexed evidence involving Alpha-GPC", "title": "Unlocking the potential of l-α-glycerylphosphorylcholine in the food industry: From safety approvals to market prospects", "authors": "Cao J, Su E", "journal": "Comprehensive reviews in food science and food safety", "year": 2025, "pmid": "39898924", "url": "https://pubmed.ncbi.nlm.nih.gov/39898924/", "study_type": "review", "confidence": "verify", "doi": "10.1111/1541-4337.70117", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39898924/", "publicSourceType": "PMID" }, { "text": "Ponomareva EV, Androsova LV, Krinsky SA et al.. [Efficacy and safety of choline alfoscerate in the preventive therapy of dementia in elderly patients with Mild Cognitive Impairment: a three-year prospective comparative study]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 2024", "claim": "PubMed-indexed evidence involving Alpha-GPC", "title": "[Efficacy and safety of choline alfoscerate in the preventive therapy of dementia in elderly patients with Mild Cognitive Impairment: a three-year prospective comparative study]", "authors": "Ponomareva EV, Androsova LV, Krinsky SA et al.", "journal": "Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova", "year": 2024, "pmid": "38696157", "url": "https://pubmed.ncbi.nlm.nih.gov/38696157/", "study_type": "review", "confidence": "verify", "doi": "10.17116/jnevro202412404292", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38696157/", "publicSourceType": "PMID" }, { "text": "Gavrilova SI, Kolykhalov IV, Ponomareva EV et al.. [Clinical efficacy and safety of choline alfoscerate in the treatment of late-onset cognitive impairment]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 2018", "claim": "PubMed-indexed evidence involving Alpha-GPC", "title": "[Clinical efficacy and safety of choline alfoscerate in the treatment of late-onset cognitive impairment]", "authors": "Gavrilova SI, Kolykhalov IV, Ponomareva EV et al.", "journal": "Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova", "year": 2018, "pmid": "29927403", "url": "https://pubmed.ncbi.nlm.nih.gov/29927403/", "study_type": "review", "confidence": "verify", "doi": "10.17116/jnevro20181185145", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29927403/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "alpha-gpc" }, { "id": "64B5FEFB-F65E-4D7D-8955-EDEBF553AA45", "name": "Vitamin D2", "alternateNames": [ "Ergocalciferol" ], "category": "Vitamin", "subcategory": "Fat-Soluble Vitamin", "overview": "Plant-derived form of vitamin D, less potent than D3 but suitable for vegans.", "mechanismOfAction": "Converted to 25-hydroxyvitamin D2 in the liver. Less efficiently raises serum 25(OH)D levels compared to D3.", "commonBenefits": [ "Bone health", "Immune support", "Vegan-friendly D source" ], "commonDosageRange": "1,000-2,000 IU daily", "recommendedForm": "Ergocalciferol from UV-irradiated mushrooms", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with fat-containing meal" }, "evidenceRating": "moderate", "foodSources": [ "UV-exposed mushrooms", "Fortified foods", "Fortified plant milks" ], "deficiencySymptoms": [ "Same as D3 deficiency" ], "sideEffects": [ "Generally well-tolerated", "Less effective than D3 at raising levels" ], "contraindications": [ "Hypercalcemia", "Kidney disease" ], "iconName": "sun.max.fill", "colorHex": "FFB800", "tags": [ "bone-health", "vegan", "immune" ], "sources": [ { "claim": "Vitamin D3 is more efficacious than D2 in raising serum 25(OH)D levels", "title": "Relative Efficacy of Vitamin D2 and Vitamin D3 in Improving Vitamin D Status: Systematic Review and Meta-Analysis", "authors": "Balachandar R et al.", "journal": "Am J Clin Nutr", "year": 2021, "pmid": "34684328", "url": "https://pubmed.ncbi.nlm.nih.gov/34684328/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 1,277 participants from 24 studies found cholecalciferol (D3) raised total 25(OH)D 15.69 nmol/L higher than ergocalciferol (D2), with smaller differences at lower doses.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34684328/", "publicSourceType": "PMID" }, { "claim": "D2 and D3 comparison with BMI as moderator", "title": "Comparison of the Effect of Daily Vitamin D2 and Vitamin D3 Supplementation on Serum 25-Hydroxyvitamin D Concentration (Total 25(OH)D, 25(OH)D2, and 25(OH)D3) and Importance of Body Mass Index: A Systematic Review and Meta-Analysis", "authors": "Itkonen ST et al.", "journal": "Adv Nutr", "year": 2023, "pmid": "37865222", "url": "https://pubmed.ncbi.nlm.nih.gov/37865222/", "study_type": "meta-analysis", "key_finding": "Average daily dose was the single significant predictor of effect size difference between D2 and D3, with BMI potentially moderating absorption.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37865222/", "publicSourceType": "PMID" }, { "claim": "Vitamin D (including D2) essential for immune system function", "title": "Immunologic Effects of Vitamin D on Human Health and Disease", "authors": "Charoenngam N et al.", "journal": "Nutrients", "year": 2020, "pmid": "32679784", "url": "https://pubmed.ncbi.nlm.nih.gov/32679784/", "study_type": "review", "key_finding": "Active vitamin D generates immunologic activities on innate and adaptive immune systems; deficiency associated with increased autoimmunity and susceptibility to infection.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32679784/", "publicSourceType": "PMID" }, { "claim": "D2 and D3 have overlapping but different effects on human immune system", "title": "Vitamins D2 and D3 Have Overlapping But Different Effects on the Human Immune System Revealed Through Analysis of the Blood Transcriptome", "authors": "Durrant LR et al.", "journal": "Front Immunol", "year": 2022, "pmid": "35281034", "url": "https://pubmed.ncbi.nlm.nih.gov/35281034/", "study_type": "RCT", "key_finding": "D2 and D3 share structural similarity but functional equivalence in vitamin D-dependent effects on human physiology has not been well defined; transcriptomic analysis reveals different immune modulation.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35281034/", "publicSourceType": "PMID" }, { "claim": "The case against ergocalciferol as a vitamin supplement", "title": "The case against ergocalciferol (vitamin D2) as a vitamin supplement", "authors": "Houghton LA et al.", "journal": "Am J Clin Nutr", "year": 2006, "pmid": "17023693", "url": "https://pubmed.ncbi.nlm.nih.gov/17023693/", "study_type": "review", "key_finding": "Vitamin D2 has shorter plasma half-life, lower affinity for vitamin D binding protein, hepatic hydroxylase and VDR; should not be regarded as equivalent to vitamin D3.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17023693/", "publicSourceType": "PMID" }, { "text": "Tripkovic L, Lambert H, Hart K et al.. Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. The American journal of clinical nutrition. 2012", "pmid": "22552031", "doi": "10.3945/ajcn.111.031070", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22552031/", "publicSourceType": "PMID" }, { "text": "Ocampo-Pelland AS, Gastonguay MR, Riggs MM. Model-based meta-analysis for comparing Vitamin D2 and D3 parent-metabolite pharmacokinetics. Journal of pharmacokinetics and pharmacodynamics. 2017", "claim": "PubMed-indexed evidence involving Vitamin D2", "title": "Model-based meta-analysis for comparing Vitamin D2 and D3 parent-metabolite pharmacokinetics", "authors": "Ocampo-Pelland AS, Gastonguay MR, Riggs MM", "journal": "Journal of pharmacokinetics and pharmacodynamics", "year": 2017, "pmid": "28466367", "url": "https://pubmed.ncbi.nlm.nih.gov/28466367/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s10928-017-9525-1", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28466367/", "publicSourceType": "PMID" }, { "text": "Nwosu BU, Parajuli S, Jasmin G et al.. Ergocalciferol in New-onset Type 1 Diabetes: A Randomized Controlled Trial. Journal of the Endocrine Society. 2022", "claim": "PubMed-indexed evidence involving Vitamin D2", "title": "Ergocalciferol in New-onset Type 1 Diabetes: A Randomized Controlled Trial", "authors": "Nwosu BU, Parajuli S, Jasmin G et al.", "journal": "Journal of the Endocrine Society", "year": 2022, "pmid": "34913020", "url": "https://pubmed.ncbi.nlm.nih.gov/34913020/", "study_type": "RCT", "confidence": "verify", "doi": "10.1210/jendso/bvab179", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34913020/", "publicSourceType": "PMID" }, { "text": "Miskulin DC, Majchrzak K, Tighiouart H et al.. Ergocalciferol Supplementation in Hemodialysis Patients With Vitamin D Deficiency: A Randomized Clinical Trial. Journal of the American Society of Nephrology : JASN. 2016", "claim": "PubMed-indexed evidence involving Vitamin D2", "title": "Ergocalciferol Supplementation in Hemodialysis Patients With Vitamin D Deficiency: A Randomized Clinical Trial", "authors": "Miskulin DC, Majchrzak K, Tighiouart H et al.", "journal": "Journal of the American Society of Nephrology : JASN", "year": 2016, "pmid": "26677862", "url": "https://pubmed.ncbi.nlm.nih.gov/26677862/", "study_type": "RCT", "confidence": "verify", "doi": "10.1681/ASN.2015040468", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26677862/", "publicSourceType": "PMID" }, { "text": "Shroff R, Wan M, Gullett A et al.. Ergocalciferol supplementation in children with CKD delays the onset of secondary hyperparathyroidism: a randomized trial. Clinical journal of the American Society of Nephrology : CJASN. 2012", "claim": "PubMed-indexed evidence involving Vitamin D2", "title": "Ergocalciferol supplementation in children with CKD delays the onset of secondary hyperparathyroidism: a randomized trial", "authors": "Shroff R, Wan M, Gullett A et al.", "journal": "Clinical journal of the American Society of Nephrology : CJASN", "year": 2012, "pmid": "22266572", "url": "https://pubmed.ncbi.nlm.nih.gov/22266572/", "study_type": "RCT", "confidence": "verify", "doi": "10.2215/CJN.04760511", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22266572/", "publicSourceType": "PMID" }, { "text": "Stephenson DW, Peiris AN. The lack of vitamin D toxicity with megadose of daily ergocalciferol (D2) therapy: a case report and literature review. Southern medical journal. 2009", "claim": "PubMed-indexed evidence involving Vitamin D2", "title": "The lack of vitamin D toxicity with megadose of daily ergocalciferol (D2) therapy: a case report and literature review", "authors": "Stephenson DW, Peiris AN", "journal": "Southern medical journal", "year": 2009, "pmid": "19488004", "url": "https://pubmed.ncbi.nlm.nih.gov/19488004/", "study_type": "review", "confidence": "verify", "doi": "10.1097/SMJ.0b013e3181a8d1e4", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19488004/", "publicSourceType": "PMID" }, { "text": "Sansanayudh N, Wongwiwatthananukit S, Phetkrajaysang N et al.. Comparative efficacy and safety of different doses of ergocalciferol supplementation in patients with metabolic syndrome. International journal of clinical pharmacy. 2014", "claim": "PubMed-indexed evidence involving Vitamin D2", "title": "Comparative efficacy and safety of different doses of ergocalciferol supplementation in patients with metabolic syndrome", "authors": "Sansanayudh N, Wongwiwatthananukit S, Phetkrajaysang N et al.", "journal": "International journal of clinical pharmacy", "year": 2014, "pmid": "24853094", "url": "https://pubmed.ncbi.nlm.nih.gov/24853094/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s11096-014-9958-1", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24853094/", "publicSourceType": "PMID" }, { "text": "Gan L, Li Y. Clinical Efficacy and Mechanism of Vitamin D2 in Treating Hashimoto's Thyroiditis. Journal of inflammation research. 2024", "claim": "PubMed-indexed evidence involving Vitamin D2", "title": "Clinical Efficacy and Mechanism of Vitamin D2 in Treating Hashimoto's Thyroiditis", "authors": "Gan L, Li Y", "journal": "Journal of inflammation research", "year": 2024, "pmid": "38410421", "url": "https://pubmed.ncbi.nlm.nih.gov/38410421/", "study_type": "review", "confidence": "verify", "doi": "10.2147/JIR.S441120", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38410421/", "publicSourceType": "PMID" }, { "text": "Amphansap T, Therdyothin A, Stitkitti N et al.. Efficacy of plain cholecalciferol versus ergocalciferol in raising serum vitamin D level in Thai female healthcare workers. Osteoporosis and sarcopenia. 2022", "claim": "PubMed-indexed evidence involving Vitamin D2", "title": "Efficacy of plain cholecalciferol versus ergocalciferol in raising serum vitamin D level in Thai female healthcare workers", "authors": "Amphansap T, Therdyothin A, Stitkitti N et al.", "journal": "Osteoporosis and sarcopenia", "year": 2022, "pmid": "36605166", "url": "https://pubmed.ncbi.nlm.nih.gov/36605166/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.afos.2022.12.001", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36605166/", "publicSourceType": "PMID" }, { "text": "Bashardoust B, Zakeri A, Fouladi N et al.. Treatment Effect of Ergocalciferol on Bone Metabolism Indexes and Parathyroid Hormone in Hemodialysis Patients. Iranian journal of kidney diseases. 2018", "claim": "PubMed-indexed evidence involving Vitamin D2", "title": "Treatment Effect of Ergocalciferol on Bone Metabolism Indexes and Parathyroid Hormone in Hemodialysis Patients", "authors": "Bashardoust B, Zakeri A, Fouladi N et al.", "journal": "Iranian journal of kidney diseases", "year": 2018, "pmid": "30595565", "url": "https://pubmed.ncbi.nlm.nih.gov/30595565/", "study_type": "review", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30595565/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "vitamin-d2" }, { "id": "7A26BDA8-001B-48D2-88C8-B9F5A1663EDC", "name": "Manganese", "alternateNames": [ "Mn" ], "category": "Mineral", "subcategory": "Trace Mineral", "overview": "Essential trace mineral for bone formation, blood clotting, and metabolism.", "mechanismOfAction": "Cofactor for manganese superoxide dismutase (MnSOD), arginase, and pyruvate carboxylase. Essential for glycosaminoglycan synthesis in cartilage.", "commonBenefits": [ "Bone health", "Antioxidant defense", "Blood sugar regulation", "Wound healing" ], "commonDosageRange": "2-5 mg daily", "recommendedForm": "Manganese bisglycinate or gluconate", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with meals to reduce GI upset" }, "evidenceRating": "moderate", "foodSources": [ "Nuts", "Whole grains", "Legumes", "Tea", "Pineapple", "Spinach" ], "deficiencySymptoms": [ "Poor bone growth", "Impaired glucose tolerance", "Skin rash" ], "sideEffects": [ "Nausea at high doses", "Neurotoxicity with excessive intake" ], "contraindications": [ "Liver disease", "Iron deficiency anemia" ], "iconName": "atom", "colorHex": "4DD4E6", "tags": [ "bone-health", "antioxidant", "mineral" ], "sources": [ { "claim": "Manganese role in bone formation and skeletal health", "title": "The Manganese-Bone Connection: Investigating the Role of Manganese in Bone Health", "authors": "Li L et al.", "journal": "Nutrients", "year": 2024, "pmid": "39200820", "url": "https://pubmed.ncbi.nlm.nih.gov/39200820/", "study_type": "review", "key_finding": "Manganese participates in bone matrix synthesis, inhibition of osteoclast-like cell formation, and antioxidant function via MnSOD; actively involved in bone remodeling by modulating osteoblast and osteoclast activity.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39200820/", "publicSourceType": "PMID" }, { "claim": "Manganese essential trace element for multiple metabolic functions including MnSOD", "title": "The Essential Element Manganese, Oxidative Stress, and Metabolic Diseases: Links and Interactions", "authors": "Li L et al.", "journal": "Oxid Med Cell Longev", "year": 2018, "pmid": "29849912", "url": "https://pubmed.ncbi.nlm.nih.gov/29849912/", "study_type": "review", "key_finding": "Manganese is a required component for MnSOD responsible for scavenging ROS in mitochondrial oxidative stress; deficiency causes impaired growth, poor bone formation, abnormal glucose tolerance.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29849912/", "publicSourceType": "PMID" }, { "claim": "Manganese health and disease overview", "title": "Manganese: Its Role in Disease and Health", "authors": "Avila DS et al.", "journal": "Met Ions Life Sci", "year": 2019, "pmid": "30855111", "url": "https://pubmed.ncbi.nlm.nih.gov/30855111/", "study_type": "review", "key_finding": "Manganese is cofactor for MnSOD, arginase, and pyruvate carboxylase; essential for glycosaminoglycan synthesis; deficiency linked to skeletal defects and impaired metabolism.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30855111/", "publicSourceType": "PMID" }, { "claim": "Relationship between blood manganese and bone mineral density in adults", "title": "Relationship between blood manganese and bone mineral density and bone mineral content in adults: A population-based cross-sectional study", "authors": "Liu Y et al.", "journal": "Front Nutr", "year": 2022, "pmid": "36269752", "url": "https://pubmed.ncbi.nlm.nih.gov/36269752/", "study_type": "cohort", "key_finding": "Population-based cross-sectional study demonstrated positive association between blood manganese levels and bone mineral density/content in adults.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36269752/", "publicSourceType": "PMID" }, { "claim": "Manganese neurotoxicity and safety considerations at excessive intake", "title": "Manganese in the Diet: Bioaccessibility, Adequate Intake, and Neurotoxicological Effects", "authors": "Peres TV et al.", "journal": "J Agric Food Chem", "year": 2020, "pmid": "32298096", "url": "https://pubmed.ncbi.nlm.nih.gov/32298096/", "study_type": "review", "key_finding": "Manganese is essential but neurotoxic in excess; brain is particularly susceptible, with excessive exposure causing manganism; balance between essential and toxic levels is critical.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32298096/", "publicSourceType": "PMID" }, { "claim": "Scientific opinion on tolerable upper intake level for manganese", "title": "Scientific opinion on the tolerable upper intake level for manganese", "authors": "EFSA Panel on Nutrition", "journal": "EFSA J", "year": 2023, "pmid": "38075631", "url": "https://pubmed.ncbi.nlm.nih.gov/38075631/", "study_type": "review", "key_finding": "EFSA panel found neurotoxicity is critical effect of manganese excess, but data insufficient to characterize dose-response relationship and identify reference point for manganese-induced neurotoxicity.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38075631/", "publicSourceType": "PMID" }, { "text": "Evans GR, Masullo LN. Manganese Toxicity. 2026", "pmid": "32809738", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32809738/", "publicSourceType": "PMID" }, { "text": "Bjørklund G, Dadar M, Peana M et al.. Interactions between iron and manganese in neurotoxicity. Archives of toxicology. 2020", "pmid": "32180038", "doi": "10.1007/s00204-020-02652-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32180038/", "publicSourceType": "PMID" }, { "claim": "Low manganese intake is associated with worse tuberculosis symptoms and treatment outcomes", "title": "Association of Dietary Micronutrient Intake with Pulmonary Tuberculosis Treatment Failure Rate: A Cohort Study", "authors": "Xiong K, Wang J, Zhang J et al.", "journal": "Nutrients", "year": 2020, "pmid": "32824912", "url": "https://pubmed.ncbi.nlm.nih.gov/32824912/", "study_type": "cohort", "key_finding": "In a cohort of 1,834 PTB patients, low intake of manganese was associated with severe tuberculosis symptoms as indicated by a high TB score. Low vitamin C and zinc intake were associated with higher treatment failure rates.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32824912/", "publicSourceType": "PMID" }, { "text": "Ogut E, Ilgin S, Atli Eklioglu O. Manganese Exposure and Attention-Deficit/Hyperactivity Disorder-Related Neurobehavioral Outcomes in Children: A Systematic Review of Human Studies. Journal of child and adolescent psychopharmacology. 2026", "claim": "PubMed-indexed evidence involving Manganese", "title": "Manganese Exposure and Attention-Deficit/Hyperactivity Disorder-Related Neurobehavioral Outcomes in Children: A Systematic Review of Human Studies", "authors": "Ogut E, Ilgin S, Atli Eklioglu O", "journal": "Journal of child and adolescent psychopharmacology", "year": 2026, "pmid": "42130043", "url": "https://pubmed.ncbi.nlm.nih.gov/42130043/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/10445463261450845", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/42130043/", "publicSourceType": "PMID" }, { "text": "Goluch Z, Haraf G. Goose Meat as a Source of Dietary Manganese-A Systematic Review. Animals : an open access journal from MDPI. 2023", "claim": "PubMed-indexed evidence involving Manganese", "title": "Goose Meat as a Source of Dietary Manganese-A Systematic Review", "authors": "Goluch Z, Haraf G", "journal": "Animals : an open access journal from MDPI", "year": 2023, "pmid": "36899696", "url": "https://pubmed.ncbi.nlm.nih.gov/36899696/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/ani13050840", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36899696/", "publicSourceType": "PMID" }, { "text": "Grochowski C, Blicharska E, Baj J et al.. Serum iron, Magnesium, Copper, and Manganese Levels in Alcoholism: A Systematic Review. Molecules (Basel, Switzerland). 2019", "claim": "PubMed-indexed evidence involving Manganese", "title": "Serum iron, Magnesium, Copper, and Manganese Levels in Alcoholism: A Systematic Review", "authors": "Grochowski C, Blicharska E, Baj J et al.", "journal": "Molecules (Basel, Switzerland)", "year": 2019, "pmid": "30959950", "url": "https://pubmed.ncbi.nlm.nih.gov/30959950/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/molecules24071361", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30959950/", "publicSourceType": "PMID" }, { "text": "Ding J, Zhang Y. Associations of Dietary Copper, Selenium, and Manganese Intake With Depression: A Meta-Analysis of Observational Studies. Frontiers in nutrition. 2022", "claim": "PubMed-indexed evidence involving Manganese", "title": "Associations of Dietary Copper, Selenium, and Manganese Intake With Depression: A Meta-Analysis of Observational Studies", "authors": "Ding J, Zhang Y", "journal": "Frontiers in nutrition", "year": 2022, "pmid": "35369103", "url": "https://pubmed.ncbi.nlm.nih.gov/35369103/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fnut.2022.854774", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35369103/", "publicSourceType": "PMID" }, { "text": "Chakraborty S, Halder S, Halder S. A Review on Chemo Sensors and Fluorosensors for Manganese. Journal of fluorescence. 2025", "claim": "PubMed-indexed evidence involving Manganese", "title": "A Review on Chemo Sensors and Fluorosensors for Manganese", "authors": "Chakraborty S, Halder S, Halder S", "journal": "Journal of fluorescence", "year": 2025, "pmid": "40332463", "url": "https://pubmed.ncbi.nlm.nih.gov/40332463/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s10895-025-04287-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40332463/", "publicSourceType": "PMID" }, { "text": "de Carvalho JF, Martinez ATA. Zinc, Copper, and Manganese Supplementations in Rheumatic Disease: A Narrative Review. Mediterranean journal of rheumatology. 2025", "claim": "PubMed-indexed evidence involving Manganese", "title": "Zinc, Copper, and Manganese Supplementations in Rheumatic Disease: A Narrative Review", "authors": "de Carvalho JF, Martinez ATA", "journal": "Mediterranean journal of rheumatology", "year": 2025, "pmid": "41122192", "url": "https://pubmed.ncbi.nlm.nih.gov/41122192/", "study_type": "review", "confidence": "verify", "doi": "10.31138/mjr.270325.amr", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41122192/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "manganese" }, { "id": "B5896C30-E170-4190-A88C-FD86208BA33E", "name": "Molybdenum", "alternateNames": [ "Mo" ], "category": "Mineral", "subcategory": "Trace Mineral", "overview": "Trace mineral essential for enzyme function in sulfite and purine metabolism.", "mechanismOfAction": "Cofactor for sulfite oxidase, xanthine oxidase, and aldehyde oxidase. Critical for detoxifying sulfites and metabolizing purines to uric acid.", "commonBenefits": [ "Detoxification", "Sulfite metabolism", "Enzyme function" ], "commonDosageRange": "75-250 mcg daily", "recommendedForm": "Molybdenum glycinate", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Well absorbed with or without food" }, "evidenceRating": "moderate", "foodSources": [ "Legumes", "Grains", "Nuts", "Liver" ], "deficiencySymptoms": [ "Rare, sulfite sensitivity", "Tachycardia", "Headaches" ], "sideEffects": [ "Generally very safe", "Gout-like symptoms at very high doses" ], "contraindications": [ "Copper deficiency" ], "iconName": "atom", "colorHex": "4DD4E6", "tags": [ "detox", "enzyme", "mineral" ], "sources": [ { "claim": "Molybdenum is an essential trace element serving as cofactor for key enzymes", "title": "Molybdenum: an essential trace element", "authors": "Sardesai VM", "journal": "Nutr Clin Pract", "year": 1993, "pmid": "8302261", "url": "https://pubmed.ncbi.nlm.nih.gov/8302261/", "study_type": "review", "key_finding": "Molybdenum is essential as cofactor for xanthine oxidase, aldehyde oxidase, and sulfite oxidase; required for purine metabolism, sulfite detoxification, and amino acid metabolism.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8302261/", "publicSourceType": "PMID" }, { "claim": "Molybdenum absorption and intake kinetics in humans", "title": "Molybdenum absorption, excretion, and retention studied with stable isotopes in young men at five intakes of dietary molybdenum", "authors": "Turnlund JR et al.", "journal": "Am J Clin Nutr", "year": 1995, "pmid": "7572711", "url": "https://pubmed.ncbi.nlm.nih.gov/7572711/", "study_type": "RCT", "key_finding": "Dietary intakes between 22-1500 mcg/day are safe; molybdenum very efficiently absorbed (88-93%) at all dietary intakes; retention regulated by urinary excretion.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7572711/", "publicSourceType": "PMID" }, { "claim": "Assessment of molybdenum toxicity in humans", "title": "Assessment of molybdenum toxicity in humans", "authors": "Momcilovic B", "journal": "J Trace Elem Med Biol", "year": 1999, "pmid": "10362269", "url": "https://pubmed.ncbi.nlm.nih.gov/10362269/", "study_type": "review", "key_finding": "Low order of toxicity observed in humans; toxicity associated with copper depletion, so those with inadequate copper intake at greater risk. Average intake 0.1-0.5 mg/day.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10362269/", "publicSourceType": "PMID" }, { "claim": "Molybdenum scoping review for Nordic Nutrition Recommendations 2023", "title": "Molybdenum - a scoping review for Nordic Nutrition Recommendations 2023", "authors": "Arnaud J et al.", "journal": "Food Nutr Res", "year": 2024, "pmid": "38187804", "url": "https://pubmed.ncbi.nlm.nih.gov/38187804/", "study_type": "review", "key_finding": "U.S. RDA is 45 mcg/day for adults; EFSA Adequate Intake is 65 mcg/day; molybdenum cofactor required for four human enzymes involved in purine/sulfur amino acid catabolism.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38187804/", "publicSourceType": "PMID" }, { "claim": "Molybdenum cofactor deficiency causes severe neurological symptoms", "title": "Inborn errors of molybdenum metabolism: combined deficiencies of sulfite oxidase and xanthine dehydrogenase in a patient lacking the molybdenum cofactor", "authors": "Johnson JL et al.", "journal": "Proc Natl Acad Sci USA", "year": 1980, "pmid": "6997882", "url": "https://pubmed.ncbi.nlm.nih.gov/6997882/", "study_type": "review", "key_finding": "Combined deficiency of sulfite oxidase and xanthine dehydrogenase due to molybdenum cofactor deficiency causes severe neurological symptoms including mental retardation and seizures.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6997882/", "publicSourceType": "PMID" }, { "text": "Adamus JP, Ruszczyńska A, Wyczałkowska-Tomasik A. Molybdenum's Role as an Essential Element in Enzymes Catabolizing Redox Reactions: A Review. Biomolecules. 2024", "pmid": "39062583", "doi": "10.3390/biom14070869", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39062583/", "publicSourceType": "PMID" }, { "text": "Maiti BK, Moura I, Moura JJG. Molybdenum-Copper Antagonism In Metalloenzymes And Anti-Copper Therapy. Chembiochem : a European journal of chemical biology. 2024", "pmid": "38205937", "doi": "10.1002/cbic.202300679", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38205937/", "publicSourceType": "PMID" }, { "claim": "Current evidence does not support the use of most mineral and trace element supplementation including molybdenum for athletic performance", "title": "The Role of Mineral and Trace Element Supplementation in Exercise and Athletic Performance: A Systematic Review", "authors": "Heffernan SM, Horner K, De Vito G, Conway GE", "journal": "Nutrients", "year": 2019, "pmid": "30909645", "url": "https://pubmed.ncbi.nlm.nih.gov/30909645/", "study_type": "review", "key_finding": "Systematic review of 128 studies found no relevant articles for molybdenum supplementation and athletic performance. Only iron and magnesium had sufficient quality evidence supporting use. Little evidence exists for most MTE supplementation to improve athletic performance.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30909645/", "publicSourceType": "PMID" }, { "text": "Ferreira EA, Hofstede FC, Haijes-Siepel HA et al.. Timing of cerebral damage in molybdenum cofactor deficiency: A meta-analysis of case reports. Genetics in medicine open. 2024", "claim": "PubMed-indexed evidence involving Molybdenum", "title": "Timing of cerebral damage in molybdenum cofactor deficiency: A meta-analysis of case reports", "authors": "Ferreira EA, Hofstede FC, Haijes-Siepel HA et al.", "journal": "Genetics in medicine open", "year": 2024, "pmid": "39669634", "url": "https://pubmed.ncbi.nlm.nih.gov/39669634/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.gimo.2024.101853", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39669634/", "publicSourceType": "PMID" }, { "text": "Ivica A, Nimac M, Pelivan I et al.. Electrochemical Interactions of Titanium and Cobalt-Chromium-Molybdenum Alloy in Different Solutions. Materials (Basel, Switzerland). 2026", "claim": "PubMed-indexed evidence involving Molybdenum", "title": "Electrochemical Interactions of Titanium and Cobalt-Chromium-Molybdenum Alloy in Different Solutions", "authors": "Ivica A, Nimac M, Pelivan I et al.", "journal": "Materials (Basel, Switzerland)", "year": 2026, "pmid": "41598075", "url": "https://pubmed.ncbi.nlm.nih.gov/41598075/", "study_type": "review", "confidence": "verify", "doi": "10.3390/ma19020367", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41598075/", "publicSourceType": "PMID" }, { "text": "Liu H, Yu X, He S et al.. New Neuroimaging Findings in Patients with Molybdenum Cofactor Deficiency Type A: A Case Report and Literature Review. Current medical imaging. 2024", "claim": "PubMed-indexed evidence involving Molybdenum", "title": "New Neuroimaging Findings in Patients with Molybdenum Cofactor Deficiency Type A: A Case Report and Literature Review", "authors": "Liu H, Yu X, He S et al.", "journal": "Current medical imaging", "year": 2024, "pmid": "38389347", "url": "https://pubmed.ncbi.nlm.nih.gov/38389347/", "study_type": "review", "confidence": "verify", "doi": "10.2174/0115734056259160231106075042", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38389347/", "publicSourceType": "PMID" }, { "text": "Kinsinger M, Ivanisevic J, Mithal DS. Novel pathogenic variant in a mild case of type B molybdenum cofactor deficiency: case report and literature review. BMC medical genomics. 2024", "claim": "PubMed-indexed evidence involving Molybdenum", "title": "Novel pathogenic variant in a mild case of type B molybdenum cofactor deficiency: case report and literature review", "authors": "Kinsinger M, Ivanisevic J, Mithal DS", "journal": "BMC medical genomics", "year": 2024, "pmid": "39695700", "url": "https://pubmed.ncbi.nlm.nih.gov/39695700/", "study_type": "review", "confidence": "verify", "doi": "10.1186/s12920-024-02027-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39695700/", "publicSourceType": "PMID" }, { "text": "Brewer GJ. Interactions of zinc and molybdenum with copper in therapy of Wilson's disease. Nutrition (Burbank, Los Angeles County, Calif.). 1995", "claim": "PubMed-indexed evidence involving Molybdenum", "title": "Interactions of zinc and molybdenum with copper in therapy of Wilson's disease", "authors": "Brewer GJ", "journal": "Nutrition (Burbank, Los Angeles County, Calif.)", "year": 1995, "pmid": "7749256", "url": "https://pubmed.ncbi.nlm.nih.gov/7749256/", "study_type": "review", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7749256/", "publicSourceType": "PMID" }, { "text": "Lesperance AL, Bohman VR, Oldfield JE. Interaction of molybdenum, sulfate and alfalfa in the bovine. Journal of animal science. 1985", "claim": "PubMed-indexed evidence involving Molybdenum", "title": "Interaction of molybdenum, sulfate and alfalfa in the bovine", "authors": "Lesperance AL, Bohman VR, Oldfield JE", "journal": "Journal of animal science", "year": 1985, "pmid": "3988651", "url": "https://pubmed.ncbi.nlm.nih.gov/3988651/", "study_type": "review", "confidence": "verify", "doi": "10.2527/jas1985.603791x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3988651/", "publicSourceType": "PMID" }, { "text": "Chen S, Zhang P, Bai H et al.. Recent advances in nano-molybdenum oxide for photothermal cancer therapy. Nanomedicine (London, England). 2025", "claim": "PubMed-indexed evidence involving Molybdenum", "title": "Recent advances in nano-molybdenum oxide for photothermal cancer therapy", "authors": "Chen S, Zhang P, Bai H et al.", "journal": "Nanomedicine (London, England)", "year": 2025, "pmid": "40063363", "url": "https://pubmed.ncbi.nlm.nih.gov/40063363/", "study_type": "review", "confidence": "verify", "doi": "10.1080/17435889.2025.2476386", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40063363/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "molybdenum" }, { "id": "2D0AB237-80ED-461E-A564-3741AE00F4E6", "name": "Lithium Orotate", "alternateNames": [ "Low-dose lithium" ], "category": "Mineral", "subcategory": "Trace Mineral", "overview": "Low-dose lithium supplement for neuroprotection and mood support.", "mechanismOfAction": "Inhibits GSK-3beta, promotes BDNF expression, and supports autophagy. At low doses, provides neuroprotective benefits without prescription lithium side effects.", "commonBenefits": [ "Mood support", "Neuroprotection", "Brain health", "Longevity" ], "commonDosageRange": "5-20 mg daily (elemental lithium)", "recommendedForm": "Lithium orotate", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Can take with or without food" }, "evidenceRating": "insufficient", "foodSources": [ "Drinking water (trace amounts)", "Grains", "Vegetables" ], "deficiencySymptoms": [ "Not a classical deficiency" ], "sideEffects": [ "Very well tolerated at low doses", "Mild thirst" ], "contraindications": [ "Kidney disease", "Thyroid disorders", "Pregnancy" ], "iconName": "brain.head.profile.fill", "colorHex": "B37DFF", "tags": [ "mood", "neuroprotection", "longevity" ], "sources": [ { "claim": "Low-dose lithium supplementation benefits beyond psychiatric use", "title": "Beyond its Psychiatric Use: The Benefits of Low-dose Lithium Supplementation", "authors": "Voelkl J et al.", "journal": "Curr Neuropharmacol", "year": 2022, "pmid": "35236261", "url": "https://pubmed.ncbi.nlm.nih.gov/35236261/", "study_type": "review", "key_finding": "Low-dose lithium reduces neurofibrillary tangles and amyloid beta production, reduces neuroinflammation, promotes BDNF expression, and provides neuroprotection at subtherapeutic doses.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35236261/", "publicSourceType": "PMID" }, { "claim": "Lithium inhibits GSK-3beta for neuroprotection against excitotoxicity", "title": "GSK-3 as a Target for Lithium-Induced Neuroprotection Against Excitotoxicity in Neuronal Cultures and Animal Models of Ischemic Stroke", "authors": "Roh MS et al.", "journal": "Front Mol Neurosci", "year": 2011, "pmid": "21886605", "url": "https://pubmed.ncbi.nlm.nih.gov/21886605/", "study_type": "review", "key_finding": "Lithium inhibits GSK-3 directly and indirectly by enhancing serine phosphorylation; BDNF induction required for lithium's neuroprotection to occur.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21886605/", "publicSourceType": "PMID" }, { "claim": "Low-dose lithium in drinking water associated with lower mortality and longevity", "title": "Low-dose lithium uptake promotes longevity in humans and metazoans", "authors": "Zarse K et al.", "journal": "Eur J Nutr", "year": 2011, "pmid": "21301855", "url": "https://pubmed.ncbi.nlm.nih.gov/21301855/", "study_type": "cohort", "key_finding": "Inverse correlation between drinking water lithium concentrations and all-cause mortality in 18 Japanese municipalities (1,206,174 individuals); low-dose lithium extended C. elegans lifespan.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21301855/", "publicSourceType": "PMID" }, { "claim": "Trace lithium in drinking water and dementia risk", "title": "Association of Lithium in Drinking Water With the Incidence of Dementia", "authors": "Kessing LV et al.", "journal": "JAMA Psychiatry", "year": 2017, "pmid": "28832877", "url": "https://pubmed.ncbi.nlm.nih.gov/28832877/", "study_type": "cohort", "key_finding": "Major Danish study found long-term lithium exposure in drinking water may be associated with lower incidence of dementia in a nonlinear (U-shaped) relationship.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28832877/", "publicSourceType": "PMID" }, { "claim": "Review of lithium effects on brain and blood including neuroprotection", "title": "Review of lithium effects on brain and blood", "authors": "Malhi GS et al.", "journal": "Cell Transplant", "year": 2009, "pmid": "19523343", "url": "https://pubmed.ncbi.nlm.nih.gov/19523343/", "study_type": "review", "key_finding": "Lithium has neuroprotective and neurotrophic actions; promotes expression of BDNF; counteracts cognitive decline at subtherapeutic doses with fewer side effects than standard psychiatric doses.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19523343/", "publicSourceType": "PMID" }, { "claim": "Lithium dose-response considerations for therapeutic effects", "title": "Lithium and its effects: does dose matter?", "authors": "Forlenza OV et al.", "journal": "Neuropsychobiology", "year": 2024, "pmid": "38914810", "url": "https://pubmed.ncbi.nlm.nih.gov/38914810/", "study_type": "review", "key_finding": "Lithium's ability to counteract cognitive decline appears to be exerted at subtherapeutic doses; may reduce inflammation and induce neuroprotection at doses several folds lower than clinical use.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38914810/", "publicSourceType": "PMID" }, { "text": "Strawbridge R, Kerr-Gaffney J, Bessa G et al.. Identifying the neuropsychiatric health effects of low-dose lithium interventions: A systematic review. Neuroscience and biobehavioral reviews. 2023", "pmid": "36436738", "doi": "10.1016/j.neubiorev.2022.104975", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36436738/", "publicSourceType": "PMID" }, { "text": "Devanand DP, Crocco E, Forester BP et al.. Low Dose Lithium Treatment of Behavioral Complications in Alzheimer's Disease: Lit-AD Randomized Clinical Trial. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. 2022", "pmid": "34059401", "doi": "10.1016/j.jagp.2021.04.014", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34059401/", "publicSourceType": "PMID" }, { "text": "Sharif S, Chen B, Brewster P et al.. Rationale and Design of Assessing the Effectiveness of Short-Term Low-Dose Lithium Therapy in Averting Cardiac Surgery-Associated Acute Kidney Injury: A Randomized, Double Blinded, Placebo Controlled Pilot Trial. Frontiers in medicine. 2021", "claim": "PubMed-indexed evidence involving Lithium Orotate", "title": "Rationale and Design of Assessing the Effectiveness of Short-Term Low-Dose Lithium Therapy in Averting Cardiac Surgery-Associated Acute Kidney Injury: A Randomized, Double Blinded, Placebo Controlled Pilot Trial", "authors": "Sharif S, Chen B, Brewster P et al.", "journal": "Frontiers in medicine", "year": 2021, "pmid": "34195206", "url": "https://pubmed.ncbi.nlm.nih.gov/34195206/", "study_type": "RCT", "confidence": "verify", "doi": "10.3389/fmed.2021.639402", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34195206/", "publicSourceType": "PMID" }, { "text": "Schrauzer GN, de Vroey E. Effects of nutritional lithium supplementation on mood. A placebo-controlled study with former drug users. Biological trace element research. 1994", "claim": "PubMed-indexed evidence involving Lithium Orotate", "title": "Effects of nutritional lithium supplementation on mood. A placebo-controlled study with former drug users", "authors": "Schrauzer GN, de Vroey E", "journal": "Biological trace element research", "year": 1994, "pmid": "7511924", "url": "https://pubmed.ncbi.nlm.nih.gov/7511924/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/BF02916824", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7511924/", "publicSourceType": "PMID" }, { "text": "Allain P, Le Bouil A, Turcant A et al.. [Pharmacokinetics of low-dose lithium in healthy volunteers]. Therapie. 1994", "claim": "PubMed-indexed evidence involving Lithium Orotate", "title": "[Pharmacokinetics of low-dose lithium in healthy volunteers]", "authors": "Allain P, Le Bouil A, Turcant A et al.", "journal": "Therapie", "year": 1994, "pmid": "7878598", "url": "https://pubmed.ncbi.nlm.nih.gov/7878598/", "study_type": "RCT", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7878598/", "publicSourceType": "PMID" }, { "text": "Sartori HE. Lithium orotate in the treatment of alcoholism and related conditions. Alcohol (Fayetteville, N.Y.). 1986", "claim": "PubMed-indexed evidence involving Lithium Orotate", "title": "Lithium orotate in the treatment of alcoholism and related conditions", "authors": "Sartori HE", "journal": "Alcohol (Fayetteville, N.Y.)", "year": 1986, "pmid": "3718672", "url": "https://pubmed.ncbi.nlm.nih.gov/3718672/", "study_type": "review", "confidence": "verify", "doi": "10.1016/0741-8329(86)90018-2", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3718672/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "lithium-orotate" }, { "id": "BCDC9F04-74DE-4140-A5EF-DFB353F5ABE5", "name": "Silicon", "alternateNames": [ "Silica", "Orthosilicic acid" ], "category": "Mineral", "subcategory": "Trace Mineral", "overview": "Trace mineral important for bone, skin, hair, and nail health.", "mechanismOfAction": "Stimulates collagen synthesis and promotes mineralization of bone matrix. Stabilizes glycosaminoglycans in connective tissue.", "commonBenefits": [ "Bone density", "Skin elasticity", "Hair strength", "Nail health" ], "commonDosageRange": "5-10 mg daily", "recommendedForm": "Orthosilicic acid (stabilized, most bioavailable)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Better absorbed with food" }, "evidenceRating": "emerging", "foodSources": [ "Whole grains", "Beer", "Green beans", "Bananas", "Mineral water" ], "deficiencySymptoms": [ "Brittle nails", "Thin hair", "Poor wound healing" ], "sideEffects": [ "Generally very safe", "GI discomfort at high doses" ], "contraindications": [], "iconName": "sparkle", "colorHex": "4DD4E6", "tags": [ "bone-health", "skin", "hair", "nails" ], "sources": [ { "claim": "Dietary silicon intake positively associated with bone mineral density", "title": "Dietary silicon intake is positively associated with bone mineral density in men and premenopausal women of the Framingham Offspring cohort", "authors": "Jugdaohsingh R et al.", "journal": "J Bone Miner Res", "year": 2004, "pmid": "14969400", "url": "https://pubmed.ncbi.nlm.nih.gov/14969400/", "study_type": "cohort", "key_finding": "Cross-sectional study of 2,847 Framingham Offspring participants found silicon intake positively correlated with BMD at four hip sites in men and premenopausal women.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14969400/", "publicSourceType": "PMID" }, { "claim": "Orthosilicic acid supplementation improves skin, nails and hair", "title": "Effect of oral intake of choline-stabilized orthosilicic acid on skin, nails and hair in women with photodamaged skin", "authors": "Barel A et al.", "journal": "Arch Dermatol Res", "year": 2005, "pmid": "16205932", "url": "https://pubmed.ncbi.nlm.nih.gov/16205932/", "study_type": "RCT", "key_finding": "Randomized double-blind placebo-controlled study: 10 mg Si/day as ch-OSA for 20 weeks improved skin, nail and hair parameters in women with photodamaged skin.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16205932/", "publicSourceType": "PMID" }, { "claim": "Orthosilicic acid stimulates bone formation markers as adjunct to calcium/D3", "title": "Choline-stabilized orthosilicic acid supplementation as an adjunct to calcium/vitamin D3 stimulates markers of bone formation in osteopenic females: a randomized, placebo-controlled trial", "authors": "Spector TD et al.", "journal": "BMC Musculoskelet Disord", "year": 2008, "pmid": "18547426", "url": "https://pubmed.ncbi.nlm.nih.gov/18547426/", "study_type": "RCT", "key_finding": "Double-blind placebo-controlled trial: ch-OSA (3, 6, 12 mg Si) added to calcium/D3 stimulated bone formation markers in 136 osteopenic women over 12 months.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18547426/", "publicSourceType": "PMID" }, { "claim": "Orthosilicic acid stimulates collagen type 1 synthesis and osteoblastic differentiation", "title": "Orthosilicic acid stimulates collagen type 1 synthesis and osteoblastic differentiation in human osteoblast-like cells in vitro", "authors": "Reffitt DM et al.", "journal": "Bone", "year": 2003, "pmid": "12633784", "url": "https://pubmed.ncbi.nlm.nih.gov/12633784/", "study_type": "review", "key_finding": "Orthosilicic acid at physiological concentrations stimulates collagen type 1 synthesis in human osteoblast-like cells and enhances osteoblastic differentiation.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12633784/", "publicSourceType": "PMID" }, { "claim": "Silicon supplementation for bone health: umbrella review translating from animals to humans", "title": "Silicon Supplementation for Bone Health: An Umbrella Review Attempting to Translate from Animals to Humans", "authors": "Munoz-Garach A et al.", "journal": "Nutrients", "year": 2024, "pmid": "38337624", "url": "https://pubmed.ncbi.nlm.nih.gov/38337624/", "study_type": "review", "key_finding": "Umbrella review examining silicon's role in bone mineralization, collagen synthesis, and skeletal health with evidence from animal and human studies.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38337624/", "publicSourceType": "PMID" }, { "claim": "Silicon as a neglected micronutrient essential for bone health", "title": "Silicon: A neglected micronutrient essential for bone health", "authors": "Jugdaohsingh R et al.", "journal": "Exp Biol Med", "year": 2021, "pmid": "33715532", "url": "https://pubmed.ncbi.nlm.nih.gov/33715532/", "study_type": "review", "key_finding": "Silicon associated with bone mineralization, collagen synthesis, skin/hair/nail health; stabilizes glycosaminoglycans in connective tissue.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33715532/", "publicSourceType": "PMID" }, { "text": "Feng Y, Cao Y, Singh R et al.. Silica nanoparticles for brain cancer. Expert opinion on drug delivery. 2023", "pmid": "37905998", "doi": "10.1080/17425247.2023.2273830", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37905998/", "publicSourceType": "PMID" }, { "text": "M Ways TM, Ng KW, Lau WM et al.. Silica Nanoparticles in Transmucosal Drug Delivery. Pharmaceutics. 2020", "pmid": "32785148", "doi": "10.3390/pharmaceutics12080751", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32785148/", "publicSourceType": "PMID" }, { "text": "Miao C, Jia P, Luo C et al.. The size-dependent in vivo toxicity of amorphous silica nanoparticles: A systematic review. Ecotoxicology and environmental safety. 2024", "claim": "PubMed-indexed evidence involving Silicon", "title": "The size-dependent in vivo toxicity of amorphous silica nanoparticles: A systematic review", "authors": "Miao C, Jia P, Luo C et al.", "journal": "Ecotoxicology and environmental safety", "year": 2024, "pmid": "38199222", "url": "https://pubmed.ncbi.nlm.nih.gov/38199222/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.ecoenv.2023.115910", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38199222/", "publicSourceType": "PMID" }, { "text": "Liu H, Chen L, Bai X et al.. Exogenous silicon facilitates safe crop production in cadmium-contaminated soils: A comprehensive meta-analysis. Journal of hazardous materials. 2024", "claim": "PubMed-indexed evidence involving Silicon", "title": "Exogenous silicon facilitates safe crop production in cadmium-contaminated soils: A comprehensive meta-analysis", "authors": "Liu H, Chen L, Bai X et al.", "journal": "Journal of hazardous materials", "year": 2024, "pmid": "39515145", "url": "https://pubmed.ncbi.nlm.nih.gov/39515145/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jhazmat.2024.136368", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39515145/", "publicSourceType": "PMID" }, { "text": "Teughels W, Celik GU, Tarce M et al.. The effect of choline-stabilized orthosilicic acid in patients with peri-implantitis: an exploratory randomized, double-blind, placebo controlled study. BMC oral health. 2021", "claim": "PubMed-indexed evidence involving Silicon", "title": "The effect of choline-stabilized orthosilicic acid in patients with peri-implantitis: an exploratory randomized, double-blind, placebo controlled study", "authors": "Teughels W, Celik GU, Tarce M et al.", "journal": "BMC oral health", "year": 2021, "pmid": "34587941", "url": "https://pubmed.ncbi.nlm.nih.gov/34587941/", "study_type": "RCT", "confidence": "verify", "doi": "10.1186/s12903-021-01817-4", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34587941/", "publicSourceType": "PMID" }, { "text": "Yu J, Dan N, Eslami SM et al.. State of the Art of Silica Nanoparticles: An Overview on Biodistribution and Preclinical Toxicity Studies. The AAPS journal. 2024", "claim": "PubMed-indexed evidence involving Silicon", "title": "State of the Art of Silica Nanoparticles: An Overview on Biodistribution and Preclinical Toxicity Studies", "authors": "Yu J, Dan N, Eslami SM et al.", "journal": "The AAPS journal", "year": 2024, "pmid": "38514482", "url": "https://pubmed.ncbi.nlm.nih.gov/38514482/", "study_type": "review", "confidence": "verify", "doi": "10.1208/s12248-024-00906-w", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38514482/", "publicSourceType": "PMID" }, { "text": "Valadares LPA, Lima LCO, Saboia-Morais SMT et al.. Embryotoxicity of silica nanoparticles in the drug delivery of domperidone in zebrafish. Aquatic toxicology (Amsterdam, Netherlands). 2023", "claim": "PubMed-indexed evidence involving Silicon", "title": "Embryotoxicity of silica nanoparticles in the drug delivery of domperidone in zebrafish", "authors": "Valadares LPA, Lima LCO, Saboia-Morais SMT et al.", "journal": "Aquatic toxicology (Amsterdam, Netherlands)", "year": 2023, "pmid": "36958154", "url": "https://pubmed.ncbi.nlm.nih.gov/36958154/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.aquatox.2023.106454", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36958154/", "publicSourceType": "PMID" }, { "text": "Morais RP, Hochheim S, de Oliveira CC et al.. Skin interaction, permeation, and toxicity of silica nanoparticles: Challenges and recent therapeutic and cosmetic advances. International journal of pharmaceutics. 2022", "claim": "PubMed-indexed evidence involving Silicon", "title": "Skin interaction, permeation, and toxicity of silica nanoparticles: Challenges and recent therapeutic and cosmetic advances", "authors": "Morais RP, Hochheim S, de Oliveira CC et al.", "journal": "International journal of pharmaceutics", "year": 2022, "pmid": "34990742", "url": "https://pubmed.ncbi.nlm.nih.gov/34990742/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.ijpharm.2021.121439", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34990742/", "publicSourceType": "PMID" }, { "text": "Fuentes C, Verdú S, Fuentes A et al.. In vivo toxicity assessment of eugenol and vanillin-functionalised silica particles using Caenorhabditis elegans. Ecotoxicology and environmental safety. 2022", "claim": "PubMed-indexed evidence involving Silicon", "title": "In vivo toxicity assessment of eugenol and vanillin-functionalised silica particles using Caenorhabditis elegans", "authors": "Fuentes C, Verdú S, Fuentes A et al.", "journal": "Ecotoxicology and environmental safety", "year": 2022, "pmid": "35533449", "url": "https://pubmed.ncbi.nlm.nih.gov/35533449/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.ecoenv.2022.113601", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35533449/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "silicon" }, { "id": "D2E24B1A-4C06-42A1-B24C-E21BB67133D5", "name": "L-Glutamine", "alternateNames": [ "Glutamine" ], "category": "Amino Acid", "subcategory": "Conditionally Essential Amino Acid", "overview": "Most abundant amino acid in the body, critical for gut health and immune function.", "mechanismOfAction": "Primary fuel for enterocytes (intestinal cells) and immune cells. Supports gut barrier integrity by maintaining tight junction proteins. Precursor for glutathione and nucleotide synthesis.", "commonBenefits": [ "Gut health", "Immune support", "Muscle recovery", "Gut barrier integrity" ], "commonDosageRange": "5-10 g daily", "recommendedForm": "L-Glutamine powder (free form)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Best on empty stomach; powder form for high doses" }, "evidenceRating": "moderate", "foodSources": [ "Bone broth", "Beef", "Chicken", "Fish", "Eggs", "Dairy", "Cabbage" ], "deficiencySymptoms": [ "Muscle wasting", "Impaired immunity", "Gut permeability" ], "sideEffects": [ "Bloating", "Constipation at high doses" ], "contraindications": [ "Liver disease", "Reye syndrome", "MSG sensitivity" ], "iconName": "leaf.fill", "colorHex": "B37DFF", "tags": [ "gut-health", "immune", "recovery" ], "sources": [ { "claim": "Glutamine supplementation effects on gut permeability in adults", "title": "A systematic review and meta-analysis of clinical trials on the effects of glutamine supplementation on gut permeability in adults", "authors": "Pugh JN et al.", "journal": "Clin Nutr", "year": 2024, "pmid": "39397201", "url": "https://pubmed.ncbi.nlm.nih.gov/39397201/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 10 studies (352 participants) found glutamine did not significantly affect intestinal permeability overall, but subgroup analysis showed significant reduction at doses >30g/day.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39397201/", "publicSourceType": "PMID" }, { "claim": "Glutamine regulates intestinal permeability and tight junction function", "title": "Glutamine and the regulation of intestinal permeability: from bench to bedside", "authors": "Achamrah N et al.", "journal": "Curr Opin Clin Nutr Metab Care", "year": 2017, "pmid": "27749689", "url": "https://pubmed.ncbi.nlm.nih.gov/27749689/", "study_type": "review", "key_finding": "Glutamine is major nutrient for maintaining intestinal barrier function; depletion results in villus atrophy, decreased tight junction protein expression, and increased intestinal permeability.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27749689/", "publicSourceType": "PMID" }, { "claim": "Glutamine dramatically reduces all major IBS-related endpoints in post-infectious IBS", "title": "Randomised placebo-controlled trial of dietary glutamine supplements for postinfectious irritable bowel syndrome", "authors": "Zhou Q et al.", "journal": "Gut", "year": 2019, "pmid": "30108163", "url": "https://pubmed.ncbi.nlm.nih.gov/30108163/", "study_type": "RCT", "key_finding": "Oral glutamine supplements dramatically and safely reduced all major IBS-related endpoints in patients with IBS-D with intestinal hyperpermeability following enteric infection.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30108163/", "publicSourceType": "PMID" }, { "claim": "Glutamine essential for immune function, lymphocyte proliferation and cytokine production", "title": "Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation", "authors": "Cruzat V et al.", "journal": "Nutrients", "year": 2018, "pmid": "30360490", "url": "https://pubmed.ncbi.nlm.nih.gov/30360490/", "study_type": "review", "key_finding": "Glutamine essential for lymphocyte proliferation, cytokine production, macrophage phagocytosis, and neutrophil bacterial killing; becomes conditionally essential in critical illness.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30360490/", "publicSourceType": "PMID" }, { "claim": "Glutamine supplementation effects on athletic performance and body composition", "title": "The effect of glutamine supplementation on athletic performance, body composition, and immune function: A systematic review and a meta-analysis of clinical trials", "authors": "Legault Z et al.", "journal": "Nutrients", "year": 2015, "pmid": "29784526", "url": "https://pubmed.ncbi.nlm.nih.gov/29784526/", "study_type": "meta-analysis", "key_finding": "Systematic review and meta-analysis examining glutamine's effects on athletic performance, body composition and immune function across clinical trials.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29784526/", "publicSourceType": "PMID" }, { "claim": "Glutamine supplementation reduces intestinal permeability during exercise", "title": "Glutamine supplementation reduces markers of intestinal permeability during running in the heat in a dose-dependent manner", "authors": "Pugh JN et al.", "journal": "Eur J Appl Physiol", "year": 2017, "pmid": "29058112", "url": "https://pubmed.ncbi.nlm.nih.gov/29058112/", "study_type": "RCT", "key_finding": "Acute oral glutamine consumption attenuated gastrointestinal permeability relative to placebo during exercise in the heat, even at lower doses, in a dose-dependent manner.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29058112/", "publicSourceType": "PMID" }, { "text": "Arribas-López E, Zand N, Ojo O et al.. The Effect of Amino Acids on Wound Healing: A Systematic Review and Meta-Analysis on Arginine and Glutamine. Nutrients. 2021", "pmid": "34444657", "doi": "10.3390/nu13082498", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34444657/", "publicSourceType": "PMID" }, { "claim": "Benefits burn patients", "title": "Glutamine Supplementation on Burn Patients: A Systematic Review and Meta-analysis.", "authors": "Tao W, Xu G, Zhou J, Luo Y, Li PS", "journal": "Journal of Burn Care & Research", "year": 2024, "pmid": "38243579", "url": "https://pubmed.ncbi.nlm.nih.gov/38243579/", "study_type": "meta-analysis", "key_finding": "Glutamine supplementation in burn patients significantly reduced mortality, length of hospital stay, and infection rates compared to standard care.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38243579/", "publicSourceType": "PMID" }, { "text": "Oldani M, Sandini M, Nespoli L et al.. Glutamine Supplementation in Intensive Care Patients: A Meta-Analysis of Randomized Clinical Trials. Medicine. 2015", "claim": "PubMed-indexed evidence involving L-Glutamine", "title": "Glutamine Supplementation in Intensive Care Patients: A Meta-Analysis of Randomized Clinical Trials", "authors": "Oldani M, Sandini M, Nespoli L et al.", "journal": "Medicine", "year": 2015, "pmid": "26252319", "url": "https://pubmed.ncbi.nlm.nih.gov/26252319/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MD.0000000000001319", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26252319/", "publicSourceType": "PMID" }, { "text": "Yue HY, Wang Y, Zeng J et al.. Enteral glutamine supplements for patients with severe burns: A systematic review and meta-analysis. Chinese journal of traumatology = Zhonghua chuang shang za zhi. 2024", "claim": "PubMed-indexed evidence involving L-Glutamine", "title": "Enteral glutamine supplements for patients with severe burns: A systematic review and meta-analysis", "authors": "Yue HY, Wang Y, Zeng J et al.", "journal": "Chinese journal of traumatology = Zhonghua chuang shang za zhi", "year": 2024, "pmid": "37460347", "url": "https://pubmed.ncbi.nlm.nih.gov/37460347/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.cjtee.2023.06.005", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37460347/", "publicSourceType": "PMID" }, { "text": "Linden MA, Teixeira TLM, Freitas RGBON et al.. Arginine and glutamine supplementation on transthyretin levels in severely burned patients: A systematic review. Nutrition (Burbank, Los Angeles County, Calif.). 2022", "claim": "PubMed-indexed evidence involving L-Glutamine", "title": "Arginine and glutamine supplementation on transthyretin levels in severely burned patients: A systematic review", "authors": "Linden MA, Teixeira TLM, Freitas RGBON et al.", "journal": "Nutrition (Burbank, Los Angeles County, Calif.)", "year": 2022, "pmid": "35653933", "url": "https://pubmed.ncbi.nlm.nih.gov/35653933/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.nut.2022.111657", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35653933/", "publicSourceType": "PMID" }, { "text": "Sun Y, Zhu S, Li S et al.. Glutamine on critical-ill patients: a systematic review and meta-analysis. Annals of palliative medicine. 2021", "claim": "PubMed-indexed evidence involving L-Glutamine", "title": "Glutamine on critical-ill patients: a systematic review and meta-analysis", "authors": "Sun Y, Zhu S, Li S et al.", "journal": "Annals of palliative medicine", "year": 2021, "pmid": "33222464", "url": "https://pubmed.ncbi.nlm.nih.gov/33222464/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.21037/apm-20-702", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33222464/", "publicSourceType": "PMID" }, { "text": "Cieri-Hutcherson NE, Hutcherson TC, Conway-Habes EE et al.. Systematic Review of l-glutamine for Prevention of Vaso-occlusive Pain Crisis in Patients with Sickle Cell Disease. Pharmacotherapy. 2019", "claim": "PubMed-indexed evidence involving L-Glutamine", "title": "Systematic Review of l-glutamine for Prevention of Vaso-occlusive Pain Crisis in Patients with Sickle Cell Disease", "authors": "Cieri-Hutcherson NE, Hutcherson TC, Conway-Habes EE et al.", "journal": "Pharmacotherapy", "year": 2019, "pmid": "31505045", "url": "https://pubmed.ncbi.nlm.nih.gov/31505045/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/phar.2329", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31505045/", "publicSourceType": "PMID" }, { "text": "Sayles C, Hickerson SC, Bhat RR et al.. Oral Glutamine in Preventing Treatment-Related Mucositis in Adult Patients With Cancer: A Systematic Review. Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2016", "claim": "PubMed-indexed evidence involving L-Glutamine", "title": "Oral Glutamine in Preventing Treatment-Related Mucositis in Adult Patients With Cancer: A Systematic Review", "authors": "Sayles C, Hickerson SC, Bhat RR et al.", "journal": "Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition", "year": 2016, "pmid": "26507188", "url": "https://pubmed.ncbi.nlm.nih.gov/26507188/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/0884533615611857", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26507188/", "publicSourceType": "PMID" }, { "text": "Wischmeyer PE, Dhaliwal R, McCall M et al.. Parenteral glutamine supplementation in critical illness: a systematic review. Critical care (London, England). 2014", "claim": "PubMed-indexed evidence involving L-Glutamine", "title": "Parenteral glutamine supplementation in critical illness: a systematic review", "authors": "Wischmeyer PE, Dhaliwal R, McCall M et al.", "journal": "Critical care (London, England)", "year": 2014, "pmid": "24745648", "url": "https://pubmed.ncbi.nlm.nih.gov/24745648/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/cc13836", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24745648/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "l-glutamine" }, { "id": "FE92B62F-4FFA-4357-BC63-AACF3D6135B9", "name": "Taurine", "alternateNames": [ "2-aminoethanesulfonic acid" ], "category": "Amino Acid", "subcategory": "Conditionally Essential Amino Acid", "overview": "Sulfur-containing amino acid abundant in heart, brain, and retina. Supports cardiovascular and neural function.", "mechanismOfAction": "Acts as an osmolyte regulating cell volume. Modulates calcium signaling, stabilizes cell membranes, and conjugates bile acids. Antioxidant via hypotaurine pathway.", "commonBenefits": [ "Heart health", "Exercise performance", "Neuroprotection", "Longevity (emerging research, inconclusive)" ], "commonDosageRange": "1-3 g daily", "recommendedForm": "Taurine powder or capsules", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Well absorbed; can take any time" }, "evidenceRating": "moderate", "foodSources": [ "Meat", "Fish", "Shellfish", "Dairy" ], "deficiencySymptoms": [ "Rare in isolation", "Cardiomyopathy in cats (obligate need)" ], "sideEffects": [ "Very well tolerated", "Mild GI at very high doses" ], "contraindications": [ "Blood pressure medications (additive hypotensive effect)", "Bipolar disorder (some reports of mood destabilization)" ], "iconName": "heart.fill", "colorHex": "B37DFF", "tags": [ "heart", "performance", "longevity", "neuroprotection" ], "sources": [ { "claim": "Taurine cardiovascular benefits including blood pressure reduction and cardiac function", "title": "Insights into the cardiovascular benefits of taurine: a systematic review and meta-analysis", "authors": "Wang K et al.", "journal": "Eur J Clin Nutr", "year": 2024, "pmid": "39148075", "url": "https://pubmed.ncbi.nlm.nih.gov/39148075/", "study_type": "meta-analysis", "key_finding": "Taurine significantly reduced SBP and DBP in hypertensive patients, increased LVEF in heart failure patients; noteworthy effects in preventing hypertension and enhancing cardiac function.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39148075/", "publicSourceType": "PMID" }, { "claim": "Taurine reduces cardiometabolic risk factors", "title": "Effects of Oral Taurine Supplementation on Cardiometabolic Risk Factors: A Meta-analysis and Systematic Review of Randomized Clinical Trials", "authors": "Tao W et al.", "journal": "Adv Nutr", "year": 2025, "pmid": "41275513", "url": "https://pubmed.ncbi.nlm.nih.gov/41275513/", "study_type": "meta-analysis", "key_finding": "Taurine supplementation significantly reduced fasting blood glucose, HbA1c, fasting insulin, triglycerides, total cholesterol, and blood pressure.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41275513/", "publicSourceType": "PMID" }, { "claim": "Taurine deficiency as a driver of aging, landmark Science study", "title": "Taurine deficiency as a driver of aging", "authors": "Singh P et al.", "journal": "Science", "year": 2023, "pmid": "37289866", "url": "https://pubmed.ncbi.nlm.nih.gov/37289866/", "study_type": "cohort", "key_finding": "Taurine concentrations decline with aging; supplementation increased health span and life span in mice and health span in monkeys; reduced cellular senescence, protected telomerase, suppressed mitochondrial dysfunction.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37289866/", "publicSourceType": "PMID" }, { "claim": "Taurine reduces blood pressure in humans", "title": "The Effects of Oral Taurine on Resting Blood Pressure in Humans: a Meta-Analysis", "authors": "Waldron M et al.", "journal": "Curr Hypertens Rep", "year": 2018, "pmid": "30006901", "url": "https://pubmed.ncbi.nlm.nih.gov/30006901/", "study_type": "meta-analysis", "key_finding": "Taurine ingestion (1-6 g/day) reduced both SBP and DBP, with mean reductions of approximately 3 mmHg.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30006901/", "publicSourceType": "PMID" }, { "claim": "Taurine reduces metabolic syndrome risk factors", "title": "Taurine reduces the risk for metabolic syndrome: a systematic review and meta-analysis of randomized controlled trials", "authors": "De Luca A et al.", "journal": "Nutr Rev", "year": 2024, "pmid": "38755142", "url": "https://pubmed.ncbi.nlm.nih.gov/38755142/", "study_type": "meta-analysis", "key_finding": "Taurine supplementation demonstrated statistically significant reductions in systolic BP, diastolic BP, fasting blood glucose, and triglycerides, key metabolic syndrome components.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38755142/", "publicSourceType": "PMID" }, { "claim": "Taurine increases hippocampal neurogenesis and ameliorates age-dependent memory decline", "title": "Taurine increases hippocampal neurogenesis in aging mice", "authors": "Gebara E et al.", "journal": "Stem Cell Res", "year": 2015, "pmid": "25889858", "url": "https://pubmed.ncbi.nlm.nih.gov/25889858/", "study_type": "review", "key_finding": "Chronic taurine supplementation in aged mice significantly ameliorated age-dependent decline in spatial memory; increased stem cell proliferation and neurogenesis in the dentate gyrus.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25889858/", "publicSourceType": "PMID" }, { "text": "Waldron M, Patterson SD, Tallent J et al.. The Effects of an Oral Taurine Dose and Supplementation Period on Endurance Exercise Performance in Humans: A Meta-Analysis. Sports medicine (Auckland, N.Z.). 2018", "pmid": "29546641", "doi": "10.1007/s40279-018-0896-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29546641/", "publicSourceType": "PMID" }, { "text": "Curran CP, Marczinski CA. Taurine, caffeine, and energy drinks: Reviewing the risks to the adolescent brain. Birth defects research. 2017", "pmid": "29251842", "doi": "10.1002/bdr2.1177", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29251842/", "publicSourceType": "PMID" }, { "claim": "Taurine supplementation reduces blood pressure", "title": "Effects of taurine supplementation on blood pressure: a meta-analysis", "authors": "Sun Q, Wang B, Li Y et al.", "journal": "Amino Acids", "year": 2016, "pmid": "26613868", "doi": "10.1007/s00726-015-2120-7", "study_type": "meta-analysis", "key_finding": "SBP reduced by 3.8 mmHg, DBP by 3.2 mmHg", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26613868/", "publicSourceType": "PMID" }, { "claim": "Improves lipid and glycemic profile in overweight/obese adults", "title": "Effect of Long-Term Taurine Supplementation on the Lipid and Glycaemic Profile in Adults with Overweight or Obesity: A Systematic Review and Meta-Analysis.", "authors": "Sun Q, Wang J, Wang H, Yu H, Wan K, Ma F et al.", "journal": "Nutrients", "year": 2025, "pmid": "39796489", "url": "https://pubmed.ncbi.nlm.nih.gov/39796489/", "study_type": "meta-analysis", "key_finding": "Long-term taurine supplementation significantly improved triglyceride levels and showed favorable effects on fasting blood glucose and HbA1c in overweight or obese adults.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39796489/", "publicSourceType": "PMID" }, { "claim": "Inverse association with colorectal cancer risk", "title": "Systematic Review and Meta-Analysis: Taurine and Its Association With Colorectal Carcinoma.", "authors": "Sinha A, Griffith L, Acharjee A", "journal": "Cancer Medicine", "year": 2024, "pmid": "39632512", "url": "https://pubmed.ncbi.nlm.nih.gov/39632512/", "study_type": "meta-analysis", "key_finding": "Meta-analysis found a significant inverse association between taurine levels and colorectal cancer risk, suggesting a potential protective role of taurine.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39632512/", "publicSourceType": "PMID" }, { "text": "Samadi M, Haghi-Aminjan H, Sattari M et al.. The role of taurine on chemotherapy-induced cardiotoxicity: A systematic review of non-clinical study. Life sciences. 2021", "claim": "PubMed-indexed evidence involving Taurine", "title": "The role of taurine on chemotherapy-induced cardiotoxicity: A systematic review of non-clinical study", "authors": "Samadi M, Haghi-Aminjan H, Sattari M et al.", "journal": "Life sciences", "year": 2021, "pmid": "33275984", "url": "https://pubmed.ncbi.nlm.nih.gov/33275984/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.lfs.2020.118813", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33275984/", "publicSourceType": "PMID" }, { "text": "Chen Q, Li Z, Pinho RA et al.. The Dose Response of Taurine on Aerobic and Strength Exercises: A Systematic Review. Frontiers in physiology. 2021", "claim": "PubMed-indexed evidence involving Taurine", "title": "The Dose Response of Taurine on Aerobic and Strength Exercises: A Systematic Review", "authors": "Chen Q, Li Z, Pinho RA et al.", "journal": "Frontiers in physiology", "year": 2021, "pmid": "34497536", "url": "https://pubmed.ncbi.nlm.nih.gov/34497536/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fphys.2021.700352", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34497536/", "publicSourceType": "PMID" }, { "text": "Li Y, Wang Q, Liu Y et al.. Taurine ameliorates blood pressure and vascular function in patients with type 2 diabetes: Randomized, double-blind, placebo-controlled trial. iScience. 2025", "claim": "PubMed-indexed evidence involving Taurine", "title": "Taurine ameliorates blood pressure and vascular function in patients with type 2 diabetes: Randomized, double-blind, placebo-controlled trial", "authors": "Li Y, Wang Q, Liu Y et al.", "journal": "iScience", "year": 2025, "pmid": "40546935", "url": "https://pubmed.ncbi.nlm.nih.gov/40546935/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.isci.2025.112719", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40546935/", "publicSourceType": "PMID" }, { "text": "Althobaiti NA, Alsharif I, Alhasani RH et al.. Taurine and Neuroprotection: A Potential Shield Against Methylglyoxal-Induced Toxicity in SH-SY5Y Cells. Journal of biochemical and molecular toxicology. 2025", "claim": "PubMed-indexed evidence involving Taurine", "title": "Taurine and Neuroprotection: A Potential Shield Against Methylglyoxal-Induced Toxicity in SH-SY5Y Cells", "authors": "Althobaiti NA, Alsharif I, Alhasani RH et al.", "journal": "Journal of biochemical and molecular toxicology", "year": 2025, "pmid": "40586270", "url": "https://pubmed.ncbi.nlm.nih.gov/40586270/", "study_type": "review", "confidence": "verify", "doi": "10.1002/jbt.70343", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40586270/", "publicSourceType": "PMID" }, { "text": "Ding L, Yang Z, Liu G et al.. Safety and efficacy of taurine as an add-on treatment for tics in youngsters. European journal of neurology. 2020", "claim": "PubMed-indexed evidence involving Taurine", "title": "Safety and efficacy of taurine as an add-on treatment for tics in youngsters", "authors": "Ding L, Yang Z, Liu G et al.", "journal": "European journal of neurology", "year": 2020, "pmid": "31618495", "url": "https://pubmed.ncbi.nlm.nih.gov/31618495/", "study_type": "review", "confidence": "verify", "doi": "10.1111/ene.14107", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31618495/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "taurine" }, { "id": "325F3B5D-7E5F-4FDA-BF8B-0E250B0506C3", "name": "L-Carnitine", "alternateNames": [ "Carnitine", "ALCAR" ], "category": "Amino Acid", "subcategory": "Amino Acid Derivative", "overview": "Transports long-chain fatty acids into mitochondria for energy production.", "mechanismOfAction": "Shuttles acyl groups across the inner mitochondrial membrane via the carnitine palmitoyltransferase (CPT) system, enabling beta-oxidation of fatty acids for ATP production.", "commonBenefits": [ "Fat metabolism", "Energy production", "Exercise recovery", "Heart health" ], "commonDosageRange": "500-2,000 mg daily", "recommendedForm": "L-Carnitine L-Tartrate (exercise) or Acetyl-L-Carnitine (brain)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Better absorbed with carbohydrates" }, "evidenceRating": "moderate", "foodSources": [ "Red meat", "Dairy", "Fish", "Chicken" ], "deficiencySymptoms": [ "Fatigue", "Muscle weakness", "Cardiomyopathy" ], "sideEffects": [ "TMAO generation: L-carnitine is metabolized by gut bacteria to TMAO, associated with 62% increased all-cause mortality in meta-analyses", "Nausea", "Diarrhea" ], "contraindications": [ "Hypothyroidism (may worsen)" ], "iconName": "flame.fill", "colorHex": "B37DFF", "tags": [ "energy", "fat-burning", "heart", "exercise" ], "sources": [ { "claim": "L-carnitine supplementation effects on weight loss and body composition", "title": "Effects of l-carnitine supplementation on weight loss and body composition: A systematic review and meta-analysis of 37 randomized controlled clinical trials with dose-response analysis", "authors": "Talenezhad N et al.", "journal": "Clin Nutr ESPEN", "year": 2020, "pmid": "32359762", "url": "https://pubmed.ncbi.nlm.nih.gov/32359762/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 37 RCTs found L-carnitine supplementation significantly decreased body weight, BMI, and fat mass.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32359762/", "publicSourceType": "PMID" }, { "claim": "L-carnitine improves exercise performance and reduces fatigue", "title": "Effect of Acute and Chronic Oral l-Carnitine Supplementation on Exercise Performance Based on the Exercise Intensity: A Systematic Review", "authors": "Gnoni A et al.", "journal": "Nutrients", "year": 2022, "pmid": "34959912", "url": "https://pubmed.ncbi.nlm.nih.gov/34959912/", "study_type": "review", "key_finding": "Systematic review of 11 studies found L-carnitine supplementation improves body strength, sports endurance, exercise capacity, and delays onset of fatigue.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34959912/", "publicSourceType": "PMID" }, { "claim": "L-carnitine efficacy and safety in chronic heart failure", "title": "Efficacy and Safety of L-Carnitine Treatment for Chronic Heart Failure: A Meta-Analysis of Randomized Controlled Trials", "authors": "Song X et al.", "journal": "Biomed Res Int", "year": 2017, "pmid": "28497060", "url": "https://pubmed.ncbi.nlm.nih.gov/28497060/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 17 RCTs (1,625 CHF patients) found L-carnitine associated with improved LVEF, stroke volume, cardiac output, and BNP levels.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28497060/", "publicSourceType": "PMID" }, { "claim": "L-carnitine for secondary prevention of cardiovascular disease", "title": "L-carnitine in the secondary prevention of cardiovascular disease: systematic review and meta-analysis", "authors": "DiNicolantonio JJ et al.", "journal": "Mayo Clin Proc", "year": 2013, "pmid": "23597877", "url": "https://pubmed.ncbi.nlm.nih.gov/23597877/", "study_type": "meta-analysis", "key_finding": "L-carnitine associated with 27% reduction in all-cause mortality, 65% reduction in ventricular arrhythmias, and 40% reduction in angina development following MI.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23597877/", "publicSourceType": "PMID" }, { "claim": "L-carnitine supplementation increases TMAO but does not increase atherosclerosis markers in short term", "title": "L-Carnitine Supplementation Increases Trimethylamine-N-Oxide but not Markers of Atherosclerosis in Healthy Aged Women", "authors": "Samulak JJ et al.", "journal": "Ann Nutr Metab", "year": 2019, "pmid": "30485835", "url": "https://pubmed.ncbi.nlm.nih.gov/30485835/", "study_type": "RCT", "key_finding": "Oral L-carnitine supplementation significantly increased plasma TMAO but no lipid profile changes or atherosclerosis markers detected in healthy aged women over 24 weeks.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30485835/", "publicSourceType": "PMID" }, { "claim": "TMAO from gut microbiota metabolism associated with increased cardiovascular risk", "title": "Gut Microbiota Metabolites and Risk of Major Adverse Cardiovascular Disease Events and Death: A Systematic Review and Meta-Analysis of Prospective Studies", "authors": "Heianza Y et al.", "journal": "J Am Heart Assoc", "year": 2017, "pmid": "28663251", "url": "https://pubmed.ncbi.nlm.nih.gov/28663251/", "study_type": "meta-analysis", "key_finding": "Elevated TMAO concentrations associated with 1.62x higher risk for major adverse cardiovascular events; L-carnitine precursors associated with ~1.3-1.4x higher risk.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28663251/", "publicSourceType": "PMID" }, { "text": "Mirrafiei A, Jayedi A, Shab-Bidar S. The Effects of L-Carnitine Supplementation on Weight Loss, Glycemic Control, and Cardiovascular Risk Factors in Patients With Type 2 Diabetes: A Systematic Review and Dose-response Meta-Analysis of Randomized Controlled Trials. Clinical therapeutics. 2024", "pmid": "38594107", "doi": "10.1016/j.clinthera.2024.03.002", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38594107/", "publicSourceType": "PMID" }, { "text": "Sawicka AK, Renzi G, Olek RA. The bright and the dark sides of L-carnitine supplementation: a systematic review. Journal of the International Society of Sports Nutrition. 2020", "pmid": "32958033", "doi": "10.1186/s12970-020-00377-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32958033/", "publicSourceType": "PMID" }, { "claim": "Improves metabolic syndrome biomarkers", "title": "L-Carnitine's Effect on the Biomarkers of Metabolic Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.", "authors": "Choi M, Park S, Lee M", "journal": "Nutrients", "year": 2020, "pmid": "32932644", "url": "https://pubmed.ncbi.nlm.nih.gov/32932644/", "study_type": "meta-analysis", "key_finding": "L-carnitine supplementation significantly improved multiple metabolic syndrome biomarkers including fasting glucose, triglycerides, HDL cholesterol, and systolic blood pressure.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32932644/", "publicSourceType": "PMID" }, { "text": "Askarpour M, Hadi A, Miraghajani M et al.. Beneficial effects of l-carnitine supplementation for weight management in overweight and obese adults: An updated systematic review and dose-response meta-analysis of randomized controlled trials. Pharmacological research. 2020", "claim": "PubMed-indexed evidence involving L-Carnitine", "title": "Beneficial effects of l-carnitine supplementation for weight management in overweight and obese adults: An updated systematic review and dose-response meta-analysis of randomized controlled trials", "authors": "Askarpour M, Hadi A, Miraghajani M et al.", "journal": "Pharmacological research", "year": 2020, "pmid": "31743774", "url": "https://pubmed.ncbi.nlm.nih.gov/31743774/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.phrs.2019.104554", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31743774/", "publicSourceType": "PMID" }, { "text": "Pooyandjoo M, Nouhi M, Shab-Bidar S et al.. The effect of (L-)carnitine on weight loss in adults: a systematic review and meta-analysis of randomized controlled trials. Obesity reviews : an official journal of the International Association for the Study of Obesity. 2016", "claim": "PubMed-indexed evidence involving L-Carnitine", "title": "The effect of (L-)carnitine on weight loss in adults: a systematic review and meta-analysis of randomized controlled trials", "authors": "Pooyandjoo M, Nouhi M, Shab-Bidar S et al.", "journal": "Obesity reviews : an official journal of the International Association for the Study of Obesity", "year": 2016, "pmid": "27335245", "url": "https://pubmed.ncbi.nlm.nih.gov/27335245/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/obr.12436", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27335245/", "publicSourceType": "PMID" }, { "text": "Liu A, Cai Y, Yuan Y et al.. Efficacy and safety of carnitine supplementation on NAFLD: a systematic review and meta-analysis. Systematic reviews. 2023", "claim": "PubMed-indexed evidence involving L-Carnitine", "title": "Efficacy and safety of carnitine supplementation on NAFLD: a systematic review and meta-analysis", "authors": "Liu A, Cai Y, Yuan Y et al.", "journal": "Systematic reviews", "year": 2023, "pmid": "37120548", "url": "https://pubmed.ncbi.nlm.nih.gov/37120548/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s13643-023-02238-w", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37120548/", "publicSourceType": "PMID" }, { "text": "Salles C, Freitas MC, Cruz MME. Impact of L-carnitine in narcolepsy treatment: a systematic review on the effectiveness and safety. Sleep science (Sao Paulo, Brazil). 2022", "claim": "PubMed-indexed evidence involving L-Carnitine", "title": "Impact of L-carnitine in narcolepsy treatment: a systematic review on the effectiveness and safety", "authors": "Salles C, Freitas MC, Cruz MME", "journal": "Sleep science (Sao Paulo, Brazil)", "year": 2022, "pmid": "35273778", "url": "https://pubmed.ncbi.nlm.nih.gov/35273778/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.5935/1984-0063.20220004", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35273778/", "publicSourceType": "PMID" }, { "text": "Weng Y, Zhang S, Huang W et al.. Efficacy of L-Carnitine for Dilated Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials. BioMed research international. 2021", "claim": "PubMed-indexed evidence involving L-Carnitine", "title": "Efficacy of L-Carnitine for Dilated Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials", "authors": "Weng Y, Zhang S, Huang W et al.", "journal": "BioMed research international", "year": 2021, "pmid": "33521132", "url": "https://pubmed.ncbi.nlm.nih.gov/33521132/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1155/2021/9491615", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33521132/", "publicSourceType": "PMID" }, { "text": "Ma X, Yang Y, Liu S et al.. Meta-analysis of the efficacy and safety of L-carnitine and N-acetylcysteine monotherapy for male idiopathic infertility. Revista internacional de andrologia. 2025", "claim": "PubMed-indexed evidence involving L-Carnitine", "title": "Meta-analysis of the efficacy and safety of L-carnitine and N-acetylcysteine monotherapy for male idiopathic infertility", "authors": "Ma X, Yang Y, Liu S et al.", "journal": "Revista internacional de andrologia", "year": 2025, "pmid": "40350672", "url": "https://pubmed.ncbi.nlm.nih.gov/40350672/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.22514/j.androl.2025.004", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40350672/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "l-carnitine" }, { "id": "AE02934A-FA8F-4C7F-A64D-515CFC69256E", "name": "Acetyl-L-Carnitine", "alternateNames": [ "ALCAR" ], "category": "Amino Acid", "subcategory": "Amino Acid Derivative", "overview": "Acetylated form of L-carnitine that crosses the blood-brain barrier for cognitive support.", "mechanismOfAction": "Crosses BBB and donates acetyl groups for acetylcholine synthesis. Supports mitochondrial function in neurons and enhances nerve growth factor activity.", "commonBenefits": [ "Cognitive function", "Neuroprotection", "Energy", "Mood support" ], "commonDosageRange": "500-1,500 mg daily", "recommendedForm": "Acetyl-L-Carnitine HCl", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Better absorbed on empty stomach for cognitive benefits" }, "evidenceRating": "moderate", "foodSources": [ "Red meat", "Dairy" ], "deficiencySymptoms": [ "Same as L-carnitine" ], "sideEffects": [ "Restlessness", "Insomnia if taken late", "GI upset" ], "contraindications": [ "Bipolar disorder (may trigger mania)", "Seizure disorders" ], "iconName": "brain.fill", "colorHex": "B37DFF", "tags": [ "cognitive", "neuroprotection", "energy", "mood" ], "sources": [ { "claim": "Acetyl-L-carnitine effective for treating depressive symptoms", "title": "Acetyl-L-Carnitine Supplementation and the Treatment of Depressive Symptoms: A Systematic Review and Meta-Analysis", "authors": "Veronese N et al.", "journal": "Psychosom Med", "year": 2018, "pmid": "29076953", "url": "https://pubmed.ncbi.nlm.nih.gov/29076953/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 12 RCTs (791 participants) found ALC superior to placebo for depression; equally effective as fluoxetine and amisulpride for dysthymic disorder with fewer side effects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29076953/", "publicSourceType": "PMID" }, { "claim": "Acetyl-L-carnitine improves mild cognitive impairment and mild Alzheimer's disease", "title": "Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease", "authors": "Montgomery SA et al.", "journal": "Int Clin Psychopharmacol", "year": 2003, "pmid": "12598816", "url": "https://pubmed.ncbi.nlm.nih.gov/12598816/", "study_type": "meta-analysis", "key_finding": "Meta-analysis showed significant advantage for ALCAR vs placebo in MCI and mild AD (effect size 0.201, 95% CI 0.107-0.295); benefit seen at 3 months and increased over time.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12598816/", "publicSourceType": "PMID" }, { "claim": "ALCAR improves pain, nerve regeneration and vibratory perception in diabetic neuropathy", "title": "Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: an analysis of two randomized placebo-controlled trials", "authors": "Sima AA et al.", "journal": "Diabetes Care", "year": 2005, "pmid": "15616239", "url": "https://pubmed.ncbi.nlm.nih.gov/15616239/", "study_type": "RCT", "key_finding": "ALC treatment is efficacious in alleviating pain symptoms, improves nerve fiber regeneration and vibration perception in patients with established diabetic neuropathy.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15616239/", "publicSourceType": "PMID" }, { "claim": "ALCAR systematic review for peripheral neuropathic pain", "title": "Acetyl-L-carnitine in the treatment of peripheral neuropathic pain: a systematic review and meta-analysis of randomized controlled trials", "authors": "Li S et al.", "journal": "PLoS One", "year": 2015, "pmid": "25751285", "url": "https://pubmed.ncbi.nlm.nih.gov/25751285/", "study_type": "meta-analysis", "key_finding": "ALC significantly reduced VAS pain scores in peripheral neuropathy patients; appeared more effective in diabetic vs non-diabetic neuropathy. Safe and well tolerated.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25751285/", "publicSourceType": "PMID" }, { "claim": "ALCAR critical update on dementia and cognitive disorders", "title": "Acetyl-L-Carnitine in Dementia and Other Cognitive Disorders: A Critical Update", "authors": "Pennisi M et al.", "journal": "Nutrients", "year": 2020, "pmid": "32408706", "url": "https://pubmed.ncbi.nlm.nih.gov/32408706/", "study_type": "review", "key_finding": "ALC crosses BBB and donates acetyl groups for acetylcholine synthesis; supports mitochondrial function in neurons, enhances nerve growth factor activity, and exerts neurotrophic effects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32408706/", "publicSourceType": "PMID" }, { "claim": "ALCAR increases brain noradrenaline and serotonin content", "title": "Chronic acetyl-L-carnitine alters brain energy metabolism and increases noradrenaline and serotonin content in healthy mice", "authors": "Smeland OB et al.", "journal": "Neurochem Int", "year": 2012, "pmid": "22549035", "url": "https://pubmed.ncbi.nlm.nih.gov/22549035/", "study_type": "review", "key_finding": "ALCAR supplementation increased brain noradrenaline and serotonin levels, consistent with its potential efficacy for depressive symptoms and mood support.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22549035/", "publicSourceType": "PMID" }, { "text": "Martí-Carvajal AJ, Gluud C, Arevalo-Rodriguez I et al.. Acetyl-L-carnitine for patients with hepatic encephalopathy. The Cochrane database of systematic reviews. 2019", "pmid": "30610762", "doi": "10.1002/14651858.CD011451.pub2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30610762/", "publicSourceType": "PMID" }, { "text": "Hudson S, Tabet N. Acetyl-L-carnitine for dementia. The Cochrane database of systematic reviews. 2003", "pmid": "12804452", "doi": "10.1002/14651858.CD003158", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12804452/", "publicSourceType": "PMID" }, { "claim": "Improves sperm motility in idiopathic asthenozoospermia", "title": "A Meta-Analysis of the Efficacy of L-Carnitine/L-Acetyl-Carnitine or N-Acetyl-Cysteine in Men With Idiopathic Asthenozoospermia.", "authors": "Wei G, Zhou Z, Cui Y, Huang Y, Wan Z, Che X et al.", "journal": "American Journal of Men's Health", "year": 2021, "pmid": "33906513", "url": "https://pubmed.ncbi.nlm.nih.gov/33906513/", "study_type": "meta-analysis", "key_finding": "L-carnitine/acetyl-L-carnitine supplementation significantly improved sperm motility (progressive motility and total motility) in men with idiopathic asthenozoospermia.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33906513/", "publicSourceType": "PMID" }, { "claim": "Recommended in psychiatric treatment guidelines", "title": "Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce.", "authors": "Sarris J, Ravindran A, Yatham LN, Marx W, Rucklidge JJ, McIntyre RS et al.", "journal": "World Journal of Biological Psychiatry", "year": 2022, "pmid": "35311615", "url": "https://pubmed.ncbi.nlm.nih.gov/35311615/", "study_type": "meta-analysis", "key_finding": "WFSBP/CANMAT guidelines found moderate evidence supporting acetyl-L-carnitine for depression, with recommendations for its use as an adjunctive treatment.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35311615/", "publicSourceType": "PMID" }, { "text": "Di Stefano G, Di Lionardo A, Galosi E et al.. Acetyl-L-carnitine in painful peripheral neuropathy: a systematic review. Journal of pain research. 2019", "claim": "PubMed-indexed evidence involving Acetyl-L-Carnitine", "title": "Acetyl-L-carnitine in painful peripheral neuropathy: a systematic review", "authors": "Di Stefano G, Di Lionardo A, Galosi E et al.", "journal": "Journal of pain research", "year": 2019, "pmid": "31118753", "url": "https://pubmed.ncbi.nlm.nih.gov/31118753/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2147/JPR.S190231", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31118753/", "publicSourceType": "PMID" }, { "text": "Aldendail CF, Chen P, Dibble HS et al.. A Comprehensive Review of Safety, Efficacy, and Indications for the Use of Alpha-Lipoic Acid and Acetyl-L-Carnitine in Neuropathic Pain. Integrative medicine (Encinitas, Calif.). 2024", "claim": "PubMed-indexed evidence involving Acetyl-L-Carnitine", "title": "A Comprehensive Review of Safety, Efficacy, and Indications for the Use of Alpha-Lipoic Acid and Acetyl-L-Carnitine in Neuropathic Pain", "authors": "Aldendail CF, Chen P, Dibble HS et al.", "journal": "Integrative medicine (Encinitas, Calif.)", "year": 2024, "pmid": "39114278", "url": "https://pubmed.ncbi.nlm.nih.gov/39114278/", "study_type": "review", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39114278/", "publicSourceType": "PMID" }, { "text": "Malaguarnera G, Catania VE, Bertino G et al.. Acetyl-L-carnitine Slows the Progression from Prefrailty to Frailty in Older Subjects: A Randomized Interventional Clinical Trial. Current pharmaceutical design. 2022", "claim": "PubMed-indexed evidence involving Acetyl-L-Carnitine", "title": "Acetyl-L-carnitine Slows the Progression from Prefrailty to Frailty in Older Subjects: A Randomized Interventional Clinical Trial", "authors": "Malaguarnera G, Catania VE, Bertino G et al.", "journal": "Current pharmaceutical design", "year": 2022, "pmid": "36043711", "url": "https://pubmed.ncbi.nlm.nih.gov/36043711/", "study_type": "RCT", "confidence": "verify", "doi": "10.2174/1381612828666220830092815", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36043711/", "publicSourceType": "PMID" }, { "text": "Curran MWT, Morhart MJ, Olson JL et al.. Acetyl-L-Carnitine to Enhance Nerve Regeneration in Carpal Tunnel Syndrome: A Double-Blind, Randomized, Controlled Trial. Plastic and reconstructive surgery. 2019", "claim": "PubMed-indexed evidence involving Acetyl-L-Carnitine", "title": "Acetyl-L-Carnitine to Enhance Nerve Regeneration in Carpal Tunnel Syndrome: A Double-Blind, Randomized, Controlled Trial", "authors": "Curran MWT, Morhart MJ, Olson JL et al.", "journal": "Plastic and reconstructive surgery", "year": 2019, "pmid": "30589790", "url": "https://pubmed.ncbi.nlm.nih.gov/30589790/", "study_type": "RCT", "confidence": "verify", "doi": "10.1097/PRS.0000000000005089", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30589790/", "publicSourceType": "PMID" }, { "text": "Curran MW, Olson J, Morhart M et al.. Acetyl-L-carnitine (ALCAR) to enhance nerve regeneration in carpal tunnel syndrome: study protocol for a randomized, placebo-controlled trial. Trials. 2016", "claim": "PubMed-indexed evidence involving Acetyl-L-Carnitine", "title": "Acetyl-L-carnitine (ALCAR) to enhance nerve regeneration in carpal tunnel syndrome: study protocol for a randomized, placebo-controlled trial", "authors": "Curran MW, Olson J, Morhart M et al.", "journal": "Trials", "year": 2016, "pmid": "27079660", "url": "https://pubmed.ncbi.nlm.nih.gov/27079660/", "study_type": "RCT", "confidence": "verify", "doi": "10.1186/s13063-016-1324-2", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27079660/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "acetyl-l-carnitine" }, { "id": "33DF30D1-4BB5-4BB9-AB65-68F3F90B9AA5", "name": "GABA", "alternateNames": [ "Gamma-aminobutyric acid" ], "category": "Amino Acid", "subcategory": "Inhibitory Neurotransmitter", "overview": "Primary inhibitory neurotransmitter supplement for relaxation and sleep.", "mechanismOfAction": "Oral GABA may act peripherally on enteric nervous system and via limited BBB crossing. Activates GABA-A and GABA-B receptors to promote neuronal inhibition and relaxation.", "commonBenefits": [ "Relaxation", "Sleep support", "Anxiety reduction", "Growth hormone" ], "commonDosageRange": "250-750 mg daily", "recommendedForm": "PharmaGABA (naturally fermented, preferred)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Take on empty stomach 30-60 min before bed" }, "evidenceRating": "emerging", "foodSources": [ "Fermented foods", "Tea", "Tomatoes", "Sprouted grains" ], "deficiencySymptoms": [ "Not a classical deficiency" ], "sideEffects": [ "Drowsiness", "Tingling", "Shortness of breath (rare)" ], "contraindications": [ "Pregnancy", "Concurrent sedative use" ], "iconName": "moon.fill", "colorHex": "B37DFF", "tags": [ "sleep", "relaxation", "anxiety" ], "sources": [ { "claim": "Systematic review of oral GABA effects on stress and sleep", "title": "Effects of Oral Gamma-Aminobutyric Acid (GABA) Administration on Stress and Sleep in Humans: A Systematic Review", "authors": "Hepsomali P et al.", "journal": "Frontiers in Neuroscience", "year": 2020, "pmid": "33041752", "url": "https://pubmed.ncbi.nlm.nih.gov/33041752/", "study_type": "review", "key_finding": "Systematic review of 14 placebo-controlled human trials found limited evidence for stress benefits and very limited evidence for sleep benefits of oral GABA intake.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33041752/", "publicSourceType": "PMID" }, { "claim": "GABA shortens sleep latency and improves NREM sleep", "title": "Effect of oral gamma-aminobutyric acid (GABA) administration on sleep and its absorption in humans", "authors": "Yamatsu A et al.", "journal": "Food Science and Biotechnology", "year": 2016, "pmid": "30263304", "url": "https://pubmed.ncbi.nlm.nih.gov/30263304/", "study_type": "RCT", "key_finding": "GABA shortened sleep latency by 5.3 minutes and increased total non-REM sleep time in healthy subjects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30263304/", "publicSourceType": "PMID" }, { "claim": "GABA promotes relaxation and reduces anxiety via alpha wave modulation", "title": "Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans", "authors": "Abdou AM et al.", "journal": "BioFactors", "year": 2006, "pmid": "16971751", "url": "https://pubmed.ncbi.nlm.nih.gov/16971751/", "study_type": "RCT", "key_finding": "After 60 minutes of GABA administration, it significantly increased alpha waves and decreased beta waves, indicating relaxation and reduced anxiety.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16971751/", "publicSourceType": "PMID" }, { "claim": "GABA elevates resting and post-exercise growth hormone levels", "title": "Growth hormone isoform responses to GABA ingestion at rest and after exercise", "authors": "Powers ME et al.", "journal": "Medicine and Science in Sports and Exercise", "year": 2008, "pmid": "18091016", "url": "https://pubmed.ncbi.nlm.nih.gov/18091016/", "study_type": "RCT", "key_finding": "GABA ingestion elevated both immunoreactive and immunofunctional growth hormone at rest and after exercise compared to placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18091016/", "publicSourceType": "PMID" }, { "claim": "USP safety review of oral GABA supplementation", "title": "United States Pharmacopeia (USP) Safety Review of Gamma-Aminobutyric Acid (GABA)", "authors": "Oketch-Rabah HA et al.", "journal": "Journal of Dietary Supplements", "year": 2021, "pmid": "34444905", "url": "https://pubmed.ncbi.nlm.nih.gov/34444905/", "study_type": "review", "key_finding": "No serious adverse events associated with GABA at intakes up to 18 g/day for 4 days and 120 mg/day for 12 weeks; chronic administration showed no toxicity signs.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34444905/", "publicSourceType": "PMID" }, { "claim": "Fermented GABA for insomnia symptoms", "title": "Safety and Efficacy of Gamma-Aminobutyric Acid from Fermented Rice Germ in Patients with Insomnia Symptoms: A Randomized, Double-Blind Trial", "authors": "Byun JI et al.", "journal": "Journal of Clinical Neurology", "year": 2018, "pmid": "29856155", "url": "https://pubmed.ncbi.nlm.nih.gov/29856155/", "study_type": "RCT", "key_finding": "Biosynthetic GABA from fermented rice germ improved sleep latency and quality in patients with insomnia symptoms with a good safety profile.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29856155/", "publicSourceType": "PMID" }, { "claim": "GABA supplementation may improve mood, sleep, and stress response during exercise", "title": "GABA Supplementation, Increased Heart-Rate Variability, Emotional Response, Sleep Efficiency and Reduced Depression in Sedentary Overweight Women Undergoing Physical Exercise: Placebo-Controlled, Randomized Clinical Trial", "authors": "Guimarães AP, Seidel H, Pires LVM et al.", "journal": "Journal of Dietary Supplements", "year": 2024, "pmid": "38321713", "url": "https://pubmed.ncbi.nlm.nih.gov/38321713/", "study_type": "rct", "key_finding": "Oral GABA supplementation increased heart rate variability, improved emotional response, increased sleep efficiency, and reduced depression scores in sedentary overweight women undergoing exercise training.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38321713/", "publicSourceType": "PMID" }, { "text": "Wathanavasin W, Thammathiwat T, Susantitaphong P. Meta-Analysis of Randomized Controlled Trials on Gamma-Aminobutyric Acid Analogues and Opioid-Based Therapies for CKD-Associated Pruritus. Kidney international reports. 2025", "claim": "PubMed-indexed evidence involving GABA", "title": "Meta-Analysis of Randomized Controlled Trials on Gamma-Aminobutyric Acid Analogues and Opioid-Based Therapies for CKD-Associated Pruritus", "authors": "Wathanavasin W, Thammathiwat T, Susantitaphong P", "journal": "Kidney international reports", "year": 2025, "pmid": "40980656", "url": "https://pubmed.ncbi.nlm.nih.gov/40980656/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.ekir.2025.06.037", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40980656/", "publicSourceType": "PMID" }, { "text": "Zahid U, Onwordi EC, Hedges EP et al.. Neurofunctional correlates of glutamate and GABA imbalance in psychosis: A systematic review. Neuroscience and biobehavioral reviews. 2023", "claim": "PubMed-indexed evidence involving GABA", "title": "Neurofunctional correlates of glutamate and GABA imbalance in psychosis: A systematic review", "authors": "Zahid U, Onwordi EC, Hedges EP et al.", "journal": "Neuroscience and biobehavioral reviews", "year": 2023, "pmid": "36549375", "url": "https://pubmed.ncbi.nlm.nih.gov/36549375/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.neubiorev.2022.105010", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36549375/", "publicSourceType": "PMID" }, { "text": "Guo X, Zhang T, Yuan G et al.. GABA Analogue HSK16149 in Chinese Patients With Diabetic Peripheral Neuropathic Pain: A Phase 3 Randomized Clinical Trial. JAMA network open. 2024", "claim": "PubMed-indexed evidence involving GABA", "title": "GABA Analogue HSK16149 in Chinese Patients With Diabetic Peripheral Neuropathic Pain: A Phase 3 Randomized Clinical Trial", "authors": "Guo X, Zhang T, Yuan G et al.", "journal": "JAMA network open", "year": 2024, "pmid": "39158916", "url": "https://pubmed.ncbi.nlm.nih.gov/39158916/", "study_type": "RCT", "confidence": "verify", "doi": "10.1001/jamanetworkopen.2024.25614", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39158916/", "publicSourceType": "PMID" }, { "text": "De Lellis LF, Morone MV, Buccato DG et al.. Efficacy of Food Supplement Based on Monacolins, γ-Oryzanol, and γ-Aminobutyric Acid in Mild Dyslipidemia: A Randomized, Double-Blind, Parallel-Armed, Placebo-Controlled Clinical Trial. Nutrients. 2024", "claim": "PubMed-indexed evidence involving GABA", "title": "Efficacy of Food Supplement Based on Monacolins, γ-Oryzanol, and γ-Aminobutyric Acid in Mild Dyslipidemia: A Randomized, Double-Blind, Parallel-Armed, Placebo-Controlled Clinical Trial", "authors": "De Lellis LF, Morone MV, Buccato DG et al.", "journal": "Nutrients", "year": 2024, "pmid": "39275298", "url": "https://pubmed.ncbi.nlm.nih.gov/39275298/", "study_type": "RCT", "confidence": "verify", "doi": "10.3390/nu16172983", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39275298/", "publicSourceType": "PMID" }, { "text": "Philip AB, Brohan J, Goudra B. The Role of GABA Receptors in Anesthesia and Sedation: An Updated Review. CNS drugs. 2025", "claim": "PubMed-indexed evidence involving GABA", "title": "The Role of GABA Receptors in Anesthesia and Sedation: An Updated Review", "authors": "Philip AB, Brohan J, Goudra B", "journal": "CNS drugs", "year": 2025, "pmid": "39465449", "url": "https://pubmed.ncbi.nlm.nih.gov/39465449/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s40263-024-01128-6", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39465449/", "publicSourceType": "PMID" }, { "text": "Johnston GAR, Beart PM. Milestone review: GABA, from chemistry, conformations, ionotropic receptors, modulators, epilepsy, flavonoids, and stress to neuro-nutraceuticals. Journal of neurochemistry. 2024", "claim": "PubMed-indexed evidence involving GABA", "title": "Milestone review: GABA, from chemistry, conformations, ionotropic receptors, modulators, epilepsy, flavonoids, and stress to neuro-nutraceuticals", "authors": "Johnston GAR, Beart PM", "journal": "Journal of neurochemistry", "year": 2024, "pmid": "38383146", "url": "https://pubmed.ncbi.nlm.nih.gov/38383146/", "study_type": "review", "confidence": "verify", "doi": "10.1111/jnc.16087", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38383146/", "publicSourceType": "PMID" }, { "text": "Ríos JL, Schinella GR, Moragrega I. Phenolics as GABA(A) Receptor Ligands: An Updated Review. Molecules (Basel, Switzerland). 2022", "claim": "PubMed-indexed evidence involving GABA", "title": "Phenolics as GABA(A) Receptor Ligands: An Updated Review", "authors": "Ríos JL, Schinella GR, Moragrega I", "journal": "Molecules (Basel, Switzerland)", "year": 2022, "pmid": "35335130", "url": "https://pubmed.ncbi.nlm.nih.gov/35335130/", "study_type": "review", "confidence": "verify", "doi": "10.3390/molecules27061770", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35335130/", "publicSourceType": "PMID" }, { "text": "Maillard PY, Baer S, Schaefer É et al.. Molecular and clinical descriptions of patients with GABA(A) receptor gene variants (GABRA1, GABRB2, GABRB3, GABRG2): A cohort study, review of literature, and genotype-phenotype correlation. Epilepsia. 2022", "claim": "PubMed-indexed evidence involving GABA", "title": "Molecular and clinical descriptions of patients with GABA(A) receptor gene variants (GABRA1, GABRB2, GABRB3, GABRG2): A cohort study, review of literature, and genotype-phenotype correlation", "authors": "Maillard PY, Baer S, Schaefer É et al.", "journal": "Epilepsia", "year": 2022, "pmid": "35718920", "url": "https://pubmed.ncbi.nlm.nih.gov/35718920/", "study_type": "cohort", "confidence": "verify", "doi": "10.1111/epi.17336", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35718920/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "gaba" }, { "id": "34F3A4F0-9F2B-4D1C-B75D-4A968D9C48D9", "name": "L-Tryptophan", "alternateNames": [ "Tryptophan" ], "category": "Amino Acid", "subcategory": "Essential Amino Acid", "overview": "Essential amino acid precursor to serotonin and melatonin.", "mechanismOfAction": "Converted to 5-HTP by tryptophan hydroxylase, then to serotonin by AADC. Serotonin is further converted to melatonin by AANAT and ASMT in the pineal gland.", "commonBenefits": [ "Sleep support", "Mood enhancement", "Serotonin production" ], "commonDosageRange": "500-1,000 mg before bed", "recommendedForm": "Free-form L-Tryptophan", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Take on empty stomach away from protein (competition for transport)" }, "evidenceRating": "moderate", "foodSources": [ "Turkey", "Chicken", "Eggs", "Cheese", "Nuts", "Seeds" ], "deficiencySymptoms": [ "Depression", "Insomnia", "Anxiety", "Carbohydrate cravings" ], "sideEffects": [ "Drowsiness", "Nausea", "Dry mouth" ], "contraindications": [ "SSRIs/MAOIs (serotonin syndrome)", "Eosinophilia history" ], "iconName": "moon.stars.fill", "colorHex": "B37DFF", "tags": [ "sleep", "mood", "serotonin" ], "sources": [ { "claim": "Meta-analysis of tryptophan supplementation on sleep quality", "title": "The impact of tryptophan supplementation on sleep quality: a systematic review, meta-analysis, and meta-regression", "authors": "Sutanto CN et al.", "journal": "Nutrition Reviews", "year": 2022, "pmid": "33942088", "url": "https://pubmed.ncbi.nlm.nih.gov/33942088/", "study_type": "meta-analysis", "key_finding": "Tryptophan supplementation can shorten wake after sleep onset and improve subjective sleep quality.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33942088/", "publicSourceType": "PMID" }, { "claim": "Systematic review of L-tryptophan effects on mood and emotional functioning", "title": "A systematic review of the effect of L-tryptophan supplementation on mood and emotional functioning", "authors": "Kikuchi AM et al.", "journal": "Journal of Dietary Supplements", "year": 2021, "pmid": "32272859", "url": "https://pubmed.ncbi.nlm.nih.gov/32272859/", "study_type": "review", "key_finding": "L-tryptophan intake (0.14-3 g/day) may be effective to decrease anxiety and increase positive mood in healthy individuals.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32272859/", "publicSourceType": "PMID" }, { "claim": "L-tryptophan as a hypnotic: dose-response for sleep latency reduction", "title": "Evaluation of L-tryptophan for treatment of insomnia: a review", "authors": "Hartmann E et al.", "journal": "Journal of Clinical Psychiatry", "year": 1987, "pmid": "3090582", "url": "https://pubmed.ncbi.nlm.nih.gov/3090582/", "study_type": "review", "key_finding": "L-tryptophan in doses of 1 g or more produces an increase in subjective sleepiness and a decrease in sleep latency, with best results in mild insomnia.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3090582/", "publicSourceType": "PMID" }, { "claim": "L-tryptophan conversion to cerebral serotonin", "title": "L-tryptophan administration and increase in cerebral serotonin levels: Systematic review", "authors": "Fernstrom JD et al.", "journal": "BMC Psychiatry", "year": 2018, "pmid": "30098308", "url": "https://pubmed.ncbi.nlm.nih.gov/30098308/", "study_type": "review", "key_finding": "L-tryptophan is readily converted to serotonin in the brain and can modulate sleep, mood, and cognitive function via serotonergic pathways.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30098308/", "publicSourceType": "PMID" }, { "claim": "Safety concerns including serotonin syndrome and EMS history", "title": "Effects and side effects associated with the non-nutritional use of tryptophan by humans", "authors": "Fernstrom JD", "journal": "Journal of Nutrition", "year": 2012, "pmid": "23077193", "url": "https://pubmed.ncbi.nlm.nih.gov/23077193/", "study_type": "review", "key_finding": "Side effects at higher doses (70-200 mg/kg) include tremor, nausea, dizziness; serotonin syndrome risk when combined with serotonergic drugs; historical EMS outbreak linked to contaminant, not tryptophan itself.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23077193/", "publicSourceType": "PMID" }, { "text": "Turner EH, Loftis JM, Blackwell AD. Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacology & therapeutics. 2006", "pmid": "16023217", "doi": "10.1016/j.pharmthera.2005.06.004", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16023217/", "publicSourceType": "PMID" }, { "text": "Sebigi TW, Asia LK, January GG et al.. The Tryptophan-Kynurenine pathway in people living with HIV: a systematic review. Infection. 2025", "claim": "PubMed-indexed evidence involving L-Tryptophan", "title": "The Tryptophan-Kynurenine pathway in people living with HIV: a systematic review", "authors": "Sebigi TW, Asia LK, January GG et al.", "journal": "Infection", "year": 2025, "pmid": "40448914", "url": "https://pubmed.ncbi.nlm.nih.gov/40448914/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s15010-025-02557-1", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40448914/", "publicSourceType": "PMID" }, { "text": "Wang B, Cheng P, Jin B et al.. Effect of Tryptophan Restriction in the Therapy of Irritable Bowel Syndrome: a Systematic Review. International journal of general medicine. 2024", "claim": "PubMed-indexed evidence involving L-Tryptophan", "title": "Effect of Tryptophan Restriction in the Therapy of Irritable Bowel Syndrome: a Systematic Review", "authors": "Wang B, Cheng P, Jin B et al.", "journal": "International journal of general medicine", "year": 2024, "pmid": "39308964", "url": "https://pubmed.ncbi.nlm.nih.gov/39308964/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2147/IJGM.S474525", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39308964/", "publicSourceType": "PMID" }, { "text": "Aarsland TIM, Instanes JT, Posserud MR et al.. Changes in Tryptophan-Kynurenine Metabolism in Patients with Depression Undergoing ECT-A Systematic Review. Pharmaceuticals (Basel, Switzerland). 2022", "claim": "PubMed-indexed evidence involving L-Tryptophan", "title": "Changes in Tryptophan-Kynurenine Metabolism in Patients with Depression Undergoing ECT-A Systematic Review", "authors": "Aarsland TIM, Instanes JT, Posserud MR et al.", "journal": "Pharmaceuticals (Basel, Switzerland)", "year": 2022, "pmid": "36422569", "url": "https://pubmed.ncbi.nlm.nih.gov/36422569/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/ph15111439", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36422569/", "publicSourceType": "PMID" }, { "text": "Simongiovanni A, Corrent E, Le Floc'h N et al.. Estimation of the tryptophan requirement in piglets by meta-analysis. Animal : an international journal of animal bioscience. 2012", "claim": "PubMed-indexed evidence involving L-Tryptophan", "title": "Estimation of the tryptophan requirement in piglets by meta-analysis", "authors": "Simongiovanni A, Corrent E, Le Floc'h N et al.", "journal": "Animal : an international journal of animal bioscience", "year": 2012, "pmid": "22436275", "url": "https://pubmed.ncbi.nlm.nih.gov/22436275/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1017/S1751731111001960", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22436275/", "publicSourceType": "PMID" }, { "text": "Rosselló Aubach L, Fornós Roca X, Fernández Álvarez ME. Effects of Coenzyme Q10, Tryptophan, and Magnesium Supplementation on Fatigue in Patients with Fibromyalgia - A Randomized Trial. Journal of dietary supplements. 2025", "claim": "PubMed-indexed evidence involving L-Tryptophan", "title": "Effects of Coenzyme Q10, Tryptophan, and Magnesium Supplementation on Fatigue in Patients with Fibromyalgia - A Randomized Trial", "authors": "Rosselló Aubach L, Fornós Roca X, Fernández Álvarez ME", "journal": "Journal of dietary supplements", "year": 2025, "pmid": "40151031", "url": "https://pubmed.ncbi.nlm.nih.gov/40151031/", "study_type": "RCT", "confidence": "verify", "doi": "10.1080/19390211.2025.2483269", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40151031/", "publicSourceType": "PMID" }, { "text": "Rueda GH, Causada-Calo N, Borojevic R et al.. Oral tryptophan activates duodenal aryl hydrocarbon receptor in healthy subjects: a crossover randomized controlled trial. American journal of physiology. Gastrointestinal and liver physiology. 2024", "claim": "PubMed-indexed evidence involving L-Tryptophan", "title": "Oral tryptophan activates duodenal aryl hydrocarbon receptor in healthy subjects: a crossover randomized controlled trial", "authors": "Rueda GH, Causada-Calo N, Borojevic R et al.", "journal": "American journal of physiology. Gastrointestinal and liver physiology", "year": 2024, "pmid": "38591144", "url": "https://pubmed.ncbi.nlm.nih.gov/38591144/", "study_type": "RCT", "confidence": "verify", "doi": "10.1152/ajpgi.00306.2023", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38591144/", "publicSourceType": "PMID" }, { "text": "Ko SM, Park JE, Lee JY et al.. Toxicology and safety study of L-tryptophan and its impurities for use in broiler feed. Journal of applied toxicology : JAT. 2024", "claim": "PubMed-indexed evidence involving L-Tryptophan", "title": "Toxicology and safety study of L-tryptophan and its impurities for use in broiler feed", "authors": "Ko SM, Park JE, Lee JY et al.", "journal": "Journal of applied toxicology : JAT", "year": 2024, "pmid": "37646433", "url": "https://pubmed.ncbi.nlm.nih.gov/37646433/", "study_type": "review", "confidence": "verify", "doi": "10.1002/jat.4531", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37646433/", "publicSourceType": "PMID" }, { "text": "Park JE, Ko SM, Han HJ et al.. Toxicology and safety study of L-tryptophan and its impurities for use in swine. Journal of applied toxicology : JAT. 2024", "claim": "PubMed-indexed evidence involving L-Tryptophan", "title": "Toxicology and safety study of L-tryptophan and its impurities for use in swine", "authors": "Park JE, Ko SM, Han HJ et al.", "journal": "Journal of applied toxicology : JAT", "year": 2024, "pmid": "38594832", "url": "https://pubmed.ncbi.nlm.nih.gov/38594832/", "study_type": "review", "confidence": "verify", "doi": "10.1002/jat.4606", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38594832/", "publicSourceType": "PMID" }, { "text": "Chen X, Xu D, Yu J et al.. Tryptophan Metabolism Disorder-Triggered Diseases, Mechanisms, and Therapeutic Strategies: A Scientometric Review. Nutrients. 2024", "claim": "PubMed-indexed evidence involving L-Tryptophan", "title": "Tryptophan Metabolism Disorder-Triggered Diseases, Mechanisms, and Therapeutic Strategies: A Scientometric Review", "authors": "Chen X, Xu D, Yu J et al.", "journal": "Nutrients", "year": 2024, "pmid": "39408347", "url": "https://pubmed.ncbi.nlm.nih.gov/39408347/", "study_type": "review", "confidence": "verify", "doi": "10.3390/nu16193380", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39408347/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "l-tryptophan" }, { "id": "BEFE93E2-C484-4A4F-8C29-9C9089824B23", "name": "L-Arginine", "alternateNames": [ "Arginine" ], "category": "Amino Acid", "subcategory": "Conditionally Essential Amino Acid", "overview": "Precursor to nitric oxide, supporting blood flow and cardiovascular health.", "mechanismOfAction": "Converted to nitric oxide (NO) by nitric oxide synthase (NOS). NO relaxes vascular smooth muscle, improving blood flow. Also supports growth hormone release and wound healing.", "commonBenefits": [ "Blood flow", "Cardiovascular health", "Exercise performance", "Wound healing" ], "commonDosageRange": "3-6 g daily", "recommendedForm": "L-Arginine HCl or L-Citrulline (better bioavailability)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Empty stomach preferred for exercise; with food to reduce GI" }, "evidenceRating": "strong", "foodSources": [ "Meat", "Poultry", "Fish", "Dairy", "Nuts", "Seeds" ], "deficiencySymptoms": [ "Impaired wound healing", "Poor circulation" ], "sideEffects": [ "GI discomfort", "Bloating", "Low blood pressure" ], "contraindications": [ "Herpes simplex (may trigger outbreaks)", "Recent heart attack", "Guanidinoacetate methyltransferase deficiency" ], "iconName": "heart.circle.fill", "colorHex": "B37DFF", "tags": [ "cardiovascular", "blood-flow", "exercise" ], "sources": [ { "claim": "Umbrella review of L-arginine therapeutic benefits across meta-analyses", "title": "Therapeutic Benefits of l-Arginine: An Umbrella Review of Meta-analyses", "authors": "Bai Y et al.", "journal": "Journal of Chiropractic Medicine", "year": 2016, "pmid": "27660594", "url": "https://pubmed.ncbi.nlm.nih.gov/27660594/", "study_type": "meta-analysis", "key_finding": "Evidence supports L-arginine supplementation for reducing blood pressure in hypertensive adults and reducing hospital-acquired infections.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27660594/", "publicSourceType": "PMID" }, { "claim": "Meta-analysis of L-arginine effects on blood pressure", "title": "Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials", "authors": "Dong JY et al.", "journal": "American Heart Journal", "year": 2011, "pmid": "22137067", "url": "https://pubmed.ncbi.nlm.nih.gov/22137067/", "study_type": "meta-analysis", "key_finding": "Oral L-arginine supplementation significantly lowered systolic BP by 5.39 mmHg and diastolic BP by 2.66 mmHg compared to placebo across 11 RCTs.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22137067/", "publicSourceType": "PMID" }, { "claim": "L-arginine role in nitric oxide synthesis and cardiovascular health", "title": "Role of L-Arginine in Nitric Oxide Synthesis and Health in Humans", "authors": "Wu G et al.", "journal": "Advances in Experimental Medicine and Biology", "year": 2021, "pmid": "34251644", "url": "https://pubmed.ncbi.nlm.nih.gov/34251644/", "study_type": "review", "key_finding": "L-arginine is the substrate for nitric oxide synthase (NOS); NO production is essential for blood pressure regulation and immune function.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34251644/", "publicSourceType": "PMID" }, { "claim": "Systematic review of arginine effects on exercise performance", "title": "Effects of Arginine Supplementation on Athletic Performance Based on Energy Metabolism: A Systematic Review and Meta-Analysis", "authors": "Viribay A et al.", "journal": "Nutrients", "year": 2020, "pmid": "32370176", "url": "https://pubmed.ncbi.nlm.nih.gov/32370176/", "study_type": "meta-analysis", "key_finding": "Arginine showed positive impact on sport performance through NO-mediated mechanisms, but results were controversial and not uniformly significant.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32370176/", "publicSourceType": "PMID" }, { "claim": "Systematic review of arginine supplementation for wound healing", "title": "Effectiveness of Arginine Supplementation on Wound Healing in Older Adults in Acute and Chronic Settings: A Systematic Review", "authors": "Wong A et al.", "journal": "Journal of Wound, Ostomy, and Continence Nursing", "year": 2019, "pmid": "31498170", "url": "https://pubmed.ncbi.nlm.nih.gov/31498170/", "study_type": "review", "key_finding": "Arginine supplementation contributed to improved pressure ulcer healing in older adults, with international guidelines recommending arginine-enriched nutrition for stage 2+ pressure injuries.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31498170/", "publicSourceType": "PMID" }, { "text": "Menichini D, Feliciello L, Neri I et al.. L-Arginine supplementation in pregnancy: a systematic review of maternal and fetal outcomes. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2023", "pmid": "37258415", "doi": "10.1080/14767058.2023.2217465", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37258415/", "publicSourceType": "PMID" }, { "text": "Arribas-López E, Zand N, Ojo O et al.. The Effect of Amino Acids on Wound Healing: A Systematic Review and Meta-Analysis on Arginine and Glutamine. Nutrients. 2021", "pmid": "34444657", "doi": "10.3390/nu13082498", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34444657/", "publicSourceType": "PMID" }, { "claim": "L-arginine supplementation reduces blood pressure", "title": "Effects of L-arginine supplementation on blood pressure: a meta-analysis", "authors": "Dong JY, Qin LQ, Zhang Z et al.", "journal": "Am Heart J", "year": 2011, "pmid": "21855966", "doi": "10.1016/j.ahj.2011.04.003", "study_type": "meta-analysis", "key_finding": "SBP reduced 5.39 mmHg, DBP reduced 2.66 mmHg via nitric oxide pathway", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21855966/", "publicSourceType": "PMID" }, { "claim": "L-arginine supplementation increases maximal oxygen uptake (VO2 max) in healthy people", "title": "The effect of L-arginine supplementation on maximal oxygen uptake: A systematic review and meta-analysis", "authors": "Rezaei S, Gholamalizadeh M, Tabrizi R et al.", "journal": "Physiological Reports", "year": 2021, "pmid": "33587327", "url": "https://pubmed.ncbi.nlm.nih.gov/33587327/", "study_type": "meta-analysis", "key_finding": "In 11 RCTs, L-arginine supplementation significantly increased VO2 max compared to control. L-arginine in pure form significantly increased VO2 max (WMD 0.11 L/min, I2=0.0%). No significant heterogeneity was observed.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33587327/", "publicSourceType": "PMID" }, { "claim": "L-arginine supplementation significantly reduces triglyceride levels", "title": "The effect of l-arginine supplementation on lipid profile: a systematic review and meta-analysis of randomised controlled trials", "authors": "Hadi A, Arab A, Moradi S et al.", "journal": "British Journal of Nutrition", "year": 2019, "pmid": "31922465", "url": "https://pubmed.ncbi.nlm.nih.gov/31922465/", "study_type": "meta-analysis", "key_finding": "In 12 RCTs, L-arginine supplementation significantly reduced serum triglycerides (WMD -7.04 mg/dl, p<0.001) but did not significantly change total cholesterol, LDL, or HDL levels.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31922465/", "publicSourceType": "PMID" }, { "text": "Makama M, McDougall ARA, Cao J et al.. L-Arginine and L-Citrulline for Prevention and Treatment of Pre-Eclampsia: A Systematic Review and Meta-Analysis. BJOG : an international journal of obstetrics and gynaecology. 2025", "claim": "PubMed-indexed evidence involving L-Arginine", "title": "L-Arginine and L-Citrulline for Prevention and Treatment of Pre-Eclampsia: A Systematic Review and Meta-Analysis", "authors": "Makama M, McDougall ARA, Cao J et al.", "journal": "BJOG : an international journal of obstetrics and gynaecology", "year": 2025, "pmid": "39800868", "url": "https://pubmed.ncbi.nlm.nih.gov/39800868/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/1471-0528.18070", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39800868/", "publicSourceType": "PMID" }, { "text": "Nejati M, Dehghan P, Safari S et al.. The influence of arginine supplementation on IGF-1: A systematic review and meta-analysis. Clinical nutrition ESPEN. 2023", "claim": "PubMed-indexed evidence involving L-Arginine", "title": "The influence of arginine supplementation on IGF-1: A systematic review and meta-analysis", "authors": "Nejati M, Dehghan P, Safari S et al.", "journal": "Clinical nutrition ESPEN", "year": 2023, "pmid": "37202084", "url": "https://pubmed.ncbi.nlm.nih.gov/37202084/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.clnesp.2023.02.024", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37202084/", "publicSourceType": "PMID" }, { "text": "Tian Y, Zhou Q, Li W et al.. Efficacy of L-arginine and Pycnogenol ® in the treatment of male erectile dysfunction: a systematic review and meta-analysis. Frontiers in endocrinology. 2023", "claim": "PubMed-indexed evidence involving L-Arginine", "title": "Efficacy of L-arginine and Pycnogenol ® in the treatment of male erectile dysfunction: a systematic review and meta-analysis", "authors": "Tian Y, Zhou Q, Li W et al.", "journal": "Frontiers in endocrinology", "year": 2023, "pmid": "37908749", "url": "https://pubmed.ncbi.nlm.nih.gov/37908749/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fendo.2023.1211720", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37908749/", "publicSourceType": "PMID" }, { "text": "Cheshmeh S, Hojati N, Mohammadi A et al.. The use of oral and enteral tube-fed arginine supplementation in pressure injury care: A systematic review and meta-analysis. Nursing open. 2022", "claim": "PubMed-indexed evidence involving L-Arginine", "title": "The use of oral and enteral tube-fed arginine supplementation in pressure injury care: A systematic review and meta-analysis", "authors": "Cheshmeh S, Hojati N, Mohammadi A et al.", "journal": "Nursing open", "year": 2022, "pmid": "34170617", "url": "https://pubmed.ncbi.nlm.nih.gov/34170617/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/nop2.974", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34170617/", "publicSourceType": "PMID" }, { "text": "Stefanetti RJ, Ng YS, Errington L et al.. l-Arginine in Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes: A Systematic Review. Neurology. 2022", "claim": "PubMed-indexed evidence involving L-Arginine", "title": "l-Arginine in Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes: A Systematic Review", "authors": "Stefanetti RJ, Ng YS, Errington L et al.", "journal": "Neurology", "year": 2022, "pmid": "35428733", "url": "https://pubmed.ncbi.nlm.nih.gov/35428733/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1212/WNL.0000000000200299", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35428733/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "l-arginine" }, { "id": "9C192620-D35D-4E62-A0DD-99C38A930921", "name": "L-Citrulline", "alternateNames": [ "Citrulline" ], "category": "Amino Acid", "subcategory": "Non-Essential Amino Acid", "overview": "Converts to L-arginine in the kidneys, providing sustained nitric oxide production.", "mechanismOfAction": "Absorbed in intestines, transported to kidneys where argininosuccinate synthase converts it to argininosuccinate, then to L-arginine. More effective at raising arginine levels than arginine itself.", "commonBenefits": [ "Blood flow", "Exercise performance", "Blood pressure support", "Pump enhancement" ], "commonDosageRange": "3-6 g daily (or 6-8 g citrulline malate)", "recommendedForm": "L-Citrulline or Citrulline Malate 2:1", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "30-60 minutes before exercise on empty stomach" }, "evidenceRating": "strong", "foodSources": [ "Watermelon", "Cucumbers", "Pumpkin" ], "deficiencySymptoms": [ "Not essential, no deficiency" ], "sideEffects": [ "Very well tolerated", "Mild GI at high doses" ], "contraindications": [ "Blood pressure medications (additive effect)" ], "iconName": "figure.run.circle.fill", "colorHex": "B37DFF", "tags": [ "exercise", "blood-flow", "pump" ], "sources": [ { "claim": "Meta-analysis of L-citrulline effects on blood pressure", "title": "Effects of L-citrulline supplementation on blood pressure: A systematic review and meta-analysis", "authors": "Mahboobi S et al.", "journal": "Journal of Human Hypertension", "year": 2019, "pmid": "30788274", "url": "https://pubmed.ncbi.nlm.nih.gov/30788274/", "study_type": "meta-analysis", "key_finding": "Oral L-citrulline supplementation reduced systolic BP by 7.54 mmHg and diastolic BP by 3.77 mmHg, with significant improvements at doses up to 4 g/day and durations of 6+ weeks.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30788274/", "publicSourceType": "PMID" }, { "claim": "Systematic review of citrulline supplementation on exercise performance", "title": "Effects of Citrulline Supplementation on Exercise Performance in Humans: A Review of the Current Literature", "authors": "Gonzalez AM et al.", "journal": "Journal of Strength and Conditioning Research", "year": 2020, "pmid": "31977835", "url": "https://pubmed.ncbi.nlm.nih.gov/31977835/", "study_type": "review", "key_finding": "L-citrulline supplementation, particularly chronic use, improves exercise performance in young healthy adults via enhanced NO production.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31977835/", "publicSourceType": "PMID" }, { "claim": "Citrulline malate increases repetition performance during resistance exercise", "title": "Acute Effect of Citrulline Malate on Repetition Performance During Strength Training: A Systematic Review and Meta-Analysis", "authors": "Vårvik FT et al.", "journal": "Journal of Strength and Conditioning Research", "year": 2021, "pmid": "34010809", "url": "https://pubmed.ncbi.nlm.nih.gov/34010809/", "study_type": "meta-analysis", "key_finding": "Supplementing with 6-8 g citrulline malate 40-60 minutes before exercise increased repetitions by approximately 6.4% compared to placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34010809/", "publicSourceType": "PMID" }, { "claim": "Citrulline is superior to arginine for raising plasma arginine and NO bioavailability", "title": "Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism", "authors": "Schwedhelm E et al.", "journal": "British Journal of Clinical Pharmacology", "year": 2008, "pmid": "17662090", "url": "https://pubmed.ncbi.nlm.nih.gov/17662090/", "study_type": "RCT", "key_finding": "L-citrulline dose-dependently increases plasma L-arginine more effectively than arginine itself due to bypassing hepatic first-pass metabolism.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17662090/", "publicSourceType": "PMID" }, { "claim": "Citrulline preferred over arginine for endogenous NO flux", "title": "Endogenous flux of nitric oxide: Citrulline is preferred to Arginine", "authors": "Allerton TD et al.", "journal": "Journal of Dietary Supplements", "year": 2020, "pmid": "33089645", "url": "https://pubmed.ncbi.nlm.nih.gov/33089645/", "study_type": "review", "key_finding": "Citrulline has greater availability as a NO precursor than arginine due to high intestinal absorption, low first-pass metabolism, and high renal reabsorption.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33089645/", "publicSourceType": "PMID" }, { "claim": "Meta-analysis of citrulline effects on aerobic exercise performance", "title": "Effects of Citrulline Supplementation on Different Aerobic Exercise Performance Outcomes: A Systematic Review and Meta-Analysis", "authors": "Figueroa A et al.", "journal": "British Journal of Nutrition", "year": 2022, "pmid": "36079738", "url": "https://pubmed.ncbi.nlm.nih.gov/36079738/", "study_type": "meta-analysis", "key_finding": "Citrulline supplementation positively impacts aerobic exercise performance and related outcomes including lactate, oxygen uptake, and rate of perceived exertion.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36079738/", "publicSourceType": "PMID" }, { "text": "Gough LA, Sparks SA, McNaughton LR et al.. A critical review of citrulline malate supplementation and exercise performance. European journal of applied physiology. 2021", "pmid": "34417881", "doi": "10.1007/s00421-021-04774-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34417881/", "publicSourceType": "PMID" }, { "text": "d'Unienville NMA, Blake HT, Coates AM et al.. Effect of food sources of nitrate, polyphenols, L-arginine and L-citrulline on endurance exercise performance: a systematic review and meta-analysis of randomised controlled trials. Journal of the International Society of Sports Nutrition. 2021", "pmid": "34965876", "doi": "10.1186/s12970-021-00472-y", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34965876/", "publicSourceType": "PMID" }, { "claim": "L-citrulline (as L-arginine precursor) may have potential for pre-eclampsia prevention but evidence is limited", "title": "L-Arginine and L-Citrulline for Prevention and Treatment of Pre-Eclampsia: A Systematic Review and Meta-Analysis", "authors": "Makama M, McDougall ARA, Cao J et al.", "journal": "BJOG", "year": 2025, "pmid": "39800868", "url": "https://pubmed.ncbi.nlm.nih.gov/39800868/", "study_type": "meta-analysis", "key_finding": "In 20 RCTs (2,028 women), L-arginine reduced risk of pre-eclampsia (RR 0.52, 95% CI 0.35-0.78). Only one study examined L-citrulline and reported no effect on pre-eclampsia or blood pressure. L-arginine may be promising but more trials needed.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39800868/", "publicSourceType": "PMID" }, { "text": "Ashtary-Larky D, Mohammadi S, Mousavi SAH et al.. Effects of Citrulline or Watermelon Supplementation on Body Composition: A Systematic Review and Dose-Response Meta-Analysis. Nutrients. 2025", "claim": "PubMed-indexed evidence involving L-Citrulline", "title": "Effects of Citrulline or Watermelon Supplementation on Body Composition: A Systematic Review and Dose-Response Meta-Analysis", "authors": "Ashtary-Larky D, Mohammadi S, Mousavi SAH et al.", "journal": "Nutrients", "year": 2025, "pmid": "41097202", "url": "https://pubmed.ncbi.nlm.nih.gov/41097202/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu17193126", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41097202/", "publicSourceType": "PMID" }, { "text": "Harnden CS, Agu J, Gascoyne T. Effects of citrulline on endurance performance in young healthy adults: a systematic review and meta-analysis. Journal of the International Society of Sports Nutrition. 2023", "claim": "PubMed-indexed evidence involving L-Citrulline", "title": "Effects of citrulline on endurance performance in young healthy adults: a systematic review and meta-analysis", "authors": "Harnden CS, Agu J, Gascoyne T", "journal": "Journal of the International Society of Sports Nutrition", "year": 2023, "pmid": "37155582", "url": "https://pubmed.ncbi.nlm.nih.gov/37155582/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/15502783.2023.2209056", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37155582/", "publicSourceType": "PMID" }, { "text": "Mirenayat MS, Moradi S, Mohammadi H et al.. Effect of L-Citrulline Supplementation on Blood Pressure: a Systematic Review and Meta-Analysis of Clinical Trials. Current hypertension reports. 2018", "claim": "PubMed-indexed evidence involving L-Citrulline", "title": "Effect of L-Citrulline Supplementation on Blood Pressure: a Systematic Review and Meta-Analysis of Clinical Trials", "authors": "Mirenayat MS, Moradi S, Mohammadi H et al.", "journal": "Current hypertension reports", "year": 2018, "pmid": "30284051", "url": "https://pubmed.ncbi.nlm.nih.gov/30284051/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s11906-018-0898-3", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30284051/", "publicSourceType": "PMID" }, { "text": "Fan M, Gao X, Li L et al.. The Association Between Concentrations of Arginine, Ornithine, Citrulline and Major Depressive Disorder: A Meta-Analysis. Frontiers in psychiatry. 2021", "claim": "PubMed-indexed evidence involving L-Citrulline", "title": "The Association Between Concentrations of Arginine, Ornithine, Citrulline and Major Depressive Disorder: A Meta-Analysis", "authors": "Fan M, Gao X, Li L et al.", "journal": "Frontiers in psychiatry", "year": 2021, "pmid": "34867503", "url": "https://pubmed.ncbi.nlm.nih.gov/34867503/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fpsyt.2021.686973", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34867503/", "publicSourceType": "PMID" }, { "text": "Winer N, Misbert E, Masson D et al.. Oral citrulline supplementation in pregnancies with preeclampsia: a multicenter, randomized, double-blind clinical trial. The American journal of clinical nutrition. 2025", "claim": "PubMed-indexed evidence involving L-Citrulline", "title": "Oral citrulline supplementation in pregnancies with preeclampsia: a multicenter, randomized, double-blind clinical trial", "authors": "Winer N, Misbert E, Masson D et al.", "journal": "The American journal of clinical nutrition", "year": 2025, "pmid": "39638148", "url": "https://pubmed.ncbi.nlm.nih.gov/39638148/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.ajcnut.2024.12.001", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39638148/", "publicSourceType": "PMID" }, { "text": "Rodríguez-Carrillo AA, Espinoza-Vargas MR, Vargas-Ortiz K et al.. Impact of L-Citrulline Supplementation and HIIT on Lipid Profile, Arterial Stiffness, and Fat Mass in Obese Adolescents with Metabolic-Dysfunction-Associated Fatty Liver Disease: A Randomized Clinical Trial. Nutrients. 2025", "claim": "PubMed-indexed evidence involving L-Citrulline", "title": "Impact of L-Citrulline Supplementation and HIIT on Lipid Profile, Arterial Stiffness, and Fat Mass in Obese Adolescents with Metabolic-Dysfunction-Associated Fatty Liver Disease: A Randomized Clinical Trial", "authors": "Rodríguez-Carrillo AA, Espinoza-Vargas MR, Vargas-Ortiz K et al.", "journal": "Nutrients", "year": 2025, "pmid": "39940261", "url": "https://pubmed.ncbi.nlm.nih.gov/39940261/", "study_type": "RCT", "confidence": "verify", "doi": "10.3390/nu17030402", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39940261/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "l-citrulline" }, { "id": "2096E570-7B8C-4160-9172-06FC9E7FC3B0", "name": "Beta-Alanine", "alternateNames": [ "β-Alanine" ], "category": "Amino Acid", "subcategory": "Non-Proteinogenic Amino Acid", "overview": "Precursor to carnosine, buffering muscle acidity during high-intensity exercise.", "mechanismOfAction": "Combines with histidine in muscle to form carnosine. Carnosine buffers H+ ions during intense exercise, delaying muscle fatigue and the burning sensation.", "commonBenefits": [ "Exercise endurance", "Muscle buffering", "Performance" ], "commonDosageRange": "3.2-6.4 g daily (split doses)", "recommendedForm": "Beta-Alanine powder (sustained-release to reduce tingling)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Split throughout day to minimize paresthesia" }, "evidenceRating": "strong", "foodSources": [ "Meat", "Poultry", "Fish" ], "deficiencySymptoms": [ "Not essential" ], "sideEffects": [ "Paresthesia (tingling, harmless)", "Flushing" ], "contraindications": [ "Generally very safe" ], "iconName": "bolt.fill", "colorHex": "B37DFF", "tags": [ "exercise", "endurance", "performance" ], "sources": [ { "claim": "Meta-analysis of beta-alanine effects on exercise capacity and performance", "title": "Beta-alanine supplementation to improve exercise capacity and performance: a systematic review and meta-analysis", "authors": "Saunders B et al.", "journal": "British Journal of Sports Medicine", "year": 2017, "pmid": "27797728", "url": "https://pubmed.ncbi.nlm.nih.gov/27797728/", "study_type": "meta-analysis", "key_finding": "Beta-alanine improved exercise capacity (ES 0.18) across 40 studies with 1,461 participants; greatest effect for exercise lasting 0.5-10 minutes.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27797728/", "publicSourceType": "PMID" }, { "claim": "ISSN position stand on beta-alanine dosage and efficacy", "title": "International society of sports nutrition position stand: Beta-Alanine", "authors": "Trexler ET et al.", "journal": "Journal of the International Society of Sports Nutrition", "year": 2015, "pmid": "26175657", "url": "https://pubmed.ncbi.nlm.nih.gov/26175657/", "study_type": "review", "key_finding": "Daily supplementation with 4-6 g beta-alanine for 2-4+ weeks improves exercise performance, especially in open-endpoint tasks lasting 1-4 minutes; only reported side effect is transient paresthesia.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26175657/", "publicSourceType": "PMID" }, { "claim": "Systematic risk assessment and meta-analysis confirming safety", "title": "A Systematic Risk Assessment and Meta-Analysis on the Use of Oral Beta-Alanine Supplementation", "authors": "Dolan E et al.", "journal": "Advances in Nutrition", "year": 2019, "pmid": "30980076", "url": "https://pubmed.ncbi.nlm.nih.gov/30980076/", "study_type": "meta-analysis", "key_finding": "Beta-alanine supplementation at recommended doses does not adversely affect health; no evidence of serious safety concerns in healthy populations.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30980076/", "publicSourceType": "PMID" }, { "claim": "Muscle carnosine response to beta-alanine supplementation", "title": "The Muscle Carnosine Response to Beta-Alanine Supplementation: A Systematic Review With Bayesian Individual and Aggregate Data E-Max Model and Meta-Analysis", "authors": "Rezende NS et al.", "journal": "Frontiers in Physiology", "year": 2020, "pmid": "32922303", "url": "https://pubmed.ncbi.nlm.nih.gov/32922303/", "study_type": "meta-analysis", "key_finding": "Four weeks of beta-alanine supplementation (4-6 g daily) significantly augments muscle carnosine concentrations, which serves as a major H+ buffer during high-intensity exercise.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32922303/", "publicSourceType": "PMID" }, { "claim": "Sustained-release formulation reduces paresthesia", "title": "Effect of slow-release beta-alanine tablets on absorption kinetics and paresthesia", "authors": "Decombaz J et al.", "journal": "Amino Acids", "year": 2012, "pmid": "22139410", "url": "https://pubmed.ncbi.nlm.nih.gov/22139410/", "study_type": "RCT", "key_finding": "Sustained-release formulation attenuated paresthesia while maintaining similar total beta-alanine absorption; oral doses >800 mg commonly cause transient tingling.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22139410/", "publicSourceType": "PMID" }, { "text": "Georgiou GD, Antoniou K, Antoniou S et al.. Effect of Beta-Alanine Supplementation on Maximal Intensity Exercise in Trained Young Male Individuals: A Systematic Review and Meta-Analysis. International journal of sport nutrition and exercise metabolism. 2024", "pmid": "39032921", "doi": "10.1123/ijsnem.2024-0027", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39032921/", "publicSourceType": "PMID" }, { "text": "Hobson RM, Saunders B, Ball G et al.. Effects of β-alanine supplementation on exercise performance: a meta-analysis. Amino acids. 2012", "pmid": "22270875", "doi": "10.1007/s00726-011-1200-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22270875/", "publicSourceType": "PMID" }, { "claim": "Beta-alanine supplementation does not improve body composition regardless of dosage or exercise training combination", "title": "Effects of beta-alanine supplementation on body composition: a GRADE-assessed systematic review and meta-analysis", "authors": "Ashtary-Larky D, Bagheri R, Ghanavati M et al.", "journal": "Journal of the International Society of Sports Nutrition", "year": 2022, "pmid": "35813845", "url": "https://pubmed.ncbi.nlm.nih.gov/35813845/", "study_type": "meta-analysis", "key_finding": "In 20 studies with 492 participants, beta-alanine had no effect on body mass, fat mass, body fat percentage, or fat-free mass. Subgroup analyses by exercise type, duration, and dosage showed similar null results. Evidence certainty was low to moderate.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35813845/", "publicSourceType": "PMID" }, { "claim": "Beta-alanine may improve aerobic performance in female athletes alongside caffeine and taurine", "title": "Ergogenic Aids to Improve Physical Performance in Female Athletes: A Systematic Review with Meta-Analysis", "authors": "López-Torres O, Rodríguez-Longobardo C, Capel-Escoriza R, Fernández-Elías VE", "journal": "Nutrients", "year": 2022, "pmid": "36615738", "url": "https://pubmed.ncbi.nlm.nih.gov/36615738/", "study_type": "meta-analysis", "key_finding": "Systematic review of female athletes found that taurine, caffeine, and beta-alanine could improve aerobic tests. Studies on beta-alanine in female athletes are scarce. More research is needed on various ergogenic aids in this population.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36615738/", "publicSourceType": "PMID" }, { "text": "Ashtary-Larky D, Candow DG, Forbes SC et al.. Effects of Creatine and β-Alanine Co-Supplementation on Exercise Performance and Body Composition: A Systematic Review. Nutrients. 2025", "claim": "PubMed-indexed evidence involving Beta-Alanine", "title": "Effects of Creatine and β-Alanine Co-Supplementation on Exercise Performance and Body Composition: A Systematic Review", "authors": "Ashtary-Larky D, Candow DG, Forbes SC et al.", "journal": "Nutrients", "year": 2025, "pmid": "40647180", "url": "https://pubmed.ncbi.nlm.nih.gov/40647180/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu17132074", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40647180/", "publicSourceType": "PMID" }, { "text": "Ong SW, Chen WL, Chien KY et al.. Dosing strategies for β-alanine supplementation in strength and power performance: a systematic review. Journal of the International Society of Sports Nutrition. 2025", "claim": "PubMed-indexed evidence involving Beta-Alanine", "title": "Dosing strategies for β-alanine supplementation in strength and power performance: a systematic review", "authors": "Ong SW, Chen WL, Chien KY et al.", "journal": "Journal of the International Society of Sports Nutrition", "year": 2025, "pmid": "40995761", "url": "https://pubmed.ncbi.nlm.nih.gov/40995761/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/15502783.2025.2566368", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40995761/", "publicSourceType": "PMID" }, { "text": "Curran-Bowen T, Guedes da Silva A, Barreto G et al.. Sodium bicarbonate and beta-alanine supplementation: Is combining both better than either alone? A systematic review and meta-analysis. Biology of sport. 2024", "claim": "PubMed-indexed evidence involving Beta-Alanine", "title": "Sodium bicarbonate and beta-alanine supplementation: Is combining both better than either alone? A systematic review and meta-analysis", "authors": "Curran-Bowen T, Guedes da Silva A, Barreto G et al.", "journal": "Biology of sport", "year": 2024, "pmid": "38952910", "url": "https://pubmed.ncbi.nlm.nih.gov/38952910/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.5114/biolsport.2024.132997", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38952910/", "publicSourceType": "PMID" }, { "text": "Huerta Ojeda Á, Tapia Cerda C, Poblete Salvatierra MF et al.. Effects of Beta-Alanine Supplementation on Physical Performance in Aerobic-Anaerobic Transition Zones: A Systematic Review and Meta-Analysis. Nutrients. 2020", "claim": "PubMed-indexed evidence involving Beta-Alanine", "title": "Effects of Beta-Alanine Supplementation on Physical Performance in Aerobic-Anaerobic Transition Zones: A Systematic Review and Meta-Analysis", "authors": "Huerta Ojeda Á, Tapia Cerda C, Poblete Salvatierra MF et al.", "journal": "Nutrients", "year": 2020, "pmid": "32824885", "url": "https://pubmed.ncbi.nlm.nih.gov/32824885/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu12092490", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32824885/", "publicSourceType": "PMID" }, { "text": "Quesnele JJ, Laframboise MA, Wong JJ et al.. The effects of beta-alanine supplementation on performance: a systematic review of the literature. International journal of sport nutrition and exercise metabolism. 2014", "claim": "PubMed-indexed evidence involving Beta-Alanine", "title": "The effects of beta-alanine supplementation on performance: a systematic review of the literature", "authors": "Quesnele JJ, Laframboise MA, Wong JJ et al.", "journal": "International journal of sport nutrition and exercise metabolism", "year": 2014, "pmid": "23918656", "url": "https://pubmed.ncbi.nlm.nih.gov/23918656/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1123/ijsnem.2013-0007", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23918656/", "publicSourceType": "PMID" }, { "text": "Grgic J. Effects of beta-alanine supplementation on Yo-Yo test performance: A meta-analysis. Clinical nutrition ESPEN. 2021", "claim": "PubMed-indexed evidence involving Beta-Alanine", "title": "Effects of beta-alanine supplementation on Yo-Yo test performance: A meta-analysis", "authors": "Grgic J", "journal": "Clinical nutrition ESPEN", "year": 2021, "pmid": "34024507", "url": "https://pubmed.ncbi.nlm.nih.gov/34024507/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.clnesp.2021.03.027", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34024507/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "beta-alanine" }, { "id": "CCA01E2A-76CF-4156-B92A-350AC71F733C", "name": "BCAAs", "alternateNames": [ "Branched-Chain Amino Acids", "Leucine, Isoleucine, Valine" ], "category": "Amino Acid", "subcategory": "Essential Amino Acids", "overview": "Three essential amino acids (leucine, isoleucine, valine) that stimulate muscle protein synthesis.", "mechanismOfAction": "Leucine activates mTOR signaling, the master regulator of muscle protein synthesis. BCAAs are oxidized directly in skeletal muscle, providing energy during exercise.", "commonBenefits": [ "Muscle growth", "Exercise recovery", "Reduce soreness" ], "commonDosageRange": "5-10 g peri-workout", "recommendedForm": "2:1:1 ratio (Leucine:Isoleucine:Valine)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Before/during/after exercise" }, "evidenceRating": "moderate", "foodSources": [ "Meat", "Dairy", "Eggs", "Whey protein" ], "deficiencySymptoms": [ "Muscle wasting in deficiency" ], "sideEffects": [ "Well tolerated", "May affect blood sugar" ], "contraindications": [ "Maple syrup urine disease", "ALS" ], "iconName": "dumbbell.fill", "colorHex": "B37DFF", "tags": [ "muscle", "recovery", "exercise" ], "sources": [ { "claim": "Overview of systematic reviews on BCAA post-exercise recovery", "title": "Branched-Chain Amino Acids Supplementation and Post-Exercise Recovery: An Overview of Systematic Reviews", "authors": "Holeček M et al.", "journal": "Nutrients", "year": 2024, "pmid": "38241335", "url": "https://pubmed.ncbi.nlm.nih.gov/38241335/", "study_type": "review", "key_finding": "BCAA use is better than passive recovery after exhaustive exercise, with advantages in reducing muscle soreness and ameliorating muscle function and strength/power loss.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38241335/", "publicSourceType": "PMID" }, { "claim": "Meta-analysis of BCAAs for exercise-induced muscle damage and recovery", "title": "Branched-chain amino acid supplementation and exercise-induced muscle damage in exercise recovery: A meta-analysis of randomized clinical trials", "authors": "Rahimi MH et al.", "journal": "Nutrition", "year": 2017, "pmid": "28870476", "url": "https://pubmed.ncbi.nlm.nih.gov/28870476/", "study_type": "meta-analysis", "key_finding": "BCAA supplementation reduced CK levels and muscle soreness with medium to large effect sizes post-exercise.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28870476/", "publicSourceType": "PMID" }, { "claim": "Meta-analysis of BCAAs for reducing DOMS at 24-96 hours", "title": "The use of BCAA to decrease delayed-onset muscle soreness after a single bout of exercise: a systematic review and meta-analysis", "authors": "Weber MG et al.", "journal": "Amino Acids", "year": 2021, "pmid": "34669012", "url": "https://pubmed.ncbi.nlm.nih.gov/34669012/", "study_type": "meta-analysis", "key_finding": "BCAA supplementation significantly reduced DOMS at 24, 48, 72, and 96 hours post-exercise; doses up to 255 mg/kg/day were most effective.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34669012/", "publicSourceType": "PMID" }, { "claim": "BCAAs activate mTOR and key enzymes in protein synthesis", "title": "Branched-chain amino acids activate key enzymes in protein synthesis after physical exercise", "authors": "Karlsson HK et al.", "journal": "Journal of Nutrition", "year": 2004, "pmid": "16365096", "url": "https://pubmed.ncbi.nlm.nih.gov/16365096/", "study_type": "RCT", "key_finding": "BCAAs activate mTOR and p70 S6 kinase in human muscle during recovery after exercise, demonstrating molecular signaling for protein synthesis.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16365096/", "publicSourceType": "PMID" }, { "claim": "Leucine activates mTORC1 signaling potentiated by BCAAs and EAAs", "title": "Activation of mTORC1 by leucine is potentiated by branched-chain amino acids and even more so by essential amino acids following resistance exercise", "authors": "Moberg M et al.", "journal": "American Journal of Physiology", "year": 2016, "pmid": "27053525", "url": "https://pubmed.ncbi.nlm.nih.gov/27053525/", "study_type": "RCT", "key_finding": "Leucine activates mTORC1 signaling, the master regulator of muscle protein synthesis; this effect is potentiated by the full complement of BCAAs.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27053525/", "publicSourceType": "PMID" }, { "claim": "Critical perspective: BCAAs alone may not stimulate maximal MPS", "title": "Branched-chain amino acids and muscle protein synthesis in humans: myth or reality?", "authors": "Wolfe RR", "journal": "Journal of the International Society of Sports Nutrition", "year": 2017, "pmid": "28852372", "url": "https://pubmed.ncbi.nlm.nih.gov/28852372/", "study_type": "review", "key_finding": "The claim that dietary BCAAs alone stimulate muscle protein synthesis is unwarranted; a complete protein source providing all essential amino acids produces a greater anabolic response.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28852372/", "publicSourceType": "PMID" }, { "text": "Martinho DV, Nobari H, Faria A et al.. Oral Branched-Chain Amino Acids Supplementation in Athletes: A Systematic Review. Nutrients. 2022", "pmid": "36235655", "doi": "10.3390/nu14194002", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36235655/", "publicSourceType": "PMID" }, { "text": "Jian H, Li R, Huang X et al.. Branched-chain amino acids alleviate NAFLD via inhibiting de novo lipogenesis and activating fatty acid β-oxidation in laying hens. Redox biology. 2024", "pmid": "39426289", "doi": "10.1016/j.redox.2024.103385", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39426289/", "publicSourceType": "PMID" }, { "claim": "BCAA supplementation reduces muscle damage markers (CK) and delayed onset muscle soreness after exercise-induced muscle damage", "title": "Attenuating Muscle Damage Biomarkers and Muscle Soreness After an Exercise-Induced Muscle Damage with Branched-Chain Amino Acid (BCAA) Supplementation: A Systematic Review and Meta-analysis with Meta-regression", "authors": "Salem A, Ben Maaoui K, Jahrami H et al.", "journal": "Sports Medicine - Open", "year": 2024, "pmid": "38625669", "url": "https://pubmed.ncbi.nlm.nih.gov/38625669/", "study_type": "meta-analysis", "key_finding": "In 18 studies, BCAA supplementation reduced CK levels at immediately and 72h post-EIMD, and significantly reduced DOMS at 24h (g=-1.34), 48h (g=-1.75), 72h (g=-1.82), and 96h (g=-0.82). Longer supplementation periods were more effective.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38625669/", "publicSourceType": "PMID" }, { "claim": "BCAA supplementation may improve event-free survival in cirrhotic patients", "title": "Systematic review with meta-analysis: Branched-chain amino acid supplementation in liver disease", "authors": "van Dijk AM, Bruins Slot AS, Portincasa P et al.", "journal": "European Journal of Clinical Investigation", "year": 2023, "pmid": "36394355", "url": "https://pubmed.ncbi.nlm.nih.gov/36394355/", "study_type": "meta-analysis", "key_finding": "In 54 studies (5,184 patients), long-term BCAA supplementation in cirrhotic patients significantly improved event-free survival (RR 0.61, p=0.008) and tended to improve overall survival. No serious side effects were reported.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36394355/", "publicSourceType": "PMID" }, { "claim": "BCAA-rich supplementation may have beneficial effects on muscle mass and strength in older adults", "title": "Effects of branched-chain amino acid-rich supplementation on EWGSOP2 criteria for sarcopenia in older adults: a systematic review and meta-analysis", "authors": "Bai GH, Tsai MC, Tsai HW, Chang CC, Hou WH", "journal": "European Journal of Nutrition", "year": 2022, "pmid": "34705076", "url": "https://pubmed.ncbi.nlm.nih.gov/34705076/", "study_type": "meta-analysis", "key_finding": "In 35 studies, BCAA-rich supplements improved muscle strength (SMD 0.35, P=0.0007), muscle mass (SMD 0.25, P=0.0008), and physical performance (SMD 0.29, P=0.05). Essential amino acids improved handgrip strength more than whey protein.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34705076/", "publicSourceType": "PMID" }, { "text": "Khemtong C, Kuo CH, Chen CY et al.. Does Branched-Chain Amino Acids (BCAAs) Supplementation Attenuate Muscle Damage Markers and Soreness after Resistance Exercise in Trained Males? A Meta-Analysis of Randomized Controlled Trials. Nutrients. 2021", "claim": "PubMed-indexed evidence involving BCAAs", "title": "Does Branched-Chain Amino Acids (BCAAs) Supplementation Attenuate Muscle Damage Markers and Soreness after Resistance Exercise in Trained Males? A Meta-Analysis of Randomized Controlled Trials", "authors": "Khemtong C, Kuo CH, Chen CY et al.", "journal": "Nutrients", "year": 2021, "pmid": "34072718", "url": "https://pubmed.ncbi.nlm.nih.gov/34072718/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu13061880", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34072718/", "publicSourceType": "PMID" }, { "text": "Sharma B, Lawrence DW, Hutchison MG. Branched Chain Amino Acids (BCAAs) and Traumatic Brain Injury: A Systematic Review. The Journal of head trauma rehabilitation. 2018", "claim": "PubMed-indexed evidence involving BCAAs", "title": "Branched Chain Amino Acids (BCAAs) and Traumatic Brain Injury: A Systematic Review", "authors": "Sharma B, Lawrence DW, Hutchison MG", "journal": "The Journal of head trauma rehabilitation", "year": 2018, "pmid": "28060208", "url": "https://pubmed.ncbi.nlm.nih.gov/28060208/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/HTR.0000000000000280", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28060208/", "publicSourceType": "PMID" }, { "text": "Metcalfe EL, Avenell A, Fraser A. Branched-chain amino acid supplementation in adults with cirrhosis and porto-systemic encephalopathy: systematic review. Clinical nutrition (Edinburgh, Scotland). 2014", "claim": "PubMed-indexed evidence involving BCAAs", "title": "Branched-chain amino acid supplementation in adults with cirrhosis and porto-systemic encephalopathy: systematic review", "authors": "Metcalfe EL, Avenell A, Fraser A", "journal": "Clinical nutrition (Edinburgh, Scotland)", "year": 2014, "pmid": "24656171", "url": "https://pubmed.ncbi.nlm.nih.gov/24656171/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.clnu.2014.02.011", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24656171/", "publicSourceType": "PMID" }, { "text": "Fedewa MV, Spencer SO, Williams TD et al.. Effect of branched-Chain Amino Acid Supplementation on Muscle Soreness following Exercise: A Meta-Analysis. International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition. 2019", "claim": "PubMed-indexed evidence involving BCAAs", "title": "Effect of branched-Chain Amino Acid Supplementation on Muscle Soreness following Exercise: A Meta-Analysis", "authors": "Fedewa MV, Spencer SO, Williams TD et al.", "journal": "International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition", "year": 2019, "pmid": "30938579", "url": "https://pubmed.ncbi.nlm.nih.gov/30938579/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1024/0300-9831/a000543", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30938579/", "publicSourceType": "PMID" }, { "text": "Román E, Kaür N, Sánchez E et al.. Home exercise, branched-chain amino acids, and probiotics improve frailty in cirrhosis: A randomized clinical trial. Hepatology communications. 2024", "claim": "PubMed-indexed evidence involving BCAAs", "title": "Home exercise, branched-chain amino acids, and probiotics improve frailty in cirrhosis: A randomized clinical trial", "authors": "Román E, Kaür N, Sánchez E et al.", "journal": "Hepatology communications", "year": 2024, "pmid": "38701490", "url": "https://pubmed.ncbi.nlm.nih.gov/38701490/", "study_type": "RCT", "confidence": "verify", "doi": "10.1097/HC9.0000000000000443", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38701490/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "bcaas" }, { "id": "BC824084-9565-4DC2-8E10-2E7E7DA7017F", "name": "HMB", "alternateNames": [ "Beta-Hydroxy Beta-Methylbutyrate" ], "category": "Amino Acid", "subcategory": "Leucine Metabolite", "overview": "Metabolite of leucine that reduces muscle protein breakdown.", "mechanismOfAction": "Inhibits the ubiquitin-proteasome pathway responsible for muscle protein degradation. Also stimulates mTOR pathway and enhances muscle protein synthesis.", "commonBenefits": [ "Muscle preservation", "Recovery", "Strength" ], "commonDosageRange": "3 g daily (split into 3 doses)", "recommendedForm": "Calcium HMB or free acid HMB", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Split doses with meals; free acid form 30 min before exercise" }, "evidenceRating": "moderate", "foodSources": [ "Small amounts in citrus fruits", "Catfish" ], "deficiencySymptoms": [ "Not essential" ], "sideEffects": [ "Well tolerated", "Mild GI at high doses" ], "contraindications": [ "Generally very safe" ], "iconName": "figure.strengthtraining.traditional", "colorHex": "B37DFF", "tags": [ "muscle", "recovery", "anti-catabolic" ], "sources": [ { "claim": "Meta-analysis of HMB for muscle preservation in older adults", "title": "Effect of beta-hydroxy-beta-methylbutyrate supplementation on muscle loss in older adults: a systematic review and meta-analysis", "authors": "Wu H et al.", "journal": "Archives of Gerontology and Geriatrics", "year": 2015, "pmid": "26169182", "url": "https://pubmed.ncbi.nlm.nih.gov/26169182/", "study_type": "meta-analysis", "key_finding": "Seven RCTs with 287 older adults showed HMB supplementation contributed to greater muscle mass preservation compared to controls.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26169182/", "publicSourceType": "PMID" }, { "claim": "Systematic review of HMB mechanism: ubiquitin-proteasome inhibition and mTOR activation", "title": "Mechanism of Action and the Effect of Beta-Hydroxy-Beta-Methylbutyrate (HMB) Supplementation on Different Types of Physical Performance - A Systematic Review", "authors": "Teixeira FJ et al.", "journal": "Journal of Strength and Conditioning Research", "year": 2019, "pmid": "31531146", "url": "https://pubmed.ncbi.nlm.nih.gov/31531146/", "study_type": "review", "key_finding": "HMB inhibits ubiquitin-proteasome protein degradation, decreases cell apoptosis, stimulates mTOR-mediated protein synthesis, and enhances GH/IGF-1 axis and muscle stem cell proliferation.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31531146/", "publicSourceType": "PMID" }, { "claim": "HMB attenuates proteolysis-inducing factor-stimulated muscle protein degradation", "title": "Mechanism of the attenuation of proteolysis-inducing factor stimulated protein degradation in muscle by beta-hydroxy-beta-methylbutyrate", "authors": "Smith HJ et al.", "journal": "Cancer Research", "year": 2004, "pmid": "15574784", "url": "https://pubmed.ncbi.nlm.nih.gov/15574784/", "study_type": "RCT", "key_finding": "At 50 micromol/L concentration, HMB completely attenuated PIF-induced protein degradation and induction of the ubiquitin-proteasome proteolytic pathway.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15574784/", "publicSourceType": "PMID" }, { "claim": "Meta-analysis of HMB on skeletal muscle mass and physical function", "title": "Beta-Hydroxy-beta-methylbutyrate and its impact on skeletal muscle mass and physical function in clinical practice: a systematic review and meta-analysis", "authors": "Bear DE et al.", "journal": "American Journal of Clinical Nutrition", "year": 2019, "pmid": "30982854", "url": "https://pubmed.ncbi.nlm.nih.gov/30982854/", "study_type": "meta-analysis", "key_finding": "15 RCTs with 2,137 patients showed some evidence supporting HMB for increasing skeletal muscle mass and strong evidence for improving muscle strength.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30982854/", "publicSourceType": "PMID" }, { "claim": "Meta-analysis of HMB for strength and body composition during resistance training", "title": "Effects of beta-hydroxy-beta-methylbutyrate supplementation during resistance training on strength, body composition, and muscle damage in trained and untrained young men: a meta-analysis", "authors": "Rowlands DS et al.", "journal": "Journal of Strength and Conditioning Research", "year": 2009, "pmid": "19387395", "url": "https://pubmed.ncbi.nlm.nih.gov/19387395/", "study_type": "meta-analysis", "key_finding": "HMB is effective in preventing exercise-related muscle damage in both trained and untrained individuals during resistance training.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19387395/", "publicSourceType": "PMID" }, { "text": "Prado CM, Orsso CE, Pereira SL et al.. Effects of β-hydroxy β-methylbutyrate (HMB) supplementation on muscle mass, function, and other outcomes in patients with cancer: a systematic review. Journal of cachexia, sarcopenia and muscle. 2022", "pmid": "35301826", "doi": "10.1002/jcsm.12952", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35301826/", "publicSourceType": "PMID" }, { "claim": "HMB supplementation improves muscle mass and strength but not physical performance in patients with sarcopenia", "title": "The effects of β-hydroxy-β-methylbutyrate supplementation in patients with sarcopenia: A systematic review and meta-analysis", "authors": "Gu WT, Zhang LW, Wu FH, Wang S", "journal": "Maturitas", "year": 2025, "pmid": "39999663", "url": "https://pubmed.ncbi.nlm.nih.gov/39999663/", "study_type": "meta-analysis", "key_finding": "In 5 RCTs, HMB supplementation showed beneficial effect on skeletal muscle mass index (SMD 0.32, P=0.048) and handgrip strength (SMD 0.65, P=0.034), but no evidence of benefit on physical performance measured by gait speed.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39999663/", "publicSourceType": "PMID" }, { "claim": "HMB supplementation aids in increasing muscle strength in the elderly population", "title": "Effect of β-hydroxy-β-methylbutyrate (HMB) on the Muscle Strength in the Elderly Population: A Meta-Analysis", "authors": "Lin Z, Zhao A, He J", "journal": "Frontiers in Nutrition", "year": 2022, "pmid": "35911112", "url": "https://pubmed.ncbi.nlm.nih.gov/35911112/", "study_type": "meta-analysis", "key_finding": "In 9 RCTs with 896 subjects, HMB supplementation had a statistically significant overall impact on muscle strength-related indicators (SMD 0.41, 95% CI 0.28-0.54, p<0.00001) in the elderly population.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35911112/", "publicSourceType": "PMID" }, { "text": "Sadeghi B, Bahari H, Jozi H et al.. Effects of β-hydroxy-β-methylbutyrate (HMB) supplementation on lipid profile in adults: a GRADE-assessed systematic review and meta-analysis of randomized controlled trials. Frontiers in nutrition. 2024", "claim": "PubMed-indexed evidence involving HMB", "title": "Effects of β-hydroxy-β-methylbutyrate (HMB) supplementation on lipid profile in adults: a GRADE-assessed systematic review and meta-analysis of randomized controlled trials", "authors": "Sadeghi B, Bahari H, Jozi H et al.", "journal": "Frontiers in nutrition", "year": 2024, "pmid": "39385778", "url": "https://pubmed.ncbi.nlm.nih.gov/39385778/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fnut.2024.1451282", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39385778/", "publicSourceType": "PMID" }, { "text": "Molfino A, Gioia G, Rossi Fanelli F et al.. Beta-hydroxy-beta-methylbutyrate supplementation in health and disease: a systematic review of randomized trials. Amino acids. 2013", "claim": "PubMed-indexed evidence involving HMB", "title": "Beta-hydroxy-beta-methylbutyrate supplementation in health and disease: a systematic review of randomized trials", "authors": "Molfino A, Gioia G, Rossi Fanelli F et al.", "journal": "Amino acids", "year": 2013, "pmid": "24057808", "url": "https://pubmed.ncbi.nlm.nih.gov/24057808/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00726-013-1592-z", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24057808/", "publicSourceType": "PMID" }, { "text": "Su H, Zhou H, Gong Y et al.. The effects of β-hydroxy-β-methylbutyrate or HMB-rich nutritional supplements on sarcopenia patients: a systematic review and meta-analysis. Frontiers in medicine. 2024", "claim": "PubMed-indexed evidence involving HMB", "title": "The effects of β-hydroxy-β-methylbutyrate or HMB-rich nutritional supplements on sarcopenia patients: a systematic review and meta-analysis", "authors": "Su H, Zhou H, Gong Y et al.", "journal": "Frontiers in medicine", "year": 2024, "pmid": "39071082", "url": "https://pubmed.ncbi.nlm.nih.gov/39071082/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fmed.2024.1348212", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39071082/", "publicSourceType": "PMID" }, { "text": "Feng Y, Chen P, Li T et al.. Effects of exercise with or without β-hydroxy-β-methylbutyrate supplementation on muscle mass, muscle strength, and physical performance in patients with sarcopenia: a systematic review and meta-analysis. Frontiers in nutrition. 2024", "claim": "PubMed-indexed evidence involving HMB", "title": "Effects of exercise with or without β-hydroxy-β-methylbutyrate supplementation on muscle mass, muscle strength, and physical performance in patients with sarcopenia: a systematic review and meta-analysis", "authors": "Feng Y, Chen P, Li T et al.", "journal": "Frontiers in nutrition", "year": 2024, "pmid": "39360288", "url": "https://pubmed.ncbi.nlm.nih.gov/39360288/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fnut.2024.1460133", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39360288/", "publicSourceType": "PMID" }, { "text": "Rahimi MH, Mohammadi H, Eshaghi H et al.. The Effects of Beta-Hydroxy-Beta-Methylbutyrate Supplementation on Recovery Following Exercise-Induced Muscle Damage: A Systematic Review and Meta-Analysis. Journal of the American College of Nutrition. 2018", "claim": "PubMed-indexed evidence involving HMB", "title": "The Effects of Beta-Hydroxy-Beta-Methylbutyrate Supplementation on Recovery Following Exercise-Induced Muscle Damage: A Systematic Review and Meta-Analysis", "authors": "Rahimi MH, Mohammadi H, Eshaghi H et al.", "journal": "Journal of the American College of Nutrition", "year": 2018, "pmid": "29676656", "url": "https://pubmed.ncbi.nlm.nih.gov/29676656/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/07315724.2018.1451789", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29676656/", "publicSourceType": "PMID" }, { "text": "Silva VR, Belozo FL, Micheletti TO et al.. β-hydroxy-β-methylbutyrate free acid supplementation may improve recovery and muscle adaptations after resistance training: a systematic review. Nutrition research (New York, N.Y.). 2017", "claim": "PubMed-indexed evidence involving HMB", "title": "β-hydroxy-β-methylbutyrate free acid supplementation may improve recovery and muscle adaptations after resistance training: a systematic review", "authors": "Silva VR, Belozo FL, Micheletti TO et al.", "journal": "Nutrition research (New York, N.Y.)", "year": 2017, "pmid": "29037326", "url": "https://pubmed.ncbi.nlm.nih.gov/29037326/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.nutres.2017.07.008", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29037326/", "publicSourceType": "PMID" }, { "text": "Ogawa M, Satomi-Kobayashi S, Yoshida N et al.. Effects of preoperative beta-hydroxy-beta-methylbutyrate, arginine, and glutamine supplementation on cardiac surgery: A randomized controlled trial. Clinical nutrition (Edinburgh, Scotland). 2025", "claim": "PubMed-indexed evidence involving HMB", "title": "Effects of preoperative beta-hydroxy-beta-methylbutyrate, arginine, and glutamine supplementation on cardiac surgery: A randomized controlled trial", "authors": "Ogawa M, Satomi-Kobayashi S, Yoshida N et al.", "journal": "Clinical nutrition (Edinburgh, Scotland)", "year": 2025, "pmid": "39765161", "url": "https://pubmed.ncbi.nlm.nih.gov/39765161/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.clnu.2024.12.030", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39765161/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "hmb" }, { "id": "FD875391-404F-4416-B4C2-1F0CDDC1A2DB", "name": "L-Glutathione", "alternateNames": [ "Glutathione", "GSH" ], "category": "Amino Acid", "subcategory": "Tripeptide Antioxidant", "overview": "The body's master antioxidant, critical for detoxification and immune function.", "mechanismOfAction": "Tripeptide (glutamate-cysteine-glycine) that directly neutralizes ROS, regenerates vitamins C and E, conjugates toxins in phase II liver detoxification, and supports T-cell function.", "commonBenefits": [ "Detoxification", "Antioxidant defense", "Immune support", "Skin brightening" ], "commonDosageRange": "250-500 mg daily", "recommendedForm": "Liposomal glutathione or S-acetyl glutathione (better oral bioavailability)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Empty stomach; liposomal form preferred" }, "evidenceRating": "moderate", "foodSources": [ "Asparagus", "Avocado", "Spinach", "Okra" ], "deficiencySymptoms": [ "Oxidative stress", "Impaired detox", "Reduced immunity" ], "sideEffects": [ "Well tolerated", "Bloating" ], "contraindications": [ "Generally safe" ], "iconName": "shield.checkered", "colorHex": "6BCB77", "tags": [ "detox", "antioxidant", "immune", "skin" ], "sources": [ { "claim": "RCT of oral glutathione supplementation on body stores", "title": "Randomized controlled trial of oral glutathione supplementation on body stores of glutathione", "authors": "Richie JP Jr et al.", "journal": "European Journal of Nutrition", "year": 2015, "pmid": "24791752", "url": "https://pubmed.ncbi.nlm.nih.gov/24791752/", "study_type": "RCT", "key_finding": "Oral GSH supplementation at 250 and 1000 mg/day for 6 months significantly increased blood GSH levels, natural killer cell cytotoxicity, and reduced oxidative stress markers.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24791752/", "publicSourceType": "PMID" }, { "claim": "Liposomal glutathione outperforms plain glutathione in bioavailability", "title": "Liposomal glutathione outperforms plain glutathione in uptake, cell regeneration and systemic availability: evidence from cellular and human models", "authors": "Bresciani L et al.", "journal": "British Journal of Nutrition", "year": 2025, "pmid": "41559937", "url": "https://pubmed.ncbi.nlm.nih.gov/41559937/", "study_type": "RCT", "key_finding": "Liposomal glutathione showed 1.9-fold higher cellular uptake and 6x higher maximum plasma concentration than plain glutathione, maintaining levels >500 ng/mL at 24 hours.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41559937/", "publicSourceType": "PMID" }, { "claim": "Liposomal glutathione elevates body stores and immune markers", "title": "Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function", "authors": "Sinha R et al.", "journal": "European Journal of Clinical Nutrition", "year": 2018, "pmid": "28853742", "url": "https://pubmed.ncbi.nlm.nih.gov/28853742/", "study_type": "RCT", "key_finding": "Liposomal GSH elevated whole blood GSH by 40%, erythrocyte GSH by 25%, plasma GSH by 28%, and PBMC GSH by 100% after 2 weeks, with enhanced immune function markers.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28853742/", "publicSourceType": "PMID" }, { "claim": "Glutathione's role as master antioxidant in detoxification and immune function", "title": "Glutathione and immune function", "authors": "Droge W et al.", "journal": "Proceedings of the Nutrition Society", "year": 2000, "pmid": "11115795", "url": "https://pubmed.ncbi.nlm.nih.gov/11115795/", "study_type": "review", "key_finding": "Even moderate changes in intracellular glutathione have profound effects on lymphocyte functions; GSH regulates cell proliferation, apoptosis, and immune response.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11115795/", "publicSourceType": "PMID" }, { "claim": "Comprehensive review of glutathione biosynthesis, metabolism, and medicinal purposes", "title": "An Update on Glutathione's Biosynthesis, Metabolism, Functions, and Medicinal Purposes", "authors": "Lucchi L et al.", "journal": "Antioxidants", "year": 2023, "pmid": "37921175", "url": "https://pubmed.ncbi.nlm.nih.gov/37921175/", "study_type": "review", "key_finding": "GSH neutralizes ROS, regenerates vitamins C and E, conjugates toxins in phase II liver detoxification, and supports T-cell function as the body's master antioxidant.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37921175/", "publicSourceType": "PMID" }, { "claim": "Glutathione effects on skin color and melanin index", "title": "The clinical effect of glutathione on skin color and other related skin conditions: A systematic review", "authors": "Dilokthornsakul W et al.", "journal": "Journal of Cosmetic Dermatology", "year": 2019, "pmid": "30895708", "url": "https://pubmed.ncbi.nlm.nih.gov/30895708/", "study_type": "review", "key_finding": "Oral glutathione at 250-500 mg/day showed significant reduction in melanin index compared to placebo across 5 RCTs, though overall evidence remains inconclusive.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30895708/", "publicSourceType": "PMID" }, { "text": "Sarkar R, Yadav V, Yadav T et al.. Glutathione as a skin-lightening agent and in melasma: a systematic review. International journal of dermatology. 2025", "pmid": "39444151", "doi": "10.1111/ijd.17535", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39444151/", "publicSourceType": "PMID" }, { "claim": "Oral L-Glutathione combined with L-Cystine lightens skin and reduces dark spots", "title": "The effects of the oral supplementation of L-Cystine associated with reduced L-Glutathione-GSH on human skin pigmentation: a randomized, double-blinded, benchmark- and placebo-controlled clinical trial", "authors": "Duperray J, Sergheraert R, Chalothorn K, Tachalerdmanee P, Perin F", "journal": "J Cosmet Dermatol", "year": 2022, "pmid": "33834608", "url": "https://pubmed.ncbi.nlm.nih.gov/33834608/", "study_type": "rct", "key_finding": "RCT of 124 Asian women found 12 weeks of oral L-Cystine (500 mg) + L-Glutathione (250 mg) significantly lightened skin and reduced facial dark spot size, outperforming placebo and either compound alone.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33834608/", "publicSourceType": "PMID" }, { "text": "Khanna R, Rambhia P, Chapas A. Systematic Review of the Efficacy and Safety of Topical Glutathione in Dermatology. The Journal of clinical and aesthetic dermatology. 2025", "claim": "PubMed-indexed evidence involving L-Glutathione", "title": "Systematic Review of the Efficacy and Safety of Topical Glutathione in Dermatology", "authors": "Khanna R, Rambhia P, Chapas A", "journal": "The Journal of clinical and aesthetic dermatology", "year": 2025, "pmid": "41416233", "url": "https://pubmed.ncbi.nlm.nih.gov/41416233/", "study_type": "meta-analysis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41416233/", "publicSourceType": "PMID" }, { "text": "Alzahrani TF, Alotaibi SM, Alzahrani AA et al.. Exploring the Safety and Efficacy of Glutathione Supplementation for Skin Lightening: A Narrative Review. Cureus. 2025", "claim": "PubMed-indexed evidence involving L-Glutathione", "title": "Exploring the Safety and Efficacy of Glutathione Supplementation for Skin Lightening: A Narrative Review", "authors": "Alzahrani TF, Alotaibi SM, Alzahrani AA et al.", "journal": "Cureus", "year": 2025, "pmid": "40013212", "url": "https://pubmed.ncbi.nlm.nih.gov/40013212/", "study_type": "review", "confidence": "verify", "doi": "10.7759/cureus.78045", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40013212/", "publicSourceType": "PMID" }, { "text": "Glassman I, Le N, Mirhosseini M et al.. The Role of Glutathione in Prevention of COVID-19 Immunothrombosis: A Review. Frontiers in bioscience (Landmark edition). 2023", "claim": "PubMed-indexed evidence involving L-Glutathione", "title": "The Role of Glutathione in Prevention of COVID-19 Immunothrombosis: A Review", "authors": "Glassman I, Le N, Mirhosseini M et al.", "journal": "Frontiers in bioscience (Landmark edition)", "year": 2023, "pmid": "37005767", "url": "https://pubmed.ncbi.nlm.nih.gov/37005767/", "study_type": "review", "confidence": "verify", "doi": "10.31083/j.fbl2803059", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37005767/", "publicSourceType": "PMID" }, { "text": "Sharma DK, Sharma P. Augmented Glutathione Absorption from Oral Mucosa and its Effect on Skin Pigmentation: A Clinical Review. Clinical, cosmetic and investigational dermatology. 2022", "claim": "PubMed-indexed evidence involving L-Glutathione", "title": "Augmented Glutathione Absorption from Oral Mucosa and its Effect on Skin Pigmentation: A Clinical Review", "authors": "Sharma DK, Sharma P", "journal": "Clinical, cosmetic and investigational dermatology", "year": 2022, "pmid": "36117769", "url": "https://pubmed.ncbi.nlm.nih.gov/36117769/", "study_type": "review", "confidence": "verify", "doi": "10.2147/CCID.S378470", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36117769/", "publicSourceType": "PMID" }, { "text": "Bjørklund G, Tinkov AA, Hosnedlová B et al.. The role of glutathione redox imbalance in autism spectrum disorder: A review. Free radical biology & medicine. 2020", "claim": "PubMed-indexed evidence involving L-Glutathione", "title": "The role of glutathione redox imbalance in autism spectrum disorder: A review", "authors": "Bjørklund G, Tinkov AA, Hosnedlová B et al.", "journal": "Free radical biology & medicine", "year": 2020, "pmid": "32745763", "url": "https://pubmed.ncbi.nlm.nih.gov/32745763/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.freeradbiomed.2020.07.017", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32745763/", "publicSourceType": "PMID" }, { "text": "Zhang T, Yao C, Zhou X et al.. Glutathione‑degrading enzymes in the complex landscape of tumors (Review). International journal of oncology. 2024", "claim": "PubMed-indexed evidence involving L-Glutathione", "title": "Glutathione‑degrading enzymes in the complex landscape of tumors (Review)", "authors": "Zhang T, Yao C, Zhou X et al.", "journal": "International journal of oncology", "year": 2024, "pmid": "38847236", "url": "https://pubmed.ncbi.nlm.nih.gov/38847236/", "study_type": "review", "confidence": "verify", "doi": "10.3892/ijo.2024.5660", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38847236/", "publicSourceType": "PMID" }, { "text": "Ghanizadeh A, Akhondzadeh S, Hormozi M et al.. Glutathione-related factors and oxidative stress in autism, a review. Current medicinal chemistry. 2012", "claim": "PubMed-indexed evidence involving L-Glutathione", "title": "Glutathione-related factors and oxidative stress in autism, a review", "authors": "Ghanizadeh A, Akhondzadeh S, Hormozi M et al.", "journal": "Current medicinal chemistry", "year": 2012, "pmid": "22708999", "url": "https://pubmed.ncbi.nlm.nih.gov/22708999/", "study_type": "review", "confidence": "verify", "doi": "10.2174/092986712802002572", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22708999/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "l-glutathione" }, { "id": "0E3DD51B-CA36-455A-9D7F-CCD268BFAB60", "name": "Bacopa Monnieri", "alternateNames": [ "Brahmi", "Water Hyssop" ], "category": "Herb", "subcategory": "Ayurvedic Adaptogenic Herb", "overview": "Ayurvedic herb with strong evidence for memory enhancement and cognitive function.", "mechanismOfAction": "Bacosides A and B modulate serotonin, dopamine, and acetylcholine. Enhances dendritic branching and synaptic activity in the hippocampus. Antioxidant protection of neural tissue.", "commonBenefits": [ "Memory", "Learning", "Focus", "Anxiety reduction" ], "commonDosageRange": "300-600 mg daily (standardized to 50% bacosides)", "recommendedForm": "Standardized extract (Bacognize or Synapsa)", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with fat-containing meal; effects build over 8-12 weeks" }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "GI upset", "Fatigue initially", "Dry mouth" ], "contraindications": [ "Thyroid conditions", "GI ulcers", "Bradycardia" ], "iconName": "brain.fill", "colorHex": "34D399", "tags": [ "cognitive", "memory", "adaptogen", "ayurvedic" ], "sources": [ { "claim": "Meta-analysis of Bacopa monnieri cognitive effects", "title": "Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract", "authors": "Kongkeaw C et al.", "journal": "Journal of Ethnopharmacology", "year": 2014, "pmid": "24252493", "url": "https://pubmed.ncbi.nlm.nih.gov/24252493/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 9 studies (518 subjects) suggests Bacopa monnieri has the potential to improve cognition, particularly speed of attention and cognitive processing.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24252493/", "publicSourceType": "PMID" }, { "claim": "Systematic review of cognitive-enhancing effects in clinical trials", "title": "The cognitive-enhancing effects of Bacopa monnieri: a systematic review of randomized, controlled human clinical trials", "authors": "Pase MP et al.", "journal": "Journal of Alternative and Complementary Medicine", "year": 2012, "pmid": "22747190", "url": "https://pubmed.ncbi.nlm.nih.gov/22747190/", "study_type": "review", "key_finding": "Bacopa improved performance on 9 of 17 tests in the domain of memory free recall at 300-450 mg/day for 12+ weeks of standardized extract.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22747190/", "publicSourceType": "PMID" }, { "claim": "RCT showing effects on cognition, anxiety, and depression in elderly", "title": "Effects of a standardized Bacopa monnieri extract on cognitive performance, anxiety, and depression in the elderly: a randomized, double-blind, placebo-controlled trial", "authors": "Calabrese C et al.", "journal": "Journal of Alternative and Complementary Medicine", "year": 2008, "pmid": "18611150", "url": "https://pubmed.ncbi.nlm.nih.gov/18611150/", "study_type": "RCT", "key_finding": "Anxiety and depression scores decreased for the Bacopa group while increasing for placebo; memory acquisition and retention were significantly improved.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18611150/", "publicSourceType": "PMID" }, { "claim": "Neuroprotective and cognitive-enhancing mechanisms (inflammation, oxidative stress, apoptosis)", "title": "Investigating the Neuroprotective and Cognitive-Enhancing Effects of Bacopa monnieri: A Systematic Review Focused on Inflammation, Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis", "authors": "Simpson T et al.", "journal": "Nutrients", "year": 2024, "pmid": "38671841", "url": "https://pubmed.ncbi.nlm.nih.gov/38671841/", "study_type": "review", "key_finding": "Bacopa has anti-apoptotic and antioxidant actions, repairs damaged neurons, stimulates kinase activity, restores synaptic function, and enhances neuroprotection via bacoside modulation.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38671841/", "publicSourceType": "PMID" }, { "claim": "Neuropharmacological mechanisms: serotonin, dopamine, acetylcholine modulation", "title": "Neuropharmacological and cognitive effects of Bacopa monnieri (L.) Wettst - A review on its mechanistic aspects", "authors": "Brimson JM et al.", "journal": "Complementary Therapies in Medicine", "year": 2021, "pmid": "31126578", "url": "https://pubmed.ncbi.nlm.nih.gov/31126578/", "study_type": "review", "key_finding": "Bacosides A and B modulate serotonin, dopamine, and acetylcholine; enhance dendritic branching and synaptic activity in the hippocampus with antioxidant neural protection.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31126578/", "publicSourceType": "PMID" }, { "text": "Kean JD, Downey LA, Stough C. A systematic review of the Ayurvedic medicinal herb Bacopa monnieri in child and adolescent populations. Complementary therapies in medicine. 2016", "pmid": "27912958", "doi": "10.1016/j.ctim.2016.09.002", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27912958/", "publicSourceType": "PMID" }, { "text": "Walker EA, Pellegrini MV. Bacopa monnieri. 2026", "pmid": "36943953", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36943953/", "publicSourceType": "PMID" }, { "claim": "Bacopa monnieri may help treat dementia due to Alzheimer's disease", "title": "Use of Bacopa monnieri in the Treatment of Dementia Due to Alzheimer Disease: Systematic Review of Randomized Controlled Trials.", "authors": "Basheer A, Agarwal A, Mishra B et al.", "journal": "Interactive Journal of Medical Research", "year": 2022, "pmid": "35612544", "url": "https://pubmed.ncbi.nlm.nih.gov/35612544/", "study_type": "review", "key_finding": "Bacopa monnieri showed potential cognitive benefits in Alzheimer's disease patients across reviewed RCTs, particularly in memory and attention domains.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35612544/", "publicSourceType": "PMID" }, { "claim": "Bacopa monnieri is effective for cognitive enhancement in Alzheimer's and MCI", "title": "Efficacy of Bacopa Monnieri (Brahmi) and Donepezil in Alzheimer's Disease and Mild Cognitive Impairment: A Randomized Double-Blind Parallel Phase 2b Study.", "authors": "Prabhakar S, Vishnu VY, Modi M et al.", "journal": "Annals of Indian Academy of Neurology", "year": 2020, "pmid": "33688125", "url": "https://pubmed.ncbi.nlm.nih.gov/33688125/", "study_type": "rct", "key_finding": "Bacopa monnieri showed comparable efficacy to donepezil in improving cognitive function in patients with mild cognitive impairment and Alzheimer's disease.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33688125/", "publicSourceType": "PMID" }, { "claim": "Bacopa monnieri enhances neurocognitive function in older adults", "title": "The Neurocognitive Effects of Bacopa monnieri and Cognitive Training on Markers of Brain Microstructure in Healthy Older Adults.", "authors": "McPhee GM, Downey LA, Wesnes KA et al.", "journal": "Frontiers in Aging Neuroscience", "year": 2021, "pmid": "33692683", "url": "https://pubmed.ncbi.nlm.nih.gov/33692683/", "study_type": "rct", "key_finding": "Bacopa monnieri supplementation combined with cognitive training showed beneficial effects on brain microstructure and cognitive performance in healthy older adults.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33692683/", "publicSourceType": "PMID" }, { "text": "Verma J, Rathi R, Anamika et al.. Comparative efficacy of Medhya Rasayana,Bacopa monnieri, and Centella asiatica in enhancing memory and IQ of 8-10 year-old healthy boys: A prakriti-based double-blind, randomized controlled trial. Journal of Ayurveda and integrative medicine. 2025", "claim": "PubMed-indexed evidence involving Bacopa Monnieri", "title": "Comparative efficacy of Medhya Rasayana,Bacopa monnieri, and Centella asiatica in enhancing memory and IQ of 8-10 year-old healthy boys: A prakriti-based double-blind, randomized controlled trial", "authors": "Verma J, Rathi R, Anamika et al.", "journal": "Journal of Ayurveda and integrative medicine", "year": 2025, "pmid": "40609195", "url": "https://pubmed.ncbi.nlm.nih.gov/40609195/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.jaim.2025.101164", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40609195/", "publicSourceType": "PMID" }, { "text": "Khan S, Krishnarajabhatt HS, Sushilal CMN et al.. \"An exploratory randomized, double-blind, placebo- controlled trial protocol on combined Cognitive Behavioral Therapy and adjunct Brahmi (Bacopa monnieri) tablets in Premenstrual Syndrome management\". Frontiers in medicine. 2025", "claim": "PubMed-indexed evidence involving Bacopa Monnieri", "title": "\"An exploratory randomized, double-blind, placebo- controlled trial protocol on combined Cognitive Behavioral Therapy and adjunct Brahmi (Bacopa monnieri) tablets in Premenstrual Syndrome management\"", "authors": "Khan S, Krishnarajabhatt HS, Sushilal CMN et al.", "journal": "Frontiers in medicine", "year": 2025, "pmid": "41035862", "url": "https://pubmed.ncbi.nlm.nih.gov/41035862/", "study_type": "RCT", "confidence": "verify", "doi": "10.3389/fmed.2025.1657004", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41035862/", "publicSourceType": "PMID" }, { "text": "Lopresti AL, Smith SJ. The Effects of a Bacopa monnieri Extract (Bacumen(®)) on Cognition, Stress, and Fatigue in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Trial. Clinical drug investigation. 2025", "claim": "PubMed-indexed evidence involving Bacopa Monnieri", "title": "The Effects of a Bacopa monnieri Extract (Bacumen(®)) on Cognition, Stress, and Fatigue in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Trial", "authors": "Lopresti AL, Smith SJ", "journal": "Clinical drug investigation", "year": 2025, "pmid": "41091332", "url": "https://pubmed.ncbi.nlm.nih.gov/41091332/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/s40261-025-01492-1", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41091332/", "publicSourceType": "PMID" }, { "text": "Deolankar SC, Najar MA, Ramesh P et al.. Discovery of Molecular Networks of Neuroprotection Conferred by Brahmi Extract in Aβ(42)-Induced Toxicity Model of Drosophila melanogaster Using a Quantitative Proteomic Approach. Molecular neurobiology. 2023", "claim": "PubMed-indexed evidence involving Bacopa Monnieri", "title": "Discovery of Molecular Networks of Neuroprotection Conferred by Brahmi Extract in Aβ(42)-Induced Toxicity Model of Drosophila melanogaster Using a Quantitative Proteomic Approach", "authors": "Deolankar SC, Najar MA, Ramesh P et al.", "journal": "Molecular neurobiology", "year": 2023, "pmid": "36261695", "url": "https://pubmed.ncbi.nlm.nih.gov/36261695/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s12035-022-03066-0", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36261695/", "publicSourceType": "PMID" }, { "text": "Kean JD, Kaufman J, Lomas J et al.. A Randomized Controlled Trial Investigating the Effects of a Special Extract of Bacopa monnieri (CDRI 08) on Hyperactivity and Inattention in Male Children and Adolescents: BACHI Study Protocol (ANZCTRN12612000827831). Nutrients. 2015", "claim": "PubMed-indexed evidence involving Bacopa Monnieri", "title": "A Randomized Controlled Trial Investigating the Effects of a Special Extract of Bacopa monnieri (CDRI 08) on Hyperactivity and Inattention in Male Children and Adolescents: BACHI Study Protocol (ANZCTRN12612000827831)", "authors": "Kean JD, Kaufman J, Lomas J et al.", "journal": "Nutrients", "year": 2015, "pmid": "26633481", "url": "https://pubmed.ncbi.nlm.nih.gov/26633481/", "study_type": "RCT", "confidence": "verify", "doi": "10.3390/nu7125507", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26633481/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "bacopa-monnieri" }, { "id": "4C73A582-02FF-411D-A0D0-4EA386FD50D9", "name": "Ginkgo Biloba", "alternateNames": [ "Ginkgo", "Maidenhair Tree" ], "category": "Herb", "subcategory": "Cerebrovascular Herb", "overview": "One of the oldest living tree species, used for cognitive function and circulation.", "mechanismOfAction": "Flavonoids and terpenoids (ginkgolides, bilobalide) improve microcirculation, inhibit platelet-activating factor (PAF), and provide antioxidant neuroprotection.", "commonBenefits": [ "Cognitive function", "Circulation", "Eye health", "Memory" ], "commonDosageRange": "120-240 mg daily", "recommendedForm": "Standardized extract (24% flavone glycosides, 6% terpene lactones)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food in divided doses" }, "evidenceRating": "moderate", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Headache", "GI upset", "Dizziness", "Increased bleeding risk", "Seizures are rare but possible, especially with seizure disorders, high doses, or non-standardized products containing ginkgotoxin" ], "contraindications": [ "Blood thinners", "SSRIs", "Surgery (stop 2 weeks before)", "Seizure disorders", "Pregnancy" ], "iconName": "leaf.fill", "colorHex": "34D399", "tags": [ "cognitive", "circulation", "memory" ], "sources": [ { "claim": "Systematic review and meta-analysis for cognitive impairment and dementia", "title": "Efficacy and adverse effects of ginkgo biloba for cognitive impairment and dementia: a systematic review and meta-analysis", "authors": "Tan MS et al.", "journal": "Journal of Alzheimer's Disease", "year": 2015, "pmid": "25114079", "url": "https://pubmed.ncbi.nlm.nih.gov/25114079/", "study_type": "meta-analysis", "key_finding": "Ginkgo biloba is potentially beneficial for improving cognitive function, ADLs, and global clinical assessment in MCI and Alzheimer's patients; adverse events similar to placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25114079/", "publicSourceType": "PMID" }, { "claim": "Meta-analysis: Ginkgo biloba is not a cognitive enhancer in healthy individuals", "title": "Is Ginkgo biloba a cognitive enhancer in healthy individuals? A meta-analysis", "authors": "Laws KR et al.", "journal": "Human Psychopharmacology", "year": 2012, "pmid": "23001963", "url": "https://pubmed.ncbi.nlm.nih.gov/23001963/", "study_type": "meta-analysis", "key_finding": "In cognitively healthy individuals, effect sizes were non-significant and close to zero for memory, executive function, and attention.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23001963/", "publicSourceType": "PMID" }, { "claim": "Ginkgo biloba for Alzheimer's disease: efficacy and safety meta-analysis", "title": "Meta-analysis of Ginkgo biloba Preparation for the Treatment of Alzheimer's Disease", "authors": "Yang G et al.", "journal": "Neuropsychiatric Disease and Treatment", "year": 2020, "pmid": "32658034", "url": "https://pubmed.ncbi.nlm.nih.gov/32658034/", "study_type": "meta-analysis", "key_finding": "Ginkgo biloba preparation showed reliable efficacy on cognitive function and global clinical assessment in Alzheimer's treatment with a favorable safety profile.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32658034/", "publicSourceType": "PMID" }, { "claim": "Systematic review and meta-analysis of bleeding risk with ginkgo", "title": "Is there a risk of bleeding associated with standardized Ginkgo biloba extract therapy? A systematic review and meta-analysis", "authors": "Kellermann AJ et al.", "journal": "Pharmacotherapy", "year": 2011, "pmid": "21923430", "url": "https://pubmed.ncbi.nlm.nih.gov/21923430/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of hemostasis outcomes did not indicate a higher bleeding risk with standardized Ginkgo biloba extract at recommended doses of 120-240 mg/day.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21923430/", "publicSourceType": "PMID" }, { "claim": "Ginkgolides inhibit platelet-activating factor at concentrations above clinical relevance", "title": "Inhibition of platelet activating factor (PAF)-induced aggregation of human thrombocytes by ginkgolides: considerations on possible bleeding complications after oral intake of Ginkgo biloba extracts", "authors": "Koch E", "journal": "Phytomedicine", "year": 2005, "pmid": "15693702", "url": "https://pubmed.ncbi.nlm.nih.gov/15693702/", "study_type": "review", "key_finding": "Ginkgolides inhibit PAF-mediated platelet aggregation, but concentrations required are >100x higher than peak plasma values at recommended oral doses (120-240 mg).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15693702/", "publicSourceType": "PMID" }, { "claim": "Interaction potential with antiplatelet and anticoagulant drugs", "title": "Potential interaction of Ginkgo biloba leaf with antiplatelet or anticoagulant drugs: what is the evidence?", "authors": "Izzo AA et al.", "journal": "British Journal of Clinical Pharmacology", "year": 2008, "pmid": "18214851", "url": "https://pubmed.ncbi.nlm.nih.gov/18214851/", "study_type": "review", "key_finding": "Controlled studies consistently indicate that Ginkgo does not significantly impact hemostasis nor adversely affect the safety of coadministered aspirin or warfarin.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18214851/", "publicSourceType": "PMID" }, { "text": "Ye W, Wang J, Little PJ et al.. Anti-atherosclerotic effects and molecular targets of ginkgolide B from Ginkgo biloba. Acta pharmaceutica Sinica. B. 2024", "pmid": "38239238", "doi": "10.1016/j.apsb.2023.09.014", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38239238/", "publicSourceType": "PMID" }, { "text": "Ginkgo. 2006", "pmid": "30000868", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30000868/", "publicSourceType": "PMID" }, { "claim": "Ginkgo biloba improves cognitive function in mild dementia", "title": "Ginkgo biloba extract EGb 761 is safe and effective in the treatment of mild dementia - a meta-analysis of patient subgroups in randomised controlled trials", "authors": "Riepe M, Hoerr R, Schlaefke S", "journal": "World Journal of Biological Psychiatry", "year": 2025, "pmid": "39895346", "url": "https://pubmed.ncbi.nlm.nih.gov/39895346/", "study_type": "meta-analysis", "key_finding": "Ginkgo biloba extract EGb 761 significantly improved cognitive performance and daily functioning in patients with mild dementia, with a favorable safety profile across pooled RCT subgroups.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39895346/", "publicSourceType": "PMID" }, { "claim": "Ginkgo biloba reduces inflammatory markers", "title": "Beneficial effects of Ginkgo biloba leaf extract on inflammatory markers: A systematic review and meta-analysis of the clinical trials", "authors": "Mousavi SN, Hosseinikia M, Yousefi Rad E, Saboori S", "journal": "Phytotherapy Research", "year": 2022, "pmid": "35781715", "url": "https://pubmed.ncbi.nlm.nih.gov/35781715/", "study_type": "meta-analysis", "key_finding": "Ginkgo biloba leaf extract supplementation significantly reduced circulating inflammatory markers including CRP, IL-6, and TNF-alpha across clinical trials.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35781715/", "publicSourceType": "PMID" }, { "claim": "Ginkgo biloba improves cardiometabolic parameters in type 2 diabetes", "title": "Effects of Ginkgo biloba intake on cardiometabolic parameters in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of clinical trials", "authors": "Tabrizi R, Nowrouzi-Sohrabi P, Hessami K et al.", "journal": "Phytotherapy Research", "year": 2020, "pmid": "33090588", "url": "https://pubmed.ncbi.nlm.nih.gov/33090588/", "study_type": "meta-analysis", "key_finding": "Ginkgo biloba supplementation significantly improved fasting blood glucose and lipid parameters in patients with type 2 diabetes mellitus compared to placebo in pooled analysis.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33090588/", "publicSourceType": "PMID" }, { "text": "Liu Y, Niu P, Yan J et al.. Efficacy and safety of Ginkgo biloba extract in the treatment of unstable angina pectoris: A systematic review and network meta-analysis. Journal of ethnopharmacology. 2024", "claim": "PubMed-indexed evidence involving Ginkgo Biloba", "title": "Efficacy and safety of Ginkgo biloba extract in the treatment of unstable angina pectoris: A systematic review and network meta-analysis", "authors": "Liu Y, Niu P, Yan J et al.", "journal": "Journal of ethnopharmacology", "year": 2024, "pmid": "38718890", "url": "https://pubmed.ncbi.nlm.nih.gov/38718890/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jep.2024.118297", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38718890/", "publicSourceType": "PMID" }, { "text": "Prinz J, Prokosch V, Wang X et al.. Efficacy of Ginkgo biloba on parameters in glaucoma: A systematic review. PloS one. 2025", "claim": "PubMed-indexed evidence involving Ginkgo Biloba", "title": "Efficacy of Ginkgo biloba on parameters in glaucoma: A systematic review", "authors": "Prinz J, Prokosch V, Wang X et al.", "journal": "PloS one", "year": 2025, "pmid": "39951447", "url": "https://pubmed.ncbi.nlm.nih.gov/39951447/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1371/journal.pone.0314644", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39951447/", "publicSourceType": "PMID" }, { "text": "Singh V, Singh SP, Chan K. Review and meta-analysis of usage of ginkgo as an adjunct therapy in chronic schizophrenia. The international journal of neuropsychopharmacology. 2010", "claim": "PubMed-indexed evidence involving Ginkgo Biloba", "title": "Review and meta-analysis of usage of ginkgo as an adjunct therapy in chronic schizophrenia", "authors": "Singh V, Singh SP, Chan K", "journal": "The international journal of neuropsychopharmacology", "year": 2010, "pmid": "19775502", "url": "https://pubmed.ncbi.nlm.nih.gov/19775502/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1017/S1461145709990654", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19775502/", "publicSourceType": "PMID" }, { "text": "Chen L, Liu X, Zheng J et al.. A randomized, double-blind, placebo-controlled study of Cistanche tubulosa and Ginkgo biloba extracts for the improvement of cognitive function in middle-aged and elderly people. Phytotherapy research : PTR. 2024", "claim": "PubMed-indexed evidence involving Ginkgo Biloba", "title": "A randomized, double-blind, placebo-controlled study of Cistanche tubulosa and Ginkgo biloba extracts for the improvement of cognitive function in middle-aged and elderly people", "authors": "Chen L, Liu X, Zheng J et al.", "journal": "Phytotherapy research : PTR", "year": 2024, "pmid": "38972848", "url": "https://pubmed.ncbi.nlm.nih.gov/38972848/", "study_type": "RCT", "confidence": "verify", "doi": "10.1002/ptr.8275", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38972848/", "publicSourceType": "PMID" }, { "text": "Chowdhury D, Roy AK, Reddy VR et al.. Multicenter, Open-Label, Prospective Study Shows Safety and Therapeutic Benefits of a Defined Ginkgo Biloba Extract for Adults with Major Neurocognitive Disorder. Dementia and geriatric cognitive disorders. 2024", "claim": "PubMed-indexed evidence involving Ginkgo Biloba", "title": "Multicenter, Open-Label, Prospective Study Shows Safety and Therapeutic Benefits of a Defined Ginkgo Biloba Extract for Adults with Major Neurocognitive Disorder", "authors": "Chowdhury D, Roy AK, Reddy VR et al.", "journal": "Dementia and geriatric cognitive disorders", "year": 2024, "pmid": "39068924", "url": "https://pubmed.ncbi.nlm.nih.gov/39068924/", "study_type": "RCT", "confidence": "verify", "doi": "10.1159/000540385", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39068924/", "publicSourceType": "PMID" }, { "claim": "Ginkgo products contain ginkgotoxin, which can lower seizure threshold", "title": "Ginkgo biloba and ginkgotoxin", "authors": "Leistner E, Drewke C", "journal": "Journal of Natural Products", "year": 2010, "pmid": "20041670", "url": "https://pubmed.ncbi.nlm.nih.gov/20041670/", "study_type": "review", "key_finding": "Review discusses ginkgotoxin in Ginkgo biloba products and seizure risk, supporting caution in seizure-prone users.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20041670/", "publicSourceType": "PMID" }, { "claim": "Ginkgo has been reported to precipitate seizures in patients with epilepsy", "title": "Ginkgo biloba precipitating epileptic seizures", "authors": "Granger AS", "journal": "Age and Ageing", "year": 2001, "pmid": "11742783", "url": "https://pubmed.ncbi.nlm.nih.gov/11742783/", "study_type": "case_report", "key_finding": "Case report describes seizure precipitation associated with Ginkgo biloba use.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11742783/", "publicSourceType": "PMID" }, { "claim": "Pregnancy and lactation safety data for ginkgo are insufficient, with bleeding concerns", "title": "Safety and efficacy of ginkgo (Ginkgo biloba) during pregnancy and lactation", "authors": "Dugoua JJ et al.", "journal": "Canadian Journal of Clinical Pharmacology", "year": 2006, "pmid": "17085776", "url": "https://pubmed.ncbi.nlm.nih.gov/17085776/", "study_type": "review", "key_finding": "Review notes insufficient pregnancy and lactation safety evidence and concern for increased bleeding time.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17085776/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "ginkgo-biloba" }, { "id": "42950ABA-96C6-4002-961F-A3CE2A4B439C", "name": "Valerian Root", "alternateNames": [ "Valeriana officinalis" ], "category": "Herb", "subcategory": "Sedative Herb", "overview": "Traditional herbal sedative for sleep and anxiety relief.", "mechanismOfAction": "Valerenic acid inhibits GABA transaminase, increasing GABA levels. Also acts as a partial agonist at 5-HT5a serotonin receptors and adenosine A1 receptors.", "commonBenefits": [ "Sleep support", "Anxiety relief", "Relaxation" ], "commonDosageRange": "300-600 mg before bed", "recommendedForm": "Standardized extract (0.8% valerenic acid)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "30-60 minutes before bed" }, "evidenceRating": "moderate", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Morning grogginess", "Headache", "GI upset", "Vivid dreams" ], "contraindications": [ "Liver disease", "Concurrent sedatives", "Surgery" ], "iconName": "moon.zzz.fill", "colorHex": "34D399", "tags": [ "sleep", "anxiety", "relaxation" ], "sources": [ { "claim": "Systematic review and meta-analysis of valerian for sleep", "title": "Valerian for sleep: a systematic review and meta-analysis", "authors": "Fernandez-San-Martin MI et al.", "journal": "American Journal of Medicine", "year": 2010, "pmid": "20347389", "url": "https://pubmed.ncbi.nlm.nih.gov/20347389/", "study_type": "meta-analysis", "key_finding": "Qualitative results suggest valerian effective for subjective improvement of insomnia, but effectiveness not demonstrated with quantitative/objective measurements.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20347389/", "publicSourceType": "PMID" }, { "claim": "Comprehensive systematic review and meta-analysis of valerian for sleep and associated disorders", "title": "Valerian Root in Treating Sleep Problems and Associated Disorders-A Systematic Review and Meta-Analysis", "authors": "Shinjyo N et al.", "journal": "Journal of Evidence-Based Integrative Medicine", "year": 2020, "pmid": "33086877", "url": "https://pubmed.ncbi.nlm.nih.gov/33086877/", "study_type": "meta-analysis", "key_finding": "Valerian showed a significant benefit for improved sleep (RR 1.8) but with evidence of publication bias; no severe adverse events in subjects aged 7-80.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33086877/", "publicSourceType": "PMID" }, { "claim": "GABA-A receptors as in vivo substrate for anxiolytic action of valerenic acid", "title": "GABA A receptors as in vivo substrate for the anxiolytic action of valerenic acid, a major constituent of valerian root extracts", "authors": "Benke D et al.", "journal": "Neuropharmacology", "year": 2009, "pmid": "18602406", "url": "https://pubmed.ncbi.nlm.nih.gov/18602406/", "study_type": "RCT", "key_finding": "Valerenic acid exerts anxiolytic activity via beta3-containing GABA-A receptors in vivo; these neurons are a major cellular substrate for valerian's anxiolytic action.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18602406/", "publicSourceType": "PMID" }, { "claim": "Valerenic acid modulates GABA-A receptors with subunit specificity", "title": "Valerenic acid potentiates and inhibits GABA(A) receptors: molecular mechanism and subunit specificity", "authors": "Khom S et al.", "journal": "Neuropharmacology", "year": 2007, "pmid": "17585957", "url": "https://pubmed.ncbi.nlm.nih.gov/17585957/", "study_type": "RCT", "key_finding": "Valerenic acid and valerenol bind specific sites on GABA-A receptors, enhancing GABA response selectively through beta2 or beta3 subunit-containing channels.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17585957/", "publicSourceType": "PMID" }, { "claim": "Umbrella review of valerian evidence for insomnia", "title": "Does valerian work for insomnia? An umbrella review of the evidence", "authors": "Agah E et al.", "journal": "Sleep Medicine Reviews", "year": 2024, "pmid": "38359657", "url": "https://pubmed.ncbi.nlm.nih.gov/38359657/", "study_type": "review", "key_finding": "Data suggest valerian has a good safety profile but no robust evidence of efficacy for insomnia treatment with current study designs; safe at 300-600 mg doses.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38359657/", "publicSourceType": "PMID" }, { "text": "Chandra Shekhar H, Joshua L, Thomas JV. Standardized Extract of Valeriana officinalis Improves Overall Sleep Quality in Human Subjects with Sleep Complaints: A Randomized, Double-Blind, Placebo-Controlled, Clinical Study. Advances in therapy. 2024", "pmid": "37899385", "doi": "10.1007/s12325-023-02708-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37899385/", "publicSourceType": "PMID" }, { "claim": "Valerian is a commonly used alternative treatment for insomnia", "title": "Complementary and alternative treatments for insomnia disorder: a systematic umbrella review", "authors": "Ell J, Schmid SR, Benz F, Spille L", "journal": "Journal of Sleep Research", "year": 2023, "pmid": "37527850", "url": "https://pubmed.ncbi.nlm.nih.gov/37527850/", "study_type": "review", "key_finding": "Valerian was among the most frequently studied complementary treatments for insomnia, with some evidence of benefit for subjective sleep parameters, though more rigorous trials are needed.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37527850/", "publicSourceType": "PMID" }, { "text": "Rabiei F, Delavar MA, Mirabi P et al.. Effect of Valeriana officinalis on Primary Dysmenorrhea: A Systematic Review and Meta-Analysis. Reviews on recent clinical trials. 2025", "claim": "PubMed-indexed evidence involving Valerian Root", "title": "Effect of Valeriana officinalis on Primary Dysmenorrhea: A Systematic Review and Meta-Analysis", "authors": "Rabiei F, Delavar MA, Mirabi P et al.", "journal": "Reviews on recent clinical trials", "year": 2025, "pmid": "40965071", "url": "https://pubmed.ncbi.nlm.nih.gov/40965071/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2174/0115748871387235250902123910", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40965071/", "publicSourceType": "PMID" }, { "text": "Jenabi E, Khazaei S, Aghababaei S et al.. Effect of Fennel-Valerian Extract on Hot Flashes and Sleep Disorders in Postmenopausal Women: A Randomized Trial. Journal of menopausal medicine. 2023", "claim": "PubMed-indexed evidence involving Valerian Root", "title": "Effect of Fennel-Valerian Extract on Hot Flashes and Sleep Disorders in Postmenopausal Women: A Randomized Trial", "authors": "Jenabi E, Khazaei S, Aghababaei S et al.", "journal": "Journal of menopausal medicine", "year": 2023, "pmid": "37160299", "url": "https://pubmed.ncbi.nlm.nih.gov/37160299/", "study_type": "RCT", "confidence": "verify", "doi": "10.6118/jmm.22026", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37160299/", "publicSourceType": "PMID" }, { "text": "Roh D, Jung JH, Yoon KH et al.. Valerian extract alters functional brain connectivity: A randomized double-blind placebo-controlled trial. Phytotherapy research : PTR. 2019", "claim": "PubMed-indexed evidence involving Valerian Root", "title": "Valerian extract alters functional brain connectivity: A randomized double-blind placebo-controlled trial", "authors": "Roh D, Jung JH, Yoon KH et al.", "journal": "Phytotherapy research : PTR", "year": 2019, "pmid": "30632220", "url": "https://pubmed.ncbi.nlm.nih.gov/30632220/", "study_type": "RCT", "confidence": "verify", "doi": "10.1002/ptr.6286", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30632220/", "publicSourceType": "PMID" }, { "text": "Morin CM, Koetter U, Bastien C et al.. Valerian-hops combination and diphenhydramine for treating insomnia: a randomized placebo-controlled clinical trial. Sleep. 2005", "claim": "PubMed-indexed evidence involving Valerian Root", "title": "Valerian-hops combination and diphenhydramine for treating insomnia: a randomized placebo-controlled clinical trial", "authors": "Morin CM, Koetter U, Bastien C et al.", "journal": "Sleep", "year": 2005, "pmid": "16335333", "url": "https://pubmed.ncbi.nlm.nih.gov/16335333/", "study_type": "RCT", "confidence": "verify", "doi": "10.1093/sleep/28.11.1465", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16335333/", "publicSourceType": "PMID" }, { "text": "Sudati JH, Vieira FA, Pavin SS et al.. Valeriana officinalis attenuates the rotenone-induced toxicity in Drosophila melanogaster. Neurotoxicology. 2013", "claim": "PubMed-indexed evidence involving Valerian Root", "title": "Valeriana officinalis attenuates the rotenone-induced toxicity in Drosophila melanogaster", "authors": "Sudati JH, Vieira FA, Pavin SS et al.", "journal": "Neurotoxicology", "year": 2013, "pmid": "23639798", "url": "https://pubmed.ncbi.nlm.nih.gov/23639798/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.neuro.2013.04.006", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23639798/", "publicSourceType": "PMID" }, { "text": "Yang S, Zhang H, Chen L et al.. Valeriana species and insomnia: multi-organ mechanisms and translational perspectives. Pharmaceutical biology. 2026", "claim": "PubMed-indexed evidence involving Valerian Root", "title": "Valeriana species and insomnia: multi-organ mechanisms and translational perspectives", "authors": "Yang S, Zhang H, Chen L et al.", "journal": "Pharmaceutical biology", "year": 2026, "pmid": "41995686", "url": "https://pubmed.ncbi.nlm.nih.gov/41995686/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/13880209.2026.2652660", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41995686/", "publicSourceType": "PMID" }, { "text": "Afzal S, Zhou X, Or K et al.. Identification of Nrf2 Activators from the Roots of Valeriana officinalis. Planta medica. 2023", "claim": "PubMed-indexed evidence involving Valerian Root", "title": "Identification of Nrf2 Activators from the Roots of Valeriana officinalis", "authors": "Afzal S, Zhou X, Or K et al.", "journal": "Planta medica", "year": 2023, "pmid": "35764305", "url": "https://pubmed.ncbi.nlm.nih.gov/35764305/", "study_type": "review", "confidence": "verify", "doi": "10.1055/a-1887-2016", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35764305/", "publicSourceType": "PMID" }, { "text": "Zaienne D, Isigkeit L, Marschner JA et al.. Structural Modification of the Natural Product Valerenic Acid Tunes RXR Homodimer Agonism. ChemMedChem. 2023", "claim": "PubMed-indexed evidence involving Valerian Root", "title": "Structural Modification of the Natural Product Valerenic Acid Tunes RXR Homodimer Agonism", "authors": "Zaienne D, Isigkeit L, Marschner JA et al.", "journal": "ChemMedChem", "year": 2023, "pmid": "37697963", "url": "https://pubmed.ncbi.nlm.nih.gov/37697963/", "study_type": "review", "confidence": "verify", "doi": "10.1002/cmdc.202300404", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37697963/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "valerian-root" }, { "id": "7B56DA79-64D1-48EC-BDF1-8AB9848E0D0B", "name": "Passionflower", "alternateNames": [ "Passiflora incarnata" ], "category": "Herb", "subcategory": "Anxiolytic Herb", "overview": "Gentle calming herb for anxiety and sleep with fewer side effects than valerian.", "mechanismOfAction": "Chrysin and other flavonoids bind GABA-A benzodiazepine receptors. Also inhibits MAO and modulates GABA reuptake.", "commonBenefits": [ "Anxiety relief", "Sleep support", "Calm without sedation" ], "commonDosageRange": "200-400 mg daily", "recommendedForm": "Standardized extract", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Can take during the day for anxiety or before bed for sleep" }, "evidenceRating": "moderate", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Drowsiness", "Dizziness", "Rarely nausea" ], "contraindications": [ "MAOIs", "Sedatives", "Pregnancy" ], "iconName": "leaf.circle.fill", "colorHex": "34D399", "tags": [ "anxiety", "sleep", "calming" ], "sources": [ { "claim": "Systematic review of Passiflora incarnata in neuropsychiatric disorders", "title": "Passiflora incarnata in Neuropsychiatric Disorders-A Systematic Review", "authors": "Janda K et al.", "journal": "Complementary Therapies in Medicine", "year": 2020, "pmid": "33352740", "url": "https://pubmed.ncbi.nlm.nih.gov/33352740/", "study_type": "review", "key_finding": "Majority of clinical trials (9 total) found reduced anxiety levels following Passiflora incarnata; no adverse effects including memory loss or psychometric function collapse observed.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33352740/", "publicSourceType": "PMID" }, { "claim": "RCT: Passionflower comparable to oxazepam for generalized anxiety disorder", "title": "Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam", "authors": "Akhondzadeh S et al.", "journal": "Journal of Clinical Pharmacy and Therapeutics", "year": 2001, "pmid": "11679026", "url": "https://pubmed.ncbi.nlm.nih.gov/11679026/", "study_type": "RCT", "key_finding": "Passiflora extract and oxazepam were equally effective in treating GAD; passionflower showed significantly lower job performance impairment than the benzodiazepine.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11679026/", "publicSourceType": "PMID" }, { "claim": "RCT: Passionflower improves polysomnographic sleep parameters", "title": "Effects of Passiflora incarnata Linnaeus on polysomnographic sleep parameters in subjects with insomnia disorder: a double-blind randomized placebo-controlled study", "authors": "Lee J et al.", "journal": "International Clinical Psychopharmacology", "year": 2020, "pmid": "31714321", "url": "https://pubmed.ncbi.nlm.nih.gov/31714321/", "study_type": "RCT", "key_finding": "Total sleep time was significantly increased in the passionflower group compared to placebo in a double-blind RCT with 110 participants.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31714321/", "publicSourceType": "PMID" }, { "claim": "GABA-A receptor modulation by Passiflora incarnata flavonoids", "title": "Modulation of the gamma-aminobutyric acid (GABA) system by Passiflora incarnata L.", "authors": "Appel K et al.", "journal": "Phytotherapy Research", "year": 2011, "pmid": "21089181", "url": "https://pubmed.ncbi.nlm.nih.gov/21089181/", "study_type": "review", "key_finding": "Whole passionflower extract induced dose-dependent direct GABA-A currents in hippocampal slices; GABA itself is a prominent ingredient of the extract.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21089181/", "publicSourceType": "PMID" }, { "claim": "Chrysin acts as partial agonist at central benzodiazepine receptors", "title": "Possible anxiolytic effects of chrysin, a central benzodiazepine receptor ligand isolated from Passiflora coerulea", "authors": "Medina JH et al.", "journal": "Pharmacology Biochemistry and Behavior", "year": 1990, "pmid": "7906886", "url": "https://pubmed.ncbi.nlm.nih.gov/7906886/", "study_type": "RCT", "key_finding": "Chrysin (5,7-dihydroxyflavone) displaces benzodiazepine receptor binding and produces anxiolytic effects without sedation, suggesting partial agonist activity at GABA-A BDZ sites.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7906886/", "publicSourceType": "PMID" }, { "claim": "Ethnopharmacology, clinical application, and safety evaluation", "title": "Passiflora incarnata L.: ethnopharmacology, clinical application, safety and evaluation of clinical trials", "authors": "Miroddi M et al.", "journal": "Journal of Ethnopharmacology", "year": 2013, "pmid": "24140586", "url": "https://pubmed.ncbi.nlm.nih.gov/24140586/", "study_type": "review", "key_finding": "Clinical trials support passionflower for anxiety and sleep; overall safe with no reported hepatotoxicity; limited but growing evidence base.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24140586/", "publicSourceType": "PMID" }, { "text": "Carminati M, Tondello M, Zanardi R. Passiflora incarnata L., herba, in benzodiazepine tapering: long-term safety and efficacy in a real-world setting. Frontiers in psychiatry. 2024", "pmid": "39429529", "doi": "10.3389/fpsyt.2024.1471083", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39429529/", "publicSourceType": "PMID" }, { "text": "Akhondzadeh S, Kashani L, Mobaseri M et al.. Passionflower in the treatment of opiates withdrawal: a double-blind randomized controlled trial. Journal of clinical pharmacy and therapeutics. 2001", "pmid": "11679027", "doi": "10.1046/j.1365-2710.2001.00366.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11679027/", "publicSourceType": "PMID" }, { "claim": "Passiflora incarnata reduces anxiety during dental procedures similar to pharmaceutical anxiolytics", "title": "Effects of passiflora incarnata and midazolam for control of anxiety in patients undergoing dental extraction", "authors": "Dantas LP, de Oliveira-Ribeiro A, de Almeida-Souza LM, Groppo FC", "journal": "Med Oral Patol Oral Cir Bucal", "year": 2017, "pmid": "27918731", "url": "https://pubmed.ncbi.nlm.nih.gov/27918731/", "study_type": "rct", "key_finding": "Double-blind crossover RCT of 40 volunteers found Passiflora incarnata showed anxiolytic effect similar to midazolam for conscious sedation during dental extraction, without the amnesia side effect of midazolam.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27918731/", "publicSourceType": "PMID" }, { "claim": "Passiflora incarnata reduces anxiety during tooth extraction procedures", "title": "Effects of Passiflora incarnata and Valeriana officinalis in the control of anxiety due to tooth extraction: a randomized controlled clinical trial", "authors": "Velasquez ACA, Tsuji M, Dos Santos Cordeiro L et al.", "journal": "Oral Maxillofac Surg", "year": 2024, "pmid": "38743126", "url": "https://pubmed.ncbi.nlm.nih.gov/38743126/", "study_type": "rct", "key_finding": "Triple-blind RCT of 54 patients found both Passiflora incarnata and Valeriana officinalis significantly reduced state anxiety scores compared to placebo during third molar extraction.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38743126/", "publicSourceType": "PMID" }, { "text": "Christoffoli MT, Bachesk AB, Farah GJ et al.. Assessment of Passiflora incarnata L for conscious sedation of patients during the extraction of mandibular third molars: a randomized, split-mouth, double-blind, crossover study. Quintessence international (Berlin, Germany : 1985). 2021", "claim": "PubMed-indexed evidence involving Passionflower", "title": "Assessment of Passiflora incarnata L for conscious sedation of patients during the extraction of mandibular third molars: a randomized, split-mouth, double-blind, crossover study", "authors": "Christoffoli MT, Bachesk AB, Farah GJ et al.", "journal": "Quintessence international (Berlin, Germany : 1985)", "year": 2021, "pmid": "34076379", "url": "https://pubmed.ncbi.nlm.nih.gov/34076379/", "study_type": "RCT", "confidence": "verify", "doi": "10.3290/j.qi.b1492199", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34076379/", "publicSourceType": "PMID" }, { "text": "Movafegh A, Alizadeh R, Hajimohamadi F et al.. Preoperative oral Passiflora incarnata reduces anxiety in ambulatory surgery patients: a double-blind, placebo-controlled study. Anesthesia and analgesia. 2008", "claim": "PubMed-indexed evidence involving Passionflower", "title": "Preoperative oral Passiflora incarnata reduces anxiety in ambulatory surgery patients: a double-blind, placebo-controlled study", "authors": "Movafegh A, Alizadeh R, Hajimohamadi F et al.", "journal": "Anesthesia and analgesia", "year": 2008, "pmid": "18499602", "url": "https://pubmed.ncbi.nlm.nih.gov/18499602/", "study_type": "RCT", "confidence": "verify", "doi": "10.1213/ane.0b013e318172c3f9", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18499602/", "publicSourceType": "PMID" }, { "text": "Fisher AA, Purcell P, Le Couteur DG. Toxicity of Passiflora incarnata L. Journal of toxicology. Clinical toxicology. 2000", "claim": "PubMed-indexed evidence involving Passionflower", "title": "Toxicity of Passiflora incarnata L", "authors": "Fisher AA, Purcell P, Le Couteur DG", "journal": "Journal of toxicology. Clinical toxicology", "year": 2000, "pmid": "10696928", "url": "https://pubmed.ncbi.nlm.nih.gov/10696928/", "study_type": "review", "confidence": "verify", "doi": "10.1081/clt-100100919", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10696928/", "publicSourceType": "PMID" }, { "text": "Carminati M, Tondello M, Zappia M et al.. Synergistic Effect of Passiflora incarnata L., Herba and Cognitive Behavioural Therapy in the Management of Benzodiazepine Misuse. Pharmaceuticals (Basel, Switzerland). 2026", "claim": "PubMed-indexed evidence involving Passionflower", "title": "Synergistic Effect of Passiflora incarnata L., Herba and Cognitive Behavioural Therapy in the Management of Benzodiazepine Misuse", "authors": "Carminati M, Tondello M, Zappia M et al.", "journal": "Pharmaceuticals (Basel, Switzerland)", "year": 2026, "pmid": "41599739", "url": "https://pubmed.ncbi.nlm.nih.gov/41599739/", "study_type": "review", "confidence": "verify", "doi": "10.3390/ph19010141", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41599739/", "publicSourceType": "PMID" }, { "text": "Brouns A, Lechtenberg M, Hensel A. Passionflower (Passiflora incarnata): Quality of Food Supplements Versus Registered Herbal Medicinal Products. Planta medica. 2025", "claim": "PubMed-indexed evidence involving Passionflower", "title": "Passionflower (Passiflora incarnata): Quality of Food Supplements Versus Registered Herbal Medicinal Products", "authors": "Brouns A, Lechtenberg M, Hensel A", "journal": "Planta medica", "year": 2025, "pmid": "40245939", "url": "https://pubmed.ncbi.nlm.nih.gov/40245939/", "study_type": "review", "confidence": "verify", "doi": "10.1055/a-2591-3765", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40245939/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "passionflower" }, { "id": "4BABA54C-7E25-4CF5-A4FE-7FD89CFEDD91", "name": "Saw Palmetto", "alternateNames": [ "Serenoa repens" ], "category": "Herb", "subcategory": "Prostate Support Herb", "overview": "Berry extract traditionally used for prostate and urinary symptoms; larger reviews find mixed-to-negative evidence for BPH symptom relief.", "mechanismOfAction": "Saw palmetto extracts may weakly influence androgen and inflammatory pathways in vitro, but clinically meaningful androgen-pathway effects and urinary benefit are not well established.", "commonBenefits": [ "Prostate symptom support (mixed evidence)", "Urinary symptom support (not established)" ], "commonDosageRange": "320 mg daily", "recommendedForm": "Liposterolic extract (standardized to 85-95% fatty acids)", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with fat-containing meal" }, "evidenceRating": "insufficient", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Mild GI", "Headache", "Decreased libido (rare)" ], "contraindications": [ "Hormone-sensitive conditions", "Blood thinners", "Oral contraceptives" ], "iconName": "cross.case.fill", "colorHex": "34D399", "tags": [ "prostate", "hormonal", "urinary" ], "sources": [ { "claim": "Cochrane review: Serenoa repens monotherapy for BPH", "title": "Serenoa repens monotherapy for benign prostatic hyperplasia (BPH): an updated Cochrane systematic review", "authors": "Tacklind J et al.", "journal": "BJU International", "year": 2012, "pmid": "22551330", "url": "https://pubmed.ncbi.nlm.nih.gov/22551330/", "study_type": "meta-analysis", "key_finding": "Serenoa repens therapy does not improve LUTS or maximum urinary flow compared with placebo, even at double and triple the usual dose in recent well-designed trials.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22551330/", "publicSourceType": "PMID" }, { "claim": "Meta-analysis of Permixon (hexanic extract) for LUTS/BPH", "title": "Efficacy and safety of a hexanic extract of Serenoa repens (Permixon) for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH): systematic review and meta-analysis", "authors": "Vela-Navarrete R et al.", "journal": "BJU International", "year": 2018, "pmid": "29694707", "url": "https://pubmed.ncbi.nlm.nih.gov/29694707/", "study_type": "meta-analysis", "key_finding": "Some extract-specific meta-analyses report modest nocturia or urinary-flow improvements, but findings conflict with Cochrane/placebo-controlled evidence and should not be generalized to all saw palmetto products.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29694707/", "publicSourceType": "PMID" }, { "claim": "Pharmacological effects of saw palmetto remain clinically uncertain", "title": "Pharmacological effects of saw palmetto extract in the lower urinary tract", "authors": "Pais P", "journal": "Acta Pharmacologica Sinica", "year": 2009, "pmid": "19262550", "url": "https://pubmed.ncbi.nlm.nih.gov/19262550/", "study_type": "review", "key_finding": "Mechanistic reviews describe possible 5-alpha-reductase, androgen-receptor, and anti-inflammatory effects, but clinical relevance for symptom improvement remains uncertain.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19262550/", "publicSourceType": "PMID" }, { "claim": "Systematic review of adverse events with Serenoa repens", "title": "Serenoa repens (saw palmetto): a systematic review of adverse events", "authors": "Agbabiaka TB et al.", "journal": "Drug Safety", "year": 2009, "pmid": "19591529", "url": "https://pubmed.ncbi.nlm.nih.gov/19591529/", "study_type": "review", "key_finding": "Adverse events are mild and similar to placebo, including abdominal pain, diarrhea, nausea, fatigue, headache, and decreased libido (rare).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19591529/", "publicSourceType": "PMID" }, { "claim": "Detailed safety assessment of saw palmetto extract", "title": "A detailed safety assessment of a saw palmetto extract", "authors": "Avins AL et al.", "journal": "Complementary Therapies in Medicine", "year": 2008, "pmid": "18534327", "url": "https://pubmed.ncbi.nlm.nih.gov/18534327/", "study_type": "RCT", "key_finding": "No evidence for serious toxicity of saw palmetto extract in a well-conducted clinical trial; safety profile comparable to placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18534327/", "publicSourceType": "PMID" }, { "text": "Evron E, Juhasz M, Babadjouni A et al.. Natural Hair Supplement: Friend or Foe? Saw Palmetto, a Systematic Review in Alopecia. Skin appendage disorders. 2020", "pmid": "33313047", "doi": "10.1159/000509905", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33313047/", "publicSourceType": "PMID" }, { "text": "Avins AL, Bent S. Saw palmetto and lower urinary tract symptoms: what is the latest evidence?. Current urology reports. 2006", "pmid": "16930496", "doi": "10.1007/s11934-996-0004-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16930496/", "publicSourceType": "PMID" }, { "claim": "Mixed evidence on Serenoa repens for LUTS/BPH", "title": "Efficacy and safety of Serenoa repens in patients with lower urinary tract symptoms: A systematic review and meta-analysis.", "authors": "Vela-Navarrete R, Alcaraz A et al.", "journal": "Journal of Urology", "year": 2024, "pmid": "38164033", "url": "https://pubmed.ncbi.nlm.nih.gov/38164033/", "study_type": "meta-analysis", "key_finding": "Some meta-analyses report improvements in LUTS measures, while higher-quality placebo-controlled reviews have found no clinically important benefit; present as mixed evidence, not established BPH treatment.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38164033/", "publicSourceType": "PMID" }, { "claim": "Serenoa repens versus finasteride evidence is not sufficient to claim equivalence", "title": "Serenoa repens vs. finasteride for treatment of benign prostatic hyperplasia: A systematic review and meta-analysis.", "authors": "Zhang W, Wang X et al.", "journal": "Medicine", "year": 2022, "pmid": "35165019", "url": "https://pubmed.ncbi.nlm.nih.gov/35165019/", "study_type": "meta-analysis", "key_finding": "Comparative analyses report similar symptom scores in included trials, but this does not overcome the broader mixed placebo-controlled evidence or support an app-level equivalence claim.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35165019/", "publicSourceType": "PMID" }, { "claim": "Mixed RCT meta-analysis findings for saw palmetto and nocturia/BPH symptoms", "title": "Impact of Serenoa repens on urinary symptoms and quality of life in men with BPH: A meta-analysis of randomized controlled trials.", "authors": "Shi RJ, Zhang LL et al.", "journal": "American Journal of Men's Health", "year": 2022, "pmid": "34933534", "url": "https://pubmed.ncbi.nlm.nih.gov/34933534/", "study_type": "meta-analysis", "key_finding": "Some RCT meta-analyses report nocturia or symptom-score improvements, but results are extract-specific and conflict with negative Cochrane evidence.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34933534/", "publicSourceType": "PMID" }, { "text": "Novara G, Giannarini G, Alcaraz A et al.. Efficacy and Safety of Hexanic Lipidosterolic Extract of Serenoa repens (Permixon) in the Treatment of Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia: Systematic Review and Meta-analysis of Randomized Controlled Trials. European urology focus. 2016", "claim": "PubMed-indexed evidence involving Saw Palmetto", "title": "Efficacy and Safety of Hexanic Lipidosterolic Extract of Serenoa repens (Permixon) in the Treatment of Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia: Systematic Review and Meta-analysis of Randomized Controlled Trials", "authors": "Novara G, Giannarini G, Alcaraz A et al.", "journal": "European urology focus", "year": 2016, "pmid": "28723522", "url": "https://pubmed.ncbi.nlm.nih.gov/28723522/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.euf.2016.04.002", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28723522/", "publicSourceType": "PMID" }, { "text": "Russo GI, Scandura C, Di Mauro M et al.. Clinical Efficacy of Serenoa repens Versus Placebo Versus Alpha-blockers for the Treatment of Lower Urinary Tract Symptoms/Benign Prostatic Enlargement: A Systematic Review and Network Meta-analysis of Randomized Placebo-controlled Clinical Trials. European urology focus. 2021", "claim": "PubMed-indexed evidence involving Saw Palmetto", "title": "Clinical Efficacy of Serenoa repens Versus Placebo Versus Alpha-blockers for the Treatment of Lower Urinary Tract Symptoms/Benign Prostatic Enlargement: A Systematic Review and Network Meta-analysis of Randomized Placebo-controlled Clinical Trials", "authors": "Russo GI, Scandura C, Di Mauro M et al.", "journal": "European urology focus", "year": 2021, "pmid": "31952967", "url": "https://pubmed.ncbi.nlm.nih.gov/31952967/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.euf.2020.01.002", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31952967/", "publicSourceType": "PMID" }, { "text": "Schwartzmann I, Redondo A, Farré A et al.. Efficacy and safety of Serenoa repens in benign prostatic disorders: a systematic review of recent clinical evidence. Drugs in context. 2026", "claim": "PubMed-indexed evidence involving Saw Palmetto", "title": "Efficacy and safety of Serenoa repens in benign prostatic disorders: a systematic review of recent clinical evidence", "authors": "Schwartzmann I, Redondo A, Farré A et al.", "journal": "Drugs in context", "year": 2026, "pmid": "42157952", "url": "https://pubmed.ncbi.nlm.nih.gov/42157952/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7573/dic.2025-10-2", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/42157952/", "publicSourceType": "PMID" }, { "text": "Wilt TJ, Ishani A, Stark G et al.. Saw palmetto extracts for treatment of benign prostatic hyperplasia: a systematic review. JAMA. 1998", "claim": "PubMed-indexed evidence involving Saw Palmetto", "title": "Saw palmetto extracts for treatment of benign prostatic hyperplasia: a systematic review", "authors": "Wilt TJ, Ishani A, Stark G et al.", "journal": "JAMA", "year": 1998, "pmid": "9820264", "url": "https://pubmed.ncbi.nlm.nih.gov/9820264/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1001/jama.280.18.1604", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9820264/", "publicSourceType": "PMID" }, { "text": "Nguyen KT, Verma KK, Matthew E et al.. The Over-The-Counter Finasteride Alternative: A Critical Review of Saw Palmetto's Efficacy, Safety, and Regulatory Concerns. International journal of dermatology. 2026", "claim": "PubMed-indexed evidence involving Saw Palmetto", "title": "The Over-The-Counter Finasteride Alternative: A Critical Review of Saw Palmetto's Efficacy, Safety, and Regulatory Concerns", "authors": "Nguyen KT, Verma KK, Matthew E et al.", "journal": "International journal of dermatology", "year": 2026, "pmid": "40928144", "url": "https://pubmed.ncbi.nlm.nih.gov/40928144/", "study_type": "review", "confidence": "verify", "doi": "10.1111/ijd.17987", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40928144/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "saw-palmetto" }, { "id": "A5106AE7-0D5B-4D08-83F4-E55FE650403F", "name": "Echinacea", "alternateNames": [ "Echinacea purpurea", "Purple Coneflower" ], "category": "Herb", "subcategory": "Immune-Stimulating Herb", "overview": "Popular immune-stimulating herb used at the onset of colds.", "mechanismOfAction": "Alkamides and polysaccharides activate macrophages, NK cells, and increase phagocytosis. Modulates TNF-alpha and interleukin production.", "commonBenefits": [ "Immune stimulation", "Cold/flu duration reduction", "Upper respiratory support" ], "commonDosageRange": "300-500 mg 3x daily (at onset of illness)", "recommendedForm": "Echinacea purpurea aerial parts extract", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Start at first sign of illness; use for 7-10 days max" }, "evidenceRating": "moderate", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Allergic reactions (ragweed family)", "GI upset", "Dizziness" ], "contraindications": [ "Autoimmune diseases", "Immunosuppressant drugs", "Ragweed allergy" ], "iconName": "allergens.fill", "colorHex": "34D399", "tags": [ "immune", "cold-flu", "acute" ], "sources": [ { "claim": "Meta-analysis: Echinacea reduces odds of developing common cold and shortens duration", "title": "Evaluation of echinacea for the prevention and treatment of the common cold: a meta-analysis", "authors": "Shah SA et al.", "journal": "The Lancet Infectious Diseases", "year": 2007, "pmid": "17597571", "url": "https://pubmed.ncbi.nlm.nih.gov/17597571/", "study_type": "meta-analysis", "key_finding": "Echinacea decreased the odds of developing the common cold by 58% (OR 0.42) and reduced cold duration by 1.4 days across 14 unique studies.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17597571/", "publicSourceType": "PMID" }, { "claim": "Cochrane review of Echinacea for preventing and treating common cold", "title": "Echinacea for preventing and treating the common cold", "authors": "Karsch-Volk M et al.", "journal": "Cochrane Database of Systematic Reviews", "year": 2014, "pmid": "24554461", "url": "https://pubmed.ncbi.nlm.nih.gov/24554461/", "study_type": "meta-analysis", "key_finding": "Echinacea purpurea is the most consistently useful variety, effective in 5 of 6 treatment trials; moderate evidence supports its use for treatment of URI.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24554461/", "publicSourceType": "PMID" }, { "claim": "Immunomodulation with echinacea: systematic review of controlled clinical trials", "title": "Immunomodulation with echinacea - a systematic review of controlled clinical trials", "authors": "Block KI et al.", "journal": "Integrative Cancer Therapies", "year": 2003, "pmid": "23195946", "url": "https://pubmed.ncbi.nlm.nih.gov/23195946/", "study_type": "review", "key_finding": "Macrophage activation was demonstrated most convincingly, including enhanced phagocytotic indices and macrophage-derived cytokine concentrations.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23195946/", "publicSourceType": "PMID" }, { "claim": "Echinacea activates NK cell cytotoxicity and enhances innate immunity", "title": "Enhancement of innate and adaptive immune functions by multiple Echinacea species", "authors": "Zhai Z et al.", "journal": "Journal of Medicinal Food", "year": 2007, "pmid": "17887935", "url": "https://pubmed.ncbi.nlm.nih.gov/17887935/", "study_type": "RCT", "key_finding": "Echinacea extracts are potent activators of NK cell cytotoxicity, stimulate production of IL-6, TNF, IL-12, and NO from macrophages via ERK, p38, JNK, and NF-kappaB pathways.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17887935/", "publicSourceType": "PMID" }, { "claim": "Safety assessment of oral Echinacea preparations", "title": "Review and Assessment of Medicinal Safety Data of Orally Used Echinacea Preparations", "authors": "Ardjomand-Woelkart K et al.", "journal": "Planta Medica", "year": 2016, "pmid": "26441065", "url": "https://pubmed.ncbi.nlm.nih.gov/26441065/", "study_type": "review", "key_finding": "Adverse events during clinical trials were generally mild and mostly without causality; long-term use up to 6 months showed no toxicological concerns.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26441065/", "publicSourceType": "PMID" }, { "text": "Burlou-Nagy C, Bănică F, Jurca T et al.. Echinacea purpurea (L.) Moench: Biological and Pharmacological Properties. A Review. Plants (Basel, Switzerland). 2022", "pmid": "35567246", "doi": "10.3390/plants11091244", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35567246/", "publicSourceType": "PMID" }, { "text": "Ross SM. Echinacea purpurea: A Proprietary Extract of Echinacea purpurea Is Shown to be Safe and Effective in the Prevention of the Common Cold. Holistic nursing practice. 2016", "pmid": "26633727", "doi": "10.1097/HNP.0000000000000130", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26633727/", "publicSourceType": "PMID" }, { "claim": "Echinacea prevents and treats upper respiratory tract infections", "title": "Echinacea for the prevention and treatment of upper respiratory tract infections: A systematic review and meta-analysis", "authors": "David S, Cunningham R", "journal": "Complementary Therapies in Medicine", "year": 2019, "pmid": "31126553", "url": "https://pubmed.ncbi.nlm.nih.gov/31126553/", "study_type": "meta-analysis", "key_finding": "Echinacea extracts significantly reduced the risk of developing upper respiratory tract infections and decreased symptom duration when used for both prevention and treatment.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31126553/", "publicSourceType": "PMID" }, { "claim": "Echinacea purpurea is effective for upper respiratory infections in children", "title": "Efficacy and safety of Echinacea purpurea in treating upper respiratory infections and complications of otitis media in children: Systematic review and meta-analysis", "authors": "Pham TP, Vu TM, Doan PM et al.", "journal": "Clinical Nutrition ESPEN", "year": 2025, "pmid": "40311928", "url": "https://pubmed.ncbi.nlm.nih.gov/40311928/", "study_type": "meta-analysis", "key_finding": "Echinacea purpurea was effective and safe for treating upper respiratory infections in children, reducing symptom severity and duration with a favorable safety profile.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40311928/", "publicSourceType": "PMID" }, { "text": "Gancitano G, Mucci N, Stange R et al.. Echinacea Reduces Antibiotics by Preventing Respiratory Infections: A Meta-Analysis (ERA-PRIMA). Antibiotics (Basel, Switzerland). 2024", "claim": "PubMed-indexed evidence involving Echinacea", "title": "Echinacea Reduces Antibiotics by Preventing Respiratory Infections: A Meta-Analysis (ERA-PRIMA)", "authors": "Gancitano G, Mucci N, Stange R et al.", "journal": "Antibiotics (Basel, Switzerland)", "year": 2024, "pmid": "38667040", "url": "https://pubmed.ncbi.nlm.nih.gov/38667040/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/antibiotics13040364", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38667040/", "publicSourceType": "PMID" }, { "text": "Deccy S, Bartkowiak C, Rodricks N et al.. Echinacea Supplementation Does Not Impact Aerobic Capacity and Erythropoiesis in Athletes: A Meta-Analysis. Nutrients. 2024", "claim": "PubMed-indexed evidence involving Echinacea", "title": "Echinacea Supplementation Does Not Impact Aerobic Capacity and Erythropoiesis in Athletes: A Meta-Analysis", "authors": "Deccy S, Bartkowiak C, Rodricks N et al.", "journal": "Nutrients", "year": 2024, "pmid": "38999738", "url": "https://pubmed.ncbi.nlm.nih.gov/38999738/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu16131991", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38999738/", "publicSourceType": "PMID" }, { "text": "Schoop R, Klein P, Suter A et al.. Echinacea in the prevention of induced rhinovirus colds: a meta-analysis. Clinical therapeutics. 2006", "claim": "PubMed-indexed evidence involving Echinacea", "title": "Echinacea in the prevention of induced rhinovirus colds: a meta-analysis", "authors": "Schoop R, Klein P, Suter A et al.", "journal": "Clinical therapeutics", "year": 2006, "pmid": "16678640", "url": "https://pubmed.ncbi.nlm.nih.gov/16678640/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.clinthera.2006.02.001", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16678640/", "publicSourceType": "PMID" }, { "text": "Xu W, Zhu H, Hu B et al.. Echinacea in hepatopathy: A review of its phytochemistry, pharmacology, and safety. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2021", "claim": "PubMed-indexed evidence involving Echinacea", "title": "Echinacea in hepatopathy: A review of its phytochemistry, pharmacology, and safety", "authors": "Xu W, Zhu H, Hu B et al.", "journal": "Phytomedicine : international journal of phytotherapy and phytopharmacology", "year": 2021, "pmid": "34029938", "url": "https://pubmed.ncbi.nlm.nih.gov/34029938/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.phymed.2021.153572", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34029938/", "publicSourceType": "PMID" }, { "text": "Ahmadi F. Phytochemistry, Mechanisms, and Preclinical Studies of Echinacea Extracts in Modulating Immune Responses to Bacterial and Viral Infections: A Comprehensive Review. Antibiotics (Basel, Switzerland). 2024", "claim": "PubMed-indexed evidence involving Echinacea", "title": "Phytochemistry, Mechanisms, and Preclinical Studies of Echinacea Extracts in Modulating Immune Responses to Bacterial and Viral Infections: A Comprehensive Review", "authors": "Ahmadi F", "journal": "Antibiotics (Basel, Switzerland)", "year": 2024, "pmid": "39452214", "url": "https://pubmed.ncbi.nlm.nih.gov/39452214/", "study_type": "review", "confidence": "verify", "doi": "10.3390/antibiotics13100947", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39452214/", "publicSourceType": "PMID" }, { "text": "Moltó J, Valle M, Miranda C et al.. Herb-drug interaction between Echinacea purpurea and etravirine in HIV-infected patients. Antimicrobial agents and chemotherapy. 2012", "claim": "PubMed-indexed evidence involving Echinacea", "title": "Herb-drug interaction between Echinacea purpurea and etravirine in HIV-infected patients", "authors": "Moltó J, Valle M, Miranda C et al.", "journal": "Antimicrobial agents and chemotherapy", "year": 2012, "pmid": "22869560", "url": "https://pubmed.ncbi.nlm.nih.gov/22869560/", "study_type": "RCT", "confidence": "verify", "doi": "10.1128/AAC.01205-12", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22869560/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "echinacea" }, { "id": "49718D57-6280-4101-AC48-FB35AB206C18", "name": "Elderberry", "alternateNames": [ "Sambucus nigra", "Black Elder" ], "category": "Herb", "subcategory": "Antiviral Berry", "overview": "Rich in anthocyanins with antiviral properties, popular for cold and flu support.", "mechanismOfAction": "Anthocyanins and flavonoids inhibit viral neuraminidase (similar to oseltamivir), preventing viral entry into cells. Stimulates cytokine production for immune activation.", "commonBenefits": [ "Antiviral", "Immune support", "Cold/flu recovery" ], "commonDosageRange": "500-1,000 mg daily during illness", "recommendedForm": "Standardized extract (elderberry syrup or capsules)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Raw elderberries are toxic, use prepared extracts only" }, "evidenceRating": "moderate", "foodSources": [ "Elderberries (cooked)" ], "deficiencySymptoms": [], "sideEffects": [ "GI upset", "Allergic reactions (rare)" ], "contraindications": [ "Autoimmune diseases", "Immunosuppressants", "Never eat raw elderberries" ], "iconName": "leaf.arrow.circlepath", "colorHex": "34D399", "tags": [ "immune", "antiviral", "cold-flu" ], "sources": [ { "claim": "Meta-analysis of elderberry for upper respiratory symptoms", "title": "Black elderberry (Sambucus nigra) supplementation effectively treats upper respiratory symptoms: A meta-analysis of randomized, controlled clinical trials", "authors": "Hawkins J et al.", "journal": "Complementary Therapies in Medicine", "year": 2019, "pmid": "30670267", "url": "https://pubmed.ncbi.nlm.nih.gov/30670267/", "study_type": "meta-analysis", "key_finding": "Elderberry supplementation substantially reduced upper respiratory symptoms in meta-analysis of randomized controlled clinical trials.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30670267/", "publicSourceType": "PMID" }, { "claim": "RCT of elderberry extract for influenza A and B", "title": "Randomized study of the efficacy and safety of oral elderberry extract in the treatment of influenza A and B virus infections", "authors": "Zakay-Rones Z et al.", "journal": "Journal of International Medical Research", "year": 2004, "pmid": "15080016", "url": "https://pubmed.ncbi.nlm.nih.gov/15080016/", "study_type": "RCT", "key_finding": "Elderberry extract reduced the duration of flu symptoms to 3-4 days compared to 7-8 days for placebo; rescue medication use was significantly less.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15080016/", "publicSourceType": "PMID" }, { "claim": "Systematic review of elderberry for viral respiratory illnesses", "title": "Elderberry for prevention and treatment of viral respiratory illnesses: a systematic review", "authors": "Wieland LS et al.", "journal": "BMC Complementary Medicine and Therapies", "year": 2021, "pmid": "33827515", "url": "https://pubmed.ncbi.nlm.nih.gov/33827515/", "study_type": "review", "key_finding": "Five RCTs included; elderberry may reduce duration and severity of colds and influenza, but evidence quality is uncertain and more research is needed.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33827515/", "publicSourceType": "PMID" }, { "claim": "Elderberry stimulates inflammatory cytokine production for immune activation", "title": "The effect of Sambucol, a black elderberry-based, natural product, on the production of human cytokines: I. Inflammatory cytokines", "authors": "Barak V et al.", "journal": "European Cytokine Network", "year": 2001, "pmid": "11399518", "url": "https://pubmed.ncbi.nlm.nih.gov/11399518/", "study_type": "RCT", "key_finding": "Sambucol increased inflammatory cytokine production (IL-1 beta, TNF-alpha, IL-6, IL-8) by 2-45 fold, activating the healthy immune system.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11399518/", "publicSourceType": "PMID" }, { "claim": "Elderberry flavonoids bind to and inhibit H1N1 influenza virus", "title": "Elderberry flavonoids bind to and prevent H1N1 infection in vitro", "authors": "Roschek B Jr et al.", "journal": "Phytochemistry", "year": 2009, "pmid": "19682714", "url": "https://pubmed.ncbi.nlm.nih.gov/19682714/", "study_type": "RCT", "key_finding": "Elderberry flavonoids bind to and inhibit H1N1 neuraminidase activity in vitro, comparable to Oseltamivir (Tamiflu) anti-influenza activity.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19682714/", "publicSourceType": "PMID" }, { "claim": "Safety and pros/cons of elderberry for immune support", "title": "The Pros and Cons of Using Elderberry (Sambucus nigra) for Prevention and Treatment of COVID-19", "authors": "Chen C et al.", "journal": "Complementary Therapies in Clinical Practice", "year": 2023, "pmid": "36518861", "url": "https://pubmed.ncbi.nlm.nih.gov/36518861/", "study_type": "review", "key_finding": "Elderberry may be a safe option for treating viral respiratory illness; no evidence it overstimulates the immune system. Raw berries contain toxic sambunigrin but cooked extracts are safe.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36518861/", "publicSourceType": "PMID" }, { "text": "Porter RS, Bode RF. A Review of the Antiviral Properties of Black Elder (Sambucus nigra L.) Products. Phytotherapy research : PTR. 2017", "pmid": "28198157", "doi": "10.1002/ptr.5782", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28198157/", "publicSourceType": "PMID" }, { "text": "Anusha Siddiqui S, Redha AA, Esmaeili Y et al.. Novel insights on extraction and encapsulation techniques of elderberry bioactive compounds. Critical reviews in food science and nutrition. 2023", "pmid": "35021911", "doi": "10.1080/10408398.2022.2026290", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35021911/", "publicSourceType": "PMID" }, { "claim": "Elderberry supplementation reduces cold duration and symptoms", "title": "Elderberry Supplementation Reduces Cold Duration and Symptoms in Air-Travellers: A Randomized, Double-Blind Placebo-Controlled Clinical Trial", "authors": "Tiralongo E, Wee SS, Lea RA", "journal": "Nutrients", "year": 2016, "pmid": "27023596", "doi": "10.3390/nu8040182", "study_type": "rct", "key_finding": "Reduced cold duration by 2 days and severity scores significantly", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27023596/", "publicSourceType": "PMID" }, { "text": "Kirichenko TV, Sobenin IA, Markina YV et al.. Clinical Effectiveness of a Combination of Black Elder Berries, Violet Herb, and Calendula Flowers in Chronic Obstructive Pulmonary Disease: The Results of a Double-Blinded Placebo-Controlled Study. Biology. 2020", "claim": "PubMed-indexed evidence involving Elderberry", "title": "Clinical Effectiveness of a Combination of Black Elder Berries, Violet Herb, and Calendula Flowers in Chronic Obstructive Pulmonary Disease: The Results of a Double-Blinded Placebo-Controlled Study", "authors": "Kirichenko TV, Sobenin IA, Markina YV et al.", "journal": "Biology", "year": 2020, "pmid": "32331341", "url": "https://pubmed.ncbi.nlm.nih.gov/32331341/", "study_type": "RCT", "confidence": "verify", "doi": "10.3390/biology9040083", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32331341/", "publicSourceType": "PMID" }, { "text": "Della Volpe A, Ricci G, Ralli M et al.. The effects of oral supplements with Sambucus nigra, Zinc, Tyndallized Lactobacillus acidophilus (HA122), Arabinogalactans, vitamin D, vitamin E and vitamin C in otitis media with effusion in children: a randomized controlled trial. European review for medical and pharmacological sciences. 2019", "claim": "PubMed-indexed evidence involving Elderberry", "title": "The effects of oral supplements with Sambucus nigra, Zinc, Tyndallized Lactobacillus acidophilus (HA122), Arabinogalactans, vitamin D, vitamin E and vitamin C in otitis media with effusion in children: a randomized controlled trial", "authors": "Della Volpe A, Ricci G, Ralli M et al.", "journal": "European review for medical and pharmacological sciences", "year": 2019, "pmid": "31364144", "url": "https://pubmed.ncbi.nlm.nih.gov/31364144/", "study_type": "RCT", "confidence": "verify", "doi": "10.26355/eurrev_201907_18460", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31364144/", "publicSourceType": "PMID" }, { "text": "Tiralongo E, Wee SS, Lea RA. Elderberry Supplementation Reduces Cold Duration and Symptoms in Air-Travellers: A Randomized, Double-Blind Placebo-Controlled Clinical Trial. Nutrients. 2016", "claim": "PubMed-indexed evidence involving Elderberry", "title": "Elderberry Supplementation Reduces Cold Duration and Symptoms in Air-Travellers: A Randomized, Double-Blind Placebo-Controlled Clinical Trial", "authors": "Tiralongo E, Wee SS, Lea RA", "journal": "Nutrients", "year": 2016, "pmid": "27023596", "url": "https://pubmed.ncbi.nlm.nih.gov/27023596/", "study_type": "RCT", "confidence": "verify", "doi": "10.3390/nu8040182", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27023596/", "publicSourceType": "PMID" }, { "text": "Osman AG, Avula B, Katragunta K et al.. Elderberry Extracts: Characterization of the Polyphenolic Chemical Composition, Quality Consistency, Safety, Adulteration, and Attenuation of Oxidative Stress- and Inflammation-Induced Health Disorders. Molecules (Basel, Switzerland). 2023", "claim": "PubMed-indexed evidence involving Elderberry", "title": "Elderberry Extracts: Characterization of the Polyphenolic Chemical Composition, Quality Consistency, Safety, Adulteration, and Attenuation of Oxidative Stress- and Inflammation-Induced Health Disorders", "authors": "Osman AG, Avula B, Katragunta K et al.", "journal": "Molecules (Basel, Switzerland)", "year": 2023, "pmid": "37049909", "url": "https://pubmed.ncbi.nlm.nih.gov/37049909/", "study_type": "review", "confidence": "verify", "doi": "10.3390/molecules28073148", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37049909/", "publicSourceType": "PMID" }, { "text": "Murkovic M, Abuja PM, Bergmann AR et al.. Effects of elderberry juice on fasting and postprandial serum lipids and low-density lipoprotein oxidation in healthy volunteers: a randomized, double-blind, placebo-controlled study. European journal of clinical nutrition. 2004", "claim": "PubMed-indexed evidence involving Elderberry", "title": "Effects of elderberry juice on fasting and postprandial serum lipids and low-density lipoprotein oxidation in healthy volunteers: a randomized, double-blind, placebo-controlled study", "authors": "Murkovic M, Abuja PM, Bergmann AR et al.", "journal": "European journal of clinical nutrition", "year": 2004, "pmid": "14749743", "url": "https://pubmed.ncbi.nlm.nih.gov/14749743/", "study_type": "RCT", "confidence": "verify", "doi": "10.1038/sj.ejcn.1601773", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14749743/", "publicSourceType": "PMID" }, { "text": "Strugała P, Loi S, Bażanów B et al.. A Comprehensive Study on the Biological Activity of Elderberry Extract and Cyanidin 3-O-Glucoside and Their Interactions with Membranes and Human Serum Albumin. Molecules (Basel, Switzerland). 2018", "claim": "PubMed-indexed evidence involving Elderberry", "title": "A Comprehensive Study on the Biological Activity of Elderberry Extract and Cyanidin 3-O-Glucoside and Their Interactions with Membranes and Human Serum Albumin", "authors": "Strugała P, Loi S, Bażanów B et al.", "journal": "Molecules (Basel, Switzerland)", "year": 2018, "pmid": "30297646", "url": "https://pubmed.ncbi.nlm.nih.gov/30297646/", "study_type": "review", "confidence": "verify", "doi": "10.3390/molecules23102566", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30297646/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "elderberry" }, { "id": "8AE05884-B6D9-4BFB-A2B5-892CA311DE57", "name": "Garlic Extract", "alternateNames": [ "Allium sativum", "Aged Garlic Extract" ], "category": "Herb", "subcategory": "Cardiovascular Herb", "overview": "Aged garlic extract supports cardiovascular health and immune function.", "mechanismOfAction": "Allicin and S-allyl cysteine inhibit HMG-CoA reductase (mild), reduce platelet aggregation, lower blood pressure via H2S and NO pathways, and provide antioxidant/antimicrobial effects.", "commonBenefits": [ "Cardiovascular health", "Blood pressure", "Cholesterol", "Immune support" ], "commonDosageRange": "600-1,200 mg daily (aged garlic extract)", "recommendedForm": "Aged garlic extract (Kyolic is well-studied)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with meals to reduce GI distress" }, "evidenceRating": "strong", "foodSources": [ "Garlic cloves" ], "deficiencySymptoms": [], "sideEffects": [ "Bad breath", "GI upset", "Increased bleeding risk" ], "contraindications": [ "Blood thinners", "Surgery (stop 2 weeks before)", "HIV protease inhibitors" ], "iconName": "heart.circle", "colorHex": "34D399", "tags": [ "cardiovascular", "blood-pressure", "immune" ], "sources": [ { "claim": "Dose-response meta-analysis of aged garlic on blood pressure and lipid profile", "title": "The Effect of Aged Garlic Supplementation on Blood Pressure and Lipid Profile: A Dose-Response Grade-Assessed Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Haghighatdoost F et al.", "journal": "Phytotherapy Research", "year": 2025, "pmid": "40628369", "url": "https://pubmed.ncbi.nlm.nih.gov/40628369/", "study_type": "meta-analysis", "key_finding": "Aged garlic significantly reduced systolic BP by 2.49 mmHg and LDL cholesterol by 4.41 mg/dL across 19 randomized controlled trials.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40628369/", "publicSourceType": "PMID" }, { "claim": "Meta-analysis and review of garlic for blood pressure, cholesterol, and immunity", "title": "Garlic Lowers Blood Pressure in Hypertensive Individuals, Regulates Serum Cholesterol, and Stimulates Immunity: An Updated Meta-analysis and Review", "authors": "Ried K", "journal": "Journal of Nutrition", "year": 2016, "pmid": "26764326", "url": "https://pubmed.ncbi.nlm.nih.gov/26764326/", "study_type": "meta-analysis", "key_finding": "Garlic supplements lowered systolic BP by 8.3 mmHg and diastolic BP by 5.5 mmHg in hypertensives, similarly to standard anti-hypertensive medications.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26764326/", "publicSourceType": "PMID" }, { "claim": "Kyolic aged garlic extract for blood pressure, arterial stiffness, and gut microbiota", "title": "The Effect of Kyolic Aged Garlic Extract on Gut Microbiota, Inflammation, and Cardiovascular Markers in Hypertensives: The GarGIC Trial", "authors": "Ried K et al.", "journal": "Frontiers in Nutrition", "year": 2018, "pmid": "30619868", "url": "https://pubmed.ncbi.nlm.nih.gov/30619868/", "study_type": "RCT", "key_finding": "Kyolic aged garlic extract effectively reduced central blood pressure, pulse pressure, and arterial stiffness while improving gut microbiota in hypertensive patients.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30619868/", "publicSourceType": "PMID" }, { "claim": "Aged garlic extract reduces blood pressure in uncontrolled hypertension", "title": "Aged garlic extract lowers blood pressure in patients with treated but uncontrolled hypertension: a randomised controlled trial", "authors": "Ried K et al.", "journal": "Maturitas", "year": 2010, "pmid": "20594781", "url": "https://pubmed.ncbi.nlm.nih.gov/20594781/", "study_type": "RCT", "key_finding": "Aged garlic extract is superior to placebo in lowering systolic blood pressure similarly to first-line medications in patients with treated but uncontrolled hypertension.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20594781/", "publicSourceType": "PMID" }, { "claim": "Allicin and garlic compound antimicrobial and antioxidant properties", "title": "Antimicrobial properties of allicin from garlic", "authors": "Ankri S et al.", "journal": "Microbes and Infection", "year": 1999, "pmid": "10594976", "url": "https://pubmed.ncbi.nlm.nih.gov/10594976/", "study_type": "review", "key_finding": "Allicin demonstrates broad-spectrum antibacterial activity against Gram-negative and Gram-positive bacteria, antifungal, antiparasitic, and antiviral properties via thiol-reactive mechanisms.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10594976/", "publicSourceType": "PMID" }, { "claim": "S-allyl cysteine antioxidant and cardioprotective properties in aged garlic", "title": "The antioxidant properties of garlic compounds: allyl cysteine, alliin, allicin, and allyl disulfide", "authors": "Chung LY", "journal": "Journal of Medicinal Food", "year": 2006, "pmid": "16822206", "url": "https://pubmed.ncbi.nlm.nih.gov/16822206/", "study_type": "review", "key_finding": "S-allyl cysteine, the most abundant bioactive in aged garlic extract, has potent antioxidant, anti-inflammatory, cardioprotective, and neuroprotective properties.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16822206/", "publicSourceType": "PMID" }, { "text": "Serrano JCE, Castro-Boqué E, García-Carrasco A et al.. Antihypertensive Effects of an Optimized Aged Garlic Extract in Subjects with Grade I Hypertension and Antihypertensive Drug Therapy: A Randomized, Triple-Blind Controlled Trial. Nutrients. 2023", "pmid": "37686723", "doi": "10.3390/nu15173691", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37686723/", "publicSourceType": "PMID" }, { "text": "Rauf A, Abu-Izneid T, Thiruvengadam M et al.. Garlic (Allium sativum L.): Its Chemistry, Nutritional Composition, Toxicity, and Anticancer Properties. Current topics in medicinal chemistry. 2022", "pmid": "34749610", "doi": "10.2174/1568026621666211105094939", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34749610/", "publicSourceType": "PMID" }, { "claim": "Aged garlic extract lowers blood pressure in hypertensive patients", "title": "Effects of aged garlic extract on blood pressure in hypertensive patients: A systematic review and meta-analysis of randomized controlled trials", "authors": "Saadh MJ, Kariem M, Shukla M et al.", "journal": "Prostaglandins & Other Lipid Mediators", "year": 2024, "pmid": "39437887", "url": "https://pubmed.ncbi.nlm.nih.gov/39437887/", "study_type": "meta-analysis", "key_finding": "Aged garlic extract supplementation significantly reduced both systolic and diastolic blood pressure in hypertensive patients compared to placebo across pooled RCTs.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39437887/", "publicSourceType": "PMID" }, { "claim": "Garlic extract improves lipid metabolism and reduces inflammation in CAD", "title": "Effect of garlic extract on markers of lipid metabolism and inflammation in coronary artery disease (CAD) patients: A systematic review and meta-analysis", "authors": "Gadidala SK, Johny E, Thomas C et al.", "journal": "Phytotherapy Research", "year": 2023, "pmid": "36640154", "url": "https://pubmed.ncbi.nlm.nih.gov/36640154/", "study_type": "meta-analysis", "key_finding": "Garlic extract supplementation significantly improved lipid markers (reducing total cholesterol and LDL) and inflammatory markers in patients with coronary artery disease.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36640154/", "publicSourceType": "PMID" }, { "claim": "Garlic supplementation reduces systemic inflammation", "title": "Effects of garlic supplementation on serum inflammatory markers: A systematic review and meta-analysis of randomized controlled trials", "authors": "Mirzavandi F, Mollahosseini M, Salehi-Abargouei A et al.", "journal": "Diabetes & Metabolic Syndrome", "year": 2020, "pmid": "32673835", "url": "https://pubmed.ncbi.nlm.nih.gov/32673835/", "study_type": "meta-analysis", "key_finding": "Garlic supplementation significantly reduced serum CRP, TNF-alpha, and IL-6 levels across randomized controlled trials, indicating broad anti-inflammatory effects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32673835/", "publicSourceType": "PMID" }, { "text": "Fu Z, Lv J, Gao X et al.. Effects of garlic supplementation on components of metabolic syndrome: a systematic review, meta-analysis, and meta-regression of randomized controlled trials. BMC complementary medicine and therapies. 2023", "claim": "PubMed-indexed evidence involving Garlic Extract", "title": "Effects of garlic supplementation on components of metabolic syndrome: a systematic review, meta-analysis, and meta-regression of randomized controlled trials", "authors": "Fu Z, Lv J, Gao X et al.", "journal": "BMC complementary medicine and therapies", "year": 2023, "pmid": "37481521", "url": "https://pubmed.ncbi.nlm.nih.gov/37481521/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12906-023-04038-0", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37481521/", "publicSourceType": "PMID" }, { "text": "Mollahosseini M, Hosseini-Marnani E, Panjeshahin A et al.. A systematic review of randomized controlled trials related to the effects of garlic supplementation on platelet aggregation. Phytotherapy research : PTR. 2022", "claim": "PubMed-indexed evidence involving Garlic Extract", "title": "A systematic review of randomized controlled trials related to the effects of garlic supplementation on platelet aggregation", "authors": "Mollahosseini M, Hosseini-Marnani E, Panjeshahin A et al.", "journal": "Phytotherapy research : PTR", "year": 2022, "pmid": "36222178", "url": "https://pubmed.ncbi.nlm.nih.gov/36222178/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/ptr.7556", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36222178/", "publicSourceType": "PMID" }, { "text": "Panjeshahin A, Mollahosseini M, Panbehkar-Jouybari M et al.. Effects of garlic supplementation on liver enzymes: A systematic review and meta-analysis of randomized controlled trials. Phytotherapy research : PTR. 2020", "claim": "PubMed-indexed evidence involving Garlic Extract", "title": "Effects of garlic supplementation on liver enzymes: A systematic review and meta-analysis of randomized controlled trials", "authors": "Panjeshahin A, Mollahosseini M, Panbehkar-Jouybari M et al.", "journal": "Phytotherapy research : PTR", "year": 2020, "pmid": "32135032", "url": "https://pubmed.ncbi.nlm.nih.gov/32135032/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/ptr.6659", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32135032/", "publicSourceType": "PMID" }, { "text": "Xiaohui L, Jinqi L, Xiaofang X et al.. Garlic supplementation for the treatment of chronic liver disease: a meta-analysis of randomized controlled trials. African health sciences. 2023", "claim": "PubMed-indexed evidence involving Garlic Extract", "title": "Garlic supplementation for the treatment of chronic liver disease: a meta-analysis of randomized controlled trials", "authors": "Xiaohui L, Jinqi L, Xiaofang X et al.", "journal": "African health sciences", "year": 2023, "pmid": "38223588", "url": "https://pubmed.ncbi.nlm.nih.gov/38223588/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.4314/ahs.v23i2.47", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38223588/", "publicSourceType": "PMID" }, { "text": "Freire de Carvalho J, Lerner A, Benzvi C. Garlic Extract in Rheumatological Diseases: A Systematic Review. Complementary medicine research. 2025", "claim": "PubMed-indexed evidence involving Garlic Extract", "title": "Garlic Extract in Rheumatological Diseases: A Systematic Review", "authors": "Freire de Carvalho J, Lerner A, Benzvi C", "journal": "Complementary medicine research", "year": 2025, "pmid": "40602379", "url": "https://pubmed.ncbi.nlm.nih.gov/40602379/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1159/000547181", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40602379/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "garlic-extract" }, { "id": "2AD03291-E1EF-4F78-AA42-3890D1EA08BE", "name": "Ginger Extract", "alternateNames": [ "Zingiber officinale" ], "category": "Herb", "subcategory": "Anti-Nausea Herb", "overview": "Warming root studied for nausea, digestion, and inflammatory-marker contexts.", "mechanismOfAction": "Gingerols and shogaols act on 5-HT3 serotonin receptors in the GI tract (antiemetic), inhibit COX-2 and LOX inflammatory enzymes, and enhance gastric motility.", "commonBenefits": [ "Nausea support", "Digestion", "Inflammatory-marker research" ], "commonDosageRange": "250-1,000 mg daily", "recommendedForm": "Standardized extract (5% gingerols)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with meals for digestive benefits" }, "evidenceRating": "strong", "foodSources": [ "Fresh ginger", "Dried ginger" ], "deficiencySymptoms": [], "sideEffects": [ "Heartburn", "Mild blood thinning", "Mouth irritation" ], "contraindications": [ "Blood thinners (high doses)", "Gallstone disease" ], "iconName": "flame.fill", "colorHex": "34D399", "tags": [ "digestion", "nausea", "anti-inflammatory" ], "sources": [ { "claim": "Comprehensive review of ginger health effects across 109 RCTs including nausea, pain, and metabolic benefits", "title": "Ginger on Human Health: A Comprehensive Systematic Review of 109 Randomized Controlled Trials", "authors": "Anh NH et al.", "journal": "Nutrients", "year": 2020, "pmid": "31935866", "url": "https://pubmed.ncbi.nlm.nih.gov/31935866/", "study_type": "review", "key_finding": "Systematic review of 109 RCTs showing promising efficacy of ginger for nausea/vomiting, metabolic syndrome, and pain management", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31935866/", "publicSourceType": "PMID" }, { "claim": "Anti-nausea efficacy for chemotherapy-induced nausea and vomiting", "title": "Does the Oral Administration of Ginger Reduce Chemotherapy-Induced Nausea and Vomiting?: A Meta-analysis of 10 Randomized Controlled Trials", "authors": "Saneei Totmaj A et al.", "journal": "Phytother Res", "year": 2019, "pmid": "30299420", "url": "https://pubmed.ncbi.nlm.nih.gov/30299420/", "study_type": "meta-analysis", "key_finding": "Ginger displayed significant efficacy in controlling chemotherapy-induced nausea and vomiting with an odds ratio of 0.71", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30299420/", "publicSourceType": "PMID" }, { "claim": "Anti-inflammatory mechanism via COX-2 and inflammatory marker reduction", "title": "Effect of ginger (Zingiber officinale) on inflammatory markers: A systematic review and meta-analysis of randomized controlled trials", "authors": "Jalali M et al.", "journal": "Phytother Res", "year": 2020, "pmid": "32763761", "url": "https://pubmed.ncbi.nlm.nih.gov/32763761/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 16 RCTs (1,010 participants) demonstrated significant reduction in CRP, hs-CRP, and TNF-alpha levels with ginger supplementation", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32763761/", "publicSourceType": "PMID" }, { "claim": "Gingerols inhibit COX-2 via p38 MAP kinase and NF-kappaB pathway", "title": "[6]-Gingerol inhibits COX-2 expression by blocking the activation of p38 MAP kinase and NF-kappaB in phorbol ester-stimulated mouse skin", "authors": "Kim SO et al.", "journal": "Oncogene", "year": 2005, "pmid": "15735738", "url": "https://pubmed.ncbi.nlm.nih.gov/15735738/", "study_type": "preclinical", "key_finding": "[6]-Gingerol inhibits TPA-induced COX-2 expression by blocking the p38 MAP kinase-NF-kappaB signaling pathway", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15735738/", "publicSourceType": "PMID" }, { "claim": "Efficacy and safety in osteoarthritis (anti-inflammatory application)", "title": "Efficacy and safety of ginger in osteoarthritis patients: a meta-analysis of randomized placebo-controlled trials", "authors": "Bartels EM et al.", "journal": "Osteoarthritis Cartilage", "year": 2015, "pmid": "25300574", "url": "https://pubmed.ncbi.nlm.nih.gov/25300574/", "study_type": "meta-analysis", "key_finding": "Ginger showed moderate efficacy for osteoarthritis pain relief with an acceptable safety profile", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25300574/", "publicSourceType": "PMID" }, { "claim": "Umbrella review of overall ginger safety and health effects in humans", "title": "Orally consumed ginger and human health: an umbrella review", "authors": "Anh NH et al.", "journal": "Crit Rev Food Sci Nutr", "year": 2022, "pmid": "35147170", "url": "https://pubmed.ncbi.nlm.nih.gov/35147170/", "study_type": "review", "key_finding": "Dietary consumption of ginger appears safe and may exert beneficial effects on human health and well-being across multiple conditions", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35147170/", "publicSourceType": "PMID" }, { "claim": "Ginger for gastrointestinal disorders including gastroparesis and digestion", "title": "Ginger in gastrointestinal disorders: A systematic review of clinical trials", "authors": "Nikkhah Bodagh M et al.", "journal": "Food Sci Nutr", "year": 2019, "pmid": "30680163", "url": "https://pubmed.ncbi.nlm.nih.gov/30680163/", "study_type": "review", "key_finding": "Systematic review showed ginger enhances gastric motility and has anti-nausea properties for various gastrointestinal conditions", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30680163/", "publicSourceType": "PMID" }, { "text": "Zhang S, Kou X, Zhao H et al.. Zingiber officinale var. rubrum: Red Ginger's Medicinal Uses. Molecules (Basel, Switzerland). 2022", "pmid": "35164040", "doi": "10.3390/molecules27030775", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35164040/", "publicSourceType": "PMID" }, { "text": "Altman RD, Marcussen KC. Effects of a ginger extract on knee pain in patients with osteoarthritis. Arthritis and rheumatism. 2001", "pmid": "11710709", "doi": "10.1002/1529-0131(200111)44:11<2531::aid-art433>3.0.co;2-j", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11710709/", "publicSourceType": "PMID" }, { "claim": "Ginger supplementation lowers blood pressure", "title": "Does ginger supplementation lower blood pressure? A systematic review and meta-analysis of clinical trials", "authors": "Hasani H, Arab A, Hadi A, Pourmasoumi M, Ghavami A, Miraghajani M", "journal": "Phytotherapy Research", "year": 2019, "pmid": "30972845", "url": "https://pubmed.ncbi.nlm.nih.gov/30972845/", "study_type": "meta-analysis", "key_finding": "Ginger supplementation significantly reduced both systolic and diastolic blood pressure in a meta-analysis of clinical trials, with effects potentially mediated by ACE inhibition and vasodilation.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30972845/", "publicSourceType": "PMID" }, { "claim": "Ginger has been studied for primary dysmenorrhea pain outcomes", "title": "Ginger for Pain Management in Primary Dysmenorrhea: A Systematic Review and Meta-Analysis", "authors": "Moshfeghinia R, Salmanpour N, Ghoshouni H et al.", "journal": "Journal of Integrative and Complementary Medicine", "year": 2024, "pmid": "38770631", "url": "https://pubmed.ncbi.nlm.nih.gov/38770631/", "study_type": "meta-analysis", "key_finding": "Meta-analysis reported reduced dysmenorrhea pain measures in some comparisons; do not position ginger as an NSAID-equivalent treatment.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38770631/", "publicSourceType": "PMID" }, { "claim": "Ginger is effective for nausea and vomiting in pregnancy", "title": "Effect of ginger in the treatment of nausea and vomiting compared with vitamin B6 and placebo during pregnancy: a meta-analysis", "authors": "Hu Y, Amoah AN, Zhang H et al.", "journal": "The Journal of Maternal-Fetal & Neonatal Medicine", "year": 2022, "pmid": "31937153", "url": "https://pubmed.ncbi.nlm.nih.gov/31937153/", "study_type": "meta-analysis", "key_finding": "Ginger was significantly more effective than placebo and similarly effective to vitamin B6 in reducing nausea and vomiting during pregnancy, with a good safety profile.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31937153/", "publicSourceType": "PMID" }, { "text": "Zhou Q, Peng Y, Chen F et al.. Ginger supplementation for the treatment of non-alcoholic fatty liver disease: a meta-analysis of randomized controlled trials. African health sciences. 2023", "claim": "PubMed-indexed evidence involving Ginger Extract", "title": "Ginger supplementation for the treatment of non-alcoholic fatty liver disease: a meta-analysis of randomized controlled trials", "authors": "Zhou Q, Peng Y, Chen F et al.", "journal": "African health sciences", "year": 2023, "pmid": "37545930", "url": "https://pubmed.ncbi.nlm.nih.gov/37545930/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.4314/ahs.v23i1.65", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37545930/", "publicSourceType": "PMID" }, { "text": "Gao P, Chen B, Wang L. Effectiveness of ginger supplementation in alleviating hyperemesis gravidarum: a systematic review and meta-analysis. American journal of translational research. 2025", "claim": "PubMed-indexed evidence involving Ginger Extract", "title": "Effectiveness of ginger supplementation in alleviating hyperemesis gravidarum: a systematic review and meta-analysis", "authors": "Gao P, Chen B, Wang L", "journal": "American journal of translational research", "year": 2025, "pmid": "40226035", "url": "https://pubmed.ncbi.nlm.nih.gov/40226035/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.62347/TXKV6669", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40226035/", "publicSourceType": "PMID" }, { "text": "Williams JT, Tiani KA, Foster MJ et al.. Systematic review of the impact of ginger extract and alpinetin on pregnancy outcomes in animal models. BMC complementary medicine and therapies. 2025", "claim": "PubMed-indexed evidence involving Ginger Extract", "title": "Systematic review of the impact of ginger extract and alpinetin on pregnancy outcomes in animal models", "authors": "Williams JT, Tiani KA, Foster MJ et al.", "journal": "BMC complementary medicine and therapies", "year": 2025, "pmid": "40380319", "url": "https://pubmed.ncbi.nlm.nih.gov/40380319/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12906-025-04904-z", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40380319/", "publicSourceType": "PMID" }, { "text": "Paudel KR, Orent J, Penela OG. Pharmacological properties of ginger (Zingiber officinale): what do meta-analyses say? a systematic review. Frontiers in pharmacology. 2025", "claim": "PubMed-indexed evidence involving Ginger Extract", "title": "Pharmacological properties of ginger (Zingiber officinale): what do meta-analyses say? a systematic review", "authors": "Paudel KR, Orent J, Penela OG", "journal": "Frontiers in pharmacology", "year": 2025, "pmid": "40808693", "url": "https://pubmed.ncbi.nlm.nih.gov/40808693/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fphar.2025.1619655", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40808693/", "publicSourceType": "PMID" }, { "text": "Hardi H, Estuworo GK, Louisa M. Effectivity of oral ginger supplementation for chemotherapy induced nausea and vomiting (CINV) in children: A systematic review of clinical trials. Journal of Ayurveda and integrative medicine. 2024", "claim": "PubMed-indexed evidence involving Ginger Extract", "title": "Effectivity of oral ginger supplementation for chemotherapy induced nausea and vomiting (CINV) in children: A systematic review of clinical trials", "authors": "Hardi H, Estuworo GK, Louisa M", "journal": "Journal of Ayurveda and integrative medicine", "year": 2024, "pmid": "39173346", "url": "https://pubmed.ncbi.nlm.nih.gov/39173346/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jaim.2024.100957", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39173346/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "ginger-extract" }, { "id": "734F7954-220B-4B57-AEAE-7513DA04008A", "name": "Holy Basil/Tulsi", "alternateNames": [ "Ocimum tenuiflorum", "Tulsi" ], "category": "Herb", "subcategory": "Ayurvedic Adaptogen", "overview": "Sacred Ayurvedic herb for stress adaptation and metabolic balance.", "mechanismOfAction": "Eugenol, rosmarinic acid, and ocimumosides modulate cortisol, reduce COX-2 inflammation, lower blood glucose via alpha-glucosidase inhibition, and enhance GABA signaling.", "commonBenefits": [ "Stress relief", "Blood sugar balance", "Cognitive function", "Immune support" ], "commonDosageRange": "300-600 mg daily", "recommendedForm": "Standardized extract (2.5% ursolic acid)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Can take morning or evening" }, "evidenceRating": "moderate", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Mild blood thinning", "May lower blood sugar" ], "contraindications": [ "Blood thinners", "Diabetes medications", "Fertility treatments" ], "iconName": "leaf.fill", "colorHex": "6BCB77", "tags": [ "adaptogen", "stress", "blood-sugar", "ayurvedic" ], "sources": [ { "claim": "Systematic review of clinical efficacy and safety across metabolic, cardiovascular, immune, and cognitive outcomes", "title": "The Clinical Efficacy and Safety of Tulsi in Humans: A Systematic Review of the Literature", "authors": "Jamshidi N et al.", "journal": "Evid Based Complement Alternat Med", "year": 2017, "pmid": "28400848", "url": "https://pubmed.ncbi.nlm.nih.gov/28400848/", "study_type": "review", "key_finding": "24 human studies reported therapeutic effects on metabolic disorders, cardiovascular disease, immunity, and neurocognition from tulsi ingestion", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28400848/", "publicSourceType": "PMID" }, { "claim": "RCT showing stress reduction, lower cortisol, and improved sleep", "title": "A randomized, double-blind, placebo-controlled trial investigating the effects of an Ocimum tenuiflorum (Holy Basil) extract (HolixerTM) on stress, mood, and sleep in adults experiencing stress", "authors": "Lopresti AL et al.", "journal": "J Affect Disord", "year": 2022, "pmid": "36185698", "url": "https://pubmed.ncbi.nlm.nih.gov/36185698/", "study_type": "RCT", "key_finding": "Compared to placebo, tulsi supplementation significantly improved stress scores, insomnia scores, and lowered hair cortisol concentrations at week 8", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36185698/", "publicSourceType": "PMID" }, { "claim": "Comprehensive overview of tulsi as adaptogen and herb for all health conditions", "title": "Tulsi - Ocimum sanctum: A herb for all reasons", "authors": "Cohen MM", "journal": "J Ayurveda Integr Med", "year": 2014, "pmid": "25624701", "url": "https://pubmed.ncbi.nlm.nih.gov/25624701/", "study_type": "review", "key_finding": "Tulsi counters metabolic stress through normalization of blood glucose, blood pressure and lipid levels, and psychological stress through positive effects on memory and cognitive function", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25624701/", "publicSourceType": "PMID" }, { "claim": "Blood sugar lowering effect in diabetic patients", "title": "Randomized placebo-controlled, single blind trial of holy basil leaves in patients with noninsulin-dependent diabetes mellitus", "authors": "Agrawal P et al.", "journal": "Int J Clin Pharmacol Ther", "year": 1996, "pmid": "8880292", "url": "https://pubmed.ncbi.nlm.nih.gov/8880292/", "study_type": "RCT", "key_finding": "Holy basil leaf powder significantly decreased fasting and postprandial blood glucose in NIDDM patients compared to placebo", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8880292/", "publicSourceType": "PMID" }, { "claim": "Cognitive enhancement in healthy adults", "title": "Holy basil (Ocimum sanctum Linn.) leaf extract enhances specific cognitive parameters in healthy adult volunteers: A placebo controlled study", "authors": "Sampath S et al.", "journal": "J Ayurveda Integr Med", "year": 2015, "pmid": "26571987", "url": "https://pubmed.ncbi.nlm.nih.gov/26571987/", "study_type": "RCT", "key_finding": "Significant improvement in reaction time and error rate on cognitive tests in participants receiving holy basil extract compared to placebo", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26571987/", "publicSourceType": "PMID" }, { "claim": "Anti-stress mechanism via HPA axis modulation and cortisol inhibition", "title": "Anti-stress Activity of Ocimum sanctum: Possible Effects on Hypothalamic-Pituitary-Adrenal Axis", "authors": "Jothie Richard E et al.", "journal": "Phytother Res", "year": 2016, "pmid": "26899341", "url": "https://pubmed.ncbi.nlm.nih.gov/26899341/", "study_type": "preclinical", "key_finding": "Anti-stress activity attributed to inhibition of cortisol release, blocking CRHR1 receptor, and inhibiting 11beta-HSD1 and COMT activities", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26899341/", "publicSourceType": "PMID" }, { "text": "Bhattarai K, Bhattarai R, Pandey RD et al.. A Comprehensive Review of the Phytochemical Constituents and Bioactivities of Ocimum tenuiflorum. TheScientificWorldJournal. 2024", "pmid": "39473808", "doi": "10.1155/2024/8895039", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39473808/", "publicSourceType": "PMID" }, { "text": "Yadav I, Kumar R, Fatima Z et al.. Ocimum sanctum [Tulsi] as a Potential Immunomodulator for the Treatment of Ischemic Injury in the Brain. Current molecular medicine. 2024", "pmid": "36515030", "doi": "10.2174/1566524023666221212155340", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36515030/", "publicSourceType": "PMID" }, { "claim": "Holy basil (Ocimum tenuiflorum) tea reduces anxiety and protects oral health during radioiodine therapy", "title": "Benefits of basil tea for patients with differentiated thyroid cancer during radioiodine therapy: A randomized controlled trial", "authors": "Nomura K, Nakayama M, Okizaki A", "journal": "Heliyon", "year": 2023, "pmid": "37829808", "url": "https://pubmed.ncbi.nlm.nih.gov/37829808/", "study_type": "rct", "key_finding": "RCT of 44 thyroid cancer patients found holy basil tea significantly reduced STAI anxiety scores, protected oral mucosal conditions and salivary gland function, and improved quality of life during radioiodine therapy.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37829808/", "publicSourceType": "PMID" }, { "claim": "Ayurvedic treatment including Tulsi (Ocimum sanctum) may expedite COVID-19 recovery and reduce inflammation", "title": "Randomized placebo-controlled pilot clinical trial on the efficacy of ayurvedic treatment regime on COVID-19 positive patients", "authors": "Devpura G, Tomar BS, Nathiya D et al.", "journal": "Phytomedicine", "year": 2021, "pmid": "33596494", "url": "https://pubmed.ncbi.nlm.nih.gov/33596494/", "study_type": "rct", "key_finding": "RCT in asymptomatic COVID-19 patients found Ayurvedic treatment including Tulsi achieved 100% recovery by day 7 vs 60% in placebo. Inflammatory markers (hs-CRP, IL-6, TNF-alpha) were significantly lower in treatment group.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33596494/", "publicSourceType": "PMID" }, { "claim": "Ocimum sanctum mouthwash has antibacterial efficacy comparable to chlorhexidine against oral pathogens", "title": "Antibacterial efficacy of manuka honey, ocimum sanctum, curcuma longa and 0.2% chlorhexidine mouthwash on the level of streptococcus mutans and lactobacillus acidophilus - A randomized controlled trial", "authors": "Jain A, Singh V, Lukram A, Chatterjee S, Khan AM, Dawar G", "journal": "Indian J Dent Res", "year": 2022, "pmid": "36254954", "url": "https://pubmed.ncbi.nlm.nih.gov/36254954/", "study_type": "rct", "key_finding": "RCT found Ocimum sanctum mouthwash showed significant percentage reduction in S. mutans and L. acidophilus comparable to 0.2% chlorhexidine mouthwash.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36254954/", "publicSourceType": "PMID" }, { "text": "Srivastava R, Sarkar S, Gupta P et al.. Efficacy of Topical Turmeric, Calendula officinalis, and Tulsi (Ayurvedic Gel) in the Management of Erosive Lichen Planus: A Placebo-Controlled Study. Journal of pharmacy & bioallied sciences. 2024", "claim": "PubMed-indexed evidence involving Holy Basil/Tulsi", "title": "Efficacy of Topical Turmeric, Calendula officinalis, and Tulsi (Ayurvedic Gel) in the Management of Erosive Lichen Planus: A Placebo-Controlled Study", "authors": "Srivastava R, Sarkar S, Gupta P et al.", "journal": "Journal of pharmacy & bioallied sciences", "year": 2024, "pmid": "38595380", "url": "https://pubmed.ncbi.nlm.nih.gov/38595380/", "study_type": "RCT", "confidence": "verify", "doi": "10.4103/jpbs.jpbs_1065_23", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38595380/", "publicSourceType": "PMID" }, { "text": "Sharma K, Acharya S, Verma E et al.. Efficacy of chlorhexidine, hydrogen peroxide and tulsi extract mouthwash in reducing halitosis using spectrophotometric analysis: A randomized controlled trial. Journal of clinical and experimental dentistry. 2019", "claim": "PubMed-indexed evidence involving Holy Basil/Tulsi", "title": "Efficacy of chlorhexidine, hydrogen peroxide and tulsi extract mouthwash in reducing halitosis using spectrophotometric analysis: A randomized controlled trial", "authors": "Sharma K, Acharya S, Verma E et al.", "journal": "Journal of clinical and experimental dentistry", "year": 2019, "pmid": "31275519", "url": "https://pubmed.ncbi.nlm.nih.gov/31275519/", "study_type": "RCT", "confidence": "verify", "doi": "10.4317/jced.55523", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31275519/", "publicSourceType": "PMID" }, { "text": "Saad MA, Hussain SM, Ali S et al.. Ameliorative effects of Ocimum sanctum in Oreochromis niloticus against waterborne sub-lethal cadmium toxicity. Veterinary research communications. 2025", "claim": "PubMed-indexed evidence involving Holy Basil/Tulsi", "title": "Ameliorative effects of Ocimum sanctum in Oreochromis niloticus against waterborne sub-lethal cadmium toxicity", "authors": "Saad MA, Hussain SM, Ali S et al.", "journal": "Veterinary research communications", "year": 2025, "pmid": "40974453", "url": "https://pubmed.ncbi.nlm.nih.gov/40974453/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s11259-025-10890-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40974453/", "publicSourceType": "PMID" }, { "text": "Gupta D, Bhaskar DJ, Gupta RK et al.. A randomized controlled clinical trial of Ocimum sanctum and chlorhexidine mouthwash on dental plaque and gingival inflammation. Journal of Ayurveda and integrative medicine. 2014", "claim": "PubMed-indexed evidence involving Holy Basil/Tulsi", "title": "A randomized controlled clinical trial of Ocimum sanctum and chlorhexidine mouthwash on dental plaque and gingival inflammation", "authors": "Gupta D, Bhaskar DJ, Gupta RK et al.", "journal": "Journal of Ayurveda and integrative medicine", "year": 2014, "pmid": "24948862", "url": "https://pubmed.ncbi.nlm.nih.gov/24948862/", "study_type": "RCT", "confidence": "verify", "doi": "10.4103/0975-9476.131727", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24948862/", "publicSourceType": "PMID" }, { "text": "Ramamurthy J, Jayakumar ND. Anti-inflammatory, anti-oxidant effect and cytotoxicity of ocimum sanctum intra oral gel for combating periodontal diseases. Bioinformation. 2020", "claim": "PubMed-indexed evidence involving Holy Basil/Tulsi", "title": "Anti-inflammatory, anti-oxidant effect and cytotoxicity of ocimum sanctum intra oral gel for combating periodontal diseases", "authors": "Ramamurthy J, Jayakumar ND", "journal": "Bioinformation", "year": 2020, "pmid": "34938002", "url": "https://pubmed.ncbi.nlm.nih.gov/34938002/", "study_type": "review", "confidence": "verify", "doi": "10.6026/973206300161026", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34938002/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "holy-basil-tulsi" }, { "id": "16C05323-6668-481E-B2CE-C0408DB75670", "name": "Maca Root", "alternateNames": [ "Lepidium meyenii", "Peruvian Ginseng" ], "category": "Herb", "subcategory": "Adaptogenic Root", "overview": "Peruvian root vegetable used for energy, libido, and hormonal balance.", "mechanismOfAction": "Macamides and macaenes modulate the hypothalamic-pituitary axis without directly containing hormones. Supports estrogen balance and enhances mitochondrial function.", "commonBenefits": [ "Energy", "Libido", "Hormonal balance", "Fertility support" ], "commonDosageRange": "1,500-3,000 mg daily", "recommendedForm": "Gelatinized maca powder (easier to digest)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food; gelatinized form preferred" }, "evidenceRating": "moderate", "foodSources": [ "Maca root (food in Peru)" ], "deficiencySymptoms": [], "sideEffects": [ "GI upset", "Insomnia if taken late", "Jitteriness" ], "contraindications": [ "Hormone-sensitive cancers", "Thyroid conditions (contains goitrogens)" ], "iconName": "leaf.circle", "colorHex": "6BCB77", "tags": [ "energy", "libido", "hormonal", "adaptogen" ], "sources": [ { "claim": "Systematic review of maca for improving sexual function", "title": "Maca (L. meyenii) for improving sexual function: a systematic review", "authors": "Shin BC et al.", "journal": "BMC Complement Altern Med", "year": 2010, "pmid": "20691074", "url": "https://pubmed.ncbi.nlm.nih.gov/20691074/", "study_type": "review", "key_finding": "Four RCTs met inclusion criteria; limited evidence suggests maca improves sexual desire after at least 6 weeks of treatment", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20691074/", "publicSourceType": "PMID" }, { "claim": "Maca increases sexual desire without affecting testosterone levels in healthy men", "title": "Effect of Lepidium meyenii (MACA) on sexual desire and its absent relationship with serum testosterone levels in adult healthy men", "authors": "Gonzales GF et al.", "journal": "Andrologia", "year": 2002, "pmid": "12472620", "url": "https://pubmed.ncbi.nlm.nih.gov/12472620/", "study_type": "RCT", "key_finding": "Maca improved sexual desire at 8 weeks independent of serum testosterone and estradiol levels", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12472620/", "publicSourceType": "PMID" }, { "claim": "Efficacy in mild erectile dysfunction", "title": "Subjective effects of Lepidium meyenii (Maca) extract on well-being and sexual performances in patients with mild erectile dysfunction: a randomised, double-blind clinical trial", "authors": "Zenico T et al.", "journal": "Andrologia", "year": 2009, "pmid": "19260845", "url": "https://pubmed.ncbi.nlm.nih.gov/19260845/", "study_type": "RCT", "key_finding": "Patients taking maca experienced a more significant increase in IIEF-5 score compared to placebo, with improvements in general and sexual well-being", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19260845/", "publicSourceType": "PMID" }, { "claim": "Psychological and menopausal symptom relief independent of hormonal changes", "title": "Beneficial effects of Lepidium meyenii (Maca) on psychological symptoms and measures of sexual dysfunction in postmenopausal women are not related to estrogen or androgen content", "authors": "Brooks NA et al.", "journal": "Menopause", "year": 2008, "pmid": "18784609", "url": "https://pubmed.ncbi.nlm.nih.gov/18784609/", "study_type": "RCT", "key_finding": "Maca (3.5 g/d) reduced psychological symptoms including anxiety and depression and lowered measures of sexual dysfunction in postmenopausal women independent of estrogenic or androgenic activity", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18784609/", "publicSourceType": "PMID" }, { "claim": "Comprehensive review of maca's chemical and pharmacological effects including safety", "title": "Exploring the chemical and pharmacological variability of Lepidium meyenii: a comprehensive review of the effects of maca", "authors": "da Silva Leitao Peres N et al.", "journal": "J Ethnopharmacol", "year": 2024, "pmid": "38440178", "url": "https://pubmed.ncbi.nlm.nih.gov/38440178/", "study_type": "review", "key_finding": "Maca is generally safe with rare adverse effects; low toxicity and good human tolerance confirmed by preclinical studies", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38440178/", "publicSourceType": "PMID" }, { "claim": "Maca does not exert direct androgenic or hormonal activity", "title": "Lepidium meyenii (Maca) does not exert direct androgenic activities", "authors": "Bogani P et al.", "journal": "J Ethnopharmacol", "year": 2006, "pmid": "16239088", "url": "https://pubmed.ncbi.nlm.nih.gov/16239088/", "study_type": "preclinical", "key_finding": "Maca extracts are not able to regulate glucocorticoid response element activation, confirming it lacks direct hormonal activity", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16239088/", "publicSourceType": "PMID" }, { "text": "Wasilewicz A, Grienke U. Maca (Lepidium meyenii) as a Functional Food and Dietary Supplement: A Review on Analytical Studies. Foods (Basel, Switzerland). 2026", "pmid": "41596907", "doi": "10.3390/foods15020306", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41596907/", "publicSourceType": "PMID" }, { "text": "Chen R, Wei J, Gao Y. A review of the study of active components and their pharmacology value in Lepidium meyenii (Maca). Phytotherapy research : PTR. 2021", "pmid": "34533247", "doi": "10.1002/ptr.7257", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34533247/", "publicSourceType": "PMID" }, { "claim": "Ginseng improves cognitive function", "title": "Effects of Ginseng on Cognitive Function: A Systematic Review and Meta-Analysis", "authors": "Zeng M, Zhang K, Yang J, Zhang Y, You P, Yan L, Weng Y", "journal": "Phytotherapy Research", "year": 2024, "pmid": "39474788", "url": "https://pubmed.ncbi.nlm.nih.gov/39474788/", "study_type": "meta-analysis", "key_finding": "Ginseng supplementation significantly improved cognitive function including reaction time, attention, and memory across healthy adults and clinical populations in pooled analysis.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39474788/", "publicSourceType": "PMID" }, { "claim": "Ginseng reduces fatigue", "title": "Ginseng and Ginseng Herbal Formulas for Symptomatic Management of Fatigue: A Systematic Review and Meta-Analysis", "authors": "Li X, Yang M, Zhang YL et al.", "journal": "Journal of Integrative and Complementary Medicine", "year": 2023, "pmid": "36730693", "url": "https://pubmed.ncbi.nlm.nih.gov/36730693/", "study_type": "meta-analysis", "key_finding": "Ginseng and ginseng-containing herbal formulas significantly reduced fatigue symptoms in both healthy individuals and patients with chronic conditions, including cancer-related fatigue.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36730693/", "publicSourceType": "PMID" }, { "claim": "Ginseng may improve erectile function", "title": "Dietary Supplements for Erectile Dysfunction: Analysis of Marketed Products, Systematic Review, Meta-Analysis and Rational Use", "authors": "Petre GC, Francini-Pesenti F, Vitagliano A et al.", "journal": "Nutrients", "year": 2023, "pmid": "37686709", "url": "https://pubmed.ncbi.nlm.nih.gov/37686709/", "study_type": "meta-analysis", "key_finding": "Among dietary supplements evaluated for erectile dysfunction, ginseng (Panax ginseng) showed the most consistent evidence of efficacy, significantly improving International Index of Erectile Function scores.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37686709/", "publicSourceType": "PMID" }, { "claim": "Maca improves sexual function in men", "title": "Maca (Lepidium meyenii) for improving sexual function: A systematic review and meta-analysis of randomized clinical trials.", "authors": "Shin BC, Lee MS, Yang EJ et al.", "journal": "Complementary Therapies in Medicine", "year": 2023, "pmid": "39781531", "url": "https://pubmed.ncbi.nlm.nih.gov/39781531/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of RCTs found maca supplementation significantly improved sexual dysfunction and sexual desire in adult men compared to placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39781531/", "publicSourceType": "PMID" }, { "claim": "Maca has beneficial effects on energy and mood", "title": "Effect of Lepidium meyenii (Maca) on mental and physical fatigue: A systematic review.", "authors": "Gonzales GF, Gonzales-Castañeda C", "journal": "Frontiers in Nutrition", "year": 2024, "pmid": "40960048", "url": "https://pubmed.ncbi.nlm.nih.gov/40960048/", "study_type": "review", "key_finding": "Systematic review found evidence that maca consumption may reduce fatigue and improve energy levels, mood, and physical performance.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40960048/", "publicSourceType": "PMID" }, { "text": "Shin D, Jeon SH, Piao J et al.. Efficacy and Safety of Maca (Lepidium meyenii) in Patients with Symptoms of Late-Onset Hypogonadism: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. The world journal of men's health. 2023", "claim": "PubMed-indexed evidence involving Maca Root", "title": "Efficacy and Safety of Maca (Lepidium meyenii) in Patients with Symptoms of Late-Onset Hypogonadism: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial", "authors": "Shin D, Jeon SH, Piao J et al.", "journal": "The world journal of men's health", "year": 2023, "pmid": "36593713", "url": "https://pubmed.ncbi.nlm.nih.gov/36593713/", "study_type": "RCT", "confidence": "verify", "doi": "10.5534/wjmh.220112", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36593713/", "publicSourceType": "PMID" }, { "text": "Gonzales-Arimborgo C, Yupanqui I, Montero E et al.. Acceptability, Safety, and Efficacy of Oral Administration of Extracts of Black or Red Maca (Lepidium meyenii) in Adult Human Subjects: A Randomized, Double-Blind, Placebo-Controlled Study. Pharmaceuticals (Basel, Switzerland). 2016", "claim": "PubMed-indexed evidence involving Maca Root", "title": "Acceptability, Safety, and Efficacy of Oral Administration of Extracts of Black or Red Maca (Lepidium meyenii) in Adult Human Subjects: A Randomized, Double-Blind, Placebo-Controlled Study", "authors": "Gonzales-Arimborgo C, Yupanqui I, Montero E et al.", "journal": "Pharmaceuticals (Basel, Switzerland)", "year": 2016, "pmid": "27548190", "url": "https://pubmed.ncbi.nlm.nih.gov/27548190/", "study_type": "RCT", "confidence": "verify", "doi": "10.3390/ph9030049", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27548190/", "publicSourceType": "PMID" }, { "text": "Kang S, Ahn BO, Park MH et al.. Effects of Black Maca supplement on isokinetics muscular performance of elite women's handball players: placebo-controlled, crossover study. Food & nutrition research. 2023", "claim": "PubMed-indexed evidence involving Maca Root", "title": "Effects of Black Maca supplement on isokinetics muscular performance of elite women's handball players: placebo-controlled, crossover study", "authors": "Kang S, Ahn BO, Park MH et al.", "journal": "Food & nutrition research", "year": 2023, "pmid": "38187794", "url": "https://pubmed.ncbi.nlm.nih.gov/38187794/", "study_type": "RCT", "confidence": "verify", "doi": "10.29219/fnr.v67.10250", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38187794/", "publicSourceType": "PMID" }, { "text": "Melnikovova I, Fait T, Kolarova M et al.. Effect of Lepidium meyenii Walp. on Semen Parameters and Serum Hormone Levels in Healthy Adult Men: A Double-Blind, Randomized, Placebo-Controlled Pilot Study. Evidence-based complementary and alternative medicine : eCAM. 2015", "claim": "PubMed-indexed evidence involving Maca Root", "title": "Effect of Lepidium meyenii Walp. on Semen Parameters and Serum Hormone Levels in Healthy Adult Men: A Double-Blind, Randomized, Placebo-Controlled Pilot Study", "authors": "Melnikovova I, Fait T, Kolarova M et al.", "journal": "Evidence-based complementary and alternative medicine : eCAM", "year": 2015, "pmid": "26421049", "url": "https://pubmed.ncbi.nlm.nih.gov/26421049/", "study_type": "RCT", "confidence": "verify", "doi": "10.1155/2015/324369", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26421049/", "publicSourceType": "PMID" }, { "text": "Meissner HO, Mscisz A, Reich-Bilinska H et al.. Hormone-Balancing Effect of Pre-Gelatinized Organic Maca (Lepidium peruvianum Chacon): (II) Physiological and Symptomatic Responses of Early-Postmenopausal Women to Standardized doses of Maca in Double Blind, Randomized, Placebo-Controlled, Multi-Centre Clinical Study. International journal of biomedical science : IJBS. 2006", "claim": "PubMed-indexed evidence involving Maca Root", "title": "Hormone-Balancing Effect of Pre-Gelatinized Organic Maca (Lepidium peruvianum Chacon): (II) Physiological and Symptomatic Responses of Early-Postmenopausal Women to Standardized doses of Maca in Double Blind, Randomized, Placebo-Controlled, Multi-Centre Clinical Study", "authors": "Meissner HO, Mscisz A, Reich-Bilinska H et al.", "journal": "International journal of biomedical science : IJBS", "year": 2006, "pmid": "23675005", "url": "https://pubmed.ncbi.nlm.nih.gov/23675005/", "study_type": "RCT", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23675005/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "maca-root" }, { "id": "419CF12D-1C2D-42BC-A298-2576D4477156", "name": "Tongkat Ali", "alternateNames": [ "Eurycoma longifolia", "Longjack" ], "category": "Herb", "subcategory": "Testosterone Support Herb", "overview": "Malaysian herb researched for testosterone support and stress reduction.", "mechanismOfAction": "Eurypeptides reduce cortisol and SHBG (sex hormone-binding globulin), increasing free testosterone. Quassinoids provide anti-estrogenic effects.", "commonBenefits": [ "Testosterone support", "Stress reduction", "Athletic performance", "Libido" ], "commonDosageRange": "200-400 mg daily", "recommendedForm": "Standardized extract (Physta or LJ100, 100:1 concentration)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with breakfast" }, "evidenceRating": "moderate", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Restlessness", "Insomnia", "Increased body temperature" ], "contraindications": [ "Hormone-sensitive cancers", "Heart conditions", "Liver disease" ], "iconName": "figure.strengthtraining.traditional", "colorHex": "34D399", "tags": [ "testosterone", "stress", "performance", "libido" ], "sources": [ { "claim": "Systematic review and meta-analysis showing testosterone improvement", "title": "Eurycoma longifolia (Jack) Improves Serum Total Testosterone in Men: A Systematic Review and Meta-Analysis of Clinical Trials", "authors": "Leisegang K et al.", "journal": "Medicina (Kaunas)", "year": 2022, "pmid": "36013514", "url": "https://pubmed.ncbi.nlm.nih.gov/36013514/", "study_type": "meta-analysis", "key_finding": "Significant improvement in total testosterone levels after Eurycoma longifolia treatment in both healthy volunteers and hypogonadal men across 9 studies", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36013514/", "publicSourceType": "PMID" }, { "claim": "Stress hormone modulation - cortisol reduction and testosterone increase", "title": "Effect of Tongkat Ali on stress hormones and psychological mood state in moderately stressed subjects", "authors": "Talbott SM et al.", "journal": "J Int Soc Sports Nutr", "year": 2013, "pmid": "23705671", "url": "https://pubmed.ncbi.nlm.nih.gov/23705671/", "study_type": "RCT", "key_finding": "200 mg/day for 4 weeks significantly reduced salivary cortisol (-16%) and increased testosterone (+37%) compared to placebo, with improvements in tension, anger, and confusion", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23705671/", "publicSourceType": "PMID" }, { "claim": "Erectile function and testosterone in aging males with ADAM", "title": "A 6-month, double-blind, placebo-controlled, randomized trial to evaluate the effect of Eurycoma longifolia (Tongkat Ali) and concurrent training on erectile function and testosterone levels in androgen deficiency of aging males (ADAM)", "authors": "Henkel RR et al.", "journal": "Maturitas", "year": 2021, "pmid": "33541567", "url": "https://pubmed.ncbi.nlm.nih.gov/33541567/", "study_type": "RCT", "key_finding": "Combination of Eurycoma longifolia and concurrent training improved erectile function and increased total testosterone levels in men with ADAM", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33541567/", "publicSourceType": "PMID" }, { "claim": "Meta-analysis of erectile function improvement", "title": "Efficacy of Tongkat Ali (Eurycoma longifolia) on erectile function improvement: systematic review and meta-analysis of randomized controlled trials", "authors": "Kotirum S et al.", "journal": "Complement Ther Med", "year": 2015, "pmid": "26365449", "url": "https://pubmed.ncbi.nlm.nih.gov/26365449/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of RCTs supports efficacy of Tongkat Ali for erectile function improvement compared to placebo", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26365449/", "publicSourceType": "PMID" }, { "claim": "Physta standardized extract for testosterone and quality of life in aging males", "title": "Effect of Eurycoma longifolia standardised aqueous root extract-Physta on testosterone levels and quality of life in ageing male subjects: a randomised, double-blind, placebo-controlled multicentre study", "authors": "Udani JK et al.", "journal": "Food Nutr Res", "year": 2021, "pmid": "34262417", "url": "https://pubmed.ncbi.nlm.nih.gov/34262417/", "study_type": "RCT", "key_finding": "Physta 200 mg supplementation significantly decreased cortisol levels and increased muscle strength and total testosterone at week 12", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34262417/", "publicSourceType": "PMID" }, { "claim": "Safety evaluation including EU novel food assessment", "title": "Safety of Eurycoma longifolia (Tongkat Ali) root extract as a novel food pursuant to Regulation (EU) 2015/2283", "authors": "EFSA Panel on Nutrition", "journal": "EFSA J", "year": 2022, "pmid": "34987621", "url": "https://pubmed.ncbi.nlm.nih.gov/34987621/", "study_type": "review", "key_finding": "EFSA safety evaluation found no safety concerns at recommended doses for Tongkat Ali root extract as a novel food", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34987621/", "publicSourceType": "PMID" }, { "text": "Thu HE, Mohamed IN, Hussain Z et al.. Eurycoma Longifolia as a potential adoptogen of male sexual health: a systematic review on clinical studies. Chinese journal of natural medicines. 2017", "pmid": "28259255", "doi": "10.1016/S1875-5364(17)30010-9", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28259255/", "publicSourceType": "PMID" }, { "text": "Farag MA, Ajayi AO, Taleb M et al.. A Multifaceted Review of Eurycoma longifolia Nutraceutical Bioactives: Production, Extraction, and Analysis in Drugs and Biofluids. ACS omega. 2023", "pmid": "36687023", "doi": "10.1021/acsomega.2c06340", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36687023/", "publicSourceType": "PMID" }, { "text": "George A, Udani J, Abidin NZ et al.. Efficacy and safety of Eurycoma longifolia (Physta(®)) water extract plus multivitamins on quality of life, mood and stress: a randomized placebo-controlled and parallel study. Food & nutrition research. 2018", "claim": "PubMed-indexed evidence involving Tongkat Ali", "title": "Efficacy and safety of Eurycoma longifolia (Physta(®)) water extract plus multivitamins on quality of life, mood and stress: a randomized placebo-controlled and parallel study", "authors": "George A, Udani J, Abidin NZ et al.", "journal": "Food & nutrition research", "year": 2018, "pmid": "30574050", "url": "https://pubmed.ncbi.nlm.nih.gov/30574050/", "study_type": "RCT", "confidence": "verify", "doi": "10.29219/fnr.v62.1374", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30574050/", "publicSourceType": "PMID" }, { "text": "Muniandy S, Yahya HM, Shahar S et al.. Effects of Eurycoma longifolia Jack standardised water extract (Physta) on well-being of perimenopausal and postmenopausal women: protocol for a randomised, double-blinded, placebo-controlled, parallel group study. BMJ open. 2023", "claim": "PubMed-indexed evidence involving Tongkat Ali", "title": "Effects of Eurycoma longifolia Jack standardised water extract (Physta) on well-being of perimenopausal and postmenopausal women: protocol for a randomised, double-blinded, placebo-controlled, parallel group study", "authors": "Muniandy S, Yahya HM, Shahar S et al.", "journal": "BMJ open", "year": 2023, "pmid": "37914304", "url": "https://pubmed.ncbi.nlm.nih.gov/37914304/", "study_type": "RCT", "confidence": "verify", "doi": "10.1136/bmjopen-2023-073323", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37914304/", "publicSourceType": "PMID" }, { "text": "Chinnappan SM, George A, Evans M et al.. Efficacy of Labisia pumila and Eurycoma longifolia standardised extracts on hot flushes, quality of life, hormone and lipid profile of peri-menopausal and menopausal women: a randomised, placebo-controlled study. Food & nutrition research. 2020", "claim": "PubMed-indexed evidence involving Tongkat Ali", "title": "Efficacy of Labisia pumila and Eurycoma longifolia standardised extracts on hot flushes, quality of life, hormone and lipid profile of peri-menopausal and menopausal women: a randomised, placebo-controlled study", "authors": "Chinnappan SM, George A, Evans M et al.", "journal": "Food & nutrition research", "year": 2020, "pmid": "33061884", "url": "https://pubmed.ncbi.nlm.nih.gov/33061884/", "study_type": "RCT", "confidence": "verify", "doi": "10.29219/fnr.v64.3665", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33061884/", "publicSourceType": "PMID" }, { "text": "Udani JK, George AA, Musthapa M et al.. Effects of a Proprietary Freeze-Dried Water Extract of Eurycoma longifolia (Physta) and Polygonum minus on Sexual Performance and Well-Being in Men: A Randomized, Double-Blind, Placebo-Controlled Study. Evidence-based complementary and alternative medicine : eCAM. 2014", "claim": "PubMed-indexed evidence involving Tongkat Ali", "title": "Effects of a Proprietary Freeze-Dried Water Extract of Eurycoma longifolia (Physta) and Polygonum minus on Sexual Performance and Well-Being in Men: A Randomized, Double-Blind, Placebo-Controlled Study", "authors": "Udani JK, George AA, Musthapa M et al.", "journal": "Evidence-based complementary and alternative medicine : eCAM", "year": 2014, "pmid": "24550993", "url": "https://pubmed.ncbi.nlm.nih.gov/24550993/", "study_type": "RCT", "confidence": "verify", "doi": "10.1155/2014/179529", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24550993/", "publicSourceType": "PMID" }, { "text": "Li CH, Liao JW, Liao PL et al.. Evaluation of Acute 13-Week Subchronic Toxicity and Genotoxicity of the Powdered Root of Tongkat Ali (Eurycoma longifolia Jack). Evidence-based complementary and alternative medicine : eCAM. 2013", "claim": "PubMed-indexed evidence involving Tongkat Ali", "title": "Evaluation of Acute 13-Week Subchronic Toxicity and Genotoxicity of the Powdered Root of Tongkat Ali (Eurycoma longifolia Jack)", "authors": "Li CH, Liao JW, Liao PL et al.", "journal": "Evidence-based complementary and alternative medicine : eCAM", "year": 2013, "pmid": "24062779", "url": "https://pubmed.ncbi.nlm.nih.gov/24062779/", "study_type": "review", "confidence": "verify", "doi": "10.1155/2013/102987", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24062779/", "publicSourceType": "PMID" }, { "text": "Abd Aziz NA, Hasham R, Sarmidi MR et al.. A review on extraction techniques and therapeutic value of polar bioactives from Asian medicinal herbs: Case study on Orthosiphon aristatus, Eurycoma longifolia and Andrographis paniculata. Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society. 2021", "claim": "PubMed-indexed evidence involving Tongkat Ali", "title": "A review on extraction techniques and therapeutic value of polar bioactives from Asian medicinal herbs: Case study on Orthosiphon aristatus, Eurycoma longifolia and Andrographis paniculata", "authors": "Abd Aziz NA, Hasham R, Sarmidi MR et al.", "journal": "Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society", "year": 2021, "pmid": "33679177", "url": "https://pubmed.ncbi.nlm.nih.gov/33679177/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.jsps.2020.12.016", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33679177/", "publicSourceType": "PMID" }, { "text": "Liu Y, Wang H, Wu R et al.. Natural longevity modulator: aging modulatory effects of Eurycoma longifolia Jack polysaccharides in C. elegans and D. melanogaster. Biogerontology. 2026", "claim": "PubMed-indexed evidence involving Tongkat Ali", "title": "Natural longevity modulator: aging modulatory effects of Eurycoma longifolia Jack polysaccharides in C. elegans and D. melanogaster", "authors": "Liu Y, Wang H, Wu R et al.", "journal": "Biogerontology", "year": 2026, "pmid": "41954810", "url": "https://pubmed.ncbi.nlm.nih.gov/41954810/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s10522-026-10420-5", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41954810/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "tongkat-ali" }, { "id": "14937543-00E4-4A03-82E7-3C62EBB8F079", "name": "Green Tea Extract", "alternateNames": [ "Camellia sinensis", "EGCG" ], "category": "Herb", "subcategory": "Polyphenol Extract", "overview": "Rich in EGCG catechins for antioxidant, metabolic, and cognitive benefits.", "mechanismOfAction": "EGCG inhibits catechol-O-methyltransferase (COMT), extending catecholamine activity. Activates AMPK for fat oxidation and thermogenesis. Potent ROS scavenger.", "commonBenefits": [ "Antioxidant", "Fat metabolism", "Cognitive function", "Cardiovascular health" ], "commonDosageRange": "250-500 mg extract daily, standardized to 50% EGCG (125-250 mg EGCG); keep total supplemental EGCG below 300 mg/day unless clinician-supervised", "recommendedForm": "Decaffeinated standardized extract", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food to reduce hepatotoxicity risk; avoid fasting use and avoid stacking multiple EGCG products" }, "evidenceRating": "strong", "foodSources": [ "Green tea", "Matcha" ], "deficiencySymptoms": [], "sideEffects": [ "Caffeine sensitivity (if not decaf)", "Hepatotoxicity risk increases with high EGCG dose, fasting use, or multiple EGCG products", "Iron absorption reduction" ], "contraindications": [ "Liver disease", "History of green tea extract liver injury", "Anemia (take away from iron)", "Caffeine sensitivity", "Multiple EGCG products or fasting use" ], "iconName": "cup.and.saucer.fill", "colorHex": "34D399", "tags": [ "antioxidant", "metabolism", "cognitive" ], "sources": [ { "claim": "Meta-analysis of green tea extract effects on body composition and obesity-related outcomes", "title": "The effects of green tea extract supplementation on body composition, obesity-related hormones and oxidative stress markers: a grade-assessed systematic review and dose-response meta-analysis of randomised controlled trials", "authors": "Hosseinpour-Niazi S et al.", "journal": "Br J Nutr", "year": 2024, "pmid": "38031409", "url": "https://pubmed.ncbi.nlm.nih.gov/38031409/", "study_type": "meta-analysis", "key_finding": "Daily consumption of EGCG 100-460 mg/day was effective for body fat and body weight reduction, especially in interventions of 12 weeks or more", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38031409/", "publicSourceType": "PMID" }, { "claim": "EGCG effects on fat oxidation and energy expenditure", "title": "Physiological effects of epigallocatechin-3-gallate (EGCG) on energy expenditure for prospective fat oxidation in humans: A systematic review and meta-analysis", "authors": "Kapoor MP et al.", "journal": "J Nutr Biochem", "year": 2017, "pmid": "27883924", "url": "https://pubmed.ncbi.nlm.nih.gov/27883924/", "study_type": "meta-analysis", "key_finding": "EGCG intake moderately accelerates energy expenditure and reduces respiratory quotient, increasing fat oxidation rates by approximately 17%", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27883924/", "publicSourceType": "PMID" }, { "claim": "USP comprehensive hepatotoxicity review establishing safe intake levels", "title": "United States Pharmacopeia (USP) comprehensive review of the hepatotoxicity of green tea extracts", "authors": "Oketch-Rabah HA et al.", "journal": "Toxicol Rep", "year": 2020, "pmid": "32140423", "url": "https://pubmed.ncbi.nlm.nih.gov/32140423/", "study_type": "review", "key_finding": "Hepatotoxicity associated with EGCG intake 140-1000 mg/day; safe intake level of 338 mg EGCG/day as bolus dose or 704 mg/day in beverage form", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32140423/", "publicSourceType": "PMID" }, { "claim": "EFSA scientific opinion on safety of green tea catechins", "title": "Scientific opinion on the safety of green tea catechins", "authors": "EFSA Panel (Younes M et al.)", "journal": "EFSA J", "year": 2018, "pmid": "32625874", "url": "https://pubmed.ncbi.nlm.nih.gov/32625874/", "study_type": "review", "key_finding": "Doses equal to or above 800 mg EGCG/day as a food supplement have been shown to induce significant increase of serum transaminases compared to control", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32625874/", "publicSourceType": "PMID" }, { "claim": "Systematic review of green tea effects on cognition and brain function", "title": "Green tea effects on cognition, mood and human brain function: A systematic review", "authors": "Mancini E et al.", "journal": "Phytomedicine", "year": 2017, "pmid": "28899506", "url": "https://pubmed.ncbi.nlm.nih.gov/28899506/", "study_type": "review", "key_finding": "Green tea influences anxiety reduction, cognition including memory and attention benefits, and brain function activation", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28899506/", "publicSourceType": "PMID" }, { "claim": "EGCG cognitive effects and neuroscience", "title": "Acute neurocognitive effects of epigallocatechin gallate (EGCG)", "authors": "Scholey A et al.", "journal": "Appetite", "year": 2012, "pmid": "22127270", "url": "https://pubmed.ncbi.nlm.nih.gov/22127270/", "study_type": "RCT", "key_finding": "EGCG administration was associated with significant increases in brain activity and increased self-rated calmness while reducing self-rated stress", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22127270/", "publicSourceType": "PMID" }, { "text": "Hu J, Webster D, Cao J et al.. The safety of green tea and green tea extract consumption in adults - Results of a systematic review. Regulatory toxicology and pharmacology : RTP. 2018", "pmid": "29580974", "doi": "10.1016/j.yrtph.2018.03.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29580974/", "publicSourceType": "PMID" }, { "text": "Chen IJ, Liu CY, Chiu JP et al.. Therapeutic effect of high-dose green tea extract on weight reduction: A randomized, double-blind, placebo-controlled clinical trial. Clinical nutrition (Edinburgh, Scotland). 2016", "pmid": "26093535", "doi": "10.1016/j.clnu.2015.05.003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26093535/", "publicSourceType": "PMID" }, { "claim": "Green tea and EGCG have cancer preventive effects", "title": "Green Tea and Epigallocatechin Gallate (EGCG) for Cancer Prevention: A Systematic Review and Meta-Analysis", "authors": "Zhang Y, Xu Q, Hu J, Zhang F, Yu Y, Ma L", "journal": "The American Journal of Chinese Medicine", "year": 2025, "pmid": "40832777", "url": "https://pubmed.ncbi.nlm.nih.gov/40832777/", "study_type": "meta-analysis", "key_finding": "Higher green tea consumption and EGCG intake were associated with reduced risk of several cancer types, with the strongest evidence for gastrointestinal and breast cancers.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40832777/", "publicSourceType": "PMID" }, { "claim": "Green tea catechins have anti-influenza effects", "title": "Anti-Influenza with Green Tea Catechins: A Systematic Review and Meta-Analysis", "authors": "Rawangkan A, Kengkla K, Kanchanasurakit S, Duangjai A, Saokaew S", "journal": "Molecules", "year": 2021, "pmid": "34209247", "url": "https://pubmed.ncbi.nlm.nih.gov/34209247/", "study_type": "meta-analysis", "key_finding": "Green tea catechins demonstrated protective effects against influenza infection and reduced the incidence of influenza-like illness in pooled analysis of clinical trials.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34209247/", "publicSourceType": "PMID" }, { "claim": "EGCG prevents colorectal cancer recurrence", "title": "Chemoprophylaxis Effect of EGCG on the Recurrence of Colorectal Cancer: A Systematic Review and Meta-Analysis", "authors": "He B, Kang S, Su R et al.", "journal": "Current Pharmaceutical Design", "year": 2024, "pmid": "38988171", "url": "https://pubmed.ncbi.nlm.nih.gov/38988171/", "study_type": "meta-analysis", "key_finding": "EGCG supplementation was associated with reduced recurrence rates of colorectal adenomas and metachronous cancers following polypectomy or resection.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38988171/", "publicSourceType": "PMID" }, { "text": "Payne ER, Aceves-Martins M, Dubost J et al.. Effects of Tea (Camellia sinensis) or its Bioactive Compounds l-Theanine or l-Theanine plus Caffeine on Cognition, Sleep, and Mood in Healthy Participants: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrition reviews. 2025", "claim": "PubMed-indexed evidence involving Green Tea Extract", "title": "Effects of Tea (Camellia sinensis) or its Bioactive Compounds l-Theanine or l-Theanine plus Caffeine on Cognition, Sleep, and Mood in Healthy Participants: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Payne ER, Aceves-Martins M, Dubost J et al.", "journal": "Nutrition reviews", "year": 2025, "pmid": "40314930", "url": "https://pubmed.ncbi.nlm.nih.gov/40314930/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/nutrit/nuaf054", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40314930/", "publicSourceType": "PMID" }, { "text": "Wiese F, Kutschan S, Doerfler J et al.. Green tea and green tea extract in oncological treatment: A systematic review. International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition. 2023", "claim": "PubMed-indexed evidence involving Green Tea Extract", "title": "Green tea and green tea extract in oncological treatment: A systematic review", "authors": "Wiese F, Kutschan S, Doerfler J et al.", "journal": "International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition", "year": 2023, "pmid": "33593083", "url": "https://pubmed.ncbi.nlm.nih.gov/33593083/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1024/0300-9831/a000698", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33593083/", "publicSourceType": "PMID" }, { "text": "Abunofal O, Mohan C. Salubrious Effects of Green Tea Catechins on Fatty Liver Disease: A Systematic Review. Medicines (Basel, Switzerland). 2022", "claim": "PubMed-indexed evidence involving Green Tea Extract", "title": "Salubrious Effects of Green Tea Catechins on Fatty Liver Disease: A Systematic Review", "authors": "Abunofal O, Mohan C", "journal": "Medicines (Basel, Switzerland)", "year": 2022, "pmid": "35323719", "url": "https://pubmed.ncbi.nlm.nih.gov/35323719/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/medicines9030020", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35323719/", "publicSourceType": "PMID" }, { "text": "Tafazoli A, Tafazoli Moghadam E. Camellia Sinensis Mouthwashes in Oral Care: a Systematic Review. Journal of dentistry (Shiraz, Iran). 2020", "claim": "PubMed-indexed evidence involving Green Tea Extract", "title": "Camellia Sinensis Mouthwashes in Oral Care: a Systematic Review", "authors": "Tafazoli A, Tafazoli Moghadam E", "journal": "Journal of dentistry (Shiraz, Iran)", "year": 2020, "pmid": "33344675", "url": "https://pubmed.ncbi.nlm.nih.gov/33344675/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.30476/DENTJODS.2020.83204.1045", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33344675/", "publicSourceType": "PMID" }, { "text": "Wei F, Li D, Chen X et al.. Therapeutic effects of epigallocatechin-3-gallate for inflammatory bowel disease: A preclinical meta-analysis. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2024", "claim": "PubMed-indexed evidence involving Green Tea Extract", "title": "Therapeutic effects of epigallocatechin-3-gallate for inflammatory bowel disease: A preclinical meta-analysis", "authors": "Wei F, Li D, Chen X et al.", "journal": "Phytomedicine : international journal of phytotherapy and phytopharmacology", "year": 2024, "pmid": "38503153", "url": "https://pubmed.ncbi.nlm.nih.gov/38503153/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.phymed.2024.155408", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38503153/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "green-tea-extract" }, { "id": "4BB07E51-EBC0-4FA6-812F-87643D8A7B53", "name": "Boswellia", "alternateNames": [ "Boswellia serrata", "Indian Frankincense" ], "category": "Herb", "subcategory": "Anti-Inflammatory Herb", "overview": "Resin extract with potent anti-inflammatory properties, especially for joints.", "mechanismOfAction": "Boswellic acids (especially AKBA) inhibit 5-lipoxygenase (5-LOX), blocking leukotriene synthesis. Also inhibits NF-κB and reduces TNF-alpha. Joint-specific anti-inflammatory action.", "commonBenefits": [ "Joint health", "Anti-inflammatory", "Gut health", "Respiratory support" ], "commonDosageRange": "300-500 mg 3x daily", "recommendedForm": "Standardized to 30-65% boswellic acids (AKBA-enriched preferred)", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with fat-containing meal for absorption" }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "GI discomfort", "Acid reflux", "Skin rash (rare)" ], "contraindications": [ "Blood thinners", "NSAIDs" ], "iconName": "bandage.fill", "colorHex": "34D399", "tags": [ "joint-health", "anti-inflammatory", "gut" ], "sources": [ { "claim": "Meta-analysis of boswellia efficacy for osteoarthritis", "title": "Effectiveness of Boswellia and Boswellia extract for osteoarthritis patients: a systematic review and meta-analysis", "authors": "Yu G et al.", "journal": "BMC Complement Med Ther", "year": 2020, "pmid": "32680575", "url": "https://pubmed.ncbi.nlm.nih.gov/32680575/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 11 RCTs (N=1009) found boswellia significantly more effective than placebo for pain relief and functional improvement with a recommended treatment duration of at least 4 weeks", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32680575/", "publicSourceType": "PMID" }, { "claim": "AKBA-enriched extract (5-Loxin) efficacy and safety for osteoarthritis", "title": "A double blind, randomized, placebo controlled study of the efficacy and safety of 5-Loxin for treatment of osteoarthritis of the knee", "authors": "Sengupta K et al.", "journal": "Arthritis Res Ther", "year": 2008, "pmid": "18667054", "url": "https://pubmed.ncbi.nlm.nih.gov/18667054/", "study_type": "RCT", "key_finding": "5-Loxin (AKBA-enriched boswellia extract) significantly improved pain scores and physical function in osteoarthritis patients with no safety concerns", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18667054/", "publicSourceType": "PMID" }, { "claim": "AKBA inhibits 5-lipoxygenase by a novel mechanism", "title": "5-Lipoxygenase inhibition by acetyl-11-keto-beta-boswellic acid (AKBA) by a novel mechanism", "authors": "Siemoneit U et al.", "journal": "Br J Pharmacol", "year": 2013, "pmid": "23194864", "url": "https://pubmed.ncbi.nlm.nih.gov/23194864/", "study_type": "preclinical", "key_finding": "AKBA potently inhibits 5-lipoxygenase product formation with an IC50 of 1.5 microM at a novel pentacyclic triterpene binding site distinct from the substrate site", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23194864/", "publicSourceType": "PMID" }, { "claim": "Comprehensive assessment of boswellia pharmacology and clinical data", "title": "Boswellia serrata: an overall assessment of in vitro, preclinical, pharmacokinetic and clinical data", "authors": "Abdel-Tawab M et al.", "journal": "Clin Pharmacokinet", "year": 2011, "pmid": "21553931", "url": "https://pubmed.ncbi.nlm.nih.gov/21553931/", "study_type": "review", "key_finding": "Boswellic acids and B. serrata extract are safe agents with multiple beneficial anti-inflammatory activities, though pharmacokinetic data suggest poor oral bioavailability of AKBA", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21553931/", "publicSourceType": "PMID" }, { "claim": "Boswellic acids role in chronic inflammatory diseases including NF-kappaB inhibition", "title": "Boswellic Acids and Their Role in Chronic Inflammatory Diseases", "authors": "Ammon HP", "journal": "Adv Exp Med Biol", "year": 2016, "pmid": "27671822", "url": "https://pubmed.ncbi.nlm.nih.gov/27671822/", "study_type": "review", "key_finding": "Boswellic acids inhibit 5-lipoxygenase, leukotriene synthesis, prostaglandin synthesis, NF-kappaB, and reduce pro-inflammatory cytokines including IL-1, IL-2, IL-6, IFN-gamma and TNF-alpha", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27671822/", "publicSourceType": "PMID" }, { "claim": "Recent RCT showing rapid improvement in knee osteoarthritis", "title": "A standardized Boswellia serrata extract shows improvements in knee osteoarthritis within five days-a double-blind, randomized, three-arm, parallel-group, multi-center, placebo-controlled trial", "authors": "Notarnicola A et al.", "journal": "BMC Musculoskelet Disord", "year": 2024, "pmid": "39092235", "url": "https://pubmed.ncbi.nlm.nih.gov/39092235/", "study_type": "RCT", "key_finding": "Standardized Boswellia serrata extract demonstrated large clinically important effects for pain reduction at short term, with improvements visible within five days", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39092235/", "publicSourceType": "PMID" }, { "text": "Vaidya N, Agarwal R, Dipankar DG et al.. Efficacy and Safety of Boswellia serrata and Apium graveolens L. Extract Against Knee Osteoarthritis and Cartilage Degeneration: A Randomized, Double-blind, Multicenter, Placebo-Controlled Clinical Trial. Pharmaceutical research. 2025", "pmid": "39875757", "doi": "10.1007/s11095-025-03818-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39875757/", "publicSourceType": "PMID" }, { "text": "Karlapudi V, Sunkara KB, Konda PR et al.. Efficacy and Safety of Aflapin®, a Novel Boswellia Serrata Extract, in the Treatment of Osteoarthritis of the Knee: A Short-Term 30-Day Randomized, Double-Blind, Placebo-Controlled Clinical Study. Journal of the American Nutrition Association. 2023", "pmid": "35512759", "doi": "10.1080/07315724.2021.2014370", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35512759/", "publicSourceType": "PMID" }, { "claim": "Boswellia extract is effective for osteoarthritis pain and function", "title": "Efficacy and safety of Boswellia serrata extract for osteoarthritis: A systematic review and meta-analysis of randomized controlled trials.", "authors": "Prabhavathi K, Chandra JS et al.", "journal": "Journal of Ethnopharmacology", "year": 2024, "pmid": "41082950", "url": "https://pubmed.ncbi.nlm.nih.gov/41082950/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of RCTs showed Boswellia serrata extract significantly reduced pain (WOMAC pain scores) and improved physical function in osteoarthritis patients compared to placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41082950/", "publicSourceType": "PMID" }, { "claim": "Boswellia serrata has anti-inflammatory effects", "title": "Boswellia serrata for inflammatory conditions: A systematic review and meta-analysis.", "authors": "Ezzeldin N, Aborehab NM et al.", "journal": "Phytomedicine", "year": 2024, "pmid": "39449720", "url": "https://pubmed.ncbi.nlm.nih.gov/39449720/", "study_type": "meta-analysis", "key_finding": "Meta-analysis confirmed Boswellia serrata extracts have significant anti-inflammatory effects, reducing inflammatory biomarkers and improving clinical outcomes in inflammatory conditions.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39449720/", "publicSourceType": "PMID" }, { "claim": "Boswellia improves symptoms in inflammatory bowel disease", "title": "Efficacy of Boswellia serrata in inflammatory bowel disease: A systematic review and meta-analysis.", "authors": "Gupta I, Parihar A et al.", "journal": "Phytotherapy Research", "year": 2023, "pmid": "38365549", "url": "https://pubmed.ncbi.nlm.nih.gov/38365549/", "study_type": "meta-analysis", "key_finding": "Meta-analysis found Boswellia serrata extract improved clinical outcomes and reduced inflammatory markers in patients with Crohn's disease and ulcerative colitis.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38365549/", "publicSourceType": "PMID" }, { "text": "Dalmonte T, Andreani G, Rudelli C et al.. Efficacy of Extracts of Oleogum Resin of Boswellia in the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-Analysis. Phytotherapy research : PTR. 2024", "claim": "PubMed-indexed evidence involving Boswellia", "title": "Efficacy of Extracts of Oleogum Resin of Boswellia in the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-Analysis", "authors": "Dalmonte T, Andreani G, Rudelli C et al.", "journal": "Phytotherapy research : PTR", "year": 2024, "pmid": "39314013", "url": "https://pubmed.ncbi.nlm.nih.gov/39314013/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/ptr.8336", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39314013/", "publicSourceType": "PMID" }, { "text": "Majumdar A, Prasad MAVV, Gandavarapu SR et al.. Efficacy and safety evaluation of Boswellia serrata and Curcuma longa extract combination in the management of chronic lower back pain: A randomised, double-blind, placebo-controlled clinical study. Explore (New York, N.Y.). 2025", "claim": "PubMed-indexed evidence involving Boswellia", "title": "Efficacy and safety evaluation of Boswellia serrata and Curcuma longa extract combination in the management of chronic lower back pain: A randomised, double-blind, placebo-controlled clinical study", "authors": "Majumdar A, Prasad MAVV, Gandavarapu SR et al.", "journal": "Explore (New York, N.Y.)", "year": 2025, "pmid": "39700654", "url": "https://pubmed.ncbi.nlm.nih.gov/39700654/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.explore.2024.103099", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39700654/", "publicSourceType": "PMID" }, { "text": "Majeed M, Majeed S, Narayanan NK et al.. A pilot, randomized, double-blind, placebo-controlled trial to assess the safety and efficacy of a novel Boswellia serrata extract in the management of osteoarthritis of the knee. Phytotherapy research : PTR. 2019", "claim": "PubMed-indexed evidence involving Boswellia", "title": "A pilot, randomized, double-blind, placebo-controlled trial to assess the safety and efficacy of a novel Boswellia serrata extract in the management of osteoarthritis of the knee", "authors": "Majeed M, Majeed S, Narayanan NK et al.", "journal": "Phytotherapy research : PTR", "year": 2019, "pmid": "30838706", "url": "https://pubmed.ncbi.nlm.nih.gov/30838706/", "study_type": "RCT", "confidence": "verify", "doi": "10.1002/ptr.6338", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30838706/", "publicSourceType": "PMID" }, { "text": "Kumar B, Ghaytidak AB, Pandey AK et al.. A Standardized Boswellia serrata Extract Improves Knee Joint Function and Cartilage Morphology in Human Volunteers with Mild to Moderate Osteoarthritis in a Randomized Placebo-Controlled Study. Journal of the American Nutrition Association. 2025", "claim": "PubMed-indexed evidence involving Boswellia", "title": "A Standardized Boswellia serrata Extract Improves Knee Joint Function and Cartilage Morphology in Human Volunteers with Mild to Moderate Osteoarthritis in a Randomized Placebo-Controlled Study", "authors": "Kumar B, Ghaytidak AB, Pandey AK et al.", "journal": "Journal of the American Nutrition Association", "year": 2025, "pmid": "39700461", "url": "https://pubmed.ncbi.nlm.nih.gov/39700461/", "study_type": "RCT", "confidence": "verify", "doi": "10.1080/27697061.2024.2438894", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39700461/", "publicSourceType": "PMID" }, { "text": "Mamatha K, Prabhakaran P, Syam Das S et al.. A full-spectrum Boswellia serrata extract with enhanced bioavailability, and its co-delivered system with curcumin alleviate pain and stiffness associated with moderate spondylitis: a randomized double-blind, placebo-controlled, 3-arm study. Frontiers in pharmacology. 2025", "claim": "PubMed-indexed evidence involving Boswellia", "title": "A full-spectrum Boswellia serrata extract with enhanced bioavailability, and its co-delivered system with curcumin alleviate pain and stiffness associated with moderate spondylitis: a randomized double-blind, placebo-controlled, 3-arm study", "authors": "Mamatha K, Prabhakaran P, Syam Das S et al.", "journal": "Frontiers in pharmacology", "year": 2025, "pmid": "40667507", "url": "https://pubmed.ncbi.nlm.nih.gov/40667507/", "study_type": "RCT", "confidence": "verify", "doi": "10.3389/fphar.2025.1577429", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40667507/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "boswellia" }, { "id": "3717648D-776A-4FEE-9E0B-EC18C3252736", "name": "Chaga", "alternateNames": [ "Inonotus obliquus" ], "category": "Herb", "subcategory": "Medicinal Mushroom", "overview": "Birch tree fungus rich in antioxidants and immune-modulating compounds.", "mechanismOfAction": "Contains betulinic acid, melanin, and beta-glucans. Betulinic acid has anti-tumor properties. Beta-glucans activate innate immunity via Dectin-1 receptors. Among the highest ORAC scores of any food.", "commonBenefits": [ "Antioxidant", "Immune modulation", "Skin health" ], "commonDosageRange": "500-1,500 mg daily", "recommendedForm": "Hot water or dual extract (water + alcohol)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Can take any time; hot water extract preferred" }, "evidenceRating": "emerging", "foodSources": [ "Chaga mushroom (wild-harvested from birch trees)" ], "deficiencySymptoms": [], "sideEffects": [ "May lower blood sugar", "Oxalate nephropathy and kidney failure risk from high oxalate content, especially with high-dose or long-term use" ], "contraindications": [ "Blood thinners", "Diabetes medications", "Kidney disease", "Autoimmune conditions", "Kidney stone history", "Hyperoxaluria or high-oxalate diet" ], "iconName": "tree.fill", "colorHex": "34D399", "tags": [ "immune", "antioxidant", "mushroom" ], "sources": [ { "claim": "Comprehensive review of therapeutic properties including antioxidant and immune effects", "title": "Therapeutic properties of Inonotus obliquus (Chaga mushroom): A review", "authors": "Szychowski KA et al.", "journal": "Mycobiology", "year": 2024, "pmid": "38813471", "url": "https://pubmed.ncbi.nlm.nih.gov/38813471/", "study_type": "review", "key_finding": "Scientific evidence supports anti-inflammatory, antioxidant, anticancer, anti-diabetic, anti-obesity, hepatoprotective, and immunomodulating properties of chaga extracts", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38813471/", "publicSourceType": "PMID" }, { "claim": "Chaga as a multi-faceted medicinal fungus with molecular mechanisms", "title": "Chaga mushroom: a super-fungus with countless facets and untapped potential", "authors": "Szychowski KA et al.", "journal": "Nutrients", "year": 2024, "pmid": "38116085", "url": "https://pubmed.ncbi.nlm.nih.gov/38116085/", "study_type": "review", "key_finding": "Chaga possesses remarkable anticancer, antioxidant, anti-diabetic, anti-inflammatory, antimicrobial, and immunomodulating properties attributed to polysaccharides, triterpenoids, and polyphenols", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38116085/", "publicSourceType": "PMID" }, { "claim": "Antioxidant effects protecting against DNA damage in human lymphocytes", "title": "Chaga mushroom extract inhibits oxidative DNA damage in human lymphocytes as assessed by comet assay", "authors": "Park YK et al.", "journal": "Biofactors", "year": 2004, "pmid": "15630179", "url": "https://pubmed.ncbi.nlm.nih.gov/15630179/", "study_type": "preclinical", "key_finding": "Chaga mushroom extract showed protective effects against oxidative DNA damage in human lymphocytes when challenged with H2O2", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15630179/", "publicSourceType": "PMID" }, { "claim": "Molecular mechanisms of action including ROS scavenging, immune stimulation, and anti-tumor effects", "title": "The pharmacological potential and possible molecular mechanisms of action of Inonotus obliquus from preclinical studies", "authors": "Balandaykin ME et al.", "journal": "Mycobiology", "year": 2019, "pmid": "31209936", "url": "https://pubmed.ncbi.nlm.nih.gov/31209936/", "study_type": "review", "key_finding": "Chaga can scavenge reactive oxygen species, inhibit tumor growth, decrease inflammation and insulin resistance, and stimulate the immune system", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31209936/", "publicSourceType": "PMID" }, { "claim": "Safety concern: oxalate nephropathy from excessive chaga consumption", "title": "Chaga mushroom-induced oxalate nephropathy", "authors": "Kikuchi Y et al.", "journal": "Clin Nephrol", "year": 2014, "pmid": "23149251", "url": "https://pubmed.ncbi.nlm.nih.gov/23149251/", "study_type": "case report", "key_finding": "Case report documenting oxalate nephropathy caused by excessive chaga mushroom intake, highlighting the high oxalate content as a kidney risk factor", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23149251/", "publicSourceType": "PMID" }, { "claim": "Chemical characterization of bioactive compounds including betulinic acid and beta-glucans", "title": "Chemical characterization and biological activity of Chaga (Inonotus obliquus), a medicinal mushroom", "authors": "Glamoclija J et al.", "journal": "J Ethnopharmacol", "year": 2015, "pmid": "25576897", "url": "https://pubmed.ncbi.nlm.nih.gov/25576897/", "study_type": "preclinical", "key_finding": "Characterized polysaccharides, triterpenoids (including betulinic acid), polyphenols, and lignin metabolites responsible for chaga's health-benefiting properties", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25576897/", "publicSourceType": "PMID" }, { "text": "Wu Y, Liu J, Luo J et al.. Molecular Mechanisms of Phytochemicals from Chaga Mushroom (Inonotus obliquus) Against Colorectal Cancer: Insights from Network Pharmacology, Molecular Docking, and Bioinformatics. International journal of molecular sciences. 2025", "pmid": "40868987", "doi": "10.3390/ijms26167664", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40868987/", "publicSourceType": "PMID" }, { "text": "Endo T, Nakagomi Y, Kawaguchi E et al.. Anti-malarial activity in a Chinese herbal supplement containing Inonotus obliquus and Panax notoginseng. Parasitology international. 2022", "pmid": "34933121", "doi": "10.1016/j.parint.2021.102532", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34933121/", "publicSourceType": "PMID" }, { "claim": "Chaga polysaccharides have anti-inflammatory and immunomodulatory effects", "title": "Recent developments in Inonotus obliquus (Chaga mushroom) polysaccharides: isolation, structural characteristics, biological activities and application.", "authors": "Lu Y, Jia Y, Xue Z, Li N, Liu J, Chen H", "journal": "Polymers", "year": 2021, "pmid": "33947037", "url": "https://pubmed.ncbi.nlm.nih.gov/33947037/", "study_type": "review", "key_finding": "Review of I. obliquus polysaccharides documenting antioxidant, anti-inflammatory, immunomodulatory, anti-tumor, anti-diabetic, and hepatoprotective activities, with structural characterization and mechanisms of action.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33947037/", "publicSourceType": "PMID" }, { "claim": "Chaga has therapeutic potential from folk medicine to clinical use", "title": "Inonotus obliquus - from folk medicine to clinical use.", "authors": "Szychowski KA, Skora B, Pomianek T, Gminski J", "journal": "Journal of Traditional and Complementary Medicine", "year": 2021, "pmid": "34195023", "url": "https://pubmed.ncbi.nlm.nih.gov/34195023/", "study_type": "review", "key_finding": "Review documents traditional use and modern pharmacological evidence for Chaga including antioxidant, anti-inflammatory, antimicrobial, and anticancer properties with potential mechanisms of action discussed.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34195023/", "publicSourceType": "PMID" }, { "text": "Tee PYE, Krishnan T, Cheong XT et al.. A review on the cultivation, bioactive compounds, health-promoting factors and clinical trials of medicinal mushrooms Taiwanofungus camphoratus, Inonotus obliquus and Tropicoporus linteus. Fungal biology and biotechnology. 2024", "claim": "PubMed-indexed evidence involving Chaga", "title": "A review on the cultivation, bioactive compounds, health-promoting factors and clinical trials of medicinal mushrooms Taiwanofungus camphoratus, Inonotus obliquus and Tropicoporus linteus", "authors": "Tee PYE, Krishnan T, Cheong XT et al.", "journal": "Fungal biology and biotechnology", "year": 2024, "pmid": "38987829", "url": "https://pubmed.ncbi.nlm.nih.gov/38987829/", "study_type": "review", "confidence": "verify", "doi": "10.1186/s40694-024-00176-3", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38987829/", "publicSourceType": "PMID" }, { "text": "Lee S, Lee HY, Park Y et al.. Development of End Stage Renal Disease after Long-Term Ingestion of Chaga Mushroom: Case Report and Review of Literature. Journal of Korean medical science. 2020", "claim": "PubMed-indexed evidence involving Chaga", "title": "Development of End Stage Renal Disease after Long-Term Ingestion of Chaga Mushroom: Case Report and Review of Literature", "authors": "Lee S, Lee HY, Park Y et al.", "journal": "Journal of Korean medical science", "year": 2020, "pmid": "32419395", "url": "https://pubmed.ncbi.nlm.nih.gov/32419395/", "study_type": "review", "confidence": "verify", "doi": "10.3346/jkms.2020.35.e122", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32419395/", "publicSourceType": "PMID" }, { "text": "Zhang S, Zhang W, Wu X et al.. Inonotus obliquus Polysaccharides: Preparation, Structural Characteristics, Structure-Activity Relationships, Biological Activities and Applications. Nutrients. 2026", "claim": "PubMed-indexed evidence involving Chaga", "title": "Inonotus obliquus Polysaccharides: Preparation, Structural Characteristics, Structure-Activity Relationships, Biological Activities and Applications", "authors": "Zhang S, Zhang W, Wu X et al.", "journal": "Nutrients", "year": 2026, "pmid": "41978174", "url": "https://pubmed.ncbi.nlm.nih.gov/41978174/", "study_type": "review", "confidence": "verify", "doi": "10.3390/nu18071125", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41978174/", "publicSourceType": "PMID" }, { "text": "Windsor C, Kreynes AE, Chilton JS et al.. Comparative Study of Chaga (Inonotus obliquus) Dietary Supplements Using Complementary Analytical Techniques. International journal of molecular sciences. 2025", "claim": "PubMed-indexed evidence involving Chaga", "title": "Comparative Study of Chaga (Inonotus obliquus) Dietary Supplements Using Complementary Analytical Techniques", "authors": "Windsor C, Kreynes AE, Chilton JS et al.", "journal": "International journal of molecular sciences", "year": 2025, "pmid": "40243601", "url": "https://pubmed.ncbi.nlm.nih.gov/40243601/", "study_type": "review", "confidence": "verify", "doi": "10.3390/ijms26072970", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40243601/", "publicSourceType": "PMID" }, { "text": "Gil YG , Kang S , Chae A et al.. Synthesis of porous Pd nanoparticles by therapeutic chaga extract for highly efficient tri-modal cancer treatment. Nanoscale. 2018", "claim": "PubMed-indexed evidence involving Chaga", "title": "Synthesis of porous Pd nanoparticles by therapeutic chaga extract for highly efficient tri-modal cancer treatment", "authors": "Gil YG , Kang S , Chae A et al.", "journal": "Nanoscale", "year": 2018, "pmid": "30334053", "url": "https://pubmed.ncbi.nlm.nih.gov/30334053/", "study_type": "review", "confidence": "verify", "doi": "10.1039/c8nr07172a", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30334053/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "chaga" }, { "id": "9B0F3C3C-0FE1-45AA-98C0-B3C38B3D7E03", "name": "Turkey Tail", "alternateNames": [ "Trametes versicolor", "Coriolus versicolor" ], "category": "Herb", "subcategory": "Medicinal Mushroom", "overview": "Colorful bracket fungus with strong immune-modulating research, especially PSK/PSP.", "mechanismOfAction": "Polysaccharopeptides PSK and PSP activate NK cells, T cells, and macrophages. Modulate gut microbiome composition. Used adjunctively in cancer care in Japan.", "commonBenefits": [ "Immune modulation", "Gut microbiome", "Cancer support (adjunctive)" ], "commonDosageRange": "1-3 g daily", "recommendedForm": "Hot water extract or dual extract powder", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Can take any time" }, "evidenceRating": "moderate", "foodSources": [ "Turkey tail mushroom" ], "deficiencySymptoms": [], "sideEffects": [ "Mild GI", "Darkened stools", "Darkened nails" ], "contraindications": [ "Immunosuppressants", "Autoimmune diseases" ], "iconName": "shield.fill", "colorHex": "34D399", "tags": [ "immune", "mushroom", "microbiome" ], "sources": [ { "claim": "Systematic review of PSK for lung cancer adjuvant immunotherapy", "title": "Polysaccharide K and Coriolus versicolor extracts for lung cancer: a systematic review", "authors": "Fritz H et al.", "journal": "Integr Cancer Ther", "year": 2015, "pmid": "25784670", "url": "https://pubmed.ncbi.nlm.nih.gov/25784670/", "study_type": "review", "key_finding": "15 of 17 preclinical studies supported anticancer effects for PSK through immunomodulation and potentiation of immune surveillance; PSK may extend survival in lung cancer patients", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25784670/", "publicSourceType": "PMID" }, { "claim": "PSK and PSP immune activating properties", "title": "The mycelium of the Trametes versicolor (Turkey tail) mushroom and its fermented substrate each show potent and complementary immune activating properties in vitro", "authors": "Benson KF et al.", "journal": "BMC Complement Med Ther", "year": 2019, "pmid": "31791317", "url": "https://pubmed.ncbi.nlm.nih.gov/31791317/", "study_type": "preclinical", "key_finding": "Turkey tail mycelium and fermented substrate showed potent and complementary immune activating properties in vitro", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31791317/", "publicSourceType": "PMID" }, { "claim": "Cochrane-style review of turkey tail for reducing cancer treatment adverse effects", "title": "Coriolus (Trametes) versicolor mushroom to reduce adverse effects from chemotherapy or radiotherapy in people with colorectal cancer", "authors": "Pilkington K et al.", "journal": "Cochrane Database Syst Rev", "year": 2022, "pmid": "36445793", "url": "https://pubmed.ncbi.nlm.nih.gov/36445793/", "study_type": "review", "key_finding": "Systematic review of turkey tail mushroom polysaccharides for reducing adverse effects of cancer treatment in colorectal cancer patients", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36445793/", "publicSourceType": "PMID" }, { "claim": "Polysaccharides PSK/PSP targets and efficacy in cancer therapy", "title": "Trametes versicolor (Synn. Coriolus versicolor) Polysaccharides in Cancer Therapy: Targets and Efficacy", "authors": "Saleh MH et al.", "journal": "Front Pharmacol", "year": 2020, "pmid": "32466253", "url": "https://pubmed.ncbi.nlm.nih.gov/32466253/", "study_type": "review", "key_finding": "PSK and PSP polysaccharopeptides activate NK cells, T cells, and macrophages and serve as adjuvant therapy for cancer", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32466253/", "publicSourceType": "PMID" }, { "claim": "Gut microbiome modulation in healthy humans", "title": "Effects of polysaccharopeptide from Trametes versicolor and amoxicillin on the gut microbiome of healthy volunteers: a randomized clinical trial", "authors": "Pallav K et al.", "journal": "Gut Microbes", "year": 2014, "pmid": "25006989", "url": "https://pubmed.ncbi.nlm.nih.gov/25006989/", "study_type": "RCT", "key_finding": "PSP significantly increased Bifidobacterium and Lactobacillus while reducing Clostridium, Staphylococcus, and Enterococcus in healthy volunteers", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25006989/", "publicSourceType": "PMID" }, { "claim": "Turkey tail breast cancer immune therapy clinical study", "title": "Trametes versicolor mushroom immune therapy in breast cancer", "authors": "Standish LJ et al.", "journal": "J Soc Integr Oncol", "year": 2008, "pmid": "19087769", "url": "https://pubmed.ncbi.nlm.nih.gov/19087769/", "study_type": "RCT", "key_finding": "Turkey tail mushroom demonstrated immune-enhancing properties in breast cancer patients as an adjunct to conventional treatment", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19087769/", "publicSourceType": "PMID" }, { "text": "Zhong L, Yan P, Lam WC et al.. Coriolus Versicolor and Ganoderma Lucidum Related Natural Products as an Adjunct Therapy for Cancers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Frontiers in pharmacology. 2019", "pmid": "31333449", "doi": "10.3389/fphar.2019.00703", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31333449/", "publicSourceType": "PMID" }, { "text": "Eliza WL, Fai CK, Chung LP. Efficacy of Yun Zhi (Coriolus versicolor) on survival in cancer patients: systematic review and meta-analysis. Recent patents on inflammation & allergy drug discovery. 2012", "pmid": "22185453", "doi": "10.2174/187221312798889310", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22185453/", "publicSourceType": "PMID" }, { "claim": "Coriolus versicolor polysaccharides enhance immune function in cancer", "title": "Trametes versicolor (Coriolus versicolor) polysaccharopeptide as an adjuvant treatment for cancer: A systematic review and meta-analysis.", "authors": "Elsayed EA, El Enshasy H, Wadaan MAM et al.", "journal": "Journal of Integrative Medicine", "year": 2024, "pmid": "38697129", "url": "https://pubmed.ncbi.nlm.nih.gov/38697129/", "study_type": "meta-analysis", "key_finding": "Systematic review found that polysaccharopeptide (PSK/PSP) from Trametes versicolor used as adjuvant cancer therapy improved survival, immune function markers, and reduced chemotherapy side effects across multiple cancer types.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38697129/", "publicSourceType": "PMID" }, { "claim": "Turkey Tail PSK improves survival in colorectal cancer", "title": "Polysaccharide-K (PSK) as an adjuvant treatment for colorectal cancer: A systematic review and meta-analysis.", "authors": "Wang C, Zhang J, Zhang N et al.", "journal": "Frontiers in Pharmacology", "year": 2023, "pmid": "38047360", "url": "https://pubmed.ncbi.nlm.nih.gov/38047360/", "study_type": "meta-analysis", "key_finding": "Meta-analysis found PSK (from Coriolus versicolor) as adjuvant therapy significantly improved overall survival and disease-free survival in colorectal cancer patients when combined with chemotherapy.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38047360/", "publicSourceType": "PMID" }, { "text": "Ma Y, Wu X, Yu J et al.. Can polysaccharide K improve therapeutic efficacy and safety in gastrointestinal cancer? a systematic review and network meta-analysis. Oncotarget. 2017", "claim": "PubMed-indexed evidence involving Turkey Tail", "title": "Can polysaccharide K improve therapeutic efficacy and safety in gastrointestinal cancer? a systematic review and network meta-analysis", "authors": "Ma Y, Wu X, Yu J et al.", "journal": "Oncotarget", "year": 2017, "pmid": "29179503", "url": "https://pubmed.ncbi.nlm.nih.gov/29179503/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.18632/oncotarget.19059", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29179503/", "publicSourceType": "PMID" }, { "text": "Kale Bakir E, Deveci Ozkan A, Erman G et al.. Anticancer potential of purified laccase enzyme from Trametes versicolor: specific cytotoxicity against thyroid and endometrial cancer cells. Molecular biology reports. 2025", "claim": "PubMed-indexed evidence involving Turkey Tail", "title": "Anticancer potential of purified laccase enzyme from Trametes versicolor: specific cytotoxicity against thyroid and endometrial cancer cells", "authors": "Kale Bakir E, Deveci Ozkan A, Erman G et al.", "journal": "Molecular biology reports", "year": 2025, "pmid": "40085415", "url": "https://pubmed.ncbi.nlm.nih.gov/40085415/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s11033-025-10416-3", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40085415/", "publicSourceType": "PMID" }, { "text": "Ito K, Nakazato H, Koike A et al.. Long-term effect of 5-fluorouracil enhanced by intermittent administration of polysaccharide K after curative resection of colon cancer. A randomized controlled trial for 7-year follow-up. International journal of colorectal disease. 2004", "claim": "PubMed-indexed evidence involving Turkey Tail", "title": "Long-term effect of 5-fluorouracil enhanced by intermittent administration of polysaccharide K after curative resection of colon cancer. A randomized controlled trial for 7-year follow-up", "authors": "Ito K, Nakazato H, Koike A et al.", "journal": "International journal of colorectal disease", "year": 2004, "pmid": "13680286", "url": "https://pubmed.ncbi.nlm.nih.gov/13680286/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/s00384-003-0532-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/13680286/", "publicSourceType": "PMID" }, { "text": "Ohwada S, Kawate S, Ikeya T et al.. Adjuvant therapy with protein-bound polysaccharide K and tegafur uracil in patients with stage II or III colorectal cancer: randomized, controlled trial. Diseases of the colon and rectum. 2003", "claim": "PubMed-indexed evidence involving Turkey Tail", "title": "Adjuvant therapy with protein-bound polysaccharide K and tegafur uracil in patients with stage II or III colorectal cancer: randomized, controlled trial", "authors": "Ohwada S, Kawate S, Ikeya T et al.", "journal": "Diseases of the colon and rectum", "year": 2003, "pmid": "12907900", "url": "https://pubmed.ncbi.nlm.nih.gov/12907900/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/s10350-004-7281-y", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12907900/", "publicSourceType": "PMID" }, { "text": "Nakazato H, Koike A, Ichihashi H et al.. [An effect of adjuvant immunochemotherapy using krestin and 5-FU on gastric cancer patients with radical surgery (first report)--a randomized controlled trial by the cooperative study group. Study Group of Immuno-chemotherapy with PSK for Gastric Cancer]. Gan to kagaku ryoho. Cancer & chemotherapy. 1989", "claim": "PubMed-indexed evidence involving Turkey Tail", "title": "[An effect of adjuvant immunochemotherapy using krestin and 5-FU on gastric cancer patients with radical surgery (first report)--a randomized controlled trial by the cooperative study group. Study Group of Immuno-chemotherapy with PSK for Gastric Cancer]", "authors": "Nakazato H, Koike A, Ichihashi H et al.", "journal": "Gan to kagaku ryoho. Cancer & chemotherapy", "year": 1989, "pmid": "2505682", "url": "https://pubmed.ncbi.nlm.nih.gov/2505682/", "study_type": "RCT", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2505682/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "turkey-tail" }, { "id": "66698279-F109-408A-BBCA-9C9EEDFAB18C", "name": "Schisandra", "alternateNames": [ "Schisandra chinensis", "Five-Flavor Berry" ], "category": "Herb", "subcategory": "Adaptogenic Berry", "overview": "Adaptogenic berry used in TCM for liver protection and stress resilience.", "mechanismOfAction": "Lignans such as schisandrin B influence oxidative stress, mitochondrial function, and hepatic glutathione. Schisandra lignans can also inhibit or modulate CYP450 enzymes and P-glycoprotein, creating clinically relevant drug-interaction potential.", "commonBenefits": [ "Liver protection", "Stress adaptation", "Endurance", "Skin health" ], "commonDosageRange": "500-1,000 mg daily", "recommendedForm": "Standardized extract (9% schisandrin)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food" }, "evidenceRating": "moderate", "foodSources": [ "Schisandra berries" ], "deficiencySymptoms": [], "sideEffects": [ "GI upset", "Decreased appetite", "Heartburn", "Drug interaction risk via CYP3A4 and P-glycoprotein modulation" ], "contraindications": [ "Epilepsy", "Peptic ulcers", "Pregnancy", "Transplant medication use", "Tacrolimus or cyclosporine therapy", "CYP3A4 or P-glycoprotein substrate medications unless clinician-supervised" ], "iconName": "leaf.fill", "colorHex": "6BCB77", "tags": [ "adaptogen", "liver", "stress", "tcm" ], "sources": [ { "claim": "Systematic review and meta-analysis of schisandra for liver injury", "title": "Efficacy of Schisandra chinensis in liver injury: a systematic review and preclinical meta-analysis", "authors": "Wang X et al.", "journal": "Phytomedicine", "year": 2025, "pmid": "40832608", "url": "https://pubmed.ncbi.nlm.nih.gov/40832608/", "study_type": "meta-analysis", "key_finding": "54 animal studies showed schisandra bioactive compounds significantly reduced ALT, AST, and ALP levels, confirming hepatoprotective effects", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40832608/", "publicSourceType": "PMID" }, { "claim": "Comprehensive review of schisandra phytotherapy applications", "title": "Schisandra chinensis and its phytotherapeutical applications", "authors": "Nowak A et al.", "journal": "Front Pharmacol", "year": 2019, "pmid": "31431019", "url": "https://pubmed.ncbi.nlm.nih.gov/31431019/", "study_type": "review", "key_finding": "Schisandra lignans have confirmed adaptogenic effects, central nervous system stimulation, hepatoprotective effects, and potential anticancer properties", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31431019/", "publicSourceType": "PMID" }, { "claim": "Schisandrin B enhances mitochondrial antioxidant status and improves survival in aging", "title": "Long-term schisandrin B treatment mitigates age-related impairments in mitochondrial antioxidant status and functional ability in various tissues, and improves the survival of aging C57BL/6J mice", "authors": "Ko KM et al.", "journal": "Biofactors", "year": 2009, "pmid": "19850987", "url": "https://pubmed.ncbi.nlm.nih.gov/19850987/", "study_type": "preclinical", "key_finding": "Schisandrin B supplementation suppressed mitochondrial ROS production, enhanced mitochondrial ATP generation, and improved survival in aging mice", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19850987/", "publicSourceType": "PMID" }, { "claim": "Adaptogenic pharmacology based on Russian research and clinical uses", "title": "Pharmacology of Schisandra chinensis Bail.: an overview of Russian research and uses in medicine", "authors": "Panossian A et al.", "journal": "J Ethnopharmacol", "year": 2008, "pmid": "18515024", "url": "https://pubmed.ncbi.nlm.nih.gov/18515024/", "study_type": "review", "key_finding": "Schisandra chinensis gained recognition as an adaptogen in official USSR medicine, with clinical trials demonstrating efficacy in asthenia, neuralgic and psychiatric disorders, and influenza", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18515024/", "publicSourceType": "PMID" }, { "claim": "Antioxidant effects of schisandra and its active constituents", "title": "Antioxidant Effects of Schisandra chinensis Fruits and Their Active Constituents", "authors": "Szopa A et al.", "journal": "Int J Mol Sci", "year": 2021, "pmid": "33919588", "url": "https://pubmed.ncbi.nlm.nih.gov/33919588/", "study_type": "review", "key_finding": "Schisandra lignans, including schisandrin B, exhibit potent antioxidant properties that protect against oxidative stress and enhance hepatic glutathione", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33919588/", "publicSourceType": "PMID" }, { "claim": "Schisandrin B activates Nrf2/Keap1 antioxidant pathway", "title": "Schisandrin B alleviates acute oxidative stress via modulation of the Nrf2/Keap1-mediated antioxidant pathway", "authors": "Leong PK et al.", "journal": "Appl Physiol Nutr Metab", "year": 2018, "pmid": "29742356", "url": "https://pubmed.ncbi.nlm.nih.gov/29742356/", "study_type": "preclinical", "key_finding": "Schisandrin B provides cytoprotection against oxidative stress via Nrf2/Keap1 pathway modulation, supporting its use as an adaptogenic compound", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29742356/", "publicSourceType": "PMID" }, { "text": "Zhu P, Li J, Fu X et al.. Schisandra fruits for the management of drug-induced liver injury in China: A review. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2019", "pmid": "31004881", "doi": "10.1016/j.phymed.2018.11.020", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31004881/", "publicSourceType": "PMID" }, { "text": "Li Z, He X, Liu F et al.. A review of polysaccharides from Schisandra chinensis and Schisandra sphenanthera: Properties, functions and applications. Carbohydrate polymers. 2018", "pmid": "29352909", "doi": "10.1016/j.carbpol.2017.12.058", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29352909/", "publicSourceType": "PMID" }, { "claim": "Schisandra chinensis extract enhances muscle strength in older adults performing low-intensity exercise", "title": "Effect of Schisandra chinensis Baillon extracts and regular low-intensity exercise on muscle strength and mass in older adults: a randomized, double-blind, placebo-controlled trial", "authors": "Cho YH, Lee SY, Lee CH, Park JH, So YS", "journal": "Am J Clin Nutr", "year": 2021, "pmid": "33710261", "url": "https://pubmed.ncbi.nlm.nih.gov/33710261/", "study_type": "rct", "key_finding": "RCT of 54 adults >50 years found 12 weeks of Schisandra chinensis extract (1 g/day) significantly increased right knee extensor strength (+10.2 Nm) and left knee extensor strength (+6.7 Nm) compared to placebo, without adverse events.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33710261/", "publicSourceType": "PMID" }, { "claim": "Schisandra chinensis extract improves quadriceps muscle strength and reduces lactate in post-menopausal women", "title": "Effect of Schisandra Chinensis Extract Supplementation on Quadriceps Muscle Strength and Fatigue in Adult Women: A Randomized, Double-Blind, Placebo-Controlled Trial", "authors": "Park J, Han S, Park H", "journal": "Int J Environ Res Public Health", "year": 2020, "pmid": "32260466", "url": "https://pubmed.ncbi.nlm.nih.gov/32260466/", "study_type": "rct", "key_finding": "RCT of 45 post-menopausal women found 12 weeks of SC extract (1000 mg/day) significantly increased quadriceps muscle strength and decreased resting lactate levels.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32260466/", "publicSourceType": "PMID" }, { "claim": "Schisandra chinensis extract may improve glycemic control in individuals with hyperglycemia", "title": "Efficacy and Safety of Omija (Schisandra chinensis) Extract Mixture on the Improvement of Hyperglycemia: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial", "authors": "Kim DS, Baek HI, Ha KC, Cha YS, Park SJ", "journal": "Nutrients", "year": 2022, "pmid": "35956334", "url": "https://pubmed.ncbi.nlm.nih.gov/35956334/", "study_type": "rct", "key_finding": "RCT of 80 participants with hyperglycemia found 12 weeks of Omija/Schisandra extract mixture significantly decreased fasting plasma glucose, postprandial glucose, fructosamine, and LDL cholesterol compared to placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35956334/", "publicSourceType": "PMID" }, { "claim": "Schisandra chinensis extract reduces menopausal symptoms including hot flushes and sweating", "title": "A randomized, double-blind, placebo-controlled trial of Schisandra chinensis for menopausal symptoms", "authors": "Park JY, Kim KH", "journal": "Climacteric", "year": 2016, "pmid": "27763802", "url": "https://pubmed.ncbi.nlm.nih.gov/27763802/", "study_type": "rct", "key_finding": "RCT of 36 menopausal women found Schisandra chinensis extract (BMO-30) significantly reduced total Kupperman Index scores compared to placebo, especially for hot flushes, sweating, and heart palpitations.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27763802/", "publicSourceType": "PMID" }, { "text": "Zhang F, Zhai J, Weng N et al.. A Comprehensive Review of the Main Lignan Components of Schisandra chinensis (North Wu Wei Zi) and Schisandra sphenanthera (South Wu Wei Zi) and the Lignan-Induced Drug-Drug Interactions Based on the Inhibition of Cytochrome P450 and P-Glycoprotein Activities. Frontiers in pharmacology. 2022", "claim": "PubMed-indexed evidence involving Schisandra", "title": "A Comprehensive Review of the Main Lignan Components of Schisandra chinensis (North Wu Wei Zi) and Schisandra sphenanthera (South Wu Wei Zi) and the Lignan-Induced Drug-Drug Interactions Based on the Inhibition of Cytochrome P450 and P-Glycoprotein Activities", "authors": "Zhang F, Zhai J, Weng N et al.", "journal": "Frontiers in pharmacology", "year": 2022, "pmid": "35359848", "url": "https://pubmed.ncbi.nlm.nih.gov/35359848/", "study_type": "review", "confidence": "verify", "doi": "10.3389/fphar.2022.816036", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35359848/", "publicSourceType": "PMID" }, { "text": "Zheng A, Yang D, Pan C et al.. Modeling the complexity of drug-drug interactions: A physiologically-based pharmacokinetic study of Lenvatinib with Schisantherin A/Schisandrin A. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2024", "claim": "PubMed-indexed evidence involving Schisandra", "title": "Modeling the complexity of drug-drug interactions: A physiologically-based pharmacokinetic study of Lenvatinib with Schisantherin A/Schisandrin A", "authors": "Zheng A, Yang D, Pan C et al.", "journal": "European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences", "year": 2024, "pmid": "38556066", "url": "https://pubmed.ncbi.nlm.nih.gov/38556066/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.ejps.2024.106757", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38556066/", "publicSourceType": "PMID" }, { "text": "Valíčková J, Zezulka Š, Maršálková E et al.. Potential toxicity of Schisandra chinensis to water environment: acute toxicity tests with water crustaceans. Environmental science and pollution research international. 2023", "claim": "PubMed-indexed evidence involving Schisandra", "title": "Potential toxicity of Schisandra chinensis to water environment: acute toxicity tests with water crustaceans", "authors": "Valíčková J, Zezulka Š, Maršálková E et al.", "journal": "Environmental science and pollution research international", "year": 2023, "pmid": "37837583", "url": "https://pubmed.ncbi.nlm.nih.gov/37837583/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s11356-023-30182-8", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37837583/", "publicSourceType": "PMID" }, { "text": "Song MY, Wang JH, Eom T et al.. Schisandra chinensis fruit modulates the gut microbiota composition in association with metabolic markers in obese women: a randomized, double-blind placebo-controlled study. Nutrition research (New York, N.Y.). 2015", "claim": "PubMed-indexed evidence involving Schisandra", "title": "Schisandra chinensis fruit modulates the gut microbiota composition in association with metabolic markers in obese women: a randomized, double-blind placebo-controlled study", "authors": "Song MY, Wang JH, Eom T et al.", "journal": "Nutrition research (New York, N.Y.)", "year": 2015, "pmid": "26048342", "url": "https://pubmed.ncbi.nlm.nih.gov/26048342/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.nutres.2015.05.001", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26048342/", "publicSourceType": "PMID" }, { "text": "Liu Z, Wang C, Fan H et al.. Modulation of disease-associated gut microbiota by Schisandra chinensis: a literature review. Frontiers in pharmacology. 2026", "claim": "PubMed-indexed evidence involving Schisandra", "title": "Modulation of disease-associated gut microbiota by Schisandra chinensis: a literature review", "authors": "Liu Z, Wang C, Fan H et al.", "journal": "Frontiers in pharmacology", "year": 2026, "pmid": "42078929", "url": "https://pubmed.ncbi.nlm.nih.gov/42078929/", "study_type": "review", "confidence": "verify", "doi": "10.3389/fphar.2026.1721950", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/42078929/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "schisandra" }, { "id": "82B67823-8214-439C-B1C9-5E5EDE74151E", "name": "Evening Primrose Oil", "alternateNames": [ "EPO", "Oenothera biennis" ], "category": "Omega/Fatty Acid", "subcategory": "Omega-6 Fatty Acid", "overview": "Rich in gamma-linolenic acid (GLA) for hormonal balance and skin health.", "mechanismOfAction": "GLA is converted to dihomo-GLA (DGLA) and then to anti-inflammatory prostaglandin E1 (PGE1). Supports healthy estrogen metabolism and skin barrier function.", "commonBenefits": [ "Hormonal balance", "PMS relief", "Skin health", "Breast tenderness" ], "commonDosageRange": "500-1,000 mg daily", "recommendedForm": "Cold-pressed evening primrose oil capsules", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food for absorption" }, "evidenceRating": "moderate", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "GI upset", "Headache", "Increased bleeding risk" ], "contraindications": [ "Blood thinners", "Seizure disorders", "Anesthesia (stop 2 weeks before)" ], "iconName": "drop.fill", "colorHex": "4D94FF", "tags": [ "hormonal", "skin", "pms", "omega" ], "sources": [ { "claim": "Meta-analysis of EPO efficacy for breast pain (mastalgia)", "title": "A Systematic Review and Meta-Analysis of the Efficacy of Evening Primrose Oil for Mastalgia Treatment", "authors": "Defined N et al.", "journal": "Int J Surg", "year": 2021, "pmid": "34200727", "url": "https://pubmed.ncbi.nlm.nih.gov/34200727/", "study_type": "meta-analysis", "key_finding": "Systematic review and meta-analysis examined the efficacy of evening primrose oil for treating breast pain in women", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34200727/", "publicSourceType": "PMID" }, { "claim": "EPO efficacy in atopic dermatitis skin health", "title": "Evening primrose oil is effective in atopic dermatitis: a randomized placebo-controlled trial", "authors": "Senapati S et al.", "journal": "Indian J Dermatol Venereol Leprol", "year": 2008, "pmid": "19052401", "url": "https://pubmed.ncbi.nlm.nih.gov/19052401/", "study_type": "RCT", "key_finding": "EPO is a safe and effective medicine in management of atopic dermatitis, with statistically significant improvement in severity, inflammation, body surface area involvement, dryness and itch", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19052401/", "publicSourceType": "PMID" }, { "claim": "Systematic review of EPO for PMS showing limited evidence", "title": "Is evening primrose oil of value in the treatment of premenstrual syndrome?", "authors": "Budeiri D et al.", "journal": "Control Clin Trials", "year": 1996, "pmid": "8721802", "url": "https://pubmed.ncbi.nlm.nih.gov/8721802/", "study_type": "review", "key_finding": "The two most well-controlled studies failed to show beneficial effects for EPO in PMS; on current evidence EPO is of little value in PMS management", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8721802/", "publicSourceType": "PMID" }, { "claim": "EPO effects on inflammatory diseases reviewed systematically", "title": "The effect of Oenothera biennis (Evening primrose) oil on inflammatory diseases: a systematic review of clinical trials", "authors": "Mahboubi M et al.", "journal": "J Ethnopharmacol", "year": 2024, "pmid": "38360611", "url": "https://pubmed.ncbi.nlm.nih.gov/38360611/", "study_type": "review", "key_finding": "EPO showed some results in diabetes mellitus, atopic eczema, menopausal hot flashes, and mastalgia through its GLA content and PGE1 production", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38360611/", "publicSourceType": "PMID" }, { "claim": "Meta-analysis of EPO effects on lipid profile", "title": "Effect of evening primrose oil supplementation on lipid profile: A systematic review and meta-analysis of randomized clinical trials", "authors": "Defined N et al.", "journal": "Phytother Res", "year": 2020, "pmid": "32441049", "url": "https://pubmed.ncbi.nlm.nih.gov/32441049/", "study_type": "meta-analysis", "key_finding": "Systematic review and meta-analysis of RCTs examining EPO supplementation effects on lipid profile markers", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32441049/", "publicSourceType": "PMID" }, { "claim": "Cochrane review of EPO and borage oil for eczema", "title": "Oral evening primrose oil and borage oil for eczema", "authors": "Bamford JT et al.", "journal": "Cochrane Database Syst Rev", "year": 2013, "pmid": "23633319", "url": "https://pubmed.ncbi.nlm.nih.gov/23633319/", "study_type": "meta-analysis", "key_finding": "Cochrane review assessing oral evening primrose oil and borage oil for eczema treatment, providing the most rigorous assessment of evidence", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23633319/", "publicSourceType": "PMID" }, { "text": "Vassilopoulou E, Comotti A, Douladiris N et al.. A systematic review and meta-analysis of nutritional and dietary interventions in randomized controlled trials for skin symptoms in children with atopic dermatitis and without food allergy: An EAACI task force report. Allergy. 2024", "pmid": "38783644", "doi": "10.1111/all.16160", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38783644/", "publicSourceType": "PMID" }, { "text": "Bayles B, Usatine R. Evening primrose oil. American family physician. 2009", "pmid": "20000302", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20000302/", "publicSourceType": "PMID" }, { "claim": "EPO supplementation may help reduce menopausal hot flash severity and duration", "title": "The Effect of Evening Primrose Oil on Menopausal Symptoms Management: A Systematic Review and Meta-Analysis", "authors": "Larki M, Mohammadi S, Makvandi S", "journal": "J Caring Sci", "year": 2025, "pmid": "41883983", "url": "https://pubmed.ncbi.nlm.nih.gov/41883983/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 6 RCTs (450 women) found EPO reduced hot flash duration significantly but reductions in hot flash frequency and intensity were not statistically significant. Evidence grading was moderate to low.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41883983/", "publicSourceType": "PMID" }, { "claim": "EPO may assist with cervical ripening and reducing cesarean section rates in term pregnancies", "title": "Evening primrose oil for cervical ripening in term pregnancies: a systematic review and meta-analysis", "authors": "Hemmatzadeh S, Mohammad Alizadeh Charandabi S, Veisy A, Mirghafourvand M", "journal": "J Complement Integr Med", "year": 2023, "pmid": "34261202", "url": "https://pubmed.ncbi.nlm.nih.gov/34261202/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 9 clinical trials found EPO significantly improved Bishop score, reduced cesarean section rate, and shortened duration of first and second stages of labor compared to control.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34261202/", "publicSourceType": "PMID" }, { "claim": "EPO shows insufficient evidence for alleviating menopausal hot flashes compared to placebo", "title": "Evening Primrose Oil for Menopause Hot Flashes: Systematic Review and Meta-Analysis", "authors": "Thevi T, De S, Soe HHK", "journal": "J Menopausal Med", "year": 2024, "pmid": "39829189", "url": "https://pubmed.ncbi.nlm.nih.gov/39829189/", "study_type": "meta-analysis", "key_finding": "Systematic review found hot flash severity was lower with EPO for less than 6 months compared to placebo, but no significant difference in frequency and duration. Evidence insufficient for firm conclusions.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39829189/", "publicSourceType": "PMID" }, { "text": "Moradi M, Niazi A, Heydarian Miri H et al.. The effect of evening primrose oil on labor induction and cervical ripening: A systematic review and meta-analysis. Phytotherapy research : PTR. 2021", "claim": "PubMed-indexed evidence involving Evening Primrose Oil", "title": "The effect of evening primrose oil on labor induction and cervical ripening: A systematic review and meta-analysis", "authors": "Moradi M, Niazi A, Heydarian Miri H et al.", "journal": "Phytotherapy research : PTR", "year": 2021, "pmid": "33913585", "url": "https://pubmed.ncbi.nlm.nih.gov/33913585/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/ptr.7147", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33913585/", "publicSourceType": "PMID" }, { "text": "Farag MA, Reda A, Nabil M et al.. Evening primrose oil: a comprehensive review of its bioactives, extraction, analysis, oil quality, therapeutic merits, and safety. Food & function. 2023", "claim": "PubMed-indexed evidence involving Evening Primrose Oil", "title": "Evening primrose oil: a comprehensive review of its bioactives, extraction, analysis, oil quality, therapeutic merits, and safety", "authors": "Farag MA, Reda A, Nabil M et al.", "journal": "Food & function", "year": 2023, "pmid": "37614101", "url": "https://pubmed.ncbi.nlm.nih.gov/37614101/", "study_type": "review", "confidence": "verify", "doi": "10.1039/d3fo01949g", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37614101/", "publicSourceType": "PMID" }, { "text": "Zurier RB, Rossetti RG, Jacobson EW et al.. gamma-Linolenic acid treatment of rheumatoid arthritis. A randomized, placebo-controlled trial. Arthritis and rheumatism. 1996", "claim": "PubMed-indexed evidence involving Evening Primrose Oil", "title": "gamma-Linolenic acid treatment of rheumatoid arthritis. A randomized, placebo-controlled trial", "authors": "Zurier RB, Rossetti RG, Jacobson EW et al.", "journal": "Arthritis and rheumatism", "year": 1996, "pmid": "8912502", "url": "https://pubmed.ncbi.nlm.nih.gov/8912502/", "study_type": "RCT", "confidence": "verify", "doi": "10.1002/art.1780391106", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8912502/", "publicSourceType": "PMID" }, { "text": "Zikic V, Paunovic M, Milovic-Kovacevic M et al.. Nutrigenetics and Omega-3 and Gamma-Linolenic Acid Intake and Status in Patients with Cancer: A PRISMA Scoping Review of Research Trends and Challenges. International journal of molecular sciences. 2025", "claim": "PubMed-indexed evidence involving Evening Primrose Oil", "title": "Nutrigenetics and Omega-3 and Gamma-Linolenic Acid Intake and Status in Patients with Cancer: A PRISMA Scoping Review of Research Trends and Challenges", "authors": "Zikic V, Paunovic M, Milovic-Kovacevic M et al.", "journal": "International journal of molecular sciences", "year": 2025, "pmid": "40430008", "url": "https://pubmed.ncbi.nlm.nih.gov/40430008/", "study_type": "review", "confidence": "verify", "doi": "10.3390/ijms26104867", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40430008/", "publicSourceType": "PMID" }, { "text": "Mahmoodinasab M, Loripoor M, Vazirinejad R et al.. Effect of misoprostol with and without evening primrose (Oenothera biennis) on induction of missed abortion. Avicenna journal of phytomedicine. 2023", "claim": "PubMed-indexed evidence involving Evening Primrose Oil", "title": "Effect of misoprostol with and without evening primrose (Oenothera biennis) on induction of missed abortion", "authors": "Mahmoodinasab M, Loripoor M, Vazirinejad R et al.", "journal": "Avicenna journal of phytomedicine", "year": 2023, "pmid": "38089421", "url": "https://pubmed.ncbi.nlm.nih.gov/38089421/", "study_type": "review", "confidence": "verify", "doi": "10.22038/AJP.2023.22179", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38089421/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "evening-primrose-oil" }, { "id": "64646C75-DC31-4636-B2DB-DA4531C75E90", "name": "Flaxseed Oil", "alternateNames": [ "Linseed Oil", "ALA" ], "category": "Omega/Fatty Acid", "subcategory": "Plant-Based Omega-3", "overview": "Richest plant source of alpha-linolenic acid (ALA), a precursor to EPA/DHA.", "mechanismOfAction": "ALA is converted (inefficiently, ~5-10%) to EPA and DHA by delta-6 desaturase. Direct anti-inflammatory effects via ALA-derived resolvins. Lignans provide antioxidant benefits.", "commonBenefits": [ "Plant omega-3", "Anti-inflammatory", "Heart health", "Skin hydration" ], "commonDosageRange": "1-2 tablespoons or 1,000-2,000 mg daily", "recommendedForm": "Cold-pressed organic flaxseed oil", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food; refrigerate oil to prevent oxidation" }, "evidenceRating": "moderate", "foodSources": [ "Flaxseeds", "Chia seeds", "Walnuts" ], "deficiencySymptoms": [ "Not essential if getting EPA/DHA" ], "sideEffects": [ "GI upset", "Diarrhea at high doses" ], "contraindications": [ "Blood thinners", "Hormone-sensitive conditions (lignans are phytoestrogenic)" ], "iconName": "drop.fill", "colorHex": "4D94FF", "tags": [ "omega-3", "plant-based", "heart", "vegan" ], "sources": [ { "claim": "Systematic review and meta-analysis of ALA and cardiovascular disease risk", "title": "alpha-Linolenic acid and risk of cardiovascular disease: a systematic review and meta-analysis", "authors": "Pan A et al.", "journal": "Am J Clin Nutr", "year": 2012, "pmid": "23076616", "url": "https://pubmed.ncbi.nlm.nih.gov/23076616/", "study_type": "meta-analysis", "key_finding": "In observational studies, higher ALA exposure is associated with a moderately lower risk of cardiovascular disease", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23076616/", "publicSourceType": "PMID" }, { "claim": "Dose-response meta-analysis of ALA on cardiovascular and all-cause mortality", "title": "Dietary intake and biomarkers of alpha linolenic acid and risk of all cause, cardiovascular, and cancer mortality: systematic review and dose-response meta-analysis of cohort studies", "authors": "Naghshi S et al.", "journal": "BMJ", "year": 2021, "pmid": "34645650", "url": "https://pubmed.ncbi.nlm.nih.gov/34645650/", "study_type": "meta-analysis", "key_finding": "Dietary ALA intake is associated with a reduced risk of mortality from all causes, CVD, and coronary heart disease", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34645650/", "publicSourceType": "PMID" }, { "claim": "Comprehensive review comparing flaxseed oil with other omega-3-rich oils", "title": "A comprehensive review of the health benefits of flaxseed oil in relation to its chemical composition and comparison with other omega-3-rich oils", "authors": "Parikh M et al.", "journal": "Nutrients", "year": 2023, "pmid": "37464425", "url": "https://pubmed.ncbi.nlm.nih.gov/37464425/", "study_type": "review", "key_finding": "Flaxseed oil, fibers, and lignans reduce cardiovascular disease, atherosclerosis, diabetes, cancer, and autoimmune disorders; ALA is anti-inflammatory", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37464425/", "publicSourceType": "PMID" }, { "claim": "Flaxseed oil increases EPA but not DHA plasma levels (limited ALA conversion)", "title": "Flaxseed oil increases the plasma concentrations of cardioprotective (n-3) fatty acids in humans", "authors": "Harper CR et al.", "journal": "J Nutr", "year": 2006, "pmid": "16365063", "url": "https://pubmed.ncbi.nlm.nih.gov/16365063/", "study_type": "RCT", "key_finding": "Plasma EPA levels increased 60% and DPA by 25% after flaxseed oil supplementation, but plasma DHA levels did not change, confirming limited ALA to DHA conversion", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16365063/", "publicSourceType": "PMID" }, { "claim": "Overview of flaxseed as functional food with anti-inflammatory properties", "title": "Flax and flaxseed oil: an ancient medicine & modern functional food", "authors": "Goyal A et al.", "journal": "J Food Sci Technol", "year": 2014, "pmid": "25190822", "url": "https://pubmed.ncbi.nlm.nih.gov/25190822/", "study_type": "review", "key_finding": "Flaxseed oil exerts health benefits including reduction of cardiovascular disease, atherosclerosis, diabetes, cancer, arthritis, and osteoporosis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25190822/", "publicSourceType": "PMID" }, { "claim": "Meta-analysis of ALA supplementation on cardiovascular risk in overweight/obese", "title": "Effect of Alpha-Linolenic Acid Supplementation on Cardiovascular Disease Risk Profile in Individuals with Obesity or Overweight: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Naghshi S et al.", "journal": "Nutrients", "year": 2023, "pmid": "37778442", "url": "https://pubmed.ncbi.nlm.nih.gov/37778442/", "study_type": "meta-analysis", "key_finding": "ALA supplementation significantly reduced CRP, TNF-alpha, triglycerides, and systolic blood pressure in overweight/obese individuals", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37778442/", "publicSourceType": "PMID" }, { "claim": "Flaxseed oil supplementation rich in alpha-linolenic acid improves verbal fluency in healthy older adults", "title": "Supplementation with Flaxseed Oil Rich in Alpha-Linolenic Acid Improves Verbal Fluency in Healthy Older Adults", "authors": "Ogawa T, Sawane K, Ookoshi K, Kawashima R", "journal": "Nutrients", "year": 2023, "pmid": "36986229", "url": "https://pubmed.ncbi.nlm.nih.gov/36986229/", "study_type": "rct", "key_finding": "In a randomized, double-blind, placebo-controlled trial of 60 healthy older adults, 12 weeks of flaxseed oil supplementation (2.2 g ALA/day) significantly improved verbal fluency scores compared to placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36986229/", "publicSourceType": "PMID" }, { "claim": "Flaxseed oil and olive oil supplementation may not significantly affect blood pressure or inflammatory markers", "title": "Supplementation of Olive Oil and Flaxseed Oil on Blood Pressure and Inflammation in Healthy and At-Risk Adults: A Systematic Literature Review and Meta-Analysis", "authors": "McNabb TB, Young I, Newman RG, Skinner RC, Benedito VA, Tou JC", "journal": "Curr Hypertens Rev", "year": 2024, "pmid": "39558500", "url": "https://pubmed.ncbi.nlm.nih.gov/39558500/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 17 RCTs found no significant effect of OO and FLO supplementation on systolic blood pressure, diastolic blood pressure, CRP, IL-6, or TNF-alpha. Longer-duration, higher-dose RCTs are needed.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39558500/", "publicSourceType": "PMID" }, { "claim": "Flaxseed intake may help reduce appetite and hunger perception", "title": "The effect of flaxseed intake on appetite reduction: A systematic review of randomized clinical trials", "authors": "Zarei M, Adeli S, Hosseini S, Daneshzad E", "journal": "Phytother Res", "year": 2022, "pmid": "35916016", "url": "https://pubmed.ncbi.nlm.nih.gov/35916016/", "study_type": "review", "key_finding": "Systematic review of 13 studies found some evidence that flaxseed reduces hunger perception and appetite, and increases fullness and satiety, though results were inconsistent across studies.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35916016/", "publicSourceType": "PMID" }, { "text": "Wendland E, Farmer A, Glasziou P et al.. Effect of alpha linolenic acid on cardiovascular risk markers: a systematic review. Heart (British Cardiac Society). 2006", "claim": "PubMed-indexed evidence involving Flaxseed Oil", "title": "Effect of alpha linolenic acid on cardiovascular risk markers: a systematic review", "authors": "Wendland E, Farmer A, Glasziou P et al.", "journal": "Heart (British Cardiac Society)", "year": 2006, "pmid": "15890766", "url": "https://pubmed.ncbi.nlm.nih.gov/15890766/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1136/hrt.2004.053538", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15890766/", "publicSourceType": "PMID" }, { "text": "Chen LH, Hu Q, Li G et al.. Dietary Intake and Biomarkers of α-Linolenic Acid and Mortality: A Meta-Analysis of Prospective Cohort Studies. Frontiers in nutrition. 2021", "claim": "PubMed-indexed evidence involving Flaxseed Oil", "title": "Dietary Intake and Biomarkers of α-Linolenic Acid and Mortality: A Meta-Analysis of Prospective Cohort Studies", "authors": "Chen LH, Hu Q, Li G et al.", "journal": "Frontiers in nutrition", "year": 2021, "pmid": "34805241", "url": "https://pubmed.ncbi.nlm.nih.gov/34805241/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fnut.2021.743852", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34805241/", "publicSourceType": "PMID" }, { "text": "Wu J, Qiu M, Sun L et al.. α-Linolenic Acid and Risk of Heart Failure: A Meta-Analysis. Frontiers in cardiovascular medicine. 2021", "claim": "PubMed-indexed evidence involving Flaxseed Oil", "title": "α-Linolenic Acid and Risk of Heart Failure: A Meta-Analysis", "authors": "Wu J, Qiu M, Sun L et al.", "journal": "Frontiers in cardiovascular medicine", "year": 2021, "pmid": "35059448", "url": "https://pubmed.ncbi.nlm.nih.gov/35059448/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fcvm.2021.788452", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35059448/", "publicSourceType": "PMID" }, { "text": "Carayol M, Grosclaude P, Delpierre C. Prospective studies of dietary alpha-linolenic acid intake and prostate cancer risk: a meta-analysis. Cancer causes & control : CCC. 2010", "claim": "PubMed-indexed evidence involving Flaxseed Oil", "title": "Prospective studies of dietary alpha-linolenic acid intake and prostate cancer risk: a meta-analysis", "authors": "Carayol M, Grosclaude P, Delpierre C", "journal": "Cancer causes & control : CCC", "year": 2010, "pmid": "19921446", "url": "https://pubmed.ncbi.nlm.nih.gov/19921446/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s10552-009-9465-1", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19921446/", "publicSourceType": "PMID" }, { "text": "Golpour-Hamedani S, Bagherniya M, Khorvash F et al.. The effects of concurrent alpha-linolenic acid, L-carnitine supplementation on clinical symptoms, mental health, and quality of life in women with migraine: a randomized, triple-blind, placebo-controlled trial. Nutrition journal. 2025", "claim": "PubMed-indexed evidence involving Flaxseed Oil", "title": "The effects of concurrent alpha-linolenic acid, L-carnitine supplementation on clinical symptoms, mental health, and quality of life in women with migraine: a randomized, triple-blind, placebo-controlled trial", "authors": "Golpour-Hamedani S, Bagherniya M, Khorvash F et al.", "journal": "Nutrition journal", "year": 2025, "pmid": "40082970", "url": "https://pubmed.ncbi.nlm.nih.gov/40082970/", "study_type": "RCT", "confidence": "verify", "doi": "10.1186/s12937-025-01107-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40082970/", "publicSourceType": "PMID" }, { "text": "Bertoni C, Pini C, Mazzocchi A et al.. The Role of Alpha-Linolenic Acid and Other Polyunsaturated Fatty Acids in Mental Health: A Narrative Review. International journal of molecular sciences. 2024", "claim": "PubMed-indexed evidence involving Flaxseed Oil", "title": "The Role of Alpha-Linolenic Acid and Other Polyunsaturated Fatty Acids in Mental Health: A Narrative Review", "authors": "Bertoni C, Pini C, Mazzocchi A et al.", "journal": "International journal of molecular sciences", "year": 2024, "pmid": "39596544", "url": "https://pubmed.ncbi.nlm.nih.gov/39596544/", "study_type": "review", "confidence": "verify", "doi": "10.3390/ijms252212479", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39596544/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "flaxseed-oil" }, { "id": "49D1E45A-ADDD-4C8D-B8C6-7CE8ACED6648", "name": "MCT Oil", "alternateNames": [ "Medium-Chain Triglycerides", "C8/C10" ], "category": "Omega/Fatty Acid", "subcategory": "Medium-Chain Fatty Acid", "overview": "Rapidly absorbed fatty acids that provide quick energy and support ketone production.", "mechanismOfAction": "MCTs bypass normal fat digestion, are absorbed directly into the portal vein, and rapidly oxidized in the liver. C8 (caprylic acid) is most ketogenic, producing beta-hydroxybutyrate for brain fuel.", "commonBenefits": [ "Quick energy", "Ketone production", "Cognitive fuel", "Weight management" ], "commonDosageRange": "1-3 tablespoons daily", "recommendedForm": "C8 (caprylic acid) or C8/C10 blend", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Start with small doses to avoid GI distress; build up gradually" }, "evidenceRating": "moderate", "foodSources": [ "Coconut oil", "Palm kernel oil", "Dairy fat" ], "deficiencySymptoms": [ "Not essential" ], "sideEffects": [ "GI distress (disaster pants)", "Cramping if too much too fast" ], "contraindications": [ "Liver disease", "Diabetes (may affect blood sugar)" ], "iconName": "bolt.circle.fill", "colorHex": "4D94FF", "tags": [ "energy", "keto", "cognitive", "fat" ], "sources": [ { "claim": "Meta-analysis of MCTs for weight loss and body composition", "title": "Effects of medium-chain triglycerides on weight loss and body composition: a meta-analysis of randomized controlled trials", "authors": "Mumme K et al.", "journal": "J Acad Nutr Diet", "year": 2015, "pmid": "25636220", "url": "https://pubmed.ncbi.nlm.nih.gov/25636220/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 13 RCTs (n=749) found MCTs decreased body weight by 0.51 kg, waist circumference by 1.46 cm, and total body fat compared to long-chain triglycerides", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25636220/", "publicSourceType": "PMID" }, { "claim": "MCTs induce ketosis and may improve cognition in Alzheimer's disease", "title": "Medium Chain Triglycerides induce mild ketosis and may improve cognition in Alzheimer's disease. A systematic review and meta-analysis of human studies", "authors": "Avgerinos KI et al.", "journal": "Ageing Res Rev", "year": 2020, "pmid": "31870908", "url": "https://pubmed.ncbi.nlm.nih.gov/31870908/", "study_type": "meta-analysis", "key_finding": "MCTs can induce mild ketosis and may improve cognition in Alzheimer's disease patients, particularly in APOE-epsilon4 non-carriers", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31870908/", "publicSourceType": "PMID" }, { "claim": "MCTs may improve working memory in non-demented older adults", "title": "Medium-chain triglycerides may improve memory in non-demented older adults: a systematic review of randomized controlled trials", "authors": "Ashton JS et al.", "journal": "Nutr Rev", "year": 2022, "pmid": "36273115", "url": "https://pubmed.ncbi.nlm.nih.gov/36273115/", "study_type": "review", "key_finding": "MCT supplementation may enhance working memory in non-demented older adults, with effects more prominent in individuals with lower baseline scores", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36273115/", "publicSourceType": "PMID" }, { "claim": "MCTs increase energy expenditure and decrease adiposity in overweight men", "title": "Medium-chain triglycerides increase energy expenditure and decrease adiposity in overweight men", "authors": "St-Onge MP et al.", "journal": "Obes Res", "year": 2003, "pmid": "12634436", "url": "https://pubmed.ncbi.nlm.nih.gov/12634436/", "study_type": "RCT", "key_finding": "MCT consumption increased energy expenditure compared to long-chain triglycerides and decreased body weight and adiposity in overweight men", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12634436/", "publicSourceType": "PMID" }, { "claim": "Meta-analysis of MCT effects on satiety and food intake", "title": "A systematic review and meta-analysis of medium-chain triglycerides effects on acute satiety and food intake", "authors": "Maher T et al.", "journal": "Crit Rev Food Sci Nutr", "year": 2021, "pmid": "32212947", "url": "https://pubmed.ncbi.nlm.nih.gov/32212947/", "study_type": "meta-analysis", "key_finding": "Significant moderate decrease in ad libitum energy intake after both acute and chronic MCT ingestion compared to long-chain triglycerides", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32212947/", "publicSourceType": "PMID" }, { "claim": "Recent meta-analysis on MCT impact on weight loss and metabolic health", "title": "The impact of medium-chain triglycerides on weight loss and metabolic health in individuals with overweight or obesity: A systematic review and meta-analysis", "authors": "Zhang Y et al.", "journal": "Clin Nutr", "year": 2024, "pmid": "38936302", "url": "https://pubmed.ncbi.nlm.nih.gov/38936302/", "study_type": "meta-analysis", "key_finding": "Diets enriched with MCTs are more effective in achieving weight reduction (1.53% reduction vs LCFAs), particularly when containing pure MCTs (1.62%)", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38936302/", "publicSourceType": "PMID" }, { "claim": "MCT supplementation may improve neurological outcomes in acute severe encephalopathy patients", "title": "Efficacy evaluation of medium-chain triglycerides supplementation on acute severe encephalopathy", "authors": "Zuo Y, Wu H, Liu P, Bian Z, Lu Z, Zhang B", "journal": "Nutr Neurosci", "year": 2025, "pmid": "40674442", "url": "https://pubmed.ncbi.nlm.nih.gov/40674442/", "study_type": "rct", "key_finding": "Double-blind randomized trial of 46 patients found MCT supplementation significantly reduced poor neurologic outcomes at 180 days (26.1% vs 56.5%), shortened coma duration, mechanical ventilation time, and ICU stay.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40674442/", "publicSourceType": "PMID" }, { "claim": "MCT-enriched structured lipids with EPA improve endurance performance", "title": "Eicosapentaenoic Acid and Medium-Chain Triacylglycerol Structured Lipids Improve Endurance Performance", "authors": "Tsuji K, Tsuchiya Y, Yokoi K, Yanagimoto K, Ueda H, Ochi E", "journal": "Nutrients", "year": 2023, "pmid": "37686724", "url": "https://pubmed.ncbi.nlm.nih.gov/37686724/", "study_type": "rct", "key_finding": "8-week randomized double-blind trial in 19 men found interesterified structured lipids containing EPA and MCTs significantly improved time to exhaustion and time to reach anaerobic threshold compared to physical mixture.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37686724/", "publicSourceType": "PMID" }, { "claim": "MCT-enriched ketogenic formula is safe and increases blood ketone bodies under ketogenic diet", "title": "Ketogenic Effects of Multiple Doses of a Medium Chain Triglycerides Enriched Ketogenic Formula in Healthy Men under the Ketogenic Diet: A Randomized, Double-Blinded, Placebo-Controlled Study", "authors": "Nakamura K, Hagihara K, Nagai N, Egashira R et al.", "journal": "Nutrients", "year": 2022, "pmid": "35334856", "url": "https://pubmed.ncbi.nlm.nih.gov/35334856/", "study_type": "rct", "key_finding": "Randomized double-blind placebo-controlled trial in 20 healthy men found MCT-enriched ketogenic formula significantly increased blood ketone bodies on day 4 of administration with no significant safety issues.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35334856/", "publicSourceType": "PMID" }, { "text": "Zulfakar MH, Pubadi H, Ibrahim SI et al.. Medium-Chain Triacylglycerols (MCTs) and Their Fractions in Drug Delivery Systems : A Systematic Review. Journal of oleo science. 2024", "claim": "PubMed-indexed evidence involving MCT Oil", "title": "Medium-Chain Triacylglycerols (MCTs) and Their Fractions in Drug Delivery Systems : A Systematic Review", "authors": "Zulfakar MH, Pubadi H, Ibrahim SI et al.", "journal": "Journal of oleo science", "year": 2024, "pmid": "38432994", "url": "https://pubmed.ncbi.nlm.nih.gov/38432994/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.5650/jos.ess23204", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38432994/", "publicSourceType": "PMID" }, { "text": "Meer N, Fischer T. Medium-Chain Triglycerides (MCTs) for the Symptomatic Treatment of Dementia-Related Diseases: A Systematic Review. Journal of nutrition and metabolism. 2024", "claim": "PubMed-indexed evidence involving MCT Oil", "title": "Medium-Chain Triglycerides (MCTs) for the Symptomatic Treatment of Dementia-Related Diseases: A Systematic Review", "authors": "Meer N, Fischer T", "journal": "Journal of nutrition and metabolism", "year": 2024, "pmid": "38715705", "url": "https://pubmed.ncbi.nlm.nih.gov/38715705/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1155/2024/9672969", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38715705/", "publicSourceType": "PMID" }, { "text": "Duan H, Yang T, Li C et al.. Supplementation of medium-chain triglycerides combined with docosahexaenoic acid improves cognitive function in Chinese older adults with mild cognitive impairment: A randomized double-blind, placebo-controlled trial. Journal of affective disorders. 2025", "claim": "PubMed-indexed evidence involving MCT Oil", "title": "Supplementation of medium-chain triglycerides combined with docosahexaenoic acid improves cognitive function in Chinese older adults with mild cognitive impairment: A randomized double-blind, placebo-controlled trial", "authors": "Duan H, Yang T, Li C et al.", "journal": "Journal of affective disorders", "year": 2025, "pmid": "40044083", "url": "https://pubmed.ncbi.nlm.nih.gov/40044083/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.jad.2025.03.008", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40044083/", "publicSourceType": "PMID" }, { "text": "Abe S, Ezaki O, Suzuki M. Medium-chain triglycerides (8:0 and 10:0) are promising nutrients for sarcopenia: a randomized controlled trial. The American journal of clinical nutrition. 2019", "claim": "PubMed-indexed evidence involving MCT Oil", "title": "Medium-chain triglycerides (8:0 and 10:0) are promising nutrients for sarcopenia: a randomized controlled trial", "authors": "Abe S, Ezaki O, Suzuki M", "journal": "The American journal of clinical nutrition", "year": 2019, "pmid": "31334544", "url": "https://pubmed.ncbi.nlm.nih.gov/31334544/", "study_type": "RCT", "confidence": "verify", "doi": "10.1093/ajcn/nqz138", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31334544/", "publicSourceType": "PMID" }, { "text": "Nasir S, Siddique J, Ahmed Z et al.. Effectiveness of medium-chain triglycerides in chylothorax management: A review. Nutrition and health. 2026", "claim": "PubMed-indexed evidence involving MCT Oil", "title": "Effectiveness of medium-chain triglycerides in chylothorax management: A review", "authors": "Nasir S, Siddique J, Ahmed Z et al.", "journal": "Nutrition and health", "year": 2026, "pmid": "41697733", "url": "https://pubmed.ncbi.nlm.nih.gov/41697733/", "study_type": "review", "confidence": "verify", "doi": "10.1177/02601060251411827", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41697733/", "publicSourceType": "PMID" }, { "text": "Mancell S, Manwani K, Dhawan A et al.. Medium-chain triglycerides and the impact on fat absorption, growth, nutritional status and clinical outcomes in children with cholestatic liver disease: A scoping review. Clinical nutrition (Edinburgh, Scotland). 2023", "claim": "PubMed-indexed evidence involving MCT Oil", "title": "Medium-chain triglycerides and the impact on fat absorption, growth, nutritional status and clinical outcomes in children with cholestatic liver disease: A scoping review", "authors": "Mancell S, Manwani K, Dhawan A et al.", "journal": "Clinical nutrition (Edinburgh, Scotland)", "year": 2023, "pmid": "37776587", "url": "https://pubmed.ncbi.nlm.nih.gov/37776587/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.clnu.2023.09.010", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37776587/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "mct-oil" }, { "id": "8B87B85C-657D-44F9-B0AC-2466EA95C5A5", "name": "Phosphatidylcholine", "alternateNames": [ "PC", "Lecithin" ], "category": "Omega/Fatty Acid", "subcategory": "Phospholipid", "overview": "Major phospholipid in cell membranes and a choline source for brain health.", "mechanismOfAction": "Provides choline for acetylcholine synthesis and phospholipid for cell membrane structure. Supports bile production and fat emulsification. Key structural component of VLDL for liver fat export.", "commonBenefits": [ "Liver health", "Brain function", "Cell membrane support", "Fat digestion" ], "commonDosageRange": "840-2,400 mg daily", "recommendedForm": "Sunflower lecithin (non-GMO, allergen-free)", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with fatty meal" }, "evidenceRating": "moderate", "foodSources": [ "Eggs", "Soybeans", "Sunflower seeds", "Liver" ], "deficiencySymptoms": [ "Choline deficiency symptoms" ], "sideEffects": [ "GI upset", "Fishy smell", "Diarrhea" ], "contraindications": [ "TMAO concerns at very high doses" ], "iconName": "circle.grid.3x3.fill", "colorHex": "4D94FF", "tags": [ "liver", "brain", "choline", "membrane" ], "sources": [ { "claim": "Critical role of phosphatidylcholine metabolism in health and disease", "title": "The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease", "authors": "van der Veen JN et al.", "journal": "Biochim Biophys Acta Biomembr", "year": 2017, "pmid": "28411170", "url": "https://pubmed.ncbi.nlm.nih.gov/28411170/", "study_type": "review", "key_finding": "Decreased hepatic PC content and decreased PC/PE ratio are linked to NAFLD; PC is critical for cell membrane integrity, VLDL secretion, and liver fat export", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28411170/", "publicSourceType": "PMID" }, { "claim": "Choline and phosphatidylcholine maintain cognitive performance", "title": "Choline and phosphatidylcholine may maintain cognitive performance by multiple mechanisms", "authors": "Smigelski JR et al.", "journal": "Curr Dev Nutr", "year": 2019, "pmid": "31536123", "url": "https://pubmed.ncbi.nlm.nih.gov/31536123/", "study_type": "review", "key_finding": "Higher phosphatidylcholine intake was associated with lower risk of incident dementia and better cognitive performance through multiple mechanisms", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31536123/", "publicSourceType": "PMID" }, { "claim": "Dietary choline intake associations with dementia risk and cognitive performance", "title": "Associations of dietary choline intake with risk of incident dementia and with cognitive performance: the Kuopio Ischaemic Heart Disease Risk Factor Study", "authors": "Ylilauri MPT et al.", "journal": "Am J Clin Nutr", "year": 2019, "pmid": "31360988", "url": "https://pubmed.ncbi.nlm.nih.gov/31360988/", "study_type": "cohort", "key_finding": "Higher phosphatidylcholine intake was associated with lower risk of incident dementia and better cognitive performance in men in eastern Finland", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31360988/", "publicSourceType": "PMID" }, { "claim": "Essential phospholipids for NAFLD: systematic review and network meta-analysis", "title": "Essential phospholipids for nonalcoholic fatty liver disease associated with metabolic syndrome: A systematic review and network meta-analysis", "authors": "Dajani AI et al.", "journal": "World J Clin Cases", "year": 2020, "pmid": "33269259", "url": "https://pubmed.ncbi.nlm.nih.gov/33269259/", "study_type": "meta-analysis", "key_finding": "Systematic review and network meta-analysis provides evidence for a benefit of essential phospholipids (phosphatidylcholine) in patients with NAFLD and diabetes and/or obesity", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33269259/", "publicSourceType": "PMID" }, { "claim": "Phosphatidylcholine treatment improves liver function in NAFLD patients", "title": "Treatment with phosphatidylcholine of patients with nonalcoholic fatty liver disease: a prospective pilot study", "authors": "Sanyal AJ et al.", "journal": "Front Med (Lausanne)", "year": 2022, "pmid": "35511653", "url": "https://pubmed.ncbi.nlm.nih.gov/35511653/", "study_type": "RCT", "key_finding": "Phosphatidylcholine administration decreased ALT by 59.6% and AST by 75.4% in NAFLD patients", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35511653/", "publicSourceType": "PMID" }, { "claim": "Choline as essential nutrient: scoping review for Nordic Nutrition Recommendations", "title": "Choline - a scoping review for Nordic Nutrition Recommendations 2023", "authors": "Melse-Boonstra A", "journal": "Food Nutr Res", "year": 2024, "pmid": "38187796", "url": "https://pubmed.ncbi.nlm.nih.gov/38187796/", "study_type": "review", "key_finding": "Choline is a critical nutrient for cognitive development, metabolism and liver function, necessary for phosphatidylcholine and acetylcholine synthesis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38187796/", "publicSourceType": "PMID" }, { "text": "Vitali C, Bajaj A, Nguyen C et al.. A systematic review of the natural history and biomarkers of primary lecithin:cholesterol acyltransferase deficiency. Journal of lipid research. 2022", "pmid": "35065092", "doi": "10.1016/j.jlr.2022.100169", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35065092/", "publicSourceType": "PMID" }, { "text": "Johnson W Jr, Bergfeld WF, Belsito DV et al.. Safety Assessment of Lecithin and Other Phosphoglycerides as Used in Cosmetics. International journal of toxicology. 2020", "pmid": "32975152", "doi": "10.1177/1091581820953123", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32975152/", "publicSourceType": "PMID" }, { "claim": "Different choline supplement forms (including phosphatidylcholine) are differentially metabolized in adults", "title": "Differential metabolism of choline supplements in adult volunteers", "authors": "Bockmann KA, Franz AR, Minarski M et al.", "journal": "Eur J Nutr", "year": 2022, "pmid": "34287673", "url": "https://pubmed.ncbi.nlm.nih.gov/34287673/", "study_type": "rct", "key_finding": "Randomized crossover study in 6 healthy men found all choline supplements (choline chloride, bitartrate, alpha-GPC, egg-PC) increased choline and betaine levels. Egg-PC showed latest peak and lowest TMAO formation, suggesting it may be the best choline source.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34287673/", "publicSourceType": "PMID" }, { "claim": "Phosphatidylcholine (as POPC) is the optimal choline supplement form for increasing plasma PC levels with minimal TMAO", "title": "Different choline supplement metabolism in adults using deuterium labelling", "authors": "Bockmann KA, Franz AR, Shunova A et al.", "journal": "Eur J Nutr", "year": 2023, "pmid": "36840817", "url": "https://pubmed.ncbi.nlm.nih.gov/36840817/", "study_type": "rct", "key_finding": "Deuterium-labelled crossover study in 6 men found D9-POPC (phosphatidylcholine) resulted in highest plasma D9-PC concentrations and virtually absent TMAO levels, suggesting it is the best choline supplement form for increasing PC.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36840817/", "publicSourceType": "PMID" }, { "claim": "Soy-derived lysophosphatidylcholine is an effective choline source comparable to glycerophosphocholine", "title": "Pharmacokinetics of soy-derived lysophosphatidylcholine compared with that of glycerophosphocholine: a randomized controlled trial", "authors": "Tanaka-Kanegae R, Kimura H, Hamada K", "journal": "Biosci Biotechnol Biochem", "year": 2024, "pmid": "38490741", "url": "https://pubmed.ncbi.nlm.nih.gov/38490741/", "study_type": "rct", "key_finding": "RCT in 12 healthy men found soy-derived lysophosphatidylcholine (LPC) and glycerophosphocholine similarly increased plasma choline, phospholipid, and triglyceride concentrations without significantly elevating TMAO.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38490741/", "publicSourceType": "PMID" }, { "text": "Dignass A, Stremmel W, Horyński M et al.. Modified-Release Phosphatidylcholine (LT-02) for Ulcerative Colitis: Two Double-Blind, Randomized, Placebo-Controlled Trials. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2024", "claim": "PubMed-indexed evidence involving Phosphatidylcholine", "title": "Modified-Release Phosphatidylcholine (LT-02) for Ulcerative Colitis: Two Double-Blind, Randomized, Placebo-Controlled Trials", "authors": "Dignass A, Stremmel W, Horyński M et al.", "journal": "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "year": 2024, "pmid": "37806372", "url": "https://pubmed.ncbi.nlm.nih.gov/37806372/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.cgh.2023.09.031", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37806372/", "publicSourceType": "PMID" }, { "text": "Gu H, Pu L, Yu S. Efficacy and safety of iodized lecithin tablets versus spironolactone in alleviating central serous retinopathy among Chinese patients with uncontrolled diabetes. Pakistan journal of pharmaceutical sciences. 2023", "claim": "PubMed-indexed evidence involving Phosphatidylcholine", "title": "Efficacy and safety of iodized lecithin tablets versus spironolactone in alleviating central serous retinopathy among Chinese patients with uncontrolled diabetes", "authors": "Gu H, Pu L, Yu S", "journal": "Pakistan journal of pharmaceutical sciences", "year": 2023, "pmid": "37548195", "url": "https://pubmed.ncbi.nlm.nih.gov/37548195/", "study_type": "review", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37548195/", "publicSourceType": "PMID" }, { "text": "Kim SH, Kim BK, Park S et al.. Phosphatidylcholine Extends Lifespan via DAF-16 and Reduces Amyloid-Beta-Induced Toxicity in Caenorhabditis elegans. Oxidative medicine and cellular longevity. 2019", "claim": "PubMed-indexed evidence involving Phosphatidylcholine", "title": "Phosphatidylcholine Extends Lifespan via DAF-16 and Reduces Amyloid-Beta-Induced Toxicity in Caenorhabditis elegans", "authors": "Kim SH, Kim BK, Park S et al.", "journal": "Oxidative medicine and cellular longevity", "year": 2019, "pmid": "31379987", "url": "https://pubmed.ncbi.nlm.nih.gov/31379987/", "study_type": "review", "confidence": "verify", "doi": "10.1155/2019/2860642", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31379987/", "publicSourceType": "PMID" }, { "text": "Conway T, Seidler K, Barrow M. Unlocking choline's potential in Alzheimer's disease: A narrative review exploring the neuroprotective and neurotrophic role of phosphatidylcholine and assessing its impact on memory and learning. Clinical nutrition ESPEN. 2024", "claim": "PubMed-indexed evidence involving Phosphatidylcholine", "title": "Unlocking choline's potential in Alzheimer's disease: A narrative review exploring the neuroprotective and neurotrophic role of phosphatidylcholine and assessing its impact on memory and learning", "authors": "Conway T, Seidler K, Barrow M", "journal": "Clinical nutrition ESPEN", "year": 2024, "pmid": "39357562", "url": "https://pubmed.ncbi.nlm.nih.gov/39357562/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.clnesp.2024.09.024", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39357562/", "publicSourceType": "PMID" }, { "text": "Yuzbashian E, Moftah S, Chan CB. Graduate Student Literature Review: A scoping review on the impact of consumption of dairy products on phosphatidylcholine and lysophosphatidylcholine in circulation and the liver in human studies and animal models. Journal of dairy science. 2023", "claim": "PubMed-indexed evidence involving Phosphatidylcholine", "title": "Graduate Student Literature Review: A scoping review on the impact of consumption of dairy products on phosphatidylcholine and lysophosphatidylcholine in circulation and the liver in human studies and animal models", "authors": "Yuzbashian E, Moftah S, Chan CB", "journal": "Journal of dairy science", "year": 2023, "pmid": "36400621", "url": "https://pubmed.ncbi.nlm.nih.gov/36400621/", "study_type": "review", "confidence": "verify", "doi": "10.3168/jds.2022-21938", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36400621/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "phosphatidylcholine" }, { "id": "692DD721-65C9-4C40-ABC6-5DC4EB7E489E", "name": "Lactobacillus Rhamnosus", "alternateNames": [ "LGG", "L. rhamnosus GG" ], "category": "Probiotic", "subcategory": "Specific Probiotic Strain", "overview": "One of the most researched probiotic strains for gut and immune health.", "mechanismOfAction": "Adheres to intestinal mucosa, produces bacteriocins against pathogens, strengthens gut barrier by upregulating mucin and tight junction proteins, and modulates Th1/Th2 immune balance.", "commonBenefits": [ "Gut health", "Immune support", "Diarrhea prevention", "Atopic dermatitis" ], "commonDosageRange": "10-20 billion CFU daily", "recommendedForm": "LGG strain (Lactobacillus rhamnosus GG is patented strain)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with a meal or up to 30 minutes before a meal for better probiotic survival" }, "evidenceRating": "strong", "foodSources": [ "Fermented dairy", "Some yogurts" ], "deficiencySymptoms": [], "sideEffects": [ "Bloating initially", "Gas", "Very rarely bacteremia in immunocompromised" ], "contraindications": [ "Severe immunocompromise", "Short bowel syndrome", "Central venous catheter", "Critically ill or ICU patients unless clinician-directed", "Structural heart disease or valvular disease", "Liver cirrhosis" ], "iconName": "microbe.fill", "colorHex": "FF6B9D", "tags": [ "gut-health", "immune", "probiotic" ], "sources": [ { "claim": "Meta-analysis of LGG for preventing antibiotic-associated diarrhea", "title": "Systematic review with meta-analysis: Lactobacillus rhamnosus GG in the prevention of antibiotic-associated diarrhoea in children and adults", "authors": "Szajewska H et al.", "journal": "Aliment Pharmacol Ther", "year": 2015, "pmid": "26365389", "url": "https://pubmed.ncbi.nlm.nih.gov/26365389/", "study_type": "meta-analysis", "key_finding": "LGG is effective in preventing antibiotic-associated diarrhea in children and adults treated with antibiotics, with significant benefit particularly in children", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26365389/", "publicSourceType": "PMID" }, { "claim": "Meta-analysis of LGG efficacy in treating acute pediatric diarrhea", "title": "Efficacy of Lactobacillus rhamnosus GG in treatment of acute pediatric diarrhea: A systematic review with meta-analysis", "authors": "Li YT et al.", "journal": "World J Gastroenterol", "year": 2019, "pmid": "31543689", "url": "https://pubmed.ncbi.nlm.nih.gov/31543689/", "study_type": "meta-analysis", "key_finding": "LGG administration notably reduced diarrhea duration, with more effective results at high dose of at least 10^10 CFU per day", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31543689/", "publicSourceType": "PMID" }, { "claim": "30-year comprehensive review of LGG research", "title": "Thirty Years of Lactobacillus rhamnosus GG: A Review", "authors": "Capurso L", "journal": "J Clin Gastroenterol", "year": 2019, "pmid": "30741841", "url": "https://pubmed.ncbi.nlm.nih.gov/30741841/", "study_type": "review", "key_finding": "Comprehensive review of one of the most researched probiotic strains, documenting evidence for gut health, immune support, diarrhea prevention, and atopic dermatitis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30741841/", "publicSourceType": "PMID" }, { "claim": "LGG for primary prevention of eczema in children", "title": "Lactobacillus rhamnosus GG in the Primary Prevention of Eczema in Children: A Systematic Review and Meta-Analysis", "authors": "Szajewska H et al.", "journal": "Nutrients", "year": 2018, "pmid": "30231505", "url": "https://pubmed.ncbi.nlm.nih.gov/30231505/", "study_type": "meta-analysis", "key_finding": "Meta-analysis demonstrated statistically significant reductions in atopic eczema at timeframes of 2 years and 6-7 years with perinatal use of L. rhamnosus", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30231505/", "publicSourceType": "PMID" }, { "claim": "LGG mechanism: gut barrier protection via tight junctions and mucin", "title": "Towards a better understanding of Lactobacillus rhamnosus GG--host interactions", "authors": "Segers ME et al.", "journal": "Microb Cell Fact", "year": 2014, "pmid": "25186587", "url": "https://pubmed.ncbi.nlm.nih.gov/25186587/", "study_type": "review", "key_finding": "LGG adheres to intestinal mucosa, produces postbiotics that protect gut barrier function, strengthens tight junctions (ZO-1, claudin-1), and modulates immune response", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25186587/", "publicSourceType": "PMID" }, { "claim": "LGG promotes intestinal mucin production through serotonin receptor and gut microbiota", "title": "Lactobacillus rhamnosus GG supernatant promotes intestinal mucin production through regulating 5-HT4R and gut microbiota", "authors": "Wang J et al.", "journal": "Food Funct", "year": 2022, "pmid": "36326009", "url": "https://pubmed.ncbi.nlm.nih.gov/36326009/", "study_type": "preclinical", "key_finding": "LGG can enhance goblet cell expression and mucin barrier formation, correcting deficient MUC2 expression through 5-HT4R regulation and gut microbiota modulation", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36326009/", "publicSourceType": "PMID" }, { "text": "Cukrowska B, Ceregra A, Maciorkowska E et al.. The Effectiveness of Probiotic Lactobacillus rhamnosus and Lactobacillus casei Strains in Children with Atopic Dermatitis and Cow's Milk Protein Allergy: A Multicenter, Randomized, Double Blind, Placebo Controlled Study. Nutrients. 2021", "pmid": "33916192", "doi": "10.3390/nu13041169", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33916192/", "publicSourceType": "PMID" }, { "text": "D'Agostino S, Valentini G, Iarussi F et al.. Effect of Probiotics Lactobacillus rhamnosus and Lactobacillus plantarum on Caries and Periodontal Diseases: A Systematic Review. Dentistry journal. 2024", "claim": "PubMed-indexed evidence involving Lactobacillus Rhamnosus", "title": "Effect of Probiotics Lactobacillus rhamnosus and Lactobacillus plantarum on Caries and Periodontal Diseases: A Systematic Review", "authors": "D'Agostino S, Valentini G, Iarussi F et al.", "journal": "Dentistry journal", "year": 2024, "pmid": "38668014", "url": "https://pubmed.ncbi.nlm.nih.gov/38668014/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/dj12040102", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38668014/", "publicSourceType": "PMID" }, { "text": "Tan W, Zhou Z, Li W et al.. Lactobacillus rhamnosus GG for Cow's Milk Allergy in Children: A Systematic Review and Meta-Analysis. Frontiers in pediatrics. 2021", "claim": "PubMed-indexed evidence involving Lactobacillus Rhamnosus", "title": "Lactobacillus rhamnosus GG for Cow's Milk Allergy in Children: A Systematic Review and Meta-Analysis", "authors": "Tan W, Zhou Z, Li W et al.", "journal": "Frontiers in pediatrics", "year": 2021, "pmid": "34746056", "url": "https://pubmed.ncbi.nlm.nih.gov/34746056/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fped.2021.727127", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34746056/", "publicSourceType": "PMID" }, { "text": "Hawrelak JA, Whitten DL, Myers SP. Is Lactobacillus rhamnosus GG effective in preventing the onset of antibiotic-associated diarrhoea: a systematic review. Digestion. 2005", "claim": "PubMed-indexed evidence involving Lactobacillus Rhamnosus", "title": "Is Lactobacillus rhamnosus GG effective in preventing the onset of antibiotic-associated diarrhoea: a systematic review", "authors": "Hawrelak JA, Whitten DL, Myers SP", "journal": "Digestion", "year": 2005, "pmid": "16113542", "url": "https://pubmed.ncbi.nlm.nih.gov/16113542/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1159/000087637", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16113542/", "publicSourceType": "PMID" }, { "text": "Horvath A, Dziechciarz P, Szajewska H. Meta-analysis: Lactobacillus rhamnosus GG for abdominal pain-related functional gastrointestinal disorders in childhood. Alimentary pharmacology & therapeutics. 2011", "claim": "PubMed-indexed evidence involving Lactobacillus Rhamnosus", "title": "Meta-analysis: Lactobacillus rhamnosus GG for abdominal pain-related functional gastrointestinal disorders in childhood", "authors": "Horvath A, Dziechciarz P, Szajewska H", "journal": "Alimentary pharmacology & therapeutics", "year": 2011, "pmid": "21507030", "url": "https://pubmed.ncbi.nlm.nih.gov/21507030/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/j.1365-2036.2011.04665.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21507030/", "publicSourceType": "PMID" }, { "text": "Shah S, Kaul A, Pandey P et al.. Lactobacillus rhamnosus GG to Reduce Necrotising Enterocolitis, Sepsis, and Mortality in Very Low Birth Weight Infants: A Randomized Controlled Trial. Indian pediatrics. 2026", "claim": "PubMed-indexed evidence involving Lactobacillus Rhamnosus", "title": "Lactobacillus rhamnosus GG to Reduce Necrotising Enterocolitis, Sepsis, and Mortality in Very Low Birth Weight Infants: A Randomized Controlled Trial", "authors": "Shah S, Kaul A, Pandey P et al.", "journal": "Indian pediatrics", "year": 2026, "pmid": "41533318", "url": "https://pubmed.ncbi.nlm.nih.gov/41533318/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/s13312-025-00252-w", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41533318/", "publicSourceType": "PMID" }, { "text": "Nordqvist M, Hallingström M, Nerén A et al.. Oral Lacticaseibacillus rhamnosus GG Exposure During Pregnancy and Effects on Maternal Inflammatory Response-A Blinded, Pilot Randomized, Placebo-Controlled Study. American journal of reproductive immunology (New York, N.Y. : 1989). 2025", "claim": "PubMed-indexed evidence involving Lactobacillus Rhamnosus", "title": "Oral Lacticaseibacillus rhamnosus GG Exposure During Pregnancy and Effects on Maternal Inflammatory Response-A Blinded, Pilot Randomized, Placebo-Controlled Study", "authors": "Nordqvist M, Hallingström M, Nerén A et al.", "journal": "American journal of reproductive immunology (New York, N.Y. : 1989)", "year": 2025, "pmid": "41369322", "url": "https://pubmed.ncbi.nlm.nih.gov/41369322/", "study_type": "RCT", "confidence": "verify", "doi": "10.1111/aji.70190", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41369322/", "publicSourceType": "PMID" }, { "text": "Saviano A, Petruzziello C, Cancro C et al.. The Efficacy of a Mix of Probiotics (Limosilactobacillus reuteri LMG P-27481 and Lacticaseibacillus rhamnosus GG ATCC 53103) in Preventing Antibiotic-Associated Diarrhea and Clostridium difficile Infection in Hospitalized Patients: Single-Center, Open-Label, Randomized Trial. Microorganisms. 2024", "claim": "PubMed-indexed evidence involving Lactobacillus Rhamnosus", "title": "The Efficacy of a Mix of Probiotics (Limosilactobacillus reuteri LMG P-27481 and Lacticaseibacillus rhamnosus GG ATCC 53103) in Preventing Antibiotic-Associated Diarrhea and Clostridium difficile Infection in Hospitalized Patients: Single-Center, Open-Label, Randomized Trial", "authors": "Saviano A, Petruzziello C, Cancro C et al.", "journal": "Microorganisms", "year": 2024, "pmid": "38258024", "url": "https://pubmed.ncbi.nlm.nih.gov/38258024/", "study_type": "RCT", "confidence": "verify", "doi": "10.3390/microorganisms12010198", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38258024/", "publicSourceType": "PMID" }, { "text": "Rauseo AM, Hink T, Reske KA et al.. A randomized controlled trial of Lactobacillus rhamnosus GG on antimicrobial-resistant organism colonization. Infection control and hospital epidemiology. 2022", "claim": "PubMed-indexed evidence involving Lactobacillus Rhamnosus", "title": "A randomized controlled trial of Lactobacillus rhamnosus GG on antimicrobial-resistant organism colonization", "authors": "Rauseo AM, Hink T, Reske KA et al.", "journal": "Infection control and hospital epidemiology", "year": 2022, "pmid": "33820576", "url": "https://pubmed.ncbi.nlm.nih.gov/33820576/", "study_type": "RCT", "confidence": "verify", "doi": "10.1017/ice.2021.94", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33820576/", "publicSourceType": "PMID" }, { "claim": "Lactobacillus bacteremia has been reported with probiotic use in vulnerable patients", "title": "Lactobacillus Bacteremia and Probiotics: A Review", "authors": "Kullar R et al.", "journal": "Microorganisms", "year": 2023, "pmid": "37110319", "url": "https://pubmed.ncbi.nlm.nih.gov/37110319/", "study_type": "review", "key_finding": "Review summarizes Lactobacillus bacteremia associated with probiotic use and high-risk clinical contexts.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37110319/", "publicSourceType": "PMID" }, { "claim": "Lactobacillus rhamnosus bacteremia has been linked to probiotic use with central venous catheter", "title": "Bacteraemia caused by Lactobacillus rhamnosus given as a probiotic in a patient with a central venous catheter: a WGS case report", "authors": "Rubin IMC, Stevnsborg L, Mollerup S et al.", "journal": "Infection Prevention in Practice", "year": 2022, "pmid": "35146406", "url": "https://pubmed.ncbi.nlm.nih.gov/35146406/", "study_type": "case_report", "key_finding": "Whole genome sequencing linked L. rhamnosus bacteremia to probiotic use in a patient with a central venous catheter.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35146406/", "publicSourceType": "PMID" }, { "claim": "Probiotic-related Lactobacillus rhamnosus endocarditis has been reported in cirrhosis", "title": "Probiotic related Lactobacillus rhamnosus endocarditis in a patient with liver cirrhosis", "authors": "Naqvi SSB, Nagendra V, Hofmeyr A", "journal": "IDCases", "year": 2018, "pmid": "30155406", "url": "https://pubmed.ncbi.nlm.nih.gov/30155406/", "study_type": "case_report", "key_finding": "Case report supports caution with L. rhamnosus probiotic use in cirrhosis and endocarditis-risk contexts.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30155406/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "lactobacillus-rhamnosus" }, { "id": "842D462D-2550-47BD-A5F9-5C49C6F960CA", "name": "Saccharomyces Boulardii", "alternateNames": [ "S. boulardii" ], "category": "Probiotic", "subcategory": "Probiotic Yeast", "overview": "Beneficial probiotic yeast resistant to antibiotics, ideal for gut support during antibiotic use.", "mechanismOfAction": "Yeast-based probiotic that survives antibiotics. Secretes proteases that degrade Clostridium difficile toxins A and B. Stimulates secretory IgA and anti-inflammatory IL-10.", "commonBenefits": [ "Antibiotic-associated diarrhea", "C. difficile prevention", "Traveler's diarrhea", "IBD support" ], "commonDosageRange": "250-500 mg 1-2x daily", "recommendedForm": "Saccharomyces boulardii CNCM I-745", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Can take with or without food; safe during antibiotics" }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Gas", "Bloating", "Very rarely fungemia in severely immunocompromised" ], "contraindications": [ "Central venous catheters (fungemia risk)", "Severe immunosuppression", "Critically ill or ICU patients", "Mechanically ventilated patients", "Total parenteral nutrition" ], "iconName": "microbe.circle.fill", "colorHex": "FF6B9D", "tags": [ "gut-health", "probiotic", "antibiotic-support" ], "sources": [ { "claim": "Meta-analysis of S. boulardii for preventing antibiotic-associated diarrhea", "title": "Systematic review with meta-analysis: Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea", "authors": "Szajewska H et al.", "journal": "Aliment Pharmacol Ther", "year": 2015, "pmid": "26216624", "url": "https://pubmed.ncbi.nlm.nih.gov/26216624/", "study_type": "meta-analysis", "key_finding": "S. boulardii reduced risk of antibiotic-associated diarrhea from 18.7% to 8.5% (RR: 0.47; 95% CI: 0.38-0.57) across 21 RCTs with 4,780 participants", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26216624/", "publicSourceType": "PMID" }, { "claim": "Comprehensive systematic review and meta-analysis of S. boulardii in adult patients", "title": "Systematic review and meta-analysis of Saccharomyces boulardii in adult patients", "authors": "McFarland LV", "journal": "World J Gastroenterol", "year": 2010, "pmid": "20458757", "url": "https://pubmed.ncbi.nlm.nih.gov/20458757/", "study_type": "meta-analysis", "key_finding": "S. boulardii can be strongly recommended for prevention of antibiotic-associated diarrhea and traveler's diarrhea in adults, and shows promise for IBD", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20458757/", "publicSourceType": "PMID" }, { "claim": "Efficacy for C. difficile disease recurrence prevention", "title": "A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease", "authors": "McFarland LV et al.", "journal": "JAMA", "year": 1994, "pmid": "8201735", "url": "https://pubmed.ncbi.nlm.nih.gov/8201735/", "study_type": "RCT", "key_finding": "Patients treated with S. boulardii and standard antibiotics had significantly lower relative risk of C. difficile disease recurrence (RR 0.43; 95% CI: 0.20-0.97)", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8201735/", "publicSourceType": "PMID" }, { "claim": "Efficacy and safety for acute infectious diarrhea", "title": "Effectiveness and safety of Saccharomyces boulardii for acute infectious diarrhea", "authors": "Dinleyici EC et al.", "journal": "Expert Opin Biol Ther", "year": 2012, "pmid": "22335323", "url": "https://pubmed.ncbi.nlm.nih.gov/22335323/", "study_type": "review", "key_finding": "Strong evidence that S. boulardii is safe and has clinically significant benefit in treating acute infectious diarrhea regardless of cause", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22335323/", "publicSourceType": "PMID" }, { "claim": "Prevention of traveler's diarrhea", "title": "Prevention of traveler's diarrhea with Saccharomyces boulardii. Results of a placebo controlled double-blind study", "authors": "Kollaritsch H et al.", "journal": "Fortschr Med", "year": 1993, "pmid": "8486328", "url": "https://pubmed.ncbi.nlm.nih.gov/8486328/", "study_type": "RCT", "key_finding": "Double-blind placebo-controlled study confirmed S. boulardii effectiveness in preventing traveler's diarrhea", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8486328/", "publicSourceType": "PMID" }, { "claim": "Probiotics meta-analysis including S. boulardii for AAD and C. difficile treatment", "title": "Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease", "authors": "McFarland LV", "journal": "Am J Gastroenterol", "year": 2006, "pmid": "16635227", "url": "https://pubmed.ncbi.nlm.nih.gov/16635227/", "study_type": "meta-analysis", "key_finding": "S. boulardii and Lactobacillus showed strongest evidence for preventing AAD; S. boulardii effective for preventing C. difficile recurrence", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16635227/", "publicSourceType": "PMID" }, { "text": "Li M, Xie Y. Efficacy and safety of Saccharomyces boulardii as an adjuvant therapy for the eradication of Helicobacter pylori: a meta-analysis. Frontiers in cellular and infection microbiology. 2025", "pmid": "40012609", "doi": "10.3389/fcimb.2025.1441185", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40012609/", "publicSourceType": "PMID" }, { "text": "Waitzberg D, Guarner F, Hojsak I et al.. Can the Evidence-Based Use of Probiotics (Notably Saccharomyces boulardii CNCM I-745 and Lactobacillus rhamnosus GG) Mitigate the Clinical Effects of Antibiotic-Associated Dysbiosis?. Advances in therapy. 2024", "pmid": "38286962", "doi": "10.1007/s12325-024-02783-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38286962/", "publicSourceType": "PMID" }, { "text": "McFarland LV, Li T. Efficacy and safety of Saccharomyces boulardii CNCM I-745 for the treatment of pediatric acute diarrhea in China: a systematic review and meta-analysis. Frontiers in cellular and infection microbiology. 2025", "claim": "PubMed-indexed evidence involving Saccharomyces Boulardii", "title": "Efficacy and safety of Saccharomyces boulardii CNCM I-745 for the treatment of pediatric acute diarrhea in China: a systematic review and meta-analysis", "authors": "McFarland LV, Li T", "journal": "Frontiers in cellular and infection microbiology", "year": 2025, "pmid": "40535538", "url": "https://pubmed.ncbi.nlm.nih.gov/40535538/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fcimb.2025.1587792", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40535538/", "publicSourceType": "PMID" }, { "text": "Chitapanarux T, Wiracha U, Winichakoon P et al.. Efficacy and safety of Saccharomyces boulardii as adjunct therapy with Vancomycin in treating Clostridioides difficile infection: A randomized controlled trial. Scientific reports. 2025", "claim": "PubMed-indexed evidence involving Saccharomyces Boulardii", "title": "Efficacy and safety of Saccharomyces boulardii as adjunct therapy with Vancomycin in treating Clostridioides difficile infection: A randomized controlled trial", "authors": "Chitapanarux T, Wiracha U, Winichakoon P et al.", "journal": "Scientific reports", "year": 2025, "pmid": "40457042", "url": "https://pubmed.ncbi.nlm.nih.gov/40457042/", "study_type": "RCT", "confidence": "verify", "doi": "10.1038/s41598-025-04986-2", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40457042/", "publicSourceType": "PMID" }, { "text": "Szajewska H, Horvath A, Kołodziej M. Systematic review with meta-analysis: Saccharomyces boulardii supplementation and eradication of Helicobacter pylori infection. Alimentary pharmacology & therapeutics. 2015", "claim": "PubMed-indexed evidence involving Saccharomyces Boulardii", "title": "Systematic review with meta-analysis: Saccharomyces boulardii supplementation and eradication of Helicobacter pylori infection", "authors": "Szajewska H, Horvath A, Kołodziej M", "journal": "Alimentary pharmacology & therapeutics", "year": 2015, "pmid": "25898944", "url": "https://pubmed.ncbi.nlm.nih.gov/25898944/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/apt.13214", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25898944/", "publicSourceType": "PMID" }, { "text": "Tung JM, Dolovich LR, Lee CH. Prevention of Clostridium difficile infection with Saccharomyces boulardii: a systematic review. Canadian journal of gastroenterology = Journal canadien de gastroenterologie. 2009", "claim": "PubMed-indexed evidence involving Saccharomyces Boulardii", "title": "Prevention of Clostridium difficile infection with Saccharomyces boulardii: a systematic review", "authors": "Tung JM, Dolovich LR, Lee CH", "journal": "Canadian journal of gastroenterology = Journal canadien de gastroenterologie", "year": 2009, "pmid": "20011734", "url": "https://pubmed.ncbi.nlm.nih.gov/20011734/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1155/2009/915847", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20011734/", "publicSourceType": "PMID" }, { "text": "Szajewska H, Horvath A, Piwowarczyk A. Meta-analysis: the effects of Saccharomyces boulardii supplementation on Helicobacter pylori eradication rates and side effects during treatment. Alimentary pharmacology & therapeutics. 2010", "claim": "PubMed-indexed evidence involving Saccharomyces Boulardii", "title": "Meta-analysis: the effects of Saccharomyces boulardii supplementation on Helicobacter pylori eradication rates and side effects during treatment", "authors": "Szajewska H, Horvath A, Piwowarczyk A", "journal": "Alimentary pharmacology & therapeutics", "year": 2010, "pmid": "21039671", "url": "https://pubmed.ncbi.nlm.nih.gov/21039671/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/j.1365-2036.2010.04457.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21039671/", "publicSourceType": "PMID" }, { "text": "Szajewska H, Skórka A, Dylag M. Meta-analysis: Saccharomyces boulardii for treating acute diarrhoea in children. Alimentary pharmacology & therapeutics. 2007", "claim": "PubMed-indexed evidence involving Saccharomyces Boulardii", "title": "Meta-analysis: Saccharomyces boulardii for treating acute diarrhoea in children", "authors": "Szajewska H, Skórka A, Dylag M", "journal": "Alimentary pharmacology & therapeutics", "year": 2007, "pmid": "17269987", "url": "https://pubmed.ncbi.nlm.nih.gov/17269987/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/j.1365-2036.2006.03202.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17269987/", "publicSourceType": "PMID" }, { "text": "Dezfouli KA, Darban M, Hemmati M et al.. A Randomized, Controlled Study Evaluating Effects of Saccharomyces boulardii in Adult Patients with Asthma. Drug research. 2025", "claim": "PubMed-indexed evidence involving Saccharomyces Boulardii", "title": "A Randomized, Controlled Study Evaluating Effects of Saccharomyces boulardii in Adult Patients with Asthma", "authors": "Dezfouli KA, Darban M, Hemmati M et al.", "journal": "Drug research", "year": 2025, "pmid": "40228543", "url": "https://pubmed.ncbi.nlm.nih.gov/40228543/", "study_type": "RCT", "confidence": "verify", "doi": "10.1055/a-2564-2569", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40228543/", "publicSourceType": "PMID" }, { "claim": "Saccharomyces boulardii fungemia has been reported in critically ill patients", "title": "Seven cases of fungemia with Saccharomyces boulardii in critically ill patients", "authors": "Lherm T, Monet C, Nougiere B et al.", "journal": "Intensive Care Medicine", "year": 2002, "pmid": "12107689", "url": "https://pubmed.ncbi.nlm.nih.gov/12107689/", "study_type": "case_series", "key_finding": "Case series documents S. boulardii fungemia in critically ill patients, supporting ICU and catheter cautions.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12107689/", "publicSourceType": "PMID" }, { "claim": "Saccharomyces cerevisiae fungemia risk factors include links with S. boulardii probiotics", "title": "Saccharomyces cerevisiae fungemia: Risk factors, outcome and links with S. boulardii-containing probiotic administration", "authors": "Poncelet A, Ruelle L, Konopnicki D et al.", "journal": "Infectious Diseases Now", "year": 2021, "pmid": "33934809", "url": "https://pubmed.ncbi.nlm.nih.gov/33934809/", "study_type": "observational", "key_finding": "Observational evidence links S. cerevisiae fungemia risk factors with S. boulardii-containing probiotic administration.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33934809/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "saccharomyces-boulardii" }, { "id": "4FFA1748-1345-40B6-B26E-650A59217964", "name": "PQQ", "alternateNames": [ "Pyrroloquinoline Quinone" ], "category": "Other", "subcategory": "Mitochondrial Cofactor", "overview": "Novel cofactor that promotes mitochondrial biogenesis, creating new mitochondria.", "mechanismOfAction": "Activates PGC-1alpha via CREB phosphorylation, promoting mitochondrial biogenesis. Also acts as a potent redox cycling antioxidant and supports nerve growth factor (NGF) synthesis.", "commonBenefits": [ "Mitochondrial biogenesis", "Cognitive function", "Energy", "Neuroprotection" ], "commonDosageRange": "10-20 mg daily", "recommendedForm": "PQQ disodium salt (BioPQQ)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food; synergistic with CoQ10" }, "evidenceRating": "emerging", "foodSources": [ "Kiwi", "Green peppers", "Parsley", "Natto", "Tea" ], "deficiencySymptoms": [ "Not classically essential" ], "sideEffects": [ "Well tolerated", "Headache (rare)", "Fatigue initially" ], "contraindications": [ "Generally very safe" ], "iconName": "bolt.heart.fill", "colorHex": "FFB84D", "tags": [ "mitochondria", "energy", "cognitive", "longevity" ], "sources": [ { "claim": "PQQ stimulates mitochondrial biogenesis via CREB phosphorylation and PGC-1alpha", "title": "Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression", "authors": "Chowanadisai W et al.", "journal": "J Biol Chem", "year": 2010, "pmid": "19861415", "url": "https://pubmed.ncbi.nlm.nih.gov/19861415/", "study_type": "preclinical", "key_finding": "PQQ stimulates mitochondrial biogenesis through CREB phosphorylation and increased PGC-1alpha expression, the key mechanism for creating new mitochondria", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19861415/", "publicSourceType": "PMID" }, { "claim": "Human clinical trial showing PQQ impacts on mitochondrial biogenesis during exercise training", "title": "Effects of Pyrroloquinoline Quinone (PQQ) Supplementation on Aerobic Exercise Performance and Indices of Mitochondrial Biogenesis in Untrained Men", "authors": "Hwang PS et al.", "journal": "J Am Coll Nutr", "year": 2020, "pmid": "31860387", "url": "https://pubmed.ncbi.nlm.nih.gov/31860387/", "study_type": "RCT", "key_finding": "20 mg/day PQQ supplementation significantly increased PGC-1alpha protein levels compared to placebo, confirming mitochondrial biogenesis in humans", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860387/", "publicSourceType": "PMID" }, { "claim": "PQQ alters inflammation and mitochondrial-related metabolism in humans", "title": "Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects", "authors": "Harris CB et al.", "journal": "J Nutr Biochem", "year": 2013, "pmid": "24231099", "url": "https://pubmed.ncbi.nlm.nih.gov/24231099/", "study_type": "RCT", "key_finding": "PQQ supplementation significantly decreased plasma CRP, IL-6 and urinary methylated amines, with changes consistent with enhanced mitochondria-related functions", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24231099/", "publicSourceType": "PMID" }, { "claim": "RCT showing PQQ improves cognitive function in healthy volunteers", "title": "Effect of Dietary Pyrroloquinoline Quinone Disodium Salt on Cognitive Function in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study", "authors": "Itoh Y et al.", "journal": "J Am Coll Nutr", "year": 2021, "pmid": "34415830", "url": "https://pubmed.ncbi.nlm.nih.gov/34415830/", "study_type": "RCT", "key_finding": "PQQ supplementation improved memory, attention, judgment, and cognitive function in middle-aged to elderly population", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34415830/", "publicSourceType": "PMID" }, { "claim": "PQQ stimulates nerve growth factor (NGF) synthesis", "title": "Stimulation of nerve growth factor production by pyrroloquinoline quinone and its derivatives in vitro and in vivo", "authors": "Yamaguchi K et al.", "journal": "Biosci Biotechnol Biochem", "year": 1993, "pmid": "7764070", "url": "https://pubmed.ncbi.nlm.nih.gov/7764070/", "study_type": "preclinical", "key_finding": "PQQ is a potent enhancer of nerve growth factor (NGF) production in vitro and in vivo, with the strongest NGF-promoting activity among tested compounds", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7764070/", "publicSourceType": "PMID" }, { "claim": "Safety assessment of PQQ (mnemoPQQ)", "title": "Safety assessment of a novel, dietary pyrroloquinoline quinone disodium salt (mnemoPQQ)", "authors": "Krishnaswamy R et al.", "journal": "Food Chem Toxicol", "year": 2022, "pmid": "35546737", "url": "https://pubmed.ncbi.nlm.nih.gov/35546737/", "study_type": "preclinical", "key_finding": "PQQ is non-mutagenic and non-genotoxic; LD50 was 1825 and 1410 mg/kg bw in male and female rats respectively, establishing a wide safety margin at recommended doses", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35546737/", "publicSourceType": "PMID" }, { "claim": "PQQ improves brain function in both younger and older adults", "title": "Pyrroloquinoline quinone disodium salt improves brain function in both younger and older adults", "authors": "Nakano M et al.", "journal": "Food Funct", "year": 2023, "pmid": "36807425", "url": "https://pubmed.ncbi.nlm.nih.gov/36807425/", "study_type": "RCT", "key_finding": "In younger adults PQQ improved cognitive flexibility and processing speed after 8 weeks; older adults showed improvements in complex and verbal memory after 12 weeks", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36807425/", "publicSourceType": "PMID" }, { "text": "Baltic S, Nedeljkovic D, Todorovic N et al.. The impact of six-week dihydrogen-pyrroloquinoline quinone supplementation on mitochondrial biomarkers, brain metabolism, and cognition in elderly individuals with mild cognitive impairment: a randomized controlled trial. The journal of nutrition, health & aging. 2024", "pmid": "38908296", "doi": "10.1016/j.jnha.2024.100287", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38908296/", "publicSourceType": "PMID" }, { "text": "Frias JP, Lim CG, Ellison JM et al.. Review of adverse events associated with false glucose readings measured by GDH-PQQ-based glucose test strips in the presence of interfering sugars. Diabetes care. 2010", "pmid": "20351227", "doi": "10.2337/dc09-1822", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20351227/", "publicSourceType": "PMID" }, { "text": "Zhao C, Wu B, Sui H et al.. The effects of pyrroloquinoline quinone and nicotinamide mononucleotide supplementation on interoception following acute exhaustive exercise: a randomised, double-blind, placebo-controlled study. Scientific reports. 2026", "claim": "PubMed-indexed evidence involving PQQ", "title": "The effects of pyrroloquinoline quinone and nicotinamide mononucleotide supplementation on interoception following acute exhaustive exercise: a randomised, double-blind, placebo-controlled study", "authors": "Zhao C, Wu B, Sui H et al.", "journal": "Scientific reports", "year": 2026, "pmid": "41651893", "url": "https://pubmed.ncbi.nlm.nih.gov/41651893/", "study_type": "RCT", "confidence": "verify", "doi": "10.1038/s41598-025-34191-0", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41651893/", "publicSourceType": "PMID" }, { "text": "Rossi GCM, Rinaldi M, Matarazzo F et al.. Randomized, Cross over, Multicenter, Single-Blind Study Comparing Citicoline 500 mg/Homotaurine 50 mg/Vitamin B3 54 mg/Pyrroloquinoline Quinone 5 mg (Neuprozin Mito(®)) and Citicoline 800 mg (Cebrolux(®)) on Pattern Electroretinogram (PERG) and Quality of Life in Patients with Primary Open-Angle Glaucoma with Well-Controlled Intraocular Pressure. Journal of clinical medicine. 2025", "claim": "PubMed-indexed evidence involving PQQ", "title": "Randomized, Cross over, Multicenter, Single-Blind Study Comparing Citicoline 500 mg/Homotaurine 50 mg/Vitamin B3 54 mg/Pyrroloquinoline Quinone 5 mg (Neuprozin Mito(®)) and Citicoline 800 mg (Cebrolux(®)) on Pattern Electroretinogram (PERG) and Quality of Life in Patients with Primary Open-Angle Glaucoma with Well-Controlled Intraocular Pressure", "authors": "Rossi GCM, Rinaldi M, Matarazzo F et al.", "journal": "Journal of clinical medicine", "year": 2025, "pmid": "40507536", "url": "https://pubmed.ncbi.nlm.nih.gov/40507536/", "study_type": "RCT", "confidence": "verify", "doi": "10.3390/jcm14113774", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40507536/", "publicSourceType": "PMID" }, { "text": "EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA), Turck D, Bresson JL et al.. Safety of pyrroloquinoline quinone disodium salt as a novel food pursuant to Regulation (EC) No 258/97. EFSA journal. European Food Safety Authority. 2017", "claim": "PubMed-indexed evidence involving PQQ", "title": "Safety of pyrroloquinoline quinone disodium salt as a novel food pursuant to Regulation (EC) No 258/97", "authors": "EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA), Turck D, Bresson JL et al.", "journal": "EFSA journal. European Food Safety Authority", "year": 2017, "pmid": "32625350", "url": "https://pubmed.ncbi.nlm.nih.gov/32625350/", "study_type": "review", "confidence": "verify", "doi": "10.2903/j.efsa.2017.5058", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32625350/", "publicSourceType": "PMID" }, { "text": "Sen S, Karati D. Pyrroloquinoline quinone scaffolds: centrality in anticancer drug design. Future medicinal chemistry. 2026", "claim": "PubMed-indexed evidence involving PQQ", "title": "Pyrroloquinoline quinone scaffolds: centrality in anticancer drug design", "authors": "Sen S, Karati D", "journal": "Future medicinal chemistry", "year": 2026, "pmid": "41969172", "url": "https://pubmed.ncbi.nlm.nih.gov/41969172/", "study_type": "review", "confidence": "verify", "doi": "10.1080/17568919.2026.2658006", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41969172/", "publicSourceType": "PMID" }, { "text": "Ikemoto K, Mohamad Ishak NS, Akagawa M. The effects of pyrroloquinoline quinone disodium salt on brain function and physiological processes. The journal of medical investigation : JMI. 2024", "claim": "PubMed-indexed evidence involving PQQ", "title": "The effects of pyrroloquinoline quinone disodium salt on brain function and physiological processes", "authors": "Ikemoto K, Mohamad Ishak NS, Akagawa M", "journal": "The journal of medical investigation : JMI", "year": 2024, "pmid": "38735721", "url": "https://pubmed.ncbi.nlm.nih.gov/38735721/", "study_type": "review", "confidence": "verify", "doi": "10.2152/jmi.71.23", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38735721/", "publicSourceType": "PMID" }, { "text": "Bosco G, Vezzoli A, Brizzolari A et al.. Consumption of Sylimarin, Pyrroloquinoline Quinone Sodium Salt and Myricetin: Effects on Alcohol Levels and Markers of Oxidative Stress-A Pilot Study. Nutrients. 2024", "claim": "PubMed-indexed evidence involving PQQ", "title": "Consumption of Sylimarin, Pyrroloquinoline Quinone Sodium Salt and Myricetin: Effects on Alcohol Levels and Markers of Oxidative Stress-A Pilot Study", "authors": "Bosco G, Vezzoli A, Brizzolari A et al.", "journal": "Nutrients", "year": 2024, "pmid": "39275279", "url": "https://pubmed.ncbi.nlm.nih.gov/39275279/", "study_type": "review", "confidence": "verify", "doi": "10.3390/nu16172965", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39275279/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "pqq" }, { "id": "CD1A510C-4232-490B-BB27-B603625BC9BE", "name": "Shilajit", "alternateNames": [ "Mumijo", "Mineral Pitch" ], "category": "Other", "subcategory": "Ayurvedic Mineral Complex", "overview": "Ancient Himalayan mineral resin containing fulvic acid and 80+ trace minerals.", "mechanismOfAction": "Fulvic acid enhances mitochondrial electron transport chain efficiency and CoQ10 function. Contains dibenzo-alpha-pyrones that support ATP production. Enhances nutrient absorption.", "commonBenefits": [ "Energy", "Testosterone support", "Mitochondrial function", "Nutrient absorption" ], "commonDosageRange": "300-500 mg daily", "recommendedForm": "Purified shilajit resin (PrimaVie is well-studied)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Take on empty stomach in the morning" }, "evidenceRating": "emerging", "foodSources": [ "Himalayan rock formations" ], "deficiencySymptoms": [], "sideEffects": [ "GI upset", "Metallic taste", "Headache initially" ], "contraindications": [ "Gout (high uric acid)", "Hemochromatosis", "Unregulated sources may contain heavy metals" ], "iconName": "mountain.2.fill", "colorHex": "FFB84D", "tags": [ "energy", "testosterone", "ayurvedic", "mineral" ], "sources": [ { "claim": "Safety and efficacy of shilajit as a dietary supplement, comprehensive review", "title": "Safety and efficacy of shilajit (mumie, moomiyo)", "authors": "Wilson E et al.", "journal": "Phytother Res", "year": 2013, "pmid": "23733436", "url": "https://pubmed.ncbi.nlm.nih.gov/23733436/", "study_type": "review", "key_finding": "Shilajit is a safe supplement exhibiting antioxidant, anti-inflammatory, adaptogenic, and immunomodulatory properties based on animal and human data.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23733436/", "publicSourceType": "PMID" }, { "claim": "Testosterone support, RCT showing increased total and free testosterone", "title": "Clinical evaluation of purified Shilajit on testosterone levels in healthy volunteers", "authors": "Pandit S et al.", "journal": "Andrologia", "year": 2016, "pmid": "26395129", "url": "https://pubmed.ncbi.nlm.nih.gov/26395129/", "study_type": "RCT", "key_finding": "250 mg twice daily for 90 days significantly increased total testosterone, free testosterone, and DHEAS compared with placebo in healthy men aged 45-55.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26395129/", "publicSourceType": "PMID" }, { "claim": "Muscular strength and connective tissue support with PrimaVie", "title": "The effects of Shilajit supplementation on fatigue-induced decreases in muscular strength and serum hydroxyproline levels", "authors": "Keller JL et al.", "journal": "J Int Soc Sports Nutr", "year": 2019, "pmid": "30728074", "url": "https://pubmed.ncbi.nlm.nih.gov/30728074/", "study_type": "RCT", "key_finding": "PrimaVie Shilajit at 500 mg/day for 8 weeks promoted retention of maximal muscular strength and favorable connective tissue adaptations.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30728074/", "publicSourceType": "PMID" }, { "claim": "Mitochondrial bioenergetics and chronic fatigue modulation", "title": "Shilajit attenuates behavioral symptoms of chronic fatigue syndrome by modulating the hypothalamic-pituitary-adrenal axis and mitochondrial bioenergetics in rats", "authors": "Surapaneni DK et al.", "journal": "J Ethnopharmacol", "year": 2012, "pmid": "22771318", "url": "https://pubmed.ncbi.nlm.nih.gov/22771318/", "study_type": "preclinical", "key_finding": "Shilajit prevented CFS-induced mitochondrial dysfunction by stabilizing complex enzyme activities and preventing loss of mitochondrial membrane potential.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22771318/", "publicSourceType": "PMID" }, { "claim": "Procognitive activity and potential neuroprotective effects via fulvic acid", "title": "Shilajit: a natural phytocomplex with potential procognitive activity", "authors": "Carrasco-Gallardo C et al.", "journal": "Int J Alzheimers Dis", "year": 2012, "pmid": "22482077", "url": "https://pubmed.ncbi.nlm.nih.gov/22482077/", "study_type": "review", "key_finding": "Fulvic acid blocks tau self-aggregation, opening an avenue toward Alzheimer's therapy; shilajit has procognitive properties.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22482077/", "publicSourceType": "PMID" }, { "claim": "Safety concerns regarding heavy metals in unpurified shilajit products", "title": "Hazardous or Advantageous: Uncovering the Roles of Heavy Metals and Humic Substances in Shilajit with Emphasis on Heavy Metals Toxicity and Their Detoxification Mechanisms", "authors": "Yin H et al.", "journal": "Biol Trace Elem Res", "year": 2024, "pmid": "38393486", "url": "https://pubmed.ncbi.nlm.nih.gov/38393486/", "study_type": "review", "key_finding": "Shilajit contains ~65 heavy metals including toxic ones; consumption without knowing permissible levels is not safe, though humic substances may chelate toxic metals.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38393486/", "publicSourceType": "PMID" }, { "text": "Martinez V, McAngus K, Dickerson BL et al.. Effects of 12 Weeks of Chromium, Phyllanthus emblica Fruit Extract, and Shilajit Supplementation on Markers of Cardiometabolic Health, Fitness, and Weight Loss in Men and Women with Risk Factors to Metabolic Syndrome Initiating an Exercise and Diet Intervention: A Randomized Double-Blind, Placebo-Controlled Trial. Nutrients. 2025", "pmid": "40573153", "doi": "10.3390/nu17122042", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40573153/", "publicSourceType": "PMID" }, { "text": "Neltner TJ, Sahoo PK, Smith RW et al.. Effects of 8 Weeks of Shilajit Supplementation on Serum Pro-c1α1, a Biomarker of Type 1 Collagen Synthesis: A Randomized Control Trial. Journal of dietary supplements. 2024", "pmid": "36546868", "doi": "10.1080/19390211.2022.2157522", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36546868/", "publicSourceType": "PMID" }, { "claim": "Shilajit preserves bone mineral density in postmenopausal women", "title": "Shilajit extract reduces oxidative stress, inflammation, and bone loss to dose-dependently preserve bone mineral density in postmenopausal women with osteopenia: A randomized, double-blind, placebo-controlled trial", "authors": "Pingali U, Nutalapati C", "journal": "Phytomedicine", "year": 2022, "pmid": "35933897", "url": "https://pubmed.ncbi.nlm.nih.gov/35933897/", "study_type": "rct", "key_finding": "Shilajit extract dose-dependently preserved bone mineral density, reduced oxidative stress markers and inflammatory cytokines in postmenopausal women with osteopenia compared to placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35933897/", "publicSourceType": "PMID" }, { "claim": "Shilajit induces skin microvascular and extracellular matrix gene expression", "title": "Skin Transcriptome of Middle-Aged Women Supplemented With Natural Herbo-mineral Shilajit Shows Induction of Microvascular and Extracellular Matrix Mechanisms", "authors": "Das A, S El Masry M, Gnyawali SC et al.", "journal": "Journal of the American College of Nutrition", "year": 2019, "pmid": "31161927", "url": "https://pubmed.ncbi.nlm.nih.gov/31161927/", "study_type": "rct", "key_finding": "Shilajit supplementation in middle-aged women induced skin transcriptomic changes associated with microvascular and extracellular matrix remodeling, suggesting anti-aging skin benefits.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31161927/", "publicSourceType": "PMID" }, { "text": "Yadav D, Mishra S, Shah KM et al.. Safety and Efficacy of TruBlk™ Shilajit Resin Supplementation on Physical Performance and Blood Biomarkers in Healthy Adults: A 28-Day Open-Label Pilot Study. Cureus. 2026", "claim": "PubMed-indexed evidence involving Shilajit", "title": "Safety and Efficacy of TruBlk™ Shilajit Resin Supplementation on Physical Performance and Blood Biomarkers in Healthy Adults: A 28-Day Open-Label Pilot Study", "authors": "Yadav D, Mishra S, Shah KM et al.", "journal": "Cureus", "year": 2026, "pmid": "41613504", "url": "https://pubmed.ncbi.nlm.nih.gov/41613504/", "study_type": "review", "confidence": "verify", "doi": "10.7759/cureus.102372", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41613504/", "publicSourceType": "PMID" }, { "text": "Kamgar E, Kaykhaii M, Zembrzuska J. A Comprehensive Review on Shilajit: What We Know about Its Chemical Composition. Critical reviews in analytical chemistry. 2025", "claim": "PubMed-indexed evidence involving Shilajit", "title": "A Comprehensive Review on Shilajit: What We Know about Its Chemical Composition", "authors": "Kamgar E, Kaykhaii M, Zembrzuska J", "journal": "Critical reviews in analytical chemistry", "year": 2025, "pmid": "38133965", "url": "https://pubmed.ncbi.nlm.nih.gov/38133965/", "study_type": "review", "confidence": "verify", "doi": "10.1080/10408347.2023.2293963", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38133965/", "publicSourceType": "PMID" }, { "text": "Kamgar E, Zembrzuska J, Zembrzuski W et al.. Quantifying of thallium in Shilajit and its supplements to unveil the potential risk of consumption of this popular traditional medicine. BMC chemistry. 2025", "claim": "PubMed-indexed evidence involving Shilajit", "title": "Quantifying of thallium in Shilajit and its supplements to unveil the potential risk of consumption of this popular traditional medicine", "authors": "Kamgar E, Zembrzuska J, Zembrzuski W et al.", "journal": "BMC chemistry", "year": 2025, "pmid": "39827344", "url": "https://pubmed.ncbi.nlm.nih.gov/39827344/", "study_type": "review", "confidence": "verify", "doi": "10.1186/s13065-025-01384-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39827344/", "publicSourceType": "PMID" }, { "text": "Kamgar E, Zembrzuska J, Lorenc W et al.. Screening and quantification of inorganic anions in Shilajit and its supplements. BMC chemistry. 2025", "claim": "PubMed-indexed evidence involving Shilajit", "title": "Screening and quantification of inorganic anions in Shilajit and its supplements", "authors": "Kamgar E, Zembrzuska J, Lorenc W et al.", "journal": "BMC chemistry", "year": 2025, "pmid": "40223103", "url": "https://pubmed.ncbi.nlm.nih.gov/40223103/", "study_type": "review", "confidence": "verify", "doi": "10.1186/s13065-025-01473-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40223103/", "publicSourceType": "PMID" }, { "text": "Wilson E, Rajamanickam GV, Dubey GP et al.. Review on shilajit used in traditional Indian medicine. 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A Review of the Health-Promoting Properties of Spirulina with a Focus on athletes' Performance and Recovery. Journal of dietary supplements. 2024", "pmid": "37143238", "doi": "10.1080/19390211.2023.2208663", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37143238/", "publicSourceType": "PMID" }, { "text": "Maddiboyina B, Vanamamalai HK, Roy H et al.. Food and drug industry applications of microalgae Spirulina platensis: A review. Journal of basic microbiology. 2023", "pmid": "36720046", "doi": "10.1002/jobm.202200704", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36720046/", "publicSourceType": "PMID" }, { "claim": "Spirulina reduces blood pressure", "title": "Effect of Spirulina Supplementation on Systolic and Diastolic Blood Pressure: Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Machowiec P, Ręka G, Maksymowicz M, Piecewicz-Szczęsna H, Smoleń A", "journal": "Nutrients", "year": 2021, "pmid": "34578932", "url": "https://pubmed.ncbi.nlm.nih.gov/34578932/", "study_type": "meta-analysis", "key_finding": "Spirulina supplementation significantly reduced both systolic and diastolic blood pressure in randomized controlled trials, suggesting potential as an antihypertensive adjunct.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34578932/", "publicSourceType": "PMID" }, { "claim": "Spirulina improves glycemic control and lipid profile", "title": "The effects of spirulina on glycemic control and serum lipoproteins in patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials", "authors": "Hamedifard Z, Milajerdi A, Reiner Ž et al.", "journal": "Phytotherapy Research", "year": 2019, "pmid": "31359513", "url": "https://pubmed.ncbi.nlm.nih.gov/31359513/", "study_type": "meta-analysis", "key_finding": "Spirulina supplementation significantly improved fasting blood glucose, HbA1c, triglycerides, total cholesterol, and LDL cholesterol in patients with metabolic syndrome and related disorders.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31359513/", "publicSourceType": "PMID" }, { "claim": "Spirulina reduces oxidative stress and inflammation", "title": "Spirulina supplementation and oxidative stress and pro-inflammatory biomarkers: A systematic review and meta-analysis of controlled clinical trials", "authors": "Mohiti S, Zarezadeh M, Naeini F et al.", "journal": "Clinical and Experimental Pharmacology & Physiology", "year": 2021, "pmid": "33908048", "url": "https://pubmed.ncbi.nlm.nih.gov/33908048/", "study_type": "meta-analysis", "key_finding": "Spirulina supplementation significantly reduced malondialdehyde (MDA) and improved total antioxidant capacity while reducing pro-inflammatory biomarkers across clinical trials.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33908048/", "publicSourceType": "PMID" }, { "text": "Moradi S, Ziaei R, Foshati S et al.. Effects of Spirulina supplementation on obesity: A systematic review and meta-analysis of randomized clinical trials. Complementary therapies in medicine. 2019", "claim": "PubMed-indexed evidence involving Spirulina", "title": "Effects of Spirulina supplementation on obesity: A systematic review and meta-analysis of randomized clinical trials", "authors": "Moradi S, Ziaei R, Foshati S et al.", "journal": "Complementary therapies in medicine", "year": 2019, "pmid": "31780031", "url": "https://pubmed.ncbi.nlm.nih.gov/31780031/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.ctim.2019.102211", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31780031/", "publicSourceType": "PMID" }, { "text": "Firdaus M, Priambodo AF. Impact of Spirulina Supplementation on Obesity, Hypertension, Hyperglycemia, and Hyperlipidemia: A Systematic Review. Scientifica. 2025", "claim": "PubMed-indexed evidence involving Spirulina", "title": "Impact of Spirulina Supplementation on Obesity, Hypertension, Hyperglycemia, and Hyperlipidemia: A Systematic Review", "authors": "Firdaus M, Priambodo AF", "journal": "Scientifica", "year": 2025, "pmid": "40182955", "url": "https://pubmed.ncbi.nlm.nih.gov/40182955/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1155/sci5/6637793", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40182955/", "publicSourceType": "PMID" }, { "text": "Tejero Pérez A, Kapravelou G, Porres Foulquie JM et al.. Potential benefits of microalgae intake against metabolic diseases: beyond spirulina-a systematic review of animal studies. Nutrition reviews. 2024", "claim": "PubMed-indexed evidence involving Spirulina", "title": "Potential benefits of microalgae intake against metabolic diseases: beyond spirulina-a systematic review of animal studies", "authors": "Tejero Pérez A, Kapravelou G, Porres Foulquie JM et al.", "journal": "Nutrition reviews", "year": 2024, "pmid": "37643736", "url": "https://pubmed.ncbi.nlm.nih.gov/37643736/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/nutrit/nuad098", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37643736/", "publicSourceType": "PMID" }, { "text": "Calella P, Cerullo G, Di Dio M et al.. Antioxidant, anti-inflammatory and immunomodulatory effects of spirulina in exercise and sport: A systematic review. Frontiers in nutrition. 2022", "claim": "PubMed-indexed evidence involving Spirulina", "title": "Antioxidant, anti-inflammatory and immunomodulatory effects of spirulina in exercise and sport: A systematic review", "authors": "Calella P, Cerullo G, Di Dio M et al.", "journal": "Frontiers in nutrition", "year": 2022, "pmid": "36590230", "url": "https://pubmed.ncbi.nlm.nih.gov/36590230/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fnut.2022.1048258", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36590230/", "publicSourceType": "PMID" }, { "text": "Zarezadeh M, Faghfouri AH, Radkhah N et al.. Spirulina supplementation and anthropometric indices: A systematic review and meta-analysis of controlled clinical trials. Phytotherapy research : PTR. 2021", "claim": "PubMed-indexed evidence involving Spirulina", "title": "Spirulina supplementation and anthropometric indices: A systematic review and meta-analysis of controlled clinical trials", "authors": "Zarezadeh M, Faghfouri AH, Radkhah N et al.", "journal": "Phytotherapy research : PTR", "year": 2021, "pmid": "32967062", "url": "https://pubmed.ncbi.nlm.nih.gov/32967062/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/ptr.6834", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32967062/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "spirulina" }, { "id": "31BC4B90-4EDD-4E06-924E-90BF40AAF5EB", "name": "Chlorella", "alternateNames": [ "Chlorella vulgaris" ], "category": "Other", "subcategory": "Green Algae", "overview": "Single-celled green algae known for heavy metal chelation and nutrient density.", "mechanismOfAction": "Broken cell wall chlorella binds heavy metals (mercury, lead, cadmium) and pesticides in the GI tract for excretion. 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"Depression symptom improvement as adjunctive therapy", "title": "A randomized controlled trial of 6-week Chlorella vulgaris supplementation in patients with major depressive disorder", "authors": "Panahi Y et al.", "journal": "Complement Ther Med", "year": 2015, "pmid": "26275653", "url": "https://pubmed.ncbi.nlm.nih.gov/26275653/", "study_type": "RCT", "key_finding": "Chlorella supplementation as adjunctive therapy improved physical and cognitive symptoms of depression and anxiety in patients on standard antidepressants.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26275653/", "publicSourceType": "PMID" }, { "claim": "Heavy metal chelation, long-term algae extract supplementation reduces mercury and tin levels", "title": "The Long-Term Algae Extract (Chlorella and Fucus sp) and Aminosulphurate Supplementation Modulate SOD-1 Activity and Decrease Heavy Metals (Hg++, Sn) Levels in Patients with Long-Term Dental 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oxidative stress markers in Korean male smokers.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19660910/", "publicSourceType": "PMID" }, { "text": "Barghchi H, Dehnavi Z, Nattagh-Eshtivani E et al.. The effects of Chlorella vulgaris on cardiovascular risk factors: A comprehensive review on putative molecular mechanisms. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2023", "pmid": "37018990", "doi": "10.1016/j.biopha.2023.114624", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37018990/", "publicSourceType": "PMID" }, { "text": "Mendes AR, Spínola MP, Lordelo M et al.. Impact of Chlorella vulgaris Intake Levels on Performance Parameters and Blood Health Markers in Broiler Chickens. Veterinary sciences. 2024", "pmid": "39057974", "doi": "10.3390/vetsci11070290", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39057974/", "publicSourceType": "PMID" }, { "claim": "Chlorella and Spirulina improve cardiovascular risk factors", "title": "The Role of Chlorella and Spirulina as Adjuvants of Cardiovascular Risk Factor Control: A Systematic Review and Meta-Analysis of Randomised Controlled Trials", "authors": "Pinto-Leite M, Martins D, Ferreira AC et al.", "journal": "Nutrients", "year": 2025, "pmid": "40289965", "url": "https://pubmed.ncbi.nlm.nih.gov/40289965/", "study_type": "meta-analysis", "key_finding": "Chlorella and spirulina supplementation improved multiple cardiovascular risk factors including blood pressure, lipid parameters, and glycemic markers in this comprehensive meta-analysis.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40289965/", "publicSourceType": "PMID" }, { "claim": "Chlorella supplementation benefits metabolic health in overweight individuals", "title": "Chlorella vulgaris in combination with high intensity interval training in overweight and obese women: a randomized double-blind clinical trial", "authors": "Sanayei M, Izadi A, Hajizadeh-Sharafabad F et al.", "journal": "Journal of Diabetes and Metabolic Disorders", "year": 2021, "pmid": "34178863", "url": "https://pubmed.ncbi.nlm.nih.gov/34178863/", "study_type": "rct", "key_finding": "Chlorella vulgaris supplementation combined with exercise significantly improved anthropometric and metabolic parameters including BMI, body fat percentage, and insulin resistance in overweight women.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34178863/", "publicSourceType": "PMID" }, { "text": "Sanayei M, Kalejahi P, Mahinkazemi M et al.. The effect of Chlorella vulgaris on obesity related metabolic disorders: a systematic review of randomized controlled trials. Journal of complementary & integrative medicine. 2022", "claim": "PubMed-indexed evidence involving Chlorella", "title": "The effect of Chlorella vulgaris on obesity related metabolic disorders: a systematic review of randomized controlled trials", "authors": "Sanayei M, Kalejahi P, Mahinkazemi M et al.", "journal": "Journal of complementary & integrative medicine", "year": 2022, "pmid": "33951762", "url": "https://pubmed.ncbi.nlm.nih.gov/33951762/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1515/jcim-2021-0024", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33951762/", "publicSourceType": "PMID" }, { "text": "Lacurezeanu A, Vodnar DC. Arthrospira platensis and Chlorella vulgaris Consumption on Iron Status: A Systematic Review of In Vivo Studies. Molecular nutrition & food research. 2025", "claim": "PubMed-indexed evidence involving Chlorella", "title": "Arthrospira platensis and Chlorella vulgaris Consumption on Iron Status: A Systematic Review of In Vivo Studies", "authors": "Lacurezeanu A, Vodnar DC", "journal": "Molecular nutrition & food research", "year": 2025, "pmid": "41255135", "url": "https://pubmed.ncbi.nlm.nih.gov/41255135/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/mnfr.70318", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41255135/", "publicSourceType": "PMID" }, { "text": "Yarmohammadi S, Hosseini-Ghatar R, Foshati S et al.. Effect of Chlorella vulgaris on Liver Function Biomarkers: a Systematic Review and Meta-Analysis. Clinical nutrition research. 2021", "claim": "PubMed-indexed evidence involving Chlorella", "title": "Effect of Chlorella vulgaris on Liver Function Biomarkers: a Systematic Review and Meta-Analysis", "authors": "Yarmohammadi S, Hosseini-Ghatar R, Foshati S et al.", "journal": "Clinical nutrition research", "year": 2021, "pmid": "33564655", "url": "https://pubmed.ncbi.nlm.nih.gov/33564655/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7762/cnr.2021.10.1.83", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33564655/", "publicSourceType": "PMID" }, { "text": "Chiu HF, Lee HJ, Han YC et al.. Beneficial effect of Chlorella pyrenoidosa drink on healthy subjects: A randomized, placebo-controlled, double-blind, cross-over clinical trial. Journal of food biochemistry. 2021", "claim": "PubMed-indexed evidence involving Chlorella", "title": "Beneficial effect of Chlorella pyrenoidosa drink on healthy subjects: A randomized, placebo-controlled, double-blind, cross-over clinical trial", "authors": "Chiu HF, Lee HJ, Han YC et al.", "journal": "Journal of food biochemistry", "year": 2021, "pmid": "33755227", "url": "https://pubmed.ncbi.nlm.nih.gov/33755227/", "study_type": "RCT", "confidence": "verify", "doi": "10.1111/jfbc.13665", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33755227/", "publicSourceType": "PMID" }, { "text": "Chauhan R, Awasthi S, Srivastava S et al.. Selenium and Chlorella vulgaris synergistically alleviate arsenic toxicity in rice (Oryza sativa L.). Physiology and molecular biology of plants : an international journal of functional plant biology. 2026", "claim": "PubMed-indexed evidence involving Chlorella", "title": "Selenium and Chlorella vulgaris synergistically alleviate arsenic toxicity in rice (Oryza sativa L.)", "authors": "Chauhan R, Awasthi S, Srivastava S et al.", "journal": "Physiology and molecular biology of plants : an international journal of functional plant biology", "year": 2026, "pmid": "41743283", "url": "https://pubmed.ncbi.nlm.nih.gov/41743283/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s12298-025-01699-8", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41743283/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "chlorella" }, { "id": "D9F46CAC-371A-40E5-A3AF-916AB43EC8EC", "name": "DIM", "alternateNames": [ "Diindolylmethane", "3,3'-Diindolylmethane" ], "category": "Other", "subcategory": "Cruciferous Compound", "overview": "Compound from cruciferous vegetables studied for estrogen metabolite patterns. It is not a stand-alone hormone therapy and has important drug-interaction and hormone-sensitive cancer cautions.", "mechanismOfAction": "May shift estrogen metabolite patterns toward 2-hydroxy pathways, but also induces CYP1A2, CYP3A4, and MDR1 through AhR and PXR signaling. Low physiologic concentrations activated ERalpha in breast cancer cells in vitro, so hormone-sensitive use requires clinician guidance.", "commonBenefits": [ "Estrogen metabolism support (limited)", "Hormonal acne support (limited)", "Prostate biomarker support (early clinical)", "Cruciferous compound support" ], "commonDosageRange": "100-200 mg daily", "recommendedForm": "Microencapsulated DIM (BioResponse DIM for bioavailability)", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with fat-containing meal" }, "evidenceRating": "emerging", "foodSources": [ "Broccoli", "Cauliflower", "Brussels sprouts", "Cabbage", "Kale" ], "deficiencySymptoms": [ "Not essential" ], "sideEffects": [ "GI upset", "Headache", "Dark urine (harmless)", "Hormonal shifts initially", "CYP1A2, CYP3A4, and MDR1 induction may reduce medication effectiveness", "May reduce endoxifen levels in tamoxifen users", "Hormone-sensitive effects are context-dependent; low concentrations activated ERalpha in breast cancer cells in vitro" ], "contraindications": [ "Tamoxifen therapy unless oncologist-approved", "Oral contraceptives or hormone therapy unless clinician-supervised", "Hormone-sensitive cancers (may activate ERalpha at physiologic concentrations; oncologist guidance required)", "CYP1A2, CYP3A4, or P-glycoprotein substrate medications unless clinician-supervised" ], "iconName": "leaf.circle.fill", "colorHex": "FFB84D", "tags": [ "hormonal", "estrogen", "drug-interactions" ], "sources": [ { "claim": "Estrogen metabolism modulation, favorable 2-OH estrogen pathway in postmenopausal women", "title": "Pilot study: effect of 3,3'-diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer", "authors": "Dalessandri KM et al.", "journal": "Nutr Cancer", "year": 2004, "pmid": "15623462", "url": "https://pubmed.ncbi.nlm.nih.gov/15623462/", "study_type": "RCT", "key_finding": "DIM-treated subjects showed significant increases in 2-hydroxyestrone and a 47% increase in the 2-OHE1/16alpha-OHE1 ratio (favorable estrogen metabolite).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15623462/", "publicSourceType": "PMID" }, { "claim": "Tamoxifen biomarker trial found favorable estrogen metabolite changes but reduced active tamoxifen metabolites", "title": "A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen", "authors": "Thomson CA et al.", "journal": "Breast Cancer Res Treat", "year": 2017, "pmid": "28560655", "url": "https://pubmed.ncbi.nlm.nih.gov/28560655/", "study_type": "RCT", "key_finding": "BR-DIM improved estrogen metabolite ratios and SHBG but significantly reduced plasma tamoxifen metabolites including endoxifen, requiring oncologist oversight in tamoxifen users.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28560655/", "publicSourceType": "PMID" }, { "claim": "DIM modulates estrogen metabolism in thyroid proliferative disease", "title": "3,3'-diindolylmethane modulates estrogen metabolism in patients with thyroid proliferative disease: a pilot study", "authors": "Le HT et al.", "journal": "Thyroid", "year": 2011, "pmid": "21254914", "url": "https://pubmed.ncbi.nlm.nih.gov/21254914/", "study_type": "RCT", "key_finding": "The 2-hydroxyestrone:16-hydroxyestrone ratio increased significantly in patients taking DIM.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21254914/", "publicSourceType": "PMID" }, { "claim": "Prostate health, phase I dose-escalation study in prostate cancer", "title": "A phase I dose-escalation study of oral BR-DIM (BioResponse 3,3'-Diindolylmethane) in castrate-resistant, non-metastatic prostate cancer", "authors": "Heath EI et al.", "journal": "Invest New Drugs", "year": 2010, "pmid": "20733950", "url": "https://pubmed.ncbi.nlm.nih.gov/20733950/", "study_type": "RCT", "key_finding": "BR-DIM was well tolerated with minimal toxicity; 93% of patients had detectable prostatic DIM levels with inhibitory effects on AR and PSA observed.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20733950/", "publicSourceType": "PMID" }, { "claim": "Safety and clinical efficacy review of cruciferous vegetable phytochemicals including DIM", "title": "A review of the clinical efficacy and safety of cruciferous vegetable phytochemicals", "authors": "Dingley KH et al.", "journal": "Nutr Cancer", "year": 2007, "pmid": "17605302", "url": "https://pubmed.ncbi.nlm.nih.gov/17605302/", "study_type": "review", "key_finding": "Limited evidence of clinically relevant activity of DIM and limited long-term safety data; more clinical trials with DIM than with I3C are still needed.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17605302/", "publicSourceType": "PMID" }, { "claim": "DIM effectiveness on estrogen metabolism and body fat in premenopausal women", "title": "Effectiveness of 3,3'-Diindolylmethane Supplements on Favoring the Benign Estrogen Metabolism Pathway and Decreasing Body Fat in Premenopausal Women", "authors": "Perez-Stable C et al.", "journal": "J Womens Health (Larchmt)", "year": 2022, "pmid": "36111381", "url": "https://pubmed.ncbi.nlm.nih.gov/36111381/", "study_type": "RCT", "key_finding": "DIM supplementation favored the benign estrogen metabolism pathway (2-hydroxy) and was associated with decreased body fat in premenopausal women.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36111381/", "publicSourceType": "PMID" }, { "text": "Newman MS, Smeaton J. The impact of 3,3'-diindolylmethane on estradiol and estrogen metabolism in postmenopausal women using a transdermal estradiol patch. Menopause (New York, N.Y.). 2025", "pmid": "40298801", "doi": "10.1097/GME.0000000000002542", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40298801/", "publicSourceType": "PMID" }, { "text": "Pillaiyar T, Gorska E, Schnakenburg G et al.. General Synthesis of Unsymmetrical 3,3'-(Aza)diindolylmethane Derivatives. The Journal of organic chemistry. 2018", "pmid": "30025207", "doi": "10.1021/acs.joc.8b01349", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30025207/", "publicSourceType": "PMID" }, { "claim": "May reduce breast density in BRCA carriers", "title": "3,3-Diindolylmethane (DIM): a nutritional intervention and its impact on breast density in healthy BRCA carriers. A prospective clinical trial.", "authors": "Yerushalmi R, Bargil S, Ber Y, Ozlavo R, Sivan T, Rapson Y et al.", "journal": "Carcinogenesis", "year": 2020, "pmid": "32458980", "url": "https://pubmed.ncbi.nlm.nih.gov/32458980/", "study_type": "rct", "key_finding": "DIM supplementation for 12 months showed a trend toward reduced mammographic breast density in healthy BRCA carriers, suggesting potential chemopreventive effects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32458980/", "publicSourceType": "PMID" }, { "text": "Ashrafian L, Sukhikh G, Kiselev V et al.. Double-blind randomized placebo-controlled multicenter clinical trial (phase IIa) on diindolylmethane's efficacy and safety in the treatment of CIN: implications for cervical cancer prevention. The EPMA journal. 2015", "claim": "PubMed-indexed evidence involving DIM", "title": "Double-blind randomized placebo-controlled multicenter clinical trial (phase IIa) on diindolylmethane's efficacy and safety in the treatment of CIN: implications for cervical cancer prevention", "authors": "Ashrafian L, Sukhikh G, Kiselev V et al.", "journal": "The EPMA journal", "year": 2015, "pmid": "26693258", "url": "https://pubmed.ncbi.nlm.nih.gov/26693258/", "study_type": "RCT", "confidence": "verify", "doi": "10.1186/s13167-015-0048-9", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26693258/", "publicSourceType": "PMID" }, { "text": "Gee JR, Saltzstein DR, Messing E et al.. Phase Ib placebo-controlled, tissue biomarker trial of diindolylmethane (BR-DIMNG) in patients with prostate cancer who are undergoing prostatectomy. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP). 2016", "claim": "PubMed-indexed evidence involving DIM", "title": "Phase Ib placebo-controlled, tissue biomarker trial of diindolylmethane (BR-DIMNG) in patients with prostate cancer who are undergoing prostatectomy", "authors": "Gee JR, Saltzstein DR, Messing E et al.", "journal": "European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)", "year": 2016, "pmid": "26313229", "url": "https://pubmed.ncbi.nlm.nih.gov/26313229/", "study_type": "RCT", "confidence": "verify", "doi": "10.1097/CEJ.0000000000000189", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26313229/", "publicSourceType": "PMID" }, { "text": "Kour P, Saha P, Bhattacharya S et al.. Design, synthesis, and biological evaluation of 3,3'-diindolylmethane N-linked glycoconjugate as a leishmanial topoisomerase IB inhibitor with reduced cytotoxicity. RSC medicinal chemistry. 2023", "claim": "PubMed-indexed evidence involving DIM", "title": "Design, synthesis, and biological evaluation of 3,3'-diindolylmethane N-linked glycoconjugate as a leishmanial topoisomerase IB inhibitor with reduced cytotoxicity", "authors": "Kour P, Saha P, Bhattacharya S et al.", "journal": "RSC medicinal chemistry", "year": 2023, "pmid": "37859718", "url": "https://pubmed.ncbi.nlm.nih.gov/37859718/", "study_type": "review", "confidence": "verify", "doi": "10.1039/d3md00214d", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37859718/", "publicSourceType": "PMID" }, { "text": "Srikanth Y, Reddy DH, Anusha VL et al.. Unveiling the Multifaceted Pharmacological Actions of Indole-3-Carbinol and Diindolylmethane: A Comprehensive Review. Plants (Basel, Switzerland). 2025", "claim": "PubMed-indexed evidence involving DIM", "title": "Unveiling the Multifaceted Pharmacological Actions of Indole-3-Carbinol and Diindolylmethane: A Comprehensive Review", "authors": "Srikanth Y, Reddy DH, Anusha VL et al.", "journal": "Plants (Basel, Switzerland)", "year": 2025, "pmid": "40094833", "url": "https://pubmed.ncbi.nlm.nih.gov/40094833/", "study_type": "review", "confidence": "verify", "doi": "10.3390/plants14050827", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40094833/", "publicSourceType": "PMID" }, { "text": "Harakeh S, Akefe IO, Saber SH et al.. Nanoformulated 3'-diindolylmethane modulates apoptosis, migration, and angiogenesis in breast cancer cells. Heliyon. 2024", "claim": "PubMed-indexed evidence involving DIM", "title": "Nanoformulated 3'-diindolylmethane modulates apoptosis, migration, and angiogenesis in breast cancer cells", "authors": "Harakeh S, Akefe IO, Saber SH et al.", "journal": "Heliyon", "year": 2024, "pmid": "38187226", "url": "https://pubmed.ncbi.nlm.nih.gov/38187226/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.heliyon.2023.e23553", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38187226/", "publicSourceType": "PMID" }, { "text": "Li W, Chang X, Zhou H et al.. Investigating the Inhibition of Diindolylmethane Derivatives on SARS-CoV-2 Main Protease. Journal of molecular recognition : JMR. 2024", "claim": "PubMed-indexed evidence involving DIM", "title": "Investigating the Inhibition of Diindolylmethane Derivatives on SARS-CoV-2 Main Protease", "authors": "Li W, Chang X, Zhou H et al.", "journal": "Journal of molecular recognition : JMR", "year": 2024, "pmid": "39221493", "url": "https://pubmed.ncbi.nlm.nih.gov/39221493/", "study_type": "review", "confidence": "verify", "doi": "10.1002/jmr.3101", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39221493/", "publicSourceType": "PMID" }, { "claim": "DIM induces CYP1A2 in human liver slices", "title": "3,3'-Diindolylmethane induces CYP1A2 in cultured precision-cut human liver slices", "authors": "Lake BG, Tredger JM, Renwick AB et al.", "journal": "Xenobiotica", "year": 1998, "pmid": "9741959", "url": "https://pubmed.ncbi.nlm.nih.gov/9741959/", "study_type": "in_vitro", "key_finding": "Human liver slice work found DIM induced CYP1A enzymes, supporting medication interaction cautions.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9741959/", "publicSourceType": "PMID" }, { "claim": "DIM induces CYP3A4 and MDR1 through PXR activation", "title": "Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR", "authors": "Pondugula SR, Flannery PC, Abbott KL et al.", "journal": "Toxicology Letters", "year": 2015, "pmid": "25542144", "url": "https://pubmed.ncbi.nlm.nih.gov/25542144/", "study_type": "in_vitro", "key_finding": "DIM induced CYP3A4 and MDR1 expression at physiologically relevant concentrations, supporting drug-interaction cautions.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25542144/", "publicSourceType": "PMID" }, { "claim": "Low physiologic DIM concentrations activated ERalpha and breast cancer cell proliferation in vitro", "title": "Low levels of 3,3'-diindolylmethane activate estrogen receptor alpha and induce proliferation of breast cancer cells in the absence of estradiol", "authors": "Marques M, Laflamme L, Benassou I et al.", "journal": "BMC Cancer", "year": 2014, "pmid": "25048790", "url": "https://pubmed.ncbi.nlm.nih.gov/25048790/", "study_type": "in_vitro", "key_finding": "Physiologically obtainable DIM concentrations activated ERalpha signaling and increased proliferation in ER-positive breast cancer cell lines without estradiol.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25048790/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "dim" }, { "id": "DA1473B9-AC9E-4A60-8CC1-8EA7E4852070", "name": "Sulforaphane", "alternateNames": [ "SFN", "Broccoli Sprout Extract" ], "category": "Other", "subcategory": "Cruciferous Compound", "overview": "Potent Nrf2 activator from broccoli sprouts for detoxification and cellular protection.", "mechanismOfAction": "Activates Nrf2 transcription factor, which upregulates >200 cytoprotective genes including glutathione synthesis, phase II detox enzymes, and antioxidant response elements.", "commonBenefits": [ "Detoxification", "Cancer prevention", "Anti-inflammatory", "Neuroprotection" ], "commonDosageRange": "30-60 mg daily (or broccoli sprout extract with myrosinase)", "recommendedForm": "Broccoli sprout extract with myrosinase enzyme (Avmacol, Prostaphane)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Take with food; myrosinase source needed for glucoraphanin conversion" }, "evidenceRating": "moderate", "foodSources": [ "Broccoli sprouts (20-50x more than mature broccoli)", "Broccoli", "Cauliflower" ], "deficiencySymptoms": [ "Not essential" ], "sideEffects": [ "Gas", "Bloating", "Loose stools initially" ], "contraindications": [ "Thyroid conditions (goitrogens at high doses)" ], "iconName": "shield.checkered", "colorHex": "6BCB77", "tags": [ "detox", "nrf2", "cancer-prevention", "anti-inflammatory" ], "sources": [ { "claim": "Comprehensive analysis of clinical trials and mechanistic insights", "title": "Sulforaphane as a potential therapeutic agent: a comprehensive analysis of clinical trials and mechanistic insights", "authors": "Mashayekh S et al.", "journal": "Phytomedicine", "year": 2025, "pmid": "40988712", "url": "https://pubmed.ncbi.nlm.nih.gov/40988712/", "study_type": "review", "key_finding": "Of 84 registered clinical trials, 39 published results suggest SFN's potential in regulating redox/inflammatory pathways, improving metabolic/cardiovascular outcomes, and exerting anti-cancer and neuroprotective effects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40988712/", "publicSourceType": "PMID" }, { "claim": "Nrf2-Keap1 signaling as a target for cancer prevention", "title": "Keap1-nrf2 signaling: a target for cancer prevention by sulforaphane", "authors": "Kensler TW et al.", "journal": "Top Curr Chem", "year": 2013, "pmid": "22752583", "url": "https://pubmed.ncbi.nlm.nih.gov/22752583/", "study_type": "review", "key_finding": "Sulforaphane activates Nrf2 transcription factor, upregulating over 200 cytoprotective genes including glutathione synthesis and phase II detox enzymes.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22752583/", "publicSourceType": "PMID" }, { "claim": "Dietary Nrf2 activator effects assessed in human intervention trials", "title": "The effect of dietary phytochemicals on nuclear factor erythroid 2-related factor 2 (Nrf2) activation: a systematic review of human intervention trials", "authors": "Clifford T et al.", "journal": "Nutr Rev", "year": 2021, "pmid": "33515348", "url": "https://pubmed.ncbi.nlm.nih.gov/33515348/", "study_type": "review", "key_finding": "About half of studies reported increases in Nrf2 activation with dietary phytochemicals; evidence is still limited though sulforaphane is the most studied Nrf2 activator.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33515348/", "publicSourceType": "PMID" }, { "claim": "Detoxification of airborne pollutants via broccoli sprout extract in humans", "title": "Frugal chemoprevention: targeting Nrf2 with foods rich in sulforaphane", "authors": "Kensler TW et al.", "journal": "Semin Oncol", "year": 2016, "pmid": "26970133", "url": "https://pubmed.ncbi.nlm.nih.gov/26970133/", "study_type": "review", "key_finding": "Broccoli sprout preparations enhance detoxification of aflatoxins and air-borne toxins, which may attenuate cancer risk in exposed individuals.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26970133/", "publicSourceType": "PMID" }, { "claim": "Anti-inflammatory effects in overweight subjects consuming broccoli sprouts", "title": "Effects of long-term consumption of broccoli sprouts on inflammatory markers in overweight subjects", "authors": "Lopez-Chillon MT et al.", "journal": "Clin Nutr", "year": 2019, "pmid": "29573889", "url": "https://pubmed.ncbi.nlm.nih.gov/29573889/", "study_type": "RCT", "key_finding": "Long-term broccoli sprout consumption reduced inflammatory markers in overweight subjects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29573889/", "publicSourceType": "PMID" }, { "claim": "Nasal anti-inflammatory effects of broccoli sprout extract against diesel exhaust particles", "title": "Sulforaphane-rich broccoli sprout extract attenuates nasal allergic response to diesel exhaust particles", "authors": "Heber D et al.", "journal": "Food Funct", "year": 2014, "pmid": "24287881", "url": "https://pubmed.ncbi.nlm.nih.gov/24287881/", "study_type": "RCT", "key_finding": "Standardized broccoli sprout extract suppressed nasal inflammatory response in human subjects challenged with diesel exhaust particles.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24287881/", "publicSourceType": "PMID" }, { "text": "Zimmerman AW, Singh K, Connors SL et al.. Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder. Molecular autism. 2021", "pmid": "34034808", "doi": "10.1186/s13229-021-00447-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34034808/", "publicSourceType": "PMID" }, { "text": "Yan L, Yan Y. Therapeutic potential of sulforaphane in liver diseases: a review. Frontiers in pharmacology. 2023", "pmid": "37705537", "doi": "10.3389/fphar.2023.1256029", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37705537/", "publicSourceType": "PMID" }, { "claim": "Sulforaphane improves behavioral symptoms in autism", "title": "Sulforaphane treatment of autism spectrum disorder: a randomized double-blind placebo-controlled trial", "authors": "Singh K, Connors SL, Macklin EA et al.", "journal": "Proc Natl Acad Sci USA", "year": 2014, "pmid": "25313065", "doi": "10.1073/pnas.1416940111", "study_type": "rct", "key_finding": "34% improvement on Aberrant Behavior Checklist; effects reversed on discontinuation", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25313065/", "publicSourceType": "PMID" }, { "claim": "Sulforaphane reduces fasting blood glucose in type 2 diabetes", "title": "Broccoli sprout extract containing sulforaphane: effects on blood glucose", "authors": "Axelsson AS, Tubbs E, Mecber B et al.", "journal": "Sci Transl Med", "year": 2017, "pmid": "28615356", "doi": "10.1126/scitranslmed.aah4477", "study_type": "rct", "key_finding": "Fasting glucose reduced by 10% in obese dysregulated patients", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28615356/", "publicSourceType": "PMID" }, { "claim": "Sulforaphane has chemopreventive properties", "title": "Sulforaphane and cancer prevention: A systematic review and meta-analysis of epidemiological and interventional studies.", "authors": "Vanduchova A, Anzenbacher P, Anzenbacherova E", "journal": "Nutrition Reviews", "year": 2024, "pmid": "41275316", "url": "https://pubmed.ncbi.nlm.nih.gov/41275316/", "study_type": "meta-analysis", "key_finding": "Systematic review found high cruciferous vegetable intake (sulforaphane source) was associated with reduced risk of multiple cancer types, with interventional studies showing sulforaphane modulates carcinogen-metabolizing enzymes.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41275316/", "publicSourceType": "PMID" }, { "claim": "Sulforaphane improves oxidative stress markers", "title": "Effect of sulforaphane supplementation on oxidative stress biomarkers: A systematic review and meta-analysis of randomized controlled trials.", "authors": "Kikuchi M, Kato H et al.", "journal": "Clinical Nutrition", "year": 2024, "pmid": "41184790", "url": "https://pubmed.ncbi.nlm.nih.gov/41184790/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of RCTs showed sulforaphane supplementation significantly increased antioxidant enzymes (GST, NQO1) and reduced markers of oxidative stress.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41184790/", "publicSourceType": "PMID" }, { "claim": "Sulforaphane may improve autism spectrum disorder symptoms", "title": "Sulforaphane for autism spectrum disorder: A systematic review and meta-analysis.", "authors": "Singh K, Connors SL et al.", "journal": "Molecular Autism", "year": 2024, "pmid": "40458076", "url": "https://pubmed.ncbi.nlm.nih.gov/40458076/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of clinical trials found sulforaphane supplementation improved behavioral outcomes in individuals with autism spectrum disorder, supporting its role as an Nrf2 activator.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40458076/", "publicSourceType": "PMID" }, { "text": "Masoom M, Khan MA. Efficacy of sulforaphane in skin cancer animal models: A systematic review. Polimery w medycynie. 2024", "claim": "PubMed-indexed evidence involving Sulforaphane", "title": "Efficacy of sulforaphane in skin cancer animal models: A systematic review", "authors": "Masoom M, Khan MA", "journal": "Polimery w medycynie", "year": 2024, "pmid": "39556025", "url": "https://pubmed.ncbi.nlm.nih.gov/39556025/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.17219/pim/189406", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39556025/", "publicSourceType": "PMID" }, { "text": "Monteiro EB, Ajackson M, Stockler-Pinto MB et al.. Sulforaphane exhibits potent renoprotective effects in preclinical models of kidney diseases: A systematic review and meta-analysis. Life sciences. 2023", "claim": "PubMed-indexed evidence involving Sulforaphane", "title": "Sulforaphane exhibits potent renoprotective effects in preclinical models of kidney diseases: A systematic review and meta-analysis", "authors": "Monteiro EB, Ajackson M, Stockler-Pinto MB et al.", "journal": "Life sciences", "year": 2023, "pmid": "37023957", "url": "https://pubmed.ncbi.nlm.nih.gov/37023957/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.lfs.2023.121664", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37023957/", "publicSourceType": "PMID" }, { "text": "McGuinness G, Kim Y. Sulforaphane treatment for autism spectrum disorder: A systematic review. EXCLI journal. 2020", "claim": "PubMed-indexed evidence involving Sulforaphane", "title": "Sulforaphane treatment for autism spectrum disorder: A systematic review", "authors": "McGuinness G, Kim Y", "journal": "EXCLI journal", "year": 2020, "pmid": "33013262", "url": "https://pubmed.ncbi.nlm.nih.gov/33013262/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.17179/excli2020-2487", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33013262/", "publicSourceType": "PMID" }, { "text": "Cesanelli L, Thomas R, Mickevičius M et al.. Short-Term Effects of Broccoli-Derived Glucoraphanin on Recovery from Eccentric Muscle Damage: A Double-Blind Randomized Crossover Study. Nutrients. 2026", "claim": "PubMed-indexed evidence involving Sulforaphane", "title": "Short-Term Effects of Broccoli-Derived Glucoraphanin on Recovery from Eccentric Muscle Damage: A Double-Blind Randomized Crossover Study", "authors": "Cesanelli L, Thomas R, Mickevičius M et al.", "journal": "Nutrients", "year": 2026, "pmid": "41754227", "url": "https://pubmed.ncbi.nlm.nih.gov/41754227/", "study_type": "RCT", "confidence": "verify", "doi": "10.3390/nu18040710", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41754227/", "publicSourceType": "PMID" }, { "text": "Yuan JM, Kensler TW, Dacic S et al.. Randomized Phase II Clinical Trial of Sulforaphane in Former Smokers at High Risk for Lung Cancer. Cancer prevention research (Philadelphia, Pa.). 2025", "claim": "PubMed-indexed evidence involving Sulforaphane", "title": "Randomized Phase II Clinical Trial of Sulforaphane in Former Smokers at High Risk for Lung Cancer", "authors": "Yuan JM, Kensler TW, Dacic S et al.", "journal": "Cancer prevention research (Philadelphia, Pa.)", "year": 2025, "pmid": "40041932", "url": "https://pubmed.ncbi.nlm.nih.gov/40041932/", "study_type": "RCT", "confidence": "verify", "doi": "10.1158/1940-6207.CAPR-24-0386", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40041932/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "sulforaphane" }, { "id": "09A45570-132F-4DE9-83E5-78E0873D7EEF", "name": "Nattokinase", "alternateNames": [ "NK", "Subtilisin NAT" ], "category": "Other", "subcategory": "Fibrinolytic Enzyme", "overview": "Enzyme from fermented soybeans (natto) with blood clot-dissolving properties.", "mechanismOfAction": "Serine protease that directly cleaves fibrin in blood clots. Also converts plasminogen to plasmin (endogenous fibrinolysis), degrades PAI-1, and mildly inhibits ACE for blood pressure support.", "commonBenefits": [ "Cardiovascular health", "Blood flow", "Clot prevention", "Blood pressure" ], "commonDosageRange": "2,000-4,000 FU daily", "recommendedForm": "Nattokinase (measured in fibrinolytic units, FU)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Take on empty stomach for systemic absorption; with food for GI benefit" }, "evidenceRating": "moderate", "foodSources": [ "Natto (Japanese fermented soybeans)" ], "deficiencySymptoms": [], "sideEffects": [ "Increased bleeding risk", "Bruising" ], "contraindications": [ "Blood thinners (warfarin, aspirin)", "Bleeding disorders", "Surgery (stop 2 weeks before)" ], "iconName": "waveform.path.ecg", "colorHex": "FFB84D", "tags": [ "cardiovascular", "blood-flow", "fibrinolytic" ], "sources": [ { "claim": "Cardiovascular risk factor reduction, systematic review and meta-analysis of RCTs", "title": "Nattokinase Supplementation and Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Gallelli G et al.", "journal": "Nutrients", "year": 2024, "pmid": "39076715", "url": "https://pubmed.ncbi.nlm.nih.gov/39076715/", "study_type": "meta-analysis", "key_finding": "Six RCTs (546 participants) showed nattokinase significantly reduced systolic BP by -3.45 mmHg and diastolic BP by -2.32 mmHg with no notable adverse events.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39076715/", "publicSourceType": "PMID" }, { "claim": "Blood pressure reduction, randomized controlled trial", "title": "Effects of nattokinase on blood pressure: a randomized, controlled trial", "authors": "Kim JY et al.", "journal": "Hypertens Res", "year": 2008, "pmid": "18971533", "url": "https://pubmed.ncbi.nlm.nih.gov/18971533/", "study_type": "RCT", "key_finding": "8-week nattokinase trial showed net reductions of -5.55 mmHg in systolic and -2.84 mmHg in diastolic blood pressure vs control.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18971533/", "publicSourceType": "PMID" }, { "claim": "Fibrinolytic effects, reduction in fibrinogen and clotting factors", "title": "Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects", "authors": "Hsia CH et al.", "journal": "Nutr Res", "year": 2009, "pmid": "19358933", "url": "https://pubmed.ncbi.nlm.nih.gov/19358933/", "study_type": "RCT", "key_finding": "After 2 months of nattokinase administration, fibrinogen decreased 9%, factor VII 14%, and factor VIII 17% in healthy subjects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19358933/", "publicSourceType": "PMID" }, { "claim": "Atherothrombotic prevention, long-term RCT", "title": "Nattokinase atherothrombotic prevention study: A randomized controlled trial", "authors": "Hodis HN et al.", "journal": "J Am Heart Assoc", "year": 2021, "pmid": "33843667", "url": "https://pubmed.ncbi.nlm.nih.gov/33843667/", "study_type": "RCT", "key_finding": "In 265 subjects over median 3 years, nattokinase 2,000 FU daily did not significantly differ from placebo in carotid intima-media thickness progression.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33843667/", "publicSourceType": "PMID" }, { "claim": "Atherosclerosis management with large sample clinical study", "title": "Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants", "authors": "Chen H et al.", "journal": "Front Cardiovasc Med", "year": 2022, "pmid": "36072877", "url": "https://pubmed.ncbi.nlm.nih.gov/36072877/", "study_type": "cohort", "key_finding": "Nattokinase was effective in managing atherosclerosis progression and hyperlipidemia in 1,062 participants.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36072877/", "publicSourceType": "PMID" }, { "claim": "Safety in vascular disease patients, real-world safety data", "title": "Data Recorded in Real Life Support the Safety of Nattokinase in Patients with Vascular Diseases", "authors": "Gallelli G et al.", "journal": "Nutrients", "year": 2021, "pmid": "34199189", "url": "https://pubmed.ncbi.nlm.nih.gov/34199189/", "study_type": "cohort", "key_finding": "Nattokinase improved clinical symptoms without adverse drug reactions or drug interactions in 153 patients with vascular diseases.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34199189/", "publicSourceType": "PMID" }, { "text": "Liu X, Zeng X, Mahe J et al.. The Effect of Nattokinase-Monascus Supplements on Dyslipidemia: A Four-Month Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Nutrients. 2023", "pmid": "37836525", "doi": "10.3390/nu15194239", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37836525/", "publicSourceType": "PMID" }, { "text": "Selvarajan E, Bhatnagar N. Nattokinase: an updated critical review on challenges and perspectives. Cardiovascular & hematological agents in medicinal chemistry. 2017", "pmid": "29219060", "doi": "10.2174/1871525716666171207153332", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29219060/", "publicSourceType": "PMID" }, { "claim": "Improves insulin resistance in prediabetic adults", "title": "Efficacy and Safety of Aronia, Red Ginseng, Shiitake Mushroom, and Nattokinase Mixture on Insulin Resistance in Prediabetic Adults: A Randomized, Double-Blinded, Placebo-Controlled Trial.", "authors": "Park S, Kim CJ, Ha KC, Baek HI, Yang HJ, Kim MJ et al.", "journal": "Foods (Basel)", "year": 2021, "pmid": "34359426", "url": "https://pubmed.ncbi.nlm.nih.gov/34359426/", "study_type": "rct", "key_finding": "A supplement mixture containing nattokinase significantly improved HOMA-IR (insulin resistance index) and glycemic markers in prediabetic adults compared to placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34359426/", "publicSourceType": "PMID" }, { "text": "Zhang K, Zhang X, Wang A et al.. Nattokinase supplementation for cognitive enhancement in asymptomatic intracranial/carotid stenosis: A randomized controlled trial. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association. 2026", "claim": "PubMed-indexed evidence involving Nattokinase", "title": "Nattokinase supplementation for cognitive enhancement in asymptomatic intracranial/carotid stenosis: A randomized controlled trial", "authors": "Zhang K, Zhang X, Wang A et al.", "journal": "Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association", "year": 2026, "pmid": "41325794", "url": "https://pubmed.ncbi.nlm.nih.gov/41325794/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.jstrokecerebrovasdis.2025.108511", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41325794/", "publicSourceType": "PMID" }, { "text": "Liu M, Xu Z, Wang Z et al.. Lipid-lowering, antihypertensive, and antithrombotic effects of nattokinase combined with red yeast rice in patients with stable coronary artery disease: a randomized, double-blinded, placebo-controlled trial. Frontiers in nutrition. 2024", "claim": "PubMed-indexed evidence involving Nattokinase", "title": "Lipid-lowering, antihypertensive, and antithrombotic effects of nattokinase combined with red yeast rice in patients with stable coronary artery disease: a randomized, double-blinded, placebo-controlled trial", "authors": "Liu M, Xu Z, Wang Z et al.", "journal": "Frontiers in nutrition", "year": 2024, "pmid": "38812930", "url": "https://pubmed.ncbi.nlm.nih.gov/38812930/", "study_type": "RCT", "confidence": "verify", "doi": "10.3389/fnut.2024.1380727", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38812930/", "publicSourceType": "PMID" }, { "text": "Nara N, Kurosawa Y, Fuse-Hamaoka S et al.. A single dose of oral nattokinase accelerates skin temperature recovery after cold water immersion: A double-blind, placebo-controlled crossover study. Heliyon. 2023", "claim": "PubMed-indexed evidence involving Nattokinase", "title": "A single dose of oral nattokinase accelerates skin temperature recovery after cold water immersion: A double-blind, placebo-controlled crossover study", "authors": "Nara N, Kurosawa Y, Fuse-Hamaoka S et al.", "journal": "Heliyon", "year": 2023, "pmid": "37483751", "url": "https://pubmed.ncbi.nlm.nih.gov/37483751/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.heliyon.2023.e17951", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37483751/", "publicSourceType": "PMID" }, { "text": "Cheng Y, Tong Y, Tao S et al.. Enhancing nattokinase stability through synergistic interactions:Construction and mechanism analysis of multi-level encapsulation structures in fig-like gel beads. Food research international (Ottawa, Ont.). 2026", "claim": "PubMed-indexed evidence involving Nattokinase", "title": "Enhancing nattokinase stability through synergistic interactions:Construction and mechanism analysis of multi-level encapsulation structures in fig-like gel beads", "authors": "Cheng Y, Tong Y, Tao S et al.", "journal": "Food research international (Ottawa, Ont.)", "year": 2026, "pmid": "42116475", "url": "https://pubmed.ncbi.nlm.nih.gov/42116475/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.foodres.2026.119216", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/42116475/", "publicSourceType": "PMID" }, { "text": "Granito M, Alvarenga L, Ribeiro M et al.. Nattokinase as an adjuvant therapeutic strategy for non-communicable diseases: a review of fibrinolytic, antithrombotic, anti-inflammatory, and antioxidant effects. Expert review of cardiovascular therapy. 2024", "claim": "PubMed-indexed evidence involving Nattokinase", "title": "Nattokinase as an adjuvant therapeutic strategy for non-communicable diseases: a review of fibrinolytic, antithrombotic, anti-inflammatory, and antioxidant effects", "authors": "Granito M, Alvarenga L, Ribeiro M et al.", "journal": "Expert review of cardiovascular therapy", "year": 2024, "pmid": "39404094", "url": "https://pubmed.ncbi.nlm.nih.gov/39404094/", "study_type": "review", "confidence": "verify", "doi": "10.1080/14779072.2024.2416663", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39404094/", "publicSourceType": "PMID" }, { "text": "Zhang F, Zhang J, Linhardt RJ. Interactions between nattokinase and heparin/GAGs. Glycoconjugate journal. 2015", "claim": "PubMed-indexed evidence involving Nattokinase", "title": "Interactions between nattokinase and heparin/GAGs", "authors": "Zhang F, Zhang J, Linhardt RJ", "journal": "Glycoconjugate journal", "year": 2015, "pmid": "26412225", "url": "https://pubmed.ncbi.nlm.nih.gov/26412225/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s10719-015-9620-8", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26412225/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "nattokinase" }, { "id": "435B6058-2833-43AC-B617-55ADD7F10FB3", "name": "Bromelain", "alternateNames": [ "Pineapple Enzyme" ], "category": "Other", "subcategory": "Proteolytic Enzyme", "overview": "Proteolytic enzyme from pineapple with anti-inflammatory and digestive benefits.", "mechanismOfAction": "Cysteine protease that breaks down proteins, reduces kinin and fibrin, and inhibits prostaglandin synthesis. Enhances absorption of other supplements, especially quercetin and curcumin.", "commonBenefits": [ "Anti-inflammatory", "Digestion", "Sinus relief", "Recovery from surgery/injury" ], "commonDosageRange": "500-1,000 mg daily (2,400 GDU/g)", "recommendedForm": "Enteric-coated for systemic effects; regular for digestion", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Empty stomach for anti-inflammatory effects; with food for digestion" }, "evidenceRating": "moderate", "foodSources": [ "Pineapple (stem has most)" ], "deficiencySymptoms": [], "sideEffects": [ "GI upset", "Diarrhea", "Allergic reactions", "Increased bleeding risk" ], "contraindications": [ "Blood thinners", "Pineapple/latex allergy", "Surgery" ], "iconName": "leaf.fill", "colorHex": "FFB84D", "tags": [ "anti-inflammatory", "digestion", "enzyme", "recovery" ], "sources": [ { "claim": "Efficacy and safety, systematic review and meta-analysis", "title": "Efficacy and safety of bromelain: A systematic review and meta-analysis", "authors": "Zeng Q et al.", "journal": "Complement Ther Med", "year": 2023, "pmid": "37157782", "url": "https://pubmed.ncbi.nlm.nih.gov/37157782/", "study_type": "meta-analysis", "key_finding": "Bromelain may be effective against sinusitis but was not effective for cardiovascular diseases; overall safety profile is favorable.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37157782/", "publicSourceType": "PMID" }, { "claim": "Anti-inflammatory effects, systematic review of clinical trials", "title": "Bromelain supplementation and inflammatory markers: A systematic review of clinical trials", "authors": "Rocha MRS et al.", "journal": "Clin Nutr ESPEN", "year": 2023, "pmid": "37202035", "url": "https://pubmed.ncbi.nlm.nih.gov/37202035/", "study_type": "review", "key_finding": "Seven RCTs showed bromelain reduced inflammatory parameters in most studies, though effect was inconsistent due to population heterogeneity and dose variation.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37202035/", "publicSourceType": "PMID" }, { "claim": "Post-surgical recovery, meta-analysis for third molar surgery", "title": "Efficacy of proteolytic enzyme bromelain on health outcomes after third molar surgery. Systematic review and meta-analysis of randomized clinical trials", "authors": "de Souza GM et al.", "journal": "J Dent", "year": 2019, "pmid": "30573710", "url": "https://pubmed.ncbi.nlm.nih.gov/30573710/", "study_type": "meta-analysis", "key_finding": "Bromelain has a beneficial effect in reducing pain after third molar surgery and positive impact on patient quality of life.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30573710/", "publicSourceType": "PMID" }, { "claim": "Sinus relief, pilot study in chronic rhinosinusitis", "title": "Efficacy and tolerability of bromelain in patients with chronic rhinosinusitis--a pilot study", "authors": "Helms S et al.", "journal": "Altern Ther Health Med", "year": 2013, "pmid": "24273953", "url": "https://pubmed.ncbi.nlm.nih.gov/24273953/", "study_type": "RCT", "key_finding": "Bromelain improved symptom scores and quality of life in chronic rhinosinusitis, more effective in cases without nasal polyps.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24273953/", "publicSourceType": "PMID" }, { "claim": "Comprehensive pharmacological review of mechanisms and applications", "title": "Properties and therapeutic application of bromelain: a review", "authors": "Pavan R et al.", "journal": "Biotechnol Res Int", "year": 2012, "pmid": "23304525", "url": "https://pubmed.ncbi.nlm.nih.gov/23304525/", "study_type": "review", "key_finding": "Bromelain is absorbable without losing proteolytic activity; treats sinusitis, surgical trauma, thrombophlebitis; enhances absorption of antibiotics and other drugs.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23304525/", "publicSourceType": "PMID" }, { "claim": "Bromelain mechanisms, comprehensive pharmacological review", "title": "Bromelain: a review of its mechanisms, pharmacological effects and potential applications", "authors": "Hikisz P et al.", "journal": "Food Funct", "year": 2023, "pmid": "37650738", "url": "https://pubmed.ncbi.nlm.nih.gov/37650738/", "study_type": "review", "key_finding": "Bromelain is a cysteine protease that reduces kinin and fibrin, inhibits prostaglandin synthesis, and has anti-inflammatory, anti-edematous, and fibrinolytic activities.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37650738/", "publicSourceType": "PMID" }, { "text": "Colletti A, Procchio C, Pisano M et al.. An Evaluation of the Effects of Pineapple-Extract and Bromelain-Based Treatment after Mandibular Third Molar Surgery: A Randomized Three-Arm Clinical Study. Nutrients. 2024", "pmid": "38542694", "doi": "10.3390/nu16060784", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38542694/", "publicSourceType": "PMID" }, { "text": "Tacias-Pascacio VG, Castañeda-Valbuena D, Tavano O et al.. A review on the immobilization of bromelain. International journal of biological macromolecules. 2024", "pmid": "38878936", "doi": "10.1016/j.ijbiomac.2024.133089", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38878936/", "publicSourceType": "PMID" }, { "claim": "Reduces postoperative sequelae when combined with other enzymes", "title": "Comparison of Efficacy of Combination of Bromelain, Rutocide, and Trypsin With Serratiopeptidase on Postoperative Sequelae Following Mandibular Third Molar Surgery: A Randomized Clinical Trial.", "authors": "Bhuvan Chandra R, Selvarasu K, Krishnan M", "journal": "Cureus", "year": 2023, "pmid": "38090449", "url": "https://pubmed.ncbi.nlm.nih.gov/38090449/", "study_type": "rct", "key_finding": "Bromelain-rutoside-trypsin combination showed comparable efficacy to serratiopeptidase in reducing postoperative swelling, pain, and trismus following mandibular third molar surgery.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38090449/", "publicSourceType": "PMID" }, { "text": "Pereira IC, Pedrosa-Santos ÁMC, Martins JA et al.. Bromelain and liver health: A comprehensive systematic review of preclinical studies. Clinical nutrition ESPEN. 2025", "claim": "PubMed-indexed evidence involving Bromelain", "title": "Bromelain and liver health: A comprehensive systematic review of preclinical studies", "authors": "Pereira IC, Pedrosa-Santos ÁMC, Martins JA et al.", "journal": "Clinical nutrition ESPEN", "year": 2025, "pmid": "39947465", "url": "https://pubmed.ncbi.nlm.nih.gov/39947465/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.clnesp.2025.02.001", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39947465/", "publicSourceType": "PMID" }, { "text": "Pereira IC, Passos RB, Viana CMC et al.. Supplementation Containing Bromelain on the Side Effects of Oncological Treatment: Systematic Review. Journal of medicinal food. 2025", "claim": "PubMed-indexed evidence involving Bromelain", "title": "Supplementation Containing Bromelain on the Side Effects of Oncological Treatment: Systematic Review", "authors": "Pereira IC, Passos RB, Viana CMC et al.", "journal": "Journal of medicinal food", "year": 2025, "pmid": "40372963", "url": "https://pubmed.ncbi.nlm.nih.gov/40372963/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1089/jmf.2023.0027", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40372963/", "publicSourceType": "PMID" }, { "text": "Mohammed JS, Ahmed AT, Singh M et al.. Evaluating the role of bromelain in diabetes management: a systematic review of research evidence and mechanisms of action. The Journal of pharmacy and pharmacology. 2025", "claim": "PubMed-indexed evidence involving Bromelain", "title": "Evaluating the role of bromelain in diabetes management: a systematic review of research evidence and mechanisms of action", "authors": "Mohammed JS, Ahmed AT, Singh M et al.", "journal": "The Journal of pharmacy and pharmacology", "year": 2025, "pmid": "40440445", "url": "https://pubmed.ncbi.nlm.nih.gov/40440445/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/jpp/rgaf021", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40440445/", "publicSourceType": "PMID" }, { "text": "Shekhar A, Maddheshiya N, Adit et al.. Anti-inflammatory Role of Trypsin, Rutoside, and Bromelain Combination in Temporomandibular Joint Osteoarthritis: A Systematic Review. Cureus. 2024", "claim": "PubMed-indexed evidence involving Bromelain", "title": "Anti-inflammatory Role of Trypsin, Rutoside, and Bromelain Combination in Temporomandibular Joint Osteoarthritis: A Systematic Review", "authors": "Shekhar A, Maddheshiya N, Adit et al.", "journal": "Cureus", "year": 2024, "pmid": "38322061", "url": "https://pubmed.ncbi.nlm.nih.gov/38322061/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7759/cureus.51749", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38322061/", "publicSourceType": "PMID" }, { "text": "Liu S, Zhao H, Wang Y et al.. Oral Bromelain for the Control of Facial Swelling, Trismus, and Pain After Mandibular Third Molar Surgery: A Systematic Review and Meta-Analysis. Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. 2019", "claim": "PubMed-indexed evidence involving Bromelain", "title": "Oral Bromelain for the Control of Facial Swelling, Trismus, and Pain After Mandibular Third Molar Surgery: A Systematic Review and Meta-Analysis", "authors": "Liu S, Zhao H, Wang Y et al.", "journal": "Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons", "year": 2019, "pmid": "30986376", "url": "https://pubmed.ncbi.nlm.nih.gov/30986376/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.joms.2019.02.044", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30986376/", "publicSourceType": "PMID" }, { "text": "Ho D, Jagdeo J, Waldorf HA. Is There a Role for Arnica and Bromelain in Prevention of Post-Procedure Ecchymosis or Edema? A Systematic Review of the Literature. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]. 2016", "claim": "PubMed-indexed evidence involving Bromelain", "title": "Is There a Role for Arnica and Bromelain in Prevention of Post-Procedure Ecchymosis or Edema? A Systematic Review of the Literature", "authors": "Ho D, Jagdeo J, Waldorf HA", "journal": "Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]", "year": 2016, "pmid": "27035499", "url": "https://pubmed.ncbi.nlm.nih.gov/27035499/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/DSS.0000000000000701", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27035499/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "bromelain" }, { "id": "5BE922DE-CCC0-41A3-B438-651CE60C7603", "name": "Lutein", "alternateNames": [ "Lutein", "Xanthophyll" ], "category": "Other", "subcategory": "Carotenoid", "overview": "Macular carotenoid essential for eye health and blue light protection.", "mechanismOfAction": "Accumulates in the macula lutea of the retina, filtering harmful blue light (400-500nm) and quenching singlet oxygen/free radicals. Also found in brain tissue supporting cognitive function.", "commonBenefits": [ "Eye health", "Macular degeneration prevention", "Blue light protection", "Cognitive function" ], "commonDosageRange": "10-20 mg daily", "recommendedForm": "FloraGLO Lutein (from marigold flowers)", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with fat-containing meal for absorption" }, "evidenceRating": "strong", "foodSources": [ "Kale", "Spinach", "Egg yolks", "Corn", "Marigold flowers" ], "deficiencySymptoms": [ "Macular degeneration", "Poor night vision" ], "sideEffects": [ "Very well tolerated", "Carotenodermia (harmless skin yellowing)" ], "contraindications": [ "Generally very safe" ], "iconName": "eye.fill", "colorHex": "FFB84D", "tags": [ "eye-health", "vision", "carotenoid", "brain" ], "sources": [ { "claim": "AREDS2 trial, lutein/zeaxanthin for age-related macular degeneration", "title": "Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial", "authors": "Age-Related Eye Disease Study 2 Research Group", "journal": "JAMA", "year": 2013, "pmid": "23644932", "url": "https://pubmed.ncbi.nlm.nih.gov/23644932/", "study_type": "RCT", "key_finding": "Lutein/zeaxanthin did not further reduce AMD progression in primary analysis, but is an appropriate carotenoid substitute for beta-carotene (which increased lung cancer risk in smokers).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23644932/", "publicSourceType": "PMID" }, { "claim": "AREDS2 long-term follow-up, lutein/zeaxanthin as beta-carotene replacement", "title": "Long-term Outcomes of Adding Lutein/Zeaxanthin and omega-3 Fatty Acids to the AREDS Supplements on Age-Related Macular Degeneration Progression: AREDS2 Report 28", "authors": "Chew EY et al.", "journal": "JAMA Ophthalmol", "year": 2022, "pmid": "35653117", "url": "https://pubmed.ncbi.nlm.nih.gov/35653117/", "study_type": "RCT", "key_finding": "Long-term epidemiologic follow-up confirmed lutein/zeaxanthin was an appropriate and safer replacement for beta-carotene in AREDS2 supplements.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35653117/", "publicSourceType": "PMID" }, { "claim": "Meta-analysis of lutein/zeaxanthin intake and AMD risk", "title": "Lutein and zeaxanthin intake and the risk of age-related macular degeneration: a systematic review and meta-analysis", "authors": "Ma L et al.", "journal": "Br J Nutr", "year": 2012, "pmid": "21899805", "url": "https://pubmed.ncbi.nlm.nih.gov/21899805/", "study_type": "meta-analysis", "key_finding": "Dietary lutein/zeaxanthin intake was significantly associated with reduced risk of late AMD (RR 0.74) and neovascular AMD (RR 0.68).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21899805/", "publicSourceType": "PMID" }, { "claim": "Cognitive function, meta-analysis of RCTs on dietary lutein", "title": "Dietary Lutein and Cognitive Function in Adults: A Meta-Analysis of Randomized Controlled Trials", "authors": "Nouchi R et al.", "journal": "Nutrients", "year": 2021, "pmid": "34641336", "url": "https://pubmed.ncbi.nlm.nih.gov/34641336/", "study_type": "meta-analysis", "key_finding": "Lutein was associated with slight improvements in complex attention, executive function, and memory; may prevent cognitive decline, especially in executive function.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34641336/", "publicSourceType": "PMID" }, { "claim": "Brain health, systematic review of RCTs and cohort studies in older adults", "title": "Lutein Has a Positive Impact on Brain Health in Healthy Older Adults: A Systematic Review of Randomized Controlled Trials and Cohort Studies", "authors": "Nouchi R et al.", "journal": "Nutrients", "year": 2021, "pmid": "34063827", "url": "https://pubmed.ncbi.nlm.nih.gov/34063827/", "study_type": "review", "key_finding": "10 mg lutein over 12 months had positive impact on brain activities during learning and resting-state connectivity in healthy older adults.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34063827/", "publicSourceType": "PMID" }, { "claim": "Macular pigment optical density improvement, meta-analysis", "title": "Lutein, Zeaxanthin and Meso-zeaxanthin Supplementation Associated with Macular Pigment Optical Density", "authors": "Liu R et al.", "journal": "Nutrients", "year": 2016, "pmid": "27420092", "url": "https://pubmed.ncbi.nlm.nih.gov/27420092/", "study_type": "meta-analysis", "key_finding": "Xanthophyll supplementation significantly increased MPOD in both AMD patients (WMD 0.07) and healthy subjects (WMD 0.09).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27420092/", "publicSourceType": "PMID" }, { "text": "Parekh R, Hammond BR Jr, Chandradhara D. Lutein and Zeaxanthin Supplementation Improves Dynamic Visual and Cognitive Performance in Children: A Randomized, Double-Blind, Parallel, Placebo-Controlled Study. Advances in therapy. 2024", "pmid": "38363462", "doi": "10.1007/s12325-024-02785-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38363462/", "publicSourceType": "PMID" }, { "text": "Li LH, Lee JC, Leung HH et al.. Lutein Supplementation for Eye Diseases. Nutrients. 2020", "pmid": "32526861", "doi": "10.3390/nu12061721", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32526861/", "publicSourceType": "PMID" }, { "claim": "Improves outcomes in age-related macular degeneration", "title": "Effects of lutein supplementation in age-related macular degeneration.", "authors": "Feng L, Nie K, Jiang H, Fan W", "journal": "PLoS One", "year": 2019, "pmid": "31887124", "url": "https://pubmed.ncbi.nlm.nih.gov/31887124/", "study_type": "meta-analysis", "key_finding": "Lutein supplementation significantly improved visual acuity and macular pigment optical density in patients with age-related macular degeneration.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31887124/", "publicSourceType": "PMID" }, { "claim": "Reduces retinopathy of prematurity", "title": "Lutein supplementation and retinopathy of prematurity: a meta-analysis.", "authors": "Cota F, Costa S, Giannantonio C, Purcaro V, Catenazzi P, Vento G", "journal": "Journal of Maternal-Fetal & Neonatal Medicine", "year": 2022, "pmid": "32041442", "url": "https://pubmed.ncbi.nlm.nih.gov/32041442/", "study_type": "meta-analysis", "key_finding": "Lutein supplementation in preterm infants was associated with a significant reduction in the incidence of retinopathy of prematurity.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32041442/", "publicSourceType": "PMID" }, { "claim": "Improves lipid profile", "title": "The effect of lutein and Zeaxanthine on dyslipidemia: A meta-analysis study.", "authors": "Ghasemi F, Navab F, Rouhani MH, Amini P, Shokri-Mashhadi N", "journal": "Prostaglandins & Other Lipid Mediators", "year": 2023, "pmid": "36336325", "url": "https://pubmed.ncbi.nlm.nih.gov/36336325/", "study_type": "meta-analysis", "key_finding": "Lutein and zeaxanthin supplementation significantly improved lipid profiles, reducing triglycerides and total cholesterol while increasing HDL cholesterol.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36336325/", "publicSourceType": "PMID" }, { "text": "Firozjae AA, Shiran MR, Rashidi M. The neuropharmacological and clinical effects of lutein: a systematic review. Hormone molecular biology and clinical investigation. 2025", "claim": "PubMed-indexed evidence involving Lutein", "title": "The neuropharmacological and clinical effects of lutein: a systematic review", "authors": "Firozjae AA, Shiran MR, Rashidi M", "journal": "Hormone molecular biology and clinical investigation", "year": 2025, "pmid": "39436867", "url": "https://pubmed.ncbi.nlm.nih.gov/39436867/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1515/hmbci-2024-0053", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39436867/", "publicSourceType": "PMID" }, { "text": "Ponce-García V, Bautista-Llamas MJ, García-Romera MC. \"Analysis of Macular Pigment Optical Density in Childhood: A Systematic Review\". Seminars in ophthalmology. 2024", "claim": "PubMed-indexed evidence involving Lutein", "title": "\"Analysis of Macular Pigment Optical Density in Childhood: A Systematic Review\"", "authors": "Ponce-García V, Bautista-Llamas MJ, García-Romera MC", "journal": "Seminars in ophthalmology", "year": 2024, "pmid": "38717910", "url": "https://pubmed.ncbi.nlm.nih.gov/38717910/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/08820538.2024.2346750", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38717910/", "publicSourceType": "PMID" }, { "text": "Chu YC, Huang CC. Role of Lutein Supplements in the Management of Dry Eye Syndrome: A Systematic Review. International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition. 2024", "claim": "PubMed-indexed evidence involving Lutein", "title": "Role of Lutein Supplements in the Management of Dry Eye Syndrome: A Systematic Review", "authors": "Chu YC, Huang CC", "journal": "International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition", "year": 2024, "pmid": "40134251", "url": "https://pubmed.ncbi.nlm.nih.gov/40134251/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.31083/IJVNR36626", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40134251/", "publicSourceType": "PMID" }, { "text": "García-Romera MC, Silva-Viguera MC, López-Izquierdo I et al.. Effect of macular pigment carotenoids on cognitive functions: A systematic review. Physiology & behavior. 2022", "claim": "PubMed-indexed evidence involving Lutein", "title": "Effect of macular pigment carotenoids on cognitive functions: A systematic review", "authors": "García-Romera MC, Silva-Viguera MC, López-Izquierdo I et al.", "journal": "Physiology & behavior", "year": 2022, "pmid": "35752349", "url": "https://pubmed.ncbi.nlm.nih.gov/35752349/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.physbeh.2022.113891", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35752349/", "publicSourceType": "PMID" }, { "text": "Alharbi AM, Kilani MA, Berendschot TT. Overflow phenomenon in serum lutein after supplementation: a systematic review supported with SNPs analyses. International journal of ophthalmology. 2021", "claim": "PubMed-indexed evidence involving Lutein", "title": "Overflow phenomenon in serum lutein after supplementation: a systematic review supported with SNPs analyses", "authors": "Alharbi AM, Kilani MA, Berendschot TT", "journal": "International journal of ophthalmology", "year": 2021, "pmid": "34282399", "url": "https://pubmed.ncbi.nlm.nih.gov/34282399/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.18240/ijo.2021.07.22", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34282399/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "lutein" }, { "id": "6E8ECE98-5F7A-480A-B711-6C601F71B473", "name": "Zeaxanthin", "alternateNames": [ "Zeaxanthin", "Meso-Zeaxanthin" ], "category": "Other", "subcategory": "Carotenoid", "overview": "Partner carotenoid to lutein for comprehensive macular protection.", "mechanismOfAction": "Concentrated in the central fovea (lutein is more peripheral). Provides the most critical blue light filtration at the point of highest visual acuity. Potent singlet oxygen quencher.", "commonBenefits": [ "Eye health", "Central vision protection", "Blue light filtration" ], "commonDosageRange": "2-4 mg daily (often combined with lutein)", "recommendedForm": "Often paired with lutein in 5:1 ratio (lutein:zeaxanthin)", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with fat; usually combined with lutein supplement" }, "evidenceRating": "strong", "foodSources": [ "Goji berries", "Egg yolks", "Corn", "Orange peppers" ], "deficiencySymptoms": [ "Same as lutein" ], "sideEffects": [ "Very well tolerated" ], "contraindications": [ "Generally very safe" ], "iconName": "eye.circle.fill", "colorHex": "FFB84D", "tags": [ "eye-health", "vision", "carotenoid" ], "sources": [ { "claim": "AREDS2 trial, zeaxanthin (with lutein) for macular degeneration", "title": "Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial", "authors": "Age-Related Eye Disease Study 2 Research Group", "journal": "JAMA", "year": 2013, "pmid": "23644932", "url": "https://pubmed.ncbi.nlm.nih.gov/23644932/", "study_type": "RCT", "key_finding": "Lutein/zeaxanthin is an appropriate carotenoid substitute for beta-carotene in AREDS supplements with a better safety profile (no lung cancer risk).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23644932/", "publicSourceType": "PMID" }, { "claim": "Systematic review of lutein/zeaxanthin effect on macular pigment optical density", "title": "The Effect of Lutein/Zeaxanthin Intake on Human Macular Pigment Optical Density: A Systematic Review and Meta-Analysis", "authors": "Yao L et al.", "journal": "Nutrients", "year": 2021, "pmid": "34157098", "url": "https://pubmed.ncbi.nlm.nih.gov/34157098/", "study_type": "meta-analysis", "key_finding": "MPOD increased dose-dependently: 0.04 units at 5-20 mg/day and 0.11 units at 20+ mg/day; no significant change below 5 mg/day.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34157098/", "publicSourceType": "PMID" }, { "claim": "Zeaxanthin and Visual Function Study in atrophic AMD", "title": "Randomized, double-blind, placebo-controlled study of zeaxanthin and visual function in patients with atrophic age-related macular degeneration: the Zeaxanthin and Visual Function Study (ZVF) FDA IND #78, 973", "authors": "Richer SP et al.", "journal": "Optometry", "year": 2011, "pmid": "22027699", "url": "https://pubmed.ncbi.nlm.nih.gov/22027699/", "study_type": "RCT", "key_finding": "Zeaxanthin supplementation improved visual function in patients with atrophic age-related macular degeneration.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22027699/", "publicSourceType": "PMID" }, { "claim": "Macular pigment response to supplementation in glaucoma", "title": "Macular Pigment Response to Lutein, Zeaxanthin, and Meso-zeaxanthin Supplementation in Open-Angle Glaucoma: A Randomized Controlled Trial", "authors": "Siah WF et al.", "journal": "Ophthalmol Sci", "year": 2022, "pmid": "36247822", "url": "https://pubmed.ncbi.nlm.nih.gov/36247822/", "study_type": "RCT", "key_finding": "Macular pigment can be augmented in glaucomatous eyes by supplementation with lutein, zeaxanthin, and meso-zeaxanthin.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36247822/", "publicSourceType": "PMID" }, { "claim": "Blue light protection and visual function improvement with screen time", "title": "Beneficial Effects of a Lutein-Zeaxanthin Complex on Macular Pigment Optical Density Levels of Healthy Individuals With Prolonged Screen Time", "authors": "Faria PM et al.", "journal": "Nutrients", "year": 2025, "pmid": "40135032", "url": "https://pubmed.ncbi.nlm.nih.gov/40135032/", "study_type": "RCT", "key_finding": "Lutein-zeaxanthin supplementation significantly improved MPOD, contrast sensitivity, and sleep quality in healthy subjects with prolonged screen time.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40135032/", "publicSourceType": "PMID" }, { "text": "Lopresti AL, Smith SJ. The effects of lutein/ zeaxanthin (Lute-gen(®)) on eye health, eye strain, sleep quality, and attention in high electronic screen users: a randomized, double-blind, placebo-controlled study. Frontiers in nutrition. 2025", "pmid": "39963662", "doi": "10.3389/fnut.2025.1522302", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39963662/", "publicSourceType": "PMID" }, { "text": "Parekh R, Hammond BR Jr, Chandradhara D. Lutein and Zeaxanthin Supplementation Improves Dynamic Visual and Cognitive Performance in Children: A Randomized, Double-Blind, Parallel, Placebo-Controlled Study. Advances in therapy. 2024", "pmid": "38363462", "doi": "10.1007/s12325-024-02785-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38363462/", "publicSourceType": "PMID" }, { "claim": "Improves lipid profile (with lutein)", "title": "The effect of lutein and Zeaxanthine on dyslipidemia: A meta-analysis study.", "authors": "Ghasemi F, Navab F, Rouhani MH, Amini P, Shokri-Mashhadi N", "journal": "Prostaglandins & Other Lipid Mediators", "year": 2023, "pmid": "36336325", "url": "https://pubmed.ncbi.nlm.nih.gov/36336325/", "study_type": "meta-analysis", "key_finding": "Zeaxanthin and lutein supplementation significantly improved lipid profiles, reducing triglycerides and total cholesterol while increasing HDL cholesterol.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36336325/", "publicSourceType": "PMID" }, { "claim": "Reduces inflammation as part of carotenoid supplementation", "title": "Carotenoids supplementation and inflammation: a systematic review and meta-analysis of randomized clinical trials.", "authors": "Hajizadeh-Sharafabad F, Zahabi ES, Malekahmadi M, Zarrin R, Alizadeh M", "journal": "Critical Reviews in Food Science and Nutrition", "year": 2022, "pmid": "33998846", "url": "https://pubmed.ncbi.nlm.nih.gov/33998846/", "study_type": "meta-analysis", "key_finding": "Carotenoid supplementation (including lutein, zeaxanthin, lycopene, and beta-carotene) significantly reduced inflammatory markers including CRP, IL-6, and TNF-alpha.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33998846/", "publicSourceType": "PMID" }, { "text": "Choe BS, C A, Mk P et al.. Enhanced Oral Bioavailability of Lutein and Zeaxanthin via a Self-Emulsifying Delivery System: A Randomized, Double-Blind Cross-Over Study. Journal of medicinal food. 2025", "claim": "PubMed-indexed evidence involving Zeaxanthin", "title": "Enhanced Oral Bioavailability of Lutein and Zeaxanthin via a Self-Emulsifying Delivery System: A Randomized, Double-Blind Cross-Over Study", "authors": "Choe BS, C A, Mk P et al.", "journal": "Journal of medicinal food", "year": 2025, "pmid": "40601523", "url": "https://pubmed.ncbi.nlm.nih.gov/40601523/", "study_type": "RCT", "confidence": "verify", "doi": "10.1089/jmf.2025.k.0060", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40601523/", "publicSourceType": "PMID" }, { "text": "Wang L, Ma M, Li Y et al.. Effect of supplementation with lutein, zeaxanthin, and omega-3 fatty acids on macular pigment and visual function in young adults with long-term use of digital devices: study protocol for a randomized double-blind placebo-controlled study. Frontiers in nutrition. 2024", "claim": "PubMed-indexed evidence involving Zeaxanthin", "title": "Effect of supplementation with lutein, zeaxanthin, and omega-3 fatty acids on macular pigment and visual function in young adults with long-term use of digital devices: study protocol for a randomized double-blind placebo-controlled study", "authors": "Wang L, Ma M, Li Y et al.", "journal": "Frontiers in nutrition", "year": 2024, "pmid": "39494312", "url": "https://pubmed.ncbi.nlm.nih.gov/39494312/", "study_type": "RCT", "confidence": "verify", "doi": "10.3389/fnut.2024.1422468", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39494312/", "publicSourceType": "PMID" }, { "text": "Goh KM, Tan ESS, Lim CSY et al.. Effect of Dietary Supplementation with Lutein, Zeaxanthin, and Elderberries on Dry Eye Disease (DED) and Immunity: A Randomized Controlled Trial. Nutrients. 2024", "claim": "PubMed-indexed evidence involving Zeaxanthin", "title": "Effect of Dietary Supplementation with Lutein, Zeaxanthin, and Elderberries on Dry Eye Disease (DED) and Immunity: A Randomized Controlled Trial", "authors": "Goh KM, Tan ESS, Lim CSY et al.", "journal": "Nutrients", "year": 2024, "pmid": "39770987", "url": "https://pubmed.ncbi.nlm.nih.gov/39770987/", "study_type": "RCT", "confidence": "verify", "doi": "10.3390/nu16244366", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39770987/", "publicSourceType": "PMID" }, { "text": "Kumar P, Banik SP, Ohia SE et al.. Current Insights on the Photoprotective Mechanism of the Macular Carotenoids, Lutein and Zeaxanthin: Safety, Efficacy and Bio-Delivery. Journal of the American Nutrition Association. 2024", "claim": "PubMed-indexed evidence involving Zeaxanthin", "title": "Current Insights on the Photoprotective Mechanism of the Macular Carotenoids, Lutein and Zeaxanthin: Safety, Efficacy and Bio-Delivery", "authors": "Kumar P, Banik SP, Ohia SE et al.", "journal": "Journal of the American Nutrition Association", "year": 2024, "pmid": "38393321", "url": "https://pubmed.ncbi.nlm.nih.gov/38393321/", "study_type": "review", "confidence": "verify", "doi": "10.1080/27697061.2024.2319090", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38393321/", "publicSourceType": "PMID" }, { "text": "Keenan TDL, Agrón E, Keane PA et al.. Oral Antioxidant and Lutein/Zeaxanthin Supplements Slow Geographic Atrophy Progression to the Fovea in Age-Related Macular Degeneration. Ophthalmology. 2025", "claim": "PubMed-indexed evidence involving Zeaxanthin", "title": "Oral Antioxidant and Lutein/Zeaxanthin Supplements Slow Geographic Atrophy Progression to the Fovea in Age-Related Macular Degeneration", "authors": "Keenan TDL, Agrón E, Keane PA et al.", "journal": "Ophthalmology", "year": 2025, "pmid": "39025435", "url": "https://pubmed.ncbi.nlm.nih.gov/39025435/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.ophtha.2024.07.014", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39025435/", "publicSourceType": "PMID" }, { "text": "Choo YM, Yip KX, Fiander M et al.. Lutein and zeaxanthin for reducing morbidity and mortality in preterm infants. The Cochrane database of systematic reviews. 2025", "claim": "PubMed-indexed evidence involving Zeaxanthin", "title": "Lutein and zeaxanthin for reducing morbidity and mortality in preterm infants", "authors": "Choo YM, Yip KX, Fiander M et al.", "journal": "The Cochrane database of systematic reviews", "year": 2025, "pmid": "40292760", "url": "https://pubmed.ncbi.nlm.nih.gov/40292760/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/14651858.CD012178.pub2", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40292760/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "zeaxanthin" }, { "id": "0B70BF6D-FFA2-4795-BA90-A0D69238B05C", "name": "SAMe", "alternateNames": [ "S-Adenosyl-L-Methionine" ], "category": "Other", "subcategory": "Methyl Donor", "overview": "Universal methyl donor involved in over 100 methylation reactions in the body.", "mechanismOfAction": "Donates methyl groups for DNA methylation, neurotransmitter synthesis (dopamine, serotonin, norepinephrine), phospholipid metabolism, and glutathione production.", "commonBenefits": [ "Mood support", "Joint health", "Liver health", "Methylation support" ], "commonDosageRange": "400-1,600 mg daily", "recommendedForm": "Enteric-coated SAMe (unstable, quality matters)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Take on empty stomach; enteric coating essential; refrigerate" }, "evidenceRating": "strong", "foodSources": [ "Made endogenously from methionine + ATP" ], "deficiencySymptoms": [], "sideEffects": [ "GI upset", "Anxiety", "Insomnia", "Mania or hypomania, especially in bipolar disorder", "Serotonin syndrome risk when combined with serotonergic agents" ], "contraindications": [ "Bipolar disorder", "SSRIs, SNRIs, MAOIs, St. John's Wort, 5-HTP, L-Tryptophan, or other serotonergic agents unless closely clinician-supervised", "Parkinson's medications" ], "iconName": "brain.head.profile.fill", "colorHex": "FFB84D", "tags": [ "mood", "methylation", "liver", "joints" ], "sources": [ { "claim": "Efficacy for depression, systematic review and meta-analysis", "title": "Efficacy and acceptability of S-adenosyl-L-methionine (SAMe) for depressed patients: A systematic review and meta-analysis", "authors": "Li Q et al.", "journal": "J Affect Disord", "year": 2024, "pmid": "38423354", "url": "https://pubmed.ncbi.nlm.nih.gov/38423354/", "study_type": "meta-analysis", "key_finding": "23 trials (N=2183) assessed SAMe for depression as monotherapy, adjunctive, and comparator; evidence shows promising but mixed efficacy.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38423354/", "publicSourceType": "PMID" }, { "claim": "SAMe as adjuvant therapy for depression, updated meta-analysis", "title": "S-Adenosylmethionine (SAMe) as an adjuvant therapy for patients with depression: An updated systematic review and meta-analysis", "authors": "Lin YT et al.", "journal": "J Psychiatr Res", "year": 2024, "pmid": "38199136", "url": "https://pubmed.ncbi.nlm.nih.gov/38199136/", "study_type": "meta-analysis", "key_finding": "14 trials (1,522 subjects): no significant difference in depression with SAMe vs comparison when used as monotherapy or adjunctive therapy.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38199136/", "publicSourceType": "PMID" }, { "claim": "Osteoarthritis relief, Cochrane systematic review", "title": "S-Adenosylmethionine for osteoarthritis of the knee or hip", "authors": "Rutjes AW et al.", "journal": "Cochrane Database Syst Rev", "year": 2009, "pmid": "19821403", "url": "https://pubmed.ncbi.nlm.nih.gov/19821403/", "study_type": "meta-analysis", "key_finding": "Four trials (656 patients) showed small standardized mean difference of -0.17 for pain; inconclusive due to small trial size and quality issues.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19821403/", "publicSourceType": "PMID" }, { "claim": "Liver health, systematic review and meta-analysis", "title": "S-adenosyl-L-methionine for the treatment of chronic liver disease: a systematic review and meta-analysis", "authors": "Guo T et al.", "journal": "PLoS One", "year": 2015, "pmid": "25774783", "url": "https://pubmed.ncbi.nlm.nih.gov/25774783/", "study_type": "meta-analysis", "key_finding": "SAMe significantly improved total bilirubin and AST levels in chronic liver disease with few adverse events (primarily mild GI complaints).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25774783/", "publicSourceType": "PMID" }, { "claim": "SAMe for liver health, recent comprehensive systematic review", "title": "S-Adenosylmethionine (SAMe) for Liver Health: A Systematic Review", "authors": "Ahmed S et al.", "journal": "Cureus", "year": 2024, "pmid": "39519500", "url": "https://pubmed.ncbi.nlm.nih.gov/39519500/", "study_type": "review", "key_finding": "SAMe (commonly 1000-1200 mg/day) was effective for liver function improvement with favorable safety profile; no serious adverse events reported.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39519500/", "publicSourceType": "PMID" }, { "claim": "Neuropsychiatric applications, clinician-oriented review", "title": "S-Adenosylmethionine (SAMe) for Neuropsychiatric Disorders: A Clinician-Oriented Review of Research", "authors": "Sharma A et al.", "journal": "J Clin Psychiatry", "year": 2017, "pmid": "28682528", "url": "https://pubmed.ncbi.nlm.nih.gov/28682528/", "study_type": "review", "key_finding": "SAMe shows promise for major depressive disorder with limited evidence as monotherapy and augmentation; involved in methylation for neurotransmitter synthesis.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28682528/", "publicSourceType": "PMID" }, { "claim": "Effective for intrahepatic cholestasis of pregnancy", "title": "Pharmacological interventions for treating intrahepatic cholestasis of pregnancy.", "authors": "Walker KF, Chappell LC, Hague WM, Middleton P, Thornton JG", "journal": "Cochrane Database of Systematic Reviews", "year": 2020, "pmid": "32716060", "url": "https://pubmed.ncbi.nlm.nih.gov/32716060/", "study_type": "meta-analysis", "key_finding": "SAMe was among the pharmacological interventions evaluated; it reduced pruritus and liver enzymes in intrahepatic cholestasis of pregnancy, though UDCA showed more consistent benefits.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32716060/", "publicSourceType": "PMID" }, { "claim": "Influences DNA methylation through one-carbon metabolism", "title": "Influence of nutrients involved in one-carbon metabolism on DNA methylation in adults-a systematic review and meta-analysis.", "authors": "Amenyah SD, Hughes CF, Ward M, Rosborough S, Deane J, Thursby SJ et al.", "journal": "Nutrition Reviews", "year": 2020, "pmid": "31977026", "url": "https://pubmed.ncbi.nlm.nih.gov/31977026/", "study_type": "meta-analysis", "key_finding": "Nutrients involved in one-carbon metabolism, including SAMe pathway components (folate, B12, betaine), significantly influenced global DNA methylation status in adults.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31977026/", "publicSourceType": "PMID" }, { "text": "Baden KER, McClain H, Craig E et al.. S-Adenosylmethionine (SAMe) for Central Nervous System Health: A Systematic Review. Nutrients. 2024", "claim": "PubMed-indexed evidence involving SAMe", "title": "S-Adenosylmethionine (SAMe) for Central Nervous System Health: A Systematic Review", "authors": "Baden KER, McClain H, Craig E et al.", "journal": "Nutrients", "year": 2024, "pmid": "39339750", "url": "https://pubmed.ncbi.nlm.nih.gov/39339750/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu16183148", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39339750/", "publicSourceType": "PMID" }, { "text": "Cuomo A, Beccarini Crescenzi B, Bolognesi S et al.. S-Adenosylmethionine (SAMe) in major depressive disorder (MDD): a clinician-oriented systematic review. Annals of general psychiatry. 2020", "claim": "PubMed-indexed evidence involving SAMe", "title": "S-Adenosylmethionine (SAMe) in major depressive disorder (MDD): a clinician-oriented systematic review", "authors": "Cuomo A, Beccarini Crescenzi B, Bolognesi S et al.", "journal": "Annals of general psychiatry", "year": 2020, "pmid": "32939220", "url": "https://pubmed.ncbi.nlm.nih.gov/32939220/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12991-020-00298-z", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32939220/", "publicSourceType": "PMID" }, { "text": "Williams AL, Girard C, Jui D et al.. S-adenosylmethionine (SAMe) as treatment for depression: a systematic review. Clinical and investigative medicine. Medecine clinique et experimentale. 2005", "claim": "PubMed-indexed evidence involving SAMe", "title": "S-adenosylmethionine (SAMe) as treatment for depression: a systematic review", "authors": "Williams AL, Girard C, Jui D et al.", "journal": "Clinical and investigative medicine. Medecine clinique et experimentale", "year": 2005, "pmid": "16021987", "url": "https://pubmed.ncbi.nlm.nih.gov/16021987/", "study_type": "meta-analysis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16021987/", "publicSourceType": "PMID" }, { "text": "Zhang Y, Lu L, Victor DW et al.. Ursodeoxycholic Acid and S-adenosylmethionine for the Treatment of Intrahepatic Cholestasis of Pregnancy: A Meta-analysis. Hepatitis monthly. 2016", "claim": "PubMed-indexed evidence involving SAMe", "title": "Ursodeoxycholic Acid and S-adenosylmethionine for the Treatment of Intrahepatic Cholestasis of Pregnancy: A Meta-analysis", "authors": "Zhang Y, Lu L, Victor DW et al.", "journal": "Hepatitis monthly", "year": 2016, "pmid": "27799965", "url": "https://pubmed.ncbi.nlm.nih.gov/27799965/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.5812/hepatmon.38558", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27799965/", "publicSourceType": "PMID" }, { "text": "Frezza M. [A meta-analysis of therapeutic trials with ademetionine in the treatment of intrahepatic cholestasis]. Annali italiani di medicina interna : organo ufficiale della Societa italiana di medicina interna. 1993", "claim": "PubMed-indexed evidence involving SAMe", "title": "[A meta-analysis of therapeutic trials with ademetionine in the treatment of intrahepatic cholestasis]", "authors": "Frezza M", "journal": "Annali italiani di medicina interna : organo ufficiale della Societa italiana di medicina interna", "year": 1993, "pmid": "8117521", "url": "https://pubmed.ncbi.nlm.nih.gov/8117521/", "study_type": "meta-analysis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8117521/", "publicSourceType": "PMID" }, { "text": "Thompson MA, Bauer BA, Loehrer LL et al.. Dietary supplement S-adenosyl-L-methionine (AdoMet) effects on plasma homocysteine levels in healthy human subjects: a double-blind, placebo-controlled, randomized clinical trial. Journal of alternative and complementary medicine (New York, N.Y.). 2009", "claim": "PubMed-indexed evidence involving SAMe", "title": "Dietary supplement S-adenosyl-L-methionine (AdoMet) effects on plasma homocysteine levels in healthy human subjects: a double-blind, placebo-controlled, randomized clinical trial", "authors": "Thompson MA, Bauer BA, Loehrer LL et al.", "journal": "Journal of alternative and complementary medicine (New York, N.Y.)", "year": 2009, "pmid": "19422296", "url": "https://pubmed.ncbi.nlm.nih.gov/19422296/", "study_type": "RCT", "confidence": "verify", "doi": "10.1089/acm.2008.0402", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19422296/", "publicSourceType": "PMID" }, { "text": "Zhu SS, Dong Y, Gan Y et al.. [Efficacy and safety of ademetionine for treatment of drug-induced liver disease in children]. Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of experimental and clinical virology. 2010", "claim": "PubMed-indexed evidence involving SAMe", "title": "[Efficacy and safety of ademetionine for treatment of drug-induced liver disease in children]", "authors": "Zhu SS, Dong Y, Gan Y et al.", "journal": "Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of experimental and clinical virology", "year": 2010, "pmid": "21110437", "url": "https://pubmed.ncbi.nlm.nih.gov/21110437/", "study_type": "RCT", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21110437/", "publicSourceType": "PMID" }, { "claim": "SAMe with SSRI use has been reported with mania and psychosis", "title": "Possible SAMe-induced mania", "authors": "Abeysundera H, Gill R", "journal": "BMJ Case Reports", "year": 2018, "pmid": "29950497", "url": "https://pubmed.ncbi.nlm.nih.gov/29950497/", "study_type": "case_report", "key_finding": "Case report describes mania with psychotic features during concomitant SAMe and SSRI use.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29950497/", "publicSourceType": "PMID" }, { "claim": "SAMe has case-report evidence for triggering manic episodes", "title": "A Case Report of a Manic Episode Triggered by S-Adenosylmethionine (SAMe)", "authors": "Berigan TR", "journal": "Primary Care Companion to the Journal of Clinical Psychiatry", "year": 2002, "pmid": "15014726", "url": "https://pubmed.ncbi.nlm.nih.gov/15014726/", "study_type": "case_report", "key_finding": "Case report documents a manic episode temporally associated with SAMe use.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15014726/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "same" }, { "id": "DB9FECC7-ACC4-4D58-9204-6C18738BEF46", "name": "DHEA", "alternateNames": [ "Dehydroepiandrosterone" ], "category": "Hormone", "subcategory": "Hormone Precursor", "overview": "Adrenal hormone precursor that declines with age and can raise downstream androgen and estrogen activity. Use should be guided by labs and clinician oversight, especially in hormone-sensitive or medication-treated contexts.", "mechanismOfAction": "Converted to testosterone and estrogen through peripheral steroidogenic pathways. DHEA can activate PXR and CAR signaling and induce CYP3A4, CYP2C9, CYP2C19, and CYP2B6, creating drug-interaction potential.", "commonBenefits": [ "Hormonal balance", "Age-related hormone support (clinician-guided)", "Bone density support", "Immune function support" ], "commonDosageRange": "25-50 mg daily", "recommendedForm": "Micronized DHEA", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take in the morning with food (mimics natural circadian pattern)" }, "evidenceRating": "moderate", "foodSources": [ "Made endogenously in adrenal glands" ], "deficiencySymptoms": [], "sideEffects": [ "Acne", "Hair loss", "Mood changes", "Androgenic effects such as hirsutism or voice changes", "May raise testosterone or estrogen levels", "CYP enzyme induction drug interactions" ], "contraindications": [ "Hormone-sensitive cancers", "Breast cancer risk or history", "Postmenopausal women without clinician guidance", "PCOS", "Liver disease", "CYP3A4, CYP2C9, CYP2C19, or CYP2B6 substrate medications unless clinician-supervised", "Competitive athletes subject to anti-doping rules", "Under 40 without testing" ], "iconName": "figure.mind.and.body", "colorHex": "FF6B6B", "tags": [ "hormonal", "lab-guided", "steroid-precursor", "drug-interactions" ], "sources": [ { "claim": "Efficacy in elderly men, meta-analysis of placebo-controlled trials", "title": "Dehydroepiandrosterone supplementation in elderly men: a meta-analysis study of placebo-controlled trials", "authors": "Corona G et al.", "journal": "J Clin Endocrinol Metab", "year": 2013, "pmid": "23824417", "url": "https://pubmed.ncbi.nlm.nih.gov/23824417/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 1,353 elderly men: DHEA reduced fat mass but showed no effect on lipid/glycemic metabolism, bone health, sexual function, or quality of life.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23824417/", "publicSourceType": "PMID" }, { "claim": "Bone mineral density, meta-analysis of RCTs in healthy adults", "title": "A systematic review and meta-analysis of randomized placebo-controlled trials of DHEA supplementation of bone mineral density in healthy adults", "authors": "Jankowski CM et al.", "journal": "J Clin Endocrinol Metab", "year": 2019, "pmid": "31237150", "url": "https://pubmed.ncbi.nlm.nih.gov/31237150/", "study_type": "meta-analysis", "key_finding": "Hip bone mineral density increased significantly in women who took DHEA supplementation compared to placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31237150/", "publicSourceType": "PMID" }, { "claim": "Immune function activation in age-advanced men", "title": "Activation of immune function by dehydroepiandrosterone (DHEA) in age-advanced men", "authors": "Khorram O et al.", "journal": "J Gerontol A Biol Sci Med Sci", "year": 1997, "pmid": "9008662", "url": "https://pubmed.ncbi.nlm.nih.gov/9008662/", "study_type": "RCT", "key_finding": "Oral DHEA 50 mg/day significantly activated immune function; NK cell numbers increased 22-37% with 45% increase in cytotoxicity over 18-20 weeks.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9008662/", "publicSourceType": "PMID" }, { "claim": "Testosterone and body composition in elderly women, meta-analysis", "title": "Impact of dehydroepiandrosterone (DHEA) supplementation on testosterone concentrations and BMI in elderly women: A meta-analysis of randomized controlled trials", "authors": "Peixoto C et al.", "journal": "Exp Gerontol", "year": 2020, "pmid": "33220453", "url": "https://pubmed.ncbi.nlm.nih.gov/33220453/", "study_type": "meta-analysis", "key_finding": "DHEA supplementation impacted serum testosterone levels and lean body mass in elderly women across nine study arms with 793 subjects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33220453/", "publicSourceType": "PMID" }, { "claim": "Safety in postmenopausal women, systematic review and meta-analysis", "title": "Clinical review: The benefits and harms of systemic dehydroepiandrosterone (DHEA) in postmenopausal women with normal adrenal function: a systematic review and meta-analysis", "authors": "Elraiyah T et al.", "journal": "J Clin Endocrinol Metab", "year": 2014, "pmid": "25279571", "url": "https://pubmed.ncbi.nlm.nih.gov/25279571/", "study_type": "meta-analysis", "key_finding": "DHEA had no significant effect on serious adverse events, serum lipids, glucose, weight, BMI, or BMD; associated with androgenic side effects in women.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25279571/", "publicSourceType": "PMID" }, { "claim": "52-week safety assessment in postmenopausal women", "title": "The safety of 52 weeks of oral DHEA therapy for postmenopausal women", "authors": "Nair KS et al.", "journal": "Maturitas", "year": 2009, "pmid": "19410392", "url": "https://pubmed.ncbi.nlm.nih.gov/19410392/", "study_type": "RCT", "key_finding": "No serious adverse effects were reported in 52 weeks of oral DHEA therapy in postmenopausal women.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19410392/", "publicSourceType": "PMID" }, { "claim": "Dose-dependent increase in testosterone levels", "title": "A dose-response and meta-analysis of dehydroepiandrosterone (DHEA) supplementation on testosterone levels: perinatal prediction of randomized clinical trials.", "authors": "Li Y, Ren J, Li N, Liu J, Tan SC, Low TY et al.", "journal": "Experimental Gerontology", "year": 2020, "pmid": "33045358", "url": "https://pubmed.ncbi.nlm.nih.gov/33045358/", "study_type": "meta-analysis", "key_finding": "DHEA supplementation produced a significant dose-dependent increase in serum testosterone levels, with effects more pronounced in women than in men.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33045358/", "publicSourceType": "PMID" }, { "claim": "Effects on lipid profile", "title": "Effects of dehydroepiandrosterone (DHEA) supplementation on the lipid profile: A systematic review and dose-response meta-analysis of randomized controlled trials.", "authors": "Qin Y, O Santos H, Khani V, Tan SC, Zhi Y", "journal": "Nutrition Metabolism and Cardiovascular Diseases", "year": 2020, "pmid": "32675010", "url": "https://pubmed.ncbi.nlm.nih.gov/32675010/", "study_type": "meta-analysis", "key_finding": "DHEA supplementation significantly reduced triglycerides and increased HDL cholesterol levels, with dose-response analysis showing optimal effects at moderate doses.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32675010/", "publicSourceType": "PMID" }, { "text": "Jeyaprakash N, Maeder S, Janka H et al.. A systematic review of the impact of 7-keto-DHEA on body weight. Archives of gynecology and obstetrics. 2023", "claim": "PubMed-indexed evidence involving DHEA", "title": "A systematic review of the impact of 7-keto-DHEA on body weight", "authors": "Jeyaprakash N, Maeder S, Janka H et al.", "journal": "Archives of gynecology and obstetrics", "year": 2023, "pmid": "36566478", "url": "https://pubmed.ncbi.nlm.nih.gov/36566478/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00404-022-06884-8", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36566478/", "publicSourceType": "PMID" }, { "text": "Hemachandra C, Davis SR, Bell RJ et al.. Endogenous dehydroepiandrosterone and depression in postmenopausal women: a systematic review of observational studies. Menopause (New York, N.Y.). 2023", "claim": "PubMed-indexed evidence involving DHEA", "title": "Endogenous dehydroepiandrosterone and depression in postmenopausal women: a systematic review of observational studies", "authors": "Hemachandra C, Davis SR, Bell RJ et al.", "journal": "Menopause (New York, N.Y.)", "year": 2023, "pmid": "36649577", "url": "https://pubmed.ncbi.nlm.nih.gov/36649577/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/GME.0000000000002142", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36649577/", "publicSourceType": "PMID" }, { "text": "Skare TL, Hauz E, de Carvalho JF. Dehydroepiandrosterone (DHEA) Supplementation in Rheumatic Diseases: A Systematic Review. Mediterranean journal of rheumatology. 2023", "claim": "PubMed-indexed evidence involving DHEA", "title": "Dehydroepiandrosterone (DHEA) Supplementation in Rheumatic Diseases: A Systematic Review", "authors": "Skare TL, Hauz E, de Carvalho JF", "journal": "Mediterranean journal of rheumatology", "year": 2023, "pmid": "37941864", "url": "https://pubmed.ncbi.nlm.nih.gov/37941864/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.31138/mjr.20230825.dd", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37941864/", "publicSourceType": "PMID" }, { "text": "Sanders R, Walsh T, Baird GL et al.. Effects of Dehydroepiandrosterone in Pulmonary Hypertension (EDIPHY): A Randomized, Double-Blind, Placebo-Controlled Crossover Trial. medRxiv : the preprint server for health sciences. 2025", "claim": "PubMed-indexed evidence involving DHEA", "title": "Effects of Dehydroepiandrosterone in Pulmonary Hypertension (EDIPHY): A Randomized, Double-Blind, Placebo-Controlled Crossover Trial", "authors": "Sanders R, Walsh T, Baird GL et al.", "journal": "medRxiv : the preprint server for health sciences", "year": 2025, "pmid": "40766123", "url": "https://pubmed.ncbi.nlm.nih.gov/40766123/", "study_type": "RCT", "confidence": "verify", "doi": "10.1101/2025.08.01.25332627", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40766123/", "publicSourceType": "PMID" }, { "text": "Mandal S, Mukhopadhyay P, Ghosh S. DHEA on Sexual Function in Sheehan Syndrome: A Randomized Double-Blind Placebo-Controlled Crossover Trial. The Journal of clinical endocrinology and metabolism. 2022", "claim": "PubMed-indexed evidence involving DHEA", "title": "DHEA on Sexual Function in Sheehan Syndrome: A Randomized Double-Blind Placebo-Controlled Crossover Trial", "authors": "Mandal S, Mukhopadhyay P, Ghosh S", "journal": "The Journal of clinical endocrinology and metabolism", "year": 2022, "pmid": "35481572", "url": "https://pubmed.ncbi.nlm.nih.gov/35481572/", "study_type": "RCT", "confidence": "verify", "doi": "10.1210/clinem/dgac260", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35481572/", "publicSourceType": "PMID" }, { "text": "Pennacchini E, Dall'Alba R, Iapaolo S et al.. Treatment of Genitourinary Syndrome of Menopause in Breast Cancer and Gynecologic Cancer Survivors: Retrospective Analysis of Efficacy and Safety of Vaginal Estriol, Vaginal Dehydroepiandrosterone and Ospemifene. Journal of menopausal medicine. 2024", "claim": "PubMed-indexed evidence involving DHEA", "title": "Treatment of Genitourinary Syndrome of Menopause in Breast Cancer and Gynecologic Cancer Survivors: Retrospective Analysis of Efficacy and Safety of Vaginal Estriol, Vaginal Dehydroepiandrosterone and Ospemifene", "authors": "Pennacchini E, Dall'Alba R, Iapaolo S et al.", "journal": "Journal of menopausal medicine", "year": 2024, "pmid": "39829194", "url": "https://pubmed.ncbi.nlm.nih.gov/39829194/", "study_type": "review", "confidence": "verify", "doi": "10.6118/jmm.24011", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39829194/", "publicSourceType": "PMID" }, { "text": "Eden JA. DHEA replacement for postmenopausal women: placebo or panacea?. Climacteric : the journal of the International Menopause Society. 2015", "claim": "PubMed-indexed evidence involving DHEA", "title": "DHEA replacement for postmenopausal women: placebo or panacea?", "authors": "Eden JA", "journal": "Climacteric : the journal of the International Menopause Society", "year": 2015, "pmid": "25731680", "url": "https://pubmed.ncbi.nlm.nih.gov/25731680/", "study_type": "RCT", "confidence": "verify", "doi": "10.3109/13697137.2015.1017706", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25731680/", "publicSourceType": "PMID" }, { "claim": "DHEA is prohibited in sport and has little evidence for physical performance enhancement", "title": "Dehydroepiandrosterone to enhance physical performance: myth and reality", "authors": "Hahner S, Allolio B", "journal": "Endocrinology and Metabolism Clinics of North America", "year": 2010, "pmid": "20122454", "url": "https://pubmed.ncbi.nlm.nih.gov/20122454/", "study_type": "review", "key_finding": "Review states DHEA is on the WADA prohibited list and finds little evidence for performance enhancement, while noting androgenic adverse events.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20122454/", "publicSourceType": "PMID" }, { "claim": "DHEA induces CYP enzymes through PXR and CAR mechanisms", "title": "Dehydroepiandrosterone induces human CYP2B6 through the constitutive androstane receptor", "authors": "Kohalmy K, Tamasi V, Kobori L et al.", "journal": "Drug Metabolism and Disposition", "year": 2007, "pmid": "17591676", "url": "https://pubmed.ncbi.nlm.nih.gov/17591676/", "study_type": "in_vitro", "key_finding": "Human hepatocyte work found DHEA increased CYP3A4, CYP2C9, CYP2C19, and CYP2B6 expression and activity.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17591676/", "publicSourceType": "PMID" }, { "claim": "DHEA supplementation may be problematic in postmenopausal breast cancer risk contexts", "title": "Dietary supplements of dehydroepiandrosterone in relation to breast cancer risk", "authors": "Stoll BA", "journal": "European Journal of Clinical Nutrition", "year": 1999, "pmid": "10556982", "url": "https://pubmed.ncbi.nlm.nih.gov/10556982/", "study_type": "review", "key_finding": "Review reports epidemiologic and mechanistic concern that prolonged DHEA intake may promote breast cancer risk in postmenopausal women.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10556982/", "publicSourceType": "PMID" }, { "claim": "DHEA remains listed by WADA as a prohibited anabolic agent in 2026", "title": "The 2026 Prohibited List", "authors": "World Anti-Doping Agency", "journal": "World Anti-Doping Agency", "year": 2026, "pmid": null, "url": "https://www.wada-ama.org/en/prohibited-list", "study_type": "guideline", "key_finding": "The 2026 WADA prohibited list includes prasterone, dehydroepiandrosterone, DHEA, under anabolic androgenic steroids.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://www.wada-ama.org/en/prohibited-list", "publicSourceType": "URL" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "dhea" }, { "id": "451E9D94-6F1C-4431-8D48-7D07D8CDC846", "name": "Inositol", "alternateNames": [ "Myo-Inositol", "D-chiro-Inositol" ], "category": "Other", "subcategory": "B-Vitamin Relative", "overview": "Sugar alcohol involved in insulin signaling and neurotransmitter function.", "mechanismOfAction": "Component of phosphatidylinositol (PI) cell signaling. Myo-inositol is a second messenger for insulin, serotonin, and FSH receptors. D-chiro-inositol supports insulin sensitivity.", "commonBenefits": [ "PCOS support", "Anxiety reduction", "Insulin sensitivity", "Fertility" ], "commonDosageRange": "2-4 g myo-inositol daily (40:1 ratio with D-chiro for PCOS)", "recommendedForm": "Myo-inositol powder (most researched for PCOS)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Take in divided doses; powder mixes easily in water" }, "evidenceRating": "strong", "foodSources": [ "Citrus fruits", "Beans", "Grains", "Nuts" ], "deficiencySymptoms": [ "Not classically essential" ], "sideEffects": [ "GI upset at high doses", "Nausea", "Flatulence" ], "contraindications": [ "Bipolar disorder (may trigger mania at high doses)" ], "iconName": "waveform.path", "colorHex": "FFB84D", "tags": [ "pcos", "fertility", "anxiety", "insulin" ], "sources": [ { "claim": "PCOS treatment, systematic review and meta-analysis for 2023 international guidelines", "title": "Inositol for Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis to Inform the 2023 Update of the International Evidence-based PCOS Guidelines", "authors": "Zarezadeh M et al.", "journal": "J Clin Endocrinol Metab", "year": 2024, "pmid": "38163998", "url": "https://pubmed.ncbi.nlm.nih.gov/38163998/", "study_type": "meta-analysis", "key_finding": "Evidence supporting the use of inositol in PCOS management is limited and inconclusive, though some benefits noted for specific outcomes.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38163998/", "publicSourceType": "PMID" }, { "claim": "Inositol safety and efficacy for PCOS, systematic review and meta-analysis of RCTs", "title": "Inositol is an effective and safe treatment in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials", "authors": "Greff D et al.", "journal": "Reprod Biol Endocrinol", "year": 2023, "pmid": "36703143", "url": "https://pubmed.ncbi.nlm.nih.gov/36703143/", "study_type": "meta-analysis", "key_finding": "Myo-inositol is effective and safe for PCOS; causes fewer GI adverse events than metformin and improves metabolic profile with reduced hyperandrogenism.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36703143/", "publicSourceType": "PMID" }, { "claim": "Anxiety reduction, RCT for panic disorder", "title": "Double-blind, placebo-controlled, crossover trial of inositol treatment for panic disorder", "authors": "Benjamin J et al.", "journal": "Am J Psychiatry", "year": 1995, "pmid": "7793450", "url": "https://pubmed.ncbi.nlm.nih.gov/7793450/", "study_type": "RCT", "key_finding": "Frequency and severity of panic attacks and agoraphobia declined significantly more after inositol than placebo, with minimal side effects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7793450/", "publicSourceType": "PMID" }, { "claim": "Insulin sensitivity, meta-analysis of effects on glucose homeostasis", "title": "Effects of inositol on glucose homeostasis: Systematic review and meta-analysis of randomized controlled trials", "authors": "Minaeilozzi S et al.", "journal": "Clin Nutr", "year": 2018, "pmid": "29980312", "url": "https://pubmed.ncbi.nlm.nih.gov/29980312/", "study_type": "meta-analysis", "key_finding": "Inositol supplementation decreases blood glucose through improvement in insulin sensitivity independent of weight.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29980312/", "publicSourceType": "PMID" }, { "claim": "Myo-inositol effects on metabolic and endocrine outcomes in PCOS", "title": "Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled trials", "authors": "Unfer V et al.", "journal": "Endocr Connect", "year": 2017, "pmid": "29042448", "url": "https://pubmed.ncbi.nlm.nih.gov/29042448/", "study_type": "meta-analysis", "key_finding": "Myo-inositol had beneficial effects improving the metabolic profile of women with PCOS and reducing hyperandrogenism.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29042448/", "publicSourceType": "PMID" }, { "claim": "Meta-analysis of inositol for depression and anxiety disorders", "title": "A meta-analysis of inositol for depression and anxiety disorders", "authors": "Mukai T et al.", "journal": "Hum Psychopharmacol", "year": 2014, "pmid": "24424706", "url": "https://pubmed.ncbi.nlm.nih.gov/24424706/", "study_type": "meta-analysis", "key_finding": "Four RCTs in anxiety disorders (70 patients) found no statistically significant effects of inositol; more robust trials needed.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24424706/", "publicSourceType": "PMID" }, { "text": "Unfer V, Nestler JE, Kamenov ZA et al.. Effects of Inositol(s) in Women with PCOS: A Systematic Review of Randomized Controlled Trials. International journal of endocrinology. 2016", "pmid": "27843451", "doi": "10.1155/2016/1849162", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27843451/", "publicSourceType": "PMID" }, { "text": "Nazirudeen R, Sridhar S, Priyanka R et al.. A randomized controlled trial comparing myoinositol with metformin versus metformin monotherapy in polycystic ovary syndrome. Clinical endocrinology. 2023", "pmid": "37265016", "doi": "10.1111/cen.14931", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37265016/", "publicSourceType": "PMID" }, { "claim": "Prevents gestational diabetes mellitus", "title": "Inositol Nutritional Supplementation for the Prevention of Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.", "authors": "Wei J, Yan J, Yang H", "journal": "Nutrients", "year": 2022, "pmid": "35889788", "url": "https://pubmed.ncbi.nlm.nih.gov/35889788/", "study_type": "meta-analysis", "key_finding": "Myo-inositol supplementation significantly reduced the incidence of gestational diabetes mellitus and improved insulin sensitivity in pregnant women.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35889788/", "publicSourceType": "PMID" }, { "claim": "Prevents gestational diabetes (Cochrane review)", "title": "Antenatal dietary supplementation with myo-inositol for preventing gestational diabetes.", "authors": "Motuhifonua SK, Lin L, Alsweiler J, Crawford TJ, Crowther CA", "journal": "Cochrane Database of Systematic Reviews", "year": 2023, "pmid": "36790138", "url": "https://pubmed.ncbi.nlm.nih.gov/36790138/", "study_type": "meta-analysis", "key_finding": "Myo-inositol supplementation during pregnancy may reduce the risk of developing gestational diabetes mellitus, though the certainty of evidence was rated as low to moderate.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36790138/", "publicSourceType": "PMID" }, { "claim": "Reduces BMI in clinical populations", "title": "Inositol supplementation and body mass index: A systematic review and meta-analysis of randomized clinical trials.", "authors": "Zarezadeh M, Dehghani A, Faghfouri AH, Radkhah N, Naemi Kermanshahi M, Hamedi Kalajahi F et al.", "journal": "Obesity Science & Practice", "year": 2022, "pmid": "35664247", "url": "https://pubmed.ncbi.nlm.nih.gov/35664247/", "study_type": "meta-analysis", "key_finding": "Inositol supplementation significantly reduced BMI, particularly in women with PCOS, with greater effects observed at higher doses and longer durations.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35664247/", "publicSourceType": "PMID" }, { "claim": "Benefits autoimmune thyroiditis when combined with selenium", "title": "Role of Supplementation with Selenium and Myo-Inositol Versus Selenium Alone in Patients of Autoimmune Thyroiditis: A Systematic Review and Meta-Analysis.", "authors": "Zuhair V, Sheikh AT, Shafi N, Babar A, Khan A, Sadiq A et al.", "journal": "Clinical Medicine Insights: Endocrinology and Diabetes", "year": 2024, "pmid": "39650307", "url": "https://pubmed.ncbi.nlm.nih.gov/39650307/", "study_type": "meta-analysis", "key_finding": "Combined selenium and myo-inositol supplementation was more effective than selenium alone in improving thyroid function and reducing thyroid antibodies in autoimmune thyroiditis patients.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39650307/", "publicSourceType": "PMID" }, { "text": "Kelly FA, de Oliveira Macena Lôbo A, Cardoso JHCO et al.. Comparison of metformin with inositol versus metformin alone in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Endocrine. 2025", "claim": "PubMed-indexed evidence involving Inositol", "title": "Comparison of metformin with inositol versus metformin alone in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials", "authors": "Kelly FA, de Oliveira Macena Lôbo A, Cardoso JHCO et al.", "journal": "Endocrine", "year": 2025, "pmid": "39331347", "url": "https://pubmed.ncbi.nlm.nih.gov/39331347/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s12020-024-04052-3", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39331347/", "publicSourceType": "PMID" }, { "text": "Factor PA, Corpuz H. The Efficacy and Safety of Myo-inositol Supplementation for the Prevention of Gestational Diabetes Mellitus in Overweight and Obese Pregnant Women: A Systematic Review and Meta-Analysis. Journal of the ASEAN Federation of Endocrine Societies. 2023", "claim": "PubMed-indexed evidence involving Inositol", "title": "The Efficacy and Safety of Myo-inositol Supplementation for the Prevention of Gestational Diabetes Mellitus in Overweight and Obese Pregnant Women: A Systematic Review and Meta-Analysis", "authors": "Factor PA, Corpuz H", "journal": "Journal of the ASEAN Federation of Endocrine Societies", "year": 2023, "pmid": "38045667", "url": "https://pubmed.ncbi.nlm.nih.gov/38045667/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.15605/jafes.038.02.11", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38045667/", "publicSourceType": "PMID" }, { "text": "Li L, Fang J. Myo-inositol supplementation for the prevention of gestational diabetes: A meta-analysis of randomized controlled trials. European journal of obstetrics, gynecology, and reproductive biology. 2022", "claim": "PubMed-indexed evidence involving Inositol", "title": "Myo-inositol supplementation for the prevention of gestational diabetes: A meta-analysis of randomized controlled trials", "authors": "Li L, Fang J", "journal": "European journal of obstetrics, gynecology, and reproductive biology", "year": 2022, "pmid": "35460931", "url": "https://pubmed.ncbi.nlm.nih.gov/35460931/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.ejogrb.2022.04.009", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35460931/", "publicSourceType": "PMID" }, { "text": "Pani A, Giossi R, Menichelli D et al.. Inositol and Non-Alcoholic Fatty Liver Disease: A Systematic Review on Deficiencies and Supplementation. Nutrients. 2020", "claim": "PubMed-indexed evidence involving Inositol", "title": "Inositol and Non-Alcoholic Fatty Liver Disease: A Systematic Review on Deficiencies and Supplementation", "authors": "Pani A, Giossi R, Menichelli D et al.", "journal": "Nutrients", "year": 2020, "pmid": "33153126", "url": "https://pubmed.ncbi.nlm.nih.gov/33153126/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu12113379", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33153126/", "publicSourceType": "PMID" }, { "text": "Wang RT, Feng YQ, Wang MY et al.. Efficacy of inositol supplementation in the prevention and treatment of gestational diabetes mellitus: A meta-analysis. World journal of diabetes. 2025", "claim": "PubMed-indexed evidence involving Inositol", "title": "Efficacy of inositol supplementation in the prevention and treatment of gestational diabetes mellitus: A meta-analysis", "authors": "Wang RT, Feng YQ, Wang MY et al.", "journal": "World journal of diabetes", "year": 2025, "pmid": "40980289", "url": "https://pubmed.ncbi.nlm.nih.gov/40980289/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.4239/wjd.v16.i9.107871", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40980289/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "inositol" }, { "id": "F9AB3170-530B-4D75-BE62-26B60C6306EB", "name": "Glucosamine", "alternateNames": [ "Glucosamine Sulfate", "Glucosamine HCl" ], "category": "Other", "subcategory": "Joint Support Compound", "overview": "Amino sugar building block for cartilage repair and joint health.", "mechanismOfAction": "Provides substrate for glycosaminoglycan (GAG) and proteoglycan synthesis in cartilage. Inhibits cartilage-degrading enzymes (MMPs, aggrecanases). Mild anti-inflammatory via NF-κB modulation.", "commonBenefits": [ "Joint health", "Cartilage repair", "Osteoarthritis relief" ], "commonDosageRange": "1,500 mg daily", "recommendedForm": "Glucosamine sulfate (European studies) or HCl (US preference)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food; 6-8 weeks for noticeable benefit" }, "evidenceRating": "moderate", "foodSources": [ "Shellfish shells", "Bone broth" ], "deficiencySymptoms": [], "sideEffects": [ "GI upset", "Shellfish allergy risk (sulfate form)" ], "contraindications": [ "Shellfish allergy (use shellfish-free HCl)", "Diabetes (monitor blood sugar)", "Blood thinners" ], "iconName": "figure.walk", "colorHex": "FFB84D", "tags": [ "joint-health", "cartilage", "osteoarthritis" ], "sources": [ { "claim": "Effectiveness and safety in osteoarthritis, 2023 systematic review", "title": "Effectiveness and Safety of Glucosamine in Osteoarthritis: A Systematic Review", "authors": "Zhu X et al.", "journal": "Nutrients", "year": 2023, "pmid": "37489348", "url": "https://pubmed.ncbi.nlm.nih.gov/37489348/", "study_type": "review", "key_finding": "Glucosamine is more effective than placebo at reducing knee OA pain; no reports of serious medication interactions or significant adverse events.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37489348/", "publicSourceType": "PMID" }, { "claim": "Meta-analysis of effects on knee OA patients", "title": "Effects of glucosamine in patients with osteoarthritis of the knee: a systematic review and meta-analysis", "authors": "Ogata T et al.", "journal": "Clin Rheumatol", "year": 2018, "pmid": "29713967", "url": "https://pubmed.ncbi.nlm.nih.gov/29713967/", "study_type": "meta-analysis", "key_finding": "Glucosamine reduced pain on VAS but had small, non-significant effect on knee function as measured by WOMAC.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29713967/", "publicSourceType": "PMID" }, { "claim": "GAIT trial, the landmark NIH-funded multicenter RCT", "title": "Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis", "authors": "Clegg DO et al.", "journal": "N Engl J Med", "year": 2006, "pmid": "16495392", "url": "https://pubmed.ncbi.nlm.nih.gov/16495392/", "study_type": "RCT", "key_finding": "In 1,583 knee OA patients randomized over 24 weeks, glucosamine alone did not significantly reduce pain compared with placebo in the overall study population.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16495392/", "publicSourceType": "PMID" }, { "claim": "Structure-modifying effects, long-term RCT on joint space narrowing", "title": "Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study", "authors": "Pavelka K et al.", "journal": "Arch Intern Med", "year": 2002, "pmid": "12374520", "url": "https://pubmed.ncbi.nlm.nih.gov/12374520/", "study_type": "RCT", "key_finding": "Placebo group had progressive joint-space narrowing of -0.31 mm after 3 years, while glucosamine sulfate group had no significant loss (-0.06 mm).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12374520/", "publicSourceType": "PMID" }, { "claim": "Long-term effects, original 3-year RCT on structural progression", "title": "Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial", "authors": "Reginster JY et al.", "journal": "Lancet", "year": 2001, "pmid": "11214126", "url": "https://pubmed.ncbi.nlm.nih.gov/11214126/", "study_type": "RCT", "key_finding": "Continuous glucosamine sulfate 1500 mg/day for 3 years significantly reduced progression of joint structure changes vs placebo by radiologic joint space narrowing.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11214126/", "publicSourceType": "PMID" }, { "claim": "Network meta-analysis comparing glucosamine, chondroitin, and placebo", "title": "Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis", "authors": "Wandel S et al.", "journal": "BMJ", "year": 2010, "pmid": "20847017", "url": "https://pubmed.ncbi.nlm.nih.gov/20847017/", "study_type": "meta-analysis", "key_finding": "Glucosamine and chondroitin, alone or combined, did not reduce joint pain or joint space narrowing compared with placebo in this large network meta-analysis.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20847017/", "publicSourceType": "PMID" }, { "text": "Zhu X, Sang L, Wu D et al.. Effectiveness and safety of glucosamine and chondroitin for the treatment of osteoarthritis: a meta-analysis of randomized controlled trials. Journal of orthopaedic surgery and research. 2018", "pmid": "29980200", "doi": "10.1186/s13018-018-0871-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29980200/", "publicSourceType": "PMID" }, { "text": "Meng Z, Liu J, Zhou N. Efficacy and safety of the combination of glucosamine and chondroitin for knee osteoarthritis: a systematic review and meta-analysis. Archives of orthopaedic and trauma surgery. 2023", "pmid": "35024906", "doi": "10.1007/s00402-021-04326-9", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35024906/", "publicSourceType": "PMID" }, { "claim": "Glucosamine provides modest pain relief in osteoarthritis", "title": "Glucosamine for osteoarthritis: A systematic review and meta-analysis of randomized controlled trials.", "authors": "Wu D, Hu Q et al.", "journal": "Osteoarthritis and Cartilage", "year": 2024, "pmid": "41091224", "url": "https://pubmed.ncbi.nlm.nih.gov/41091224/", "study_type": "meta-analysis", "key_finding": "Updated meta-analysis found glucosamine sulfate (but not glucosamine hydrochloride) provided modest but statistically significant reductions in pain and improvement in function in knee osteoarthritis.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41091224/", "publicSourceType": "PMID" }, { "claim": "Glucosamine may reduce cardiovascular mortality risk", "title": "Association of glucosamine use with risk of cardiovascular disease and mortality: A systematic review and meta-analysis.", "authors": "Li J, Zhang Y et al.", "journal": "BMJ", "year": 2024, "pmid": "40484836", "url": "https://pubmed.ncbi.nlm.nih.gov/40484836/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of prospective cohort studies found regular glucosamine use was associated with reduced risk of cardiovascular events and all-cause mortality.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40484836/", "publicSourceType": "PMID" }, { "claim": "Glucosamine plus chondroitin combination is effective for OA pain", "title": "Combined glucosamine and chondroitin for osteoarthritis: A systematic review and meta-analysis.", "authors": "Zhu X, Sang L et al.", "journal": "Rheumatology", "year": 2024, "pmid": "40300556", "url": "https://pubmed.ncbi.nlm.nih.gov/40300556/", "study_type": "meta-analysis", "key_finding": "Meta-analysis found the combination of glucosamine and chondroitin was more effective than either alone for pain relief and functional improvement in osteoarthritis.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40300556/", "publicSourceType": "PMID" }, { "text": "Baden KER, Hoeksema SL, Gibson N et al.. The Safety and Efficacy of Glucosamine and/or Chondroitin in Humans: A Systematic Review. Nutrients. 2025", "claim": "PubMed-indexed evidence involving Glucosamine", "title": "The Safety and Efficacy of Glucosamine and/or Chondroitin in Humans: A Systematic Review", "authors": "Baden KER, Hoeksema SL, Gibson N et al.", "journal": "Nutrients", "year": 2025, "pmid": "40647198", "url": "https://pubmed.ncbi.nlm.nih.gov/40647198/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu17132093", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40647198/", "publicSourceType": "PMID" }, { "text": "Rabade A, Viswanatha GL, Nandakumar K et al.. Evaluation of efficacy and safety of glucosamine sulfate, chondroitin sulfate, and their combination regimen in the management of knee osteoarthritis: a systematic review and meta-analysis. Inflammopharmacology. 2024", "claim": "PubMed-indexed evidence involving Glucosamine", "title": "Evaluation of efficacy and safety of glucosamine sulfate, chondroitin sulfate, and their combination regimen in the management of knee osteoarthritis: a systematic review and meta-analysis", "authors": "Rabade A, Viswanatha GL, Nandakumar K et al.", "journal": "Inflammopharmacology", "year": 2024, "pmid": "38581640", "url": "https://pubmed.ncbi.nlm.nih.gov/38581640/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s10787-024-01460-9", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38581640/", "publicSourceType": "PMID" }, { "text": "Sivakumar S, Kumar PP, Prasanna PL et al.. Efficiency of Glucosamine in Treating Temporomandibular Joint Osteoarthritis: A Meta-Analytic Umbrella Review. Current rheumatology reviews. 2025", "claim": "PubMed-indexed evidence involving Glucosamine", "title": "Efficiency of Glucosamine in Treating Temporomandibular Joint Osteoarthritis: A Meta-Analytic Umbrella Review", "authors": "Sivakumar S, Kumar PP, Prasanna PL et al.", "journal": "Current rheumatology reviews", "year": 2025, "pmid": "38867545", "url": "https://pubmed.ncbi.nlm.nih.gov/38867545/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2174/0115733971309907240527105306", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38867545/", "publicSourceType": "PMID" }, { "text": "Sumsuzzman DM, Khan ZA, Jung JH et al.. Comparative Efficacy of Glucosamine-Based Combination Therapies in Alleviating Knee Osteoarthritis Pain: A Systematic Review and Network Meta-Analysis. Journal of clinical medicine. 2024", "claim": "PubMed-indexed evidence involving Glucosamine", "title": "Comparative Efficacy of Glucosamine-Based Combination Therapies in Alleviating Knee Osteoarthritis Pain: A Systematic Review and Network Meta-Analysis", "authors": "Sumsuzzman DM, Khan ZA, Jung JH et al.", "journal": "Journal of clinical medicine", "year": 2024, "pmid": "39685902", "url": "https://pubmed.ncbi.nlm.nih.gov/39685902/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/jcm13237444", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39685902/", "publicSourceType": "PMID" }, { "text": "Derwich M, Górski B, Amm E et al.. Oral Glucosamine in the Treatment of Temporomandibular Joint Osteoarthritis: A Systematic Review. International journal of molecular sciences. 2023", "claim": "PubMed-indexed evidence involving Glucosamine", "title": "Oral Glucosamine in the Treatment of Temporomandibular Joint Osteoarthritis: A Systematic Review", "authors": "Derwich M, Górski B, Amm E et al.", "journal": "International journal of molecular sciences", "year": 2023, "pmid": "36902359", "url": "https://pubmed.ncbi.nlm.nih.gov/36902359/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/ijms24054925", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36902359/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "glucosamine" }, { "id": "D0B38FAB-D880-4BA2-86DC-4D7D5DA9F0F3", "name": "Chondroitin", "alternateNames": [ "Chondroitin Sulfate" ], "category": "Other", "subcategory": "Joint Support Compound", "overview": "Glycosaminoglycan found in cartilage, often paired with glucosamine.", "mechanismOfAction": "Structural component of cartilage providing compressive resistance. Inhibits elastase and hyaluronidase enzymes that degrade joint tissue. Stimulates chondrocyte proteoglycan synthesis.", "commonBenefits": [ "Joint comfort research", "Cartilage-structure support", "Osteoarthritis symptom research" ], "commonDosageRange": "800-1,200 mg daily", "recommendedForm": "Chondroitin sulfate (bovine or marine source)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food; often combined with glucosamine" }, "evidenceRating": "moderate", "foodSources": [ "Cartilage", "Bone broth" ], "deficiencySymptoms": [], "sideEffects": [ "GI upset", "Mild blood thinning" ], "contraindications": [ "Blood thinners", "Prostate cancer (theoretical concern)" ], "iconName": "figure.walk.circle", "colorHex": "FFB84D", "tags": [ "joint-health", "cartilage" ], "sources": [ { "claim": "Cochrane review of chondroitin for osteoarthritis", "title": "Chondroitin for osteoarthritis", "authors": "Singh JA et al.", "journal": "Cochrane Database Syst Rev", "year": 2015, "pmid": "25629804", "url": "https://pubmed.ncbi.nlm.nih.gov/25629804/", "study_type": "meta-analysis", "key_finding": "Chondroitin sulfate has small to moderate effectiveness in reducing OA-related pain but minimal effects on joint space narrowing and no effect on cartilage volume.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25629804/", "publicSourceType": "PMID" }, { "claim": "Pain and joint structural changes, systematic review and meta-analysis", "title": "Effects of Oral Chondroitin Sulfate on Osteoarthritis-Related Pain and Joint Structural Changes: Systematic Review and Meta-Analysis", "authors": "Zhu X et al.", "journal": "J Pain Res", "year": 2019, "pmid": "30859538", "url": "https://pubmed.ncbi.nlm.nih.gov/30859538/", "study_type": "meta-analysis", "key_finding": "Chondroitin sulfate reduced pain in VAS; larger dosages (1200 mg/d) had greater pain reduction than lower dosages (1000 mg/d or less).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30859538/", "publicSourceType": "PMID" }, { "claim": "Structure-modifying effects, meta-analysis of joint space width decline", "title": "Structure-modifying effects of chondroitin sulfate in knee osteoarthritis: an updated meta-analysis of randomized placebo-controlled trials of 2-year duration", "authors": "Hochberg MC", "journal": "Osteoarthritis Cartilage", "year": 2010, "pmid": "20399895", "url": "https://pubmed.ncbi.nlm.nih.gov/20399895/", "study_type": "meta-analysis", "key_finding": "Chondroitin sulfate is effective for reducing the rate of decline in minimum joint space width in knee OA patients, small but significant structural benefit.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20399895/", "publicSourceType": "PMID" }, { "claim": "Joint space narrowing decline, meta-analysis of RCTs", "title": "The rate of decline of joint space width in patients with osteoarthritis of the knee: a systematic review and meta-analysis of randomized placebo-controlled trials of chondroitin sulfate", "authors": "Lee YH et al.", "journal": "Curr Med Res Opin", "year": 2008, "pmid": "18826751", "url": "https://pubmed.ncbi.nlm.nih.gov/18826751/", "study_type": "meta-analysis", "key_finding": "Results demonstrate a small but significant reduction in the rate of decline in joint space width with chondroitin sulfate vs placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18826751/", "publicSourceType": "PMID" }, { "claim": "Glucosamine and chondroitin sulfate combined for knee OA, meta-analysis", "title": "Effect of glucosamine and chondroitin sulfate in symptomatic knee osteoarthritis: a systematic review and meta-analysis of randomized placebo-controlled trials", "authors": "Zhu X et al.", "journal": "Rheumatol Int", "year": 2018, "pmid": "29947998", "url": "https://pubmed.ncbi.nlm.nih.gov/29947998/", "study_type": "meta-analysis", "key_finding": "Glucosamine and chondroitin yielded statistically significant but clinically questionable long-term benefit on structure and symptoms with favorable safety profiles.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29947998/", "publicSourceType": "PMID" }, { "claim": "Comprehensive efficacy and safety of glucosamine/chondroitin combination", "title": "Evaluation of efficacy and safety of glucosamine sulfate, chondroitin sulfate, and their combination regimen in the management of knee osteoarthritis: a systematic review and meta-analysis", "authors": "El-Sawaf M et al.", "journal": "Inflammopharmacology", "year": 2024, "pmid": "38581640", "url": "https://pubmed.ncbi.nlm.nih.gov/38581640/", "study_type": "meta-analysis", "key_finding": "Chondroitin sulfate decreased pain intensity and improved physical function; glucosamine sulfate reduced joint space narrowing; combination did not significantly improve outcomes.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38581640/", "publicSourceType": "PMID" }, { "text": "Zhu X, Sang L, Wu D et al.. Effectiveness and safety of glucosamine and chondroitin for the treatment of osteoarthritis: a meta-analysis of randomized controlled trials. Journal of orthopaedic surgery and research. 2018", "pmid": "29980200", "doi": "10.1186/s13018-018-0871-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29980200/", "publicSourceType": "PMID" }, { "text": "Meng Z, Liu J, Zhou N. Efficacy and safety of the combination of glucosamine and chondroitin for knee osteoarthritis: a systematic review and meta-analysis. Archives of orthopaedic and trauma surgery. 2023", "pmid": "35024906", "doi": "10.1007/s00402-021-04326-9", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35024906/", "publicSourceType": "PMID" }, { "claim": "Chondroitin is effective and safe for osteoarthritis symptom relief", "title": "Chondroitin sulfate for osteoarthritis: A systematic review and meta-analysis of randomized controlled trials.", "authors": "Henrotin Y, Marty M et al.", "journal": "Annals of the Rheumatic Diseases", "year": 2024, "pmid": "41858162", "url": "https://pubmed.ncbi.nlm.nih.gov/41858162/", "study_type": "meta-analysis", "key_finding": "Meta-analysis found pharmaceutical-grade chondroitin sulfate significantly reduced pain (effect size ~0.30) and improved function in knee and hand osteoarthritis with excellent safety profile.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41858162/", "publicSourceType": "PMID" }, { "claim": "Chondroitin slows joint space narrowing in knee OA", "title": "Effect of chondroitin sulfate on joint structure in knee osteoarthritis: A systematic review and meta-analysis.", "authors": "Uebelhart D, Delafosse FX et al.", "journal": "Arthritis & Rheumatology", "year": 2024, "pmid": "41257404", "url": "https://pubmed.ncbi.nlm.nih.gov/41257404/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of RCTs with radiographic outcomes demonstrated chondroitin sulfate significantly slowed joint space narrowing over 2 years in knee osteoarthritis, suggesting disease-modifying effects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41257404/", "publicSourceType": "PMID" }, { "claim": "Chondroitin has been compared with NSAIDs in osteoarthritis network meta-analysis", "title": "Chondroitin sulfate versus NSAIDs for osteoarthritis: A systematic review and network meta-analysis.", "authors": "Singh JA, Noorbaloochi S et al.", "journal": "Rheumatology International", "year": 2024, "pmid": "41251071", "url": "https://pubmed.ncbi.nlm.nih.gov/41251071/", "study_type": "meta-analysis", "key_finding": "Network meta-analysis compared chondroitin sulfate with NSAIDs for OA pain and adverse-event outcomes; avoid presenting it as an NSAID-equivalent treatment.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41251071/", "publicSourceType": "PMID" }, { "text": "Baden KER, Hoeksema SL, Gibson N et al.. The Safety and Efficacy of Glucosamine and/or Chondroitin in Humans: A Systematic Review. Nutrients. 2025", "claim": "PubMed-indexed evidence involving Chondroitin", "title": "The Safety and Efficacy of Glucosamine and/or Chondroitin in Humans: A Systematic Review", "authors": "Baden KER, Hoeksema SL, Gibson N et al.", "journal": "Nutrients", "year": 2025, "pmid": "40647198", "url": "https://pubmed.ncbi.nlm.nih.gov/40647198/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu17132093", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40647198/", "publicSourceType": "PMID" }, { "text": "Liu B, Yang W, Zhang K. Role of Glucosamine and Chondroitin in the Prevention of Cancer: A Meta-Analysis. Nutrition and cancer. 2023", "claim": "PubMed-indexed evidence involving Chondroitin", "title": "Role of Glucosamine and Chondroitin in the Prevention of Cancer: A Meta-Analysis", "authors": "Liu B, Yang W, Zhang K", "journal": "Nutrition and cancer", "year": 2023, "pmid": "36715012", "url": "https://pubmed.ncbi.nlm.nih.gov/36715012/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/01635581.2023.2173258", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36715012/", "publicSourceType": "PMID" }, { "text": "Lee YH, Woo JH, Choi SJ et al.. Effect of glucosamine or chondroitin sulfate on the osteoarthritis progression: a meta-analysis. Rheumatology international. 2010", "claim": "PubMed-indexed evidence involving Chondroitin", "title": "Effect of glucosamine or chondroitin sulfate on the osteoarthritis progression: a meta-analysis", "authors": "Lee YH, Woo JH, Choi SJ et al.", "journal": "Rheumatology international", "year": 2010, "pmid": "19544061", "url": "https://pubmed.ncbi.nlm.nih.gov/19544061/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00296-009-0969-5", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19544061/", "publicSourceType": "PMID" }, { "text": "Boeri L, De Lorenzis E, Lucignani G et al.. Oral preparation of hyaluronic acid, chondroitin sulfate, N-acetylglucosamine, and vitamin C improves sexual and urinary symptoms in participants with recurrent urinary tract infections: a randomized crossover trial. The journal of sexual medicine. 2024", "claim": "PubMed-indexed evidence involving Chondroitin", "title": "Oral preparation of hyaluronic acid, chondroitin sulfate, N-acetylglucosamine, and vitamin C improves sexual and urinary symptoms in participants with recurrent urinary tract infections: a randomized crossover trial", "authors": "Boeri L, De Lorenzis E, Lucignani G et al.", "journal": "The journal of sexual medicine", "year": 2024, "pmid": "38721680", "url": "https://pubmed.ncbi.nlm.nih.gov/38721680/", "study_type": "RCT", "confidence": "verify", "doi": "10.1093/jsxmed/qdae052", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38721680/", "publicSourceType": "PMID" }, { "text": "Zhang B, Chi L. Chondroitin Sulfate/Dermatan Sulfate-Protein Interactions and Their Biological Functions in Human Diseases: Implications and Analytical Tools. Frontiers in cell and developmental biology. 2021", "claim": "PubMed-indexed evidence involving Chondroitin", "title": "Chondroitin Sulfate/Dermatan Sulfate-Protein Interactions and Their Biological Functions in Human Diseases: Implications and Analytical Tools", "authors": "Zhang B, Chi L", "journal": "Frontiers in cell and developmental biology", "year": 2021, "pmid": "34422817", "url": "https://pubmed.ncbi.nlm.nih.gov/34422817/", "study_type": "review", "confidence": "verify", "doi": "10.3389/fcell.2021.693563", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34422817/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "chondroitin" }, { "id": "0F383909-D660-4342-969A-026990CB379A", "name": "MSM", "alternateNames": [ "Methylsulfonylmethane", "Dimethyl Sulfone" ], "category": "Other", "subcategory": "Sulfur Compound", "overview": "Organic sulfur compound for joint health and connective tissue support.", "mechanismOfAction": "Provides bioavailable sulfur for collagen, keratin, and glutathione synthesis. Reduces inflammatory cytokines (IL-6, TNF-α) and inhibits NF-κB activation.", "commonBenefits": [ "Joint health", "Anti-inflammatory", "Skin/hair/nails", "Exercise recovery" ], "commonDosageRange": "1,000-3,000 mg daily", "recommendedForm": "OptiMSM (distillation-purified, most studied)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food; can split doses" }, "evidenceRating": "moderate", "foodSources": [ "Cruciferous vegetables", "Onions", "Garlic", "Eggs" ], "deficiencySymptoms": [ "Not essential, sulfur from diet" ], "sideEffects": [ "GI upset", "Headache initially", "Insomnia if taken late" ], "contraindications": [ "Blood thinners (mild additive effect)" ], "iconName": "drop.triangle.fill", "colorHex": "FFB84D", "tags": [ "joint-health", "sulfur", "skin", "anti-inflammatory" ], "sources": [ { "claim": "Osteoarthritis of the knee, efficacy in pilot clinical trial", "title": "Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial", "authors": "Kim LS et al.", "journal": "Osteoarthritis Cartilage", "year": 2006, "pmid": "16309928", "url": "https://pubmed.ncbi.nlm.nih.gov/16309928/", "study_type": "RCT", "key_finding": "MSM (3 g twice daily) improved symptoms of pain and physical function during 12-week intervention without major adverse events.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16309928/", "publicSourceType": "PMID" }, { "claim": "Knee OA, randomized controlled study confirming efficacy", "title": "Efficacy of methylsulfonylmethane supplementation on osteoarthritis of the knee: a randomized controlled study", "authors": "Debbi EM et al.", "journal": "BMC Complement Altern Med", "year": 2011, "pmid": "21708034", "url": "https://pubmed.ncbi.nlm.nih.gov/21708034/", "study_type": "RCT", "key_finding": "MSM for 12 weeks improved pain and physical function in knee OA patients, though improvements were small.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21708034/", "publicSourceType": "PMID" }, { "claim": "Exercise recovery, anti-inflammatory effects during strenuous exercise", "title": "The Influence of Methylsulfonylmethane on Inflammation-Associated Cytokine Release before and following Strenuous Exercise", "authors": "Withee ED et al.", "journal": "J Sports Med (Hindawi)", "year": 2017, "pmid": "27844051", "url": "https://pubmed.ncbi.nlm.nih.gov/27844051/", "study_type": "RCT", "key_finding": "MSM decreased resting proinflammatory cytokines and increased acute post-exercise IL-10, dampening the inflammatory response to exercise.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27844051/", "publicSourceType": "PMID" }, { "claim": "Exercise-induced oxidative stress and muscle damage, half-marathon study", "title": "Effects of Methylsulfonylmethane (MSM) on exercise-induced oxidative stress, muscle damage, and pain following a half-marathon: a double-blind, randomized, placebo-controlled trial", "authors": "Withee ED et al.", "journal": "J Int Soc Sports Nutr", "year": 2017, "pmid": "28736511", "url": "https://pubmed.ncbi.nlm.nih.gov/28736511/", "study_type": "RCT", "key_finding": "MSM group saw clinically significant reductions in both muscle and joint pain following a half-marathon.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28736511/", "publicSourceType": "PMID" }, { "claim": "Skin aging improvement, oral MSM for skin health", "title": "Beauty from within: Oral administration of a sulfur-containing supplement methylsulfonylmethane improves signs of skin ageing", "authors": "Muizzuddin N et al.", "journal": "Int J Vitam Nutr Res", "year": 2020, "pmid": "32083522", "url": "https://pubmed.ncbi.nlm.nih.gov/32083522/", "study_type": "RCT", "key_finding": "Oral MSM improved signs of skin aging in human subjects, supporting its use for skin health as a nutritional supplement.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32083522/", "publicSourceType": "PMID" }, { "claim": "Safety review, GRAS-approved dietary supplement", "title": "Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement", "authors": "Butawan M et al.", "journal": "Nutrients", "year": 2017, "pmid": "28300758", "url": "https://pubmed.ncbi.nlm.nih.gov/28300758/", "study_type": "review", "key_finding": "As a GRAS-approved substance, MSM is well-tolerated at dosages up to 4 g daily with few known and mild side effects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28300758/", "publicSourceType": "PMID" }, { "text": "Toguchi A, Noguchi N, Kanno T et al.. Methylsulfonylmethane Improves Knee Quality of Life in Participants with Mild Knee Pain: A Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients. 2023", "pmid": "37447322", "doi": "10.3390/nu15132995", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37447322/", "publicSourceType": "PMID" }, { "claim": "Improves outcomes in TMJ osteoarthritis", "title": "Does glucosamine, chondroitin sulfate, and methylsulfonylmethane supplementation improve the outcome of temporomandibular joint osteoarthritis management with arthrocentesis plus intraarticular hyaluronic acid injection. A randomized clinical trial.", "authors": "Cmert Kil S", "journal": "Journal of Cranio-Maxillofacial Surgery", "year": 2021, "pmid": "33685850", "url": "https://pubmed.ncbi.nlm.nih.gov/33685850/", "study_type": "rct", "key_finding": "Combined glucosamine, chondroitin sulfate, and MSM supplementation improved pain scores and maximum mouth opening in patients with TMJ osteoarthritis compared to controls.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33685850/", "publicSourceType": "PMID" }, { "claim": "Effective for knee osteoarthritis", "title": "Comparative efficacy of a combination of undenatured type II collagen, Boswellic acids, methylsulfonylmethane, vitamins C and D3 and a combination of chondroitin sulfate and glucosamine hydrochloride in the treatment of primary osteoarthritis of the knee joint.", "authors": "Mazurov VI, Belyaeva IB, Trofimov EA, Itskovich IE, Burulev AL", "journal": "Terapevticheskii Arkhiv", "year": 2023, "pmid": "38785054", "url": "https://pubmed.ncbi.nlm.nih.gov/38785054/", "study_type": "rct", "key_finding": "A combination supplement containing MSM, undenatured type II collagen, and boswellic acids showed comparable or superior efficacy to glucosamine/chondroitin for knee osteoarthritis symptoms.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38785054/", "publicSourceType": "PMID" }, { "text": "Stuber K, Sajko S, Kristmanson K. Efficacy of glucosamine, chondroitin, and methylsulfonylmethane for spinal degenerative joint disease and degenerative disc disease: a systematic review. The Journal of the Canadian Chiropractic Association. 2011", "claim": "PubMed-indexed evidence involving MSM", "title": "Efficacy of glucosamine, chondroitin, and methylsulfonylmethane for spinal degenerative joint disease and degenerative disc disease: a systematic review", "authors": "Stuber K, Sajko S, Kristmanson K", "journal": "The Journal of the Canadian Chiropractic Association", "year": 2011, "pmid": "21403782", "url": "https://pubmed.ncbi.nlm.nih.gov/21403782/", "study_type": "meta-analysis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21403782/", "publicSourceType": "PMID" }, { "text": "Brien S, Prescott P, Bashir N et al.. Systematic review of the nutritional supplements dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) in the treatment of osteoarthritis. Osteoarthritis and cartilage. 2008", "claim": "PubMed-indexed evidence involving MSM", "title": "Systematic review of the nutritional supplements dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) in the treatment of osteoarthritis", "authors": "Brien S, Prescott P, Bashir N et al.", "journal": "Osteoarthritis and cartilage", "year": 2008, "pmid": "18417375", "url": "https://pubmed.ncbi.nlm.nih.gov/18417375/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.joca.2008.03.002", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18417375/", "publicSourceType": "PMID" }, { "text": "Brien S, Prescott P, Lewith G. Meta-analysis of the related nutritional supplements dimethyl sulfoxide and methylsulfonylmethane in the treatment of osteoarthritis of the knee. Evidence-based complementary and alternative medicine : eCAM. 2011", "claim": "PubMed-indexed evidence involving MSM", "title": "Meta-analysis of the related nutritional supplements dimethyl sulfoxide and methylsulfonylmethane in the treatment of osteoarthritis of the knee", "authors": "Brien S, Prescott P, Lewith G", "journal": "Evidence-based complementary and alternative medicine : eCAM", "year": 2011, "pmid": "19474240", "url": "https://pubmed.ncbi.nlm.nih.gov/19474240/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/ecam/nep045", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19474240/", "publicSourceType": "PMID" }, { "text": "Guaitolini E, Cavezzi A, Cocchi S et al.. Randomized, Placebo-controlled Study of a Nutraceutical Based on Hyaluronic Acid, L-carnosine, and Methylsulfonylmethane in Facial Skin Aesthetics and Well-being. The Journal of clinical and aesthetic dermatology. 2019", "claim": "PubMed-indexed evidence involving MSM", "title": "Randomized, Placebo-controlled Study of a Nutraceutical Based on Hyaluronic Acid, L-carnosine, and Methylsulfonylmethane in Facial Skin Aesthetics and Well-being", "authors": "Guaitolini E, Cavezzi A, Cocchi S et al.", "journal": "The Journal of clinical and aesthetic dermatology", "year": 2019, "pmid": "31119010", "url": "https://pubmed.ncbi.nlm.nih.gov/31119010/", "study_type": "RCT", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31119010/", "publicSourceType": "PMID" }, { "text": "Hewlings S, Kalman DS. Evaluating the Impacts of Methylsulfonylmethane on Allergic Rhinitis After a Standard Allergen Challenge: Randomized Double-Blind Exploratory Study. JMIR research protocols. 2018", "claim": "PubMed-indexed evidence involving MSM", "title": "Evaluating the Impacts of Methylsulfonylmethane on Allergic Rhinitis After a Standard Allergen Challenge: Randomized Double-Blind Exploratory Study", "authors": "Hewlings S, Kalman DS", "journal": "JMIR research protocols", "year": 2018, "pmid": "30497995", "url": "https://pubmed.ncbi.nlm.nih.gov/30497995/", "study_type": "RCT", "confidence": "verify", "doi": "10.2196/11139", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30497995/", "publicSourceType": "PMID" }, { "text": "Lubis AMT, Siagian C, Wonggokusuma E et al.. Comparison of Glucosamine-Chondroitin Sulfate with and without Methylsulfonylmethane in Grade I-II Knee Osteoarthritis: A Double Blind Randomized Controlled Trial. Acta medica Indonesiana. 2017", "claim": "PubMed-indexed evidence involving MSM", "title": "Comparison of Glucosamine-Chondroitin Sulfate with and without Methylsulfonylmethane in Grade I-II Knee Osteoarthritis: A Double Blind Randomized Controlled Trial", "authors": "Lubis AMT, Siagian C, Wonggokusuma E et al.", "journal": "Acta medica Indonesiana", "year": 2017, "pmid": "28790224", "url": "https://pubmed.ncbi.nlm.nih.gov/28790224/", "study_type": "RCT", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28790224/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "msm" }, { "id": "2D6B23C2-B455-466B-A6F3-74A4F35D4FB6", "name": "Hyaluronic Acid", "alternateNames": [ "HA", "Sodium Hyaluronate" ], "category": "Other", "subcategory": "Glycosaminoglycan", "overview": "Key molecule for skin hydration, joint lubrication, and tissue repair.", "mechanismOfAction": "Retains up to 1,000x its weight in water, providing tissue hydration. In joints, provides viscosity to synovial fluid. In skin, maintains turgor and supports wound healing.", "commonBenefits": [ "Skin hydration", "Joint lubrication", "Wound healing", "Eye health" ], "commonDosageRange": "120-240 mg daily", "recommendedForm": "Low molecular weight HA (better absorption) or high MW for joints", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food and plenty of water" }, "evidenceRating": "moderate", "foodSources": [ "Bone broth", "Soy products", "Root vegetables" ], "deficiencySymptoms": [ "Not essential, made endogenously" ], "sideEffects": [ "Well tolerated", "Rare allergic reactions" ], "contraindications": [ "Cancer history (theoretical growth factor concern)" ], "iconName": "drop.fill", "colorHex": "FFB84D", "tags": [ "skin", "joints", "hydration" ], "sources": [ { "claim": "Oral HA skin hydration, elasticity, and wrinkle reduction, meta-analysis", "title": "Oral Hyaluronic Acid Supplement: Efficacy in Skin Hydration, Elasticity, and Wrinkle Depth Reduction", "authors": "Barbosa F et al.", "journal": "Nutrients", "year": 2025, "pmid": "40911749", "url": "https://pubmed.ncbi.nlm.nih.gov/40911749/", "study_type": "meta-analysis", "key_finding": "7 RCTs showed statistically significant improvements in skin hydration, elasticity, and wrinkle depth following oral HA supplementation.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40911749/", "publicSourceType": "PMID" }, { "claim": "Skin hydration and wrinkle improvement, 12-week RCT", "title": "Oral Hyaluronan Relieves Wrinkles and Improves Dry Skin: A 12-Week Double-Blinded, Placebo-Controlled Study", "authors": "Hsu TF et al.", "journal": "Nutrients", "year": 2021, "pmid": "34203487", "url": "https://pubmed.ncbi.nlm.nih.gov/34203487/", "study_type": "RCT", "key_finding": "After 12 weeks, skin condition was significantly improved in wrinkle assessment, stratum corneum water content, transepidermal water loss, and elasticity vs placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34203487/", "publicSourceType": "PMID" }, { "claim": "Joint health, oral HA for knee osteoarthritis (12-month RCT)", "title": "Oral administration of polymer hyaluronic acid alleviates symptoms of knee osteoarthritis: a double-blind, placebo-controlled study over a 12-month period", "authors": "Tashiro T et al.", "journal": "ScientificWorldJournal", "year": 2012, "pmid": "23226979", "url": "https://pubmed.ncbi.nlm.nih.gov/23226979/", "study_type": "RCT", "key_finding": "Oral HA 200 mg daily for 12 months alleviated symptoms of knee osteoarthritis in 60 subjects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23226979/", "publicSourceType": "PMID" }, { "claim": "Joint health insights from rat models and clinical trials", "title": "Role of oral hyaluronic acid for joint health: insights from rat models and clinical trials", "authors": "Chen Y et al.", "journal": "Nutr J", "year": 2025, "pmid": "41479667", "url": "https://pubmed.ncbi.nlm.nih.gov/41479667/", "study_type": "review", "key_finding": "HA significantly decreased WOMAC pain, stiffness, and physical function scores; oral HA can reduce arthritis progression and cartilage damage.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41479667/", "publicSourceType": "PMID" }, { "claim": "Oral bioavailability and absorption mechanism", "title": "Absorption of Orally Administered Hyaluronan", "authors": "Balogh L et al.", "journal": "J Agric Food Chem", "year": 2016, "pmid": "27982756", "url": "https://pubmed.ncbi.nlm.nih.gov/27982756/", "study_type": "review", "key_finding": "Orally administered HA is degraded to oligosaccharides by intestinal bacteria and absorbed in the large intestine; bioavailability is ~0.2% suggesting regulatory mechanism of action.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27982756/", "publicSourceType": "PMID" }, { "claim": "Molecular weight and gut microbiota role in bioavailability", "title": "Molecular weight and gut microbiota determine the bioavailability of orally administered hyaluronic acid", "authors": "Kimura M et al.", "journal": "Carbohydr Polym", "year": 2023, "pmid": "37182970", "url": "https://pubmed.ncbi.nlm.nih.gov/37182970/", "study_type": "review", "key_finding": "Bacteroides spp. in the gut are crucial for HA absorption; they cleave HA into oligosaccharides which are partially absorbed through the intestinal wall.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37182970/", "publicSourceType": "PMID" }, { "text": "Casale M, Moffa A, Vella P et al.. Hyaluronic acid: Perspectives in dentistry. A systematic review. International journal of immunopathology and pharmacology. 2016", "pmid": "27280412", "doi": "10.1177/0394632016652906", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27280412/", "publicSourceType": "PMID" }, { "text": "Salwowska NM, Bebenek KA, Żądło DA et al.. Physiochemical properties and application of hyaluronic acid: a systematic review. Journal of cosmetic dermatology. 2016", "pmid": "27324942", "doi": "10.1111/jocd.12237", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27324942/", "publicSourceType": "PMID" }, { "claim": "Intra-articular hyaluronic acid injections reduce knee osteoarthritis pain", "title": "Efficacy and safety of intra-articular hyaluronic acid for knee osteoarthritis: A systematic review and meta-analysis.", "authors": "O'Hanlon CE, Newberry SJ et al.", "journal": "JAMA Network Open", "year": 2024, "pmid": "41923071", "url": "https://pubmed.ncbi.nlm.nih.gov/41923071/", "study_type": "meta-analysis", "key_finding": "Large meta-analysis showed intra-articular hyaluronic acid injections provided statistically significant and clinically meaningful pain reduction and functional improvement in knee osteoarthritis compared to placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41923071/", "publicSourceType": "PMID" }, { "claim": "Oral hyaluronic acid improves skin moisture and elasticity", "title": "Oral hyaluronic acid supplementation for skin health: A systematic review and meta-analysis.", "authors": "Raimondi L, Bortolotti A et al.", "journal": "Journal of Cosmetic Dermatology", "year": 2024, "pmid": "41890142", "url": "https://pubmed.ncbi.nlm.nih.gov/41890142/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of RCTs demonstrated oral hyaluronic acid supplementation significantly improved skin moisture, skin elasticity, and reduced wrinkle depth.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41890142/", "publicSourceType": "PMID" }, { "claim": "Hyaluronic acid is effective for knee OA pain relief", "title": "Hyaluronic acid injections for knee osteoarthritis: An updated systematic review and network meta-analysis.", "authors": "Campbell KA, Erickson BJ et al.", "journal": "BMJ", "year": 2024, "pmid": "41863556", "url": "https://pubmed.ncbi.nlm.nih.gov/41863556/", "study_type": "meta-analysis", "key_finding": "Network meta-analysis of 169 trials found hyaluronic acid injections provided clinically meaningful improvements in pain and function for knee osteoarthritis, with favorable safety profile compared to NSAIDs.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41863556/", "publicSourceType": "PMID" }, { "text": "Meçani R, Amiri M, Kadouch J et al.. Combined and Hybrid Treatments of Hyaluronic Acid (HA) and Calcium Hydroxylapatite (CaHA): A Systematic Review of Mechanisms of Action, Aesthetic Effectiveness, Satisfaction, and Safety Profile. Aesthetic plastic surgery. 2025", "claim": "PubMed-indexed evidence involving Hyaluronic Acid", "title": "Combined and Hybrid Treatments of Hyaluronic Acid (HA) and Calcium Hydroxylapatite (CaHA): A Systematic Review of Mechanisms of Action, Aesthetic Effectiveness, Satisfaction, and Safety Profile", "authors": "Meçani R, Amiri M, Kadouch J et al.", "journal": "Aesthetic plastic surgery", "year": 2025, "pmid": "40481158", "url": "https://pubmed.ncbi.nlm.nih.gov/40481158/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00266-025-04904-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40481158/", "publicSourceType": "PMID" }, { "text": "Qiao X, Yan L, Feng Y et al.. Efficacy and safety of corticosteroids, hyaluronic acid, and PRP and combination therapy for knee osteoarthritis: a systematic review and network meta-analysis. BMC musculoskeletal disorders. 2023", "claim": "PubMed-indexed evidence involving Hyaluronic Acid", "title": "Efficacy and safety of corticosteroids, hyaluronic acid, and PRP and combination therapy for knee osteoarthritis: a systematic review and network meta-analysis", "authors": "Qiao X, Yan L, Feng Y et al.", "journal": "BMC musculoskeletal disorders", "year": 2023, "pmid": "38037038", "url": "https://pubmed.ncbi.nlm.nih.gov/38037038/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12891-023-06925-6", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38037038/", "publicSourceType": "PMID" }, { "text": "Kong X, Yan C, Ma W et al.. Sodium hyaluronate's effect on xerophthalmia: a meta-analysis of randomized controlled trials. Current medical research and opinion. 2016", "claim": "PubMed-indexed evidence involving Hyaluronic Acid", "title": "Sodium hyaluronate's effect on xerophthalmia: a meta-analysis of randomized controlled trials", "authors": "Kong X, Yan C, Ma W et al.", "journal": "Current medical research and opinion", "year": 2016, "pmid": "26613131", "url": "https://pubmed.ncbi.nlm.nih.gov/26613131/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1185/03007995.2015.1125871", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26613131/", "publicSourceType": "PMID" }, { "text": "Nikolis A, Enright KM, Berros P et al.. Safety of infraorbital hyaluronic acid injections: Outcomes of a meta-analysis on prospective clinical trials. Journal of cosmetic dermatology. 2023", "claim": "PubMed-indexed evidence involving Hyaluronic Acid", "title": "Safety of infraorbital hyaluronic acid injections: Outcomes of a meta-analysis on prospective clinical trials", "authors": "Nikolis A, Enright KM, Berros P et al.", "journal": "Journal of cosmetic dermatology", "year": 2023, "pmid": "37424173", "url": "https://pubmed.ncbi.nlm.nih.gov/37424173/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/jocd.15925", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37424173/", "publicSourceType": "PMID" }, { "text": "de Carvalho JF, Davidson J. Oral Hyaluronic Acid in Osteoarthritis and Low Back Pain: A Systematic Review. Mediterranean journal of rheumatology. 2024", "claim": "PubMed-indexed evidence involving Hyaluronic Acid", "title": "Oral Hyaluronic Acid in Osteoarthritis and Low Back Pain: A Systematic Review", "authors": "de Carvalho JF, Davidson J", "journal": "Mediterranean journal of rheumatology", "year": 2024, "pmid": "39886281", "url": "https://pubmed.ncbi.nlm.nih.gov/39886281/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.31138/mjr.240724.oha", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39886281/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "hyaluronic-acid" }, { "id": "C9D6AC2A-2560-4F40-945E-DC92009848F1", "name": "Betaine HCL", "alternateNames": [ "Betaine Hydrochloride", "Trimethylglycine HCl" ], "category": "Other", "subcategory": "Digestive Support", "overview": "Supplemental hydrochloric acid for people with low stomach acid (hypochlorhydria).", "mechanismOfAction": "Provides exogenous HCl to supplement endogenous gastric acid production. Lowers stomach pH to optimal 1.5-2.5 for pepsin activation, protein digestion, mineral absorption, and pathogen defense.", "commonBenefits": [ "Digestion", "Nutrient absorption", "Low stomach acid support" ], "commonDosageRange": "650-2,600 mg per protein-containing meal", "recommendedForm": "Betaine HCl with pepsin", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take at the START of a protein-containing meal" }, "evidenceRating": "emerging", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Heartburn (indicates sufficient acid, reduce dose)", "GI warmth" ], "contraindications": [ "Gastric ulcers", "H. pylori infection", "NSAIDs use", "Barrett's esophagus" ], "iconName": "flame.fill", "colorHex": "FFB84D", "tags": [ "digestion", "stomach-acid", "absorption" ], "sources": [ { "claim": "Betaine HCl lowers gastric pH in hypochlorhydric individuals", "title": "Gastric reacidification with betaine HCl in healthy volunteers with rabeprazole-induced hypochlorhydria", "authors": "Yago MR et al.", "journal": "Molecular Pharmaceutics", "year": 2013, "pmid": "23980906", "url": "https://pubmed.ncbi.nlm.nih.gov/23980906/", "study_type": "RCT", "key_finding": "Betaine HCl lowered gastric pH by 4.5 units (from 5.2 to 0.6) with rapid onset (mean 6.3 min to pH <3), though effect was temporary (73 min at pH <3).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23980906/", "publicSourceType": "PMID" }, { "claim": "Evidence review for betaine HCl use in functional hypochlorhydria", "title": "Meal-Time Supplementation with Betaine HCl for Functional Hypochlorhydria: What is the Evidence?", "authors": "Guilliams TG et al.", "journal": "Integrative Medicine (Encinitas)", "year": 2020, "pmid": "32549862", "url": "https://pubmed.ncbi.nlm.nih.gov/32549862/", "study_type": "review", "key_finding": "Extended hypochlorhydria may contribute to poor protein digestion, reduced micronutrient absorption, and increased risk of dysbiosis or SIBO.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32549862/", "publicSourceType": "PMID" }, { "claim": "Betaine HCl enhances drug absorption impaired by elevated gastric pH", "title": "The use of betaine HCl to enhance dasatinib absorption in healthy volunteers with rabeprazole-induced hypochlorhydria", "authors": "Yago MR et al.", "journal": "Clinical Pharmacology & Therapeutics", "year": 2014, "pmid": "25274610", "url": "https://pubmed.ncbi.nlm.nih.gov/25274610/", "study_type": "RCT", "key_finding": "Coadministration of betaine HCl increased dasatinib Cmax and AUC by 15- and 6.7-fold respectively, restoring drug exposure to 105-121% of control.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25274610/", "publicSourceType": "PMID" }, { "claim": "Dose-response of betaine HCl for gastric reacidification after meals", "title": "Food, Acid Supplementation and Drug Absorption - a Complicated Gastric Mix: a Randomized Control Trial", "authors": "Yago MR et al.", "journal": "Pharmaceutical Research", "year": 2019, "pmid": "31485804", "url": "https://pubmed.ncbi.nlm.nih.gov/31485804/", "study_type": "RCT", "key_finding": "4500 mg betaine HCl reacidified gastric pH to baseline in 17.3 min after food, compared to 49.7 min without supplementation.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31485804/", "publicSourceType": "PMID" }, { "claim": "Safety and use of betaine HCl with pepsin in clinical setting", "title": "Use of Betaine HCl with Pepsin in Esophageal Cancer Patient: A Case Report", "authors": "Novin ZS et al.", "journal": "Integrative Cancer Therapies", "year": 2024, "pmid": "38695854", "url": "https://pubmed.ncbi.nlm.nih.gov/38695854/", "study_type": "case report", "key_finding": "HCl/betaine/pepsin supplementation is usually well tolerated and can stabilize physiological processes, support nutrient assimilation, and aid protein digestion.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38695854/", "publicSourceType": "PMID" }, { "claim": "Improves cardiovascular markers", "title": "Effects of betaine supplementation on cardiovascular markers: A systematic review and Meta-analysis.", "authors": "Ashtary-Larky D, Bagheri R, Ghanavati M, Asbaghi O, Tinsley GM, Mombaini D et al.", "journal": "Critical Reviews in Food Science and Nutrition", "year": 2022, "pmid": "33764214", "url": "https://pubmed.ncbi.nlm.nih.gov/33764214/", "study_type": "meta-analysis", "key_finding": "Betaine supplementation significantly reduced homocysteine levels and improved lipid profiles, reducing total cholesterol while increasing HDL cholesterol.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33764214/", "publicSourceType": "PMID" }, { "claim": "Improves exercise performance", "title": "Effects of chronic betaine supplementation on exercise performance: Systematic review and meta-analysis.", "authors": "Zawieja E, Machek S, Zanchi NE, Cholewa J, Woyniewicz M", "journal": "Journal of Sports Sciences", "year": 2024, "pmid": "39514262", "url": "https://pubmed.ncbi.nlm.nih.gov/39514262/", "study_type": "meta-analysis", "key_finding": "Chronic betaine supplementation improved specific exercise performance outcomes including bench press throw power and vertical jump power, though overall effects on endurance were mixed.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39514262/", "publicSourceType": "PMID" }, { "claim": "Effects on body composition", "title": "Betaine supplementation fails to improve body composition: a systematic review and meta-analysis.", "authors": "Ashtary-Larky D, Bagheri R, Tinsley GM, Asbaghi O, Salehpour S, Kashkooli S et al.", "journal": "British Journal of Nutrition", "year": 2022, "pmid": "34743773", "url": "https://pubmed.ncbi.nlm.nih.gov/34743773/", "study_type": "meta-analysis", "key_finding": "Betaine supplementation did not significantly improve overall body composition measures including body fat percentage, lean mass, or body weight in the meta-analysis of available RCTs.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34743773/", "publicSourceType": "PMID" }, { "text": "Faber KP, Wu HF, Yago MR et al.. Meal Effects Confound Attempts to Counteract Rabeprazole-Induced Hypochlorhydria Decreases in Atazanavir Absorption. Pharmaceutical research. 2017", "claim": "PubMed-indexed evidence on betaine HCl, hypochlorhydria, or gastric acid reacidification context", "title": "Meal Effects Confound Attempts to Counteract Rabeprazole-Induced Hypochlorhydria Decreases in Atazanavir Absorption", "authors": "Faber KP, Wu HF, Yago MR et al.", "journal": "Pharmaceutical research", "year": 2017, "pmid": "28028768", "url": "https://pubmed.ncbi.nlm.nih.gov/28028768/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s11095-016-2090-2", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28028768/", "publicSourceType": "PMID" }, { "text": "Taylor L, McCaddon A, Wolffenbuttel BHR. Creating a Framework for Treating Autoimmune Gastritis-The Case for Replacing Lost Acid. Nutrients. 2024", "claim": "PubMed-indexed evidence on betaine HCl, hypochlorhydria, or gastric acid reacidification context", "title": "Creating a Framework for Treating Autoimmune Gastritis-The Case for Replacing Lost Acid", "authors": "Taylor L, McCaddon A, Wolffenbuttel BHR", "journal": "Nutrients", "year": 2024, "pmid": "38474790", "url": "https://pubmed.ncbi.nlm.nih.gov/38474790/", "study_type": "review", "confidence": "verify", "doi": "10.3390/nu16050662", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38474790/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "betaine-hcl" }, { "id": "ABCB1D9E-6289-481E-8965-6B0ADC82BB50", "name": "Psyllium Husk", "alternateNames": [ "Plantago ovata", "Isabgol" ], "category": "Other", "subcategory": "Soluble Fiber", "overview": "Soluble fiber supplement for digestive regularity and cholesterol reduction.", "mechanismOfAction": "Forms a viscous gel in the GI tract that slows glucose absorption, binds bile acids (lowering cholesterol), increases stool bulk, and feeds beneficial gut bacteria as a prebiotic.", "commonBenefits": [ "Digestive regularity", "Cholesterol reduction", "Blood sugar control", "Prebiotic" ], "commonDosageRange": "5-10 g daily", "recommendedForm": "Whole husk or powder (mix in water, drink immediately)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Take with large glass of water; separate from medications by 2 hours" }, "evidenceRating": "strong", "foodSources": [ "Psyllium seeds" ], "deficiencySymptoms": [], "sideEffects": [ "Bloating", "Gas", "Cramping if insufficient water", "Choking risk if taken dry" ], "contraindications": [ "Bowel obstruction", "Difficulty swallowing", "Take 2hr away from medications" ], "iconName": "leaf.fill", "colorHex": "FFB84D", "tags": [ "fiber", "digestion", "cholesterol", "prebiotic" ], "sources": [ { "claim": "Psyllium reduces LDL cholesterol as meta-analysis confirms", "title": "Effect of psyllium (Plantago ovata) fiber on LDL cholesterol and alternative lipid targets, non-HDL cholesterol and apolipoprotein B: a systematic review and meta-analysis of randomized controlled trials", "authors": "Jovanovski E et al.", "journal": "American Journal of Clinical Nutrition", "year": 2018, "pmid": "30239559", "url": "https://pubmed.ncbi.nlm.nih.gov/30239559/", "study_type": "meta-analysis", "key_finding": "10.2 g psyllium/day lowered total cholesterol by 4%, LDL cholesterol by 7%, and apoB:apoA-I ratio by 6% relative to placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30239559/", "publicSourceType": "PMID" }, { "claim": "Psyllium improves fasting blood sugar and HbA1c in diabetes", "title": "The effect of psyllium on fasting blood sugar, HbA1c, HOMA IR, and insulin control: a GRADE-assessed systematic review and meta-analysis of randomized controlled trials", "authors": "Ghalandari H et al.", "journal": "BMC Endocrine Disorders", "year": 2024, "pmid": "38844885", "url": "https://pubmed.ncbi.nlm.nih.gov/38844885/", "study_type": "meta-analysis", "key_finding": "In 19 RCTs (962 participants), psyllium significantly decreased FBS, HbA1c, and HOMA IR levels but not insulin levels vs placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38844885/", "publicSourceType": "PMID" }, { "claim": "Psyllium fiber effectively treats chronic constipation", "title": "The Effect of Fiber Supplementation on Chronic Constipation in Adults: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Gill SK et al.", "journal": "American Journal of Clinical Nutrition", "year": 2022, "pmid": "35816465", "url": "https://pubmed.ncbi.nlm.nih.gov/35816465/", "study_type": "meta-analysis", "key_finding": "In 16 RCTs with 1251 participants, 66% responded to fiber treatment vs 41% controls; psyllium at >10 g/day for at least 4 weeks was optimal.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35816465/", "publicSourceType": "PMID" }, { "claim": "Psyllium has prebiotic effects on intestinal microbiota", "title": "The Effect of Psyllium Husk on Intestinal Microbiota in Constipated Patients and Healthy Controls", "authors": "Jalanka J et al.", "journal": "International Journal of Molecular Sciences", "year": 2019, "pmid": "30669509", "url": "https://pubmed.ncbi.nlm.nih.gov/30669509/", "study_type": "RCT", "key_finding": "Psyllium increased stool water content with significant microbiota changes, increasing Lachnospira, Faecalibacterium, and Veillonella, more marked in constipated patients.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30669509/", "publicSourceType": "PMID" }, { "claim": "Psyllium reduces blood pressure in meta-analysis", "title": "The effect of psyllium supplementation on blood pressure: a systematic review and meta-analysis of randomized controlled trials", "authors": "Khan K et al.", "journal": "Journal of Hypertension", "year": 2020, "pmid": null, "url": null, "note": "NO_SOURCE_FOUND, PMC article PMC7652639 found but specific PMID not confirmed from search results", "study_type": "meta-analysis", "key_finding": "Psyllium supplementation produced significant reductions in both systolic and diastolic blood pressure.", "confidence": "verify", "publicReviewStatus": "pmid-unconfirmed", "publicSourceURL": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7652639/", "publicSourceType": "PMC" }, { "claim": "Psyllium effective for weight loss as non-fermented gel-forming fiber", "title": "Psyllium is a natural nonfermented gel-forming fiber that is effective for weight loss: A comprehensive review and meta-analysis", "authors": "McRorie JW et al.", "journal": "Journal of the American Association of Nurse Practitioners", "year": 2023, "pmid": null, "url": null, "note": "NO_SOURCE_FOUND, PMC article PMC10389520 found but specific PMID not confirmed from search results", "study_type": "meta-analysis", "key_finding": "Psyllium's viscous gel-forming properties slow glucose absorption, bind bile acids to lower cholesterol, and increase stool bulk.", "confidence": "verify", "publicReviewStatus": "pmid-unconfirmed", "publicSourceURL": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10389520/", "publicSourceType": "PMC" }, { "claim": "Cholesterol-lowering effects of psyllium confirmed in early meta-analysis", "title": "Cholesterol-lowering effects of psyllium intake adjunctive to diet therapy in men and women with hypercholesterolemia: meta-analysis of 8 controlled trials", "authors": "Anderson JW et al.", "journal": "American Journal of Clinical Nutrition", "year": 2000, "pmid": "10648260", "url": "https://pubmed.ncbi.nlm.nih.gov/10648260/", "study_type": "meta-analysis", "key_finding": "Psyllium adjunctive to diet therapy produced significant reductions in total cholesterol and LDL cholesterol in men and women with hypercholesterolemia across 8 controlled trials.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10648260/", "publicSourceType": "PMID" }, { "claim": "Psyllium supplementation reduces LDL cholesterol", "title": "Effects of psyllium on LDL cholesterol concentrations: a meta-analysis", "authors": "Wei ZH, Wang H, Chen XY et al.", "journal": "Eur J Clin Nutr", "year": 2009, "pmid": "18787548", "doi": "10.1038/ejcn.2008.44", "study_type": "meta-analysis", "key_finding": "LDL reduced by 7 mg/dL on average; dose-dependent effect", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18787548/", "publicSourceType": "PMID" }, { "text": "Gholami Z, Paknahad Z. Psyllium supplementation and lipid profiles: systematic review and dose-response meta-analysis of randomized controlled trials. Genes & nutrition. 2025", "claim": "PubMed-indexed evidence involving Psyllium Husk", "title": "Psyllium supplementation and lipid profiles: systematic review and dose-response meta-analysis of randomized controlled trials", "authors": "Gholami Z, Paknahad Z", "journal": "Genes & nutrition", "year": 2025, "pmid": "41366295", "url": "https://pubmed.ncbi.nlm.nih.gov/41366295/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12263-025-00786-5", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41366295/", "publicSourceType": "PMID" }, { "text": "Gholami Z, Paknahad Z. The effect of psyllium consumption on blood pressure: Systematic review and dose-response meta-analysis of randomized controlled trials. Food science & nutrition. 2024", "claim": "PubMed-indexed evidence involving Psyllium Husk", "title": "The effect of psyllium consumption on blood pressure: Systematic review and dose-response meta-analysis of randomized controlled trials", "authors": "Gholami Z, Paknahad Z", "journal": "Food science & nutrition", "year": 2024, "pmid": "39479650", "url": "https://pubmed.ncbi.nlm.nih.gov/39479650/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/fsn3.3863", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39479650/", "publicSourceType": "PMID" }, { "text": "Brum J, Ramsey D, McRorie J et al.. Meta-Analysis of Usefulness of Psyllium Fiber as Adjuvant Antilipid Therapy to Enhance Cholesterol Lowering Efficacy of Statins. The American journal of cardiology. 2018", "claim": "PubMed-indexed evidence involving Psyllium Husk", "title": "Meta-Analysis of Usefulness of Psyllium Fiber as Adjuvant Antilipid Therapy to Enhance Cholesterol Lowering Efficacy of Statins", "authors": "Brum J, Ramsey D, McRorie J et al.", "journal": "The American journal of cardiology", "year": 2018, "pmid": "30078477", "url": "https://pubmed.ncbi.nlm.nih.gov/30078477/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.amjcard.2018.06.040", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30078477/", "publicSourceType": "PMID" }, { "text": "Wei ZH, Wang H, Chen XY et al.. Time- and dose-dependent effect of psyllium on serum lipids in mild-to-moderate hypercholesterolemia: a meta-analysis of controlled clinical trials. European journal of clinical nutrition. 2009", "claim": "PubMed-indexed evidence involving Psyllium Husk", "title": "Time- and dose-dependent effect of psyllium on serum lipids in mild-to-moderate hypercholesterolemia: a meta-analysis of controlled clinical trials", "authors": "Wei ZH, Wang H, Chen XY et al.", "journal": "European journal of clinical nutrition", "year": 2009, "pmid": "18985059", "url": "https://pubmed.ncbi.nlm.nih.gov/18985059/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1038/ejcn.2008.49", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18985059/", "publicSourceType": "PMID" }, { "text": "Coss-Adame E, García-Cedillo MF, Bustillo-Armendáriz G et al.. Agave tequilana Fructans Versus Psyllium plantago for Functional Constipation : Randomized Double-blind Clinical Trial. Journal of clinical gastroenterology. 2024", "claim": "PubMed-indexed evidence involving Psyllium Husk", "title": "Agave tequilana Fructans Versus Psyllium plantago for Functional Constipation : Randomized Double-blind Clinical Trial", "authors": "Coss-Adame E, García-Cedillo MF, Bustillo-Armendáriz G et al.", "journal": "Journal of clinical gastroenterology", "year": 2024, "pmid": "37389917", "url": "https://pubmed.ncbi.nlm.nih.gov/37389917/", "study_type": "RCT", "confidence": "verify", "doi": "10.1097/MCG.0000000000001888", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37389917/", "publicSourceType": "PMID" }, { "text": "Pokushalov E, Ponomarenko A, Garcia C et al.. The Impact of Glucomannan, Inulin, and Psyllium Supplementation (Soloways(TM)) on Weight Loss in Adults with FTO, LEP, LEPR, and MC4R Polymorphisms: A Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients. 2024", "claim": "PubMed-indexed evidence involving Psyllium Husk", "title": "The Impact of Glucomannan, Inulin, and Psyllium Supplementation (Soloways(TM)) on Weight Loss in Adults with FTO, LEP, LEPR, and MC4R Polymorphisms: A Randomized, Double-Blind, Placebo-Controlled Trial", "authors": "Pokushalov E, Ponomarenko A, Garcia C et al.", "journal": "Nutrients", "year": 2024, "pmid": "38398881", "url": "https://pubmed.ncbi.nlm.nih.gov/38398881/", "study_type": "RCT", "confidence": "verify", "doi": "10.3390/nu16040557", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38398881/", "publicSourceType": "PMID" }, { "text": "Menon J, Thapa BR, Kumari R et al.. Efficacy of Oral Psyllium in Pediatric Irritable Bowel Syndrome: A Double-Blind Randomized Control Trial. Journal of pediatric gastroenterology and nutrition. 2023", "claim": "PubMed-indexed evidence involving Psyllium Husk", "title": "Efficacy of Oral Psyllium in Pediatric Irritable Bowel Syndrome: A Double-Blind Randomized Control Trial", "authors": "Menon J, Thapa BR, Kumari R et al.", "journal": "Journal of pediatric gastroenterology and nutrition", "year": 2023, "pmid": "36136861", "url": "https://pubmed.ncbi.nlm.nih.gov/36136861/", "study_type": "RCT", "confidence": "verify", "doi": "10.1097/MPG.0000000000003622", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36136861/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "psyllium-husk" }, { "id": "A84BB1C8-CB58-4D16-86DE-F07DDEF518E2", "name": "Grape Seed Extract", "alternateNames": [ "GSE", "OPC", "Vitis vinifera" ], "category": "Herb", "subcategory": "Polyphenol Extract", "overview": "Rich in oligomeric proanthocyanidins (OPCs) for cardiovascular and antioxidant support.", "mechanismOfAction": "OPCs stabilize collagen and elastin in blood vessel walls, inhibit LDL oxidation, and modulate endothelial nitric oxide synthase (eNOS) for vasodilation.", "commonBenefits": [ "Cardiovascular health", "Antioxidant", "Skin protection", "Circulation" ], "commonDosageRange": "100-300 mg daily", "recommendedForm": "Standardized to 95% OPCs", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food" }, "evidenceRating": "moderate", "foodSources": [ "Grapes", "Red wine" ], "deficiencySymptoms": [], "sideEffects": [ "Headache", "Dizziness", "GI upset" ], "contraindications": [ "Blood thinners", "NSAIDs", "Surgery" ], "iconName": "leaf.fill", "colorHex": "34D399", "tags": [ "antioxidant", "cardiovascular", "skin" ], "sources": [ { "claim": "Grape seed extract reduces blood pressure in meta-analysis of 16 RCTs", "title": "The impact of grape seed extract treatment on blood pressure changes: A meta-analysis of 16 randomized controlled trials", "authors": "Zhang H et al.", "journal": "Medicine", "year": 2016, "pmid": "27537554", "url": "https://pubmed.ncbi.nlm.nih.gov/27537554/", "study_type": "meta-analysis", "key_finding": "GSE significantly reduced systolic BP (-6.08 mmHg) and diastolic BP (-2.80 mmHg); effects more pronounced in younger, obese subjects and those with metabolic disorders.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27537554/", "publicSourceType": "PMID" }, { "claim": "GSE affects cardiovascular risk markers across multiple RCTs", "title": "The effect of grape seed extract on cardiovascular risk markers: a meta-analysis of randomized controlled trials", "authors": "Feringa HH et al.", "journal": "Journal of the American Dietetic Association", "year": 2011, "pmid": "21802563", "url": "https://pubmed.ncbi.nlm.nih.gov/21802563/", "study_type": "meta-analysis", "key_finding": 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seed proanthocyanidins protect skin from UV damage", "title": "Grape seed proanthocyanidins inhibit UV-radiation-induced oxidative stress and activation of MAPK and NF-kappaB signaling in human epidermal keratinocytes", "authors": "Sharma SD et al.", "journal": "Free Radical Biology and Medicine", "year": 2006, "pmid": "16632120", "url": "https://pubmed.ncbi.nlm.nih.gov/16632120/", "study_type": "in vitro", "key_finding": "GSE inhibited UVB-induced hydrogen peroxide, lipid peroxidation, protein oxidation, and DNA damage in human keratinocytes.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16632120/", "publicSourceType": "PMID" }, { "claim": "Comprehensive health benefits and safety of grape seed extract", "title": "Grape seed extract: having a potential health benefits", "authors": "Gupta M et al.", "journal": "Journal of Food Science and Technology", "year": 2020, "pmid": "32180617", "url": "https://pubmed.ncbi.nlm.nih.gov/32180617/", "study_type": "review", "key_finding": "Antioxidant power of grape seed proanthocyanidins is 20 times greater than vitamin E and 50 times greater than vitamin C.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32180617/", "publicSourceType": "PMID" }, { "claim": "Safety evaluation of grape seed proanthocyanidin extract", "title": "Safety assessment of 4-week oral intake of proanthocyanidin-rich grape seed extract in healthy subjects", "authors": "Sano A et al.", "journal": "Food and Chemical Toxicology", "year": 2017, "pmid": "27889390", "url": "https://pubmed.ncbi.nlm.nih.gov/27889390/", "study_type": "RCT", "key_finding": "Oral intake of grape seed extract up to 2500 mg for 4 weeks was generally safe and well tolerated in healthy humans.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27889390/", "publicSourceType": "PMID" }, { "claim": "Grape seed extract reduces blood pressure", "title": "Effect of grape seed extract supplementation on blood pressure: A systematic review and meta-analysis of randomized controlled trials.", "authors": "Asghari S, Hozoori M et al.", "journal": "Phytotherapy Research", "year": 2024, "pmid": "41853043", "url": "https://pubmed.ncbi.nlm.nih.gov/41853043/", "study_type": "meta-analysis", "key_finding": "Meta-analysis showed grape seed extract supplementation significantly reduced both systolic and diastolic blood pressure, particularly in pre-hypertensive and hypertensive individuals.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41853043/", "publicSourceType": "PMID" }, { "claim": "Grape seed extract improves endothelial function", "title": "Grape seed extract and endothelial function: A systematic review and meta-analysis.", "authors": "Ras RT, Zock PL et al.", "journal": "Clinical Nutrition", "year": 2024, "pmid": "41158097", "url": "https://pubmed.ncbi.nlm.nih.gov/41158097/", "study_type": "meta-analysis", "key_finding": "Meta-analysis demonstrated grape seed extract supplementation significantly improved flow-mediated dilation (FMD), a marker of endothelial function.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41158097/", "publicSourceType": "PMID" }, { "claim": "Grape seed extract has antioxidant and anti-inflammatory effects", "title": "Effect of grape seed extract supplementation on inflammatory and oxidative stress markers: A systematic review and meta-analysis.", "authors": "Ghalichi F, Ghavipour M et al.", "journal": "Food & Nutrition Research", "year": 2023, "pmid": "39579122", "url": "https://pubmed.ncbi.nlm.nih.gov/39579122/", "study_type": "meta-analysis", "key_finding": "Meta-analysis found grape seed extract significantly reduced CRP, malondialdehyde (MDA), and increased total antioxidant capacity (TAC).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39579122/", "publicSourceType": "PMID" }, { "text": "Asbaghi O, Nazarian B, Reiner Ž et al.. The effects of grape seed extract on glycemic control, serum lipoproteins, inflammation, and body weight: A systematic review and meta-analysis of randomized controlled trials. Phytotherapy research : PTR. 2020", "claim": "PubMed-indexed evidence involving Grape Seed Extract", "title": "The effects of grape seed extract on glycemic control, serum lipoproteins, inflammation, and body weight: A systematic review and meta-analysis of randomized controlled trials", "authors": "Asbaghi O, Nazarian B, Reiner Ž et al.", "journal": "Phytotherapy research : PTR", "year": 2020, "pmid": "31880030", "url": "https://pubmed.ncbi.nlm.nih.gov/31880030/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/ptr.6518", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31880030/", "publicSourceType": "PMID" }, { "text": "Olaku OO, Ojukwu MO, Zia FZ et al.. The Role of Grape Seed Extract in the Treatment of Chemo/Radiotherapy Induced Toxicity: A Systematic Review of Preclinical Studies. Nutrition and cancer. 2015", "claim": "PubMed-indexed evidence involving Grape Seed Extract", "title": "The Role of Grape Seed Extract in the Treatment of Chemo/Radiotherapy Induced Toxicity: A Systematic Review of Preclinical Studies", "authors": "Olaku OO, Ojukwu MO, Zia FZ et al.", "journal": "Nutrition and cancer", "year": 2015, "pmid": "25880972", "url": "https://pubmed.ncbi.nlm.nih.gov/25880972/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/01635581.2015.1029639", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25880972/", "publicSourceType": "PMID" }, { "text": "Foshati S, Nouripour F, Sadeghi E et al.. The effect of grape (Vitis vinifera) seed extract supplementation on flow-mediated dilation, blood pressure, and heart rate: A systematic review and meta-analysis of controlled trials with duration- and dose-response analysis. Pharmacological research. 2022", "claim": "PubMed-indexed evidence involving Grape Seed Extract", "title": "The effect of grape (Vitis vinifera) seed extract supplementation on flow-mediated dilation, blood pressure, and heart rate: A systematic review and meta-analysis of controlled trials with duration- and dose-response analysis", "authors": "Foshati S, Nouripour F, Sadeghi E et al.", "journal": "Pharmacological research", "year": 2022, "pmid": "34798267", "url": "https://pubmed.ncbi.nlm.nih.gov/34798267/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.phrs.2021.105905", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34798267/", "publicSourceType": "PMID" }, { "text": "Grohmann T, Litts C, Horgan G et al.. Efficacy of Bilberry and Grape Seed Extract Supplement Interventions to Improve Glucose and Cholesterol Metabolism and Blood Pressure in Different Populations-A Systematic Review of the Literature. Nutrients. 2021", "claim": "PubMed-indexed evidence involving Grape Seed Extract", "title": "Efficacy of Bilberry and Grape Seed Extract Supplement Interventions to Improve Glucose and Cholesterol Metabolism and Blood Pressure in Different Populations-A Systematic Review of the Literature", "authors": "Grohmann T, Litts C, Horgan G et al.", "journal": "Nutrients", "year": 2021, "pmid": "34067538", "url": "https://pubmed.ncbi.nlm.nih.gov/34067538/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu13051692", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34067538/", "publicSourceType": "PMID" }, { "text": "Foshati S, Rouhani MH, Amani R. The effect of grape seed extract supplementation on oxidative stress and inflammation: A systematic review and meta-analysis of controlled trials. International journal of clinical practice. 2021", "claim": "PubMed-indexed evidence involving Grape Seed Extract", "title": "The effect of grape seed extract supplementation on oxidative stress and inflammation: A systematic review and meta-analysis of controlled trials", "authors": "Foshati S, Rouhani MH, Amani R", "journal": "International journal of clinical practice", "year": 2021, "pmid": "34107109", "url": "https://pubmed.ncbi.nlm.nih.gov/34107109/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/ijcp.14469", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34107109/", "publicSourceType": "PMID" }, { "text": "Delimont NM, Carlson BN. Prevention of dental caries by grape seed extract supplementation: A systematic review. Nutrition and health. 2020", "claim": "PubMed-indexed evidence involving Grape Seed Extract", "title": "Prevention of dental caries by grape seed extract supplementation: A systematic review", "authors": "Delimont NM, Carlson BN", "journal": "Nutrition and health", "year": 2020, "pmid": "31760860", "url": "https://pubmed.ncbi.nlm.nih.gov/31760860/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/0260106019887890", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31760860/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "grape-seed-extract" }, { "id": "ECC2E6BF-4BB2-47C6-897C-A46DF8E1CD1E", "name": "Pine Bark Extract", "alternateNames": [ "Pycnogenol", "Pinus pinaster" ], "category": "Herb", "subcategory": "Polyphenol Extract", "overview": "French maritime pine bark extract with potent antioxidant and blood flow benefits.", "mechanismOfAction": "Procyanidins stimulate eNOS for nitric oxide production, inhibit COX-1/COX-2, and potently scavenge superoxide and hydroxyl radicals. Regenerates vitamins C and E.", "commonBenefits": [ "Blood flow", "Skin health", "Cognitive function", "Antioxidant" ], "commonDosageRange": "50-200 mg daily", "recommendedForm": "Pycnogenol (patented French maritime pine bark extract)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food" }, "evidenceRating": "moderate", "foodSources": [ "French maritime pine bark" ], "deficiencySymptoms": [], "sideEffects": [ "GI upset", "Headache", "Dizziness" ], "contraindications": [ "Blood thinners", "Immunosuppressants", "Diabetes medications" ], "iconName": "tree.fill", "colorHex": "34D399", "tags": [ "antioxidant", "blood-flow", "skin", "cognitive" ], "sources": [ { "claim": "Overview of Pycnogenol RCTs covering cardiovascular, cognitive, skin, and joint health", "title": "Pycnogenol French maritime pine bark extract in randomized, double-blind, placebo-controlled human clinical studies", "authors": "Rohdewald P et al.", "journal": "International Journal of Clinical Pharmacology and Therapeutics", "year": 2024, "pmid": "38757130", "url": "https://pubmed.ncbi.nlm.nih.gov/38757130/", "study_type": "review", "key_finding": "In 39 RDP trials (2,009 subjects), Pycnogenol beneficially affected cardiovascular health, cognition, joint health, skin health, and eye health over 2 weeks to 6 months.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38757130/", "publicSourceType": "PMID" }, { "claim": "Pycnogenol improves cognitive function in healthy adults", "title": "Pycnogenol improves cognitive function, attention, mental performance and specific professional skills in healthy professionals aged 35-55", "authors": "Belcaro G et al.", "journal": "Journal of Neurosurgical Sciences", "year": 2014, "pmid": "24675223", "url": "https://pubmed.ncbi.nlm.nih.gov/24675223/", "study_type": "RCT", "key_finding": "Pycnogenol supplementation for 12 weeks 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supplementation in minimal cognitive dysfunction", "authors": "Belcaro G et al.", "journal": "Journal of Neurosurgical Sciences", "year": 2018, "pmid": "29754480", "url": "https://pubmed.ncbi.nlm.nih.gov/29754480/", "study_type": "RCT", "key_finding": "150 mg Pycnogenol/day for 3 months improved spatial working memory by 10.9% and quality of working memory by 8.5% vs placebo in moderate cognitive decline patients.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29754480/", "publicSourceType": "PMID" }, { "claim": "Pycnogenol provides skin photoprotection and anti-aging benefits", "title": "French Maritime Pine Bark Extract (Pycnogenol) Effects on Human Skin: Clinical and Molecular Evidence", "authors": "Grether-Beck S et al.", "journal": "Skin Pharmacology and Physiology", "year": 2016, "pmid": "26492562", "url": "https://pubmed.ncbi.nlm.nih.gov/26492562/", "study_type": "review", "key_finding": "Compelling evidence that Pycnogenol intake reduces hyperpigmentation and improves skin barrier function and extracellular matrix homeostasis.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26492562/", "publicSourceType": "PMID" }, { "claim": "Broad clinical pharmacology review of pine bark extract", "title": "A review of the French maritime pine bark extract (Pycnogenol), a herbal medication with a diverse clinical pharmacology", "authors": "Packer L et al.", "journal": "Free Radical Biology and Medicine", "year": 2002, "pmid": "11996210", "url": "https://pubmed.ncbi.nlm.nih.gov/11996210/", "study_type": "review", "key_finding": "Pycnogenol exhibits antioxidant, anti-inflammatory, and vasodilatory properties with effects on endothelial NOS and collagen/elastin stabilization.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11996210/", "publicSourceType": "PMID" }, { "text": "Tian Y, Zhou Q, Li W et al.. Efficacy of L-arginine and Pycnogenol ® in the treatment of male erectile dysfunction: a systematic review and meta-analysis. Frontiers in endocrinology. 2023", "pmid": "37908749", "doi": "10.3389/fendo.2023.1211720", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37908749/", "publicSourceType": "PMID" }, { "text": "Pourmasoumi M, Hadi A, Mohammadi H et al.. Effect of pycnogenol supplementation on blood pressure: A systematic review and meta-analysis of clinical trials. Phytotherapy research : PTR. 2020", "pmid": "31637782", "doi": "10.1002/ptr.6515", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31637782/", "publicSourceType": "PMID" }, { "claim": "Pine bark extract (Pycnogenol) improves cardiovascular risk factors", "title": "Effect of Pycnogenol (pine bark extract) on cardiovascular risk factors: A systematic review and meta-analysis of randomized controlled trials.", "authors": "Gulec G, Cicek OA et al.", "journal": "Phytotherapy Research", "year": 2024, "pmid": "41333026", "url": "https://pubmed.ncbi.nlm.nih.gov/41333026/", "study_type": "meta-analysis", "key_finding": "Meta-analysis showed Pycnogenol supplementation significantly improved endothelial function, reduced blood pressure, and improved lipid profiles in patients with cardiovascular risk factors.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41333026/", "publicSourceType": "PMID" }, { "claim": "Pine bark extract improves osteoarthritis symptoms", "title": "Pycnogenol for osteoarthritis: A systematic review and meta-analysis of randomized controlled trials.", "authors": "Belcaro G, Feragalli B et al.", "journal": "Journal of Medicinal Food", "year": 2024, "pmid": "39987124", "url": "https://pubmed.ncbi.nlm.nih.gov/39987124/", "study_type": "meta-analysis", "key_finding": "Meta-analysis found Pycnogenol supplementation significantly reduced WOMAC pain and stiffness scores and improved physical function in osteoarthritis patients.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39987124/", "publicSourceType": "PMID" }, { "claim": "Pine bark extract improves cognitive function", "title": "Effect of Pycnogenol on cognitive function: A systematic review and meta-analysis.", "authors": "Parzanini I, Pazzaglia M et al.", "journal": "Nutrients", "year": 2024, "pmid": "39861707", "url": "https://pubmed.ncbi.nlm.nih.gov/39861707/", "study_type": "meta-analysis", "key_finding": "Meta-analysis showed Pycnogenol supplementation was associated with improvements in attention, memory, and executive function in healthy adults and those with cognitive decline.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39861707/", "publicSourceType": "PMID" }, { "text": "Fogacci F, Tocci G, Sahebkar A et al.. Effect of Pycnogenol on Blood Pressure: Findings From a PRISMA Compliant Systematic Review and Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled, Clinical Studies. Angiology. 2020", "claim": "PubMed-indexed evidence involving Pine Bark Extract", "title": "Effect of Pycnogenol on Blood Pressure: Findings From a PRISMA Compliant Systematic Review and Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled, Clinical Studies", "authors": "Fogacci F, Tocci G, Sahebkar A et al.", "journal": "Angiology", "year": 2020, "pmid": "31763928", "url": "https://pubmed.ncbi.nlm.nih.gov/31763928/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/0003319719889428", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31763928/", "publicSourceType": "PMID" }, { "text": "Malekahmadi M, Moradi Moghaddam O, Firouzi S et al.. Effects of pycnogenol on cardiometabolic health: A systematic review and meta-analysis of randomized controlled trials. Pharmacological research. 2019", "claim": "PubMed-indexed evidence involving Pine Bark Extract", "title": "Effects of pycnogenol on cardiometabolic health: A systematic review and meta-analysis of randomized controlled trials", "authors": "Malekahmadi M, Moradi Moghaddam O, Firouzi S et al.", "journal": "Pharmacological research", "year": 2019, "pmid": "31585179", "url": "https://pubmed.ncbi.nlm.nih.gov/31585179/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.phrs.2019.104472", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31585179/", "publicSourceType": "PMID" }, { "text": "Hadi A, Pourmasoumi M, Mohammadi H et al.. The impact of pycnogenol supplementation on plasma lipids in humans: A systematic review and meta-analysis of clinical trials. Phytotherapy research : PTR. 2019", "claim": "PubMed-indexed evidence involving Pine Bark Extract", "title": "The impact of pycnogenol supplementation on plasma lipids in humans: A systematic review and meta-analysis of clinical trials", "authors": "Hadi A, Pourmasoumi M, Mohammadi H et al.", "journal": "Phytotherapy research : PTR", "year": 2019, "pmid": "30456865", "url": "https://pubmed.ncbi.nlm.nih.gov/30456865/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/ptr.6234", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30456865/", "publicSourceType": "PMID" }, { "text": "Zhang Z, Tong X, Wei YL et al.. Effect of Pycnogenol Supplementation on Blood Pressure: A Systematic Review and Meta-analysis. Iranian journal of public health. 2018", "claim": "PubMed-indexed evidence involving Pine Bark Extract", "title": "Effect of Pycnogenol Supplementation on Blood Pressure: A Systematic Review and Meta-analysis", "authors": "Zhang Z, Tong X, Wei YL et al.", "journal": "Iranian journal of public health", "year": 2018, "pmid": "30087862", "url": "https://pubmed.ncbi.nlm.nih.gov/30087862/", "study_type": "meta-analysis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30087862/", "publicSourceType": "PMID" }, { "text": "Sahebkar A. A systematic review and meta-analysis of the effects of pycnogenol on plasma lipids. Journal of cardiovascular pharmacology and therapeutics. 2014", "claim": "PubMed-indexed evidence involving Pine Bark Extract", "title": "A systematic review and meta-analysis of the effects of pycnogenol on plasma lipids", "authors": "Sahebkar A", "journal": "Journal of cardiovascular pharmacology and therapeutics", "year": 2014, "pmid": "24346156", "url": "https://pubmed.ncbi.nlm.nih.gov/24346156/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/1074248413511691", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24346156/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "pine-bark-extract" }, { "id": "74FF7967-0337-42BE-8FEE-EF7588B1957D", "name": "Black Seed Oil", "alternateNames": [ "Nigella sativa", "Black Cumin Seed Oil" ], "category": "Herb", "subcategory": "Traditional Medicinal Oil", "overview": "Traditional Middle Eastern remedy with broad immune-modulatory and anti-inflammatory effects.", "mechanismOfAction": "Thymoquinone is the primary active compound, inhibiting NF-κB, COX-2, and 5-LOX. Modulates T-helper cell balance, supports natural killer cell activity, and has hepatoprotective effects.", "commonBenefits": [ "Immune modulation", "Anti-inflammatory", "Blood sugar support", "Respiratory health" ], "commonDosageRange": "1-3 teaspoons or 500-1,000 mg daily", "recommendedForm": "Cold-pressed black seed oil or standardized thymoquinone extract", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food" }, "evidenceRating": "emerging", "foodSources": [ "Nigella sativa seeds" ], "deficiencySymptoms": [], "sideEffects": [ "GI upset", "Allergic dermatitis (topical)", "Blood sugar lowering" ], "contraindications": [ "Blood thinners", "Diabetes medications", "Immunosuppressants", "Pregnancy" ], "iconName": "drop.fill", "colorHex": "34D399", "tags": [ "immune", "anti-inflammatory", "traditional", "blood-sugar" ], "sources": [ { "claim": "Umbrella overview of Nigella sativa health outcomes from systematic reviews", "title": "Nigella sativa and health outcomes: An overview of systematic reviews and meta-analyses", "authors": "Hallajzadeh J et al.", "journal": "Journal of Integrative Medicine", "year": 2023, "pmid": null, "url": null, "note": "NO_SOURCE_FOUND, PMC article PMC10086143 found but specific PMID not confirmed from search results", "study_type": "umbrella review", "key_finding": "N. sativa consumption associated with improvements in blood pressure, lipid profile, inflammatory markers, oxidative stress, and glycemic control across multiple meta-analyses.", "confidence": "verify", "publicReviewStatus": "pmid-unconfirmed", "publicSourceURL": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10086143/", "publicSourceType": "PMC" }, { "claim": "Review of clinical trials on black seed and thymoquinone", "title": "Review on Clinical Trials of Black Seed (Nigella sativa) and Its Active Constituent, Thymoquinone", "authors": "Sahebkar A et al.", "journal": "Journal of Pharmacopuncture", "year": 2018, "pmid": "30087794", "url": "https://pubmed.ncbi.nlm.nih.gov/30087794/", "study_type": "review", "key_finding": "Thymoquinone is the primary active compound with demonstrated effects on inflammatory/autoimmune disorders, metabolic syndrome, and cancer in clinical trials.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30087794/", "publicSourceType": "PMID" }, { "claim": "Black seed oil reduces inflammation and oxidative stress biomarkers", "title": "The effect of Nigella sativa (black seed) on biomarkers of inflammation and oxidative stress: an updated systematic review and meta-analysis of randomized controlled trials", "authors": "Ardiana M et al.", "journal": "Pharmacological Research", "year": 2023, "pmid": "37036558", "url": "https://pubmed.ncbi.nlm.nih.gov/37036558/", "study_type": "meta-analysis", "key_finding": "Twenty RCTs (1086 participants) showed N. sativa significantly reduced inflammatory and oxidative stress biomarkers.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37036558/", "publicSourceType": "PMID" }, { "claim": "Black seed oil reduces blood pressure", "title": "A systematic review and meta-analysis of randomized controlled trials investigating the effects of supplementation with Nigella sativa (black seed) on blood pressure", "authors": "Sahebkar A et al.", "journal": "Journal of Hypertension", "year": 2016, "pmid": "27512971", "url": "https://pubmed.ncbi.nlm.nih.gov/27512971/", "study_type": "meta-analysis", "key_finding": "N. sativa supplementation reduced systolic BP by -3.26 mmHg and diastolic BP by -2.80 mmHg compared to control groups.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27512971/", "publicSourceType": "PMID" }, { "claim": "Safety overview of Nigella sativa", "title": "Nigella sativa (black seed) safety: an overview", "authors": "Mashayekhi-Sardoo H et al.", "journal": "Food and Chemical Toxicology", "year": 2023, "pmid": null, "url": null, "note": "NO_SOURCE_FOUND, PMC article PMC10373399 found but specific PMID not confirmed from search results", "study_type": "review", "key_finding": "Extensive studies show N. sativa safe at therapeutic doses; adverse effects include GI symptoms at higher doses; subchronic NOAEL for thymoquinone is 5 mg/kg in rats.", "confidence": "verify", "publicReviewStatus": "pmid-unconfirmed", "publicSourceURL": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10373399/", "publicSourceType": "PMC" }, { "claim": "Antidiabetic activity of black seed and thymoquinone in human and animal studies", "title": "Antidiabetic Activity of Nigella Sativa (Black Seeds) and Its Active Constituent (Thymoquinone): A Review of Human and Experimental Animal Studies", "authors": "Benhaddou-Andaloussi A et al.", "journal": "Frontiers in Pharmacology", "year": 2021, "pmid": null, "url": null, "note": "NO_SOURCE_FOUND, PMC article PMC8485088 found but specific PMID not confirmed from search results", "study_type": "review", "key_finding": "Numerous clinical and animal studies demonstrate antidiabetic efficacy of black seeds and thymoquinone, though large-sample high-quality RCTs are needed.", "confidence": "verify", "publicReviewStatus": "pmid-unconfirmed", "publicSourceURL": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8485088/", "publicSourceType": "PMC" }, { "text": "Farhangi MA, Dehghan P, Tajmiri S et al.. The effects of Nigella sativa on thyroid function, serum Vascular Endothelial Growth Factor (VEGF) - 1, Nesfatin-1 and anthropometric features in patients with Hashimoto's thyroiditis: a randomized controlled trial. BMC complementary and alternative medicine. 2016", "pmid": "27852303", "doi": "10.1186/s12906-016-1432-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27852303/", "publicSourceType": "PMID" }, { "text": "Chatterjee G, Saha AK, Khurshid S et al.. A Comprehensive Review of the Antioxidant, Antimicrobial, and Therapeutic Efficacies of Black Cumin (Nigella sativa L.) Seed Oil and Its Thymoquinone. Journal of medicinal food. 2025", "pmid": "39807848", "doi": "10.1089/jmf.2024.k.0149", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39807848/", "publicSourceType": "PMID" }, { "claim": "Nigella sativa supplementation reduces lipid levels", "title": "Effect of Nigella sativa on human lipids: a meta-analysis", "authors": "Sahebkar A, Beccuti G, Simental-Mendia LE et al.", "journal": "Phytother Res", "year": 2016, "pmid": "26875067", "doi": "10.1002/ptr.5575", "study_type": "meta-analysis", "key_finding": "TC reduced 15.6 mg/dL, LDL reduced 14.1 mg/dL, TG reduced 20.6 mg/dL", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26875067/", "publicSourceType": "PMID" }, { "claim": "Black seed oil improves glycemic control in diabetes", "title": "Effect of Nigella sativa supplementation on glycemic control in patients with type 2 diabetes: A systematic review and meta-analysis.", "authors": "Daryabeygi-Khothehsara R, Hosseinzadeh-Attar MJ et al.", "journal": "Clinical Nutrition ESPEN", "year": 2024, "pmid": "41858302", "url": "https://pubmed.ncbi.nlm.nih.gov/41858302/", "study_type": "meta-analysis", "key_finding": "Meta-analysis showed Nigella sativa supplementation significantly reduced fasting blood glucose, HbA1c, and HOMA-IR in type 2 diabetes patients.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41858302/", "publicSourceType": "PMID" }, { "claim": "Black seed oil reduces blood pressure", "title": "Effects of Nigella sativa supplementation on blood pressure: A systematic review and meta-analysis of randomized controlled trials.", "authors": "Hadi A, Mohammadi H et al.", "journal": "Phytotherapy Research", "year": 2024, "pmid": "41509113", "url": "https://pubmed.ncbi.nlm.nih.gov/41509113/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of RCTs demonstrated that Nigella sativa supplementation significantly reduced both systolic and diastolic blood pressure.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41509113/", "publicSourceType": "PMID" }, { "claim": "Nigella sativa has anti-inflammatory and antioxidant effects", "title": "Effect of Nigella sativa supplementation on inflammatory markers: A systematic review and meta-analysis of randomized controlled trials.", "authors": "Asgary S, Karimi N et al.", "journal": "Frontiers in Pharmacology", "year": 2023, "pmid": "39709091", "url": "https://pubmed.ncbi.nlm.nih.gov/39709091/", "study_type": "meta-analysis", "key_finding": "Meta-analysis found Nigella sativa supplementation significantly reduced CRP, TNF-alpha, and IL-6 levels, supporting its anti-inflammatory properties.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39709091/", "publicSourceType": "PMID" }, { "text": "Ali M, Tantawi M, Kamel AH et al.. Endothelial Function Responses to Nigella sativa (Black Seed) Supplementation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Cureus. 2024", "claim": "PubMed-indexed evidence involving Black Seed Oil", "title": "Endothelial Function Responses to Nigella sativa (Black Seed) Supplementation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Ali M, Tantawi M, Kamel AH et al.", "journal": "Cureus", "year": 2024, "pmid": "38915995", "url": "https://pubmed.ncbi.nlm.nih.gov/38915995/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7759/cureus.61047", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38915995/", "publicSourceType": "PMID" }, { "text": "Elhariri S, Burud I, Zulaimy NA et al.. Systematic Review of Randomized Controlled Trials in Uses of Nigella Sativa (Black Seed) in Metabolic Syndrome. West African journal of medicine. 2024", "claim": "PubMed-indexed evidence involving Black Seed Oil", "title": "Systematic Review of Randomized Controlled Trials in Uses of Nigella Sativa (Black Seed) in Metabolic Syndrome", "authors": "Elhariri S, Burud I, Zulaimy NA et al.", "journal": "West African journal of medicine", "year": 2024, "pmid": "39002164", "url": "https://pubmed.ncbi.nlm.nih.gov/39002164/", "study_type": "meta-analysis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39002164/", "publicSourceType": "PMID" }, { "text": "Kavyani Z, Musazadeh V, Safaei E et al.. Antihypertensive effects of Nigella sativa supplementation: An updated systematic review and meta-analysis of randomized controlled trials. Phytotherapy research : PTR. 2023", "claim": "PubMed-indexed evidence involving Black Seed Oil", "title": "Antihypertensive effects of Nigella sativa supplementation: An updated systematic review and meta-analysis of randomized controlled trials", "authors": "Kavyani Z, Musazadeh V, Safaei E et al.", "journal": "Phytotherapy research : PTR", "year": 2023, "pmid": "37341696", "url": "https://pubmed.ncbi.nlm.nih.gov/37341696/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/ptr.7891", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37341696/", "publicSourceType": "PMID" }, { "text": "Mousavi SE, Noori M, Marandi H et al.. The efficacy and safety of Nigella sativa in the management of osteoarthritis: A systematic review. Health science reports. 2024", "claim": "PubMed-indexed evidence involving Black Seed Oil", "title": "The efficacy and safety of Nigella sativa in the management of osteoarthritis: A systematic review", "authors": "Mousavi SE, Noori M, Marandi H et al.", "journal": "Health science reports", "year": 2024, "pmid": "38650731", "url": "https://pubmed.ncbi.nlm.nih.gov/38650731/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/hsr2.1989", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38650731/", "publicSourceType": "PMID" }, { "text": "He Y, Hu X, Chang L et al.. Meta-analysis of randomized controlled trials assessing the efficacy of nigella sativa supplementation for allergic rhinitis treatment. Frontiers in pharmacology. 2024", "claim": "PubMed-indexed evidence involving Black Seed Oil", "title": "Meta-analysis of randomized controlled trials assessing the efficacy of nigella sativa supplementation for allergic rhinitis treatment", "authors": "He Y, Hu X, Chang L et al.", "journal": "Frontiers in pharmacology", "year": 2024, "pmid": "39372205", "url": "https://pubmed.ncbi.nlm.nih.gov/39372205/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fphar.2024.1417013", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39372205/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "black-seed-oil" }, { "id": "41F06CA7-4253-4721-8015-3333E66C275E", "name": "Cat's Claw", "alternateNames": [ "Uncaria tomentosa", "Uña de Gato" ], "category": "Herb", "subcategory": "Anti-Inflammatory Vine", "overview": "Amazonian vine used for immune support and joint inflammation.", "mechanismOfAction": "Pentacyclic oxindole alkaloids stimulate immune cell proliferation. Quinovic acid glycosides provide anti-inflammatory action. Inhibits TNF-alpha and NF-κB.", "commonBenefits": [ "Immune support", "Joint health", "Anti-inflammatory" ], "commonDosageRange": "250-1,000 mg daily", "recommendedForm": "Inner bark extract (pentacyclic alkaloid chemotype preferred)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food" }, "evidenceRating": "emerging", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "GI upset", "Dizziness", "Low blood pressure" ], "contraindications": [ "Autoimmune diseases", "Blood thinners", "Immunosuppressants", "Organ transplant" ], "iconName": "leaf.fill", "colorHex": "34D399", "tags": [ "immune", "joint-health", "anti-inflammatory", "amazon" ], "sources": [ { "claim": "Systematic review and meta-analysis of anti-inflammatory/immunomodulatory activities", "title": "Anti-inflammatory and/or immunomodulatory activities of Uncaria tomentosa (cat's claw) extracts: A systematic review and meta-analysis of in vivo studies", "authors": "Batiha GE et al.", "journal": "Journal of Ethnopharmacology", "year": 2024, "pmid": "38881881", "url": "https://pubmed.ncbi.nlm.nih.gov/38881881/", "study_type": "meta-analysis", "key_finding": "Extracts decreased NF-kB and IL-6 with low toxicity; findings suggest potential to treat inflammatory diseases where these markers are elevated.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38881881/", "publicSourceType": "PMID" }, { "claim": "Cat's claw acts as potent TNF-alpha inhibitor via NF-kB", "title": "Uncaria tomentosa acts as a potent TNF-alpha inhibitor through NF-kappaB", "authors": "Allen-Hall L et al.", "journal": "Journal of Ethnopharmacology", "year": 2010, "pmid": "19995599", "url": "https://pubmed.ncbi.nlm.nih.gov/19995599/", "study_type": "in vitro", "key_finding": "U. tomentosa inhibits TNF-alpha production through NF-kB-dependent mechanism; LPS-dependent TNF-alpha expression inhibited 5.5-fold.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19995599/", "publicSourceType": "PMID" }, { "claim": "Clinical efficacy and safety in knee osteoarthritis", "title": "Efficacy and safety of freeze-dried cat's claw in osteoarthritis of the knee: mechanisms of action of the species Uncaria guianensis", "authors": "Piscoya J et al.", "journal": "Inflammation Research", "year": 2001, "pmid": "11603848", "url": "https://pubmed.ncbi.nlm.nih.gov/11603848/", "study_type": "RCT", "key_finding": "In 45 patients, freeze-dried cat's claw significantly reduced pain with activity; benefits occurred within the first week of therapy.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11603848/", "publicSourceType": "PMID" }, { "claim": "Cat's claw reduces inflammation in osteoarthritis", "title": "Cat's claw: an Amazonian vine decreases inflammation in osteoarthritis", "authors": "Hardin SR", "journal": "Complementary Therapies in Clinical Practice", "year": 2007, "pmid": "17210508", "url": "https://pubmed.ncbi.nlm.nih.gov/17210508/", "study_type": "review", "key_finding": "Pain associated with activity, medical and patient assessment scores were all significantly reduced with cat's claw treatment.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17210508/", "publicSourceType": "PMID" }, { "claim": "Cat's claw inhibits TNF-alpha and scavenges free radicals", "title": "Cat's claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection", "authors": "Sandoval M et al.", "journal": "Free Radical Biology and Medicine", "year": 2000, "pmid": "10962207", "url": "https://pubmed.ncbi.nlm.nih.gov/10962207/", "study_type": "in vitro", "key_finding": "Cat's claw species are effective antioxidants; anti-inflammatory properties result from ability to inhibit TNF-alpha and PGE2 production.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10962207/", "publicSourceType": "PMID" }, { "claim": "Anti-inflammatory actions via NF-kappaB inhibition", "title": "Antiinflammatory actions of cat's claw: the role of NF-kappaB", "authors": "Sandoval-Chacon M et al.", "journal": "Alimentary Pharmacology & Therapeutics", "year": 1998, "pmid": "9882039", "url": "https://pubmed.ncbi.nlm.nih.gov/9882039/", "study_type": "in vitro", "key_finding": "Cat's claw inhibits NF-kappaB activation, which is a key mechanism underlying its anti-inflammatory effects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9882039/", "publicSourceType": "PMID" }, { "text": "Marques O, Figueirinha A, Pina ME et al.. Uncaria tomentosa as a Promising Natural Source of Molecules with Multiple Activities: Review of Its Ethnomedicinal Uses, Phytochemistry and Pharmacology. International journal of molecular sciences. 2025", "pmid": "40725012", "doi": "10.3390/ijms26146758", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40725012/", "publicSourceType": "PMID" }, { "text": "Yepes-Pérez AF, Herrera-Calderon O, Quintero-Saumeth J. Uncaria tomentosa (cat's claw): a promising herbal medicine against SARS-CoV-2/ACE-2 junction and SARS-CoV-2 spike protein based on molecular modeling. Journal of biomolecular structure & dynamics. 2022", "pmid": "33118480", "doi": "10.1080/07391102.2020.1837676", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33118480/", "publicSourceType": "PMID" }, { "claim": "Uncaria tomentosa (cat's claw) gel is effective as topical treatment for denture stomatitis", "title": "Evaluation of different treatment methods against denture stomatitis: a randomized clinical study", "authors": "Tay LY, Jorge JH, Herrera DR, Campanha NH, Gomes BP, Andre Dos Santos F", "journal": "Oral Surg Oral Med Oral Pathol Oral Radiol", "year": 2014, "pmid": "24908596", "url": "https://pubmed.ncbi.nlm.nih.gov/24908596/", "study_type": "rct", "key_finding": "RCT of 50 patients with denture stomatitis found 2% Uncaria tomentosa gel was equally effective as 2% miconazole gel in treating denture stomatitis, reducing both severity and Candida colony counts.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24908596/", "publicSourceType": "PMID" }, { "text": "Duchnowicz P, Pilarski R, Michałowicz J et al.. Changes in Human Erythrocyte Membrane Exposed to Aqueous and Ethanolic Extracts from Uncaria tomentosa. Molecules (Basel, Switzerland). 2021", "claim": "PubMed-indexed evidence involving Cat's Claw", "title": "Changes in Human Erythrocyte Membrane Exposed to Aqueous and Ethanolic Extracts from Uncaria tomentosa", "authors": "Duchnowicz P, Pilarski R, Michałowicz J et al.", "journal": "Molecules (Basel, Switzerland)", "year": 2021, "pmid": "34073461", "url": "https://pubmed.ncbi.nlm.nih.gov/34073461/", "study_type": "review", "confidence": "verify", "doi": "10.3390/molecules26113189", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34073461/", "publicSourceType": "PMID" }, { "text": "Reich A, Lopez Estebaranz JL, Bahadoran P et al.. A spray containing extracts of oat plantlets and Uncaria tomentosa relieves pain associated with chronic inflammatory skin diseases and dermatological procedures. Journal of the European Academy of Dermatology and Venereology : JEADV. 2020", "claim": "PubMed-indexed evidence involving Cat's Claw", "title": "A spray containing extracts of oat plantlets and Uncaria tomentosa relieves pain associated with chronic inflammatory skin diseases and dermatological procedures", "authors": "Reich A, Lopez Estebaranz JL, Bahadoran P et al.", "journal": "Journal of the European Academy of Dermatology and Venereology : JEADV", "year": 2020, "pmid": "32476176", "url": "https://pubmed.ncbi.nlm.nih.gov/32476176/", "study_type": "review", "confidence": "verify", "doi": "10.1111/jdv.16428", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32476176/", "publicSourceType": "PMID" }, { "text": "Yepes-Pérez AF, Herrera-Calderon O, Sánchez-Aparicio JE et al.. Investigating Potential Inhibitory Effect of Uncaria tomentosa (Cat's Claw) against the Main Protease 3CL(pro) of SARS-CoV-2 by Molecular Modeling. Evidence-based complementary and alternative medicine : eCAM. 2020", "claim": "PubMed-indexed evidence involving Cat's Claw", "title": "Investigating Potential Inhibitory Effect of Uncaria tomentosa (Cat's Claw) against the Main Protease 3CL(pro) of SARS-CoV-2 by Molecular Modeling", "authors": "Yepes-Pérez AF, Herrera-Calderon O, Sánchez-Aparicio JE et al.", "journal": "Evidence-based complementary and alternative medicine : eCAM", "year": 2020, "pmid": "33029165", "url": "https://pubmed.ncbi.nlm.nih.gov/33029165/", "study_type": "review", "confidence": "verify", "doi": "10.1155/2020/4932572", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33029165/", "publicSourceType": "PMID" }, { "text": "Dietrich F, Kaiser S, Rockenbach L et al.. Quinovic acid glycosides purified fraction from Uncaria tomentosa induces cell death by apoptosis in the T24 human bladder cancer cell line. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2014", "claim": "PubMed-indexed evidence involving Cat's Claw", "title": "Quinovic acid glycosides purified fraction from Uncaria tomentosa induces cell death by apoptosis in the T24 human bladder cancer cell line", "authors": "Dietrich F, Kaiser S, Rockenbach L et al.", "journal": "Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association", "year": 2014, "pmid": "24607820", "url": "https://pubmed.ncbi.nlm.nih.gov/24607820/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.fct.2014.02.037", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24607820/", "publicSourceType": "PMID" }, { "text": "de Oliveira LZ, Farias IL, Rigo ML et al.. Effect of Uncaria tomentosa Extract on Apoptosis Triggered by Oxaliplatin Exposure on HT29 Cells. Evidence-based complementary and alternative medicine : eCAM. 2014", "claim": "PubMed-indexed evidence involving Cat's Claw", "title": "Effect of Uncaria tomentosa Extract on Apoptosis Triggered by Oxaliplatin Exposure on HT29 Cells", "authors": "de Oliveira LZ, Farias IL, Rigo ML et al.", "journal": "Evidence-based complementary and alternative medicine : eCAM", "year": 2014, "pmid": "25505920", "url": "https://pubmed.ncbi.nlm.nih.gov/25505920/", "study_type": "review", "confidence": "verify", "doi": "10.1155/2014/274786", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25505920/", "publicSourceType": "PMID" }, { "text": "Cosentino C, Torres L. Reversible worsening of Parkinson disease motor symptoms after oral intake of Uncaria tomentosa (cat's claw). Clinical neuropharmacology. 2008", "claim": "PubMed-indexed evidence involving Cat's Claw", "title": "Reversible worsening of Parkinson disease motor symptoms after oral intake of Uncaria tomentosa (cat's claw)", "authors": "Cosentino C, Torres L", "journal": "Clinical neuropharmacology", "year": 2008, "pmid": "18836348", "url": "https://pubmed.ncbi.nlm.nih.gov/18836348/", "study_type": "review", "confidence": "verify", "doi": "10.1097/WNF.0b013e31815a5eef", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18836348/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "cat-s-claw" }, { "id": "B9BBB9B2-3F96-44C6-AB22-EE595B238CFD", "name": "Fenugreek", "alternateNames": [ "Trigonella foenum-graecum" ], "category": "Herb", "subcategory": "Galactagogue & Testosterone Herb", "overview": "Seed extract used for blood sugar control, testosterone support, and milk production.", "mechanismOfAction": "4-hydroxyisoleucine stimulates insulin secretion. Furostanolic saponins inhibit aromatase and 5-alpha-reductase, potentially increasing free testosterone. Galactomannans slow glucose absorption.", "commonBenefits": [ "Blood sugar control", "Testosterone support", "Lactation", "Appetite control" ], "commonDosageRange": "500-600 mg daily (standardized to 50% saponins)", "recommendedForm": "Testofen or standardized fenugreek extract", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food" }, "evidenceRating": "moderate", "foodSources": [ "Fenugreek seeds", "Fenugreek leaves (methi)" ], "deficiencySymptoms": [], "sideEffects": [ "Maple syrup-scented sweat/urine", "GI upset", "Blood sugar lowering" ], "contraindications": [ "Blood thinners", "Diabetes medications", "Pregnancy", "Hormone-sensitive conditions" ], "iconName": "leaf.fill", "colorHex": "34D399", "tags": [ "blood-sugar", "testosterone", "lactation" ], "sources": [ { "claim": "Fenugreek extract increases testosterone levels in men", "title": "Effect of fenugreek extract supplement on testosterone levels in male: A meta-analysis of clinical trials", "authors": "Mansoori A et al.", "journal": "Phytotherapy Research", "year": 2020, "pmid": "32048383", "url": "https://pubmed.ncbi.nlm.nih.gov/32048383/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of clinical trials demonstrated fenugreek extract significantly increases total and free testosterone levels in males.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32048383/", "publicSourceType": "PMID" }, { "claim": "Anabolic effects of fenugreek on testosterone, lean mass, and strength", "title": "The Anabolic Effect of Fenugreek: A Systematic Review with Meta-analysis", "authors": "Smith SJ et al.", "journal": "Journal of the International Society of Sports Nutrition", "year": 2023, "pmid": "37253363", "url": "https://pubmed.ncbi.nlm.nih.gov/37253363/", "study_type": "meta-analysis", "key_finding": "Seven studies (449 participants) showed small but significant effects on total testosterone, free testosterone, lean body mass, fat mass, and leg press performance in male athletes.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37253363/", "publicSourceType": "PMID" }, { "claim": "Testofen fenugreek extract improves testosterone and sexual function in aging males", "title": "Testofen, a specialised Trigonella foenum-graecum seed extract reduces age-related symptoms of androgen decrease, increases testosterone levels and improves sexual function in healthy aging males in a double-blind randomised clinical study", "authors": "Rao A et al.", "journal": "Aging Male", "year": 2016, "pmid": "26791805", "url": "https://pubmed.ncbi.nlm.nih.gov/26791805/", "study_type": "RCT", "key_finding": "600 mg/day Testofen for 12 weeks significantly increased total and free testosterone vs placebo in 120 healthy men aged 43-70.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26791805/", "publicSourceType": "PMID" }, { "claim": "Fenugreek reduces blood sugar in type 2 diabetes and prediabetes", "title": "The Effect of Fenugreek in Type 2 Diabetes and Prediabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Ranade M et al.", "journal": "Nutrients", "year": 2023, "pmid": "37762302", "url": "https://pubmed.ncbi.nlm.nih.gov/37762302/", "study_type": "meta-analysis", "key_finding": "Fenugreek significantly reduced fasting blood glucose (-0.96 mmol/L), 2-hour postload glucose (-2.19 mmol/L), and HbA1c (-0.85%) vs controls.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37762302/", "publicSourceType": "PMID" }, { "claim": "Fenugreek glycoside supplementation benefits resistance training males", "title": "Beneficial effects of fenugreek glycoside supplementation in male subjects during resistance training: A randomized controlled pilot study", "authors": "Wankhede S et al.", "journal": "Journal of Sport and Health Science", "year": 2018, "pmid": "30356905", "url": "https://pubmed.ncbi.nlm.nih.gov/30356905/", "study_type": "RCT", "key_finding": "Fenugreek glycoside fraction improved androgenic hormones and body composition during 8-week resistance training in a double-blind, placebo-controlled design.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30356905/", "publicSourceType": "PMID" }, { "claim": "Safety profile and adverse effects of fenugreek including maple syrup odor", "title": "Fenugreek", "authors": "National Library of Medicine", "journal": "LiverTox: Clinical and Research Information on Drug-Induced Liver Injury", "year": 2020, "pmid": "30000838", "url": "https://pubmed.ncbi.nlm.nih.gov/30000838/", "study_type": "NIH_ODS", "key_finding": "Adverse effects include GI discomfort, maple syrup-scented urine/sweat; caution with diabetes medications and blood thinners; cross-reactivity possible in legume-allergic individuals.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30000838/", "publicSourceType": "PMID" }, { "claim": "Fenugreek increases testosterone levels", "title": "Effects of fenugreek seed extract on testosterone: a meta-analysis", "authors": "Mansoori A, Hosseini S, Zilaee M et al.", "journal": "Phytother Res", "year": 2020, "pmid": "31943591", "doi": "10.1002/ptr.6627", "study_type": "meta-analysis", "key_finding": "Significant increase in total and free testosterone via furostanolic saponins", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31943591/", "publicSourceType": "PMID" }, { "claim": "Fenugreek supplementation improves glycemic control in type 2 diabetes", "title": "Effect of fenugreek (Trigonella foenum-graecum) supplementation on glycemic control in patients with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials.", "authors": "Shishehbor F, Ghavipour M et al.", "journal": "Phytotherapy Research", "year": 2024, "pmid": "40037045", "url": "https://pubmed.ncbi.nlm.nih.gov/40037045/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of RCTs showed fenugreek supplementation significantly reduced fasting blood glucose, HbA1c, and 2-hour postprandial glucose in type 2 diabetes patients.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40037045/", "publicSourceType": "PMID" }, { "claim": "Fenugreek improves testosterone levels and sexual function in men", "title": "Effects of fenugreek supplementation on male reproductive health: A systematic review and meta-analysis of clinical trials.", "authors": "Rao A, Steels E et al.", "journal": "Phytotherapy Research", "year": 2024, "pmid": "39286181", "url": "https://pubmed.ncbi.nlm.nih.gov/39286181/", "study_type": "meta-analysis", "key_finding": "Meta-analysis found fenugreek extract supplementation was associated with significant increases in serum testosterone levels and improvements in sexual function in men.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39286181/", "publicSourceType": "PMID" }, { "text": "Chehregosha F, Fakhr L, Tarighat-Esfanjani A et al.. The effects of fenugreek (Trigonella foenum-graecum) seed on glycemic parameters: An updated systematic review and meta-analysis of randomized controlled trials. Avicenna journal of phytomedicine. 2025", "claim": "PubMed-indexed evidence involving Fenugreek", "title": "The effects of fenugreek (Trigonella foenum-graecum) seed on glycemic parameters: An updated systematic review and meta-analysis of randomized controlled trials", "authors": "Chehregosha F, Fakhr L, Tarighat-Esfanjani A et al.", "journal": "Avicenna journal of phytomedicine", "year": 2025, "pmid": "41509111", "url": "https://pubmed.ncbi.nlm.nih.gov/41509111/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.22038/ajp.2025.26043", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41509111/", "publicSourceType": "PMID" }, { "text": "Amini MR, Payandeh N, Sheikhhossein F et al.. The Effects of Fenugreek Seed Consumption on Blood Pressure: A Systematic Review and Meta-analysis of Randomized Controlled Trials. High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension. 2023", "claim": "PubMed-indexed evidence involving Fenugreek", "title": "The Effects of Fenugreek Seed Consumption on Blood Pressure: A Systematic Review and Meta-analysis of Randomized Controlled Trials", "authors": "Amini MR, Payandeh N, Sheikhhossein F et al.", "journal": "High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension", "year": 2023, "pmid": "36763260", "url": "https://pubmed.ncbi.nlm.nih.gov/36763260/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s40292-023-00565-6", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36763260/", "publicSourceType": "PMID" }, { "text": "Askarpour M, Alami F, Campbell MS et al.. Effect of fenugreek supplementation on blood lipids and body weight: A systematic review and meta-analysis of randomized controlled trials. Journal of ethnopharmacology. 2020", "claim": "PubMed-indexed evidence involving Fenugreek", "title": "Effect of fenugreek supplementation on blood lipids and body weight: A systematic review and meta-analysis of randomized controlled trials", "authors": "Askarpour M, Alami F, Campbell MS et al.", "journal": "Journal of ethnopharmacology", "year": 2020, "pmid": "32087319", "url": "https://pubmed.ncbi.nlm.nih.gov/32087319/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jep.2019.112538", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32087319/", "publicSourceType": "PMID" }, { "text": "Albaker WI. Fenugreek and Its Effects on Muscle Performance: A Systematic Review. Journal of personalized medicine. 2023", "claim": "PubMed-indexed evidence involving Fenugreek", "title": "Fenugreek and Its Effects on Muscle Performance: A Systematic Review", "authors": "Albaker WI", "journal": "Journal of personalized medicine", "year": 2023, "pmid": "36983608", "url": "https://pubmed.ncbi.nlm.nih.gov/36983608/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/jpm13030427", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36983608/", "publicSourceType": "PMID" }, { "text": "Correia AGDS, Alencar MB, Dos Santos AN et al.. Effect of saffron and fenugreek on lowering blood glucose: A systematic review with meta-analysis. Phytotherapy research : PTR. 2023", "claim": "PubMed-indexed evidence involving Fenugreek", "title": "Effect of saffron and fenugreek on lowering blood glucose: A systematic review with meta-analysis", "authors": "Correia AGDS, Alencar MB, Dos Santos AN et al.", "journal": "Phytotherapy research : PTR", "year": 2023, "pmid": "36992660", "url": "https://pubmed.ncbi.nlm.nih.gov/36992660/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/ptr.7817", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36992660/", "publicSourceType": "PMID" }, { "text": "Heshmat-Ghahdarijani K, Mashayekhiasl N, Amerizadeh A et al.. Effect of fenugreek consumption on serum lipid profile: A systematic review and meta-analysis. Phytotherapy research : PTR. 2020", "claim": "PubMed-indexed evidence involving Fenugreek", "title": "Effect of fenugreek consumption on serum lipid profile: A systematic review and meta-analysis", "authors": "Heshmat-Ghahdarijani K, Mashayekhiasl N, Amerizadeh A et al.", "journal": "Phytotherapy research : PTR", "year": 2020, "pmid": "32385866", "url": "https://pubmed.ncbi.nlm.nih.gov/32385866/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/ptr.6690", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32385866/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "fenugreek" }, { "id": "E5E43F5E-46CC-4682-A8CB-9498A91B1331", "name": "Olive Leaf Extract", "alternateNames": [ "Olea europaea" ], "category": "Herb", "subcategory": "Antimicrobial Polyphenol", "overview": "Rich in oleuropein with antimicrobial, antioxidant, and cardiovascular benefits.", "mechanismOfAction": "Oleuropein and hydroxytyrosol inhibit bacterial, viral, and fungal growth. Modulate eNOS for blood pressure support. Potent antioxidant via radical scavenging and metal chelation.", "commonBenefits": [ "Immune support", "Blood pressure", "Antioxidant", "Antimicrobial" ], "commonDosageRange": "500-1,000 mg daily (standardized to 18-20% oleuropein)", "recommendedForm": "Standardized extract", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food" }, "evidenceRating": "emerging", "foodSources": [ "Olives", "Olive oil" ], "deficiencySymptoms": [], "sideEffects": [ "GI upset", "Headache (Herxheimer reaction)", "Dizziness" ], "contraindications": [ "Blood pressure medications", "Diabetes medications", "Blood thinners" ], "iconName": "leaf.fill", "colorHex": "34D399", "tags": [ "immune", "blood-pressure", "antimicrobial", "antioxidant" ], "sources": [ { "claim": "Olive leaf extract reduces blood pressure in hypertensive individuals", "title": "Olive leaf extract effect on cardiometabolic profile among adults with prehypertension and hypertension: a systematic review and meta-analysis", "authors": "Ismail MA et al.", "journal": "European Journal of Integrative Medicine", "year": 2021, "pmid": "33868820", "url": "https://pubmed.ncbi.nlm.nih.gov/33868820/", "study_type": "meta-analysis", "key_finding": "Five trials (325 patients) showed olive leaf extract decreased 24-hour BP, BP load, and diastolic BP variability with improvements in lipid profile and inflammation.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33868820/", "publicSourceType": "PMID" }, { "claim": "Olive leaf extract affects cardiovascular risk factors", "title": "The effects of olive leaf extract on cardiovascular risk factors in the general adult population: a systematic review and meta-analysis of randomized controlled trials", "authors": "Marx W et al.", "journal": "Nutrition Reviews", "year": 2022, "pmid": null, "url": null, "note": "NO_SOURCE_FOUND, PMC article PMC9585795 found but specific PMID not confirmed from search results", "study_type": "meta-analysis", "key_finding": "Reductions in total cholesterol, LDL cholesterol, triglycerides, and interleukin-8 observed with olive leaf extract compared to control.", "confidence": "verify", "publicReviewStatus": "pmid-unconfirmed", "publicSourceURL": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9585795/", "publicSourceType": "PMC" }, { "claim": "Phenolic-rich olive leaf extract impacts blood pressure and inflammatory markers in RCT", "title": "Impact of phenolic-rich olive leaf extract on blood pressure, plasma lipids and inflammatory markers: a randomised controlled trial", "authors": "Lockyer S et al.", "journal": "European Journal of Nutrition", "year": 2017, "pmid": "26951205", "url": "https://pubmed.ncbi.nlm.nih.gov/26951205/", "study_type": "RCT", "key_finding": "In pre-hypertensive males, 136 mg oleuropein daily significantly lowered daytime and 24-hour systolic and diastolic blood pressure.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26951205/", "publicSourceType": "PMID" }, { "claim": "Olive leaf extract cardiovascular health markers in RCT", "title": "The effect of olive leaf extract on cardiovascular health markers: a randomized placebo-controlled clinical trial", "authors": "Boss A et al.", "journal": "European Journal of Nutrition", "year": 2021, "pmid": "33034707", "url": "https://pubmed.ncbi.nlm.nih.gov/33034707/", "study_type": "RCT", "key_finding": "Olive leaf extract supplementation demonstrated effects on cardiovascular health markers in a placebo-controlled trial.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33034707/", "publicSourceType": "PMID" }, { "claim": "Olive leaf extract reduces sick days via immune support in athletes", "title": "The Effect of Olive Leaf Extract on Upper Respiratory Illness in High School Athletes: A Randomised Control Trial", "authors": "Somerville V et al.", "journal": "Nutrients", "year": 2019, "pmid": "30744092", "url": "https://pubmed.ncbi.nlm.nih.gov/30744092/", "study_type": "RCT", "key_finding": "Olive leaf extract supplementation produced a significant 28% reduction in sick days in high school athletes, though illness incidence was not significantly different.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30744092/", "publicSourceType": "PMID" }, { "claim": "Antimicrobial activity of olive leaf extract against food pathogens", "title": "Assessment of the Antimicrobial Activity of Olive Leaf Extract Against Foodborne Bacterial Pathogens", "authors": "Liu Y et al.", "journal": "Frontiers in Microbiology", "year": 2017, "pmid": null, "url": null, "note": "NO_SOURCE_FOUND, PMC article PMC5288333 found but specific PMID not confirmed from search results", "study_type": "in vitro", "key_finding": "At 62.5 mg/ml concentration, olive leaf extract almost completely inhibited growth of Listeria monocytogenes, E. coli O157:H7, and Salmonella Enteritidis.", "confidence": "verify", "publicReviewStatus": "pmid-unconfirmed", "publicSourceURL": "https://pmc.ncbi.nlm.nih.gov/articles/PMC5288333/", "publicSourceType": "PMC" }, { "text": "Lamti F, Trabelsi I, Dhaoui R et al.. Efficacy of olive leaf extracts in controlling blood pressure in hypertensive patients: a double-blind randomized clinical trial. Journal of hypertension. 2025", "pmid": "40990594", "doi": "10.1097/HJH.0000000000004141", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40990594/", "publicSourceType": "PMID" }, { "text": "Imperatrice M, Lasfar A, van Kalkeren CAJ et al.. Olive Leaf Extract Supplementation Improves Postmenopausal Symptoms: A Randomized, Double-Blind, Placebo-Controlled Parallel Study on Postmenopausal Women. Nutrients. 2024", "pmid": "39599665", "doi": "10.3390/nu16223879", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39599665/", "publicSourceType": "PMID" }, { "claim": "Olive leaf extract may improve cardiometabolic risk factors including blood pressure and glucose metabolism", "title": "Olive leaf extract effect on cardiometabolic risk factors: a systematic review and meta-analysis of randomized clinical trials", "authors": "Alvares AA, Garcez A, Silva LT, Averbuch N, Garavaglia J", "journal": "Nutr Rev", "year": 2024, "pmid": "38287654", "url": "https://pubmed.ncbi.nlm.nih.gov/38287654/", "study_type": "meta-analysis", "key_finding": "Systematic review and meta-analysis of 12 RCTs (703 patients) found OLE showed positive correlations with glucose metabolism (4 RCTs), blood pressure (2 RCTs), lipid profile (2 RCTs), and inflammatory markers (2 RCTs).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38287654/", "publicSourceType": "PMID" }, { "claim": "Olive leaf extract reduces oxidative stress markers (malondialdehyde) in obese women on a calorie-restricted diet", "title": "Phenolic-rich extract of olive leaf with a hypocaloric diet alleviates oxidative stress in obese females: a randomized double-blind placebo controlled trial", "authors": "Haidari F, Mohammad-Shahi M, Jalali MT, Ahmadi-Angali K, Shayesteh F", "journal": "Nutr Metab Cardiovasc Dis", "year": 2025, "pmid": "40685267", "url": "https://pubmed.ncbi.nlm.nih.gov/40685267/", "study_type": "rct", "key_finding": "RCT of 70 obese women found OLE (250 mg/day) combined with a hypocaloric diet for 8 weeks significantly reduced serum malondialdehyde compared to placebo + hypocaloric diet.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40685267/", "publicSourceType": "PMID" }, { "claim": "Olive leaf extract reduces pain and improves physical functioning in elderly patients with knee osteoarthritis", "title": "Impact of olive leaf extract on pain management and functional improvement in elderly patients with knee osteoarthritis: A randomized controlled trial", "authors": "Roshani M, Delfan B, Yarahmadi S, Saki M, Birjandi M", "journal": "Explore (NY)", "year": 2025, "pmid": "39955806", "url": "https://pubmed.ncbi.nlm.nih.gov/39955806/", "study_type": "rct", "key_finding": "RCT of 100 elderly patients with knee osteoarthritis found OLE (oral and/or topical) significantly reduced pain scores and improved daily functioning. Combination of oral and topical showed the most pronounced effects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39955806/", "publicSourceType": "PMID" }, { "text": "Menezes RCR, Peres KK, Costa-Valle MT et al.. Oral administration of oleuropein and olive leaf extract has cardioprotective effects in rodents: A systematic review. Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology. 2022", "claim": "PubMed-indexed evidence involving Olive Leaf Extract", "title": "Oral administration of oleuropein and olive leaf extract has cardioprotective effects in rodents: A systematic review", "authors": "Menezes RCR, Peres KK, Costa-Valle MT et al.", "journal": "Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology", "year": 2022, "pmid": "36062705", "url": "https://pubmed.ncbi.nlm.nih.gov/36062705/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.repc.2021.05.011", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36062705/", "publicSourceType": "PMID" }, { "text": "Fladerer-Grollitsch JP, Bucar F, Klein T et al.. Effects of a combination of olive leaf extract and potassium on blood pressure in participants with mild to moderate hypertension: A double blind, randomized, placebo-controlled trial. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2026", "claim": "PubMed-indexed evidence involving Olive Leaf Extract", "title": "Effects of a combination of olive leaf extract and potassium on blood pressure in participants with mild to moderate hypertension: A double blind, randomized, placebo-controlled trial", "authors": "Fladerer-Grollitsch JP, Bucar F, Klein T et al.", "journal": "Phytomedicine : international journal of phytotherapy and phytopharmacology", "year": 2026, "pmid": "41935461", "url": "https://pubmed.ncbi.nlm.nih.gov/41935461/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.phymed.2026.158138", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41935461/", "publicSourceType": "PMID" }, { "text": "Forbes-Hernández TY, Vargas-Corral FG, Bullón B et al.. Adjuvant treatment with an oleuropein-enriched olive leaf extract improves periodontal outcomes in older adults with periodontitis: Metabolomic insights from a randomized controlled trial. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2026", "claim": "PubMed-indexed evidence involving Olive Leaf Extract", "title": "Adjuvant treatment with an oleuropein-enriched olive leaf extract improves periodontal outcomes in older adults with periodontitis: Metabolomic insights from a randomized controlled trial", "authors": "Forbes-Hernández TY, Vargas-Corral FG, Bullón B et al.", "journal": "Phytomedicine : international journal of phytotherapy and phytopharmacology", "year": 2026, "pmid": "42061085", "url": "https://pubmed.ncbi.nlm.nih.gov/42061085/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.phymed.2026.158222", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/42061085/", "publicSourceType": "PMID" }, { "text": "Lasfar A, van Stratum SLM, Imperatrice M et al.. Effects of olive leaf extract supplementation on systemic markers of tissue aging and remodeling in postmenopausal women: a randomized controlled trial with exploratory skin outcomes. Frontiers in nutrition. 2025", "claim": "PubMed-indexed evidence involving Olive Leaf Extract", "title": "Effects of olive leaf extract supplementation on systemic markers of tissue aging and remodeling in postmenopausal women: a randomized controlled trial with exploratory skin outcomes", "authors": "Lasfar A, van Stratum SLM, Imperatrice M et al.", "journal": "Frontiers in nutrition", "year": 2025, "pmid": "41340653", "url": "https://pubmed.ncbi.nlm.nih.gov/41340653/", "study_type": "RCT", "confidence": "verify", "doi": "10.3389/fnut.2025.1670194", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41340653/", "publicSourceType": "PMID" }, { "text": "Gaizeh Al-Hallak MA, Hsaian JA, Aljoujou AA. Evaluating the effectiveness of topical olive leaf extract emulgel in managing recurrent herpes labialis: a randomized controlled clinical study. Scientific reports. 2024", "claim": "PubMed-indexed evidence involving Olive Leaf Extract", "title": "Evaluating the effectiveness of topical olive leaf extract emulgel in managing recurrent herpes labialis: a randomized controlled clinical study", "authors": "Gaizeh Al-Hallak MA, Hsaian JA, Aljoujou AA", "journal": "Scientific reports", "year": 2024, "pmid": "39623211", "url": "https://pubmed.ncbi.nlm.nih.gov/39623211/", "study_type": "RCT", "confidence": "verify", "doi": "10.1038/s41598-024-81805-0", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39623211/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "olive-leaf-extract" }, { "id": "DFFE0927-FB3A-4F8A-AA4E-45D47510E4F3", "name": "Moringa", "alternateNames": [ "Moringa oleifera", "Drumstick Tree" ], "category": "Herb", "subcategory": "Nutrient-Dense Superfood Herb", "overview": "Tropical tree leaf with exceptional nutrient density, often called the 'miracle tree.'", "mechanismOfAction": "Contains isothiocyanates (moringin) that activate Nrf2 antioxidant pathways. Rich in quercetin, chlorogenic acid, and beta-carotene. Provides complete protein with all essential amino acids.", "commonBenefits": [ "Nutrient density", "Anti-inflammatory", "Blood sugar support", "Antioxidant" ], "commonDosageRange": "500-2,000 mg daily", "recommendedForm": "Organic moringa leaf powder or capsules", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food" }, "evidenceRating": "emerging", "foodSources": [ "Moringa leaves", "Moringa pods" ], "deficiencySymptoms": [], "sideEffects": [ "GI upset", "Blood sugar lowering", "Thyroid effects" ], "contraindications": [ "Thyroid medications (contains goitrogens)", "Blood thinners", "Diabetes medications", "Pregnancy (bark/root are uterotonic)" ], "iconName": "tree.fill", "colorHex": "6BCB77", "tags": [ "superfood", "nutrient-dense", "antioxidant", "anti-inflammatory" ], "sources": [ { "claim": "Safety and efficacy review of Moringa oleifera", "title": "Review of the Safety and Efficacy of Moringa oleifera", "authors": "Stohs SJ et al.", "journal": "Phytotherapy Research", "year": 2015, "pmid": "25808883", "url": "https://pubmed.ncbi.nlm.nih.gov/25808883/", "study_type": "review", "key_finding": "Five human studies using powdered whole leaf preparations demonstrated anti-hyperglycemic and anti-dyslipidemic activities with no adverse effects reported.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25808883/", "publicSourceType": "PMID" }, { "claim": "Moringa supplementation effects on glycaemia and insulin levels", "title": "Effects of Moringa oleifera on Glycaemia and Insulin Levels: A Review of Animal and Human Studies", "authors": "Nova E et al.", "journal": "Nutrients", "year": 2020, "pmid": "31810205", "url": "https://pubmed.ncbi.nlm.nih.gov/31810205/", "study_type": "review", "key_finding": "Acute antihyperglycemic effects of moringa are robust in animal models; of 7 human studies, 5 found significant blood glucose reductions in diabetic patients.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31810205/", "publicSourceType": "PMID" }, { "claim": "Moringa isothiocyanates activate Nrf2 antioxidant pathways", "title": "Development of Moringa oleifera as functional food targeting NRF2 signaling: antioxidant and anti-inflammatory activity in experimental model systems", "authors": "Tumer TB et al.", "journal": "Food and Function", "year": 2023, "pmid": "37114361", "url": "https://pubmed.ncbi.nlm.nih.gov/37114361/", "study_type": "in vitro/in vivo", "key_finding": "Oral moringa leaf preparation significantly increased Nrf2-regulated antioxidant genes in small intestine, liver, and lungs.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37114361/", "publicSourceType": "PMID" }, { "claim": "Umbrella review of moringa for inflammatory diseases across 26 systematic reviews", "title": "Effect of Moringa oleifera on inflammatory diseases: an umbrella review of 26 systematic reviews", "authors": "Wang Y et al.", "journal": "BMC Complementary Medicine and Therapies", "year": 2025, "pmid": "40458803", "url": "https://pubmed.ncbi.nlm.nih.gov/40458803/", "study_type": "umbrella review", "key_finding": "Promising efficacy for diabetes, obesity, cancer, hypertension, and dyslipidemia but quality of evidence predominantly low by AMSTAR-2 evaluation.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40458803/", "publicSourceType": "PMID" }, { "claim": "Comprehensive review of moringa pharmacology, phytochemistry, and toxicology", "title": "Moringa oleifera: a systematic review of its botany, traditional uses, phytochemistry, pharmacology and toxicity", "authors": "Kou X et al.", "journal": "Journal of Pharmacy and Pharmacology", "year": 2022, "pmid": "34718669", "url": "https://pubmed.ncbi.nlm.nih.gov/34718669/", "study_type": "review", "key_finding": "Moringa contains isothiocyanates (moringin), quercetin, chlorogenic acid, beta-carotene, and complete protein; single oral dose of 5000 mg/kg showed no adverse reactions in rats.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34718669/", "publicSourceType": "PMID" }, { "claim": "Moringa effects on thyroid regulation", "title": "Role of Moringa oleifera leaf extract in the regulation of thyroid hormone status in adult male and female rats", "authors": "Tahiliani P et al.", "journal": "Pharmacological Research", "year": 2000, "pmid": "10675284", "url": "https://pubmed.ncbi.nlm.nih.gov/10675284/", "study_type": "animal study", "key_finding": "In female rats, moringa decreased serum T3 and increased T4; these thyroid effects should be considered in patients on thyroid medications.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10675284/", "publicSourceType": "PMID" }, { "text": "Ammar M, Russo GL, Altamimi A et al.. Moringa oleifera Supplementation as a Natural Galactagogue: A Systematic Review on Its Role in Supporting Milk Volume and Prolactin Levels. Foods (Basel, Switzerland). 2025", "pmid": "40724308", "doi": "10.3390/foods14142487", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40724308/", "publicSourceType": "PMID" }, { "text": "Klimek-Szczykutowicz M, Gaweł-Bęben K, Rutka A et al.. Moringa oleifera (drumstick tree)-nutraceutical, cosmetological and medicinal importance: a review. Frontiers in pharmacology. 2024", "pmid": "38370483", "doi": "10.3389/fphar.2024.1288382", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38370483/", "publicSourceType": "PMID" }, { "claim": "Moringa oleifera leaf supplementation improves glycemic control in subjects with prediabetes", "title": "Moringa oleifera Leaf Supplementation as a Glycemic Control Strategy in Subjects with Prediabetes", "authors": "Gomez-Martinez S, Diaz-Prieto LE, Vicente Castro I et al.", "journal": "Nutrients", "year": 2021, "pmid": "35010932", "url": "https://pubmed.ncbi.nlm.nih.gov/35010932/", "study_type": "rct", "key_finding": "Double-blind RCT of 65 subjects with prediabetes found 12 weeks of Moringa oleifera leaf supplementation (2400 mg/day) resulted in favorable changes in fasting blood glucose and HbA1c compared to placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35010932/", "publicSourceType": "PMID" }, { "claim": "Moringa supplementation shows modest reduction in diastolic blood pressure but no consistent cardiometabolic benefits", "title": "Effects of Moringa oleifera Lam. Supplementation on Cardiometabolic Outcomes: A Meta-Analysis of Randomized Controlled Trials with GRADE Assessment", "authors": "Crisan D, Gavrilas L, Paltinean R, Frumuzachi O, Mocan A, Crisan G", "journal": "Nutrients", "year": 2025, "pmid": "41305552", "url": "https://pubmed.ncbi.nlm.nih.gov/41305552/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 9 RCTs (649 participants) found moringa showed a modest reduction in diastolic blood pressure (SMD: -0.41) but no significant effects on most cardiometabolic outcomes. Overall certainty of evidence was very low.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41305552/", "publicSourceType": "PMID" }, { "claim": "Moringa oleifera combined with Allium sativum improves lipid profile in hyperlipidemic patients", "title": "Synergistic effect of Moringa oleifera and Allium sativum on BMI and lipid profile: A randomized controlled trial", "authors": "Sarfraz A, Hussain MI, Ibtisam R et al.", "journal": "Pak J Pharm Sci", "year": 2023, "pmid": "38008957", "url": "https://pubmed.ncbi.nlm.nih.gov/38008957/", "study_type": "rct", "key_finding": "RCT of 60 hyperlipidemic patients found Moringa oleifera supplementation (2 g/day for 45 days) significantly improved total cholesterol, triglycerides, and LDL compared to statin alone.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38008957/", "publicSourceType": "PMID" }, { "text": "Nurhayati T, Ridho MF, Santoso PTR et al.. Effects of Moringa oleifera Leaf Extract on Liver Histopathology: A Systematic Review. Journal of nutrition and metabolism. 2024", "claim": "PubMed-indexed evidence involving Moringa", "title": "Effects of Moringa oleifera Leaf Extract on Liver Histopathology: A Systematic Review", "authors": "Nurhayati T, Ridho MF, Santoso PTR et al.", "journal": "Journal of nutrition and metabolism", "year": 2024, "pmid": "38993633", "url": "https://pubmed.ncbi.nlm.nih.gov/38993633/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1155/2024/6815993", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38993633/", "publicSourceType": "PMID" }, { "text": "Soto JA, Gómez AC, Vásquez M et al.. Biological properties of Moringa oleifera: A systematic review of the last decade. F1000Research. 2024", "claim": "PubMed-indexed evidence involving Moringa", "title": "Biological properties of Moringa oleifera: A systematic review of the last decade", "authors": "Soto JA, Gómez AC, Vásquez M et al.", "journal": "F1000Research", "year": 2024, "pmid": "39895949", "url": "https://pubmed.ncbi.nlm.nih.gov/39895949/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.12688/f1000research.157194.2", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39895949/", "publicSourceType": "PMID" }, { "text": "Ogbuewu IP, Mbajiorgu CA. Lipid profiles and production performance responses of laying hens to dietary Moringa oleifera leaf meal: systematic review and meta-analysis. Tropical animal health and production. 2023", "claim": "PubMed-indexed evidence involving Moringa", "title": "Lipid profiles and production performance responses of laying hens to dietary Moringa oleifera leaf meal: systematic review and meta-analysis", "authors": "Ogbuewu IP, Mbajiorgu CA", "journal": "Tropical animal health and production", "year": 2023, "pmid": "37500961", "url": "https://pubmed.ncbi.nlm.nih.gov/37500961/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s11250-023-03693-2", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37500961/", "publicSourceType": "PMID" }, { "text": "Waruguru P, Mulwa DW, Okoth M et al.. Moringa oleifera regulates the health of people living with HIV in developing countries: a systematic review. African journal of AIDS research : AJAR. 2023", "claim": "PubMed-indexed evidence involving Moringa", "title": "Moringa oleifera regulates the health of people living with HIV in developing countries: a systematic review", "authors": "Waruguru P, Mulwa DW, Okoth M et al.", "journal": "African journal of AIDS research : AJAR", "year": 2023, "pmid": "38015892", "url": "https://pubmed.ncbi.nlm.nih.gov/38015892/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2989/16085906.2023.2277894", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38015892/", "publicSourceType": "PMID" }, { "text": "Brar S, Haugh C, Robertson N et al.. The impact of Moringa oleifera leaf supplementation on human and animal nutrition, growth, and milk production: A systematic review. Phytotherapy research : PTR. 2022", "claim": "PubMed-indexed evidence involving Moringa", "title": "The impact of Moringa oleifera leaf supplementation on human and animal nutrition, growth, and milk production: A systematic review", "authors": "Brar S, Haugh C, Robertson N et al.", "journal": "Phytotherapy research : PTR", "year": 2022, "pmid": "35302264", "url": "https://pubmed.ncbi.nlm.nih.gov/35302264/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/ptr.7415", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35302264/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "moringa" }, { "id": "46FDFB6B-2CE3-4CB2-AFB0-3B2744BEA0E6", "name": "Colostrum", "alternateNames": [ "Bovine Colostrum" ], "category": "Other", "subcategory": "Immune Protein Complex", "overview": "First milk containing concentrated immunoglobulins, growth factors, and lactoferrin.", "mechanismOfAction": "IgG antibodies provide passive immune support. Lactoferrin has antimicrobial and iron-modulating effects. Growth factors (IGF-1, TGF-β) support gut repair and mucosal immunity.", "commonBenefits": [ "Gut health", "Immune support", "Athletic recovery", "Gut barrier repair" ], "commonDosageRange": "500-2,000 mg daily", "recommendedForm": "Bovine colostrum (first milking, cold-processed)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Take on empty stomach; 30 min before food" }, "evidenceRating": "emerging", "foodSources": [ "First milk from cows" ], "deficiencySymptoms": [], "sideEffects": [ "GI discomfort", "Bloating" ], "contraindications": [ "Dairy allergy", "Lactose intolerance (small amounts present)" ], "iconName": "shield.fill", "colorHex": "FFB84D", "tags": [ "immune", "gut-health", "recovery" ], "sources": [ { "claim": "Bovine colostrum reduces exercise-induced gut permeability", "title": "The nutriceutical bovine colostrum truncates the increase in gut permeability caused by heavy exercise in athletes", "authors": "Marchbank T et al.", "journal": "American Journal of Physiology-Gastrointestinal and Liver Physiology", "year": 2011, "pmid": "21148400", "url": "https://pubmed.ncbi.nlm.nih.gov/21148400/", "study_type": "RCT", "key_finding": "In a double-blind crossover study, exercise increased intestinal permeability 2.5-fold with placebo, while colostrum truncated the rise by 80%.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21148400/", "publicSourceType": "PMID" }, { "claim": "Meta-analysis of colostrum effects on intestinal permeability", "title": "Bovine Colostrum in Increased Intestinal Permeability in Healthy Athletes and Patients: A Meta-Analysis of Randomized Clinical Trials", "authors": "Dziewiecka H et al.", "journal": "Nutrients", "year": 2024, "pmid": "38361147", "url": "https://pubmed.ncbi.nlm.nih.gov/38361147/", "study_type": "meta-analysis", "key_finding": "BC supplementation significantly reduced intestinal permeability as measured by lactulose/rhamnose ratio across randomized clinical trials.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38361147/", "publicSourceType": "PMID" }, { "claim": "Systematic review of colostrum effects on gastrointestinal diseases", "title": "Therapeutics effects of bovine colostrum applications on gastrointestinal diseases: a systematic review", "authors": "Barakat SH et al.", "journal": "BMC Complementary Medicine and Therapies", "year": 2024, "pmid": "38409162", "url": "https://pubmed.ncbi.nlm.nih.gov/38409162/", "study_type": "review", "key_finding": "In 22 clinical trials (1427 patients), diarrhea frequency decreased with BC supplementation in 15 of 20 interventional arms.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38409162/", "publicSourceType": "PMID" }, { "claim": "Colostrum composition and immune effects review", "title": "Diverse Immune Effects of Bovine Colostrum and Benefits in Human Health and Disease", "authors": "Playford RJ et al.", "journal": "Nutrients", "year": 2021, "pmid": "34836054", "url": "https://pubmed.ncbi.nlm.nih.gov/34836054/", "study_type": "review", "key_finding": "Bovine colostrum contains concentrated immunoglobulins (IgG 75-90% of total), lactoferrin, growth factors (IGF-1, TGF-beta), and over 250 functional constituents.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34836054/", "publicSourceType": "PMID" }, { "claim": "Immunological outcomes of colostrum supplementation in athletes", "title": "Immunological Outcomes of Bovine Colostrum Supplementation in Trained and Physically Active People: A Systematic Review and Meta-Analysis", "authors": "Jones AW et al.", "journal": "Sports Medicine", "year": 2020, "pmid": "32276466", "url": "https://pubmed.ncbi.nlm.nih.gov/32276466/", "study_type": "meta-analysis", "key_finding": "In 10 RCTs (239 participants), BC supplementation had no or low impact on serum immunoglobulins and lymphocytes, but reduced upper respiratory tract symptom days.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32276466/", "publicSourceType": "PMID" }, { "claim": "Colostrum growth factors for GI treatment", "title": "Colostrum and milk-derived peptide growth factors for the treatment of gastrointestinal disorders", "authors": "Playford RJ et al.", "journal": "American Journal of Clinical Nutrition", "year": 2000, "pmid": "10871554", "url": "https://pubmed.ncbi.nlm.nih.gov/10871554/", "study_type": "review", "key_finding": "Lactoferrin has antimicrobial and iron-modulating effects; growth factors (IGF-1, TGF-beta) support gut repair and mucosal immunity.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10871554/", "publicSourceType": "PMID" }, { "text": "Anne RP, Kumar J, Kumar P et al.. Effect of oropharyngeal colostrum therapy on neonatal sepsis in preterm neonates: A systematic review and meta-analysis. Journal of pediatric gastroenterology and nutrition. 2024", "pmid": "38314925", "doi": "10.1002/jpn3.12085", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38314925/", "publicSourceType": "PMID" }, { "text": "Slouha E, Anderson ZS, Ankrah NMN et al.. Colostrum and Preterm Babies: A Systematic Review. Cureus. 2023", "pmid": "37593258", "doi": "10.7759/cureus.42021", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37593258/", "publicSourceType": "PMID" }, { "claim": "Bovine colostrum supplementation increases post-exercise salivary IgA in endurance athletes", "title": "The effect of 12-week high-dose Colostrum Bovinum supplementation on immunological, hematological and biochemical markers in endurance athletes: a randomized crossover placebo-controlled study", "authors": "Durkalec-Michalski K, Glowka N, Podgorski T, Wozniewicz M, Nowaczyk PM", "journal": "Front Immunol", "year": 2024, "pmid": "39497827", "url": "https://pubmed.ncbi.nlm.nih.gov/39497827/", "study_type": "rct", "key_finding": "Randomized crossover study in 28 endurance-trained males found 12-week bovine colostrum supplementation (25 g/day) significantly increased post-exercise secretory IgA concentration in saliva, suggesting enhanced local immune defense.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39497827/", "publicSourceType": "PMID" }, { "claim": "Bovine colostrum supplementation in preterm infants did not reduce time to full enteral feeding", "title": "Bovine colostrum to supplement the first feeding of very preterm infants: The PreColos randomized controlled trial", "authors": "Yan X, Pan X, Ding L et al.", "journal": "Clin Nutr", "year": 2023, "pmid": "37437359", "url": "https://pubmed.ncbi.nlm.nih.gov/37437359/", "study_type": "rct", "key_finding": "Multicenter RCT of 350 very preterm infants found bovine colostrum supplementation during the first 14 days of life did not reduce time to full enteral feeding and had only marginal effects on clinical variables compared to preterm formula.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37437359/", "publicSourceType": "PMID" }, { "claim": "Bovine colostrum is identified as potentially effective for improving athletic performance in soccer players", "title": "Effects of different dietary supplements on athletic performance in soccer players: a systematic review and network meta-analysis", "authors": "Luo H, Tengku Kamalden TF, Zhu X, Xiang C, Nasharuddin NA", "journal": "J Int Soc Sports Nutr", "year": 2025, "pmid": "39972597", "url": "https://pubmed.ncbi.nlm.nih.gov/39972597/", "study_type": "meta-analysis", "key_finding": "Network meta-analysis of 80 RCTs identified bovine colostrum as having a moderate significant effect on increasing distance covered in soccer players compared to placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39972597/", "publicSourceType": "PMID" }, { "text": "Oswal D, Angolkar M, Mahantashetti NS et al.. Effect of bovine colostrum supplementation on gut health of children: A systematic review. Journal of pediatric gastroenterology and nutrition. 2025", "claim": "PubMed-indexed evidence involving Colostrum", "title": "Effect of bovine colostrum supplementation on gut health of children: A systematic review", "authors": "Oswal D, Angolkar M, Mahantashetti NS et al.", "journal": "Journal of pediatric gastroenterology and nutrition", "year": 2025, "pmid": "40150801", "url": "https://pubmed.ncbi.nlm.nih.gov/40150801/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/jpn3.70033", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40150801/", "publicSourceType": "PMID" }, { "text": "Colonetti T, de Carvalho Florêncio I, Figueiredo P et al.. Colostrum Use and the Immune System of Premature Newborns: A Systematic Review and Meta-Analysis. Journal of human lactation : official journal of International Lactation Consultant Association. 2022", "claim": "PubMed-indexed evidence involving Colostrum", "title": "Colostrum Use and the Immune System of Premature Newborns: A Systematic Review and Meta-Analysis", "authors": "Colonetti T, de Carvalho Florêncio I, Figueiredo P et al.", "journal": "Journal of human lactation : official journal of International Lactation Consultant Association", "year": 2022, "pmid": "35416063", "url": "https://pubmed.ncbi.nlm.nih.gov/35416063/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/08903344221087967", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35416063/", "publicSourceType": "PMID" }, { "text": "Guberti M, Botti S, Capuzzo MT et al.. Bovine Colostrum Applications in Sick and Healthy People: A Systematic Review. Nutrients. 2021", "claim": "PubMed-indexed evidence involving Colostrum", "title": "Bovine Colostrum Applications in Sick and Healthy People: A Systematic Review", "authors": "Guberti M, Botti S, Capuzzo MT et al.", "journal": "Nutrients", "year": 2021, "pmid": "34202206", "url": "https://pubmed.ncbi.nlm.nih.gov/34202206/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu13072194", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34202206/", "publicSourceType": "PMID" }, { "text": "Panchal H, Athalye-Jape G, Patole S. Oropharyngeal Colostrum for Preterm Infants: A Systematic Review and Meta-Analysis. Advances in nutrition (Bethesda, Md.). 2019", "claim": "PubMed-indexed evidence involving Colostrum", "title": "Oropharyngeal Colostrum for Preterm Infants: A Systematic Review and Meta-Analysis", "authors": "Panchal H, Athalye-Jape G, Patole S", "journal": "Advances in nutrition (Bethesda, Md.)", "year": 2019, "pmid": "31147686", "url": "https://pubmed.ncbi.nlm.nih.gov/31147686/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/advances/nmz033", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31147686/", "publicSourceType": "PMID" }, { "text": "Fu ZY, Huang C, Lei L et al.. The effect of oropharyngeal colostrum administration on the clinical outcomes of premature infants: A meta-analysis. International journal of nursing studies. 2023", "claim": "PubMed-indexed evidence involving Colostrum", "title": "The effect of oropharyngeal colostrum administration on the clinical outcomes of premature infants: A meta-analysis", "authors": "Fu ZY, Huang C, Lei L et al.", "journal": "International journal of nursing studies", "year": 2023, "pmid": "37295286", "url": "https://pubmed.ncbi.nlm.nih.gov/37295286/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.ijnurstu.2023.104527", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37295286/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "colostrum" }, { "id": "097F9805-B6FB-47CB-A990-DBD3DC4E43D7", "name": "Methylfolate", "alternateNames": [ "5-MTHF", "L-Methylfolate", "Levomefolic acid" ], "category": "Vitamin", "subcategory": "Active Folate", "overview": "The active, methylated form of folate, essential for those with MTHFR variants.", "mechanismOfAction": "Direct methyl donor in the methionine cycle via methionine synthase. Bypasses MTHFR enzyme entirely, crucial for the ~30-40% of population with MTHFR C677T or A1298C variants.", "commonBenefits": [ "Methylation support", "Mood", "Pregnancy health", "MTHFR support" ], "commonDosageRange": "400-1,000 mcg daily", "recommendedForm": "Quatrefolic (glucosamine salt of 5-MTHF) or Metafolin", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Can take any time; essential for MTHFR variant carriers" }, "evidenceRating": "strong", "foodSources": [ "Dark leafy greens", "Legumes", "Fortified foods (folic acid, requires conversion)" ], "deficiencySymptoms": [ "Depression", "Neural tube defects", "Elevated homocysteine", "Fatigue" ], "sideEffects": [ "Overmethylation symptoms (anxiety, insomnia) if dose too high" ], "contraindications": [ "Undiagnosed B12 deficiency (can mask it)" ], "iconName": "dna", "colorHex": "FFB800", "tags": [ "methylation", "mthfr", "pregnancy", "mood" ], "sources": [ { "claim": "L-methylfolate augmentation efficacy in depressive disorders", "title": "Systematic Review and Meta-Analysis of L-Methylfolate Augmentation in Depressive Disorders", "authors": "Jain R et al.", "journal": "Journal of Clinical Psychiatry", "year": 2021, "pmid": "34794190", "url": "https://pubmed.ncbi.nlm.nih.gov/34794190/", "study_type": "meta-analysis", "key_finding": "Adjunctive L-methylfolate may have modest efficacy in antidepressant-treated adults with major depressive disorder.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34794190/", "publicSourceType": "PMID" }, { "claim": "L-methylfolate as adjunctive therapy for SSRI-resistant depression", "title": "L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials", "authors": "Papakostas GI et al.", "journal": "American Journal of Psychiatry", "year": 2012, "pmid": "23212058", "url": "https://pubmed.ncbi.nlm.nih.gov/23212058/", "study_type": "RCT", "key_finding": "Adjunctive L-methylfolate at 15 mg/day showed significantly greater efficacy vs placebo for response rate and symptom severity in SSRI-resistant MDD.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23212058/", "publicSourceType": "PMID" }, { "claim": "5-MTHF vs folic acid: role in human health and MTHFR bypass", "title": "Active Folate Versus Folic Acid: The Role of 5-MTHF (Methylfolate) in Human Health", "authors": "Samblas M et al.", "journal": "Nutrients", "year": 2022, "pmid": "35999905", "url": "https://pubmed.ncbi.nlm.nih.gov/35999905/", "study_type": "review", "key_finding": "5-MTHF bypasses MTHFR enzyme entirely; bioavailability unaffected by genetic polymorphisms; better option than folic acid for MTHFR variant carriers.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35999905/", "publicSourceType": "PMID" }, { "claim": "MTHFR C677T polymorphism associated with neural tube defects risk", "title": "Association of the maternal MTHFR C677T polymorphism with susceptibility to neural tube defects in offsprings: evidence from 25 case-control studies", "authors": "Zhang T et al.", "journal": "PLoS ONE", "year": 2012, "pmid": "23056169", "url": "https://pubmed.ncbi.nlm.nih.gov/23056169/", "study_type": "meta-analysis", "key_finding": "In 25 case-control studies (2429 cases, 3570 controls), maternal MTHFR C677T TT genotype increased NTD risk (OR 2.02, 95% CI 1.51-2.71).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23056169/", "publicSourceType": "PMID" }, { "claim": "Folate supplementation as beneficial add-on for depression", "title": "Folate supplementation as a beneficial add-on treatment in relieving depressive symptoms: A meta-analysis of meta-analyses", "authors": "Zheng X et al.", "journal": "Journal of Affective Disorders", "year": 2024, "pmid": "38873435", "url": "https://pubmed.ncbi.nlm.nih.gov/38873435/", "study_type": "umbrella review", "key_finding": "Folate supplementation significantly relieved depression symptoms; active forms (L-methylfolate, SAMe) more beneficial than folic acid; MTHFR TT carriers particularly benefit.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38873435/", "publicSourceType": "PMID" }, { "claim": "Folic acid vs L-5-MTHF clinical pharmacokinetics comparison", "title": "Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics", "authors": "Pietrzik K et al.", "journal": "Clinical Pharmacokinetics", "year": 2010, "pmid": "20608755", "url": "https://pubmed.ncbi.nlm.nih.gov/20608755/", "study_type": "review", "key_finding": "L-5-MTHF and folic acid have comparable physiological activity at equimolar doses, but 5-MTHF's bioavailability is not affected by metabolic defects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20608755/", "publicSourceType": "PMID" }, { "text": "Sakuma K, Matsunaga S, Nomura I et al.. Folic acid/methylfolate for the treatment of psychopathology in schizophrenia: a systematic review and meta-analysis. Psychopharmacology. 2018", "pmid": "29785555", "doi": "10.1007/s00213-018-4926-4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29785555/", "publicSourceType": "PMID" }, { "text": "Maletic V, Shelton R, Holmes V. A Review of l-Methylfolate as Adjunctive Therapy in the Treatment of Major Depressive Disorder. The primary care companion for CNS disorders. 2023", "pmid": "37192264", "doi": "10.4088/PCC.22nr03361", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37192264/", "publicSourceType": "PMID" }, { "text": "Prado LIA, Junger AL, Caixeta LF et al.. The Effects of Methylfolate on Cognitive Decline and Dementia: A Protocol for Systematic Review and Meta-Analysis. Journal of clinical medicine. 2023", "claim": "PubMed-indexed evidence involving Methylfolate", "title": "The Effects of Methylfolate on Cognitive Decline and Dementia: A Protocol for Systematic Review and Meta-Analysis", "authors": "Prado LIA, Junger AL, Caixeta LF et al.", "journal": "Journal of clinical medicine", "year": 2023, "pmid": "37176516", "url": "https://pubmed.ncbi.nlm.nih.gov/37176516/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/jcm12093075", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37176516/", "publicSourceType": "PMID" }, { "text": "Troesch B, Demmelmair J, Gimpfl M et al.. Suitability and safety of L-5-methyltetrahydrofolate as a folate source in infant formula: A randomized-controlled trial. PloS one. 2019", "claim": "PubMed-indexed evidence involving Methylfolate", "title": "Suitability and safety of L-5-methyltetrahydrofolate as a folate source in infant formula: A randomized-controlled trial", "authors": "Troesch B, Demmelmair J, Gimpfl M et al.", "journal": "PloS one", "year": 2019, "pmid": "31425504", "url": "https://pubmed.ncbi.nlm.nih.gov/31425504/", "study_type": "RCT", "confidence": "verify", "doi": "10.1371/journal.pone.0216790", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31425504/", "publicSourceType": "PMID" }, { "text": "Ledowsky C, Scarf V, Rogers K et al.. Feasibility of a randomized clinical trial comparing 5-methyltetrahydrofolate and folic acid prenatal multivitamins in couples with recurrent pregnancy loss. Nutrition research (New York, N.Y.). 2026", "claim": "PubMed-indexed evidence involving Methylfolate", "title": "Feasibility of a randomized clinical trial comparing 5-methyltetrahydrofolate and folic acid prenatal multivitamins in couples with recurrent pregnancy loss", "authors": "Ledowsky C, Scarf V, Rogers K et al.", "journal": "Nutrition research (New York, N.Y.)", "year": 2026, "pmid": "41544303", "url": "https://pubmed.ncbi.nlm.nih.gov/41544303/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.nutres.2025.12.008", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41544303/", "publicSourceType": "PMID" }, { "text": "Pokushalov E, Ponomarenko A, Bayramova S et al.. Effect of Methylfolate, Pyridoxal-5'-Phosphate, and Methylcobalamin (Soloways(TM)) Supplementation on Homocysteine and Low-Density Lipoprotein Cholesterol Levels in Patients with Methylenetetrahydrofolate Reductase, Methionine Synthase, and Methionine Synthase Reductase Polymorphisms: A Randomized Controlled Trial. Nutrients. 2024", "claim": "PubMed-indexed evidence involving Methylfolate", "title": "Effect of Methylfolate, Pyridoxal-5'-Phosphate, and Methylcobalamin (Soloways(TM)) Supplementation on Homocysteine and Low-Density Lipoprotein Cholesterol Levels in Patients with Methylenetetrahydrofolate Reductase, Methionine Synthase, and Methionine Synthase Reductase Polymorphisms: A Randomized Controlled Trial", "authors": "Pokushalov E, Ponomarenko A, Bayramova S et al.", "journal": "Nutrients", "year": 2024, "pmid": "38892484", "url": "https://pubmed.ncbi.nlm.nih.gov/38892484/", "study_type": "RCT", "confidence": "verify", "doi": "10.3390/nu16111550", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38892484/", "publicSourceType": "PMID" }, { "text": "Vukotic R, Di Donato R, Roncarati G et al.. 5-MTHF enhances the portal pressure reduction achieved with propranolol in patients with cirrhosis: A randomized placebo-controlled trial. Journal of hepatology. 2023", "claim": "PubMed-indexed evidence involving Methylfolate", "title": "5-MTHF enhances the portal pressure reduction achieved with propranolol in patients with cirrhosis: A randomized placebo-controlled trial", "authors": "Vukotic R, Di Donato R, Roncarati G et al.", "journal": "Journal of hepatology", "year": 2023, "pmid": "37482222", "url": "https://pubmed.ncbi.nlm.nih.gov/37482222/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.jhep.2023.06.017", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37482222/", "publicSourceType": "PMID" }, { "text": "Surman C, Ceranoglu A, Vaudreuil C et al.. Does L-Methylfolate Supplement Methylphenidate Pharmacotherapy in Attention-Deficit/Hyperactivity Disorder?: Evidence of Lack of Benefit From a Double-Blind, Placebo-Controlled, Randomized Clinical Trial. Journal of clinical psychopharmacology. 2019", "claim": "PubMed-indexed evidence involving Methylfolate", "title": "Does L-Methylfolate Supplement Methylphenidate Pharmacotherapy in Attention-Deficit/Hyperactivity Disorder?: Evidence of Lack of Benefit From a Double-Blind, Placebo-Controlled, Randomized Clinical Trial", "authors": "Surman C, Ceranoglu A, Vaudreuil C et al.", "journal": "Journal of clinical psychopharmacology", "year": 2019, "pmid": "30566416", "url": "https://pubmed.ncbi.nlm.nih.gov/30566416/", "study_type": "RCT", "confidence": "verify", "doi": "10.1097/JCP.0000000000000990", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30566416/", "publicSourceType": "PMID" }, { "text": "Roffman JL, Petruzzi LJ, Tanner AS et al.. Biochemical, physiological and clinical effects of l-methylfolate in schizophrenia: a randomized controlled trial. Molecular psychiatry. 2018", "claim": "PubMed-indexed evidence involving Methylfolate", "title": "Biochemical, physiological and clinical effects of l-methylfolate in schizophrenia: a randomized controlled trial", "authors": "Roffman JL, Petruzzi LJ, Tanner AS et al.", "journal": "Molecular psychiatry", "year": 2018, "pmid": "28289280", "url": "https://pubmed.ncbi.nlm.nih.gov/28289280/", "study_type": "RCT", "confidence": "verify", "doi": "10.1038/mp.2017.41", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28289280/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "methylfolate" }, { "id": "C8F21448-6C19-4A9C-A16E-52645DB0BF22", "name": "D-Mannose", "alternateNames": [ "Mannose" ], "category": "Other", "subcategory": "Simple Sugar", "overview": "Natural sugar that prevents UTI-causing bacteria from adhering to urinary tract walls.", "mechanismOfAction": "E. coli bacteria have FimH lectins that bind mannose residues. Oral D-mannose saturates these binding sites, preventing E. coli adhesion to uroepithelial cells and promoting bacterial flushing.", "commonBenefits": [ "UTI prevention", "Urinary tract health", "Bladder support" ], "commonDosageRange": "500-2,000 mg daily (prevention) or 1,500 mg 3x daily (acute)", "recommendedForm": "D-Mannose powder or capsules", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Dissolve in water; take on empty stomach for quick urinary excretion" }, "evidenceRating": "moderate", "foodSources": [ "Cranberries", "Apples", "Peaches", "Oranges" ], "deficiencySymptoms": [ "Not essential" ], "sideEffects": [ "Bloating", "Loose stools at high doses" ], "contraindications": [ "Diabetes (monitor blood sugar, it is a sugar)" ], "iconName": "drop.fill", "colorHex": "FFB84D", "tags": [ "urinary", "uti-prevention", "bladder" ], "sources": [ { "claim": "D-mannose vs other agents for recurrent UTI prevention meta-analysis", "title": "D-mannose vs other agents for recurrent urinary tract infection prevention in adult women: a systematic review and meta-analysis", "authors": "Lenger SM et al.", "journal": "Journal of Urology", "year": 2020, "pmid": "32497610", "url": "https://pubmed.ncbi.nlm.nih.gov/32497610/", "study_type": "meta-analysis", "key_finding": "Pooled RR of UTI recurrence comparing D-mannose to placebo was 0.23 (95% CI 0.14-0.37), suggesting protective effect against UTI recurrence.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32497610/", "publicSourceType": "PMID" }, { "claim": "D-mannose powder for UTI prophylaxis compared to antibiotic", "title": "D-mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial", "authors": "Kranjcec B et al.", "journal": "World Journal of Urology", "year": 2014, "pmid": "23633128", "url": "https://pubmed.ncbi.nlm.nih.gov/23633128/", "study_type": "RCT", "key_finding": "In 308 women, D-mannose (2g/day) reduced recurrent UTI rate to 14.6% vs 60.8% no prophylaxis; comparable to nitrofurantoin (20.4%) with fewer side effects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23633128/", "publicSourceType": "PMID" }, { "claim": "Narrative review of D-mannose role in UTIs and FimH mechanism", "title": "Role of D-mannose in urinary tract infections - a narrative review", "authors": "Tabares G et al.", "journal": "Annals of Nutrition and Metabolism", "year": 2022, "pmid": "35313893", "url": "https://pubmed.ncbi.nlm.nih.gov/35313893/", "study_type": "review", "key_finding": "Exogenous D-mannose saturates E. coli FimH adhesins, preventing adhesion to uroplakin receptors on bladder epithelium and facilitating bacterial clearance.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35313893/", "publicSourceType": "PMID" }, { "claim": "Cochrane review of D-mannose for preventing and treating UTIs", "title": "D-mannose for preventing and treating urinary tract infections", "authors": "Cooper TE et al.", "journal": "Cochrane Database of Systematic Reviews", "year": 2022, "pmid": "36041061", "url": "https://pubmed.ncbi.nlm.nih.gov/36041061/", "study_type": "meta-analysis", "key_finding": "Evidence is uncertain whether D-mannose prevents or treats UTIs; more well-designed RCTs with adequate power are needed.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36041061/", "publicSourceType": "PMID" }, { "claim": "D-mannose does not induce bacterial resistance or FimH modifications", "title": "d-Mannose Treatment neither Affects Uropathogenic Escherichia coli Properties nor Induces Stable FimH Modifications", "authors": "Scribano D et al.", "journal": "International Journal of Molecular Sciences", "year": 2020, "pmid": "31941080", "url": "https://pubmed.ncbi.nlm.nih.gov/31941080/", "study_type": "in vitro", "key_finding": "D-mannose at clinical dosages does not affect E. coli metabolism or induce stable FimH variants, supporting long-term safety.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31941080/", "publicSourceType": "PMID" }, { "claim": "Network meta-analysis finds D-mannose reduces UTI incidence vs placebo", "title": "Nonantibiotic prophylaxis for urinary tract infections: a network meta-analysis of randomized controlled trials", "authors": "Solomkin JS et al.", "journal": "British Journal of Surgery", "year": 2024, "pmid": "39095666", "url": "https://pubmed.ncbi.nlm.nih.gov/39095666/", "study_type": "meta-analysis", "key_finding": "Network meta-analysis of 50 RCTs found D-mannose significantly reduced UTI incidence vs placebo (RR 0.34, 0.21-0.56).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39095666/", "publicSourceType": "PMID" }, { "text": "Salvatore S, Ruffolo AF, Stabile G et al.. A Randomized Controlled Trial Comparing a New D-Mannose-based Dietary Supplement to Placebo for the Treatment of Uncomplicated Escherichia coli Urinary Tract Infections. European urology focus. 2023", "pmid": "36621376", "doi": "10.1016/j.euf.2022.12.013", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36621376/", "publicSourceType": "PMID" }, { "text": "Lin J, Yang L, Liu T et al.. Mannose-modified exosomes loaded with MiR-23b-3p target alveolar macrophages to alleviate acute lung injury in Sepsis. Journal of controlled release : official journal of the Controlled Release Society. 2025", "pmid": "39870316", "doi": "10.1016/j.jconrel.2025.01.073", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39870316/", "publicSourceType": "PMID" }, { "claim": "D-mannose prevents recurrent urinary tract infections", "title": "D-mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial", "authors": "Kranjčec B, Papeš D, Altarac S", "journal": "World journal of urology", "year": 2014, "pmid": "23633128", "doi": "10.1007/s00345-013-1091-6", "study_type": "rct", "key_finding": "14.6% UTI recurrence with D-mannose vs 60.8% no prophylaxis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23633128/", "publicSourceType": "PMID" }, { "text": "Vargas CEF, Mutarelli A, Menegardo LG et al.. Efficacy of D-mannose as prophylaxis of recurrent urinary tract infection: a systematic review and meta-analysis of randomized controlled trials. Jornal brasileiro de nefrologia. 2025", "claim": "PubMed-indexed evidence involving D-Mannose", "title": "Efficacy of D-mannose as prophylaxis of recurrent urinary tract infection: a systematic review and meta-analysis of randomized controlled trials", "authors": "Vargas CEF, Mutarelli A, Menegardo LG et al.", "journal": "Jornal brasileiro de nefrologia", "year": 2025, "pmid": "41004704", "url": "https://pubmed.ncbi.nlm.nih.gov/41004704/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1590/2175-8239-JBN-2025-0169en", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41004704/", "publicSourceType": "PMID" }, { "text": "Kyriakides R, Jones P, Somani BK. Role of D-Mannose in the Prevention of Recurrent Urinary Tract Infections: Evidence from a Systematic Review of the Literature. European urology focus. 2021", "claim": "PubMed-indexed evidence involving D-Mannose", "title": "Role of D-Mannose in the Prevention of Recurrent Urinary Tract Infections: Evidence from a Systematic Review of the Literature", "authors": "Kyriakides R, Jones P, Somani BK", "journal": "European urology focus", "year": 2021, "pmid": "32972899", "url": "https://pubmed.ncbi.nlm.nih.gov/32972899/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.euf.2020.09.004", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32972899/", "publicSourceType": "PMID" }, { "text": "Singh RG, Nguyen E, Zhao Y et al.. A randomized, triple-blind, placebo-controlled, parallel study of the efficacy of D-mannose for urinary tract infection symptoms in women. Current urology. 2026", "claim": "PubMed-indexed evidence involving D-Mannose", "title": "A randomized, triple-blind, placebo-controlled, parallel study of the efficacy of D-mannose for urinary tract infection symptoms in women", "authors": "Singh RG, Nguyen E, Zhao Y et al.", "journal": "Current urology", "year": 2026, "pmid": "41743922", "url": "https://pubmed.ncbi.nlm.nih.gov/41743922/", "study_type": "RCT", "confidence": "verify", "doi": "10.1097/CU9.0000000000000303", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41743922/", "publicSourceType": "PMID" }, { "text": "Riemma G, Vinci D, La Verde M et al.. Adding collagen, propolis plus quercetin, bacillus coagulans, hyaluronic acid and chondroitin sulphate to D-mannose avoids symptoms and prevents recurrence in women with recurrent urinary tract infections: a single-blind randomized controlled trial. Expert review of anti-infective therapy. 2025", "claim": "PubMed-indexed evidence involving D-Mannose", "title": "Adding collagen, propolis plus quercetin, bacillus coagulans, hyaluronic acid and chondroitin sulphate to D-mannose avoids symptoms and prevents recurrence in women with recurrent urinary tract infections: a single-blind randomized controlled trial", "authors": "Riemma G, Vinci D, La Verde M et al.", "journal": "Expert review of anti-infective therapy", "year": 2025, "pmid": "40162673", "url": "https://pubmed.ncbi.nlm.nih.gov/40162673/", "study_type": "RCT", "confidence": "verify", "doi": "10.1080/14787210.2025.2487162", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40162673/", "publicSourceType": "PMID" }, { "text": "Wang J, Mei L, Wen H et al.. D-mannose enhances immune function and modulates gut microbiota composition in adult cats: A randomized controlled trial. Research in veterinary science. 2025", "claim": "PubMed-indexed evidence involving D-Mannose", "title": "D-mannose enhances immune function and modulates gut microbiota composition in adult cats: A randomized controlled trial", "authors": "Wang J, Mei L, Wen H et al.", "journal": "Research in veterinary science", "year": 2025, "pmid": "41166862", "url": "https://pubmed.ncbi.nlm.nih.gov/41166862/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.rvsc.2025.105945", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41166862/", "publicSourceType": "PMID" }, { "text": "Rau M, Santelli A, Martí S et al.. Randomized clinical trial of non-antibiotic prophylaxis with d-Mannose plus Proanthocyanidins vs. Proanthocyanidins alone for urinary tract infections and asymptomatic bacteriuria in de novo kidney transplant recipients: The Manotras study. Nefrologia. 2024", "claim": "PubMed-indexed evidence involving D-Mannose", "title": "Randomized clinical trial of non-antibiotic prophylaxis with d-Mannose plus Proanthocyanidins vs. Proanthocyanidins alone for urinary tract infections and asymptomatic bacteriuria in de novo kidney transplant recipients: The Manotras study", "authors": "Rau M, Santelli A, Martí S et al.", "journal": "Nefrologia", "year": 2024, "pmid": "38637262", "url": "https://pubmed.ncbi.nlm.nih.gov/38637262/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.nefroe.2024.02.011", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38637262/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "d-mannose" }, { "id": "64BCFAE0-94D5-4F78-9088-91738CA0CEE1", "name": "Lycopene", "alternateNames": [ "Trans-Lycopene" ], "category": "Other", "subcategory": "Carotenoid", "overview": "Red carotenoid pigment with potent antioxidant properties, especially for prostate health.", "mechanismOfAction": "Most efficient singlet oxygen quencher among carotenoids (2x stronger than beta-carotene). Accumulates in prostate, skin, and adrenal tissue. Inhibits androgen receptor signaling in prostate.", "commonBenefits": [ "Prostate health", "Antioxidant", "Cardiovascular health", "Skin UV protection" ], "commonDosageRange": "10-30 mg daily", "recommendedForm": "Tomato oleoresin extract (LycoRed)", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with fat; cooking increases bioavailability" }, "evidenceRating": "moderate", "foodSources": [ "Tomatoes (cooked)", "Watermelon", "Pink grapefruit", "Guava" ], "deficiencySymptoms": [ "Not essential" ], "sideEffects": [ "Very well tolerated", "Orange skin tint at high doses" ], "contraindications": [ "Generally very safe" ], "iconName": "circle.fill", "colorHex": "FF6B6B", "tags": [ "prostate", "antioxidant", "cardiovascular", "skin" ], "sources": [ { "claim": "Lycopene is the most efficient carotenoid singlet oxygen quencher", "title": "Lycopene as the most efficient biological carotenoid singlet oxygen quencher", "authors": "Di Mascio P et al.", "journal": "Archives of Biochemistry and Biophysics", "year": 1989, "pmid": "2802626", "url": "https://pubmed.ncbi.nlm.nih.gov/2802626/", "study_type": "in vitro", "key_finding": "Lycopene has the highest singlet oxygen quenching rate constant (kq = 31 x 10^9 M-1 s-1), more than twice that of beta-carotene (kq = 14 x 10^9).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2802626/", "publicSourceType": "PMID" }, { "claim": "Higher lycopene intake/levels associated with reduced prostate cancer risk", "title": "Increased dietary and circulating lycopene are associated with reduced prostate cancer risk: a systematic review and meta-analysis", "authors": "Rowles JL et al.", "journal": "Prostate Cancer and Prostatic Diseases", "year": 2017, "pmid": "28440323", "url": "https://pubmed.ncbi.nlm.nih.gov/28440323/", "study_type": "meta-analysis", "key_finding": "In 42 studies (692,012 participants), both dietary intake and circulating lycopene were significantly inversely associated with prostate cancer risk (1% decrease per additional 2 mg consumed).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28440323/", "publicSourceType": "PMID" }, { "claim": "Tomato/lycopene reduces UV skin damage markers", "title": "The effect of tomato and lycopene on clinical characteristics and molecular markers of UV-induced skin deterioration: A systematic review and meta-analysis of intervention trials", "authors": "Liang Z et al.", "journal": "Critical Reviews in Food Science and Nutrition", "year": 2023, "pmid": "36606553", "url": "https://pubmed.ncbi.nlm.nih.gov/36606553/", "study_type": "meta-analysis", "key_finding": "Tomato/lycopene interventions significantly reduced skin damage markers and increased minimal erythema dose, skin thickness and density.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36606553/", "publicSourceType": "PMID" }, { "claim": "Oral lycopene protects skin against UV radiation", "title": "Molecular evidence that oral supplementation with lycopene or lutein protects human skin against ultraviolet radiation: results from a double-blinded, placebo-controlled, crossover study", "authors": "Groten K et al.", "journal": "British Journal of Dermatology", "year": 2017, "pmid": "27662341", "url": "https://pubmed.ncbi.nlm.nih.gov/27662341/", "study_type": "RCT", "key_finding": "Lycopene-rich tomato nutrient complex completely inhibited UV-induced upregulation of genes associated with oxidative stress and photoageing.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27662341/", "publicSourceType": "PMID" }, { "claim": "Lycopene as a natural antioxidant for human health disorders", "title": "Lycopene as a Natural Antioxidant Used to Prevent Human Health Disorders", "authors": "Imran M et al.", "journal": "Antioxidants", "year": 2020, "pmid": "32759751", "url": "https://pubmed.ncbi.nlm.nih.gov/32759751/", "study_type": "review", "key_finding": "Lycopene is efficient in ameliorating cancer, diabetes, cardiac complications, oxidative stress-mediated malfunctions, inflammatory events, and skin disorders.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32759751/", "publicSourceType": "PMID" }, { "claim": "Lycopene effect on prostate-specific antigen (PSA)", "title": "The effect of lycopene supplement from different sources on prostate specific antigen (PSA): A systematic review and meta-analysis of randomized controlled trials", "authors": "Mirahmadi M et al.", "journal": "Complementary Therapies in Medicine", "year": 2022, "pmid": "35031434", "url": "https://pubmed.ncbi.nlm.nih.gov/35031434/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of RCTs examined lycopene supplementation effects on PSA levels as a prostate health biomarker.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35031434/", "publicSourceType": "PMID" }, { "text": "Wylenzek F, Bühling KJ, Laakmann E. A systematic review on the impact of nutrition and possible supplementation on the deficiency of vitamin complexes, iron, omega-3-fatty acids, and lycopene in relation to increased morbidity in women after menopause. Archives of gynecology and obstetrics. 2024", "pmid": "38935105", "doi": "10.1007/s00404-024-07555-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38935105/", "publicSourceType": "PMID" }, { "text": "Li N, Wu X, Zhuang W et al.. Tomato and lycopene and multiple health outcomes: Umbrella review. Food chemistry. 2021", "pmid": "33131949", "doi": "10.1016/j.foodchem.2020.128396", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33131949/", "publicSourceType": "PMID" }, { "claim": "Reduces cardiovascular risk factors", "title": "Effect of Dietary and Supplemental Lycopene on Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis.", "authors": "Tierney AC, Rumble CE, Billings LM, George ES", "journal": "Advances in Nutrition", "year": 2020, "pmid": "32652029", "url": "https://pubmed.ncbi.nlm.nih.gov/32652029/", "study_type": "meta-analysis", "key_finding": "Lycopene supplementation significantly reduced systolic blood pressure, total cholesterol, and LDL cholesterol, with potential cardiovascular protective effects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32652029/", "publicSourceType": "PMID" }, { "claim": "Improves cardiovascular risk factors in adults", "title": "The Effects of Lycopene and Tomato Consumption on Cardiovascular Risk Factors in Adults: A Grade Assessment Systematic Review and Meta-analysis.", "authors": "Zamani M, Behmanesh Nia F, Ghaedi K, Mohammadpour S, Amirani N, Goudarzi K et al.", "journal": "Current Pharmaceutical Design", "year": 2023, "pmid": "37496241", "url": "https://pubmed.ncbi.nlm.nih.gov/37496241/", "study_type": "meta-analysis", "key_finding": "Lycopene and tomato consumption significantly improved multiple cardiovascular risk factors including blood pressure, lipid profiles, and oxidative stress markers.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37496241/", "publicSourceType": "PMID" }, { "text": "Głąbska D, Guzek D, Jílková A et al.. Influence of Lycopene Intake on Mental Health: A Systematic Review of Randomized Controlled Trials (RCTs). Nutrients. 2025", "claim": "PubMed-indexed evidence involving Lycopene", "title": "Influence of Lycopene Intake on Mental Health: A Systematic Review of Randomized Controlled Trials (RCTs)", "authors": "Głąbska D, Guzek D, Jílková A et al.", "journal": "Nutrients", "year": 2025, "pmid": "40507061", "url": "https://pubmed.ncbi.nlm.nih.gov/40507061/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu17111793", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40507061/", "publicSourceType": "PMID" }, { "text": "Viña I, Viña JR. Association of Lycopene and Male Reproductive Health: Systematic Review and Meta-Analysis. International journal of molecular sciences. 2025", "claim": "PubMed-indexed evidence involving Lycopene", "title": "Association of Lycopene and Male Reproductive Health: Systematic Review and Meta-Analysis", "authors": "Viña I, Viña JR", "journal": "International journal of molecular sciences", "year": 2025, "pmid": "40806357", "url": "https://pubmed.ncbi.nlm.nih.gov/40806357/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/ijms26157224", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40806357/", "publicSourceType": "PMID" }, { "text": "Al-Maweri SA, Halboub E, Al-Qadhi G et al.. Efficacy of lycopene for management of oral potentially malignant disorders: A systematic review and meta-analysis. Oral surgery, oral medicine, oral pathology and oral radiology. 2023", "claim": "PubMed-indexed evidence involving Lycopene", "title": "Efficacy of lycopene for management of oral potentially malignant disorders: A systematic review and meta-analysis", "authors": "Al-Maweri SA, Halboub E, Al-Qadhi G et al.", "journal": "Oral surgery, oral medicine, oral pathology and oral radiology", "year": 2023, "pmid": "36167720", "url": "https://pubmed.ncbi.nlm.nih.gov/36167720/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.oooo.2022.08.004", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36167720/", "publicSourceType": "PMID" }, { "text": "van Steenwijk HP, Bast A, de Boer A. The Role of Circulating Lycopene in Low-Grade Chronic Inflammation: A Systematic Review of the Literature. Molecules (Basel, Switzerland). 2020", "claim": "PubMed-indexed evidence involving Lycopene", "title": "The Role of Circulating Lycopene in Low-Grade Chronic Inflammation: A Systematic Review of the Literature", "authors": "van Steenwijk HP, Bast A, de Boer A", "journal": "Molecules (Basel, Switzerland)", "year": 2020, "pmid": "32977711", "url": "https://pubmed.ncbi.nlm.nih.gov/32977711/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/molecules25194378", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32977711/", "publicSourceType": "PMID" }, { "text": "Gupta N, Kalaskar A, Kalaskar R. Efficacy of lycopene in management of Oral Submucous Fibrosis- A systematic review and meta-analysis. Journal of oral biology and craniofacial research. 2020", "claim": "PubMed-indexed evidence involving Lycopene", "title": "Efficacy of lycopene in management of Oral Submucous Fibrosis- A systematic review and meta-analysis", "authors": "Gupta N, Kalaskar A, Kalaskar R", "journal": "Journal of oral biology and craniofacial research", "year": 2020, "pmid": "33072506", "url": "https://pubmed.ncbi.nlm.nih.gov/33072506/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jobcr.2020.09.004", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33072506/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "lycopene" }, { "id": "073A7EC8-30A3-41FB-A82D-4CBAD7A62C13", "name": "Beta-Carotene", "alternateNames": [ "Provitamin A" ], "category": "Other", "subcategory": "Carotenoid", "overview": "Orange carotenoid that converts to vitamin A as needed, safer than preformed retinol.", "mechanismOfAction": "Cleaved by BCO1 (beta-carotene oxygenase 1) into retinal, then converted to retinol or retinoic acid. Conversion is regulated by vitamin A status, prevents toxicity unlike preformed A.", "commonBenefits": [ "Vitamin A precursor", "Antioxidant", "Skin health", "Immune support" ], "commonDosageRange": "6-15 mg daily (from food or supplement)", "recommendedForm": "Natural mixed carotenoids (not synthetic isolate)", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with fat-containing meal" }, "evidenceRating": "moderate", "foodSources": [ "Carrots", "Sweet potatoes", "Spinach", "Kale", "Cantaloupe" ], "deficiencySymptoms": [ "Vitamin A deficiency symptoms" ], "sideEffects": [ "Carotenodermia (harmless orange skin)", "Lung cancer risk in smokers (synthetic high-dose)" ], "contraindications": [ "Smokers (increased lung cancer risk at high doses)", "Asbestos exposure" ], "iconName": "carrot.fill", "colorHex": "FFB800", "tags": [ "vitamin-a", "antioxidant", "skin", "immune" ], "sources": [ { "claim": "ATBC trial showed increased lung cancer risk in smokers with beta-carotene supplementation", "title": "Beta-Carotene Supplementation and Lung Cancer Incidence in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study: The Role of Tar and Nicotine", "authors": "Albanes D et al.", "journal": "Nicotine & Tobacco Research", "year": 2019, "pmid": "29889248", "url": "https://pubmed.ncbi.nlm.nih.gov/29889248/", "study_type": "RCT", "key_finding": "ATBC Study (29,133 male smokers) reported 18% excess lung cancer incidence and 8% excess mortality with 20 mg/day beta-carotene over 5-8 years.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29889248/", "publicSourceType": "PMID" }, { "claim": "CARET trial confirmed increased lung cancer in smokers taking beta-carotene", "title": "The Beta-Carotene and Retinol Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping beta-carotene and retinol supplements", "authors": "Goodman GE et al.", "journal": "Journal of the National Cancer Institute", "year": 2004, "pmid": "15572756", "url": "https://pubmed.ncbi.nlm.nih.gov/15572756/", "study_type": "RCT", "key_finding": "CARET was stopped early due to 28% increase in lung cancer incidence and 17% increase in mortality in beta-carotene/retinol group vs placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15572756/", "publicSourceType": "PMID" }, { "claim": "Beta-carotene is an important provitamin A source for humans", "title": "Beta-carotene is an important vitamin A source for humans", "authors": "Tang G", "journal": "Journal of Nutrition", "year": 2010, "pmid": "20980645", "url": "https://pubmed.ncbi.nlm.nih.gov/20980645/", "study_type": "review", "key_finding": "BCO1 enzyme cleaves beta-carotene into retinal; conversion is regulated by vitamin A status, providing a safety mechanism against toxicity unlike preformed vitamin A.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20980645/", "publicSourceType": "PMID" }, { "claim": "Carotenoids including beta-carotene modulate immune response", "title": "Carotenoid action on the immune response", "authors": "Hughes DA", "journal": "Journal of Nutrition", "year": 2004, "pmid": "14704330", "url": "https://pubmed.ncbi.nlm.nih.gov/14704330/", "study_type": "review", "key_finding": "Both provitamin A and non-provitamin A carotenoids enhance cell-mediated and humoral immune response; individual BCO1 polymorphisms determine strong vs weak responders.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14704330/", "publicSourceType": "PMID" }, { "claim": "Ingestible carotenoids provide skin photoprotection", "title": "Role of ingestible carotenoids in skin protection: A review of clinical evidence", "authors": "Davinelli S et al.", "journal": "Photodermatology, Photoimmunology & Photomedicine", "year": 2021, "pmid": "33955073", "url": "https://pubmed.ncbi.nlm.nih.gov/33955073/", "study_type": "review", "key_finding": "Carotenoid supplementation boosts skin's innate UV resistance and provides photoprotection beyond UVB-induced erythema, including UVA-induced pigmentation.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33955073/", "publicSourceType": "PMID" }, { "claim": "Systematic review of beta-carotene role in lung cancer chemoprevention", "title": "Role of Beta-Carotene in Lung Cancer Primary Chemoprevention: A Systematic Review with Meta-Analysis and Meta-Regression", "authors": "Defined H et al.", "journal": "International Journal of Environmental Research and Public Health", "year": 2022, "pmid": null, "url": null, "note": "NO_SOURCE_FOUND, PMC article PMC9003277 found but specific PMID not confirmed from search results", "study_type": "meta-analysis", "key_finding": "Meta-analysis confirmed that high-dose synthetic beta-carotene increases lung cancer risk in smokers; smokers should avoid supplementation.", "confidence": "verify", "publicReviewStatus": "pmid-unconfirmed", "publicSourceURL": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9003277/", "publicSourceType": "PMC" }, { "text": "Beta-Carotene. 2006", "pmid": "30000966", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30000966/", "publicSourceType": "PMID" }, { "text": "Zhang Y, Yang J, Na X et al.. Association between β-carotene supplementation and risk of cancer: a meta-analysis of randomized controlled trials. Nutrition reviews. 2023", "claim": "PubMed-indexed evidence involving Beta-Carotene", "title": "Association between β-carotene supplementation and risk of cancer: a meta-analysis of randomized controlled trials", "authors": "Zhang Y, Yang J, Na X et al.", "journal": "Nutrition reviews", "year": 2023, "pmid": "36715090", "url": "https://pubmed.ncbi.nlm.nih.gov/36715090/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/nutrit/nuac110", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36715090/", "publicSourceType": "PMID" }, { "text": "Jeon YJ, Myung SK, Lee EH et al.. Effects of beta-carotene supplements on cancer prevention: meta-analysis of randomized controlled trials. Nutrition and cancer. 2011", "claim": "PubMed-indexed evidence involving Beta-Carotene", "title": "Effects of beta-carotene supplements on cancer prevention: meta-analysis of randomized controlled trials", "authors": "Jeon YJ, Myung SK, Lee EH et al.", "journal": "Nutrition and cancer", "year": 2011, "pmid": "21981610", "url": "https://pubmed.ncbi.nlm.nih.gov/21981610/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/01635581.2011.607541", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21981610/", "publicSourceType": "PMID" }, { "text": "Gao SS, Zhao Y. The effects of β-carotene on osteoporosis: a systematic review and meta-analysis of observational studies. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2023", "claim": "PubMed-indexed evidence involving Beta-Carotene", "title": "The effects of β-carotene on osteoporosis: a systematic review and meta-analysis of observational studies", "authors": "Gao SS, Zhao Y", "journal": "Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA", "year": 2023, "pmid": "36380163", "url": "https://pubmed.ncbi.nlm.nih.gov/36380163/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00198-022-06593-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36380163/", "publicSourceType": "PMID" }, { "text": "Kotepui KU, Mahittikorn A, Wilairatana P et al.. The Association between Malaria and β-Carotene Levels: A Systematic Review and Meta-Analysis. Antioxidants (Basel, Switzerland). 2023", "claim": "PubMed-indexed evidence involving Beta-Carotene", "title": "The Association between Malaria and β-Carotene Levels: A Systematic Review and Meta-Analysis", "authors": "Kotepui KU, Mahittikorn A, Wilairatana P et al.", "journal": "Antioxidants (Basel, Switzerland)", "year": 2023, "pmid": "37759990", "url": "https://pubmed.ncbi.nlm.nih.gov/37759990/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/antiox12091687", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37759990/", "publicSourceType": "PMID" }, { "text": "Abrego-Guandique DM, Bonet ML, Caroleo MC et al.. The Effect of Beta-Carotene on Cognitive Function: A Systematic Review. Brain sciences. 2023", "claim": "PubMed-indexed evidence involving Beta-Carotene", "title": "The Effect of Beta-Carotene on Cognitive Function: A Systematic Review", "authors": "Abrego-Guandique DM, Bonet ML, Caroleo MC et al.", "journal": "Brain sciences", "year": 2023, "pmid": "37891835", "url": "https://pubmed.ncbi.nlm.nih.gov/37891835/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/brainsci13101468", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37891835/", "publicSourceType": "PMID" }, { "text": "Charkos TG, Liu Y, Oumer KS et al.. Effects of β-carotene intake on the risk of fracture: a Bayesian meta-analysis. BMC musculoskeletal disorders. 2020", "claim": "PubMed-indexed evidence involving Beta-Carotene", "title": "Effects of β-carotene intake on the risk of fracture: a Bayesian meta-analysis", "authors": "Charkos TG, Liu Y, Oumer KS et al.", "journal": "BMC musculoskeletal disorders", "year": 2020, "pmid": "33129293", "url": "https://pubmed.ncbi.nlm.nih.gov/33129293/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12891-020-03733-0", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33129293/", "publicSourceType": "PMID" }, { "text": "Köpcke W, Krutmann J. Protection from sunburn with beta-Carotene--a meta-analysis. Photochemistry and photobiology. 2008", "claim": "PubMed-indexed evidence involving Beta-Carotene", "title": "Protection from sunburn with beta-Carotene--a meta-analysis", "authors": "Köpcke W, Krutmann J", "journal": "Photochemistry and photobiology", "year": 2008, "pmid": "18086246", "url": "https://pubmed.ncbi.nlm.nih.gov/18086246/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/j.1751-1097.2007.00253.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18086246/", "publicSourceType": "PMID" }, { "text": "Chewcharat A, Chewcharat P, Rexrode KM et al.. The Effect of Randomized Beta-Carotene Supplementation on CKD in Men. Kidney international reports. 2024", "claim": "PubMed-indexed evidence involving Beta-Carotene", "title": "The Effect of Randomized Beta-Carotene Supplementation on CKD in Men", "authors": "Chewcharat A, Chewcharat P, Rexrode KM et al.", "journal": "Kidney international reports", "year": 2024, "pmid": "38899218", "url": "https://pubmed.ncbi.nlm.nih.gov/38899218/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.ekir.2024.04.001", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38899218/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "beta-carotene" }, { "id": "D32CD703-735C-45E9-BE88-5911576FD98E", "name": "Pregnenolone", "alternateNames": [ "Pregnenolone" ], "category": "Hormone", "subcategory": "Master Hormone Precursor", "overview": "Precursor to all steroid hormones, the starting point of the steroidogenic pathway.", "mechanismOfAction": "Synthesized from cholesterol via CYP11A1. Converted to progesterone, DHEA, cortisol, testosterone, and estrogen through branching enzymatic pathways. Neurosteroid with direct GABA and NMDA effects.", "commonBenefits": [ "Hormonal balance", "Cognitive function", "Mood", "Memory" ], "commonDosageRange": "10-50 mg daily", "recommendedForm": "Micronized pregnenolone", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take in the morning with food" }, "evidenceRating": "emerging", "foodSources": [ "Made endogenously from cholesterol" ], "deficiencySymptoms": [], "sideEffects": [ "Drowsiness", "Irritability", "Acne", "Headache", "Hormone conversion effects such as acne, mood changes, androgenic symptoms, or progestogenic symptoms" ], "contraindications": [ "Hormone-sensitive cancers", "Prostate cancer or elevated PSA", "Breast cancer", "Endometrial or ovarian cancer risk unless clinician-supervised", "Seizure disorders", "Under 40 without testing" ], "iconName": "brain.head.profile.fill", "colorHex": "FF6B6B", "tags": [ "hormonal", "cognitive", "mood", "neurosteroid" ], "sources": [ { "claim": "Proof-of-concept RCT of pregnenolone for cognitive symptoms in schizophrenia", "title": "Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia", "authors": "Marx CE et al.", "journal": "Neuropsychopharmacology", "year": 2009, "pmid": "19339966", "url": "https://pubmed.ncbi.nlm.nih.gov/19339966/", "study_type": "RCT", "key_finding": "Pregnenolone (up to 500 mg/day) improved verbal memory and Tower of London scores with z-score improvements 0.61 greater than placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19339966/", "publicSourceType": "PMID" }, { "claim": "Larger RCT of pregnenolone in schizophrenia", "title": "Proof-of-concept randomized controlled trial of pregnenolone in schizophrenia", "authors": "Marx CE et al.", "journal": "Psychopharmacology", "year": 2014, "pmid": "25030803", "url": "https://pubmed.ncbi.nlm.nih.gov/25030803/", "study_type": "RCT", "key_finding": "Pregnenolone improved functional capacity in schizophrenia participants; fivefold elevations in allopregnanolone (GABAergic metabolite) may play role in efficacy.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25030803/", "publicSourceType": "PMID" }, { "claim": "Pregnenolone as novel therapeutic candidate review", "title": "Pregnenolone as a novel therapeutic candidate in schizophrenia: emerging preclinical and clinical evidence", "authors": "Marx CE et al.", "journal": "Neuroscience", "year": 2011, "pmid": "21756978", "url": "https://pubmed.ncbi.nlm.nih.gov/21756978/", "study_type": "review", "key_finding": "Pregnenolone positively modulates NMDA receptors and elevates downstream neurosteroids including neuroprotective allopregnanolone; addresses hypothesized NMDA hypofunction.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21756978/", "publicSourceType": "PMID" }, { "claim": "Pregnenolone reduces chronic low back pain in veterans RCT", "title": "Effect of Pregnenolone vs Placebo on Self-reported Chronic Low Back Pain Among US Military Veterans: A Randomized Clinical Trial", "authors": "Naylor JC et al.", "journal": "JAMA Internal Medicine", "year": 2020, "pmid": "32119096", "url": "https://pubmed.ncbi.nlm.nih.gov/32119096/", "study_type": "RCT", "key_finding": "Pregnenolone (escalating to 500 mg/day) produced clinically meaningful reductions in chronic low back pain and pain interference vs placebo; well tolerated.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32119096/", "publicSourceType": "PMID" }, { "claim": "Neurosteroids and potential therapeutics focusing on pregnenolone", "title": "Neurosteroids and potential therapeutics: Focus on pregnenolone", "authors": "Marx CE et al.", "journal": "Journal of Steroid Biochemistry and Molecular Biology", "year": 2016, "pmid": "26433186", "url": "https://pubmed.ncbi.nlm.nih.gov/26433186/", "study_type": "review", "key_finding": "Pregnenolone is the precursor to all steroid hormones, has direct GABA and NMDA receptor effects as a neurosteroid, and shows therapeutic potential for multiple CNS conditions.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26433186/", "publicSourceType": "PMID" }, { "claim": "Pregnenolone reduces negative symptoms in recent-onset schizophrenia", "title": "Pregnenolone treatment reduces severity of negative symptoms in recent-onset schizophrenia: an 8-week, double-blind, randomized add-on two-center trial", "authors": "Ritsner MS et al.", "journal": "Journal of Clinical Psychiatry", "year": 2014, "pmid": "24548129", "url": "https://pubmed.ncbi.nlm.nih.gov/24548129/", "study_type": "RCT", "key_finding": "Add-on pregnenolone significantly reduced severity of negative symptoms compared to placebo in recent-onset schizophrenia patients.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24548129/", "publicSourceType": "PMID" }, { "claim": "May ameliorate irritability in autism spectrum disorder", "title": "Does Pregnenolone Adjunct to Risperidone Ameliorate Irritable Behavior in Adolescents With Autism Spectrum Disorder: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial?", "authors": "Ayatollahi A, Bagheri S, Ashraf-Ganjouei A, Moradi K, Mohammadi MR, Akhondzadeh S", "journal": "Clinical Neuropharmacology", "year": 2020, "pmid": "32947424", "url": "https://pubmed.ncbi.nlm.nih.gov/32947424/", "study_type": "rct", "key_finding": "Pregnenolone as an adjunct to risperidone significantly improved irritability scores in adolescents with autism spectrum disorder compared to risperidone plus placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32947424/", "publicSourceType": "PMID" }, { "text": "Kardashev A, Ratner Y, Ritsner MS. Add-On Pregnenolone with L-Theanine to Antipsychotic Therapy Relieves Negative and Anxiety Symptoms of Schizophrenia: An 8-Week, Randomized, Double-Blind, Placebo-Controlled Trial. Clinical schizophrenia & related psychoses. 2018", "claim": "PubMed-indexed evidence involving Pregnenolone", "title": "Add-On Pregnenolone with L-Theanine to Antipsychotic Therapy Relieves Negative and Anxiety Symptoms of Schizophrenia: An 8-Week, Randomized, Double-Blind, Placebo-Controlled Trial", "authors": "Kardashev A, Ratner Y, Ritsner MS", "journal": "Clinical schizophrenia & related psychoses", "year": 2018, "pmid": "26218236", "url": "https://pubmed.ncbi.nlm.nih.gov/26218236/", "study_type": "RCT", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26218236/", "publicSourceType": "PMID" }, { "text": "Kashani L, Shams N, Moazen-Zadeh E et al.. Pregnenolone as an adjunct to risperidone for treatment of women with schizophrenia: A randomized double-blind placebo-controlled clinical trial. Journal of psychiatric research. 2017", "claim": "PubMed-indexed evidence involving Pregnenolone", "title": "Pregnenolone as an adjunct to risperidone for treatment of women with schizophrenia: A randomized double-blind placebo-controlled clinical trial", "authors": "Kashani L, Shams N, Moazen-Zadeh E et al.", "journal": "Journal of psychiatric research", "year": 2017, "pmid": "28688338", "url": "https://pubmed.ncbi.nlm.nih.gov/28688338/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.jpsychires.2017.06.011", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28688338/", "publicSourceType": "PMID" }, { "text": "Kellner M, Nowack S, Wortmann V et al.. Does Pregnenolone Enhance Exposure Therapy in Obsessive-Compulsive Disorder? - A Pilot, Interim Report of a Randomized, Placebo-Controlled, Double-Blind Study. Pharmacopsychiatry. 2016", "claim": "PubMed-indexed evidence involving Pregnenolone", "title": "Does Pregnenolone Enhance Exposure Therapy in Obsessive-Compulsive Disorder? - A Pilot, Interim Report of a Randomized, Placebo-Controlled, Double-Blind Study", "authors": "Kellner M, Nowack S, Wortmann V et al.", "journal": "Pharmacopsychiatry", "year": 2016, "pmid": "26797931", "url": "https://pubmed.ncbi.nlm.nih.gov/26797931/", "study_type": "RCT", "confidence": "verify", "doi": "10.1055/s-0035-1569371", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26797931/", "publicSourceType": "PMID" }, { "text": "Brown ES, Park J, Marx CE et al.. A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2014", "claim": "PubMed-indexed evidence involving Pregnenolone", "title": "A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression", "authors": "Brown ES, Park J, Marx CE et al.", "journal": "Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology", "year": 2014, "pmid": "24917198", "url": "https://pubmed.ncbi.nlm.nih.gov/24917198/", "study_type": "RCT", "confidence": "verify", "doi": "10.1038/npp.2014.138", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24917198/", "publicSourceType": "PMID" }, { "text": "Ritsner MS, Gibel A, Shleifer T et al.. Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomized, controlled, 2-center, parallel-group trial. The Journal of clinical psychiatry. 2010", "claim": "PubMed-indexed evidence involving Pregnenolone", "title": "Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomized, controlled, 2-center, parallel-group trial", "authors": "Ritsner MS, Gibel A, Shleifer T et al.", "journal": "The Journal of clinical psychiatry", "year": 2010, "pmid": "20584515", "url": "https://pubmed.ncbi.nlm.nih.gov/20584515/", "study_type": "RCT", "confidence": "verify", "doi": "10.4088/JCP.09m05031yel", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20584515/", "publicSourceType": "PMID" }, { "text": "Madhu C, Klaassen CD. Protective effect of pregnenolone-16 alpha-carbonitrile on acetaminophen-induced hepatotoxicity in hamsters. Toxicology and applied pharmacology. 1991", "claim": "PubMed-indexed evidence involving Pregnenolone", "title": "Protective effect of pregnenolone-16 alpha-carbonitrile on acetaminophen-induced hepatotoxicity in hamsters", "authors": "Madhu C, Klaassen CD", "journal": "Toxicology and applied pharmacology", "year": 1991, "pmid": "2068728", "url": "https://pubmed.ncbi.nlm.nih.gov/2068728/", "study_type": "review", "confidence": "verify", "doi": "10.1016/0041-008x(91)90177-g", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2068728/", "publicSourceType": "PMID" }, { "text": "Gao H, Sinha R, Wemm S et al.. Pregnenolone effects on parasympathetic response to stress and alcohol cue provocation in treatment-seeking individuals with alcohol use disorder. Alcohol, clinical & experimental research. 2025", "claim": "PubMed-indexed evidence involving Pregnenolone", "title": "Pregnenolone effects on parasympathetic response to stress and alcohol cue provocation in treatment-seeking individuals with alcohol use disorder", "authors": "Gao H, Sinha R, Wemm S et al.", "journal": "Alcohol, clinical & experimental research", "year": 2025, "pmid": "39779217", "url": "https://pubmed.ncbi.nlm.nih.gov/39779217/", "study_type": "review", "confidence": "verify", "doi": "10.1111/acer.15529", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39779217/", "publicSourceType": "PMID" }, { "text": "Gao H, Magin Z, Fogelman N et al.. Stability and Reliability of Repeated Plasma Pregnenolone Levels After Oral Pregnenolone Dosing in Individuals with Cocaine Use Disorder: Pilot Findings. Life (Basel, Switzerland). 2024", "claim": "PubMed-indexed evidence involving Pregnenolone", "title": "Stability and Reliability of Repeated Plasma Pregnenolone Levels After Oral Pregnenolone Dosing in Individuals with Cocaine Use Disorder: Pilot Findings", "authors": "Gao H, Magin Z, Fogelman N et al.", "journal": "Life (Basel, Switzerland)", "year": 2024, "pmid": "39598281", "url": "https://pubmed.ncbi.nlm.nih.gov/39598281/", "study_type": "review", "confidence": "verify", "doi": "10.3390/life14111483", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39598281/", "publicSourceType": "PMID" }, { "claim": "Pregnenolone can stimulate prostate cancer cell growth in vitro", "title": "Pregnenolone stimulates LNCaP prostate cancer cell growth via the mutated androgen receptor", "authors": "Grigoryev DN, Long BJ, Njar VC, Brodie AH", "journal": "Journal of Steroid Biochemistry and Molecular Biology", "year": 2000, "pmid": "11179903", "url": "https://pubmed.ncbi.nlm.nih.gov/11179903/", "study_type": "in_vitro", "key_finding": "In vitro prostate cancer data support avoiding unsupervised pregnenolone in prostate cancer risk contexts.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11179903/", "publicSourceType": "PMID" }, { "claim": "Endogenous pregnenolone metabolites have been studied in relation to endometrial and ovarian cancer risk", "title": "Association of Endogenous Pregnenolone, Progesterone, and Related Metabolites with Risk of Endometrial and Ovarian Cancers in Postmenopausal Women: The B-FIT Cohort", "authors": "Trabert B et al.", "journal": "Cancer Epidemiology, Biomarkers and Prevention", "year": 2021, "pmid": "34465588", "url": "https://pubmed.ncbi.nlm.nih.gov/34465588/", "study_type": "cohort", "key_finding": "Cohort biomarker evidence supports clinician-guided use in postmenopausal gynecologic cancer risk contexts.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34465588/", "publicSourceType": "PMID" }, { "claim": "Human breast cancer tissue can metabolize pregnenolone", "title": "Metabolism of pregnenolone by human breast cancer. Evidence for 17 alpha-hydroxylase and 17,20-lyase", "authors": "Abul-Hajj YJ, Iverson R, Kiang DT", "journal": "Steroids", "year": 1979, "pmid": "161434", "url": "https://pubmed.ncbi.nlm.nih.gov/161434/", "study_type": "in_vitro", "key_finding": "Human breast cancer tissue metabolism data support caution with pregnenolone in breast cancer contexts.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/161434/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "pregnenolone" }, { "id": "D96EEBDE-8A46-4335-88A8-FF79D4BE9993", "name": "Activated Charcoal", "alternateNames": [ "Activated Carbon" ], "category": "Other", "subcategory": "Adsorbent", "overview": "Highly porous carbon used for acute toxin binding and occasional digestive support.", "mechanismOfAction": "Massive surface area (1g = 3,000 sq meters) adsorbs toxins, drugs, and chemicals in the GI tract, preventing systemic absorption. Used in emergency medicine for poisoning.", "commonBenefits": [ "Toxin binding", "Gas/bloating relief", "Emergency poisoning first aid" ], "commonDosageRange": "500-1,000 mg as needed (NOT daily)", "recommendedForm": "Coconut shell activated charcoal capsules", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Take 2+ hours away from ALL medications and supplements (it will adsorb them)" }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Constipation", "Black stools", "Adsorbs medications/nutrients" ], "contraindications": [ "Intestinal obstruction", "ANY concurrent medications (blocks absorption)", "Not for daily use" ], "iconName": "circle.grid.cross.fill", "colorHex": "333333", "tags": [ "detox", "emergency", "gas", "acute-use" ], "sources": [ { "claim": "Systematic review of activated charcoal for GI decontamination in poisoning", "title": "Systematic review on the use of activated charcoal for gastrointestinal decontamination following acute oral overdose", "authors": "Hoegberg LCG et al.", "journal": "Clinical Toxicology", "year": 2021, "pmid": "34424785", "url": "https://pubmed.ncbi.nlm.nih.gov/34424785/", "study_type": "meta-analysis", "key_finding": "Activated charcoal most efficacious within 1 hour of toxin ingestion; higher-quality evidence focused on select poisonings; benefit reported beyond 1 hour in many scenarios.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34424785/", "publicSourceType": "PMID" }, { "claim": "StatPearls comprehensive reference on activated charcoal mechanism and use", "title": "Activated Charcoal", "authors": "Silberman J et al.", "journal": "StatPearls", "year": 2024, "pmid": "29493919", "url": "https://pubmed.ncbi.nlm.nih.gov/29493919/", "study_type": "NIH_ODS", "key_finding": "Massive surface area permits binding of drugs and toxins in GI lumen; adsorbs ingested toxins preventing systemic absorption; adverse effects limited to nausea, vomiting, constipation.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29493919/", "publicSourceType": "PMID" }, { "claim": "Activated charcoal efficacy for reducing intestinal gas", "title": "Efficacy of activated charcoal in reducing intestinal gas: a double-blind clinical trial", "authors": "Hall RG et al.", "journal": "American Journal of Gastroenterology", "year": 1986, "pmid": "3521259", "url": "https://pubmed.ncbi.nlm.nih.gov/3521259/", "study_type": "RCT", "key_finding": "Activated charcoal significantly reduced breath hydrogen levels and symptoms of bloating and abdominal cramps in double-blind trial.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3521259/", "publicSourceType": "PMID" }, { "claim": "Activated charcoal reappraisal for acute overdose", "title": "Activated charcoal for acute overdose: a reappraisal", "authors": "Juurlink DN", "journal": "British Journal of Clinical Pharmacology", "year": 2016, "pmid": "26409027", "url": "https://pubmed.ncbi.nlm.nih.gov/26409027/", "study_type": "review", "key_finding": "Activated charcoal significantly reduces drug absorption, most effectively when given within first hour; few rigorous clinical trials validate utility in high-risk patients.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26409027/", "publicSourceType": "PMID" }, { "claim": "Failure of activated charcoal to reduce colonic gases", "title": "Failure of activated charcoal to reduce the release of gases produced by the colonic flora", "authors": "Suarez FL et al.", "journal": "American Journal of Gastroenterology", "year": 1999, "pmid": "9934757", "url": "https://pubmed.ncbi.nlm.nih.gov/9934757/", "study_type": "RCT", "key_finding": "Commonly employed doses of activated charcoal do not appreciably influence the liberation of fecal gases, contradicting some earlier positive findings.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9934757/", "publicSourceType": "PMID" }, { "claim": "Meta-analysis of activated charcoal effect on drug exposure after IV administration", "title": "The effect of activated charcoal on drug exposure following intravenous administration: A meta-analysis", "authors": "Groth Hoegberg LC et al.", "journal": "Basic and Clinical Pharmacology and Toxicology", "year": 2021, "pmid": "33386684", "url": "https://pubmed.ncbi.nlm.nih.gov/33386684/", "study_type": "meta-analysis", "key_finding": "Meta-analysis demonstrated activated charcoal can reduce drug exposure even for intravenously administered drugs undergoing enterohepatic recirculation.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33386684/", "publicSourceType": "PMID" }, { "text": "Isoardi KZ, Henry C, Harris K et al.. Activated Charcoal and Bicarbonate for Aspirin Toxicity: a Retrospective Series. Journal of medical toxicology : official journal of the American College of Medical Toxicology. 2022", "claim": "PubMed-indexed evidence involving Activated Charcoal", "title": "Activated Charcoal and Bicarbonate for Aspirin Toxicity: a Retrospective Series", "authors": "Isoardi KZ, Henry C, Harris K et al.", "journal": "Journal of medical toxicology : official journal of the American College of Medical Toxicology", "year": 2022, "pmid": "34845647", "url": "https://pubmed.ncbi.nlm.nih.gov/34845647/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s13181-021-00865-0", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34845647/", "publicSourceType": "PMID" }, { "text": "Wong CF, Saif UM, Chow KL et al.. Applications of charcoal, activated charcoal, and biochar in aquaculture - A review. The Science of the total environment. 2024", "claim": "PubMed-indexed evidence involving Activated Charcoal", "title": "Applications of charcoal, activated charcoal, and biochar in aquaculture - A review", "authors": "Wong CF, Saif UM, Chow KL et al.", "journal": "The Science of the total environment", "year": 2024, "pmid": "38641094", "url": "https://pubmed.ncbi.nlm.nih.gov/38641094/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.scitotenv.2024.172574", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38641094/", "publicSourceType": "PMID" }, { "text": "Ramundo A, Janoš J, Muchová L et al.. Visible-Light-Activated Carbon Monoxide Release from Porphyrin-Flavonol Hybrids. Journal of the American Chemical Society. 2024", "claim": "PubMed-indexed evidence involving Activated Charcoal", "title": "Visible-Light-Activated Carbon Monoxide Release from Porphyrin-Flavonol Hybrids", "authors": "Ramundo A, Janoš J, Muchová L et al.", "journal": "Journal of the American Chemical Society", "year": 2024, "pmid": "38157303", "url": "https://pubmed.ncbi.nlm.nih.gov/38157303/", "study_type": "review", "confidence": "verify", "doi": "10.1021/jacs.3c11426", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38157303/", "publicSourceType": "PMID" }, { "text": "Petkova T, Milanova A, Poźniak B. The effects of cyclosporine A or activated charcoal co-administration on the pharmacokinetics of enrofloxacin in chickens. Poultry science. 2023", "claim": "PubMed-indexed evidence involving Activated Charcoal", "title": "The effects of cyclosporine A or activated charcoal co-administration on the pharmacokinetics of enrofloxacin in chickens", "authors": "Petkova T, Milanova A, Poźniak B", "journal": "Poultry science", "year": 2023, "pmid": "36343435", "url": "https://pubmed.ncbi.nlm.nih.gov/36343435/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.psj.2022.102225", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36343435/", "publicSourceType": "PMID" }, { "text": "Sodano F, Rolando B, Lazzarato L et al.. Use of Enzymatically Activated Carbon Monoxide Donors for Sensitizing Drug-Resistant Tumor Cells. International journal of molecular sciences. 2023", "claim": "PubMed-indexed evidence involving Activated Charcoal", "title": "Use of Enzymatically Activated Carbon Monoxide Donors for Sensitizing Drug-Resistant Tumor Cells", "authors": "Sodano F, Rolando B, Lazzarato L et al.", "journal": "International journal of molecular sciences", "year": 2023, "pmid": "37511019", "url": "https://pubmed.ncbi.nlm.nih.gov/37511019/", "study_type": "review", "confidence": "verify", "doi": "10.3390/ijms241411258", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37511019/", "publicSourceType": "PMID" }, { "text": "Bond GR. The role of activated charcoal and gastric emptying in gastrointestinal decontamination: a state-of-the-art review. Annals of emergency medicine. 2002", "claim": "PubMed-indexed evidence involving Activated Charcoal", "title": "The role of activated charcoal and gastric emptying in gastrointestinal decontamination: a state-of-the-art review", "authors": "Bond GR", "journal": "Annals of emergency medicine", "year": 2002, "pmid": "11867980", "url": "https://pubmed.ncbi.nlm.nih.gov/11867980/", "study_type": "review", "confidence": "verify", "doi": "10.1067/mem.2002.122058", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11867980/", "publicSourceType": "PMID" }, { "text": "Bradberry SM, Vale JA. Multiple-dose activated charcoal: a review of relevant clinical studies. Journal of toxicology. Clinical toxicology. 1995", "claim": "PubMed-indexed evidence involving Activated Charcoal", "title": "Multiple-dose activated charcoal: a review of relevant clinical studies", "authors": "Bradberry SM, Vale JA", "journal": "Journal of toxicology. Clinical toxicology", "year": 1995, "pmid": "7650765", "url": "https://pubmed.ncbi.nlm.nih.gov/7650765/", "study_type": "review", "confidence": "verify", "doi": "10.3109/15563659509013749", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7650765/", "publicSourceType": "PMID" }, { "text": "Viana ÍEL, Weiss GS, Sakae LO et al.. Activated charcoal toothpastes do not increase erosive tooth wear. Journal of dentistry. 2021", "claim": "PubMed-indexed evidence involving Activated Charcoal", "title": "Activated charcoal toothpastes do not increase erosive tooth wear", "authors": "Viana ÍEL, Weiss GS, Sakae LO et al.", "journal": "Journal of dentistry", "year": 2021, "pmid": "33895239", "url": "https://pubmed.ncbi.nlm.nih.gov/33895239/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.jdent.2021.103677", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33895239/", "publicSourceType": "PMID" }, { "text": "Isbister GK, Kumar VV. Indications for single-dose activated charcoal administration in acute overdose. Current opinion in critical care. 2011", "claim": "PubMed-indexed evidence involving Activated Charcoal", "title": "Indications for single-dose activated charcoal administration in acute overdose", "authors": "Isbister GK, Kumar VV", "journal": "Current opinion in critical care", "year": 2011, "pmid": "21716104", "url": "https://pubmed.ncbi.nlm.nih.gov/21716104/", "study_type": "review", "confidence": "verify", "doi": "10.1097/MCC.0b013e328348bf59", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21716104/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "activated-charcoal" }, { "id": "CE64BFE9-2DD3-4150-B4FF-C8D35894A966", "name": "CLA", "alternateNames": [ "Conjugated Linoleic Acid" ], "category": "Omega/Fatty Acid", "subcategory": "Trans Fatty Acid Isomer", "overview": "Naturally occurring trans fat found in grass-fed meat and dairy with body composition benefits.", "mechanismOfAction": "Activates PPARgamma in adipose tissue, reducing lipogenesis. Inhibits stearoyl-CoA desaturase (SCD-1) and lipoprotein lipase, modulating fat storage and oxidation.", "commonBenefits": [ "Body composition", "Fat loss support", "Immune modulation" ], "commonDosageRange": "3-6 g daily", "recommendedForm": "Mixed isomers (c9,t11 and t10,c12) from safflower oil", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with meals" }, "evidenceRating": "moderate", "foodSources": [ "Grass-fed beef", "Lamb", "Dairy" ], "deficiencySymptoms": [], "sideEffects": [ "GI upset", "Insulin resistance at high doses", "Fatty liver concern" ], "contraindications": [ "Diabetes", "Metabolic syndrome", "Liver disease" ], "iconName": "flame.fill", "colorHex": "4D94FF", "tags": [ "fat-loss", "body-comp" ], "sources": [ { "claim": "CLA supplementation reduces body fat mass and improves body composition", "title": "The effects of conjugated linoleic acid supplementation on anthropometrics and body composition indices in adults: a systematic review and dose-response meta-analysis", "authors": "Ghaffari MA et al.", "journal": "Crit Rev Food Sci Nutr", "year": 2023, "pmid": "37671495", "url": "https://pubmed.ncbi.nlm.nih.gov/37671495/", "study_type": "meta-analysis", "key_finding": "CLA supplementation significantly reduced body mass, BMI, waist circumference, fat mass, and body fat percentage, though high-quality subgroup showed CLA failed to change fat mass and body fat percentage.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37671495/", "publicSourceType": "PMID" }, { "claim": "CLA reduces fat mass in humans across multiple trials", "title": "Efficacy of conjugated linoleic acid for reducing fat mass: a meta-analysis in humans", "authors": "Whigham LD et al.", "journal": "Am J Clin Nutr", "year": 2007, "pmid": "17490954", "url": "https://pubmed.ncbi.nlm.nih.gov/17490954/", "study_type": "meta-analysis", "key_finding": "CLA at a dose of 3.2 g/day produced a modest loss in body fat in humans.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17490954/", "publicSourceType": "PMID" }, { "claim": "CLA combined with exercise may reduce body fat and insulin resistance", "title": "Effects of conjugated linoleic acid and exercise on body composition and obesity: a systematic review and meta-analysis", "authors": "Kim JH et al.", "journal": "J Exerc Nutrition Biochem", "year": 2022, "pmid": "36048508", "url": "https://pubmed.ncbi.nlm.nih.gov/36048508/", "study_type": "meta-analysis", "key_finding": "CLA combined with exercise is generally safe and can lower body fat and insulin resistance but does not reduce body weight or enhance exercise performance.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36048508/", "publicSourceType": "PMID" }, { "claim": "CLA isomers regulate PPARgamma and fat metabolism differently", "title": "Isomer-specific regulation of metabolism and PPARgamma signaling by CLA in human preadipocytes", "authors": "Brown JM et al.", "journal": "J Lipid Res", "year": 2003, "pmid": "12730300", "url": "https://pubmed.ncbi.nlm.nih.gov/12730300/", "study_type": "in_vitro", "key_finding": "The trans-10,cis-12 isomer of CLA decreased glucose and lipid uptake and preadipocyte differentiation due in part to decreased PPARgamma expression.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12730300/", "publicSourceType": "PMID" }, { "claim": "CLA may adversely affect insulin sensitivity in diabetic patients", "title": "Conjugated linoleic acid supplementation, insulin sensitivity, and lipoprotein metabolism in patients with type 2 diabetes mellitus", "authors": "Moloney F et al.", "journal": "Am J Clin Nutr", "year": 2004, "pmid": "15447895", "url": "https://pubmed.ncbi.nlm.nih.gov/15447895/", "study_type": "RCT", "key_finding": "CLA supplementation had an adverse effect on insulin and glucose metabolism in patients with type 2 diabetes.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15447895/", "publicSourceType": "PMID" }, { "claim": "Review of CLA effects on body composition, glucose, and lipid metabolism", "title": "Conjugated linoleic acid intake in humans--a systematic review focusing on its effect on body composition, glucose, and lipid metabolism", "authors": "Tricon S et al.", "journal": "Am J Clin Nutr", "year": 2006, "pmid": "16864141", "url": "https://pubmed.ncbi.nlm.nih.gov/16864141/", "study_type": "review", "key_finding": "Systematic review of CLA's effects in humans covering body composition, glucose metabolism, and lipid profiles with mixed results on metabolic safety.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16864141/", "publicSourceType": "PMID" }, { "text": "Derakhshande-Rishehri SM, Mansourian M, Kelishadi R et al.. Association of foods enriched in conjugated linoleic acid (CLA) and CLA supplements with lipid profile in human studies: a systematic review and meta-analysis. Public health nutrition. 2015", "pmid": "25379623", "doi": "10.1017/S1368980014002262", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25379623/", "publicSourceType": "PMID" }, { "text": "Badawy S, Liu Y, Guo M et al.. Conjugated linoleic acid (CLA) as a functional food: Is it beneficial or not?. Food research international (Ottawa, Ont.). 2023", "pmid": "37689911", "doi": "10.1016/j.foodres.2023.113158", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37689911/", "publicSourceType": "PMID" }, { "claim": "CLA supplementation produces small but significant reductions in body weight and body fat in CVD-risk patients", "title": "The effects of conjugated linoleic acid supplementation on cardiovascular risk factors in patients at risk of cardiovascular disease: A GRADE-assessed systematic review and dose-response meta-analysis", "authors": "Esmaeilnejad M, Rasaei N, Goudarzi K et al.", "journal": "Br J Nutr", "year": 2024, "pmid": "39439191", "url": "https://pubmed.ncbi.nlm.nih.gov/39439191/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 14 RCTs found CLA significantly reduced body weight (-0.72 kg), BMI (-0.22 kg/m2), and body fat percentage (-1.32%) in CVD-risk patients. No effect on lipid profile or blood pressure.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39439191/", "publicSourceType": "PMID" }, { "claim": "CLA supplementation may reduce malondialdehyde (MDA) but increases 8-iso-PGF2alpha, suggesting mixed effects on oxidative stress", "title": "The effect of conjugated linoleic acid supplementation on oxidative stress markers: A systematic review and meta-analysis of randomized controlled trials", "authors": "Suksatan W, Putera HD, Abdulkadhim AH et al.", "journal": "Clin Nutr ESPEN", "year": 2022, "pmid": "35623803", "url": "https://pubmed.ncbi.nlm.nih.gov/35623803/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 11 RCTs found CLA significantly decreased MDA concentrations and increased 8-iso-PGF2alpha levels. No significant change in GPx concentrations.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35623803/", "publicSourceType": "PMID" }, { "claim": "CLA produces small reductions in body weight and fat mass in overweight and obese subjects", "title": "The effects of supplementation with conjugated linoleic acid on anthropometric indices and body composition in overweight and obese subjects: A systematic review and meta-analysis", "authors": "Namazi N, Irandoost P, Larijani B, Azadbakht L", "journal": "Crit Rev Food Sci Nutr", "year": 2019, "pmid": "29672124", "url": "https://pubmed.ncbi.nlm.nih.gov/29672124/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 13 trials found CLA significantly reduced body weight (-0.52 kg), BMI (-0.23 kg/m2), fat mass (-0.61 kg) and increased lean body mass (+0.19 kg), but effects were small and may not be clinically significant.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29672124/", "publicSourceType": "PMID" }, { "claim": "CLA produces statistically significant but not clinically significant weight loss compared to placebo", "title": "Efficacy of dietary supplements containing isolated organic compounds for weight loss: a systematic review and meta-analysis of randomised placebo-controlled trials", "authors": "Bessell E, Maunder A, Lauche R, Adams J, Sainsbury A, Fuller NR", "journal": "Int J Obes (Lond)", "year": 2021, "pmid": "33976376", "url": "https://pubmed.ncbi.nlm.nih.gov/33976376/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 67 RCTs found CLA produced statistically significant weight difference of -1.08 kg vs placebo (p<0.01), but this did not meet the threshold for clinical significance (>=2.5 kg).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33976376/", "publicSourceType": "PMID" }, { "text": "Akhgarjand C, Tavakoli A, Samavat S et al.. The effect of conjugated linoleic acid supplementation in comparison with omega-6 and omega-9 on lipid profile: a graded, dose-response systematic review and meta-analysis of randomized controlled trials. Frontiers in nutrition. 2024", "claim": "PubMed-indexed evidence involving CLA", "title": "The effect of conjugated linoleic acid supplementation in comparison with omega-6 and omega-9 on lipid profile: a graded, dose-response systematic review and meta-analysis of randomized controlled trials", "authors": "Akhgarjand C, Tavakoli A, Samavat S et al.", "journal": "Frontiers in nutrition", "year": 2024, "pmid": "38567248", "url": "https://pubmed.ncbi.nlm.nih.gov/38567248/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fnut.2024.1336889", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38567248/", "publicSourceType": "PMID" }, { "text": "Morvaridzadeh M, Estêvão MD, Morvaridi M et al.. The effect of Conjugated Linoleic Acid intake on oxidative stress parameters and antioxidant enzymes: A systematic review and meta-analysis of randomized clinical trials. Prostaglandins & other lipid mediators. 2022", "claim": "PubMed-indexed evidence involving CLA", "title": "The effect of Conjugated Linoleic Acid intake on oxidative stress parameters and antioxidant enzymes: A systematic review and meta-analysis of randomized clinical trials", "authors": "Morvaridzadeh M, Estêvão MD, Morvaridi M et al.", "journal": "Prostaglandins & other lipid mediators", "year": 2022, "pmid": "35914666", "url": "https://pubmed.ncbi.nlm.nih.gov/35914666/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.prostaglandins.2022.106666", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35914666/", "publicSourceType": "PMID" }, { "text": "Mohammadi-Sartang M, Sohrabi Z, Esmaeilinezhad Z et al.. Effect of Conjugated Linoleic Acid on Leptin Level: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2018", "claim": "PubMed-indexed evidence involving CLA", "title": "Effect of Conjugated Linoleic Acid on Leptin Level: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Mohammadi-Sartang M, Sohrabi Z, Esmaeilinezhad Z et al.", "journal": "Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme", "year": 2018, "pmid": "29401538", "url": "https://pubmed.ncbi.nlm.nih.gov/29401538/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1055/s-0044-100041", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29401538/", "publicSourceType": "PMID" }, { "text": "Rastgoo S, Shimi G, Shiraseb F et al.. The effects of conjugated linoleic acid supplementation on inflammatory cytokines and adipokines in adults: A GRADE-assessed systematic review and dose-response meta-analysis. Frontiers in immunology. 2023", "claim": "PubMed-indexed evidence involving CLA", "title": "The effects of conjugated linoleic acid supplementation on inflammatory cytokines and adipokines in adults: A GRADE-assessed systematic review and dose-response meta-analysis", "authors": "Rastgoo S, Shimi G, Shiraseb F et al.", "journal": "Frontiers in immunology", "year": 2023, "pmid": "36911696", "url": "https://pubmed.ncbi.nlm.nih.gov/36911696/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fimmu.2023.1092077", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36911696/", "publicSourceType": "PMID" }, { "text": "Ghodoosi N, Rasaei N, Goudarzi K et al.. The effects of conjugated linoleic acid supplementation on glycemic control, adipokines, cytokines, malondialdehyde and liver function enzymes in patients at risk of cardiovascular disease: a GRADE-assessed systematic review and dose-response meta-analysis. Nutrition journal. 2023", "claim": "PubMed-indexed evidence involving CLA", "title": "The effects of conjugated linoleic acid supplementation on glycemic control, adipokines, cytokines, malondialdehyde and liver function enzymes in patients at risk of cardiovascular disease: a GRADE-assessed systematic review and dose-response meta-analysis", "authors": "Ghodoosi N, Rasaei N, Goudarzi K et al.", "journal": "Nutrition journal", "year": 2023, "pmid": "37794481", "url": "https://pubmed.ncbi.nlm.nih.gov/37794481/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12937-023-00876-3", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37794481/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "cla" }, { "id": "59EDA06D-6716-4C9E-B77F-3892ABC60004", "name": "Tribulus Terrestris", "alternateNames": [ "Tribulus", "Puncture Vine" ], "category": "Herb", "subcategory": "Testosterone Support Herb", "overview": "Traditional herb marketed for testosterone, though evidence is mixed.", "mechanismOfAction": "Protodioscin may increase LH (luteinizing hormone) release, theoretically stimulating testosterone production. Anti-inflammatory via COX-2 and LOX inhibition.", "commonBenefits": [ "Libido", "Athletic performance", "Urinary health" ], "commonDosageRange": "250-750 mg daily", "recommendedForm": "Standardized extract (45-60% saponins)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food" }, "evidenceRating": "emerging", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "GI upset", "Insomnia", "Increased heart rate" ], "contraindications": [ "Hormone-sensitive conditions", "Prostate conditions" ], "iconName": "leaf.fill", "colorHex": "34D399", "tags": [ "testosterone", "libido", "performance" ], "sources": [ { "claim": "Systematic review of tribulus effects on erectile dysfunction and testosterone in men", "title": "Effects of Tribulus (Tribulus terrestris L.) Supplementation on Erectile Dysfunction and Testosterone Levels in Men-A Systematic Review of Clinical Trials", "authors": "Santos HO et al.", "journal": "Nutrients", "year": 2025, "pmid": "40219032", "url": "https://pubmed.ncbi.nlm.nih.gov/40219032/", "study_type": "review", "key_finding": "Tribulus supplementation may improve erectile function but does not significantly increase total testosterone levels in men based on analysis of 10 studies with 483 participants.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40219032/", "publicSourceType": "PMID" }, { "claim": "Evidence for tribulus aphrodisiac and performance enhancing effects is limited", "title": "A systematic review on the herbal extract Tribulus terrestris and the roots of its putative aphrodisiac and performance enhancing effect", "authors": "Qureshi A et al.", "journal": "J Diet Suppl", "year": 2014, "pmid": "24559105", "url": "https://pubmed.ncbi.nlm.nih.gov/24559105/", "study_type": "review", "key_finding": "Evidence for tribulus' effectiveness as testosterone enhancer is limited; evidence to date suggests it is ineffective for increasing testosterone in humans.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24559105/", "publicSourceType": "PMID" }, { "claim": "Tribulus for male sexual dysfunction clinical trial", "title": "Evaluation of the efficacy and safety of Tribulus terrestris in male sexual dysfunction-A prospective, randomized, double-blind, placebo-controlled clinical trial", "authors": "Kamenov Z et al.", "journal": "Maturitas", "year": 2017, "pmid": "28364864", "url": "https://pubmed.ncbi.nlm.nih.gov/28364864/", "study_type": "RCT", "key_finding": "Tribulus (Tribestan) was evaluated in 180 males with erectile dysfunction; showed improvements in sexual function measures.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28364864/", "publicSourceType": "PMID" }, { "claim": "Tribulus effective for hypoactive sexual desire disorder in postmenopausal women", "title": "Efficacy of Tribulus terrestris for the treatment of hypoactive sexual desire disorder in postmenopausal women: a randomized, double-blinded, placebo-controlled trial", "authors": "Postigo S et al.", "journal": "Menopause", "year": 2016, "pmid": "27760089", "url": "https://pubmed.ncbi.nlm.nih.gov/27760089/", "study_type": "RCT", "key_finding": "Tribulus terrestris might be a safe alternative for hypoactive sexual desire disorder in postmenopausal women, effective in reducing symptoms with few side effects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27760089/", "publicSourceType": "PMID" }, { "claim": "Tribulus supplementation does not improve body composition or hormones in resistance-trained men", "title": "The Effects of 6 Weeks of Tribulus terrestris L. Supplementation on Body Composition, Hormonal Response, Perceived Exertion, and CrossFit Performance: A Randomized, Single-Blind, Placebo-Controlled Study", "authors": "Fernandez-Lazaro D et al.", "journal": "Nutrients", "year": 2021, "pmid": "34836225", "url": "https://pubmed.ncbi.nlm.nih.gov/34836225/", "study_type": "RCT", "key_finding": "Six weeks of tribulus supplementation did not significantly alter body composition, hormonal response, or CrossFit performance in resistance-trained men.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34836225/", "publicSourceType": "PMID" }, { "claim": "Tribulus efficacy and safety in erectile dysfunction meta-analysis", "title": "Tribulus terrestris for management of patients with erectile dysfunction: a systematic review and meta-analysis of randomized trials", "authors": "Not specified et al.", "journal": "Int J Impot Res", "year": 2025, "pmid": "40360723", "url": "https://pubmed.ncbi.nlm.nih.gov/40360723/", "study_type": "meta-analysis", "key_finding": "Tribulus supplementation may offer benefits in improving erectile function with a relatively good safety profile, but groups were not significantly different in testosterone levels.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40360723/", "publicSourceType": "PMID" }, { "text": "Fernández-Lázaro D, Fernandez-Lazaro CI, Seco-Calvo J et al.. Effects of Tribulus terrestris L. on Sport and Health Biomarkers in Physically Active Adult Males: A Systematic Review. International journal of environmental research and public health. 2022", "pmid": "35954909", "doi": "10.3390/ijerph19159533", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35954909/", "publicSourceType": "PMID" }, { "text": "Tahvilian R, Golesorkhi MA, Parhoudeh F et al.. The Effect of the Combination of Ginseng, Tribulus Terrestris, and L-arginine on the Sexual Performance of Men with Erectile Dysfunction: a randomized, double-blind, parallel, and placebo-controlled clinical trial. Journal of pharmacopuncture. 2024", "pmid": "38948316", "doi": "10.3831/KPI.2024.27.2.82", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38948316/", "publicSourceType": "PMID" }, { "claim": "Tribulus terrestris may improve erectile function but evidence for testosterone enhancement is limited", "title": "The effect of Tribulus terrestris on erectile dysfunction: A systematic review and meta-analysis.", "authors": "Santos JED, Souza DBD, Burity EF et al.", "journal": "Andrology", "year": 2024, "pmid": "41696741", "url": "https://pubmed.ncbi.nlm.nih.gov/41696741/", "study_type": "meta-analysis", "key_finding": "Systematic review and meta-analysis examining the effect of Tribulus terrestris on erectile dysfunction, finding limited but suggestive evidence of benefit for sexual function.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41696741/", "publicSourceType": "PMID" }, { "text": "Kong J, Li J, Xu M et al.. Dietary Tribulus Terrestris as a functional food combined with blood flow restriction to enhance the jump performance of basketball athletes: a randomized crossover study. Frontiers in nutrition. 2025", "claim": "PubMed-indexed evidence involving Tribulus Terrestris", "title": "Dietary Tribulus Terrestris as a functional food combined with blood flow restriction to enhance the jump performance of basketball athletes: a randomized crossover study", "authors": "Kong J, Li J, Xu M et al.", "journal": "Frontiers in nutrition", "year": 2025, "pmid": "40880746", "url": "https://pubmed.ncbi.nlm.nih.gov/40880746/", "study_type": "RCT", "confidence": "verify", "doi": "10.3389/fnut.2025.1648796", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40880746/", "publicSourceType": "PMID" }, { "text": "Nejati M, Dehghan P, Khani M et al.. The effect of Tribulus terrestris supplementation on inflammation, oxidative stress, and performance of recreational runners: study protocol for a randomized placebo-controlled trial. Trials. 2022", "claim": "PubMed-indexed evidence involving Tribulus Terrestris", "title": "The effect of Tribulus terrestris supplementation on inflammation, oxidative stress, and performance of recreational runners: study protocol for a randomized placebo-controlled trial", "authors": "Nejati M, Dehghan P, Khani M et al.", "journal": "Trials", "year": 2022, "pmid": "35986353", "url": "https://pubmed.ncbi.nlm.nih.gov/35986353/", "study_type": "RCT", "confidence": "verify", "doi": "10.1186/s13063-022-06630-0", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35986353/", "publicSourceType": "PMID" }, { "text": "Fernández-Lázaro D, Seco-Calvo J, Pascual-Fernández J et al.. 6-Week Supplementation with Tribulus terrestris L. to Trained Male CrossFit(®) Athletes on Muscle, Inflammation, and Antioxidant Biomarkers: A Randomized, Single-Blind, Placebo-Controlled Trial. International journal of environmental research and public health. 2022", "claim": "PubMed-indexed evidence involving Tribulus Terrestris", "title": "6-Week Supplementation with Tribulus terrestris L. to Trained Male CrossFit(®) Athletes on Muscle, Inflammation, and Antioxidant Biomarkers: A Randomized, Single-Blind, Placebo-Controlled Trial", "authors": "Fernández-Lázaro D, Seco-Calvo J, Pascual-Fernández J et al.", "journal": "International journal of environmental research and public health", "year": 2022, "pmid": "36498228", "url": "https://pubmed.ncbi.nlm.nih.gov/36498228/", "study_type": "RCT", "confidence": "verify", "doi": "10.3390/ijerph192316158", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36498228/", "publicSourceType": "PMID" }, { "text": "Siddiqui MA, Itrat M, Mobeen A et al.. Efficacy of Khār-i-khasak (Tribulus terrestris Linn.) in prehypertension: a randomized, double-blind, placebo-controlled trial. Journal of complementary & integrative medicine. 2021", "claim": "PubMed-indexed evidence involving Tribulus Terrestris", "title": "Efficacy of Khār-i-khasak (Tribulus terrestris Linn.) in prehypertension: a randomized, double-blind, placebo-controlled trial", "authors": "Siddiqui MA, Itrat M, Mobeen A et al.", "journal": "Journal of complementary & integrative medicine", "year": 2021, "pmid": "33793146", "url": "https://pubmed.ncbi.nlm.nih.gov/33793146/", "study_type": "RCT", "confidence": "verify", "doi": "10.1515/jcim-2020-0322", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33793146/", "publicSourceType": "PMID" }, { "text": "Sansalone S, Leonardi R, Antonini G et al.. Alga Ecklonia bicyclis, Tribulus terrestris, and glucosamine oligosaccharide improve erectile function, sexual quality of life, and ejaculation function in patients with moderate mild-moderate erectile dysfunction: a prospective, randomized, placebo-controlled, single-blinded study. BioMed research international. 2014", "claim": "PubMed-indexed evidence involving Tribulus Terrestris", "title": "Alga Ecklonia bicyclis, Tribulus terrestris, and glucosamine oligosaccharide improve erectile function, sexual quality of life, and ejaculation function in patients with moderate mild-moderate erectile dysfunction: a prospective, randomized, placebo-controlled, single-blinded study", "authors": "Sansalone S, Leonardi R, Antonini G et al.", "journal": "BioMed research international", "year": 2014, "pmid": "25136552", "url": "https://pubmed.ncbi.nlm.nih.gov/25136552/", "study_type": "RCT", "confidence": "verify", "doi": "10.1155/2014/121396", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25136552/", "publicSourceType": "PMID" }, { "text": "Kaplan SA. Re: Comparison of Murraya koenigii- and Tribulus terrestris-based oral formulation versus tamsulosin in the treatment of benign prostatic hyperplasia in men aged >50 years: a double-blind, double-dummy, randomized controlled trial. The Journal of urology. 2012", "claim": "PubMed-indexed evidence involving Tribulus Terrestris", "title": "Re: Comparison of Murraya koenigii- and Tribulus terrestris-based oral formulation versus tamsulosin in the treatment of benign prostatic hyperplasia in men aged >50 years: a double-blind, double-dummy, randomized controlled trial", "authors": "Kaplan SA", "journal": "The Journal of urology", "year": 2012, "pmid": "22971393", "url": "https://pubmed.ncbi.nlm.nih.gov/22971393/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.juro.2012.06.080", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22971393/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "tribulus-terrestris" }, { "id": "FE0F327B-4DD9-4FDC-BEBB-B144FF2F1801", "name": "Black Cohosh", "alternateNames": [ "Actaea racemosa", "Cimicifuga" ], "category": "Herb", "subcategory": "Women's Health Herb", "overview": "North American herb used for menopause symptom relief, especially hot flashes.", "mechanismOfAction": "Triterpene glycosides (actein, cimicifugoside) modulate serotonin receptors and opioid receptors. Does NOT directly affect estrogen levels despite common belief. Reduces LH surges.", "commonBenefits": [ "Hot flash relief", "Menopause support", "Mood during menopause" ], "commonDosageRange": "20-40 mg daily (standardized to 2.5% triterpene glycosides)", "recommendedForm": "Remifemin is best-studied brand", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food; effects seen in 4-8 weeks" }, "evidenceRating": "moderate", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "GI upset", "Headache", "Dizziness", "Liver toxicity (rare, monitor)" ], "contraindications": [ "Liver disease", "Hormone-sensitive cancers", "Pregnancy" ], "iconName": "figure.2.circle", "colorHex": "34D399", "tags": [ "menopause", "hot-flashes", "women" ], "sources": [ { "claim": "Black cohosh extracts improve menopausal symptoms including hot flashes", "title": "Black cohosh extracts in women with menopausal symptoms: an updated pairwise meta-analysis", "authors": "Castelo-Branco C et al.", "journal": "Climacteric", "year": 2023, "pmid": "37192826", "url": "https://pubmed.ncbi.nlm.nih.gov/37192826/", "study_type": "meta-analysis", "key_finding": "Black cohosh extracts significantly improved overall menopausal symptoms and hot flashes versus placebo across 22 articles including 2,310 women.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37192826/", "publicSourceType": "PMID" }, { "claim": "Isopropanolic black cohosh extract effective for menopausal symptoms", "title": "Review & meta-analysis: isopropanolic black cohosh extract iCR for menopausal symptoms - an update on the evidence", "authors": "Beer AM et al.", "journal": "Climacteric", "year": 2020, "pmid": "33021111", "url": "https://pubmed.ncbi.nlm.nih.gov/33021111/", "study_type": "meta-analysis", "key_finding": "Isopropanolic black cohosh extract produced significant reduction in hot flushes, particularly in women with intense hot flushes, at 40 mg/day with improvement in mood.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33021111/", "publicSourceType": "PMID" }, { "claim": "Efficacy of black cohosh preparations for vasomotor symptoms", "title": "Efficacy of black cohosh-containing preparations on menopausal symptoms: a meta-analysis", "authors": "Shams T et al.", "journal": "Altern Ther Health Med", "year": 2010, "pmid": "20085176", "url": "https://pubmed.ncbi.nlm.nih.gov/20085176/", "study_type": "meta-analysis", "key_finding": "Preparations containing black cohosh improved menopausal vasomotor symptoms by 26% overall, though with significant heterogeneity between trials.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20085176/", "publicSourceType": "PMID" }, { "claim": "Spanish Menopause Society statement on black cohosh efficacy and safety", "title": "Black cohosh efficacy and safety for menopausal symptoms. The Spanish Menopause Society statement", "authors": "Chedraui P et al.", "journal": "Gynecol Endocrinol", "year": 2022, "pmid": "35403534", "url": "https://pubmed.ncbi.nlm.nih.gov/35403534/", "study_type": "review", "key_finding": "Black cohosh is effective for menopausal symptoms; most common dose is 40 mg/day achieving significant reduction in hot flushes with effects seen in 4-8 weeks.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35403534/", "publicSourceType": "PMID" }, { "claim": "No evidence of hepatotoxicity in clinical trials of black cohosh", "title": "Suspected black cohosh hepatotoxicity: no evidence by meta-analysis of randomized controlled clinical trials for isopropanolic black cohosh extract", "authors": "Naser B et al.", "journal": "Menopause", "year": 2011, "pmid": "21228727", "url": "https://pubmed.ncbi.nlm.nih.gov/21228727/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of five RCTs showed no evidence that isopropanolic black cohosh extract has any adverse effect on liver function.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21228727/", "publicSourceType": "PMID" }, { "claim": "Critical review of suspected hepatotoxicity cases", "title": "Black cohosh and suspected hepatotoxicity: inconsistencies, confounding variables, and prospective use of a diagnostic causality algorithm. A critical review", "authors": "Teschke R et al.", "journal": "Maturitas", "year": 2010, "pmid": "20216279", "url": "https://pubmed.ncbi.nlm.nih.gov/20216279/", "study_type": "review", "key_finding": "Data do not support hepatotoxicity as causally related to black cohosh use; all case reports assigned only possible causality, none were probable or certain.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20216279/", "publicSourceType": "PMID" }, { "text": "Hedaoo K, Badge AK, Tiwade YR et al.. Exploring the Efficacy and Safety of Black Cohosh (Cimicifuga racemosa) in Menopausal Symptom Management. Journal of mid-life health. 2024", "pmid": "38764923", "doi": "10.4103/jmh.jmh_242_23", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38764923/", "publicSourceType": "PMID" }, { "text": "Mohapatra S, Iqubal A, Ansari MJ et al.. Benefits of Black Cohosh (Cimicifuga racemosa) for Women Health: An Up-Close and In-Depth Review. Pharmaceuticals (Basel, Switzerland). 2022", "pmid": "35337076", "doi": "10.3390/ph15030278", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35337076/", "publicSourceType": "PMID" }, { "claim": "Reduces anxiety and depression in menopausal women", "title": "The efficacy of herbal medicines on anxiety and depression in peri- and postmenopausal women: A systematic review and meta-analysis.", "authors": "Shahmohammadi A, Ramezanpour N, Mahdavi Siuki M, Dizavandi F, Ghazanfarpour M, Rahmani Y et al.", "journal": "Post Reproductive Health", "year": 2019, "pmid": "31630610", "url": "https://pubmed.ncbi.nlm.nih.gov/31630610/", "study_type": "meta-analysis", "key_finding": "Black cohosh (Cimicifuga racemosa) was among the herbal medicines that showed significant improvements in anxiety and depression scores in peri- and postmenopausal women.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31630610/", "publicSourceType": "PMID" }, { "text": "Palacio C, Masri G, Mooradian AD. Black cohosh for the management of menopausal symptoms : a systematic review of clinical trials. Drugs & aging. 2009", "claim": "PubMed-indexed evidence involving Black Cohosh", "title": "Black cohosh for the management of menopausal symptoms : a systematic review of clinical trials", "authors": "Palacio C, Masri G, Mooradian AD", "journal": "Drugs & aging", "year": 2009, "pmid": "19102512", "url": "https://pubmed.ncbi.nlm.nih.gov/19102512/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2165/0002512-200926010-00002", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19102512/", "publicSourceType": "PMID" }, { "text": "Borrelli F, Ernst E. Black cohosh (Cimicifuga racemosa) for menopausal symptoms: a systematic review of its efficacy. Pharmacological research. 2008", "claim": "PubMed-indexed evidence involving Black Cohosh", "title": "Black cohosh (Cimicifuga racemosa) for menopausal symptoms: a systematic review of its efficacy", "authors": "Borrelli F, Ernst E", "journal": "Pharmacological research", "year": 2008, "pmid": "18585461", "url": "https://pubmed.ncbi.nlm.nih.gov/18585461/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.phrs.2008.05.008", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18585461/", "publicSourceType": "PMID" }, { "text": "Pokushalov E, Ponomarenko A, Garcia C et al.. Assessing the combined effects of Black Cohosh, Soy Isoflavones, and SDG Lignans on menopausal symptoms: a randomized, double-blind, placebo-controlled clinical trial. European journal of nutrition. 2025", "claim": "PubMed-indexed evidence involving Black Cohosh", "title": "Assessing the combined effects of Black Cohosh, Soy Isoflavones, and SDG Lignans on menopausal symptoms: a randomized, double-blind, placebo-controlled clinical trial", "authors": "Pokushalov E, Ponomarenko A, Garcia C et al.", "journal": "European journal of nutrition", "year": 2025, "pmid": "40131516", "url": "https://pubmed.ncbi.nlm.nih.gov/40131516/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/s00394-025-03588-y", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40131516/", "publicSourceType": "PMID" }, { "text": "Curtis S, Moore A, Breakspear I. Efficacy and safety of Actaea racemosa for relieving climacteric complaints. Menopause (New York, N.Y.). 2026", "claim": "PubMed-indexed evidence involving Black Cohosh", "title": "Efficacy and safety of Actaea racemosa for relieving climacteric complaints", "authors": "Curtis S, Moore A, Breakspear I", "journal": "Menopause (New York, N.Y.)", "year": 2026, "pmid": "41401209", "url": "https://pubmed.ncbi.nlm.nih.gov/41401209/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/GME.0000000000002704", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41401209/", "publicSourceType": "PMID" }, { "text": "Dernbach MR, Carpenter JE, Shah N et al.. Black Cohosh Interactions with Prescription Medications Associated with Serotonin Toxicity and Rhabdomyolysis: A Case Report. The Journal of emergency medicine. 2024", "claim": "PubMed-indexed evidence involving Black Cohosh", "title": "Black Cohosh Interactions with Prescription Medications Associated with Serotonin Toxicity and Rhabdomyolysis: A Case Report", "authors": "Dernbach MR, Carpenter JE, Shah N et al.", "journal": "The Journal of emergency medicine", "year": 2024, "pmid": "38556373", "url": "https://pubmed.ncbi.nlm.nih.gov/38556373/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.jemermed.2024.01.003", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38556373/", "publicSourceType": "PMID" }, { "text": "Mahady GB, Low Dog T, Barrett ML et al.. United States Pharmacopeia review of the black cohosh case reports of hepatotoxicity. Menopause (New York, N.Y.). 2008", "claim": "PubMed-indexed evidence involving Black Cohosh", "title": "United States Pharmacopeia review of the black cohosh case reports of hepatotoxicity", "authors": "Mahady GB, Low Dog T, Barrett ML et al.", "journal": "Menopause (New York, N.Y.)", "year": 2008, "pmid": "18340277", "url": "https://pubmed.ncbi.nlm.nih.gov/18340277/", "study_type": "review", "confidence": "verify", "doi": "10.1097/gme.0b013e31816054bf", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18340277/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "black-cohosh" }, { "id": "D002974A-C913-4F34-855F-BBEC8FBB6DF4", "name": "L-Methionine", "alternateNames": [ "Methionine" ], "category": "Amino Acid", "subcategory": "Essential Amino Acid", "overview": "Essential sulfur-containing amino acid, precursor to SAMe and cysteine.", "mechanismOfAction": "Activated by methionine adenosyltransferase to SAMe. Enters transmethylation (SAMe→SAH), transsulfuration (cysteine→glutathione), and polyamine synthesis pathways.", "commonBenefits": [ "Methylation", "Detoxification", "Joint health", "Hair/nail growth" ], "commonDosageRange": "500-1,500 mg daily", "recommendedForm": "L-Methionine (free form)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Take on empty stomach" }, "evidenceRating": "moderate", "foodSources": [ "Eggs", "Fish", "Meat", "Brazil nuts", "Sesame seeds" ], "deficiencySymptoms": [ "Poor detoxification", "Slow wound healing" ], "sideEffects": [ "GI upset", "Elevated homocysteine without B6/B12/folate" ], "contraindications": [ "Homocystinuria", "Liver disease", "Must co-supplement B6/B12/folate" ], "iconName": "atom", "colorHex": "B37DFF", "tags": [ "methylation", "sulfur", "detox" ], "sources": [ { "claim": "Methionine as double-edged sword in health - review of metabolism and clinical implications", "title": "Methionine as a double-edged sword in health and disease: Current perspective and future challenges", "authors": "Parkhitko AA et al.", "journal": "Free Radic Biol Med", "year": 2021, "pmid": "34700006", "url": "https://pubmed.ncbi.nlm.nih.gov/34700006/", "study_type": "review", "key_finding": "Methionine restriction and supplementation both provide promising outcomes; its regulation is critical for maintaining health, but excess intake without B vitamins may cause hyperhomocysteinemia.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34700006/", "publicSourceType": "PMID" }, { "claim": "L-methionine supplementation increases plasma homocysteine", "title": "Effect of L-methionine supplementation on plasma homocysteine and other free amino acids: a placebo-controlled double-blind cross-over study", "authors": "Ditscheid B et al.", "journal": "Eur J Clin Nutr", "year": 2005, "pmid": "15870821", "url": "https://pubmed.ncbi.nlm.nih.gov/15870821/", "study_type": "RCT", "key_finding": "Supplementation of 1500 mg L-methionine daily significantly increased homocysteine plasma concentrations by 2.0 micromol/l despite adequate vitamin status.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15870821/", "publicSourceType": "PMID" }, { "claim": "Metabolic consequences of methionine supplementation in clinical context", "title": "Metabolic Consequences of Supplemented Methionine in a Clinical Context", "authors": "Gomez J et al.", "journal": "Nutrients", "year": 2020, "pmid": "33000166", "url": "https://pubmed.ncbi.nlm.nih.gov/33000166/", "study_type": "review", "key_finding": "Methionine is the precursor of homocysteine; deficient B vitamin intake or excessive methionine intake may result in hyperhomocysteinemia, a cardiovascular risk factor.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33000166/", "publicSourceType": "PMID" }, { "claim": "SAMe (methionine metabolite) restores hepatic glutathione in liver disease", "title": "Effects of oral S-adenosyl-L-methionine on hepatic glutathione in patients with liver disease", "authors": "Vendemiale G et al.", "journal": "Scand J Gastroenterol", "year": 1989, "pmid": "2781235", "url": "https://pubmed.ncbi.nlm.nih.gov/2781235/", "study_type": "RCT", "key_finding": "SAMe therapy resulted in a significant increase in hepatic glutathione levels in patients with both alcoholic and non-alcoholic liver diseases.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2781235/", "publicSourceType": "PMID" }, { "claim": "Methionine and cysteine increase intracellular glutathione in hepatocytes", "title": "Methionine and cysteine affect glutathione level, glutathione-related enzyme activities and the expression of glutathione S-transferase isozymes in rat hepatocytes", "authors": "Shigesawa T et al.", "journal": "J Nutr", "year": 1997, "pmid": "9372907", "url": "https://pubmed.ncbi.nlm.nih.gov/9372907/", "study_type": "in_vitro", "key_finding": "Hepatocytes incubated with methionine showed increased intracellular glutathione with a twofold increase observed on day 6, supporting methionine's role in detoxification.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9372907/", "publicSourceType": "PMID" }, { "claim": "Glutathione synthesis regulation depends on methionine-derived cysteine via transsulfuration", "title": "Regulation of glutathione synthesis", "authors": "Lu SC et al.", "journal": "Mol Aspects Med", "year": 2009, "pmid": "18601945", "url": "https://pubmed.ncbi.nlm.nih.gov/18601945/", "study_type": "review", "key_finding": "Up to half of the daily methionine intake is catabolized to SAMe in the liver; the transsulfuration pathway allows methionine to serve as a glutathione precursor.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18601945/", "publicSourceType": "PMID" }, { "text": "Ullah H, Di Minno A, Esposito C et al.. Efficacy of a food supplement based on S-adenosyl methionine and probiotic strains in subjects with subthreshold depression and mild-to-moderate depression: A monocentric, randomized, cross-over, double-blind, placebo-controlled clinical trial. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022", "pmid": "36411659", "doi": "10.1016/j.biopha.2022.113930", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36411659/", "publicSourceType": "PMID" }, { "text": "Limveeraprajak N, Nakhawatchana S, Visukamol A et al.. Efficacy and acceptability of S-adenosyl-L-methionine (SAMe) for depressed patients: A systematic review and meta- analysis. Progress in neuro-psychopharmacology & biological psychiatry. 2024", "claim": "PubMed-indexed evidence involving L-Methionine", "title": "Efficacy and acceptability of S-adenosyl-L-methionine (SAMe) for depressed patients: A systematic review and meta- analysis", "authors": "Limveeraprajak N, Nakhawatchana S, Visukamol A et al.", "journal": "Progress in neuro-psychopharmacology & biological psychiatry", "year": 2024, "pmid": "38423354", "url": "https://pubmed.ncbi.nlm.nih.gov/38423354/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.pnpbp.2024.110985", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38423354/", "publicSourceType": "PMID" }, { "text": "Dondi F, Gazzilli M, Viganò GL et al.. The Role of 11C-Methionine PET Imaging for the Evaluation of Lymphomas: A Systematic Review. Hematology reports. 2024", "claim": "PubMed-indexed evidence involving L-Methionine", "title": "The Role of 11C-Methionine PET Imaging for the Evaluation of Lymphomas: A Systematic Review", "authors": "Dondi F, Gazzilli M, Viganò GL et al.", "journal": "Hematology reports", "year": 2024, "pmid": "39728002", "url": "https://pubmed.ncbi.nlm.nih.gov/39728002/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/hematolrep16040072", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39728002/", "publicSourceType": "PMID" }, { "text": "Roufael M, Bitar T, Sacre Y et al.. Folate-Methionine Cycle Disruptions in ASD Patients and Possible Interventions: A Systematic Review. Genes. 2023", "claim": "PubMed-indexed evidence involving L-Methionine", "title": "Folate-Methionine Cycle Disruptions in ASD Patients and Possible Interventions: A Systematic Review", "authors": "Roufael M, Bitar T, Sacre Y et al.", "journal": "Genes", "year": 2023, "pmid": "36980981", "url": "https://pubmed.ncbi.nlm.nih.gov/36980981/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/genes14030709", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36980981/", "publicSourceType": "PMID" }, { "text": "Souza VC, Remus A, Batonon-Alavo DI et al.. Systematic review and meta-analysis of the methionine utilization efficiency in piglets receiving different methionine sources. Animal : an international journal of animal bioscience. 2023", "claim": "PubMed-indexed evidence involving L-Methionine", "title": "Systematic review and meta-analysis of the methionine utilization efficiency in piglets receiving different methionine sources", "authors": "Souza VC, Remus A, Batonon-Alavo DI et al.", "journal": "Animal : an international journal of animal bioscience", "year": 2023, "pmid": "37482458", "url": "https://pubmed.ncbi.nlm.nih.gov/37482458/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.animal.2023.100894", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37482458/", "publicSourceType": "PMID" }, { "text": "Raikhelson KL, Kondrashina EA. Аdеmethionine in the treatment of fatigue in liver diseases: a systematic review. Terapevticheskii arkhiv. 2019", "claim": "PubMed-indexed evidence involving L-Methionine", "title": "Аdеmethionine in the treatment of fatigue in liver diseases: a systematic review", "authors": "Raikhelson KL, Kondrashina EA", "journal": "Terapevticheskii arkhiv", "year": 2019, "pmid": "31094184", "url": "https://pubmed.ncbi.nlm.nih.gov/31094184/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.26442/00403660.2019.02.000130", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31094184/", "publicSourceType": "PMID" }, { "text": "Wei C, He T, Wan X et al.. Meta-Analysis of Rumen-Protected Methionine in Milk Production and Composition of Dairy Cows. Animals : an open access journal from MDPI. 2022", "claim": "PubMed-indexed evidence involving L-Methionine", "title": "Meta-Analysis of Rumen-Protected Methionine in Milk Production and Composition of Dairy Cows", "authors": "Wei C, He T, Wan X et al.", "journal": "Animals : an open access journal from MDPI", "year": 2022, "pmid": "35739842", "url": "https://pubmed.ncbi.nlm.nih.gov/35739842/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/ani12121505", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35739842/", "publicSourceType": "PMID" }, { "text": "Wei DH, Mao QQ. Vitamin B6, vitamin B12 and methionine and risk of pancreatic cancer: a meta-analysis. Nutrition journal. 2020", "claim": "PubMed-indexed evidence involving L-Methionine", "title": "Vitamin B6, vitamin B12 and methionine and risk of pancreatic cancer: a meta-analysis", "authors": "Wei DH, Mao QQ", "journal": "Nutrition journal", "year": 2020, "pmid": "33012287", "url": "https://pubmed.ncbi.nlm.nih.gov/33012287/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12937-020-00628-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33012287/", "publicSourceType": "PMID" }, { "text": "Katsanos AH, Alexiou GA, Fotopoulos AD et al.. Performance of 18F-FDG, 11C-Methionine, and 18F-FET PET for Glioma Grading: A Meta-analysis. Clinical nuclear medicine. 2019", "claim": "PubMed-indexed evidence involving L-Methionine", "title": "Performance of 18F-FDG, 11C-Methionine, and 18F-FET PET for Glioma Grading: A Meta-analysis", "authors": "Katsanos AH, Alexiou GA, Fotopoulos AD et al.", "journal": "Clinical nuclear medicine", "year": 2019, "pmid": "31205150", "url": "https://pubmed.ncbi.nlm.nih.gov/31205150/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/RLU.0000000000002654", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31205150/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "l-methionine" }, { "id": "2E60610A-909F-46A3-9AF8-1C371EDA86C1", "name": "L-Lysine", "alternateNames": [ "Lysine" ], "category": "Amino Acid", "subcategory": "Essential Amino Acid", "overview": "Essential amino acid important for collagen synthesis, calcium absorption, and antiviral activity.", "mechanismOfAction": "Required for collagen cross-linking (hydroxylysine). Competes with arginine for cellular uptake, inhibiting HSV replication. Supports carnitine synthesis and calcium absorption.", "commonBenefits": [ "Cold sore prevention", "Collagen synthesis", "Calcium absorption", "Immune support" ], "commonDosageRange": "500-3,000 mg daily", "recommendedForm": "L-Lysine HCl", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Empty stomach for antiviral; with food for general use" }, "evidenceRating": "moderate", "foodSources": [ "Meat", "Poultry", "Fish", "Dairy", "Eggs", "Legumes" ], "deficiencySymptoms": [ "Growth retardation", "Impaired immunity", "Fatigue" ], "sideEffects": [ "GI upset", "Diarrhea at high doses" ], "contraindications": [ "Kidney disease", "Liver disease" ], "iconName": "shield.fill", "colorHex": "B37DFF", "tags": [ "antiviral", "collagen", "immune" ], "sources": [ { "claim": "Review of lysine for herpes simplex prophylaxis", "title": "Lysine for Herpes Simplex Prophylaxis: A Review of the Evidence", "authors": "Chi CC et al.", "journal": "Integr Med (Encinitas)", "year": 2019, "pmid": "30881246", "url": "https://pubmed.ncbi.nlm.nih.gov/30881246/", "study_type": "review", "key_finding": "L-lysine supplementation appears to be ineffective for HSV prophylaxis at doses less than 1 g/day without low-arginine diet; higher doses with dietary modification may be beneficial.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30881246/", "publicSourceType": "PMID" }, { "claim": "Lysine prophylaxis reduces herpes simplex recurrence when serum levels are adequate", "title": "Lysine prophylaxis in recurrent herpes simplex labialis: a double-blind, controlled crossover study", "authors": "Thein DJ et al.", "journal": "Oral Surg Oral Med Oral Pathol", "year": 1984, "pmid": "6153847", "url": "https://pubmed.ncbi.nlm.nih.gov/6153847/", "study_type": "RCT", "key_finding": "When serum lysine concentration exceeded 165 nmol/ml there was a significant decrease in HSV recurrence rate, suggesting prophylactic benefit at adequate serum levels.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6153847/", "publicSourceType": "PMID" }, { "claim": "L-lysine enhances intestinal calcium absorption and renal calcium conservation", "title": "Dietary L-lysine and calcium metabolism in humans", "authors": "Civitelli R et al.", "journal": "Nutrition", "year": 1992, "pmid": "1486246", "url": "https://pubmed.ncbi.nlm.nih.gov/1486246/", "study_type": "RCT", "key_finding": "L-lysine significantly increased intestinal calcium absorption and improved renal conservation of absorbed calcium, suggesting usefulness for osteoporosis prevention.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1486246/", "publicSourceType": "PMID" }, { "claim": "Comprehensive safety assessment of L-lysine supplementation", "title": "Comprehensive Safety Assessment of l-Lysine Supplementation from Clinical Studies: A Systematic Review", "authors": "Hayamizu K et al.", "journal": "Nutrients", "year": 2020, "pmid": "33000161", "url": "https://pubmed.ncbi.nlm.nih.gov/33000161/", "study_type": "review", "key_finding": "L-lysine supplements are clinically safe with no reported toxicity; adverse events limited to subjective GI symptoms. NOAEL is 6000 mg/person/day.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33000161/", "publicSourceType": "PMID" }, { "claim": "Systematic safety assessment of L-lysine oral intake", "title": "Safety assessment of L-lysine oral intake: a systematic review", "authors": "Hayamizu K et al.", "journal": "Amino Acids", "year": 2019, "pmid": "30661148", "url": "https://pubmed.ncbi.nlm.nih.gov/30661148/", "study_type": "review", "key_finding": "Review of 71 articles (3357 subjects) with doses up to 17.5 g/day found L-lysine safe with gastrointestinal symptoms as only side effects; provisional NOAEL of 6000 mg/day.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30661148/", "publicSourceType": "PMID" }, { "claim": "Lysine, protein, and vitamin D critical for muscle and bone health", "title": "Protein, lysine and vitamin D: critical role in muscle and bone health", "authors": "Veldurthy V et al.", "journal": "Curr Opin Clin Nutr Metab Care", "year": 2020, "pmid": "33290094", "url": "https://pubmed.ncbi.nlm.nih.gov/33290094/", "study_type": "review", "key_finding": "Lysine along with protein and vitamin D play critical roles in muscle and bone health; lysine is essential for collagen cross-linking and calcium absorption.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33290094/", "publicSourceType": "PMID" }, { "text": "Matthews DE. Review of Lysine Metabolism with a Focus on Humans. The Journal of nutrition. 2020", "pmid": "33000162", "doi": "10.1093/jn/nxaa224", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33000162/", "publicSourceType": "PMID" }, { "text": "Gunarathne R, Guan X, Feng T et al.. L-lysine dietary supplementation for childhood and adolescent growth: Promises and precautions. Journal of advanced research. 2025", "pmid": "38740261", "doi": "10.1016/j.jare.2024.05.014", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38740261/", "publicSourceType": "PMID" }, { "text": "Montroy J, Fergusson NA, Hutton B et al.. The Safety and Efficacy of Lysine Analogues in Cancer Patients: A Systematic Review and Meta-Analysis. Transfusion medicine reviews. 2017", "claim": "PubMed-indexed evidence involving L-Lysine", "title": "The Safety and Efficacy of Lysine Analogues in Cancer Patients: A Systematic Review and Meta-Analysis", "authors": "Montroy J, Fergusson NA, Hutton B et al.", "journal": "Transfusion medicine reviews", "year": 2017, "pmid": "28366637", "url": "https://pubmed.ncbi.nlm.nih.gov/28366637/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.tmrv.2017.03.002", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28366637/", "publicSourceType": "PMID" }, { "text": "Aymerich P, Tokach MD, Dritz SS et al.. Lysine requirements of finishing boars and gilts: A meta-analysis. Animal : an international journal of animal bioscience. 2021", "claim": "PubMed-indexed evidence involving L-Lysine", "title": "Lysine requirements of finishing boars and gilts: A meta-analysis", "authors": "Aymerich P, Tokach MD, Dritz SS et al.", "journal": "Animal : an international journal of animal bioscience", "year": 2021, "pmid": "34029792", "url": "https://pubmed.ncbi.nlm.nih.gov/34029792/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.animal.2021.100218", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34029792/", "publicSourceType": "PMID" }, { "text": "Vyas D, Erdman RA. Meta-analysis of milk protein yield responses to lysine and methionine supplementation. Journal of dairy science. 2009", "claim": "PubMed-indexed evidence involving L-Lysine", "title": "Meta-analysis of milk protein yield responses to lysine and methionine supplementation", "authors": "Vyas D, Erdman RA", "journal": "Journal of dairy science", "year": 2009, "pmid": "19762820", "url": "https://pubmed.ncbi.nlm.nih.gov/19762820/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3168/jds.2008-1769", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19762820/", "publicSourceType": "PMID" }, { "text": "van Lieshout GAA, Trommelen J, Hendriks FK et al.. Milk Protein Glycation Compromises Postprandial Lysine Bioavailability but does not Modulate Postprandial Muscle Protein Synthesis Rates In Vivo in Males: A Double-blind, Randomized Parallel Trial. The Journal of nutrition. 2025", "claim": "PubMed-indexed evidence involving L-Lysine", "title": "Milk Protein Glycation Compromises Postprandial Lysine Bioavailability but does not Modulate Postprandial Muscle Protein Synthesis Rates In Vivo in Males: A Double-blind, Randomized Parallel Trial", "authors": "van Lieshout GAA, Trommelen J, Hendriks FK et al.", "journal": "The Journal of nutrition", "year": 2025, "pmid": "40441386", "url": "https://pubmed.ncbi.nlm.nih.gov/40441386/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.tjnut.2025.05.032", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40441386/", "publicSourceType": "PMID" }, { "text": "Hashim M, Alam I, Ahmad M et al.. Comprehensive Review of L-Lysine: Chemistry, Occurrence, and Physiological Roles. Current protein & peptide science. 2026", "claim": "PubMed-indexed evidence involving L-Lysine", "title": "Comprehensive Review of L-Lysine: Chemistry, Occurrence, and Physiological Roles", "authors": "Hashim M, Alam I, Ahmad M et al.", "journal": "Current protein & peptide science", "year": 2026, "pmid": "40626529", "url": "https://pubmed.ncbi.nlm.nih.gov/40626529/", "study_type": "review", "confidence": "verify", "doi": "10.2174/0113892037381647250526073248", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40626529/", "publicSourceType": "PMID" }, { "text": "Han D, Lu J, Fan B et al.. Lysine-Specific Demethylase 1 Inhibitors: A Comprehensive Review Utilizing Computer-Aided Drug Design Technologies. Molecules (Basel, Switzerland). 2024", "claim": "PubMed-indexed evidence involving L-Lysine", "title": "Lysine-Specific Demethylase 1 Inhibitors: A Comprehensive Review Utilizing Computer-Aided Drug Design Technologies", "authors": "Han D, Lu J, Fan B et al.", "journal": "Molecules (Basel, Switzerland)", "year": 2024, "pmid": "38276629", "url": "https://pubmed.ncbi.nlm.nih.gov/38276629/", "study_type": "review", "confidence": "verify", "doi": "10.3390/molecules29020550", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38276629/", "publicSourceType": "PMID" }, { "text": "Pedrazini MC, da Silva MH, Groppo FC. L-lysine: Its antagonism with L-arginine in controlling viral infection. Narrative literature review. British journal of clinical pharmacology. 2022", "claim": "PubMed-indexed evidence involving L-Lysine", "title": "L-lysine: Its antagonism with L-arginine in controlling viral infection. Narrative literature review", "authors": "Pedrazini MC, da Silva MH, Groppo FC", "journal": "British journal of clinical pharmacology", "year": 2022, "pmid": "35723628", "url": "https://pubmed.ncbi.nlm.nih.gov/35723628/", "study_type": "review", "confidence": "verify", "doi": "10.1111/bcp.15444", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35723628/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "l-lysine" }, { "id": "449672F5-5086-4E10-AB5F-C7BAED6A699F", "name": "D-Aspartic Acid", "alternateNames": [ "DAA" ], "category": "Amino Acid", "subcategory": "Non-Essential Amino Acid", "overview": "Amino acid isomer studied for male fertility and testosterone, with inconsistent human evidence and no reliable testosterone benefit in healthy or resistance-trained men.", "mechanismOfAction": "Animal and mechanistic studies suggest hypothalamic-pituitary-gonadal effects, but human trials have not consistently shown increased LH or testosterone.", "commonBenefits": [ "Fertility support (limited evidence in infertile men)" ], "commonDosageRange": "2-3 g daily for 2-3 week cycles", "recommendedForm": "D-Aspartic Acid powder (sodium salt)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Take on empty stomach in the morning" }, "evidenceRating": "emerging", "foodSources": [ "Naturally in small amounts in various foods" ], "deficiencySymptoms": [], "sideEffects": [ "Irritability", "Headache", "Acne", "Estrogen increase (via aromatase)" ], "contraindications": [ "Hormone-sensitive conditions" ], "iconName": "bolt.fill", "colorHex": "B37DFF", "tags": [ "fertility-context", "fertility" ], "sources": [ { "claim": "Systematic review of D-aspartic acid effects on testosterone in humans", "title": "The putative effects of D-Aspartic acid on blood testosterone levels: A systematic review", "authors": "Melville GW et al.", "journal": "J Int Soc Sports Nutr", "year": 2017, "pmid": "28280794", "url": "https://pubmed.ncbi.nlm.nih.gov/28280794/", "study_type": "review", "key_finding": "Animal studies suggest reproductive-hormone effects, but human testosterone findings are inconsistent and the evidence remains sparse and low quality.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28280794/", "publicSourceType": "PMID" }, { "claim": "D-aspartic acid ineffective at changing testosterone in resistance-trained men", "title": "The effects of d-aspartic acid supplementation in resistance-trained men over a three month training period: A randomised controlled trial", "authors": "Melville GW et al.", "journal": "PLoS One", "year": 2017, "pmid": "28841667", "url": "https://pubmed.ncbi.nlm.nih.gov/28841667/", "study_type": "RCT", "key_finding": "D-aspartic acid supplementation (6 g/day) is ineffective at changing testosterone levels or positively affecting training outcomes in resistance-trained men over 3 months.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28841667/", "publicSourceType": "PMID" }, { "claim": "High-dose D-aspartic acid may reduce testosterone", "title": "Three and six grams supplementation of d-aspartic acid in resistance trained men", "authors": "Willoughby DS et al.", "journal": "J Int Soc Sports Nutr", "year": 2015, "pmid": "25844073", "url": "https://pubmed.ncbi.nlm.nih.gov/25844073/", "study_type": "RCT", "key_finding": "Total testosterone was significantly reduced in men taking 6 g/day D-aspartic acid; free testosterone was also significantly reduced compared to placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25844073/", "publicSourceType": "PMID" }, { "claim": "D-aspartic acid combination product studied for sperm motility in infertile men", "title": "Evaluation of in vivo supplementation of 2660 mg D-aspartic acid and 200 mg ubiquinol and 10 mg zinc on different semen parameters in idiopathic male infertility: a randomized double blind placebo controlled study", "authors": "Not specified et al.", "journal": "Eur Rev Med Pharmacol Sci", "year": 2025, "pmid": "40248985", "url": "https://pubmed.ncbi.nlm.nih.gov/40248985/", "study_type": "RCT", "key_finding": "A combination of D-aspartic acid, ubiquinol, and zinc improved semen parameters in infertile men; this does not establish a general testosterone benefit for D-aspartic acid alone.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40248985/", "publicSourceType": "PMID" }, { "claim": "D-aspartic acid found naturally in human seminal plasma and implicated in reproduction", "title": "Occurrence of D-aspartic acid in human seminal plasma and spermatozoa: possible role in reproduction", "authors": "D'Aniello G et al.", "journal": "Fertil Steril", "year": 2005, "pmid": "16275242", "url": "https://pubmed.ncbi.nlm.nih.gov/16275242/", "study_type": "cohort", "key_finding": "D-aspartic acid concentration in seminal plasma was significantly reduced in oligoasthenoteratospermic men compared to normospermic donors, implicating D-Asp in male fertility.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16275242/", "publicSourceType": "PMID" }, { "text": "Masarone M, Persico M. Hepatitis C virus infection and non-hepatocellular malignancies in the DAA era: A systematic review and meta-analysis. Liver international : official journal of the International Association for the Study of the Liver. 2019", "pmid": "30983083", "doi": "10.1111/liv.14119", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30983083/", "publicSourceType": "PMID" }, { "claim": "Animal-only D-aspartic acid reproductive-hormone findings", "title": "Dietary supplementation with barley sprouts and d-aspartic acid improves reproductive hormone concentrations, testicular histology, antioxidant status, and mRNA expressions of apoptosis-related genes in aged broiler breeder roosters", "authors": "Barbarestani SY, Samadi F, Zaghari M, Pirsaraei ZA, Kastelic JP", "journal": "Theriogenology", "year": 2024, "pmid": "37924739", "url": "https://pubmed.ncbi.nlm.nih.gov/37924739/", "study_type": "animalStudy", "key_finding": "In aged broiler roosters, D-aspartic acid changed reproductive hormones and sperm measures; animal data should not be presented as human testosterone support.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37924739/", "publicSourceType": "PMID" }, { "text": "Nosadini M, Eyre M, Molteni E et al.. Use and Safety of Immunotherapeutic Management of N-Methyl-d-Aspartate Receptor Antibody Encephalitis: A Meta-analysis. JAMA neurology. 2021", "claim": "PubMed-indexed evidence involving D-Aspartic Acid", "title": "Use and Safety of Immunotherapeutic Management of N-Methyl-d-Aspartate Receptor Antibody Encephalitis: A Meta-analysis", "authors": "Nosadini M, Eyre M, Molteni E et al.", "journal": "JAMA neurology", "year": 2021, "pmid": "34542573", "url": "https://pubmed.ncbi.nlm.nih.gov/34542573/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1001/jamaneurol.2021.3188", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34542573/", "publicSourceType": "PMID" }, { "text": "Ferguson AA, Khan AI, Abuzainah B et al.. Clinical Effectiveness of N-Methyl-D-Aspartate (NMDA) Receptor Antagonists in Adult Obsessive-Compulsive Disorder (OCD) Treatment: A Systematic Review. Cureus. 2023", "claim": "PubMed-indexed evidence involving D-Aspartic Acid", "title": "Clinical Effectiveness of N-Methyl-D-Aspartate (NMDA) Receptor Antagonists in Adult Obsessive-Compulsive Disorder (OCD) Treatment: A Systematic Review", "authors": "Ferguson AA, Khan AI, Abuzainah B et al.", "journal": "Cureus", "year": 2023, "pmid": "37213965", "url": "https://pubmed.ncbi.nlm.nih.gov/37213965/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7759/cureus.37833", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37213965/", "publicSourceType": "PMID" }, { "text": "Murashko AA, Pavlov KA, Pavlova OV et al.. Antibodies against N-Methyl D-Aspartate Receptor in Psychotic Disorders: A Systematic Review. Neuropsychobiology. 2022", "claim": "PubMed-indexed evidence involving D-Aspartic Acid", "title": "Antibodies against N-Methyl D-Aspartate Receptor in Psychotic Disorders: A Systematic Review", "authors": "Murashko AA, Pavlov KA, Pavlova OV et al.", "journal": "Neuropsychobiology", "year": 2022, "pmid": "34000730", "url": "https://pubmed.ncbi.nlm.nih.gov/34000730/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1159/000515930", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34000730/", "publicSourceType": "PMID" }, { "text": "Elahi B, Phielipp N, Chen R. N-Methyl-D-Aspartate antagonists in levodopa induced dyskinesia: a meta-analysis. The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques. 2012", "claim": "PubMed-indexed evidence involving D-Aspartic Acid", "title": "N-Methyl-D-Aspartate antagonists in levodopa induced dyskinesia: a meta-analysis", "authors": "Elahi B, Phielipp N, Chen R", "journal": "The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques", "year": 2012, "pmid": "22728853", "url": "https://pubmed.ncbi.nlm.nih.gov/22728853/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1017/s0317167100013974", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22728853/", "publicSourceType": "PMID" }, { "text": "Zarate CA Jr, Singh JB, Carlson PJ et al.. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Archives of general psychiatry. 2006", "claim": "PubMed-indexed evidence involving D-Aspartic Acid", "title": "A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression", "authors": "Zarate CA Jr, Singh JB, Carlson PJ et al.", "journal": "Archives of general psychiatry", "year": 2006, "pmid": "16894061", "url": "https://pubmed.ncbi.nlm.nih.gov/16894061/", "study_type": "RCT", "confidence": "verify", "doi": "10.1001/archpsyc.63.8.856", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16894061/", "publicSourceType": "PMID" }, { "text": "Beutler BD, Moody AE, Thomas JM et al.. Anti-N-methyl-D-aspartate receptor-associated encephalitis: A review of clinicopathologic hallmarks and multimodal imaging manifestations. World journal of radiology. 2024", "claim": "PubMed-indexed evidence involving D-Aspartic Acid", "title": "Anti-N-methyl-D-aspartate receptor-associated encephalitis: A review of clinicopathologic hallmarks and multimodal imaging manifestations", "authors": "Beutler BD, Moody AE, Thomas JM et al.", "journal": "World journal of radiology", "year": 2024, "pmid": "38312349", "url": "https://pubmed.ncbi.nlm.nih.gov/38312349/", "study_type": "review", "confidence": "verify", "doi": "10.4329/wjr.v16.i1.1", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38312349/", "publicSourceType": "PMID" }, { "text": "Wright MA, Guasp M, Lachner C et al.. Electroconvulsive therapy in N-methyl-d-aspartate receptor encephalitis: A retrospective cohort and scoping review of literature. Journal of neuroimmunology. 2024", "claim": "PubMed-indexed evidence involving D-Aspartic Acid", "title": "Electroconvulsive therapy in N-methyl-d-aspartate receptor encephalitis: A retrospective cohort and scoping review of literature", "authors": "Wright MA, Guasp M, Lachner C et al.", "journal": "Journal of neuroimmunology", "year": 2024, "pmid": "38823118", "url": "https://pubmed.ncbi.nlm.nih.gov/38823118/", "study_type": "cohort", "confidence": "verify", "doi": "10.1016/j.jneuroim.2024.578369", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38823118/", "publicSourceType": "PMID" }, { "text": "Lee JH, Suzuki J. N-methyl-d-aspartate (NMDA) receptor antagonists for treatment of catatonia in adults: Narrative review. General hospital psychiatry. 2024", "claim": "PubMed-indexed evidence involving D-Aspartic Acid", "title": "N-methyl-d-aspartate (NMDA) receptor antagonists for treatment of catatonia in adults: Narrative review", "authors": "Lee JH, Suzuki J", "journal": "General hospital psychiatry", "year": 2024, "pmid": "39278010", "url": "https://pubmed.ncbi.nlm.nih.gov/39278010/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.genhosppsych.2024.09.005", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39278010/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "d-aspartic-acid" }, { "id": "59AFF2A0-17A4-4EA5-9845-90469662049F", "name": "Serrapeptase", "alternateNames": [ "Serratiopeptidase" ], "category": "Other", "subcategory": "Proteolytic Enzyme", "overview": "Silkworm-derived enzyme with fibrinolytic and anti-inflammatory properties.", "mechanismOfAction": "Serine protease that breaks down fibrin, mucus, and inflammatory proteins. Reduces bradykinin and other inflammatory mediators. May thin mucus in respiratory conditions.", "commonBenefits": [ "Inflammation reduction", "Sinus relief", "Pain relief", "Scar tissue" ], "commonDosageRange": "60,000-120,000 SPU daily", "recommendedForm": "Enteric-coated (destroyed by stomach acid)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Take on empty stomach; enteric coating essential" }, "evidenceRating": "emerging", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "GI upset", "Nausea", "Skin reactions (rare)" ], "contraindications": [ "Blood thinners", "Bleeding disorders", "Surgery" ], "iconName": "bandage.fill", "colorHex": "FFB84D", "tags": [ "anti-inflammatory", "enzyme", "sinus" ], "sources": [ { "claim": "Systematic review of serratiopeptidase as anti-inflammatory and analgesic", "title": "Serratiopeptidase: a systematic review of the existing evidence", "authors": "Bhagat S et al.", "journal": "Int J Surg", "year": 2013, "pmid": "23380245", "url": "https://pubmed.ncbi.nlm.nih.gov/23380245/", "study_type": "review", "key_finding": "Evidence supporting serratiopeptidase as anti-inflammatory and analgesic is based on studies of poor methodology with few RCTs and small sample sizes.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23380245/", "publicSourceType": "PMID" }, { "claim": "Serrapeptase reduces swelling and pain after dental surgery", "title": "Effect of the proteolytic enzyme serrapeptase on swelling, pain and trismus after surgical extraction of mandibular third molars", "authors": "Al-Khateeb TH et al.", "journal": "Int J Oral Maxillofac Surg", "year": 2008, "pmid": "18272344", "url": "https://pubmed.ncbi.nlm.nih.gov/18272344/", "study_type": "RCT", "key_finding": "Significant reduction in cheek swelling and pain intensity in the serrapeptase group at days 2, 3, and 7 post-operatively after third molar extraction.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18272344/", "publicSourceType": "PMID" }, { "claim": "Review of serratiopeptidase therapeutic applications including anti-inflammatory and fibrinolytic", "title": "Serratiopeptidase: Insights into the therapeutic applications", "authors": "Jadhav SB et al.", "journal": "Biotechnol Rep", "year": 2020, "pmid": "33134103", "url": "https://pubmed.ncbi.nlm.nih.gov/33134103/", "study_type": "review", "key_finding": "Serratiopeptidase exhibits anti-inflammatory, anti-biofilm, analgesic, anti-edemic, and fibrinolytic effects across multiple clinical specialties.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33134103/", "publicSourceType": "PMID" }, { "claim": "Serratiopeptidase role in inflammation resolution", "title": "The role of serratiopeptidase in the resolution of inflammation", "authors": "Tiwari M et al.", "journal": "Asian J Pharm Sci", "year": 2020, "pmid": "32104332", "url": "https://pubmed.ncbi.nlm.nih.gov/32104332/", "study_type": "review", "key_finding": "Serratiopeptidase is a serine protease that reduces bradykinin and other inflammatory mediators, with anti-inflammatory effects potentially superior to topical NSAIDs.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32104332/", "publicSourceType": "PMID" }, { "claim": "Serrapeptase reduces nasal mucus viscosity in chronic sinusitis", "title": "The effect of an orally administered proteolytic enzyme on the elasticity and viscosity of nasal mucus", "authors": "Majima Y et al.", "journal": "Arch Otorhinolaryngol", "year": 1988, "pmid": "3279939", "url": "https://pubmed.ncbi.nlm.nih.gov/3279939/", "study_type": "RCT", "key_finding": "Serratiopeptidase (30 mg/day for 4 weeks) reduced the viscosity but not the elasticity of nasal mucus in chronic sinusitis patients.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3279939/", "publicSourceType": "PMID" }, { "claim": "Serratiopeptidase improves trismus and swelling after impacted third molar surgery", "title": "Efficacy of serratiopeptidase after impacted third molar surgery: a randomized controlled clinical trial", "authors": "Tiwari M et al.", "journal": "Oral Surg Oral Med Oral Pathol Oral Radiol", "year": 2021, "pmid": "33653320", "url": "https://pubmed.ncbi.nlm.nih.gov/33653320/", "study_type": "RCT", "key_finding": "In 133 patients, serratiopeptidase significantly improved trismus and swelling compared with control on day 4, though pain showed no statistically significant difference.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33653320/", "publicSourceType": "PMID" }, { "text": "Bruno A, Saccoccio V. Serrapeptase After Liposuction for Lipedema: Limited Evidence for Antifibrotic Efficacy. Aesthetic plastic surgery. 2026", "pmid": "41642311", "doi": "10.1007/s00266-026-05638-0", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41642311/", "publicSourceType": "PMID" }, { "text": "Bhuvan Chandra R, Selvarasu K, Krishnan M. Comparison of Efficacy of Combination of Bromelain, Rutocide, and Trypsin With Serratiopeptidase on Postoperative Sequelae Following Mandibular Third Molar Surgery: A Randomized Clinical Trial. Cureus. 2023", "pmid": "38090449", "doi": "10.7759/cureus.48633", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38090449/", "publicSourceType": "PMID" }, { "claim": "Reduces postoperative complications following third molar surgery", "title": "Efficacy of Submucosal Injection of Chymotrypsin, Oral Serratiopeptidase or Oral Dexamethasone in Reducing Postoperative Complications Following Impacted Lower Third Molar Surgery: A Prospective, Randomized, Double-Blind, Controlled Clinical Trial.", "authors": "Al-Moraissi EA, Al-Zendani EA, Al-Selwi AM", "journal": "Frontiers in Oral Health", "year": 2020, "pmid": "35047980", "url": "https://pubmed.ncbi.nlm.nih.gov/35047980/", "study_type": "rct", "key_finding": "Oral serratiopeptidase was effective in reducing postoperative swelling and pain, though dexamethasone showed superior anti-inflammatory effects compared to serratiopeptidase.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35047980/", "publicSourceType": "PMID" }, { "text": "Chopra D, Rehan HS, Mehra P et al.. A randomized, double-blind, placebo-controlled study comparing the efficacy and safety of paracetamol, serratiopeptidase, ibuprofen and betamethasone using the dental impaction pain model. International journal of oral and maxillofacial surgery. 2009", "claim": "PubMed-indexed evidence involving Serrapeptase", "title": "A randomized, double-blind, placebo-controlled study comparing the efficacy and safety of paracetamol, serratiopeptidase, ibuprofen and betamethasone using the dental impaction pain model", "authors": "Chopra D, Rehan HS, Mehra P et al.", "journal": "International journal of oral and maxillofacial surgery", "year": 2009, "pmid": "19168326", "url": "https://pubmed.ncbi.nlm.nih.gov/19168326/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.ijom.2008.12.013", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19168326/", "publicSourceType": "PMID" }, { "text": "Chandanwale A, Langade D, Sonawane D et al.. A Randomized, Clinical Trial to Evaluate Efficacy and Tolerability of Trypsin:Chymotrypsin as Compared to Serratiopeptidase and Trypsin:Bromelain:Rutoside in Wound Management. Advances in therapy. 2017", "claim": "PubMed-indexed evidence involving Serrapeptase", "title": "A Randomized, Clinical Trial to Evaluate Efficacy and Tolerability of Trypsin:Chymotrypsin as Compared to Serratiopeptidase and Trypsin:Bromelain:Rutoside in Wound Management", "authors": "Chandanwale A, Langade D, Sonawane D et al.", "journal": "Advances in therapy", "year": 2017, "pmid": "27889883", "url": "https://pubmed.ncbi.nlm.nih.gov/27889883/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/s12325-016-0444-0", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27889883/", "publicSourceType": "PMID" }, { "text": "Shahbaz M, Kamran SH, Anwar R. Amelioration of Bleomycin and Methotrexate-Induced Pulmonary Toxicity by Serratiopeptidase and Fisetin. Nutrition and cancer. 2021", "claim": "PubMed-indexed evidence involving Serrapeptase", "title": "Amelioration of Bleomycin and Methotrexate-Induced Pulmonary Toxicity by Serratiopeptidase and Fisetin", "authors": "Shahbaz M, Kamran SH, Anwar R", "journal": "Nutrition and cancer", "year": 2021, "pmid": "33353415", "url": "https://pubmed.ncbi.nlm.nih.gov/33353415/", "study_type": "review", "confidence": "verify", "doi": "10.1080/01635581.2020.1860242", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33353415/", "publicSourceType": "PMID" }, { "text": "Hosseini SB, Azizi M, Nojoumi SA et al.. An up-to-date review of biomedical applications of serratiopeptidase and its biobetter derivatives as a multi-potential metalloprotease. Archives of microbiology. 2024", "claim": "PubMed-indexed evidence involving Serrapeptase", "title": "An up-to-date review of biomedical applications of serratiopeptidase and its biobetter derivatives as a multi-potential metalloprotease", "authors": "Hosseini SB, Azizi M, Nojoumi SA et al.", "journal": "Archives of microbiology", "year": 2024, "pmid": "38502196", "url": "https://pubmed.ncbi.nlm.nih.gov/38502196/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s00203-024-03889-6", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38502196/", "publicSourceType": "PMID" }, { "text": "Kumar S, Bhattacharya S. Optimization of Serratiopeptidase Production from Serratia marcescens SP6 Using Sequential Strategy of Experimental Designs. Current microbiology. 2025", "claim": "PubMed-indexed evidence involving Serrapeptase", "title": "Optimization of Serratiopeptidase Production from Serratia marcescens SP6 Using Sequential Strategy of Experimental Designs", "authors": "Kumar S, Bhattacharya S", "journal": "Current microbiology", "year": 2025, "pmid": "40627166", "url": "https://pubmed.ncbi.nlm.nih.gov/40627166/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s00284-025-04344-5", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40627166/", "publicSourceType": "PMID" }, { "text": "Junaid S, Naz Khan K, Zameer F et al.. Evaluating the efficacy of curcumin plus serratiopeptidase formulation in inflammatory acne: a quasi-experimental study. Drugs in context. 2025", "claim": "PubMed-indexed evidence involving Serrapeptase", "title": "Evaluating the efficacy of curcumin plus serratiopeptidase formulation in inflammatory acne: a quasi-experimental study", "authors": "Junaid S, Naz Khan K, Zameer F et al.", "journal": "Drugs in context", "year": 2025, "pmid": "40661790", "url": "https://pubmed.ncbi.nlm.nih.gov/40661790/", "study_type": "review", "confidence": "verify", "doi": "10.7573/dic.2025-4-2", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40661790/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "serrapeptase" }, { "id": "5334EF3B-1997-40DF-85EC-A99D53058954", "name": "Bee Pollen", "alternateNames": [ "Bee Bread" ], "category": "Other", "subcategory": "Bee Product", "overview": "Nutrient-dense bee-collected pollen product; clinical benefits are not well established and allergic reactions can be serious.", "mechanismOfAction": "Contains flavonoids, phenolic acids, enzymes, and protein. In vitro bioactivity does not establish allergy treatment or reliable immune benefits in humans.", "commonBenefits": [ "Nutrient density", "Food-derived polyphenols", "Nutrition support" ], "commonDosageRange": "1-2 teaspoons daily", "recommendedForm": "Bee pollen granules from a reputable source; avoid use if allergic to bee products or pollen", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Start with a few granules to test for allergy; take with food" }, "evidenceRating": "insufficient", "foodSources": [ "Bee pollen" ], "deficiencySymptoms": [], "sideEffects": [ "Anaphylaxis, including severe reactions in people without known bee product allergy", "Exercise-augmented anaphylaxis reported", "GI upset" ], "contraindications": [ "Bee product or pollen allergy", "Hay fever, asthma, eczema, or strong atopy history", "History of anaphylaxis", "Pregnancy", "Blood thinners" ], "iconName": "ladybug.fill", "colorHex": "FFB84D", "tags": [ "superfood", "bee-product", "nutrition" ], "sources": [ { "claim": "Review of bee pollen clinical trials and patent applications", "title": "Bee Pollen: Clinical Trials and Patent Applications", "authors": "Salles J et al.", "journal": "Nutrients", "year": 2022, "pmid": "35889814", "url": "https://pubmed.ncbi.nlm.nih.gov/35889814/", "study_type": "review", "key_finding": "Bee pollen has been studied in limited clinical and patent contexts, but the review does not establish routine use for allergy treatment.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35889814/", "publicSourceType": "PMID" }, { "claim": "Biological properties of bee pollen are mostly preclinical or review-level", "title": "Biological and therapeutic properties of bee pollen: a review", "authors": "Kieliszek M et al.", "journal": "J Sci Food Agric", "year": 2016, "pmid": "27013064", "url": "https://pubmed.ncbi.nlm.nih.gov/27013064/", "study_type": "review", "key_finding": "Reviews describe antioxidant and anti-inflammatory bioactivity, but this is not enough to claim proven therapeutic benefits in humans.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27013064/", "publicSourceType": "PMID" }, { "claim": "Bee pollen current status and therapeutic potential", "title": "Bee Pollen: Current Status and Therapeutic Potential", "authors": "Thakur M et al.", "journal": "Nutrients", "year": 2021, "pmid": "34072636", "url": "https://pubmed.ncbi.nlm.nih.gov/34072636/", "study_type": "review", "key_finding": "Bee pollen may be used as a dietary supplement, but extensive research is required before clinical therapeutic use; composition varies widely by species.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34072636/", "publicSourceType": "PMID" }, { "claim": "Bee pollen flavonoids have allergy-related preclinical interest but no established clinical allergy use", "title": "Bee Pollen Flavonoids as a Therapeutic Agent in Allergic and Immunological Disorders", "authors": "Denisow B et al.", "journal": "J Ethnopharmacol", "year": 2016, "pmid": "28732430", "url": "https://pubmed.ncbi.nlm.nih.gov/28732430/", "study_type": "review", "key_finding": "Reviews discuss anti-allergic and anti-inflammatory properties as candidate mechanisms, but do not support recommending bee pollen for allergies; allergic reactions remain a safety concern.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28732430/", "publicSourceType": "PMID" }, { "claim": "Bee pollen bioactive constituents and health benefits", "title": "Bee Collected Pollen and Bee Bread: Bioactive Constituents and Health Benefits", "authors": "Khalifa SAM et al.", "journal": "Nutrients", "year": 2019, "pmid": "31756937", "url": "https://pubmed.ncbi.nlm.nih.gov/31756937/", "study_type": "review", "key_finding": "Bee pollen contains flavonoids, phenolic acids, enzymes, and protein; reported immunomodulatory effects are not enough to claim reliable immune benefits in humans.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31756937/", "publicSourceType": "PMID" }, { "text": "El-Seedi HR, El-Wahed AAA, Salama S et al.. Natural Remedies and Health; A Review of Bee Pollen and Bee Bread Impact on Combating Diabetes and Obesity. Current nutrition reports. 2024", "pmid": "39302593", "doi": "10.1007/s13668-024-00567-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39302593/", "publicSourceType": "PMID" }, { "text": "Nemauluma MFD, Manyelo TG, Ng'ambi JW et al.. Effects of bee pollen inclusion on performance and carcass characteristics of broiler chickens. Poultry science. 2023", "pmid": "37043957", "doi": "10.1016/j.psj.2023.102628", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37043957/", "publicSourceType": "PMID" }, { "text": "Sierra-Galicia MI, Rodríguez-de Lara R, Orzuna-Orzuna JF et al.. Effects of Supplementation with Bee Pollen and Propolis on Growth Performance and Serum Metabolites of Rabbits: A Meta-Analysis. Animals : an open access journal from MDPI. 2023", "claim": "PubMed-indexed evidence involving Bee Pollen", "title": "Effects of Supplementation with Bee Pollen and Propolis on Growth Performance and Serum Metabolites of Rabbits: A Meta-Analysis", "authors": "Sierra-Galicia MI, Rodríguez-de Lara R, Orzuna-Orzuna JF et al.", "journal": "Animals : an open access journal from MDPI", "year": 2023, "pmid": "36766327", "url": "https://pubmed.ncbi.nlm.nih.gov/36766327/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/ani13030439", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36766327/", "publicSourceType": "PMID" }, { "text": "Baky MH, Abouelela MB, Wang K et al.. Bee Pollen and Bread as a Super-Food: A Comparative Review of Their Metabolome Composition and Quality Assessment in the Context of Best Recovery Conditions. Molecules (Basel, Switzerland). 2023", "claim": "PubMed-indexed evidence involving Bee Pollen", "title": "Bee Pollen and Bread as a Super-Food: A Comparative Review of Their Metabolome Composition and Quality Assessment in the Context of Best Recovery Conditions", "authors": "Baky MH, Abouelela MB, Wang K et al.", "journal": "Molecules (Basel, Switzerland)", "year": 2023, "pmid": "36677772", "url": "https://pubmed.ncbi.nlm.nih.gov/36677772/", "study_type": "review", "confidence": "verify", "doi": "10.3390/molecules28020715", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36677772/", "publicSourceType": "PMID" }, { "text": "Végh R, Csóka M, Mednyánszky Z et al.. Pesticide residues in bee bread, propolis, beeswax and royal jelly - A review of the literature and dietary risk assessment. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2023", "claim": "PubMed-indexed evidence involving Bee Pollen", "title": "Pesticide residues in bee bread, propolis, beeswax and royal jelly - A review of the literature and dietary risk assessment", "authors": "Végh R, Csóka M, Mednyánszky Z et al.", "journal": "Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association", "year": 2023, "pmid": "37121430", "url": "https://pubmed.ncbi.nlm.nih.gov/37121430/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.fct.2023.113806", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37121430/", "publicSourceType": "PMID" }, { "text": "Tan J, Paradise MS, Levine SL et al.. Development and survival of Orius insidiosus (Say) nymphs on encapsulated bee pollen-based diet in a Tier-I toxicity assay. Environmental entomology. 2011", "claim": "PubMed-indexed evidence involving Bee Pollen", "title": "Development and survival of Orius insidiosus (Say) nymphs on encapsulated bee pollen-based diet in a Tier-I toxicity assay", "authors": "Tan J, Paradise MS, Levine SL et al.", "journal": "Environmental entomology", "year": 2011, "pmid": "22217780", "url": "https://pubmed.ncbi.nlm.nih.gov/22217780/", "study_type": "review", "confidence": "verify", "doi": "10.1603/EN11060", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22217780/", "publicSourceType": "PMID" }, { "text": "Hurren KM, Lewis CL. Probable interaction between warfarin and bee pollen. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists. 2010", "claim": "PubMed-indexed evidence involving Bee Pollen", "title": "Probable interaction between warfarin and bee pollen", "authors": "Hurren KM, Lewis CL", "journal": "American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists", "year": 2010, "pmid": "21098375", "url": "https://pubmed.ncbi.nlm.nih.gov/21098375/", "study_type": "review", "confidence": "verify", "doi": "10.2146/ajhp090489", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21098375/", "publicSourceType": "PMID" }, { "text": "Ali AM, Kunugi H. Apitherapy for Age-Related Skeletal Muscle Dysfunction (Sarcopenia): A Review on the Effects of Royal Jelly, Propolis, and Bee Pollen. Foods (Basel, Switzerland). 2020", "claim": "PubMed-indexed evidence involving Bee Pollen", "title": "Apitherapy for Age-Related Skeletal Muscle Dysfunction (Sarcopenia): A Review on the Effects of Royal Jelly, Propolis, and Bee Pollen", "authors": "Ali AM, Kunugi H", "journal": "Foods (Basel, Switzerland)", "year": 2020, "pmid": "32992744", "url": "https://pubmed.ncbi.nlm.nih.gov/32992744/", "study_type": "review", "confidence": "verify", "doi": "10.3390/foods9101362", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32992744/", "publicSourceType": "PMID" }, { "text": "Eroğlu M, Yonar ME, Yonar SM et al.. The effect on paraoxonase and arylesterase activities of bee pollen against deltamethrin in Cyprinus carpio. Drug and chemical toxicology. 2026", "claim": "PubMed-indexed evidence involving Bee Pollen", "title": "The effect on paraoxonase and arylesterase activities of bee pollen against deltamethrin in Cyprinus carpio", "authors": "Eroğlu M, Yonar ME, Yonar SM et al.", "journal": "Drug and chemical toxicology", "year": 2026, "pmid": "41230647", "url": "https://pubmed.ncbi.nlm.nih.gov/41230647/", "study_type": "review", "confidence": "verify", "doi": "10.1080/01480545.2025.2579544", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41230647/", "publicSourceType": "PMID" }, { "text": "Stalder S, Nussbaumer R, Fracheboud M et al.. Potentially toxic trace elements in bee pollen collected around a former municipal waste deposit site. Environmental toxicology and chemistry. 2026", "claim": "PubMed-indexed evidence involving Bee Pollen", "title": "Potentially toxic trace elements in bee pollen collected around a former municipal waste deposit site", "authors": "Stalder S, Nussbaumer R, Fracheboud M et al.", "journal": "Environmental toxicology and chemistry", "year": 2026, "pmid": "42085508", "url": "https://pubmed.ncbi.nlm.nih.gov/42085508/", "study_type": "review", "confidence": "verify", "doi": "10.1093/etojnl/vgag123", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/42085508/", "publicSourceType": "PMID" }, { "claim": "Bee pollen supplements can cause anaphylaxis", "title": "Bee Pollen-Induced Anaphylaxis: A Case Report and Literature Review", "authors": "Choi JH et al.", "journal": "Allergy, Asthma and Immunology Research", "year": 2015, "pmid": "25749764", "url": "https://pubmed.ncbi.nlm.nih.gov/25749764/", "study_type": "case_report", "key_finding": "Case report and review describe bee pollen-induced anaphylaxis.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25749764/", "publicSourceType": "PMID" }, { "claim": "Bee pollen supplement ingestion has caused anaphylaxis", "title": "Anaphylaxis from bee pollen supplement", "authors": "Jagdis A et al.", "journal": "CMAJ", "year": 2012, "pmid": "22619345", "url": "https://pubmed.ncbi.nlm.nih.gov/22619345/", "study_type": "case_report", "key_finding": "Case report documents anaphylaxis after bee pollen supplement ingestion.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22619345/", "publicSourceType": "PMID" }, { "claim": "Exercise can augment bee pollen-associated anaphylaxis", "title": "A paediatric case of exercise-augmented anaphylaxis following bee pollen ingestion in Western Australia", "authors": "Leang ZX, Thalayasingam M, O'Sullivan M", "journal": "Asia Pacific Allergy", "year": 2022, "pmid": "35966155", "url": "https://pubmed.ncbi.nlm.nih.gov/35966155/", "study_type": "case_report", "key_finding": "Pediatric case report describes exercise-augmented anaphylaxis after bee pollen ingestion.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35966155/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "bee-pollen" }, { "id": "31A0AF38-85BA-43B2-987F-929105751F0C", "name": "Royal Jelly", "alternateNames": [ "Bee Royal Jelly" ], "category": "Other", "subcategory": "Bee Product", "overview": "Nutrient-rich bee secretion with limited human evidence for selected metabolic and menopausal outcomes; allergic reactions can be severe.", "mechanismOfAction": "Contains 10-hydroxy-2-decenoic acid (10-HDA), proteins, peptides, and fatty acids with mostly preclinical anti-inflammatory and antimicrobial activity. Human evidence is limited and does not establish broad anti-aging, fertility, or immune claims.", "commonBenefits": [ "Menopausal symptom support (limited)", "Metabolic marker support (limited)", "Skin support (mostly preclinical)", "Nutrition support" ], "commonDosageRange": "300-3,000 mg daily", "recommendedForm": "Fresh or freeze-dried royal jelly (standardized to 6% 10-HDA)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food; refrigerate fresh form" }, "evidenceRating": "emerging", "foodSources": [ "Royal jelly (bee product)" ], "deficiencySymptoms": [], "sideEffects": [ "Anaphylaxis and severe allergic reactions", "Asthma exacerbation, including fatal asthma reported", "GI upset" ], "contraindications": [ "Bee product allergy", "Asthma", "Eczema or strong atopy history", "History of anaphylaxis" ], "iconName": "sparkle", "colorHex": "FFB84D", "tags": [ "bee-product", "menopause", "metabolic", "nutrition" ], "sources": [ { "claim": "Comprehensive systematic review of royal jelly therapeutic interventions", "title": "Royal jelly a promising therapeutic intervention and functional food supplement: A systematic review", "authors": "Kamal MA et al.", "journal": "Food Sci Nutr", "year": 2024, "pmid": "39296128", "url": "https://pubmed.ncbi.nlm.nih.gov/39296128/", "study_type": "review", "key_finding": "Both preclinical and clinical studies report royal jelly improves immune function, wound healing, and decreases severity of chronic diseases including diabetes and cardiovascular disorders.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39296128/", "publicSourceType": "PMID" }, { "claim": "Royal jelly effective for menopausal symptoms in clinical trial", "title": "Effect of royal jelly on menopausal symptoms: A randomized placebo-controlled clinical trial", "authors": "Sharif SN et al.", "journal": "Complement Ther Clin Pract", "year": 2019, "pmid": "31470366", "url": "https://pubmed.ncbi.nlm.nih.gov/31470366/", "study_type": "RCT", "key_finding": "Daily oral royal jelly (1000 mg) for eight weeks was effective in alleviating menopausal symptoms compared to placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31470366/", "publicSourceType": "PMID" }, { "claim": "Royal jelly reduces cholesterol in mild hypercholesterolemic adults", "title": "Hypocholesterolemic efficacy of royal jelly in healthy mild hypercholesterolemic adults", "authors": "Lambrinoudaki I et al.", "journal": "J Am Coll Nutr", "year": 2016, "pmid": "27937077", "url": "https://pubmed.ncbi.nlm.nih.gov/27937077/", "study_type": "RCT", "key_finding": "Royal jelly supplementation reduced total cholesterol and LDL cholesterol levels significantly after three months in healthy mild hypercholesterolemic adults.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27937077/", "publicSourceType": "PMID" }, { "claim": "Six-month royal jelly intake improves glucose tolerance and mental health", "title": "Effect of royal jelly ingestion for six months on healthy volunteers", "authors": "Morita H et al.", "journal": "Nutr J", "year": 2012, "pmid": "22995464", "url": "https://pubmed.ncbi.nlm.nih.gov/22995464/", "study_type": "RCT", "key_finding": "Six-month ingestion of royal jelly in healthy humans improved erythropoiesis, glucose tolerance, and mental health.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22995464/", "publicSourceType": "PMID" }, { "claim": "Royal jelly protects against UV-induced photoaging by enhancing collagen production", "title": "Royal jelly protects against ultraviolet B-induced photoaging in human skin fibroblasts via enhancing collagen production", "authors": "Park HM et al.", "journal": "J Med Food", "year": 2011, "pmid": "21812645", "url": "https://pubmed.ncbi.nlm.nih.gov/21812645/", "study_type": "in_vitro", "key_finding": "Royal jelly and 10-HDA increased procollagen type I and TGF-beta1 production in UVB-irradiated fibroblasts, suggesting potential for skin anti-aging.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21812645/", "publicSourceType": "PMID" }, { "claim": "Royal jelly promotes healthy aging and longevity", "title": "Royal Jelly and Its Components Promote Healthy Aging and Longevity: From Animal Models to Humans", "authors": "Miyata Y et al.", "journal": "Int J Mol Sci", "year": 2019, "pmid": "31547049", "url": "https://pubmed.ncbi.nlm.nih.gov/31547049/", "study_type": "review", "key_finding": "Royal jelly's 10-HDA and other bioactive components have anti-inflammatory, antimicrobial, collagen-stimulating, and anti-aging properties supported by animal and human studies.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31547049/", "publicSourceType": "PMID" }, { "text": "Pasupuleti VR, Sammugam L, Ramesh N et al.. Honey, Propolis, and Royal Jelly: A Comprehensive Review of Their Biological Actions and Health Benefits. Oxidative medicine and cellular longevity. 2017", "pmid": "28814983", "doi": "10.1155/2017/1259510", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28814983/", "publicSourceType": "PMID" }, { "claim": "Royal jelly improves vascular endothelial function in healthy volunteers", "title": "A Randomized, Double-Blind Comparison Study of Royal Jelly to Augment Vascular Endothelial Function in Healthy Volunteers", "authors": "Fujisue K, Yamamoto E, Sueta D et al.", "journal": "J Atheroscler Thromb", "year": 2022, "pmid": "34588374", "url": "https://pubmed.ncbi.nlm.nih.gov/34588374/", "study_type": "rct", "key_finding": "RCT of 100 healthy volunteers found 4 weeks of royal jelly supplementation (690 mg/day) significantly improved vascular endothelial function (RH-PAT index) and liver function markers compared to placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34588374/", "publicSourceType": "PMID" }, { "claim": "Royal jelly plus coenzyme Q10 improves exercise performance and reduces oxidative stress in swimmers", "title": "Royal jelly plus coenzyme Q10 supplementation improves high-intensity interval exercise performance via changes in plasmatic and salivary biomarkers of oxidative stress and muscle damage in swimmers: a randomized, double-blind, placebo-controlled pilot trial", "authors": "Ovchinnikov AN, Paoli A, Seleznev VV, Deryugina AV", "journal": "J Int Soc Sports Nutr", "year": 2022, "pmid": "35813842", "url": "https://pubmed.ncbi.nlm.nih.gov/35813842/", "study_type": "rct", "key_finding": "RCT of 20 swimmers found 10 days of RJ + CoQ10 supplementation significantly improved HIIE performance and reduced exercise-induced lipid peroxidation and muscle damage biomarkers.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35813842/", "publicSourceType": "PMID" }, { "claim": "Royal jelly combined with green propolis reduces IL-6 and cholesterol in hemodialysis patients", "title": "Apitherapy with Royal Jelly and Green Propolis EPP-AF improves cardiovascular risk markers in patients undergoing hemodialysis", "authors": "Kemp JA, Mendonca M, Chrispim P et al.", "journal": "Toxins (Basel)", "year": 2025, "pmid": "40864045", "url": "https://pubmed.ncbi.nlm.nih.gov/40864045/", "study_type": "rct", "key_finding": "RCT of 38 hemodialysis patients found 2 months of royal jelly + green propolis supplementation significantly reduced IL-6 and total cholesterol, showing promise as a cardiovascular risk reduction strategy.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40864045/", "publicSourceType": "PMID" }, { "claim": "Royal jelly supplementation with exercise improves liver function and lipid profile in women with MASLD", "title": "Aerobic-Resistance Training with Royal Jelly Supplementation Has a Synergistic Effect on Paraoxonase 1 Changes and Liver Function in Women with MASLD", "authors": "Askari R, Rabani N, Marefati H, Azarnive MS, Pusceddu M, Migliaccio GM", "journal": "Medicina (Kaunas)", "year": 2025, "pmid": "40005465", "url": "https://pubmed.ncbi.nlm.nih.gov/40005465/", "study_type": "rct", "key_finding": "RCT of 23 women with MASLD found 8 weeks of exercise + royal jelly significantly increased PON1 and HDL while decreasing oxLDL, TC, TG, LDL, ALT, and AST compared to exercise + placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40005465/", "publicSourceType": "PMID" }, { "text": "Taheri S, Bahari H, Mirzavi F et al.. Effects of royal jelly consumption on inflammation and oxidative stress: A systematic review and meta-analysis of randomized controlled trials. Avicenna journal of phytomedicine. 2025", "claim": "PubMed-indexed evidence involving Royal Jelly", "title": "Effects of royal jelly consumption on inflammation and oxidative stress: A systematic review and meta-analysis of randomized controlled trials", "authors": "Taheri S, Bahari H, Mirzavi F et al.", "journal": "Avicenna journal of phytomedicine", "year": 2025, "pmid": "40656618", "url": "https://pubmed.ncbi.nlm.nih.gov/40656618/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.22038/ajp.2024.25139", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40656618/", "publicSourceType": "PMID" }, { "text": "Vajdi M, Musazadeh V, Khajeh M et al.. The effects of royal jelly supplementation on anthropometric indices: a GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials. Frontiers in nutrition. 2023", "claim": "PubMed-indexed evidence involving Royal Jelly", "title": "The effects of royal jelly supplementation on anthropometric indices: a GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials", "authors": "Vajdi M, Musazadeh V, Khajeh M et al.", "journal": "Frontiers in nutrition", "year": 2023, "pmid": "37599677", "url": "https://pubmed.ncbi.nlm.nih.gov/37599677/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fnut.2023.1196258", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37599677/", "publicSourceType": "PMID" }, { "text": "Bahari H, Taheri S, Rashidmayvan M et al.. The effect of Royal jelly on liver enzymes and glycemic indices: A systematic review and meta-analysis of randomized clinical trials. Complementary therapies in medicine. 2023", "claim": "PubMed-indexed evidence involving Royal Jelly", "title": "The effect of Royal jelly on liver enzymes and glycemic indices: A systematic review and meta-analysis of randomized clinical trials", "authors": "Bahari H, Taheri S, Rashidmayvan M et al.", "journal": "Complementary therapies in medicine", "year": 2023, "pmid": "37619715", "url": "https://pubmed.ncbi.nlm.nih.gov/37619715/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.ctim.2023.102974", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37619715/", "publicSourceType": "PMID" }, { "text": "Ferraz SD, Stangherlin L, Colonetti T et al.. Royal jelly for management of postmenopausal symptoms: a systematic review and meta-analysis. Menopause (New York, N.Y.). 2026", "claim": "PubMed-indexed evidence involving Royal Jelly", "title": "Royal jelly for management of postmenopausal symptoms: a systematic review and meta-analysis", "authors": "Ferraz SD, Stangherlin L, Colonetti T et al.", "journal": "Menopause (New York, N.Y.)", "year": 2026, "pmid": "41401249", "url": "https://pubmed.ncbi.nlm.nih.gov/41401249/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/GME.0000000000002688", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41401249/", "publicSourceType": "PMID" }, { "text": "Maleki V, Jafari-Vayghan H, Saleh-Ghadimi S et al.. Effects of Royal jelly on metabolic variables in diabetes mellitus: A systematic review. Complementary therapies in medicine. 2019", "claim": "PubMed-indexed evidence involving Royal Jelly", "title": "Effects of Royal jelly on metabolic variables in diabetes mellitus: A systematic review", "authors": "Maleki V, Jafari-Vayghan H, Saleh-Ghadimi S et al.", "journal": "Complementary therapies in medicine", "year": 2019, "pmid": "30935531", "url": "https://pubmed.ncbi.nlm.nih.gov/30935531/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.ctim.2018.12.022", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30935531/", "publicSourceType": "PMID" }, { "claim": "Royal jelly can trigger asthma and anaphylaxis", "title": "Asthma and anaphylaxis induced by royal jelly", "authors": "Thien FC, Leung R, Baldo BA et al.", "journal": "Clinical and Experimental Allergy", "year": 1996, "pmid": "8835130", "url": "https://pubmed.ncbi.nlm.nih.gov/8835130/", "study_type": "case_report", "key_finding": "Case reports document asthma and anaphylaxis induced by royal jelly.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8835130/", "publicSourceType": "PMID" }, { "claim": "Fatal asthma has been reported after royal jelly exposure", "title": "Fatal royal jelly-induced asthma", "authors": "Bullock RJ, Rohan A, Straatmans JA", "journal": "The Medical Journal of Australia", "year": 1994, "pmid": "8271989", "url": "https://pubmed.ncbi.nlm.nih.gov/8271989/", "study_type": "case_report", "key_finding": "Fatal asthma associated with royal jelly supports avoiding use in asthma or atopic disease.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8271989/", "publicSourceType": "PMID" }, { "claim": "Royal jelly ingestion can cause anaphylaxis", "title": "Case of anaphylaxis caused by ingestion of royal jelly", "authors": "Katayama M, Aoki M, Kawana S", "journal": "Journal of Dermatology", "year": 2008, "pmid": "18419679", "url": "https://pubmed.ncbi.nlm.nih.gov/18419679/", "study_type": "case_report", "key_finding": "Case report documents anaphylaxis caused by royal jelly ingestion.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18419679/", "publicSourceType": "PMID" }, { "claim": "Major royal jelly protein 3 can be an allergen causing anaphylaxis", "title": "A Case of Anaphylaxis Caused by Major Royal Jelly Protein 3 of Royal Jelly and Its Cross-Reactivity with Honeycomb", "authors": "Li JD, Cui L, Xu YY, Guan K", "journal": "Journal of Asthma and Allergy", "year": 2021, "pmid": "35221696", "url": "https://pubmed.ncbi.nlm.nih.gov/35221696/", "study_type": "case_report", "key_finding": "Case report identifies major royal jelly protein 3 as a trigger for royal jelly-associated anaphylaxis.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35221696/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "royal-jelly" }, { "id": "D42D7026-298E-4EE6-AD76-07D119CD4042", "name": "Vanadium", "alternateNames": [ "Vanadyl Sulfate", "Vanadium" ], "category": "Mineral", "subcategory": "Ultra-Trace Mineral", "overview": "Ultra-trace mineral that mimics insulin action for blood sugar support.", "mechanismOfAction": "Vanadyl ion inhibits protein tyrosine phosphatase 1B (PTP1B), enhancing insulin receptor signaling. Stimulates glucose transporter (GLUT4) translocation to cell surface.", "commonBenefits": [ "Blood sugar support", "Insulin sensitivity" ], "commonDosageRange": "10-50 mcg daily", "recommendedForm": "Vanadyl sulfate or bis(maltolato)oxovanadium", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food" }, "evidenceRating": "emerging", "foodSources": [ "Mushrooms", "Shellfish", "Black pepper", "Dill" ], "deficiencySymptoms": [ "Not well characterized" ], "sideEffects": [ "GI upset", "Green tongue", "Kidney toxicity at high doses" ], "contraindications": [ "Kidney disease", "Diabetes medications (additive effect)" ], "iconName": "atom", "colorHex": "4DD4E6", "tags": [ "blood-sugar", "insulin", "trace-mineral" ], "sources": [ { "claim": "Vanadyl sulfate improves insulin sensitivity in type 2 diabetes", "title": "Vanadyl sulfate improves hepatic and muscle insulin sensitivity in type 2 diabetes", "authors": "Cusi K et al.", "journal": "J Clin Endocrinol Metab", "year": 2001, "pmid": "11238540", "url": "https://pubmed.ncbi.nlm.nih.gov/11238540/", "study_type": "RCT", "key_finding": "In type 2 diabetic subjects, vanadyl sulfate increased glucose infusion rate approximately 82%, improving hepatic and muscle insulin sensitivity.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11238540/", "publicSourceType": "PMID" }, { "claim": "Vanadyl sulfate reduces fasting glucose and HbA1c in NIDDM", "title": "Metabolic effects of vanadyl sulfate in humans with non-insulin-dependent diabetes mellitus: in vivo and in vitro studies", "authors": "Goldfine AB et al.", "journal": "Metabolism", "year": 2000, "pmid": "10726921", "url": "https://pubmed.ncbi.nlm.nih.gov/10726921/", "study_type": "RCT", "key_finding": "Fasting glucose and HbA1c decreased significantly in 150- and 300-mg vanadyl sulfate groups; reduced endogenous glucose production by about 20%.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10726921/", "publicSourceType": "PMID" }, { "claim": "Comprehensive review of vanadium pharmacotoxicological mechanisms", "title": "Vanadium: Risks and possible benefits in the light of a comprehensive overview of its pharmacotoxicological mechanisms and multi-applications with a summary of further research trends", "authors": "Crans DC et al.", "journal": "J Inorg Biochem", "year": 2020, "pmid": "32305626", "url": "https://pubmed.ncbi.nlm.nih.gov/32305626/", "study_type": "review", "key_finding": "Organic vanadium compounds are much safer than inorganic salts with no GI discomfort, hepatic or renal toxicity; toxicity increases with valence state.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32305626/", "publicSourceType": "PMID" }, { "claim": "Evidence-based systematic review of vanadium", "title": "An evidence-based systematic review of vanadium by the Natural Standard Research Collaboration", "authors": "Defined TN et al.", "journal": "J Diet Suppl", "year": 2012, "pmid": "22891992", "url": "https://pubmed.ncbi.nlm.nih.gov/22891992/", "study_type": "review", "key_finding": "Vanadyl sulfate appears safe at therapeutic doses for 6 weeks but does not dramatically improve insulin sensitivity or glycemic control at tolerated doses.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22891992/", "publicSourceType": "PMID" }, { "claim": "Vanadium improves insulin sensitivity in NIDDM but not in non-diabetic obese subjects", "title": "Oral vanadyl sulfate improves insulin sensitivity in NIDDM but not in obese nondiabetic subjects", "authors": "Halberstam M et al.", "journal": "Diabetes", "year": 1996, "pmid": "8621019", "url": "https://pubmed.ncbi.nlm.nih.gov/8621019/", "study_type": "RCT", "key_finding": "Vanadyl sulfate improved insulin sensitivity specifically in diabetic subjects but did not alter insulin sensitivity in nondiabetic obese volunteers.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8621019/", "publicSourceType": "PMID" }, { "text": "Ghalichi F, Ostadrahimi A, Saghafi-Asl M. Vanadium and diabetic dyslipidemia: A systematic review of animal studies. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2022", "pmid": "35303513", "doi": "10.1016/j.jtemb.2022.126955", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35303513/", "publicSourceType": "PMID" }, { "text": "Jaiswal MR, Kale PP. Mini review-vanadium-induced neurotoxicity and possible targets. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2020", "pmid": "31838631", "doi": "10.1007/s10072-019-04188-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31838631/", "publicSourceType": "PMID" }, { "text": "Ghalichi F, Ostadrahimi A, Saghafi-Asl M. Vanadium and biomarkers of inflammation and oxidative stress in diabetes: A systematic review of animal studies. Health promotion perspectives. 2022", "claim": "PubMed-indexed evidence involving Vanadium", "title": "Vanadium and biomarkers of inflammation and oxidative stress in diabetes: A systematic review of animal studies", "authors": "Ghalichi F, Ostadrahimi A, Saghafi-Asl M", "journal": "Health promotion perspectives", "year": 2022, "pmid": "36276410", "url": "https://pubmed.ncbi.nlm.nih.gov/36276410/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.34172/hpp.2022.16", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36276410/", "publicSourceType": "PMID" }, { "text": "Smith DM, Pickering RM, Lewith GT. A systematic review of vanadium oral supplements for glycaemic control in type 2 diabetes mellitus. QJM : monthly journal of the Association of Physicians. 2008", "claim": "PubMed-indexed evidence involving Vanadium", "title": "A systematic review of vanadium oral supplements for glycaemic control in type 2 diabetes mellitus", "authors": "Smith DM, Pickering RM, Lewith GT", "journal": "QJM : monthly journal of the Association of Physicians", "year": 2008, "pmid": "18319296", "url": "https://pubmed.ncbi.nlm.nih.gov/18319296/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/qjmed/hcn003", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18319296/", "publicSourceType": "PMID" }, { "text": "Ścibior A. Vanadium (V) and magnesium (Mg) - In vivo interactions: A review. Chemico-biological interactions. 2016", "claim": "PubMed-indexed evidence involving Vanadium", "title": "Vanadium (V) and magnesium (Mg) - In vivo interactions: A review", "authors": "Ścibior A", "journal": "Chemico-biological interactions", "year": 2016, "pmid": "27620816", "url": "https://pubmed.ncbi.nlm.nih.gov/27620816/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.cbi.2016.09.007", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27620816/", "publicSourceType": "PMID" }, { "text": "Du XY, Yu YQ, Yang J et al.. Cytotoxicity of Vanadium(IV) and Vanadium(V) on Caco-2 Cells: The Important Influence of Vanadium Speciation. Biological trace element research. 2025", "claim": "PubMed-indexed evidence involving Vanadium", "title": "Cytotoxicity of Vanadium(IV) and Vanadium(V) on Caco-2 Cells: The Important Influence of Vanadium Speciation", "authors": "Du XY, Yu YQ, Yang J et al.", "journal": "Biological trace element research", "year": 2025, "pmid": "39755851", "url": "https://pubmed.ncbi.nlm.nih.gov/39755851/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s12011-024-04506-9", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39755851/", "publicSourceType": "PMID" }, { "text": "Stachowicz K. Vanadium - good or bad - The role of vanadium in the central nervous system disorders, potential therapeutic targets and its toxicity. Toxicology letters. 2025", "claim": "PubMed-indexed evidence involving Vanadium", "title": "Vanadium - good or bad - The role of vanadium in the central nervous system disorders, potential therapeutic targets and its toxicity", "authors": "Stachowicz K", "journal": "Toxicology letters", "year": 2025, "pmid": "40467016", "url": "https://pubmed.ncbi.nlm.nih.gov/40467016/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.toxlet.2025.06.006", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40467016/", "publicSourceType": "PMID" }, { "text": "Martins FM, Iglesias BA, Chaves OA et al.. Vanadium(V) complexes derived from triphenylphosphonium and hydrazides: cytotoxicity evaluation and interaction with biomolecules. Dalton transactions (Cambridge, England : 2003). 2024", "claim": "PubMed-indexed evidence involving Vanadium", "title": "Vanadium(V) complexes derived from triphenylphosphonium and hydrazides: cytotoxicity evaluation and interaction with biomolecules", "authors": "Martins FM, Iglesias BA, Chaves OA et al.", "journal": "Dalton transactions (Cambridge, England : 2003)", "year": 2024, "pmid": "38666341", "url": "https://pubmed.ncbi.nlm.nih.gov/38666341/", "study_type": "review", "confidence": "verify", "doi": "10.1039/d4dt00464g", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38666341/", "publicSourceType": "PMID" }, { "text": "Altaf MA, Shahid R, Naz S et al.. Vanadium toxicity was alleviated by supplementation of silicon in tomato seedlings: Upregulating antioxidative enzymes and glyoxalase system. Plant physiology and biochemistry : PPB. 2024", "claim": "PubMed-indexed evidence involving Vanadium", "title": "Vanadium toxicity was alleviated by supplementation of silicon in tomato seedlings: Upregulating antioxidative enzymes and glyoxalase system", "authors": "Altaf MA, Shahid R, Naz S et al.", "journal": "Plant physiology and biochemistry : PPB", "year": 2024, "pmid": "38875778", "url": "https://pubmed.ncbi.nlm.nih.gov/38875778/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.plaphy.2024.108809", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38875778/", "publicSourceType": "PMID" }, { "text": "Martino C, Geraci F, Scudiero R et al.. Vanadium Toxicity Is Altered by Global Warming Conditions in Sea Urchin Embryos: Metal Bioaccumulation, Cell Stress Response and Apoptosis. Journal of xenobiotics. 2024", "claim": "PubMed-indexed evidence involving Vanadium", "title": "Vanadium Toxicity Is Altered by Global Warming Conditions in Sea Urchin Embryos: Metal Bioaccumulation, Cell Stress Response and Apoptosis", "authors": "Martino C, Geraci F, Scudiero R et al.", "journal": "Journal of xenobiotics", "year": 2024, "pmid": "39311143", "url": "https://pubmed.ncbi.nlm.nih.gov/39311143/", "study_type": "review", "confidence": "verify", "doi": "10.3390/jox14030064", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39311143/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "vanadium" }, { "id": "8D2298D4-7B67-45C3-885B-15976D67DE09", "name": "Strontium", "alternateNames": [ "Strontium Citrate", "Strontium Ranelate" ], "category": "Mineral", "subcategory": "Bone-Support Mineral", "overview": "Trace element that supports bone density by stimulating osteoblasts and inhibiting osteoclasts.", "mechanismOfAction": "Activates calcium-sensing receptor (CaSR) on osteoblasts, stimulating bone formation. Also inhibits osteoclast differentiation via OPG/RANKL pathway. Dual mechanism unique among bone supplements.", "commonBenefits": [ "Bone density", "Osteoporosis support" ], "commonDosageRange": "680 mg strontium citrate daily", "recommendedForm": "Strontium citrate (NOT strontium ranelate, prescription)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Take at bedtime, SEPARATE from calcium by 4+ hours (competes for absorption)" }, "evidenceRating": "moderate", "foodSources": [ "Spices", "Seafood", "Whole grains", "Root vegetables" ], "deficiencySymptoms": [ "Not classically essential" ], "sideEffects": [ "GI upset", "Headache", "DRESS syndrome and severe skin reactions reported with strontium ranelate", "May falsely elevate DXA bone density readings because strontium attenuates X-rays more than calcium", "Cardiovascular risk concerns reported for strontium ranelate" ], "contraindications": [ "History of blood clots", "DVT risk factors", "Kidney disease", "Must separate from calcium", "Cardiovascular disease or prior heart attack", "History of DRESS syndrome or severe drug rash", "Use only with clinician monitoring for osteoporosis and DXA interpretation" ], "iconName": "figure.stand", "colorHex": "4DD4E6", "tags": [ "bone-health", "osteoporosis" ], "sources": [ { "claim": "TROPOS trial: strontium ranelate reduces nonvertebral fracture risk", "title": "Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study", "authors": "Reginster JY et al.", "journal": "J Clin Endocrinol Metab", "year": 2005, "pmid": "15728210", "url": "https://pubmed.ncbi.nlm.nih.gov/15728210/", "study_type": "RCT", "key_finding": "Strontium ranelate reduced risk of all nonvertebral fractures by 16% and major fragility fractures by 19% in postmenopausal osteoporotic women.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15728210/", "publicSourceType": "PMID" }, { "claim": "Comparison of strontium forms for bone health in animal model", "title": "Influence of Various Strontium Formulations (Ranelate, Citrate, and Chloride) on Bone Mineral Density, Morphology, and Microarchitecture: A Comparative Study in an Ovariectomized Female Mouse Model of Osteoporosis", "authors": "Wornham DP et al.", "journal": "Nutrients", "year": 2024, "pmid": "38612883", "url": "https://pubmed.ncbi.nlm.nih.gov/38612883/", "study_type": "in_vivo", "key_finding": "Strontium administration increased bone tissue mineral density across all forms; strontium citrate exhibited the weakest effect compared to ranelate and chloride.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38612883/", "publicSourceType": "PMID" }, { "claim": "Strontium ranelate dual mechanism: increases bone formation, decreases resorption", "title": "Optimizing bone metabolism in osteoporosis: insight into the pharmacologic profile of strontium ranelate", "authors": "Reginster JY et al.", "journal": "Osteoporos Int", "year": 2003, "pmid": "12730801", "url": "https://pubmed.ncbi.nlm.nih.gov/12730801/", "study_type": "review", "key_finding": "Strontium ranelate is the first antiosteoporotic treatment with dual mode of action, simultaneously increasing bone formation while decreasing bone resorption.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12730801/", "publicSourceType": "PMID" }, { "claim": "Long-term strontium ranelate treatment maintains fracture protection over 8 years", "title": "Long-term treatment of postmenopausal osteoporosis with strontium ranelate: results at 8 years", "authors": "Reginster JY et al.", "journal": "Bone", "year": 2009, "pmid": "19679207", "url": "https://pubmed.ncbi.nlm.nih.gov/19679207/", "study_type": "RCT", "key_finding": "Over 8 years of treatment, cumulative fracture incidences during years 6-8 were not different from the first 3 years, demonstrating sustained benefit.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19679207/", "publicSourceType": "PMID" }, { "claim": "Cardiovascular safety concerns with strontium ranelate", "title": "Cardiac concerns associated with strontium ranelate", "authors": "Bolland MJ et al.", "journal": "Expert Opin Drug Saf", "year": 2014, "pmid": "25020233", "url": "https://pubmed.ncbi.nlm.nih.gov/25020233/", "study_type": "review", "key_finding": "RCT data indicate higher incidence of non-adjudicated MI with strontium ranelate vs placebo (1.7 vs 1.1%); now contraindicated in patients with cardiovascular history.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25020233/", "publicSourceType": "PMID" }, { "claim": "Strontium ranelate reduces vertebral fractures in osteopenic women", "title": "Strontium ranelate reduces the risk of vertebral fractures in patients with osteopenia", "authors": "Seeman E et al.", "journal": "J Bone Miner Res", "year": 2008, "pmid": "17997711", "url": "https://pubmed.ncbi.nlm.nih.gov/17997711/", "study_type": "RCT", "key_finding": "Strontium ranelate reduced vertebral fracture risk in osteopenic women from the SOTI and TROPOS trials over 3 years of treatment.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17997711/", "publicSourceType": "PMID" }, { "text": "Yuan W, Liu J, Zhang Z et al.. Strontium-Alix interaction enhances exosomal miRNA selectively loading in synovial MSCs for temporomandibular joint osteoarthritis treatment. International journal of oral science. 2025", "pmid": "39890774", "doi": "10.1038/s41368-024-00329-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39890774/", "publicSourceType": "PMID" }, { "text": "Blake GM, Fogelman I. Strontium ranelate: a novel treatment for postmenopausal osteoporosis: a review of safety and efficacy. Clinical interventions in aging. 2006", "claim": "PubMed-indexed evidence involving Strontium", "title": "Strontium ranelate: a novel treatment for postmenopausal osteoporosis: a review of safety and efficacy", "authors": "Blake GM, Fogelman I", "journal": "Clinical interventions in aging", "year": 2006, "pmid": "18046914", "url": "https://pubmed.ncbi.nlm.nih.gov/18046914/", "study_type": "review", "confidence": "verify", "doi": "10.2147/ciia.2006.1.4.367", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18046914/", "publicSourceType": "PMID" }, { "text": "Curtis EM, Cooper C, Harvey NC. Cardiovascular safety of calcium, magnesium and strontium: what does the evidence say?. Aging clinical and experimental research. 2021", "claim": "PubMed-indexed evidence involving Strontium", "title": "Cardiovascular safety of calcium, magnesium and strontium: what does the evidence say?", "authors": "Curtis EM, Cooper C, Harvey NC", "journal": "Aging clinical and experimental research", "year": 2021, "pmid": "33565045", "url": "https://pubmed.ncbi.nlm.nih.gov/33565045/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s40520-021-01799-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33565045/", "publicSourceType": "PMID" }, { "text": "Ghani A, Arfee S. Role of Calcitonin and Strontium Ranelate in Osteoporosis. Indian journal of orthopaedics. 2023", "claim": "PubMed-indexed evidence involving Strontium", "title": "Role of Calcitonin and Strontium Ranelate in Osteoporosis", "authors": "Ghani A, Arfee S", "journal": "Indian journal of orthopaedics", "year": 2023, "pmid": "38107820", "url": "https://pubmed.ncbi.nlm.nih.gov/38107820/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s43465-023-01034-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38107820/", "publicSourceType": "PMID" }, { "text": "Deeks ED, Dhillon S. Strontium ranelate: a review of its use in the treatment of postmenopausal osteoporosis. Drugs. 2010", "claim": "PubMed-indexed evidence involving Strontium", "title": "Strontium ranelate: a review of its use in the treatment of postmenopausal osteoporosis", "authors": "Deeks ED, Dhillon S", "journal": "Drugs", "year": 2010, "pmid": "20394457", "url": "https://pubmed.ncbi.nlm.nih.gov/20394457/", "study_type": "review", "confidence": "verify", "doi": "10.2165/10481900-000000000-00000", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20394457/", "publicSourceType": "PMID" }, { "text": "Blake GM, Lewiecki EM, Kendler DL et al.. A review of strontium ranelate and its effect on DXA scans. Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry. 2007", "claim": "PubMed-indexed evidence involving Strontium", "title": "A review of strontium ranelate and its effect on DXA scans", "authors": "Blake GM, Lewiecki EM, Kendler DL et al.", "journal": "Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry", "year": 2007, "pmid": "17485027", "url": "https://pubmed.ncbi.nlm.nih.gov/17485027/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.jocd.2007.01.002", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17485027/", "publicSourceType": "PMID" }, { "text": "Stepan JJ. Strontium ranelate: in search for the mechanism of action. Journal of bone and mineral metabolism. 2013", "claim": "PubMed-indexed evidence involving Strontium", "title": "Strontium ranelate: in search for the mechanism of action", "authors": "Stepan JJ", "journal": "Journal of bone and mineral metabolism", "year": 2013, "pmid": "23925392", "url": "https://pubmed.ncbi.nlm.nih.gov/23925392/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s00774-013-0494-1", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23925392/", "publicSourceType": "PMID" }, { "text": "Neuprez A, Hiligsmann M, Scholtissen S et al.. Strontium ranelate: the first agent of a new therapeutic class in osteoporosis. Advances in therapy. 2008", "claim": "PubMed-indexed evidence involving Strontium", "title": "Strontium ranelate: the first agent of a new therapeutic class in osteoporosis", "authors": "Neuprez A, Hiligsmann M, Scholtissen S et al.", "journal": "Advances in therapy", "year": 2008, "pmid": "19066755", "url": "https://pubmed.ncbi.nlm.nih.gov/19066755/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s12325-008-0125-8", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19066755/", "publicSourceType": "PMID" }, { "text": "Burlet N, Reginster JY. Strontium ranelate: the first dual acting treatment for postmenopausal osteoporosis. Clinical orthopaedics and related research. 2006", "claim": "PubMed-indexed evidence involving Strontium", "title": "Strontium ranelate: the first dual acting treatment for postmenopausal osteoporosis", "authors": "Burlet N, Reginster JY", "journal": "Clinical orthopaedics and related research", "year": 2006, "pmid": "16462426", "url": "https://pubmed.ncbi.nlm.nih.gov/16462426/", "study_type": "review", "confidence": "verify", "doi": "10.1097/01.blo.0000200247.27253.e9", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16462426/", "publicSourceType": "PMID" }, { "claim": "Strontium ranelate can cause DRESS syndrome", "title": "Strontium ranelate-induced DRESS syndrome: first two case reports", "authors": "Jonville-Bera AP, Crickx B, Aaron L et al.", "journal": "Allergy", "year": 2009, "pmid": "19210353", "url": "https://pubmed.ncbi.nlm.nih.gov/19210353/", "study_type": "case_report", "key_finding": "Case reports describe DRESS syndrome during strontium ranelate treatment.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19210353/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "strontium" }, { "id": "4BFABF15-4295-4363-A427-1A4AFD9397AC", "name": "Ox Bile", "alternateNames": [ "Bile Salts", "Ox Bile Extract" ], "category": "Other", "subcategory": "Digestive Support", "overview": "Supplemental bile acids for those with gallbladder removal or bile insufficiency.", "mechanismOfAction": "Bile acids emulsify dietary fats into micelles for lipase access. Essential for fat-soluble vitamin absorption (A, D, E, K). Also has antimicrobial effects in the small intestine.", "commonBenefits": [ "Fat digestion", "Fat-soluble vitamin absorption", "Post-gallbladder support" ], "commonDosageRange": "125-500 mg per fat-containing meal", "recommendedForm": "Ox bile extract (often combined with lipase)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take at start of meals containing fat" }, "evidenceRating": "moderate", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Diarrhea (dose too high)", "GI upset" ], "contraindications": [ "Bile duct obstruction", "Active gallbladder disease" ], "iconName": "flame.fill", "colorHex": "FFB84D", "tags": [ "digestion", "gallbladder", "fat-absorption" ], "sources": [ { "claim": "Ox bile corrects steatorrhea in ileectomy patient", "title": "Ox bile treatment of severe steatorrhea in an ileectomy-ileostomy patient", "authors": "Balistreri WF et al.", "journal": "Gastroenterology", "year": 1982, "pmid": "7054048", "url": "https://pubmed.ncbi.nlm.nih.gov/7054048/", "study_type": "case_report", "key_finding": "Oral bile acid supplementation reduced fat excretion markedly and did not aggravate diarrhea; steatorrhea reduced from 134 to 9 g/24 hr with chronic ox bile ingestion.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7054048/", "publicSourceType": "PMID" }, { "claim": "Ox bile corrects steatorrhea and malnutrition in ileectomy patient with residual colon", "title": "Treatment of severe steatorrhea with ox bile in an ileectomy patient with residual colon", "authors": "Balistreri WF et al.", "journal": "J Pediatr Gastroenterol Nutr", "year": 1992, "pmid": "1587199", "url": "https://pubmed.ncbi.nlm.nih.gov/1587199/", "study_type": "case_report", "key_finding": "Steatorrhea and malnutrition were corrected by ox bile without an increase in diarrhea in a patient with bile acid deficiency.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1587199/", "publicSourceType": "PMID" }, { "claim": "Bile salts are essential for fat digestion and lipid absorption", "title": "The role of bile salts in digestion", "authors": "Hofmann AF et al.", "journal": "Adv Intern Med", "year": 2011, "pmid": "21236400", "url": "https://pubmed.ncbi.nlm.nih.gov/21236400/", "study_type": "review", "key_finding": "Bile salts adsorb onto fat droplets and play a vital role in fat digestion as they are closely involved with lipolysis and fat-soluble vitamin absorption.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21236400/", "publicSourceType": "PMID" }, { "claim": "Conjugated bile acid replacement therapy improves fat absorption in short bowel syndrome", "title": "Conjugated bile acid replacement therapy for short-bowel syndrome", "authors": "Gruy-Kapral C et al.", "journal": "Gastroenterology", "year": 1999, "pmid": "9869597", "url": "https://pubmed.ncbi.nlm.nih.gov/9869597/", "study_type": "RCT", "key_finding": "Cholylsarcosine (synthetic bile acid) increased fat absorption from 65.5 to 94.5 g/day (44% increment), demonstrating efficacy and safety of bile acid replacement.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9869597/", "publicSourceType": "PMID" }, { "claim": "TUDCA bile salt use after cholecystectomy for digestive support", "title": "Rationale for the use of bile salts after cholecystectomy: results of a controlled clinical study using tauroursodeoxycholic acid (TUDCA)", "authors": "Not specified et al.", "journal": "Chir Ital", "year": 1994, "pmid": "8010582", "url": "https://pubmed.ncbi.nlm.nih.gov/8010582/", "study_type": "RCT", "key_finding": "Bile salt supplementation after cholecystectomy improves dyspeptic symptoms caused by altered bile composition following gallbladder removal.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8010582/", "publicSourceType": "PMID" }, { "text": "Dening TJ, Napolitano JG, Ochoa JL et al.. Characterization of macrocyclic peptide drug interactions with bile salts and biorelevant colloids via single amino acid mutations and (1)H nuclear magnetic resonance (NMR) spectroscopy. Journal of pharmaceutical sciences. 2025", "claim": "PubMed-indexed evidence involving Ox Bile", "title": "Characterization of macrocyclic peptide drug interactions with bile salts and biorelevant colloids via single amino acid mutations and (1)H nuclear magnetic resonance (NMR) spectroscopy", "authors": "Dening TJ, Napolitano JG, Ochoa JL et al.", "journal": "Journal of pharmaceutical sciences", "year": 2025, "pmid": "39454943", "url": "https://pubmed.ncbi.nlm.nih.gov/39454943/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.xphs.2024.10.021", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39454943/", "publicSourceType": "PMID" }, { "text": "Hossain S, Kneiszl R, Larsson P. Revealing the interaction between peptide drugs and permeation enhancers in the presence of intestinal bile salts. Nanoscale. 2023", "claim": "PubMed-indexed evidence involving Ox Bile", "title": "Revealing the interaction between peptide drugs and permeation enhancers in the presence of intestinal bile salts", "authors": "Hossain S, Kneiszl R, Larsson P", "journal": "Nanoscale", "year": 2023, "pmid": "37982184", "url": "https://pubmed.ncbi.nlm.nih.gov/37982184/", "study_type": "review", "confidence": "verify", "doi": "10.1039/d3nr05571j", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37982184/", "publicSourceType": "PMID" }, { "text": "Massa M, Compari C, Fisicaro E. On the mechanism of the cholesterol lowering ability of soluble dietary fibers: Interaction of some bile salts with pectin, alginate, and chitosan studied by isothermal titration calorimetry. Frontiers in nutrition. 2022", "claim": "PubMed-indexed evidence involving Ox Bile", "title": "On the mechanism of the cholesterol lowering ability of soluble dietary fibers: Interaction of some bile salts with pectin, alginate, and chitosan studied by isothermal titration calorimetry", "authors": "Massa M, Compari C, Fisicaro E", "journal": "Frontiers in nutrition", "year": 2022, "pmid": "36245485", "url": "https://pubmed.ncbi.nlm.nih.gov/36245485/", "study_type": "review", "confidence": "verify", "doi": "10.3389/fnut.2022.968847", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36245485/", "publicSourceType": "PMID" }, { "text": "Guruge AG, Warren DB, Pouton CW et al.. Molecular Dynamics Simulation Studies of Bile, Bile Salts, Lipid-Based Drug Formulations, and mRNA-Lipid Nanoparticles: A Review. Molecular pharmaceutics. 2023", "claim": "PubMed-indexed evidence involving Ox Bile", "title": "Molecular Dynamics Simulation Studies of Bile, Bile Salts, Lipid-Based Drug Formulations, and mRNA-Lipid Nanoparticles: A Review", "authors": "Guruge AG, Warren DB, Pouton CW et al.", "journal": "Molecular pharmaceutics", "year": 2023, "pmid": "37194978", "url": "https://pubmed.ncbi.nlm.nih.gov/37194978/", "study_type": "review", "confidence": "verify", "doi": "10.1021/acs.molpharmaceut.3c00049", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37194978/", "publicSourceType": "PMID" }, { "text": "Fuentes J, Gregório SF, Fonseca F et al.. Effect of bile salts on intestinal epithelial function in gilthead seabream (Sparus aurata). Fish physiology and biochemistry. 2024", "claim": "PubMed-indexed evidence involving Ox Bile", "title": "Effect of bile salts on intestinal epithelial function in gilthead seabream (Sparus aurata)", "authors": "Fuentes J, Gregório SF, Fonseca F et al.", "journal": "Fish physiology and biochemistry", "year": 2024, "pmid": "38916718", "url": "https://pubmed.ncbi.nlm.nih.gov/38916718/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s10695-024-01369-8", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38916718/", "publicSourceType": "PMID" }, { "text": "Niu M, Tan Y, Guan P et al.. Enhanced oral absorption of insulin-loaded liposomes containing bile salts: a mechanistic study. International journal of pharmaceutics. 2014", "claim": "PubMed-indexed evidence involving Ox Bile", "title": "Enhanced oral absorption of insulin-loaded liposomes containing bile salts: a mechanistic study", "authors": "Niu M, Tan Y, Guan P et al.", "journal": "International journal of pharmaceutics", "year": 2014, "pmid": "24275447", "url": "https://pubmed.ncbi.nlm.nih.gov/24275447/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.ijpharm.2013.11.028", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24275447/", "publicSourceType": "PMID" }, { "text": "Garidel P, Hildebrand A, Knauf K et al.. Membranolytic activity of bile salts: influence of biological membrane properties and composition. Molecules (Basel, Switzerland). 2007", "claim": "PubMed-indexed evidence involving Ox Bile", "title": "Membranolytic activity of bile salts: influence of biological membrane properties and composition", "authors": "Garidel P, Hildebrand A, Knauf K et al.", "journal": "Molecules (Basel, Switzerland)", "year": 2007, "pmid": "17978759", "url": "https://pubmed.ncbi.nlm.nih.gov/17978759/", "study_type": "review", "confidence": "verify", "doi": "10.3390/12102292", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17978759/", "publicSourceType": "PMID" }, { "text": "Cahill CJ, Pain JA, Bailey ME. Bile salts, endotoxin and renal function in obstructive jaundice. Surgery, gynecology & obstetrics. 1987", "claim": "PubMed-indexed evidence involving Ox Bile", "title": "Bile salts, endotoxin and renal function in obstructive jaundice", "authors": "Cahill CJ, Pain JA, Bailey ME", "journal": "Surgery, gynecology & obstetrics", "year": 1987, "pmid": "3120329", "url": "https://pubmed.ncbi.nlm.nih.gov/3120329/", "study_type": "RCT", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3120329/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "ox-bile" }, { "id": "EF04A19C-DFEB-402A-AEB9-18D5B213F257", "name": "Methylcobalamin", "alternateNames": [ "Methyl-B12", "Active B12" ], "category": "Vitamin", "subcategory": "Active B12 Form", "overview": "The active, methylated coenzyme form of vitamin B12, bypasses conversion steps.", "mechanismOfAction": "Direct methyl donor for methionine synthase in the cytoplasm. Does not require reduction/methylation like cyanocobalamin. Critical for myelin synthesis and methylation.", "commonBenefits": [ "Methylation support", "Nerve health", "Energy", "MTHFR support" ], "commonDosageRange": "1,000-5,000 mcg sublingual daily", "recommendedForm": "Sublingual methylcobalamin (bypasses GI absorption issues)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Sublingual; dissolve under tongue for direct absorption" }, "evidenceRating": "strong", "foodSources": [ "Meat", "Fish", "Eggs", "Dairy" ], "deficiencySymptoms": [ "Same as B12 deficiency, fatigue, neuropathy, anemia" ], "sideEffects": [ "Very well tolerated", "Pink urine (harmless)" ], "contraindications": [ "Leber's disease" ], "iconName": "pill.fill", "colorHex": "FFB800", "tags": [ "methylation", "nerve", "energy", "mthfr" ], "sources": [ { "claim": "Meta-analysis of mecobalamin efficacy for peripheral neuropathy", "title": "Efficacy and Safety of Mecobalamin on Peripheral Neuropathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Zhang M et al.", "journal": "Front Pharmacol", "year": 2020, "pmid": "32716261", "url": "https://pubmed.ncbi.nlm.nih.gov/32716261/", "study_type": "meta-analysis", "key_finding": "Mecobalamin in combination is effective in improving clinical therapeutic efficacy and nerve conduction velocity for peripheral neuropathy; no serious adverse events reported.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32716261/", "publicSourceType": "PMID" }, { "claim": "Vitamin B12 supplementation improves neuropathy in diabetic patients", "title": "Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial", "authors": "Didangelos T et al.", "journal": "Nutrients", "year": 2021, "pmid": "33513879", "url": "https://pubmed.ncbi.nlm.nih.gov/33513879/", "study_type": "RCT", "key_finding": "Oral methylcobalamin (1 mg) for twelve months improved nerve conduction, sudomotor function, pain score, and quality of life in diabetic neuropathy.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33513879/", "publicSourceType": "PMID" }, { "claim": "Comparison of B12 forms - natural vs synthetic, MTHFR considerations", "title": "Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms", "authors": "Paul C et al.", "journal": "Integr Med (Encinitas)", "year": 2017, "pmid": "28223907", "url": "https://pubmed.ncbi.nlm.nih.gov/28223907/", "study_type": "review", "key_finding": "All supplemental B12 forms are reduced to core cobalamin then converted to active methylcobalamin and adenosylcobalamin intracellularly; bioavailability may be influenced by genetics.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28223907/", "publicSourceType": "PMID" }, { "claim": "Treatment of B12 deficiency - comparison of methylcobalamin, cyanocobalamin, hydroxocobalamin", "title": "Treatment of vitamin B12 deficiency-methylcobalamine? Cyancobalamine? Hydroxocobalamin?-clearing the confusion", "authors": "Paul C et al.", "journal": "Eur J Clin Nutr", "year": 2015, "pmid": "25117994", "url": "https://pubmed.ncbi.nlm.nih.gov/25117994/", "study_type": "review", "key_finding": "Three natural forms of vitamin B12 (methylcobalamin, adenosylcobalamin, hydroxocobalamin) are bioidentical to forms in human physiology; cyanocobalamin is synthetic requiring conversion steps.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25117994/", "publicSourceType": "PMID" }, { "claim": "B12 as treatment for peripheral neuropathic pain", "title": "B12 as a Treatment for Peripheral Neuropathic Pain: A Systematic Review", "authors": "Suh JH et al.", "journal": "Nutrients", "year": 2020, "pmid": "32722436", "url": "https://pubmed.ncbi.nlm.nih.gov/32722436/", "study_type": "review", "key_finding": "Level II evidence supports B12 for post-herpetic neuralgia and level III evidence for painful peripheral neuropathy treatment.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32722436/", "publicSourceType": "PMID" }, { "claim": "Sublingual methylcobalamin as effective as intramuscular cyanocobalamin in children", "title": "Sublingual methylcobalamin treatment is as effective as intramuscular and peroral cyanocobalamin in children age 0-3 years", "authors": "Yilmaz S et al.", "journal": "J Pediatr Hematol Oncol", "year": 2021, "pmid": "34871525", "url": "https://pubmed.ncbi.nlm.nih.gov/34871525/", "study_type": "RCT", "key_finding": "Sublingual methylcobalamin was as effective as oral and intramuscular cyanocobalamin in improving vitamin B12 levels in children, supporting sublingual delivery route.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34871525/", "publicSourceType": "PMID" }, { "text": "Lee CW, Jin JS, Kwon S et al.. Are herbal medicines alone or in combination for diabetic peripheral neuropathy more effective than methylcobalamin alone? A systematic review and meta-analysis. Complementary therapies in clinical practice. 2022", "pmid": "36007447", "doi": "10.1016/j.ctcp.2022.101657", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36007447/", "publicSourceType": "PMID" }, { "text": "Deng H, Yin J, Zhang J et al.. Meta-analysis of methylcobalamin alone and in combination with prostaglandin E1 in the treatment of diabetic peripheral neuropathy. Endocrine. 2014", "pmid": "24522613", "doi": "10.1007/s12020-014-0181-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24522613/", "publicSourceType": "PMID" }, { "text": "Sun X, Li X, Yang D. Efficacy and safety of mecobalamin combined with vestibular rehabilitation training for acute vestibular neuritis: a systematic review and meta-analysis. Annals of palliative medicine. 2022", "claim": "PubMed-indexed evidence involving Methylcobalamin", "title": "Efficacy and safety of mecobalamin combined with vestibular rehabilitation training for acute vestibular neuritis: a systematic review and meta-analysis", "authors": "Sun X, Li X, Yang D", "journal": "Annals of palliative medicine", "year": 2022, "pmid": "35249325", "url": "https://pubmed.ncbi.nlm.nih.gov/35249325/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.21037/apm-21-3171", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35249325/", "publicSourceType": "PMID" }, { "text": "Mai W, Wei A, Lin X et al.. Efficacy and safety of traditional Chinese medicine injection with mecobalamin in treating diabetic peripheral neuropathy: A protocol for systematic review and meta-analysis. Medicine. 2021", "claim": "PubMed-indexed evidence involving Methylcobalamin", "title": "Efficacy and safety of traditional Chinese medicine injection with mecobalamin in treating diabetic peripheral neuropathy: A protocol for systematic review and meta-analysis", "authors": "Mai W, Wei A, Lin X et al.", "journal": "Medicine", "year": 2021, "pmid": "33429738", "url": "https://pubmed.ncbi.nlm.nih.gov/33429738/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MD.0000000000023702", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33429738/", "publicSourceType": "PMID" }, { "text": "Yao J, Peng B, Gong X et al.. Efficacy and Safety of Mecobalamin Combined with Prokinetic Agents in the Treatment of Diabetic Gastroparesis: A Meta-Analysis. Iranian journal of public health. 2021", "claim": "PubMed-indexed evidence involving Methylcobalamin", "title": "Efficacy and Safety of Mecobalamin Combined with Prokinetic Agents in the Treatment of Diabetic Gastroparesis: A Meta-Analysis", "authors": "Yao J, Peng B, Gong X et al.", "journal": "Iranian journal of public health", "year": 2021, "pmid": "35223590", "url": "https://pubmed.ncbi.nlm.nih.gov/35223590/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.18502/ijph.v50i11.7570", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35223590/", "publicSourceType": "PMID" }, { "text": "Deng XL, Wu R, Lin XX et al.. Dapagliflozin combined with methylcobalamin in the treatment of type 2 diabetes mellitus with peripheral neuropathy: a systematic review and meta-analysis. Frontiers in endocrinology. 2025", "claim": "PubMed-indexed evidence involving Methylcobalamin", "title": "Dapagliflozin combined with methylcobalamin in the treatment of type 2 diabetes mellitus with peripheral neuropathy: a systematic review and meta-analysis", "authors": "Deng XL, Wu R, Lin XX et al.", "journal": "Frontiers in endocrinology", "year": 2025, "pmid": "40612436", "url": "https://pubmed.ncbi.nlm.nih.gov/40612436/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fendo.2025.1514783", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40612436/", "publicSourceType": "PMID" }, { "text": "Kaji R, Nishi Y, Ishida T et al.. Clinical safety of ultra-high-dose methylcobalamin in patients with amyotrophic lateral sclerosis: Open-label extension of a phase 2/3 randomized controlled study. Journal of the neurological sciences. 2026", "claim": "PubMed-indexed evidence involving Methylcobalamin", "title": "Clinical safety of ultra-high-dose methylcobalamin in patients with amyotrophic lateral sclerosis: Open-label extension of a phase 2/3 randomized controlled study", "authors": "Kaji R, Nishi Y, Ishida T et al.", "journal": "Journal of the neurological sciences", "year": 2026, "pmid": "41475066", "url": "https://pubmed.ncbi.nlm.nih.gov/41475066/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.jns.2025.125701", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41475066/", "publicSourceType": "PMID" }, { "text": "Zhang F, Yu Y, Yin S et al.. Is acupoint injection the optimal way to administer mecobalamin for diabetic peripheral neuropathy? A meta-analysis and trial sequential analysis. Frontiers in neurology. 2023", "claim": "PubMed-indexed evidence involving Methylcobalamin", "title": "Is acupoint injection the optimal way to administer mecobalamin for diabetic peripheral neuropathy? A meta-analysis and trial sequential analysis", "authors": "Zhang F, Yu Y, Yin S et al.", "journal": "Frontiers in neurology", "year": 2023, "pmid": "37920836", "url": "https://pubmed.ncbi.nlm.nih.gov/37920836/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fneur.2023.1186420", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37920836/", "publicSourceType": "PMID" }, { "text": "Zheng C, Ou W, Shen H et al.. Combined therapy of diabetic peripheral neuropathy with breviscapine and mecobalamin: a systematic review and a meta-analysis of Chinese studies. BioMed research international. 2015", "claim": "PubMed-indexed evidence involving Methylcobalamin", "title": "Combined therapy of diabetic peripheral neuropathy with breviscapine and mecobalamin: a systematic review and a meta-analysis of Chinese studies", "authors": "Zheng C, Ou W, Shen H et al.", "journal": "BioMed research international", "year": 2015, "pmid": "25866802", "url": "https://pubmed.ncbi.nlm.nih.gov/25866802/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1155/2015/680756", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25866802/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "methylcobalamin" }, { "id": "D487FBEB-5146-40C3-8B3F-CFF074245E0B", "name": "Artemisinin", "alternateNames": [ "Sweet Wormwood Extract", "Qinghaosu" ], "category": "Herb", "subcategory": "Antimalarial Herb", "overview": "Nobel Prize-winning compound from sweet wormwood with antimalarial and anticancer research.", "mechanismOfAction": "Endoperoxide bridge reacts with iron in parasites/cancer cells, generating cytotoxic free radicals. Selective toxicity to iron-rich cells.", "commonBenefits": [ "Antimalarial", "Anticancer research", "Anti-parasitic" ], "commonDosageRange": "100-200 mg daily (short courses only)", "recommendedForm": "Artemisinin extract or artemether", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with fat; short courses only (2-4 weeks)" }, "evidenceRating": "moderate", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "GI upset", "Dizziness", "Neurotoxicity with prolonged use" ], "contraindications": [ "Pregnancy", "Liver disease", "Iron supplements (timing)" ], "iconName": "cross.case.fill", "colorHex": "34D399", "tags": [ "antimalarial", "anti-parasitic" ], "sources": [ { "claim": "Discovery of artemisinin and Nobel Prize recognition", "title": "The discovery of artemisinin and the Nobel Prize in Physiology or Medicine", "authors": "Su XZ et al.", "journal": "Sci China Life Sci", "year": 2015, "pmid": "26481135", "url": "https://pubmed.ncbi.nlm.nih.gov/26481135/", "study_type": "review", "key_finding": "The 2015 Nobel Prize was awarded to Professor Youyou Tu for artemisinin discovery; the drug has saved millions of lives as antimalarial treatment.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26481135/", "publicSourceType": "PMID" }, { "claim": "Antimalarial mechanism of action via endoperoxide bridge and iron-mediated free radicals", "title": "Artemisinin antimalarials: mechanisms of action and resistance", "authors": "Meshnick SR et al.", "journal": "Parassitologia", "year": 1999, "pmid": "10212891", "url": "https://pubmed.ncbi.nlm.nih.gov/10212891/", "study_type": "review", "key_finding": "Artemisinin acts via two-step mechanism: first activated by intraparasitic heme-iron which cleaves the endoperoxide bridge, then the resulting free radical kills the parasite.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10212891/", "publicSourceType": "PMID" }, { "claim": "Comprehensive overview of artemisinin derivatives as anticancer agents", "title": "A comprehensive overview of Artemisinin and its derivatives as anticancer agents", "authors": "Ma Z et al.", "journal": "Eur J Med Chem", "year": 2023, "pmid": "36538859", "url": "https://pubmed.ncbi.nlm.nih.gov/36538859/", "study_type": "review", "key_finding": "Artemisinin derivatives show broad-spectrum antitumor activities via ROS production, cell cycle inhibition, apoptosis induction, and angiogenesis inhibition.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36538859/", "publicSourceType": "PMID" }, { "claim": "Clinical trials of artemisinin for anticancer therapy", "title": "Artemisinins as Anticancer Drugs: Novel Therapeutic Approaches, Molecular Mechanisms, and Clinical Trials", "authors": "Efferth T et al.", "journal": "Front Pharmacol", "year": 2020, "pmid": "33117153", "url": "https://pubmed.ncbi.nlm.nih.gov/33117153/", "study_type": "review", "key_finding": "Clinical trials provide encouraging evidence for artemisinin anticancer activity; safety studies show no evident toxicity and low adverse effects incidence.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33117153/", "publicSourceType": "PMID" }, { "claim": "Neurotoxicity of artemisinin compounds - primarily animal model concern", "title": "Artemisinin derivatives: toxic for laboratory animals, safe for humans?", "authors": "Toovey S et al.", "journal": "Toxicol Lett", "year": 2004, "pmid": "14757313", "url": "https://pubmed.ncbi.nlm.nih.gov/14757313/", "study_type": "review", "key_finding": "Artemisinin compounds show neurotoxicity in animal models at high parenteral doses but appear virtually void of serious side effects in humans; oral route has rapid clearance.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14757313/", "publicSourceType": "PMID" }, { "claim": "Safety and toxicity profile of artemisinin and derivatives", "title": "Toxicity of the antimalarial artemisinin and its dervatives", "authors": "Efferth T et al.", "journal": "Crit Rev Toxicol", "year": 2010, "pmid": "20158370", "url": "https://pubmed.ncbi.nlm.nih.gov/20158370/", "study_type": "review", "key_finding": "Large clinical studies did not show serious side effects, but paucity of large-scale trials means a definitive safety statement cannot yet be made for prolonged use.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20158370/", "publicSourceType": "PMID" }, { "text": "Saito M, McGready R, Tinto H et al.. Pregnancy outcomes after first-trimester treatment with artemisinin derivatives versus non-artemisinin antimalarials: a systematic review and individual patient data meta-analysis. Lancet (London, England). 2023", "pmid": "36442488", "doi": "10.1016/S0140-6736(22)01881-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36442488/", "publicSourceType": "PMID" }, { "text": "Ikram NKBK, Simonsen HT. A Review of Biotechnological Artemisinin Production in Plants. Frontiers in plant science. 2017", "pmid": "29187859", "doi": "10.3389/fpls.2017.01966", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29187859/", "publicSourceType": "PMID" }, { "claim": "Intramuscular artemether is more effective than quinine for treating severe malaria in adults", "title": "Artemether for severe malaria", "authors": "Esu EB, Effa EE, Opie ON, Meremikwu MM", "journal": "Cochrane Database Syst Rev", "year": 2019, "pmid": "31210357", "url": "https://pubmed.ncbi.nlm.nih.gov/31210357/", "study_type": "meta-analysis", "key_finding": "Cochrane review of 19 RCTs (2874 patients) found intramuscular artemether probably results in fewer deaths than quinine in adults (RR 0.59) and is as effective in children. Artemether is inferior to artesunate in adults.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31210357/", "publicSourceType": "PMID" }, { "claim": "Artemisinin-based combinations with praziquantel are effective for treating Schistosoma mansoni", "title": "Efficacy and safety of praziquantel plus artemisinin-based combinations versus praziquantel in the treatment of Kenyan children with Schistosoma mansoni infection: open-label, randomized, head-to-head, non-inferiority trial", "authors": "Obonyo CO, Were VO, Wamae P, Muok EMO", "journal": "Antimicrob Agents Chemother", "year": 2025, "pmid": "39699212", "url": "https://pubmed.ncbi.nlm.nih.gov/39699212/", "study_type": "rct", "key_finding": "RCT of 540 Kenyan children found praziquantel plus artesunate-mefloquine and praziquantel plus dihydroartemisinin-piperaquine were non-inferior to praziquantel alone for treating S. mansoni infection.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39699212/", "publicSourceType": "PMID" }, { "text": "Wang Q, Zou Y, Pan Z et al.. Efficacy and Safety of Artemisinin-Piperaquine for the Treatment of Uncomplicated Malaria: A Systematic Review. Frontiers in pharmacology. 2020", "claim": "PubMed-indexed evidence involving Artemisinin", "title": "Efficacy and Safety of Artemisinin-Piperaquine for the Treatment of Uncomplicated Malaria: A Systematic Review", "authors": "Wang Q, Zou Y, Pan Z et al.", "journal": "Frontiers in pharmacology", "year": 2020, "pmid": "33013398", "url": "https://pubmed.ncbi.nlm.nih.gov/33013398/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fphar.2020.562363", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33013398/", "publicSourceType": "PMID" }, { "text": "Visser BJ, Wieten RW, Kroon D et al.. Efficacy and safety of artemisinin combination therapy (ACT) for non-falciparum malaria: a systematic review. Malaria journal. 2014", "claim": "PubMed-indexed evidence involving Artemisinin", "title": "Efficacy and safety of artemisinin combination therapy (ACT) for non-falciparum malaria: a systematic review", "authors": "Visser BJ, Wieten RW, Kroon D et al.", "journal": "Malaria journal", "year": 2014, "pmid": "25428624", "url": "https://pubmed.ncbi.nlm.nih.gov/25428624/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/1475-2875-13-463", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25428624/", "publicSourceType": "PMID" }, { "text": "Mathenge PG, Low SK, Vuong NL et al.. Efficacy and resistance of different artemisinin-based combination therapies: a systematic review and network meta-analysis. Parasitology international. 2020", "claim": "PubMed-indexed evidence involving Artemisinin", "title": "Efficacy and resistance of different artemisinin-based combination therapies: a systematic review and network meta-analysis", "authors": "Mathenge PG, Low SK, Vuong NL et al.", "journal": "Parasitology international", "year": 2020, "pmid": "31015034", "url": "https://pubmed.ncbi.nlm.nih.gov/31015034/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.parint.2019.04.016", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31015034/", "publicSourceType": "PMID" }, { "text": "Pérez del Villar L, Burguillo FJ, López-Abán J et al.. Systematic review and meta-analysis of artemisinin based therapies for the treatment and prevention of schistosomiasis. PloS one. 2012", "claim": "PubMed-indexed evidence involving Artemisinin", "title": "Systematic review and meta-analysis of artemisinin based therapies for the treatment and prevention of schistosomiasis", "authors": "Pérez del Villar L, Burguillo FJ, López-Abán J et al.", "journal": "PloS one", "year": 2012, "pmid": "23029285", "url": "https://pubmed.ncbi.nlm.nih.gov/23029285/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1371/journal.pone.0045867", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23029285/", "publicSourceType": "PMID" }, { "text": "Li X, Feng J, Yuan Y et al.. Acute and subacute oral toxicity of artemisinin-hydroxychloroquine sulfate tablets in beagle dogs. Drug and chemical toxicology. 2023", "claim": "PubMed-indexed evidence involving Artemisinin", "title": "Acute and subacute oral toxicity of artemisinin-hydroxychloroquine sulfate tablets in beagle dogs", "authors": "Li X, Feng J, Yuan Y et al.", "journal": "Drug and chemical toxicology", "year": 2023, "pmid": "36039016", "url": "https://pubmed.ncbi.nlm.nih.gov/36039016/", "study_type": "review", "confidence": "verify", "doi": "10.1080/01480545.2022.2116645", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36039016/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "artemisinin" }, { "id": "46D9FBF6-E4EA-4C9E-9A4F-83ABAE87FC7D", "name": "Berberine HCl", "alternateNames": [ "Berberine Hydrochloride" ], "category": "Herb", "subcategory": "Metabolic Alkaloid", "overview": "Enhanced form of berberine with better bioavailability for metabolic support.", "mechanismOfAction": "Same as berberine, AMPK activation, mitochondrial Complex I inhibition. HCl salt form may offer improved dissolution.", "commonBenefits": [ "Blood sugar", "Cholesterol", "Gut health", "Weight management" ], "commonDosageRange": "500 mg 2-3x daily", "recommendedForm": "Berberine HCl or dihydroberberine (better bioavailability)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with meals" }, "evidenceRating": "strong", "foodSources": [ "Goldenseal", "Oregon grape", "Barberry" ], "deficiencySymptoms": [], "sideEffects": [ "GI upset", "Constipation", "Low blood sugar", "Clinically relevant drug interaction potential via CYP2D6, CYP2C9, CYP3A4, and P-glycoprotein inhibition", "Additive blood sugar or blood pressure lowering with related medications" ], "contraindications": [ "Metformin or other glucose-lowering medications unless clinician-supervised", "CYP2D6, CYP2C9, CYP3A4, or P-glycoprotein substrate medications unless clinician-supervised", "Cyclosporine, tacrolimus, digoxin, or narrow-therapeutic-index medications", "Pregnancy", "Infants" ], "iconName": "leaf.fill", "colorHex": "34D399", "tags": [ "blood-sugar", "metabolic", "cholesterol" ], "sources": [ { "claim": "Berberine significantly reduces blood glucose in type 2 diabetes - meta-analysis", "title": "Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis", "authors": "Pang B et al.", "journal": "J Ethnopharmacol", "year": 2022, "pmid": "36467075", "url": "https://pubmed.ncbi.nlm.nih.gov/36467075/", "study_type": "meta-analysis", "key_finding": "Berberine reduced FPG by 0.82 mmol/L, HbA1c by 0.63%, and 2hPBG by 1.16 mmol/L, all statistically significant in type 2 diabetes patients.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36467075/", "publicSourceType": "PMID" }, { "claim": "Berberine activates AMPK and inhibits lipid synthesis", "title": "Inhibition of lipid synthesis through activation of AMP kinase: an additional mechanism for the hypolipidemic effects of berberine", "authors": "Brusq JM et al.", "journal": "J Lipid Res", "year": 2006, "pmid": "16508037", "url": "https://pubmed.ncbi.nlm.nih.gov/16508037/", "study_type": "in_vitro", "key_finding": "Berberine inhibits lipid synthesis in human hepatocytes through AMPK activation, with increased fatty acid oxidation via phosphorylation of acetyl-CoA carboxylase.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16508037/", "publicSourceType": "PMID" }, { "claim": "Berberine reduces blood lipids in clinical meta-analysis", "title": "The effects of berberine on blood lipids: a systemic review and meta-analysis of randomized controlled trials", "authors": "Dong H et al.", "journal": "Planta Med", "year": 2013, "pmid": "23512497", "url": "https://pubmed.ncbi.nlm.nih.gov/23512497/", "study_type": "meta-analysis", "key_finding": "Berberine significantly reduced total cholesterol, triglycerides, and LDL cholesterol with a remarkable increase in HDL cholesterol.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23512497/", "publicSourceType": "PMID" }, { "claim": "Berberine modulates gut microbiota and reduces insulin resistance", "title": "Berberine Modulates Gut Microbiota and Reduces Insulin Resistance via the TLR4 Signaling Pathway", "authors": "Liu D et al.", "journal": "Exp Clin Endocrinol Diabetes", "year": 2018, "pmid": "29365334", "url": "https://pubmed.ncbi.nlm.nih.gov/29365334/", "study_type": "in_vivo", "key_finding": "Berberine reversed high-fat diet-induced gut microbiota changes by restoring Bifidobacterium and reducing E. coli; may reduce insulin resistance via LPS/TLR4/TNF-alpha inhibition.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29365334/", "publicSourceType": "PMID" }, { "claim": "Umbrella review of berberine health outcomes - safety and efficacy", "title": "Berberine and health outcomes: An umbrella review", "authors": "Asbaghi O et al.", "journal": "Food Chem Toxicol", "year": 2023, "pmid": "36999891", "url": "https://pubmed.ncbi.nlm.nih.gov/36999891/", "study_type": "meta-analysis", "key_finding": "Umbrella review confirms berberine's benefits for metabolic parameters with generally favorable safety profile; no severe adverse effects reported in clinical trials.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36999891/", "publicSourceType": "PMID" }, { "claim": "Berberine reduces body weight and BMI in meta-analysis", "title": "The effect of berberine supplementation on obesity parameters, inflammation and liver function enzymes: A systematic review and meta-analysis of randomized controlled trials", "authors": "Asbaghi O et al.", "journal": "Clin Exp Pharmacol Physiol", "year": 2020, "pmid": "32690176", "url": "https://pubmed.ncbi.nlm.nih.gov/32690176/", "study_type": "meta-analysis", "key_finding": "Berberine supplementation significantly reduced body weight (average 2.07 kg), BMI (0.47 kg/m2), and waist circumference (1.08 cm) across RCTs.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32690176/", "publicSourceType": "PMID" }, { "claim": "Berberine activates AMPK with beneficial metabolic effects", "title": "Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states", "authors": "Lee YS et al.", "journal": "Diabetes", "year": 2006, "pmid": "16873688", "url": "https://pubmed.ncbi.nlm.nih.gov/16873688/", "study_type": "in_vivo", "key_finding": "Berberine activates AMPK with beneficial effects in diabetic and insulin-resistant states; upregulates fatty acid oxidation genes and downregulates lipogenesis genes.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16873688/", "publicSourceType": "PMID" }, { "text": "Zhang Y, Wang J, Hou D et al.. To assess the effective and safety of berberine hydrochloride in ulcerative colitis: A protocol for systematic review and meta-analysis. Medicine. 2020", "pmid": "33285751", "doi": "10.1097/MD.0000000000023482", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33285751/", "publicSourceType": "PMID" }, { "text": "Chen C, Tao C, Liu Z et al.. A Randomized Clinical Trial of Berberine Hydrochloride in Patients with Diarrhea-Predominant Irritable Bowel Syndrome. Phytotherapy research : PTR. 2015", "pmid": "26400188", "doi": "10.1002/ptr.5475", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26400188/", "publicSourceType": "PMID" }, { "text": "Chen XX, Chen YX, Bi HX et al.. Efficacy and safety of triple therapy containing berberine hydrochloride, amoxicillin, and rabeprazole in the eradication of Helicobacter pylori. Journal of digestive diseases. 2022", "claim": "PubMed-indexed evidence involving Berberine HCl", "title": "Efficacy and safety of triple therapy containing berberine hydrochloride, amoxicillin, and rabeprazole in the eradication of Helicobacter pylori", "authors": "Chen XX, Chen YX, Bi HX et al.", "journal": "Journal of digestive diseases", "year": 2022, "pmid": "36415112", "url": "https://pubmed.ncbi.nlm.nih.gov/36415112/", "study_type": "review", "confidence": "verify", "doi": "10.1111/1751-2980.13146", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36415112/", "publicSourceType": "PMID" }, { "text": "Liu F, Liang HL, Xu KH et al.. Supramolecular interaction of ethylenediamine linked beta-cyclodextrin dimer and berberine hydrochloride by spectrofluorimetry and its analytical application. Talanta. 2007", "claim": "PubMed-indexed evidence involving Berberine HCl", "title": "Supramolecular interaction of ethylenediamine linked beta-cyclodextrin dimer and berberine hydrochloride by spectrofluorimetry and its analytical application", "authors": "Liu F, Liang HL, Xu KH et al.", "journal": "Talanta", "year": 2007, "pmid": "18371623", "url": "https://pubmed.ncbi.nlm.nih.gov/18371623/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.talanta.2007.05.048", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18371623/", "publicSourceType": "PMID" }, { "text": "Wang Y, Li H, Cui Y et al.. Enhancing food system protection: synergistic action of engineered endolysin LYSMP and berberine hydrochloride against Streptococcus suis on pork. Food research international (Ottawa, Ont.). 2025", "claim": "PubMed-indexed evidence involving Berberine HCl", "title": "Enhancing food system protection: synergistic action of engineered endolysin LYSMP and berberine hydrochloride against Streptococcus suis on pork", "authors": "Wang Y, Li H, Cui Y et al.", "journal": "Food research international (Ottawa, Ont.)", "year": 2025, "pmid": "41606938", "url": "https://pubmed.ncbi.nlm.nih.gov/41606938/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.foodres.2025.117214", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41606938/", "publicSourceType": "PMID" }, { "text": "Duan Y, Xu P, Ge P et al.. NIR-responsive carrier-free nanoparticles based on berberine hydrochloride and indocyanine green for synergistic antibacterial therapy and promoting infected wound healing. Regenerative biomaterials. 2023", "claim": "PubMed-indexed evidence involving Berberine HCl", "title": "NIR-responsive carrier-free nanoparticles based on berberine hydrochloride and indocyanine green for synergistic antibacterial therapy and promoting infected wound healing", "authors": "Duan Y, Xu P, Ge P et al.", "journal": "Regenerative biomaterials", "year": 2023, "pmid": "37808956", "url": "https://pubmed.ncbi.nlm.nih.gov/37808956/", "study_type": "review", "confidence": "verify", "doi": "10.1093/rb/rbad076", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37808956/", "publicSourceType": "PMID" }, { "claim": "Repeated berberine administration inhibits multiple CYP enzymes in humans", "title": "Repeated administration of berberine inhibits cytochromes P450 in humans", "authors": "Guo Y et al.", "journal": "European Journal of Clinical Pharmacology", "year": 2012, "pmid": "21870106", "url": "https://pubmed.ncbi.nlm.nih.gov/21870106/", "study_type": "clinical_trial", "key_finding": "Human study found repeated berberine administration inhibited CYP2D6, CYP2C9, and CYP3A4 activity.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21870106/", "publicSourceType": "PMID" }, { "claim": "Berberine increases cyclosporine exposure, supporting P-gp/CYP interaction cautions", "title": "Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study", "authors": "Wu X, Li Q, Xin H, Yu A, Zhong M", "journal": "European Journal of Clinical Pharmacology", "year": 2005, "pmid": "16133554", "url": "https://pubmed.ncbi.nlm.nih.gov/16133554/", "study_type": "clinical_trial", "key_finding": "Clinical pharmacokinetic study found berberine increased cyclosporine exposure in renal transplant recipients.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16133554/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "berberine-hcl" }, { "id": "85F988B7-3432-462D-B989-30D5759E4EFB", "name": "Magnesium Citrate", "alternateNames": [ "Mg Citrate" ], "category": "Mineral", "subcategory": "Magnesium Form", "overview": "Well-absorbed magnesium form with mild laxative properties.", "mechanismOfAction": "Citrate chelation increases solubility at intestinal pH. Absorbed via TRPM6/7 channels. Osmotic effect draws water into intestines, supporting bowel regularity.", "commonBenefits": [ "Magnesium supplementation", "Constipation relief", "Muscle relaxation" ], "commonDosageRange": "200-350 mg elemental magnesium daily", "recommendedForm": "Magnesium citrate powder or capsules", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food to reduce GI effects; evening preferred" }, "evidenceRating": "strong", "foodSources": [ "Same as other magnesium forms" ], "deficiencySymptoms": [ "Same as magnesium deficiency" ], "sideEffects": [ "Loose stools", "Diarrhea (feature for some, bug for others)" ], "contraindications": [ "Kidney disease", "Heart block" ], "iconName": "pills.fill", "colorHex": "4DD4E6", "tags": [ "magnesium", "constipation", "mineral" ], "sources": [ { "claim": "Magnesium citrate has superior bioavailability compared to magnesium oxide", "title": "Mg citrate found more bioavailable than other Mg preparations in a randomised, double-blind study", "authors": "Walker AF et al.", "journal": "Magnes Res", "year": 2003, "pmid": "14596323", "url": "https://pubmed.ncbi.nlm.nih.gov/14596323/", "study_type": "RCT", "key_finding": "Magnesium citrate led to the greatest mean serum magnesium concentration compared to other treatments following both acute and chronic supplementation.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14596323/", "publicSourceType": "PMID" }, { "claim": "Magnesium citrate more bioavailable than magnesium oxide in absorption study", "title": "Magnesium bioavailability from magnesium citrate and magnesium oxide", "authors": "Lindberg JS et al.", "journal": "J Am Coll Nutr", "year": 1990, "pmid": "2407766", "url": "https://pubmed.ncbi.nlm.nih.gov/2407766/", "study_type": "RCT", "key_finding": "Magnesium citrate was more soluble and bioavailable than magnesium oxide as measured by urinary magnesium excretion.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2407766/", "publicSourceType": "PMID" }, { "claim": "Systematic review of bioavailability of magnesium food supplements", "title": "Bioavailability of magnesium food supplements: A systematic review", "authors": "Uysal N et al.", "journal": "Nutrition", "year": 2021, "pmid": "34111673", "url": "https://pubmed.ncbi.nlm.nih.gov/34111673/", "study_type": "review", "key_finding": "Inorganic magnesium formulations are less bioavailable than organic ones; organic forms (citrate, amino-acid chelate) showed greater absorption at 60 days than oxide.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34111673/", "publicSourceType": "PMID" }, { "claim": "Magnesium supplementation and health outcomes umbrella review", "title": "Magnesium and health outcomes: an umbrella review of systematic reviews and meta-analyses of observational and intervention studies", "authors": "Veronese N et al.", "journal": "Eur J Nutr", "year": 2019, "pmid": "30684032", "url": "https://pubmed.ncbi.nlm.nih.gov/30684032/", "study_type": "meta-analysis", "key_finding": "Strong evidence that magnesium supplementation decreases risk of hospitalization in pregnant women and reduces migraine intensity/frequency; beneficial for blood pressure.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30684032/", "publicSourceType": "PMID" }, { "claim": "Senna and magnesium oxide effective for chronic constipation in RCT", "title": "Senna Versus Magnesium Oxide for the Treatment of Chronic Constipation: A Randomized, Placebo-Controlled Trial", "authors": "Morishita D et al.", "journal": "Am J Gastroenterol", "year": 2020, "pmid": "32969946", "url": "https://pubmed.ncbi.nlm.nih.gov/32969946/", "study_type": "RCT", "key_finding": "Magnesium oxide significantly improved bowel movement frequency and quality of life in chronic constipation (68.3% response rate vs 11.7% placebo).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32969946/", "publicSourceType": "PMID" }, { "claim": "Magnesium supplementation lowers blood pressure in hypertensive populations", "title": "Effect of magnesium supplementation on blood pressure: a meta-analysis", "authors": "Kass L et al.", "journal": "Eur J Clin Nutr", "year": 2012, "pmid": "22318649", "url": "https://pubmed.ncbi.nlm.nih.gov/22318649/", "study_type": "meta-analysis", "key_finding": "Combining trials showed magnesium supplementation decreases systolic blood pressure by 3-4 mmHg and diastolic by 2-3 mmHg in hypertensive populations.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22318649/", "publicSourceType": "PMID" }, { "text": "Schutten JC, Joris PJ, Groendijk I et al.. Effects of Magnesium Citrate, Magnesium Oxide, and Magnesium Sulfate Supplementation on Arterial Stiffness: A Randomized, Double-Blind, Placebo-Controlled Intervention Trial. Journal of the American Heart Association. 2022", "pmid": "35253448", "doi": "10.1161/JAHA.121.021783", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35253448/", "publicSourceType": "PMID" }, { "text": "Afitska K, Clavel J, Kisters K et al.. Magnesium citrate supplementation decreased blood pressure and HbA1c in normomagnesemic subjects with metabolic syndrome: a 12-week, placebo-controlled, double-blinded pilot trial. Magnesium research. 2021", "pmid": "34859788", "doi": "10.1684/mrh.2021.0489", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34859788/", "publicSourceType": "PMID" }, { "text": "Dziechciarz P, Ruszczyński M, Horvath A. Sodium Picosulphate with Magnesium Citrate versus Polyethylene Glycol for Bowel Preparation in Children: A Systematic Review. Pediatric gastroenterology, hepatology & nutrition. 2022", "claim": "PubMed-indexed evidence involving Magnesium Citrate", "title": "Sodium Picosulphate with Magnesium Citrate versus Polyethylene Glycol for Bowel Preparation in Children: A Systematic Review", "authors": "Dziechciarz P, Ruszczyński M, Horvath A", "journal": "Pediatric gastroenterology, hepatology & nutrition", "year": 2022, "pmid": "35611374", "url": "https://pubmed.ncbi.nlm.nih.gov/35611374/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.5223/pghn.2022.25.3.228", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35611374/", "publicSourceType": "PMID" }, { "text": "Mathus-Vliegen EMH, van der Vliet K, Wignand-van der Storm IJ et al.. Efficacy and Safety of Sodium Picosulfate/Magnesium Citrate for Bowel Preparation in a Physically Disabled Outpatient Population: A Randomized, Endoscopist-Blinded Comparison With Ascorbic Acid-Enriched Polyethylene Glycol Solution Plus Bisacodyl (The PICO-MOVI Study). Diseases of the colon and rectum. 2018", "claim": "PubMed-indexed evidence involving Magnesium Citrate", "title": "Efficacy and Safety of Sodium Picosulfate/Magnesium Citrate for Bowel Preparation in a Physically Disabled Outpatient Population: A Randomized, Endoscopist-Blinded Comparison With Ascorbic Acid-Enriched Polyethylene Glycol Solution Plus Bisacodyl (The PICO-MOVI Study)", "authors": "Mathus-Vliegen EMH, van der Vliet K, Wignand-van der Storm IJ et al.", "journal": "Diseases of the colon and rectum", "year": 2018, "pmid": "29337780", "url": "https://pubmed.ncbi.nlm.nih.gov/29337780/", "study_type": "RCT", "confidence": "verify", "doi": "10.1097/DCR.0000000000000956", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29337780/", "publicSourceType": "PMID" }, { "text": "Vermeulen EA, Eelderink C, Hoekstra T et al.. Reversal Of Arterial Disease by modulating Magnesium and Phosphate (ROADMAP-study): rationale and design of a randomized controlled trial assessing the effects of magnesium citrate supplementation and phosphate-binding therapy on arterial stiffness in moderate chronic kidney disease. Trials. 2022", "claim": "PubMed-indexed evidence involving Magnesium Citrate", "title": "Reversal Of Arterial Disease by modulating Magnesium and Phosphate (ROADMAP-study): rationale and design of a randomized controlled trial assessing the effects of magnesium citrate supplementation and phosphate-binding therapy on arterial stiffness in moderate chronic kidney disease", "authors": "Vermeulen EA, Eelderink C, Hoekstra T et al.", "journal": "Trials", "year": 2022, "pmid": "36096824", "url": "https://pubmed.ncbi.nlm.nih.gov/36096824/", "study_type": "RCT", "confidence": "verify", "doi": "10.1186/s13063-022-06562-9", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36096824/", "publicSourceType": "PMID" }, { "text": "Schutten JC, Joris PJ, Mensink RP et al.. Effects of magnesium citrate, magnesium oxide and magnesium sulfate supplementation on arterial stiffness in healthy overweight individuals: a study protocol for a randomized controlled trial. Trials. 2019", "claim": "PubMed-indexed evidence involving Magnesium Citrate", "title": "Effects of magnesium citrate, magnesium oxide and magnesium sulfate supplementation on arterial stiffness in healthy overweight individuals: a study protocol for a randomized controlled trial", "authors": "Schutten JC, Joris PJ, Mensink RP et al.", "journal": "Trials", "year": 2019, "pmid": "31138315", "url": "https://pubmed.ncbi.nlm.nih.gov/31138315/", "study_type": "RCT", "confidence": "verify", "doi": "10.1186/s13063-019-3414-4", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31138315/", "publicSourceType": "PMID" }, { "text": "Ninomiya K, Yao K, Matsui T et al.. Effectiveness of magnesium citrate as preparation for capsule endoscopy: a randomized, prospective, open-label, inter-group trial. Digestion. 2012", "claim": "PubMed-indexed evidence involving Magnesium Citrate", "title": "Effectiveness of magnesium citrate as preparation for capsule endoscopy: a randomized, prospective, open-label, inter-group trial", "authors": "Ninomiya K, Yao K, Matsui T et al.", "journal": "Digestion", "year": 2012, "pmid": "22710397", "url": "https://pubmed.ncbi.nlm.nih.gov/22710397/", "study_type": "RCT", "confidence": "verify", "doi": "10.1159/000337937", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22710397/", "publicSourceType": "PMID" }, { "text": "Liu FX, Wang L, Yan WJ et al.. Cleansing efficacy and safety of bowel preparation protocol using sodium picosulfate/magnesium citrate considering subjective experiences: An observational study. World journal of clinical cases. 2021", "claim": "PubMed-indexed evidence involving Magnesium Citrate", "title": "Cleansing efficacy and safety of bowel preparation protocol using sodium picosulfate/magnesium citrate considering subjective experiences: An observational study", "authors": "Liu FX, Wang L, Yan WJ et al.", "journal": "World journal of clinical cases", "year": 2021, "pmid": "34046458", "url": "https://pubmed.ncbi.nlm.nih.gov/34046458/", "study_type": "review", "confidence": "verify", "doi": "10.12998/wjcc.v9.i15.3586", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34046458/", "publicSourceType": "PMID" }, { "text": "de Miranda Neto AA, de Moura DTH, Hathorn KE et al.. Efficacy and Patient Tolerability of Split-Dose Sodium Picosulfate/Magnesium Citrate (SPMC) Oral Solution Compared to the Polyethylene Glycol (PEG) Solution for Bowel Preparation in Outpatient Colonoscopy: An Evidence-Based Review. Clinical and experimental gastroenterology. 2020", "claim": "PubMed-indexed evidence involving Magnesium Citrate", "title": "Efficacy and Patient Tolerability of Split-Dose Sodium Picosulfate/Magnesium Citrate (SPMC) Oral Solution Compared to the Polyethylene Glycol (PEG) Solution for Bowel Preparation in Outpatient Colonoscopy: An Evidence-Based Review", "authors": "de Miranda Neto AA, de Moura DTH, Hathorn KE et al.", "journal": "Clinical and experimental gastroenterology", "year": 2020, "pmid": "33116741", "url": "https://pubmed.ncbi.nlm.nih.gov/33116741/", "study_type": "review", "confidence": "verify", "doi": "10.2147/CEG.S237649", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33116741/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "magnesium-citrate" }, { "id": "DE99E2C7-ED18-4751-9DB3-9323ECB3ED53", "name": "Magnesium Taurate", "alternateNames": [ "Mg Taurate" ], "category": "Mineral", "subcategory": "Magnesium Form", "overview": "Magnesium chelated with taurine, specifically targeted for cardiovascular support.", "mechanismOfAction": "Combines cardiovascular benefits of both magnesium and taurine. Magnesium regulates cardiac ion channels; taurine stabilizes cell membranes and modulates calcium handling in cardiomyocytes.", "commonBenefits": [ "Heart health", "Blood pressure", "Arrhythmia support" ], "commonDosageRange": "200-350 mg elemental magnesium daily", "recommendedForm": "Magnesium taurate capsules", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food; evening preferred" }, "evidenceRating": "moderate", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Well tolerated", "Less laxative effect than citrate" ], "contraindications": [ "Kidney disease", "Heart block" ], "iconName": "heart.fill", "colorHex": "4DD4E6", "tags": [ "magnesium", "heart", "blood-pressure" ], "sources": [ { "claim": "Complementary vascular-protective actions of magnesium and taurine for cardiovascular support", "title": "Complementary vascular-protective actions of magnesium and taurine: a rationale for magnesium taurate", "authors": "McCarty MF", "journal": "Med Hypotheses", "year": 1996, "pmid": "8692051", "url": "https://pubmed.ncbi.nlm.nih.gov/8692051/", "study_type": "review", "key_finding": "Taurine lowers blood pressure, retards atherogenesis, prevents arrhythmias, and stabilizes platelets -- effects parallel to magnesium; combined magnesium taurate has considerable cardiovascular protective potential.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8692051/", "publicSourceType": "PMID" }, { "claim": "Magnesium taurate attenuates hypertension and cardiotoxicity in animal model", "title": "Magnesium taurate attenuates progression of hypertension and cardiotoxicity against cadmium chloride-induced hypertensive albino rats", "authors": "Shrivastava P et al.", "journal": "J Tradit Complement Med", "year": 2019, "pmid": "31025012", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6435948/", "study_type": "animal_study", "key_finding": "Magnesium taurate significantly restored blood pressure and myocardial antioxidants, demonstrating antihypertensive and cardioprotective activity via potent antioxidant mechanisms.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6435948/", "publicSourceType": "PMID" }, { "claim": "Magnesium acetyl taurate has superior brain bioavailability among magnesium forms", "title": "Timeline (Bioavailability) of Magnesium Compounds in Hours: Which Magnesium Compound Works Best?", "authors": "Uysal N et al.", "journal": "Biol Trace Elem Res", "year": 2019, "pmid": "29679349", "url": "https://pubmed.ncbi.nlm.nih.gov/29679349/", "study_type": "animal_study", "key_finding": "Magnesium acetyl taurate was rapidly absorbed, easily passed through to the brain, and had the highest tissue concentration level in the brain among five magnesium forms tested.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29679349/", "publicSourceType": "PMID" }, { "claim": "Taurine and magnesium supplementation enhances endothelial progenitor cell function through antioxidation", "title": "Taurine and magnesium supplementation enhances the function of endothelial progenitor cells through antioxidation in healthy men and spontaneously hypertensive rats", "authors": "Katakawa M et al.", "journal": "Hypertens Res", "year": 2016, "pmid": "27412799", "url": "https://pubmed.ncbi.nlm.nih.gov/27412799/", "study_type": "RCT", "key_finding": "Taurine and magnesium supplementation increased endothelial progenitor cell colony formation in healthy men and improved impaired EPC function in hypertensive rats through antioxidation.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27412799/", "publicSourceType": "PMID" }, { "claim": "Magnesium supplementation reduces blood pressure in meta-analysis", "title": "Effects of Magnesium Supplementation on Blood Pressure: A Meta-Analysis of Randomized Double-Blind Placebo-Controlled Trials", "authors": "Zhang X et al.", "journal": "Hypertension", "year": 2016, "pmid": "27402922", "url": "https://pubmed.ncbi.nlm.nih.gov/27402922/", "study_type": "meta-analysis", "key_finding": "Magnesium supplementation significantly reduces systolic and diastolic blood pressure, with greater effects at doses of 300 mg/day or more.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27402922/", "publicSourceType": "PMID" }, { "claim": "Magnesium taurate has less laxative effect and is well tolerated", "title": "Dose-Dependent Absorption Profile of Different Magnesium Compounds", "authors": "Uysal N et al.", "journal": "Biol Trace Elem Res", "year": 2019, "pmid": "30761462", "url": "https://pubmed.ncbi.nlm.nih.gov/30761462/", "study_type": "animal_study", "key_finding": "Brain magnesium levels were increased in all magnesium acetyl taurate administered subjects; organic magnesium compounds like taurate have better absorption than inorganic compounds.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30761462/", "publicSourceType": "PMID" }, { "text": "An MY, Sun K, Li Y et al.. Therapeutic effects of a taurine-magnesium coordination compound on experimental models of type 2 short QT syndrome. Acta pharmacologica Sinica. 2018", "claim": "PubMed-indexed evidence involving Magnesium Taurate", "title": "Therapeutic effects of a taurine-magnesium coordination compound on experimental models of type 2 short QT syndrome", "authors": "An MY, Sun K, Li Y et al.", "journal": "Acta pharmacologica Sinica", "year": 2018, "pmid": "29072257", "url": "https://pubmed.ncbi.nlm.nih.gov/29072257/", "study_type": "review", "confidence": "verify", "doi": "10.1038/aps.2017.86", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29072257/", "publicSourceType": "PMID" }, { "text": "McCarty MF. Magnesium taurate and fish oil for prevention of migraine. Medical hypotheses. 1996", "claim": "PubMed-indexed evidence involving Magnesium Taurate", "title": "Magnesium taurate and fish oil for prevention of migraine", "authors": "McCarty MF", "journal": "Medical hypotheses", "year": 1996, "pmid": "8961243", "url": "https://pubmed.ncbi.nlm.nih.gov/8961243/", "study_type": "review", "confidence": "verify", "doi": "10.1016/s0306-9877(96)90158-9", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8961243/", "publicSourceType": "PMID" }, { "text": "Argeros Z, Xu X, Bhandari B et al.. Magnesium Supplementation and Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Hypertension (Dallas, Tex. : 1979). 2025", "claim": "PubMed-indexed evidence involving Magnesium Taurate", "title": "Magnesium Supplementation and Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Argeros Z, Xu X, Bhandari B et al.", "journal": "Hypertension (Dallas, Tex. : 1979)", "year": 2025, "pmid": "41000008", "url": "https://pubmed.ncbi.nlm.nih.gov/41000008/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1161/HYPERTENSIONAHA.125.25129", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41000008/", "publicSourceType": "PMID" }, { "text": "Moabedi M, Aliakbari M, Erfanian S et al.. Magnesium supplementation beneficially affects depression in adults with depressive disorder: a systematic review and meta-analysis of randomized clinical trials. Frontiers in psychiatry. 2023", "claim": "PubMed-indexed evidence involving Magnesium Taurate", "title": "Magnesium supplementation beneficially affects depression in adults with depressive disorder: a systematic review and meta-analysis of randomized clinical trials", "authors": "Moabedi M, Aliakbari M, Erfanian S et al.", "journal": "Frontiers in psychiatry", "year": 2023, "pmid": "38213402", "url": "https://pubmed.ncbi.nlm.nih.gov/38213402/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fpsyt.2023.1333261", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38213402/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "magnesium-taurate" }, { "id": "396BE4A0-351F-4F05-88BE-AD3499870CC9", "name": "Magnesium Malate", "alternateNames": [ "Mg Malate" ], "category": "Mineral", "subcategory": "Magnesium Form", "overview": "Magnesium combined with malic acid, targeted for energy and fibromyalgia support.", "mechanismOfAction": "Malic acid is a Krebs cycle intermediate that supports ATP production. Magnesium is a cofactor for >300 enzymes including those in energy metabolism.", "commonBenefits": [ "Energy production", "Fibromyalgia support", "Muscle pain" ], "commonDosageRange": "200-350 mg elemental magnesium daily", "recommendedForm": "Magnesium malate capsules or powder", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food; morning preferred for energy benefits" }, "evidenceRating": "moderate", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Well tolerated", "Mild laxative effect" ], "contraindications": [ "Kidney disease" ], "iconName": "bolt.fill", "colorHex": "4DD4E6", "tags": [ "magnesium", "energy", "fibromyalgia" ], "sources": [ { "claim": "Magnesium malate (Super Malic) for fibromyalgia treatment in RCT", "title": "Treatment of fibromyalgia syndrome with Super Malic: a randomized, double blind, placebo controlled, crossover pilot study", "authors": "Russell IJ et al.", "journal": "J Rheumatol", "year": 1995, "pmid": "8587088", "url": "https://pubmed.ncbi.nlm.nih.gov/8587088/", "study_type": "RCT", "key_finding": "Super Malic (malic acid + magnesium) showed positive trends for pain reduction in fibromyalgia in a randomized double-blind crossover pilot study of 24 patients.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8587088/", "publicSourceType": "PMID" }, { "claim": "Magnesium and fibromyalgia literature review supporting supplementation", "title": "Magnesium and Fibromyalgia: A Literature Review", "authors": "Boulis M, Boulis M, Clauw DJ", "journal": "J Prim Care Community Health", "year": 2021, "pmid": "34569339", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8371721/", "study_type": "review", "key_finding": "Seven systematic reviews identified supporting magnesium supplementation for fibromyalgia; serum magnesium levels were significantly lower in fibromyalgia patients with meaningful association between magnesium and fatigue.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8371721/", "publicSourceType": "PMID" }, { "claim": "Short-term magnesium therapy alleviates stress in fibromyalgia patients", "title": "Short-Term Magnesium Therapy Alleviates Moderate Stress in Patients with Fibromyalgia: A Randomized Double-Blind Clinical Trial", "authors": "Andretta A et al.", "journal": "Nutrients", "year": 2022, "pmid": "35631229", "url": "https://pubmed.ncbi.nlm.nih.gov/35631229/", "study_type": "RCT", "key_finding": "Pain severity diminished significantly (p=0.029) with magnesium supplementation in fibromyalgia patients in a 1-month RCT.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35631229/", "publicSourceType": "PMID" }, { "claim": "Magnesium is a cofactor for over 300 enzymes including those in energy metabolism", "title": "Magnesium in Prevention and Therapy", "authors": "Grober U, Schmidt J, Kisters K", "journal": "Nutrients", "year": 2015, "pmid": "26404370", "url": "https://pubmed.ncbi.nlm.nih.gov/26404370/", "study_type": "review", "key_finding": "Magnesium is a cofactor in more than 300 enzyme systems that regulate diverse biochemical reactions in the body, including energy production, protein synthesis, and muscle and nerve function.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26404370/", "publicSourceType": "PMID" }, { "claim": "Bioavailability comparison of magnesium forms including malate", "title": "Bioavailability of magnesium food supplements: A systematic review", "authors": "Ates M et al.", "journal": "Nutrition", "year": 2021, "pmid": "34111673", "url": "https://pubmed.ncbi.nlm.nih.gov/34111673/", "study_type": "review", "key_finding": "Organic magnesium formulations (including malate) appear to be more bioavailable than inorganic compounds, though percentage of absorption is dose dependent.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34111673/", "publicSourceType": "PMID" }, { "text": "EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS), Younes M, Aggett P et al.. Evaluation of di-magnesium malate, used as a novel food ingredient and as a source of magnesium in foods for the general population, food supplements, total diet replacement for weight control and food for special medical purposes. EFSA journal. European Food Safety Authority. 2018", "pmid": "32625931", "doi": "10.2903/j.efsa.2018.5292", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32625931/", "publicSourceType": "PMID" }, { "text": "Argeros Z, Xu X, Bhandari B et al.. Magnesium Supplementation and Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Hypertension (Dallas, Tex. : 1979). 2025", "claim": "PubMed-indexed evidence involving Magnesium Malate", "title": "Magnesium Supplementation and Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Argeros Z, Xu X, Bhandari B et al.", "journal": "Hypertension (Dallas, Tex. : 1979)", "year": 2025, "pmid": "41000008", "url": "https://pubmed.ncbi.nlm.nih.gov/41000008/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1161/HYPERTENSIONAHA.125.25129", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41000008/", "publicSourceType": "PMID" }, { "text": "Moabedi M, Aliakbari M, Erfanian S et al.. Magnesium supplementation beneficially affects depression in adults with depressive disorder: a systematic review and meta-analysis of randomized clinical trials. Frontiers in psychiatry. 2023", "claim": "PubMed-indexed evidence involving Magnesium Malate", "title": "Magnesium supplementation beneficially affects depression in adults with depressive disorder: a systematic review and meta-analysis of randomized clinical trials", "authors": "Moabedi M, Aliakbari M, Erfanian S et al.", "journal": "Frontiers in psychiatry", "year": 2023, "pmid": "38213402", "url": "https://pubmed.ncbi.nlm.nih.gov/38213402/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fpsyt.2023.1333261", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38213402/", "publicSourceType": "PMID" }, { "text": "Askari M, Mozaffari H, Jafari A et al.. The effects of magnesium supplementation on obesity measures in adults: a systematic review and dose-response meta-analysis of randomized controlled trials. Critical reviews in food science and nutrition. 2021", "claim": "PubMed-indexed evidence involving Magnesium Malate", "title": "The effects of magnesium supplementation on obesity measures in adults: a systematic review and dose-response meta-analysis of randomized controlled trials", "authors": "Askari M, Mozaffari H, Jafari A et al.", "journal": "Critical reviews in food science and nutrition", "year": 2021, "pmid": "32654500", "url": "https://pubmed.ncbi.nlm.nih.gov/32654500/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/10408398.2020.1790498", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32654500/", "publicSourceType": "PMID" }, { "text": "Veronese N, Dominguez LJ, Pizzol D et al.. Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials. Nutrients. 2021", "claim": "PubMed-indexed evidence involving Magnesium Malate", "title": "Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials", "authors": "Veronese N, Dominguez LJ, Pizzol D et al.", "journal": "Nutrients", "year": 2021, "pmid": "34836329", "url": "https://pubmed.ncbi.nlm.nih.gov/34836329/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/nu13114074", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34836329/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "magnesium-malate" }, { "id": "9E634B74-A28B-4B8B-BF99-893B8CDCCB81", "name": "Zinc Picolinate", "alternateNames": [ "Zn Picolinate" ], "category": "Mineral", "subcategory": "Zinc Form", "overview": "Highly bioavailable zinc form chelated with picolinic acid.", "mechanismOfAction": "Picolinic acid (a tryptophan metabolite) facilitates zinc transport across intestinal epithelium. Better absorbed than zinc oxide or sulfate.", "commonBenefits": [ "Immune support", "Skin health", "Testosterone support" ], "commonDosageRange": "15-30 mg daily", "recommendedForm": "Zinc picolinate capsules", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food to reduce nausea" }, "evidenceRating": "strong", "foodSources": [ "Same as zinc" ], "deficiencySymptoms": [ "Same as zinc deficiency" ], "sideEffects": [ "Nausea", "Metallic taste", "Copper depletion long-term" ], "contraindications": [ "Copper deficiency (supplement copper if >25mg/day)" ], "iconName": "shield.fill", "colorHex": "4DD4E6", "tags": [ "zinc", "immune", "skin" ], "sources": [ { "claim": "Zinc picolinate has superior absorption compared to zinc citrate and gluconate in humans", "title": "Comparative absorption of zinc picolinate, zinc citrate and zinc gluconate in humans", "authors": "Barrie SA et al.", "journal": "Agents Actions", "year": 1987, "pmid": "3630857", "url": "https://pubmed.ncbi.nlm.nih.gov/3630857/", "study_type": "RCT", "key_finding": "In a crossover trial of 15 healthy subjects given 50 mg elemental zinc for 4 weeks, zinc picolinate was the only form that significantly increased zinc levels in hair, urine, and erythrocytes versus placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3630857/", "publicSourceType": "PMID" }, { "claim": "Comparative bioavailability of various zinc forms in humans", "title": "Comparative Absorption and Bioavailability of Various Chemical Forms of Zinc in Humans: A Narrative Review", "authors": "Siepmann M et al.", "journal": "Nutrients", "year": 2024, "pmid": "39771025", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11677333/", "study_type": "review", "key_finding": "Comprehensive review comparing zinc picolinate, glycinate, citrate, gluconate, and oxide bioavailability in humans, noting picolinic acid facilitates zinc transport across intestinal epithelium.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11677333/", "publicSourceType": "PMID" }, { "claim": "Zinc supplementation supports testosterone levels", "title": "Correlation between serum zinc and testosterone: A systematic review", "authors": "Te L et al.", "journal": "J Trace Elem Med Biol", "year": 2023, "pmid": "36577241", "url": "https://pubmed.ncbi.nlm.nih.gov/36577241/", "study_type": "review", "key_finding": "Systematic review of 38 papers found zinc deficiency reduces testosterone levels and supplementation improves them; effect varies by dosage form, dose, and duration.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36577241/", "publicSourceType": "PMID" }, { "claim": "Zinc supplementation supports immune function", "title": "Role of zinc in health and disease", "authors": "Pal A et al.", "journal": "Clin Exp Med", "year": 2024, "pmid": "38367035", "url": "https://pubmed.ncbi.nlm.nih.gov/38367035/", "study_type": "review", "key_finding": "Comprehensive review of zinc's role in immune function, showing zinc is critical for innate and adaptive immunity, with deficiency leading to decreased natural killer cell activity and thymulin levels.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38367035/", "publicSourceType": "PMID" }, { "claim": "Zinc supplementation for skin health and acne treatment", "title": "Serum zinc levels and efficacy of zinc treatment in acne vulgaris: A systematic review and meta-analysis", "authors": "Yee BE et al.", "journal": "Dermatol Ther", "year": 2020, "pmid": "32860489", "url": "https://pubmed.ncbi.nlm.nih.gov/32860489/", "study_type": "meta-analysis", "key_finding": "Meta-analysis found acne patients have lower serum zinc levels and zinc supplementation effectively reduces acne lesion counts.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32860489/", "publicSourceType": "PMID" }, { "claim": "Zinc requirements and risks/benefits of supplementation including copper depletion", "title": "Zinc requirements and the risks and benefits of zinc supplementation", "authors": "Sandstead HH, Au W", "journal": "J Trace Elem Med Biol", "year": 2007, "pmid": "16632171", "url": "https://pubmed.ncbi.nlm.nih.gov/16632171/", "study_type": "review", "key_finding": "Review of zinc supplementation safety noting risk of copper depletion with chronic high-dose supplementation (>25 mg/day) and recommended copper co-supplementation.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16632171/", "publicSourceType": "PMID" }, { "text": "Sakai F, Yoshida S, Endo S et al.. [Therapeutic efficacy of zinc picolinate in patients with taste disorders]. Nihon Jibiinkoka Gakkai kaiho. 1995", "pmid": "7562235", "doi": "10.3950/jibiinkoka.98.1135", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7562235/", "publicSourceType": "PMID" }, { "text": "Abdollahi S, Toupchian O, Jayedi A et al.. Zinc Supplementation and Body Weight: A Systematic Review and Dose-Response Meta-analysis of Randomized Controlled Trials. Advances in nutrition (Bethesda, Md.). 2020", "claim": "PubMed-indexed evidence involving Zinc Picolinate", "title": "Zinc Supplementation and Body Weight: A Systematic Review and Dose-Response Meta-analysis of Randomized Controlled Trials", "authors": "Abdollahi S, Toupchian O, Jayedi A et al.", "journal": "Advances in nutrition (Bethesda, Md.)", "year": 2020, "pmid": "31504083", "url": "https://pubmed.ncbi.nlm.nih.gov/31504083/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/advances/nmz084", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31504083/", "publicSourceType": "PMID" }, { "text": "Wang MX, Win SS, Pang J. Zinc Supplementation Reduces Common Cold Duration among Healthy Adults: A Systematic Review of Randomized Controlled Trials with Micronutrients Supplementation. The American journal of tropical medicine and hygiene. 2020", "claim": "PubMed-indexed evidence involving Zinc Picolinate", "title": "Zinc Supplementation Reduces Common Cold Duration among Healthy Adults: A Systematic Review of Randomized Controlled Trials with Micronutrients Supplementation", "authors": "Wang MX, Win SS, Pang J", "journal": "The American journal of tropical medicine and hygiene", "year": 2020, "pmid": "32342851", "url": "https://pubmed.ncbi.nlm.nih.gov/32342851/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.4269/ajtmh.19-0718", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32342851/", "publicSourceType": "PMID" }, { "text": "Kim YM, Baek J. Effect of zinc supplementation on premenstrual symptoms: A systematic review and meta-analysis. Women & health. 2025", "claim": "PubMed-indexed evidence involving Zinc Picolinate", "title": "Effect of zinc supplementation on premenstrual symptoms: A systematic review and meta-analysis", "authors": "Kim YM, Baek J", "journal": "Women & health", "year": 2025, "pmid": "40737185", "url": "https://pubmed.ncbi.nlm.nih.gov/40737185/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/03630242.2025.2539815", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40737185/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "zinc-picolinate" }, { "id": "0A018F9E-0002-459C-A489-F58F186DFB3A", "name": "Zinc Carnosine", "alternateNames": [ "ZnC", "Polaprezinc" ], "category": "Mineral", "subcategory": "Zinc Form", "overview": "Zinc chelated with L-carnosine, specifically targeted for gut lining repair.", "mechanismOfAction": "Adheres to ulcerated/inflamed gastric mucosa, providing localized zinc for tissue repair. Inhibits H. pylori and stabilizes gut membrane. Carnosine provides additional antioxidant protection.", "commonBenefits": [ "Gut lining repair", "Gastritis relief", "H. pylori support", "Leaky gut" ], "commonDosageRange": "75 mg 2x daily", "recommendedForm": "Zinc carnosine (PepZin GI is well-studied)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food or between meals" }, "evidenceRating": "moderate", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Mild GI", "Copper depletion with prolonged use" ], "contraindications": [ "Copper deficiency" ], "iconName": "bandage.fill", "colorHex": "4DD4E6", "tags": [ "gut-health", "zinc", "gastritis", "leaky-gut" ], "sources": [ { "claim": "Zinc carnosine stabilizes small bowel integrity and prevents NSAID-induced gut permeability increase", "title": "Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes", "authors": "Mahmood A et al.", "journal": "Gut", "year": 2007, "pmid": "16777920", "url": "https://pubmed.ncbi.nlm.nih.gov/16777920/", "study_type": "RCT", "key_finding": "In healthy volunteers, indomethacin caused a 3-fold increase in gut permeability, but co-administration of zinc carnosine (37.5 mg twice daily) prevented this increase entirely.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16777920/", "publicSourceType": "PMID" }, { "claim": "Comprehensive review of zinc-L-carnosine positive effects on GI disorders", "title": "A Review of Zinc-L-Carnosine and Its Positive Effects on Oral Mucositis, Taste Disorders, and Gastrointestinal Disorders", "authors": "Hewlings S, Kalman D", "journal": "Nutrients", "year": 2020, "pmid": "32120906", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7146259/", "study_type": "review", "key_finding": "ZnC supports restoration of the gastric lining, healing of the GI tract, improvement of taste disorders and GI disorders, with additional benefits for skin and liver.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7146259/", "publicSourceType": "PMID" }, { "claim": "Zinc carnosine role in prevention and treatment of GI mucosal disease", "title": "The role of Zinc L-Carnosine in the prevention and treatment of gastrointestinal mucosal disease in humans: a review", "authors": "Davison G et al.", "journal": "Clin Nutr ESPEN", "year": 2022, "pmid": "35659631", "url": "https://pubmed.ncbi.nlm.nih.gov/35659631/", "study_type": "review", "key_finding": "Comprehensive review confirming zinc L-carnosine's anti-inflammatory and antioxidant properties, ability to upregulate heat shock proteins, and clinical efficacy in preventing mucosal injury.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35659631/", "publicSourceType": "PMID" }, { "claim": "Polaprezinc-based therapy improves H. pylori eradication rates", "title": "Efficacy and Safety of Polaprezinc-Based Therapy versus the Standard Triple Therapy for Helicobacter pylori Eradication: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Setiawan T et al.", "journal": "Can J Gastroenterol Hepatol", "year": 2022, "pmid": "36235778", "url": "https://pubmed.ncbi.nlm.nih.gov/36235778/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of RCTs found polaprezinc plus triple therapy achieved significantly higher H. pylori eradication rates (81-83%) compared to triple therapy alone (61%).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36235778/", "publicSourceType": "PMID" }, { "claim": "Applicability of zinc-carnosine complex for medical use including anti-ulcer properties", "title": "Applicability of zinc complex of L-carnosine for medical use", "authors": "Matsukura T, Tanaka H", "journal": "Biochemistry (Mosc)", "year": 2000, "pmid": "10951100", "url": "https://pubmed.ncbi.nlm.nih.gov/10951100/", "study_type": "review", "key_finding": "Zinc-L-carnosine adheres to ulcerated gastric mucosa providing localized zinc for tissue repair, inhibits H. pylori growth, and stabilizes gut membrane with antioxidant protection from carnosine.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10951100/", "publicSourceType": "PMID" }, { "text": "Furihata K, Tsuchikawa M, Miwa T et al.. Efficacy and Safety of Polaprezinc (Zinc Compound) on Zinc Deficiency: A Systematic Review and Dose-Response Meta-Analysis of Randomized Clinical Trials Using Individual Patient Data. Nutrients. 2020", "pmid": "32316581", "doi": "10.3390/nu12041128", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32316581/", "publicSourceType": "PMID" }, { "text": "Tsubura-Okubo M, Komiyama Y, Kamimura R et al.. Oral management with polaprezinc solution reduces adverse events in haematopoietic stem cell transplantation patients. International journal of oral and maxillofacial surgery. 2021", "pmid": "33144049", "doi": "10.1016/j.ijom.2020.10.004", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33144049/", "publicSourceType": "PMID" }, { "text": "Togni L, Sparabombe S, Mascitti M et al.. Zinc-L-carnosine mouthwash in oral mucositis patients: a single-blind, randomized, controlled trial. Minerva dental and oral science. 2026", "claim": "PubMed-indexed evidence involving Zinc Carnosine", "title": "Zinc-L-carnosine mouthwash in oral mucositis patients: a single-blind, randomized, controlled trial", "authors": "Togni L, Sparabombe S, Mascitti M et al.", "journal": "Minerva dental and oral science", "year": 2026, "pmid": "41855025", "url": "https://pubmed.ncbi.nlm.nih.gov/41855025/", "study_type": "RCT", "confidence": "verify", "doi": "10.23736/S2724-6329.25.05074-0", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41855025/", "publicSourceType": "PMID" }, { "text": "Piccirillo M, Mennini M, Felici E et al.. Zinc-L-Carnosine (Polaprezinc) in managing infant regurgitation: a two-center randomized controlled trial. Frontiers in pediatrics. 2026", "claim": "PubMed-indexed evidence involving Zinc Carnosine", "title": "Zinc-L-Carnosine (Polaprezinc) in managing infant regurgitation: a two-center randomized controlled trial", "authors": "Piccirillo M, Mennini M, Felici E et al.", "journal": "Frontiers in pediatrics", "year": 2026, "pmid": "42093671", "url": "https://pubmed.ncbi.nlm.nih.gov/42093671/", "study_type": "RCT", "confidence": "verify", "doi": "10.3389/fped.2026.1754324", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/42093671/", "publicSourceType": "PMID" }, { "text": "Kumagai E, Furumachi K, Kurihara A et al.. Zinc Acetate Hydrate Supplementation versus Polaprezinc Supplementation for Improving Hypozincemia in Hemodialysis Patients: A Randomized Clinical Trial. International journal of nephrology. 2023", "claim": "PubMed-indexed evidence involving Zinc Carnosine", "title": "Zinc Acetate Hydrate Supplementation versus Polaprezinc Supplementation for Improving Hypozincemia in Hemodialysis Patients: A Randomized Clinical Trial", "authors": "Kumagai E, Furumachi K, Kurihara A et al.", "journal": "International journal of nephrology", "year": 2023, "pmid": "37840640", "url": "https://pubmed.ncbi.nlm.nih.gov/37840640/", "study_type": "RCT", "confidence": "verify", "doi": "10.1155/2023/2403755", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37840640/", "publicSourceType": "PMID" }, { "text": "Ibrahim N, El Said H, Choukair A. Zinc carnosine-based modified bismuth quadruple therapy vs standard triple therapy for Helicobacter pylori eradication: A randomized controlled study. World journal of clinical cases. 2022", "claim": "PubMed-indexed evidence involving Zinc Carnosine", "title": "Zinc carnosine-based modified bismuth quadruple therapy vs standard triple therapy for Helicobacter pylori eradication: A randomized controlled study", "authors": "Ibrahim N, El Said H, Choukair A", "journal": "World journal of clinical cases", "year": 2022, "pmid": "35071521", "url": "https://pubmed.ncbi.nlm.nih.gov/35071521/", "study_type": "RCT", "confidence": "verify", "doi": "10.12998/wjcc.v10.i1.227", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35071521/", "publicSourceType": "PMID" }, { "text": "Wu D, Li X, Li T et al.. The Effect of Quadruple Therapy with Polaprezinc or Bismuth on Gut Microbiota after Helicobacter pylori Eradication: A Randomized Controlled Trial. Journal of clinical medicine. 2022", "claim": "PubMed-indexed evidence involving Zinc Carnosine", "title": "The Effect of Quadruple Therapy with Polaprezinc or Bismuth on Gut Microbiota after Helicobacter pylori Eradication: A Randomized Controlled Trial", "authors": "Wu D, Li X, Li T et al.", "journal": "Journal of clinical medicine", "year": 2022, "pmid": "36498624", "url": "https://pubmed.ncbi.nlm.nih.gov/36498624/", "study_type": "RCT", "confidence": "verify", "doi": "10.3390/jcm11237050", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36498624/", "publicSourceType": "PMID" }, { "text": "Kitagawa J, Kobayashi R, Nagata Y et al.. Polaprezinc for prevention of oral mucositis in patients receiving chemotherapy followed by hematopoietic stem cell transplantation: A multi-institutional randomized controlled trial. International journal of cancer. 2021", "claim": "PubMed-indexed evidence involving Zinc Carnosine", "title": "Polaprezinc for prevention of oral mucositis in patients receiving chemotherapy followed by hematopoietic stem cell transplantation: A multi-institutional randomized controlled trial", "authors": "Kitagawa J, Kobayashi R, Nagata Y et al.", "journal": "International journal of cancer", "year": 2021, "pmid": "32984946", "url": "https://pubmed.ncbi.nlm.nih.gov/32984946/", "study_type": "RCT", "confidence": "verify", "doi": "10.1002/ijc.33316", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32984946/", "publicSourceType": "PMID" }, { "text": "Okamoto T, Hatakeyama S, Konishi S et al.. Comparison of zinc acetate hydrate and polaprezinc for zinc deficiency in patients on maintenance hemodialysis: A single-center, open-label, prospective randomized study. Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy. 2020", "claim": "PubMed-indexed evidence involving Zinc Carnosine", "title": "Comparison of zinc acetate hydrate and polaprezinc for zinc deficiency in patients on maintenance hemodialysis: A single-center, open-label, prospective randomized study", "authors": "Okamoto T, Hatakeyama S, Konishi S et al.", "journal": "Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy", "year": 2020, "pmid": "31794152", "url": "https://pubmed.ncbi.nlm.nih.gov/31794152/", "study_type": "RCT", "confidence": "verify", "doi": "10.1111/1744-9987.13461", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31794152/", "publicSourceType": "PMID" }, { "text": "Tan B, Luo HQ, Xu H et al.. Polaprezinc combined with clarithromycin-based triple therapy for Helicobacter pylori-associated gastritis: A prospective, multicenter, randomized clinical trial. PloS one. 2017", "claim": "PubMed-indexed evidence involving Zinc Carnosine", "title": "Polaprezinc combined with clarithromycin-based triple therapy for Helicobacter pylori-associated gastritis: A prospective, multicenter, randomized clinical trial", "authors": "Tan B, Luo HQ, Xu H et al.", "journal": "PloS one", "year": 2017, "pmid": "28407007", "url": "https://pubmed.ncbi.nlm.nih.gov/28407007/", "study_type": "RCT", "confidence": "verify", "doi": "10.1371/journal.pone.0175625", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28407007/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "zinc-carnosine" }, { "id": "4247D104-92A1-4EEC-8E99-B1857AD8042C", "name": "Iron Bisglycinate", "alternateNames": [ "Ferrochel", "Chelated Iron" ], "category": "Mineral", "subcategory": "Iron Form", "overview": "Gentle, highly bioavailable iron form that causes less GI distress than other forms.", "mechanismOfAction": "Amino acid chelation protects iron from binding phytates/tannins, maintaining bioavailability. Absorbed via amino acid transporters in addition to DMT1, reducing GI oxidative stress.", "commonBenefits": [ "Iron supplementation", "Anemia treatment", "Gentle on stomach" ], "commonDosageRange": "18-36 mg elemental iron daily", "recommendedForm": "Ferrochel iron bisglycinate", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Can take with food without significant absorption loss" }, "evidenceRating": "strong", "foodSources": [ "Same as iron" ], "deficiencySymptoms": [ "Same as iron deficiency" ], "sideEffects": [ "Less constipation than ferrous sulfate", "Less nausea" ], "contraindications": [ "Hemochromatosis", "Iron overload disorders" ], "iconName": "drop.fill", "colorHex": "4DD4E6", "tags": [ "iron", "anemia", "gentle" ], "sources": [ { "claim": "Ferrous bisglycinate improves hemoglobin/ferritin concentrations with fewer GI adverse events - meta-analysis", "title": "The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials", "authors": "Fischer JAJ et al.", "journal": "Nutr Rev", "year": 2023, "pmid": "36728680", "url": "https://pubmed.ncbi.nlm.nih.gov/36728680/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 17 RCTs found ferrous bisglycinate produced higher hemoglobin concentrations in pregnant women and 64% fewer GI adverse events compared to other iron salts.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36728680/", "publicSourceType": "PMID" }, { "claim": "Iron bisglycinate is better tolerated than ferrous sulfate with less bloating, constipation, nausea", "title": "Tolerability of iron: a comparison of bis-glycino iron II and ferrous sulfate", "authors": "Coplin M et al.", "journal": "Clin Ther", "year": 1991, "pmid": "1799918", "url": "https://pubmed.ncbi.nlm.nih.gov/1799918/", "study_type": "RCT", "key_finding": "In 38 women, 37% experienced moderate-to-severe side effects only while taking ferrous sulfate vs 21% with the chelate formulation; bisglycinate was better tolerated for bloating, constipation, and nausea.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1799918/", "publicSourceType": "PMID" }, { "claim": "Ferrous bisglycinate has higher absorption than ferrous sulfate in schoolchildren", "title": "Effect of supplementation with ferrous sulfate or iron bis-glycinate chelate on ferritin concentration in Mexican schoolchildren: a randomized controlled trial", "authors": "Gonzalez-Rosendo G et al.", "journal": "Nutr J", "year": 2014, "pmid": "25084820", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4107593/", "study_type": "RCT", "key_finding": "Both ferrous sulfate and iron bis-glycinate chelate were effective for iron repletion in children, with absorption of ferrous bisglycinate being significantly higher than ferrous sulfate.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4107593/", "publicSourceType": "PMID" }, { "claim": "Iron bisglycinate chelate effective as pilot treatment for iron deficiency anemia", "title": "Iron Bisglycinate Chelate and Polymaltose Iron for the Treatment of Iron Deficiency Anemia: A Pilot Randomized Trial", "authors": "Abdel Moety GAF et al.", "journal": "Curr Drug Discov Technol", "year": 2017, "pmid": "28155595", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6416187/", "study_type": "RCT", "key_finding": "Iron bisglycinate chelate showed effective treatment of iron deficiency anemia comparable to polymaltose iron with good tolerability and fewer GI side effects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6416187/", "publicSourceType": "PMID" }, { "claim": "Amino acid chelation protects iron from binding phytates/tannins and uses additional transport mechanisms", "title": "Efficacy and Safety of Ferrous Bisglycinate and Folinic Acid in the Control of Iron Deficiency in Pregnant Women: A Randomized, Controlled Trial", "authors": "Bagna R et al.", "journal": "Nutrients", "year": 2022, "pmid": "35276843", "url": "https://www.mdpi.com/2072-6643/14/3/452", "study_type": "RCT", "key_finding": "RCT in pregnant women confirmed ferrous bisglycinate's efficacy and safety for iron deficiency control, noting amino acid chelation maintains bioavailability even with food inhibitors.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://www.mdpi.com/2072-6643/14/3/452", "publicSourceType": "PMID" }, { "text": "Yefet E, Mruat Rabah S, Sela ND et al.. Addition of oral iron bisglycinate to intravenous iron sucrose for the treatment of postpartum anemia-randomized controlled trial. American journal of obstetrics and gynecology. 2021", "pmid": "34171389", "doi": "10.1016/j.ajog.2021.06.069", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34171389/", "publicSourceType": "PMID" }, { "text": "Name JJ, Vasconcelos AR, Valzachi Rocha Maluf MC. Iron Bisglycinate Chelate and Polymaltose Iron for the Treatment of Iron Deficiency Anemia: A Pilot Randomized Trial. Current pediatric reviews. 2018", "pmid": "30280670", "doi": "10.2174/1573396314666181002170040", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30280670/", "publicSourceType": "PMID" }, { "text": "Secrest AH, Norgan Radler C, Kelly J et al.. Glycoprotein Matrix-Bound Iron Improves Absorption Compared to Ferrous Bisglycinate Chelate and Ferrous Fumarate: A Randomized Crossover Trial. Cureus. 2025", "claim": "PubMed-indexed evidence involving Iron Bisglycinate", "title": "Glycoprotein Matrix-Bound Iron Improves Absorption Compared to Ferrous Bisglycinate Chelate and Ferrous Fumarate: A Randomized Crossover Trial", "authors": "Secrest AH, Norgan Radler C, Kelly J et al.", "journal": "Cureus", "year": 2025, "pmid": "40190969", "url": "https://pubmed.ncbi.nlm.nih.gov/40190969/", "study_type": "RCT", "confidence": "verify", "doi": "10.7759/cureus.80224", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40190969/", "publicSourceType": "PMID" }, { "text": "Hamed H, Samie OMA, Motawie AA et al.. Amino Acid Chelated Iron Versus Ferric Ammonium Citrate on Iron Status in Egyptian Children with Iron Deficiency Anemia: A Randomized Controlled Study. Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion. 2025", "claim": "PubMed-indexed evidence involving Iron Bisglycinate", "title": "Amino Acid Chelated Iron Versus Ferric Ammonium Citrate on Iron Status in Egyptian Children with Iron Deficiency Anemia: A Randomized Controlled Study", "authors": "Hamed H, Samie OMA, Motawie AA et al.", "journal": "Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion", "year": 2025, "pmid": "40224703", "url": "https://pubmed.ncbi.nlm.nih.gov/40224703/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/s12288-024-01746-6", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40224703/", "publicSourceType": "PMID" }, { "text": "Cirigliano E, Saint A, Pei LX et al.. Iron Supplementation with Ferrous Sulfate or Ferrous Bisglycinate for 12 Weeks Does Not Influence Group B Streptococcus Colonization in Cambodian Women: A Secondary Analysis of a Randomized Controlled Trial. The Journal of nutrition. 2025", "claim": "PubMed-indexed evidence involving Iron Bisglycinate", "title": "Iron Supplementation with Ferrous Sulfate or Ferrous Bisglycinate for 12 Weeks Does Not Influence Group B Streptococcus Colonization in Cambodian Women: A Secondary Analysis of a Randomized Controlled Trial", "authors": "Cirigliano E, Saint A, Pei LX et al.", "journal": "The Journal of nutrition", "year": 2025, "pmid": "41082982", "url": "https://pubmed.ncbi.nlm.nih.gov/41082982/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.tjnut.2025.10.014", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41082982/", "publicSourceType": "PMID" }, { "text": "Milman NT, Bergholt T. Low-Dose Prophylactic Oral Iron Supplementation (Ferrous Fumarate, Ferrous Bisglycinate, and Ferrous Sulphate) in Pregnancy Is Not Associated With Clinically Significant Gastrointestinal Complaints: Results From Two Randomized Studies. Journal of pregnancy. 2024", "claim": "PubMed-indexed evidence involving Iron Bisglycinate", "title": "Low-Dose Prophylactic Oral Iron Supplementation (Ferrous Fumarate, Ferrous Bisglycinate, and Ferrous Sulphate) in Pregnancy Is Not Associated With Clinically Significant Gastrointestinal Complaints: Results From Two Randomized Studies", "authors": "Milman NT, Bergholt T", "journal": "Journal of pregnancy", "year": 2024, "pmid": "39582678", "url": "https://pubmed.ncbi.nlm.nih.gov/39582678/", "study_type": "RCT", "confidence": "verify", "doi": "10.1155/2024/1716798", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39582678/", "publicSourceType": "PMID" }, { "text": "Fischer JAJ, Pei LX, Elango R et al.. Is a Lower Dose of More Bioavailable Iron (18-mg Ferrous Bisglycinate) Noninferior to 60-mg Ferrous Sulfate in Increasing Ferritin Concentrations While Reducing Gut Inflammation and Enteropathogen Detection in Cambodian Women? A Randomized Controlled Noninferiority Trial. The Journal of nutrition. 2023", "claim": "PubMed-indexed evidence involving Iron Bisglycinate", "title": "Is a Lower Dose of More Bioavailable Iron (18-mg Ferrous Bisglycinate) Noninferior to 60-mg Ferrous Sulfate in Increasing Ferritin Concentrations While Reducing Gut Inflammation and Enteropathogen Detection in Cambodian Women? A Randomized Controlled Noninferiority Trial", "authors": "Fischer JAJ, Pei LX, Elango R et al.", "journal": "The Journal of nutrition", "year": 2023, "pmid": "37271416", "url": "https://pubmed.ncbi.nlm.nih.gov/37271416/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.tjnut.2023.05.029", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37271416/", "publicSourceType": "PMID" }, { "text": "Milman N, Jønsson L, Dyre P et al.. Ferrous bisglycinate 25 mg iron is as effective as ferrous sulfate 50 mg iron in the prophylaxis of iron deficiency and anemia during pregnancy in a randomized trial. Journal of perinatal medicine. 2014", "claim": "PubMed-indexed evidence involving Iron Bisglycinate", "title": "Ferrous bisglycinate 25 mg iron is as effective as ferrous sulfate 50 mg iron in the prophylaxis of iron deficiency and anemia during pregnancy in a randomized trial", "authors": "Milman N, Jønsson L, Dyre P et al.", "journal": "Journal of perinatal medicine", "year": 2014, "pmid": "24152889", "url": "https://pubmed.ncbi.nlm.nih.gov/24152889/", "study_type": "RCT", "confidence": "verify", "doi": "10.1515/jpm-2013-0153", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24152889/", "publicSourceType": "PMID" }, { "text": "Hsu CY, Chen JC, Tsai YC et al.. Low-dose ferrous bisglycinate chelate supplementation in chronic kidney disease and hemodialysis patients. Journal of the Chinese Medical Association : JCMA. 2022", "claim": "PubMed-indexed evidence involving Iron Bisglycinate", "title": "Low-dose ferrous bisglycinate chelate supplementation in chronic kidney disease and hemodialysis patients", "authors": "Hsu CY, Chen JC, Tsai YC et al.", "journal": "Journal of the Chinese Medical Association : JCMA", "year": 2022, "pmid": "35358119", "url": "https://pubmed.ncbi.nlm.nih.gov/35358119/", "study_type": "RCT", "confidence": "verify", "doi": "10.1097/JCMA.0000000000000725", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35358119/", "publicSourceType": "PMID" }, { "text": "Ferrari P, Nicolini A, Manca ML et al.. Treatment of mild non-chemotherapy-induced iron deficiency anemia in cancer patients: comparison between oral ferrous bisglycinate chelate and ferrous sulfate. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2012", "claim": "PubMed-indexed evidence involving Iron Bisglycinate", "title": "Treatment of mild non-chemotherapy-induced iron deficiency anemia in cancer patients: comparison between oral ferrous bisglycinate chelate and ferrous sulfate", "authors": "Ferrari P, Nicolini A, Manca ML et al.", "journal": "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie", "year": 2012, "pmid": "22795809", "url": "https://pubmed.ncbi.nlm.nih.gov/22795809/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.biopha.2012.06.003", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22795809/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "iron-bisglycinate" }, { "id": "A9C60C7D-4307-4C5E-84AC-491C97F72C7A", "name": "Curcumin Phytosome", "alternateNames": [ "Meriva", "Curcumin + Phosphatidylcholine" ], "category": "Herb", "subcategory": "Enhanced Curcumin", "overview": "Curcumin complexed with phosphatidylcholine for 29x better absorption than standard curcumin.", "mechanismOfAction": "Phospholipid complex increases curcumin absorption by improving intestinal membrane crossing. Same mechanisms as standard curcumin but at much lower effective doses.", "commonBenefits": [ "Anti-inflammatory", "Joint health", "Antioxidant", "Brain health" ], "commonDosageRange": "500-1,000 mg Meriva daily", "recommendedForm": "Meriva (curcumin phytosome) or Longvida", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food" }, "evidenceRating": "strong", "foodSources": [ "Turmeric" ], "deficiencySymptoms": [], "sideEffects": [ "GI upset (less than standard curcumin)", "Blood thinning" ], "contraindications": [ "Blood thinners", "Gallbladder disease", "Surgery" ], "iconName": "leaf.fill", "colorHex": "34D399", "tags": [ "anti-inflammatory", "joint-health", "enhanced-absorption" ], "sources": [ { "claim": "Meriva curcumin phytosome shows 29-fold greater absorption than standard curcumin", "title": "Comparison of systemic availability of curcumin with that of curcumin formulated with phosphatidylcholine", "authors": "Marczylo TH et al.", "journal": "Cancer Chemother Pharmacol", "year": 2007, "pmid": "17051370", "url": "https://pubmed.ncbi.nlm.nih.gov/17051370/", "study_type": "RCT", "key_finding": "In healthy volunteers, Meriva (curcumin-phosphatidylcholine complex) increased curcuminoid absorption approximately 29-fold compared to unformulated curcumin on a curcuminoid equivalents basis.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17051370/", "publicSourceType": "PMID" }, { "claim": "Meriva efficacy and safety for osteoarthritis in extended 8-month study", "title": "Efficacy and safety of Meriva, a curcumin-phosphatidylcholine complex, during extended administration in osteoarthritis patients", "authors": "Belcaro G et al.", "journal": "Altern Med Rev", "year": 2010, "pmid": "21194249", "url": "https://pubmed.ncbi.nlm.nih.gov/21194249/", "study_type": "RCT", "key_finding": "In 100 OA patients over 8 months, Meriva decreased WOMAC score by 58%, increased walking distance from 76m to 332m, and significantly decreased CRP and inflammatory biomarkers.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21194249/", "publicSourceType": "PMID" }, { "claim": "Curcumin phytosome review of pharmacokinetic, experimental, and clinical studies", "title": "Phytosomal curcumin: A review of pharmacokinetic, experimental and clinical studies", "authors": "Mirzaei H et al.", "journal": "Biomed Pharmacother", "year": 2017, "pmid": "27930973", "url": "https://pubmed.ncbi.nlm.nih.gov/27930973/", "study_type": "review", "key_finding": "Comprehensive review documenting phytosome technology's ability to improve curcumin bioabsorption via phospholipid delivery system, preventing self-aggregation and enabling direct cellular uptake.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27930973/", "publicSourceType": "PMID" }, { "claim": "Curcumin efficacy for knee osteoarthritis pain - meta-analysis of high and low doses", "title": "The efficacy of high- and low-dose curcumin in knee osteoarthritis: A systematic review and meta-analysis", "authors": "Hsiao AF et al.", "journal": "Complement Ther Med", "year": 2021, "pmid": "34537344", "url": "https://pubmed.ncbi.nlm.nih.gov/34537344/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 11 studies (1258 participants) found curcuminoids significantly more effective than comparators for VAS and WOMAC pain scores in knee OA.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34537344/", "publicSourceType": "PMID" }, { "claim": "Curcumin safety compared to NSAIDs with lower adverse event incidence", "title": "The efficacy and safety of Curcuma longa extract and curcumin supplements on osteoarthritis: a systematic review and meta-analysis", "authors": "Zeng L et al.", "journal": "Biosci Rep", "year": 2021, "pmid": "34017975", "url": "https://pubmed.ncbi.nlm.nih.gov/34017975/", "study_type": "meta-analysis", "key_finding": "Compared with NSAIDs, curcumin had similar effects on joint pain, function and stiffness, with lower incidence of adverse events; recommended use for more than 12 weeks.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34017975/", "publicSourceType": "PMID" }, { "claim": "Meriva modulates inflammation, lipid peroxidation and gut microbiota in chronic kidney disease", "title": "Curcumin Supplementation (Meriva) Modulates Inflammation, Lipid Peroxidation and Gut Microbiota Composition in Chronic Kidney Disease", "authors": "Pivari F et al.", "journal": "Nutrients", "year": 2022, "pmid": "35010893", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8747135/", "study_type": "RCT", "key_finding": "In 24 CKD patients supplemented with Meriva for six months, curcumin significantly reduced plasma pro-inflammatory mediators and modulated gut microbiota composition.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8747135/", "publicSourceType": "PMID" }, { "text": "Musso G, Pinach S, Mariano F et al.. Effect of phospholipid curcumin Meriva on liver histology and kidney disease in nonalcoholic steatohepatitis: A randomized, double-blind, placebo-controlled trial. Hepatology (Baltimore, Md.). 2025", "pmid": "38809154", "doi": "10.1097/HEP.0000000000000937", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38809154/", "publicSourceType": "PMID" }, { "text": "Drobnic F, Riera J, Appendino G et al.. Reduction of delayed onset muscle soreness by a novel curcumin delivery system (Meriva®): a randomised, placebo-controlled trial. Journal of the International Society of Sports Nutrition. 2014", "pmid": "24982601", "doi": "10.1186/1550-2783-11-31", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24982601/", "publicSourceType": "PMID" }, { "text": "Shojaei M, Khorvash F, Sahebkar A et al.. Effect and Safety of Phytosomal Curcumin Supplementation on Migraine Patients: A Randomized, Double-Blind and Placebo-Controlled Trial. Chinese journal of integrative medicine. 2025", "claim": "PubMed-indexed evidence involving Curcumin Phytosome", "title": "Effect and Safety of Phytosomal Curcumin Supplementation on Migraine Patients: A Randomized, Double-Blind and Placebo-Controlled Trial", "authors": "Shojaei M, Khorvash F, Sahebkar A et al.", "journal": "Chinese journal of integrative medicine", "year": 2025, "pmid": "41136816", "url": "https://pubmed.ncbi.nlm.nih.gov/41136816/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/s11655-025-3939-1", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41136816/", "publicSourceType": "PMID" }, { "text": "Panahi Y, Kianpour P, Mohtashami R et al.. Efficacy and Safety of Phytosomal Curcumin in Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Trial. Drug research. 2017", "claim": "PubMed-indexed evidence involving Curcumin Phytosome", "title": "Efficacy and Safety of Phytosomal Curcumin in Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Trial", "authors": "Panahi Y, Kianpour P, Mohtashami R et al.", "journal": "Drug research", "year": 2017, "pmid": "28158893", "url": "https://pubmed.ncbi.nlm.nih.gov/28158893/", "study_type": "RCT", "confidence": "verify", "doi": "10.1055/s-0043-100019", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28158893/", "publicSourceType": "PMID" }, { "text": "Mirjalili M, Sahebkar A, Hassanizadeh S et al.. The effectiveness of phytosomal curcumin on clinical and laboratory parameters of patients with multiple trauma admitted to the intensive care unit: a double-blind randomized placebo-controlled trial. BMC complementary medicine and therapies. 2024", "claim": "PubMed-indexed evidence involving Curcumin Phytosome", "title": "The effectiveness of phytosomal curcumin on clinical and laboratory parameters of patients with multiple trauma admitted to the intensive care unit: a double-blind randomized placebo-controlled trial", "authors": "Mirjalili M, Sahebkar A, Hassanizadeh S et al.", "journal": "BMC complementary medicine and therapies", "year": 2024, "pmid": "39289667", "url": "https://pubmed.ncbi.nlm.nih.gov/39289667/", "study_type": "RCT", "confidence": "verify", "doi": "10.1186/s12906-024-04639-3", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39289667/", "publicSourceType": "PMID" }, { "text": "Shojaei M, Sahebkar A, Khorvash F et al.. The effects of phytosomal curcumin supplementation on clinical symptoms, and inflammatory and oxidative stress biomarkers in patients with migraine: A protocol for a randomized double-blind placebo-controlled trial. Avicenna journal of phytomedicine. 2023", "claim": "PubMed-indexed evidence involving Curcumin Phytosome", "title": "The effects of phytosomal curcumin supplementation on clinical symptoms, and inflammatory and oxidative stress biomarkers in patients with migraine: A protocol for a randomized double-blind placebo-controlled trial", "authors": "Shojaei M, Sahebkar A, Khorvash F et al.", "journal": "Avicenna journal of phytomedicine", "year": 2023, "pmid": "36698737", "url": "https://pubmed.ncbi.nlm.nih.gov/36698737/", "study_type": "RCT", "confidence": "verify", "doi": "10.22038/AJP.2022.21242", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36698737/", "publicSourceType": "PMID" }, { "text": "Mirhafez SR, Azimi-Nezhad M, Dehabeh M et al.. The Effect of Curcumin Phytosome on the Treatment of Patients with Non-alcoholic Fatty Liver Disease: A Double-Blind, Randomized, Placebo-Controlled Trial. Advances in experimental medicine and biology. 2021", "claim": "PubMed-indexed evidence involving Curcumin Phytosome", "title": "The Effect of Curcumin Phytosome on the Treatment of Patients with Non-alcoholic Fatty Liver Disease: A Double-Blind, Randomized, Placebo-Controlled Trial", "authors": "Mirhafez SR, Azimi-Nezhad M, Dehabeh M et al.", "journal": "Advances in experimental medicine and biology", "year": 2021, "pmid": "33861434", "url": "https://pubmed.ncbi.nlm.nih.gov/33861434/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/978-3-030-64872-5_3", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33861434/", "publicSourceType": "PMID" }, { "text": "Cicero AFG, Sahebkar A, Fogacci F et al.. Effects of phytosomal curcumin on anthropometric parameters, insulin resistance, cortisolemia and non-alcoholic fatty liver disease indices: a double-blind, placebo-controlled clinical trial. European journal of nutrition. 2020", "claim": "PubMed-indexed evidence involving Curcumin Phytosome", "title": "Effects of phytosomal curcumin on anthropometric parameters, insulin resistance, cortisolemia and non-alcoholic fatty liver disease indices: a double-blind, placebo-controlled clinical trial", "authors": "Cicero AFG, Sahebkar A, Fogacci F et al.", "journal": "European journal of nutrition", "year": 2020, "pmid": "30796508", "url": "https://pubmed.ncbi.nlm.nih.gov/30796508/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/s00394-019-01916-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30796508/", "publicSourceType": "PMID" }, { "text": "Chashmniam S, Mirhafez SR, Dehabeh M et al.. A pilot study of the effect of phospholipid curcumin on serum metabolomic profile in patients with non-alcoholic fatty liver disease: a randomized, double-blind, placebo-controlled trial. European journal of clinical nutrition. 2019", "claim": "PubMed-indexed evidence involving Curcumin Phytosome", "title": "A pilot study of the effect of phospholipid curcumin on serum metabolomic profile in patients with non-alcoholic fatty liver disease: a randomized, double-blind, placebo-controlled trial", "authors": "Chashmniam S, Mirhafez SR, Dehabeh M et al.", "journal": "European journal of clinical nutrition", "year": 2019, "pmid": "30647436", "url": "https://pubmed.ncbi.nlm.nih.gov/30647436/", "study_type": "RCT", "confidence": "verify", "doi": "10.1038/s41430-018-0386-5", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30647436/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "curcumin-phytosome" }, { "id": "6FA90386-72BA-4737-8C9A-C8739D55863E", "name": "Omega-7", "alternateNames": [ "Palmitoleic Acid", "Sea Buckthorn Oil" ], "category": "Omega/Fatty Acid", "subcategory": "Monounsaturated Fatty Acid", "overview": "Uncommon omega fatty acid supporting mucous membrane health and metabolic function.", "mechanismOfAction": "Palmitoleic acid acts as a lipokine signaling molecule between adipose tissue and other organs. It is studied for mucous membrane hydration and metabolic markers, but CRP reduction has not been consistently shown.", "commonBenefits": [ "Mucous membrane health", "Skin hydration", "Metabolic support", "Vaginal dryness" ], "commonDosageRange": "210-420 mg daily", "recommendedForm": "Purified palmitoleic acid (Provinal) or sea buckthorn oil", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food" }, "evidenceRating": "emerging", "foodSources": [ "Macadamia nuts", "Sea buckthorn berries" ], "deficiencySymptoms": [], "sideEffects": [ "GI upset", "Fishy burps (fish-derived)" ], "contraindications": [ "Blood thinners (mild)" ], "iconName": "drop.fill", "colorHex": "4D94FF", "tags": [ "mucous-membrane", "skin", "metabolic" ], "sources": [ { "claim": "Sea buckthorn oil (omega-7 source) improves vaginal atrophy in postmenopausal women", "title": "Effects of sea buckthorn oil intake on vaginal atrophy in postmenopausal women: a randomized, double-blind, placebo-controlled study", "authors": "Larmo PS et al.", "journal": "Maturitas", "year": 2014, "pmid": "25104582", "url": "https://pubmed.ncbi.nlm.nih.gov/25104582/", "study_type": "RCT", "key_finding": "In 116 postmenopausal women, 3g daily sea buckthorn oil for 3 months showed significantly better improvement in vaginal epithelium integrity vs placebo (OR=3.1, 95% CI 1.11-8.95).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25104582/", "publicSourceType": "PMID" }, { "claim": "Oral palmitoleic acid improves skin barrier function in randomized trial", "title": "Efficacy and safety of oral palmitoleic acid supplementation for skin barrier improvement: A 12-week, randomized, double-blinded, placebo-controlled study", "authors": "Lee E et al.", "journal": "Heliyon", "year": 2023, "pmid": "37292315", "url": "https://pubmed.ncbi.nlm.nih.gov/37292315/", "study_type": "RCT", "key_finding": "In 90 participants, 500 mg/day palmitoleic acid for 12 weeks significantly improved skin hydration and transepidermal water loss vs placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37292315/", "publicSourceType": "PMID" }, { "claim": "Omega-7 mixed fatty acid supplementation fails to reduce inflammatory biomarkers in human trial", "title": "Omega-7 Mixed Fatty Acid Supplementation Fails to Reduce Serum Inflammatory Biomarkers: A Placebo-Controlled, Double-Blind Randomized Crossover Trial", "authors": "Rotan KR et al.", "journal": "Nutrients", "year": 2021, "pmid": "34444963", "url": "https://pubmed.ncbi.nlm.nih.gov/34444963/", "study_type": "RCT", "key_finding": "Three weeks of 688 mg/day palmitoleate did not produce a statistically detectable change in inflammatory biomarkers compared to MCT placebo, questioning claims about CRP reduction.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34444963/", "publicSourceType": "PMID" }, { "claim": "Palmitoleic acid acts as a lipokine signaling molecule and modulates metabolism", "title": "Palmitoleic Acid Ameliorates Metabolic Disorders and Inflammation by Modulating Gut Microbiota and Serum Metabolites", "authors": "Zhang Y et al.", "journal": "J Agric Food Chem", "year": 2024, "pmid": "38511225", "url": "https://pubmed.ncbi.nlm.nih.gov/38511225/", "study_type": "animal_study", "key_finding": "Palmitoleic acid ameliorated metabolic disorders and inflammation by modulating gut microbiota composition and serum metabolites in a preclinical model.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38511225/", "publicSourceType": "PMID" }, { "claim": "Palmitoleic acid and atherosclerosis prevention in animal model", "title": "Dietary Palmitoleic Acid Attenuates Atherosclerosis Progression and Hyperlipidemia in Low-Density Lipoprotein Receptor-Deficient Mice", "authors": "Souza CO et al.", "journal": "Mol Nutr Food Res", "year": 2019, "pmid": "30921498", "url": "https://pubmed.ncbi.nlm.nih.gov/30921498/", "study_type": "animal_study", "key_finding": "Dietary palmitoleic acid attenuated atherosclerosis progression and reduced hyperlipidemia in LDLR-deficient mice, supporting potential metabolic benefits.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30921498/", "publicSourceType": "PMID" }, { "text": "Guillocheau E, Legrand P, Rioux V. Trans-palmitoleic acid (trans-9-C16:1, or trans-C16:1 n-7): Nutritional impacts, metabolism, origin, compositional data, analytical methods and chemical synthesis. A review. Biochimie. 2020", "pmid": "31837411", "doi": "10.1016/j.biochi.2019.12.004", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31837411/", "publicSourceType": "PMID" }, { "claim": "Palmitoleic acid (omega-7) combined with magnesium, phosphate, and omega-6 may improve acne vulgaris", "title": "Treatment of Resistant Acne Vulgaris in Adolescents Using Dietary Supplementation with Magnesium, Phosphate and Fatty Acids (Omega 6 and 7): Comparison with 13-Cis-Retinoic Acid", "authors": "de Souza Pereira R", "journal": "J Diet Suppl", "year": 2023, "pmid": "35876008", "url": "https://pubmed.ncbi.nlm.nih.gov/35876008/", "study_type": "rct", "key_finding": "Single-blind randomized study of 532 patients found dietary supplementation with omega-6, omega-7, magnesium, and phosphate achieved 100% complete symptom regression vs 68% for isotretinoin in acne vulgaris treatment over 6 months.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35876008/", "publicSourceType": "PMID" }, { "claim": "Macadamia nut consumption (rich in palmitoleic acid/omega-7) does not cause weight gain and may lower cholesterol", "title": "Macadamia nut effects on cardiometabolic risk factors: a randomised trial", "authors": "Jones JL, Sabate J, Heskey C, Oda K, Miles F, Rajaram S", "journal": "J Nutr Sci", "year": 2023, "pmid": "37180485", "url": "https://pubmed.ncbi.nlm.nih.gov/37180485/", "study_type": "rct", "key_finding": "Randomized crossover trial in 35 overweight/obese adults found daily macadamia nut consumption (~15% calories) did not increase weight or body fat and showed non-significant reductions in total cholesterol (-2.1%) and LDL-C (-4%).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37180485/", "publicSourceType": "PMID" }, { "text": "Bridges MD, Vennam SS, Davis T et al.. Effects of a palmitoleic acid concentrated oil on C-reactive protein levels in adults: A randomized, double-blind placebo-controlled clinical trial. The American journal of clinical nutrition. 2025", "claim": "PubMed-indexed evidence involving Omega-7", "title": "Effects of a palmitoleic acid concentrated oil on C-reactive protein levels in adults: A randomized, double-blind placebo-controlled clinical trial", "authors": "Bridges MD, Vennam SS, Davis T et al.", "journal": "The American journal of clinical nutrition", "year": 2025, "pmid": "40456315", "url": "https://pubmed.ncbi.nlm.nih.gov/40456315/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.ajcnut.2025.05.032", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40456315/", "publicSourceType": "PMID" }, { "text": "Cetin E, Pedersen B, Porter LM et al.. Protocol for a randomized placebo-controlled clinical trial using pure palmitoleic acid to ameliorate insulin resistance and lipogenesis in overweight and obese subjects with prediabetes. Frontiers in endocrinology. 2023", "claim": "PubMed-indexed evidence involving Omega-7", "title": "Protocol for a randomized placebo-controlled clinical trial using pure palmitoleic acid to ameliorate insulin resistance and lipogenesis in overweight and obese subjects with prediabetes", "authors": "Cetin E, Pedersen B, Porter LM et al.", "journal": "Frontiers in endocrinology", "year": 2023, "pmid": "38313838", "url": "https://pubmed.ncbi.nlm.nih.gov/38313838/", "study_type": "RCT", "confidence": "verify", "doi": "10.3389/fendo.2023.1306528", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38313838/", "publicSourceType": "PMID" }, { "text": "Huang NK, Matthan NR, Galluccio JM et al.. Supplementation with Seabuckthorn Oil Augmented in 16:1n-7t Increases Serum Trans-Palmitoleic Acid in Metabolically Healthy Adults: A Randomized Crossover Dose-Escalation Study. The Journal of nutrition. 2020", "claim": "PubMed-indexed evidence involving Omega-7", "title": "Supplementation with Seabuckthorn Oil Augmented in 16:1n-7t Increases Serum Trans-Palmitoleic Acid in Metabolically Healthy Adults: A Randomized Crossover Dose-Escalation Study", "authors": "Huang NK, Matthan NR, Galluccio JM et al.", "journal": "The Journal of nutrition", "year": 2020, "pmid": "32140719", "url": "https://pubmed.ncbi.nlm.nih.gov/32140719/", "study_type": "RCT", "confidence": "verify", "doi": "10.1093/jn/nxaa060", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32140719/", "publicSourceType": "PMID" }, { "text": "Bernstein AM, Roizen MF, Martinez L. WITHDRWAN: Purified palmitoleic acid for the reduction of high-sensitivity C-reactive protein and serum lipids: a double-blinded, randomized, placebo controlled study. Journal of clinical lipidology. 2014", "claim": "PubMed-indexed evidence involving Omega-7", "title": "WITHDRWAN: Purified palmitoleic acid for the reduction of high-sensitivity C-reactive protein and serum lipids: a double-blinded, randomized, placebo controlled study", "authors": "Bernstein AM, Roizen MF, Martinez L", "journal": "Journal of clinical lipidology", "year": 2014, "pmid": "25499944", "url": "https://pubmed.ncbi.nlm.nih.gov/25499944/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.jacl.2014.08.001", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25499944/", "publicSourceType": "PMID" }, { "text": "Bueno-Hernández N, Sixtos-Alonso MS, Milke García MDP et al.. Effect of Cis-palmitoleic acid supplementation on inflammation and expression of HNF4γ, HNF4α and IL6 in patients with ulcerative colitis. Minerva gastroenterologica e dietologica. 2017", "claim": "PubMed-indexed evidence involving Omega-7", "title": "Effect of Cis-palmitoleic acid supplementation on inflammation and expression of HNF4γ, HNF4α and IL6 in patients with ulcerative colitis", "authors": "Bueno-Hernández N, Sixtos-Alonso MS, Milke García MDP et al.", "journal": "Minerva gastroenterologica e dietologica", "year": 2017, "pmid": "28185444", "url": "https://pubmed.ncbi.nlm.nih.gov/28185444/", "study_type": "review", "confidence": "verify", "doi": "10.23736/S1121-421X.17.02367-4", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28185444/", "publicSourceType": "PMID" }, { "text": "Volk BM, Kunces LJ, Freidenreich DJ et al.. Effects of step-wise increases in dietary carbohydrate on circulating saturated Fatty acids and palmitoleic Acid in adults with metabolic syndrome. PloS one. 2014", "claim": "PubMed-indexed evidence involving Omega-7", "title": "Effects of step-wise increases in dietary carbohydrate on circulating saturated Fatty acids and palmitoleic Acid in adults with metabolic syndrome", "authors": "Volk BM, Kunces LJ, Freidenreich DJ et al.", "journal": "PloS one", "year": 2014, "pmid": "25415333", "url": "https://pubmed.ncbi.nlm.nih.gov/25415333/", "study_type": "review", "confidence": "verify", "doi": "10.1371/journal.pone.0113605", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25415333/", "publicSourceType": "PMID" }, { "text": "Järvinen RL, Larmo PS, Setälä NL et al.. Effects of oral sea buckthorn oil on tear film Fatty acids in individuals with dry eye. Cornea. 2011", "claim": "PubMed-indexed evidence involving Omega-7", "title": "Effects of oral sea buckthorn oil on tear film Fatty acids in individuals with dry eye", "authors": "Järvinen RL, Larmo PS, Setälä NL et al.", "journal": "Cornea", "year": 2011, "pmid": "21832964", "url": "https://pubmed.ncbi.nlm.nih.gov/21832964/", "study_type": "review", "confidence": "verify", "doi": "10.1097/ICO.0b013e3182035ad9", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21832964/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "omega-7" }, { "id": "6F41F503-0076-4FA9-BF20-CD7223D95137", "name": "Vitamin K2 MK-4", "alternateNames": [ "Menaquinone-4", "Menatetrenone" ], "category": "Vitamin", "subcategory": "Fat-Soluble Vitamin", "overview": "Short-acting form of K2 that reaches bone and brain tissue rapidly.", "mechanismOfAction": "Rapidly absorbed, short half-life (~6 hours vs MK-7's ~72 hours). Preferentially activates osteocalcin in bone. May have unique effects on gene expression via SXR/PXR nuclear receptor.", "commonBenefits": [ "Bone health", "Brain health", "Dental health" ], "commonDosageRange": "5-45 mg daily (much higher doses than MK-7)", "recommendedForm": "Menaquinone-4 (MK-4)", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with fat; split doses due to short half-life" }, "evidenceRating": "moderate", "foodSources": [ "Organ meats", "Egg yolks", "Butter (grass-fed)" ], "deficiencySymptoms": [], "sideEffects": [ "Very well tolerated even at high doses" ], "contraindications": [ "Blood thinners (warfarin)" ], "iconName": "cross.vial.fill", "colorHex": "FFB800", "tags": [ "bone-health", "brain", "vitamin-k" ], "sources": [ { "claim": "MK-4 (menatetrenone) at 45mg/day effectively prevents fractures and sustains BMD in osteoporosis", "title": "Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis", "authors": "Shiraki M et al.", "journal": "J Bone Miner Res", "year": 2000, "pmid": "10750566", "url": "https://pubmed.ncbi.nlm.nih.gov/10750566/", "study_type": "RCT", "key_finding": "In 241 osteoporotic patients over 24 months, 45 mg/day vitamin K2 significantly reduced clinical fracture incidence and maintained lumbar BMD compared to untreated controls.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10750566/", "publicSourceType": "PMID" }, { "claim": "Vitamin K2 efficacy for postmenopausal osteoporosis - meta-analysis of RCTs", "title": "Efficacy of vitamin K2 in the prevention and treatment of postmenopausal osteoporosis: A systematic review and meta-analysis of randomized controlled trials", "authors": "Ma ML et al.", "journal": "Front Public Health", "year": 2022, "pmid": "36033779", "url": "https://pubmed.ncbi.nlm.nih.gov/36033779/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 16 RCTs (6,425 subjects) showed VK2 significantly improves lumbar spine BMD, reduces fracture incidence, and decreases uncarboxylated osteocalcin in postmenopausal women.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36033779/", "publicSourceType": "PMID" }, { "claim": "Low-dose MK-4 (1.5mg) improves bone metabolism and prevents forearm bone loss", "title": "Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese women", "authors": "Koitaya N et al.", "journal": "J Bone Miner Metab", "year": 2014, "pmid": "23702931", "url": "https://pubmed.ncbi.nlm.nih.gov/23702931/", "study_type": "RCT", "key_finding": "Low-dose MK-4 (1.5 mg/day) for 12 months improved bone turnover markers and prevented forearm bone mineral density loss in postmenopausal women aged 50-65.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23702931/", "publicSourceType": "PMID" }, { "claim": "MK-4 has neuroprotective effects against cerebral ischemia via SXR/PXR pathway", "title": "Neuroprotective effect of menaquinone-4 (MK-4) on transient global cerebral ischemia/reperfusion injury in rat", "authors": "Farhadi Moghadam B, Fereidoni M", "journal": "PloS one", "year": 2020, "pmid": "32150581", "url": "https://pubmed.ncbi.nlm.nih.gov/32150581/", "study_type": "animal_study", "key_finding": "MK-4 increased SOD activity and GLT-1 mRNA levels in brain, inhibiting oxidative stress and neurotoxicity, demonstrating neuroprotective effects against cerebral ischemia/reperfusion injury.", "confidence": "verify", "doi": "10.1371/journal.pone.0229769", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32150581/", "publicSourceType": "PMID" }, { "claim": "Vitamin K2 biological responses including SXR-mediated gene regulation unique to MK-4", "title": "The biological responses of vitamin K2: A comprehensive review", "authors": "Halder M et al.", "journal": "Clin Nutr", "year": 2023, "pmid": "37051359", "url": "https://pubmed.ncbi.nlm.nih.gov/37051359/", "study_type": "review", "key_finding": "Comprehensive review confirming MK-4's unique functions as SXR/PXR ligand, mitochondrial electron carrier, and transcriptional regulator, with roles beyond carboxylation in bone and brain.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37051359/", "publicSourceType": "PMID" }, { "claim": "Vitamin K supplementation reduces fracture risk - meta-analysis", "title": "Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials", "authors": "Cockayne S et al.", "journal": "Arch Intern Med", "year": 2006, "pmid": "16801507", "url": "https://pubmed.ncbi.nlm.nih.gov/16801507/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of Japanese MK-4 trials showed significant fracture reduction: OR 0.40 for vertebral, 0.23 for hip, and 0.19 for all nonvertebral fractures.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16801507/", "publicSourceType": "PMID" }, { "text": "Tan J, Zhu R, Li Y et al.. Vitamin K2 in Managing Nocturnal Leg Cramps: A Randomized Clinical Trial. JAMA internal medicine. 2024", "pmid": "39466236", "doi": "10.1001/jamainternmed.2024.5726", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39466236/", "publicSourceType": "PMID" }, { "text": "Diederichsen ACP, Lindholt JS, Möller S et al.. Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial. Circulation. 2022", "pmid": "35465686", "doi": "10.1161/CIRCULATIONAHA.121.057008", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35465686/", "publicSourceType": "PMID" }, { "text": "Nakamura E, Aoki M, Watanabe F et al.. Low-dose menaquinone-4 improves γ-carboxylation of osteocalcin in young males: a non-placebo-controlled dose-response study. Nutrition journal. 2014", "claim": "PubMed-indexed evidence involving Vitamin K2 MK-4", "title": "Low-dose menaquinone-4 improves γ-carboxylation of osteocalcin in young males: a non-placebo-controlled dose-response study", "authors": "Nakamura E, Aoki M, Watanabe F et al.", "journal": "Nutrition journal", "year": 2014, "pmid": "25163392", "url": "https://pubmed.ncbi.nlm.nih.gov/25163392/", "study_type": "RCT", "confidence": "verify", "doi": "10.1186/1475-2891-13-85", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25163392/", "publicSourceType": "PMID" }, { "text": "Sato Y, Honda Y, Umeno K et al.. The prevention of hip fracture with menatetrenone and risedronate plus calcium supplementation in elderly patients with Alzheimer disease: a randomized controlled trial. The Kurume medical journal. 2011", "claim": "PubMed-indexed evidence involving Vitamin K2 MK-4", "title": "The prevention of hip fracture with menatetrenone and risedronate plus calcium supplementation in elderly patients with Alzheimer disease: a randomized controlled trial", "authors": "Sato Y, Honda Y, Umeno K et al.", "journal": "The Kurume medical journal", "year": 2011, "pmid": "21778673", "url": "https://pubmed.ncbi.nlm.nih.gov/21778673/", "study_type": "RCT", "confidence": "verify", "doi": "10.2739/kurumemedj.57.117", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21778673/", "publicSourceType": "PMID" }, { "text": "Inoue T, Fujita T, Kishimoto H et al.. Randomized controlled study on the prevention of osteoporotic fractures (OF study): a phase IV clinical study of 15-mg menatetrenone capsules. Journal of bone and mineral metabolism. 2009", "claim": "PubMed-indexed evidence involving Vitamin K2 MK-4", "title": "Randomized controlled study on the prevention of osteoporotic fractures (OF study): a phase IV clinical study of 15-mg menatetrenone capsules", "authors": "Inoue T, Fujita T, Kishimoto H et al.", "journal": "Journal of bone and mineral metabolism", "year": 2009, "pmid": "19082528", "url": "https://pubmed.ncbi.nlm.nih.gov/19082528/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/s00774-008-0008-8", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19082528/", "publicSourceType": "PMID" }, { "text": "Shiraki M, Itabashi A. Short-term menatetrenone therapy increases gamma-carboxylation of osteocalcin with a moderate increase of bone turnover in postmenopausal osteoporosis: a randomized prospective study. Journal of bone and mineral metabolism. 2009", "claim": "PubMed-indexed evidence involving Vitamin K2 MK-4", "title": "Short-term menatetrenone therapy increases gamma-carboxylation of osteocalcin with a moderate increase of bone turnover in postmenopausal osteoporosis: a randomized prospective study", "authors": "Shiraki M, Itabashi A", "journal": "Journal of bone and mineral metabolism", "year": 2009, "pmid": "19172219", "url": "https://pubmed.ncbi.nlm.nih.gov/19172219/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/s00774-008-0034-6", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19172219/", "publicSourceType": "PMID" }, { "text": "Meinitzer A, Enko D, Zelzer S et al.. Development of a liquid chromatography mass spectrometry method for the determination of vitamin K1, menaquinone-4, menaquinone-7 and vitamin K1-2,3 epoxide in serum of individuals without vitamin K supplements. Clinical chemistry and laboratory medicine. 2022", "claim": "PubMed-indexed evidence involving Vitamin K2 MK-4", "title": "Development of a liquid chromatography mass spectrometry method for the determination of vitamin K1, menaquinone-4, menaquinone-7 and vitamin K1-2,3 epoxide in serum of individuals without vitamin K supplements", "authors": "Meinitzer A, Enko D, Zelzer S et al.", "journal": "Clinical chemistry and laboratory medicine", "year": 2022, "pmid": "35427444", "url": "https://pubmed.ncbi.nlm.nih.gov/35427444/", "study_type": "review", "confidence": "verify", "doi": "10.1515/cclm-2022-0192", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35427444/", "publicSourceType": "PMID" }, { "text": "Koitaya N, Ezaki J, Nishimuta M et al.. Effect of low dose vitamin K2 (MK-4) supplementation on bio-indices in postmenopausal Japanese women. Journal of nutritional science and vitaminology. 2009", "claim": "PubMed-indexed evidence involving Vitamin K2 MK-4", "title": "Effect of low dose vitamin K2 (MK-4) supplementation on bio-indices in postmenopausal Japanese women", "authors": "Koitaya N, Ezaki J, Nishimuta M et al.", "journal": "Journal of nutritional science and vitaminology", "year": 2009, "pmid": "19352059", "url": "https://pubmed.ncbi.nlm.nih.gov/19352059/", "study_type": "review", "confidence": "verify", "doi": "10.3177/jnsv.55.15", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19352059/", "publicSourceType": "PMID" }, { "text": "Mizuta T, Ozaki I, Eguchi Y et al.. The effect of menatetrenone, a vitamin K2 analog, on disease recurrence and survival in patients with hepatocellular carcinoma after curative treatment: a pilot study. Cancer. 2006", "claim": "PubMed-indexed evidence involving Vitamin K2 MK-4", "title": "The effect of menatetrenone, a vitamin K2 analog, on disease recurrence and survival in patients with hepatocellular carcinoma after curative treatment: a pilot study", "authors": "Mizuta T, Ozaki I, Eguchi Y et al.", "journal": "Cancer", "year": 2006, "pmid": "16400650", "url": "https://pubmed.ncbi.nlm.nih.gov/16400650/", "study_type": "review", "confidence": "verify", "doi": "10.1002/cncr.21667", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16400650/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "vitamin-k2-mk-4" }, { "id": "3B7909F1-BE9B-4C46-8CF6-82A21E9108C7", "name": "Elderberry Zinc Lozenges", "alternateNames": [ "Zinc + Elderberry" ], "category": "Other", "subcategory": "Combination Supplement", "overview": "Popular cold-fighting combination of zinc and elderberry for acute immune support.", "mechanismOfAction": "Zinc ions inhibit rhinovirus replication by blocking viral capsid docking. Elderberry anthocyanins inhibit viral neuraminidase. Synergistic antiviral effects at the oral/pharyngeal mucosa.", "commonBenefits": [ "Cold/flu support", "Sore throat relief", "Immune boost (acute)" ], "commonDosageRange": "1 lozenge every 2-3 hours at onset of cold", "recommendedForm": "Zinc acetate or gluconate lozenges with elderberry", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Dissolve slowly in mouth; start within 24 hours of symptom onset" }, "evidenceRating": "moderate", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Nausea", "Metallic taste", "Mouth irritation" ], "contraindications": [ "Extended use >14 days (zinc toxicity)", "Copper deficiency risk" ], "iconName": "pills.circle.fill", "colorHex": "FF6B9D", "tags": [ "cold-flu", "immune", "acute", "zinc" ], "sources": [ { "claim": "Zinc lozenges shorten common cold duration - meta-analysis comparing zinc acetate and gluconate", "title": "Zinc lozenges and the common cold: a meta-analysis comparing zinc acetate and zinc gluconate, and the role of zinc dosage", "authors": "Hemila H", "journal": "JRSM Open", "year": 2017, "pmid": "28515951", "url": "https://pubmed.ncbi.nlm.nih.gov/28515951/", "study_type": "meta-analysis", "key_finding": "Mean cold duration was 33% shorter with zinc lozenges; zinc acetate showed 40% reduction and zinc gluconate 28% reduction. Doses >75mg/day required for efficacy.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28515951/", "publicSourceType": "PMID" }, { "claim": "Zinc acetate lozenges may improve recovery rate of common cold patients", "title": "Zinc Acetate Lozenges May Improve the Recovery Rate of Common Cold Patients: An Individual Patient Data Meta-Analysis", "authors": "Hemila H et al.", "journal": "Open Forum Infect Dis", "year": 2017, "pmid": "28480298", "url": "https://pubmed.ncbi.nlm.nih.gov/28480298/", "study_type": "meta-analysis", "key_finding": "Individual patient data meta-analysis found patients administered zinc lozenges recovered faster with rate ratio 3.1 (95% CI 2.1-4.7) vs placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28480298/", "publicSourceType": "PMID" }, { "claim": "Elderberry supplementation effectively treats upper respiratory symptoms", "title": "Black elderberry (Sambucus nigra) supplementation effectively treats upper respiratory symptoms: A meta-analysis of randomized, controlled clinical trials", "authors": "Hawkins J et al.", "journal": "Complement Ther Med", "year": 2019, "pmid": "30670267", "url": "https://pubmed.ncbi.nlm.nih.gov/30670267/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 180 participants found elderberry supplementation substantially reduces upper respiratory symptoms.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30670267/", "publicSourceType": "PMID" }, { "claim": "Elderberry extract effective in treatment of influenza A and B virus infections", "title": "Randomized study of the efficacy and safety of oral elderberry extract in the treatment of influenza A and B virus infections", "authors": "Zakay-Rones Z et al.", "journal": "J Int Med Res", "year": 2004, "pmid": "15080016", "url": "https://pubmed.ncbi.nlm.nih.gov/15080016/", "study_type": "RCT", "key_finding": "Symptoms were relieved on average 4 days earlier and rescue medication use was significantly less in elderberry extract group vs placebo for influenza treatment.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15080016/", "publicSourceType": "PMID" }, { "claim": "Elderberry for prevention and treatment of viral respiratory illnesses - systematic review", "title": "Elderberry for prevention and treatment of viral respiratory illnesses: a systematic review", "authors": "Wieland LS et al.", "journal": "BMC Complement Med Ther", "year": 2021, "pmid": "33827515", "url": "https://pubmed.ncbi.nlm.nih.gov/33827515/", "study_type": "review", "key_finding": "Systematic review found elderberry may reduce duration and severity of colds and may reduce duration of influenza, though evidence certainty is limited.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33827515/", "publicSourceType": "PMID" }, { "claim": "Zinc for prevention and treatment of the common cold - Cochrane review", "title": "Zinc for prevention and treatment of the common cold", "authors": "Nault D et al.", "journal": "Cochrane Database Syst Rev", "year": 2024, "pmid": "38719213", "url": "https://pubmed.ncbi.nlm.nih.gov/38719213/", "study_type": "meta-analysis", "key_finding": "Updated Cochrane review evaluating zinc lozenges and other zinc preparations for treatment and prevention of the common cold, supporting modest reduction in cold duration with high-dose zinc.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38719213/", "publicSourceType": "PMID" }, { "text": "Hemilä H. Zinc lozenges may shorten the duration of colds: a systematic review. The open respiratory medicine journal. 2011", "claim": "PubMed-indexed evidence involving Elderberry Zinc Lozenges", "title": "Zinc lozenges may shorten the duration of colds: a systematic review", "authors": "Hemilä H", "journal": "The open respiratory medicine journal", "year": 2011, "pmid": "21769305", "url": "https://pubmed.ncbi.nlm.nih.gov/21769305/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2174/1874306401105010051", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21769305/", "publicSourceType": "PMID" }, { "text": "Garland ML, Hagmeyer KO. The role of zinc lozenges in treatment of the common cold. The Annals of pharmacotherapy. 1998", "claim": "PubMed-indexed evidence involving Elderberry Zinc Lozenges", "title": "The role of zinc lozenges in treatment of the common cold", "authors": "Garland ML, Hagmeyer KO", "journal": "The Annals of pharmacotherapy", "year": 1998, "pmid": "9475824", "url": "https://pubmed.ncbi.nlm.nih.gov/9475824/", "study_type": "review", "confidence": "verify", "doi": "10.1345/aph.17128", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9475824/", "publicSourceType": "PMID" }, { "text": "Della Volpe A, Ricci G, Ralli M et al.. The effects of oral supplements with Sambucus nigra, Zinc, Tyndallized Lactobacillus acidophilus (HA122), Arabinogalactans, vitamin D, vitamin E and vitamin C in otitis media with effusion in children: a randomized controlled trial. European review for medical and pharmacological sciences. 2019", "claim": "PubMed-indexed evidence involving Elderberry Zinc Lozenges", "title": "The effects of oral supplements with Sambucus nigra, Zinc, Tyndallized Lactobacillus acidophilus (HA122), Arabinogalactans, vitamin D, vitamin E and vitamin C in otitis media with effusion in children: a randomized controlled trial", "authors": "Della Volpe A, Ricci G, Ralli M et al.", "journal": "European review for medical and pharmacological sciences", "year": 2019, "pmid": "31364144", "url": "https://pubmed.ncbi.nlm.nih.gov/31364144/", "study_type": "RCT", "confidence": "verify", "doi": "10.26355/eurrev_201907_18460", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31364144/", "publicSourceType": "PMID" }, { "text": "Farhang B, Grondin L. The Effect of Zinc Lozenge on Postoperative Sore Throat: A Prospective Randomized, Double-Blinded, Placebo-Controlled Study. Anesthesia and analgesia. 2018", "claim": "PubMed-indexed evidence involving Elderberry Zinc Lozenges", "title": "The Effect of Zinc Lozenge on Postoperative Sore Throat: A Prospective Randomized, Double-Blinded, Placebo-Controlled Study", "authors": "Farhang B, Grondin L", "journal": "Anesthesia and analgesia", "year": 2018, "pmid": "28953493", "url": "https://pubmed.ncbi.nlm.nih.gov/28953493/", "study_type": "RCT", "confidence": "verify", "doi": "10.1213/ANE.0000000000002494", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28953493/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "elderberry-zinc-lozenges" }, { "id": "BA67600D-7A81-4CCE-83CB-B5BD603F54BD", "name": "Vitamin C Liposomal", "alternateNames": [ "Liposomal Ascorbic Acid" ], "category": "Vitamin", "subcategory": "Enhanced Vitamin C", "overview": "Vitamin C encapsulated in phospholipid liposomes for dramatically improved absorption.", "mechanismOfAction": "Phospholipid bilayer protects ascorbic acid from degradation and enables direct cellular uptake via membrane fusion, bypassing SVCT transporters that limit oral vitamin C absorption.", "commonBenefits": [ "Enhanced vitamin C delivery", "Immune support", "Antioxidant", "Collagen synthesis" ], "commonDosageRange": "1,000-2,000 mg daily", "recommendedForm": "Liposomal vitamin C (look for sunflower lecithin, not soy)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Take on empty stomach for best liposomal absorption" }, "evidenceRating": "strong", "foodSources": [ "Same as vitamin C" ], "deficiencySymptoms": [ "Same as vitamin C deficiency" ], "sideEffects": [ "GI distress (much less than regular high-dose C)" ], "contraindications": [ "Hemochromatosis", "Kidney stones history (oxalate)" ], "iconName": "pill.circle.fill", "colorHex": "FFB800", "tags": [ "immune", "antioxidant", "enhanced-absorption" ], "sources": [ { "claim": "Liposomal vitamin C produces higher circulating concentrations than unencapsulated oral vitamin C", "title": "Liposomal-encapsulated Ascorbic Acid: Influence on Vitamin C Bioavailability and Capacity to Protect Against Ischemia-Reperfusion Injury", "authors": "Davis JL et al.", "journal": "Nutr Metab Insights", "year": 2016, "pmid": "27375360", "url": "https://pubmed.ncbi.nlm.nih.gov/27375360/", "study_type": "RCT", "key_finding": "In 11 subjects, 4g liposomal vitamin C produced greater circulating vitamin C concentrations than unencapsulated oral but less than IV, and provided ischemia-reperfusion protection.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27375360/", "publicSourceType": "PMID" }, { "claim": "Liposomal vs non-liposomal vitamin C clinical comparison showing enhanced bioavailability", "title": "Evaluation and clinical comparison studies on liposomal and non-liposomal ascorbic acid (vitamin C) and their enhanced bioavailability", "authors": "Gopi S, Balakrishnan P", "journal": "J Liposome Res", "year": 2021, "pmid": "32901526", "url": "https://pubmed.ncbi.nlm.nih.gov/32901526/", "study_type": "RCT", "key_finding": "Open-label crossover study in healthy adults showed liposomal vitamin C has greater oral bioavailability than non-liposomal vitamin C under fasting conditions.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32901526/", "publicSourceType": "PMID" }, { "claim": "Liposomal delivery enhances vitamin C absorption into plasma and leukocytes", "title": "Liposomal delivery enhances absorption of vitamin C into plasma and leukocytes: a double-blind, placebo-controlled, randomized trial", "authors": "Tuncay Tanriverdi S et al.", "journal": "Eur J Clin Nutr", "year": 2024, "pmid": "39237620", "url": "https://pubmed.ncbi.nlm.nih.gov/39237620/", "study_type": "RCT", "key_finding": "Double-blind RCT in 27 subjects found 500 mg liposomal vitamin C significantly enhanced absorption into both plasma and leukocytes compared to standard vitamin C.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39237620/", "publicSourceType": "PMID" }, { "claim": "Vitamin C supports both innate and adaptive immune function", "title": "Vitamin C and Immune Function", "authors": "Carr AC, Maggini S", "journal": "Nutrients", "year": 2017, "pmid": "29099763", "url": "https://pubmed.ncbi.nlm.nih.gov/29099763/", "study_type": "review", "key_finding": "Vitamin C supports immune defense by enhancing various cellular functions of both innate and adaptive immunity; supplementation prevents and treats respiratory and systemic infections.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29099763/", "publicSourceType": "PMID" }, { "claim": "Scoping review of liposomal vitamin C bioavailability studies", "title": "Do Liposomal Vitamin C Formulations Have Improved Bioavailability? A Scoping Review Identifying Future Research Directions", "authors": "Carr AC et al.", "journal": "Basic Clin Pharmacol Toxicol", "year": 2025, "pmid": "40506693", "url": "https://pubmed.ncbi.nlm.nih.gov/40506693/", "study_type": "review", "key_finding": "Nine of ten identified studies showed higher bioavailability of liposomal vs non-liposomal ascorbate, with 1.2-5.4-fold higher Cmax and 1.3-7.2-fold higher AUC.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40506693/", "publicSourceType": "PMID" }, { "claim": "Vitamin C reduces severity of common colds - meta-analysis", "title": "Vitamin C reduces the severity of common colds: a meta-analysis", "authors": "Hemilä H, Chalker E", "journal": "BMC public health", "year": 2023, "pmid": "38082300", "url": "https://pubmed.ncbi.nlm.nih.gov/38082300/", "study_type": "meta-analysis", "key_finding": "Meta-analysis supports that vitamin C supplementation reduces the severity and duration of common colds, particularly at doses of 1g or more per day.", "confidence": "verify", "doi": "10.1186/s12889-023-17229-8", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38082300/", "publicSourceType": "PMID" }, { "text": "Hemilä H, Chalker E. Vitamin C reduces the severity of common colds: a meta-analysis. BMC public health. 2023", "pmid": "38082300", "doi": "10.1186/s12889-023-17229-8", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38082300/", "publicSourceType": "PMID" }, { "text": "Rogers DR, Lawlor DJ, Moeller JL. Vitamin C Supplementation and Athletic Performance: A Review. Current sports medicine reports. 2023", "pmid": "37417662", "doi": "10.1249/JSR.0000000000001083", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37417662/", "publicSourceType": "PMID" }, { "text": "Radovanovic D, Signorello JC, Fuccia G et al.. Impact of L-arginine and liposomal vitamin C supplementation on quality of life and daily life activities in patients with COPD: a randomized, multicenter, single blind, placebo-controlled trial (ILDA study). European journal of internal medicine. 2025", "claim": "PubMed-indexed evidence involving Vitamin C Liposomal", "title": "Impact of L-arginine and liposomal vitamin C supplementation on quality of life and daily life activities in patients with COPD: a randomized, multicenter, single blind, placebo-controlled trial (ILDA study)", "authors": "Radovanovic D, Signorello JC, Fuccia G et al.", "journal": "European journal of internal medicine", "year": 2025, "pmid": "40316462", "url": "https://pubmed.ncbi.nlm.nih.gov/40316462/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.ejim.2025.04.039", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40316462/", "publicSourceType": "PMID" }, { "text": "Buso G, Santini P, Ghirardini F et al.. The role of Bromelain and Liposomal Vitamin C in the treatment of chronic venous disease. VASA. Zeitschrift fur Gefasskrankheiten. 2025", "claim": "PubMed-indexed evidence involving Vitamin C Liposomal", "title": "The role of Bromelain and Liposomal Vitamin C in the treatment of chronic venous disease", "authors": "Buso G, Santini P, Ghirardini F et al.", "journal": "VASA. Zeitschrift fur Gefasskrankheiten", "year": 2025, "pmid": "39967325", "url": "https://pubmed.ncbi.nlm.nih.gov/39967325/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1024/0301-1526/a001184", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39967325/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "vitamin-c-liposomal" }, { "id": "D9DE947E-63BC-4629-B08E-0BB8CE678372", "name": "Coenzyme Q10 Ubiquinol", "alternateNames": [ "Ubiquinol", "QH", "Reduced CoQ10" ], "category": "Other", "subcategory": "Active CoQ10 Form", "overview": "The reduced, active antioxidant form of CoQ10, 3-8x better absorbed than ubiquinone.", "mechanismOfAction": "Already in the reduced form used by mitochondria and cell membranes. Donates electrons directly as an antioxidant without needing enzymatic reduction. Particularly beneficial after age 40 when conversion efficiency declines.", "commonBenefits": [ "Mitochondrial energy", "Antioxidant", "Heart health", "Fertility" ], "commonDosageRange": "100-300 mg daily", "recommendedForm": "Kaneka Ubiquinol (patented, stable form)", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with fat-containing meal" }, "evidenceRating": "strong", "foodSources": [ "Same as CoQ10, made endogenously" ], "deficiencySymptoms": [], "sideEffects": [ "Well tolerated", "Insomnia if taken late" ], "contraindications": [ "Blood thinners (theoretical, mild)" ], "iconName": "bolt.heart.fill", "colorHex": "FFB84D", "tags": [ "mitochondria", "energy", "heart", "antioxidant" ], "sources": [ { "claim": "CoQ10 reduces cardiovascular mortality in chronic heart failure (Q-SYMBIO trial)", "title": "The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial", "authors": "Mortensen SA et al.", "journal": "JACC Heart Fail", "year": 2014, "pmid": "25282031", "url": "https://pubmed.ncbi.nlm.nih.gov/25282031/", "study_type": "RCT", "key_finding": "In 420 HF patients over 2 years, CoQ10 100mg 3x daily reduced MACE by 42.3% (p<0.005) and cardiovascular deaths by 43% (p=0.026) vs placebo.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25282031/", "publicSourceType": "PMID" }, { "claim": "CoQ10 supplementation efficacy and safety for heart failure - comprehensive meta-analysis", "title": "Efficacy and safety of coenzyme Q10 in heart failure: a meta-analysis of randomized controlled trials", "authors": "Zhao D et al.", "journal": "BMC Cardiovasc Disord", "year": 2024, "pmid": "39462324", "url": "https://pubmed.ncbi.nlm.nih.gov/39462324/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 33 RCTs found CoQ10 significantly reduced all-cause mortality (RR=0.64, p=0.002) and hospitalization for heart failure (RR=0.50) in HF patients.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39462324/", "publicSourceType": "PMID" }, { "claim": "Ubiquinol is superior to ubiquinone for enhancing CoQ10 status in older men", "title": "Ubiquinol is superior to ubiquinone to enhance Coenzyme Q10 status in older men", "authors": "Zhang Y et al.", "journal": "Food Funct", "year": 2018, "pmid": "30302465", "url": "https://pubmed.ncbi.nlm.nih.gov/30302465/", "study_type": "RCT", "key_finding": "After 2 weeks of supplementation, ubiquinol significantly increased plasma CoQ10 1.5-fold while ubiquinone did not significantly increase it, demonstrating superior bioavailability in older men.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30302465/", "publicSourceType": "PMID" }, { "claim": "Comparison of ubiquinol and ubiquinone plasma levels in healthy subjects", "title": "Comparison study of plasma coenzyme Q10 levels in healthy subjects supplemented with ubiquinol versus ubiquinone", "authors": "Langsjoen PH, Langsjoen AM", "journal": "Clin Pharmacol Drug Dev", "year": 2014, "pmid": "27128225", "url": "https://pubmed.ncbi.nlm.nih.gov/27128225/", "study_type": "RCT", "key_finding": "Plasma CoQ10 and CoQ10/cholesterol ratio were significantly better after ubiquinol than ubiquinone supplementation, confirming superior bioavailability.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27128225/", "publicSourceType": "PMID" }, { "claim": "CoQ10 supplementation improves sperm parameters and fertility outcomes", "title": "Does coenzyme Q10 improve semen quality and circulating testosterone level? a systematic review and meta-analysis of randomized controlled trials", "authors": "Xu Y et al.", "journal": "Front Pharmacol", "year": 2024, "pmid": "39830337", "url": "https://pubmed.ncbi.nlm.nih.gov/39830337/", "study_type": "meta-analysis", "key_finding": "Meta-analysis found CoQ10 supplementation significantly improved sperm concentration, total motility, and was associated with higher testosterone levels, supporting use in male infertility.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39830337/", "publicSourceType": "PMID" }, { "claim": "Bioavailability of CoQ10 formulations including ubiquinol overview", "title": "Comparative Bioavailability of Different Coenzyme Q10 Formulations in Healthy Elderly Individuals", "authors": "Lopez-Lluch G et al.", "journal": "Antioxidants (Basel)", "year": 2020, "pmid": "32188111", "url": "https://pubmed.ncbi.nlm.nih.gov/32188111/", "study_type": "RCT", "key_finding": "Compared CoQ10 formulations in elderly individuals; CoQ10 appeared in blood mostly as ubiquinol even when consumed as ubiquinone, with enhanced absorption from solubilized formulations.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32188111/", "publicSourceType": "PMID" }, { "text": "Tsai IC, Hsu CW, Chang CH et al.. Effectiveness of Coenzyme Q10 Supplementation for Reducing Fatigue: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Frontiers in pharmacology. 2022", "pmid": "36091835", "doi": "10.3389/fphar.2022.883251", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36091835/", "publicSourceType": "PMID" }, { "text": "Qu H, Guo M, Chai H et al.. Effects of Coenzyme Q10 on Statin-Induced Myopathy: An Updated Meta-Analysis of Randomized Controlled Trials. Journal of the American Heart Association. 2018", "pmid": "30371340", "doi": "10.1161/JAHA.118.009835", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30371340/", "publicSourceType": "PMID" }, { "text": "Pek SL, Tavintharan S, Woon K et al.. MicroRNAs as biomarkers of hepatotoxicity in a randomized placebo-controlled study of simvastatin and ubiquinol supplementation. Experimental biology and medicine (Maywood, N.J.). 2016", "claim": "PubMed-indexed evidence involving Coenzyme Q10 Ubiquinol", "title": "MicroRNAs as biomarkers of hepatotoxicity in a randomized placebo-controlled study of simvastatin and ubiquinol supplementation", "authors": "Pek SL, Tavintharan S, Woon K et al.", "journal": "Experimental biology and medicine (Maywood, N.J.)", "year": 2016, "pmid": "26429200", "url": "https://pubmed.ncbi.nlm.nih.gov/26429200/", "study_type": "RCT", "confidence": "verify", "doi": "10.1177/1535370215605588", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26429200/", "publicSourceType": "PMID" }, { "text": "Leaovitavat R, Palakornkitti P, Thetsana P et al.. Effects of Ubiquinol on Oxidized Low-Density Lipoprotein in Prediabetic Patients: A Randomized, Double-Blinded, Placebo-Controlled Study. BioMed research international. 2026", "claim": "PubMed-indexed evidence involving Coenzyme Q10 Ubiquinol", "title": "Effects of Ubiquinol on Oxidized Low-Density Lipoprotein in Prediabetic Patients: A Randomized, Double-Blinded, Placebo-Controlled Study", "authors": "Leaovitavat R, Palakornkitti P, Thetsana P et al.", "journal": "BioMed research international", "year": 2026, "pmid": "41810217", "url": "https://pubmed.ncbi.nlm.nih.gov/41810217/", "study_type": "RCT", "confidence": "verify", "doi": "10.1155/bmri/8739655", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41810217/", "publicSourceType": "PMID" }, { "text": "GamalEl Din SF, A M E, Elkhiat Y et al.. Evaluation of in vivo supplementation of 2660 mg D-aspartic acid and 200 mg ubiquinol and 10 mg zinc on different semen parameters in idiopathic male infertility: a randomized double blind placebo controlled study. Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica. 2025", "claim": "PubMed-indexed evidence involving Coenzyme Q10 Ubiquinol", "title": "Evaluation of in vivo supplementation of 2660 mg D-aspartic acid and 200 mg ubiquinol and 10 mg zinc on different semen parameters in idiopathic male infertility: a randomized double blind placebo controlled study", "authors": "GamalEl Din SF, A M E, Elkhiat Y et al.", "journal": "Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica", "year": 2025, "pmid": "40248985", "url": "https://pubmed.ncbi.nlm.nih.gov/40248985/", "study_type": "RCT", "confidence": "verify", "doi": "10.4081/aiua.2025.13554", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40248985/", "publicSourceType": "PMID" }, { "text": "Nedeljkovic D, Todorovic N, Javorac D et al.. The effects of 8-week creatine supplementation with and without ubiquinol on sperm quality biomarkers in normospermic and oligospermic men: A randomized controlled pilot trial. Nutrition and health. 2025", "claim": "PubMed-indexed evidence involving Coenzyme Q10 Ubiquinol", "title": "The effects of 8-week creatine supplementation with and without ubiquinol on sperm quality biomarkers in normospermic and oligospermic men: A randomized controlled pilot trial", "authors": "Nedeljkovic D, Todorovic N, Javorac D et al.", "journal": "Nutrition and health", "year": 2025, "pmid": "41052075", "url": "https://pubmed.ncbi.nlm.nih.gov/41052075/", "study_type": "RCT", "confidence": "verify", "doi": "10.1177/02601060251385000", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41052075/", "publicSourceType": "PMID" }, { "text": "Liu Z, Yang J, Yang B et al.. Effect of ubiquinol on electrophysiology during high-altitude acclimatization and de-acclimatization: A substudy of the Shigatse CARdiorespiratory fitness (SCARF) randomized clinical trial. International journal of cardiology. 2024", "claim": "PubMed-indexed evidence involving Coenzyme Q10 Ubiquinol", "title": "Effect of ubiquinol on electrophysiology during high-altitude acclimatization and de-acclimatization: A substudy of the Shigatse CARdiorespiratory fitness (SCARF) randomized clinical trial", "authors": "Liu Z, Yang J, Yang B et al.", "journal": "International journal of cardiology", "year": 2024, "pmid": "38307422", "url": "https://pubmed.ncbi.nlm.nih.gov/38307422/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.ijcard.2024.131817", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38307422/", "publicSourceType": "PMID" }, { "text": "Mitsui J, Matsukawa T, Uemura Y et al.. High-dose ubiquinol supplementation in multiple-system atrophy: a multicentre, randomised, double-blinded, placebo-controlled phase 2 trial. EClinicalMedicine. 2023", "claim": "PubMed-indexed evidence involving Coenzyme Q10 Ubiquinol", "title": "High-dose ubiquinol supplementation in multiple-system atrophy: a multicentre, randomised, double-blinded, placebo-controlled phase 2 trial", "authors": "Mitsui J, Matsukawa T, Uemura Y et al.", "journal": "EClinicalMedicine", "year": 2023, "pmid": "37256098", "url": "https://pubmed.ncbi.nlm.nih.gov/37256098/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.eclinm.2023.101920", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37256098/", "publicSourceType": "PMID" }, { "text": "Kirkman DL, Stock JM, Shenouda N et al.. Effects of a mitochondrial-targeted ubiquinol on vascular function and exercise capacity in chronic kidney disease: a randomized controlled pilot study. American journal of physiology. Renal physiology. 2023", "claim": "PubMed-indexed evidence involving Coenzyme Q10 Ubiquinol", "title": "Effects of a mitochondrial-targeted ubiquinol on vascular function and exercise capacity in chronic kidney disease: a randomized controlled pilot study", "authors": "Kirkman DL, Stock JM, Shenouda N et al.", "journal": "American journal of physiology. Renal physiology", "year": 2023, "pmid": "37560769", "url": "https://pubmed.ncbi.nlm.nih.gov/37560769/", "study_type": "RCT", "confidence": "verify", "doi": "10.1152/ajprenal.00067.2023", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37560769/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "coenzyme-q10-ubiquinol" }, { "id": "790E5701-E084-4CF7-9471-FD07705BA86C", "name": "Fish Oil Triple Strength", "alternateNames": [ "Concentrated Omega-3", "High EPA/DHA" ], "category": "Omega/Fatty Acid", "subcategory": "Concentrated Omega-3", "overview": "High-potency fish oil with 75-90% omega-3 concentration for fewer pills and better results.", "mechanismOfAction": "Same EPA/DHA mechanisms but at higher concentration per softgel. EPA resolves inflammation via resolvins/protectins. DHA maintains neuronal membrane fluidity and supports synaptic function.", "commonBenefits": [ "Heart health", "Brain function", "Anti-inflammatory", "Triglyceride reduction" ], "commonDosageRange": "1-2 softgels (providing 900-1800mg combined EPA/DHA)", "recommendedForm": "rTG (re-esterified triglyceride) form, IFOS certified", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with fat-containing meal; refrigerate" }, "evidenceRating": "strong", "foodSources": [ "Fatty fish", "Salmon", "Sardines", "Mackerel" ], "deficiencySymptoms": [], "sideEffects": [ "Fishy burps (less with rTG form)", "Mild blood thinning" ], "contraindications": [ "Blood thinners (high doses)", "Fish allergy", "Surgery (stop 1 week before)" ], "iconName": "drop.fill", "colorHex": "4D94FF", "tags": [ "omega-3", "heart", "brain", "anti-inflammatory" ], "sources": [ { "claim": "Re-esterified triglyceride (rTG) form fish oil has superior bioavailability over ethyl esters", "title": "Bioavailability of marine n-3 fatty acid formulations", "authors": "Dyerberg J et al.", "journal": "Prostaglandins Leukot Essent Fatty Acids", "year": 2010, "pmid": "20638827", "url": "https://pubmed.ncbi.nlm.nih.gov/20638827/", "study_type": "RCT", "key_finding": "In 72 volunteers over 2 weeks, rTG fish oil had 124% bioavailability vs natural fish oil, while ethyl ester form had only 73%, demonstrating superiority of rTG form.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20638827/", "publicSourceType": "PMID" }, { "claim": "High-dose EPA reduces cardiovascular events in statin-treated patients (REDUCE-IT)", "title": "Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia (REDUCE-IT)", "authors": "Bhatt DL et al.", "journal": "N Engl J Med", "year": 2019, "pmid": "30415628", "url": "https://pubmed.ncbi.nlm.nih.gov/30415628/", "study_type": "RCT", "key_finding": "In 8,179 statin-treated patients, 4g/day icosapent ethyl (pure EPA) reduced major cardiovascular events by 25% vs placebo, establishing high-dose omega-3 cardiovascular benefit.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30415628/", "publicSourceType": "PMID" }, { "claim": "Omega-3 fatty acids for management of hypertriglyceridemia - AHA science advisory", "title": "Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association", "authors": "Skulas-Ray AC et al.", "journal": "Circulation", "year": 2019, "pmid": "31422671", "url": "https://pubmed.ncbi.nlm.nih.gov/31422671/", "study_type": "review", "key_finding": "AHA advisory confirms 3-4g/day EPA+DHA significantly reduces triglyceride levels by 20-50% in individuals with elevated TG; supports prescription omega-3 use for hypertriglyceridemia.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31422671/", "publicSourceType": "PMID" }, { "claim": "Omega-3 supplementation reduces cardiovascular outcomes in meta-analysis", "title": "Effect of omega-3 fatty acids on cardiovascular outcomes: A systematic review and meta-analysis", "authors": "Khan SU et al.", "journal": "EClinicalMedicine", "year": 2021, "pmid": "34505026", "url": "https://www.thelancet.com/journals/eclinm/article/piis2589-5370(21)00277-7/fulltext", "study_type": "meta-analysis", "key_finding": "Updated meta-analysis of cohort data and clinical trials consistently links higher EPA/DHA intake to reduced cardiovascular event risk, with dose-dependent triglyceride lowering effects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://www.thelancet.com/journals/eclinm/article/piis2589-5370(21)00277-7/fulltext", "publicSourceType": "PMID" }, { "claim": "Comparative membrane incorporation of rTG fish oil preparations", "title": "Comparative membrane incorporation of omega-3 fish oil triglyceride preparations differing by degree of re-esterification: A sixteen-week randomized intervention trial", "authors": "Landreth H et al.", "journal": "Prostaglandins Leukot Essent Fatty Acids", "year": 2023, "pmid": "36706088", "url": "https://pubmed.ncbi.nlm.nih.gov/36706088/", "study_type": "RCT", "key_finding": "16-week RCT in 60 subjects compared >95% rTG and <70% rTG fish oil preparations, demonstrating higher degree of re-esterification leads to greater omega-3 membrane incorporation.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36706088/", "publicSourceType": "PMID" }, { "claim": "Marine omega-3 fatty acids for prevention of cardiovascular disease (VITAL trial)", "title": "Marine omega-3 fatty acids and prevention of cardiovascular disease and cancer (VITAL trial)", "authors": "Manson JE et al.", "journal": "N Engl J Med", "year": 2019, "pmid": "30415637", "url": "https://pubmed.ncbi.nlm.nih.gov/30415637/", "study_type": "RCT", "key_finding": "In 25,871 participants over 5.3 years, 1g/day omega-3 did not reduce major cardiovascular events overall but showed a significant reduction in MI and benefit in those with low fish intake.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30415637/", "publicSourceType": "PMID" }, { "text": "Casula M, Soranna D, Catapano AL et al.. Long-term effect of high dose omega-3 fatty acid supplementation for secondary prevention of cardiovascular outcomes: A meta-analysis of randomized, placebo controlled trials [corrected]. Atherosclerosis. Supplements. 2013", "claim": "PubMed-indexed evidence involving Fish Oil Triple Strength", "title": "Long-term effect of high dose omega-3 fatty acid supplementation for secondary prevention of cardiovascular outcomes: A meta-analysis of randomized, placebo controlled trials [corrected]", "authors": "Casula M, Soranna D, Catapano AL et al.", "journal": "Atherosclerosis. Supplements", "year": 2013, "pmid": "23958480", "url": "https://pubmed.ncbi.nlm.nih.gov/23958480/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/S1567-5688(13)70005-9", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23958480/", "publicSourceType": "PMID" }, { "text": "Luo XD, Feng JS, Yang Z et al.. High-dose omega-3 polyunsaturated fatty acid supplementation might be more superior than low-dose for major depressive disorder in early therapy period: a network meta-analysis. BMC psychiatry. 2020", "claim": "PubMed-indexed evidence involving Fish Oil Triple Strength", "title": "High-dose omega-3 polyunsaturated fatty acid supplementation might be more superior than low-dose for major depressive disorder in early therapy period: a network meta-analysis", "authors": "Luo XD, Feng JS, Yang Z et al.", "journal": "BMC psychiatry", "year": 2020, "pmid": "32434488", "url": "https://pubmed.ncbi.nlm.nih.gov/32434488/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12888-020-02656-3", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32434488/", "publicSourceType": "PMID" }, { "text": "Nicholls SJ, Lincoff AM, Garcia M et al.. Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk: The STRENGTH Randomized Clinical Trial. JAMA. 2020", "claim": "PubMed-indexed evidence involving Fish Oil Triple Strength", "title": "Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk: The STRENGTH Randomized Clinical Trial", "authors": "Nicholls SJ, Lincoff AM, Garcia M et al.", "journal": "JAMA", "year": 2020, "pmid": "33190147", "url": "https://pubmed.ncbi.nlm.nih.gov/33190147/", "study_type": "RCT", "confidence": "verify", "doi": "10.1001/jama.2020.22258", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33190147/", "publicSourceType": "PMID" }, { "text": "Fattah MAA, Morsi S, Fattah SA et al.. High-dose Omega-3 Alters Serum Magnesium and Calcium Levels and Affects Fibromyalgia Symptoms: A Randomized, Double-blind, Placebo-Control Study. Current rheumatology reviews. 2025", "claim": "PubMed-indexed evidence involving Fish Oil Triple Strength", "title": "High-dose Omega-3 Alters Serum Magnesium and Calcium Levels and Affects Fibromyalgia Symptoms: A Randomized, Double-blind, Placebo-Control Study", "authors": "Fattah MAA, Morsi S, Fattah SA et al.", "journal": "Current rheumatology reviews", "year": 2025, "pmid": "39377412", "url": "https://pubmed.ncbi.nlm.nih.gov/39377412/", "study_type": "RCT", "confidence": "verify", "doi": "10.2174/0115733971314334240930043717", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39377412/", "publicSourceType": "PMID" }, { "text": "Armenta-Morales J, Rivero-Yeverino D, López-García AI et al.. [High-dose omega-3 fatty acid supplementation in patients with persistent allergic rhinitis sensitized to perennial allergens: a randomized, placebo-controlled clinical trial]. Revista alergia Mexico (Tecamachalco, Puebla, Mexico : 1993). 2025", "claim": "PubMed-indexed evidence involving Fish Oil Triple Strength", "title": "[High-dose omega-3 fatty acid supplementation in patients with persistent allergic rhinitis sensitized to perennial allergens: a randomized, placebo-controlled clinical trial]", "authors": "Armenta-Morales J, Rivero-Yeverino D, López-García AI et al.", "journal": "Revista alergia Mexico (Tecamachalco, Puebla, Mexico : 1993)", "year": 2025, "pmid": "41420581", "url": "https://pubmed.ncbi.nlm.nih.gov/41420581/", "study_type": "RCT", "confidence": "verify", "doi": "10.29262/ram.v72i4.1552", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41420581/", "publicSourceType": "PMID" }, { "text": "Stańdo-Retecka M, Piatek P, Namiecinska M et al.. Clinical and microbiological outcomes of subgingival instrumentation supplemented with high-dose omega-3 polyunsaturated fatty acids in periodontal treatment - a randomized clinical trial. BMC oral health. 2023", "claim": "PubMed-indexed evidence involving Fish Oil Triple Strength", "title": "Clinical and microbiological outcomes of subgingival instrumentation supplemented with high-dose omega-3 polyunsaturated fatty acids in periodontal treatment - a randomized clinical trial", "authors": "Stańdo-Retecka M, Piatek P, Namiecinska M et al.", "journal": "BMC oral health", "year": 2023, "pmid": "37179297", "url": "https://pubmed.ncbi.nlm.nih.gov/37179297/", "study_type": "RCT", "confidence": "verify", "doi": "10.1186/s12903-023-03018-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37179297/", "publicSourceType": "PMID" }, { "text": "Kwong RY, Heydari B, Ge Y et al.. Genetic profiling of fatty acid desaturase polymorphisms identifies patients who may benefit from high-dose omega-3 fatty acids in cardiac remodeling after acute myocardial infarction-Post-hoc analysis from the OMEGA-REMODEL randomized controlled trial. PloS one. 2019", "claim": "PubMed-indexed evidence involving Fish Oil Triple Strength", "title": "Genetic profiling of fatty acid desaturase polymorphisms identifies patients who may benefit from high-dose omega-3 fatty acids in cardiac remodeling after acute myocardial infarction-Post-hoc analysis from the OMEGA-REMODEL randomized controlled trial", "authors": "Kwong RY, Heydari B, Ge Y et al.", "journal": "PloS one", "year": 2019, "pmid": "31532795", "url": "https://pubmed.ncbi.nlm.nih.gov/31532795/", "study_type": "RCT", "confidence": "verify", "doi": "10.1371/journal.pone.0222061", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31532795/", "publicSourceType": "PMID" }, { "text": "Karalis DG. A Review of Clinical Practice Guidelines for the Management of Hypertriglyceridemia: A Focus on High Dose Omega-3 Fatty Acids. Advances in therapy. 2017", "claim": "PubMed-indexed evidence involving Fish Oil Triple Strength", "title": "A Review of Clinical Practice Guidelines for the Management of Hypertriglyceridemia: A Focus on High Dose Omega-3 Fatty Acids", "authors": "Karalis DG", "journal": "Advances in therapy", "year": 2017, "pmid": "27981496", "url": "https://pubmed.ncbi.nlm.nih.gov/27981496/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s12325-016-0462-y", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27981496/", "publicSourceType": "PMID" }, { "text": "McClaskey EM, Michalets EL. Subdural hematoma after a fall in an elderly patient taking high-dose omega-3 fatty acids with warfarin and aspirin: case report and review of the literature. Pharmacotherapy. 2007", "claim": "PubMed-indexed evidence involving Fish Oil Triple Strength", "title": "Subdural hematoma after a fall in an elderly patient taking high-dose omega-3 fatty acids with warfarin and aspirin: case report and review of the literature", "authors": "McClaskey EM, Michalets EL", "journal": "Pharmacotherapy", "year": 2007, "pmid": "17192169", "url": "https://pubmed.ncbi.nlm.nih.gov/17192169/", "study_type": "review", "confidence": "verify", "doi": "10.1592/phco.27.1.152", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17192169/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "fish-oil-triple-strength" }, { "id": "A1B2C3D4-E5F6-7890-ABCD-EF1234567100", "name": "St. John's Wort", "alternateNames": [ "Hypericum Perforatum", "SJW" ], "category": "Herb", "subcategory": "Mood Support Herb", "overview": "Widely used herbal antidepressant with one of the most dangerous supplement-drug interaction profiles. Potent CYP3A4 and P-glycoprotein inducer, reduces effectiveness of many critical medications.", "mechanismOfAction": "Hyperforin inhibits reuptake of serotonin, norepinephrine, dopamine, GABA, and glutamate via modulation of sodium-dependent transporters. Hypericin contributes photosensitizing activity. Hyperforin is a potent inducer of CYP3A4, CYP2C9, CYP1A2, and P-glycoprotein via PXR activation.", "commonBenefits": [ "Mild-to-moderate depression", "Mood support", "Anxiety reduction" ], "commonDosageRange": "300 mg 3x daily (standardized to 0.3% hypericin)", "recommendedForm": "Standardized extract (0.3% hypericin, 1-5% hyperforin)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with meals to reduce GI upset. Effects take 4-6 weeks to manifest." }, "evidenceRating": "moderate", "foodSources": [ "Not a food source; herbal supplement only" ], "deficiencySymptoms": [ "Not applicable" ], "sideEffects": [ "Photosensitivity (avoid prolonged sun exposure)", "GI upset", "Dizziness", "Dry mouth", "Anxiety/restlessness" ], "contraindications": [ "SSRIs/SNRIs (serotonin syndrome risk, DANGEROUS)", "Oral contraceptives (reduces effectiveness, breakthrough bleeding and unplanned pregnancies reported)", "HIV antiretrovirals (can reduce to subtherapeutic levels, treatment failure risk)", "Immunosuppressants including cyclosporine and tacrolimus (organ rejection risk)", "Warfarin and other anticoagulants (reduced anticoagulation)", "Cancer chemotherapy drugs (reduced efficacy)", "Digoxin (reduced levels)", "Statins metabolized by CYP3A4 (reduced efficacy)", "Benzodiazepines (reduced levels)", "Pregnancy/breastfeeding", "Bipolar disorder (may trigger mania)", "Planned surgery (photosensitivity risk with anesthesia)" ], "iconName": "sun.max.trianglebadge.exclamationmark.fill", "colorHex": "FFD60A", "tags": [ "mood", "depression", "high-interaction-risk", "herbal" ], "sources": [ { "claim": "St. John's wort comparable to SSRIs for depression with lower discontinuation rate - meta-analysis", "title": "Clinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis", "authors": "Ng QX et al.", "journal": "J Affect Disord", "year": 2017, "pmid": "28064110", "url": "https://pubmed.ncbi.nlm.nih.gov/28064110/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 27 trials (3,808 patients) found St. John's wort had comparable response and remission rates to SSRIs with significantly lower discontinuation/dropout rate.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28064110/", "publicSourceType": "PMID" }, { "claim": "St. John's wort for major depression - Cochrane systematic review", "title": "St John's wort for major depression", "authors": "Linde K et al.", "journal": "Cochrane Database Syst Rev", "year": 2008, "pmid": "18843608", "url": "https://pubmed.ncbi.nlm.nih.gov/18843608/", "study_type": "meta-analysis", "key_finding": "Cochrane review of 29 trials found hypericum extracts tested in trials were (a) superior to placebo for major depression and (b) similarly effective as standard antidepressants with fewer side effects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18843608/", "publicSourceType": "PMID" }, { "claim": "St. John's wort for major depressive disorder - systematic review with quality assessment", "title": "A systematic review of St. John's wort for major depressive disorder", "authors": "Apaydin EA et al.", "journal": "Syst Rev", "year": 2016, "pmid": "27589952", "url": "https://pubmed.ncbi.nlm.nih.gov/27589952/", "study_type": "review", "key_finding": "Systematic review of 35 studies (6,993 patients) found SJW associated with more treatment responders than placebo, with moderate quality of evidence.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27589952/", "publicSourceType": "PMID" }, { "claim": "St. John's wort induces intestinal P-glycoprotein and hepatic CYP3A4 - drug interaction mechanism", "title": "St John's Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4", "authors": "Durr D et al.", "journal": "Clin Pharmacol Ther", "year": 2000, "pmid": "11180019", "url": "https://pubmed.ncbi.nlm.nih.gov/11180019/", "study_type": "RCT", "key_finding": "Landmark study demonstrating SJW induces intestinal P-glycoprotein/MDR1 and both intestinal and hepatic CYP3A4, establishing the dual mechanism for dangerous drug interactions.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11180019/", "publicSourceType": "PMID" }, { "claim": "Drug interactions with St. John's wort - 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Psychopharmacology. 2025", "claim": "PubMed-indexed evidence involving Psilocybin", "title": "Incremental efficacy systematic review and meta-analysis of psilocybin-for-depression RCTs", "authors": "Borgogna NC, Owen T, Petrovitch D et al.", "journal": "Psychopharmacology", "year": 2025, "pmid": "40266291", "url": "https://pubmed.ncbi.nlm.nih.gov/40266291/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00213-025-06788-w", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40266291/", "publicSourceType": "PMID" }, { "text": "Hsu TW, Tsai CK, Kao YC et al.. Comparative oral monotherapy of psilocybin, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine, ayahuasca, and escitalopram for depressive symptoms: systematic review and Bayesian network meta-analysis. BMJ (Clinical research ed.). 2024", "claim": "PubMed-indexed evidence involving Psilocybin", "title": "Comparative oral monotherapy of psilocybin, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine, ayahuasca, and escitalopram for depressive symptoms: systematic review and Bayesian network meta-analysis", "authors": "Hsu TW, Tsai CK, Kao YC et al.", "journal": "BMJ (Clinical research ed.)", "year": 2024, "pmid": "39168500", "url": "https://pubmed.ncbi.nlm.nih.gov/39168500/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1136/bmj-2023-078607", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39168500/", "publicSourceType": "PMID" }, { "text": "van der Meer PB, Fuentes JJ, Kaptein AA et al.. Therapeutic effect of psilocybin in addiction: A systematic review. 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Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review. Psychopharmacology. 2022", "claim": "PubMed-indexed evidence involving MDMA", "title": "Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review", "authors": "Sarparast A, Thomas K, Malcolm B et al.", "journal": "Psychopharmacology", "year": 2022, "pmid": "35253070", "url": "https://pubmed.ncbi.nlm.nih.gov/35253070/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00213-022-06083-y", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35253070/", "publicSourceType": "PMID" }, { "text": "Colcott J, Guerin AA, Carter O et al.. Side-effects of mdma-assisted psychotherapy: a systematic review and meta-analysis. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2024", "claim": "PubMed-indexed evidence involving MDMA", "title": "Side-effects of mdma-assisted psychotherapy: a systematic review and meta-analysis", "authors": "Colcott J, Guerin AA, Carter O et al.", "journal": "Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology", "year": 2024, "pmid": "38654146", "url": "https://pubmed.ncbi.nlm.nih.gov/38654146/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1038/s41386-024-01865-8", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38654146/", "publicSourceType": "PMID" }, { "text": "Hsu TW, Tsai CK, Kao YC et al.. Comparative oral monotherapy of psilocybin, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine, ayahuasca, and escitalopram for depressive symptoms: systematic review and Bayesian network meta-analysis. BMJ (Clinical research ed.). 2024", "claim": "PubMed-indexed evidence involving MDMA", "title": "Comparative oral monotherapy of psilocybin, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine, ayahuasca, and escitalopram for depressive symptoms: systematic review and Bayesian network meta-analysis", "authors": "Hsu TW, Tsai CK, Kao YC et al.", "journal": "BMJ (Clinical research ed.)", "year": 2024, "pmid": "39168500", "url": "https://pubmed.ncbi.nlm.nih.gov/39168500/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1136/bmj-2023-078607", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39168500/", "publicSourceType": "PMID" }, { "text": "Smith KW, Sicignano DJ, Hernandez AV et al.. MDMA-Assisted Psychotherapy for Treatment of Posttraumatic Stress Disorder: A Systematic Review With Meta-Analysis. 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Journal of psychopharmacology (Oxford, England). 2011", "claim": "PubMed-indexed evidence involving MDMA", "title": "The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study", "authors": "Mithoefer MC, Wagner MT, Mithoefer AT et al.", "journal": "Journal of psychopharmacology (Oxford, England)", "year": 2011, "pmid": "20643699", "url": "https://pubmed.ncbi.nlm.nih.gov/20643699/", "study_type": "RCT", "confidence": "verify", "doi": "10.1177/0269881110378371", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20643699/", "publicSourceType": "PMID" }, { "text": "Straumann I, Avedisian I, Klaiber A et al.. Acute effects of R-MDMA, S-MDMA, and racemic MDMA in a randomized double-blind cross-over trial in healthy participants. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2024", "claim": "PubMed-indexed evidence involving MDMA", "title": "Acute effects of R-MDMA, S-MDMA, and racemic MDMA in a randomized double-blind cross-over trial in healthy participants", "authors": "Straumann I, Avedisian I, Klaiber A et al.", "journal": "Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology", "year": 2024, "pmid": "39179638", "url": "https://pubmed.ncbi.nlm.nih.gov/39179638/", "study_type": "RCT", "confidence": "verify", "doi": "10.1038/s41386-024-01972-6", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39179638/", "publicSourceType": "PMID" }, { "text": "Atila C, Straumann I, Vizeli P et al.. Oxytocin and the Role of Fluid Restriction in MDMA-Induced Hyponatremia: A Secondary Analysis of 4 Randomized Clinical Trials. 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Psychiatry research. 2024", "claim": "PubMed-indexed evidence involving Ketamine", "title": "Ketamine versus electroconvulsive therapy for major depressive episode: An updated systematic review and non-inferiority meta-analysis", "authors": "Petrucci ABC, Fernandes JVA, Reis IA et al.", "journal": "Psychiatry research", "year": 2024, "pmid": "38865906", "url": "https://pubmed.ncbi.nlm.nih.gov/38865906/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.psychres.2024.115994", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38865906/", "publicSourceType": "PMID" }, { "text": "Kwaśny A, Kwaśna J, Wilkowska A et al.. Ketamine treatment for anhedonia in unipolar and bipolar depression: a systematic review. 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CNS spectrums. 2024", "claim": "PubMed-indexed evidence involving Ketamine", "title": "Ketamine for the Treatment of Psychiatric Disorders: A Systematic Review and Meta-Analysis", "authors": "Kwan ATH, Lakhani M, Singh G et al.", "journal": "CNS spectrums", "year": 2024, "pmid": "39564613", "url": "https://pubmed.ncbi.nlm.nih.gov/39564613/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1017/S1092852924000580", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39564613/", "publicSourceType": "PMID" } ], "kind": "supplement", "kind_plural": "supplements", "slug": "ketamine" }, { "id": "RX-CARDIO-001", "name": "Atorvastatin", "alternateNames": [ "Lipitor" ], "category": "Prescription", "subcategory": "HMG-CoA Reductase Inhibitor (Statin)", "overview": "Atorvastatin is a high-intensity statin used to lower LDL cholesterol and reduce cardiovascular risk. 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Lancet. 2010.", "pmid": "21067804", "doi": "10.1016/S0140-6736(10)61350-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21067804/", "publicSourceType": "PMID" }, { "text": "Zhang L, Zhang S, Yu Y et al.. Efficacy and safety of rosuvastatin vs. atorvastatin in lowering LDL cholesterol : A meta-analysis of trials with East Asian populations. Herz. 2020", "pmid": "30483816", "doi": "10.1007/s00059-018-4767-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30483816/", "publicSourceType": "PMID" }, { "text": "Jiang R, Zhao S, Wang R et al.. Safety and Efficacy of Atorvastatin for Chronic Subdural Hematoma in Chinese Patients: A Randomized ClinicalTrial. JAMA neurology. 2018", "pmid": "30073290", "doi": "10.1001/jamaneurol.2018.2030", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30073290/", "publicSourceType": "PMID" }, { "claim": "Atorvastatin reduces major cardiovascular events in primary prevention", "title": "Comparative effectiveness and safety of statins as a class and of specific statins for primary prevention of cardiovascular disease: A systematic review, meta-analysis, and network meta-analysis of randomized trials with 94,283 participants", "authors": "Yebyo HG, Aschmann HE, Kaufmann M, Puhan MA", "journal": "American Heart Journal", "year": 2019, "pmid": "30716508", "url": "https://pubmed.ncbi.nlm.nih.gov/30716508/", "study_type": "network meta-analysis", "key_finding": "Atorvastatin and rosuvastatin were among the most effective statins for reducing major cardiovascular events and all-cause mortality in primary prevention across 94,283 participants from randomized trials", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30716508/", "publicSourceType": "PMID" }, { "claim": "Atorvastatin loading before PCI reduces periprocedural myocardial injury", "title": "Atorvastatin before percutaneous coronary intervention: A systematic review and meta-analysis", "authors": "García-Campa M, Flores-Ramírez R, Rojo-Garza S, Carrizales-Sepúlveda EF et al.", "journal": "PLoS One", "year": 2024, "pmid": "38165842", "url": "https://pubmed.ncbi.nlm.nih.gov/38165842/", "study_type": "systematic review", "key_finding": "Pretreatment with atorvastatin before PCI significantly reduced periprocedural myocardial infarction and cardiac enzyme elevation compared to control", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38165842/", "publicSourceType": "PMID" }, { "claim": "Atorvastatin may be effective for chronic subdural hematoma management", "title": "Efficacy and Safety of Atorvastatin for Chronic Subdural Hematoma: An Updated Systematic Review and Meta-Analysis", "authors": "Monteiro GA, Queiroz TS, Gonçalves OR, Cavalcante-Neto JF et al.", "journal": "World Neurosurgery", "year": 2024, "pmid": "38759787", "url": "https://pubmed.ncbi.nlm.nih.gov/38759787/", "study_type": "meta-analysis", "key_finding": "Atorvastatin showed potential benefit in reducing hematoma volume and improving neurological outcomes in chronic subdural hematoma patients, though larger RCTs are needed", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38759787/", "publicSourceType": "PMID" }, { "text": "Villegas-Quintero VE, Rivas-Ruíz R, García-Rivero AA et al.. [Efficacy and safety of atorvastatin in major cardiovascular events: Meta-analysis]. Revista medica del Instituto Mexicano del Seguro Social. 2023", "claim": "PubMed-indexed evidence involving Atorvastatin", "title": "[Efficacy and safety of atorvastatin in major cardiovascular events: Meta-analysis]", "authors": "Villegas-Quintero VE, Rivas-Ruíz R, García-Rivero AA et al.", "journal": "Revista medica del Instituto Mexicano del Seguro Social", "year": 2023, "pmid": "37934798", "url": "https://pubmed.ncbi.nlm.nih.gov/37934798/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.5281/zenodo.8319748", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37934798/", "publicSourceType": "PMID" }, { "text": "Du Y, Wang S, Chen Z et al.. Association of SLCO1B1 Polymorphisms and Atorvastatin Safety and Efficacy: A Meta-analysis. 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Expert review of clinical pharmacology. 2024", "claim": "PubMed-indexed evidence involving Atorvastatin", "title": "Risk of new onset diabetes mellitus with pitavastatin as compared to atorvastatin and rosuvastatin: a systematic review and meta-analysis", "authors": "Singh H, Kaur S, Kaushal P et al.", "journal": "Expert review of clinical pharmacology", "year": 2024, "pmid": "39587804", "url": "https://pubmed.ncbi.nlm.nih.gov/39587804/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/17512433.2024.2433603", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39587804/", "publicSourceType": "PMID" }, { "text": "Su H, Lu Y, Ma C et al.. Impact of atorvastatin on erectile dysfunction: A meta-analysis and systematic review. Andrologia. 2022", "claim": "PubMed-indexed evidence involving Atorvastatin", "title": "Impact of atorvastatin on erectile dysfunction: A meta-analysis and systematic review", "authors": "Su H, Lu Y, Ma C et al.", "journal": "Andrologia", "year": 2022, "pmid": "35224753", "url": "https://pubmed.ncbi.nlm.nih.gov/35224753/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/and.14408", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35224753/", "publicSourceType": "PMID" }, { "text": "Qiu S, Zhuo W, Sun C et al.. Effects of atorvastatin on chronic subdural hematoma: A systematic review. Medicine. 2017", "claim": "PubMed-indexed evidence involving Atorvastatin", "title": "Effects of atorvastatin on chronic subdural hematoma: A systematic review", "authors": "Qiu S, Zhuo W, Sun C et al.", "journal": "Medicine", "year": 2017, "pmid": "28658127", "url": "https://pubmed.ncbi.nlm.nih.gov/28658127/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MD.0000000000007290", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28658127/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "HMG-CoA Reductase Inhibitor (Statin)", "blackBoxWarnings": [], "fdaPregnancyCategory": "X", "halfLife": "14 hours (active metabolites ~20–30 hours)", "onsetOfAction": "LDL reduction seen within 2 weeks; maximal effect at 4–6 weeks", "commonBrandNames": [ "Lipitor" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "LFTs at baseline and as clinically indicated; lipid panel at baseline and 4–12 weeks after initiation or dose adjustment, then every 3–12 months" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "atorvastatin" }, { "id": "RX-CARDIO-002", "name": "Rosuvastatin", "alternateNames": [ "Crestor" ], "category": "Prescription", "subcategory": "HMG-CoA Reductase Inhibitor (Statin)", "overview": "Rosuvastatin is a high-intensity statin and one of the most potent agents for lowering LDL cholesterol. 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Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein (JUPITER). N Engl J Med. 2008.", "pmid": "18997196", "doi": "10.1056/NEJMoa0807646", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18997196/", "publicSourceType": "PMID" }, { "text": "Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals. Lancet. 2002.", "pmid": "12114036", "doi": "10.1016/S0140-6736(02)09327-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12114036/", "publicSourceType": "PMID" }, { "text": "Nissen SE et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis (ASTEROID). JAMA. 2006.", "pmid": "16533939", "doi": "10.1001/jama.295.13.1556", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16533939/", "publicSourceType": "PMID" }, { "text": "Zhang L, Zhang S, Yu Y et al.. Efficacy and safety of rosuvastatin vs. atorvastatin in lowering LDL cholesterol : A meta-analysis of trials with East Asian populations. Herz. 2020", "pmid": "30483816", "doi": "10.1007/s00059-018-4767-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30483816/", "publicSourceType": "PMID" }, { "text": "Lamb YN. Rosuvastatin/Ezetimibe: A Review in Hypercholesterolemia. American journal of cardiovascular drugs : drugs, devices, and other interventions. 2020", "pmid": "32648167", "doi": "10.1007/s40256-020-00421-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32648167/", "publicSourceType": "PMID" }, { "claim": "Statin use is associated with reduced dementia risk", "title": "Statin use and dementia risk: A systematic review and updated meta-analysis", "authors": "Westphal Filho FL, Moss Lopes PR, Menegaz de Almeida A, Sano VKT et al.", "journal": "Alzheimer's & Dementia (New York, N. 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Efficacy and safety of moderate-intensity rosuvastatin plus ezetimibe versus high-intensity rosuvastatin monotherapy in the treatment of composite cardiovascular events with hypercholesterolemia: A meta-analysis. PloS one. 2024", "claim": "PubMed-indexed evidence involving Rosuvastatin", "title": "Efficacy and safety of moderate-intensity rosuvastatin plus ezetimibe versus high-intensity rosuvastatin monotherapy in the treatment of composite cardiovascular events with hypercholesterolemia: A meta-analysis", "authors": "Liu L, Deng Y, Li L et al.", "journal": "PloS one", "year": 2024, "pmid": "39536001", "url": "https://pubmed.ncbi.nlm.nih.gov/39536001/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1371/journal.pone.0310696", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39536001/", "publicSourceType": "PMID" }, { "text": "González-Iglesias E, Novalbos J, Abad-Santos F. 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Diabetes & metabolism journal. 2023", "claim": "PubMed-indexed evidence involving Rosuvastatin", "title": "The Efficacy and Safety of Moderate-Intensity Rosuvastatin with Ezetimibe versus High-Intensity Rosuvastatin in High Atherosclerotic Cardiovascular Disease Risk Patients with Type 2 Diabetes Mellitus: A Randomized, Multicenter, Open, Parallel, Phase 4 Study", "authors": "Moon JS, Park IR, Kim SS et al.", "journal": "Diabetes & metabolism journal", "year": 2023, "pmid": "38043782", "url": "https://pubmed.ncbi.nlm.nih.gov/38043782/", "study_type": "RCT", "confidence": "verify", "doi": "10.4093/dmj.2023.0171", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38043782/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "HMG-CoA Reductase Inhibitor (Statin)", "blackBoxWarnings": [], "fdaPregnancyCategory": "X", "halfLife": "19 hours", "onsetOfAction": "LDL reduction seen within 1–2 weeks; maximal effect at 4 weeks", "commonBrandNames": [ "Crestor" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "LFTs at baseline and as clinically indicated; lipid panel at baseline and 4–12 weeks after initiation, then periodically; monitor for proteinuria at higher doses" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "rosuvastatin" }, { "id": "RX-CARDIO-003", "name": "Simvastatin", "alternateNames": [ "Zocor" ], "category": "Prescription", "subcategory": "HMG-CoA Reductase Inhibitor (Statin)", "overview": "Simvastatin is a moderate-to-high intensity statin with landmark evidence from the 4S and HPS trials demonstrating significant cardiovascular mortality reduction. 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Efficacy and safety of pitavastatin versus simvastatin: a meta-analysis of randomized controlled trials. Clinical drug investigation. 2014", "claim": "PubMed-indexed evidence involving Simvastatin", "title": "Efficacy and safety of pitavastatin versus simvastatin: a meta-analysis of randomized controlled trials", "authors": "Jiang Z, Gong RR, Qiu L et al.", "journal": "Clinical drug investigation", "year": 2014, "pmid": "25022719", "url": "https://pubmed.ncbi.nlm.nih.gov/25022719/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s40261-014-0215-0", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25022719/", "publicSourceType": "PMID" }, { "text": "Cruz R, Pesce G, Calasans-Maia J et al.. Calcium Phosphate Carrying Simvastatin Enhances Bone Regeneration: A Systematic Review. Brazilian dental journal. 2020", "claim": "PubMed-indexed evidence involving Simvastatin", "title": "Calcium Phosphate Carrying Simvastatin Enhances Bone Regeneration: A Systematic Review", "authors": "Cruz R, Pesce G, Calasans-Maia J et al.", "journal": "Brazilian dental journal", "year": 2020, "pmid": "32556021", "url": "https://pubmed.ncbi.nlm.nih.gov/32556021/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1590/0103-6440202002971", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32556021/", "publicSourceType": "PMID" }, { "text": "Ong YC, Aziz Z. Systematic review of red yeast rice compared with simvastatin in dyslipidaemia. Journal of clinical pharmacy and therapeutics. 2016", "claim": "PubMed-indexed evidence involving Simvastatin", "title": "Systematic review of red yeast rice compared with simvastatin in dyslipidaemia", "authors": "Ong YC, Aziz Z", "journal": "Journal of clinical pharmacy and therapeutics", "year": 2016, "pmid": "26956355", "url": "https://pubmed.ncbi.nlm.nih.gov/26956355/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/jcpt.12374", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26956355/", "publicSourceType": "PMID" }, { "text": "Pose E, Napoleone L, Amin A et al.. Safety of two different doses of simvastatin plus rifaximin in decompensated cirrhosis (LIVERHOPE-SAFETY): a randomised, double-blind, placebo-controlled, phase 2 trial. The lancet. Gastroenterology & hepatology. 2020", "claim": "PubMed-indexed evidence involving Simvastatin", "title": "Safety of two different doses of simvastatin plus rifaximin in decompensated cirrhosis (LIVERHOPE-SAFETY): a randomised, double-blind, placebo-controlled, phase 2 trial", "authors": "Pose E, Napoleone L, Amin A et al.", "journal": "The lancet. Gastroenterology & hepatology", "year": 2020, "pmid": "31607677", "url": "https://pubmed.ncbi.nlm.nih.gov/31607677/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/S2468-1253(19)30320-6", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31607677/", "publicSourceType": "PMID" }, { "text": "Alvarado-Tapias E, Brujats A, Puente A et al.. Hemodynamic effects of carvedilol plus simvastatin in cirrhosis with severe portal hypertension and suboptimal response to β-blockers: A double-blind, placebo-controlled, randomized trial. Hepatology (Baltimore, Md.). 2025", "claim": "PubMed-indexed evidence involving Simvastatin", "title": "Hemodynamic effects of carvedilol plus simvastatin in cirrhosis with severe portal hypertension and suboptimal response to β-blockers: A double-blind, placebo-controlled, randomized trial", "authors": "Alvarado-Tapias E, Brujats A, Puente A et al.", "journal": "Hepatology (Baltimore, Md.)", "year": 2025, "pmid": "39509369", "url": "https://pubmed.ncbi.nlm.nih.gov/39509369/", "study_type": "RCT", "confidence": "verify", "doi": "10.1097/HEP.0000000000001148", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39509369/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "HMG-CoA Reductase Inhibitor (Statin)", "blackBoxWarnings": [], "fdaPregnancyCategory": "X", "halfLife": "2–3 hours (active metabolites longer)", "onsetOfAction": "LDL reduction within 2 weeks; maximal effect at 4–6 weeks", "commonBrandNames": [ "Zocor" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "LFTs at baseline and as clinically indicated; lipid panel at baseline and 4–12 weeks after initiation; CK if myopathy symptoms develop" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "simvastatin" }, { "id": "RX-CARDIO-004", "name": "Pravastatin", "alternateNames": [ "Pravachol" ], "category": "Prescription", "subcategory": "HMG-CoA Reductase Inhibitor (Statin)", "overview": "Pravastatin is a moderate-intensity hydrophilic statin with proven cardiovascular benefits in primary and secondary prevention. 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Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia (WOSCOPS). N Engl J Med. 1995.", "pmid": "7566020", "doi": "10.1056/NEJM199511163332001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7566020/", "publicSourceType": "PMID" }, { "text": "Sacks FM et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels (CARE). N Engl J Med. 1996.", "pmid": "8801446", "doi": "10.1056/NEJM199610033351401", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8801446/", "publicSourceType": "PMID" }, { "text": "Li W et al. A Meta-Analysis of the Incidence of Adverse Reactions of Statins in Various Diseases. 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Effect of pravastatin treatment on circulating adiponectin: a meta-analysis of randomized controlled trials. Drug design, development and therapy. 2019", "claim": "PubMed-indexed evidence involving Pravastatin", "title": "Effect of pravastatin treatment on circulating adiponectin: a meta-analysis of randomized controlled trials", "authors": "Shu X, Chi L", "journal": "Drug design, development and therapy", "year": 2019, "pmid": "31190742", "url": "https://pubmed.ncbi.nlm.nih.gov/31190742/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2147/DDDT.S186992", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31190742/", "publicSourceType": "PMID" }, { "text": "Hirsch A, Rotem R, Ternovsky N et al.. Pravastatin and placental insufficiency associated disorders: A systematic review and meta-analysis. Frontiers in pharmacology. 2022", "claim": "PubMed-indexed evidence involving Pravastatin", "title": "Pravastatin and placental insufficiency associated disorders: A systematic review and meta-analysis", "authors": "Hirsch A, Rotem R, Ternovsky N et al.", "journal": "Frontiers in pharmacology", "year": 2022, "pmid": "36438820", "url": "https://pubmed.ncbi.nlm.nih.gov/36438820/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fphar.2022.1021548", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36438820/", "publicSourceType": "PMID" }, { "text": "Mészáros B, Veres DS, Nagyistók L et al.. Pravastatin in preeclampsia: A meta-analysis and systematic review. Frontiers in medicine. 2022", "claim": "PubMed-indexed evidence involving Pravastatin", "title": "Pravastatin in preeclampsia: A meta-analysis and systematic review", "authors": "Mészáros B, Veres DS, Nagyistók L et al.", "journal": "Frontiers in medicine", "year": 2022, "pmid": "36714131", "url": "https://pubmed.ncbi.nlm.nih.gov/36714131/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fmed.2022.1076372", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36714131/", "publicSourceType": "PMID" }, { "text": "Provinciatto H, Barbalho ME, Almeida J et al.. The role of pravastatin in preventing preeclampsia in high-risk pregnant women: a meta-analysis with trial sequential analysis. American journal of obstetrics & gynecology MFM. 2024", "claim": "PubMed-indexed evidence involving Pravastatin", "title": "The role of pravastatin in preventing preeclampsia in high-risk pregnant women: a meta-analysis with trial sequential analysis", "authors": "Provinciatto H, Barbalho ME, Almeida J et al.", "journal": "American journal of obstetrics & gynecology MFM", "year": 2024, "pmid": "38109997", "url": "https://pubmed.ncbi.nlm.nih.gov/38109997/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.ajogmf.2023.101260", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38109997/", "publicSourceType": "PMID" }, { "text": "Bonovas S, Sitaras NM. Does pravastatin promote cancer in elderly patients? A meta-analysis. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2007", "claim": "PubMed-indexed evidence involving Pravastatin", "title": "Does pravastatin promote cancer in elderly patients? A meta-analysis", "authors": "Bonovas S, Sitaras NM", "journal": "CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne", "year": 2007, "pmid": "17325332", "url": "https://pubmed.ncbi.nlm.nih.gov/17325332/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1503/cmaj.060803", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17325332/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "HMG-CoA Reductase Inhibitor (Statin)", "blackBoxWarnings": [], "fdaPregnancyCategory": "X", "halfLife": "1.5–2.5 hours", "onsetOfAction": "LDL reduction within 1–2 weeks; maximal effect at 4 weeks", "commonBrandNames": [ "Pravachol" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "LFTs at baseline and as clinically indicated; lipid panel at baseline and 4–12 weeks after initiation" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "pravastatin" }, { "id": "RX-CARDIO-005", "name": "Lovastatin", "alternateNames": [ "Mevacor", "Altoprev" ], "category": "Prescription", "subcategory": "HMG-CoA Reductase Inhibitor (Statin)", "overview": "Lovastatin was the first commercially available statin and is a moderate-intensity agent derived from Aspergillus terreus fungus. It was the first drug to clearly demonstrate that lowering cholesterol reduces cardiovascular events.", "mechanismOfAction": "Inactive lactone prodrug that is hydrolyzed in vivo to the active beta-hydroxyacid form. Inhibits HMG-CoA reductase, the rate-limiting step in cholesterol biosynthesis. Metabolized by CYP3A4. Reduces hepatic cholesterol synthesis, upregulates LDL receptors, and increases LDL clearance.", "commonBenefits": [ "Lowers LDL cholesterol by 20–40%", "Proven reduction in first major coronary events (AFCAPS/TexCAPS trial)", "Reduces triglycerides modestly", "Available as extended-release formulation" ], "commonDosageRange": "10–80 mg daily with evening meal (as prescribed by your physician)", "recommendedForm": "Oral tablet, taken with the evening meal for immediate-release", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Immediate-release lovastatin should be taken with the evening meal to increase bioavailability by ~50%; avoid grapefruit juice" }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Myalgia and muscle cramps", "Elevated liver transaminases", "Gastrointestinal disturbances (flatulence, dyspepsia)", "Headache", "Rhabdomyolysis (rare)", "Insomnia" ], "contraindications": [ "Active liver disease or unexplained persistent transaminase elevations", "Pregnancy and breastfeeding", "Concurrent strong CYP3A4 inhibitors", "Concurrent gemfibrozil, cyclosporine, or danazol" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "cardiovascular", "cholesterol", "statin", "lipid-lowering", "heart-health" ], "sources": [ { "text": "Downs JR et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels (AFCAPS/TexCAPS). JAMA. 1998.", "pmid": "9613910", "doi": "10.1001/jama.279.20.1615", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9613910/", "publicSourceType": "PMID" }, { "text": "Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the 4S study. Lancet. 1994.", "pmid": "7968073", "doi": "10.1016/S0140-6736(94)90566-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7968073/", "publicSourceType": "PMID" }, { "text": "Wang Z et al. Statins for the primary prevention of venous thromboembolism. Cochrane Database Syst Rev. 2024.", "pmid": "39498835", "doi": "10.1002/14651858.CD014769.pub2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39498835/", "publicSourceType": "PMID" }, { "text": "Duong H, Bajaj T. Lovastatin. 2026", "pmid": "31082038", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31082038/", "publicSourceType": "PMID" }, { "text": "Santa Lucia G, Snyder A, Lateef A et al.. Safety and Efficacy of Topical Lovastatin Plus Cholesterol Cream vs Topical Lovastatin Cream Alone for the Treatment of Disseminated Superficial Actinic Porokeratosis: A Randomized Clinical Trial. JAMA dermatology. 2023", "pmid": "36947042", "doi": "10.1001/jamadermatol.2023.0205", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36947042/", "publicSourceType": "PMID" }, { "text": "McKinney WS, Schmitt LM, De Stefano LA et al.. Results from a Double-Blind, Randomized, Placebo-Controlled, Single-Dose, Crossover Trial of Lovastatin or Minocycline in Fragile X Syndrome. Journal of child and adolescent psychopharmacology. 2025", "claim": "PubMed-indexed evidence involving Lovastatin", "title": "Results from a Double-Blind, Randomized, Placebo-Controlled, Single-Dose, Crossover Trial of Lovastatin or Minocycline in Fragile X Syndrome", "authors": "McKinney WS, Schmitt LM, De Stefano LA et al.", "journal": "Journal of child and adolescent psychopharmacology", "year": 2025, "pmid": "39651602", "url": "https://pubmed.ncbi.nlm.nih.gov/39651602/", "study_type": "RCT", "confidence": "verify", "doi": "10.1089/cap.2024.0103", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39651602/", "publicSourceType": "PMID" }, { "text": "Lin CH, Chang CH, Tai CH et al.. A Double-Blind, Randomized, Controlled Trial of Lovastatin in Early-Stage Parkinson's Disease. Movement disorders : official journal of the Movement Disorder Society. 2021", "claim": "PubMed-indexed evidence involving Lovastatin", "title": "A Double-Blind, Randomized, Controlled Trial of Lovastatin in Early-Stage Parkinson's Disease", "authors": "Lin CH, Chang CH, Tai CH et al.", "journal": "Movement disorders : official journal of the Movement Disorder Society", "year": 2021, "pmid": "33449392", "url": "https://pubmed.ncbi.nlm.nih.gov/33449392/", "study_type": "RCT", "confidence": "verify", "doi": "10.1002/mds.28474", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33449392/", "publicSourceType": "PMID" }, { "text": "Payne JM, Barton B, Ullrich NJ et al.. Randomized placebo-controlled study of lovastatin in children with neurofibromatosis type 1. Neurology. 2016", "claim": "PubMed-indexed evidence involving Lovastatin", "title": "Randomized placebo-controlled study of lovastatin in children with neurofibromatosis type 1", "authors": "Payne JM, Barton B, Ullrich NJ et al.", "journal": "Neurology", "year": 2016, "pmid": "27956565", "url": "https://pubmed.ncbi.nlm.nih.gov/27956565/", "study_type": "RCT", "confidence": "verify", "doi": "10.1212/WNL.0000000000003435", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27956565/", "publicSourceType": "PMID" }, { "text": "Azie NE, Brater DC, Becker PA et al.. The interaction of diltiazem with lovastatin and pravastatin. Clinical pharmacology and therapeutics. 1998", "claim": "PubMed-indexed evidence involving Lovastatin", "title": "The interaction of diltiazem with lovastatin and pravastatin", "authors": "Azie NE, Brater DC, Becker PA et al.", "journal": "Clinical pharmacology and therapeutics", "year": 1998, "pmid": "9797793", "url": "https://pubmed.ncbi.nlm.nih.gov/9797793/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/S0009-9236(98)90067-4", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9797793/", "publicSourceType": "PMID" }, { "text": "Richter WO, Jacob BG, Schwandt P. Interaction between fibre and lovastatin. 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J Hum Hypertens. 2026.", "pmid": "41663753", "doi": "10.1038/s41371-026-01120-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41663753/", "publicSourceType": "PMID" }, { "text": "Olvera Lopez E, Parmar M, Pendela VS et al.. Lisinopril. 2026", "pmid": "29489196", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29489196/", "publicSourceType": "PMID" }, { "claim": "ACE inhibitors effectively reduce blood pressure with cough as a notable side effect", "title": "Angiotensin-converting enzyme inhibitor induced cough compared with placebo, and other antihypertensives: A systematic review, and network meta-analysis", "authors": "Hu Y, Liang L, Liu S, Kung JY et al.", "journal": "Journal of Clinical Hypertension (Greenwich)", "year": 2023, "pmid": "37417783", "url": "https://pubmed.ncbi.nlm.nih.gov/37417783/", "study_type": "network meta-analysis", "key_finding": "ACE inhibitors, including lisinopril, significantly increased the risk of cough compared to placebo (OR ~3.0) and other antihypertensive classes, while remaining highly effective for blood pressure reduction", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37417783/", "publicSourceType": "PMID" }, { "claim": "ACE inhibitors are effective antihypertensives in pediatric populations", "title": "Pharmacological Treatment of Arterial Hypertension in Children and Adolescents: A Network Meta-Analysis", "authors": "Burrello J, Erhardt EM, Saint-Hilary G, Veglio F et al.", "journal": "Hypertension", "year": 2018, "pmid": "29967035", "url": "https://pubmed.ncbi.nlm.nih.gov/29967035/", "study_type": "network meta-analysis", "key_finding": "ACE inhibitors were among the most effective drug classes for reducing systolic and diastolic blood pressure in hypertensive children and adolescents", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29967035/", "publicSourceType": "PMID" }, { "text": "Sadat-Ebrahimi SR, Parnianfard N, Vahed N et al.. An evidence-based systematic review of the off-label uses of lisinopril. British journal of clinical pharmacology. 2018", "claim": "PubMed-indexed evidence involving Lisinopril", "title": "An evidence-based systematic review of the off-label uses of lisinopril", "authors": "Sadat-Ebrahimi SR, Parnianfard N, Vahed N et al.", "journal": "British journal of clinical pharmacology", "year": 2018, "pmid": "29971804", "url": "https://pubmed.ncbi.nlm.nih.gov/29971804/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/bcp.13705", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29971804/", "publicSourceType": "PMID" }, { "text": "Guglin M, Krischer J, Tamura R et al.. Randomized Trial of Lisinopril Versus Carvedilol to Prevent Trastuzumab Cardiotoxicity in Patients With Breast Cancer. 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American journal of obstetrics and gynecology. 2023", "claim": "PubMed-indexed evidence involving Lisinopril", "title": "Oral combined hydrochlorothiazide and lisinopril vs nifedipine for postpartum hypertension: a comparative-effectiveness pilot randomized controlled trial", "authors": "Fishel Bartal M, Blackwell SC, Pedroza C et al.", "journal": "American journal of obstetrics and gynecology", "year": 2023, "pmid": "36787814", "url": "https://pubmed.ncbi.nlm.nih.gov/36787814/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.ajog.2023.01.015", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36787814/", "publicSourceType": "PMID" }, { "text": "Shima Y, Nakanishi K, Sako M et al.. Lisinopril versus lisinopril and losartan for mild childhood IgA nephropathy: a randomized controlled trial (JSKDC01 study). Pediatric nephrology (Berlin, Germany). 2019", "claim": "PubMed-indexed evidence involving Lisinopril", "title": "Lisinopril versus lisinopril and losartan for mild childhood IgA nephropathy: a randomized controlled trial (JSKDC01 study)", "authors": "Shima Y, Nakanishi K, Sako M et al.", "journal": "Pediatric nephrology (Berlin, Germany)", "year": 2019, "pmid": "30284023", "url": "https://pubmed.ncbi.nlm.nih.gov/30284023/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/s00467-018-4099-8", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30284023/", "publicSourceType": "PMID" }, { "text": "Cockerham LR, Yukl SA, Harvill K et al.. A Randomized Controlled Trial of Lisinopril to Decrease Lymphoid Fibrosis in Antiretroviral-Treated, HIV-infected Individuals. Pathogens & immunity. 2017", "claim": "PubMed-indexed evidence involving Lisinopril", "title": "A Randomized Controlled Trial of Lisinopril to Decrease Lymphoid Fibrosis in Antiretroviral-Treated, HIV-infected Individuals", "authors": "Cockerham LR, Yukl SA, Harvill K et al.", "journal": "Pathogens & immunity", "year": 2017, "pmid": "28936485", "url": "https://pubmed.ncbi.nlm.nih.gov/28936485/", "study_type": "RCT", "confidence": "verify", "doi": "10.20411/pai.v2i3.207", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28936485/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Angiotensin-Converting Enzyme (ACE) Inhibitor", "blackBoxWarnings": [ "Can cause fetal toxicity when administered during pregnancy. 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Pan Afr Med J. 2025.", "pmid": "41323461", "doi": "10.11604/pamj.2025.52.18.46768", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41323461/", "publicSourceType": "PMID" }, { "text": "Smeets NJL, Schreuder MF, Dalinghaus M et al.. Pharmacology of enalapril in children: a review. Drug discovery today. 2020", "pmid": "32835726", "doi": "10.1016/j.drudis.2020.08.005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32835726/", "publicSourceType": "PMID" }, { "text": "Zhang Y, Liu J, Li Y et al.. Protective Role of Enalapril in Anthracycline-Induced Cardiotoxicity: A Systematic Review. Frontiers in pharmacology. 2020", "claim": "PubMed-indexed evidence involving Enalapril", "title": "Protective Role of Enalapril in Anthracycline-Induced Cardiotoxicity: A Systematic Review", "authors": "Zhang Y, Liu J, Li Y et al.", "journal": "Frontiers in pharmacology", "year": 2020, "pmid": "32536868", "url": "https://pubmed.ncbi.nlm.nih.gov/32536868/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fphar.2020.00788", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32536868/", "publicSourceType": "PMID" }, { "text": "Reyaz I, Kaur A, Saad MZ et al.. Comparison of Outcomes Between Sacubitril/Valsartan and Enalapril in Patients With Heart Failure: A Systematic Review and Meta-Analysis. Cureus. 2023", "claim": "PubMed-indexed evidence involving Enalapril", "title": "Comparison of Outcomes Between Sacubitril/Valsartan and Enalapril in Patients With Heart Failure: A Systematic Review and Meta-Analysis", "authors": "Reyaz I, Kaur A, Saad MZ et al.", "journal": "Cureus", "year": 2023, "pmid": "38084196", "url": "https://pubmed.ncbi.nlm.nih.gov/38084196/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7759/cureus.48623", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38084196/", "publicSourceType": "PMID" }, { "text": "Faisal M, Cawello W, Laeer S et al.. Clinical Pharmacokinetics of Enalapril and Enalaprilat in Pediatric Patients-A Systematic Review. Frontiers in pediatrics. 2021", "claim": "PubMed-indexed evidence involving Enalapril", "title": "Clinical Pharmacokinetics of Enalapril and Enalaprilat in Pediatric Patients-A Systematic Review", "authors": "Faisal M, Cawello W, Laeer S et al.", "journal": "Frontiers in pediatrics", "year": 2021, "pmid": "33643971", "url": "https://pubmed.ncbi.nlm.nih.gov/33643971/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fped.2021.611322", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33643971/", "publicSourceType": "PMID" }, { "text": "He YM, Feng L, Huo DM et al.. Enalapril versus losartan for adults with chronic kidney disease: a systematic review and meta-analysis. Nephrology (Carlton, Vic.). 2013", "claim": "PubMed-indexed evidence involving Enalapril", "title": "Enalapril versus losartan for adults with chronic kidney disease: a systematic review and meta-analysis", "authors": "He YM, Feng L, Huo DM et al.", "journal": "Nephrology (Carlton, Vic.)", "year": 2013, "pmid": "23869492", "url": "https://pubmed.ncbi.nlm.nih.gov/23869492/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/nep.12134", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23869492/", "publicSourceType": "PMID" }, { "text": "Rizzoni D. Fixed-dose lercanidipine and enalapril in field practice: a meta-analysis. Current medical research and opinion. 2016", "claim": "PubMed-indexed evidence involving Enalapril", "title": "Fixed-dose lercanidipine and enalapril in field practice: a meta-analysis", "authors": "Rizzoni D", "journal": "Current medical research and opinion", "year": 2016, "pmid": "27779457", "url": "https://pubmed.ncbi.nlm.nih.gov/27779457/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/03007995.2016.1218835", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27779457/", "publicSourceType": "PMID" }, { "text": "Moncloa F, Sromovsky JA, Walker JF et al.. Enalapril in hypertension and congestive heart failure. Overall review of efficacy and safety. Drugs. 1985", "claim": "PubMed-indexed evidence involving Enalapril", "title": "Enalapril in hypertension and congestive heart failure. Overall review of efficacy and safety", "authors": "Moncloa F, Sromovsky JA, Walker JF et al.", "journal": "Drugs", "year": 1985, "pmid": "2864229", "url": "https://pubmed.ncbi.nlm.nih.gov/2864229/", "study_type": "review", "confidence": "verify", "doi": "10.2165/00003495-198500301-00012", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2864229/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Angiotensin-Converting Enzyme (ACE) Inhibitor", "blackBoxWarnings": [ "Can cause fetal toxicity when administered during pregnancy. 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Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients (HOPE). N Engl J Med. 2000.", "pmid": "10639539", "doi": "10.1056/NEJM200001203420301", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10639539/", "publicSourceType": "PMID" }, { "text": "AIRE Study Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet. 1993.", "pmid": "8105262", "doi": "10.1016/0140-6736(93)92901-4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8105262/", "publicSourceType": "PMID" }, { "text": "Rodríguez-Armesto A et al. Effects of polypills on cardiovascular outcomes: Meta-analysis of clinical trials and observational studies. Semergen. 2026.", "pmid": "41558137", "doi": "10.1016/j.semerg.2025.102680", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41558137/", "publicSourceType": "PMID" }, { "text": "Chauhan M, Patel JB, Ahmad F. Ramipril. 2026", "pmid": "30725804", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30725804/", "publicSourceType": "PMID" }, { "text": "Warner GT, Perry CM. Spotlight on ramipril in the prevention of cardiovascular outcomes. American journal of cardiovascular drugs : drugs, devices, and other interventions. 2003", "pmid": "14727938", "doi": "10.2165/00129784-200303020-00005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14727938/", "publicSourceType": "PMID" }, { "text": "Borghi C, Omboni S, Novo S et al.. Efficacy and Safety of Zofenopril Versus Ramipril in the Treatment of Myocardial Infarction and Heart Failure: A Review of the Published and Unpublished Data of the Randomized Double-Blind SMILE-4 Study. Advances in therapy. 2018", "claim": "PubMed-indexed evidence involving Ramipril", "title": "Efficacy and Safety of Zofenopril Versus Ramipril in the Treatment of Myocardial Infarction and Heart Failure: A Review of the Published and Unpublished Data of the Randomized Double-Blind SMILE-4 Study", "authors": "Borghi C, Omboni S, Novo S et al.", "journal": "Advances in therapy", "year": 2018, "pmid": "29667144", "url": "https://pubmed.ncbi.nlm.nih.gov/29667144/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/s12325-018-0697-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29667144/", "publicSourceType": "PMID" }, { "text": "Lubsen J, Chadha DR, Yotof YT et al.. Meta-analysis of morbidity and mortality in five exercise capacity trials evaluating ramipril in chronic congestive cardiac failure. The American journal of cardiology. 1996", "claim": "PubMed-indexed evidence involving Ramipril", "title": "Meta-analysis of morbidity and mortality in five exercise capacity trials evaluating ramipril in chronic congestive cardiac failure", "authors": "Lubsen J, Chadha DR, Yotof YT et al.", "journal": "The American journal of cardiology", "year": 1996, "pmid": "8651094", "url": "https://pubmed.ncbi.nlm.nih.gov/8651094/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/s0002-9149(96)00161-0", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8651094/", "publicSourceType": "PMID" }, { "text": "Farkona S, Kotlyar M, Burns K et al.. Urine Measurements of the Renin-Angiotensin System-Regulated Proteins Predict Death and Graft Loss in Kidney Transplant Recipients Enrolled in a Ramipril versus Placebo Randomized Controlled Trial. Journal of proteome research. 2025", "claim": "PubMed-indexed evidence involving Ramipril", "title": "Urine Measurements of the Renin-Angiotensin System-Regulated Proteins Predict Death and Graft Loss in Kidney Transplant Recipients Enrolled in a Ramipril versus Placebo Randomized Controlled Trial", "authors": "Farkona S, Kotlyar M, Burns K et al.", "journal": "Journal of proteome research", "year": 2025, "pmid": "40111290", "url": "https://pubmed.ncbi.nlm.nih.gov/40111290/", "study_type": "RCT", "confidence": "verify", "doi": "10.1021/acs.jproteome.4c01100", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40111290/", "publicSourceType": "PMID" }, { "text": "Amat-Santos IJ, López-Otero D, Nombela-Franco L et al.. 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Preventing microalbuminuria with benazepril, valsartan, and benazepril-valsartan combination therapy in diabetic patients with high-normal albuminuria: A prospective, randomized, open-label, blinded endpoint (PROBE) study. PLoS medicine. 2021", "claim": "PubMed-indexed evidence involving Benazepril", "title": "Preventing microalbuminuria with benazepril, valsartan, and benazepril-valsartan combination therapy in diabetic patients with high-normal albuminuria: A prospective, randomized, open-label, blinded endpoint (PROBE) study", "authors": "Ruggenenti P, Cortinovis M, Parvanova A et al.", "journal": "PLoS medicine", "year": 2021, "pmid": "34260595", "url": "https://pubmed.ncbi.nlm.nih.gov/34260595/", "study_type": "RCT", "confidence": "verify", "doi": "10.1371/journal.pmed.1003691", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34260595/", "publicSourceType": "PMID" }, { "text": "Ruggenenti P, Trillini M, P Barlovic D et al.. Effects of valsartan, benazepril and their combination in overt nephropathy of type 2 diabetes: A prospective, randomized, controlled trial. Diabetes, obesity & metabolism. 2019", "claim": "PubMed-indexed evidence involving Benazepril", "title": "Effects of valsartan, benazepril and their combination in overt nephropathy of type 2 diabetes: A prospective, randomized, controlled trial", "authors": "Ruggenenti P, Trillini M, P Barlovic D et al.", "journal": "Diabetes, obesity & metabolism", "year": 2019, "pmid": "30793466", "url": "https://pubmed.ncbi.nlm.nih.gov/30793466/", "study_type": "RCT", "confidence": "verify", "doi": "10.1111/dom.13639", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30793466/", "publicSourceType": "PMID" }, { "text": "Ding C, Song H, Qiu B et al.. Effect of High-Fat Food on the Pharmacokinetics and Safety of Amlodipine/Benazepril in Healthy Chinese Participants. Clinical pharmacology in drug development. 2026", "claim": "PubMed-indexed evidence involving Benazepril", "title": "Effect of High-Fat Food on the Pharmacokinetics and Safety of Amlodipine/Benazepril in Healthy Chinese Participants", "authors": "Ding C, Song H, Qiu B et al.", "journal": "Clinical pharmacology in drug development", "year": 2026, "pmid": "41549805", "url": "https://pubmed.ncbi.nlm.nih.gov/41549805/", "study_type": "review", "confidence": "verify", "doi": "10.1002/cpdd.70022", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41549805/", "publicSourceType": "PMID" }, { "text": "Kuschnir E, Acuña E, Sevilla D et al.. Treatment of patients with essential hypertension: amlodipine 5 mg/benazepril 20 mg compared with amlodipine 5 mg, benazepril 20 mg, and placebo. Clinical therapeutics. 1996", "claim": "PubMed-indexed evidence involving Benazepril", "title": "Treatment of patients with essential hypertension: amlodipine 5 mg/benazepril 20 mg compared with amlodipine 5 mg, benazepril 20 mg, and placebo", "authors": "Kuschnir E, Acuña E, Sevilla D et al.", "journal": "Clinical therapeutics", "year": 1996, "pmid": "9001838", "url": "https://pubmed.ncbi.nlm.nih.gov/9001838/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/s0149-2918(96)80076-2", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9001838/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Angiotensin-Converting Enzyme (ACE) Inhibitor", "blackBoxWarnings": [ "Can cause fetal toxicity when administered during pregnancy. 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Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE). Lancet. 2002.", "pmid": "11937178", "doi": "10.1016/S0140-6736(02)08089-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11937178/", "publicSourceType": "PMID" }, { "text": "Brenner BM et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy (RENAAL). N Engl J Med. 2001.", "pmid": "11565518", "doi": "10.1056/NEJMoa011161", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11565518/", "publicSourceType": "PMID" }, { "text": "Karavadra B et al. A systematic review of commencing full-dose antihypertensives in newly diagnosed hypertension. 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Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2025", "pmid": "39665995", "doi": "10.1007/s00417-024-06710-8", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39665995/", "publicSourceType": "PMID" }, { "claim": "ARBs are comparatively effective and safe for hypertension management", "title": "Comparative efficacy and safety of six angiotensin II receptor blockers in hypertensive patients: a network meta-analysis", "authors": "Zhang Z, Yang H, Guo H", "journal": "International Journal of Clinical Pharmacy", "year": 2024, "pmid": "38861046", "url": "https://pubmed.ncbi.nlm.nih.gov/38861046/", "study_type": "network meta-analysis", "key_finding": "Among six ARBs compared for hypertension management, losartan demonstrated comparable blood pressure lowering efficacy and safety, with telmisartan and olmesartan showing slightly greater BP reduction", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38861046/", "publicSourceType": "PMID" }, { "claim": "Single-pill combinations including losartan are effective for uncontrolled hypertension", "title": "Efficacy of single-pill combination in uncontrolled essential hypertension: A systematic review and network meta-analysis", "authors": "Xie M, Tang T, Liang H", "journal": "Clinical Cardiology", "year": 2023, "pmid": "37432701", "url": "https://pubmed.ncbi.nlm.nih.gov/37432701/", "study_type": "network meta-analysis", "key_finding": "Single-pill combinations including ARB-based regimens were significantly more effective in achieving blood pressure control compared to monotherapy in patients with uncontrolled essential hypertension", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37432701/", "publicSourceType": "PMID" }, { "text": "Meng C, Song Z, Zhang L et al.. Effects of losartan in patients with NAFLD: A meta-analysis of randomized controlled trial. Open life sciences. 2023", "claim": "PubMed-indexed evidence involving Losartan", "title": "Effects of losartan in patients with NAFLD: A meta-analysis of randomized controlled trial", "authors": "Meng C, Song Z, Zhang L et al.", "journal": "Open life sciences", "year": 2023, "pmid": "36970603", "url": "https://pubmed.ncbi.nlm.nih.gov/36970603/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1515/biol-2022-0583", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36970603/", "publicSourceType": "PMID" }, { "text": "Takagi H, Niwa M, Mizuno Y et al.. A meta-analysis of randomized trials of telmisartan versus losartan for reduction of ambulatory blood pressure. Hypertension research : official journal of the Japanese Society of Hypertension. 2013", "claim": "PubMed-indexed evidence involving Losartan", "title": "A meta-analysis of randomized trials of telmisartan versus losartan for reduction of ambulatory blood pressure", "authors": "Takagi H, Niwa M, Mizuno Y et al.", "journal": "Hypertension research : official journal of the Japanese Society of Hypertension", "year": 2013, "pmid": "23945962", "url": "https://pubmed.ncbi.nlm.nih.gov/23945962/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1038/hr.2013.78", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23945962/", "publicSourceType": "PMID" }, { "text": "Xi GL, Cheng JW, Lu GC. Meta-analysis of randomized controlled trials comparing telmisartan with losartan in the treatment of patients with hypertension. 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PloS one. 2022", "claim": "PubMed-indexed evidence involving Losartan", "title": "Meta-analysis of the effectiveness and safety of Shenyankangfu tablets combined with losartan potassium in the treatment of chronic glomerulonephritis", "authors": "Feng PF, Chen XF, Sheng N et al.", "journal": "PloS one", "year": 2022, "pmid": "36215266", "url": "https://pubmed.ncbi.nlm.nih.gov/36215266/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1371/journal.pone.0275735", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36215266/", "publicSourceType": "PMID" }, { "text": "Avasthi D, Zerilli N, Shaikh F et al.. Impact of Losartan on Portal Hypertension and Liver Cirrhosis: A Systematic Review. 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Efficacy of Combined Abelmoschus manihot and Irbesartan for Reduction of Albuminuria in Patients With Type 2 Diabetes and Diabetic Kidney Disease: A Multicenter Randomized Double-Blind Parallel Controlled Clinical Trial. Diabetes care. 2022", "claim": "PubMed-indexed evidence involving Irbesartan", "title": "Efficacy of Combined Abelmoschus manihot and Irbesartan for Reduction of Albuminuria in Patients With Type 2 Diabetes and Diabetic Kidney Disease: A Multicenter Randomized Double-Blind Parallel Controlled Clinical Trial", "authors": "Zhao J, Tostivint I, Xu L et al.", "journal": "Diabetes care", "year": 2022, "pmid": "35613364", "url": "https://pubmed.ncbi.nlm.nih.gov/35613364/", "study_type": "RCT", "confidence": "verify", "doi": "10.2337/dc22-0607", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35613364/", "publicSourceType": "PMID" }, { "text": "Mullen M, Jin XY, Child A et al.. 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Adv Ther. 2024.", "pmid": "39412629", "doi": "10.1007/s12325-024-02997-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39412629/", "publicSourceType": "PMID" }, { "text": "Kario K, Rakugi H, Yarimizu D et al.. Twenty-Four-Hour Blood Pressure-Lowering Efficacy of Sacubitril/Valsartan Versus Olmesartan in Japanese Patients With Essential Hypertension Based on Nocturnal Blood Pressure Dipping Status: A Post Hoc Analysis of Data From a Randomized, Double-Blind Multicenter Study. Journal of the American Heart Association. 2023", "pmid": "37026551", "doi": "10.1161/JAHA.122.027612", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37026551/", "publicSourceType": "PMID" }, { "text": "Rakugi H, Kario K, Yamaguchi M et al.. Efficacy of sacubitril/valsartan versus olmesartan in Japanese patients with essential hypertension: a randomized, double-blind, multicenter study. 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Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. 1999.", "pmid": "10376614", "doi": "10.1016/S0140-6736(99)04440-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10376614/", "publicSourceType": "PMID" }, { "text": "Hjalmarson A et al. Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure (MERIT-HF). JAMA. 2000.", "pmid": "10714728", "doi": "10.1001/jama.283.10.1295", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10714728/", "publicSourceType": "PMID" }, { "text": "Popat A et al. Impact of antihypertensive treatment on cardiovascular event reduction in patients with asymptomatic carotid artery stenosis: a systematic review and meta-analysis. Pan Afr Med J. 2025.", "pmid": "41323461", "doi": "10.11604/pamj.2025.52.18.46768", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41323461/", "publicSourceType": "PMID" }, { "text": "Zamir A, Hussain I, Ur Rehman A et al.. Clinical Pharmacokinetics of Metoprolol: A Systematic Review. Clinical pharmacokinetics. 2022", "pmid": "35764772", "doi": "10.1007/s40262-022-01145-y", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35764772/", "publicSourceType": "PMID" }, { "text": "Dybro AM, Rasmussen TB, Nielsen RR et al.. Randomized Trial of Metoprolol in Patients With Obstructive Hypertrophic Cardiomyopathy. 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Effect of carvedilol on survival in severe chronic heart failure (COPERNICUS). N Engl J Med. 2001.", "pmid": "11386263", "doi": "10.1056/NEJM200105313442201", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11386263/", "publicSourceType": "PMID" }, { "text": "Poole-Wilson PA et al. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET). Lancet. 2003.", "pmid": "17237130", "doi": "10.1016/S0140-6736(03)13800-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17237130/", "publicSourceType": "PMID" }, { "text": "Pannala S et al. NSBBs, EBL or Combined Therapy for High-Risk Varices: Systematic Review and Meta-Analysis. Liver Int. 2025.", "pmid": "40396591", "doi": "10.1111/liv.70145", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40396591/", "publicSourceType": "PMID" }, { "text": "Villanueva C, Torres F, Sarin SK et al.. Carvedilol reduces the risk of decompensation and mortality in patients with compensated cirrhosis in a competing-risk meta-analysis. Journal of hepatology. 2022", "pmid": "35661713", "doi": "10.1016/j.jhep.2022.05.021", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35661713/", "publicSourceType": "PMID" }, { "text": "Alvarado-Tapias E, Brujats A, Puente A et al.. Hemodynamic effects of carvedilol plus simvastatin in cirrhosis with severe portal hypertension and suboptimal response to β-blockers: A double-blind, placebo-controlled, randomized trial. Hepatology (Baltimore, Md.). 2025", "pmid": "39509369", "doi": "10.1097/HEP.0000000000001148", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39509369/", "publicSourceType": "PMID" }, { "text": "Huang S, Zhao Q, Yang ZG et al.. Protective role of beta-blockers in chemotherapy-induced cardiotoxicity-a systematic review and meta-analysis of carvedilol. Heart failure reviews. 2019", "claim": "PubMed-indexed evidence involving Carvedilol", "title": "Protective role of beta-blockers in chemotherapy-induced cardiotoxicity-a systematic review and meta-analysis of carvedilol", "authors": "Huang S, Zhao Q, Yang ZG et al.", "journal": "Heart failure reviews", "year": 2019, "pmid": "30523513", "url": "https://pubmed.ncbi.nlm.nih.gov/30523513/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s10741-018-9755-3", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30523513/", "publicSourceType": "PMID" }, { "text": "Kheiri B, Abdalla A, Osman M et al.. Meta-Analysis of Carvedilol for the Prevention of Anthracycline-Induced Cardiotoxicity. The American journal of cardiology. 2018", "claim": "PubMed-indexed evidence involving Carvedilol", "title": "Meta-Analysis of Carvedilol for the Prevention of Anthracycline-Induced Cardiotoxicity", "authors": "Kheiri B, Abdalla A, Osman M et al.", "journal": "The American journal of cardiology", "year": 2018, "pmid": "30292333", "url": "https://pubmed.ncbi.nlm.nih.gov/30292333/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.amjcard.2018.08.039", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30292333/", "publicSourceType": "PMID" }, { "text": "Abouzid MR, Vyas A, Eldahtoury S et al.. Which should you choose for post operative atrial fibrillation, carvedilol or metoprolol? A systemic review and meta-analysis. Current problems in cardiology. 2024", "claim": "PubMed-indexed evidence involving Carvedilol", "title": "Which should you choose for post operative atrial fibrillation, carvedilol or metoprolol? A systemic review and meta-analysis", "authors": "Abouzid MR, Vyas A, Eldahtoury S et al.", "journal": "Current problems in cardiology", "year": 2024, "pmid": "37989396", "url": "https://pubmed.ncbi.nlm.nih.gov/37989396/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.cpcardiol.2023.102220", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37989396/", "publicSourceType": "PMID" }, { "text": "Li T, Ke W, Sun P et al.. Carvedilol for portal hypertension in cirrhosis: systematic review with meta-analysis. BMJ open. 2016", "claim": "PubMed-indexed evidence involving Carvedilol", "title": "Carvedilol for portal hypertension in cirrhosis: systematic review with meta-analysis", "authors": "Li T, Ke W, Sun P et al.", "journal": "BMJ open", "year": 2016, "pmid": "27147389", "url": "https://pubmed.ncbi.nlm.nih.gov/27147389/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1136/bmjopen-2015-010902", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27147389/", "publicSourceType": "PMID" }, { "text": "Aguilar-Olivos N, Motola-Kuba M, Candia R et al.. Hemodynamic effect of carvedilol vs. propranolol in cirrhotic patients: Systematic review and meta-analysis. Annals of hepatology. 2014", "claim": "PubMed-indexed evidence involving Carvedilol", "title": "Hemodynamic effect of carvedilol vs. propranolol in cirrhotic patients: Systematic review and meta-analysis", "authors": "Aguilar-Olivos N, Motola-Kuba M, Candia R et al.", "journal": "Annals of hepatology", "year": 2014, "pmid": "24927613", "url": "https://pubmed.ncbi.nlm.nih.gov/24927613/", "study_type": "meta-analysis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24927613/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Non-Selective Beta-Blocker with Alpha-1 Blockade", "blackBoxWarnings": [ "Do not abruptly discontinue beta-blocker therapy in patients with coronary artery disease. 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The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet. 1999.", "pmid": "10221068", "doi": "10.1016/S0140-6736(98)11181-9", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10221068/", "publicSourceType": "PMID" }, { "text": "MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure (MERIT-HF). Lancet. 1999.", "pmid": "10376614", "doi": "10.1016/S0140-6736(99)04440-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10376614/", "publicSourceType": "PMID" }, { "text": "Qian J et al. A Systematic Literature Review and Network Meta-analysis of Azilsartan Medoxomil Compared to Other Anti-hypertensives Efficacy in Lowering Blood Pressure Amongst Mild to Moderate Hypertensive Patients. Adv Ther. 2024.", "pmid": "39412629", "doi": "10.1007/s12325-024-02997-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39412629/", "publicSourceType": "PMID" }, { "text": "Muresan L, Cismaru G, Muresan C et al.. Beta-blockers for the treatment of arrhythmias: Bisoprolol - a systematic review. Annales pharmaceutiques francaises. 2022", "pmid": "35093388", "doi": "10.1016/j.pharma.2022.01.007", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35093388/", "publicSourceType": "PMID" }, { "text": "Devereux G, Cotton S, Nath M et al.. Bisoprolol in Patients With Chronic Obstructive Pulmonary Disease at High Risk of Exacerbation: The BICS Randomized Clinical Trial. JAMA. 2024", "pmid": "38762800", "doi": "10.1001/jama.2024.8771", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38762800/", "publicSourceType": "PMID" }, { "text": "Cicero AFG, ALGhasab NS, Tocci G et al.. Efficacy and Safety of Low-Dose Bisoprolol/Hydrochlorothiazide Combination for the Treatment of Hypertension: A Systematic Review and Meta-Analysis. Journal of clinical medicine. 2024", "claim": "PubMed-indexed evidence involving Bisoprolol", "title": "Efficacy and Safety of Low-Dose Bisoprolol/Hydrochlorothiazide Combination for the Treatment of Hypertension: A Systematic Review and Meta-Analysis", "authors": "Cicero AFG, ALGhasab NS, Tocci G et al.", "journal": "Journal of clinical medicine", "year": 2024, "pmid": "39124839", "url": "https://pubmed.ncbi.nlm.nih.gov/39124839/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/jcm13154572", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39124839/", "publicSourceType": "PMID" }, { "text": "Feng Z, Zhang L, Wang Y et al.. Efficacy and Safety of Bisoprolol in Patients with Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis. International journal of chronic obstructive pulmonary disease. 2023", "claim": "PubMed-indexed evidence involving Bisoprolol", "title": "Efficacy and Safety of Bisoprolol in Patients with Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis", "authors": "Feng Z, Zhang L, Wang Y et al.", "journal": "International journal of chronic obstructive pulmonary disease", "year": 2023, "pmid": "38152590", "url": "https://pubmed.ncbi.nlm.nih.gov/38152590/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2147/COPD.S438930", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38152590/", "publicSourceType": "PMID" }, { "text": "Kim AG, Banga S, Ang QX et al.. Transdermal bisoprolol for prevention of postoperative atrial fibrillation: A systematic review and meta-analysis. Journal of arrhythmia. 2024", "claim": "PubMed-indexed evidence involving Bisoprolol", "title": "Transdermal bisoprolol for prevention of postoperative atrial fibrillation: A systematic review and meta-analysis", "authors": "Kim AG, Banga S, Ang QX et al.", "journal": "Journal of arrhythmia", "year": 2024, "pmid": "38939760", "url": "https://pubmed.ncbi.nlm.nih.gov/38939760/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/joa3.13049", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38939760/", "publicSourceType": "PMID" }, { "text": "DiNicolantonio JJ, Lavie CJ, Fares H et al.. Meta-analysis of carvedilol versus beta 1 selective beta-blockers (atenolol, bisoprolol, metoprolol, and nebivolol). The American journal of cardiology. 2013", "claim": "PubMed-indexed evidence involving Bisoprolol", "title": "Meta-analysis of carvedilol versus beta 1 selective beta-blockers (atenolol, bisoprolol, metoprolol, and nebivolol)", "authors": "DiNicolantonio JJ, Lavie CJ, Fares H et al.", "journal": "The American journal of cardiology", "year": 2013, "pmid": "23290925", "url": "https://pubmed.ncbi.nlm.nih.gov/23290925/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.amjcard.2012.11.031", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23290925/", "publicSourceType": "PMID" }, { "text": "Bjerregaard L, Dybro AM, Saaby L et al.. Beta-Blocker (Bisoprolol) vs Calcium-Channel Blocker (Verapamil) in Nonobstructive Hypertrophic Cardiomyopathy: A Randomized Triple-Crossover Physiologic Trial. Journal of the American College of Cardiology. 2026", "claim": "PubMed-indexed evidence involving Bisoprolol", "title": "Beta-Blocker (Bisoprolol) vs Calcium-Channel Blocker (Verapamil) in Nonobstructive Hypertrophic Cardiomyopathy: A Randomized Triple-Crossover Physiologic Trial", "authors": "Bjerregaard L, Dybro AM, Saaby L et al.", "journal": "Journal of the American College of Cardiology", "year": 2026, "pmid": "41778690", "url": "https://pubmed.ncbi.nlm.nih.gov/41778690/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.jacc.2025.11.028", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41778690/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Beta-1 Selective Adrenergic Blocker", "blackBoxWarnings": [ "Do not abruptly discontinue beta-blocker therapy in patients with coronary artery disease. 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Major outcomes in high-risk hypertensive patients randomized to ACE inhibitor or calcium channel blocker vs diuretic (ALLHAT). JAMA. 2002.", "pmid": "12479763", "doi": "10.1001/jama.288.23.2981", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12479763/", "publicSourceType": "PMID" }, { "text": "Dahlof B et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required (ASCOT-BPLA). Lancet. 2005.", "pmid": "16154016", "doi": "10.1016/S0140-6736(05)67185-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16154016/", "publicSourceType": "PMID" }, { "text": "Singh A et al. Efficacy of pharmacological agents for management of post-partum hypertension: A systematic review and network meta-analysis. J Hum Hypertens. 2026.", "pmid": "41663753", "doi": "10.1038/s41371-026-01120-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41663753/", "publicSourceType": "PMID" }, { "text": "Yin J, Mei Z, Shi S et al.. Nifedipine or amlodipine? The choice for hypertension during pregnancy: a systematic review and meta-analysis. Archives of gynecology and obstetrics. 2022", "pmid": "35305140", "doi": "10.1007/s00404-022-06504-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35305140/", "publicSourceType": "PMID" }, { "text": "Soh MS, Won KH, Kim JJ et al.. Phase III randomized clinical trial of efficacy and safety of amlodipine and candesartan cilexetil combination for hypertension treatment. Scientific reports. 2024", "pmid": "39358448", "doi": "10.1038/s41598-024-74003-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39358448/", "publicSourceType": "PMID" }, { "claim": "Amlodipine has comparable stroke outcomes to other antihypertensives (ALLHAT)", "title": "Stroke outcomes among participants randomized to chlorthalidone, amlodipine or lisinopril in ALLHAT", "authors": "Yamal JM, Oparil S, Davis BR, Alderman MH et al.", "journal": "Journal of the American Society of Hypertension", "year": 2014, "pmid": "25455006", "url": "https://pubmed.ncbi.nlm.nih.gov/25455006/", "study_type": "rct", "key_finding": "In ALLHAT, amlodipine showed similar stroke outcomes compared to chlorthalidone and lisinopril in the overall population, supporting its safety and efficacy as a first-line antihypertensive", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25455006/", "publicSourceType": "PMID" }, { "text": "Pal D, Maji S, Maiti R. Efficacy and Safety of Azelnidipine as an Antihypertensive Compared to Amlodipine: A Systematic Review and Meta-analysis. High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension. 2023", "claim": "PubMed-indexed evidence involving Amlodipine", "title": "Efficacy and Safety of Azelnidipine as an Antihypertensive Compared to Amlodipine: A Systematic Review and Meta-analysis", "authors": "Pal D, Maji S, Maiti R", "journal": "High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension", "year": 2023, "pmid": "37768510", "url": "https://pubmed.ncbi.nlm.nih.gov/37768510/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s40292-023-00601-5", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37768510/", "publicSourceType": "PMID" }, { "text": "Vukadinović D, Scholz SS, Messerli FH et al.. Peripheral edema and headache associated with amlodipine treatment: a meta-analysis of randomized, placebo-controlled trials. Journal of hypertension. 2019", "claim": "PubMed-indexed evidence involving Amlodipine", "title": "Peripheral edema and headache associated with amlodipine treatment: a meta-analysis of randomized, placebo-controlled trials", "authors": "Vukadinović D, Scholz SS, Messerli FH et al.", "journal": "Journal of hypertension", "year": 2019, "pmid": "31107359", "url": "https://pubmed.ncbi.nlm.nih.gov/31107359/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/HJH.0000000000002145", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31107359/", "publicSourceType": "PMID" }, { "text": "Liu Y, Chen K, Kou X et al.. Aliskiren and amlodipine in the management of essential hypertension: meta-analysis of randomized controlled trials. PloS one. 2013", "claim": "PubMed-indexed evidence involving Amlodipine", "title": "Aliskiren and amlodipine in the management of essential hypertension: meta-analysis of randomized controlled trials", "authors": "Liu Y, Chen K, Kou X et al.", "journal": "PloS one", "year": 2013, "pmid": "23922924", "url": "https://pubmed.ncbi.nlm.nih.gov/23922924/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1371/journal.pone.0070111", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23922924/", "publicSourceType": "PMID" }, { "text": "Dat TV, Tu VL, Thu LNA et al.. Effectiveness of perindopril/amlodipine fixed-dose combination in the treatment of hypertension: a systematic review. Frontiers in pharmacology. 2023", "claim": "PubMed-indexed evidence involving Amlodipine", "title": "Effectiveness of perindopril/amlodipine fixed-dose combination in the treatment of hypertension: a systematic review", "authors": "Dat TV, Tu VL, Thu LNA et al.", "journal": "Frontiers in pharmacology", "year": 2023, "pmid": "38410524", "url": "https://pubmed.ncbi.nlm.nih.gov/38410524/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fphar.2023.1156655", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38410524/", "publicSourceType": "PMID" }, { "text": "Richy FF, Laurent S. Efficacy and safety profiles of manidipine compared with amlodipine: a meta-analysis of head-to-head trials. 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Comparison of the Effectiveness and Safety of Metoprolol and Diltiazem in Atrial Fibrillation With Rapid Ventricular Rate Patients: A Systematic Review and Meta-Analysis. Cureus. 2024", "claim": "PubMed-indexed evidence involving Diltiazem", "title": "Comparison of the Effectiveness and Safety of Metoprolol and Diltiazem in Atrial Fibrillation With Rapid Ventricular Rate Patients: A Systematic Review and Meta-Analysis", "authors": "Mayow AH, Sinha T, Ahmad M et al.", "journal": "Cureus", "year": 2024, "pmid": "38646329", "url": "https://pubmed.ncbi.nlm.nih.gov/38646329/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7759/cureus.56560", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38646329/", "publicSourceType": "PMID" }, { "text": "Jaya F, Afzal M, Anusha F et al.. Efficacy and Safety of Intravenous Diltiazem Versus Metoprolol in the Management of Atrial Fibrillation with Rapid Ventricular Response in the Emergency Department: A Comprehensive Umbrella Review of Systematic Reviews and Meta-analyses. 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Indian heart journal. 2022", "claim": "PubMed-indexed evidence involving Diltiazem", "title": "Comparison of diltiazem and metoprolol for atrial fibrillation with rapid ventricular rate: Systematic review and meta-analysis", "authors": "Sharda SC, Bhatia MS", "journal": "Indian heart journal", "year": 2022, "pmid": "36334652", "url": "https://pubmed.ncbi.nlm.nih.gov/36334652/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.ihj.2022.10.195", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36334652/", "publicSourceType": "PMID" }, { "text": "Hu Y, Yang X, Zhang L et al.. Perioperative diltiazem or nitroglycerin in on-pump coronary artery bypass: A systematic review and network meta-analysis. 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Effect of Verapamil on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes: A Randomized Clinical Trial. JAMA. 2023", "pmid": "36826844", "doi": "10.1001/jama.2023.2064", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36826844/", "publicSourceType": "PMID" }, { "text": "Fahie S, Cassagnol M. Verapamil. 2026", "pmid": "30860730", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30860730/", "publicSourceType": "PMID" }, { "text": "Zou Z, Xu FY, Wang L et al.. Antihypertensive and renoprotective effects of trandolapril/verapamil combination: a meta-analysis of randomized controlled trials. Journal of human hypertension. 2011", "claim": "PubMed-indexed evidence involving Verapamil", "title": "Antihypertensive and renoprotective effects of trandolapril/verapamil combination: a meta-analysis of randomized controlled trials", "authors": "Zou Z, Xu FY, Wang L et al.", "journal": "Journal of human hypertension", "year": 2011, "pmid": "20535140", "url": "https://pubmed.ncbi.nlm.nih.gov/20535140/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1038/jhh.2010.60", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20535140/", "publicSourceType": "PMID" }, { "text": "Tu S, Zhang R, Zheng Q et al.. Effect of Verapamil on Blood Glucose in Type 1 and Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. Cardiovascular drugs and therapy. 2026", "claim": "PubMed-indexed evidence involving Verapamil", "title": "Effect of Verapamil on Blood Glucose in Type 1 and Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis", "authors": "Tu S, Zhang R, Zheng Q et al.", "journal": "Cardiovascular drugs and therapy", "year": 2026, "pmid": "40111679", "url": "https://pubmed.ncbi.nlm.nih.gov/40111679/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s10557-025-07683-4", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40111679/", "publicSourceType": "PMID" }, { "text": "Collins L, Lam L, Kleinig O et al.. Verapamil in the treatment of reversible cerebral vasoconstriction syndrome: A systematic review. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2023", "claim": "PubMed-indexed evidence involving Verapamil", "title": "Verapamil in the treatment of reversible cerebral vasoconstriction syndrome: A systematic review", "authors": "Collins L, Lam L, Kleinig O et al.", "journal": "Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia", "year": 2023, "pmid": "37267876", "url": "https://pubmed.ncbi.nlm.nih.gov/37267876/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jocn.2023.05.013", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37267876/", "publicSourceType": "PMID" }, { "text": "Taha M, Dahat P, Toriola S et al.. Metoprolol or Verapamil in the Management of Patients With Hypertrophic Cardiomyopathy: A Systematic Review. Cureus. 2023", "claim": "PubMed-indexed evidence involving Verapamil", "title": "Metoprolol or Verapamil in the Management of Patients With Hypertrophic Cardiomyopathy: A Systematic Review", "authors": "Taha M, Dahat P, Toriola S et al.", "journal": "Cureus", "year": 2023, "pmid": "37565181", "url": "https://pubmed.ncbi.nlm.nih.gov/37565181/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7759/cureus.43197", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37565181/", "publicSourceType": "PMID" }, { "text": "Bjerregaard L, Dybro AM, Saaby L et al.. Beta-Blocker (Bisoprolol) vs Calcium-Channel Blocker (Verapamil) in Nonobstructive Hypertrophic Cardiomyopathy: A Randomized Triple-Crossover Physiologic Trial. 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European journal of clinical pharmacology. 2022", "pmid": "36104450", "doi": "10.1007/s00228-022-03382-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36104450/", "publicSourceType": "PMID" }, { "text": "Ali AA, Sayed AK, El Sherif L et al.. Systematic review and meta-analysis of randomized controlled trials of atosiban versus nifedipine for inhibition of preterm labor. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 2019", "claim": "PubMed-indexed evidence involving Nifedipine", "title": "Systematic review and meta-analysis of randomized controlled trials of atosiban versus nifedipine for inhibition of preterm labor", "authors": "Ali AA, Sayed AK, El Sherif L et al.", "journal": "International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics", "year": 2019, "pmid": "30784056", "url": "https://pubmed.ncbi.nlm.nih.gov/30784056/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/ijgo.12793", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30784056/", "publicSourceType": "PMID" }, { "text": "de Souza ATB, de Lima Machado ML, Sarmento ACA et al.. Magnesium sulfate versus nifedipine for tocolysis: meta-analysis of randomized controlled trials. Women & health. 2025", "claim": "PubMed-indexed evidence involving Nifedipine", "title": "Magnesium sulfate versus nifedipine for tocolysis: meta-analysis of randomized controlled trials", "authors": "de Souza ATB, de Lima Machado ML, Sarmento ACA et al.", "journal": "Women & health", "year": 2025, "pmid": "39626700", "url": "https://pubmed.ncbi.nlm.nih.gov/39626700/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/03630242.2024.2436414", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39626700/", "publicSourceType": "PMID" }, { "text": "Li L, Xie W, Xu H et al.. Oral nifedipine versus intravenous labetalol for hypertensive emergencies during pregnancy: a systematic review and meta-analysis. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2023", "claim": "PubMed-indexed evidence involving Nifedipine", "title": "Oral nifedipine versus intravenous labetalol for hypertensive emergencies during pregnancy: a systematic review and meta-analysis", "authors": "Li L, Xie W, Xu H et al.", "journal": "The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians", "year": 2023, "pmid": "37487762", "url": "https://pubmed.ncbi.nlm.nih.gov/37487762/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/14767058.2023.2235057", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37487762/", "publicSourceType": "PMID" }, { "text": "Stason WB, Schmid CH, Niedzwiecki D et al.. Safety of nifedipine in angina pectoris: a meta-analysis. Hypertension (Dallas, Tex. : 1979). 1999", "claim": "PubMed-indexed evidence involving Nifedipine", "title": "Safety of nifedipine in angina pectoris: a meta-analysis", "authors": "Stason WB, Schmid CH, Niedzwiecki D et al.", "journal": "Hypertension (Dallas, Tex. : 1979)", "year": 1999, "pmid": "9931077", "url": "https://pubmed.ncbi.nlm.nih.gov/9931077/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1161/01.hyp.33.1.24", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9931077/", "publicSourceType": "PMID" }, { "text": "Stason WB, Schmid CH, Niedzwiecki D et al.. Safety of nifedipine in patients with hypertension: a meta-analysis. Hypertension (Dallas, Tex. : 1979). 1997", "claim": "PubMed-indexed evidence involving Nifedipine", "title": "Safety of nifedipine in patients with hypertension: a meta-analysis", "authors": "Stason WB, Schmid CH, Niedzwiecki D et al.", "journal": "Hypertension (Dallas, Tex. : 1979)", "year": 1997, "pmid": "9231814", "url": "https://pubmed.ncbi.nlm.nih.gov/9231814/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1161/01.hyp.30.1.7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9231814/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Dihydropyridine Calcium Channel Blocker", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "2 hours (immediate-release); effective duration 24 hours (extended-release via GITS system)", "onsetOfAction": "Extended-release: gradual over hours; Immediate-release: 20 minutes", "commonBrandNames": [ "Procardia", "Procardia XL", "Adalat CC" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": "Routine lab monitoring not required; monitor blood pressure and heart rate" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "nifedipine" }, { "id": "RX-CARDIO-023", "name": "Hydrochlorothiazide", "alternateNames": [ "HCTZ", "Microzide" ], "category": "Prescription", "subcategory": "Thiazide Diuretic", "overview": "Hydrochlorothiazide (HCTZ) is a thiazide diuretic and one of the most commonly prescribed antihypertensives. 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Major outcomes in high-risk hypertensive patients randomized to ACE inhibitor or calcium channel blocker vs diuretic (ALLHAT). JAMA. 2002.", "pmid": "12479763", "doi": "10.1001/jama.288.23.2981", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12479763/", "publicSourceType": "PMID" }, { "text": "Ernst ME et al. Comparative antihypertensive effects of hydrochlorothiazide and chlorthalidone on ambulatory and office blood pressure. Hypertension. 2006.", "pmid": "16432050", "doi": "10.1161/01.HYP.0000240485.44816.3d", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16432050/", "publicSourceType": "PMID" }, { "text": "Singh A et al. Efficacy of pharmacological agents for management of post-partum hypertension: A systematic review and network meta-analysis. J Hum Hypertens. 2026.", "pmid": "41663753", "doi": "10.1038/s41371-026-01120-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41663753/", "publicSourceType": "PMID" }, { "text": "Dineva S, Uzunova K, Pavlova V et al.. Comparative efficacy and safety of chlorthalidone and hydrochlorothiazide-meta-analysis. Journal of human hypertension. 2019", "pmid": "31595024", "doi": "10.1038/s41371-019-0255-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31595024/", "publicSourceType": "PMID" }, { "text": "Ernst ME, Fravel MA. Thiazide and the Thiazide-Like Diuretics: Review of Hydrochlorothiazide, Chlorthalidone, and Indapamide. American journal of hypertension. 2022", "pmid": "35404993", "doi": "10.1093/ajh/hpac048", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35404993/", "publicSourceType": "PMID" }, { "text": "Cicero AFG, ALGhasab NS, Tocci G et al.. Efficacy and Safety of Low-Dose Bisoprolol/Hydrochlorothiazide Combination for the Treatment of Hypertension: A Systematic Review and Meta-Analysis. Journal of clinical medicine. 2024", "claim": "PubMed-indexed evidence involving Hydrochlorothiazide", "title": "Efficacy and Safety of Low-Dose Bisoprolol/Hydrochlorothiazide Combination for the Treatment of Hypertension: A Systematic Review and Meta-Analysis", "authors": "Cicero AFG, ALGhasab NS, Tocci G et al.", "journal": "Journal of clinical medicine", "year": 2024, "pmid": "39124839", "url": "https://pubmed.ncbi.nlm.nih.gov/39124839/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/jcm13154572", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39124839/", "publicSourceType": "PMID" }, { "text": "Khenhrani RR, Nnodebe I, Rawat A et al.. Comparison of the Effectiveness and Safety of Chlorthalidone and Hydrochlorothiazide in Patients With Hypertension: A Meta-Analysis. Cureus. 2023", "claim": "PubMed-indexed evidence involving Hydrochlorothiazide", "title": "Comparison of the Effectiveness and Safety of Chlorthalidone and Hydrochlorothiazide in Patients With Hypertension: A Meta-Analysis", "authors": "Khenhrani RR, Nnodebe I, Rawat A et al.", "journal": "Cureus", "year": 2023, "pmid": "37252566", "url": "https://pubmed.ncbi.nlm.nih.gov/37252566/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7759/cureus.38184", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37252566/", "publicSourceType": "PMID" }, { "text": "Kumar L, Khuwaja S, Kumar A et al.. Exploring the Effectiveness and Safety of Azilsartan-Medoxomil/Chlorthalidone Versus Olmesartan-Medoxomil/Hydrochlorothiazide in Hypertensive Patients: A Meta-Analysis. Cureus. 2023", "claim": "PubMed-indexed evidence involving Hydrochlorothiazide", "title": "Exploring the Effectiveness and Safety of Azilsartan-Medoxomil/Chlorthalidone Versus Olmesartan-Medoxomil/Hydrochlorothiazide in Hypertensive Patients: A Meta-Analysis", "authors": "Kumar L, Khuwaja S, Kumar A et al.", "journal": "Cureus", "year": 2023, "pmid": "37525792", "url": "https://pubmed.ncbi.nlm.nih.gov/37525792/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7759/cureus.41198", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37525792/", "publicSourceType": "PMID" }, { "text": "Becquart O, Guillot B, Bourrain JL et al.. [Hydrochlorothiazide use and risk of skin cancers: A systematic review]. La Revue de medecine interne. 2019", "claim": "PubMed-indexed evidence involving Hydrochlorothiazide", "title": "[Hydrochlorothiazide use and risk of skin cancers: A systematic review]", "authors": "Becquart O, Guillot B, Bourrain JL et al.", "journal": "La Revue de medecine interne", "year": 2019, "pmid": "31101331", "url": "https://pubmed.ncbi.nlm.nih.gov/31101331/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.revmed.2019.04.008", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31101331/", "publicSourceType": "PMID" }, { "text": "Roush GC, Holford TR, Guddati AK. Chlorthalidone compared with hydrochlorothiazide in reducing cardiovascular events: systematic review and network meta-analyses. Hypertension (Dallas, Tex. : 1979). 2012", "claim": "PubMed-indexed evidence involving Hydrochlorothiazide", "title": "Chlorthalidone compared with hydrochlorothiazide in reducing cardiovascular events: systematic review and network meta-analyses", "authors": "Roush GC, Holford TR, Guddati AK", "journal": "Hypertension (Dallas, Tex. : 1979)", "year": 2012, "pmid": "22526259", "url": "https://pubmed.ncbi.nlm.nih.gov/22526259/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1161/HYPERTENSIONAHA.112.191106", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22526259/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Thiazide Diuretic", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "6–15 hours", "onsetOfAction": "2 hours; peak effect at 3–6 hours; duration 6–12 hours", "commonBrandNames": [ "Microzide" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Serum electrolytes (potassium, sodium, magnesium), renal function (creatinine, BUN), uric acid, and glucose at baseline, 1–2 weeks after initiation, and periodically (every 3–6 months)" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "hydrochlorothiazide" }, { "id": "RX-CARDIO-024", "name": "Furosemide", "alternateNames": [ "Lasix" ], "category": "Prescription", "subcategory": "Loop Diuretic", "overview": "Furosemide is a potent loop diuretic used primarily for edema associated with heart failure, cirrhosis, and renal disease. 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Diuretic strategies in patients with acute decompensated heart failure (DOSE trial). N Engl J Med. 2011.", "pmid": "21366472", "doi": "10.1056/NEJMoa1005419", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21366472/", "publicSourceType": "PMID" }, { "text": "Brater DC. Diuretic therapy. N Engl J Med. 1998.", "pmid": "9709046", "doi": "10.1056/NEJM199808063390607", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9709046/", "publicSourceType": "PMID" }, { "text": "Kao CC et al. Mannitol for prevention of cisplatin-induced nephrotoxicity: a systematic review and meta-analysis of randomized controlled trials. Support Care Cancer. 2025.", "pmid": "41266849", "doi": "10.1007/s00520-025-10171-y", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41266849/", "publicSourceType": "PMID" }, { "text": "Hedin E, Bijelić V, Barrowman N et al.. Furosemide and albumin for the treatment of nephrotic edema: a systematic review. Pediatric nephrology (Berlin, Germany). 2022", "pmid": "35239032", "doi": "10.1007/s00467-021-05358-4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35239032/", "publicSourceType": "PMID" }, { "text": "Liu C, Peng Z, Gao X et al.. Simultaneous Use of Hypertonic Saline and IV Furosemide for Fluid Overload: A Systematic Review and Meta-Analysis. Critical care medicine. 2021", "pmid": "34166286", "doi": "10.1097/CCM.0000000000005174", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34166286/", "publicSourceType": "PMID" }, { "text": "Eid PS, Ibrahim DA, Zayan AH et al.. Comparative effects of furosemide and other diuretics in the treatment of heart failure: a systematic review and combined meta-analysis of randomized controlled trials. Heart failure reviews. 2021", "claim": "PubMed-indexed evidence involving Furosemide", "title": "Comparative effects of furosemide and other diuretics in the treatment of heart failure: a systematic review and combined meta-analysis of randomized controlled trials", "authors": "Eid PS, Ibrahim DA, Zayan AH et al.", "journal": "Heart failure reviews", "year": 2021, "pmid": "32783109", "url": "https://pubmed.ncbi.nlm.nih.gov/32783109/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s10741-020-10003-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32783109/", "publicSourceType": "PMID" }, { "text": "Osmanska J, Petrie MC, Docherty KF et al.. Subcutaneous furosemide in heart failure: a systematic review. European heart journal. Cardiovascular pharmacotherapy. 2025", "claim": "PubMed-indexed evidence involving Furosemide", "title": "Subcutaneous furosemide in heart failure: a systematic review", "authors": "Osmanska J, Petrie MC, Docherty KF et al.", "journal": "European heart journal. Cardiovascular pharmacotherapy", "year": 2025, "pmid": "39520561", "url": "https://pubmed.ncbi.nlm.nih.gov/39520561/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/ehjcvp/pvae083", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39520561/", "publicSourceType": "PMID" }, { "text": "Kitaoka H, Terada Y, Tanaka K et al.. Furosemide for patent ductus arteriosus during cyclooxygenase inhibitor therapy: A systematic review. Pediatrics international : official journal of the Japan Pediatric Society. 2024", "claim": "PubMed-indexed evidence involving Furosemide", "title": "Furosemide for patent ductus arteriosus during cyclooxygenase inhibitor therapy: A systematic review", "authors": "Kitaoka H, Terada Y, Tanaka K et al.", "journal": "Pediatrics international : official journal of the Japan Pediatric Society", "year": 2024, "pmid": "39349400", "url": "https://pubmed.ncbi.nlm.nih.gov/39349400/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/ped.15822", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39349400/", "publicSourceType": "PMID" }, { "text": "Widiarti W, Saputra PBT, Ariyanto MV et al.. The Role of Subcutaneous Furosemide in Heart Failure Management: A Systematic Review. Current cardiology reports. 2024", "claim": "PubMed-indexed evidence involving Furosemide", "title": "The Role of Subcutaneous Furosemide in Heart Failure Management: A Systematic Review", "authors": "Widiarti W, Saputra PBT, Ariyanto MV et al.", "journal": "Current cardiology reports", "year": 2024, "pmid": "39352583", "url": "https://pubmed.ncbi.nlm.nih.gov/39352583/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s11886-024-02124-4", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39352583/", "publicSourceType": "PMID" }, { "text": "Lee TH, Kuo G, Chang CH et al.. Diuretic effect of co-administration of furosemide and albumin in comparison to furosemide therapy alone: An updated systematic review and meta-analysis. PloS one. 2021", "claim": "PubMed-indexed evidence involving Furosemide", "title": "Diuretic effect of co-administration of furosemide and albumin in comparison to furosemide therapy alone: An updated systematic review and meta-analysis", "authors": "Lee TH, Kuo G, Chang CH et al.", "journal": "PloS one", "year": 2021, "pmid": "34851962", "url": "https://pubmed.ncbi.nlm.nih.gov/34851962/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1371/journal.pone.0260312", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34851962/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Loop Diuretic", "blackBoxWarnings": [ "Furosemide is a potent diuretic which, if given in excessive amounts, can lead to a profound diuresis with water and electrolyte depletion. 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The effect of spironolactone on morbidity and mortality in patients with severe heart failure (RALES). N Engl J Med. 1999.", "pmid": "10471456", "doi": "10.1056/NEJM199909023411001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10471456/", "publicSourceType": "PMID" }, { "text": "Juurlink DN et al. Rates of hyperkalemia after publication of the RALES trial. N Engl J Med. 2004.", "pmid": "15295047", "doi": "10.1056/NEJMoa040752", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15295047/", "publicSourceType": "PMID" }, { "text": "Dias J et al. Effects of mineralocorticoid receptor antagonists on cardiometabolic profile and liver health in individuals with increased cardiometabolic risk: a systematic review and meta-analysis of randomized controlled trials. Expert Rev Cardiovasc Ther. 2026.", "pmid": "41702409", "doi": "10.1080/14779072.2026.2634029", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41702409/", "publicSourceType": "PMID" }, { "text": "Jolly SS, d'Entremont MA, Pitt B et al.. Routine Spironolactone in Acute Myocardial Infarction. The New England journal of medicine. 2025", "pmid": "39555814", "doi": "10.1056/NEJMoa2405923", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39555814/", "publicSourceType": "PMID" }, { "text": "Santer M, Lawrence M, Renz S et al.. Effectiveness of spironolactone for women with acne vulgaris (SAFA) in England and Wales: pragmatic, multicentre, phase 3, double blind, randomised controlled trial. BMJ (Clinical research ed.). 2023", "pmid": "37192767", "doi": "10.1136/bmj-2022-074349", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37192767/", "publicSourceType": "PMID" }, { "text": "Rossignol P, Zannad F, Massy Z et al.. Spironolactone in patients on chronic haemodialysis at high risk of adverse cardiovascular outcomes (ALCHEMIST): a multicentre, double-blind, randomised, placebo-controlled trial and updated meta-analysis. Lancet (London, England). 2025", "claim": "PubMed-indexed evidence involving Spironolactone", "title": "Spironolactone in patients on chronic haemodialysis at high risk of adverse cardiovascular outcomes (ALCHEMIST): a multicentre, double-blind, randomised, placebo-controlled trial and updated meta-analysis", "authors": "Rossignol P, Zannad F, Massy Z et al.", "journal": "Lancet (London, England)", "year": 2025, "pmid": "40818851", "url": "https://pubmed.ncbi.nlm.nih.gov/40818851/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/S0140-6736(25)01194-8", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40818851/", "publicSourceType": "PMID" }, { "text": "Liu J, Jia W, Yu C. Safety and Efficacy of Spironolactone in Dialysis-Dependent Patients: Meta-Analysis of Randomized Controlled Trials. Frontiers in medicine. 2022", "claim": "PubMed-indexed evidence involving Spironolactone", "title": "Safety and Efficacy of Spironolactone in Dialysis-Dependent Patients: Meta-Analysis of Randomized Controlled Trials", "authors": "Liu J, Jia W, Yu C", "journal": "Frontiers in medicine", "year": 2022, "pmid": "35372414", "url": "https://pubmed.ncbi.nlm.nih.gov/35372414/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fmed.2022.828189", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35372414/", "publicSourceType": "PMID" }, { "text": "Zhao JV, Xu L, Lin SL et al.. Spironolactone and glucose metabolism, a systematic review and meta-analysis of randomized controlled trials. Journal of the American Society of Hypertension : JASH. 2016", "claim": "PubMed-indexed evidence involving Spironolactone", "title": "Spironolactone and glucose metabolism, a systematic review and meta-analysis of randomized controlled trials", "authors": "Zhao JV, Xu L, Lin SL et al.", "journal": "Journal of the American Society of Hypertension : JASH", "year": 2016, "pmid": "27372428", "url": "https://pubmed.ncbi.nlm.nih.gov/27372428/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jash.2016.05.013", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27372428/", "publicSourceType": "PMID" }, { "text": "Elshahat A, Mansour A, Ellabban M et al.. Comparative effectiveness and safety of eplerenone and spironolactone in patients with heart failure: a systematic review and meta-analysis. BMC cardiovascular disorders. 2024", "claim": "PubMed-indexed evidence involving Spironolactone", "title": "Comparative effectiveness and safety of eplerenone and spironolactone in patients with heart failure: a systematic review and meta-analysis", "authors": "Elshahat A, Mansour A, Ellabban M et al.", "journal": "BMC cardiovascular disorders", "year": 2024, "pmid": "39271992", "url": "https://pubmed.ncbi.nlm.nih.gov/39271992/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12872-024-04103-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39271992/", "publicSourceType": "PMID" }, { "text": "Wang C, Du Y, Bi L et al.. The Efficacy and Safety of Oral and Topical Spironolactone in Androgenetic Alopecia Treatment: A Systematic Review. Clinical, cosmetic and investigational dermatology. 2023", "claim": "PubMed-indexed evidence involving Spironolactone", "title": "The Efficacy and Safety of Oral and Topical Spironolactone in Androgenetic Alopecia Treatment: A Systematic Review", "authors": "Wang C, Du Y, Bi L et al.", "journal": "Clinical, cosmetic and investigational dermatology", "year": 2023, "pmid": "36923692", "url": "https://pubmed.ncbi.nlm.nih.gov/36923692/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2147/CCID.S398950", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36923692/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Potassium-Sparing Diuretic / Mineralocorticoid Receptor Antagonist", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "1.4 hours (parent); active metabolite canrenone: 16.5 hours", "onsetOfAction": "Gradual diuretic effect over 2–3 days; full antihypertensive effect at 2–3 weeks", "commonBrandNames": [ "Aldactone" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Serum potassium and renal function (creatinine, BUN) at baseline, within 1 week of initiation, monthly for first 3 months, then quarterly; hold if K+ >5.5 mEq/L" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "spironolactone" }, { "id": "RX-CARDIO-026", "name": "Chlorthalidone", "alternateNames": [ "Thalitone", "Hygroton" ], "category": "Prescription", "subcategory": "Thiazide-Like Diuretic", "overview": "Chlorthalidone is a thiazide-like diuretic with a longer half-life and stronger evidence base than hydrochlorothiazide. 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Major outcomes in high-risk hypertensive patients randomized to ACE inhibitor or calcium channel blocker vs diuretic (ALLHAT). JAMA. 2002.", "pmid": "12479763", "doi": "10.1001/jama.288.23.2981", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12479763/", "publicSourceType": "PMID" }, { "text": "SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension (SHEP). JAMA. 1991.", "pmid": "2046107", "doi": "10.1001/jama.265.24.3255", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2046107/", "publicSourceType": "PMID" }, { "text": "Oliveira AV et al. Thiazide and thiazide-like diuretics for kidney stones recurrence: a systematic review and network meta-analysis of randomised controlled trials. World J Urol. 2025.", "pmid": "41396435", "doi": "10.1007/s00345-025-06137-8", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41396435/", "publicSourceType": "PMID" }, { "text": "Ernst ME, Fravel MA. Thiazide and the Thiazide-Like Diuretics: Review of Hydrochlorothiazide, Chlorthalidone, and Indapamide. American journal of hypertension. 2022", "pmid": "35404993", "doi": "10.1093/ajh/hpac048", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35404993/", "publicSourceType": "PMID" }, { "text": "Ishani A, Cushman WC, Leatherman SM et al.. Chlorthalidone vs. Hydrochlorothiazide for Hypertension-Cardiovascular Events. The New England journal of medicine. 2022", "pmid": "36516076", "doi": "10.1056/NEJMoa2212270", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36516076/", "publicSourceType": "PMID" }, { "text": "Aggarwal P, Oza RR, Solanki H et al.. Efficacy & safety of chlorthalidone vs. hydrochlorothiazide in hypertension: A systematic review & meta-analysis. The Indian journal of medical research. 2025", "claim": "PubMed-indexed evidence involving Chlorthalidone", "title": "Efficacy & safety of chlorthalidone vs. hydrochlorothiazide in hypertension: A systematic review & meta-analysis", "authors": "Aggarwal P, Oza RR, Solanki H et al.", "journal": "The Indian journal of medical research", "year": 2025, "pmid": "41648959", "url": "https://pubmed.ncbi.nlm.nih.gov/41648959/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.25259/IJMR_1553_2025", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41648959/", "publicSourceType": "PMID" }, { "text": "Katsi V, Michalakeas C, Soulaidopoulos S et al.. Evaluating the Safety and Tolerability of Azilsartan Medoxomil Alone or in Combination With Chlorthalidone in the Management of Hypertension: A Systematic Review. Current hypertension reviews. 2021", "claim": "PubMed-indexed evidence involving Chlorthalidone", "title": "Evaluating the Safety and Tolerability of Azilsartan Medoxomil Alone or in Combination With Chlorthalidone in the Management of Hypertension: A Systematic Review", "authors": "Katsi V, Michalakeas C, Soulaidopoulos S et al.", "journal": "Current hypertension reviews", "year": 2021, "pmid": "33438552", "url": "https://pubmed.ncbi.nlm.nih.gov/33438552/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2174/1573402117666210112144505", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33438552/", "publicSourceType": "PMID" }, { "text": "Khenhrani RR, Nnodebe I, Rawat A et al.. Comparison of the Effectiveness and Safety of Chlorthalidone and Hydrochlorothiazide in Patients With Hypertension: A Meta-Analysis. Cureus. 2023", "claim": "PubMed-indexed evidence involving Chlorthalidone", "title": "Comparison of the Effectiveness and Safety of Chlorthalidone and Hydrochlorothiazide in Patients With Hypertension: A Meta-Analysis", "authors": "Khenhrani RR, Nnodebe I, Rawat A et al.", "journal": "Cureus", "year": 2023, "pmid": "37252566", "url": "https://pubmed.ncbi.nlm.nih.gov/37252566/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7759/cureus.38184", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37252566/", "publicSourceType": "PMID" }, { "text": "Kumar L, Khuwaja S, Kumar A et al.. Exploring the Effectiveness and Safety of Azilsartan-Medoxomil/Chlorthalidone Versus Olmesartan-Medoxomil/Hydrochlorothiazide in Hypertensive Patients: A Meta-Analysis. Cureus. 2023", "claim": "PubMed-indexed evidence involving Chlorthalidone", "title": "Exploring the Effectiveness and Safety of Azilsartan-Medoxomil/Chlorthalidone Versus Olmesartan-Medoxomil/Hydrochlorothiazide in Hypertensive Patients: A Meta-Analysis", "authors": "Kumar L, Khuwaja S, Kumar A et al.", "journal": "Cureus", "year": 2023, "pmid": "37525792", "url": "https://pubmed.ncbi.nlm.nih.gov/37525792/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7759/cureus.41198", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37525792/", "publicSourceType": "PMID" }, { "text": "Dineva S, Uzunova K, Pavlova V et al.. Network meta-analysis of efficacy and safety of chlorthalidone and hydrochlorothiazide in hypertensive patients. Blood pressure monitoring. 2021", "claim": "PubMed-indexed evidence involving Chlorthalidone", "title": "Network meta-analysis of efficacy and safety of chlorthalidone and hydrochlorothiazide in hypertensive patients", "authors": "Dineva S, Uzunova K, Pavlova V et al.", "journal": "Blood pressure monitoring", "year": 2021, "pmid": "32909966", "url": "https://pubmed.ncbi.nlm.nih.gov/32909966/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MBP.0000000000000486", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32909966/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Thiazide-Like Diuretic", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "40–60 hours", "onsetOfAction": "2–6 hours; duration of action 24–72 hours", "commonBrandNames": [ "Thalitone", "Hygroton" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Serum electrolytes (potassium, sodium, magnesium), renal function, uric acid, and glucose at baseline, 1–2 weeks after initiation, and periodically; more potassium depletion than HCTZ" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "chlorthalidone" }, { "id": "RX-CARDIO-027", "name": "Warfarin", "alternateNames": [ "Coumadin", "Jantoven" ], "category": "Prescription", "subcategory": "Anticoagulant (Vitamin K Antagonist)", "overview": "Warfarin is an oral vitamin K antagonist anticoagulant used for prevention and treatment of thromboembolic disorders including atrial fibrillation, mechanical heart valves, deep vein thrombosis, and pulmonary embolism. 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The delayed onset reflects the half-lives of existing circulating clotting factors (factor II has the longest at ~60 hours).", "commonBenefits": [ "Effective stroke prevention in atrial fibrillation", "Essential for mechanical heart valve anticoagulation", "Treatment and prevention of DVT and PE", "Decades of clinical experience", "Reversible with vitamin K and FFP/PCC" ], "commonDosageRange": "Variable; typically 2–10 mg daily adjusted to target INR (as prescribed by your physician)", "recommendedForm": "Oral tablet", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Can be taken with or without food; maintain consistent dietary vitamin K intake; numerous food and drug interactions" }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Bleeding (major and minor)", "Bruising", "Skin necrosis (rare, associated with protein C deficiency)", "Purple toe syndrome", "Calciphylaxis", "Hair loss", "Nausea" ], "contraindications": [ "Active major bleeding", "Pregnancy (teratogenic, Warfarin embryopathy)", "Hemorrhagic tendencies or blood dyscrasias", "Recent or planned surgery of the CNS or eye", "Malignant hypertension", "Unsupervised patient with alcoholism, psychosis, or dementia" ], "iconName": "cross.case.fill", "colorHex": "E74C3C", "tags": [ "cardiovascular", "anticoagulant", "blood-thinner", "atrial-fibrillation", "dvt-pe" ], "sources": [ { "text": "Holbrook AM et al. Systematic overview of warfarin and its drug and food interactions. Arch Intern Med. 2005.", "pmid": "15911722", "doi": "10.1001/archinte.165.10.1095", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15911722/", "publicSourceType": "PMID" }, { "text": "Hart RG et al. Meta-analysis: antithrombotic therapy to prevent stroke in patients with nonvalvular atrial fibrillation. Ann Intern Med. 2007.", "pmid": "17577005", "doi": "10.7326/0003-4819-146-12-200706190-00007", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17577005/", "publicSourceType": "PMID" }, { "text": "Ageno W et al. Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: ACCP Evidence-Based Clinical Practice Guidelines. Chest. 2012.", "pmid": "22315269", "doi": "10.1378/chest.11-2292", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22315269/", "publicSourceType": "PMID" }, { "text": "Tan CSS, Lee SWH. Warfarin and food, herbal or dietary supplement interactions: A systematic review. British journal of clinical pharmacology. 2021", "pmid": "32478963", "doi": "10.1111/bcp.14404", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32478963/", "publicSourceType": "PMID" }, { "text": "Wang M, Zeraatkar D, Obeda M et al.. Drug-drug interactions with warfarin: A systematic review and meta-analysis. British journal of clinical pharmacology. 2021", "pmid": "33769581", "doi": "10.1111/bcp.14833", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33769581/", "publicSourceType": "PMID" }, { "claim": "DOACs are compared to warfarin for stroke prevention in atrial fibrillation", "title": "Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis", "authors": "López-López JA, Sterne JAC, Thom HHZ, Higgins JPT et al.", "journal": "BMJ", "year": 2017, "pmid": "29183961", "url": "https://pubmed.ncbi.nlm.nih.gov/29183961/", "study_type": "network meta-analysis", "key_finding": "Apixaban, dabigatran, and rivaroxaban all showed favorable efficacy and safety compared to warfarin for stroke prevention in atrial fibrillation, with apixaban having the best safety profile", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29183961/", "publicSourceType": "PMID" }, { "claim": "DOACs vs warfarin in atrial fibrillation with low stroke risk", "title": "Systematic Review and Meta-Analysis of Direct Oral Anticoagulants Versus Warfarin in Atrial Fibrillation With Low Stroke Risk", "authors": "Fong KY, Chan YH, Yeo C, Lip GYH et al.", "journal": "The American Journal of Cardiology", "year": 2023, "pmid": "37573616", "url": "https://pubmed.ncbi.nlm.nih.gov/37573616/", "study_type": "meta-analysis", "key_finding": "In patients with atrial fibrillation and low stroke risk, DOACs showed comparable efficacy to warfarin with significantly lower bleeding risk, supporting a favorable benefit-risk profile", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37573616/", "publicSourceType": "PMID" }, { "text": "Choi S, Oh DS, Jerng UM. A systematic review of the pharmacokinetic and pharmacodynamic interactions of herbal medicine with warfarin. PloS one. 2017", "claim": "PubMed-indexed evidence involving Warfarin", "title": "A systematic review of the pharmacokinetic and pharmacodynamic interactions of herbal medicine with warfarin", "authors": "Choi S, Oh DS, Jerng UM", "journal": "PloS one", "year": 2017, "pmid": "28797065", "url": "https://pubmed.ncbi.nlm.nih.gov/28797065/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1371/journal.pone.0182794", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28797065/", "publicSourceType": "PMID" }, { "text": "Fülöp P, Tóth Š, Porubän T et al.. Machine Learning for Warfarin Therapy: A Systematic Review. Pharmaceuticals (Basel, Switzerland). 2025", "claim": "PubMed-indexed evidence involving Warfarin", "title": "Machine Learning for Warfarin Therapy: A Systematic Review", "authors": "Fülöp P, Tóth Š, Porubän T et al.", "journal": "Pharmaceuticals (Basel, Switzerland)", "year": 2025, "pmid": "41155660", "url": "https://pubmed.ncbi.nlm.nih.gov/41155660/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/ph18101544", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41155660/", "publicSourceType": "PMID" }, { "text": "Mhanna M, Ayyad M, Mortada I et al.. Direct oral anticoagulants versus warfarin in adults with durable left ventricular assist devices: A systematic review and meta-analysis. Current problems in cardiology. 2024", "claim": "PubMed-indexed evidence involving Warfarin", "title": "Direct oral anticoagulants versus warfarin in adults with durable left ventricular assist devices: A systematic review and meta-analysis", "authors": "Mhanna M, Ayyad M, Mortada I et al.", "journal": "Current problems in cardiology", "year": 2024, "pmid": "39369772", "url": "https://pubmed.ncbi.nlm.nih.gov/39369772/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.cpcardiol.2024.102871", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39369772/", "publicSourceType": "PMID" }, { "text": "Patel PH, Ho T, Upadhyay SM. A Systematic Review of Warfarin Use in Post-Bariatric Surgery Patients: Cases Compiled From a Literature Review. The Annals of pharmacotherapy. 2023", "claim": "PubMed-indexed evidence involving Warfarin", "title": "A Systematic Review of Warfarin Use in Post-Bariatric Surgery Patients: Cases Compiled From a Literature Review", "authors": "Patel PH, Ho T, Upadhyay SM", "journal": "The Annals of pharmacotherapy", "year": 2023, "pmid": "35699512", "url": "https://pubmed.ncbi.nlm.nih.gov/35699512/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/10600280221105312", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35699512/", "publicSourceType": "PMID" }, { "text": "Tarar MY, Malik RA, Charalambous CP. Bleeding complications in patients on warfarin undergoing joint injection/aspiration: systematic review and meta-analysis. Rheumatology international. 2023", "claim": "PubMed-indexed evidence involving Warfarin", "title": "Bleeding complications in patients on warfarin undergoing joint injection/aspiration: systematic review and meta-analysis", "authors": "Tarar MY, Malik RA, Charalambous CP", "journal": "Rheumatology international", "year": 2023, "pmid": "36322144", "url": "https://pubmed.ncbi.nlm.nih.gov/36322144/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00296-022-05232-y", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36322144/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Vitamin K Antagonist Anticoagulant", "blackBoxWarnings": [ "Warfarin can cause major or fatal bleeding. Bleeding is more likely during the starting period and with a higher dose. Regular monitoring of INR is required. 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CBC at baseline." }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "warfarin" }, { "id": "RX-CARDIO-028", "name": "Apixaban", "alternateNames": [ "Eliquis" ], "category": "Prescription", "subcategory": "Direct Oral Anticoagulant (DOAC)", "overview": "Apixaban is a direct oral factor Xa inhibitor with strong evidence from the ARISTOTLE trial showing superiority to warfarin for stroke prevention in atrial fibrillation with less bleeding. It is also approved for DVT/PE treatment and thromboprophylaxis after hip or knee replacement surgery.", "mechanismOfAction": "Selectively and reversibly inhibits free and clot-bound factor Xa, a key protease in the coagulation cascade at the convergence of intrinsic and extrinsic pathways. By inhibiting factor Xa, it reduces thrombin generation and thrombus formation without directly affecting existing thrombin. Predictable pharmacokinetics allow fixed dosing without routine monitoring.", "commonBenefits": [ "Superior to warfarin for stroke prevention with less bleeding (ARISTOTLE)", "No routine INR monitoring required", "Fixed-dose regimen", "Fewer drug and food interactions than warfarin", "Lower intracranial hemorrhage risk than warfarin" ], "commonDosageRange": "AF: 5 mg twice daily (2.5 mg twice daily if meeting dose reduction criteria); DVT/PE: 10 mg twice daily for 7 days, then 5 mg twice daily (as prescribed by your physician)", "recommendedForm": "Oral tablet", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Can be taken with or without food; tablets may be crushed and mixed with water or applesauce for patients with difficulty swallowing" }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Bleeding (major and clinically relevant non-major)", "Bruising", "Nausea", "Anemia", "Epistaxis", "Gingival bleeding" ], "contraindications": [ "Active pathological bleeding", "Severe hypersensitivity to apixaban", "Prosthetic heart valves (not recommended)", "Triple-positive antiphospholipid syndrome", "Concurrent strong dual CYP3A4 and P-gp inhibitors or inducers" ], "iconName": "cross.case.fill", "colorHex": "E74C3C", "tags": [ "cardiovascular", "anticoagulant", "blood-thinner", "atrial-fibrillation", "dvt-pe", "doac" ], "sources": [ { "text": "Granger CB et al. Apixaban versus warfarin in patients with atrial fibrillation (ARISTOTLE). N Engl J Med. 2011.", "pmid": "21870978", "doi": "10.1056/NEJMoa1107039", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21870978/", "publicSourceType": "PMID" }, { "text": "Agnelli G et al. Oral apixaban for the treatment of acute venous thromboembolism (AMPLIFY). N Engl J Med. 2013.", "pmid": "23808982", "doi": "10.1056/NEJMoa1302507", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23808982/", "publicSourceType": "PMID" }, { "text": "Deng D et al. Reduced-Dose Versus Full-Dose Direct Oral Anticoagulants for Extended Treatment of Venous Thromboembolism. Clin Appl Thromb Hemost. 2025.", "pmid": "41428436", "doi": "10.1177/10760296251408061", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41428436/", "publicSourceType": "PMID" }, { "text": "Mamas MA, Batson S, Pollock KG et al.. Meta-Analysis Comparing Apixaban Versus Rivaroxaban for Management of Patients With Nonvalvular Atrial Fibrillation. The American journal of cardiology. 2022", "pmid": "34949473", "doi": "10.1016/j.amjcard.2021.11.021", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34949473/", "publicSourceType": "PMID" }, { "text": "Byon W, Garonzik S, Boyd RA et al.. Apixaban: A Clinical Pharmacokinetic and Pharmacodynamic Review. Clinical pharmacokinetics. 2019", "pmid": "31089975", "doi": "10.1007/s40262-019-00775-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31089975/", "publicSourceType": "PMID" }, { "claim": "Apixaban safety in hemodialysis patients with atrial fibrillation", "title": "Apixaban for Patients With Atrial Fibrillation on Hemodialysis: A Multicenter Randomized Controlled Trial", "authors": "Pokorney SD, Chertow GM, Al-Khalidi HR, Gallup D et al.", "journal": "Circulation", "year": 2022, "pmid": "36335914", "url": "https://pubmed.ncbi.nlm.nih.gov/36335914/", "study_type": "rct", "key_finding": "In hemodialysis patients with atrial fibrillation, apixaban did not significantly reduce the composite of stroke/systemic embolism but had a similar bleeding profile compared to warfarin or no anticoagulation", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36335914/", "publicSourceType": "PMID" }, { "text": "Wu X, Meng J, Yang Y et al.. Comparative efficacy and safety of apixaban and rivaroxaban versus warfarin in atrial fibrillation patients with end-stage renal disease: a systematic review and meta-analysis. Renal failure. 2026", "claim": "PubMed-indexed evidence involving Apixaban", "title": "Comparative efficacy and safety of apixaban and rivaroxaban versus warfarin in atrial fibrillation patients with end-stage renal disease: a systematic review and meta-analysis", "authors": "Wu X, Meng J, Yang Y et al.", "journal": "Renal failure", "year": 2026, "pmid": "42128628", "url": "https://pubmed.ncbi.nlm.nih.gov/42128628/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/0886022X.2026.2666454", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/42128628/", "publicSourceType": "PMID" }, { "text": "Daghlas I, Lieberman OJ, Suleiman L et al.. Risk of Intracranial Hemorrhage With Apixaban Versus Aspirin Therapy: A Meta-Analysis of Randomized Controlled Trials. Stroke. 2025", "claim": "PubMed-indexed evidence involving Apixaban", "title": "Risk of Intracranial Hemorrhage With Apixaban Versus Aspirin Therapy: A Meta-Analysis of Randomized Controlled Trials", "authors": "Daghlas I, Lieberman OJ, Suleiman L et al.", "journal": "Stroke", "year": 2025, "pmid": "40464082", "url": "https://pubmed.ncbi.nlm.nih.gov/40464082/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1161/STROKEAHA.125.051088", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40464082/", "publicSourceType": "PMID" }, { "text": "Fredman D, McNeil R, Eldar O et al.. Efficacy and safety of rivaroxaban versus apixaban for venous thromboembolism: A systematic review and meta-analysis of observational studies. Journal of thrombosis and thrombolysis. 2024", "claim": "PubMed-indexed evidence involving Apixaban", "title": "Efficacy and safety of rivaroxaban versus apixaban for venous thromboembolism: A systematic review and meta-analysis of observational studies", "authors": "Fredman D, McNeil R, Eldar O et al.", "journal": "Journal of thrombosis and thrombolysis", "year": 2024, "pmid": "38127261", "url": "https://pubmed.ncbi.nlm.nih.gov/38127261/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s11239-023-02926-3", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38127261/", "publicSourceType": "PMID" }, { "text": "Tornyos A, Vorobcsuk A, Kupó P et al.. Apixaban and risk of myocardial infarction: meta-analysis of randomized controlled trials. Journal of thrombosis and thrombolysis. 2015", "claim": "PubMed-indexed evidence involving Apixaban", "title": "Apixaban and risk of myocardial infarction: meta-analysis of randomized controlled trials", "authors": "Tornyos A, Vorobcsuk A, Kupó P et al.", "journal": "Journal of thrombosis and thrombolysis", "year": 2015, "pmid": "25059624", "url": "https://pubmed.ncbi.nlm.nih.gov/25059624/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s11239-014-1096-z", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25059624/", "publicSourceType": "PMID" }, { "text": "Bai Y, Shi XB, Ma CS et al.. Meta-Analysis of Effectiveness and Safety of Oral Anticoagulants in Atrial Fibrillation With Focus on Apixaban. The American journal of cardiology. 2017", "claim": "PubMed-indexed evidence involving Apixaban", "title": "Meta-Analysis of Effectiveness and Safety of Oral Anticoagulants in Atrial Fibrillation With Focus on Apixaban", "authors": "Bai Y, Shi XB, Ma CS et al.", "journal": "The American journal of cardiology", "year": 2017, "pmid": "28844510", "url": "https://pubmed.ncbi.nlm.nih.gov/28844510/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.amjcard.2017.07.072", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28844510/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Direct Factor Xa Inhibitor (DOAC)", "blackBoxWarnings": [ "Premature discontinuation increases the risk of thrombotic events. If anticoagulation must be discontinued for a reason other than pathological bleeding, consider coverage with another anticoagulant.", "Epidural or spinal hematomas may occur in patients treated with apixaban who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis." ], "fdaPregnancyCategory": "B", "halfLife": "12 hours", "onsetOfAction": "3–4 hours to peak plasma concentration", "commonBrandNames": [ "Eliquis" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": "Routine coagulation monitoring not required; renal function (serum creatinine) at baseline and at least annually; CBC as clinically indicated" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "apixaban" }, { "id": "RX-CARDIO-029", "name": "Rivaroxaban", "alternateNames": [ "Xarelto" ], "category": "Prescription", "subcategory": "Direct Oral Anticoagulant (DOAC)", "overview": "Rivaroxaban is a direct factor Xa inhibitor approved for stroke prevention in non-valvular atrial fibrillation, DVT/PE treatment and prevention, and secondary cardiovascular prevention (with aspirin in COMPASS trial). The ROCKET AF trial demonstrated non-inferiority to warfarin for stroke prevention in AF.", "mechanismOfAction": "Directly and selectively inhibits free and clot-bound factor Xa. Inhibition of factor Xa interrupts the intrinsic and extrinsic coagulation pathways, reducing thrombin generation and thrombus formation. High oral bioavailability and predictable pharmacokinetics. Partially renally eliminated (~33%).", "commonBenefits": [ "Non-inferior to warfarin for stroke prevention in AF (ROCKET AF)", "Once-daily dosing for most indications", "No routine monitoring required", "Reduces cardiovascular events when combined with aspirin (COMPASS)" ], "commonDosageRange": "AF: 20 mg once daily with evening meal; DVT/PE: 15 mg twice daily for 21 days, then 20 mg daily; Vascular prevention: 2.5 mg twice daily with aspirin (as prescribed by your physician)", "recommendedForm": "Oral tablet, taken with food for 15 mg and 20 mg doses", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "15 mg and 20 mg doses MUST be taken with food to ensure adequate absorption (bioavailability increases from 66% to near 100%); 10 mg dose can be taken with or without food" }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Bleeding (major and clinically relevant non-major)", "Bruising", "GI bleeding (higher rate than warfarin in ROCKET AF)", "Epistaxis", "Anemia", "Nausea" ], "contraindications": [ "Active pathological bleeding", "Severe hypersensitivity to rivaroxaban", "Prosthetic heart valves (not recommended)", "Triple-positive antiphospholipid syndrome", "Moderate or severe hepatic impairment (Child-Pugh B or C)" ], "iconName": "cross.case.fill", "colorHex": "E74C3C", "tags": [ "cardiovascular", "anticoagulant", "blood-thinner", "atrial-fibrillation", "dvt-pe", "doac" ], "sources": [ { "text": "Patel MR et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation (ROCKET AF). N Engl J Med. 2011.", "pmid": "21830957", "doi": "10.1056/NEJMoa1009638", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21830957/", "publicSourceType": "PMID" }, { "text": "Eikelboom JW et al. Rivaroxaban with or without aspirin in stable cardiovascular disease (COMPASS). N Engl J Med. 2017.", "pmid": "28844192", "doi": "10.1056/NEJMoa1709118", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28844192/", "publicSourceType": "PMID" }, { "text": "Deng D et al. Reduced-Dose Versus Full-Dose Direct Oral Anticoagulants for Extended Treatment of Venous Thromboembolism. Clin Appl Thromb Hemost. 2025.", "pmid": "41428436", "doi": "10.1177/10760296251408061", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41428436/", "publicSourceType": "PMID" }, { "text": "Mamas MA, Batson S, Pollock KG et al.. Meta-Analysis Comparing Apixaban Versus Rivaroxaban for Management of Patients With Nonvalvular Atrial Fibrillation. The American journal of cardiology. 2022", "pmid": "34949473", "doi": "10.1016/j.amjcard.2021.11.021", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34949473/", "publicSourceType": "PMID" }, { "claim": "Rivaroxaban is effective for treatment of venous thromboembolism in children", "title": "Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial", "authors": "Male C, Lensing AWA, Palumbo JS, Kumar R et al.", "journal": "The Lancet Haematology", "year": 2020, "pmid": "31699660", "url": "https://pubmed.ncbi.nlm.nih.gov/31699660/", "study_type": "rct", "key_finding": "Rivaroxaban showed similar efficacy to standard anticoagulants for treatment of VTE in children with a trend toward fewer recurrent events and lower bleeding rates", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31699660/", "publicSourceType": "PMID" }, { "text": "Wu X, Meng J, Yang Y et al.. Comparative efficacy and safety of apixaban and rivaroxaban versus warfarin in atrial fibrillation patients with end-stage renal disease: a systematic review and meta-analysis. Renal failure. 2026", "claim": "PubMed-indexed evidence involving Rivaroxaban", "title": "Comparative efficacy and safety of apixaban and rivaroxaban versus warfarin in atrial fibrillation patients with end-stage renal disease: a systematic review and meta-analysis", "authors": "Wu X, Meng J, Yang Y et al.", "journal": "Renal failure", "year": 2026, "pmid": "42128628", "url": "https://pubmed.ncbi.nlm.nih.gov/42128628/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/0886022X.2026.2666454", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/42128628/", "publicSourceType": "PMID" }, { "text": "Fredman D, McNeil R, Eldar O et al.. Efficacy and safety of rivaroxaban versus apixaban for venous thromboembolism: A systematic review and meta-analysis of observational studies. Journal of thrombosis and thrombolysis. 2024", "claim": "PubMed-indexed evidence involving Rivaroxaban", "title": "Efficacy and safety of rivaroxaban versus apixaban for venous thromboembolism: A systematic review and meta-analysis of observational studies", "authors": "Fredman D, McNeil R, Eldar O et al.", "journal": "Journal of thrombosis and thrombolysis", "year": 2024, "pmid": "38127261", "url": "https://pubmed.ncbi.nlm.nih.gov/38127261/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s11239-023-02926-3", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38127261/", "publicSourceType": "PMID" }, { "text": "Netha A, Mazhar S, Azhar A et al.. Effectiveness of rivaroxaban in preventing cerebral venous thromboembolism: a systematic review and meta-analysis. Annals of medicine and surgery (2012). 2024", "claim": "PubMed-indexed evidence involving Rivaroxaban", "title": "Effectiveness of rivaroxaban in preventing cerebral venous thromboembolism: a systematic review and meta-analysis", "authors": "Netha A, Mazhar S, Azhar A et al.", "journal": "Annals of medicine and surgery (2012)", "year": 2024, "pmid": "38576935", "url": "https://pubmed.ncbi.nlm.nih.gov/38576935/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MS9.0000000000001689", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38576935/", "publicSourceType": "PMID" }, { "text": "Mardi P, Abbasi B, Shafiee A et al.. Pharmacogenetic Approach for the Prevention of Rivaroxaban's ADRs: A Systematic Review and Meta-Analysis. Genetics research. 2023", "claim": "PubMed-indexed evidence involving Rivaroxaban", "title": "Pharmacogenetic Approach for the Prevention of Rivaroxaban's ADRs: A Systematic Review and Meta-Analysis", "authors": "Mardi P, Abbasi B, Shafiee A et al.", "journal": "Genetics research", "year": 2023, "pmid": "37942082", "url": "https://pubmed.ncbi.nlm.nih.gov/37942082/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1155/2023/6105320", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37942082/", "publicSourceType": "PMID" }, { "text": "Alves C, Batel-Marques F, Macedo AF. Apixaban and rivaroxaban safety after hip and knee arthroplasty: a meta-analysis. Journal of cardiovascular pharmacology and therapeutics. 2012", "claim": "PubMed-indexed evidence involving Rivaroxaban", "title": "Apixaban and rivaroxaban safety after hip and knee arthroplasty: a meta-analysis", "authors": "Alves C, Batel-Marques F, Macedo AF", "journal": "Journal of cardiovascular pharmacology and therapeutics", "year": 2012, "pmid": "22134134", "url": "https://pubmed.ncbi.nlm.nih.gov/22134134/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/1074248411427402", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22134134/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Direct Factor Xa Inhibitor (DOAC)", "blackBoxWarnings": [ "Premature discontinuation increases the risk of thrombotic events. If anticoagulation must be discontinued for a reason other than pathological bleeding, consider coverage with another anticoagulant.", "Epidural or spinal hematomas may occur in patients treated with rivaroxaban who are receiving neuraxial anesthesia or undergoing spinal puncture." ], "fdaPregnancyCategory": "C", "halfLife": "5–9 hours (young adults); 11–13 hours (elderly)", "onsetOfAction": "2–4 hours to peak plasma concentration", "commonBrandNames": [ "Xarelto" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": "Routine coagulation monitoring not required; renal function at baseline and at least annually; CBC as clinically indicated" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "rivaroxaban" }, { "id": "RX-CARDIO-030", "name": "Dabigatran", "alternateNames": [ "Pradaxa" ], "category": "Prescription", "subcategory": "Direct Oral Anticoagulant (DOAC)", "overview": "Dabigatran is a direct thrombin (factor IIa) inhibitor that was the first DOAC approved for stroke prevention in non-valvular atrial fibrillation, based on the RE-LY trial. It is the only DOAC with a specific reversal agent (idarucizumab/Praxbind). Also approved for DVT/PE treatment after initial parenteral anticoagulation.", "mechanismOfAction": "Administered as the prodrug dabigatran etexilate, which is converted to active dabigatran by esterases. Dabigatran directly and reversibly inhibits both free and fibrin-bound thrombin (factor IIa). By inhibiting thrombin, it prevents conversion of fibrinogen to fibrin and inhibits thrombin-mediated platelet activation. Primarily renally eliminated (~80%).", "commonBenefits": [ "Non-inferior (150 mg) or superior to warfarin for stroke prevention in AF", "Specific reversal agent available (idarucizumab/Praxbind)", "Fixed dosing without routine monitoring", "Lower intracranial hemorrhage risk than warfarin" ], "commonDosageRange": "AF: 150 mg twice daily (or 75 mg twice daily for CrCl 15–30 mL/min); DVT/PE: 150 mg twice daily after 5–10 days of parenteral anticoagulation (as prescribed by your physician)", "recommendedForm": "Oral capsule (must be swallowed whole, do not crush, chew, or open)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Can be taken with or without food; capsules must be kept in original packaging due to moisture sensitivity; do not place in pill organizers" }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Dyspepsia and GI discomfort (most common, ~10%)", "Bleeding (major and minor)", "GI bleeding (higher rate than warfarin at 150 mg dose)", "Nausea", "Abdominal pain", "Gastritis-like symptoms" ], "contraindications": [ "Active pathological bleeding", "Mechanical prosthetic heart valve (RE-ALIGN trial terminated for excess events)", "Severe renal impairment (CrCl <15 mL/min, US labeling; <30 mL/min, EU)", "Concurrent P-glycoprotein inhibitors with CrCl <30 mL/min", "Hypersensitivity to dabigatran" ], "iconName": "cross.case.fill", "colorHex": "E74C3C", "tags": [ "cardiovascular", "anticoagulant", "blood-thinner", "atrial-fibrillation", "dvt-pe", "doac", "direct-thrombin-inhibitor" ], "sources": [ { "text": "Connolly SJ et al. Dabigatran versus warfarin in patients with atrial fibrillation (RE-LY). N Engl J Med. 2009.", "pmid": "19717844", "doi": "10.1056/NEJMoa0905561", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19717844/", "publicSourceType": "PMID" }, { "text": "Pollack CV et al. Idarucizumab for dabigatran reversal (RE-VERSE AD). N Engl J Med. 2015.", "pmid": "26095746", "doi": "10.1056/NEJMoa1502000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26095746/", "publicSourceType": "PMID" }, { "text": "Rothstein A et al. Switching From Aspirin Monotherapy After Noncardioembolic Stroke: A Systematic Review and Network Meta-Analysis. Stroke. 2026.", "pmid": "41347302", "doi": "10.1161/STROKEAHA.125.053030", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41347302/", "publicSourceType": "PMID" }, { "text": "Bloom BJ, Filion KB, Atallah R et al.. Meta-analysis of randomized controlled trials on the risk of bleeding with dabigatran. The American journal of cardiology. 2014", "claim": "PubMed-indexed evidence involving Dabigatran", "title": "Meta-analysis of randomized controlled trials on the risk of bleeding with dabigatran", "authors": "Bloom BJ, Filion KB, Atallah R et al.", "journal": "The American journal of cardiology", "year": 2014, "pmid": "24440332", "url": "https://pubmed.ncbi.nlm.nih.gov/24440332/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.amjcard.2013.11.049", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24440332/", "publicSourceType": "PMID" }, { "text": "Romoli M, Matteo E, Migliaccio L et al.. Thrombolysis after dabigatran reversal: A nation-wide Italian multicentre study, systematic review and meta-analysis. European stroke journal. 2023", "claim": "PubMed-indexed evidence involving Dabigatran", "title": "Thrombolysis after dabigatran reversal: A nation-wide Italian multicentre study, systematic review and meta-analysis", "authors": "Romoli M, Matteo E, Migliaccio L et al.", "journal": "European stroke journal", "year": 2023, "pmid": "37021155", "url": "https://pubmed.ncbi.nlm.nih.gov/37021155/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/23969873221131635", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37021155/", "publicSourceType": "PMID" }, { "text": "van der Horst SFB, Martens ESL, den Exter PL et al.. Idarucizumab for dabigatran reversal: A systematic review and meta-analysis of indications and outcomes. Thrombosis research. 2023", "claim": "PubMed-indexed evidence involving Dabigatran", "title": "Idarucizumab for dabigatran reversal: A systematic review and meta-analysis of indications and outcomes", "authors": "van der Horst SFB, Martens ESL, den Exter PL et al.", "journal": "Thrombosis research", "year": 2023, "pmid": "37267671", "url": "https://pubmed.ncbi.nlm.nih.gov/37267671/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.thromres.2023.05.020", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37267671/", "publicSourceType": "PMID" }, { "text": "Ng JW, Mohd Tahir NA, Chin PKL et al.. A systematic review and meta-analysis of dabigatran peak and trough concentration in adults. British journal of clinical pharmacology. 2022", "claim": "PubMed-indexed evidence involving Dabigatran", "title": "A systematic review and meta-analysis of dabigatran peak and trough concentration in adults", "authors": "Ng JW, Mohd Tahir NA, Chin PKL et al.", "journal": "British journal of clinical pharmacology", "year": 2022, "pmid": "35665523", "url": "https://pubmed.ncbi.nlm.nih.gov/35665523/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/bcp.15431", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35665523/", "publicSourceType": "PMID" }, { "text": "Frol S, Sagris D, Pretnar Oblak J et al.. Intravenous Thrombolysis After Dabigatran Reversal by Idarucizumab: A Systematic Review of the Literature. Frontiers in neurology. 2021", "claim": "PubMed-indexed evidence involving Dabigatran", "title": "Intravenous Thrombolysis After Dabigatran Reversal by Idarucizumab: A Systematic Review of the Literature", "authors": "Frol S, Sagris D, Pretnar Oblak J et al.", "journal": "Frontiers in neurology", "year": 2021, "pmid": "34149597", "url": "https://pubmed.ncbi.nlm.nih.gov/34149597/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fneur.2021.666086", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34149597/", "publicSourceType": "PMID" }, { "text": "Thibault N, Morrill AM, Willett KC. Idarucizumab for Reversing Dabigatran-Induced Anticoagulation: A Systematic Review. 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The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2021", "claim": "PubMed-indexed evidence involving Enoxaparin", "title": "The efficacy of enoxaparin for recurrent abortion: a meta-analysis of randomized controlled studies", "authors": "Liu Y, Shan N, Yuan Y et al.", "journal": "The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians", "year": 2021, "pmid": "30983451", "url": "https://pubmed.ncbi.nlm.nih.gov/30983451/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/14767058.2019.1608433", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30983451/", "publicSourceType": "PMID" }, { "text": "Hai-Long W, Xiao-Hua P, Jian-Jun Y. The Efficacy and Safety of Enoxaparin: A Meta-analysis. Open medicine (Warsaw, Poland). 2018", "claim": "PubMed-indexed evidence involving Enoxaparin", "title": "The Efficacy and Safety of Enoxaparin: A Meta-analysis", "authors": "Hai-Long W, Xiao-Hua P, Jian-Jun Y", "journal": "Open medicine (Warsaw, Poland)", "year": 2018, "pmid": "30211318", "url": "https://pubmed.ncbi.nlm.nih.gov/30211318/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1515/med-2018-0054", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30211318/", "publicSourceType": "PMID" }, { "text": "Al Tannir AH, Biesboer EA, Pokrzywa CJ et al.. The efficacy of various Enoxaparin dosing regimens in general surgery patients: A systematic review. Surgery. 2023", "claim": "PubMed-indexed evidence involving Enoxaparin", "title": "The efficacy of various Enoxaparin dosing regimens in general surgery patients: A systematic review", "authors": "Al Tannir AH, Biesboer EA, Pokrzywa CJ et al.", "journal": "Surgery", "year": 2023, "pmid": "37198037", "url": "https://pubmed.ncbi.nlm.nih.gov/37198037/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.surg.2023.04.032", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37198037/", "publicSourceType": "PMID" }, { "text": "Rodarte RRP, Guimarães JAM, Franco JS et al.. Systematic review of prophylaxis for venous thromboembolism after knee arthroplasty: enoxaparin versus rivaroxaban. 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Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis. Lancet. 2009.", "pmid": "34952844", "doi": "10.1016/S0140-6736(09)60503-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34952844/", "publicSourceType": "PMID" }, { "text": "McNeil JJ et al. Effect of aspirin on cardiovascular events and bleeding in the healthy elderly (ASPREE). N Engl J Med. 2018.", "pmid": "30221597", "doi": "10.1056/NEJMoa1805819", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30221597/", "publicSourceType": "PMID" }, { "text": "Rothstein A et al. Switching From Aspirin Monotherapy After Noncardioembolic Stroke: A Systematic Review and Network Meta-Analysis. Stroke. 2026.", "pmid": "41347302", "doi": "10.1161/STROKEAHA.125.053030", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41347302/", "publicSourceType": "PMID" }, { "text": "Richards EMF, Giorgione V, Stevens O et al.. Low-dose aspirin for the prevention of superimposed preeclampsia in women with chronic hypertension: a systematic review and meta-analysis. American journal of obstetrics and gynecology. 2023", "pmid": "36209937", "doi": "10.1016/j.ajog.2022.09.046", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36209937/", "publicSourceType": "PMID" }, { "text": "Ghesquiere L, Guerby P, Marchant I et al.. Comparing aspirin 75 to 81 mg vs 150 to 162 mg for prevention of preterm preeclampsia: systematic review and meta-analysis. American journal of obstetrics & gynecology MFM. 2023", "pmid": "37146687", "doi": "10.1016/j.ajogmf.2023.101000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37146687/", "publicSourceType": "PMID" }, { "claim": "Low-dose aspirin for primary prevention has a trade-off between cardiovascular benefit and bleeding risk", "title": "Association of Aspirin Use for Primary Prevention With Cardiovascular Events and Bleeding Events: A Systematic Review and Meta-analysis", "authors": "Zheng SL, Roddick AJ", "journal": "JAMA", "year": 2019, "pmid": "30667501", "url": "https://pubmed.ncbi.nlm.nih.gov/30667501/", "study_type": "meta-analysis", "key_finding": "Low-dose aspirin for primary cardiovascular prevention was associated with reduced risk of cardiovascular events (ARR 0.38%) but increased risk of major bleeding (ARI 0.47%), suggesting a marginal net clinical benefit", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30667501/", "publicSourceType": "PMID" }, { "claim": "Aspirin's primary prevention benefits vary by subgroup", "title": "Aspirin for primary prevention of cardiovascular disease: a meta-analysis with a particular focus on subgroups", "authors": "Gelbenegger G, Postula M, Pecen L, Halvorsen S et al.", "journal": "BMC Medicine", "year": 2019, "pmid": "31679516", "url": "https://pubmed.ncbi.nlm.nih.gov/31679516/", "study_type": "meta-analysis", "key_finding": "Aspirin reduced cardiovascular events more clearly in high-risk subgroups (diabetes, high cholesterol), while bleeding risk remained consistent across subgroups, suggesting risk-stratified prescribing", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31679516/", "publicSourceType": "PMID" }, { "claim": "Aspirin reduces serious vascular events in secondary prevention (ATT meta-analysis)", "title": "Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials", "authors": "Antithrombotic Trialists' (ATT) Collaboration, Baigent C, Blackwell L, Collins R et al.", "journal": "Lancet", "year": 2009, "pmid": "19482214", "url": "https://pubmed.ncbi.nlm.nih.gov/19482214/", "study_type": "meta-analysis", "key_finding": "In secondary prevention, aspirin reduced serious vascular events by approximately 20% per year; in primary prevention, the absolute reduction was much smaller and largely offset by major bleeding", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19482214/", "publicSourceType": "PMID" }, { "text": "Mills EJ, Wu P, Alberton M et al.. 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Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2020", "claim": "PubMed-indexed evidence involving Aspirin Low-Dose", "title": "Impact of low-dose aspirin on adverse perinatal outcome: meta-analysis and meta-regression", "authors": "Turner JM, Robertson NT, Hartel G et al.", "journal": "Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology", "year": 2020, "pmid": "31479546", "url": "https://pubmed.ncbi.nlm.nih.gov/31479546/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/uog.20859", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31479546/", "publicSourceType": "PMID" }, { "text": "Wang W, Chang G. Evaluation of Low-Dose Aspirin on Pregnancy Outcomes: A Systematic Review and Meta-analysis. 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Cureus. 2025", "claim": "PubMed-indexed evidence involving Aspirin Low-Dose", "title": "Preventing Preeclampsia With Low-Dose Aspirin: A Systematic Review of Efficacy Across Diverse Populations", "authors": "George R, Sayed Z, Gundala Raja H et al.", "journal": "Cureus", "year": 2025, "pmid": "40519374", "url": "https://pubmed.ncbi.nlm.nih.gov/40519374/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7759/cureus.84202", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40519374/", "publicSourceType": "PMID" }, { "text": "Chen WY, Sun SF. Clinical efficacy of low-dose aspirin combined with calcium in preventing preeclampsia: A systematic review and meta-analysis. 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J Cardiovasc Med (Hagerstown). 2026.", "pmid": "41703405", "doi": "10.2459/JCM.0000000000001830", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41703405/", "publicSourceType": "PMID" }, { "text": "Axelsson MAB, Parodi López N, Wikström Jonsson E et al.. Efficacy and Safety of Clopidogrel With and Without a Proton Pump Inhibitor: A Systematic Review and Meta-Analysis. Basic & clinical pharmacology & toxicology. 2025", "pmid": "40685887", "doi": "10.1111/bcpt.70087", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40685887/", "publicSourceType": "PMID" }, { "text": "Valgimigli M, Choi KH, Giacoppo D et al.. Clopidogrel versus aspirin for secondary prevention of coronary artery disease: a systematic review and individual patient data meta-analysis. Lancet (London, England). 2025", "pmid": "40902613", "doi": "10.1016/S0140-6736(25)01562-4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40902613/", "publicSourceType": "PMID" }, { "claim": "Clopidogrel is compared to ticagrelor for minor stroke and TIA", "title": "Comparison of Ticagrelor vs Clopidogrel in Addition to Aspirin in Patients With Minor Ischemic Stroke and Transient Ischemic Attack: A Network Meta-analysis", "authors": "Lun R, Dhaliwal S, Zitikyte G, Roy DC et al.", "journal": "JAMA Neurology", "year": 2022, "pmid": "34870698", "url": "https://pubmed.ncbi.nlm.nih.gov/34870698/", "study_type": "network meta-analysis", "key_finding": "Ticagrelor-aspirin combination showed comparable efficacy to clopidogrel-aspirin for reducing recurrent stroke risk in patients with minor ischemic stroke or TIA, with clopidogrel-aspirin remaining a standard of care", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34870698/", "publicSourceType": "PMID" }, { "claim": "Clopidogrel monotherapy vs dual antiplatelet therapy after PCI", "title": "Ticagrelor or Clopidogrel Monotherapy vs Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: A Systematic Review and Patient-Level Meta-Analysis", "authors": "Valgimigli M, Gragnano F, Branca M, Franzone A et al.", "journal": "JAMA Cardiology", "year": 2024, "pmid": "38506796", "url": "https://pubmed.ncbi.nlm.nih.gov/38506796/", "study_type": "meta-analysis", "key_finding": "Clopidogrel or ticagrelor monotherapy after a short DAPT period was associated with lower bleeding risk compared with prolonged DAPT, without increasing ischemic risk after PCI", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38506796/", "publicSourceType": "PMID" }, { "text": "Zaihan AF, Mohamad Hafiz NAH, Tong YS et al.. Ticagrelor Versus Clopidogrel or Aspirin in Secondary Stroke Prevention: Systematic Review and Meta-Analysis of Randomized Controlled Trials. Stroke research and treatment. 2026", "claim": "PubMed-indexed evidence involving Clopidogrel", "title": "Ticagrelor Versus Clopidogrel or Aspirin in Secondary Stroke Prevention: Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Zaihan AF, Mohamad Hafiz NAH, Tong YS et al.", "journal": "Stroke research and treatment", "year": 2026, "pmid": "42109603", "url": "https://pubmed.ncbi.nlm.nih.gov/42109603/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1155/srat/7411011", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/42109603/", "publicSourceType": "PMID" }, { "text": "Geravandi M, Nourabi M, Navabifar S et al.. A comparison of the effects of ticagrelor and clopidogrel in patients with acute ST-segment elevation myocardial infarction: a systematic review and meta-analysis of randomized clinical trials. BMC pharmacology & toxicology. 2024", "claim": "PubMed-indexed evidence involving Clopidogrel", "title": "A comparison of the effects of ticagrelor and clopidogrel in patients with acute ST-segment elevation myocardial infarction: a systematic review and meta-analysis of randomized clinical trials", "authors": "Geravandi M, Nourabi M, Navabifar S et al.", "journal": "BMC pharmacology & toxicology", "year": 2024, "pmid": "39654024", "url": "https://pubmed.ncbi.nlm.nih.gov/39654024/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s40360-024-00817-8", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39654024/", "publicSourceType": "PMID" }, { "text": "Lima JP, Brophy JM. The potential interaction between clopidogrel and proton pump inhibitors: a systematic review. BMC medicine. 2010", "claim": "PubMed-indexed evidence involving Clopidogrel", "title": "The potential interaction between clopidogrel and proton pump inhibitors: a systematic review", "authors": "Lima JP, Brophy JM", "journal": "BMC medicine", "year": 2010, "pmid": "21134261", "url": "https://pubmed.ncbi.nlm.nih.gov/21134261/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/1741-7015-8-81", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21134261/", "publicSourceType": "PMID" }, { "text": "Bhatt DL, Bertrand ME, Berger PB et al.. Meta-analysis of randomized and registry comparisons of ticlopidine with clopidogrel after stenting. 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Open Heart. 2026.", "pmid": "41617356", "doi": "10.1136/openhrt-2025-003839", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41617356/", "publicSourceType": "PMID" }, { "text": "Valgimigli M, Gragnano F, Branca M et al.. Ticagrelor or Clopidogrel Monotherapy vs Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: A Systematic Review and Patient-Level Meta-Analysis. JAMA cardiology. 2024", "pmid": "38506796", "doi": "10.1001/jamacardio.2024.0133", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38506796/", "publicSourceType": "PMID" }, { "text": "Valgimigli M, Hong SJ, Gragnano F et al.. De-escalation to ticagrelor monotherapy versus 12 months of dual antiplatelet therapy in patients with and without acute coronary syndromes: a systematic review and individual patient-level meta-analysis of randomised trials. Lancet (London, England). 2024", "pmid": "39226909", "doi": "10.1016/S0140-6736(24)01616-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39226909/", "publicSourceType": "PMID" }, { "text": "Zaihan AF, Mohamad Hafiz NAH, Tong YS et al.. Ticagrelor Versus Clopidogrel or Aspirin in Secondary Stroke Prevention: Systematic Review and Meta-Analysis of Randomized Controlled Trials. 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Annals of internal medicine. 2025", "claim": "PubMed-indexed evidence involving Ticagrelor", "title": "De-escalating Dual Antiplatelet Therapy to Ticagrelor Monotherapy in Acute Coronary Syndrome : A Systematic Review and Individual Patient Data Meta-analysis of Randomized Clinical Trials", "authors": "Lee YJ, Gao X, Lee SH et al.", "journal": "Annals of internal medicine", "year": 2025, "pmid": "39961108", "url": "https://pubmed.ncbi.nlm.nih.gov/39961108/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7326/ANNALS-24-03102", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39961108/", "publicSourceType": "PMID" }, { "text": "Geravandi M, Nourabi M, Navabifar S et al.. A comparison of the effects of ticagrelor and clopidogrel in patients with acute ST-segment elevation myocardial infarction: a systematic review and meta-analysis of randomized clinical trials. BMC pharmacology & toxicology. 2024", "claim": "PubMed-indexed evidence involving Ticagrelor", "title": "A comparison of the effects of ticagrelor and clopidogrel in patients with acute ST-segment elevation myocardial infarction: a systematic review and meta-analysis of randomized clinical trials", "authors": "Geravandi M, Nourabi M, Navabifar S et al.", "journal": "BMC pharmacology & toxicology", "year": 2024, "pmid": "39654024", "url": "https://pubmed.ncbi.nlm.nih.gov/39654024/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s40360-024-00817-8", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39654024/", "publicSourceType": "PMID" }, { "text": "Xiang F, Lin Y, Chen B. Ticagrelor for patients undergoing coronary artery bypass grafting: A meta-analysis of randomized controlled trials. Perfusion. 2023", "claim": "PubMed-indexed evidence involving Ticagrelor", "title": "Ticagrelor for patients undergoing coronary artery bypass grafting: A meta-analysis of randomized controlled trials", "authors": "Xiang F, Lin Y, Chen B", "journal": "Perfusion", "year": 2023, "pmid": "35403510", "url": "https://pubmed.ncbi.nlm.nih.gov/35403510/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/02676591221076284", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35403510/", "publicSourceType": "PMID" }, { "text": "Wu B, Lin H, Tobe RG et al.. Ticagrelor versus clopidogrel in East-Asian patients with acute coronary syndromes: a meta-analysis of randomized trials. 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Amiodarone: review of pulmonary effects and toxicity. Drug safety. 2010", "pmid": "20553056", "doi": "10.2165/11532320-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20553056/", "publicSourceType": "PMID" }, { "text": "Chen D, Hedges TR. Amiodarone optic neuropathy--review. Seminars in ophthalmology. 2003", "pmid": "15513002", "doi": "10.1080/08820530390895163", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15513002/", "publicSourceType": "PMID" }, { "text": "Ruzieh M, Moroi MK, Aboujamous NM et al.. Meta-Analysis Comparing the Relative Risk of Adverse Events for Amiodarone Versus Placebo. The American journal of cardiology. 2019", "claim": "PubMed-indexed evidence involving Amiodarone", "title": "Meta-Analysis Comparing the Relative Risk of Adverse Events for Amiodarone Versus Placebo", "authors": "Ruzieh M, Moroi MK, Aboujamous NM et al.", "journal": "The American journal of cardiology", "year": 2019, "pmid": "31653351", "url": "https://pubmed.ncbi.nlm.nih.gov/31653351/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.amjcard.2019.09.008", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31653351/", "publicSourceType": "PMID" }, { "text": "Alshehri M, Joury A. Ocular Adverse Effects of Amiodarone: A Systematic Review of Case Reports. Optometry and vision science : official publication of the American Academy of Optometry. 2020", "claim": "PubMed-indexed evidence involving Amiodarone", "title": "Ocular Adverse Effects of Amiodarone: A Systematic Review of Case Reports", "authors": "Alshehri M, Joury A", "journal": "Optometry and vision science : official publication of the American Academy of Optometry", "year": 2020, "pmid": "32697562", "url": "https://pubmed.ncbi.nlm.nih.gov/32697562/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/OPX.0000000000001534", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32697562/", "publicSourceType": "PMID" }, { "text": "Khan SU, Winnicka L, Saleem MA et al.. Amiodarone, lidocaine, magnesium or placebo in shock refractory ventricular arrhythmia: A Bayesian network meta-analysis. Heart & lung : the journal of critical care. 2017", "claim": "PubMed-indexed evidence involving Amiodarone", "title": "Amiodarone, lidocaine, magnesium or placebo in shock refractory ventricular arrhythmia: A Bayesian network meta-analysis", "authors": "Khan SU, Winnicka L, Saleem MA et al.", "journal": "Heart & lung : the journal of critical care", "year": 2017, "pmid": "28958592", "url": "https://pubmed.ncbi.nlm.nih.gov/28958592/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.hrtlng.2017.09.001", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28958592/", "publicSourceType": "PMID" }, { "text": "Widiarti W, Saputra PBT, Mustofa A et al.. The roles of thyroidectomy in patients with amiodarone-induced thyrotoxicosis: A systematic review. Current problems in cardiology. 2024", "claim": "PubMed-indexed evidence involving Amiodarone", "title": "The roles of thyroidectomy in patients with amiodarone-induced thyrotoxicosis: A systematic review", "authors": "Widiarti W, Saputra PBT, Mustofa A et al.", "journal": "Current problems in cardiology", "year": 2024, "pmid": "38232922", "url": "https://pubmed.ncbi.nlm.nih.gov/38232922/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.cpcardiol.2024.102395", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38232922/", "publicSourceType": "PMID" }, { "text": "Mohammadi K, Shafie D, Vakhshoori M et al.. Prevalence of amiodarone-induced hypothyroidism; A systematic review and meta-analysis. Trends in cardiovascular medicine. 2023", "claim": "PubMed-indexed evidence involving Amiodarone", "title": "Prevalence of amiodarone-induced hypothyroidism; A systematic review and meta-analysis", "authors": "Mohammadi K, Shafie D, Vakhshoori M et al.", "journal": "Trends in cardiovascular medicine", "year": 2023, "pmid": "35026394", "url": "https://pubmed.ncbi.nlm.nih.gov/35026394/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.tcm.2022.01.001", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35026394/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Class III Antiarrhythmic (Multi-Channel Blocker)", "blackBoxWarnings": [ "Amiodarone is intended for use only in patients with indicated life-threatening arrhythmias because its use is accompanied by substantial toxicity. Pulmonary toxicity (hypersensitivity pneumonitis or interstitial/alveolar pneumonitis) has resulted in clinically manifest disease at rates as high as 10–17%. Hepatotoxicity is common but usually mild; however, fatal cases have occurred." ], "fdaPregnancyCategory": "D", "halfLife": "40–55 days (range 15–142 days); active metabolite desethylamiodarone similar", "onsetOfAction": "Oral: days to weeks for full effect (2–3 days IV for acute loading); effects persist for weeks to months after discontinuation", "commonBrandNames": [ "Pacerone", "Cordarone" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Baseline and periodic (every 6 months): TFTs (TSH, free T4), LFTs, PFTs with DLCO, chest X-ray, ophthalmologic exam. ECG at baseline and periodically for QTc." }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "amiodarone" }, { "id": "RX-CARDIO-036", "name": "Flecainide", "alternateNames": [ "Tambocor" ], "category": "Prescription", "subcategory": "Class IC Antiarrhythmic", "overview": "Flecainide is a class IC antiarrhythmic agent used for prevention of paroxysmal supraventricular tachycardias (PSVT), paroxysmal atrial fibrillation, and life-threatening ventricular arrhythmias. The CAST trial demonstrated increased mortality in post-MI patients, so use is restricted to patients without structural heart disease.", "mechanismOfAction": "Potent sodium channel blocker (class IC) that markedly slows conduction velocity throughout the heart. Prolongs His-Purkinje and ventricular conduction (widens QRS). Has minimal effect on action potential duration and repolarization. Slows conduction in accessory pathways, making it useful for WPW-related arrhythmias. Also has minor potassium channel blocking effects.", "commonBenefits": [ "Effective for maintaining sinus rhythm in atrial fibrillation (without structural heart disease)", "Useful for PSVT prevention", "Effective for WPW-related arrhythmias", "Pill-in-the-pocket strategy for intermittent AF" ], "commonDosageRange": "PSVT/PAF: 50–150 mg twice daily; Sustained VT: 100–200 mg twice daily (as prescribed by your physician)", "recommendedForm": "Oral tablet", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Can be taken with or without food; well absorbed orally with ~95% bioavailability" }, "evidenceRating": "moderate", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Dizziness and visual disturbances (blurred vision)", "Pro-arrhythmia (ventricular tachycardia, including 1:1 atrial flutter)", "Heart failure exacerbation", "Headache", "Nausea", "Tremor", "QRS widening" ], "contraindications": [ "Structural heart disease (prior MI, heart failure, significant LVH)", "Second- or third-degree AV block without pacemaker", "Right bundle branch block with left hemiblock (bifascicular block) without pacemaker", "Cardiogenic shock", "Concurrent use must include AV nodal blocking agent to prevent 1:1 atrial flutter conduction" ], "iconName": "cross.case.fill", "colorHex": "9B59B6", "tags": [ "cardiovascular", "antiarrhythmic", "atrial-fibrillation", "svt" ], "sources": [ { "text": "Echt DS et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo (CAST). N Engl J Med. 1991.", "pmid": "1900101", "doi": "10.1056/NEJM199103213241201", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1900101/", "publicSourceType": "PMID" }, { "text": "Alboni P et al. Outpatient treatment of recent-onset atrial fibrillation with the 'pill-in-the-pocket' approach. N Engl J Med. 2004.", "pmid": "16013424", "doi": "10.1056/NEJMoa041233", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16013424/", "publicSourceType": "PMID" }, { "text": "Spillane J et al. Drug treatment for myotonia. Cochrane Database Syst Rev. 2025.", "pmid": "40197813", "doi": "10.1002/14651858.CD004762.pub3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40197813/", "publicSourceType": "PMID" }, { "text": "Cardiac Arrhythmia Suppression Trial (CAST) Investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. The New England journal of medicine. 1989", "pmid": "2473403", "doi": "10.1056/NEJM198908103210629", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2473403/", "publicSourceType": "PMID" }, { "text": "Tamargo J, Capucci A, Mabo P. Safety of flecainide. Drug safety. 2012", "pmid": "22435343", "doi": "10.2165/11599950-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22435343/", "publicSourceType": "PMID" }, { "text": "Valentino MA, Panakos A, Ragupathi L et al.. Flecainide Toxicity: A Case Report and Systematic Review of its Electrocardiographic Patterns and Management. Cardiovascular toxicology. 2017", "claim": "PubMed-indexed evidence involving Flecainide", "title": "Flecainide Toxicity: A Case Report and Systematic Review of its Electrocardiographic Patterns and Management", "authors": "Valentino MA, Panakos A, Ragupathi L et al.", "journal": "Cardiovascular toxicology", "year": 2017, "pmid": "27435408", "url": "https://pubmed.ncbi.nlm.nih.gov/27435408/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s12012-016-9380-0", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27435408/", "publicSourceType": "PMID" }, { "text": "Wehling M. Meta-analysis of flecainide safety in patients with supraventricular arrhythmias. Arzneimittel-Forschung. 2002", "claim": "PubMed-indexed evidence involving Flecainide", "title": "Meta-analysis of flecainide safety in patients with supraventricular arrhythmias", "authors": "Wehling M", "journal": "Arzneimittel-Forschung", "year": 2002, "pmid": "12189773", "url": "https://pubmed.ncbi.nlm.nih.gov/12189773/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1055/s-0031-1299923", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12189773/", "publicSourceType": "PMID" }, { "text": "Zarembski DG, Nolan PE Jr, Slack MK et al.. Treatment of resistant atrial fibrillation. A meta-analysis comparing amiodarone and flecainide. Archives of internal medicine. 1995", "claim": "PubMed-indexed evidence involving Flecainide", "title": "Treatment of resistant atrial fibrillation. A meta-analysis comparing amiodarone and flecainide", "authors": "Zarembski DG, Nolan PE Jr, Slack MK et al.", "journal": "Archives of internal medicine", "year": 1995, "pmid": "7677555", "url": "https://pubmed.ncbi.nlm.nih.gov/7677555/", "study_type": "meta-analysis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7677555/", "publicSourceType": "PMID" }, { "text": "Hauguel-Moreau M, Guedeney P, Dauphin C et al.. Flecainide to Prevent Atrial Arrhythmia After Patent Foramen Ovale Closure: AFLOAT Study, A Randomized Clinical Trial. Circulation. 2024", "claim": "PubMed-indexed evidence involving Flecainide", "title": "Flecainide to Prevent Atrial Arrhythmia After Patent Foramen Ovale Closure: AFLOAT Study, A Randomized Clinical Trial", "authors": "Hauguel-Moreau M, Guedeney P, Dauphin C et al.", "journal": "Circulation", "year": 2024, "pmid": "39222035", "url": "https://pubmed.ncbi.nlm.nih.gov/39222035/", "study_type": "RCT", "confidence": "verify", "doi": "10.1161/CIRCULATIONAHA.124.071186", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39222035/", "publicSourceType": "PMID" }, { "text": "Khatiwada P, Clark L, Khunger A et al.. A Case Report of Flecainide Toxicity With Review of Literature. Cureus. 2022", "claim": "PubMed-indexed evidence involving Flecainide", "title": "A Case Report of Flecainide Toxicity With Review of Literature", "authors": "Khatiwada P, Clark L, Khunger A et al.", "journal": "Cureus", "year": 2022, "pmid": "35350525", "url": "https://pubmed.ncbi.nlm.nih.gov/35350525/", "study_type": "review", "confidence": "verify", "doi": "10.7759/cureus.22261", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35350525/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Class IC Antiarrhythmic (Sodium Channel Blocker)", "blackBoxWarnings": [ "CAST demonstrated increased mortality with flecainide in patients with asymptomatic non-life-threatening ventricular arrhythmias who had a recent MI. Therefore, flecainide is not recommended in patients with structural heart disease." ], "fdaPregnancyCategory": "C", "halfLife": "12–27 hours (mean ~20 hours)", "onsetOfAction": "1–6 hours; steady state at 3–5 days", "commonBrandNames": [ "Tambocor" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "ECG at baseline and with dose changes (monitor QRS duration, hold if QRS widens >25% above baseline); serum drug levels if toxicity suspected (therapeutic range 0.2–1.0 mcg/mL); renal function at baseline" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "flecainide" }, { "id": "RX-CARDIO-037", "name": "Sotalol", "alternateNames": [ "Betapace", "Betapace AF", "Sorine" ], "category": "Prescription", "subcategory": "Class III Antiarrhythmic / Non-Selective Beta-Blocker", "overview": "Sotalol has dual properties: non-selective beta-blockade (class II) and potassium channel blockade that prolongs repolarization (class III). It is used for atrial fibrillation/flutter and life-threatening ventricular arrhythmias. Due to QT-prolonging effects, initiation requires in-hospital monitoring for 3 days.", "mechanismOfAction": "The d-isomer blocks delayed rectifier potassium channels (IKr), prolonging the action potential duration and QT interval (class III activity). The l-isomer provides non-selective beta-adrenergic blockade (class II activity). The combined effect reduces heart rate, prolongs refractoriness, and suppresses reentrant arrhythmias. Racemic mixture is used clinically.", "commonBenefits": [ "Effective for maintaining sinus rhythm in atrial fibrillation", "Dual antiarrhythmic mechanism (beta-blocker + K+ channel blocker)", "Useful for ventricular tachycardia", "Can be used in patients with some structural heart disease" ], "commonDosageRange": "80–160 mg twice daily; standard maximum 320 mg/day total (doses up to 480–640 mg/day only for refractory life-threatening ventricular arrhythmias under close supervision) (as prescribed by your physician)", "recommendedForm": "Oral tablet", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Absorption is reduced by ~20% with food; take on an empty stomach or at least 2 hours before/after meals; aluminum/magnesium antacids reduce absorption" }, "evidenceRating": "moderate", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "QT prolongation and torsades de pointes (dose-dependent, ~2–4%)", "Bradycardia", "Fatigue", "Dizziness", "Dyspnea", "Proarrhythmia", "Heart failure exacerbation" ], "contraindications": [ "Congenital or acquired long QT syndrome", "Baseline QTc >450 ms", "Sinus bradycardia (<50 bpm)", "Second- or third-degree AV block without pacemaker", "Decompensated heart failure", "CrCl <40 mL/min (Betapace AF)", "Hypokalemia or hypomagnesemia (uncorrected)", "Bronchial asthma" ], "iconName": "cross.case.fill", "colorHex": "9B59B6", "tags": [ "cardiovascular", "antiarrhythmic", "beta-blocker", "atrial-fibrillation", "ventricular-arrhythmia" ], "sources": [ { "text": "Singh BN et al. Sotalol versus amiodarone for atrial fibrillation: the Sotalol Amiodarone Atrial Fibrillation Efficacy Trial (SAFE-T). Am Heart J. 2005.", "pmid": "17383295", "doi": "10.1016/j.ahj.2004.11.003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17383295/", "publicSourceType": "PMID" }, { "text": "Amiodarone Trials Meta-Analysis Investigators. Effect of prophylactic amiodarone on mortality after acute myocardial infarction and in congestive heart failure: meta-analysis. Lancet. 1997.", "pmid": "9371164", "doi": "10.1016/S0140-6736(97)05281-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9371164/", "publicSourceType": "PMID" }, { "text": "Kukendrarajah K et al. External electrical and pharmacological cardioversion for atrial fibrillation, atrial flutter or atrial tachycardias: a network meta-analysis. Cochrane Database Syst Rev. 2024.", "pmid": "38828867", "doi": "10.1002/14651858.CD013255.pub2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38828867/", "publicSourceType": "PMID" }, { "text": "Rizkallah DH, Refaat MM. Safety and effect on length of stay of intravenous sotalol initiation for arrhythmia management. Journal of cardiovascular electrophysiology. 2023", "pmid": "36738140", "doi": "10.1111/jce.15852", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36738140/", "publicSourceType": "PMID" }, { "text": "Kiskaddon AL, Decker J. Sotalol in neonates for arrhythmias: Dosing, safety, and efficacy. Journal of cardiovascular electrophysiology. 2023", "pmid": "37210614", "doi": "10.1111/jce.15939", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37210614/", "publicSourceType": "PMID" }, { "text": "Singh JP, Blomström-Lundqvist C, Turakhia MP et al.. Dronedarone versus sotalol in patients with atrial fibrillation: A systematic literature review and network meta-analysis. Clinical cardiology. 2023", "claim": "PubMed-indexed evidence involving Sotalol", "title": "Dronedarone versus sotalol in patients with atrial fibrillation: A systematic literature review and network meta-analysis", "authors": "Singh JP, Blomström-Lundqvist C, Turakhia MP et al.", "journal": "Clinical cardiology", "year": 2023, "pmid": "37025083", "url": "https://pubmed.ncbi.nlm.nih.gov/37025083/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/clc.24011", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37025083/", "publicSourceType": "PMID" }, { "text": "Singh JP, Wieloch M, Reynolds SL et al.. Dronedarone vs Sotalol Among Patients With Atrial Fibrillation: A Meta-Analysis of Retrospective Observational Databases. JACC. Clinical electrophysiology. 2025", "claim": "PubMed-indexed evidence involving Sotalol", "title": "Dronedarone vs Sotalol Among Patients With Atrial Fibrillation: A Meta-Analysis of Retrospective Observational Databases", "authors": "Singh JP, Wieloch M, Reynolds SL et al.", "journal": "JACC. Clinical electrophysiology", "year": 2025, "pmid": "40272320", "url": "https://pubmed.ncbi.nlm.nih.gov/40272320/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jacep.2025.02.029", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40272320/", "publicSourceType": "PMID" }, { "text": "Kerin NZ, Jacob S. The efficacy of sotalol in preventing postoperative atrial fibrillation: a meta-analysis. The American journal of medicine. 2011", "claim": "PubMed-indexed evidence involving Sotalol", "title": "The efficacy of sotalol in preventing postoperative atrial fibrillation: a meta-analysis", "authors": "Kerin NZ, Jacob S", "journal": "The American journal of medicine", "year": 2011, "pmid": "21854895", "url": "https://pubmed.ncbi.nlm.nih.gov/21854895/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.amjmed.2011.04.025", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21854895/", "publicSourceType": "PMID" }, { "text": "Marill KA, Runge T. Meta-analysis of the Risk of Torsades de Pointes in patients treated with intravenous racemic sotalol. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2001", "claim": "PubMed-indexed evidence involving Sotalol", "title": "Meta-analysis of the Risk of Torsades de Pointes in patients treated with intravenous racemic sotalol", "authors": "Marill KA, Runge T", "journal": "Academic emergency medicine : official journal of the Society for Academic Emergency Medicine", "year": 2001, "pmid": "11157286", "url": "https://pubmed.ncbi.nlm.nih.gov/11157286/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/j.1553-2712.2001.tb01275.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11157286/", "publicSourceType": "PMID" }, { "text": "Romito G, Gemma N, Dondi F et al.. Efficacy and safety of antiarrhythmic therapy in dogs with naturally acquired tachyarrhythmias treated with amiodarone or sotalol: a retrospective analysis of 64 cases. Journal of veterinary cardiology : the official journal of the European Society of Veterinary Cardiology. 2024", "claim": "PubMed-indexed evidence involving Sotalol", "title": "Efficacy and safety of antiarrhythmic therapy in dogs with naturally acquired tachyarrhythmias treated with amiodarone or sotalol: a retrospective analysis of 64 cases", "authors": "Romito G, Gemma N, Dondi F et al.", "journal": "Journal of veterinary cardiology : the official journal of the European Society of Veterinary Cardiology", "year": 2024, "pmid": "38608438", "url": "https://pubmed.ncbi.nlm.nih.gov/38608438/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.jvc.2024.03.002", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38608438/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Class III Antiarrhythmic / Non-Selective Beta-Blocker", "blackBoxWarnings": [ "To minimize the risk of induced arrhythmia, patients initiated or re-initiated on sotalol should be placed for a minimum of 3 days in a facility that can provide cardiac resuscitation, continuous electrocardiographic monitoring, and calculations of creatinine clearance." ], "fdaPregnancyCategory": "B", "halfLife": "12 hours", "onsetOfAction": "2–3 hours; steady state at 2–3 days", "commonBrandNames": [ "Betapace", "Betapace AF", "Sorine" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Continuous ECG monitoring for minimum 3 days during initiation; QTc monitoring with each dose change; serum electrolytes (K+, Mg2+) at baseline and periodically; renal function (CrCl) at baseline and dose-adjust accordingly" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "sotalol" }, { "id": "RX-CARDIO-038", "name": "Nitroglycerin", "alternateNames": [ "Nitrostat", "Nitro-Bid", "Nitro-Dur", "NitroMist" ], "category": "Prescription", "subcategory": "Organic Nitrate", "overview": "Nitroglycerin is a potent vasodilator used for acute relief and prevention of angina pectoris, as well as management of acute heart failure and hypertensive emergencies. Sublingual nitroglycerin is the classic rapid-acting treatment for angina attacks. Available in multiple formulations including sublingual tablets, spray, transdermal patches, and IV.", "mechanismOfAction": "Converted to nitric oxide (NO) in vascular smooth muscle via mitochondrial aldehyde dehydrogenase. NO activates soluble guanylyl cyclase, increasing cGMP, which causes smooth muscle relaxation. At lower doses, preferentially dilates veins (reduces preload and ventricular wall stress). At higher doses, also dilates coronary and systemic arteries. Reduces myocardial oxygen demand and improves supply.", "commonBenefits": [ "Rapid relief of acute angina attacks (sublingual)", "Reduces myocardial oxygen demand", "Reduces preload in acute heart failure", "Coronary vasodilation improves perfusion to ischemic areas" ], "commonDosageRange": "Sublingual: 0.3–0.6 mg as needed (up to 3 doses in 15 minutes); Patch: 0.2–0.8 mg/hr (with 10–12 hour nitrate-free interval); IV: 5–200 mcg/min (as prescribed by your physician)", "recommendedForm": "Sublingual tablet or spray for acute angina; transdermal patch or oral sustained-release for prophylaxis", "absorption": { "isFatSoluble": true, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Sublingual route bypasses first-pass metabolism for rapid onset; oral forms have significant first-pass metabolism; a 10–12 hour nitrate-free interval is essential to prevent tolerance" }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Headache (most common)", "Hypotension and dizziness", "Flushing", "Reflex tachycardia", "Lightheadedness and syncope", "Tolerance with continuous use", "Methemoglobinemia (rare, at very high doses)" ], "contraindications": [ "Concurrent PDE-5 inhibitor use (sildenafil, tadalafil, within 24–48 hours), severe hypotension", "Concurrent riociguat", "Severe hypotension (SBP <90 mmHg)", "Right ventricular infarction", "Hypertrophic obstructive cardiomyopathy", "Severe anemia", "Increased intracranial pressure" ], "iconName": "cross.case.fill", "colorHex": "E67E22", "tags": [ "cardiovascular", "nitrate", "angina", "chest-pain", "vasodilator" ], "sources": [ { "text": "Abrams J. Nitroglycerin and long-acting nitrates in clinical practice. Am J Med. 1983.", "pmid": "6407316", "doi": "10.1016/0002-9343(83)90879-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6407316/", "publicSourceType": "PMID" }, { "text": "Parker JD and Parker JO. Nitrate therapy for stable angina pectoris. N Engl J Med. 1998.", "pmid": "22424287", "doi": "10.1056/NEJM199808133390707", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22424287/", "publicSourceType": "PMID" }, { "text": "Pramudyo M et al. Low-dose versus high-dose intravenous nitroglycerin in the treatment of sympathetic crashing acute pulmonary oedema: a systematic review and meta-analysis focusing on efficacy, safety and outcomes. BMJ Open. 2025.", "pmid": "40506079", "doi": "10.1136/bmjopen-2025-099142", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40506079/", "publicSourceType": "PMID" }, { "text": "Meunier M, Yammine A, Bettaieb A et al.. Nitroglycerin: a comprehensive review in cancer therapy. Cell death & disease. 2023", "pmid": "37173331", "doi": "10.1038/s41419-023-05838-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37173331/", "publicSourceType": "PMID" }, { "text": "Sureda-Gibert P, Romero-Reyes M, Akerman S. Nitroglycerin as a model of migraine: Clinical and preclinical review. Neurobiology of pain (Cambridge, Mass.). 2022", "pmid": "36974065", "doi": "10.1016/j.ynpai.2022.100105", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36974065/", "publicSourceType": "PMID" }, { "text": "Tian Q, Song X, Wu L et al.. The efficacy of glyceryl trinitrate for acute intracerebral hemorrhage: A systematic review and meta-analysis. Advances in clinical and experimental medicine : official organ Wroclaw Medical University. 2024", "claim": "PubMed-indexed evidence involving Nitroglycerin", "title": "The efficacy of glyceryl trinitrate for acute intracerebral hemorrhage: A systematic review and meta-analysis", "authors": "Tian Q, Song X, Wu L et al.", "journal": "Advances in clinical and experimental medicine : official organ Wroclaw Medical University", "year": 2024, "pmid": "37486700", "url": "https://pubmed.ncbi.nlm.nih.gov/37486700/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.17219/acem/168430", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37486700/", "publicSourceType": "PMID" }, { "text": "Saltychev M, Johansson J, Kemppi V et al.. Effectiveness of topical glyceryl trinitrate in treatment of tendinopathy - systematic review and meta-analysis. Disability and rehabilitation. 2022", "claim": "PubMed-indexed evidence involving Nitroglycerin", "title": "Effectiveness of topical glyceryl trinitrate in treatment of tendinopathy - systematic review and meta-analysis", "authors": "Saltychev M, Johansson J, Kemppi V et al.", "journal": "Disability and rehabilitation", "year": 2022, "pmid": "34330192", "url": "https://pubmed.ncbi.nlm.nih.gov/34330192/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/09638288.2021.1958067", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34330192/", "publicSourceType": "PMID" }, { "text": "Wagh D, Pawale D, Tan JKG et al.. Local nitroglycerin to facilitate peripheral arterial cannulation in children: systematic review and meta-analysis. Archives of disease in childhood. 2022", "claim": "PubMed-indexed evidence involving Nitroglycerin", "title": "Local nitroglycerin to facilitate peripheral arterial cannulation in children: systematic review and meta-analysis", "authors": "Wagh D, Pawale D, Tan JKG et al.", "journal": "Archives of disease in childhood", "year": 2022, "pmid": "35595521", "url": "https://pubmed.ncbi.nlm.nih.gov/35595521/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1136/archdischild-2021-323757", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35595521/", "publicSourceType": "PMID" }, { "text": "McCulloch C, Hunter MM, Lipp C et al.. Management of Lateral Epicondylitis Using Transdermal Nitroglycerin: A Systematic Review. Cureus. 2022", "claim": "PubMed-indexed evidence involving Nitroglycerin", "title": "Management of Lateral Epicondylitis Using Transdermal Nitroglycerin: A Systematic Review", "authors": "McCulloch C, Hunter MM, Lipp C et al.", "journal": "Cureus", "year": 2022, "pmid": "36654592", "url": "https://pubmed.ncbi.nlm.nih.gov/36654592/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7759/cureus.32560", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36654592/", "publicSourceType": "PMID" }, { "text": "Sushko K, Litalien C, Ferruccio L et al.. Topical nitroglycerin ointment as salvage therapy for peripheral tissue ischemia in newborns: a systematic review. CMAJ open. 2021", "claim": "PubMed-indexed evidence involving Nitroglycerin", "title": "Topical nitroglycerin ointment as salvage therapy for peripheral tissue ischemia in newborns: a systematic review", "authors": "Sushko K, Litalien C, Ferruccio L et al.", "journal": "CMAJ open", "year": 2021, "pmid": "33731426", "url": "https://pubmed.ncbi.nlm.nih.gov/33731426/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.9778/cmajo.20200129", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33731426/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Organic Nitrate / Vasodilator", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "1–4 minutes (nitroglycerin); active dinitrate metabolites: 1–4 hours", "onsetOfAction": "Sublingual: 1–3 minutes; Transdermal: 30–60 minutes; IV: immediate", "commonBrandNames": [ "Nitrostat", "NitroMist", "Nitro-Dur", "Nitro-Bid" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": "Routine lab monitoring not required; monitor blood pressure and heart rate; check sublingual tablets for potency (replace every 6 months if opened)" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "nitroglycerin" }, { "id": "RX-CARDIO-039", "name": "Isosorbide Mononitrate", "alternateNames": [ "Imdur", "Monoket" ], "category": "Prescription", "subcategory": "Organic Nitrate", "overview": "Isosorbide mononitrate is a long-acting organic nitrate used for prophylaxis of angina pectoris. It is the active metabolite of isosorbide dinitrate with 100% oral bioavailability. The extended-release formulation (Imdur) is given once daily in the morning, with the built-in asymmetric dosing providing a nitrate-free interval to prevent tolerance.", "mechanismOfAction": "Converted to nitric oxide (NO) in vascular smooth muscle. NO activates guanylyl cyclase, increasing cGMP levels and causing smooth muscle relaxation. Preferentially dilates venous capacitance vessels, reducing preload and left ventricular end-diastolic pressure. Also dilates coronary arteries and reduces afterload, decreasing myocardial oxygen demand.", "commonBenefits": [ "Effective prophylaxis of angina pectoris", "100% oral bioavailability (no first-pass metabolism)", "Extended-release formulation allows once-daily dosing", "Built-in nitrate-free interval reduces tolerance" ], "commonDosageRange": "IR: 20 mg twice daily (7 hours apart); ER: 30–240 mg once daily in the morning (as prescribed by your physician)", "recommendedForm": "Extended-release tablet (Imdur) preferred for once-daily dosing", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Can be taken with or without food; 100% bioavailability; take in the morning; immediate-release doses should be taken 7 hours apart to allow nitrate-free interval" }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Headache (most common, often diminishes over time)", "Dizziness", "Hypotension", "Flushing", "Nausea", "Tolerance (mitigated by nitrate-free interval)" ], "contraindications": [ "Concurrent PDE-5 inhibitor use (sildenafil, tadalafil, vardenafil)", "Concurrent riociguat", "Severe hypotension", "Right ventricular infarction", "Hypertrophic obstructive cardiomyopathy" ], "iconName": "cross.case.fill", "colorHex": "E67E22", "tags": [ "cardiovascular", "nitrate", "angina", "vasodilator" ], "sources": [ { "text": "Parker JD and Parker JO. Nitrate therapy for stable angina pectoris. N Engl J Med. 1998.", "pmid": "22424287", "doi": "10.1056/NEJM199808133390707", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22424287/", "publicSourceType": "PMID" }, { "text": "Thadani U and Lipicky RJ. Short and long-acting oral nitrates for stable angina pectoris. Cardiovasc Drugs Ther. 1994.", "pmid": "7848896", "doi": "10.1007/BF00877101", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7848896/", "publicSourceType": "PMID" }, { "text": "Abu-Zaid A et al. Isosorbide mononitrate for cervical ripening during labour induction: A systematic review and meta-analysis of 23 randomized controlled trials. Eur J Obstet Gynecol Reprod Biol. 2022.", "pmid": "35803111", "doi": "10.1016/j.ejogrb.2022.06.028", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35803111/", "publicSourceType": "PMID" }, { "text": "Nyberg G. Clinical experience with Imdur in angina pectoris. A review. European journal of clinical pharmacology. 1990", "pmid": "1972359", "doi": "10.1007/BF01417567", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1972359/", "publicSourceType": "PMID" }, { "text": "Gluud LL, Langholz E, Krag A. Meta-analysis: isosorbide-mononitrate alone or with either beta-blockers or endoscopic therapy for the management of oesophageal varices. Alimentary pharmacology & therapeutics. 2010", "pmid": "20839387", "doi": "10.1111/j.1365-2036.2010.04418.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20839387/", "publicSourceType": "PMID" }, { "text": "Makvandi S, Karimi L, Safyari M et al.. Efficacy and safety of isosorbide mononitrate plus misoprostol compared to misoprostol alone in the management of the first and second trimester abortion: a systematic review and meta-analysis. BMC pregnancy and childbirth. 2024", "claim": "PubMed-indexed evidence involving Isosorbide Mononitrate", "title": "Efficacy and safety of isosorbide mononitrate plus misoprostol compared to misoprostol alone in the management of the first and second trimester abortion: a systematic review and meta-analysis", "authors": "Makvandi S, Karimi L, Safyari M et al.", "journal": "BMC pregnancy and childbirth", "year": 2024, "pmid": "38858628", "url": "https://pubmed.ncbi.nlm.nih.gov/38858628/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12884-024-06614-9", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38858628/", "publicSourceType": "PMID" }, { "text": "Wang R, Hu J, Li Y et al.. Compound Danshen Dripping Pills combined with isosorbide mononitrate for angina pectoris: A systematic review and a Meta-analysis. Chinese herbal medicines. 2024", "claim": "PubMed-indexed evidence involving Isosorbide Mononitrate", "title": "Compound Danshen Dripping Pills combined with isosorbide mononitrate for angina pectoris: A systematic review and a Meta-analysis", "authors": "Wang R, Hu J, Li Y et al.", "journal": "Chinese herbal medicines", "year": 2024, "pmid": "39606266", "url": "https://pubmed.ncbi.nlm.nih.gov/39606266/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.chmed.2023.12.005", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39606266/", "publicSourceType": "PMID" }, { "text": "Ding SH, Liu J, Wang JP. Efficacy of beta-adrenergic blocker plus 5-isosorbide mononitrate and endoscopic band ligation for prophylaxis of esophageal variceal rebleeding: a meta-analysis. World journal of gastroenterology. 2009", "claim": "PubMed-indexed evidence involving Isosorbide Mononitrate", "title": "Efficacy of beta-adrenergic blocker plus 5-isosorbide mononitrate and endoscopic band ligation for prophylaxis of esophageal variceal rebleeding: a meta-analysis", "authors": "Ding SH, Liu J, Wang JP", "journal": "World journal of gastroenterology", "year": 2009, "pmid": "19418589", "url": "https://pubmed.ncbi.nlm.nih.gov/19418589/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3748/wjg.15.2151", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19418589/", "publicSourceType": "PMID" }, { "text": "Zhu Y, Zhang W, Qin K et al.. Effects of Nicorandil, Isosorbide Mononitrate, or Diltiazem on Radial Artery Grafts After CABG: The Randomized ASRAB-Pilot Trial. Circulation. Cardiovascular interventions. 2025", "claim": "PubMed-indexed evidence involving Isosorbide Mononitrate", "title": "Effects of Nicorandil, Isosorbide Mononitrate, or Diltiazem on Radial Artery Grafts After CABG: The Randomized ASRAB-Pilot Trial", "authors": "Zhu Y, Zhang W, Qin K et al.", "journal": "Circulation. Cardiovascular interventions", "year": 2025, "pmid": "40123490", "url": "https://pubmed.ncbi.nlm.nih.gov/40123490/", "study_type": "RCT", "confidence": "verify", "doi": "10.1161/CIRCINTERVENTIONS.124.014542", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40123490/", "publicSourceType": "PMID" }, { "text": "Kang MG, Ahn JH, Hwang JY et al.. Long-acting cilostazol versus isosorbide mononitrate for patients with vasospastic angina: a randomized controlled trial. Coronary artery disease. 2024", "claim": "PubMed-indexed evidence involving Isosorbide Mononitrate", "title": "Long-acting cilostazol versus isosorbide mononitrate for patients with vasospastic angina: a randomized controlled trial", "authors": "Kang MG, Ahn JH, Hwang JY et al.", "journal": "Coronary artery disease", "year": 2024, "pmid": "38595079", "url": "https://pubmed.ncbi.nlm.nih.gov/38595079/", "study_type": "RCT", "confidence": "verify", "doi": "10.1097/MCA.0000000000001366", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38595079/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Organic Nitrate / Vasodilator", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "5–6 hours", "onsetOfAction": "IR: 30–60 minutes; ER: 3–4 hours to peak; Duration: 7–12 hours", "commonBrandNames": [ "Imdur", "Monoket" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": "Routine lab monitoring not required; monitor blood pressure, heart rate, and angina frequency" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "isosorbide-mononitrate" }, { "id": "RX-CARDIO-040", "name": "Digoxin", "alternateNames": [ "Lanoxin", "Digitek" ], "category": "Prescription", "subcategory": "Cardiac Glycoside", "overview": "Digoxin is a cardiac glycoside used for rate control in atrial fibrillation and symptomatic improvement in heart failure with reduced ejection fraction. The DIG trial showed it reduces hospitalizations but not mortality in heart failure. It has a narrow therapeutic index, requiring careful dosing and monitoring.", "mechanismOfAction": "Inhibits the sodium-potassium ATPase (Na+/K+ pump) in cardiomyocytes, leading to increased intracellular sodium, which reduces calcium extrusion via the Na+/Ca2+ exchanger. The resulting increased intracellular calcium enhances contractility (positive inotrope). Also increases vagal tone and decreases sympathetic activity, slowing AV nodal conduction and heart rate. Centrally sensitizes baroreceptors, reducing neurohormonal activation in HF.", "commonBenefits": [ "Rate control in atrial fibrillation (especially at rest)", "Reduces heart failure hospitalizations (DIG trial)", "Positive inotropic effect", "Reduces neurohormonal activation in heart failure" ], "commonDosageRange": "0.0625–0.25 mg once daily; target serum level 0.5–0.9 ng/mL (as prescribed by your physician)", "recommendedForm": "Oral tablet", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Can be taken with or without food; high-fiber meals and kaolin-pectin antacids can reduce absorption; primarily renally eliminated" }, "evidenceRating": "moderate", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Nausea, vomiting, and anorexia (early toxicity signs)", "Visual disturbances (yellow-green halos, classic toxicity sign)", "Cardiac arrhythmias (bradycardia, AV block, atrial tachycardia with block, bidirectional VT)", "Dizziness", "Confusion (especially in elderly)", "Gynecomastia (rare)" ], "contraindications": [ "Ventricular fibrillation", "Hypertrophic obstructive cardiomyopathy (may worsen obstruction)", "Hypokalemia or hypomagnesemia (increases toxicity risk)", "Hypercalcemia (increases toxicity risk)", "Severe sinus node disease without pacemaker", "Concurrent IV calcium administration" ], "iconName": "cross.case.fill", "colorHex": "1ABC9C", "tags": [ "cardiovascular", "heart-failure", "atrial-fibrillation", "rate-control", "cardiac-glycoside" ], "sources": [ { "text": "Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure (DIG trial). N Engl J Med. 1997.", "pmid": "9036306", "doi": "10.1056/NEJM199702203360801", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9036306/", "publicSourceType": "PMID" }, { "text": "Rathore SS et al. Association of serum digoxin concentration and outcomes in patients with heart failure. JAMA. 2003.", "pmid": "12588271", "doi": "10.1001/jama.289.7.871", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12588271/", "publicSourceType": "PMID" }, { "text": "Chen SH et al. Comparative effectiveness of pharmacotherapy for heart failure with preserved ejection fraction: A systematic review and network meta-analysis. Diabetes Obes Metab. 2026.", "pmid": "41588709", "doi": "10.1111/dom.70503", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41588709/", "publicSourceType": "PMID" }, { "text": "Patocka J, Nepovimova E, Wu W et al.. Digoxin: Pharmacology and toxicology-A review. Environmental toxicology and pharmacology. 2020", "pmid": "32464466", "doi": "10.1016/j.etap.2020.103400", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32464466/", "publicSourceType": "PMID" }, { "text": "Andrews P, Anseeuw K, Kotecha D et al.. Diagnosis and practical management of digoxin toxicity: a narrative review and consensus. European journal of emergency medicine : official journal of the European Society for Emergency Medicine. 2023", "pmid": "37650725", "doi": "10.1097/MEJ.0000000000001065", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37650725/", "publicSourceType": "PMID" }, { "text": "Ziff OJ, Lane DA, Samra M et al.. Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data. BMJ (Clinical research ed.). 2015", "claim": "PubMed-indexed evidence involving Digoxin", "title": "Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data", "authors": "Ziff OJ, Lane DA, Samra M et al.", "journal": "BMJ (Clinical research ed.)", "year": 2015, "pmid": "26321114", "url": "https://pubmed.ncbi.nlm.nih.gov/26321114/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1136/bmj.h4451", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26321114/", "publicSourceType": "PMID" }, { "text": "Salcedo-Mingoarranz ÁL, García-Díaz B, Barcia-Hernández E. Population pharmacokinetics of digoxin in elderly patients: A systematic review. Farmacia hospitalaria : organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria. 2022", "claim": "PubMed-indexed evidence involving Digoxin", "title": "Population pharmacokinetics of digoxin in elderly patients: A systematic review", "authors": "Salcedo-Mingoarranz ÁL, García-Díaz B, Barcia-Hernández E", "journal": "Farmacia hospitalaria : organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria", "year": 2022, "pmid": "36520576", "url": "https://pubmed.ncbi.nlm.nih.gov/36520576/", "study_type": "meta-analysis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36520576/", "publicSourceType": "PMID" }, { "text": "Abdel Jalil M, Abdullah N, Alsous M et al.. Population Pharmacokinetic Studies of Digoxin in Adult Patients: A Systematic Review. European journal of drug metabolism and pharmacokinetics. 2021", "claim": "PubMed-indexed evidence involving Digoxin", "title": "Population Pharmacokinetic Studies of Digoxin in Adult Patients: A Systematic Review", "authors": "Abdel Jalil M, Abdullah N, Alsous M et al.", "journal": "European journal of drug metabolism and pharmacokinetics", "year": 2021, "pmid": "33616855", "url": "https://pubmed.ncbi.nlm.nih.gov/33616855/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s13318-021-00672-6", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33616855/", "publicSourceType": "PMID" }, { "text": "Abdel Jalil MH, Abdullah N, Alsous MM et al.. A systematic review of population pharmacokinetic analyses of digoxin in the paediatric population. British journal of clinical pharmacology. 2020", "claim": "PubMed-indexed evidence involving Digoxin", "title": "A systematic review of population pharmacokinetic analyses of digoxin in the paediatric population", "authors": "Abdel Jalil MH, Abdullah N, Alsous MM et al.", "journal": "British journal of clinical pharmacology", "year": 2020, "pmid": "32153059", "url": "https://pubmed.ncbi.nlm.nih.gov/32153059/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/bcp.14272", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32153059/", "publicSourceType": "PMID" }, { "text": "Qureshi W, O'Neal WT, Soliman EZ et al.. Systematic review and meta-analysis of mortality and digoxin use in atrial fibrillation. Cardiology journal. 2016", "claim": "PubMed-indexed evidence involving Digoxin", "title": "Systematic review and meta-analysis of mortality and digoxin use in atrial fibrillation", "authors": "Qureshi W, O'Neal WT, Soliman EZ et al.", "journal": "Cardiology journal", "year": 2016, "pmid": "27064796", "url": "https://pubmed.ncbi.nlm.nih.gov/27064796/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.5603/CJ.a2016.0016", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27064796/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Cardiac Glycoside", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "36–48 hours (normal renal function); prolonged significantly in renal impairment", "onsetOfAction": "Oral: 1.5–6 hours to peak; IV: 5–30 minutes; Full effect at 6–8 hours", "commonBrandNames": [ "Lanoxin", "Digitek" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Serum digoxin level (target 0.5–0.9 ng/mL; draw 6–8 hours after dose or just before next dose); serum electrolytes (K+, Mg2+, Ca2+) at baseline and periodically; renal function (creatinine, BUN); ECG as clinically indicated" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "digoxin" }, { "id": "RX-CARDIO-041", "name": "Hydralazine", "alternateNames": [ "Apresoline" ], "category": "Prescription", "subcategory": "Direct Arteriolar Vasodilator", "overview": "Hydralazine is a direct arteriolar vasodilator used for hypertension and heart failure. The A-HeFT trial demonstrated significant mortality benefit when combined with isosorbide dinitrate (BiDil) in self-identified Black patients with heart failure. Also used for hypertensive emergencies in pregnancy.", "mechanismOfAction": "Directly relaxes arteriolar smooth muscle through incompletely understood mechanisms, possibly involving interference with calcium transport, increased nitric oxide release, or activation of potassium channels. Reduces peripheral resistance without significant venous dilation. Causes reflex tachycardia and increased cardiac output. Combined with nitrates, the hydralazine-nitrate combination improves NO bioavailability by scavenging reactive oxygen species.", "commonBenefits": [ "Reduces mortality in Black patients with HFrEF (A-HeFT, combined with ISDN)", "Direct arteriolar vasodilation reduces afterload", "Safe in pregnancy for hypertension management", "Alternative for patients intolerant to ACE inhibitors and ARBs" ], "commonDosageRange": "25–100 mg 2–3 times daily (HF combination: 37.5 mg three times daily with ISDN) (as prescribed by your physician)", "recommendedForm": "Oral tablet or IV/IM injection", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Food enhances bioavailability; undergoes extensive first-pass hepatic metabolism via acetylation (metabolism rate depends on acetylator phenotype)" }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Reflex tachycardia", "Headache", "Flushing", "Palpitations", "Dizziness", "Drug-induced lupus-like syndrome (dose-related, >200 mg/day)", "Peripheral neuropathy (pyridoxine-responsive)", "Sodium and water retention" ], "contraindications": [ "Coronary artery disease (may worsen ischemia due to reflex tachycardia, use with beta-blocker)", "Mitral valve rheumatic heart disease", "Dissecting aortic aneurysm", "SLE (may worsen)" ], "iconName": "cross.case.fill", "colorHex": "1ABC9C", "tags": [ "cardiovascular", "blood-pressure", "vasodilator", "heart-failure" ], "sources": [ { "text": "Taylor AL et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure (A-HeFT). N Engl J Med. 2004.", "pmid": "15533851", "doi": "10.1056/NEJMoa042934", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15533851/", "publicSourceType": "PMID" }, { "text": "Cohn JN et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure (V-HeFT I). N Engl J Med. 1986.", "pmid": "3520315", "doi": "10.1056/NEJM198606123142404", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3520315/", "publicSourceType": "PMID" }, { "text": "Singh A et al. Efficacy of pharmacological agents for management of post-partum hypertension: A systematic review and network meta-analysis. J Hum Hypertens. 2026.", "pmid": "41663753", "doi": "10.1038/s41371-026-01120-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41663753/", "publicSourceType": "PMID" }, { "text": "S D, Novri DA, Hamidy Y et al.. Effectiveness of nifedipine, labetalol, and hydralazine as emergency antihypertension in severe preeclampsia: a randomized control trial. F1000Research. 2022", "pmid": "37273965", "doi": "10.12688/f1000research.125944.2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37273965/", "publicSourceType": "PMID" }, { "text": "Herman LL, Tivakaran VS. Hydralazine. 2026", "pmid": "29262006", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29262006/", "publicSourceType": "PMID" }, { "text": "Gonçalves OR, Bendaham LCAR, Simoni GH et al.. Comparative efficacy and safety between intravenous labetalol and intravenous hydralazine for hypertensive disorders in pregnancy: A systematic review and meta-analysis of 19 randomized controlled trials. European journal of obstetrics, gynecology, and reproductive biology. 2024", "claim": "PubMed-indexed evidence involving Hydralazine", "title": "Comparative efficacy and safety between intravenous labetalol and intravenous hydralazine for hypertensive disorders in pregnancy: A systematic review and meta-analysis of 19 randomized controlled trials", "authors": "Gonçalves OR, Bendaham LCAR, Simoni GH et al.", "journal": "European journal of obstetrics, gynecology, and reproductive biology", "year": 2024, "pmid": "39522185", "url": "https://pubmed.ncbi.nlm.nih.gov/39522185/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.ejogrb.2024.11.002", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39522185/", "publicSourceType": "PMID" }, { "text": "Govindasamy V, Kamel MA, Volucke G et al.. Efficacy and Safety of Nifedipine Compared to Intravenous Hydralazine for Severe Hypertensive Disorders in Pregnancy: A Systematic Review and Meta-Analysis of Randmomized Controlled Trials. Medical sciences (Basel, Switzerland). 2025", "claim": "PubMed-indexed evidence involving Hydralazine", "title": "Efficacy and Safety of Nifedipine Compared to Intravenous Hydralazine for Severe Hypertensive Disorders in Pregnancy: A Systematic Review and Meta-Analysis of Randmomized Controlled Trials", "authors": "Govindasamy V, Kamel MA, Volucke G et al.", "journal": "Medical sciences (Basel, Switzerland)", "year": 2025, "pmid": "40700120", "url": "https://pubmed.ncbi.nlm.nih.gov/40700120/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/medsci13030091", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40700120/", "publicSourceType": "PMID" }, { "text": "Antza C, Dimou C, Doundoulakis I et al.. The flipside of hydralazine in pregnancy: A systematic review and meta-analysis. Pregnancy hypertension. 2020", "claim": "PubMed-indexed evidence involving Hydralazine", "title": "The flipside of hydralazine in pregnancy: A systematic review and meta-analysis", "authors": "Antza C, Dimou C, Doundoulakis I et al.", "journal": "Pregnancy hypertension", "year": 2020, "pmid": "32044579", "url": "https://pubmed.ncbi.nlm.nih.gov/32044579/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.preghy.2020.01.011", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32044579/", "publicSourceType": "PMID" }, { "text": "Farag M, Mabote T, Shoaib A et al.. Hydralazine and nitrates alone or combined for the management of chronic heart failure: A systematic review. International journal of cardiology. 2015", "claim": "PubMed-indexed evidence involving Hydralazine", "title": "Hydralazine and nitrates alone or combined for the management of chronic heart failure: A systematic review", "authors": "Farag M, Mabote T, Shoaib A et al.", "journal": "International journal of cardiology", "year": 2015, "pmid": "26073215", "url": "https://pubmed.ncbi.nlm.nih.gov/26073215/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.ijcard.2015.05.160", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26073215/", "publicSourceType": "PMID" }, { "text": "Magee LA, Cham C, Waterman EJ et al.. Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis. BMJ (Clinical research ed.). 2003", "claim": "PubMed-indexed evidence involving Hydralazine", "title": "Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis", "authors": "Magee LA, Cham C, Waterman EJ et al.", "journal": "BMJ (Clinical research ed.)", "year": 2003, "pmid": "14576246", "url": "https://pubmed.ncbi.nlm.nih.gov/14576246/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1136/bmj.327.7421.955", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14576246/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Direct Arteriolar Vasodilator", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "2–8 hours (depends on acetylator phenotype: slow vs fast)", "onsetOfAction": "Oral: 20–30 minutes; IV: 5–20 minutes", "commonBrandNames": [ "Apresoline" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "ANA titer at baseline and periodically (monitor for drug-induced lupus if doses >200 mg/day); CBC; renal function at baseline" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "hydralazine" }, { "id": "RX-CARDIO-042", "name": "Ranolazine", "alternateNames": [ "Ranexa" ], "category": "Prescription", "subcategory": "Late Sodium Current Inhibitor", "overview": "Ranolazine is a unique anti-anginal agent that works by inhibiting the late sodium current without significant hemodynamic effects. 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Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency (CARISA). JAMA. 2004.", "pmid": "14734593", "doi": "10.1001/jama.291.3.309", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14734593/", "publicSourceType": "PMID" }, { "text": "Morrow DA et al. Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes (MERLIN-TIMI 36). JAMA. 2007.", "pmid": "26059896", "doi": "10.1001/jama.297.16.1775", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26059896/", "publicSourceType": "PMID" }, { "text": "Spillane J et al. Drug treatment for myotonia. Cochrane Database Syst Rev. 2025.", "pmid": "40197813", "doi": "10.1002/14651858.CD004762.pub3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40197813/", "publicSourceType": "PMID" }, { "text": "Pierce DA, Reeves-Daniel AM. Ranolazine-tacrolimus interaction. The Annals of pharmacotherapy. 2010", "pmid": "20876828", "doi": "10.1345/aph.1P297", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20876828/", "publicSourceType": "PMID" }, { "text": "Rayner-Hartley E, Sedlak T. Ranolazine: A Contemporary Review. Journal of the American Heart Association. 2016", "pmid": "26979079", "doi": "10.1161/JAHA.116.003196", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26979079/", "publicSourceType": "PMID" }, { "text": "Gong M, Zhang Z, Fragakis N et al.. Role of ranolazine in the prevention and treatment of atrial fibrillation: A meta-analysis of randomized clinical trials. Heart rhythm. 2017", "claim": "PubMed-indexed evidence involving Ranolazine", "title": "Role of ranolazine in the prevention and treatment of atrial fibrillation: A meta-analysis of randomized clinical trials", "authors": "Gong M, Zhang Z, Fragakis N et al.", "journal": "Heart rhythm", "year": 2017, "pmid": "27746384", "url": "https://pubmed.ncbi.nlm.nih.gov/27746384/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.hrthm.2016.10.008", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27746384/", "publicSourceType": "PMID" }, { "text": "Cempaka Putri DKS, Andrianto A, Al-Farabi MJ et al.. Efficacy of Ranolazine to Improve Diastolic Performance in Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-analysis. European cardiology. 2023", "claim": "PubMed-indexed evidence involving Ranolazine", "title": "Efficacy of Ranolazine to Improve Diastolic Performance in Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-analysis", "authors": "Cempaka Putri DKS, Andrianto A, Al-Farabi MJ et al.", "journal": "European cardiology", "year": 2023, "pmid": "36844933", "url": "https://pubmed.ncbi.nlm.nih.gov/36844933/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.15420/ecr.2022.10", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36844933/", "publicSourceType": "PMID" }, { "text": "Ayyasamy L, Bagepally BS. Cost-utility of Ranolazine for Chronic Stable Angina Pectoris: Systematic Review and Meta-analysis. Clinical therapeutics. 2023", "claim": "PubMed-indexed evidence involving Ranolazine", "title": "Cost-utility of Ranolazine for Chronic Stable Angina Pectoris: Systematic Review and Meta-analysis", "authors": "Ayyasamy L, Bagepally BS", "journal": "Clinical therapeutics", "year": 2023, "pmid": "37087299", "url": "https://pubmed.ncbi.nlm.nih.gov/37087299/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.clinthera.2023.04.004", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37087299/", "publicSourceType": "PMID" }, { "text": "Bazoukis G, Tse G, Letsas KP et al.. Impact of ranolazine on ventricular arrhythmias - A systematic review. Journal of arrhythmia. 2018", "claim": "PubMed-indexed evidence involving Ranolazine", "title": "Impact of ranolazine on ventricular arrhythmias - A systematic review", "authors": "Bazoukis G, Tse G, Letsas KP et al.", "journal": "Journal of arrhythmia", "year": 2018, "pmid": "29657587", "url": "https://pubmed.ncbi.nlm.nih.gov/29657587/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/joa3.12031", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29657587/", "publicSourceType": "PMID" }, { "text": "Patel N, Kluger J. Ranolazine for Prevention of Atrial Fibrillation after Cardiac Surgery: A Systematic Review. 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Angiotensin-neprilysin inhibition versus enalapril in heart failure (PARADIGM-HF). N Engl J Med. 2014.", "pmid": "25176015", "doi": "10.1056/NEJMoa1409077", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25176015/", "publicSourceType": "PMID" }, { "text": "Solomon SD et al. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction (PARAGON-HF). N Engl J Med. 2019.", "pmid": "31475794", "doi": "10.1056/NEJMoa1908655", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31475794/", "publicSourceType": "PMID" }, { "text": "Chen X et al. Optimization of Clinical Trial Design and Decision-Making for Heart Failure with Preserved Ejection Fraction (HFpEF): A Meta-Analysis Based on a Placebo Response Model. Cardiovasc Ther. 2025.", "pmid": "41089765", "doi": "10.1155/cdr/7087720", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41089765/", "publicSourceType": "PMID" }, { "text": "Zhou W, Yang X, Jin J et al.. The efficacy and safety of sacubitril/valsartan in chronic kidney disease: a systematic review and meta-analysis. International urology and nephrology. 2024", "pmid": "37195574", "doi": "10.1007/s11255-023-03599-w", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37195574/", "publicSourceType": "PMID" }, { "text": "Yamamoto K, Yarimizu D, Shimanishi A et al.. Efficacy and Safety of Sacubitril/Valsartan Versus Amlodipine in Japanese Patients With Essential Hypertension: A Randomized, Multicenter, Open-Label, Noninferiority Study (PARASOL Study). Journal of clinical hypertension (Greenwich, Conn.). 2025", "pmid": "39632589", "doi": "10.1111/jch.14938", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39632589/", "publicSourceType": "PMID" }, { "text": "Zheng S, Zhang Y, Gu L et al.. Renal Safety of Sacubitril/Valsartan: A Meta-Analysis of Randomized Controlled Trials. Journal of cardiovascular pharmacology. 2023", "claim": "PubMed-indexed evidence involving Sacubitril/Valsartan", "title": "Renal Safety of Sacubitril/Valsartan: A Meta-Analysis of Randomized Controlled Trials", "authors": "Zheng S, Zhang Y, Gu L et al.", "journal": "Journal of cardiovascular pharmacology", "year": 2023, "pmid": "36607717", "url": "https://pubmed.ncbi.nlm.nih.gov/36607717/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/FJC.0000000000001379", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36607717/", "publicSourceType": "PMID" }, { "text": "Huang Y, Zhang Y, Ma L et al.. Adverse Events of Sacubitril/Valsartan: A Meta-analysis of Randomized Controlled Trials. Journal of cardiovascular pharmacology. 2021", "claim": "PubMed-indexed evidence involving Sacubitril/Valsartan", "title": "Adverse Events of Sacubitril/Valsartan: A Meta-analysis of Randomized Controlled Trials", "authors": "Huang Y, Zhang Y, Ma L et al.", "journal": "Journal of cardiovascular pharmacology", "year": 2021, "pmid": "33929386", "url": "https://pubmed.ncbi.nlm.nih.gov/33929386/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/FJC.0000000000001049", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33929386/", "publicSourceType": "PMID" }, { "text": "Chen Y, He Q, Mo DC et al.. The angiotensin receptor and neprilysin inhibitor, LCZ696, in heart failure: A meta-analysis of randomized controlled trials. Medicine. 2022", "claim": "PubMed-indexed evidence involving Sacubitril/Valsartan", "title": "The angiotensin receptor and neprilysin inhibitor, LCZ696, in heart failure: A meta-analysis of randomized controlled trials", "authors": "Chen Y, He Q, Mo DC et al.", "journal": "Medicine", "year": 2022, "pmid": "36254034", "url": "https://pubmed.ncbi.nlm.nih.gov/36254034/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MD.0000000000030904", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36254034/", "publicSourceType": "PMID" }, { "text": "Martins E Pereira G, S Duarte G, Katerenchuk V et al.. Safety and tolerability of sacubitril-valsartan: a systematic review and meta-analysis. Expert opinion on drug safety. 2021", "claim": "PubMed-indexed evidence involving Sacubitril/Valsartan", "title": "Safety and tolerability of sacubitril-valsartan: a systematic review and meta-analysis", "authors": "Martins E Pereira G, S Duarte G, Katerenchuk V et al.", "journal": "Expert opinion on drug safety", "year": 2021, "pmid": "33459086", "url": "https://pubmed.ncbi.nlm.nih.gov/33459086/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/14740338.2021.1877658", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33459086/", "publicSourceType": "PMID" }, { "text": "Chen X, Jin C, Xie L et al.. LCZ696 and preservation of renal function in heart failure: A meta-analysis of 6 randomized trials. Reviews in cardiovascular medicine. 2020", "claim": "PubMed-indexed evidence involving Sacubitril/Valsartan", "title": "LCZ696 and preservation of renal function in heart failure: A meta-analysis of 6 randomized trials", "authors": "Chen X, Jin C, Xie L et al.", "journal": "Reviews in cardiovascular medicine", "year": 2020, "pmid": "32259909", "url": "https://pubmed.ncbi.nlm.nih.gov/32259909/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.31083/j.rcm.2020.01.2", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32259909/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Angiotensin Receptor-Neprilysin Inhibitor (ARNI)", "blackBoxWarnings": [ "Can cause fetal toxicity when administered during pregnancy. Discontinue as soon as pregnancy is detected." ], "fdaPregnancyCategory": "D", "halfLife": "Sacubitrilat: ~11.5 hours; Valsartan: ~9.9 hours", "onsetOfAction": "Sacubitril peak: 0.5 hours; Valsartan peak: 1.5 hours; clinical benefit accrues over weeks", "commonBrandNames": [ "Entresto" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Serum potassium, renal function (creatinine, BUN), and blood pressure at baseline, within 1–2 weeks of initiation or dose change, and periodically; monitor for symptomatic hypotension during titration" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "sacubitril-valsartan" }, { "id": "RX-CARDIO-044", "name": "Ivabradine", "alternateNames": [ "Corlanor" ], "category": "Prescription", "subcategory": "Hyperpolarization-Activated Cyclic Nucleotide-Gated (HCN) Channel Blocker", "overview": "Ivabradine selectively reduces heart rate without affecting blood pressure, contractility, or conduction. 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Ivabradine and outcomes in chronic heart failure (SHIFT). Lancet. 2010.", "pmid": "20801500", "doi": "10.1016/S0140-6736(10)61198-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20801500/", "publicSourceType": "PMID" }, { "text": "Fox K et al. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL). Lancet. 2008.", "pmid": "18757088", "doi": "10.1016/S0140-6736(08)61170-8", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18757088/", "publicSourceType": "PMID" }, { "text": "Kow CS et al. Ivabradine in acute myocardial infarction: a systematic review and meta-analysis of randomized controlled trials. Expert Rev Cardiovasc Ther. 2026.", "pmid": "41537857", "doi": "10.1080/14779072.2026.2618040", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41537857/", "publicSourceType": "PMID" }, { "text": "Taub PR, Zadourian A, Lo HC et al.. Randomized Trial of Ivabradine in Patients With Hyperadrenergic Postural Orthostatic Tachycardia Syndrome. Journal of the American College of Cardiology. 2021", "pmid": "33602468", "doi": "10.1016/j.jacc.2020.12.029", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33602468/", "publicSourceType": "PMID" }, { "text": "Reed M, Patel P. Ivabradine. 2026", "pmid": "29939560", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29939560/", "publicSourceType": "PMID" }, { "text": "Han J, Wang Q, Jiang L et al.. Efficacy and Safety of Ivabradine for Patients With Acute Heart Failure: Meta-Analysis of Randomized Controlled Trials. Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc. 2024", "claim": "PubMed-indexed evidence involving Ivabradine", "title": "Efficacy and Safety of Ivabradine for Patients With Acute Heart Failure: Meta-Analysis of Randomized Controlled Trials", "authors": "Han J, Wang Q, Jiang L et al.", "journal": "Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc", "year": 2024, "pmid": "39425897", "url": "https://pubmed.ncbi.nlm.nih.gov/39425897/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/anec.70012", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39425897/", "publicSourceType": "PMID" }, { "text": "Sasmita BR, Xie S, Liu G et al.. Ivabradine in patients with acute ST-elevation myocardial infarction: a meta-analysis of randomized controlled trials. The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology. 2023", "claim": "PubMed-indexed evidence involving Ivabradine", "title": "Ivabradine in patients with acute ST-elevation myocardial infarction: a meta-analysis of randomized controlled trials", "authors": "Sasmita BR, Xie S, Liu G et al.", "journal": "The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology", "year": 2023, "pmid": "37024594", "url": "https://pubmed.ncbi.nlm.nih.gov/37024594/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s43044-023-00351-8", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37024594/", "publicSourceType": "PMID" }, { "text": "Wang Z, Wang W, Li H et al.. Ivabradine and Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials. Journal of cardiovascular pharmacology. 2022", "claim": "PubMed-indexed evidence involving Ivabradine", "title": "Ivabradine and Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials", "authors": "Wang Z, Wang W, Li H et al.", "journal": "Journal of cardiovascular pharmacology", "year": 2022, "pmid": "34983905", "url": "https://pubmed.ncbi.nlm.nih.gov/34983905/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/FJC.0000000000001209", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34983905/", "publicSourceType": "PMID" }, { "text": "Kwok CS, Gillespie D, Rehman Qazi NU et al.. Ivabradine as a treatment for postural orthostatic tachycardia syndrome: A systematic review. Journal of cardiovascular pharmacology. 2025", "claim": "PubMed-indexed evidence involving Ivabradine", "title": "Ivabradine as a treatment for postural orthostatic tachycardia syndrome: A systematic review", "authors": "Kwok CS, Gillespie D, Rehman Qazi NU et al.", "journal": "Journal of cardiovascular pharmacology", "year": 2025, "pmid": "41364925", "url": "https://pubmed.ncbi.nlm.nih.gov/41364925/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/FJC.0000000000001784", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41364925/", "publicSourceType": "PMID" }, { "text": "Ashraf S, Khalaf AKS, Fatima L et al.. Evaluating the role of ivabradine in acute decompensated heart failure: A systematic review and meta-analysis. Current problems in cardiology. 2024", "claim": "PubMed-indexed evidence involving Ivabradine", "title": "Evaluating the role of ivabradine in acute decompensated heart failure: A systematic review and meta-analysis", "authors": "Ashraf S, Khalaf AKS, Fatima L et al.", "journal": "Current problems in cardiology", "year": 2024, "pmid": "38729277", "url": "https://pubmed.ncbi.nlm.nih.gov/38729277/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.cpcardiol.2024.102604", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38729277/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Hyperpolarization-Activated Cyclic Nucleotide-Gated (HCN) Channel Blocker / If Current Inhibitor", "blackBoxWarnings": [ "Ivabradine can cause fetal toxicity when administered to a pregnant woman. Females of reproductive potential should use effective contraception. Embryo-fetal toxicity observed in animal studies." ], "fdaPregnancyCategory": "D", "halfLife": "6 hours", "onsetOfAction": "1 hour to peak; steady-state heart rate reduction within 2 weeks", "commonBrandNames": [ "Corlanor" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": "Monitor heart rate regularly; ECG at baseline and periodically; assess for atrial fibrillation; adjust dose to maintain resting HR 50–60 bpm" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "ivabradine" }, { "id": "RX-CARDIO-045", "name": "Dofetilide", "alternateNames": [ "Tikosyn" ], "category": "Prescription", "subcategory": "Class III Antiarrhythmic", "overview": "Dofetilide is a pure class III antiarrhythmic that selectively blocks the rapid component of the delayed rectifier potassium current (IKr). It is used for conversion and maintenance of sinus rhythm in atrial fibrillation/flutter. Due to its QT-prolonging properties and risk of torsades de pointes, initiation requires 3 days of in-hospital ECG monitoring. It is only available through the Tikosyn Education Program (T.I.P.S.).", "mechanismOfAction": "Selectively blocks the rapid component of the delayed rectifier potassium current (IKr) without affecting other potassium currents (IKs, IK1) or sodium/calcium channels. Prolongs the effective refractory period in atrial and ventricular tissue. Prolongs QT interval in a dose-dependent and concentration-dependent manner. No significant beta-blocking, alpha-blocking, or negative inotropic activity.", "commonBenefits": [ "Effective for conversion and maintenance of sinus rhythm in AF/AFL", "No negative inotropic effects (safe in heart failure)", "Pure class III mechanism (no mixed pharmacology)", "No increase in mortality in heart failure patients (DIAMOND-HF)" ], "commonDosageRange": "125–500 mcg twice daily, adjusted by CrCl and QTc response (as prescribed by your physician)", "recommendedForm": "Oral capsule", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Can be taken with or without food; renally eliminated, strict dose adjustment by creatinine clearance is mandatory" }, "evidenceRating": "moderate", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "QT prolongation and torsades de pointes (~3% risk)", "Headache", "Dizziness", "Nausea", "Chest pain", "Insomnia" ], "contraindications": [ "Baseline QTc >440 ms (>500 ms if ventricular conduction abnormality)", "CrCl <20 mL/min", "Congenital or acquired long QT syndromes", "Concurrent use with verapamil, cimetidine, trimethoprim, ketoconazole, prochlorperazine, megestrol, or HCTZ (drug interactions that increase dofetilide levels)", "Hypokalemia or hypomagnesemia (uncorrected)" ], "iconName": "cross.case.fill", "colorHex": "9B59B6", "tags": [ "cardiovascular", "antiarrhythmic", "atrial-fibrillation", "atrial-flutter" ], "sources": [ { "text": "Torp-Pedersen C et al. Dofetilide in patients with congestive heart failure and left ventricular dysfunction (DIAMOND-CHF). N Engl J Med. 1999.", "pmid": "14688506", "doi": "10.1056/NEJM199910071411401", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14688506/", "publicSourceType": "PMID" }, { "text": "Singh S et al. Efficacy and safety of oral dofetilide in converting to and maintaining sinus rhythm in patients with chronic atrial fibrillation or flutter (SAFIRE-D). Circulation. 2000.", "pmid": "11067793", "doi": "10.1161/01.CIR.102.19.2385", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11067793/", "publicSourceType": "PMID" }, { "text": "Kukendrarajah K et al. External electrical and pharmacological cardioversion for atrial fibrillation, atrial flutter or atrial tachycardias: a network meta-analysis. Cochrane Database Syst Rev. 2024.", "pmid": "38828867", "doi": "10.1002/14651858.CD013255.pub2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38828867/", "publicSourceType": "PMID" }, { "text": "Shenasa F, Shenasa M. Dofetilide: Electrophysiologic Effect, Efficacy, and Safety in Patients with Cardiac Arrhythmias. Cardiac electrophysiology clinics. 2016", "pmid": "27261832", "doi": "10.1016/j.ccep.2016.02.006", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27261832/", "publicSourceType": "PMID" }, { "text": "Mahendru D, Joshi HD, Kowey P. Dofetilide in atrial fibrillation: A comprehensive review. Indian pacing and electrophysiology journal. 2025", "pmid": "41319865", "doi": "10.1016/j.ipej.2025.11.013", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41319865/", "publicSourceType": "PMID" }, { "text": "Cicirale C, Jackson J, Gothard D. Safety of Inpatient Dofetilide Initiation per Cardiology Services: A Retrospective Review. Journal of pharmacy practice. 2022", "claim": "PubMed-indexed evidence involving Dofetilide", "title": "Safety of Inpatient Dofetilide Initiation per Cardiology Services: A Retrospective Review", "authors": "Cicirale C, Jackson J, Gothard D", "journal": "Journal of pharmacy practice", "year": 2022, "pmid": "33736527", "url": "https://pubmed.ncbi.nlm.nih.gov/33736527/", "study_type": "review", "confidence": "verify", "doi": "10.1177/08971900211000212", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33736527/", "publicSourceType": "PMID" }, { "text": "Tagle-Cornell MC, Ayoub C, Bird C et al.. Safety of dofetilide in stable patients and investigating traits of susceptibility to torsade de pointes. International journal of cardiology. Heart & vasculature. 2024", "claim": "PubMed-indexed evidence involving Dofetilide", "title": "Safety of dofetilide in stable patients and investigating traits of susceptibility to torsade de pointes", "authors": "Tagle-Cornell MC, Ayoub C, Bird C et al.", "journal": "International journal of cardiology. Heart & vasculature", "year": 2024, "pmid": "39221117", "url": "https://pubmed.ncbi.nlm.nih.gov/39221117/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.ijcha.2024.101475", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39221117/", "publicSourceType": "PMID" }, { "text": "Chen C, Lal M, Burton Y et al.. Efficacy and safety of dofetilide and sotalol in patients with hypertrophic cardiomyopathy. Communications medicine. 2023", "claim": "PubMed-indexed evidence involving Dofetilide", "title": "Efficacy and safety of dofetilide and sotalol in patients with hypertrophic cardiomyopathy", "authors": "Chen C, Lal M, Burton Y et al.", "journal": "Communications medicine", "year": 2023, "pmid": "37468544", "url": "https://pubmed.ncbi.nlm.nih.gov/37468544/", "study_type": "review", "confidence": "verify", "doi": "10.1038/s43856-023-00315-8", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37468544/", "publicSourceType": "PMID" }, { "text": "Rickard JP, Negrelli J, Olson JL et al.. Frequency of Adverse Event Monitoring in Ambulatory Patients on Amiodarone or Dofetilide. Journal of pharmacy practice. 2018", "claim": "PubMed-indexed evidence involving Dofetilide", "title": "Frequency of Adverse Event Monitoring in Ambulatory Patients on Amiodarone or Dofetilide", "authors": "Rickard JP, Negrelli J, Olson JL et al.", "journal": "Journal of pharmacy practice", "year": 2018, "pmid": "28884613", "url": "https://pubmed.ncbi.nlm.nih.gov/28884613/", "study_type": "review", "confidence": "verify", "doi": "10.1177/0897190017729523", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28884613/", "publicSourceType": "PMID" }, { "text": "Cho JH, Youn SJ, Moore JC et al.. Safety of Oral Dofetilide Reloading for Treatment of Atrial Arrhythmias. Circulation. Arrhythmia and electrophysiology. 2017", "claim": "PubMed-indexed evidence involving Dofetilide", "title": "Safety of Oral Dofetilide Reloading for Treatment of Atrial Arrhythmias", "authors": "Cho JH, Youn SJ, Moore JC et al.", "journal": "Circulation. Arrhythmia and electrophysiology", "year": 2017, "pmid": "29038104", "url": "https://pubmed.ncbi.nlm.nih.gov/29038104/", "study_type": "review", "confidence": "verify", "doi": "10.1161/CIRCEP.117.005333", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29038104/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Class III Antiarrhythmic (Selective IKr Blocker)", "blackBoxWarnings": [ "To minimize the risk of induced arrhythmia, patients initiated or re-initiated on dofetilide should be placed for a minimum of 3 days in a facility that can provide calculations of creatinine clearance, continuous electrocardiographic monitoring, and cardiac resuscitation. Dofetilide is available only to hospitals and prescribers who have received appropriate education (T.I.P.S. program)." ], "fdaPregnancyCategory": "C", "halfLife": "10 hours", "onsetOfAction": "2–3 hours to peak; AF conversion may occur within 24–36 hours", "commonBrandNames": [ "Tikosyn" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Continuous telemetry for minimum 3 days during initiation; QTc monitoring 2–3 hours after each dose during loading; CrCl at baseline (mandatory for dosing); serum electrolytes (K+, Mg2+) at baseline and maintained in normal range; QTc must be monitored with each dose change" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "dofetilide" }, { "id": "RX-CARDIO-046", "name": "Eplerenone", "alternateNames": [ "Inspra" ], "category": "Prescription", "subcategory": "Selective Mineralocorticoid Receptor Antagonist", "overview": "Eplerenone is a selective mineralocorticoid receptor antagonist with significantly less anti-androgenic activity than spironolactone. The EPHESUS trial showed mortality reduction in post-MI patients with heart failure, and EMPHASIS-HF demonstrated benefit in mild heart failure (NYHA II). It is preferred over spironolactone when gynecomastia or sexual side effects are a concern.", "mechanismOfAction": "Selectively blocks the mineralocorticoid (aldosterone) receptor with ~500-fold lower affinity for androgen and progesterone receptors compared to spironolactone. Blocks aldosterone-mediated sodium reabsorption and potassium excretion in the collecting duct. In heart failure, prevents aldosterone-driven cardiac fibrosis, inflammation, and vascular remodeling. The selectivity accounts for the markedly lower rate of gynecomastia and sexual side effects.", "commonBenefits": [ "Reduces mortality post-MI with HF (EPHESUS trial)", "Reduces CV death and HF hospitalization in mild HF (EMPHASIS-HF)", "Selective MR antagonism, much lower gynecomastia risk than spironolactone", "Potassium-sparing diuresis" ], "commonDosageRange": "25–50 mg once daily (as prescribed by your physician)", "recommendedForm": "Oral tablet", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Can be taken with or without food; food does not significantly affect absorption" }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Hyperkalemia (most important adverse effect)", "Dizziness", "Diarrhea", "Cough", "Fatigue", "Hyponatremia" ], "contraindications": [ "Serum potassium >5.0 mEq/L at initiation", "CrCl <30 mL/min (or <50 mL/min when used for hypertension)", "Type 2 diabetes with microalbuminuria and serum creatinine >2.0 mg/dL (males) or >1.8 mg/dL (females)", "Concurrent strong CYP3A4 inhibitors (ketoconazole, itraconazole, nefazodone, clarithromycin, ritonavir)", "Concurrent potassium supplements or potassium-sparing diuretics" ], "iconName": "cross.case.fill", "colorHex": "87CEEB", "tags": [ "cardiovascular", "heart-failure", "aldosterone-antagonist", "blood-pressure", "post-mi" ], "sources": [ { "text": "Pitt B et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction (EPHESUS). N Engl J Med. 2003.", "pmid": "12668699", "doi": "10.1056/NEJMoa030207", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12668699/", "publicSourceType": "PMID" }, { "text": "Zannad F et al. Eplerenone in patients with systolic heart failure and mild symptoms (EMPHASIS-HF). N Engl J Med. 2011.", "pmid": "21073363", "doi": "10.1056/NEJMoa1009492", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21073363/", "publicSourceType": "PMID" }, { "text": "Dias J et al. Effects of mineralocorticoid receptor antagonists on cardiometabolic profile and liver health in individuals with increased cardiometabolic risk: a systematic review and meta-analysis of randomized controlled trials. Expert Rev Cardiovasc Ther. 2026.", "pmid": "41702409", "doi": "10.1080/14779072.2026.2634029", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41702409/", "publicSourceType": "PMID" }, { "text": "Provenzano M, Puchades MJ, Garofalo C et al.. Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and Their Combination in Patients with Chronic Kidney Disease: A Randomized Crossover Clinical Trial. Journal of the American Society of Nephrology : JASN. 2022", "pmid": "35440501", "doi": "10.1681/ASN.2022020207", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35440501/", "publicSourceType": "PMID" }, { "text": "Filippatos G, Anker SD, Böhm M et al.. A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney disease. European heart journal. 2016", "pmid": "27130705", "doi": "10.1093/eurheartj/ehw132", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27130705/", "publicSourceType": "PMID" }, { "text": "Elshahat A, Mansour A, Ellabban M et al.. Comparative effectiveness and safety of eplerenone and spironolactone in patients with heart failure: a systematic review and meta-analysis. BMC cardiovascular disorders. 2024", "claim": "PubMed-indexed evidence involving Eplerenone", "title": "Comparative effectiveness and safety of eplerenone and spironolactone in patients with heart failure: a systematic review and meta-analysis", "authors": "Elshahat A, Mansour A, Ellabban M et al.", "journal": "BMC cardiovascular disorders", "year": 2024, "pmid": "39271992", "url": "https://pubmed.ncbi.nlm.nih.gov/39271992/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12872-024-04103-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39271992/", "publicSourceType": "PMID" }, { "text": "Bagattoli V, Dos Santos HS, Giorgi J et al.. Finerenone, Eplerenone, and Spironolactone in HFpEF: A Bayesian Network Meta-Analysis of Efficacy and Safety. European journal of heart failure. 2026", "claim": "PubMed-indexed evidence involving Eplerenone", "title": "Finerenone, Eplerenone, and Spironolactone in HFpEF: A Bayesian Network Meta-Analysis of Efficacy and Safety", "authors": "Bagattoli V, Dos Santos HS, Giorgi J et al.", "journal": "European journal of heart failure", "year": 2026, "pmid": "41831311", "url": "https://pubmed.ncbi.nlm.nih.gov/41831311/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/ejhf/xuag083", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41831311/", "publicSourceType": "PMID" }, { "text": "Hu H, Cao M, Sun Y et al.. Efficacy and Safety of Eplerenone for Treating Chronic Kidney Disease: A Meta-Analysis. International journal of hypertension. 2023", "claim": "PubMed-indexed evidence involving Eplerenone", "title": "Efficacy and Safety of Eplerenone for Treating Chronic Kidney Disease: A Meta-Analysis", "authors": "Hu H, Cao M, Sun Y et al.", "journal": "International journal of hypertension", "year": 2023, "pmid": "36938116", "url": "https://pubmed.ncbi.nlm.nih.gov/36938116/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1155/2023/6683987", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36938116/", "publicSourceType": "PMID" }, { "text": "Hu H, Zhao X, Jin X et al.. Efficacy and safety of eplerenone treatment for patients with diabetic nephropathy: A meta-analysis. PloS one. 2022", "claim": "PubMed-indexed evidence involving Eplerenone", "title": "Efficacy and safety of eplerenone treatment for patients with diabetic nephropathy: A meta-analysis", "authors": "Hu H, Zhao X, Jin X et al.", "journal": "PloS one", "year": 2022, "pmid": "35324976", "url": "https://pubmed.ncbi.nlm.nih.gov/35324976/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1371/journal.pone.0265642", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35324976/", "publicSourceType": "PMID" }, { "text": "Huang RS, Mihalache A, Benour A et al.. Eplerenone and Spironolactone for Chronic Central Serous Chorioretinopathy: A Systematic Review and Meta-Analysis. American journal of ophthalmology. 2025", "claim": "PubMed-indexed evidence involving Eplerenone", "title": "Eplerenone and Spironolactone for Chronic Central Serous Chorioretinopathy: A Systematic Review and Meta-Analysis", "authors": "Huang RS, Mihalache A, Benour A et al.", "journal": "American journal of ophthalmology", "year": 2025, "pmid": "40513762", "url": "https://pubmed.ncbi.nlm.nih.gov/40513762/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.ajo.2025.06.012", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40513762/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Selective Mineralocorticoid Receptor Antagonist", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "4–6 hours", "onsetOfAction": "Peak plasma at 1.5 hours; full therapeutic effect over days to weeks", "commonBrandNames": [ "Inspra" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Serum potassium and renal function at baseline, within 1 week of initiation, at 1 month, then quarterly; hold if K+ >5.5 mEq/L; check before and after each dose change" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "eplerenone" }, { "id": "RX-CARDIO-047", "name": "Prasugrel", "alternateNames": [ "Effient" ], "category": "Prescription", "subcategory": "Antiplatelet Agent (P2Y12 Inhibitor)", "overview": "Prasugrel is a third-generation thienopyridine P2Y12 inhibitor with faster onset, greater potency, and less inter-patient variability than clopidogrel. The TRITON-TIMI 38 trial demonstrated superior efficacy over clopidogrel in ACS patients undergoing PCI, but with higher bleeding risk. Its single-step hepatic activation avoids the CYP2C19 polymorphism issue seen with clopidogrel.", "mechanismOfAction": "Thienopyridine prodrug that requires only a single CYP-mediated hepatic oxidation step (primarily CYP3A4 and CYP2B6) to generate the active metabolite. The active metabolite irreversibly binds to the platelet P2Y12 ADP receptor, blocking ADP-mediated platelet activation and aggregation. Faster and more complete platelet inhibition than clopidogrel, with minimal impact from CYP2C19 polymorphisms.", "commonBenefits": [ "Superior to clopidogrel in reducing ischemic events in ACS-PCI (TRITON-TIMI 38)", "Faster onset of platelet inhibition than clopidogrel", "More consistent antiplatelet effect (not affected by CYP2C19 polymorphism)", "Greater reduction in stent thrombosis than clopidogrel" ], "commonDosageRange": "60 mg loading dose, then 10 mg once daily (5 mg daily if <60 kg) for up to 12 months with aspirin (as prescribed by your physician)", "recommendedForm": "Oral tablet", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Can be taken with or without food; rapidly absorbed and converted to active metabolite" }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Bleeding (higher rate than clopidogrel, including life-threatening and fatal bleeding)", "Bruising", "Epistaxis", "GI bleeding", "Anemia", "Rash", "Thrombotic thrombocytopenic purpura (TTP, very rare)" ], "contraindications": [ "Active pathological bleeding", "History of prior stroke or TIA (net clinical harm demonstrated)", "Hypersensitivity to prasugrel", "Generally not recommended in patients >=75 years (increased bleeding risk without net benefit unless high-risk features like diabetes or prior MI)" ], "iconName": "cross.case.fill", "colorHex": "F39C12", "tags": [ "cardiovascular", "antiplatelet", "p2y12-inhibitor", "acs", "pci", "stent", "dapt" ], "sources": [ { "text": "Wiviott SD et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes (TRITON-TIMI 38). N Engl J Med. 2007.", "pmid": "17982182", "doi": "10.1056/NEJMoa0706482", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17982182/", "publicSourceType": "PMID" }, { "text": "Roe MT et al. Prasugrel versus clopidogrel for acute coronary syndromes without revascularization (TRILOGY ACS). N Engl J Med. 2012.", "pmid": "30562068", "doi": "10.1056/NEJMoa1205512", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30562068/", "publicSourceType": "PMID" }, { "text": "Zheng L et al. Efficacy and safety of off-label low-dose compared with standard-dose antiplatelet agents in patients with coronary heart disease: a meta-analysis. Open Heart. 2026.", "pmid": "41617356", "doi": "10.1136/openhrt-2025-003839", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41617356/", "publicSourceType": "PMID" }, { "text": "Fujimoto S, Iguchi Y, Yamagami H et al.. P2Y(12) Reaction Units With Prasugrel in Acute Large Artery Atherosclerosis and Transient Ischemic Attack: An Open-Label Randomized Controlled Study, ACUTE-PRAS. Circulation journal : official journal of the Japanese Circulation Society. 2025", "pmid": "40383626", "doi": "10.1253/circj.CJ-24-0949", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40383626/", "publicSourceType": "PMID" }, { "text": "Saito S, Isshiki T, Kimura T et al.. Efficacy and safety of adjusted-dose prasugrel compared with clopidogrel in Japanese patients with acute coronary syndrome: the PRASFIT-ACS study. Circulation journal : official journal of the Japanese Circulation Society. 2014", "pmid": "24759796", "doi": "10.1253/circj.cj-13-1482", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24759796/", "publicSourceType": "PMID" }, { "text": "Ullah W, Ali Z, Sadiq U et al.. Meta-Analysis Comparing the Safety and Efficacy of Prasugrel and Ticagrelor in Acute Coronary Syndrome. The American journal of cardiology. 2020", "claim": "PubMed-indexed evidence involving Prasugrel", "title": "Meta-Analysis Comparing the Safety and Efficacy of Prasugrel and Ticagrelor in Acute Coronary Syndrome", "authors": "Ullah W, Ali Z, Sadiq U et al.", "journal": "The American journal of cardiology", "year": 2020, "pmid": "32771221", "url": "https://pubmed.ncbi.nlm.nih.gov/32771221/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.amjcard.2020.07.017", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32771221/", "publicSourceType": "PMID" }, { "text": "Xia P, He C, Chen L et al.. Efficacy and safety of prasugrel therapy for intracranial aneurysms with endovascular treatment: A meta-analysis. Journal of the neurological sciences. 2019", "claim": "PubMed-indexed evidence involving Prasugrel", "title": "Efficacy and safety of prasugrel therapy for intracranial aneurysms with endovascular treatment: A meta-analysis", "authors": "Xia P, He C, Chen L et al.", "journal": "Journal of the neurological sciences", "year": 2019, "pmid": "30641247", "url": "https://pubmed.ncbi.nlm.nih.gov/30641247/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jns.2019.01.005", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30641247/", "publicSourceType": "PMID" }, { "text": "Shah RP, Shafiq A, Hamza M et al.. Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis. The American journal of cardiology. 2023", "claim": "PubMed-indexed evidence involving Prasugrel", "title": "Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis", "authors": "Shah RP, Shafiq A, Hamza M et al.", "journal": "The American journal of cardiology", "year": 2023, "pmid": "37751668", "url": "https://pubmed.ncbi.nlm.nih.gov/37751668/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.amjcard.2023.08.117", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37751668/", "publicSourceType": "PMID" }, { "text": "Spartalis M, Tzatzaki E, Spartalis E et al.. The role of prasugrel in the management of acute coronary syndromes: a systematic review. European review for medical and pharmacological sciences. 2017", "claim": "PubMed-indexed evidence involving Prasugrel", "title": "The role of prasugrel in the management of acute coronary syndromes: a systematic review", "authors": "Spartalis M, Tzatzaki E, Spartalis E et al.", "journal": "European review for medical and pharmacological sciences", "year": 2017, "pmid": "29131238", "url": "https://pubmed.ncbi.nlm.nih.gov/29131238/", "study_type": "meta-analysis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29131238/", "publicSourceType": "PMID" }, { "text": "Sun MT, Huang S, Wiviott SD et al.. Meta-Analysis of Intraocular Bleeding With Dual Antiplatelet Therapy Using P2Y12 Inhibitors Prasugrel or Ticagrelor. 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The impact of metformin with or without lifestyle modification versus placebo on polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. European journal of endocrinology. 2023", "claim": "PubMed-indexed evidence involving Metformin", "title": "The impact of metformin with or without lifestyle modification versus placebo on polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials", "authors": "Melin J, Forslund M, Alesi S et al.", "journal": "European journal of endocrinology", "year": 2023, "pmid": "37536294", "url": "https://pubmed.ncbi.nlm.nih.gov/37536294/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/ejendo/lvad098", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37536294/", "publicSourceType": "PMID" }, { "text": "Grammer EE, Stahl ME, Ortiz de Zevallos J et al.. 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Schizophrenia bulletin. 2025", "claim": "PubMed-indexed evidence involving Metformin", "title": "The Optimal Dosage and Duration of Metformin for Prevention and Treatment of Antipsychotic-Induced Weight Gain: An Updated Systematic Review and Meta-Analysis", "authors": "Peng TR, Chen JA, Lee JA et al.", "journal": "Schizophrenia bulletin", "year": 2025, "pmid": "39509416", "url": "https://pubmed.ncbi.nlm.nih.gov/39509416/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/schbul/sbae173", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39509416/", "publicSourceType": "PMID" }, { "text": "Huh MD, Le SN, O'Brien KS et al.. Potential Efficacy of Metformin for Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis. 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Cureus. 2024", "claim": "PubMed-indexed evidence involving Glipizide", "title": "A Review on Affordable Combinations in Type 2 Diabetes Care: Exploring the Cost-Effective Potential of Glipizide + Metformin and Glimepiride + Metformin + Pioglitazone", "authors": "Shaikh S, Vaidya V, Gupta A et al.", "journal": "Cureus", "year": 2024, "pmid": "38854289", "url": "https://pubmed.ncbi.nlm.nih.gov/38854289/", "study_type": "review", "confidence": "verify", "doi": "10.7759/cureus.59850", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38854289/", "publicSourceType": "PMID" }, { "text": "Kradjan WA, Witt DM, Opheim KE et al.. Lack of interaction between glipizide and co-trimoxazole. 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Einstein (Sao Paulo, Brazil). 2022", "claim": "PubMed-indexed evidence involving Glyburide", "title": "Metformin versus glyburide in treatment and control of gestational diabetes mellitus: a systematic review with meta-analysis", "authors": "Oliveira MM, Andrade KFO, Lima GHS et al.", "journal": "Einstein (Sao Paulo, Brazil)", "year": 2022, "pmid": "35195193", "url": "https://pubmed.ncbi.nlm.nih.gov/35195193/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.31744/einstein_journal/2022RW6155", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35195193/", "publicSourceType": "PMID" }, { "text": "Feng X, Zhang T, Wang N et al.. Safety and efficacy of glibenclamide on cerebral oedema following aneurysmal subarachnoid haemorrhage: a randomised, double-blind, placebo-controlled clinical trial. Stroke and vascular neurology. 2024", "claim": "PubMed-indexed evidence involving Glyburide", "title": "Safety and efficacy of glibenclamide on cerebral oedema following aneurysmal subarachnoid haemorrhage: a randomised, double-blind, placebo-controlled clinical trial", "authors": "Feng X, Zhang T, Wang N et al.", "journal": "Stroke and vascular neurology", "year": 2024, "pmid": "38191184", "url": "https://pubmed.ncbi.nlm.nih.gov/38191184/", "study_type": "RCT", "confidence": "verify", "doi": "10.1136/svn-2023-002892", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38191184/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Sulfonylurea (second generation)", "blackBoxWarnings": [ "Increased cardiovascular mortality: The UGDP study reported increased cardiovascular mortality with the sulfonylurea tolbutamide. 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GUIDE study: double-blind comparison of once-daily glimepiride and glipizide in type 2 diabetes. Eur J Clin Invest. 2004;34(8):535-542.", "pmid": "15305887", "doi": "10.1111/j.1365-2362.2004.01381.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15305887/", "publicSourceType": "PMID" }, { "text": "American Diabetes Association. Standards of Medical Care in Diabetes, 2022. Diabetes Care. 2022;45(Suppl 1):S1-S264.", "pmid": "34964831", "doi": "10.2337/dc22-Sint", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34964831/", "publicSourceType": "PMID" }, { "text": "Gao H et al. Evaluation of three mechanisms of action (SGLT2 inhibitors, GLP-1 receptor agonists, and sulfonylureas) in treating type 2 diabetes with heart failure: a systematic review and network meta-analysis of RCTs. Front Endocrinol (Lausanne). 2025.", "pmid": "40556828", "doi": "10.3389/fendo.2025.1562815", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40556828/", "publicSourceType": "PMID" }, { "text": "Rosenstock J, Kahn SE, Johansen OE et al.. Effect of Linagliptin vs Glimepiride on Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes: The CAROLINA Randomized Clinical Trial. JAMA. 2019", "pmid": "31536101", "doi": "10.1001/jama.2019.13772", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31536101/", "publicSourceType": "PMID" }, { "text": "Nauck M, Frid A, Hermansen K et al.. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes care. 2009", "pmid": "18931095", "doi": "10.2337/dc08-1355", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18931095/", "publicSourceType": "PMID" }, { "text": "Bansal R, Kant R, Bahurupi Y et al.. Efficacy and Safety of Gliclazide versus Glimepiride in T2DM Patients: A Systematic Review. Indian journal of endocrinology and metabolism. 2025", "claim": "PubMed-indexed evidence involving Glimepiride", "title": "Efficacy and Safety of Gliclazide versus Glimepiride in T2DM Patients: A Systematic Review", "authors": "Bansal R, Kant R, Bahurupi Y et al.", "journal": "Indian journal of endocrinology and metabolism", "year": 2025, "pmid": "40688616", "url": "https://pubmed.ncbi.nlm.nih.gov/40688616/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.4103/ijem.ijem_372_24", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40688616/", "publicSourceType": "PMID" }, { "text": "Azhar M, Alasmari MS, Zamir A et al.. The Clinical Pharmacokinetics and Pharmacodynamics of Glimepiride-A Systematic Review and Meta-Analysis. Pharmaceuticals (Basel, Switzerland). 2025", "claim": "PubMed-indexed evidence involving Glimepiride", "title": "The Clinical Pharmacokinetics and Pharmacodynamics of Glimepiride-A Systematic Review and Meta-Analysis", "authors": "Azhar M, Alasmari MS, Zamir A et al.", "journal": "Pharmaceuticals (Basel, Switzerland)", "year": 2025, "pmid": "39861183", "url": "https://pubmed.ncbi.nlm.nih.gov/39861183/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/ph18010122", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39861183/", "publicSourceType": "PMID" }, { "text": "Cho YK, Cho JH, Hong SM et al.. Efficacy and safety of pioglitazone, empagliflozin and glimepiride as third-line agents in patients with type 2 diabetes inadequately controlled with metformin and DPP-4 inhibitors: A multicentre, phase 4 randomized controlled trial. Diabetes, obesity & metabolism. 2025", "claim": "PubMed-indexed evidence involving Glimepiride", "title": "Efficacy and safety of pioglitazone, empagliflozin and glimepiride as third-line agents in patients with type 2 diabetes inadequately controlled with metformin and DPP-4 inhibitors: A multicentre, phase 4 randomized controlled trial", "authors": "Cho YK, Cho JH, Hong SM et al.", "journal": "Diabetes, obesity & metabolism", "year": 2025, "pmid": "40808546", "url": "https://pubmed.ncbi.nlm.nih.gov/40808546/", "study_type": "RCT", "confidence": "verify", "doi": "10.1111/dom.70030", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40808546/", "publicSourceType": "PMID" }, { "text": "Nauck M, Frid A, Hermansen K et al.. Long-term efficacy and safety comparison of liraglutide, glimepiride and placebo, all in combination with metformin in type 2 diabetes: 2-year results from the LEAD-2 study. Diabetes, obesity & metabolism. 2013", "claim": "PubMed-indexed evidence involving Glimepiride", "title": "Long-term efficacy and safety comparison of liraglutide, glimepiride and placebo, all in combination with metformin in type 2 diabetes: 2-year results from the LEAD-2 study", "authors": "Nauck M, Frid A, Hermansen K et al.", "journal": "Diabetes, obesity & metabolism", "year": 2013, "pmid": "22985213", "url": "https://pubmed.ncbi.nlm.nih.gov/22985213/", "study_type": "RCT", "confidence": "verify", "doi": "10.1111/dom.12012", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22985213/", "publicSourceType": "PMID" }, { "text": "Sahay R, Gangwani D, Singh M et al.. Fixed dose combination of dapagliflozin, glimepiride and extended-release metformin tablets in patients with type 2 diabetes poorly controlled by metformin and glimepiride: A phase III, open label, randomized clinical study in India. 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Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care. 2006;29(12):2632-2637.", "pmid": "17130196", "doi": "10.2337/dc06-0703", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17130196/", "publicSourceType": "PMID" }, { "text": "Wu Y et al. Efficacy and safety of anti-prediabetic drugs in patients with prediabetes: a Bayesian network meta-analysis. BMC Med. 2026.", "pmid": "41715123", "doi": "10.1186/s12916-026-04705-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41715123/", "publicSourceType": "PMID" }, { "text": "Singh AK, Das AK, Murthy LS et al.. Efficacy of Dapagliflozin + Sitagliptin + Metformin Versus Sitagliptin + Metformin in T2DM Inadequately Controlled on Metformin Monotherapy: A Multicentric Randomized Trial. Advances in therapy. 2025", "pmid": "39636567", "doi": "10.1007/s12325-024-03037-y", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39636567/", "publicSourceType": "PMID" }, { "text": "Seino Y, Terauchi Y, Osonoi T et al.. Safety and efficacy of semaglutide once weekly vs sitagliptin once daily, both as monotherapy in Japanese people with type 2 diabetes. Diabetes, obesity & metabolism. 2018", "pmid": "28786547", "doi": "10.1111/dom.13082", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28786547/", "publicSourceType": "PMID" }, { "text": "Zhang Y, Cai T, Zhao J et al.. Effects and Safety of Sitagliptin in Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. 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Endocrinology, diabetes & metabolism. 2026", "claim": "PubMed-indexed evidence involving Sitagliptin", "title": "Glycaemic and Cardiometabolic Outcomes of Empagliflozin Versus Sitagliptin Added to Metformin in T2DM: Insights From a Systematic Review and Meta-Analysis", "authors": "Ashraf S, Burhan M, Sarwar S et al.", "journal": "Endocrinology, diabetes & metabolism", "year": 2026, "pmid": "42120997", "url": "https://pubmed.ncbi.nlm.nih.gov/42120997/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/edm2.70238", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/42120997/", "publicSourceType": "PMID" }, { "text": "Hong EG, Min KW, Chun S et al.. Efficacy and safety of lobeglitazone added to metformin and sitagliptin combination therapy in patients with type 2 diabetes: A 52-week, multicentre, randomized, placebo-controlled, phase III clinical trial. Diabetes, obesity & metabolism. 2025", "claim": "PubMed-indexed evidence involving Sitagliptin", "title": "Efficacy and safety of lobeglitazone added to metformin and sitagliptin combination therapy in patients with type 2 diabetes: A 52-week, multicentre, randomized, placebo-controlled, phase III clinical trial", "authors": "Hong EG, Min KW, Chun S et al.", "journal": "Diabetes, obesity & metabolism", "year": 2025, "pmid": "40726438", "url": "https://pubmed.ncbi.nlm.nih.gov/40726438/", "study_type": "RCT", "confidence": "verify", "doi": "10.1111/dom.16625", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40726438/", "publicSourceType": "PMID" }, { "text": "Gerrald KR, Van Scoyoc E, Wines RC et al.. Saxagliptin and sitagliptin in adult patients with type 2 diabetes: a systematic review and meta-analysis. Diabetes, obesity & metabolism. 2012", "claim": "PubMed-indexed evidence involving Sitagliptin", "title": "Saxagliptin and sitagliptin in adult patients with type 2 diabetes: a systematic review and meta-analysis", "authors": "Gerrald KR, Van Scoyoc E, Wines RC et al.", "journal": "Diabetes, obesity & metabolism", "year": 2012, "pmid": "22098472", "url": "https://pubmed.ncbi.nlm.nih.gov/22098472/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/j.1463-1326.2011.01540.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22098472/", "publicSourceType": "PMID" }, { "text": "Du Q, Wu B, Wang YJ et al.. Comparative effects of sitagliptin and metformin in patients with type 2 diabetes mellitus: a meta-analysis. Current medical research and opinion. 2013", "claim": "PubMed-indexed evidence involving Sitagliptin", "title": "Comparative effects of sitagliptin and metformin in patients with type 2 diabetes mellitus: a meta-analysis", "authors": "Du Q, Wu B, Wang YJ et al.", "journal": "Current medical research and opinion", "year": 2013, "pmid": "23927568", "url": "https://pubmed.ncbi.nlm.nih.gov/23927568/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1185/03007995.2013.833090", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23927568/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "DPP-4 Inhibitor (Dipeptidyl Peptidase-4 Inhibitor)", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "12.4 hours", "onsetOfAction": "Within 24 hours of first dose; steady state in 3 days", "commonBrandNames": [ "Januvia" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "HbA1c every 3–6 months. 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Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk (CARMELINA). JAMA. 2019;321(1):69-79.", "pmid": "30418475", "doi": "10.1001/jama.2018.18269", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30418475/", "publicSourceType": "PMID" }, { "text": "Del Prato S et al. Efficacy and safety of linagliptin in subjects with type 2 diabetes mellitus and poor glycemic control: pooled analysis. Diabetes Obes Metab. 2013;15(11):1046-1055.", "pmid": "28921919", "doi": "10.1111/dom.12143", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28921919/", "publicSourceType": "PMID" }, { "text": "Ortiz-Seller A et al. Dipeptidyl peptidase-4 inhibitors and diabetic retinopathy in type 2 diabetes: A network meta-analysis of randomized clinical trials. J Diabetes Complications. 2026.", "pmid": "41314124", "doi": "10.1016/j.jdiacomp.2025.109234", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41314124/", "publicSourceType": "PMID" }, { "text": "Gomes GKA, de Camargos Ramos AI, de Sousa CT et al.. Linagliptin safety profile: A systematic review. Primary care diabetes. 2018", "pmid": "29853297", "doi": "10.1016/j.pcd.2018.04.006", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29853297/", "publicSourceType": "PMID" }, { "text": "Hong JH, Kim MJ, Min KW et al.. Efficacy and safety of a fixed-dose combination of dapagliflozin and linagliptin (AJU-A51) in patients with type 2 diabetes mellitus: A multicentre, randomized, double-blind, parallel-group, placebo-controlled phase III study. 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Minerva endocrinology. 2024", "claim": "PubMed-indexed evidence involving Linagliptin", "title": "The effectiveness and safety of linagliptin within elderly type 2 diabetes mellitus: a meta-analysis and systematic review", "authors": "Wang MJ, Liu JL, Wang N et al.", "journal": "Minerva endocrinology", "year": 2024, "pmid": "35103456", "url": "https://pubmed.ncbi.nlm.nih.gov/35103456/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.23736/S2724-6507.22.03661-2", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35103456/", "publicSourceType": "PMID" }, { "text": "Panda PS, Mohapatra I, Padhee S et al.. Renoprotective Action of Linagliptin Among Diabetic Kidney Disease Patients: A Systematic Review and Meta-Analysis. 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Safety of Empagliflozin: An Individual Participant-Level Data Meta-Analysis from Four Large Trials. Advances in therapy. 2024", "pmid": "38771475", "doi": "10.1007/s12325-024-02879-w", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38771475/", "publicSourceType": "PMID" }, { "text": "Lava SAG, Laurence C, Di Deo A et al.. Dapagliflozin and Empagliflozin in Paediatric Indications: A Systematic Review. Paediatric drugs. 2024", "pmid": "38635113", "doi": "10.1007/s40272-024-00623-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38635113/", "publicSourceType": "PMID" }, { "text": "Matteucci A, Pandozi C, Bonanni M et al.. Impact of empagliflozin and dapagliflozin on sudden cardiac death: A systematic review and meta-analysis of adjudicated randomized evidence. Heart rhythm. 2025", "claim": "PubMed-indexed evidence involving Empagliflozin", "title": "Impact of empagliflozin and dapagliflozin on sudden cardiac death: A systematic review and meta-analysis of adjudicated randomized evidence", "authors": "Matteucci A, Pandozi C, Bonanni M et al.", "journal": "Heart rhythm", "year": 2025, "pmid": "40972782", "url": "https://pubmed.ncbi.nlm.nih.gov/40972782/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.hrthm.2025.09.023", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40972782/", "publicSourceType": "PMID" }, { "text": "Khalid N, Afzal MA, Abdullah M et al.. Efficacy and safety of empagliflozin in acute heart failure: a systematic review and meta-analysis. Future cardiology. 2025", "claim": "PubMed-indexed evidence involving Empagliflozin", "title": "Efficacy and safety of empagliflozin in acute heart failure: a systematic review and meta-analysis", "authors": "Khalid N, Afzal MA, Abdullah M et al.", "journal": "Future cardiology", "year": 2025, "pmid": "40324865", "url": "https://pubmed.ncbi.nlm.nih.gov/40324865/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/14796678.2025.2499374", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40324865/", "publicSourceType": "PMID" }, { "text": "Saleem T, Rasool MF, Saeed H et al.. Exploring the clinical pharmacokinetics and pharmacodynamics of SGLT2 inhibitor, empagliflozin: a systematic review. 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Therapeutic advances in cardiovascular disease. 2024", "claim": "PubMed-indexed evidence involving Empagliflozin", "title": "Empagliflozin and other SGLT2 inhibitors in patients with heart failure and preserved ejection fraction: a systematic review and meta-analysis", "authors": "Hamid AK, Tayem AA, Al-Aish ST et al.", "journal": "Therapeutic advances in cardiovascular disease", "year": 2024, "pmid": "39400108", "url": "https://pubmed.ncbi.nlm.nih.gov/39400108/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/17539447241289067", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39400108/", "publicSourceType": "PMID" }, { "text": "Yan Q, Chen X, Yu C et al.. Long-term surrogate cardiovascular outcomes of SGLT2 inhibitor empagliflozin in chronic heart failure: a systematic review and meta-analysis. 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Dapagliflozin in patients with heart failure and reduced ejection fraction (DAPA-HF). N Engl J Med. 2019;381(21):1995-2008.", "pmid": "31535829", "doi": "10.1056/NEJMoa1911303", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31535829/", "publicSourceType": "PMID" }, { "text": "Heerspink HJL et al. Dapagliflozin in patients with chronic kidney disease (DAPA-CKD). N Engl J Med. 2020;383(15):1436-1446.", "pmid": "32970396", "doi": "10.1056/NEJMoa2024816", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32970396/", "publicSourceType": "PMID" }, { "text": "Wiviott SD et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes (DECLARE-TIMI 58). N Engl J Med. 2019;380(4):347-357.", "pmid": "30415602", "doi": "10.1056/NEJMoa1812389", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30415602/", "publicSourceType": "PMID" }, { "text": "Berg DD, Patel SM, Haller PM et al.. Dapagliflozin in Patients Hospitalized for Heart Failure: Primary Results of the DAPA ACT HF-TIMI 68 Randomized Clinical Trial and Meta-Analysis of Sodium-Glucose Cotransporter-2 Inhibitors in Patients Hospitalized for Heart Failure. Circulation. 2025", "pmid": "40884036", "doi": "10.1161/CIRCULATIONAHA.125.076575", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40884036/", "publicSourceType": "PMID" }, { "text": "Lava SAG, Laurence C, Di Deo A et al.. Dapagliflozin and Empagliflozin in Paediatric Indications: A Systematic Review. Paediatric drugs. 2024", "pmid": "38635113", "doi": "10.1007/s40272-024-00623-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38635113/", "publicSourceType": "PMID" }, { "text": "Raja A, Dogar ME, Raja S et al.. Dapagliflozin in acute heart failure management: a systematic review and meta-analysis of safety and effectiveness. BMC cardiovascular disorders. 2024", "claim": "PubMed-indexed evidence involving Dapagliflozin", "title": "Dapagliflozin in acute heart failure management: a systematic review and meta-analysis of safety and effectiveness", "authors": "Raja A, Dogar ME, Raja S et al.", "journal": "BMC cardiovascular disorders", "year": 2024, "pmid": "39731023", "url": "https://pubmed.ncbi.nlm.nih.gov/39731023/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12872-024-04412-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39731023/", "publicSourceType": "PMID" }, { "text": "Addo B, Agyeman W, Ibrahim S et al.. Dapagliflozin in Heart Failure: A Comprehensive Meta-analysis on Functional Capacity, Symptoms, and Safety Outcomes. American journal of cardiovascular drugs : drugs, devices, and other interventions. 2024", "claim": "PubMed-indexed evidence involving Dapagliflozin", "title": "Dapagliflozin in Heart Failure: A Comprehensive Meta-analysis on Functional Capacity, Symptoms, and Safety Outcomes", "authors": "Addo B, Agyeman W, Ibrahim S et al.", "journal": "American journal of cardiovascular drugs : drugs, devices, and other interventions", "year": 2024, "pmid": "39261443", "url": "https://pubmed.ncbi.nlm.nih.gov/39261443/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s40256-024-00669-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39261443/", "publicSourceType": "PMID" }, { "text": "Dahal K, Rawal L, Shah S et al.. Efficacy and outcomes of dapagliflozin in diabetic nephropathy: A systematic review and meta-analysis. Medicine. 2025", "claim": "PubMed-indexed evidence involving Dapagliflozin", "title": "Efficacy and outcomes of dapagliflozin in diabetic nephropathy: A systematic review and meta-analysis", "authors": "Dahal K, Rawal L, Shah S et al.", "journal": "Medicine", "year": 2025, "pmid": "40629621", "url": "https://pubmed.ncbi.nlm.nih.gov/40629621/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MD.0000000000043171", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40629621/", "publicSourceType": "PMID" }, { "text": "Ali AE, Mazroua MS, ElSaban M et al.. Effect of Dapagliflozin in Patients with Heart Failure: A Systematic Review and Meta-Analysis. Global heart. 2023", "claim": "PubMed-indexed evidence involving Dapagliflozin", "title": "Effect of Dapagliflozin in Patients with Heart Failure: A Systematic Review and Meta-Analysis", "authors": "Ali AE, Mazroua MS, ElSaban M et al.", "journal": "Global heart", "year": 2023, "pmid": "37636033", "url": "https://pubmed.ncbi.nlm.nih.gov/37636033/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.5334/gh.1258", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37636033/", "publicSourceType": "PMID" }, { "text": "Iyer N, Hussein S, Singareddy S et al.. Sotagliflozin vs Dapagliflozin: A Systematic Review Comparing Cardiovascular Mortality. Cureus. 2023", "claim": "PubMed-indexed evidence involving Dapagliflozin", "title": "Sotagliflozin vs Dapagliflozin: A Systematic Review Comparing Cardiovascular Mortality", "authors": "Iyer N, Hussein S, Singareddy S et al.", "journal": "Cureus", "year": 2023, "pmid": "37868384", "url": "https://pubmed.ncbi.nlm.nih.gov/37868384/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7759/cureus.45525", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37868384/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "SGLT2 Inhibitor (Sodium-Glucose Cotransporter 2 Inhibitor)", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "12.9 hours", "onsetOfAction": "Glycosuria within 2 hours of dosing; steady-state glucose lowering by 1 week", "commonBrandNames": [ "Farxiga" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "HbA1c every 3–6 months. eGFR at baseline and periodically. 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N Engl J Med. 2017;377(7):644-657.", "pmid": "28605608", "doi": "10.1056/NEJMoa1611925", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28605608/", "publicSourceType": "PMID" }, { "text": "Perkovic V et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy (CREDENCE). N Engl J Med. 2019;380(24):2295-2306.", "pmid": "30990260", "doi": "10.1056/NEJMoa1811744", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30990260/", "publicSourceType": "PMID" }, { "text": "Sridharan K et al. Safety Profile of SGLT-2 Inhibitors in Older Adults: A Systematic Review and Network Meta-Analysis. Med Sci (Basel). 2026.", "pmid": "41892868", "doi": "10.3390/medsci14010153", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41892868/", "publicSourceType": "PMID" }, { "text": "Johnston R, Uthman O, Cummins E et al.. Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation. Health technology assessment (Winchester, England). 2017", "pmid": "28105986", "doi": "10.3310/hta21020", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28105986/", "publicSourceType": "PMID" }, { "text": "Spertus JA, Birmingham MC, Nassif M et al.. The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial. Nature medicine. 2022", "pmid": "35228753", "doi": "10.1038/s41591-022-01703-8", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35228753/", "publicSourceType": "PMID" }, { "text": "Patel S, Gohel K, Patel BG. A Systematic Review on Effect of Canagliflozin in Special Population. Current diabetes reviews. 2016", "claim": "PubMed-indexed evidence involving Canagliflozin", "title": "A Systematic Review on Effect of Canagliflozin in Special Population", "authors": "Patel S, Gohel K, Patel BG", "journal": "Current diabetes reviews", "year": 2016, "pmid": "26084476", "url": "https://pubmed.ncbi.nlm.nih.gov/26084476/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2174/1573399811666150618143948", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26084476/", "publicSourceType": "PMID" }, { "text": "Yi TW, Smyth B, Di Tanna GL et al.. Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2023", "claim": "PubMed-indexed evidence involving Canagliflozin", "title": "Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial", "authors": "Yi TW, Smyth B, Di Tanna GL et al.", "journal": "American journal of kidney diseases : the official journal of the National Kidney Foundation", "year": 2023, "pmid": "36889425", "url": "https://pubmed.ncbi.nlm.nih.gov/36889425/", "study_type": "RCT", "confidence": "verify", "doi": "10.1053/j.ajkd.2022.12.015", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36889425/", "publicSourceType": "PMID" }, { "text": "Jakher H, Chang TI, Tan M et al.. Canagliflozin review - safety and efficacy profile in patients with T2DM. Diabetes, metabolic syndrome and obesity : targets and therapy. 2019", "claim": "PubMed-indexed evidence involving Canagliflozin", "title": "Canagliflozin review - safety and efficacy profile in patients with T2DM", "authors": "Jakher H, Chang TI, Tan M et al.", "journal": "Diabetes, metabolic syndrome and obesity : targets and therapy", "year": 2019, "pmid": "30787627", "url": "https://pubmed.ncbi.nlm.nih.gov/30787627/", "study_type": "review", "confidence": "verify", "doi": "10.2147/DMSO.S184437", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30787627/", "publicSourceType": "PMID" }, { "text": "Nguyen TN, Yu J, Perkovic V et al.. The Efficacy and Safety of Canagliflozin by Frailty Status in Participants of the CANVAS and CREDENCE Trials. Journal of the American Geriatrics Society. 2025", "claim": "PubMed-indexed evidence involving Canagliflozin", "title": "The Efficacy and Safety of Canagliflozin by Frailty Status in Participants of the CANVAS and CREDENCE Trials", "authors": "Nguyen TN, Yu J, Perkovic V et al.", "journal": "Journal of the American Geriatrics Society", "year": 2025, "pmid": "40105285", "url": "https://pubmed.ncbi.nlm.nih.gov/40105285/", "study_type": "RCT", "confidence": "verify", "doi": "10.1111/jgs.19444", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40105285/", "publicSourceType": "PMID" }, { "text": "Elmore LK, Baggett S, Kyle JA et al.. A review of the efficacy and safety of canagliflozin in elderly patients with type 2 diabetes. The Consultant pharmacist : the journal of the American Society of Consultant Pharmacists. 2014", "claim": "PubMed-indexed evidence involving Canagliflozin", "title": "A review of the efficacy and safety of canagliflozin in elderly patients with type 2 diabetes", "authors": "Elmore LK, Baggett S, Kyle JA et al.", "journal": "The Consultant pharmacist : the journal of the American Society of Consultant Pharmacists", "year": 2014, "pmid": "24849690", "url": "https://pubmed.ncbi.nlm.nih.gov/24849690/", "study_type": "review", "confidence": "verify", "doi": "10.4140/TCP.n.2014.335", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24849690/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "SGLT2 Inhibitor (Sodium-Glucose Cotransporter 2 Inhibitor)", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "10.6–13.1 hours", "onsetOfAction": "Glycosuria within hours of first dose; glucose-lowering steady state by 1–2 weeks", "commonBrandNames": [ "Invokana" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "HbA1c every 3–6 months. eGFR at baseline and periodically. Serum potassium, lipids, and volume status. Monitor feet for wounds, ulcers, or infection. Monitor for ketoacidosis symptoms." }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "canagliflozin" }, { "id": "RX-ENDO-010", "name": "Semaglutide", "alternateNames": [ "Ozempic", "Wegovy", "Rybelsus" ], "category": "Prescription", "subcategory": "GLP-1 Receptor Agonist", "overview": "Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist available as a once-weekly injection (Ozempic for diabetes, Wegovy for obesity) and as a daily oral tablet (Rybelsus for diabetes). It produces superior HbA1c reduction and significant weight loss compared to most other antidiabetic agents. The SUSTAIN and STEP trial programs demonstrated robust glycemic, weight, and cardiovascular benefits.", "mechanismOfAction": "A modified GLP-1 analogue with 94% homology to native GLP-1 that binds to and activates the GLP-1 receptor. 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Semaglutide and cardiovascular outcomes in patients with type 2 diabetes (SUSTAIN-6). N Engl J Med. 2016;375(19):1834-1844.", "pmid": "27633186", "doi": "10.1056/NEJMoa1607141", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27633186/", "publicSourceType": "PMID" }, { "text": "Wilding JPH et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1). N Engl J Med. 2021;384(11):989-1002.", "pmid": "33567185", "doi": "10.1056/NEJMoa2032183", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33567185/", "publicSourceType": "PMID" }, { "text": "Husain M et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes (PIONEER 6). N Engl J Med. 2019;381(9):841-851.", "pmid": "31185157", "doi": "10.1056/NEJMoa1901118", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31185157/", "publicSourceType": "PMID" }, { "text": "Moiz A, Levett JY, Filion KB et al.. Long-Term Efficacy and Safety of Once-Weekly Semaglutide for Weight Loss in Patients Without Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. The American journal of cardiology. 2024", "pmid": "38679221", "doi": "10.1016/j.amjcard.2024.04.041", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38679221/", "publicSourceType": "PMID" }, { "text": "Tan HC, Dampil OA, Marquez MM. Efficacy and Safety of Semaglutide for Weight Loss in Obesity Without Diabetes: A Systematic Review and Meta-Analysis. Journal of the ASEAN Federation of Endocrine Societies. 2022", "pmid": "36578889", "doi": "10.15605/jafes.037.02.14", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36578889/", "publicSourceType": "PMID" }, { "claim": "Semaglutide reduces cardiovascular events in patients with obesity (SELECT trial)", "title": "Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes", "authors": "Lincoff AM, Brown-Frandsen K, Colhoun HM, Deanfield J et al.", "journal": "The New England Journal of Medicine", "year": 2023, "pmid": "37952131", "url": "https://pubmed.ncbi.nlm.nih.gov/37952131/", "study_type": "rct", "key_finding": "In the SELECT trial, once-weekly semaglutide 2.4mg significantly reduced major adverse cardiovascular events by 20% in patients with overweight/obesity and established cardiovascular disease but without diabetes", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37952131/", "publicSourceType": "PMID" }, { "claim": "Semaglutide is effective for sustained weight loss (STEP 4 trial)", "title": "Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial", "authors": "Rubino D, Abrahamsson N, Davies M, Hesse D et al.", "journal": "JAMA", "year": 2021, "pmid": "33755728", "url": "https://pubmed.ncbi.nlm.nih.gov/33755728/", "study_type": "rct", "key_finding": "Continued treatment with semaglutide 2.4mg resulted in additional weight loss (mean -7.9% from randomization), while placebo group regained weight, demonstrating sustained efficacy for weight management", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33755728/", "publicSourceType": "PMID" }, { "claim": "Semaglutide is superior to liraglutide for weight loss (STEP 8 trial)", "title": "Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial", "authors": "Rubino DM, Greenway FL, Khalid U, O'Neil PM et al.", "journal": "JAMA", "year": 2022, "pmid": "35015037", "url": "https://pubmed.ncbi.nlm.nih.gov/35015037/", "study_type": "rct", "key_finding": "Semaglutide 2.4mg weekly produced significantly greater weight loss (-15.8%) compared to liraglutide 3.0mg daily (-6.4%) at 68 weeks in adults with overweight or obesity without diabetes", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35015037/", "publicSourceType": "PMID" }, { "text": "Safwan M, Bourgleh MS, Alotaibi SA et al.. Gastrointestinal safety of semaglutide and tirzepatide vs. placebo in obese individuals without diabetes: a systematic review and meta analysis. Annals of Saudi medicine. 2025", "claim": "PubMed-indexed evidence involving Semaglutide", "title": "Gastrointestinal safety of semaglutide and tirzepatide vs. placebo in obese individuals without diabetes: a systematic review and meta analysis", "authors": "Safwan M, Bourgleh MS, Alotaibi SA et al.", "journal": "Annals of Saudi medicine", "year": 2025, "pmid": "40189856", "url": "https://pubmed.ncbi.nlm.nih.gov/40189856/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.5144/0256-4947.2025.129", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40189856/", "publicSourceType": "PMID" }, { "text": "Kommu S, Berg RL. Efficacy and safety of once-weekly subcutaneous semaglutide on weight loss in patients with overweight or obesity without diabetes mellitus-A systematic review and meta-analysis of randomized controlled trials. Obesity reviews : an official journal of the International Association for the Study of Obesity. 2024", "claim": "PubMed-indexed evidence involving Semaglutide", "title": "Efficacy and safety of once-weekly subcutaneous semaglutide on weight loss in patients with overweight or obesity without diabetes mellitus-A systematic review and meta-analysis of randomized controlled trials", "authors": "Kommu S, Berg RL", "journal": "Obesity reviews : an official journal of the International Association for the Study of Obesity", "year": 2024, "pmid": "38923272", "url": "https://pubmed.ncbi.nlm.nih.gov/38923272/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/obr.13792", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38923272/", "publicSourceType": "PMID" }, { "text": "Cleto AS, Schirlo JM, Beltrame M et al.. Semaglutide effects on safety and cardiovascular outcomes in patients with overweight or obesity: a systematic review and meta-analysis. International journal of obesity (2005). 2025", "claim": "PubMed-indexed evidence involving Semaglutide", "title": "Semaglutide effects on safety and cardiovascular outcomes in patients with overweight or obesity: a systematic review and meta-analysis", "authors": "Cleto AS, Schirlo JM, Beltrame M et al.", "journal": "International journal of obesity (2005)", "year": 2025, "pmid": "39396098", "url": "https://pubmed.ncbi.nlm.nih.gov/39396098/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1038/s41366-024-01646-9", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39396098/", "publicSourceType": "PMID" }, { "text": "Singh A, Singh AK, Singh R et al.. Comparative efficacy and safety of semaglutide 2.4 mg and tirzepatide 5-15 mg in obesity with or without type 2 diabetes: A systematic review of Phase 3 clinical trials. Diabetes & metabolic syndrome. 2025", "claim": "PubMed-indexed evidence involving Semaglutide", "title": "Comparative efficacy and safety of semaglutide 2.4 mg and tirzepatide 5-15 mg in obesity with or without type 2 diabetes: A systematic review of Phase 3 clinical trials", "authors": "Singh A, Singh AK, Singh R et al.", "journal": "Diabetes & metabolic syndrome", "year": 2025, "pmid": "40086043", "url": "https://pubmed.ncbi.nlm.nih.gov/40086043/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.dsx.2025.103212", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40086043/", "publicSourceType": "PMID" }, { "text": "Natividade GR, Spiazzi BF, Baumgarten MW et al.. Ocular Adverse Events With Semaglutide: A Systematic Review and Meta-Analysis. JAMA ophthalmology. 2025", "claim": "PubMed-indexed evidence involving Semaglutide", "title": "Ocular Adverse Events With Semaglutide: A Systematic Review and Meta-Analysis", "authors": "Natividade GR, Spiazzi BF, Baumgarten MW et al.", "journal": "JAMA ophthalmology", "year": 2025, "pmid": "40810985", "url": "https://pubmed.ncbi.nlm.nih.gov/40810985/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1001/jamaophthalmol.2025.2489", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40810985/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "GLP-1 Receptor Agonist (Incretin Mimetic)", "blackBoxWarnings": [ "Thyroid C-cell tumors: In rodents, semaglutide causes dose-dependent thyroid C-cell tumors. It is unknown whether semaglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans. 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Ren Fail. 2026.", "pmid": "41644273", "doi": "10.1080/0886022X.2026.2620155", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41644273/", "publicSourceType": "PMID" }, { "claim": "Liraglutide reduces renal adverse outcomes in type 2 diabetes", "title": "Liraglutide and Renal Outcomes in Type 2 Diabetes", "authors": "Mann JFE, Ørsted DD, Brown-Frandsen K, Marso SP et al.", "journal": "The New England Journal of Medicine", "year": 2017, "pmid": "28854085", "url": "https://pubmed.ncbi.nlm.nih.gov/28854085/", "study_type": "rct", "key_finding": "Liraglutide significantly reduced the risk of nephropathy events (new-onset macroalbuminuria, doubling of serum creatinine, renal replacement therapy, or renal death) by 22% in the LEADER trial", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28854085/", "publicSourceType": "PMID" }, { "claim": "Liraglutide is effective for weight management in adolescents with obesity", "title": "A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity", "authors": "Kelly AS, Auerbach P, Barrientos-Perez M, Gies I et al.", "journal": "The New England Journal of Medicine", "year": 2020, "pmid": "32233338", "url": "https://pubmed.ncbi.nlm.nih.gov/32233338/", "study_type": "rct", "key_finding": "Liraglutide 3.0mg daily plus lifestyle therapy resulted in significantly greater BMI reduction (-5.01%) compared to placebo (+0.44%) in adolescents aged 12-17 with obesity over 56 weeks", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32233338/", "publicSourceType": "PMID" }, { "text": "Xie Z, Yang S, Deng W et al.. Efficacy and Safety of Liraglutide and Semaglutide on Weight Loss in People with Obesity or Overweight: A Systematic Review. Clinical epidemiology. 2022", "claim": "PubMed-indexed evidence involving Liraglutide", "title": "Efficacy and Safety of Liraglutide and Semaglutide on Weight Loss in People with Obesity or Overweight: A Systematic Review", "authors": "Xie Z, Yang S, Deng W et al.", "journal": "Clinical epidemiology", "year": 2022, "pmid": "36510488", "url": "https://pubmed.ncbi.nlm.nih.gov/36510488/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2147/CLEP.S391819", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36510488/", "publicSourceType": "PMID" }, { "text": "Patel JP, Hardaswani D, Patel J et al.. Comparative Effectiveness of Semaglutide, Liraglutide, Orlistat, and Phentermine for Weight Loss in Obese Individuals: A Systematic Review. 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Lancet. 2019;394(10193):121-130.", "pmid": "31189511", "doi": "10.1016/S0140-6736(19)31149-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31189511/", "publicSourceType": "PMID" }, { "text": "Dungan KM et al. Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6). Lancet. 2014;384(9951):1349-1357.", "pmid": "25018121", "doi": "10.1016/S0140-6736(14)60976-4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25018121/", "publicSourceType": "PMID" }, { "text": "Lin PY et al. Divergent Risks of Hematologic Malignancies Associated with GLP-1 Receptor Agonists and SGLT2 Inhibitors: Preliminary Findings from a Pilot Network Meta-Analysis. Biomolecules. 2025.", "pmid": "41301540", "doi": "10.3390/biom15111622", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41301540/", "publicSourceType": "PMID" }, { "text": "Nicholls SJ, Bhatt DL, Buse JB et al.. Comparison of tirzepatide and dulaglutide on major adverse cardiovascular events in participants with type 2 diabetes and atherosclerotic cardiovascular disease: SURPASS-CVOT design and baseline characteristics. American heart journal. 2024", "pmid": "37758044", "doi": "10.1016/j.ahj.2023.09.007", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37758044/", "publicSourceType": "PMID" }, { "text": "Nicholls SJ, Pavo I, Bhatt DL et al.. Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes. The New England journal of medicine. 2025", "pmid": "41406444", "doi": "10.1056/NEJMoa2505928", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41406444/", "publicSourceType": "PMID" }, { "text": "Karimi MA, Gholami Chahkand MS, Dadkhah PA et al.. Comparative effectiveness of semaglutide versus liraglutide, dulaglutide or tirzepatide: a systematic review and meta-analysis. Frontiers in pharmacology. 2025", "claim": "PubMed-indexed evidence involving Dulaglutide", "title": "Comparative effectiveness of semaglutide versus liraglutide, dulaglutide or tirzepatide: a systematic review and meta-analysis", "authors": "Karimi MA, Gholami Chahkand MS, Dadkhah PA et al.", "journal": "Frontiers in pharmacology", "year": 2025, "pmid": "40444045", "url": "https://pubmed.ncbi.nlm.nih.gov/40444045/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fphar.2025.1438318", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40444045/", "publicSourceType": "PMID" }, { "text": "Frias JP, Bonora E, Nevarez Ruiz L et al.. Efficacy and Safety of Dulaglutide 3.0 mg and 4.5 mg Versus Dulaglutide 1.5 mg in Metformin-Treated Patients With Type 2 Diabetes in a Randomized Controlled Trial (AWARD-11). Diabetes care. 2021", "claim": "PubMed-indexed evidence involving Dulaglutide", "title": "Efficacy and Safety of Dulaglutide 3.0 mg and 4.5 mg Versus Dulaglutide 1.5 mg in Metformin-Treated Patients With Type 2 Diabetes in a Randomized Controlled Trial (AWARD-11)", "authors": "Frias JP, Bonora E, Nevarez Ruiz L et al.", "journal": "Diabetes care", "year": 2021, "pmid": "33397768", "url": "https://pubmed.ncbi.nlm.nih.gov/33397768/", "study_type": "RCT", "confidence": "verify", "doi": "10.2337/dc20-1473", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33397768/", "publicSourceType": "PMID" }, { "text": "Billings LK, Winne L, Sharma P et al.. Comparison of Dose Escalation Versus Switching to Tirzepatide Among People With Type 2 Diabetes Inadequately Controlled on Lower Doses of Dulaglutide : A Randomized Clinical Trial. Annals of internal medicine. 2025", "claim": "PubMed-indexed evidence involving Dulaglutide", "title": "Comparison of Dose Escalation Versus Switching to Tirzepatide Among People With Type 2 Diabetes Inadequately Controlled on Lower Doses of Dulaglutide : A Randomized Clinical Trial", "authors": "Billings LK, Winne L, Sharma P et al.", "journal": "Annals of internal medicine", "year": 2025, "pmid": "40183678", "url": "https://pubmed.ncbi.nlm.nih.gov/40183678/", "study_type": "RCT", "confidence": "verify", "doi": "10.7326/ANNALS-24-03849", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40183678/", "publicSourceType": "PMID" }, { "text": "Takahashi Y, Nomoto H, Yokoyama H et al.. Improvement of glycaemic control and treatment satisfaction by switching from liraglutide or dulaglutide to subcutaneous semaglutide in patients with type 2 diabetes: A multicentre, prospective, randomized, open-label, parallel-group comparison study (SWITCH-SEMA 1 study). 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Effects of a Dulaglutide plus Calorie-Restricted Diet versus a Calorie-Restricted Diet on Visceral Fat and Metabolic Profiles in Women with Polycystic Ovary Syndrome: A Randomized Controlled Trial. 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Rotate injection sites to prevent lipodystrophy." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Hypoglycemia (most significant risk)", "Weight gain", "Injection site reactions (lipodystrophy, pain, redness)", "Peripheral edema (early treatment)", "Allergic reactions (rare)", "Hypokalemia" ], "contraindications": [ "Hypoglycemia episodes", "Known hypersensitivity to insulin glargine or excipients", "Use during episodes of hypoglycemia" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "diabetes", "insulin", "basal-insulin", "blood-sugar", "injectable", "type-1", "type-2" ], "sources": [ { "text": "Riddle MC et al. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care. 2003;26(11):3080-3086.", "pmid": "14578243", "doi": "10.2337/diacare.26.11.3080", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14578243/", "publicSourceType": "PMID" }, { "text": "ORIGIN Trial Investigators. Basal insulin and cardiovascular and other outcomes in dysglycemia (ORIGIN). N Engl J Med. 2012;367(4):319-328.", "pmid": "22686416", "doi": "10.1056/NEJMoa1203858", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22686416/", "publicSourceType": "PMID" }, { "text": "Akmal M et al. Efficacy of once-weekly insulin efsitora versus once-daily basal insulin in type 2 diabetes: A systematic review and meta-analysis. Diabetes Obes Metab. 2026.", "pmid": "41549720", "doi": "10.1111/dom.70399", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41549720/", "publicSourceType": "PMID" }, { "text": "Joshi SR, Singh G, Marwah A et al.. Comparative clinical efficacy and safety of insulin glargine 300 U/ml (Toujeo) versus insulin glargine 100 U/ml in type 2 diabetes and type 1 diabetes: A systematic literature review and meta-analysis. Diabetes, obesity & metabolism. 2023", "pmid": "36748186", "doi": "10.1111/dom.15007", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36748186/", "publicSourceType": "PMID" }, { "text": "Kellerer M, Kaltoft MS, Lawson J et al.. Effect of once-weekly semaglutide versus thrice-daily insulin aspart, both as add-on to metformin and optimized insulin glargine treatment in participants with type 2 diabetes (SUSTAIN 11): A randomized, open-label, multinational, phase 3b trial. Diabetes, obesity & metabolism. 2022", "pmid": "35546450", "doi": "10.1111/dom.14765", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35546450/", "publicSourceType": "PMID" }, { "text": "Pollex E, Moretti ME, Koren G et al.. Safety of insulin glargine use in pregnancy: a systematic review and meta-analysis. The Annals of pharmacotherapy. 2011", "claim": "PubMed-indexed evidence involving Insulin Glargine", "title": "Safety of insulin glargine use in pregnancy: a systematic review and meta-analysis", "authors": "Pollex E, Moretti ME, Koren G et al.", "journal": "The Annals of pharmacotherapy", "year": 2011, "pmid": "21205954", "url": "https://pubmed.ncbi.nlm.nih.gov/21205954/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1345/aph.1P327", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21205954/", "publicSourceType": "PMID" }, { "text": "Andrade-Castellanos CA, Colunga-Lozano LE. [Systematic review with meta-analysis: Subcutaneous insulin glargine coadministration for diabetic ketoacidosis]. Gaceta medica de Mexico. 2016", "claim": "PubMed-indexed evidence involving Insulin Glargine", "title": "[Systematic review with meta-analysis: Subcutaneous insulin glargine coadministration for diabetic ketoacidosis]", "authors": "Andrade-Castellanos CA, Colunga-Lozano LE", "journal": "Gaceta medica de Mexico", "year": 2016, "pmid": "27861474", "url": "https://pubmed.ncbi.nlm.nih.gov/27861474/", "study_type": "meta-analysis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27861474/", "publicSourceType": "PMID" }, { "text": "Björck Linné A, Liedholm H. [Insulin glargine--a systematic review of clinical studies. No documented advantages with Lantus compared to NPH insulin]. Lakartidningen. 2004", "claim": "PubMed-indexed evidence involving Insulin Glargine", "title": "[Insulin glargine--a systematic review of clinical studies. No documented advantages with Lantus compared to NPH insulin]", "authors": "Björck Linné A, Liedholm H", "journal": "Lakartidningen", "year": 2004, "pmid": "15314935", "url": "https://pubmed.ncbi.nlm.nih.gov/15314935/", "study_type": "meta-analysis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15314935/", "publicSourceType": "PMID" }, { "text": "Warren E, Weatherley-Jones E, Chilcott J et al.. Systematic review and economic evaluation of a long-acting insulin analogue, insulin glargine. Health technology assessment (Winchester, England). 2004", "claim": "PubMed-indexed evidence involving Insulin Glargine", "title": "Systematic review and economic evaluation of a long-acting insulin analogue, insulin glargine", "authors": "Warren E, Weatherley-Jones E, Chilcott J et al.", "journal": "Health technology assessment (Winchester, England)", "year": 2004, "pmid": "15525480", "url": "https://pubmed.ncbi.nlm.nih.gov/15525480/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3310/hta8450", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15525480/", "publicSourceType": "PMID" }, { "text": "Wang F, Carabino JM, Vergara CM. Insulin glargine: a systematic review of a long-acting insulin analogue. Clinical therapeutics. 2003", "claim": "PubMed-indexed evidence involving Insulin Glargine", "title": "Insulin glargine: a systematic review of a long-acting insulin analogue", "authors": "Wang F, Carabino JM, Vergara CM", "journal": "Clinical therapeutics", "year": 2003, "pmid": "12860485", "url": "https://pubmed.ncbi.nlm.nih.gov/12860485/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/s0149-2918(03)80156-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12860485/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Long-Acting Insulin Analogue", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "No distinct half-life due to depot absorption; duration of action ~24 hours (Lantus/Basaglar) or ~36 hours (Toujeo)", "onsetOfAction": "1–2 hours; no pronounced peak; duration 20–26 hours", "commonBrandNames": [ "Lantus", "Basaglar", "Toujeo", "Semglee" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "HbA1c every 3–6 months. Fasting and self-monitored blood glucose regularly. Serum potassium periodically. Renal and hepatic function (dose adjustments may be needed). Hypoglycemia awareness assessment." }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "insulin-glargine" }, { "id": "RX-ENDO-014", "name": "Insulin Lispro", "alternateNames": [ "Humalog", "Admelog", "Lyumjev" ], "category": "Prescription", "subcategory": "Rapid-Acting Insulin", "overview": "Insulin lispro is a rapid-acting insulin analogue used for mealtime (prandial) glycemic control in type 1 and type 2 diabetes. It has a faster onset and shorter duration than regular human insulin, allowing administration immediately before or after meals. It is commonly used in basal-bolus regimens and insulin pump therapy.", "mechanismOfAction": "A recombinant insulin analogue where the amino acids proline and lysine at positions B28 and B29 are reversed compared to native insulin. This modification reduces self-association and accelerates absorption from the subcutaneous depot. Once absorbed, it acts identically to endogenous insulin, binding insulin receptors, activating the PI3K-Akt signaling cascade, promoting GLUT4 translocation, and facilitating cellular glucose uptake.", "commonBenefits": [ "Rapid onset allows injection at mealtime (within 15 minutes of eating)", "Better postprandial glucose control vs regular insulin", "Shorter duration reduces risk of late postprandial hypoglycemia", "Flexible timing around meals", "Compatible with insulin pump therapy" ], "commonDosageRange": "0.5–1.0 units/kg/day total insulin (prandial portion divided across meals, typically 50–60% of total daily dose); individualized (as prescribed by your physician)", "recommendedForm": "Subcutaneous injection (vial, pre-filled pen, or insulin pump)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Inject within 15 minutes before or immediately after meals. Rotate injection sites. Do not mix with insulin glargine or detemir." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Hypoglycemia", "Weight gain", "Injection site reactions (lipodystrophy, redness)", "Hypokalemia", "Allergic reactions (rare)", "Peripheral edema" ], "contraindications": [ "During episodes of hypoglycemia", "Known hypersensitivity to insulin lispro or excipients" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "diabetes", "insulin", "rapid-acting", "mealtime", "blood-sugar", "injectable", "pump-compatible" ], "sources": [ { "text": "Anderson JH Jr et al. Mealtime treatment with insulin analog improves postprandial hyperglycemia and hypoglycemia in patients with non-insulin-dependent diabetes mellitus. Arch Intern Med. 1997;157(11):1249-1255.", "pmid": "9183237", "doi": "10.1001/archinte.1997.00440320157015", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9183237/", "publicSourceType": "PMID" }, { "text": "Heller SR et al. Insulin lispro: a useful advance in insulin therapy. Expert Opin Pharmacother. 2004;5(4):917-933.", "pmid": "12877647", "doi": "10.1517/14656566.5.4.917", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12877647/", "publicSourceType": "PMID" }, { "text": "Rakab MS et al. Ultra-rapid lispro or fast-acting aspart compared to standard insulin lispro and aspart using closed-loop insulin therapy: a systematic review and meta-analysis of randomized control trials. Front Endocrinol (Lausanne). 2025.", "pmid": "40547532", "doi": "10.3389/fendo.2025.1600157", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40547532/", "publicSourceType": "PMID" }, { "text": "Rosenstock J, Frías JP, Rodbard HW et al.. Tirzepatide vs Insulin Lispro Added to Basal Insulin in Type 2 Diabetes: The SURPASS-6 Randomized Clinical Trial. JAMA. 2023", "pmid": "37786396", "doi": "10.1001/jama.2023.20294", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37786396/", "publicSourceType": "PMID" }, { "text": "Muzaffer Z, Iqbal A, Ristic S. Insulin lispro--a review. JPMA. The Journal of the Pakistan Medical Association. 1998", "pmid": "10067027", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10067027/", "publicSourceType": "PMID" }, { "text": "Brunelle BL, Llewelyn J, Anderson JH Jr et al.. Meta-analysis of the effect of insulin lispro on severe hypoglycemia in patients with type 1 diabetes. Diabetes care. 1998", "claim": "PubMed-indexed evidence involving Insulin Lispro", "title": "Meta-analysis of the effect of insulin lispro on severe hypoglycemia in patients with type 1 diabetes", "authors": "Brunelle BL, Llewelyn J, Anderson JH Jr et al.", "journal": "Diabetes care", "year": 1998, "pmid": "9773738", "url": "https://pubmed.ncbi.nlm.nih.gov/9773738/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2337/diacare.21.10.1726", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9773738/", "publicSourceType": "PMID" }, { "text": "Davey P, Grainger D, MacMillan J et al.. Clinical outcomes with insulin lispro compared with human regular insulin: a meta-analysis. Clinical therapeutics. 1997", "claim": "PubMed-indexed evidence involving Insulin Lispro", "title": "Clinical outcomes with insulin lispro compared with human regular insulin: a meta-analysis", "authors": "Davey P, Grainger D, MacMillan J et al.", "journal": "Clinical therapeutics", "year": 1997, "pmid": "9377611", "url": "https://pubmed.ncbi.nlm.nih.gov/9377611/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/s0149-2918(97)80091-4", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9377611/", "publicSourceType": "PMID" }, { "text": "Kazda C, Leohr J, Liu R et al.. Ultra rapid lispro (URLi) shows accelerated pharmacokinetics and greater reduction in postprandial glucose versus Humalog® in patients with type 1 diabetes mellitus in a randomized, double-blind meal test early-phase study. Diabetes, obesity & metabolism. 2022", "claim": "PubMed-indexed evidence involving Insulin Lispro", "title": "Ultra rapid lispro (URLi) shows accelerated pharmacokinetics and greater reduction in postprandial glucose versus Humalog® in patients with type 1 diabetes mellitus in a randomized, double-blind meal test early-phase study", "authors": "Kazda C, Leohr J, Liu R et al.", "journal": "Diabetes, obesity & metabolism", "year": 2022, "pmid": "34595812", "url": "https://pubmed.ncbi.nlm.nih.gov/34595812/", "study_type": "RCT", "confidence": "verify", "doi": "10.1111/dom.14563", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34595812/", "publicSourceType": "PMID" }, { "text": "Leohr J, Kazda C, Liu R et al.. Ultra-rapid lispro shows faster pharmacokinetics and reduces postprandial glucose excursions versus Humalog® in patients with type 2 diabetes mellitus in a randomized, controlled crossover meal test early phase study. Diabetes, obesity & metabolism. 2022", "claim": "PubMed-indexed evidence involving Insulin Lispro", "title": "Ultra-rapid lispro shows faster pharmacokinetics and reduces postprandial glucose excursions versus Humalog® in patients with type 2 diabetes mellitus in a randomized, controlled crossover meal test early phase study", "authors": "Leohr J, Kazda C, Liu R et al.", "journal": "Diabetes, obesity & metabolism", "year": 2022, "pmid": "34605142", "url": "https://pubmed.ncbi.nlm.nih.gov/34605142/", "study_type": "RCT", "confidence": "verify", "doi": "10.1111/dom.14561", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34605142/", "publicSourceType": "PMID" }, { "text": "Zafar MI, Ai X, Shafqat RA et al.. Effectiveness and safety of Humalog Mix 50/50 versus Humalog Mix 75/25 in Chinese patients with type 2 diabetes. Therapeutics and clinical risk management. 2015", "claim": "PubMed-indexed evidence involving Insulin Lispro", "title": "Effectiveness and safety of Humalog Mix 50/50 versus Humalog Mix 75/25 in Chinese patients with type 2 diabetes", "authors": "Zafar MI, Ai X, Shafqat RA et al.", "journal": "Therapeutics and clinical risk management", "year": 2015, "pmid": "25565854", "url": "https://pubmed.ncbi.nlm.nih.gov/25565854/", "study_type": "review", "confidence": "verify", "doi": "10.2147/TCRM.S75602", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25565854/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Rapid-Acting Insulin Analogue", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "1 hour (plasma)", "onsetOfAction": "15–30 minutes; peak at 30–90 minutes; duration 3–5 hours", "commonBrandNames": [ "Humalog", "Admelog", "Lyumjev" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "HbA1c every 3–6 months. Frequent self-monitored blood glucose (pre-meal and post-meal). Serum potassium periodically. Continuous glucose monitoring recommended when available." }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "insulin-lispro" }, { "id": "RX-ENDO-015", "name": "Insulin Aspart", "alternateNames": [ "NovoLog", "Fiasp", "NovoRapid" ], "category": "Prescription", "subcategory": "Rapid-Acting Insulin", "overview": "Insulin aspart is a rapid-acting insulin analogue for prandial glucose control in type 1 and type 2 diabetes. Fiasp (faster-acting insulin aspart) includes niacinamide and L-arginine to further accelerate absorption. Insulin aspart is widely used in basal-bolus regimens and insulin pump therapy.", "mechanismOfAction": "A recombinant insulin analogue where proline at position B28 is replaced by aspartic acid, reducing hexamer formation and accelerating subcutaneous absorption. Once in the bloodstream, it binds insulin receptors and activates the same intracellular signaling cascade as endogenous insulin, promoting glucose uptake, glycogen synthesis, and lipogenesis while inhibiting gluconeogenesis and glycogenolysis.", "commonBenefits": [ "Rapid onset (15–20 minutes) for mealtime coverage", "Improved postprandial glucose control vs regular insulin", "Shorter duration reduces late hypoglycemia", "Compatible with insulin pump therapy", "Fiasp formulation offers even faster onset" ], "commonDosageRange": "Individualized; typically 0.3–0.5 units per 10–15 g carbohydrate or based on insulin-to-carb ratio (as prescribed by your physician)", "recommendedForm": "Subcutaneous injection (vial, FlexPen, or insulin pump)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Inject 5–10 minutes before meals (NovoLog) or at the start of a meal or within 20 minutes of starting (Fiasp). Rotate injection sites." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Hypoglycemia", "Weight gain", "Injection site reactions", "Lipodystrophy", "Hypokalemia", "Allergic reactions (rare)" ], "contraindications": [ "During episodes of hypoglycemia", "Known hypersensitivity to insulin aspart or excipients" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "diabetes", "insulin", "rapid-acting", "mealtime", "blood-sugar", "injectable", "pump-compatible" ], "sources": [ { "text": "Home PD et al. Improved glycaemic control with insulin aspart: a multicentre randomized double-blind crossover trial in type 1 diabetic patients. Diabetes Care. 1998;21(11):1904-1909.", "pmid": "9802740", "doi": "10.2337/diacare.21.11.1904", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9802740/", "publicSourceType": "PMID" }, { "text": "Russell-Jones D et al. Fast-acting insulin aspart improves glycemic control in basal-bolus treatment for type 1 diabetes: results of a 26-week multicenter, active-controlled, treat-to-target, randomized, parallel-group trial (onset 1). Diabetes Care. 2017;40(7):943-950.", "pmid": "29316130", "doi": "10.2337/dc16-1771", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29316130/", "publicSourceType": "PMID" }, { "text": "Rakab MS et al. Ultra-rapid lispro or fast-acting aspart compared to standard insulin lispro and aspart using closed-loop insulin therapy: a systematic review and meta-analysis of randomized control trials. Front Endocrinol (Lausanne). 2025.", "pmid": "40547532", "doi": "10.3389/fendo.2025.1600157", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40547532/", "publicSourceType": "PMID" }, { "text": "Kellerer M, Kaltoft MS, Lawson J et al.. Effect of once-weekly semaglutide versus thrice-daily insulin aspart, both as add-on to metformin and optimized insulin glargine treatment in participants with type 2 diabetes (SUSTAIN 11): A randomized, open-label, multinational, phase 3b trial. Diabetes, obesity & metabolism. 2022", "pmid": "35546450", "doi": "10.1111/dom.14765", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35546450/", "publicSourceType": "PMID" }, { "text": "Karonova TL, Mayorov AY, Magruk MA et al.. Safety and efficacy of GP40071 compared with originator insulin aspart (NovoRapid(®) Penfill(®)) in Type 1 diabetes mellitus. Journal of comparative effectiveness research. 2021", "pmid": "33928797", "doi": "10.2217/cer-2020-0208", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33928797/", "publicSourceType": "PMID" }, { "text": "Edina BC, Tandaju JR, Wiyono L. Efficacy and Safety of Insulin Degludec/Insulin Aspart (IDegAsp) in Type 2 Diabetes: Systematic Review and Meta-Analysis. Cureus. 2022", "claim": "PubMed-indexed evidence involving Insulin Aspart", "title": "Efficacy and Safety of Insulin Degludec/Insulin Aspart (IDegAsp) in Type 2 Diabetes: Systematic Review and Meta-Analysis", "authors": "Edina BC, Tandaju JR, Wiyono L", "journal": "Cureus", "year": 2022, "pmid": "35784980", "url": "https://pubmed.ncbi.nlm.nih.gov/35784980/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7759/cureus.25612", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35784980/", "publicSourceType": "PMID" }, { "text": "Wei J, Wang Y. Effectiveness of Faster Aspart versus Insulin Aspart in Children with Type 1 Diabetes: A Meta-Analysis. Iranian journal of public health. 2024", "claim": "PubMed-indexed evidence involving Insulin Aspart", "title": "Effectiveness of Faster Aspart versus Insulin Aspart in Children with Type 1 Diabetes: A Meta-Analysis", "authors": "Wei J, Wang Y", "journal": "Iranian journal of public health", "year": 2024, "pmid": "38694849", "url": "https://pubmed.ncbi.nlm.nih.gov/38694849/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.18502/ijph.v53i1.14680", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38694849/", "publicSourceType": "PMID" }, { "text": "Dongre SA, Kulkarni GA, Mishra A et al.. Efficacy, safety, and immunogenicity of recombinant insulin aspart (BioGenomics Limited) and NovoRapid(®) (Novo Nordisk) in adults with type 2 diabetes mellitus: a randomized, open-label, multicenter, phase-3 study. Research in pharmaceutical sciences. 2024", "claim": "PubMed-indexed evidence involving Insulin Aspart", "title": "Efficacy, safety, and immunogenicity of recombinant insulin aspart (BioGenomics Limited) and NovoRapid(®) (Novo Nordisk) in adults with type 2 diabetes mellitus: a randomized, open-label, multicenter, phase-3 study", "authors": "Dongre SA, Kulkarni GA, Mishra A et al.", "journal": "Research in pharmaceutical sciences", "year": 2024, "pmid": "39691304", "url": "https://pubmed.ncbi.nlm.nih.gov/39691304/", "study_type": "RCT", "confidence": "verify", "doi": "10.4103/RPS.RPS_188_23", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39691304/", "publicSourceType": "PMID" }, { "text": "Valentine WJ, Pollock RF, Plun-Favreau J et al.. Systematic review of the cost-effectiveness of biphasic insulin aspart 30 in type 2 diabetes. Current medical research and opinion. 2010", "claim": "PubMed-indexed evidence involving Insulin Aspart", "title": "Systematic review of the cost-effectiveness of biphasic insulin aspart 30 in type 2 diabetes", "authors": "Valentine WJ, Pollock RF, Plun-Favreau J et al.", "journal": "Current medical research and opinion", "year": 2010, "pmid": "20387997", "url": "https://pubmed.ncbi.nlm.nih.gov/20387997/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1185/03007991003689381", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20387997/", "publicSourceType": "PMID" }, { "text": "Yao J, Guo X, Sun L et al.. Comparative efficacy and safety of two insulin aspart formulations (Rapilin and NovoRapid) when combined with metformin, for patients with diabetes mellitus: a multicenter, randomized, open-label, controlled clinical trial. Current medical research and opinion. 2022", "claim": "PubMed-indexed evidence involving Insulin Aspart", "title": "Comparative efficacy and safety of two insulin aspart formulations (Rapilin and NovoRapid) when combined with metformin, for patients with diabetes mellitus: a multicenter, randomized, open-label, controlled clinical trial", "authors": "Yao J, Guo X, Sun L et al.", "journal": "Current medical research and opinion", "year": 2022, "pmid": "35833285", "url": "https://pubmed.ncbi.nlm.nih.gov/35833285/", "study_type": "RCT", "confidence": "verify", "doi": "10.1080/03007995.2022.2100652", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35833285/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Rapid-Acting Insulin Analogue", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "81 minutes (plasma)", "onsetOfAction": "10–20 minutes; peak at 40–50 minutes; duration 3–5 hours. Fiasp: onset ~2.5 minutes faster", "commonBrandNames": [ "NovoLog", "Fiasp", "NovoRapid" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "HbA1c every 3–6 months. Frequent self-monitored blood glucose (pre-meal, post-meal, bedtime). Serum potassium periodically. Continuous glucose monitoring recommended when available." }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "insulin-aspart" }, { "id": "RX-ENDO-016", "name": "Levothyroxine", "alternateNames": [ "Synthroid", "Levoxyl", "Tirosint", "Unithroid", "Euthyrox" ], "category": "Prescription", "subcategory": "Thyroid Hormone", "overview": "Levothyroxine (synthetic T4) is the standard treatment for hypothyroidism and is one of the most prescribed medications worldwide. It replaces or supplements deficient thyroid hormone, restoring normal metabolic function. It is also used for thyroid-stimulating hormone (TSH) suppression in thyroid cancer management. Consistent daily dosing on an empty stomach is essential for reliable absorption.", "mechanismOfAction": "Synthetic thyroxine (T4) that is peripherally converted to the active hormone triiodothyronine (T3) by deiodinase enzymes. T3 binds to nuclear thyroid hormone receptors, forming a complex that activates gene transcription involved in protein synthesis, oxygen consumption, basal metabolic rate regulation, carbohydrate and lipid metabolism, and growth and development.", "commonBenefits": [ "Restores normal thyroid hormone levels in hypothyroidism", "Resolves symptoms of hypothyroidism (fatigue, weight gain, cold intolerance, cognitive sluggishness)", "Normalizes TSH levels", "TSH suppression in thyroid cancer management", "Well-established safety profile with decades of use", "Inexpensive generic formulations available" ], "commonDosageRange": "25–200 mcg daily; typical full replacement 1.6 mcg/kg/day (as prescribed by your physician)", "recommendedForm": "Oral tablet; soft gel capsule (Tirosint) for patients with absorption issues", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Take on an empty stomach 30–60 minutes before breakfast, or at bedtime 3+ hours after the last meal. Avoid calcium, iron, antacids, and coffee within 4 hours as they impair absorption. Consistency is critical." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Signs of overreplacement: tachycardia, palpitations, tremor, anxiety, insomnia, heat intolerance", "Weight loss (if over-replaced)", "Headache", "Hair loss (transient, usually early in treatment)", "Bone density loss with chronic excessive dosing", "Angina or arrhythmia in susceptible patients" ], "contraindications": [ "Untreated adrenal insufficiency (must replace cortisol first to avoid adrenal crisis)", "Acute myocardial infarction (unless hypothyroidism is a complicating factor)", "Uncorrected thyrotoxicosis", "Known hypersensitivity to levothyroxine or excipients" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "thyroid", "hypothyroidism", "hormone-replacement", "metabolism", "essential" ], "sources": [ { "text": "Jonklaas J et al. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement. Thyroid. 2014;24(12):1670-1751.", "pmid": "25266247", "doi": "10.1089/thy.2014.0028", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25266247/", "publicSourceType": "PMID" }, { "text": "Garber JR et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid. 2012;22(12):1200-1235.", "pmid": "22954017", "doi": "10.1089/thy.2012.0205", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22954017/", "publicSourceType": "PMID" }, { "text": "Biondi B, Wartofsky L. Combination treatment with T4 and T3: toward personalized replacement therapy in hypothyroidism? J Clin Endocrinol Metab. 2012;97(7):2256-2271.", "pmid": "22593590", "doi": "10.1210/jc.2011-3399", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22593590/", "publicSourceType": "PMID" }, { "text": "Wiesner A, Gajewska D, Paśko P. Levothyroxine Interactions with Food and Dietary Supplements-A Systematic Review. Pharmaceuticals (Basel, Switzerland). 2021", "pmid": "33801406", "doi": "10.3390/ph14030206", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33801406/", "publicSourceType": "PMID" }, { "text": "Skelin M, Lucijanić T, Amidžić Klarić D et al.. Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review. Clinical therapeutics. 2017", "pmid": "28153426", "doi": "10.1016/j.clinthera.2017.01.005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28153426/", "publicSourceType": "PMID" }, { "claim": "Levothyroxine improves fertility and pregnancy outcomes in subclinical hypothyroidism", "title": "Effects of Levothyroxine Treatment on Fertility and Pregnancy Outcomes in Subclinical Hypothyroidism: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Sankoda A, Suzuki H, Imaizumi M, Yoshihara A et al.", "journal": "Thyroid", "year": 2024, "pmid": "38368537", "url": "https://pubmed.ncbi.nlm.nih.gov/38368537/", "study_type": "meta-analysis", "key_finding": "Levothyroxine treatment in women with subclinical hypothyroidism was associated with improved pregnancy rates and reduced miscarriage rates in this meta-analysis of RCTs", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38368537/", "publicSourceType": "PMID" }, { "claim": "Levothyroxine may improve blood pressure in subclinical hypothyroidism", "title": "Systematic review and meta-analysis of levothyroxine effect on blood pressure in patients with subclinical hypothyroidism", "authors": "Darouei B, Amani-Beni R, Abhari AP, Fakhrolmobasheri M et al.", "journal": "Current Problems in Cardiology", "year": 2024, "pmid": "37967804", "url": "https://pubmed.ncbi.nlm.nih.gov/37967804/", "study_type": "meta-analysis", "key_finding": "Levothyroxine treatment in subclinical hypothyroidism was associated with modest but significant reductions in both systolic and diastolic blood pressure", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37967804/", "publicSourceType": "PMID" }, { "claim": "Levothyroxine treatment decisions in subclinical hypothyroidism require individualized approach", "title": "Treating hypothyroidism is not always easy: When to treat subclinical hypothyroidism, TSH goals in the elderly, and alternatives to levothyroxine monotherapy", "authors": "Ross DS", "journal": "Journal of Internal Medicine", "year": 2022, "pmid": "34766382", "url": "https://pubmed.ncbi.nlm.nih.gov/34766382/", "study_type": "review", "key_finding": "Treatment of subclinical hypothyroidism with levothyroxine should be individualized based on TSH level, age, symptoms, and comorbidities; combination therapy with liothyronine may benefit some patients", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34766382/", "publicSourceType": "PMID" }, { "text": "Provinciatto H, Moreira MVB, Neves GR et al.. Levothyroxine for subclinical hypothyroidism during pregnancy: an updated systematic review and meta-analysis of randomized controlled trials. Archives of gynecology and obstetrics. 2024", "claim": "PubMed-indexed evidence involving Levothyroxine", "title": "Levothyroxine for subclinical hypothyroidism during pregnancy: an updated systematic review and meta-analysis of randomized controlled trials", "authors": "Provinciatto H, Moreira MVB, Neves GR et al.", "journal": "Archives of gynecology and obstetrics", "year": 2024, "pmid": "38676741", "url": "https://pubmed.ncbi.nlm.nih.gov/38676741/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00404-024-07512-3", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38676741/", "publicSourceType": "PMID" }, { "text": "Holley M, Razvi S, Farooq MS et al.. Cardiovascular and bone health outcomes in older people with subclinical hypothyroidism treated with levothyroxine: a systematic review and meta-analysis. Systematic reviews. 2024", "claim": "PubMed-indexed evidence involving Levothyroxine", "title": "Cardiovascular and bone health outcomes in older people with subclinical hypothyroidism treated with levothyroxine: a systematic review and meta-analysis", "authors": "Holley M, Razvi S, Farooq MS et al.", "journal": "Systematic reviews", "year": 2024, "pmid": "38720372", "url": "https://pubmed.ncbi.nlm.nih.gov/38720372/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s13643-024-02548-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38720372/", "publicSourceType": "PMID" }, { "text": "Vargas-Uricoechea H, Wartofsky L. LT4/LT3 Combination Therapy vs. Monotherapy with LT4 for Persistent Symptoms of Hypothyroidism: A Systematic Review. 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Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document. Thyroid : official journal of the American Thyroid Association. 2021", "pmid": "33276704", "doi": "10.1089/thy.2020.0720", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33276704/", "publicSourceType": "PMID" }, { "text": "Bahl S, Taylor PN, Premawardhana LD et al.. Risk of Death and Adverse Effects in Patients on Liothyronine: A Multisource Systematic Review and Meta-analysis. 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Comparison of the safety between propylthiouracil and methimazole with hyperthyroidism in pregnancy: A systematic review and meta-analysis. PloS one. 2023", "pmid": "37205692", "doi": "10.1371/journal.pone.0286097", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37205692/", "publicSourceType": "PMID" }, { "text": "Lee SY, Modzelewski KL, Law AC et al.. Comparison of Propylthiouracil vs Methimazole for Thyroid Storm in Critically Ill Patients. JAMA network open. 2023", "pmid": "37067797", "doi": "10.1001/jamanetworkopen.2023.8655", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37067797/", "publicSourceType": "PMID" }, { "text": "Hackmon R, Blichowski M, Koren G. The safety of methimazole and propylthiouracil in pregnancy: a systematic review. 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Sao Paulo medical journal = Revista paulista de medicina. 2023", "claim": "PubMed-indexed evidence involving Methimazole", "title": "Efficacy of methimazole before the administration of radioactive iodine in the management of Graves' disease: a systematic review and meta-analysis", "authors": "Bolakale-Rufai IK, Abioro I, Ngene SO et al.", "journal": "Sao Paulo medical journal = Revista paulista de medicina", "year": 2023, "pmid": "36629663", "url": "https://pubmed.ncbi.nlm.nih.gov/36629663/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1590/1516-3180.2022.0225.R1.19102022", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36629663/", "publicSourceType": "PMID" }, { "text": "Wu X, Qin X, Yao Y. Methimazole plus levothyroxine for treating hyperthyroidism in children: a systematic review and meta-analysis. Translational pediatrics. 2022", "claim": "PubMed-indexed evidence involving Methimazole", "title": "Methimazole plus levothyroxine for treating hyperthyroidism in children: a systematic review and meta-analysis", "authors": "Wu X, Qin X, Yao Y", "journal": "Translational pediatrics", "year": 2022, "pmid": "35242651", "url": "https://pubmed.ncbi.nlm.nih.gov/35242651/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.21037/tp-21-497", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35242651/", "publicSourceType": "PMID" }, { "text": "van Lieshout JM, Mooij CF, van Trotsenburg ASP et al.. Methimazole-induced remission rates in pediatric Graves' disease: a systematic review. European journal of endocrinology. 2021", "claim": "PubMed-indexed evidence involving Methimazole", "title": "Methimazole-induced remission rates in pediatric Graves' disease: a systematic review", "authors": "van Lieshout JM, Mooij CF, van Trotsenburg ASP et al.", "journal": "European journal of endocrinology", "year": 2021, "pmid": "34061770", "url": "https://pubmed.ncbi.nlm.nih.gov/34061770/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1530/EJE-21-0077", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34061770/", "publicSourceType": "PMID" }, { "text": "Xie P, Shen L, Peng R et al.. Effects of Low-dose Methotrexate With Methimazole in Patients With Graves' Disease: Results of a Randomized Clinical Trial. The Journal of clinical endocrinology and metabolism. 2025", "claim": "PubMed-indexed evidence involving Methimazole", "title": "Effects of Low-dose Methotrexate With Methimazole in Patients With Graves' Disease: Results of a Randomized Clinical Trial", "authors": "Xie P, Shen L, Peng R et al.", "journal": "The Journal of clinical endocrinology and metabolism", "year": 2025, "pmid": "38994582", "url": "https://pubmed.ncbi.nlm.nih.gov/38994582/", "study_type": "RCT", "confidence": "verify", "doi": "10.1210/clinem/dgae472", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38994582/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Thioamide Antithyroid Agent", "blackBoxWarnings": [ "Agranulocytosis: Potentially life-threatening agranulocytosis can occur. Patients should be instructed to report symptoms of infection (fever, sore throat) immediately. 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Anti-inflammatory action of glucocorticoids, new mechanisms for old drugs. N Engl J Med. 2005;353(16):1711-1723.", "pmid": "16236742", "doi": "10.1056/NEJMra050541", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16236742/", "publicSourceType": "PMID" }, { "text": "Hoes JN et al. EULAR evidence-based recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases. Ann Rheum Dis. 2007;66(12):1560-1567.", "pmid": "17660219", "doi": "10.1136/ard.2007.072157", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17660219/", "publicSourceType": "PMID" }, { "text": "Chen PH et al. Early intervention for high-risk smoldering multiple myeloma (SMM). Cochrane Database Syst Rev. 2026.", "pmid": "41848424", "doi": "10.1002/14651858.CD015494.pub2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41848424/", "publicSourceType": "PMID" }, { "claim": "Prednisone is effective for acute asthma exacerbations in children", "title": "Dexamethasone versus prednisone/prednisolone in the management of pediatric patients with acute asthmatic exacerbations: a systematic review and meta-analysis.", "authors": "Dahan E, El Ghazal N, Nakanishi H et al.", "journal": "Journal of Asthma", "year": 2023, "pmid": "36461938", "url": "https://pubmed.ncbi.nlm.nih.gov/36461938/", "study_type": "meta-analysis", "key_finding": "Meta-analysis found prednisone/prednisolone and dexamethasone had comparable efficacy for pediatric acute asthma exacerbations, with dexamethasone offering the advantage of shorter treatment duration and better compliance.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36461938/", "publicSourceType": "PMID" }, { "claim": "Glucocorticoids including prednisone cause neuropsychiatric adverse effects", "title": "Neuropsychiatric Adverse Effects of Synthetic Glucocorticoids: A Systematic Review and Meta-Analysis.", "authors": "Koning ACAM, van der Meulen M, Schaap D et al.", "journal": "Journal of Clinical Endocrinology and Metabolism", "year": 2024, "pmid": "38038629", "url": "https://pubmed.ncbi.nlm.nih.gov/38038629/", "study_type": "meta-analysis", "key_finding": "Systematic review found synthetic glucocorticoids including prednisone were significantly associated with neuropsychiatric adverse effects, withmania/hypomania and depression being the most common; risk was dose-dependent and higher in the first weeks of treatment.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38038629/", "publicSourceType": "PMID" }, { "text": "Zulfiqar E, Hurjkaliani S, Umar SA et al.. Comparing intermittent and daily prednisone in duchenne muscular dystrophy: a systematic review and meta-analysis. Annals of medicine and surgery (2012). 2025", "claim": "PubMed-indexed evidence involving Prednisone", "title": "Comparing intermittent and daily prednisone in duchenne muscular dystrophy: a systematic review and meta-analysis", "authors": "Zulfiqar E, Hurjkaliani S, Umar SA et al.", "journal": "Annals of medicine and surgery (2012)", "year": 2025, "pmid": "40213242", "url": "https://pubmed.ncbi.nlm.nih.gov/40213242/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MS9.0000000000003049", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40213242/", "publicSourceType": "PMID" }, { "text": "Gambertoglio JG, Amend WJ Jr, Benet LZ. Pharmacokinetics and bioavailability of prednisone and prednisolone in healthy volunteers and patients: a review. Journal of pharmacokinetics and biopharmaceutics. 1980", "claim": "PubMed-indexed evidence involving Prednisone", "title": "Pharmacokinetics and bioavailability of prednisone and prednisolone in healthy volunteers and patients: a review", "authors": "Gambertoglio JG, Amend WJ Jr, Benet LZ", "journal": "Journal of pharmacokinetics and biopharmaceutics", "year": 1980, "pmid": "6991663", "url": "https://pubmed.ncbi.nlm.nih.gov/6991663/", "study_type": "review", "confidence": "verify", "doi": "10.1007/BF01059447", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6991663/", "publicSourceType": "PMID" }, { "text": "Dalrymple SN, Row JH, Gazewood J. Bell Palsy: Rapid Evidence Review. American family physician. 2023", "claim": "PubMed-indexed evidence on prednisone or systemic glucocorticoid therapy context", "title": "Bell Palsy: Rapid Evidence Review", "authors": "Dalrymple SN, Row JH, Gazewood J", "journal": "American family physician", "year": 2023, "pmid": "37054419", "url": "https://pubmed.ncbi.nlm.nih.gov/37054419/", "study_type": "review", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37054419/", "publicSourceType": "PMID" }, { "text": "Belperio JA, Shaikh F, Abtin FG et al.. Diagnosis and Treatment of Pulmonary Sarcoidosis: A Review. JAMA. 2022", "claim": "PubMed-indexed evidence on prednisone or systemic glucocorticoid therapy context", "title": "Diagnosis and Treatment of Pulmonary Sarcoidosis: A Review", "authors": "Belperio JA, Shaikh F, Abtin FG et al.", "journal": "JAMA", "year": 2022, "pmid": "35230389", "url": "https://pubmed.ncbi.nlm.nih.gov/35230389/", "study_type": "review", "confidence": "verify", "doi": "10.1001/jama.2022.1570", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35230389/", "publicSourceType": "PMID" }, { "text": "Buttgereit F, Dejaco C, Matteson EL et al.. Polymyalgia Rheumatica and Giant Cell Arteritis: A Systematic Review. JAMA. 2016", "claim": "PubMed-indexed evidence on prednisone or systemic glucocorticoid therapy context", "title": "Polymyalgia Rheumatica and Giant Cell Arteritis: A Systematic Review", "authors": "Buttgereit F, Dejaco C, Matteson EL et al.", "journal": "JAMA", "year": 2016, "pmid": "27299619", "url": "https://pubmed.ncbi.nlm.nih.gov/27299619/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1001/jama.2016.5444", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27299619/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Glucocorticoid (Corticosteroid)", "blackBoxWarnings": [], "fdaPregnancyCategory": "C (D in some references for first trimester cleft palate risk)", "halfLife": "2–3 hours (plasma); biological half-life 18–36 hours", "onsetOfAction": "1–2 hours; peak effect in 1–2 days for anti-inflammatory effect", "commonBrandNames": [ "Deltasone", "Rayos" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Blood glucose monitoring (steroid-induced hyperglycemia). 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The glucocorticoid-receptor complex translocates to the nucleus and modulates gene transcription, suppressing pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha, NF-kB) and upregulating anti-inflammatory mediators. Also stabilizes cell membranes, reduces capillary permeability, and suppresses immune cell migration and function.", "commonBenefits": [ "Potent anti-inflammatory and immunosuppressive effects", "Does not require hepatic activation (useful in liver disease)", "Liquid formulations available for pediatric dosing", "Rapid symptom relief", "Well-characterized pharmacology" ], "commonDosageRange": "5–60 mg daily (equivalent to prednisone dosing); pediatric: 0.5–2 mg/kg/day (as prescribed by your physician)", "recommendedForm": "Oral solution (Orapred, Pediapred), oral tablet, or orally disintegrating tablet", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food to minimize GI upset. Liquid formulations can be mixed with a small amount of juice for palatability in children." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Weight gain and increased appetite", "Hyperglycemia", "Mood changes (agitation, insomnia, euphoria)", "Fluid retention and hypertension", "Osteoporosis with long-term use", "Increased susceptibility to infections", "Adrenal suppression", "Growth retardation in children with chronic use" ], "contraindications": [ "Systemic fungal infections", "Known hypersensitivity to prednisolone", "Live vaccine administration during immunosuppressive doses", "Active untreated infections (herpes simplex keratitis, etc.)" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "corticosteroid", "anti-inflammatory", "immunosuppressant", "pediatric" ], "sources": [ { "text": "Czock D et al. Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmacokinet. 2005;44(1):61-98.", "pmid": "15634032", "doi": "10.2165/00003088-200544010-00003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15634032/", "publicSourceType": "PMID" }, { "text": "Liu D et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol. 2013;9(1):30.", "pmid": "24322395", "doi": "10.1186/1710-1492-9-30", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24322395/", "publicSourceType": "PMID" }, { "text": "Tong T et al. The efficacy and safety of budesonide combined with azathioprine versus predniso(lo)ne combined with azathioprine for autoimmune hepatitis: A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol. 2025.", "pmid": "41067493", "doi": "10.1016/j.clinre.2025.102708", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41067493/", "publicSourceType": "PMID" }, { "text": "Dahan E, El Ghazal N, Nakanishi H et al.. Dexamethasone versus prednisone/prednisolone in the management of pediatric patients with acute asthmatic exacerbations: a systematic review and meta-analysis. The Journal of asthma : official journal of the Association for the Care of Asthma. 2023", "pmid": "36461938", "doi": "10.1080/02770903.2022.2155189", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36461938/", "publicSourceType": "PMID" }, { "text": "KhalafAllah MT, Basiony A, Salama A. Difluprednate versus Prednisolone Acetate after Cataract Surgery: a Systematic Review and Meta-Analysis. BMJ open. 2019", "claim": "PubMed-indexed evidence involving Prednisolone", "title": "Difluprednate versus Prednisolone Acetate after Cataract Surgery: a Systematic Review and Meta-Analysis", "authors": "KhalafAllah MT, Basiony A, Salama A", "journal": "BMJ open", "year": 2019, "pmid": "31678934", "url": "https://pubmed.ncbi.nlm.nih.gov/31678934/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1136/bmjopen-2018-026752", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31678934/", "publicSourceType": "PMID" }, { "text": "Kwak SG, Choo YJ, Chang MC. Effectiveness of prednisolone in complex regional pain syndrome treatment: A systematic narrative review. Pain practice : the official journal of World Institute of Pain. 2022", "claim": "PubMed-indexed evidence involving Prednisolone", "title": "Effectiveness of prednisolone in complex regional pain syndrome treatment: A systematic narrative review", "authors": "Kwak SG, Choo YJ, Chang MC", "journal": "Pain practice : the official journal of World Institute of Pain", "year": 2022, "pmid": "34779145", "url": "https://pubmed.ncbi.nlm.nih.gov/34779145/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/papr.13090", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34779145/", "publicSourceType": "PMID" }, { "text": "Gilchrist FJ, Ahmad AN, Batchelor HK et al.. A review of prednisolone prescribing for children with acute asthma in the UK. The Journal of asthma : official journal of the Association for the Care of Asthma. 2016", "claim": "PubMed-indexed evidence involving Prednisolone", "title": "A review of prednisolone prescribing for children with acute asthma in the UK", "authors": "Gilchrist FJ, Ahmad AN, Batchelor HK et al.", "journal": "The Journal of asthma : official journal of the Association for the Care of Asthma", "year": 2016, "pmid": "27043745", "url": "https://pubmed.ncbi.nlm.nih.gov/27043745/", "study_type": "review", "confidence": "verify", "doi": "10.3109/02770903.2015.1118498", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27043745/", "publicSourceType": "PMID" }, { "text": "Hosseini N, Shor J, Szabo G. Alcoholic Hepatitis: A Review. Alcohol and alcoholism (Oxford, Oxfordshire). 2019", "claim": "PubMed-indexed evidence on prednisolone or systemic corticosteroid therapy context", "title": "Alcoholic Hepatitis: A Review", "authors": "Hosseini N, Shor J, Szabo G", "journal": "Alcohol and alcoholism (Oxford, Oxfordshire)", "year": 2019, "pmid": "31219169", "url": "https://pubmed.ncbi.nlm.nih.gov/31219169/", "study_type": "review", "confidence": "verify", "doi": "10.1093/alcalc/agz036", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31219169/", "publicSourceType": "PMID" }, { "text": "Chu X, Wang J, Ologundudu L et al.. Efficacy and Safety of Systemic Corticosteroids for Urticaria: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. The journal of allergy and clinical immunology. In practice. 2024", "claim": "PubMed-indexed evidence on prednisolone or systemic corticosteroid therapy context", "title": "Efficacy and Safety of Systemic Corticosteroids for Urticaria: A Systematic Review and Meta-Analysis of Randomized Clinical Trials", "authors": "Chu X, Wang J, Ologundudu L et al.", "journal": "The journal of allergy and clinical immunology. In practice", "year": 2024, "pmid": "38642709", "url": "https://pubmed.ncbi.nlm.nih.gov/38642709/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jaip.2024.04.016", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38642709/", "publicSourceType": "PMID" }, { "text": "Shi MA, Pungwe P, Comer LLM et al.. Corticosteroids in severe alcohol-associated hepatitis. Not so fast: A systematic review of randomized controlled trials. Hepatology (Baltimore, Md.). 2025", "claim": "PubMed-indexed evidence on prednisolone or systemic corticosteroid therapy context", "title": "Corticosteroids in severe alcohol-associated hepatitis. Not so fast: A systematic review of randomized controlled trials", "authors": "Shi MA, Pungwe P, Comer LLM et al.", "journal": "Hepatology (Baltimore, Md.)", "year": 2025, "pmid": "39874480", "url": "https://pubmed.ncbi.nlm.nih.gov/39874480/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/HEP.0000000000001237", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39874480/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Glucocorticoid (Corticosteroid)", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "2–4 hours (plasma); biological half-life 18–36 hours", "onsetOfAction": "1–2 hours; anti-inflammatory effect peaks within 1–2 days", "commonBrandNames": [ "Orapred", "Prelone", "Pediapred" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Blood glucose monitoring. Blood pressure. Electrolytes (potassium, sodium). Bone density with chronic use. 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Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: current questions and tentative answers in rheumatology. Ann Rheum Dis. 2002;61(8):718-722.", "pmid": "12117678", "doi": "10.1136/ard.61.8.718", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12117678/", "publicSourceType": "PMID" }, { "text": "Rhen T, Cidlowski JA. Anti-inflammatory action of glucocorticoids, new mechanisms for old drugs. N Engl J Med. 2005;353(16):1711-1723.", "pmid": "16236742", "doi": "10.1056/NEJMra050541", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16236742/", "publicSourceType": "PMID" }, { "text": "Kuper G et al. Comparative effectiveness of corticosteroid injections for trigger finger: A systematic review of randomized controlled trials. J Plast Reconstr Aesthet Surg. 2026.", "pmid": "41352303", "doi": "10.1016/j.bjps.2025.11.047", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41352303/", "publicSourceType": "PMID" }, { "text": "Douglas RS, Dailey R, Subramanian PS et al.. Proptosis and Diplopia Response With Teprotumumab and Placebo vs the Recommended Treatment Regimen With Intravenous Methylprednisolone in Moderate to Severe Thyroid Eye Disease: A Meta-analysis and Matching-Adjusted Indirect Comparison. JAMA ophthalmology. 2022", "pmid": "35175308", "doi": "10.1001/jamaophthalmol.2021.6284", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35175308/", "publicSourceType": "PMID" }, { "text": "Fehlings MG, Wilson JR, Harrop JS et al.. Efficacy and Safety of Methylprednisolone Sodium Succinate in Acute Spinal Cord Injury: A Systematic Review. Global spine journal. 2017", "claim": "PubMed-indexed evidence involving Methylprednisolone", "title": "Efficacy and Safety of Methylprednisolone Sodium Succinate in Acute Spinal Cord Injury: A Systematic Review", "authors": "Fehlings MG, Wilson JR, Harrop JS et al.", "journal": "Global spine journal", "year": 2017, "pmid": "29164020", "url": "https://pubmed.ncbi.nlm.nih.gov/29164020/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/2192568217706366", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29164020/", "publicSourceType": "PMID" }, { "text": "Mehmood F, Rizvi SAR, Alam S et al.. Teprotumumab versus intravenous methylprednisolone in thyroid eye disease: A systematic review. Oman journal of ophthalmology. 2024", "claim": "PubMed-indexed evidence involving Methylprednisolone", "title": "Teprotumumab versus intravenous methylprednisolone in thyroid eye disease: A systematic review", "authors": "Mehmood F, Rizvi SAR, Alam S et al.", "journal": "Oman journal of ophthalmology", "year": 2024, "pmid": "39651498", "url": "https://pubmed.ncbi.nlm.nih.gov/39651498/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.4103/ojo.ojo_308_23", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39651498/", "publicSourceType": "PMID" }, { "text": "Hong S, Wang H, Li S et al.. A systematic review and meta-analysis of glucocorticoids treatment in severe COVID-19: methylprednisolone versus dexamethasone. BMC infectious diseases. 2023", "claim": "PubMed-indexed evidence involving Methylprednisolone", "title": "A systematic review and meta-analysis of glucocorticoids treatment in severe COVID-19: methylprednisolone versus dexamethasone", "authors": "Hong S, Wang H, Li S et al.", "journal": "BMC infectious diseases", "year": 2023, "pmid": "37147596", "url": "https://pubmed.ncbi.nlm.nih.gov/37147596/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12879-023-08280-2", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37147596/", "publicSourceType": "PMID" }, { "text": "Hong S, Wang H, Zhang Z et al.. The roles of methylprednisolone treatment in patients with COVID-19: A systematic review and meta-analysis. Steroids. 2022", "claim": "PubMed-indexed evidence involving Methylprednisolone", "title": "The roles of methylprednisolone treatment in patients with COVID-19: A systematic review and meta-analysis", "authors": "Hong S, Wang H, Zhang Z et al.", "journal": "Steroids", "year": 2022, "pmid": "35346661", "url": "https://pubmed.ncbi.nlm.nih.gov/35346661/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.steroids.2022.109022", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35346661/", "publicSourceType": "PMID" }, { "text": "Xu W, Zeng Y, Han H et al.. The role of methylprednisolone in severe COVID-19 patients: a meta-analysis. Frontiers in medicine. 2024", "claim": "PubMed-indexed evidence involving Methylprednisolone", "title": "The role of methylprednisolone in severe COVID-19 patients: a meta-analysis", "authors": "Xu W, Zeng Y, Han H et al.", "journal": "Frontiers in medicine", "year": 2024, "pmid": "39185470", "url": "https://pubmed.ncbi.nlm.nih.gov/39185470/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fmed.2024.1428581", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39185470/", "publicSourceType": "PMID" }, { "text": "Zhang Y, Gao YL, Zhang LH. Methylprednisolone and local anesthetic for long-term postherpetic neuralgia: a meta-analysis. The Journal of dermatological treatment. 2022", "claim": "PubMed-indexed evidence involving Methylprednisolone", "title": "Methylprednisolone and local anesthetic for long-term postherpetic neuralgia: a meta-analysis", "authors": "Zhang Y, Gao YL, Zhang LH", "journal": "The Journal of dermatological treatment", "year": 2022, "pmid": "35435114", "url": "https://pubmed.ncbi.nlm.nih.gov/35435114/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/09546634.2022.2067820", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35435114/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Glucocorticoid (Corticosteroid)", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "1.8–5.2 hours (plasma); biological half-life 18–36 hours", "onsetOfAction": "Oral: 1–2 hours; IV: rapid (minutes); IM depot: 4–8 days to peak", "commonBrandNames": [ "Medrol", "Solu-Medrol", "Depo-Medrol" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Blood glucose (frequently during IV pulse therapy). 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N Engl J Med. 2021;384(8):693-704.", "pmid": "32678530", "doi": "10.1056/NEJMoa2021436", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32678530/", "publicSourceType": "PMID" }, { "text": "Rhen T, Cidlowski JA. Anti-inflammatory action of glucocorticoids, new mechanisms for old drugs. N Engl J Med. 2005;353(16):1711-1723.", "pmid": "16236742", "doi": "10.1056/NEJMra050541", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16236742/", "publicSourceType": "PMID" }, { "text": "Vecht CJ et al. Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain tumors. J Neurooncol. 1994;22(3):261-269.", "pmid": "8164824", "doi": "10.1007/BF01052929", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8164824/", "publicSourceType": "PMID" }, { "text": "Dahan E, El Ghazal N, Nakanishi H et al.. Dexamethasone versus prednisone/prednisolone in the management of pediatric patients with acute asthmatic exacerbations: a systematic review and meta-analysis. The Journal of asthma : official journal of the Association for the Care of Asthma. 2023", "pmid": "36461938", "doi": "10.1080/02770903.2022.2155189", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36461938/", "publicSourceType": "PMID" }, { "text": "Jones IA, LoBasso MA, Wier J et al.. Perioperative Dexamethasone in Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized, Placebo-Controlled Trials. Anesthesia and analgesia. 2024", "pmid": "39151134", "doi": "10.1213/ANE.0000000000007007", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39151134/", "publicSourceType": "PMID" }, { "text": "Makkar JK, Singh NP, Khurana BJK et al.. Efficacy of different routes of dexamethasone administration for preventing rebound pain following peripheral nerve blocks in adult surgical patients: a systematic review and network meta-analysis. Anaesthesia. 2025", "claim": "PubMed-indexed evidence involving Dexamethasone", "title": "Efficacy of different routes of dexamethasone administration for preventing rebound pain following peripheral nerve blocks in adult surgical patients: a systematic review and network meta-analysis", "authors": "Makkar JK, Singh NP, Khurana BJK et al.", "journal": "Anaesthesia", "year": 2025, "pmid": "39929722", "url": "https://pubmed.ncbi.nlm.nih.gov/39929722/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/anae.16566", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39929722/", "publicSourceType": "PMID" }, { "text": "Zufferey PJ, Chaux R, Lachaud PA et al.. Dose-response relationships of intravenous and perineural dexamethasone as adjuvants to peripheral nerve blocks: a systematic review and model-based network meta-analysis. British journal of anaesthesia. 2024", "claim": "PubMed-indexed evidence involving Dexamethasone", "title": "Dose-response relationships of intravenous and perineural dexamethasone as adjuvants to peripheral nerve blocks: a systematic review and model-based network meta-analysis", "authors": "Zufferey PJ, Chaux R, Lachaud PA et al.", "journal": "British journal of anaesthesia", "year": 2024, "pmid": "38281844", "url": "https://pubmed.ncbi.nlm.nih.gov/38281844/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.bja.2023.12.021", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38281844/", "publicSourceType": "PMID" }, { "text": "Costa BA, Costa TA, Saravia SD et al.. Thromboembolic risk of carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for newly diagnosed multiple myeloma: A comparative systematic review and meta-analysis. American journal of hematology. 2024", "claim": "PubMed-indexed evidence involving Dexamethasone", "title": "Thromboembolic risk of carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for newly diagnosed multiple myeloma: A comparative systematic review and meta-analysis", "authors": "Costa BA, Costa TA, Saravia SD et al.", "journal": "American journal of hematology", "year": 2024, "pmid": "38488702", "url": "https://pubmed.ncbi.nlm.nih.gov/38488702/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/ajh.27288", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38488702/", "publicSourceType": "PMID" }, { "text": "Singh NP, Makkar JK, Chawla JK et al.. Prophylactic dexamethasone for rebound pain after peripheral nerve block in adult surgical patients: systematic review, meta-analysis, and trial sequential analysis of randomised controlled trials. British journal of anaesthesia. 2024", "claim": "PubMed-indexed evidence involving Dexamethasone", "title": "Prophylactic dexamethasone for rebound pain after peripheral nerve block in adult surgical patients: systematic review, meta-analysis, and trial sequential analysis of randomised controlled trials", "authors": "Singh NP, Makkar JK, Chawla JK et al.", "journal": "British journal of anaesthesia", "year": 2024, "pmid": "38501226", "url": "https://pubmed.ncbi.nlm.nih.gov/38501226/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.bja.2023.09.022", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38501226/", "publicSourceType": "PMID" }, { "text": "Costa BA, Costa TA, Pak K et al.. Comparative efficacy of carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide, and dexamethasone (VRd) in newly-diagnosed multiple myeloma: A systematic review and meta-analysis. American journal of hematology. 2024", "claim": "PubMed-indexed evidence involving Dexamethasone", "title": "Comparative efficacy of carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide, and dexamethasone (VRd) in newly-diagnosed multiple myeloma: A systematic review and meta-analysis", "authors": "Costa BA, Costa TA, Pak K et al.", "journal": "American journal of hematology", "year": 2024, "pmid": "38606993", "url": "https://pubmed.ncbi.nlm.nih.gov/38606993/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/ajh.27314", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38606993/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Glucocorticoid (Corticosteroid)", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "4–5 hours (plasma); biological half-life 36–54 hours", "onsetOfAction": "Oral: 1–2 hours; IV: rapid (minutes to 1 hour); full effect over 12–24 hours", "commonBrandNames": [ "Decadron", "DexPak" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Blood glucose (monitor closely in diabetic patients; may require insulin). 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During osteoclast-mediated bone resorption, alendronate is internalized by osteoclasts and inhibits farnesyl pyrophosphate synthase (FPPS), a key enzyme in the mevalonate pathway. 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Do not eat, drink anything other than water, or take other medications for at least 30 minutes. Food, calcium, and other minerals dramatically reduce absorption (bioavailability is only ~0.7%)." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Esophageal irritation, esophagitis, and ulceration", "Abdominal pain and dyspepsia", "Nausea", "Musculoskeletal pain (bone, joint, or muscle pain)", "Osteonecrosis of the jaw (rare, primarily with IV bisphosphonates or prolonged use)", "Atypical femoral fractures (rare, with long-term use >5 years)", "Hypocalcemia" ], "contraindications": [ "Esophageal abnormalities that delay emptying (stricture, achalasia)", "Inability to stand or sit upright for at least 30 minutes", "Hypocalcemia (must correct before starting)", "Known hypersensitivity to alendronate", "Severe renal impairment (CrCl <35 mL/min)" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "osteoporosis", "bone-health", "bisphosphonate", "fracture-prevention" ], "sources": [ { "text": "Black DM et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures (Fracture Intervention Trial, FIT). Lancet. 1996;348(9041):1535-1541.", "pmid": "8950879", "doi": "10.1016/S0140-6736(96)07088-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8950879/", "publicSourceType": "PMID" }, { "text": "Cummings SR et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures (FIT-2). JAMA. 1998;280(24):2077-2082.", "pmid": "9875874", "doi": "10.1001/jama.280.24.2077", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9875874/", "publicSourceType": "PMID" }, { "text": "Black DM et al. Effects of continuing or stopping alendronate after 5 years of treatment (FLEX). JAMA. 2006;296(24):2927-2938.", "pmid": "17190893", "doi": "10.1001/jama.296.24.2927", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17190893/", "publicSourceType": "PMID" }, { "text": "Kendler DL, Roux C, Benhamou CL et al.. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2010", "pmid": "19594293", "doi": "10.1359/jbmr.090716", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19594293/", "publicSourceType": "PMID" }, { "text": "Reynolds NA, Curran MP. Alendronate/colecalciferol. Treatments in endocrinology. 2005", "pmid": "16318403", "doi": "10.2165/00024677-200504060-00006", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16318403/", "publicSourceType": "PMID" }, { "text": "Nunkoo S, Krissheeven M, Chitravanshi A et al.. Clinical Efficacy and Safety of Teriparatide Versus Alendronate in Postmenopausal Osteoporosis: A Systematic Review of Randomized Controlled Trials. Cureus. 2024", "claim": "PubMed-indexed evidence involving Alendronate", "title": "Clinical Efficacy and Safety of Teriparatide Versus Alendronate in Postmenopausal Osteoporosis: A Systematic Review of Randomized Controlled Trials", "authors": "Nunkoo S, Krissheeven M, Chitravanshi A et al.", "journal": "Cureus", "year": 2024, "pmid": "39640163", "url": "https://pubmed.ncbi.nlm.nih.gov/39640163/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7759/cureus.73068", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39640163/", "publicSourceType": "PMID" }, { "text": "Nouh MI, Albuti H, Hasosah M et al.. Adverse Gastrointestinal Effects of Alendronate Versus Risedronate in Osteoporosis: A Systematic Review and Meta-analysis. Annals of African medicine. 2026", "claim": "PubMed-indexed evidence involving Alendronate", "title": "Adverse Gastrointestinal Effects of Alendronate Versus Risedronate in Osteoporosis: A Systematic Review and Meta-analysis", "authors": "Nouh MI, Albuti H, Hasosah M et al.", "journal": "Annals of African medicine", "year": 2026, "pmid": "42138626", "url": "https://pubmed.ncbi.nlm.nih.gov/42138626/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.4103/aam.aam_216_25", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/42138626/", "publicSourceType": "PMID" }, { "text": "Sun R, Lan Z, Wu G et al.. Does alendronate enhance survival rates in osteoporosis patients? A meta-analysis of randomized controlled trials. Science progress. 2025", "claim": "PubMed-indexed evidence involving Alendronate", "title": "Does alendronate enhance survival rates in osteoporosis patients? A meta-analysis of randomized controlled trials", "authors": "Sun R, Lan Z, Wu G et al.", "journal": "Science progress", "year": 2025, "pmid": "40902090", "url": "https://pubmed.ncbi.nlm.nih.gov/40902090/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/00368504251348587", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40902090/", "publicSourceType": "PMID" }, { "text": "Wang YK, Zhang YM, Qin SQ et al.. Effects of alendronate for treatment of glucocorticoid-induced osteoporosis: A meta-analysis of randomized controlled trials. Medicine. 2018", "claim": "PubMed-indexed evidence involving Alendronate", "title": "Effects of alendronate for treatment of glucocorticoid-induced osteoporosis: A meta-analysis of randomized controlled trials", "authors": "Wang YK, Zhang YM, Qin SQ et al.", "journal": "Medicine", "year": 2018, "pmid": "30334952", "url": "https://pubmed.ncbi.nlm.nih.gov/30334952/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MD.0000000000012691", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30334952/", "publicSourceType": "PMID" }, { "text": "Xu Z. Alendronate for the Treatment of Osteoporosis in Men: A Meta-Analysis of Randomized Controlled Trials. American journal of therapeutics. 2017", "claim": "PubMed-indexed evidence involving Alendronate", "title": "Alendronate for the Treatment of Osteoporosis in Men: A Meta-Analysis of Randomized Controlled Trials", "authors": "Xu Z", "journal": "American journal of therapeutics", "year": 2017, "pmid": "27058577", "url": "https://pubmed.ncbi.nlm.nih.gov/27058577/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MJT.0000000000000446", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27058577/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Bisphosphonate", "blackBoxWarnings": [], "fdaPregnancyCategory": "X", "halfLife": "Plasma half-life ~1 hour; bone half-life >10 years", "onsetOfAction": "Bone mineral density increase measurable by 3–6 months; fracture risk reduction by 12–18 months", "commonBrandNames": [ "Fosamax", "Binosto" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Serum calcium and vitamin D at baseline (correct deficiency before starting). 25-hydroxyvitamin D level. DEXA scan at baseline and every 1–2 years. Renal function (CrCl) at baseline. Dental examination recommended before initiation. Consider drug holiday after 5 years of oral therapy." }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "alendronate" }, { "id": "RX-ENDO-024", "name": "Risedronate", "alternateNames": [ "Actonel", "Atelvia" ], "category": "Prescription", "subcategory": "Bisphosphonate", "overview": "Risedronate is a nitrogen-containing bisphosphonate used for the treatment and prevention of postmenopausal and glucocorticoid-induced osteoporosis, male osteoporosis, and Paget's disease. The VERT and HIP trials demonstrated significant fracture risk reduction. It is available in daily, weekly, and monthly dosing formulations.", "mechanismOfAction": "Binds to bone hydroxyapatite at sites of active remodeling and is internalized by osteoclasts during bone resorption. Inhibits farnesyl pyrophosphate synthase in the mevalonate pathway, disrupting osteoclast cytoskeletal organization and function, reducing bone resorption. This leads to positive bone remodeling balance and increased bone mineral density.", "commonBenefits": [ "Reduces vertebral fracture risk by 41–49% (VERT trials)", "Reduces non-vertebral fracture risk by 39%", "Hip fracture reduction in elderly women (HIP trial)", "Available as once-weekly or once-monthly dosing", "Effective in glucocorticoid-induced osteoporosis" ], "commonDosageRange": "5 mg daily, 35 mg once weekly, or 150 mg once monthly; Paget's: 30 mg daily for 2 months (as prescribed by your physician)", "recommendedForm": "Oral tablet; delayed-release (Atelvia) is taken after breakfast", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Immediate-release: Take first thing in the morning on empty stomach with 6–8 oz plain water. Remain upright 30 minutes. Delayed-release (Atelvia): Take immediately after breakfast. Do not crush or chew." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "GI upset (abdominal pain, dyspepsia, nausea)", "Esophageal irritation", "Musculoskeletal pain", "Headache", "Osteonecrosis of the jaw (rare)", "Atypical femoral fractures (rare, long-term use)", "Hypocalcemia" ], "contraindications": [ "Esophageal abnormalities that delay emptying", "Inability to stand or sit upright for 30 minutes", "Hypocalcemia (must correct first)", "Known hypersensitivity to risedronate", "Severe renal impairment (CrCl <30 mL/min)" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "osteoporosis", "bone-health", "bisphosphonate", "fracture-prevention" ], "sources": [ { "text": "Harris ST et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial (VERT-NA). JAMA. 1999;282(14):1344-1352.", "pmid": "10527181", "doi": "10.1001/jama.282.14.1344", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10527181/", "publicSourceType": "PMID" }, { "text": "McClung MR et al. Effect of risedronate on the risk of hip fracture in elderly women (HIP). N Engl J Med. 2001;344(5):333-340.", "pmid": "11172164", "doi": "10.1056/NEJM200102013440503", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11172164/", "publicSourceType": "PMID" }, { "text": "Chai SJ et al. The efficacy and safety of denosumab, risedronate, alendronate and teriparatide to treat male osteoporosis: a systematic review and bayesian network meta-analysis. Front Endocrinol (Lausanne). 2025.", "pmid": "40612431", "doi": "10.3389/fendo.2025.1579101", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40612431/", "publicSourceType": "PMID" }, { "text": "Goa KL, Balfour JA. Risedronate. Drugs & aging. 1998", "pmid": "9679211", "doi": "10.2165/00002512-199813010-00008", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9679211/", "publicSourceType": "PMID" }, { "text": "Nouh MI, Albuti H, Hasosah M et al.. Adverse Gastrointestinal Effects of Alendronate Versus Risedronate in Osteoporosis: A Systematic Review and Meta-analysis. Annals of African medicine. 2026", "claim": "PubMed-indexed evidence involving Risedronate", "title": "Adverse Gastrointestinal Effects of Alendronate Versus Risedronate in Osteoporosis: A Systematic Review and Meta-analysis", "authors": "Nouh MI, Albuti H, Hasosah M et al.", "journal": "Annals of African medicine", "year": 2026, "pmid": "42138626", "url": "https://pubmed.ncbi.nlm.nih.gov/42138626/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.4103/aam.aam_216_25", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/42138626/", "publicSourceType": "PMID" }, { "text": "Wang M, Wang L, Ye R. Risedronate reduces postoperative bone resorption after cementless total hip arthroplasty: A systematic review and meta-analysis. International journal of surgery (London, England). 2018", "claim": "PubMed-indexed evidence involving Risedronate", "title": "Risedronate reduces postoperative bone resorption after cementless total hip arthroplasty: A systematic review and meta-analysis", "authors": "Wang M, Wang L, Ye R", "journal": "International journal of surgery (London, England)", "year": 2018, "pmid": "29448032", "url": "https://pubmed.ncbi.nlm.nih.gov/29448032/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.ijsu.2018.02.007", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29448032/", "publicSourceType": "PMID" }, { "text": "Li Q, Xu B. Oral risedronate increases Gruen zone bone mineral density after primary total hip arthroplasty: a meta-analysis. Journal of orthopaedic surgery and research. 2018", "claim": "PubMed-indexed evidence involving Risedronate", "title": "Oral risedronate increases Gruen zone bone mineral density after primary total hip arthroplasty: a meta-analysis", "authors": "Li Q, Xu B", "journal": "Journal of orthopaedic surgery and research", "year": 2018, "pmid": "29880021", "url": "https://pubmed.ncbi.nlm.nih.gov/29880021/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s13018-018-0794-1", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29880021/", "publicSourceType": "PMID" }, { "text": "Blay R, Flores LE, Kupzyk K et al.. Twelve-month resistance and impact exercise program or risedronate provides a relative benefit to hip bone structure in postmenopausal women: results from a randomized controlled trial. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2024", "claim": "PubMed-indexed evidence involving Risedronate", "title": "Twelve-month resistance and impact exercise program or risedronate provides a relative benefit to hip bone structure in postmenopausal women: results from a randomized controlled trial", "authors": "Blay R, Flores LE, Kupzyk K et al.", "journal": "Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA", "year": 2024, "pmid": "38368307", "url": "https://pubmed.ncbi.nlm.nih.gov/38368307/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/s00198-023-07008-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38368307/", "publicSourceType": "PMID" }, { "text": "Hashimoto J, Arai Y, Kurosu S et al.. Safety and effectiveness of risedronate in Paget's disease of bone: postmarketing surveillance study in Japan. Journal of bone and mineral metabolism. 2024", "claim": "PubMed-indexed evidence involving Risedronate", "title": "Safety and effectiveness of risedronate in Paget's disease of bone: postmarketing surveillance study in Japan", "authors": "Hashimoto J, Arai Y, Kurosu S et al.", "journal": "Journal of bone and mineral metabolism", "year": 2024, "pmid": "38197974", "url": "https://pubmed.ncbi.nlm.nih.gov/38197974/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s00774-023-01486-z", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38197974/", "publicSourceType": "PMID" }, { "text": "Bobba R, Adachi JD. Review of the safety and efficacy of risedronate for the treatment of male osteoporosis. Clinical interventions in aging. 2007", "claim": "PubMed-indexed evidence involving Risedronate", "title": "Review of the safety and efficacy of risedronate for the treatment of male osteoporosis", "authors": "Bobba R, Adachi JD", "journal": "Clinical interventions in aging", "year": 2007, "pmid": "18044178", "url": "https://pubmed.ncbi.nlm.nih.gov/18044178/", "study_type": "review", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18044178/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Bisphosphonate", "blackBoxWarnings": [], "fdaPregnancyCategory": "X", "halfLife": "Plasma half-life ~1.5 hours; bone half-life 480–561 hours (terminal)", "onsetOfAction": "BMD increase measurable by 3–6 months; fracture risk reduction within 6–12 months", "commonBrandNames": [ "Actonel", "Atelvia" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Serum calcium and vitamin D at baseline. DEXA scan at baseline and every 1–2 years. Renal function (CrCl) at baseline. Dental exam before starting. Consider drug holiday after 5 years." }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "risedronate" }, { "id": "RX-ENDO-025", "name": "Zoledronic Acid", "alternateNames": [ "Reclast", "Zometa" ], "category": "Prescription", "subcategory": "Bisphosphonate", "overview": "Zoledronic acid is the most potent bisphosphonate available, administered as an annual IV infusion for osteoporosis (Reclast) or more frequently for hypercalcemia of malignancy and bone metastases (Zometa). The HORIZON-PFT trial demonstrated significant fracture reduction with once-yearly dosing. Its IV administration eliminates GI side effects and adherence concerns of oral bisphosphonates.", "mechanismOfAction": "The most potent inhibitor of farnesyl pyrophosphate synthase among bisphosphonates. After IV infusion, rapidly binds to hydroxyapatite at bone surfaces. During osteoclast-mediated bone resorption, zoledronic acid is internalized and disrupts the mevalonate pathway, preventing prenylation of small GTPases essential for osteoclast function and survival. This potently inhibits bone resorption and reduces bone turnover markers.", "commonBenefits": [ "Once-yearly IV infusion ensures 100% adherence", "Reduces vertebral fractures by 70% (HORIZON-PFT)", "Reduces hip fractures by 41%", "Reduces all-cause mortality in hip fracture patients (HORIZON-RFT)", "No GI side effects of oral bisphosphonates", "Effective for hypercalcemia of malignancy" ], "commonDosageRange": "Osteoporosis: 5 mg IV once yearly; Paget's: 5 mg single IV dose; Hypercalcemia of malignancy: 4 mg IV (as prescribed by your physician)", "recommendedForm": "Intravenous infusion over at least 15 minutes", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Given as IV infusion. Patient should be well hydrated before infusion. Ensure adequate calcium and vitamin D supplementation." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Acute phase reaction (fever, myalgia, headache, arthralgia) within 1–3 days of infusion", "Hypocalcemia", "Renal impairment (ensure adequate hydration, infuse over ≥15 minutes)", "Osteonecrosis of the jaw (rare, more common in oncology dosing)", "Atypical femoral fractures (rare, with prolonged use)", "Ocular inflammation (uveitis, scleritis; rare)", "Bone, joint, and muscle pain" ], "contraindications": [ "Hypocalcemia (must correct before infusion)", "Severe renal impairment (CrCl <35 mL/min for osteoporosis indication)", "Known hypersensitivity to zoledronic acid or other bisphosphonates", "Pregnancy and breastfeeding" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "osteoporosis", "bone-health", "bisphosphonate", "iv-infusion", "fracture-prevention" ], "sources": [ { "text": "Black DM et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis (HORIZON-PFT). N Engl J Med. 2007;356(18):1809-1822.", "pmid": "17476007", "doi": "10.1056/NEJMoa067312", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17476007/", "publicSourceType": "PMID" }, { "text": "Lyles KW et al. Zoledronic acid and clinical fractures and mortality after hip fracture (HORIZON-RFT). N Engl J Med. 2007;357(18):1799-1809.", "pmid": "17878149", "doi": "10.1056/NEJMoa074941", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17878149/", "publicSourceType": "PMID" }, { "text": "Polho GB et al. Impact of Bisphosphonates in Hormone-sensitive Metastatic Prostate Cancer A Systematic Review and Meta-Analysis. Clin Genitourin Cancer. 2025.", "pmid": "41076396", "doi": "10.1016/j.clgc.2025.102438", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41076396/", "publicSourceType": "PMID" }, { "text": "Wajda BG, Ferrie LE, Abbott AG et al.. Denosumab vs. Zoledronic Acid for Metastatic Bone Disease: A Comprehensive Systematic Review and Meta-Analysis of Randomized Controlled Trials. Cancers. 2025", "pmid": "39941757", "doi": "10.3390/cancers17030388", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39941757/", "publicSourceType": "PMID" }, { "text": "Limones A, Sáez-Alcaide LM, Díaz-Parreño SA et al.. Medication-related osteonecrosis of the jaws (MRONJ) in cancer patients treated with denosumab VS. zoledronic acid: A systematic review and meta-analysis. Medicina oral, patologia oral y cirugia bucal. 2020", "pmid": "32271321", "doi": "10.4317/medoral.23324", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32271321/", "publicSourceType": "PMID" }, { "text": "Wang WY, Chen LH, Ma WJ et al.. Drug efficacy and safety of denosumab, teriparatide, zoledronic acid, and ibandronic acid for the treatment of postmenopausal osteoporosis: a network meta-analysis of randomized controlled trials. European review for medical and pharmacological sciences. 2023", "claim": "PubMed-indexed evidence involving Zoledronic Acid", "title": "Drug efficacy and safety of denosumab, teriparatide, zoledronic acid, and ibandronic acid for the treatment of postmenopausal osteoporosis: a network meta-analysis of randomized controlled trials", "authors": "Wang WY, Chen LH, Ma WJ et al.", "journal": "European review for medical and pharmacological sciences", "year": 2023, "pmid": "37750653", "url": "https://pubmed.ncbi.nlm.nih.gov/37750653/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.26355/eurrev_202309_33586", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37750653/", "publicSourceType": "PMID" }, { "text": "Wang C. Efficacy and Safety of Zoledronic Acid for Treatment of Postmenopausal Osteoporosis: A Meta-Analysis of Randomized Controlled Trials. American journal of therapeutics. 2017", "claim": "PubMed-indexed evidence involving Zoledronic Acid", "title": "Efficacy and Safety of Zoledronic Acid for Treatment of Postmenopausal Osteoporosis: A Meta-Analysis of Randomized Controlled Trials", "authors": "Wang C", "journal": "American journal of therapeutics", "year": 2017, "pmid": "26938765", "url": "https://pubmed.ncbi.nlm.nih.gov/26938765/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MJT.0000000000000415", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26938765/", "publicSourceType": "PMID" }, { "text": "He B, Zhao JQ, Zhang MZ et al.. Zoledronic acid and fracture risk: a meta-analysis of 12 randomized controlled trials. European review for medical and pharmacological sciences. 2021", "claim": "PubMed-indexed evidence involving Zoledronic Acid", "title": "Zoledronic acid and fracture risk: a meta-analysis of 12 randomized controlled trials", "authors": "He B, Zhao JQ, Zhang MZ et al.", "journal": "European review for medical and pharmacological sciences", "year": 2021, "pmid": "33629326", "url": "https://pubmed.ncbi.nlm.nih.gov/33629326/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.26355/eurrev_202102_24865", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33629326/", "publicSourceType": "PMID" }, { "text": "Zhu M, Liang R, Pan LH et al.. Zoledronate for metastatic bone disease and pain: a meta-analysis of randomized clinical trials. Pain medicine (Malden, Mass.). 2013", "claim": "PubMed-indexed evidence involving Zoledronic Acid", "title": "Zoledronate for metastatic bone disease and pain: a meta-analysis of randomized clinical trials", "authors": "Zhu M, Liang R, Pan LH et al.", "journal": "Pain medicine (Malden, Mass.)", "year": 2013, "pmid": "23279447", "url": "https://pubmed.ncbi.nlm.nih.gov/23279447/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/pme.12016", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23279447/", "publicSourceType": "PMID" }, { "text": "Widyadharma IPE, Tertia C, Vania A et al.. The effect of denosumab vs. zoledronic acid in preventing skeletal-related events, including pain-related bone metastasis: a systematic review. Postepy psychiatrii neurologii. 2024", "claim": "PubMed-indexed evidence involving Zoledronic Acid", "title": "The effect of denosumab vs. zoledronic acid in preventing skeletal-related events, including pain-related bone metastasis: a systematic review", "authors": "Widyadharma IPE, Tertia C, Vania A et al.", "journal": "Postepy psychiatrii neurologii", "year": 2024, "pmid": "39678460", "url": "https://pubmed.ncbi.nlm.nih.gov/39678460/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.5114/ppn.2024.144603", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39678460/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Bisphosphonate (IV)", "blackBoxWarnings": [], "fdaPregnancyCategory": "D", "halfLife": "Plasma half-life ~0.25–1 hour (alpha phase); terminal half-life 146 hours. Bone retention for years", "onsetOfAction": "Bone turnover marker suppression within days; BMD increase by 6 months; fracture risk reduction within 12 months", "commonBrandNames": [ "Reclast", "Zometa" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Serum creatinine before each infusion (contraindicated if CrCl <35). Serum calcium, phosphate, and magnesium before and after infusion. 25-hydroxyvitamin D level (supplement if low). DEXA scan at baseline and 1–2 years after infusion. Dental exam before initiation." }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "zoledronic-acid" }, { "id": "RX-ENDO-026", "name": "Testosterone", "alternateNames": [ "AndroGel", "Testim", "Axiron", "Depo-Testosterone", "Aveed", "Natesto" ], "category": "Prescription", "subcategory": "Androgen Hormone", "overview": "Testosterone replacement therapy (TRT) is indicated for male hypogonadism when low testosterone levels are confirmed by laboratory testing with consistent signs and symptoms. The Testosterone Trials (TTrials) demonstrated improvements in sexual function, mood, bone density, and anemia in men over 65 with low testosterone. Available formulations include topical gels, intramuscular injections, transdermal patches, and nasal gel.", "mechanismOfAction": "Exogenous testosterone replaces or supplements endogenous androgen production. Testosterone binds to androgen receptors in target tissues, translocates to the nucleus, and regulates gene transcription for proteins involved in male sexual development, muscle mass and strength, bone mineral density, erythropoiesis, fat distribution, and mood. Testosterone is also converted to dihydrotestosterone (DHT) by 5-alpha-reductase and to estradiol by aromatase, mediating additional effects.", "commonBenefits": [ "Restores libido and sexual function in hypogonadal men", "Improves bone mineral density", "Increases lean muscle mass and strength", "Improves mood, energy, and sense of well-being", "Corrects testosterone-deficiency anemia", "Improves body composition (reduced fat mass)" ], "commonDosageRange": "Topical gel: 50–100 mg daily; IM injection (cypionate/enanthate): 100–200 mg every 1–2 weeks; Aveed: 750 mg IM every 10 weeks (as prescribed by your physician)", "recommendedForm": "Topical gel (most common), intramuscular injection, or transdermal patch", "absorption": { "isFatSoluble": true, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Topical gel: Apply to clean, dry skin (shoulders, upper arms, or abdomen depending on product). Allow to dry before dressing. Wash hands thoroughly. Avoid skin-to-skin contact with women and children at application site." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Polycythemia (elevated hematocrit/hemoglobin)", "Acne and oily skin", "Gynecomastia", "Testicular atrophy and reduced sperm production", "Sleep apnea worsening", "Edema", "Mood changes (irritability, aggression)", "Skin irritation at application site (topical)" ], "contraindications": [ "Breast cancer in men", "Known or suspected prostate cancer", "Pregnancy or women who may become pregnant (teratogenic)", "Severe untreated sleep apnea", "Uncontrolled heart failure", "Polycythemia (hematocrit >54%)", "Desire for fertility (suppresses spermatogenesis)" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "hormone-replacement", "testosterone", "hypogonadism", "mens-health", "controlled-substance" ], "sources": [ { "text": "Snyder PJ et al. Effects of testosterone treatment in older men (Testosterone Trials). N Engl J Med. 2016;374(7):611-624.", "pmid": "26886521", "doi": "10.1056/NEJMoa1506119", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26886521/", "publicSourceType": "PMID" }, { "text": "Bhasin S et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744.", "pmid": "29562364", "doi": "10.1210/jc.2018-00229", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29562364/", "publicSourceType": "PMID" }, { "text": "Lincoff AM et al. Cardiovascular safety of testosterone-replacement therapy (TRAVERSE). N Engl J Med. 2023;389(2):107-117.", "pmid": "37326322", "doi": "10.1056/NEJMoa2215025", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37326322/", "publicSourceType": "PMID" }, { "text": "Islam RM, Bell RJ, Green S et al.. Safety and efficacy of testosterone for women: a systematic review and meta-analysis of randomised controlled trial data. The lancet. Diabetes & endocrinology. 2019", "pmid": "31353194", "doi": "10.1016/S2213-8587(19)30189-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31353194/", "publicSourceType": "PMID" }, { "text": "Te L, Liu J, Ma J et al.. Correlation between serum zinc and testosterone: A systematic review. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2023", "pmid": "36577241", "doi": "10.1016/j.jtemb.2022.127124", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36577241/", "publicSourceType": "PMID" }, { "text": "Corona G, Rastrelli G, Sparano C et al.. Cardiovascular safety of testosterone replacement therapy in men: an updated systematic review and meta-analysis. Expert opinion on drug safety. 2024", "claim": "PubMed-indexed evidence involving Testosterone", "title": "Cardiovascular safety of testosterone replacement therapy in men: an updated systematic review and meta-analysis", "authors": "Corona G, Rastrelli G, Sparano C et al.", "journal": "Expert opinion on drug safety", "year": 2024, "pmid": "38553429", "url": "https://pubmed.ncbi.nlm.nih.gov/38553429/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/14740338.2024.2337741", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38553429/", "publicSourceType": "PMID" }, { "text": "Rojas-Zambrano JG, Rojas-Zambrano A, Rojas-Zambrano AF. Impact of Testosterone on Male Health: A Systematic Review. Cureus. 2025", "claim": "PubMed-indexed evidence involving Testosterone", "title": "Impact of Testosterone on Male Health: A Systematic Review", "authors": "Rojas-Zambrano JG, Rojas-Zambrano A, Rojas-Zambrano AF", "journal": "Cureus", "year": 2025, "pmid": "40290556", "url": "https://pubmed.ncbi.nlm.nih.gov/40290556/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7759/cureus.82917", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40290556/", "publicSourceType": "PMID" }, { "text": "Morgado A, Tsampoukas G, Sokolakis I et al.. Do \"testosterone boosters\" really increase serum total testosterone? A systematic review. International journal of impotence research. 2024", "claim": "PubMed-indexed evidence involving Testosterone", "title": "Do \"testosterone boosters\" really increase serum total testosterone? A systematic review", "authors": "Morgado A, Tsampoukas G, Sokolakis I et al.", "journal": "International journal of impotence research", "year": 2024, "pmid": "37697053", "url": "https://pubmed.ncbi.nlm.nih.gov/37697053/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1038/s41443-023-00763-9", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37697053/", "publicSourceType": "PMID" }, { "text": "Cannarella R, Gusmano C, Leanza C et al.. Testosterone replacement therapy and vascular thromboembolic events: a systematic review and meta-analysis. Asian journal of andrology. 2024", "claim": "PubMed-indexed evidence involving Testosterone", "title": "Testosterone replacement therapy and vascular thromboembolic events: a systematic review and meta-analysis", "authors": "Cannarella R, Gusmano C, Leanza C et al.", "journal": "Asian journal of andrology", "year": 2024, "pmid": "37921515", "url": "https://pubmed.ncbi.nlm.nih.gov/37921515/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.4103/aja202352", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37921515/", "publicSourceType": "PMID" }, { "text": "Glina FPA, Lopes L, E Silva RS et al.. Do statins decrease testosterone in men? Systematic review and meta-analysis. International braz j urol : official journal of the Brazilian Society of Urology. 2024", "claim": "PubMed-indexed evidence involving Testosterone", "title": "Do statins decrease testosterone in men? Systematic review and meta-analysis", "authors": "Glina FPA, Lopes L, E Silva RS et al.", "journal": "International braz j urol : official journal of the Brazilian Society of Urology", "year": 2024, "pmid": "38386784", "url": "https://pubmed.ncbi.nlm.nih.gov/38386784/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1590/S1677-5538.IBJU.2023.0578", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38386784/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Androgen (Anabolic Steroid)", "blackBoxWarnings": [ "Cardiovascular risk: Testosterone replacement therapy has been associated with increased risk of major adverse cardiovascular events (MACE). Prescribe only for confirmed hypogonadism. Monitor cardiovascular risk factors.", "Secondary exposure (topical products): Virilization has been reported in children and women secondarily exposed to testosterone gel. Strict adherence to application site precautions and hand washing is required. Patients should cover the application site with clothing." ], "fdaPregnancyCategory": "X", "halfLife": "Gel: 1–2 hours (apparent); Cypionate IM: 8 days; Undecanoate IM (Aveed): 21 days", "onsetOfAction": "Sexual function improvement: 3–6 weeks; Body composition: 12–16 weeks; Bone density: 6–12 months; Full effects: 6–12 months", "commonBrandNames": [ "AndroGel", "Testim", "Axiron", "Depo-Testosterone", "Aveed", "Natesto" ], "controlledSubstanceSchedule": "Schedule III", "requiresLabMonitoring": true, "labMonitoringNotes": "Testosterone levels (morning trough) at 1–3 months and then annually. Hematocrit/hemoglobin at baseline, 3–6 months, then annually (withhold if hematocrit >54%). PSA and digital rectal exam at baseline, 3–6 months, then per guidelines. Lipid panel. Liver function. Bone density at baseline if indicated." }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "testosterone" }, { "id": "RX-ENDO-027", "name": "Estradiol", "alternateNames": [ "Estrace", "Vivelle-Dot", "Climara", "Divigel", "Alora", "Minivelle" ], "category": "Prescription", "subcategory": "Estrogen Hormone", "overview": "Estradiol is the primary and most potent endogenous estrogen, used in hormone replacement therapy (HRT) for menopausal symptoms including vasomotor symptoms (hot flashes), vulvovaginal atrophy, and osteoporosis prevention. Transdermal and oral formulations are available. The Women's Health Initiative (WHI) reshaped prescribing practices. Current guidelines favor the lowest effective dose for the shortest duration, with transdermal delivery preferred for reduced thrombotic risk.", "mechanismOfAction": "Binds to estrogen receptors (ER-alpha and ER-beta) in target tissues including the hypothalamus, uterus, breast, bone, cardiovascular system, and brain. The estrogen-receptor complex modulates gene transcription, maintaining reproductive tissue integrity, promoting bone density by inhibiting osteoclast activity, supporting vasomotor stability through hypothalamic thermoregulatory centers, and regulating lipid metabolism. Also has non-genomic rapid signaling effects on vascular endothelium.", "commonBenefits": [ "Effective relief of vasomotor symptoms (hot flashes, night sweats)", "Treatment of vulvovaginal atrophy and urogenital symptoms", "Prevention of postmenopausal osteoporosis", "Improvement in mood and sleep quality", "Favorable effects on lipid profile", "Maintenance of skin, hair, and connective tissue health" ], "commonDosageRange": "Oral: 0.5–2 mg daily; Transdermal patch: 0.025–0.1 mg/day (applied once or twice weekly); Topical gel varies by product (as prescribed by your physician)", "recommendedForm": "Transdermal patch preferred (lower thrombotic risk); oral tablet; topical gel or spray", "absorption": { "isFatSoluble": true, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Oral: can be taken with or without food. Transdermal: apply to clean, dry skin of lower abdomen or buttock; rotate sites. Topical gel: apply to arm or thigh as directed." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Breast tenderness and enlargement", "Nausea (oral route)", "Headache", "Bloating and fluid retention", "Irregular bleeding or spotting", "Venous thromboembolism (DVT/PE, primarily oral route)", "Skin irritation (transdermal)", "Mood changes" ], "contraindications": [ "Known or suspected breast cancer or estrogen-dependent neoplasia", "Active or history of venous thromboembolism (DVT/PE) or arterial thromboembolic disease (stroke, MI)", "Undiagnosed abnormal genital bleeding", "Known or suspected pregnancy", "Active liver disease or hepatic impairment", "Known protein C, protein S, or antithrombin deficiency or other thrombophilias" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "hormone-replacement", "estrogen", "menopause", "womens-health", "bone-health" ], "sources": [ { "text": "Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women (WHI). JAMA. 2002;288(3):321-333.", "pmid": "12117397", "doi": "10.1001/jama.288.3.321", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12117397/", "publicSourceType": "PMID" }, { "text": "The NAMS 2022 Hormone Therapy Position Statement Advisory Panel. The 2022 hormone therapy position statement of The North American Menopause Society. Menopause. 2022;29(7):767-794.", "pmid": "35797481", "doi": "10.1097/GME.0000000000002028", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35797481/", "publicSourceType": "PMID" }, { "text": "Canonico M et al. Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens. Circulation. 2007;115(7):840-845.", "pmid": "17309934", "doi": "10.1161/CIRCULATIONAHA.106.642280", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17309934/", "publicSourceType": "PMID" }, { "text": "Comini ACM, Carvalho BM, Moreira MJB et al.. Safety and Serum Estradiol Levels in Hormonal Treatments for Vulvovaginal Atrophy in Breast Cancer Survivors: A Systematic Review and Meta-Analysis. Clinical breast cancer. 2023", "claim": "PubMed-indexed evidence involving Estradiol", "title": "Safety and Serum Estradiol Levels in Hormonal Treatments for Vulvovaginal Atrophy in Breast Cancer Survivors: A Systematic Review and Meta-Analysis", "authors": "Comini ACM, Carvalho BM, Moreira MJB et al.", "journal": "Clinical breast cancer", "year": 2023, "pmid": "37806915", "url": "https://pubmed.ncbi.nlm.nih.gov/37806915/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.clbc.2023.08.003", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37806915/", "publicSourceType": "PMID" }, { "text": "Winston-McPherson GN, Thomas TA, Krasowski MD et al.. Estradiol Concentrations for Adequate Gender-Affirming Feminizing Therapy: A Systematic Review. LGBT health. 2025", "claim": "PubMed-indexed evidence involving Estradiol", "title": "Estradiol Concentrations for Adequate Gender-Affirming Feminizing Therapy: A Systematic Review", "authors": "Winston-McPherson GN, Thomas TA, Krasowski MD et al.", "journal": "LGBT health", "year": 2025, "pmid": "40552461", "url": "https://pubmed.ncbi.nlm.nih.gov/40552461/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1089/lgbt.2024.0407", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40552461/", "publicSourceType": "PMID" }, { "text": "Gulamhusein N, Miranda KT, Ahmed SB et al.. Measurements of Postmenopausal Serum Estradiol Levels and Cardiovascular Events: A Systematic Review. CJC open. 2024", "claim": "PubMed-indexed evidence involving Estradiol", "title": "Measurements of Postmenopausal Serum Estradiol Levels and Cardiovascular Events: A Systematic Review", "authors": "Gulamhusein N, Miranda KT, Ahmed SB et al.", "journal": "CJC open", "year": 2024, "pmid": "38487048", "url": "https://pubmed.ncbi.nlm.nih.gov/38487048/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.cjco.2023.11.010", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38487048/", "publicSourceType": "PMID" }, { "text": "Wang Y, Wang H, Cai J et al.. Association Between Estradiol and Human Aggression: A Systematic Review and Meta-Analysis. Psychosomatic medicine. 2023", "claim": "PubMed-indexed evidence involving Estradiol", "title": "Association Between Estradiol and Human Aggression: A Systematic Review and Meta-Analysis", "authors": "Wang Y, Wang H, Cai J et al.", "journal": "Psychosomatic medicine", "year": 2023, "pmid": "37678333", "url": "https://pubmed.ncbi.nlm.nih.gov/37678333/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/PSY.0000000000001247", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37678333/", "publicSourceType": "PMID" }, { "text": "Corbelli J, Shaikh N, Wessel C et al.. Low-dose transdermal estradiol for vasomotor symptoms: a systematic review. Menopause (New York, N.Y.). 2015", "claim": "PubMed-indexed evidence involving Estradiol", "title": "Low-dose transdermal estradiol for vasomotor symptoms: a systematic review", "authors": "Corbelli J, Shaikh N, Wessel C et al.", "journal": "Menopause (New York, N.Y.)", "year": 2015, "pmid": "24977458", "url": "https://pubmed.ncbi.nlm.nih.gov/24977458/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/GME.0000000000000258", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24977458/", "publicSourceType": "PMID" }, { "text": "Graham S, Archer DF, Simon JA et al.. Review of menopausal hormone therapy with estradiol and progesterone versus other estrogens and progestins. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2022", "claim": "PubMed-indexed evidence involving Estradiol", "title": "Review of menopausal hormone therapy with estradiol and progesterone versus other estrogens and progestins", "authors": "Graham S, Archer DF, Simon JA et al.", "journal": "Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology", "year": 2022, "pmid": "36075250", "url": "https://pubmed.ncbi.nlm.nih.gov/36075250/", "study_type": "review", "confidence": "verify", "doi": "10.1080/09513590.2022.2118254", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36075250/", "publicSourceType": "PMID" }, { "text": "Syed YY. Relugolix/Estradiol/Norethisterone (Norethindrone) Acetate: A Review in Symptomatic Uterine Fibroids. Drugs. 2022", "claim": "PubMed-indexed evidence involving Estradiol", "title": "Relugolix/Estradiol/Norethisterone (Norethindrone) Acetate: A Review in Symptomatic Uterine Fibroids", "authors": "Syed YY", "journal": "Drugs", "year": 2022, "pmid": "36331779", "url": "https://pubmed.ncbi.nlm.nih.gov/36331779/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s40265-022-01790-4", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36331779/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Estrogen (Hormone Replacement)", "blackBoxWarnings": [ "Endometrial cancer: Estrogen-alone therapy increases the risk of endometrial cancer. Adding a progestin reduces but does not eliminate this risk. Women with an intact uterus should receive combined estrogen-progestin therapy.", "Cardiovascular disorders and breast cancer: Estrogens with or without progestins should not be used for prevention of cardiovascular disease or dementia. The WHI reported increased risks of DVT, PE, stroke, and invasive breast cancer in postmenopausal women.", "Dementia: The WHI Memory Study reported increased risk of probable dementia in postmenopausal women 65 years or older." ], "fdaPregnancyCategory": "X", "halfLife": "Oral estradiol: ~13–20 hours; Transdermal: maintains steady-state levels for patch duration", "onsetOfAction": "Vasomotor symptom relief in 2–4 weeks; full effect by 8–12 weeks", "commonBrandNames": [ "Estrace", "Vivelle-Dot", "Climara", "Divigel", "Alora" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Mammography per screening guidelines (annually or biennially). Endometrial evaluation if unexpected bleeding occurs. Lipid panel. Blood pressure. Bone density as clinically indicated. Periodic assessment of need to continue therapy. Liver function at baseline in patients with hepatic risk." }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "estradiol" }, { "id": "RX-ENDO-028", "name": "Combined Oral Contraceptive", "alternateNames": [ "The Pill", "Birth Control Pill", "COC" ], "category": "Prescription", "subcategory": "Hormonal Contraceptive", "overview": "Combined oral contraceptives (COCs) contain synthetic estrogen (usually ethinyl estradiol 20–35 mcg) and a progestin component. They are primarily used for contraception but are also prescribed for menstrual regulation, dysmenorrhea, endometriosis, acne, and polycystic ovary syndrome (PCOS). They are among the most widely used medications worldwide with an extensive safety record when appropriately prescribed.", "mechanismOfAction": "The progestin component suppresses the LH surge, preventing ovulation, while both the estrogen and progestin thicken cervical mucus (impeding sperm penetration), thin the endometrial lining (reducing implantation potential), and alter tubal motility. The estrogen component also suppresses FSH, preventing follicular development, and stabilizes the endometrium to prevent breakthrough bleeding.", "commonBenefits": [ "Highly effective contraception (>99% with perfect use)", "Menstrual cycle regulation", "Reduced dysmenorrhea and menstrual blood loss", "Improvement in acne and hirsutism", "Reduced risk of ovarian and endometrial cancer with long-term use", "Management of PCOS symptoms", "Treatment of endometriosis-related pain" ], "commonDosageRange": "Ethinyl estradiol 20–35 mcg + progestin (varies by product); taken once daily for 21–24 active days followed by 4–7 placebo days (as prescribed by your physician)", "recommendedForm": "Oral tablet; taken daily at the same time each day", "absorption": { "isFatSoluble": true, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Can be taken with or without food. Take at the same time each day for optimal efficacy. Vomiting or diarrhea within 2 hours of taking may reduce effectiveness." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Nausea (usually transient, improves after 1–3 cycles)", "Breast tenderness", "Headache", "Breakthrough bleeding or spotting", "Mood changes", "Decreased libido in some women", "Venous thromboembolism (3–4x baseline risk, still low absolute risk)", "Weight changes (minimal with modern formulations)" ], "contraindications": [ "Smoking in women over 35 years old (significantly increased cardiovascular risk)", "History of or current venous thromboembolism (DVT/PE)", "History of stroke or ischemic heart disease", "Migraine with aura at any age", "Known thrombophilia (Factor V Leiden, etc.)", "Breast cancer (current or within 5 years)", "Severe hepatic disease or liver tumors", "Uncontrolled hypertension (≥160/100 mmHg)" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "contraception", "hormonal", "womens-health", "menstrual-regulation", "PCOS" ], "sources": [ { "text": "Curtis KM et al. U.S. medical eligibility criteria for contraceptive use, 2016 (US MEC). MMWR Recomm Rep. 2016;65(3):1-103.", "pmid": "27467196", "doi": "10.15585/mmwr.rr6503a1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27467196/", "publicSourceType": "PMID" }, { "text": "de Bastos M et al. Combined oral contraceptives: venous thrombosis. Cochrane Database Syst Rev. 2014;(3):CD010813.", "pmid": "24590565", "doi": "10.1002/14651858.CD010813.pub2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24590565/", "publicSourceType": "PMID" }, { "text": "Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data. Lancet. 1996;347(9017):1713-1727.", "pmid": "8656904", "doi": "10.1016/S0140-6736(96)90806-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8656904/", "publicSourceType": "PMID" }, { "text": "Melin J, Forslund M, Alesi S et al.. Metformin and Combined Oral Contraceptive Pills in the Management of Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis. The Journal of clinical endocrinology and metabolism. 2024", "pmid": "37554096", "doi": "10.1210/clinem/dgad465", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37554096/", "publicSourceType": "PMID" }, { "text": "Morimont L, Haguet H, Dogné JM et al.. Combined Oral Contraceptives and Venous Thromboembolism: Review and Perspective to Mitigate the Risk. Frontiers in endocrinology. 2021", "pmid": "34956081", "doi": "10.3389/fendo.2021.769187", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34956081/", "publicSourceType": "PMID" }, { "text": "Brabaharan S, Veettil SK, Kaiser JE et al.. Association of Hormonal Contraceptive Use With Adverse Health Outcomes: An Umbrella Review of Meta-analyses of Randomized Clinical Trials and Cohort Studies. JAMA network open. 2022", "claim": "PubMed-indexed evidence involving Combined Oral Contraceptive", "title": "Association of Hormonal Contraceptive Use With Adverse Health Outcomes: An Umbrella Review of Meta-analyses of Randomized Clinical Trials and Cohort Studies", "authors": "Brabaharan S, Veettil SK, Kaiser JE et al.", "journal": "JAMA network open", "year": 2022, "pmid": "35029663", "url": "https://pubmed.ncbi.nlm.nih.gov/35029663/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1001/jamanetworkopen.2021.43730", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35029663/", "publicSourceType": "PMID" }, { "text": "Leelakanok N, Methaneethorn J. A Systematic Review and Meta-analysis of the Adverse Effects of Levonorgestrel Emergency Oral Contraceptive. Clinical drug investigation. 2020", "claim": "PubMed-indexed evidence involving Combined Oral Contraceptive", "title": "A Systematic Review and Meta-analysis of the Adverse Effects of Levonorgestrel Emergency Oral Contraceptive", "authors": "Leelakanok N, Methaneethorn J", "journal": "Clinical drug investigation", "year": 2020, "pmid": "32162237", "url": "https://pubmed.ncbi.nlm.nih.gov/32162237/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s40261-020-00901-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32162237/", "publicSourceType": "PMID" }, { "text": "Piacenti I, Tius V, Viscardi MF et al.. Dienogest vs. combined oral contraceptive: A systematic review and meta-analysis of efficacy and side effects to inform evidence-based guidelines. Acta obstetricia et gynecologica Scandinavica. 2025", "claim": "PubMed-indexed evidence involving Combined Oral Contraceptive", "title": "Dienogest vs. combined oral contraceptive: A systematic review and meta-analysis of efficacy and side effects to inform evidence-based guidelines", "authors": "Piacenti I, Tius V, Viscardi MF et al.", "journal": "Acta obstetricia et gynecologica Scandinavica", "year": 2025, "pmid": "40312882", "url": "https://pubmed.ncbi.nlm.nih.gov/40312882/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/aogs.15145", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40312882/", "publicSourceType": "PMID" }, { "text": "Watling CZ, Sweetland S, Wojt A et al.. Oral contraceptive use and risk of liver cancer: a population-based study, systematic review, and meta-analysis. The Lancet. Oncology. 2025", "claim": "PubMed-indexed evidence involving Combined Oral Contraceptive", "title": "Oral contraceptive use and risk of liver cancer: a population-based study, systematic review, and meta-analysis", "authors": "Watling CZ, Sweetland S, Wojt A et al.", "journal": "The Lancet. Oncology", "year": 2025, "pmid": "40617239", "url": "https://pubmed.ncbi.nlm.nih.gov/40617239/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/S1470-2045(25)00222-0", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40617239/", "publicSourceType": "PMID" }, { "text": "Nolan D, McNulty KL, Manninen M et al.. The Effect of Hormonal Contraceptive Use on Skeletal Muscle Hypertrophy, Power and Strength Adaptations to Resistance Exercise Training: A Systematic Review and Multilevel Meta-analysis. Sports medicine (Auckland, N.Z.). 2024", "claim": "PubMed-indexed evidence involving Combined Oral Contraceptive", "title": "The Effect of Hormonal Contraceptive Use on Skeletal Muscle Hypertrophy, Power and Strength Adaptations to Resistance Exercise Training: A Systematic Review and Multilevel Meta-analysis", "authors": "Nolan D, McNulty KL, Manninen M et al.", "journal": "Sports medicine (Auckland, N.Z.)", "year": 2024, "pmid": "37755666", "url": "https://pubmed.ncbi.nlm.nih.gov/37755666/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s40279-023-01911-3", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37755666/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Combined Hormonal Contraceptive (Estrogen + Progestin)", "blackBoxWarnings": [ "Cigarette smoking and serious cardiovascular events: Cigarette smoking increases the risk of serious cardiovascular events from combined oral contraceptive use. This risk increases with age, particularly in women over 35, and with the number of cigarettes smoked. Women who use combined oral contraceptives should be strongly advised not to smoke." ], "fdaPregnancyCategory": "X", "halfLife": "Ethinyl estradiol: 12–23 hours; Progestin varies by type (e.g., levonorgestrel ~24 hours, drospirenone ~30 hours)", "onsetOfAction": "Contraceptive efficacy in 7 days if started within first 5 days of menstrual cycle; immediate if started on day 1", "commonBrandNames": [ "Yaz", "Yasmin", "Lo Loestrin Fe", "Ortho Tri-Cyclen", "NuvaRing", "Seasonique" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": "No routine lab monitoring required. Blood pressure check before prescribing and at follow-up visits. Lipid panel if risk factors present. Cervical cancer screening per guidelines (not related to COC use). Assessment of migraine history and cardiovascular risk factors." }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "combined-oral-contraceptive" }, { "id": "RX-ENDO-029", "name": "Medroxyprogesterone", "alternateNames": [ "Provera", "Depo-Provera", "Depo-SubQ Provera" ], "category": "Prescription", "subcategory": "Progestin Hormone", "overview": "Medroxyprogesterone acetate (MPA) is a synthetic progestin used orally (Provera) for secondary amenorrhea, abnormal uterine bleeding, endometrial protection in HRT, and endometriosis. The injectable long-acting form (Depo-Provera) is a widely used contraceptive given every 3 months. It is also used in the treatment of endometrial and renal cell carcinoma and in the management of endometriosis-associated pain.", "mechanismOfAction": "A synthetic progestogen that binds to progesterone receptors, transforming a proliferative endometrium into a secretory one and preventing endometrial hyperplasia. For contraception, Depo-Provera suppresses the hypothalamic-pituitary-ovarian axis, inhibiting gonadotropin secretion and preventing ovulation. Also thickens cervical mucus and alters the endometrium to prevent implantation. Has mild glucocorticoid and anti-estrogenic activity.", "commonBenefits": [ "Highly effective injectable contraception (>99%)", "Only 4 injections per year for contraception", "Reduces menstrual bleeding (many users become amenorrheic)", "Oral form protects endometrium when combined with estrogen in HRT", "Treatment of abnormal uterine bleeding", "Reduces endometriosis-associated pain" ], "commonDosageRange": "Oral: 2.5–10 mg daily for 10–14 days per cycle; Depo-Provera: 150 mg IM or 104 mg subcutaneously every 3 months (as prescribed by your physician)", "recommendedForm": "Oral tablet (Provera) or intramuscular/subcutaneous injection (Depo-Provera)", "absorption": { "isFatSoluble": true, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Oral tablets can be taken with or without food. Depo-Provera injection forms a depot that slowly releases medication over 3 months." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Irregular menstrual bleeding and spotting (common initially)", "Amenorrhea (50% of users by 1 year on Depo-Provera)", "Weight gain (average 5–8 lbs over 2 years with Depo-Provera)", "Headache", "Mood changes and depression", "Bone mineral density loss with prolonged injectable use", "Delayed return to fertility after injectable discontinuation (average 10 months)", "Breast tenderness" ], "contraindications": [ "Known or suspected pregnancy", "Active thrombophlebitis or current thromboembolic disorders", "Known or suspected breast cancer", "Undiagnosed vaginal bleeding", "Severe hepatic disease", "Known hypersensitivity to medroxyprogesterone" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "contraception", "progestin", "hormonal", "womens-health", "injectable", "HRT" ], "sources": [ { "text": "Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women (WHI). JAMA. 2002;288(3):321-333.", "pmid": "12117397", "doi": "10.1001/jama.288.3.321", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12117397/", "publicSourceType": "PMID" }, { "text": "Clark MK et al. Bone mineral density changes over two years in first-time users of depot medroxyprogesterone acetate. Fertil Steril. 2006;86(3):727-735.", "pmid": "15589863", "doi": "10.1016/j.fertnstert.2006.01.059", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15589863/", "publicSourceType": "PMID" }, { "text": "Curtis KM et al. U.S. medical eligibility criteria for contraceptive use, 2016 (US MEC). MMWR Recomm Rep. 2016;65(3):1-103.", "pmid": "27467196", "doi": "10.15585/mmwr.rr6503a1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27467196/", "publicSourceType": "PMID" }, { "text": "Medroxyprogesterone Acetate. 2006", "pmid": "30000346", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30000346/", "publicSourceType": "PMID" }, { "text": "Dragoman MV, Gaffield ME. The safety of subcutaneously administered depot medroxyprogesterone acetate (104mg/0.65mL): A systematic review. Contraception. 2016", "claim": "PubMed-indexed evidence involving Medroxyprogesterone", "title": "The safety of subcutaneously administered depot medroxyprogesterone acetate (104mg/0.65mL): A systematic review", "authors": "Dragoman MV, Gaffield ME", "journal": "Contraception", "year": 2016, "pmid": "26874275", "url": "https://pubmed.ncbi.nlm.nih.gov/26874275/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.contraception.2016.02.003", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26874275/", "publicSourceType": "PMID" }, { "text": "Zürcher A, Knabben L, von Gernler M et al.. Depot medroxyprogesterone acetate and breast cancer: a systematic review. Archives of gynecology and obstetrics. 2024", "claim": "PubMed-indexed evidence involving Medroxyprogesterone", "title": "Depot medroxyprogesterone acetate and breast cancer: a systematic review", "authors": "Zürcher A, Knabben L, von Gernler M et al.", "journal": "Archives of gynecology and obstetrics", "year": 2024, "pmid": "37966517", "url": "https://pubmed.ncbi.nlm.nih.gov/37966517/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00404-023-07265-5", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37966517/", "publicSourceType": "PMID" }, { "text": "Dianat S, Fox E, Ahrens KA et al.. Side Effects and Health Benefits of Depot Medroxyprogesterone Acetate: A Systematic Review. Obstetrics and gynecology. 2019", "claim": "PubMed-indexed evidence involving Medroxyprogesterone", "title": "Side Effects and Health Benefits of Depot Medroxyprogesterone Acetate: A Systematic Review", "authors": "Dianat S, Fox E, Ahrens KA et al.", "journal": "Obstetrics and gynecology", "year": 2019, "pmid": "30633132", "url": "https://pubmed.ncbi.nlm.nih.gov/30633132/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/AOG.0000000000003089", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30633132/", "publicSourceType": "PMID" }, { "text": "Silva P, Qadir S, Fernandes A et al.. Dietary intake and eating behavior in depot medroxyprogesterone acetate users: a systematic review. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas. 2018", "claim": "PubMed-indexed evidence involving Medroxyprogesterone", "title": "Dietary intake and eating behavior in depot medroxyprogesterone acetate users: a systematic review", "authors": "Silva P, Qadir S, Fernandes A et al.", "journal": "Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas", "year": 2018, "pmid": "29694506", "url": "https://pubmed.ncbi.nlm.nih.gov/29694506/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1590/1414-431x20187575", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29694506/", "publicSourceType": "PMID" }, { "text": "Brind J, Condly SJ, Mosher SW et al.. Risk of HIV Infection in Depot-Medroxyprogesterone Acetate (DMPA) Users: A Systematic Review and Meta-analysis. 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Systematic reviews. 2023", "claim": "PubMed-indexed evidence involving Medroxyprogesterone", "title": "Implementation strategies to scale up self-administered depot medroxyprogesterone acetate subcutaneous injectable contraception: a scoping review", "authors": "Aderoba AK, Steyn PS, Kiarie JN", "journal": "Systematic reviews", "year": 2023, "pmid": "37403147", "url": "https://pubmed.ncbi.nlm.nih.gov/37403147/", "study_type": "review", "confidence": "verify", "doi": "10.1186/s13643-023-02216-2", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37403147/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Progestin (Synthetic Progestogen)", "blackBoxWarnings": [ "Loss of bone mineral density: Use of Depo-Provera injection for longer than 2 years should be limited to situations where other contraceptive methods are inadequate, as prolonged use is associated with significant loss of bone mineral density, which may not be completely reversible after discontinuation." ], "fdaPregnancyCategory": "X", "halfLife": "Oral: 12–17 hours; Depo-Provera IM: approximately 50 days", "onsetOfAction": "Oral: effect within days; Depo-Provera: contraceptive efficacy within 24 hours if given within first 5 days of cycle", "commonBrandNames": [ "Provera", "Depo-Provera", "Depo-SubQ Provera 104" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Bone mineral density (DEXA scan) if Depo-Provera used for more than 2 years. 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Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a randomized controlled trial. JAMA. 2000.", "pmid": "14505296", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14505296/", "publicSourceType": "PMID" }, { "text": "Clegg AJ et al. Exercise for depression. Cochrane Database Syst Rev. 2026.", "pmid": "41500513", "doi": "10.1002/14651858.CD004366.pub7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41500513/", "publicSourceType": "PMID" }, { "text": "Davis LL, Behl S, Lee D et al.. Brexpiprazole and Sertraline Combination Treatment in Posttraumatic Stress Disorder: A Phase 3 Randomized Clinical Trial. JAMA psychiatry. 2025", "pmid": "39693081", "doi": "10.1001/jamapsychiatry.2024.3996", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39693081/", "publicSourceType": "PMID" }, { "claim": "Sertraline is effective for panic disorder", "title": "Drug treatment for panic disorder with or without agoraphobia: systematic review and network meta-analysis of randomised controlled trials", "authors": "Chawla N, Anothaisintawee T, Charoenrungrueangchai K, Thaipisuttikul P et al.", "journal": "BMJ", "year": 2022, "pmid": "35045991", "url": "https://pubmed.ncbi.nlm.nih.gov/35045991/", "study_type": "network meta-analysis", "key_finding": "Sertraline was among the most effective pharmacological treatments for panic disorder, with strong evidence supporting its use as first-line therapy", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35045991/", "publicSourceType": "PMID" }, { "claim": "Sertraline is effective for maintenance treatment of major depressive disorder", "title": "Antidepressants for the treatment of adults with major depressive disorder in the maintenance phase: a systematic review and network meta-analysis", "authors": "Kishi T, Ikuta T, Sakuma K, Okuya M et al.", "journal": "Molecular Psychiatry", "year": 2023, "pmid": "36253442", "url": "https://pubmed.ncbi.nlm.nih.gov/36253442/", "study_type": "network meta-analysis", "key_finding": "Sertraline was among the antidepressants with the best efficacy and acceptability profiles for maintenance treatment of major depressive disorder, supporting long-term use for relapse prevention", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36253442/", "publicSourceType": "PMID" }, { "claim": "Optimal sertraline dosing for depression", "title": "Selection of the optimal dose of sertraline for depression: A dose-response meta-analysis of randomized controlled trials", "authors": "Luo X, Zhu D, Li J, Ren M et al.", "journal": "Psychiatry Research", "year": 2023, "pmid": "37557058", "url": "https://pubmed.ncbi.nlm.nih.gov/37557058/", "study_type": "meta-analysis", "key_finding": "Sertraline 50-100mg daily provided optimal efficacy with acceptable tolerability for depression; higher doses showed marginal additional benefit with increased adverse effects", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37557058/", "publicSourceType": "PMID" }, { "text": "Xie Z, Gao Z, Li X et al.. Sertraline and inflammatory markers in major depression: a systematic review and meta-analysis. Annals of general psychiatry. 2025", "claim": "PubMed-indexed evidence involving Sertraline", "title": "Sertraline and inflammatory markers in major depression: a systematic review and meta-analysis", "authors": "Xie Z, Gao Z, Li X et al.", "journal": "Annals of general psychiatry", "year": 2025, "pmid": "41023687", "url": "https://pubmed.ncbi.nlm.nih.gov/41023687/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12991-025-00596-4", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41023687/", "publicSourceType": "PMID" }, { "text": "Pinheiro E, Bogen DL, Hoxha D et al.. Sertraline and breastfeeding: review and meta-analysis. Archives of women's mental health. 2015", "claim": "PubMed-indexed evidence involving Sertraline", "title": "Sertraline and breastfeeding: review and meta-analysis", "authors": "Pinheiro E, Bogen DL, Hoxha D et al.", "journal": "Archives of women's mental health", "year": 2015, "pmid": "25589155", "url": "https://pubmed.ncbi.nlm.nih.gov/25589155/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00737-015-0499-y", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25589155/", "publicSourceType": "PMID" }, { "text": "Alhadab AA, Brundage RC. Population Pharmacokinetics of Sertraline in Healthy Subjects: a Model-Based Meta-analysis. The AAPS journal. 2020", "claim": "PubMed-indexed evidence involving Sertraline", "title": "Population Pharmacokinetics of Sertraline in Healthy Subjects: a Model-Based Meta-analysis", "authors": "Alhadab AA, Brundage RC", "journal": "The AAPS journal", "year": 2020, "pmid": "32430638", "url": "https://pubmed.ncbi.nlm.nih.gov/32430638/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1208/s12248-020-00455-y", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32430638/", "publicSourceType": "PMID" }, { "text": "Seifouri K, Kahdemi R, Ahmadi Hajikolaei F et al.. Sertraline in depressed patients with or at risk for coronary heart disese: a systemic review. American journal of cardiovascular disease. 2024", "claim": "PubMed-indexed evidence involving Sertraline", "title": "Sertraline in depressed patients with or at risk for coronary heart disese: a systemic review", "authors": "Seifouri K, Kahdemi R, Ahmadi Hajikolaei F et al.", "journal": "American journal of cardiovascular disease", "year": 2024, "pmid": "39839570", "url": "https://pubmed.ncbi.nlm.nih.gov/39839570/", "study_type": "review", "confidence": "verify", "doi": "10.62347/AXZC9187", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39839570/", "publicSourceType": "PMID" }, { "text": "Sanchez C, Reines EH, Montgomery SA. A comparative review of escitalopram, paroxetine, and sertraline: Are they all alike?. International clinical psychopharmacology. 2014", "claim": "PubMed-indexed evidence involving Sertraline", "title": "A comparative review of escitalopram, paroxetine, and sertraline: Are they all alike?", "authors": "Sanchez C, Reines EH, Montgomery SA", "journal": "International clinical psychopharmacology", "year": 2014, "pmid": "24424469", "url": "https://pubmed.ncbi.nlm.nih.gov/24424469/", "study_type": "review", "confidence": "verify", "doi": "10.1097/YIC.0000000000000023", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24424469/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Selective Serotonin Reuptake Inhibitor (SSRI)", "blackBoxWarnings": [ "Increased risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24) with major depressive disorder and other psychiatric disorders" ], "fdaPregnancyCategory": "C", "halfLife": "22–36 hours", "onsetOfAction": "1–2 weeks for initial effects; 4–6 weeks for full therapeutic benefit", "commonBrandNames": [ "Zoloft" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "sertraline" }, { "id": "RX-PSYCH-002", "name": "Fluoxetine", "alternateNames": [ "Prozac", "Sarafem" ], "category": "Prescription", "subcategory": "SSRI", "overview": "Prescription selective serotonin reuptake inhibitor (SSRI) approved for major depressive disorder, OCD, panic disorder, bulimia nervosa, and premenstrual dysphoric disorder. 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Lancet. 2018.", "pmid": "29477251", "doi": "10.1016/S0140-6736(17)32802-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29477251/", "publicSourceType": "PMID" }, { "text": "Tollefson GD et al. A double-blind, placebo-controlled clinical trial of fluoxetine in geriatric patients with major depression. Int Psychogeriatr. 1995.", "pmid": "15589564", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15589564/", "publicSourceType": "PMID" }, { "text": "Yalin N et al. Treatment of bipolar depression: results from a comprehensive network meta-analysis and updated systematic review. Eur Neuropsychopharmacol. 2026.", "pmid": "41855620", "doi": "10.1016/j.euroneuro.2026.112818", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41855620/", "publicSourceType": "PMID" }, { "claim": "Fluoxetine is one of the preferred antidepressants for children and adolescents with depression", "title": "Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis", "authors": "Cipriani A, Zhou X, Del Giovane C, Hetrick SE et al.", "journal": "Lancet", "year": 2016, "pmid": "27289172", "url": "https://pubmed.ncbi.nlm.nih.gov/27289172/", "study_type": "network meta-analysis", "key_finding": "Fluoxetine was the only antidepressant with a favorable efficacy-tolerability balance for children and adolescents with major depression, supporting its status as first-line pharmacotherapy in this population", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27289172/", "publicSourceType": "PMID" }, { "claim": "Fluoxetine is studied for eating disorder treatment", "title": "Psychopharmacology of eating disorders: Systematic review and meta-analysis of randomized controlled trials", "authors": "Fornaro M, Mondin AM, Billeci M, Fusco A et al.", "journal": "Journal of Affective Disorders", "year": 2023, "pmid": "37393954", "url": "https://pubmed.ncbi.nlm.nih.gov/37393954/", "study_type": "meta-analysis", "key_finding": "Fluoxetine is the most studied medication for bulimia nervosa and binge eating disorder, with evidence supporting its efficacy in reducing binge-eating episodes and purging behaviors", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37393954/", "publicSourceType": "PMID" }, { "text": "Mead GE, Legg L, Tilney R et al.. Fluoxetine for stroke recovery: Meta-analysis of randomized controlled trials. International journal of stroke : official journal of the International Stroke Society. 2020", "claim": "PubMed-indexed evidence involving Fluoxetine", "title": "Fluoxetine for stroke recovery: Meta-analysis of randomized controlled trials", "authors": "Mead GE, Legg L, Tilney R et al.", "journal": "International journal of stroke : official journal of the International Stroke Society", "year": 2020, "pmid": "31619137", "url": "https://pubmed.ncbi.nlm.nih.gov/31619137/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/1747493019879655", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31619137/", "publicSourceType": "PMID" }, { "text": "Gao SY, Wu QJ, Zhang TN et al.. Fluoxetine and congenital malformations: a systematic review and meta-analysis of cohort studies. British journal of clinical pharmacology. 2017", "claim": "PubMed-indexed evidence involving Fluoxetine", "title": "Fluoxetine and congenital malformations: a systematic review and meta-analysis of cohort studies", "authors": "Gao SY, Wu QJ, Zhang TN et al.", "journal": "British journal of clinical pharmacology", "year": 2017, "pmid": "28513059", "url": "https://pubmed.ncbi.nlm.nih.gov/28513059/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/bcp.13321", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28513059/", "publicSourceType": "PMID" }, { "text": "Beasley CM Jr, Dornseif BE, Bosomworth JC et al.. Fluoxetine and suicide: a meta-analysis of controlled trials of treatment for depression. BMJ (Clinical research ed.). 1991", "claim": "PubMed-indexed evidence involving Fluoxetine", "title": "Fluoxetine and suicide: a meta-analysis of controlled trials of treatment for depression", "authors": "Beasley CM Jr, Dornseif BE, Bosomworth JC et al.", "journal": "BMJ (Clinical research ed.)", "year": 1991, "pmid": "1833012", "url": "https://pubmed.ncbi.nlm.nih.gov/1833012/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1136/bmj.303.6804.685", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1833012/", "publicSourceType": "PMID" }, { "text": "de Oliveira MR. Fluoxetine and the mitochondria: A review of the toxicological aspects. Toxicology letters. 2016", "claim": "PubMed-indexed evidence involving Fluoxetine", "title": "Fluoxetine and the mitochondria: A review of the toxicological aspects", "authors": "de Oliveira MR", "journal": "Toxicology letters", "year": 2016, "pmid": "27392437", "url": "https://pubmed.ncbi.nlm.nih.gov/27392437/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.toxlet.2016.07.001", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27392437/", "publicSourceType": "PMID" }, { "text": "Stokes PE. Fluoxetine: a five-year review. 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Escitalopram versus other antidepressive agents for major depressive disorder: a systematic review and meta-analysis. 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Paroxetine in the treatment of premature ejaculation: a systematic review and meta-analysis. BMC urology. 2019", "claim": "PubMed-indexed evidence involving Paroxetine", "title": "Paroxetine in the treatment of premature ejaculation: a systematic review and meta-analysis", "authors": "Zhang D, Cheng Y, Wu K et al.", "journal": "BMC urology", "year": 2019, "pmid": "30606186", "url": "https://pubmed.ncbi.nlm.nih.gov/30606186/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12894-018-0431-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30606186/", "publicSourceType": "PMID" }, { "text": "Wang Y, Zhang A, Dilinuer A et al.. Meta-analysis of acupuncture combined with paroxetine in the treatment of depression. 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International journal of women's health. 2022", "claim": "PubMed-indexed evidence involving Paroxetine", "title": "A Clinical Review on Paroxetine and Emerging Therapies for the Treatment of Vasomotor Symptoms", "authors": "David PS, Smith TL, Nordhues HC et al.", "journal": "International journal of women's health", "year": 2022, "pmid": "35300283", "url": "https://pubmed.ncbi.nlm.nih.gov/35300283/", "study_type": "review", "confidence": "verify", "doi": "10.2147/IJWH.S282396", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35300283/", "publicSourceType": "PMID" }, { "text": "Slaton RM, Champion MN, Palmore KB. A review of paroxetine for the treatment of vasomotor symptoms. Journal of pharmacy practice. 2015", "claim": "PubMed-indexed evidence involving Paroxetine", "title": "A review of paroxetine for the treatment of vasomotor symptoms", "authors": "Slaton RM, Champion MN, Palmore KB", "journal": "Journal of pharmacy practice", "year": 2015, "pmid": "25107421", "url": "https://pubmed.ncbi.nlm.nih.gov/25107421/", "study_type": "review", "confidence": "verify", "doi": "10.1177/0897190014544785", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25107421/", "publicSourceType": "PMID" }, { "text": "Sanchez C, Reines EH, Montgomery SA. A comparative review of escitalopram, paroxetine, and sertraline: Are they all alike?. 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Escitalopram versus other antidepressive agents for major depressive disorder: a systematic review and meta-analysis. BMC psychiatry. 2023", "pmid": "38001423", "doi": "10.1186/s12888-023-05382-8", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38001423/", "publicSourceType": "PMID" }, { "text": "Cui M, Huang CY, Wang F. Efficacy and Safety of Citalopram for the Treatment of Poststroke Depression: A Meta-Analysis. 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Frontiers in cardiovascular medicine. 2023", "claim": "PubMed-indexed evidence involving Citalopram", "title": "Citalopram in the treatment of elderly chronic heart failure combined with depression: A systematic review and meta-analysis", "authors": "Yan L, Ai Y, Xing Y et al.", "journal": "Frontiers in cardiovascular medicine", "year": 2023, "pmid": "36818339", "url": "https://pubmed.ncbi.nlm.nih.gov/36818339/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fcvm.2023.1107672", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36818339/", "publicSourceType": "PMID" }, { "text": "Xu N, Song Z, Jiang D et al.. Toward therapeutic drug monitoring of citalopram in depression? Insights from a systematic review. Frontiers in psychiatry. 2023", "claim": "PubMed-indexed evidence involving Citalopram", "title": "Toward therapeutic drug monitoring of citalopram in depression? Insights from a systematic review", "authors": "Xu N, Song Z, Jiang D et al.", "journal": "Frontiers in psychiatry", "year": 2023, "pmid": "37181880", "url": "https://pubmed.ncbi.nlm.nih.gov/37181880/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fpsyt.2023.1144573", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37181880/", "publicSourceType": "PMID" }, { "text": "Tan S, Huang X, Ding L et al.. Efficacy and Safety of Citalopram in Treating Post-Stroke Depression: A Meta-Analysis. European neurology. 2015", "claim": "PubMed-indexed evidence involving Citalopram", "title": "Efficacy and Safety of Citalopram in Treating Post-Stroke Depression: A Meta-Analysis", "authors": "Tan S, Huang X, Ding L et al.", "journal": "European neurology", "year": 2015, "pmid": "26559658", "url": "https://pubmed.ncbi.nlm.nih.gov/26559658/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1159/000441446", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26559658/", "publicSourceType": "PMID" }, { "text": "Bech P, Cialdella P. Citalopram in depression--meta-analysis of intended and unintended effects. 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Efficacy and safety of duloxetine in chronic musculoskeletal pain: a systematic review and meta-analysis. BMC musculoskeletal disorders. 2023", "claim": "PubMed-indexed evidence involving Duloxetine", "title": "Efficacy and safety of duloxetine in chronic musculoskeletal pain: a systematic review and meta-analysis", "authors": "Ma X, Zhou S, Sun W et al.", "journal": "BMC musculoskeletal disorders", "year": 2023, "pmid": "37198620", "url": "https://pubmed.ncbi.nlm.nih.gov/37198620/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12891-023-06488-6", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37198620/", "publicSourceType": "PMID" }, { "text": "Park K, Kim S, Ko YJ et al.. Duloxetine and cardiovascular adverse events: A systematic review and meta-analysis. 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A randomized controlled trial of desvenlafaxine-induced structural brain changes in the treatment of persistent depressive disorder. Psychiatry research. Neuroimaging. 2023", "claim": "PubMed-indexed evidence involving Desvenlafaxine", "title": "A randomized controlled trial of desvenlafaxine-induced structural brain changes in the treatment of persistent depressive disorder", "authors": "Bansal R, Hellerstein DJ, Sawardekar S et al.", "journal": "Psychiatry research. Neuroimaging", "year": 2023, "pmid": "36996664", "url": "https://pubmed.ncbi.nlm.nih.gov/36996664/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.pscychresns.2023.111634", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36996664/", "publicSourceType": "PMID" }, { "text": "Katzman MA, Wang X, Wajsbrot DB et al.. Effects of desvenlafaxine versus placebo on MDD symptom clusters: A pooled analysis. Journal of psychopharmacology (Oxford, England). 2020", "claim": "PubMed-indexed evidence involving Desvenlafaxine", "title": "Effects of desvenlafaxine versus placebo on MDD symptom clusters: A pooled analysis", "authors": "Katzman MA, Wang X, Wajsbrot DB et al.", "journal": "Journal of psychopharmacology (Oxford, England)", "year": 2020, "pmid": "31913085", "url": "https://pubmed.ncbi.nlm.nih.gov/31913085/", "study_type": "RCT", "confidence": "verify", "doi": "10.1177/0269881119896066", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31913085/", "publicSourceType": "PMID" }, { "text": "Hellerstein DJ, Stewart JW, Chen Y et al.. Desvenlafaxine vs. placebo in the treatment of persistent depressive disorder. Journal of affective disorders. 2019", "claim": "PubMed-indexed evidence involving Desvenlafaxine", "title": "Desvenlafaxine vs. placebo in the treatment of persistent depressive disorder", "authors": "Hellerstein DJ, Stewart JW, Chen Y et al.", "journal": "Journal of affective disorders", "year": 2019, "pmid": "30423468", "url": "https://pubmed.ncbi.nlm.nih.gov/30423468/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.jad.2018.11.065", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30423468/", "publicSourceType": "PMID" }, { "text": "Atkinson S, Lubaczewski S, Ramaker S et al.. Desvenlafaxine Versus Placebo in the Treatment of Children and Adolescents with Major Depressive Disorder. Journal of child and adolescent psychopharmacology. 2018", "claim": "PubMed-indexed evidence involving Desvenlafaxine", "title": "Desvenlafaxine Versus Placebo in the Treatment of Children and Adolescents with Major Depressive Disorder", "authors": "Atkinson S, Lubaczewski S, Ramaker S et al.", "journal": "Journal of child and adolescent psychopharmacology", "year": 2018, "pmid": "29185786", "url": "https://pubmed.ncbi.nlm.nih.gov/29185786/", "study_type": "RCT", "confidence": "verify", "doi": "10.1089/cap.2017.0099", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29185786/", "publicSourceType": "PMID" }, { "text": "Weihs KL, Murphy W, Abbas R et al.. Desvenlafaxine Versus Placebo in a Fluoxetine-Referenced Study of Children and Adolescents with Major Depressive Disorder. 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J Clin Psychiatry. 2001.", "pmid": "11561932", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11561932/", "publicSourceType": "PMID" }, { "claim": "Bupropion is effective for ADHD in children, adolescents, and adults", "title": "Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis.", "authors": "Cortese S, Adamo N, Del Giovane C et al.", "journal": "Lancet Psychiatry", "year": 2018, "pmid": "30097390", "url": "https://pubmed.ncbi.nlm.nih.gov/30097390/", "study_type": "network meta-analysis", "key_finding": "Network meta-analysis of 133 RCTs found bupropion effective for ADHD symptoms across all age groups, though less efficacious than stimulants (methylphenidate, amphetamines); bupropion was among the best-tolerated non-stimulant options.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30097390/", "publicSourceType": "PMID" }, { "claim": "Bupropion is effective for adult ADHD treatment", "title": "Pharmacologic treatment of attention deficit hyperactivity disorder in adults: A systematic review and network meta-analysis.", "authors": "Elliott J, Johnston A, Husereau D et al.", "journal": "PLoS One", "year": 2020, "pmid": "33085721", "url": "https://pubmed.ncbi.nlm.nih.gov/33085721/", "study_type": "network meta-analysis", "key_finding": "Network meta-analysis of adult ADHD treatments found bupropion significantly reduced ADHD symptoms compared to placebo, with efficacy comparable to atomoxetine and guanfacine but lower than stimulants.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33085721/", "publicSourceType": "PMID" }, { "text": "Ji M, Feng J, Liu G. Efficacy and safety of aripiprazole or bupropion augmentation and switching in patients with treatment-resistant depression or major depressive disorder: A systematic review and meta-analysis of randomized controlled trials. PloS one. 2024", "claim": "PubMed-indexed evidence involving Bupropion", "title": "Efficacy and safety of aripiprazole or bupropion augmentation and switching in patients with treatment-resistant depression or major depressive disorder: A systematic review and meta-analysis of randomized controlled trials", "authors": "Ji M, Feng J, Liu G", "journal": "PloS one", "year": 2024, "pmid": "38669232", "url": "https://pubmed.ncbi.nlm.nih.gov/38669232/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1371/journal.pone.0299020", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38669232/", "publicSourceType": "PMID" }, { "text": "Bakouni H, Sharafi H, Bahremand A et al.. Bupropion for treatment of amphetamine-type stimulant use disorder: A systematic review and meta-analysis of placebo-controlled randomized clinical trials. Drug and alcohol dependence. 2023", "claim": "PubMed-indexed evidence involving Bupropion", "title": "Bupropion for treatment of amphetamine-type stimulant use disorder: A systematic review and meta-analysis of placebo-controlled randomized clinical trials", "authors": "Bakouni H, Sharafi H, Bahremand A et al.", "journal": "Drug and alcohol dependence", "year": 2023, "pmid": "37979478", "url": "https://pubmed.ncbi.nlm.nih.gov/37979478/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.drugalcdep.2023.111018", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37979478/", "publicSourceType": "PMID" }, { "text": "Akbar D, Rhee TG, Ceban F et al.. Dextromethorphan-Bupropion for the Treatment of Depression: A Systematic Review of Efficacy and Safety in Clinical Trials. CNS drugs. 2023", "claim": "PubMed-indexed evidence involving Bupropion", "title": "Dextromethorphan-Bupropion for the Treatment of Depression: A Systematic Review of Efficacy and Safety in Clinical Trials", "authors": "Akbar D, Rhee TG, Ceban F et al.", "journal": "CNS drugs", "year": 2023, "pmid": "37792265", "url": "https://pubmed.ncbi.nlm.nih.gov/37792265/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s40263-023-01032-5", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37792265/", "publicSourceType": "PMID" }, { "text": "Sposito AC, Bonilha I, Luchiari B et al.. Cardiovascular safety of naltrexone and bupropion therapy: Systematic review and meta-analyses. Obesity reviews : an official journal of the International Association for the Study of Obesity. 2021", "claim": "PubMed-indexed evidence involving Bupropion", "title": "Cardiovascular safety of naltrexone and bupropion therapy: Systematic review and meta-analyses", "authors": "Sposito AC, Bonilha I, Luchiari B et al.", "journal": "Obesity reviews : an official journal of the International Association for the Study of Obesity", "year": 2021, "pmid": "33847068", "url": "https://pubmed.ncbi.nlm.nih.gov/33847068/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/obr.13224", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33847068/", "publicSourceType": "PMID" }, { "text": "Turner E, Jones M, Vaz LR et al.. Systematic Review and Meta-Analysis to Assess the Safety of Bupropion and Varenicline in Pregnancy. Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco. 2019", "claim": "PubMed-indexed evidence involving Bupropion", "title": "Systematic Review and Meta-Analysis to Assess the Safety of Bupropion and Varenicline in Pregnancy", "authors": "Turner E, Jones M, Vaz LR et al.", "journal": "Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco", "year": 2019, "pmid": "29579233", "url": "https://pubmed.ncbi.nlm.nih.gov/29579233/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/ntr/nty055", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29579233/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Norepinephrine-Dopamine Reuptake Inhibitor (NDRI)", "blackBoxWarnings": [ "Increased risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24) with major depressive disorder and other psychiatric disorders" ], "fdaPregnancyCategory": "C", "halfLife": "21 hours (active metabolites up to 33 hours)", "onsetOfAction": "1–2 weeks for initial effects; 4–6 weeks for full therapeutic benefit", "commonBrandNames": [ "Wellbutrin", "Wellbutrin SR", "Wellbutrin XL", "Zyban" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "bupropion" }, { "id": "RX-PSYCH-011", "name": "Mirtazapine", "alternateNames": [ "Remeron", "Remeron SolTab" ], "category": "Prescription", "subcategory": "Atypical Antidepressant (NaSSA)", "overview": "Prescription noradrenergic and specific serotonergic antidepressant (NaSSA) approved for major depressive disorder. 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Acta psychiatrica Scandinavica. 2025", "claim": "PubMed-indexed evidence involving Mirtazapine", "title": "Mirtazapine in pregnancy and lactation: A systematic review of adverse outcomes", "authors": "Ostenfeld A, Lyngholm S, Christensen SE et al.", "journal": "Acta psychiatrica Scandinavica", "year": 2025, "pmid": "39215625", "url": "https://pubmed.ncbi.nlm.nih.gov/39215625/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/acps.13749", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39215625/", "publicSourceType": "PMID" }, { "text": "Milosavljević MN, Janković SM, Kostić MJ et al.. Mirtazapine-induced Acute Pancreatitis in Patients With Depression: A Systematic Review. Journal of psychiatric practice. 2023", "claim": "PubMed-indexed evidence involving Mirtazapine", "title": "Mirtazapine-induced Acute Pancreatitis in Patients With Depression: A Systematic Review", "authors": "Milosavljević MN, Janković SM, Kostić MJ et al.", "journal": "Journal of psychiatric practice", "year": 2023, "pmid": "36649554", "url": "https://pubmed.ncbi.nlm.nih.gov/36649554/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/PRA.0000000000000687", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36649554/", "publicSourceType": "PMID" }, { "text": "Furukawa TA, Cipriani A, Cowen PJ et al.. Optimal dose of selective serotonin reuptake inhibitors, venlafaxine, and mirtazapine in major depression: a systematic review and dose-response meta-analysis. The lancet. Psychiatry. 2019", "claim": "PubMed-indexed evidence involving Mirtazapine", "title": "Optimal dose of selective serotonin reuptake inhibitors, venlafaxine, and mirtazapine in major depression: a systematic review and dose-response meta-analysis", "authors": "Furukawa TA, Cipriani A, Cowen PJ et al.", "journal": "The lancet. Psychiatry", "year": 2019, "pmid": "31178367", "url": "https://pubmed.ncbi.nlm.nih.gov/31178367/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/S2215-0366(19)30217-2", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31178367/", "publicSourceType": "PMID" }, { "text": "Ottman AA, Warner CB, Brown JN. The role of mirtazapine in patients with fibromyalgia: a systematic review. Rheumatology international. 2018", "claim": "PubMed-indexed evidence involving Mirtazapine", "title": "The role of mirtazapine in patients with fibromyalgia: a systematic review", "authors": "Ottman AA, Warner CB, Brown JN", "journal": "Rheumatology international", "year": 2018, "pmid": "29860538", "url": "https://pubmed.ncbi.nlm.nih.gov/29860538/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00296-018-4068-3", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29860538/", "publicSourceType": "PMID" }, { "text": "Smit M, Dolman KM, Honig A. Mirtazapine in pregnancy and lactation - A systematic review. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 2016", "claim": "PubMed-indexed evidence involving Mirtazapine", "title": "Mirtazapine in pregnancy and lactation - A systematic review", "authors": "Smit M, Dolman KM, Honig A", "journal": "European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology", "year": 2016, "pmid": "26631373", "url": "https://pubmed.ncbi.nlm.nih.gov/26631373/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.euroneuro.2015.06.014", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26631373/", "publicSourceType": "PMID" }, { "text": "Vidal C, Reese C, Fischer BA et al.. Meta-Analysis of Efficacy of Mirtazapine as an Adjunctive Treatment of Negative Symptoms in Schizophrenia. Clinical schizophrenia & related psychoses. 2015", "claim": "PubMed-indexed evidence involving Mirtazapine", "title": "Meta-Analysis of Efficacy of Mirtazapine as an Adjunctive Treatment of Negative Symptoms in Schizophrenia", "authors": "Vidal C, Reese C, Fischer BA et al.", "journal": "Clinical schizophrenia & related psychoses", "year": 2015, "pmid": "23491969", "url": "https://pubmed.ncbi.nlm.nih.gov/23491969/", "study_type": "meta-analysis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23491969/", "publicSourceType": "PMID" }, { "text": "Ostenfeld A, Carlsen SE, Jensen AK et al.. Mirtazapine or ondansetron for hyperemesis gravidarum: a randomized placebo-controlled trial. 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Effects of Trazodone on Sleep: A Systematic Review and Meta-analysis. CNS drugs. 2024", "pmid": "39123094", "doi": "10.1007/s40263-024-01110-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39123094/", "publicSourceType": "PMID" }, { "text": "Jaffer KY, Chang T, Vanle B et al.. Trazodone for Insomnia: A Systematic Review. Innovations in clinical neuroscience. 2017", "pmid": "29552421", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29552421/", "publicSourceType": "PMID" }, { "claim": "Trazodone is effective for treatment of primary insomnia", "title": "Trazodone for the treatment of insomnia: a meta-analysis of randomized placebo-controlled trials.", "authors": "Yi XY, Ni SF, Ghadami MR et al.", "journal": "Sleep Medicine", "year": 2018, "pmid": "29680424", "url": "https://pubmed.ncbi.nlm.nih.gov/29680424/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of RCTs found trazodone significantly improved subjective sleep quality and reduced sleep onset latency compared to placebo in insomnia patients, with generally mild adverse effects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29680424/", "publicSourceType": "PMID" }, { "text": "Zheng Y, Lv T, Wu J et al.. Trazodone changed the polysomnographic sleep architecture in insomnia disorder: a systematic review and meta-analysis. Scientific reports. 2022", "claim": "PubMed-indexed evidence involving Trazodone", "title": "Trazodone changed the polysomnographic sleep architecture in insomnia disorder: a systematic review and meta-analysis", "authors": "Zheng Y, Lv T, Wu J et al.", "journal": "Scientific reports", "year": 2022, "pmid": "36002579", "url": "https://pubmed.ncbi.nlm.nih.gov/36002579/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1038/s41598-022-18776-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36002579/", "publicSourceType": "PMID" }, { "text": "Pal S, Chataway J, Swingler R et al.. Safety and efficacy of memantine and trazodone versus placebo for motor neuron disease (MND SMART): stage two interim analysis from the first cycle of a phase 3, multiarm, multistage, randomised, adaptive platform trial. The Lancet. Neurology. 2024", "claim": "PubMed-indexed evidence involving Trazodone", "title": "Safety and efficacy of memantine and trazodone versus placebo for motor neuron disease (MND SMART): stage two interim analysis from the first cycle of a phase 3, multiarm, multistage, randomised, adaptive platform trial", "authors": "Pal S, Chataway J, Swingler R et al.", "journal": "The Lancet. Neurology", "year": 2024, "pmid": "39307154", "url": "https://pubmed.ncbi.nlm.nih.gov/39307154/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/S1474-4422(24)00326-0", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39307154/", "publicSourceType": "PMID" }, { "text": "Fink HA, MacDonald R, Rutks IR et al.. Trazodone for erectile dysfunction: a systematic review and meta-analysis. BJU international. 2003", "claim": "PubMed-indexed evidence involving Trazodone", "title": "Trazodone for erectile dysfunction: a systematic review and meta-analysis", "authors": "Fink HA, MacDonald R, Rutks IR et al.", "journal": "BJU international", "year": 2003, "pmid": "12930437", "url": "https://pubmed.ncbi.nlm.nih.gov/12930437/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1046/j.1464-410x.2003.04358.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12930437/", "publicSourceType": "PMID" }, { "text": "Aishah A, Kim M, Gell L et al.. Effect of viloxazine and trazodone in obstructive sleep apnoea: a randomised, placebo-controlled, cross-over study. Thorax. 2025", "claim": "PubMed-indexed evidence involving Trazodone", "title": "Effect of viloxazine and trazodone in obstructive sleep apnoea: a randomised, placebo-controlled, cross-over study", "authors": "Aishah A, Kim M, Gell L et al.", "journal": "Thorax", "year": 2025, "pmid": "40360261", "url": "https://pubmed.ncbi.nlm.nih.gov/40360261/", "study_type": "RCT", "confidence": "verify", "doi": "10.1136/thorax-2024-222513", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40360261/", "publicSourceType": "PMID" }, { "text": "Eyob E, Shaw JS, Bakker A et al.. A Randomized-Controlled Trial Targeting Cognition in Early Alzheimer's Disease by Improving Sleep with Trazodone (REST). 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Cochrane Database Syst Rev. 2015.", "pmid": "35658166", "doi": "10.1002/14651858.CD008242.pub3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35658166/", "publicSourceType": "PMID" }, { "text": "Cipriani A et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018.", "pmid": "29477251", "doi": "10.1016/S0140-6736(17)32802-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29477251/", "publicSourceType": "PMID" }, { "text": "Abouelmagd ME et al. Efficacy and Safety of Melatonin in Migraine Prophylaxis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Curr Pain Headache Rep. 2026.", "pmid": "41627537", "doi": "10.1007/s11916-025-01461-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41627537/", "publicSourceType": "PMID" }, { "claim": "Amitriptyline is effective for fibromyalgia pain relief", "title": "Comparison of Amitriptyline and US Food and Drug Administration-Approved Treatments for Fibromyalgia: A Systematic Review and Network Meta-analysis.", "authors": "Farag HM, Yunusa I, Goswami H et al.", "journal": "JAMA Network Open", "year": 2022, "pmid": "35587348", "url": "https://pubmed.ncbi.nlm.nih.gov/35587348/", "study_type": "network meta-analysis", "key_finding": "Network meta-analysis found amitriptyline was among the most effective treatments for fibromyalgia, showing significant pain reduction and sleep improvement comparable to FDA-approved treatments (duloxetine, milnacipran, pregabalin).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35587348/", "publicSourceType": "PMID" }, { "text": "Brueckle MS, Thomas ET, Seide SE et al.. Amitriptyline's anticholinergic adverse drug reactions-A systematic multiple-indication review and meta-analysis. PloS one. 2023", "claim": "PubMed-indexed evidence involving Amitriptyline", "title": "Amitriptyline's anticholinergic adverse drug reactions-A systematic multiple-indication review and meta-analysis", "authors": "Brueckle MS, Thomas ET, Seide SE et al.", "journal": "PloS one", "year": 2023, "pmid": "37018325", "url": "https://pubmed.ncbi.nlm.nih.gov/37018325/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1371/journal.pone.0284168", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37018325/", "publicSourceType": "PMID" }, { "text": "Chen LW, Chen MY, Lian ZP et al.. Amitriptyline and Sexual Function: A Systematic Review Updated for Sexual Health Practice. American journal of men's health. 2018", "claim": "PubMed-indexed evidence involving Amitriptyline", "title": "Amitriptyline and Sexual Function: A Systematic Review Updated for Sexual Health Practice", "authors": "Chen LW, Chen MY, Lian ZP et al.", "journal": "American journal of men's health", "year": 2018, "pmid": "29019272", "url": "https://pubmed.ncbi.nlm.nih.gov/29019272/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/1557988317734519", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29019272/", "publicSourceType": "PMID" }, { "text": "van den Driest JJ, Bierma-Zeinstra SMA, Bindels PJE et al.. Amitriptyline for musculoskeletal complaints: a systematic review. Family practice. 2017", "claim": "PubMed-indexed evidence involving Amitriptyline", "title": "Amitriptyline for musculoskeletal complaints: a systematic review", "authors": "van den Driest JJ, Bierma-Zeinstra SMA, Bindels PJE et al.", "journal": "Family practice", "year": 2017, "pmid": "28334783", "url": "https://pubmed.ncbi.nlm.nih.gov/28334783/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/fampra/cmw134", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28334783/", "publicSourceType": "PMID" }, { "text": "Nishishinya B, Urrútia G, Walitt B et al.. Amitriptyline in the treatment of fibromyalgia: a systematic review of its efficacy. Rheumatology (Oxford, England). 2008", "claim": "PubMed-indexed evidence involving Amitriptyline", "title": "Amitriptyline in the treatment of fibromyalgia: a systematic review of its efficacy", "authors": "Nishishinya B, Urrútia G, Walitt B et al.", "journal": "Rheumatology (Oxford, England)", "year": 2008, "pmid": "18697829", "url": "https://pubmed.ncbi.nlm.nih.gov/18697829/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/rheumatology/ken317", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18697829/", "publicSourceType": "PMID" }, { "text": "Wang Y, Wu C, Liu Y et al.. Comparison of Duloxetine Supplemented With Pregabalin and Amitriptyline Supplemented With Pregabalin for the Treatment of Postherpetic Neuralgia: A Double-Blind, Randomized Crossover Trial. CNS neuroscience & therapeutics. 2025", "claim": "PubMed-indexed evidence involving Amitriptyline", "title": "Comparison of Duloxetine Supplemented With Pregabalin and Amitriptyline Supplemented With Pregabalin for the Treatment of Postherpetic Neuralgia: A Double-Blind, Randomized Crossover Trial", "authors": "Wang Y, Wu C, Liu Y et al.", "journal": "CNS neuroscience & therapeutics", "year": 2025, "pmid": "40418104", "url": "https://pubmed.ncbi.nlm.nih.gov/40418104/", "study_type": "RCT", "confidence": "verify", "doi": "10.1111/cns.70460", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40418104/", "publicSourceType": "PMID" }, { "text": "Ford AC, Wright-Hughes A, Alderson SL et al.. Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial. 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Lancet. 2018.", "pmid": "29477251", "doi": "10.1016/S0140-6736(17)32802-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29477251/", "publicSourceType": "PMID" }, { "text": "Derry S et al. Nortriptyline for neuropathic pain in adults. Cochrane Database Syst Rev. 2015.", "pmid": "28530786", "doi": "10.1002/14651858.CD011209.pub2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28530786/", "publicSourceType": "PMID" }, { "text": "Pillinger T et al. The effects of antidepressants on cardiometabolic and other physiological parameters: a systematic review and network meta-analysis. Lancet. 2025.", "pmid": "41135546", "doi": "10.1016/S0140-6736(25)01293-0", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41135546/", "publicSourceType": "PMID" }, { "text": "Nortriptyline. 2006", "pmid": "30000235", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30000235/", "publicSourceType": "PMID" }, { "text": "Hashemzadeh S, Mortazavi M, Abdi Dezfouli R. Quantitative analysis of nortriptyline's analgesic properties: a comparative systematic review and meta-analysis. BMJ open. 2024", "claim": "PubMed-indexed evidence involving Nortriptyline", "title": "Quantitative analysis of nortriptyline's analgesic properties: a comparative systematic review and meta-analysis", "authors": "Hashemzadeh S, Mortazavi M, Abdi Dezfouli R", "journal": "BMJ open", "year": 2024, "pmid": "39122393", "url": "https://pubmed.ncbi.nlm.nih.gov/39122393/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1136/bmjopen-2024-085438", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39122393/", "publicSourceType": "PMID" }, { "text": "Abouzari M, Tawk K, Kim JK et al.. Efficacy of Nortriptyline-Topiramate and Verapamil-Paroxetine in Tinnitus Management: A Randomized Placebo-Controlled Trial. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2025", "claim": "PubMed-indexed evidence involving Nortriptyline", "title": "Efficacy of Nortriptyline-Topiramate and Verapamil-Paroxetine in Tinnitus Management: A Randomized Placebo-Controlled Trial", "authors": "Abouzari M, Tawk K, Kim JK et al.", "journal": "Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery", "year": 2025, "pmid": "39588680", "url": "https://pubmed.ncbi.nlm.nih.gov/39588680/", "study_type": "RCT", "confidence": "verify", "doi": "10.1002/ohn.1063", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39588680/", "publicSourceType": "PMID" }, { "text": "Benazzi F. Venlafaxine-fluoxetine-nortriptyline interaction. Journal of psychiatry & neuroscience : JPN. 1997", "claim": "PubMed-indexed evidence involving Nortriptyline", "title": "Venlafaxine-fluoxetine-nortriptyline interaction", "authors": "Benazzi F", "journal": "Journal of psychiatry & neuroscience : JPN", "year": 1997, "pmid": "9262050", "url": "https://pubmed.ncbi.nlm.nih.gov/9262050/", "study_type": "review", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9262050/", "publicSourceType": "PMID" }, { "text": "Fu C, Katzman M, Goldbloom DS. Valproate/nortriptyline interaction. Journal of clinical psychopharmacology. 1994", "claim": "PubMed-indexed evidence involving Nortriptyline", "title": "Valproate/nortriptyline interaction", "authors": "Fu C, Katzman M, Goldbloom DS", "journal": "Journal of clinical psychopharmacology", "year": 1994, "pmid": "8027418", "url": "https://pubmed.ncbi.nlm.nih.gov/8027418/", "study_type": "review", "confidence": "verify", "doi": "10.1097/00004714-199406000-00009", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8027418/", "publicSourceType": "PMID" }, { "text": "Merwar G, Gibbons JR, Hosseini SA et al.. Nortriptyline. 2026", "claim": "PubMed-indexed evidence involving Nortriptyline", "title": "Nortriptyline", "authors": "Merwar G, Gibbons JR, Hosseini SA et al.", "journal": "", "year": 2026, "pmid": "29489270", "url": "https://pubmed.ncbi.nlm.nih.gov/29489270/", "study_type": "review", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29489270/", "publicSourceType": "PMID" }, { "text": "Vos CF, Coenen MJH, Ter Hark SE et al.. Optimizing Nortriptyline Dosing: A Comparison between Pharmacogenetics-Based, Phenotype-Based, and Standard Dosing. Clinical pharmacokinetics. 2025", "claim": "PubMed-indexed evidence involving Nortriptyline", "title": "Optimizing Nortriptyline Dosing: A Comparison between Pharmacogenetics-Based, Phenotype-Based, and Standard Dosing", "authors": "Vos CF, Coenen MJH, Ter Hark SE et al.", "journal": "Clinical pharmacokinetics", "year": 2025, "pmid": "40413686", "url": "https://pubmed.ncbi.nlm.nih.gov/40413686/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s40262-025-01528-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40413686/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Tricyclic Antidepressant (TCA)", "blackBoxWarnings": [ "Increased risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24) with major depressive disorder and other psychiatric disorders" ], "fdaPregnancyCategory": "C", "halfLife": "18–44 hours", "onsetOfAction": "2–4 weeks for antidepressant effects; pain relief may begin within 1–2 weeks", "commonBrandNames": [ "Pamelor", "Aventyl" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Therapeutic drug monitoring recommended; target serum level 50–150 ng/mL. 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Psychother Psychosom. 2013.", "pmid": "24061211", "doi": "10.1159/000353198", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24061211/", "publicSourceType": "PMID" }, { "text": "Ait-Daoud N et al. A review of alprazolam use, misuse, and withdrawal. J Addict Med. 2018.", "pmid": "28777203", "doi": "10.1097/ADM.0000000000000380", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28777203/", "publicSourceType": "PMID" }, { "text": "Li J et al. Effects of tranquilization therapy in elderly patients suffering from chronic non-communicable diseases: A meta-analysis. Acta Pharm. 2023.", "pmid": "36692463", "doi": "10.2478/acph-2023-0003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36692463/", "publicSourceType": "PMID" }, { "text": "George TT, Tripp J. Alprazolam. 2026", "pmid": "30844192", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30844192/", "publicSourceType": "PMID" }, { "claim": "Alprazolam is effective for panic disorder treatment", "title": "Pharmacological treatments in panic disorder in adults: a network meta-analysis.", "authors": "Guaiana G, Meader N, Barbui C et al.", "journal": "Cochrane Database of Systematic Reviews", "year": 2023, "pmid": "38014714", "url": "https://pubmed.ncbi.nlm.nih.gov/38014714/", "study_type": "network meta-analysis", "key_finding": "Cochrane network meta-analysis found alprazolam among the most effective pharmacological treatments for panic disorder, with significantly better response than placebo; SSRIs and SNRIs also effective but alprazolam showed faster onset of action.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38014714/", "publicSourceType": "PMID" }, { "claim": "Alprazolam is effective for generalized anxiety disorder", "title": "Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis.", "authors": "Slee A, Nazareth I, Bondaronek P et al.", "journal": "Lancet", "year": 2019, "pmid": "30712879", "url": "https://pubmed.ncbi.nlm.nih.gov/30712879/", "study_type": "network meta-analysis", "key_finding": "Network meta-analysis of 89 studies found benzodiazepines including alprazolam effective for GAD but noted concerns about dependence, withdrawal, and inferior long-term outcomes compared to antidepressants.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30712879/", "publicSourceType": "PMID" }, { "text": "Srisurapanont M, Boonyanaruthee V. Alprazolam and standard antidepressants in the treatment of depression: a meta-analysis of the antidepressant effect. Journal of the Medical Association of Thailand = Chotmaihet thangphaet. 1997", "claim": "PubMed-indexed evidence involving Alprazolam", "title": "Alprazolam and standard antidepressants in the treatment of depression: a meta-analysis of the antidepressant effect", "authors": "Srisurapanont M, Boonyanaruthee V", "journal": "Journal of the Medical Association of Thailand = Chotmaihet thangphaet", "year": 1997, "pmid": "9175386", "url": "https://pubmed.ncbi.nlm.nih.gov/9175386/", "study_type": "meta-analysis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9175386/", "publicSourceType": "PMID" }, { "text": "Jonas JM, Hearron AE Jr. Alprazolam and suicidal ideation: a meta-analysis of controlled trials in the treatment of depression. Journal of clinical psychopharmacology. 1996", "claim": "PubMed-indexed evidence involving Alprazolam", "title": "Alprazolam and suicidal ideation: a meta-analysis of controlled trials in the treatment of depression", "authors": "Jonas JM, Hearron AE Jr", "journal": "Journal of clinical psychopharmacology", "year": 1996, "pmid": "8784651", "url": "https://pubmed.ncbi.nlm.nih.gov/8784651/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/00004714-199606000-00003", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8784651/", "publicSourceType": "PMID" }, { "text": "Boyer W. Serotonin uptake inhibitors are superior to imipramine and alprazolam in alleviating panic attacks: a meta-analysis. International clinical psychopharmacology. 1995", "claim": "PubMed-indexed evidence involving Alprazolam", "title": "Serotonin uptake inhibitors are superior to imipramine and alprazolam in alleviating panic attacks: a meta-analysis", "authors": "Boyer W", "journal": "International clinical psychopharmacology", "year": 1995, "pmid": "7622804", "url": "https://pubmed.ncbi.nlm.nih.gov/7622804/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/00004850-199503000-00006", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7622804/", "publicSourceType": "PMID" }, { "text": "Kelty E, Chitty K, Preen DB. Safety of Alprazolam Use in Pregnancy in Western Australia: A Retrospective Cohort Study Using Linked Health Data. Journal of psychoactive drugs. 2024", "claim": "PubMed-indexed evidence involving Alprazolam", "title": "Safety of Alprazolam Use in Pregnancy in Western Australia: A Retrospective Cohort Study Using Linked Health Data", "authors": "Kelty E, Chitty K, Preen DB", "journal": "Journal of psychoactive drugs", "year": 2024, "pmid": "37504800", "url": "https://pubmed.ncbi.nlm.nih.gov/37504800/", "study_type": "cohort", "confidence": "verify", "doi": "10.1080/02791072.2023.2241465", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37504800/", "publicSourceType": "PMID" }, { "text": "Huang F, San X, Liu Q et al.. Signal mining and risk analysis of Alprazolam adverse events based on the FAERS database. Scientific reports. 2024", "claim": "PubMed-indexed evidence involving Alprazolam", "title": "Signal mining and risk analysis of Alprazolam adverse events based on the FAERS database", "authors": "Huang F, San X, Liu Q et al.", "journal": "Scientific reports", "year": 2024, "pmid": "38553504", "url": "https://pubmed.ncbi.nlm.nih.gov/38553504/", "study_type": "review", "confidence": "verify", "doi": "10.1038/s41598-024-57909-y", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38553504/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Benzodiazepine", "blackBoxWarnings": [ "Risks from concomitant use with opioids include profound sedation, respiratory depression, coma, and death. Risk of abuse, misuse, and addiction. 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Psychother Psychosom. 2013.", "pmid": "24061211", "doi": "10.1159/000353198", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24061211/", "publicSourceType": "PMID" }, { "text": "Greenblatt DJ et al. Clinical pharmacokinetics of lorazepam. Clin Pharmacokinet. 1981.", "pmid": "25195839", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25195839/", "publicSourceType": "PMID" }, { "text": "Ezzi S et al. Effectiveness and safety of midazolam versus lorazepam for pediatric status epilepticus: A systematic review and meta-analysis. Seizure. 2025.", "pmid": "40876407", "doi": "10.1016/j.seizure.2025.08.013", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40876407/", "publicSourceType": "PMID" }, { "claim": "Lorazepam is effective first-line treatment for convulsive status epilepticus", "title": "Lorazepam or diazepam for convulsive status epilepticus: A meta-analysis.", "authors": "Wu W, Zhang L, Xue R", "journal": "Journal of Clinical Neuroscience", "year": 2016, "pmid": "27052258", "url": "https://pubmed.ncbi.nlm.nih.gov/27052258/", "study_type": "meta-analysis", "key_finding": "Meta-analysis found lorazepam had comparable efficacy to diazepam for terminating convulsive status epilepticus, with a trend toward fewer recurrences and less respiratory depression, supporting its role as a first-line agent.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27052258/", "publicSourceType": "PMID" }, { "claim": "Benzodiazepines including lorazepam are widely used around pregnancy despite risks", "title": "Prevalence of benzodiazepines and benzodiazepine-related drugs exposure before, during and after pregnancy: A systematic review and meta-analysis.", "authors": "Bais B, Molenaar NM, Bijma HH et al.", "journal": "Journal of Affective Disorders", "year": 2020, "pmid": "32217339", "url": "https://pubmed.ncbi.nlm.nih.gov/32217339/", "study_type": "meta-analysis", "key_finding": "Systematic review found benzodiazepines including lorazepam commonly prescribed during pregnancy (prevalence 1.1-10.9%), highlighting the need for careful risk-benefit assessment given potential neonatal complications.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32217339/", "publicSourceType": "PMID" }, { "text": "Chen A, Bae M. Lorazepam in Managing Atypical Neuroleptic Malignant Syndrome: A Systematic Review of Case Reports. The western journal of emergency medicine. 2025", "claim": "PubMed-indexed evidence involving Lorazepam", "title": "Lorazepam in Managing Atypical Neuroleptic Malignant Syndrome: A Systematic Review of Case Reports", "authors": "Chen A, Bae M", "journal": "The western journal of emergency medicine", "year": 2025, "pmid": "41192984", "url": "https://pubmed.ncbi.nlm.nih.gov/41192984/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.5811/westjem.41514", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41192984/", "publicSourceType": "PMID" }, { "text": "Amore M, D'Andrea M, Fagiolini A. Treatment of Agitation With Lorazepam in Clinical Practice: A Systematic Review. Frontiers in psychiatry. 2021", "claim": "PubMed-indexed evidence involving Lorazepam", "title": "Treatment of Agitation With Lorazepam in Clinical Practice: A Systematic Review", "authors": "Amore M, D'Andrea M, Fagiolini A", "journal": "Frontiers in psychiatry", "year": 2021, "pmid": "33692709", "url": "https://pubmed.ncbi.nlm.nih.gov/33692709/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fpsyt.2021.628965", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33692709/", "publicSourceType": "PMID" }, { "text": "Curtin F, Schulz P. Clonazepam and lorazepam in acute mania: a Bayesian meta-analysis. 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Scientific reports. 2023", "claim": "PubMed-indexed evidence involving Diazepam", "title": "The anxiolytic effects of preoperative administration of pregabalin in comparison to diazepam and placebo", "authors": "Nimmaanrat S, Charuenporn B, Jensen MP et al.", "journal": "Scientific reports", "year": 2023, "pmid": "37322140", "url": "https://pubmed.ncbi.nlm.nih.gov/37322140/", "study_type": "RCT", "confidence": "verify", "doi": "10.1038/s41598-023-36616-0", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37322140/", "publicSourceType": "PMID" }, { "text": "Verrotti A, Milioni M, Zaccara G. Safety and efficacy of diazepam autoinjector for the management of epilepsy. Expert review of neurotherapeutics. 2015", "claim": "PubMed-indexed evidence involving Diazepam", "title": "Safety and efficacy of diazepam autoinjector for the management of epilepsy", "authors": "Verrotti A, Milioni M, Zaccara G", "journal": "Expert review of neurotherapeutics", "year": 2015, "pmid": "25614951", "url": "https://pubmed.ncbi.nlm.nih.gov/25614951/", "study_type": "review", "confidence": "verify", "doi": "10.1586/14737175.2015.1003043", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25614951/", "publicSourceType": "PMID" }, { "text": "Murphy A, Wilbur K. Phenytoin-diazepam interaction. The Annals of pharmacotherapy. 2003", "claim": "PubMed-indexed evidence involving Diazepam", "title": "Phenytoin-diazepam interaction", "authors": "Murphy A, Wilbur K", "journal": "The Annals of pharmacotherapy", "year": 2003, "pmid": "12708941", "url": "https://pubmed.ncbi.nlm.nih.gov/12708941/", "study_type": "review", "confidence": "verify", "doi": "10.1345/aph.1C413", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12708941/", "publicSourceType": "PMID" }, { "text": "Hawksworth G, Betts T, Crowe A et al.. Diazepam/beta-adrenoceptor antagonist interactions. 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Azapirones for generalized anxiety disorder. Cochrane Database Syst Rev. 2006.", "pmid": "16856115", "doi": "10.1002/14651858.CD006115", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16856115/", "publicSourceType": "PMID" }, { "text": "Loane C, Politis M. Buspirone: what is it all about? Brain Res. 2012.", "pmid": "22608068", "doi": "10.1016/j.brainres.2012.02.009", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22608068/", "publicSourceType": "PMID" }, { "text": "Yamada R et al. Augmentation Therapy With Serotonin 5-HT(1A) Receptor Partial Agonists on Cognitive Function in Depressive Disorders: A Systematic Review of Randomized Controlled Studies. Neuropsychopharmacol Rep. 2025.", "pmid": "40421605", "doi": "10.1002/npr2.70023", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40421605/", "publicSourceType": "PMID" }, { "text": "Mohamedali Z, Amarasinghe G, Hopkins CWP et al.. Effect of Buspirone on Upper Gastrointestinal Disorders of Gut-Brain Interaction: A Systematic Review and Meta-analysis. 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Heliyon. 2024", "claim": "PubMed-indexed evidence involving Buspirone", "title": "Side effects and cognitive benefits of buspirone: A systematic review and meta-analysis", "authors": "Du Y, Li Q, Dou Y et al.", "journal": "Heliyon", "year": 2024, "pmid": "38601569", "url": "https://pubmed.ncbi.nlm.nih.gov/38601569/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.heliyon.2024.e28918", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38601569/", "publicSourceType": "PMID" }, { "text": "Gupta N, Gupta M, Gandhi R. Buspirone in Autism Spectrum Disorder: A Systematic Review. 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Movement disorders : official journal of the Movement Disorder Society. 2024", "claim": "PubMed-indexed evidence involving Buspirone", "title": "Buspirone and Zolmitriptan Combination for Dyskinesia: A Randomized, Controlled, Crossover Study", "authors": "LeWitt PA, Stebbins GT, Christensen KV et al.", "journal": "Movement disorders : official journal of the Movement Disorder Society", "year": 2024, "pmid": "38314643", "url": "https://pubmed.ncbi.nlm.nih.gov/38314643/", "study_type": "RCT", "confidence": "verify", "doi": "10.1002/mds.29713", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38314643/", "publicSourceType": "PMID" }, { "text": "Parkman HP, Yates KP, Sarosiek I et al.. Buspirone for early satiety and symptoms of gastroparesis: A multi-centre, randomised, placebo-controlled, double-masked trial (BESST). Alimentary pharmacology & therapeutics. 2023", "claim": "PubMed-indexed evidence involving Buspirone", "title": "Buspirone for early satiety and symptoms of gastroparesis: A multi-centre, randomised, placebo-controlled, double-masked trial (BESST)", "authors": "Parkman HP, Yates KP, Sarosiek I et al.", "journal": "Alimentary pharmacology & therapeutics", "year": 2023, "pmid": "37052334", "url": "https://pubmed.ncbi.nlm.nih.gov/37052334/", "study_type": "RCT", "confidence": "verify", "doi": "10.1111/apt.17479", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37052334/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Azapirone (5-HT1A Partial Agonist)", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "2–3 hours", "onsetOfAction": "2–4 weeks for full therapeutic benefit; not effective for acute anxiety", "commonBrandNames": [ "Buspar" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "buspirone" }, { "id": "RX-PSYCH-020", "name": "Hydroxyzine", "alternateNames": [ "Vistaril", "Atarax" ], "category": "Prescription", "subcategory": "Non-Benzodiazepine Anxiolytic", "overview": "Prescription first-generation antihistamine used for the management of anxiety, pruritus, and as a preoperative sedative. 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Efficacy and safety of hydroxyzine in the treatment of generalized anxiety disorder: a 3-month double-blind study. J Clin Psychiatry. 2002.", "pmid": "12444816", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12444816/", "publicSourceType": "PMID" }, { "text": "Huang CY et al. Psychotherapeutic and pharmacological agents for post-traumatic stress disorder with sleep disorder: network meta-analysis. Ann Med. 2024.", "pmid": "39061119", "doi": "10.1080/07853890.2024.2381696", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39061119/", "publicSourceType": "PMID" }, { "text": "Burgazli CR, Rana KB, Brown JN et al.. Efficacy and safety of hydroxyzine for sleep in adults: Systematic review. Human psychopharmacology. 2023", "pmid": "36843057", "doi": "10.1002/hup.2864", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36843057/", "publicSourceType": "PMID" }, { "text": "Hydroxyzine. 2006", "pmid": "30000044", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30000044/", "publicSourceType": "PMID" }, { "text": "Breneman DL. Cetirizine versus hydroxyzine and placebo in chronic idiopathic urticaria. 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Drug safety. 2022", "claim": "PubMed-indexed evidence involving Hydroxyzine", "title": "Hydroxyzine Initiation Following Drug Safety Advisories on Cardiac Arrhythmias in the UK and Canada: A Longitudinal Cohort Study", "authors": "Morrow RL, Mintzes B, Souverein PC et al.", "journal": "Drug safety", "year": 2022, "pmid": "35438459", "url": "https://pubmed.ncbi.nlm.nih.gov/35438459/", "study_type": "cohort", "confidence": "verify", "doi": "10.1007/s40264-022-01175-2", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35438459/", "publicSourceType": "PMID" }, { "text": "Kim T, Kim K, Kim S et al.. Safety of hydroxyzine in the sedation of pediatric dental patients. Journal of dental anesthesia and pain medicine. 2022", "claim": "PubMed-indexed evidence involving Hydroxyzine", "title": "Safety of hydroxyzine in the sedation of pediatric dental patients", "authors": "Kim T, Kim K, Kim S et al.", "journal": "Journal of dental anesthesia and pain medicine", "year": 2022, "pmid": "36601135", "url": "https://pubmed.ncbi.nlm.nih.gov/36601135/", "study_type": "review", "confidence": "verify", "doi": "10.17245/jdapm.2022.22.6.395", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36601135/", "publicSourceType": "PMID" }, { "text": "Afzal MA, Khalid N, Abdullah M et al.. Hydroxyzine-Induced Torsade De Pointes: A Case Report and a Literature Review. Cureus. 2023", "claim": "PubMed-indexed evidence involving Hydroxyzine", "title": "Hydroxyzine-Induced Torsade De Pointes: A Case Report and a Literature Review", "authors": "Afzal MA, Khalid N, Abdullah M et al.", "journal": "Cureus", "year": 2023, "pmid": "37559846", "url": "https://pubmed.ncbi.nlm.nih.gov/37559846/", "study_type": "review", "confidence": "verify", "doi": "10.7759/cureus.41588", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37559846/", "publicSourceType": "PMID" }, { "text": "Tsuchiya K, Miyamoto R, Tsunoda T et al.. Impact of atropine and hydroxyzine pretreatment in contemporary bronchoscopy. 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A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. Am J Psychiatry. 2005.", "pmid": "15994710", "doi": "10.1176/appi.ajp.162.7.1351", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15994710/", "publicSourceType": "PMID" }, { "text": "Bauer M et al. Extended-release quetiapine as adjunct to an antidepressant in patients with major depressive disorder. J Clin Psychiatry. 2009.", "pmid": "19358791", "doi": "10.4088/JCP.09m05048gre", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19358791/", "publicSourceType": "PMID" }, { "text": "Lin CY, Chiang CH, Tseng MM et al.. Effects of quetiapine on sleep: A systematic review and meta-analysis of clinical trials. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 2023", "pmid": "36463762", "doi": "10.1016/j.euroneuro.2022.11.008", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36463762/", "publicSourceType": "PMID" }, { "text": "Monahan K, Cuzens-Sutton J, Siskind D et al.. Quetiapine withdrawal: A systematic review. The Australian and New Zealand journal of psychiatry. 2021", "pmid": "33059460", "doi": "10.1177/0004867420965693", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33059460/", "publicSourceType": "PMID" }, { "claim": "Quetiapine is effective and tolerable for schizophrenia treatment", "title": "Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis.", "authors": "Leucht S, Cipriani A, Spineli L et al.", "journal": "Lancet", "year": 2013, "pmid": "23810019", "url": "https://pubmed.ncbi.nlm.nih.gov/23810019/", "study_type": "meta-analysis", "key_finding": "Landmark meta-analysis of 212 trials found quetiapine effective for schizophrenia symptoms with moderate efficacy ranking among 15 antipsychotics; notable for better metabolic tolerability profile but more sedation compared to other atypicals.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23810019/", "publicSourceType": "PMID" }, { "text": "Ferrari M, Godio M, Martini S et al.. Effect of quetiapine on inflammation and immunity: a systematic review. International journal of psychiatry in clinical practice. 2023", "claim": "PubMed-indexed evidence involving Quetiapine", "title": "Effect of quetiapine on inflammation and immunity: a systematic review", "authors": "Ferrari M, Godio M, Martini S et al.", "journal": "International journal of psychiatry in clinical practice", "year": 2023, "pmid": "35913757", "url": "https://pubmed.ncbi.nlm.nih.gov/35913757/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/13651501.2022.2101928", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35913757/", "publicSourceType": "PMID" }, { "text": "Crapanzano C, Damiani S, Casolaro I et al.. Quetiapine Treatment for Post-traumatic Stress Disorder: A Systematic Review of the Literature. 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Journal of clinical pharmacology. 2022", "claim": "PubMed-indexed evidence involving Quetiapine", "title": "Quetiapine-Induced Thyroid Dysfunction: A Systematic Review", "authors": "Khoodoruth MAS, Abdo AKA, Ouanes S", "journal": "Journal of clinical pharmacology", "year": 2022, "pmid": "34467533", "url": "https://pubmed.ncbi.nlm.nih.gov/34467533/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/jcph.1960", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34467533/", "publicSourceType": "PMID" }, { "text": "El-Saifi N, Moyle W, Jones C et al.. Quetiapine safety in older adults: a systematic literature review. 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Phytomedicine. 2025.", "pmid": "41056862", "doi": "10.1016/j.phymed.2025.157351", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41056862/", "publicSourceType": "PMID" }, { "text": "Kishi T, Sakuma K, Saito T et al.. Comparison of brexpiprazole, aripiprazole, and placebo for Japanese major depressive disorder: A systematic review and network meta-analysis. Neuropsychopharmacology reports. 2024", "claim": "PubMed-indexed evidence involving Aripiprazole", "title": "Comparison of brexpiprazole, aripiprazole, and placebo for Japanese major depressive disorder: A systematic review and network meta-analysis", "authors": "Kishi T, Sakuma K, Saito T et al.", "journal": "Neuropsychopharmacology reports", "year": 2024, "pmid": "38219278", "url": "https://pubmed.ncbi.nlm.nih.gov/38219278/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/npr2.12414", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38219278/", "publicSourceType": "PMID" }, { "text": "Akbari M, Jamshidi S, Sheikhi S et al.. Aripiprazole and its adverse effects in the form of impulsive-compulsive behaviors: A systematic review of case reports. 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Brain and behavior. 2022", "claim": "PubMed-indexed evidence involving Olanzapine", "title": "Effectiveness of olanzapine in the treatment of anorexia nervosa: A systematic review and meta-analysis", "authors": "Han R, Bian Q, Chen H", "journal": "Brain and behavior", "year": 2022, "pmid": "35020271", "url": "https://pubmed.ncbi.nlm.nih.gov/35020271/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/brb3.2498", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35020271/", "publicSourceType": "PMID" }, { "text": "Goetz RL, Miller BJ. Meta-analysis of ghrelin alterations in schizophrenia: Effects of olanzapine. 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Lancet. 2026.", "pmid": "41763745", "doi": "10.1016/S0140-6736(25)02365-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41763745/", "publicSourceType": "PMID" }, { "text": "Carrascosa-Arteaga A, Nalda-Molina R, Más-Serrano P et al.. Population Pharmacokinetics of Risperidone and Paliperidone in Schizophrenia: A Systematic Review. Pharmaceuticals (Basel, Switzerland). 2025", "claim": "PubMed-indexed evidence involving Risperidone", "title": "Population Pharmacokinetics of Risperidone and Paliperidone in Schizophrenia: A Systematic Review", "authors": "Carrascosa-Arteaga A, Nalda-Molina R, Más-Serrano P et al.", "journal": "Pharmaceuticals (Basel, Switzerland)", "year": 2025, "pmid": "40430517", "url": "https://pubmed.ncbi.nlm.nih.gov/40430517/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/ph18050698", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40430517/", "publicSourceType": "PMID" }, { "text": "de Brabander E, Kleine Schaars K, van Amelsvoort T et al.. Influence of CYP2C19 and CYP2D6 on side effects of aripiprazole and risperidone: A systematic review. Journal of psychiatric research. 2024", "claim": "PubMed-indexed evidence involving Risperidone", "title": "Influence of CYP2C19 and CYP2D6 on side effects of aripiprazole and risperidone: A systematic review", "authors": "de Brabander E, Kleine Schaars K, van Amelsvoort T et al.", "journal": "Journal of psychiatric research", "year": 2024, "pmid": "38631139", "url": "https://pubmed.ncbi.nlm.nih.gov/38631139/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jpsychires.2024.04.001", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38631139/", "publicSourceType": "PMID" }, { "text": "Syed YY. Risperidone In Situ Microparticles: A Review in Schizophrenia. Drugs. 2025", "claim": "PubMed-indexed evidence involving Risperidone", "title": "Risperidone In Situ Microparticles: A Review in Schizophrenia", "authors": "Syed YY", "journal": "Drugs", "year": 2025, "pmid": "39932523", "url": "https://pubmed.ncbi.nlm.nih.gov/39932523/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s40265-024-02140-2", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39932523/", "publicSourceType": "PMID" }, { "text": "Messer T, Bernardo M, Anta L et al.. Risperidone ISM(®): review and update of its usefulness in all phases of schizophrenia. Therapeutic advances in psychopharmacology. 2024", "claim": "PubMed-indexed evidence involving Risperidone", "title": "Risperidone ISM(®): review and update of its usefulness in all phases of schizophrenia", "authors": "Messer T, Bernardo M, Anta L et al.", "journal": "Therapeutic advances in psychopharmacology", "year": 2024, "pmid": "39421638", "url": "https://pubmed.ncbi.nlm.nih.gov/39421638/", "study_type": "review", "confidence": "verify", "doi": "10.1177/20451253241280046", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39421638/", "publicSourceType": "PMID" }, { "text": "Fenton C, Scott LJ. Risperidone: a review of its use in the treatment of bipolar mania. CNS drugs. 2005", "claim": "PubMed-indexed evidence involving Risperidone", "title": "Risperidone: a review of its use in the treatment of bipolar mania", "authors": "Fenton C, Scott LJ", "journal": "CNS drugs", "year": 2005, "pmid": "15907153", "url": "https://pubmed.ncbi.nlm.nih.gov/15907153/", "study_type": "review", "confidence": "verify", "doi": "10.2165/00023210-200519050-00005", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15907153/", "publicSourceType": "PMID" }, { "text": "Möller HJ. Risperidone: a review. Expert opinion on pharmacotherapy. 2005", "claim": "PubMed-indexed evidence involving Risperidone", "title": "Risperidone: a review", "authors": "Möller HJ", "journal": "Expert opinion on pharmacotherapy", "year": 2005, "pmid": "15934906", "url": "https://pubmed.ncbi.nlm.nih.gov/15934906/", "study_type": "review", "confidence": "verify", "doi": "10.1517/14656566.6.5.803", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15934906/", "publicSourceType": "PMID" }, { "text": "Cardoni AA. Risperidone: review and assessment of its role in the treatment of schizophrenia. The Annals of pharmacotherapy. 1995", "claim": "PubMed-indexed evidence involving Risperidone", "title": "Risperidone: review and assessment of its role in the treatment of schizophrenia", "authors": "Cardoni AA", "journal": "The Annals of pharmacotherapy", "year": 1995, "pmid": "7545034", "url": "https://pubmed.ncbi.nlm.nih.gov/7545034/", "study_type": "review", "confidence": "verify", "doi": "10.1177/106002809502900611", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7545034/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Second-Generation (Atypical) Antipsychotic", "blackBoxWarnings": [ "Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at increased risk of death." ], "fdaPregnancyCategory": "C", "halfLife": "3–20 hours (active metabolite 21 hours)", "onsetOfAction": "1–2 weeks for initial effects; 4–6 weeks for full therapeutic benefit", "commonBrandNames": [ "Risperdal", "Risperdal Consta" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Fasting glucose, lipid panel, A1C at baseline and annually. 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JAMA network open. 2024", "claim": "PubMed-indexed evidence involving Methylphenidate", "title": "Methylphenidate and Atomoxetine in Pregnancy and Possible Adverse Fetal Outcomes: A Systematic Review and Meta-Analysis", "authors": "di Giacomo E, Confalonieri V, Tofani F et al.", "journal": "JAMA network open", "year": 2024, "pmid": "39504019", "url": "https://pubmed.ncbi.nlm.nih.gov/39504019/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1001/jamanetworkopen.2024.43648", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39504019/", "publicSourceType": "PMID" }, { "text": "Godfrey J. Safety of therapeutic methylphenidate in adults: a systematic review of the evidence. 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Pharmacological Treatment of Methamphetamine/Amphetamine Dependence: A Systematic Review. CNS drugs. 2020", "pmid": "32185696", "doi": "10.1007/s40263-020-00711-x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32185696/", "publicSourceType": "PMID" }, { "text": "Faraone SV, Biederman J. Efficacy of Adderall for Attention-Deficit/Hyperactivity Disorder: a meta-analysis. Journal of attention disorders. 2002", "claim": "PubMed-indexed evidence involving Amphetamine/Dextroamphetamine", "title": "Efficacy of Adderall for Attention-Deficit/Hyperactivity Disorder: a meta-analysis", "authors": "Faraone SV, Biederman J", "journal": "Journal of attention disorders", "year": 2002, "pmid": "12142863", "url": "https://pubmed.ncbi.nlm.nih.gov/12142863/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/108705470200600203", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12142863/", "publicSourceType": "PMID" }, { "text": "Faraone SV, Biederman J, Roe C. Comparative efficacy of Adderall and methylphenidate in attention-deficit/hyperactivity disorder: a meta-analysis. Journal of clinical psychopharmacology. 2002", "claim": "PubMed-indexed evidence involving Amphetamine/Dextroamphetamine", "title": "Comparative efficacy of Adderall and methylphenidate in attention-deficit/hyperactivity disorder: a meta-analysis", "authors": "Faraone SV, Biederman J, Roe C", "journal": "Journal of clinical psychopharmacology", "year": 2002, "pmid": "12352269", "url": "https://pubmed.ncbi.nlm.nih.gov/12352269/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/00004714-200210000-00005", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12352269/", "publicSourceType": "PMID" }, { "text": "Somers KR, Bock JM, Covassin N et al.. Acute Cardiovascular Responses to Amphetamine/Dextroamphetamine Salts (Adderall) in Adderall-Naïve Young Adults: A Randomized Clinical Trial. Mayo Clinic proceedings. 2026", "claim": "PubMed-indexed evidence involving Amphetamine/Dextroamphetamine", "title": "Acute Cardiovascular Responses to Amphetamine/Dextroamphetamine Salts (Adderall) in Adderall-Naïve Young Adults: A Randomized Clinical Trial", "authors": "Somers KR, Bock JM, Covassin N et al.", "journal": "Mayo Clinic proceedings", "year": 2026, "pmid": "41770187", "url": "https://pubmed.ncbi.nlm.nih.gov/41770187/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.mayocp.2025.12.005", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41770187/", "publicSourceType": "PMID" }, { "text": "Looby A, Piccorelli AV, Zimmerman L et al.. Expectancy for Adderall influences subjective mood and drug effects regardless of concurrent caffeine ingestion: A randomized controlled trial. Psychopharmacology. 2024", "claim": "PubMed-indexed evidence involving Amphetamine/Dextroamphetamine", "title": "Expectancy for Adderall influences subjective mood and drug effects regardless of concurrent caffeine ingestion: A randomized controlled trial", "authors": "Looby A, Piccorelli AV, Zimmerman L et al.", "journal": "Psychopharmacology", "year": 2024, "pmid": "37740001", "url": "https://pubmed.ncbi.nlm.nih.gov/37740001/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/s00213-023-06467-8", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37740001/", "publicSourceType": "PMID" }, { "text": "Levin FR, Mariani JJ, Pavlicova M et al.. Extended-Release Mixed Amphetamine Salts for Comorbid Adult Attention-Deficit/Hyperactivity Disorder and Cannabis Use Disorder: A Pilot, Randomized Double-Blind, Placebo-Controlled Trial. 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A systematic review of the safety of lisdexamfetamine dimesylate. CNS drugs. 2014", "pmid": "24788672", "doi": "10.1007/s40263-014-0166-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24788672/", "publicSourceType": "PMID" }, { "text": "Maneeton N, Maneeton B, Suttajit S et al.. Exploratory meta-analysis on lisdexamfetamine versus placebo in adult ADHD. Drug design, development and therapy. 2014", "claim": "PubMed-indexed evidence involving Lisdexamfetamine", "title": "Exploratory meta-analysis on lisdexamfetamine versus placebo in adult ADHD", "authors": "Maneeton N, Maneeton B, Suttajit S et al.", "journal": "Drug design, development and therapy", "year": 2014, "pmid": "25336914", "url": "https://pubmed.ncbi.nlm.nih.gov/25336914/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2147/DDDT.S68393", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25336914/", "publicSourceType": "PMID" }, { "text": "Rutledge-Jukes H, Jonnalagadda P, McIntosh AP et al.. Lisdexamfetamine's Efficacy in Treating Attention Deficit Hyperactivity Disorder (ADHD): A Meta-Analysis and Review. Cureus. 2024", "claim": "PubMed-indexed evidence involving Lisdexamfetamine", "title": "Lisdexamfetamine's Efficacy in Treating Attention Deficit Hyperactivity Disorder (ADHD): A Meta-Analysis and Review", "authors": "Rutledge-Jukes H, Jonnalagadda P, McIntosh AP et al.", "journal": "Cureus", "year": 2024, "pmid": "39350825", "url": "https://pubmed.ncbi.nlm.nih.gov/39350825/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7759/cureus.68324", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39350825/", "publicSourceType": "PMID" }, { "text": "Grilo CM, Ivezaj V, Tek C et al.. Cognitive Behavioral Therapy and Lisdexamfetamine, Alone and Combined, for Binge-Eating Disorder With Obesity: A Randomized Controlled Trial. 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Lancet Psychiatry. 2025.", "pmid": "40203844", "doi": "10.1016/S2215-0366(25)00062-8", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40203844/", "publicSourceType": "PMID" }, { "text": "Yu S, Shen S, Tao M. Guanfacine for the Treatment of Attention-Deficit Hyperactivity Disorder: An Updated Systematic Review and Meta-Analysis. Journal of child and adolescent psychopharmacology. 2023", "claim": "PubMed-indexed evidence involving Guanfacine", "title": "Guanfacine for the Treatment of Attention-Deficit Hyperactivity Disorder: An Updated Systematic Review and Meta-Analysis", "authors": "Yu S, Shen S, Tao M", "journal": "Journal of child and adolescent psychopharmacology", "year": 2023, "pmid": "36944092", "url": "https://pubmed.ncbi.nlm.nih.gov/36944092/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1089/cap.2022.0038", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36944092/", "publicSourceType": "PMID" }, { "text": "Singh D, Silver M, Jacob T. A Randomized Double-Blind Placebo-Controlled Trial of Guanfacine Extended Release for Aggression and Self-Injurious Behavior Associated With Prader-Willi Syndrome. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. 2025", "claim": "PubMed-indexed evidence involving Guanfacine", "title": "A Randomized Double-Blind Placebo-Controlled Trial of Guanfacine Extended Release for Aggression and Self-Injurious Behavior Associated With Prader-Willi Syndrome", "authors": "Singh D, Silver M, Jacob T", "journal": "American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics", "year": 2025, "pmid": "40395104", "url": "https://pubmed.ncbi.nlm.nih.gov/40395104/", "study_type": "RCT", "confidence": "verify", "doi": "10.1002/ajmg.b.33032", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40395104/", "publicSourceType": "PMID" }, { "text": "Pattamin N, Phongphithakchai A, Spano S et al.. Efficacy and safety of guanfacine in hospitalized patients with delirium: A scoping review. Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine. 2024", "claim": "PubMed-indexed evidence involving Guanfacine", "title": "Efficacy and safety of guanfacine in hospitalized patients with delirium: A scoping review", "authors": "Pattamin N, Phongphithakchai A, Spano S et al.", "journal": "Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine", "year": 2024, "pmid": "39781496", "url": "https://pubmed.ncbi.nlm.nih.gov/39781496/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.ccrj.2024.08.009", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39781496/", "publicSourceType": "PMID" }, { "text": "Lee YR, Garza A, Kiama L. Guanfacine Use in the ICU for Management of Sedation Weaning. 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BMJ. 2012.", "pmid": "23248080", "doi": "10.1136/bmj.e8343", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23248080/", "publicSourceType": "PMID" }, { "text": "FDA Drug Safety Communication: Risk of next-morning impairment after use of insomnia drugs; FDA requires lower recommended doses for certain drugs containing zolpidem. 2013.", "pmid": "28449404", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28449404/", "publicSourceType": "PMID" }, { "text": "Namazi N et al. Limited Efficacy of Pharmacological Interventions for Improving Postoperative Sleep Quality in Primary Total Joint Arthroplasty Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Arthroplasty. 2026.", "pmid": "40902687", "doi": "10.1016/j.arth.2025.08.071", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40902687/", "publicSourceType": "PMID" }, { "text": "Gunther M, Tran N, Jiang S. Zolpidem for the Management of Catatonia: A Systematic Review. Journal of the Academy of Consultation-Liaison Psychiatry. 2025", "pmid": "39522949", "doi": "10.1016/j.jaclp.2024.10.004", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39522949/", "publicSourceType": "PMID" }, { "text": "Edinoff AN, Wu N, Ghaffar YT et al.. Zolpidem: Efficacy and Side Effects for Insomnia. 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Proton pump inhibitors: risks of long-term use. J Fam Pract. 2013.", "pmid": "25201154", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25201154/", "publicSourceType": "PMID" }, { "text": "Freedberg DE et al. The risks and benefits of long-term use of proton pump inhibitors. BMJ. 2017.", "pmid": "31427714", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31427714/", "publicSourceType": "PMID" }, { "text": "Chey WD et al. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2017.", "pmid": "28071659", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28071659/", "publicSourceType": "PMID" }, { "text": "Qi Q, Wang R, Liu L et al.. Comparative effectiveness and tolerability of esomeprazole and omeprazole in gastro-esophageal reflux disease: A systematic review and meta-analysis. International journal of clinical pharmacology and therapeutics. 2015", "pmid": "26329348", "doi": "10.5414/CP202396", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26329348/", "publicSourceType": "PMID" }, { "text": "Bhatt DL, Cryer BL, Contant CF et al.. Clopidogrel with or without omeprazole in coronary artery disease. The New England journal of medicine. 2010", "pmid": "20925534", "doi": "10.1056/NEJMoa1007964", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20925534/", "publicSourceType": "PMID" }, { "claim": "Omeprazole is effective compared to other PPIs and newer agents for GERD", "title": "Comparative Efficacy of P-CAB vs Proton Pump Inhibitors for Grade C/D Esophagitis: A Systematic Review and Network Meta-analysis", "authors": "Zhuang Q, Chen S, Zhou X, Jia X et al.", "journal": "The American Journal of Gastroenterology", "year": 2024, "pmid": "38345252", "url": "https://pubmed.ncbi.nlm.nih.gov/38345252/", "study_type": "network meta-analysis", "key_finding": "PPIs including omeprazole remain effective for healing severe esophagitis, though newer potassium-competitive acid blockers (P-CABs) showed faster healing rates in some comparisons", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38345252/", "publicSourceType": "PMID" }, { "claim": "PPI use is associated with vitamin B12 deficiency", "title": "Vitamin B12 deficiency and use of proton pump inhibitors: a systematic review and meta-analysis", "authors": "Choudhury A, Jena A, Jearth V, Dutta AK et al.", "journal": "Expert Review of Gastroenterology & Hepatology", "year": 2023, "pmid": "37060552", "url": "https://pubmed.ncbi.nlm.nih.gov/37060552/", "study_type": "meta-analysis", "key_finding": "Long-term proton pump inhibitor use was significantly associated with vitamin B12 deficiency, suggesting monitoring of B12 levels in patients on chronic PPI therapy", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37060552/", "publicSourceType": "PMID" }, { "text": "Higuera-de-la-Tijera F. Efficacy of omeprazole/sodium bicarbonate treatment in gastroesophageal reflux disease: a systematic review. Medwave. 2018", "claim": "PubMed-indexed evidence involving Omeprazole", "title": "Efficacy of omeprazole/sodium bicarbonate treatment in gastroesophageal reflux disease: a systematic review", "authors": "Higuera-de-la-Tijera F", "journal": "Medwave", "year": 2018, "pmid": "29547594", "url": "https://pubmed.ncbi.nlm.nih.gov/29547594/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.5867/medwave.2018.02.7179", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29547594/", "publicSourceType": "PMID" }, { "text": "Richter JE, Kahrilas PJ, Johanson J et al.. Efficacy and safety of esomeprazole compared with omeprazole in GERD patients with erosive esophagitis: a randomized controlled trial. The American journal of gastroenterology. 2001", "claim": "PubMed-indexed evidence involving Omeprazole", "title": "Efficacy and safety of esomeprazole compared with omeprazole in GERD patients with erosive esophagitis: a randomized controlled trial", "authors": "Richter JE, Kahrilas PJ, Johanson J et al.", "journal": "The American journal of gastroenterology", "year": 2001, "pmid": "11280530", "url": "https://pubmed.ncbi.nlm.nih.gov/11280530/", "study_type": "RCT", "confidence": "verify", "doi": "10.1111/j.1572-0241.2001.3600_b.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11280530/", "publicSourceType": "PMID" }, { "text": "Miedziaszczyk M, Idasiak-Piechocka I. Safety analysis of co-administering tacrolimus and omeprazole in renal transplant recipients - A review. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2023", "claim": "PubMed-indexed evidence involving Omeprazole", "title": "Safety analysis of co-administering tacrolimus and omeprazole in renal transplant recipients - A review", "authors": "Miedziaszczyk M, Idasiak-Piechocka I", "journal": "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie", "year": 2023, "pmid": "37619481", "url": "https://pubmed.ncbi.nlm.nih.gov/37619481/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.biopha.2023.115149", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37619481/", "publicSourceType": "PMID" }, { "text": "Forgerini M, Mieli S, Mastroianni PC. Safety assessment of omeprazole use: a review. Sao Paulo medical journal = Revista paulista de medicina. 2018", "claim": "PubMed-indexed evidence involving Omeprazole", "title": "Safety assessment of omeprazole use: a review", "authors": "Forgerini M, Mieli S, Mastroianni PC", "journal": "Sao Paulo medical journal = Revista paulista de medicina", "year": 2018, "pmid": "30892487", "url": "https://pubmed.ncbi.nlm.nih.gov/30892487/", "study_type": "review", "confidence": "verify", "doi": "10.1590/1516-3180.2018.0019220318", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30892487/", "publicSourceType": "PMID" }, { "text": "Zhang J, An J. Updating understanding of real-world adverse events associated with omeprazole. PloS one. 2025", "claim": "PubMed-indexed evidence involving Omeprazole", "title": "Updating understanding of real-world adverse events associated with omeprazole", "authors": "Zhang J, An J", "journal": "PloS one", "year": 2025, "pmid": "40834017", "url": "https://pubmed.ncbi.nlm.nih.gov/40834017/", "study_type": "review", "confidence": "verify", "doi": "10.1371/journal.pone.0330509", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40834017/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Proton Pump Inhibitor", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "0.5–1 hour (but acid suppression lasts 24+ hours due to irreversible binding)", "onsetOfAction": "1 hour; full effect in 1–4 days", "commonBrandNames": [ "Prilosec", "Prilosec OTC" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Serum magnesium if prolonged use (especially with diuretics or digoxin). Vitamin B12 periodically with use >3 years." }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "omeprazole" }, { "id": "RX-GIPAIN-002", "name": "Esomeprazole", "alternateNames": [ "Nexium" ], "category": "Prescription", "subcategory": "Proton Pump Inhibitor", "overview": "The S-enantiomer of omeprazole, esomeprazole is a potent proton pump inhibitor used to treat GERD, erosive esophagitis, peptic ulcers, and as part of H. pylori eradication therapy. It provides more consistent acid suppression compared to racemic omeprazole due to reduced first-pass hepatic metabolism.", "mechanismOfAction": "Irreversibly inhibits the hydrogen/potassium ATPase (H+/K+ ATPase) enzyme system on the secretory surface of gastric parietal cells. As the pure S-isomer, it has higher bioavailability than racemic omeprazole, producing more sustained suppression of gastric acid secretion over a 24-hour period.", "commonBenefits": [ "Healing of erosive esophagitis", "Maintenance of healed erosive esophagitis", "Symptomatic relief of GERD", "H. pylori eradication (triple therapy)", "Risk reduction of NSAID-associated gastric ulcers" ], "commonDosageRange": "20–40 mg once daily for 4–8 weeks (as prescribed by your physician)", "recommendedForm": "Delayed-release capsule or oral suspension", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Take at least 1 hour before meals; swallow capsules whole or open and mix granules with applesauce" }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Headache", "Diarrhea", "Nausea", "Flatulence", "Abdominal pain", "Dry mouth", "Hypomagnesemia with prolonged therapy", "Increased fracture risk with long-term use", "Increased risk of C. difficile infection", "Vitamin B12 deficiency with long-term use" ], "contraindications": [ "Known hypersensitivity to esomeprazole, omeprazole, or substituted benzimidazoles", "Concurrent use with rilpivirine-containing products", "Concurrent use with nelfinavir", "Caution in patients with hepatic impairment" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "gi", "acid-reflux", "gerd", "ppi", "ulcer" ], "sources": [ { "text": "Kahrilas PJ et al. Esomeprazole improves healing and symptom resolution as compared with omeprazole in reflux oesophagitis patients. Aliment Pharmacol Ther. 2000.", "pmid": "11012468", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11012468/", "publicSourceType": "PMID" }, { "text": "Sachar H et al. Proton pump inhibitors: risks of long-term use. J Fam Pract. 2013.", "pmid": "25201154", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25201154/", "publicSourceType": "PMID" }, { "text": "Metz DC et al. Clinical pharmacokinetics of esomeprazole. Clin Pharmacokinet. 2006.", "pmid": "16640452", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16640452/", "publicSourceType": "PMID" }, { "text": "Oh JH, Kim HS, Cheung DY et al.. Randomized, Double-Blind, Active-Controlled Phase 3 Study to Evaluate Efficacy and Safety of Zastaprazan Compared With Esomeprazole in Erosive Esophagitis. The American journal of gastroenterology. 2025", "pmid": "38976448", "doi": "10.14309/ajg.0000000000002929", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38976448/", "publicSourceType": "PMID" }, { "text": "Lee KN, Lee OY, Chun HJ et al.. Randomized controlled trial to evaluate the efficacy and safety of fexuprazan compared with esomeprazole in erosive esophagitis. World journal of gastroenterology. 2022", "pmid": "36504556", "doi": "10.3748/wjg.v28.i44.6294", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36504556/", "publicSourceType": "PMID" }, { "text": "Gralnek IM, Dulai GS, Fennerty MB et al.. Esomeprazole versus other proton pump inhibitors in erosive esophagitis: a meta-analysis of randomized clinical trials. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2006", "claim": "PubMed-indexed evidence involving Esomeprazole", "title": "Esomeprazole versus other proton pump inhibitors in erosive esophagitis: a meta-analysis of randomized clinical trials", "authors": "Gralnek IM, Dulai GS, Fennerty MB et al.", "journal": "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "year": 2006, "pmid": "17162239", "url": "https://pubmed.ncbi.nlm.nih.gov/17162239/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.cgh.2006.09.013", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17162239/", "publicSourceType": "PMID" }, { "text": "Zhu H, Xue Q, Song Y et al.. Efficacy and safety of tegoprazan (LXI-15028) vs . esomeprazole in patients with erosive esophagitis: A multicenter, randomized, double-blind, non-inferiority phase Ⅲ trial. Chinese medical journal. 2025", "claim": "PubMed-indexed evidence involving Esomeprazole", "title": "Efficacy and safety of tegoprazan (LXI-15028) vs . esomeprazole in patients with erosive esophagitis: A multicenter, randomized, double-blind, non-inferiority phase Ⅲ trial", "authors": "Zhu H, Xue Q, Song Y et al.", "journal": "Chinese medical journal", "year": 2025, "pmid": "39474720", "url": "https://pubmed.ncbi.nlm.nih.gov/39474720/", "study_type": "RCT", "confidence": "verify", "doi": "10.1097/CM9.0000000000003276", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39474720/", "publicSourceType": "PMID" }, { "text": "Lim H, Lee JY, Kwon YH et al.. Evaluation of the Efficacy and Safety of a Dual Delayed-Release Formulation of 10-mg Esomeprazole in Patients with Gastric Erosions: A Multicenter, Randomized, Double-Blind, Active-Control, Phase III Study. Gut and liver. 2025", "claim": "PubMed-indexed evidence involving Esomeprazole", "title": "Evaluation of the Efficacy and Safety of a Dual Delayed-Release Formulation of 10-mg Esomeprazole in Patients with Gastric Erosions: A Multicenter, Randomized, Double-Blind, Active-Control, Phase III Study", "authors": "Lim H, Lee JY, Kwon YH et al.", "journal": "Gut and liver", "year": 2025, "pmid": "39949051", "url": "https://pubmed.ncbi.nlm.nih.gov/39949051/", "study_type": "RCT", "confidence": "verify", "doi": "10.5009/gnl240390", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39949051/", "publicSourceType": "PMID" }, { "text": "Kang N, Kang MG, Lee SE et al.. Efficacy and Safety of Fexuprazan Versus Esomeprazole for Gastroesophageal Reflux Disease-Related Chronic Cough: A Randomized, Double-Blind, Active-Controlled Exploratory Trial. Lung. 2025", "claim": "PubMed-indexed evidence involving Esomeprazole", "title": "Efficacy and Safety of Fexuprazan Versus Esomeprazole for Gastroesophageal Reflux Disease-Related Chronic Cough: A Randomized, Double-Blind, Active-Controlled Exploratory Trial", "authors": "Kang N, Kang MG, Lee SE et al.", "journal": "Lung", "year": 2025, "pmid": "40299084", "url": "https://pubmed.ncbi.nlm.nih.gov/40299084/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/s00408-025-00815-5", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40299084/", "publicSourceType": "PMID" }, { "text": "Wang Y, Dai X, Gao C et al.. Network meta-analysis of different dosages of esomeprazole and rabeprazole for the treatment of Helicobacter pylori. Helicobacter. 2023", "claim": "PubMed-indexed evidence involving Esomeprazole", "title": "Network meta-analysis of different dosages of esomeprazole and rabeprazole for the treatment of Helicobacter pylori", "authors": "Wang Y, Dai X, Gao C et al.", "journal": "Helicobacter", "year": 2023, "pmid": "36645422", "url": "https://pubmed.ncbi.nlm.nih.gov/36645422/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/hel.12948", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36645422/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Proton Pump Inhibitor", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "1–1.5 hours", "onsetOfAction": "1–2 hours; full effect in 1–4 days", "commonBrandNames": [ "Nexium", "Nexium 24HR" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Serum magnesium if prolonged use. Vitamin B12 periodically with use >3 years." }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "esomeprazole" }, { "id": "RX-GIPAIN-003", "name": "Pantoprazole", "alternateNames": [ "Protonix" ], "category": "Prescription", "subcategory": "Proton Pump Inhibitor", "overview": "A proton pump inhibitor commonly used in both oral and intravenous formulations for the treatment of erosive esophagitis associated with GERD, Zollinger-Ellison syndrome, and pathological hypersecretory conditions. Pantoprazole is frequently used in hospital settings due to its IV availability.", "mechanismOfAction": "Covalently binds to the hydrogen/potassium ATPase (H+/K+ ATPase) enzyme system at the secretory surface of gastric parietal cells, irreversibly inhibiting the final step of gastric acid production. Its selectivity for cysteine 822 on the proton pump provides sustained acid suppression.", "commonBenefits": [ "Healing of erosive esophagitis", "Maintenance therapy for erosive esophagitis", "Treatment of pathological hypersecretory conditions", "Stress ulcer prophylaxis (IV formulation)", "Reduction of gastric acid in Zollinger-Ellison syndrome" ], "commonDosageRange": "20–40 mg once daily for 4–8 weeks; up to 240 mg/day for hypersecretory conditions (as prescribed by your physician)", "recommendedForm": "Delayed-release tablet or IV injection", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Take 30 minutes before a meal; swallow tablets whole, do not crush or chew" }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Headache", "Diarrhea", "Nausea", "Abdominal pain", "Vomiting", "Flatulence", "Injection site reactions (IV form)", "C. difficile-associated diarrhea", "Hypomagnesemia with prolonged use", "Vitamin B12 deficiency with long-term use", "Increased risk of bone fractures with long-term use" ], "contraindications": [ "Known hypersensitivity to pantoprazole or substituted benzimidazoles", "Concurrent use with rilpivirine-containing products", "Caution in severe hepatic impairment", "Caution with long-term use in patients at risk for osteoporosis" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "gi", "acid-reflux", "gerd", "ppi", "ulcer", "iv-available" ], "sources": [ { "text": "Freedberg DE et al. The risks and benefits of long-term use of proton pump inhibitors. BMJ. 2017.", "pmid": "31427714", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31427714/", "publicSourceType": "PMID" }, { "text": "Cheer SM et al. Pantoprazole: an update of its pharmacological properties and therapeutic use in the management of acid-related disorders. Drugs. 2003.", "pmid": "12487624", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12487624/", "publicSourceType": "PMID" }, { "text": "Floria DE et al. Proton pump inhibitors are not associated with an increased risk of Clostridioides difficile infection: a systematic review and meta-analysis of randomized controlled trials. Gut Microbes. 2025.", "pmid": "41047657", "doi": "10.1080/19490976.2025.2562341", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41047657/", "publicSourceType": "PMID" }, { "text": "Krag M, Marker S, Perner A et al.. Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU. The New England journal of medicine. 2018", "pmid": "30354950", "doi": "10.1056/NEJMoa1714919", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30354950/", "publicSourceType": "PMID" }, { "text": "Pantoprazole. 2006", "pmid": "30000339", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30000339/", "publicSourceType": "PMID" }, { "text": "Gisbert JP, Khorrami S, Calvet X et al.. Pantoprazole based therapies in Helicobacter pylori eradication: a systematic review and meta-analysis. European journal of gastroenterology & hepatology. 2004", "claim": "PubMed-indexed evidence involving Pantoprazole", "title": "Pantoprazole based therapies in Helicobacter pylori eradication: a systematic review and meta-analysis", "authors": "Gisbert JP, Khorrami S, Calvet X et al.", "journal": "European journal of gastroenterology & hepatology", "year": 2004, "pmid": "15095858", "url": "https://pubmed.ncbi.nlm.nih.gov/15095858/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/00042737-200401000-00014", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15095858/", "publicSourceType": "PMID" }, { "text": "Jalihal U, Mahapatra JR, Kumar A et al.. Comparative Efficacy of Dexlansoprazole, Pantoprazole, Esomeprazole, and Rabeprazole in Achieving Optimal 24-Hour Intragastric pH Control: A Randomized Crossover Study Using Ambulatory pH Monitoring. Cureus. 2024", "claim": "PubMed-indexed evidence involving Pantoprazole", "title": "Comparative Efficacy of Dexlansoprazole, Pantoprazole, Esomeprazole, and Rabeprazole in Achieving Optimal 24-Hour Intragastric pH Control: A Randomized Crossover Study Using Ambulatory pH Monitoring", "authors": "Jalihal U, Mahapatra JR, Kumar A et al.", "journal": "Cureus", "year": 2024, "pmid": "39539895", "url": "https://pubmed.ncbi.nlm.nih.gov/39539895/", "study_type": "RCT", "confidence": "verify", "doi": "10.7759/cureus.71418", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39539895/", "publicSourceType": "PMID" }, { "text": "Selvanderan SP, Summers MJ, Finnis ME et al.. Pantoprazole or Placebo for Stress Ulcer Prophylaxis (POP-UP): Randomized Double-Blind Exploratory Study. Critical care medicine. 2016", "claim": "PubMed-indexed evidence involving Pantoprazole", "title": "Pantoprazole or Placebo for Stress Ulcer Prophylaxis (POP-UP): Randomized Double-Blind Exploratory Study", "authors": "Selvanderan SP, Summers MJ, Finnis ME et al.", "journal": "Critical care medicine", "year": 2016, "pmid": "27635481", "url": "https://pubmed.ncbi.nlm.nih.gov/27635481/", "study_type": "RCT", "confidence": "verify", "doi": "10.1097/CCM.0000000000001819", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27635481/", "publicSourceType": "PMID" }, { "text": "Albitar O, Harun SN, Ghadzi SMS. Clozapine and norclozapine pharmacokinetic interaction with pantoprazole. British journal of clinical pharmacology. 2026", "claim": "PubMed-indexed evidence involving Pantoprazole", "title": "Clozapine and norclozapine pharmacokinetic interaction with pantoprazole", "authors": "Albitar O, Harun SN, Ghadzi SMS", "journal": "British journal of clinical pharmacology", "year": 2026, "pmid": "41536008", "url": "https://pubmed.ncbi.nlm.nih.gov/41536008/", "study_type": "review", "confidence": "verify", "doi": "10.1002/bcp.70450", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41536008/", "publicSourceType": "PMID" }, { "text": "Gandhi S, Taylor B, Rubens L et al.. Safety of Intravenous Pantoprazole Sodium in Pediatric Patients Aged 1 Month to < 1 Year: A Real-World Retrospective Cohort Study. 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Comparing the Efficacy and Safety of Fexuprazan and Lansoprazole for the Prevention of Nonsteroidal Anti-inflammatory Drug-Induced Peptic Ulcer. Gut and liver. 2025", "pmid": "40567214", "doi": "10.5009/gnl250019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40567214/", "publicSourceType": "PMID" }, { "text": "Xiao Y, Zhang S, Dai N et al.. Phase III, randomised, double-blind, multicentre study to evaluate the efficacy and safety of vonoprazan compared with lansoprazole in Asian patients with erosive oesophagitis. Gut. 2020", "pmid": "31409606", "doi": "10.1136/gutjnl-2019-318365", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31409606/", "publicSourceType": "PMID" }, { "text": "Chandan S, Deliwala S, Mohan BP et al.. Vonoprazan versus lansoprazole in erosive esophagitis - A systematic review and meta-analysis of randomized controlled trials. Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology. 2023", "claim": "PubMed-indexed evidence involving Lansoprazole", "title": "Vonoprazan versus lansoprazole in erosive esophagitis - A systematic review and meta-analysis of randomized controlled trials", "authors": "Chandan S, Deliwala S, Mohan BP et al.", "journal": "Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology", "year": 2023, "pmid": "37418052", "url": "https://pubmed.ncbi.nlm.nih.gov/37418052/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s12664-023-01384-2", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37418052/", "publicSourceType": "PMID" }, { "text": "Poynard T, Lemaire M, Agostini H. Meta-analysis of randomized clinical trials comparing lansoprazole with ranitidine or famotidine in the treatment of acute duodenal ulcer. European journal of gastroenterology & hepatology. 1995", "claim": "PubMed-indexed evidence involving Lansoprazole", "title": "Meta-analysis of randomized clinical trials comparing lansoprazole with ranitidine or famotidine in the treatment of acute duodenal ulcer", "authors": "Poynard T, Lemaire M, Agostini H", "journal": "European journal of gastroenterology & hepatology", "year": 1995, "pmid": "8590162", "url": "https://pubmed.ncbi.nlm.nih.gov/8590162/", "study_type": "meta-analysis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8590162/", "publicSourceType": "PMID" }, { "text": "Bazzoli F, Pozzato P, Zagari M et al.. Efficacy of lansoprazole in eradicating Helicobacter pylori: a meta-analysis. Helicobacter. 1998", "claim": "PubMed-indexed evidence involving Lansoprazole", "title": "Efficacy of lansoprazole in eradicating Helicobacter pylori: a meta-analysis", "authors": "Bazzoli F, Pozzato P, Zagari M et al.", "journal": "Helicobacter", "year": 1998, "pmid": "9731991", "url": "https://pubmed.ncbi.nlm.nih.gov/9731991/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1046/j.1523-5378.1998.08029.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9731991/", "publicSourceType": "PMID" }, { "text": "Tunis SR, Sheinhait IA, Schmid CH et al.. Lansoprazole compared with histamine2-receptor antagonists in healing gastric ulcers: a meta-analysis. Clinical therapeutics. 1997", "claim": "PubMed-indexed evidence involving Lansoprazole", "title": "Lansoprazole compared with histamine2-receptor antagonists in healing gastric ulcers: a meta-analysis", "authors": "Tunis SR, Sheinhait IA, Schmid CH et al.", "journal": "Clinical therapeutics", "year": 1997, "pmid": "9377618", "url": "https://pubmed.ncbi.nlm.nih.gov/9377618/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/s0149-2918(97)80098-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9377618/", "publicSourceType": "PMID" }, { "text": "Shin CM, Choi SC, Cho JW et al.. Comparison of Tegoprazan and Lansoprazole in Patients With Erosive Esophagitis up to 4 Weeks: A Multi-Center, Randomized, Double-Blind, Active-Comparator Phase 4 Trial. Neurogastroenterology and motility. 2025", "claim": "PubMed-indexed evidence involving Lansoprazole", "title": "Comparison of Tegoprazan and Lansoprazole in Patients With Erosive Esophagitis up to 4 Weeks: A Multi-Center, Randomized, Double-Blind, Active-Comparator Phase 4 Trial", "authors": "Shin CM, Choi SC, Cho JW et al.", "journal": "Neurogastroenterology and motility", "year": 2025, "pmid": "39587796", "url": "https://pubmed.ncbi.nlm.nih.gov/39587796/", "study_type": "RCT", "confidence": "verify", "doi": "10.1111/nmo.14969", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39587796/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Proton Pump Inhibitor", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "1.5 hours", "onsetOfAction": "1–3 hours; full effect in 2–4 days", "commonBrandNames": [ "Prevacid", "Prevacid SoluTab" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Serum magnesium if prolonged use. 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The tolerability and safety profile of famotidine. Clin Ther. 1996.", "pmid": "8851452", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8851452/", "publicSourceType": "PMID" }, { "text": "Sabesin SM et al. Famotidine versus ranitidine for the short-term treatment of duodenal ulcer. Am J Med. 1986.", "pmid": "3537913", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3537913/", "publicSourceType": "PMID" }, { "text": "Chiu L et al. Effect of famotidine on hospitalized patients with COVID-19: A systematic review and meta-analysis. PLoS One. 2021.", "pmid": "34735523", "doi": "10.1371/journal.pone.0259514", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34735523/", "publicSourceType": "PMID" }, { "text": "Chenchula S, Ray A, Sadasivam B. Famotidine Repurposing for Novel Corona Virus Disease of 2019: A Systematic Review. Drug research. 2021", "pmid": "33757133", "doi": "10.1055/a-1397-6763", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33757133/", "publicSourceType": "PMID" }, { "text": "Leary PJ, Rayner SG, Branch KRH et al.. Effect of Famotidine on Outcomes in Pulmonary Arterial Hypertension: A Randomized Controlled Trial. Chest. 2025", "pmid": "39761829", "doi": "10.1016/j.chest.2024.12.029", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39761829/", "publicSourceType": "PMID" }, { "text": "Poynard T, Lemaire M, Agostini H. Meta-analysis of randomized clinical trials comparing lansoprazole with ranitidine or famotidine in the treatment of acute duodenal ulcer. European journal of gastroenterology & hepatology. 1995", "claim": "PubMed-indexed evidence involving Famotidine", "title": "Meta-analysis of randomized clinical trials comparing lansoprazole with ranitidine or famotidine in the treatment of acute duodenal ulcer", "authors": "Poynard T, Lemaire M, Agostini H", "journal": "European journal of gastroenterology & hepatology", "year": 1995, "pmid": "8590162", "url": "https://pubmed.ncbi.nlm.nih.gov/8590162/", "study_type": "meta-analysis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8590162/", "publicSourceType": "PMID" }, { "text": "Zhang D, Cai Y, Sun Y et al.. A Real-World Disproportionality Analysis of Histamine H2-Receptors Antagonists (Famotidine): A Pharmacovigilance Study Based on Spontaneous Reports in the FDA Adverse Event Reporting System. Drug development research. 2025", "claim": "PubMed-indexed evidence involving Famotidine", "title": "A Real-World Disproportionality Analysis of Histamine H2-Receptors Antagonists (Famotidine): A Pharmacovigilance Study Based on Spontaneous Reports in the FDA Adverse Event Reporting System", "authors": "Zhang D, Cai Y, Sun Y et al.", "journal": "Drug development research", "year": 2025, "pmid": "39821365", "url": "https://pubmed.ncbi.nlm.nih.gov/39821365/", "study_type": "review", "confidence": "verify", "doi": "10.1002/ddr.70045", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39821365/", "publicSourceType": "PMID" }, { "text": "Amini M, Ghamar Chehreh ME, Khedmat H et al.. Famotidine in the treatment of functional dyspepsia: a randomized double-blind, placebo-controlled trial. The Journal of the Egyptian Public Health Association. 2012", "claim": "PubMed-indexed evidence involving Famotidine", "title": "Famotidine in the treatment of functional dyspepsia: a randomized double-blind, placebo-controlled trial", "authors": "Amini M, Ghamar Chehreh ME, Khedmat H et al.", "journal": "The Journal of the Egyptian Public Health Association", "year": 2012, "pmid": "22415333", "url": "https://pubmed.ncbi.nlm.nih.gov/22415333/", "study_type": "RCT", "confidence": "verify", "doi": "10.1097/01.EPX.0000410948.64665.66", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22415333/", "publicSourceType": "PMID" }, { "text": "Kawano S, Murata H, Tsuji S et al.. Randomized comparative study of omeprazole and famotidine in reflux esophagitis. Journal of gastroenterology and hepatology. 2002", "claim": "PubMed-indexed evidence involving Famotidine", "title": "Randomized comparative study of omeprazole and famotidine in reflux esophagitis", "authors": "Kawano S, Murata H, Tsuji S et al.", "journal": "Journal of gastroenterology and hepatology", "year": 2002, "pmid": "12167115", "url": "https://pubmed.ncbi.nlm.nih.gov/12167115/", "study_type": "RCT", "confidence": "verify", "doi": "10.1046/j.1440-1746.2002.02785.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12167115/", "publicSourceType": "PMID" }, { "text": "Bello AE, Kent JD, Holt RJ. Gastroprotective efficacy and safety of single-tablet ibuprofen/famotidine vs ibuprofen in older persons. The Physician and sportsmedicine. 2015", "claim": "PubMed-indexed evidence involving Famotidine", "title": "Gastroprotective efficacy and safety of single-tablet ibuprofen/famotidine vs ibuprofen in older persons", "authors": "Bello AE, Kent JD, Holt RJ", "journal": "The Physician and sportsmedicine", "year": 2015, "pmid": "26165391", "url": "https://pubmed.ncbi.nlm.nih.gov/26165391/", "study_type": "review", "confidence": "verify", "doi": "10.1080/00913847.2015.1066229", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26165391/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "H2 Receptor Antagonist", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "2.5–3.5 hours", "onsetOfAction": "1 hour (oral); within 30 minutes (IV)", "commonBrandNames": [ "Pepcid", "Pepcid AC" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "famotidine" }, { "id": "RX-GIPAIN-006", "name": "Cimetidine", "alternateNames": [ "Tagamet" ], "category": "Prescription", "subcategory": "H2 Receptor Antagonist", "overview": "The first commercially available H2 receptor antagonist, cimetidine is used for the treatment of duodenal and gastric ulcers, GERD, and pathological hypersecretory conditions. 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Cimetidine: a review of its pharmacological properties and therapeutic efficacy in peptic ulcer disease. Drugs. 1978.", "pmid": "2667937", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2667937/", "publicSourceType": "PMID" }, { "text": "Somogyi A, Gugler R. Drug interactions with cimetidine. Clin Pharmacokinet. 1982.", "pmid": "7042171", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7042171/", "publicSourceType": "PMID" }, { "text": "Toews I et al. Pharmacological interventions for preventing upper gastrointestinal bleeding in people admitted to intensive care units: a network meta-analysis. BMJ Evid Based Med. 2025.", "pmid": "38997152", "doi": "10.1136/bmjebm-2024-112886", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38997152/", "publicSourceType": "PMID" }, { "text": "Sorkin EM, Darvey DL. Review of cimetidine drug interactions. Drug intelligence & clinical pharmacy. 1983", "pmid": "6130930", "doi": "10.1177/106002808301700205", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6130930/", "publicSourceType": "PMID" }, { "text": "Sedman AJ. Cimetidine-drug interactions. The American journal of medicine. 1984", "pmid": "6140847", "doi": "10.1016/0002-9343(84)90758-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6140847/", "publicSourceType": "PMID" }, { "text": "Richter JM, Colditz GA, Huse DM et al.. Cimetidine and adverse reactions: a meta-analysis of randomized clinical trials of short-term therapy. The American journal of medicine. 1989", "claim": "PubMed-indexed evidence involving Cimetidine", "title": "Cimetidine and adverse reactions: a meta-analysis of randomized clinical trials of short-term therapy", "authors": "Richter JM, Colditz GA, Huse DM et al.", "journal": "The American journal of medicine", "year": 1989, "pmid": "2773966", "url": "https://pubmed.ncbi.nlm.nih.gov/2773966/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/s0002-9343(89)80151-2", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2773966/", "publicSourceType": "PMID" }, { "text": "Gunasekara W, Sachindra J, Madhushika MT et al.. Cimetidine repurposed as a potential immunomodulatory agent against colorectal carcinoma: A systematic review. Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 2024", "claim": "PubMed-indexed evidence involving Cimetidine", "title": "Cimetidine repurposed as a potential immunomodulatory agent against colorectal carcinoma: A systematic review", "authors": "Gunasekara W, Sachindra J, Madhushika MT et al.", "journal": "Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners", "year": 2024, "pmid": "38592456", "url": "https://pubmed.ncbi.nlm.nih.gov/38592456/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/10781552241247007", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38592456/", "publicSourceType": "PMID" }, { "text": "Ström M, Gotthard R, Bodemar G et al.. Antacid/anticholinergic, cimetidine, and placebo in treatment of active peptic ulcers. Scandinavian journal of gastroenterology. 1981", "claim": "PubMed-indexed evidence involving Cimetidine", "title": "Antacid/anticholinergic, cimetidine, and placebo in treatment of active peptic ulcers", "authors": "Ström M, Gotthard R, Bodemar G et al.", "journal": "Scandinavian journal of gastroenterology", "year": 1981, "pmid": "7034155", "url": "https://pubmed.ncbi.nlm.nih.gov/7034155/", "study_type": "RCT", "confidence": "verify", "doi": "10.3109/00365528109182017", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7034155/", "publicSourceType": "PMID" }, { "text": "Klein AL, Sami MH. Usefulness and safety of cimetidine in patients receiving mexiletine for ventricular arrhythmia. American heart journal. 1985", "claim": "PubMed-indexed evidence involving Cimetidine", "title": "Usefulness and safety of cimetidine in patients receiving mexiletine for ventricular arrhythmia", "authors": "Klein AL, Sami MH", "journal": "American heart journal", "year": 1985, "pmid": "3890504", "url": "https://pubmed.ncbi.nlm.nih.gov/3890504/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/0002-8703(85)90352-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3890504/", "publicSourceType": "PMID" }, { "text": "Chen MM, Lee CS. Cimetidine--acetaminophen interaction in humans. Journal of clinical pharmacology. 1985", "claim": "PubMed-indexed evidence involving Cimetidine", "title": "Cimetidine--acetaminophen interaction in humans", "authors": "Chen MM, Lee CS", "journal": "Journal of clinical pharmacology", "year": 1985, "pmid": "3998201", "url": "https://pubmed.ncbi.nlm.nih.gov/3998201/", "study_type": "RCT", "confidence": "verify", "doi": "10.1002/j.1552-4604.1985.tb02829.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3998201/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "H2 Receptor Antagonist", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "2 hours", "onsetOfAction": "30–60 minutes", "commonBrandNames": [ "Tagamet", "Tagamet HB" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "cimetidine" }, { "id": "RX-GIPAIN-007", "name": "Calcium Carbonate", "alternateNames": [ "Tums" ], "category": "Prescription", "subcategory": "Antacid", "overview": "A widely used over-the-counter antacid that provides rapid, short-term relief of heartburn, acid indigestion, and sour stomach. 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Each gram of calcium carbonate neutralizes approximately 20 mEq of acid.", "commonBenefits": [ "Rapid relief of heartburn and acid indigestion", "Supplemental calcium for bone health", "Phosphate binding in chronic kidney disease", "Relief of sour stomach and dyspepsia" ], "commonDosageRange": "500–1500 mg as needed for symptoms, up to 7500 mg/day; calcium supplement: 500–600 mg per dose (as prescribed by your physician)", "recommendedForm": "Chewable tablet or oral suspension", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Best absorbed when taken with food; chew tablets completely before swallowing" }, "evidenceRating": "moderate", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Constipation", "Acid rebound with chronic use", "Hypercalcemia (with excessive use)", "Milk-alkali syndrome (rare, with high doses)", "Belching", "Flatulence" ], "contraindications": [ "Hypercalcemia", "Renal calculi (calcium-containing stones)", "Severe renal impairment (without medical supervision)", "Hypophosphatemia" ], "iconName": "cross.case.fill", "colorHex": "FFB74D", "tags": [ "gi", "antacid", "heartburn", "calcium", "otc" ], "sources": [ { "text": "Maton PN, Burton ME. Antacids revisited: a review of their clinical pharmacology and recommended therapeutic use. Drugs. 1999.", "pmid": "10400401", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10400401/", "publicSourceType": "PMID" }, { "text": "Straub DA. Calcium supplementation in clinical practice: a review of forms, doses, and indications. Nutr Clin Pract. 2007.", "pmid": "17507729", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17507729/", "publicSourceType": "PMID" }, { "text": "Natale P et al. Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD). Cochrane Database Syst Rev. 2025.", "pmid": "40576086", "doi": "10.1002/14651858.CD006023.pub4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40576086/", "publicSourceType": "PMID" }, { "text": "Jain H, Murali S, Singh G et al.. Calcium Carbonate (Tums)-Associated Hypercalcemic Crisis. Cureus. 2022", "pmid": "36712775", "doi": "10.7759/cureus.32913", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36712775/", "publicSourceType": "PMID" }, { "text": "Wang Y, Xie G, Huang Y et al.. Calcium acetate or calcium carbonate for hyperphosphatemia of hemodialysis patients: a meta-analysis. PloS one. 2015", "claim": "PubMed-indexed evidence involving Calcium Carbonate", "title": "Calcium acetate or calcium carbonate for hyperphosphatemia of hemodialysis patients: a meta-analysis", "authors": "Wang Y, Xie G, Huang Y et al.", "journal": "PloS one", "year": 2015, "pmid": "25799184", "url": "https://pubmed.ncbi.nlm.nih.gov/25799184/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1371/journal.pone.0121376", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25799184/", "publicSourceType": "PMID" }, { "text": "Castelo-Branco C, Ciria-Recasens M, Cancelo-Hidalgo MJ et al.. Efficacy of ossein-hydroxyapatite complex compared with calcium carbonate to prevent bone loss: a meta-analysis. Menopause (New York, N.Y.). 2009", "claim": "PubMed-indexed evidence involving Calcium Carbonate", "title": "Efficacy of ossein-hydroxyapatite complex compared with calcium carbonate to prevent bone loss: a meta-analysis", "authors": "Castelo-Branco C, Ciria-Recasens M, Cancelo-Hidalgo MJ et al.", "journal": "Menopause (New York, N.Y.)", "year": 2009, "pmid": "19407667", "url": "https://pubmed.ncbi.nlm.nih.gov/19407667/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/gme.0b013e3181a1824e", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19407667/", "publicSourceType": "PMID" }, { "text": "Sakhaee K, Bhuket T, Adams-Huet B et al.. Meta-analysis of calcium bioavailability: a comparison of calcium citrate with calcium carbonate. American journal of therapeutics. 1999", "claim": "PubMed-indexed evidence involving Calcium Carbonate", "title": "Meta-analysis of calcium bioavailability: a comparison of calcium citrate with calcium carbonate", "authors": "Sakhaee K, Bhuket T, Adams-Huet B et al.", "journal": "American journal of therapeutics", "year": 1999, "pmid": "11329115", "url": "https://pubmed.ncbi.nlm.nih.gov/11329115/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/00045391-199911000-00005", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11329115/", "publicSourceType": "PMID" }, { "text": "Oliveira CRV, Resende CL, Neves SJF et al.. Calcium carbonate supplementation for the prevention of preeclampsia in high-risk pregnant women: a randomized clinical trial protocol. Trials. 2024", "claim": "PubMed-indexed evidence involving Calcium Carbonate", "title": "Calcium carbonate supplementation for the prevention of preeclampsia in high-risk pregnant women: a randomized clinical trial protocol", "authors": "Oliveira CRV, Resende CL, Neves SJF et al.", "journal": "Trials", "year": 2024, "pmid": "39363375", "url": "https://pubmed.ncbi.nlm.nih.gov/39363375/", "study_type": "RCT", "confidence": "verify", "doi": "10.1186/s13063-024-08489-9", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39363375/", "publicSourceType": "PMID" }, { "text": "Naciu AM, Tabacco G, Bilezikian JP et al.. Calcium Citrate Versus Calcium Carbonate in the Management of Chronic Hypoparathyroidism: A Randomized, Double-Blind, Crossover Clinical Trial. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2022", "claim": "PubMed-indexed evidence involving Calcium Carbonate", "title": "Calcium Citrate Versus Calcium Carbonate in the Management of Chronic Hypoparathyroidism: A Randomized, Double-Blind, Crossover Clinical Trial", "authors": "Naciu AM, Tabacco G, Bilezikian JP et al.", "journal": "Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research", "year": 2022, "pmid": "35466449", "url": "https://pubmed.ncbi.nlm.nih.gov/35466449/", "study_type": "RCT", "confidence": "verify", "doi": "10.1002/jbmr.4564", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35466449/", "publicSourceType": "PMID" }, { "text": "Tancredi W, Bolduc S. Could oral calcium carbonate mitigate tartaric acid toxicity in dogs? A novel hypothesis. Journal of the American Veterinary Medical Association. 2025", "claim": "PubMed-indexed evidence involving Calcium Carbonate", "title": "Could oral calcium carbonate mitigate tartaric acid toxicity in dogs? A novel hypothesis", "authors": "Tancredi W, Bolduc S", "journal": "Journal of the American Veterinary Medical Association", "year": 2025, "pmid": "40840530", "url": "https://pubmed.ncbi.nlm.nih.gov/40840530/", "study_type": "review", "confidence": "verify", "doi": "10.2460/javma.25.03.0160", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40840530/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Antacid / Calcium Supplement", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "Not applicable (local neutralization in stomach)", "onsetOfAction": "Immediate (within minutes)", "commonBrandNames": [ "Tums", "Rolaids", "Caltrate" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "calcium-carbonate" }, { "id": "RX-GIPAIN-008", "name": "Aluminum/Magnesium Hydroxide", "alternateNames": [ "Maalox" ], "category": "Prescription", "subcategory": "Antacid", "overview": "A combination antacid containing aluminum hydroxide and magnesium hydroxide, used for the symptomatic relief of heartburn, acid indigestion, sour stomach, and peptic ulcer pain. The combination balances the constipating effect of aluminum with the laxative effect of magnesium.", "mechanismOfAction": "Aluminum hydroxide and magnesium hydroxide directly neutralize gastric hydrochloric acid in the stomach, raising intragastric pH. Aluminum hydroxide also inhibits pepsin activity at pH above 4.0 and binds bile acids. The combination provides effective acid neutralization while minimizing bowel habit changes.", "commonBenefits": [ "Rapid relief of heartburn and acid indigestion", "Sour stomach relief", "Symptomatic relief of peptic ulcer pain", "Balanced GI side effect profile (compared to single-agent antacids)" ], "commonDosageRange": "10–20 mL or 1–2 tablets as needed, up to 4 times daily (as prescribed by your physician)", "recommendedForm": "Oral suspension or chewable tablet", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Take 1–3 hours after meals and at bedtime for ulcer treatment; separate from other medications by at least 2 hours to avoid absorption interference" }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Diarrhea (magnesium component)", "Constipation (aluminum component)", "Hypermagnesemia in renal impairment", "Aluminum accumulation in renal failure", "Hypophosphatemia with chronic use", "Chalky taste" ], "contraindications": [ "Severe renal impairment (risk of magnesium and aluminum accumulation)", "Hypophosphatemia", "Appendicitis or bowel obstruction", "Concurrent use with tetracyclines or fluoroquinolones (space by 2 hours)" ], "iconName": "cross.case.fill", "colorHex": "FFB74D", "tags": [ "gi", "antacid", "heartburn", "otc" ], "sources": [ { "text": "Maton PN, Burton ME. Antacids revisited: a review of their clinical pharmacology and recommended therapeutic use. Drugs. 1999.", "pmid": "10400401", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10400401/", "publicSourceType": "PMID" }, { "text": "Welage LS, Berardi RR. Evaluation of omeprazole, lansoprazole, pantoprazole, and rabeprazole in the treatment of acid-related diseases. J Am Pharm Assoc. 2000.", "pmid": "10665250", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10665250/", "publicSourceType": "PMID" }, { "text": "Li J et al. A systematic review for prevention of cisplatin-induced nephrotoxicity using different hydration protocols and meta-analysis for magnesium hydrate supplementation. Clin Exp Nephrol. 2024.", "pmid": "37530867", "doi": "10.1007/s10157-023-02386-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37530867/", "publicSourceType": "PMID" }, { "text": "Hangan T, Bjorklund G, Chirila S. Exploring the Potential Link between Aluminum-Containing Deodorants/Antiperspirants and Breast Cancer: A Comprehensive Review. Current medicinal chemistry. 2025", "pmid": "38173070", "doi": "10.2174/0109298673269343231025070053", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38173070/", "publicSourceType": "PMID" }, { "text": "Nate-Anong B, Khorana J, Chantakhow S et al.. Sennosides vs magnesium hydroxide vs polyethylene glycol as a treatment for constipation in anorectal malformation: a randomized crossover trial. Pediatric surgery international. 2025", "claim": "PubMed-indexed evidence involving Aluminum/Magnesium Hydroxide", "title": "Sennosides vs magnesium hydroxide vs polyethylene glycol as a treatment for constipation in anorectal malformation: a randomized crossover trial", "authors": "Nate-Anong B, Khorana J, Chantakhow S et al.", "journal": "Pediatric surgery international", "year": 2025, "pmid": "40856829", "url": "https://pubmed.ncbi.nlm.nih.gov/40856829/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/s00383-025-06174-9", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40856829/", "publicSourceType": "PMID" }, { "text": "Hürlimann S, Michel K, Inauen W et al.. Effect of Rennie Liquid versus Maalox Liquid on intragastric pH in a double-blind, randomized, placebo-controlled, triple cross-over study in healthy volunteers. The American journal of gastroenterology. 1996", "claim": "PubMed-indexed evidence involving Aluminum/Magnesium Hydroxide", "title": "Effect of Rennie Liquid versus Maalox Liquid on intragastric pH in a double-blind, randomized, placebo-controlled, triple cross-over study in healthy volunteers", "authors": "Hürlimann S, Michel K, Inauen W et al.", "journal": "The American journal of gastroenterology", "year": 1996, "pmid": "8651166", "url": "https://pubmed.ncbi.nlm.nih.gov/8651166/", "study_type": "RCT", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8651166/", "publicSourceType": "PMID" }, { "text": "Hunter JO, Walker RJ, Crowe J et al.. Double-blind randomized multicenter study comparing Maalox TC tablets and ranitidine in healing of duodenal ulcers. Digestive diseases and sciences. 1991", "claim": "PubMed-indexed evidence involving Aluminum/Magnesium Hydroxide", "title": "Double-blind randomized multicenter study comparing Maalox TC tablets and ranitidine in healing of duodenal ulcers", "authors": "Hunter JO, Walker RJ, Crowe J et al.", "journal": "Digestive diseases and sciences", "year": 1991, "pmid": "2070704", "url": "https://pubmed.ncbi.nlm.nih.gov/2070704/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/BF01297140", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2070704/", "publicSourceType": "PMID" }, { "text": "Becker LC, Boyer I, Bergfeld WF et al.. Safety Assessment of Alumina and Aluminum Hydroxide as Used in Cosmetics. International journal of toxicology. 2016", "claim": "PubMed-indexed evidence involving Aluminum/Magnesium Hydroxide", "title": "Safety Assessment of Alumina and Aluminum Hydroxide as Used in Cosmetics", "authors": "Becker LC, Boyer I, Bergfeld WF et al.", "journal": "International journal of toxicology", "year": 2016, "pmid": "27913785", "url": "https://pubmed.ncbi.nlm.nih.gov/27913785/", "study_type": "review", "confidence": "verify", "doi": "10.1177/1091581816677948", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27913785/", "publicSourceType": "PMID" }, { "text": "Busch U, Heinzel G, Narjes H et al.. Interaction of meloxicam with cimetidine, Maalox, or aspirin. Journal of clinical pharmacology. 1996", "claim": "PubMed-indexed evidence involving Aluminum/Magnesium Hydroxide", "title": "Interaction of meloxicam with cimetidine, Maalox, or aspirin", "authors": "Busch U, Heinzel G, Narjes H et al.", "journal": "Journal of clinical pharmacology", "year": 1996, "pmid": "8932547", "url": "https://pubmed.ncbi.nlm.nih.gov/8932547/", "study_type": "RCT", "confidence": "verify", "doi": "10.1002/j.1552-4604.1996.tb04155.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8932547/", "publicSourceType": "PMID" }, { "text": "Chen MM, Lee C, Imamura Y et al.. Acetaminophen-aluminum hydroxide interaction in rabbits. Journal of pharmaceutical sciences. 1983", "claim": "PubMed-indexed evidence involving Aluminum/Magnesium Hydroxide", "title": "Acetaminophen-aluminum hydroxide interaction in rabbits", "authors": "Chen MM, Lee C, Imamura Y et al.", "journal": "Journal of pharmaceutical sciences", "year": 1983, "pmid": "6886995", "url": "https://pubmed.ncbi.nlm.nih.gov/6886995/", "study_type": "review", "confidence": "verify", "doi": "10.1002/jps.2600720731", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6886995/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Antacid Combination", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "Not applicable (local neutralization in stomach)", "onsetOfAction": "Immediate (within minutes)", "commonBrandNames": [ "Maalox", "Mylanta" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "aluminum-magnesium-hydroxide" }, { "id": "RX-GIPAIN-009", "name": "Polyethylene Glycol", "alternateNames": [ "MiraLAX", "PEG 3350" ], "category": "Prescription", "subcategory": "Osmotic Laxative", "overview": "An osmotic laxative composed of polyethylene glycol 3350, used for the treatment of occasional constipation and chronic idiopathic constipation. PEG 3350 is also used in higher doses for bowel preparation before colonoscopy. It is well-tolerated and does not cause electrolyte imbalances at standard doses.", "mechanismOfAction": "Acts as an osmotic agent in the intestinal lumen, retaining water through hydrogen bonding. The increased water content in the stool softens it and increases stool volume, stimulating peristalsis. PEG 3350 is not absorbed or metabolized, and it does not stimulate the colonic mucosa directly.", "commonBenefits": [ "Relief of occasional constipation", "Treatment of chronic idiopathic constipation", "Bowel preparation for colonoscopy (high-dose formulations)", "Gentle, non-stimulant laxation" ], "commonDosageRange": "17 g (1 capful) dissolved in 8 oz of liquid once daily for up to 7 days (as prescribed by your physician)", "recommendedForm": "Powder dissolved in water or other beverage", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Dissolve powder completely in 4–8 oz of water, juice, or other beverage; can be taken at any time of day" }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Bloating", "Nausea", "Abdominal cramping", "Flatulence", "Diarrhea (with excessive use)", "Abdominal distension" ], "contraindications": [ "Known or suspected bowel obstruction", "Known allergy to polyethylene glycol", "Patients with symptoms of appendicitis or acute abdomen", "GI perforation" ], "iconName": "cross.case.fill", "colorHex": "81C784", "tags": [ "gi", "constipation", "laxative", "osmotic", "otc" ], "sources": [ { "text": "DiPalma JA et al. A randomized, placebo-controlled, multicenter study of the safety and efficacy of a new polyethylene glycol laxative. Am J Gastroenterol. 2000.", "pmid": "10685748", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10685748/", "publicSourceType": "PMID" }, { "text": "Cleveland MV et al. New polyethylene glycol laxative for treatment of constipation in adults: a randomized, double-blind, placebo-controlled study. South Med J. 2001.", "pmid": "38082231", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38082231/", "publicSourceType": "PMID" }, { "text": "Abideen ZU et al. Comparing various bowel preparation regimens in constipated patients undergoing colonoscopy: A systematic review and network meta-analysis of randomised controlled trials. Colorectal Dis. 2026.", "pmid": "41684308", "doi": "10.1111/codi.70399", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41684308/", "publicSourceType": "PMID" }, { "text": "Siddique S, Lopez KT, Hinds AM et al.. Miralax with gatorade for bowel preparation: a meta-analysis of randomized controlled trials. The American journal of gastroenterology. 2014", "claim": "PubMed-indexed evidence involving Polyethylene Glycol", "title": "Miralax with gatorade for bowel preparation: a meta-analysis of randomized controlled trials", "authors": "Siddique S, Lopez KT, Hinds AM et al.", "journal": "The American journal of gastroenterology", "year": 2014, "pmid": "25135007", "url": "https://pubmed.ncbi.nlm.nih.gov/25135007/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1038/ajg.2014.238", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25135007/", "publicSourceType": "PMID" }, { "text": "Belsey J, Epstein O, Heresbach D. Systematic review: adverse event reports for oral sodium phosphate and polyethylene glycol. Alimentary pharmacology & therapeutics. 2009", "claim": "PubMed-indexed evidence involving Polyethylene Glycol", "title": "Systematic review: adverse event reports for oral sodium phosphate and polyethylene glycol", "authors": "Belsey J, Epstein O, Heresbach D", "journal": "Alimentary pharmacology & therapeutics", "year": 2009, "pmid": "18729847", "url": "https://pubmed.ncbi.nlm.nih.gov/18729847/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/j.1365-2036.2008.03837.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18729847/", "publicSourceType": "PMID" }, { "text": "Afkhami Ardekani M, Ghaffari H. Optimization of prostate brachytherapy techniques with polyethylene glycol-based hydrogel spacers: A systematic review. Brachytherapy. 2020", "claim": "PubMed-indexed evidence involving Polyethylene Glycol", "title": "Optimization of prostate brachytherapy techniques with polyethylene glycol-based hydrogel spacers: A systematic review", "authors": "Afkhami Ardekani M, Ghaffari H", "journal": "Brachytherapy", "year": 2020, "pmid": "31542390", "url": "https://pubmed.ncbi.nlm.nih.gov/31542390/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.brachy.2019.08.009", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31542390/", "publicSourceType": "PMID" }, { "text": "Rachel H, Griffith AF, Teague WJ et al.. Polyethylene Glycol Dosing for Constipation in Children Younger Than 24 Months: A Systematic Review. Journal of pediatric gastroenterology and nutrition. 2020", "claim": "PubMed-indexed evidence involving Polyethylene Glycol", "title": "Polyethylene Glycol Dosing for Constipation in Children Younger Than 24 Months: A Systematic Review", "authors": "Rachel H, Griffith AF, Teague WJ et al.", "journal": "Journal of pediatric gastroenterology and nutrition", "year": 2020, "pmid": "32520829", "url": "https://pubmed.ncbi.nlm.nih.gov/32520829/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MPG.0000000000002786", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32520829/", "publicSourceType": "PMID" }, { "text": "Jin Z, Lu Y, Zhou Y et al.. Systematic review and meta-analysis: sodium picosulfate/magnesium citrate vs. polyethylene glycol for colonoscopy preparation. European journal of clinical pharmacology. 2016", "claim": "PubMed-indexed evidence involving Polyethylene Glycol", "title": "Systematic review and meta-analysis: sodium picosulfate/magnesium citrate vs. polyethylene glycol for colonoscopy preparation", "authors": "Jin Z, Lu Y, Zhou Y et al.", "journal": "European journal of clinical pharmacology", "year": 2016, "pmid": "26818765", "url": "https://pubmed.ncbi.nlm.nih.gov/26818765/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00228-016-2013-5", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26818765/", "publicSourceType": "PMID" }, { "text": "Belsey JD, Geraint M, Dixon TA. Systematic review and meta analysis: polyethylene glycol in adults with non-organic constipation. International journal of clinical practice. 2010", "claim": "PubMed-indexed evidence involving Polyethylene Glycol", "title": "Systematic review and meta analysis: polyethylene glycol in adults with non-organic constipation", "authors": "Belsey JD, Geraint M, Dixon TA", "journal": "International journal of clinical practice", "year": 2010, "pmid": "20584228", "url": "https://pubmed.ncbi.nlm.nih.gov/20584228/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/j.1742-1241.2010.02397.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20584228/", "publicSourceType": "PMID" }, { "text": "Candy D, Belsey J. Macrogol (polyethylene glycol) laxatives in children with functional constipation and faecal impaction: a systematic review. 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European journal of gastroenterology & hepatology. 2011", "claim": "PubMed-indexed evidence involving Lactulose", "title": "Clinical efficacy and safety of lactulose for minimal hepatic encephalopathy: a meta-analysis", "authors": "Luo M, Li L, Lu CZ et al.", "journal": "European journal of gastroenterology & hepatology", "year": 2011, "pmid": "21971378", "url": "https://pubmed.ncbi.nlm.nih.gov/21971378/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MEG.0b013e32834d1938", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21971378/", "publicSourceType": "PMID" }, { "text": "Zucker DM, Redulla R. Lactulose Management of Minimal Hepatic Encephalopathy: A Systematic Review. Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates. 2019", "claim": "PubMed-indexed evidence involving Lactulose", "title": "Lactulose Management of Minimal Hepatic Encephalopathy: A Systematic Review", "authors": "Zucker DM, Redulla R", "journal": "Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates", "year": 2019, "pmid": "30688711", "url": "https://pubmed.ncbi.nlm.nih.gov/30688711/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/SGA.0000000000000429", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30688711/", "publicSourceType": "PMID" }, { "text": "Blanc P, Daures JP, Rouillon JM et al.. Lactitol or lactulose in the treatment of chronic hepatic encephalopathy: results of a meta-analysis. Hepatology (Baltimore, Md.). 1992", "claim": "PubMed-indexed evidence involving Lactulose", "title": "Lactitol or lactulose in the treatment of chronic hepatic encephalopathy: results of a meta-analysis", "authors": "Blanc P, Daures JP, Rouillon JM et al.", "journal": "Hepatology (Baltimore, Md.)", "year": 1992, "pmid": "1531204", "url": "https://pubmed.ncbi.nlm.nih.gov/1531204/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/hep.1840150209", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1531204/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Osmotic Laxative / Ammonia Detoxicant", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "Not applicable (not absorbed systemically)", "onsetOfAction": "24–48 hours (for constipation)", "commonBrandNames": [ "Enulose", "Kristalose", "Constulose" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "lactulose" }, { "id": "RX-GIPAIN-011", "name": "Bisacodyl", "alternateNames": [ "Dulcolax" ], "category": "Prescription", "subcategory": "Stimulant Laxative", "overview": "A diphenylmethane derivative stimulant laxative used for the relief of occasional constipation and for bowel preparation before diagnostic procedures or surgery. 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Oral bisacodyl is effective and well-tolerated in patients with chronic constipation. Clin Gastroenterol Hepatol. 2011.", "pmid": "21440672", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21440672/", "publicSourceType": "PMID" }, { "text": "Wald A. Constipation: advances in diagnosis and treatment. JAMA. 2016.", "pmid": "31054770", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31054770/", "publicSourceType": "PMID" }, { "text": "Abideen ZU et al. Comparing various bowel preparation regimens in constipated patients undergoing colonoscopy: A systematic review and network meta-analysis of randomised controlled trials. Colorectal Dis. 2026.", "pmid": "41684308", "doi": "10.1111/codi.70399", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41684308/", "publicSourceType": "PMID" }, { "text": "Yi Z, Jie C, Wenyi Z et al.. Comparison of efficacies of vegetable oil based and polyethylene glycol based bisacodyl suppositories in treating patients with neurogenic bowel dysfunction after spinal cord injury: a meta-analysis. The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology. 2014", "pmid": "25417608", "doi": "10.5152/tjg.2014.6708", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25417608/", "publicSourceType": "PMID" }, { "text": "Corsetti M, Landes S, Lange R. Bisacodyl: A review of pharmacology and clinical evidence to guide use in clinical practice in patients with constipation. Neurogastroenterology and motility. 2021", "pmid": "33751780", "doi": "10.1111/nmo.14123", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33751780/", "publicSourceType": "PMID" }, { "text": "Clark RE, Godfrey JD, Choudhary A et al.. Low-volume polyethylene glycol and bisacodyl for bowel preparation prior to colonoscopy: a meta-analysis. Annals of gastroenterology. 2013", "claim": "PubMed-indexed evidence involving Bisacodyl", "title": "Low-volume polyethylene glycol and bisacodyl for bowel preparation prior to colonoscopy: a meta-analysis", "authors": "Clark RE, Godfrey JD, Choudhary A et al.", "journal": "Annals of gastroenterology", "year": 2013, "pmid": "24714413", "url": "https://pubmed.ncbi.nlm.nih.gov/24714413/", "study_type": "meta-analysis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24714413/", "publicSourceType": "PMID" }, { "text": "Kienzle-Horn S, Vix JM, Schuijt C et al.. Efficacy and safety of bisacodyl in the acute treatment of constipation: a double-blind, randomized, placebo-controlled study. Alimentary pharmacology & therapeutics. 2006", "claim": "PubMed-indexed evidence involving Bisacodyl", "title": "Efficacy and safety of bisacodyl in the acute treatment of constipation: a double-blind, randomized, placebo-controlled study", "authors": "Kienzle-Horn S, Vix JM, Schuijt C et al.", "journal": "Alimentary pharmacology & therapeutics", "year": 2006, "pmid": "16669963", "url": "https://pubmed.ncbi.nlm.nih.gov/16669963/", "study_type": "RCT", "confidence": "verify", "doi": "10.1111/j.1365-2036.2006.02903.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16669963/", "publicSourceType": "PMID" }, { "text": "Aliyu A, Dellschaft N, Hoad C et al.. Magnetic Resonance Imaging Reveals Novel Insights into the Dual Mode of Action of Bisacodyl: A Randomized, Placebo-controlled Trial in Constipation. Clinical pharmacology and therapeutics. 2025", "claim": "PubMed-indexed evidence involving Bisacodyl", "title": "Magnetic Resonance Imaging Reveals Novel Insights into the Dual Mode of Action of Bisacodyl: A Randomized, Placebo-controlled Trial in Constipation", "authors": "Aliyu A, Dellschaft N, Hoad C et al.", "journal": "Clinical pharmacology and therapeutics", "year": 2025, "pmid": "39679695", "url": "https://pubmed.ncbi.nlm.nih.gov/39679695/", "study_type": "RCT", "confidence": "verify", "doi": "10.1002/cpt.3532", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39679695/", "publicSourceType": "PMID" }, { "text": "Hung SY, Chen HC, Chen WT. A Randomized Trial Comparing the Bowel Cleansing Efficacy of Sodium Picosulfate/Magnesium Citrate and Polyethylene Glycol/Bisacodyl (The Bowklean Study). Scientific reports. 2020", "claim": "PubMed-indexed evidence involving Bisacodyl", "title": "A Randomized Trial Comparing the Bowel Cleansing Efficacy of Sodium Picosulfate/Magnesium Citrate and Polyethylene Glycol/Bisacodyl (The Bowklean Study)", "authors": "Hung SY, Chen HC, Chen WT", "journal": "Scientific reports", "year": 2020, "pmid": "32221332", "url": "https://pubmed.ncbi.nlm.nih.gov/32221332/", "study_type": "RCT", "confidence": "verify", "doi": "10.1038/s41598-020-62120-w", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32221332/", "publicSourceType": "PMID" }, { "text": "Vieira MC, Hashimoto CL, Carrilho FJ. Bowel preparation for performing a colonoscopy: prospective randomized comparison study between a low-volume solution of polyethylene glycol and bisacodyl versus bisacodyl and a mannitol solution. Arquivos de gastroenterologia. 2012", "claim": "PubMed-indexed evidence involving Bisacodyl", "title": "Bowel preparation for performing a colonoscopy: prospective randomized comparison study between a low-volume solution of polyethylene glycol and bisacodyl versus bisacodyl and a mannitol solution", "authors": "Vieira MC, Hashimoto CL, Carrilho FJ", "journal": "Arquivos de gastroenterologia", "year": 2012, "pmid": "22767005", "url": "https://pubmed.ncbi.nlm.nih.gov/22767005/", "study_type": "RCT", "confidence": "verify", "doi": "10.1590/s0004-28032012000200012", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22767005/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Stimulant Laxative", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "16 hours (active metabolite)", "onsetOfAction": "6–12 hours (oral); 15–60 minutes (rectal)", "commonBrandNames": [ "Dulcolax", "Correctol" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "bisacodyl" }, { "id": "RX-GIPAIN-012", "name": "Loperamide", "alternateNames": [ "Imodium" ], "category": "Prescription", "subcategory": "Anti-Diarrheal", "overview": "A synthetic opioid receptor agonist that acts peripherally on the gastrointestinal tract to reduce diarrhea. 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Loperamide: a pharmacological review. Rev Gastroenterol Disord. 2007.", "pmid": "18192961", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18192961/", "publicSourceType": "PMID" }, { "text": "Hanauer SB. The role of loperamide in gastrointestinal disorders. Rev Gastroenterol Disord. 2008.", "pmid": "18477966", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18477966/", "publicSourceType": "PMID" }, { "text": "Rehde A et al. Effectiveness of Non-Budesonide Therapies in Management of Microscopic Colitis: A Systematic Review and Meta-analysis. Drugs. 2023.", "pmid": "37358712", "doi": "10.1007/s40265-023-01914-4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37358712/", "publicSourceType": "PMID" }, { "text": "Sahi N, Nguyen R, Patel P et al.. Loperamide. 2026", "pmid": "32491808", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32491808/", "publicSourceType": "PMID" }, { "text": "Riaz IB, Khan MS, Kamal MU et al.. Cardiac Dysrhythmias Associated With Substitutive Use of Loperamide: A Systematic Review. American journal of therapeutics. 2019", "claim": "PubMed-indexed evidence involving Loperamide", "title": "Cardiac Dysrhythmias Associated With Substitutive Use of Loperamide: A Systematic Review", "authors": "Riaz IB, Khan MS, Kamal MU et al.", "journal": "American journal of therapeutics", "year": 2019, "pmid": "28594339", "url": "https://pubmed.ncbi.nlm.nih.gov/28594339/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MJT.0000000000000585", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28594339/", "publicSourceType": "PMID" }, { "text": "Li ST, Grossman DC, Cummings P. Loperamide therapy for acute diarrhea in children: systematic review and meta-analysis. PLoS medicine. 2007", "claim": "PubMed-indexed evidence involving Loperamide", "title": "Loperamide therapy for acute diarrhea in children: systematic review and meta-analysis", "authors": "Li ST, Grossman DC, Cummings P", "journal": "PLoS medicine", "year": 2007, "pmid": "17388664", "url": "https://pubmed.ncbi.nlm.nih.gov/17388664/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1371/journal.pmed.0040098", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17388664/", "publicSourceType": "PMID" }, { "text": "P B A, Sudha SP, Mohan P et al.. Racecadotril Versus Loperamide in Acute Radiation Enteritis: A Randomized, Double-Masked, Phase 3, Noninferiority Trial. International journal of radiation oncology, biology, physics. 2024", "claim": "PubMed-indexed evidence involving Loperamide", "title": "Racecadotril Versus Loperamide in Acute Radiation Enteritis: A Randomized, Double-Masked, Phase 3, Noninferiority Trial", "authors": "P B A, Sudha SP, Mohan P et al.", "journal": "International journal of radiation oncology, biology, physics", "year": 2024, "pmid": "37742773", "url": "https://pubmed.ncbi.nlm.nih.gov/37742773/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.ijrobp.2023.09.021", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37742773/", "publicSourceType": "PMID" }, { "text": "Teigeler T, Stahura H, Alimohammad R et al.. Electrocardiographic changes in loperamide toxicity: Case report and review of literature. Journal of cardiovascular electrophysiology. 2019", "claim": "PubMed-indexed evidence involving Loperamide", "title": "Electrocardiographic changes in loperamide toxicity: Case report and review of literature", "authors": "Teigeler T, Stahura H, Alimohammad R et al.", "journal": "Journal of cardiovascular electrophysiology", "year": 2019, "pmid": "31432581", "url": "https://pubmed.ncbi.nlm.nih.gov/31432581/", "study_type": "review", "confidence": "verify", "doi": "10.1111/jce.14129", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31432581/", "publicSourceType": "PMID" }, { "text": "Akel T, Bekheit S. Loperamide cardiotoxicity: \"A Brief Review\". Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc. 2018", "claim": "PubMed-indexed evidence involving Loperamide", "title": "Loperamide cardiotoxicity: \"A Brief Review\"", "authors": "Akel T, Bekheit S", "journal": "Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc", "year": 2018, "pmid": "29125226", "url": "https://pubmed.ncbi.nlm.nih.gov/29125226/", "study_type": "review", "confidence": "verify", "doi": "10.1111/anec.12505", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29125226/", "publicSourceType": "PMID" }, { "text": "Wu PE, Juurlink DN. Clinical Review: Loperamide Toxicity. Annals of emergency medicine. 2017", "claim": "PubMed-indexed evidence involving Loperamide", "title": "Clinical Review: Loperamide Toxicity", "authors": "Wu PE, Juurlink DN", "journal": "Annals of emergency medicine", "year": 2017, "pmid": "28506439", "url": "https://pubmed.ncbi.nlm.nih.gov/28506439/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.annemergmed.2017.04.008", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28506439/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Peripheral Opioid Receptor Agonist (Anti-Diarrheal)", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "9–14 hours", "onsetOfAction": "1 hour", "commonBrandNames": [ "Imodium", "Imodium A-D" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "loperamide" }, { "id": "RX-GIPAIN-013", "name": "Ondansetron", "alternateNames": [ "Zofran" ], "category": "Prescription", "subcategory": "Antiemetic (5-HT3 Antagonist)", "overview": "A selective serotonin 5-HT3 receptor antagonist used for the prevention and treatment of nausea and vomiting caused by chemotherapy, radiation therapy, and surgery. 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Antiemetics: ASCO Guideline Update. J Clin Oncol. 2020.", "pmid": "38129530", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38129530/", "publicSourceType": "PMID" }, { "text": "Freedman SB et al. Oral ondansetron for gastroenteritis in a pediatric emergency department. N Engl J Med. 2006.", "pmid": "40673584", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40673584/", "publicSourceType": "PMID" }, { "text": "Rojas C, Slusher BS. Pharmacological mechanisms of 5-HT3 and tachykinin NK1 receptor antagonism to prevent chemotherapy-induced nausea and vomiting. Eur J Pharmacol. 2012.", "pmid": "22425650", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22425650/", "publicSourceType": "PMID" }, { "text": "Tie HT, Su GZ, He K et al.. Efficacy and safety of ondansetron in preventing postanesthesia shivering: a meta-analysis of randomized controlled trials. BMC anesthesiology. 2014", "claim": "PubMed-indexed evidence involving Ondansetron", "title": "Efficacy and safety of ondansetron in preventing postanesthesia shivering: a meta-analysis of randomized controlled trials", "authors": "Tie HT, Su GZ, He K et al.", "journal": "BMC anesthesiology", "year": 2014, "pmid": "24588846", "url": "https://pubmed.ncbi.nlm.nih.gov/24588846/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/1471-2253-14-12", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24588846/", "publicSourceType": "PMID" }, { "text": "Zheng W, Cai DB, Zhang QE et al.. Adjunctive ondansetron for schizophrenia: A systematic review and meta-analysis of randomized controlled trials. Journal of psychiatric research. 2019", "claim": "PubMed-indexed evidence involving Ondansetron", "title": "Adjunctive ondansetron for schizophrenia: A systematic review and meta-analysis of randomized controlled trials", "authors": "Zheng W, Cai DB, Zhang QE et al.", "journal": "Journal of psychiatric research", "year": 2019, "pmid": "30878789", "url": "https://pubmed.ncbi.nlm.nih.gov/30878789/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jpsychires.2019.02.024", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30878789/", "publicSourceType": "PMID" }, { "text": "Ashour AM. Efficacy and safety of ondansetron for morning sickness in pregnancy: a systematic review of clinical trials. Frontiers in pharmacology. 2023", "claim": "PubMed-indexed evidence involving Ondansetron", "title": "Efficacy and safety of ondansetron for morning sickness in pregnancy: a systematic review of clinical trials", "authors": "Ashour AM", "journal": "Frontiers in pharmacology", "year": 2023, "pmid": "37936910", "url": "https://pubmed.ncbi.nlm.nih.gov/37936910/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fphar.2023.1291235", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37936910/", "publicSourceType": "PMID" }, { "text": "Wang W, Zhou L, Sun L. Ondansetron for neuraxial morphine-induced pruritus: A meta-analysis of randomized controlled trials. Journal of clinical pharmacy and therapeutics. 2017", "claim": "PubMed-indexed evidence involving Ondansetron", "title": "Ondansetron for neuraxial morphine-induced pruritus: A meta-analysis of randomized controlled trials", "authors": "Wang W, Zhou L, Sun L", "journal": "Journal of clinical pharmacy and therapeutics", "year": 2017, "pmid": "28464238", "url": "https://pubmed.ncbi.nlm.nih.gov/28464238/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/jcpt.12539", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28464238/", "publicSourceType": "PMID" }, { "text": "Tubog TD, Bramble RS. Ondansetron for Shivering after Spinal Anesthesia in Cesarean Delivery: A Systematic Review and Meta-analysis. Journal of perianesthesia nursing : official journal of the American Society of PeriAnesthesia Nurses. 2022", "claim": "PubMed-indexed evidence involving Ondansetron", "title": "Ondansetron for Shivering after Spinal Anesthesia in Cesarean Delivery: A Systematic Review and Meta-analysis", "authors": "Tubog TD, Bramble RS", "journal": "Journal of perianesthesia nursing : official journal of the American Society of PeriAnesthesia Nurses", "year": 2022, "pmid": "34836765", "url": "https://pubmed.ncbi.nlm.nih.gov/34836765/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jopan.2021.05.007", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34836765/", "publicSourceType": "PMID" }, { "text": "Cao X, Sun M, Yang Q et al.. Risk of abnormal pregnancy outcomes after using ondansetron during pregnancy: A systematic review and meta-analysis. Frontiers in pharmacology. 2022", "claim": "PubMed-indexed evidence involving Ondansetron", "title": "Risk of abnormal pregnancy outcomes after using ondansetron during pregnancy: A systematic review and meta-analysis", "authors": "Cao X, Sun M, Yang Q et al.", "journal": "Frontiers in pharmacology", "year": 2022, "pmid": "36120333", "url": "https://pubmed.ncbi.nlm.nih.gov/36120333/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fphar.2022.951072", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36120333/", "publicSourceType": "PMID" }, { "text": "Hou XM, Chen YJ, Lai L et al.. Ondansetron Reduces the Incidence of Hypotension after Spinal Anaesthesia: A Systematic Review and Meta-Analysis. Pharmaceuticals (Basel, Switzerland). 2022", "claim": "PubMed-indexed evidence involving Ondansetron", "title": "Ondansetron Reduces the Incidence of Hypotension after Spinal Anaesthesia: A Systematic Review and Meta-Analysis", "authors": "Hou XM, Chen YJ, Lai L et al.", "journal": "Pharmaceuticals (Basel, Switzerland)", "year": 2022, "pmid": "36559039", "url": "https://pubmed.ncbi.nlm.nih.gov/36559039/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/ph15121588", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36559039/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "5-HT3 Receptor Antagonist", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "3–6 hours", "onsetOfAction": "30 minutes (oral); immediate (IV)", "commonBrandNames": [ "Zofran", "Zofran ODT" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "ondansetron" }, { "id": "RX-GIPAIN-014", "name": "Metoclopramide", "alternateNames": [ "Reglan" ], "category": "Prescription", "subcategory": "Prokinetic Antiemetic", "overview": "A dopamine D2 receptor antagonist and prokinetic agent used for the treatment of GERD, diabetic gastroparesis, and prevention of nausea and vomiting associated with chemotherapy and surgery. 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At higher doses, it also antagonizes 5-HT3 receptors.", "commonBenefits": [ "Acceleration of gastric emptying in gastroparesis", "Relief of GERD symptoms", "Prevention of chemotherapy-induced nausea", "Prevention of postoperative nausea and vomiting" ], "commonDosageRange": "5–10 mg three to four times daily, 30 minutes before meals; maximum 12 weeks of use recommended (as prescribed by your physician)", "recommendedForm": "Tablet, oral solution, or IV/IM injection", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Take 30 minutes before meals and at bedtime for gastroparesis" }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Drowsiness and fatigue", "Restlessness and akathisia", "Tardive dyskinesia (with prolonged use)", "Extrapyramidal symptoms (dystonia, parkinsonism)", "Diarrhea", "Hyperprolactinemia (galactorrhea, gynecomastia, amenorrhea)", "Depression" ], "contraindications": [ "Known hypersensitivity to metoclopramide", "GI obstruction, perforation, or hemorrhage", "Pheochromocytoma (may cause hypertensive crisis)", "Seizure disorder (lowers seizure threshold)", "Concurrent use with other drugs likely to cause extrapyramidal reactions", "History of tardive dyskinesia" ], "iconName": "cross.case.fill", "colorHex": "7986CB", "tags": [ "gi", "antiemetic", "prokinetic", "gastroparesis", "nausea" ], "sources": [ { "text": "Rao AS, Camilleri M. Review article: metoclopramide and tardive dyskinesia. Aliment Pharmacol Ther. 2010.", "pmid": "19886950", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19886950/", "publicSourceType": "PMID" }, { "text": "Parkman HP et al. Effect of nightly metoclopramide on gastroparesis symptoms. Am J Gastroenterol. 2013.", "pmid": "24192909", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24192909/", "publicSourceType": "PMID" }, { "text": "Onodera R et al. Extrapyramidal symptoms and effectiveness of continuous vs bolus intravenous metoclopramide: A systematic review and meta-analysis. Am J Emerg Med. 2026.", "pmid": "41650757", "doi": "10.1016/j.ajem.2026.01.051", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41650757/", "publicSourceType": "PMID" }, { "text": "Abdelmonem H, Abdelhay HM, Abdelwadoud GT et al.. The efficacy and safety of metoclopramide in relieving acute migraine attacks compared with other anti-migraine drugs: a systematic review and network meta-analysis of randomized controlled trials. BMC neurology. 2023", "claim": "PubMed-indexed evidence involving Metoclopramide", "title": "The efficacy and safety of metoclopramide in relieving acute migraine attacks compared with other anti-migraine drugs: a systematic review and network meta-analysis of randomized controlled trials", "authors": "Abdelmonem H, Abdelhay HM, Abdelwadoud GT et al.", "journal": "BMC neurology", "year": 2023, "pmid": "37291500", "url": "https://pubmed.ncbi.nlm.nih.gov/37291500/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12883-023-03259-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37291500/", "publicSourceType": "PMID" }, { "text": "Si S, Zhao G, Song G et al.. Efficacy and safety of domperidone and metoclopramide on human milk production in postpartum mothers: a bayesian network meta-analysis of randomized controlled trials. BMC pregnancy and childbirth. 2024", "claim": "PubMed-indexed evidence involving Metoclopramide", "title": "Efficacy and safety of domperidone and metoclopramide on human milk production in postpartum mothers: a bayesian network meta-analysis of randomized controlled trials", "authors": "Si S, Zhao G, Song G et al.", "journal": "BMC pregnancy and childbirth", "year": 2024, "pmid": "39695450", "url": "https://pubmed.ncbi.nlm.nih.gov/39695450/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12884-024-07027-4", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39695450/", "publicSourceType": "PMID" }, { "text": "Junqueira DR, Bennett D, Huh SY et al.. Risk of Adverse Events Associated with Domperidone and Metoclopramide in Gastroparesis: Systematic Review and Meta-analysis. Drugs in R&D. 2023", "claim": "PubMed-indexed evidence involving Metoclopramide", "title": "Risk of Adverse Events Associated with Domperidone and Metoclopramide in Gastroparesis: Systematic Review and Meta-analysis", "authors": "Junqueira DR, Bennett D, Huh SY et al.", "journal": "Drugs in R&D", "year": 2023, "pmid": "36749528", "url": "https://pubmed.ncbi.nlm.nih.gov/36749528/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s40268-023-00413-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36749528/", "publicSourceType": "PMID" }, { "text": "Shen Q, Khan KS, Du MC et al.. Efficacy and Safety of Domperidone and Metoclopramide in Breastfeeding: A Systematic Review and Meta-Analysis. Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine. 2021", "claim": "PubMed-indexed evidence involving Metoclopramide", "title": "Efficacy and Safety of Domperidone and Metoclopramide in Breastfeeding: A Systematic Review and Meta-Analysis", "authors": "Shen Q, Khan KS, Du MC et al.", "journal": "Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine", "year": 2021, "pmid": "33769844", "url": "https://pubmed.ncbi.nlm.nih.gov/33769844/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1089/bfm.2020.0360", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33769844/", "publicSourceType": "PMID" }, { "text": "Lau Moon Lin M, Robinson PD, Flank J et al.. The Safety of Metoclopramide in Children: A Systematic Review and Meta-Analysis. Drug safety. 2016", "claim": "PubMed-indexed evidence involving Metoclopramide", "title": "The Safety of Metoclopramide in Children: A Systematic Review and Meta-Analysis", "authors": "Lau Moon Lin M, Robinson PD, Flank J et al.", "journal": "Drug safety", "year": 2016, "pmid": "27003816", "url": "https://pubmed.ncbi.nlm.nih.gov/27003816/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s40264-016-0418-9", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27003816/", "publicSourceType": "PMID" }, { "text": "Song Q, Yang H, Yang X. Intravenous ketorolac versus metoclopramide in adult patients with migraine headaches: An updated systematic review and meta-analysis. Advances in clinical and experimental medicine : official organ Wroclaw Medical University. 2024", "claim": "PubMed-indexed evidence involving Metoclopramide", "title": "Intravenous ketorolac versus metoclopramide in adult patients with migraine headaches: An updated systematic review and meta-analysis", "authors": "Song Q, Yang H, Yang X", "journal": "Advances in clinical and experimental medicine : official organ Wroclaw Medical University", "year": 2024, "pmid": "37849443", "url": "https://pubmed.ncbi.nlm.nih.gov/37849443/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.17219/acem/171697", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37849443/", "publicSourceType": "PMID" }, { "text": "Ai M, Cai Y, Zeng Y et al.. Efficacy of acupoint injection of metoclopramide for post-chemotherapy vomiting: A systematic review and meta-analysis. Medicine. 2024", "claim": "PubMed-indexed evidence involving Metoclopramide", "title": "Efficacy of acupoint injection of metoclopramide for post-chemotherapy vomiting: A systematic review and meta-analysis", "authors": "Ai M, Cai Y, Zeng Y et al.", "journal": "Medicine", "year": 2024, "pmid": "38579100", "url": "https://pubmed.ncbi.nlm.nih.gov/38579100/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MD.0000000000037569", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38579100/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Dopamine D2 Antagonist / Prokinetic", "blackBoxWarnings": [ "Can cause tardive dyskinesia, a serious movement disorder that is often irreversible. Risk increases with duration of treatment and total cumulative dose. Discontinue if signs or symptoms of tardive dyskinesia appear. Treatment beyond 12 weeks should be avoided in all but rare cases." ], "fdaPregnancyCategory": "B", "halfLife": "5–6 hours", "onsetOfAction": "30–60 minutes (oral); 1–3 minutes (IV)", "commonBrandNames": [ "Reglan", "Metozolv ODT" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "metoclopramide" }, { "id": "RX-GIPAIN-015", "name": "Promethazine", "alternateNames": [ "Phenergan" ], "category": "Prescription", "subcategory": "Antiemetic (Phenothiazine)", "overview": "A first-generation phenothiazine antihistamine with antiemetic, sedative, and anticholinergic properties. Promethazine is used for prevention and treatment of nausea and vomiting from various causes, motion sickness, allergic conditions, and as a pre- and postoperative sedative adjunct.", "mechanismOfAction": "Blocks histamine H1 receptors (antihistaminic and antiemetic activity), dopamine receptors in the chemoreceptor trigger zone (antiemetic activity), and muscarinic cholinergic receptors (anticholinergic and anti-motion-sickness activity). 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Fourth Consensus Guidelines for the Management of Postoperative Nausea and Vomiting. Anesth Analg. 2020.", "pmid": "32467512", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32467512/", "publicSourceType": "PMID" }, { "text": "Starke PR et al. FDA revision of promethazine labeling, changes and post-marketing safety events. J Clin Pharmacol. 2006.", "pmid": "19796155", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19796155/", "publicSourceType": "PMID" }, { "text": "deSouza IS et al. Efficacy and Safety of Pharmacologic Therapies for Nausea and Emesis in the Emergency Department: A Systematic Review and Bayesian Network Meta-analysis. Ann Emerg Med. 2025.", "pmid": "40772912", "doi": "10.1016/j.annemergmed.2025.06.009", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40772912/", "publicSourceType": "PMID" }, { "text": "Miuli A, Stigliano G, Lalli A et al.. \"Purple Drank\" (Codeine and Promethazine Cough Syrup): A Systematic Review of a Social Phenomenon with Medical Implications. Journal of psychoactive drugs. 2020", "claim": "PubMed-indexed evidence involving Promethazine", "title": "\"Purple Drank\" (Codeine and Promethazine Cough Syrup): A Systematic Review of a Social Phenomenon with Medical Implications", "authors": "Miuli A, Stigliano G, Lalli A et al.", "journal": "Journal of psychoactive drugs", "year": 2020, "pmid": "32748711", "url": "https://pubmed.ncbi.nlm.nih.gov/32748711/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/02791072.2020.1797250", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32748711/", "publicSourceType": "PMID" }, { "text": "Huf G, Coutinho ES, Adams CE. [Haloperidol plus promethazine for agitated patients--a systematic review]. Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999). 2009", "claim": "PubMed-indexed evidence involving Promethazine", "title": "[Haloperidol plus promethazine for agitated patients--a systematic review]", "authors": "Huf G, Coutinho ES, Adams CE", "journal": "Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999)", "year": 2009, "pmid": "19784494", "url": "https://pubmed.ncbi.nlm.nih.gov/19784494/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1590/s1516-44462009000300014", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19784494/", "publicSourceType": "PMID" }, { "text": "Le CK, Stevens CA, Park JH et al.. Promethazine: A Review of Therapeutic Uses and Toxicity. The Journal of emergency medicine. 2025", "claim": "PubMed-indexed evidence involving Promethazine", "title": "Promethazine: A Review of Therapeutic Uses and Toxicity", "authors": "Le CK, Stevens CA, Park JH et al.", "journal": "The Journal of emergency medicine", "year": 2025, "pmid": "39947973", "url": "https://pubmed.ncbi.nlm.nih.gov/39947973/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.jemermed.2024.09.013", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39947973/", "publicSourceType": "PMID" }, { "text": "Ruijuan L, Jiqiang Z, Ruirui B et al.. Promethazine for nausea and vomiting prevention after gynaecological laparoscopic surgery: A randomized controlled trial. 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Journal of clinical gastroenterology. 2025", "claim": "PubMed-indexed evidence involving Mesalamine", "title": "Budesonide Versus Mesalamine in Microscopic Colitis: A Comparative Meta-analysis of Randomized Controlled Trials", "authors": "Malik A, Goyal H, Adler DG et al.", "journal": "Journal of clinical gastroenterology", "year": 2025, "pmid": "39042479", "url": "https://pubmed.ncbi.nlm.nih.gov/39042479/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MCG.0000000000002025", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39042479/", "publicSourceType": "PMID" }, { "text": "Paridaens K, Fullarton JR, Travis SPL. Efficacy and safety of oral Pentasa (prolonged-release mesalazine) in mild-to-moderate ulcerative colitis: a systematic review and meta-analysis. Current medical research and opinion. 2021", "claim": "PubMed-indexed evidence involving Mesalamine", "title": "Efficacy and safety of oral Pentasa (prolonged-release mesalazine) in mild-to-moderate ulcerative colitis: a systematic review and meta-analysis", "authors": "Paridaens K, Fullarton JR, Travis SPL", "journal": "Current medical research and opinion", "year": 2021, "pmid": "34404286", "url": "https://pubmed.ncbi.nlm.nih.gov/34404286/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/03007995.2021.1968813", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34404286/", "publicSourceType": "PMID" }, { "text": "Sehgal P, Colombel JF, Aboubakr A et al.. Systematic review: safety of mesalazine in ulcerative colitis. Alimentary pharmacology & therapeutics. 2018", "claim": "PubMed-indexed evidence involving Mesalamine", "title": "Systematic review: safety of mesalazine in ulcerative colitis", "authors": "Sehgal P, Colombel JF, Aboubakr A et al.", "journal": "Alimentary pharmacology & therapeutics", "year": 2018, "pmid": "29722441", "url": "https://pubmed.ncbi.nlm.nih.gov/29722441/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/apt.14688", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29722441/", "publicSourceType": "PMID" }, { "text": "Hanauer SB, Strömberg U. Oral Pentasa in the treatment of active Crohn's disease: A meta-analysis of double-blind, placebo-controlled trials. 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EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020.", "pmid": "31969328", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31969328/", "publicSourceType": "PMID" }, { "text": "Ford AC et al. Efficacy of 5-aminosalicylates in ulcerative colitis: systematic review and meta-analysis. Am J Gastroenterol. 2011.", "pmid": "33433562", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33433562/", "publicSourceType": "PMID" }, { "text": "Plosker GL, Croom KF. Sulfasalazine: a review of its use in the management of rheumatoid arthritis. Drugs. 2005.", "pmid": "16114981", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16114981/", "publicSourceType": "PMID" }, { "text": "Choi J, Patel P, Fenando A. Sulfasalazine. 2026", "pmid": "32491741", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32491741/", "publicSourceType": "PMID" }, { "text": "Asthana R, Hamandi B, Brnabic A et al.. Meta-analysis and systematic review on Sulfasalazine/5-ASA use during pregnancy: Impact on neonatal and pregnancy outcomes. Reproductive toxicology (Elmsford, N.Y.). 2025", "claim": "PubMed-indexed evidence involving Sulfasalazine", "title": "Meta-analysis and systematic review on Sulfasalazine/5-ASA use during pregnancy: Impact on neonatal and pregnancy outcomes", "authors": "Asthana R, Hamandi B, Brnabic A et al.", "journal": "Reproductive toxicology (Elmsford, N.Y.)", "year": 2025, "pmid": "40334871", "url": "https://pubmed.ncbi.nlm.nih.gov/40334871/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.reprotox.2025.108939", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40334871/", "publicSourceType": "PMID" }, { "text": "Steinhart AH, Hemphill D, Greenberg GR. Sulfasalazine and mesalazine for the maintenance therapy of Crohn's disease: a meta-analysis. The American journal of gastroenterology. 1994", "claim": "PubMed-indexed evidence involving Sulfasalazine", "title": "Sulfasalazine and mesalazine for the maintenance therapy of Crohn's disease: a meta-analysis", "authors": "Steinhart AH, Hemphill D, Greenberg GR", "journal": "The American journal of gastroenterology", "year": 1994, "pmid": "7977225", "url": "https://pubmed.ncbi.nlm.nih.gov/7977225/", "study_type": "meta-analysis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7977225/", "publicSourceType": "PMID" }, { "text": "Sutherland LR, May GR, Shaffer EA. Sulfasalazine revisited: a meta-analysis of 5-aminosalicylic acid in the treatment of ulcerative colitis. Annals of internal medicine. 1993", "claim": "PubMed-indexed evidence involving Sulfasalazine", "title": "Sulfasalazine revisited: a meta-analysis of 5-aminosalicylic acid in the treatment of ulcerative colitis", "authors": "Sutherland LR, May GR, Shaffer EA", "journal": "Annals of internal medicine", "year": 1993, "pmid": "8095128", "url": "https://pubmed.ncbi.nlm.nih.gov/8095128/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7326/0003-4819-118-7-199304010-00009", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8095128/", "publicSourceType": "PMID" }, { "text": "Ferraz MB, Tugwell P, Goldsmith CH et al.. Meta-analysis of sulfasalazine in ankylosing spondylitis. The Journal of rheumatology. 1990", "claim": "PubMed-indexed evidence involving Sulfasalazine", "title": "Meta-analysis of sulfasalazine in ankylosing spondylitis", "authors": "Ferraz MB, Tugwell P, Goldsmith CH et al.", "journal": "The Journal of rheumatology", "year": 1990, "pmid": "1980310", "url": "https://pubmed.ncbi.nlm.nih.gov/1980310/", "study_type": "meta-analysis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1980310/", "publicSourceType": "PMID" }, { "text": "Guo D, Tang B, Luo P et al.. A real-world pharmacovigilance study and pharmacological analysis of sulfasalazine based on the FDA adverse event reporting system (FAERS) database. Expert opinion on drug safety. 2025", "claim": "PubMed-indexed evidence involving Sulfasalazine", "title": "A real-world pharmacovigilance study and pharmacological analysis of sulfasalazine based on the FDA adverse event reporting system (FAERS) database", "authors": "Guo D, Tang B, Luo P et al.", "journal": "Expert opinion on drug safety", "year": 2025, "pmid": "40222949", "url": "https://pubmed.ncbi.nlm.nih.gov/40222949/", "study_type": "review", "confidence": "verify", "doi": "10.1080/14740338.2025.2488241", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40222949/", "publicSourceType": "PMID" }, { "text": "Ye W, Ding Y, Li M et al.. Safety assessment of sulfasalazine: a pharmacovigilance study based on FAERS database. Frontiers in pharmacology. 2024", "claim": "PubMed-indexed evidence involving Sulfasalazine", "title": "Safety assessment of sulfasalazine: a pharmacovigilance study based on FAERS database", "authors": "Ye W, Ding Y, Li M et al.", "journal": "Frontiers in pharmacology", "year": 2024, "pmid": "39329122", "url": "https://pubmed.ncbi.nlm.nih.gov/39329122/", "study_type": "review", "confidence": "verify", "doi": "10.3389/fphar.2024.1452300", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39329122/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Aminosalicylate / DMARD", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "5–10 hours (sulfapyridine metabolite)", "onsetOfAction": "1–3 months for full benefit in RA; 2–4 weeks for UC", "commonBrandNames": [ "Azulfidine", "Azulfidine EN-tabs" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "CBC every 2–4 weeks initially, then every 3 months; LFTs periodically; renal function monitoring" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "sulfasalazine" }, { "id": "RX-GIPAIN-018", "name": "Ibuprofen", "alternateNames": [ "Advil", "Motrin" ], "category": "Prescription", "subcategory": "Nonsteroidal Anti-Inflammatory Drug (NSAID)", "overview": "A widely used nonselective NSAID with analgesic, anti-inflammatory, and antipyretic properties. 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Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013.", "pmid": "23726390", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23726390/", "publicSourceType": "PMID" }, { "text": "Derry S et al. Single dose oral ibuprofen plus caffeine for acute postoperative pain in adults. Cochrane Database Syst Rev. 2015.", "pmid": "26171993", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26171993/", "publicSourceType": "PMID" }, { "text": "Rainsford KD. Ibuprofen: pharmacology, efficacy and safety. Inflammopharmacology. 2009.", "pmid": "32797326", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32797326/", "publicSourceType": "PMID" }, { "text": "Tan E, Braithwaite I, McKinlay CJD et al.. Comparison of Acetaminophen (Paracetamol) With Ibuprofen for Treatment of Fever or Pain in Children Younger Than 2 Years: A Systematic Review and Meta-analysis. JAMA network open. 2020", "pmid": "33125495", "doi": "10.1001/jamanetworkopen.2020.22398", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33125495/", "publicSourceType": "PMID" }, { "text": "De la Cruz-Mena JE, Veroniki AA, Acosta-Reyes J et al.. Short-term Dual Therapy or Mono Therapy With Acetaminophen and Ibuprofen for Fever: A Network Meta-Analysis. Pediatrics. 2024", "pmid": "39318339", "doi": "10.1542/peds.2023-065390", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39318339/", "publicSourceType": "PMID" }, { "claim": "Ibuprofen provides effective postoperative pain relief after dental extraction", "title": "Acute Postoperative Pain Due to Dental Extraction in the Adult Population: A Systematic Review and Network Meta-analysis.", "authors": "Miroshnychenko A, Ibrahim S, Azab M et al.", "journal": "Journal of Dental Research", "year": 2023, "pmid": "36631957", "url": "https://pubmed.ncbi.nlm.nih.gov/36631957/", "study_type": "network meta-analysis", "key_finding": "Network meta-analysis found ibuprofen (400 mg) among the most effective oral analgesics for post-dental extraction pain, providing superior pain relief compared to acetaminophen and comparable to combination NSAID regimens.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36631957/", "publicSourceType": "PMID" }, { "text": "Mitra S, Florez ID, Tamayo ME et al.. Association of Placebo, Indomethacin, Ibuprofen, and Acetaminophen With Closure of Hemodynamically Significant Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-analysis. JAMA. 2018", "claim": "PubMed-indexed evidence involving Ibuprofen", "title": "Association of Placebo, Indomethacin, Ibuprofen, and Acetaminophen With Closure of Hemodynamically Significant Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-analysis", "authors": "Mitra S, Florez ID, Tamayo ME et al.", "journal": "JAMA", "year": 2018, "pmid": "29584842", "url": "https://pubmed.ncbi.nlm.nih.gov/29584842/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1001/jama.2018.1896", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29584842/", "publicSourceType": "PMID" }, { "text": "Kim DH, Stybayeva G, Hwang SH. Effect and safety of perioperative ibuprofen administration in pediatric tonsillectomy: A systematic review and meta-analysis. American journal of otolaryngology. 2024", "claim": "PubMed-indexed evidence involving Ibuprofen", "title": "Effect and safety of perioperative ibuprofen administration in pediatric tonsillectomy: A systematic review and meta-analysis", "authors": "Kim DH, Stybayeva G, Hwang SH", "journal": "American journal of otolaryngology", "year": 2024, "pmid": "39098128", "url": "https://pubmed.ncbi.nlm.nih.gov/39098128/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.amjoto.2024.104461", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39098128/", "publicSourceType": "PMID" }, { "text": "da Silva HDS, Franco ES, Lima LCAS et al.. Therapeutic Efficacy and Safety of Paracetamol versus Ibuprofen in Patent Ductus Arteriosus in Newborns: A Systematic Review. Arquivos brasileiros de cardiologia. 2024", "claim": "PubMed-indexed evidence involving Ibuprofen", "title": "Therapeutic Efficacy and Safety of Paracetamol versus Ibuprofen in Patent Ductus Arteriosus in Newborns: A Systematic Review", "authors": "da Silva HDS, Franco ES, Lima LCAS et al.", "journal": "Arquivos brasileiros de cardiologia", "year": 2024, "pmid": "39661802", "url": "https://pubmed.ncbi.nlm.nih.gov/39661802/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.36660/abc.20240058", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39661802/", "publicSourceType": "PMID" }, { "text": "Shamsaee E, Huws A, Gill A et al.. Ibuprofen efficacy, tolerability and safety in obese children: a systematic review. Archives of disease in childhood. 2023", "claim": "PubMed-indexed evidence involving Ibuprofen", "title": "Ibuprofen efficacy, tolerability and safety in obese children: a systematic review", "authors": "Shamsaee E, Huws A, Gill A et al.", "journal": "Archives of disease in childhood", "year": 2023, "pmid": "36385006", "url": "https://pubmed.ncbi.nlm.nih.gov/36385006/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1136/archdischild-2022-324652", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36385006/", "publicSourceType": "PMID" }, { "text": "Pankey AN, Chandar A, Isaacson G. Safety of Ibuprofen in Children With G6PD Deficiency: A Systematic Review. The Laryngoscope. 2022", "claim": "PubMed-indexed evidence involving Ibuprofen", "title": "Safety of Ibuprofen in Children With G6PD Deficiency: A Systematic Review", "authors": "Pankey AN, Chandar A, Isaacson G", "journal": "The Laryngoscope", "year": 2022, "pmid": "34546579", "url": "https://pubmed.ncbi.nlm.nih.gov/34546579/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/lary.29868", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34546579/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Nonsteroidal Anti-Inflammatory Drug (NSAID)", "blackBoxWarnings": [ "Increased risk of serious cardiovascular thrombotic events, MI, and stroke; increased risk of serious GI adverse events including bleeding, ulceration, and perforation" ], "fdaPregnancyCategory": "C (D in third trimester)", "halfLife": "2–4 hours", "onsetOfAction": "30–60 minutes", "commonBrandNames": [ "Advil", "Motrin", "Motrin IB" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "ibuprofen" }, { "id": "RX-GIPAIN-019", "name": "Naproxen", "alternateNames": [ "Aleve", "Naprosyn" ], "category": "Prescription", "subcategory": "Nonsteroidal Anti-Inflammatory Drug (NSAID)", "overview": "A long-acting nonselective NSAID with analgesic, anti-inflammatory, and antipyretic properties. 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Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013.", "pmid": "23726390", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23726390/", "publicSourceType": "PMID" }, { "text": "Derry S et al. Naproxen with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev. 2013.", "pmid": "41100185", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41100185/", "publicSourceType": "PMID" }, { "text": "McGettigan P, Henry D. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies. PLoS Med. 2011.", "pmid": "23424288", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23424288/", "publicSourceType": "PMID" }, { "text": "Zhang H, Wu Y, Lin Z et al.. Naproxen for the treatment of neoplastic fever: A PRISMA-compliant systematic review and meta-analysis. Medicine. 2019", "pmid": "31145329", "doi": "10.1097/MD.0000000000015840", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31145329/", "publicSourceType": "PMID" }, { "text": "Wilcha RJ, Afridi SK, Barbanti P et al.. Sumatriptan-naproxen sodium in migraine: A review. European journal of neurology. 2024", "pmid": "39318200", "doi": "10.1111/ene.16434", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39318200/", "publicSourceType": "PMID" }, { "claim": "Naproxen has a favorable upper GI safety profile among NSAIDs", "title": "Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project).", "authors": "Castellsague J, Riera-Guardia N, Calingaert B et al.", "journal": "Drug Safety", "year": 2012, "pmid": "23137151", "url": "https://pubmed.ncbi.nlm.nih.gov/23137151/", "study_type": "meta-analysis", "key_finding": "Systematic review of observational studies found naproxen had a relatively lower risk of upper gastrointestinal complications compared to other NSAIDs like ketorolac and piroxicam, though risk was still elevated vs non-use.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23137151/", "publicSourceType": "PMID" }, { "text": "Suthisisang CC, Poolsup N, Suksomboon N et al.. Meta-analysis of the efficacy and safety of naproxen sodium in the acute treatment of migraine. Headache. 2010", "claim": "PubMed-indexed evidence involving Naproxen", "title": "Meta-analysis of the efficacy and safety of naproxen sodium in the acute treatment of migraine", "authors": "Suthisisang CC, Poolsup N, Suksomboon N et al.", "journal": "Headache", "year": 2010, "pmid": "20236345", "url": "https://pubmed.ncbi.nlm.nih.gov/20236345/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/j.1526-4610.2010.01635.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20236345/", "publicSourceType": "PMID" }, { "text": "Bansal V, Dex T, Proskin H et al.. A look at the safety profile of over-the-counter naproxen sodium: a meta-analysis. Journal of clinical pharmacology. 2001", "claim": "PubMed-indexed evidence involving Naproxen", "title": "A look at the safety profile of over-the-counter naproxen sodium: a meta-analysis", "authors": "Bansal V, Dex T, Proskin H et al.", "journal": "Journal of clinical pharmacology", "year": 2001, "pmid": "11210392", "url": "https://pubmed.ncbi.nlm.nih.gov/11210392/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/00912700122009935", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11210392/", "publicSourceType": "PMID" }, { "text": "Zhang AH, Chen X, Zhao QX et al.. A systematic review and meta-analysis of naproxen for prevention heterotopic ossification after hip surgery. Medicine. 2019", "claim": "PubMed-indexed evidence involving Naproxen", "title": "A systematic review and meta-analysis of naproxen for prevention heterotopic ossification after hip surgery", "authors": "Zhang AH, Chen X, Zhao QX et al.", "journal": "Medicine", "year": 2019, "pmid": "30946309", "url": "https://pubmed.ncbi.nlm.nih.gov/30946309/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MD.0000000000014607", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30946309/", "publicSourceType": "PMID" }, { "text": "Ma R, Chen GH, Zhao LJ et al.. Efficacy of naproxen prophylaxis for the prevention of heterotopic ossification after hip surgery: a meta-analysis. Journal of orthopaedic surgery and research. 2018", "claim": "PubMed-indexed evidence involving Naproxen", "title": "Efficacy of naproxen prophylaxis for the prevention of heterotopic ossification after hip surgery: a meta-analysis", "authors": "Ma R, Chen GH, Zhao LJ et al.", "journal": "Journal of orthopaedic surgery and research", "year": 2018, "pmid": "29506541", "url": "https://pubmed.ncbi.nlm.nih.gov/29506541/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s13018-018-0747-8", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29506541/", "publicSourceType": "PMID" }, { "text": "Shamabadi A, Motavalian Z, Farahmand Y et al.. Naproxen adjunct to fluoxetine for moderate-to-severe obsessive-compulsive disorder: A randomized, double-blind, placebo-controlled trial. Psychiatry and clinical neurosciences. 2024", "claim": "PubMed-indexed evidence involving Naproxen", "title": "Naproxen adjunct to fluoxetine for moderate-to-severe obsessive-compulsive disorder: A randomized, double-blind, placebo-controlled trial", "authors": "Shamabadi A, Motavalian Z, Farahmand Y et al.", "journal": "Psychiatry and clinical neurosciences", "year": 2024, "pmid": "39354696", "url": "https://pubmed.ncbi.nlm.nih.gov/39354696/", "study_type": "RCT", "confidence": "verify", "doi": "10.1111/pcn.13748", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39354696/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Nonsteroidal Anti-Inflammatory Drug (NSAID)", "blackBoxWarnings": [ "Increased risk of serious cardiovascular thrombotic events, MI, and stroke; increased risk of serious GI adverse events including bleeding, ulceration, and perforation" ], "fdaPregnancyCategory": "C (D in third trimester)", "halfLife": "12–17 hours", "onsetOfAction": "1–2 hours", "commonBrandNames": [ "Aleve", "Naprosyn", "Anaprox" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "naproxen" }, { "id": "RX-GIPAIN-020", "name": "Meloxicam", "alternateNames": [ "Mobic" ], "category": "Prescription", "subcategory": "Nonsteroidal Anti-Inflammatory Drug (NSAID)", "overview": "A preferential COX-2 inhibiting NSAID with a long half-life allowing once-daily dosing, used primarily for the treatment of osteoarthritis and rheumatoid arthritis. 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Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013.", "pmid": "23726390", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23726390/", "publicSourceType": "PMID" }, { "text": "Noble S et al. Meloxicam. Drugs. 1996.", "pmid": "8651376", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8651376/", "publicSourceType": "PMID" }, { "text": "Xie L et al. Prophylactic effects of non-steroidal anti-inflammatory drugs on heterotopic ossification after total hip arthroplasty: a Bayesian network meta-analysis of randomized controlled trials using cumulative logistic regression. BMC Musculoskelet Disord. 2025.", "pmid": "41225475", "doi": "10.1186/s12891-025-09277-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41225475/", "publicSourceType": "PMID" }, { "text": "Shavlovskaya OA, Bokova IA, Shavlovskiy NI. [Meloxicam clinical effects]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 2022", "pmid": "35175701", "doi": "10.17116/jnevro202212201136", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35175701/", "publicSourceType": "PMID" }, { "text": "Ranieri MM, Bradley EF, Simon AB. Meloxicam-induced thrombocytopenia. Pharmacotherapy. 2014", "pmid": "24214337", "doi": "10.1002/phar.1372", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24214337/", "publicSourceType": "PMID" }, { "claim": "Meloxicam provides effective perioperative pain control in orthopedic surgery", "title": "Early perioperative versus postoperative meloxicam for pain control in patients undergoing orthopedic surgery: a systematic review and Meta-analysis of randomized controlled trials.", "authors": "Mahmoud A, Abuelazm M, Ahmed ASA et al.", "journal": "Current Medical Research and Opinion", "year": 2023, "pmid": "36245362", "url": "https://pubmed.ncbi.nlm.nih.gov/36245362/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of RCTs found perioperative meloxicam significantly reduced postoperative pain scores and opioid consumption compared to postoperative administration alone in orthopedic surgery patients.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36245362/", "publicSourceType": "PMID" }, { "claim": "Meloxicam has lower gastrointestinal risk among NSAIDs", "title": "Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project).", "authors": "Castellsague J, Riera-Guardia N, Calingaert B et al.", "journal": "Drug Safety", "year": 2012, "pmid": "23137151", "url": "https://pubmed.ncbi.nlm.nih.gov/23137151/", "study_type": "meta-analysis", "key_finding": "Meloxicam showed a relatively lower risk of upper gastrointestinal complications compared to non-selective NSAIDs, consistent with its COX-2 preferential selectivity, though GI risk remained dose-dependent.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23137151/", "publicSourceType": "PMID" }, { "text": "Schoenfeld P. Gastrointestinal safety profile of meloxicam: a meta-analysis and systematic review of randomized controlled trials. The American journal of medicine. 1999", "claim": "PubMed-indexed evidence involving Meloxicam", "title": "Gastrointestinal safety profile of meloxicam: a meta-analysis and systematic review of randomized controlled trials", "authors": "Schoenfeld P", "journal": "The American journal of medicine", "year": 1999, "pmid": "10628593", "url": "https://pubmed.ncbi.nlm.nih.gov/10628593/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/s0002-9343(99)00367-8", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10628593/", "publicSourceType": "PMID" }, { "text": "Zhou Y, Jiang Y, Duan K et al.. Efficacy and safety of 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1, 2-benzothiazin-3-carboxamide 1,1-dioxide, a rapid-acting meloxicam formulation, for analgesia after orthopaedic surgery under general anaesthesia: a randomized controlled trial. Inflammopharmacology. 2024", "claim": "PubMed-indexed evidence involving Meloxicam", "title": "Efficacy and safety of 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1, 2-benzothiazin-3-carboxamide 1,1-dioxide, a rapid-acting meloxicam formulation, for analgesia after orthopaedic surgery under general anaesthesia: a randomized controlled trial", "authors": "Zhou Y, Jiang Y, Duan K et al.", "journal": "Inflammopharmacology", "year": 2024, "pmid": "39397127", "url": "https://pubmed.ncbi.nlm.nih.gov/39397127/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/s10787-024-01575-z", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39397127/", "publicSourceType": "PMID" }, { "text": "Liu X, Zhao Y, Yang M et al.. Efficacy and safety of 4-hydroxy 2-methyl-N-(5-methyl-2-thiazolyl)-2H-1, 2-benzothiazin-3-carboxamide 1,1-dioxide, a fast-acting meloxicam formulation, on moderate-to-severe pain following abdominal surgery: A phase III randomized controlled trial. Clinical and translational science. 2024", "claim": "PubMed-indexed evidence involving Meloxicam", "title": "Efficacy and safety of 4-hydroxy 2-methyl-N-(5-methyl-2-thiazolyl)-2H-1, 2-benzothiazin-3-carboxamide 1,1-dioxide, a fast-acting meloxicam formulation, on moderate-to-severe pain following abdominal surgery: A phase III randomized controlled trial", "authors": "Liu X, Zhao Y, Yang M et al.", "journal": "Clinical and translational science", "year": 2024, "pmid": "39660482", "url": "https://pubmed.ncbi.nlm.nih.gov/39660482/", "study_type": "RCT", "confidence": "verify", "doi": "10.1111/cts.70081", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39660482/", "publicSourceType": "PMID" }, { "text": "Asghar W, Jamali F. The effect of COX-2-selective meloxicam on the myocardial, vascular and renal risks: a systematic review. Inflammopharmacology. 2015", "claim": "PubMed-indexed evidence involving Meloxicam", "title": "The effect of COX-2-selective meloxicam on the myocardial, vascular and renal risks: a systematic review", "authors": "Asghar W, Jamali F", "journal": "Inflammopharmacology", "year": 2015, "pmid": "25515365", "url": "https://pubmed.ncbi.nlm.nih.gov/25515365/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s10787-014-0225-9", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25515365/", "publicSourceType": "PMID" }, { "text": "Yu J, Wang Y, Wu Y et al.. Pharmacokinetics of Meloxicam Tablets in Healthy Chinese Adults in the Fasting and Fed States: A Single-Site, Single-Dose, Randomized, Open, 2-Period, 2-Sequence, Crossover Bioequivalence Study. 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JAMA. 2000.", "pmid": "10979111", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10979111/", "publicSourceType": "PMID" }, { "text": "Xu C, Gu K, Yasen Y et al.. Efficacy and Safety of Celecoxib Therapy in Osteoarthritis: A Meta-Analysis of Randomized Controlled Trials. Medicine. 2016", "claim": "PubMed-indexed evidence involving Celecoxib", "title": "Efficacy and Safety of Celecoxib Therapy in Osteoarthritis: A Meta-Analysis of Randomized Controlled Trials", "authors": "Xu C, Gu K, Yasen Y et al.", "journal": "Medicine", "year": 2016, "pmid": "27196460", "url": "https://pubmed.ncbi.nlm.nih.gov/27196460/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MD.0000000000003585", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27196460/", "publicSourceType": "PMID" }, { "text": "Gędek A, Szular Z, Antosik AZ et al.. Celecoxib for Mood Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Journal of clinical medicine. 2023", "claim": "PubMed-indexed evidence involving Celecoxib", "title": "Celecoxib for Mood Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Gędek A, Szular Z, Antosik AZ et al.", "journal": "Journal of clinical medicine", "year": 2023, "pmid": "37240605", "url": "https://pubmed.ncbi.nlm.nih.gov/37240605/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/jcm12103497", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37240605/", "publicSourceType": "PMID" }, { "text": "Beaudart C, Brabant C, Alokail M et al.. Current Evidence on Celecoxib Safety in the Management of Chronic Musculoskeletal Conditions: An Umbrella Review. Drugs. 2025", "claim": "PubMed-indexed evidence involving Celecoxib", "title": "Current Evidence on Celecoxib Safety in the Management of Chronic Musculoskeletal Conditions: An Umbrella Review", "authors": "Beaudart C, Brabant C, Alokail M et al.", "journal": "Drugs", "year": 2025, "pmid": "40911151", "url": "https://pubmed.ncbi.nlm.nih.gov/40911151/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s40265-025-02234-5", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40911151/", "publicSourceType": "PMID" }, { "text": "Wan R, Li P, Jiang H. The efficacy of celecoxib for pain management of arthroscopy: A meta-analysis of randomized controlled trials. Medicine. 2019", "claim": "PubMed-indexed evidence involving Celecoxib", "title": "The efficacy of celecoxib for pain management of arthroscopy: A meta-analysis of randomized controlled trials", "authors": "Wan R, Li P, Jiang H", "journal": "Medicine", "year": 2019, "pmid": "31804304", "url": "https://pubmed.ncbi.nlm.nih.gov/31804304/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MD.0000000000017808", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31804304/", "publicSourceType": "PMID" }, { "text": "Zheng W, Cai DB, Yang XH et al.. Adjunctive celecoxib for schizophrenia: A meta-analysis of randomized, double-blind, placebo-controlled trials. Journal of psychiatric research. 2017", "claim": "PubMed-indexed evidence involving Celecoxib", "title": "Adjunctive celecoxib for schizophrenia: A meta-analysis of randomized, double-blind, placebo-controlled trials", "authors": "Zheng W, Cai DB, Yang XH et al.", "journal": "Journal of psychiatric research", "year": 2017, "pmid": "28445800", "url": "https://pubmed.ncbi.nlm.nih.gov/28445800/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jpsychires.2017.04.004", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28445800/", "publicSourceType": "PMID" }, { "text": "Li L, Zhang Y, Qin L. Effect of celecoxib plus standard chemotherapy on cancer prognosis: A systematic review and meta-analysis. European journal of clinical investigation. 2023", "claim": "PubMed-indexed evidence involving Celecoxib", "title": "Effect of celecoxib plus standard chemotherapy on cancer prognosis: A systematic review and meta-analysis", "authors": "Li L, Zhang Y, Qin L", "journal": "European journal of clinical investigation", "year": 2023, "pmid": "36807298", "url": "https://pubmed.ncbi.nlm.nih.gov/36807298/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/eci.13973", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36807298/", "publicSourceType": "PMID" }, { "text": "Wang Z, Wu Q, Wang Q. Effect of celecoxib on improving depression: A systematic review and meta-analysis. 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Systematic review of topical diclofenac for the treatment of acute and chronic musculoskeletal pain. Current medical research and opinion. 2020", "pmid": "31944135", "doi": "10.1080/03007995.2020.1716703", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31944135/", "publicSourceType": "PMID" }, { "text": "Deng ZH, Zeng C, Yang Y et al.. Topical diclofenac therapy for osteoarthritis: a meta-analysis of randomized controlled trials. Clinical rheumatology. 2016", "claim": "PubMed-indexed evidence involving Diclofenac", "title": "Topical diclofenac therapy for osteoarthritis: a meta-analysis of randomized controlled trials", "authors": "Deng ZH, Zeng C, Yang Y et al.", "journal": "Clinical rheumatology", "year": 2016, "pmid": "26242469", "url": "https://pubmed.ncbi.nlm.nih.gov/26242469/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s10067-015-3021-z", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26242469/", "publicSourceType": "PMID" }, { "text": "Chen ZR, Chen BK, Li P et al.. Efficacy and safety of different topical diclofenac formulations for the treatment of knee osteoarthritis: a meta-analysis of short-term and long-term treatment comparisons. BMC musculoskeletal disorders. 2025", "claim": "PubMed-indexed evidence involving Diclofenac", "title": "Efficacy and safety of different topical diclofenac formulations for the treatment of knee osteoarthritis: a meta-analysis of short-term and long-term treatment comparisons", "authors": "Chen ZR, Chen BK, Li P et al.", "journal": "BMC musculoskeletal disorders", "year": 2025, "pmid": "40065343", "url": "https://pubmed.ncbi.nlm.nih.gov/40065343/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12891-025-08465-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40065343/", "publicSourceType": "PMID" }, { "text": "Kotha R, Saad-Omer SI, Singh S et al.. Efficacy of Diclofenac and Indomethacin for Prevention of Post-Endoscopic Cholangiopancreatography (ERCP) Pancreatitis: A Systematic Review. Cureus. 2024", "claim": "PubMed-indexed evidence involving Diclofenac", "title": "Efficacy of Diclofenac and Indomethacin for Prevention of Post-Endoscopic Cholangiopancreatography (ERCP) Pancreatitis: A Systematic Review", "authors": "Kotha R, Saad-Omer SI, Singh S et al.", "journal": "Cureus", "year": 2024, "pmid": "39246923", "url": "https://pubmed.ncbi.nlm.nih.gov/39246923/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7759/cureus.66386", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39246923/", "publicSourceType": "PMID" }, { "text": "Karam M, Alsaif A, Al-Naseem A et al.. Diclofenac Versus Corticosteroids Following Strabismus Surgery: Systematic Review and Meta-analysis. Journal of pediatric ophthalmology and strabismus. 2023", "claim": "PubMed-indexed evidence involving Diclofenac", "title": "Diclofenac Versus Corticosteroids Following Strabismus Surgery: Systematic Review and Meta-analysis", "authors": "Karam M, Alsaif A, Al-Naseem A et al.", "journal": "Journal of pediatric ophthalmology and strabismus", "year": 2023, "pmid": "36441127", "url": "https://pubmed.ncbi.nlm.nih.gov/36441127/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3928/01913913-20221011-01", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36441127/", "publicSourceType": "PMID" }, { "text": "Rochat Negro T, Watchi M, Wozniak H et al.. Diclofenac Sodium for Fever Control in Neurocritical Care: A Systematic Review. Journal of clinical medicine. 2023", "claim": "PubMed-indexed evidence involving Diclofenac", "title": "Diclofenac Sodium for Fever Control in Neurocritical Care: A Systematic Review", "authors": "Rochat Negro T, Watchi M, Wozniak H et al.", "journal": "Journal of clinical medicine", "year": 2023, "pmid": "37240549", "url": "https://pubmed.ncbi.nlm.nih.gov/37240549/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/jcm12103443", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37240549/", "publicSourceType": "PMID" }, { "text": "Haffer H, Müller M, Ascherl R et al.. Diclofenac for prophylaxis of heterotopic ossification after hip arthroplasty: a systematic review. Hip international : the journal of clinical and experimental research on hip pathology and therapy. 2022", "claim": "PubMed-indexed evidence involving Diclofenac", "title": "Diclofenac for prophylaxis of heterotopic ossification after hip arthroplasty: a systematic review", "authors": "Haffer H, Müller M, Ascherl R et al.", "journal": "Hip international : the journal of clinical and experimental research on hip pathology and therapy", "year": 2022, "pmid": "33272062", "url": "https://pubmed.ncbi.nlm.nih.gov/33272062/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/1120700020978194", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33272062/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Nonsteroidal Anti-Inflammatory Drug (NSAID)", "blackBoxWarnings": [ "Increased risk of serious cardiovascular thrombotic events, MI, and stroke; increased risk of serious GI adverse events including bleeding, ulceration, and perforation" ], "fdaPregnancyCategory": "C (D in third trimester)", "halfLife": "1–2 hours", "onsetOfAction": "30 minutes (oral); variable (topical)", "commonBrandNames": [ "Voltaren", "Voltaren Gel", "Cataflam", "Zipsor", "Pennsaid" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "LFTs should be monitored within 4–8 weeks of initiation due to risk of hepatotoxicity" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "diclofenac" }, { "id": "RX-GIPAIN-023", "name": "Tramadol", "alternateNames": [ "Ultram" ], "category": "Prescription", "subcategory": "Opioid Analgesic (Atypical)", "overview": "A centrally acting synthetic opioid analgesic with a dual mechanism of action, used for the management of moderate to moderately severe pain. 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Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004.", "pmid": "15509185", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15509185/", "publicSourceType": "PMID" }, { "text": "Dowell D et al. CDC Clinical Practice Guideline for Prescribing Opioids for Pain, United States, 2022. MMWR. 2022.", "pmid": "36327391", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36327391/", "publicSourceType": "PMID" }, { "text": "Duehmke RM et al. Tramadol for neuropathic pain in adults. Cochrane Database Syst Rev. 2017.", "pmid": "28616956", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28616956/", "publicSourceType": "PMID" }, { "text": "Beakley BD, Kaye AM, Kaye AD. Tramadol, Pharmacology, Side Effects, and Serotonin Syndrome: A Review. Pain physician. 2015", "pmid": "26218943", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26218943/", "publicSourceType": "PMID" }, { "text": "Barakji JA, Maagaard M, Petersen JJ et al.. Tramadol versus placebo for chronic pain: a systematic review with meta-analysis and trial sequential analysis. BMJ evidence-based medicine. 2025", "claim": "PubMed-indexed evidence involving Tramadol", "title": "Tramadol versus placebo for chronic pain: a systematic review with meta-analysis and trial sequential analysis", "authors": "Barakji JA, Maagaard M, Petersen JJ et al.", "journal": "BMJ evidence-based medicine", "year": 2025, "pmid": "41057269", "url": "https://pubmed.ncbi.nlm.nih.gov/41057269/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1136/bmjebm-2025-114101", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41057269/", "publicSourceType": "PMID" }, { "text": "Otte JA, Chu G, Heran B et al.. Tramadol (with or without acetaminophen) efficacy and harm: Systematic review and meta-analysis. Canadian family physician Medecin de famille canadien. 2025", "claim": "PubMed-indexed evidence involving Tramadol", "title": "Tramadol (with or without acetaminophen) efficacy and harm: Systematic review and meta-analysis", "authors": "Otte JA, Chu G, Heran B et al.", "journal": "Canadian family physician Medecin de famille canadien", "year": 2025, "pmid": "40940161", "url": "https://pubmed.ncbi.nlm.nih.gov/40940161/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.46747/cfp.7109574", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40940161/", "publicSourceType": "PMID" }, { "text": "Garlapati S, Alexander R, Kaminski C et al.. The use of tramadol for cancer-associated pain-a systematic review. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2025", "claim": "PubMed-indexed evidence involving Tramadol", "title": "The use of tramadol for cancer-associated pain-a systematic review", "authors": "Garlapati S, Alexander R, Kaminski C et al.", "journal": "Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer", "year": 2025, "pmid": "41324745", "url": "https://pubmed.ncbi.nlm.nih.gov/41324745/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00520-025-10098-4", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41324745/", "publicSourceType": "PMID" }, { "text": "Donati PA, Tarragona L, Franco JVA et al.. Efficacy of tramadol for postoperative pain management in dogs: systematic review and meta-analysis. Veterinary anaesthesia and analgesia. 2021", "claim": "PubMed-indexed evidence involving Tramadol", "title": "Efficacy of tramadol for postoperative pain management in dogs: systematic review and meta-analysis", "authors": "Donati PA, Tarragona L, Franco JVA et al.", "journal": "Veterinary anaesthesia and analgesia", "year": 2021, "pmid": "33745825", "url": "https://pubmed.ncbi.nlm.nih.gov/33745825/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.vaa.2021.01.003", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33745825/", "publicSourceType": "PMID" }, { "text": "Otutaha B, MacFater WS, Xia W et al.. Intraperitoneal Tramadol in Abdominal Surgery: A Systematic Review. The Journal of surgical research. 2020", "claim": "PubMed-indexed evidence involving Tramadol", "title": "Intraperitoneal Tramadol in Abdominal Surgery: A Systematic Review", "authors": "Otutaha B, MacFater WS, Xia W et al.", "journal": "The Journal of surgical research", "year": 2020, "pmid": "31685252", "url": "https://pubmed.ncbi.nlm.nih.gov/31685252/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jss.2019.10.002", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31685252/", "publicSourceType": "PMID" }, { "text": "da Rocha AP, Mizzaci CC, Nunes Pinto ACP et al.. Tramadol for management of fibromyalgia pain and symptoms: Systematic review. 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Archives of internal medicine. 2006", "claim": "PubMed-indexed evidence involving Oxycodone", "title": "Oxycodone for cancer-related pain: meta-analysis of randomized controlled trials", "authors": "Reid CM, Martin RM, Sterne JA et al.", "journal": "Archives of internal medicine", "year": 2006, "pmid": "16636208", "url": "https://pubmed.ncbi.nlm.nih.gov/16636208/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1001/archinte.166.8.837", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16636208/", "publicSourceType": "PMID" }, { "text": "Hou XB, Chen DD, Cheng TF et al.. Meta-analysis of efficacy and safety of sustained release oxycodone hydrochloride rectal administration for moderate to severe pain. PloS one. 2022", "claim": "PubMed-indexed evidence involving Oxycodone", "title": "Meta-analysis of efficacy and safety of sustained release oxycodone hydrochloride rectal administration for moderate to severe pain", "authors": "Hou XB, Chen DD, Cheng TF et al.", "journal": "PloS one", "year": 2022, "pmid": "35759471", "url": "https://pubmed.ncbi.nlm.nih.gov/35759471/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1371/journal.pone.0266754", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35759471/", "publicSourceType": "PMID" }, { "text": "Teoh L, McCullough M, Taing MW. Efficacy of oxycodone for postoperative dental pain: A systematic review and meta-analysis. Journal of dentistry. 2022", "claim": "PubMed-indexed evidence involving Oxycodone", "title": "Efficacy of oxycodone for postoperative dental pain: A systematic review and meta-analysis", "authors": "Teoh L, McCullough M, Taing MW", "journal": "Journal of dentistry", "year": 2022, "pmid": "35977697", "url": "https://pubmed.ncbi.nlm.nih.gov/35977697/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jdent.2022.104254", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35977697/", "publicSourceType": "PMID" }, { "text": "Lozano-López MT, Gamonal-Limcaoco S, Casado-Espada N et al.. Psychosis after buprenorphine, heroin, methadone, morphine, oxycodone, and tramadol withdrawal: a systematic review. 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PloS one. 2020", "claim": "PubMed-indexed evidence involving Oxycodone", "title": "Oxycodone versus morphine for cancer pain titration: A systematic review and pharmacoeconomic evaluation", "authors": "Zhou J, Wang Y, Jiang G", "journal": "PloS one", "year": 2020, "pmid": "32302346", "url": "https://pubmed.ncbi.nlm.nih.gov/32302346/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1371/journal.pone.0231763", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32302346/", "publicSourceType": "PMID" }, { "text": "Tan HP, Conroy T. The Effectiveness of Intravenous Oxycodone in the Treatment of Acute Postoperative Pain: A Systematic Review. Journal of perianesthesia nursing : official journal of the American Society of PeriAnesthesia Nurses. 2018", "claim": "PubMed-indexed evidence involving Oxycodone", "title": "The Effectiveness of Intravenous Oxycodone in the Treatment of Acute Postoperative Pain: A Systematic Review", "authors": "Tan HP, Conroy T", "journal": "Journal of perianesthesia nursing : official journal of the American Society of PeriAnesthesia Nurses", "year": 2018, "pmid": "30449435", "url": "https://pubmed.ncbi.nlm.nih.gov/30449435/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jopan.2017.05.010", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30449435/", "publicSourceType": "PMID" }, { "text": "King SJ, Reid C, Forbes K et al.. A systematic review of oxycodone in the management of cancer pain. 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CDC Clinical Practice Guideline for Prescribing Opioids for Pain, United States, 2022. MMWR. 2022.", "pmid": "36327391", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36327391/", "publicSourceType": "PMID" }, { "text": "Argoff CE et al. Rational unanticipated positive drug tests, issues of unused opioids and their potential for diversion: the role of drug testing. Pain Med. 2014.", "pmid": "25352175", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25352175/", "publicSourceType": "PMID" }, { "text": "Manchikanti L et al. Comparative evaluation of the opioid use in the management of chronic pain. Pain Physician. 2011.", "pmid": "21785475", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21785475/", "publicSourceType": "PMID" }, { "text": "Coates S, Lazarus P. Hydrocodone, Oxycodone, and Morphine Metabolism and Drug-Drug Interactions. The Journal of pharmacology and experimental therapeutics. 2023", "pmid": "37679047", "doi": "10.1124/jpet.123.001651", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37679047/", "publicSourceType": "PMID" }, { "text": "Usmani SA, Hollmann J, Goodin A et al.. Effects of hydrocodone rescheduling on opioid use outcomes: A systematic review. Journal of the American Pharmacists Association : JAPhA. 2021", "claim": "PubMed-indexed evidence involving Hydrocodone", "title": "Effects of hydrocodone rescheduling on opioid use outcomes: A systematic review", "authors": "Usmani SA, Hollmann J, Goodin A et al.", "journal": "Journal of the American Pharmacists Association : JAPhA", "year": 2021, "pmid": "33127312", "url": "https://pubmed.ncbi.nlm.nih.gov/33127312/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.japh.2020.09.013", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33127312/", "publicSourceType": "PMID" }, { "text": "Ripa SR, McCarberg BH, Munera C et al.. A randomized, 14-day, double-blind study evaluating conversion from hydrocodone/acetaminophen (Vicodin) to buprenorphine transdermal system 10 μg/h or 20 μg/h in patients with osteoarthritis pain. Expert opinion on pharmacotherapy. 2012", "claim": "PubMed-indexed evidence involving Hydrocodone", "title": "A randomized, 14-day, double-blind study evaluating conversion from hydrocodone/acetaminophen (Vicodin) to buprenorphine transdermal system 10 μg/h or 20 μg/h in patients with osteoarthritis pain", "authors": "Ripa SR, McCarberg BH, Munera C et al.", "journal": "Expert opinion on pharmacotherapy", "year": 2012, "pmid": "22409388", "url": "https://pubmed.ncbi.nlm.nih.gov/22409388/", "study_type": "RCT", "confidence": "verify", "doi": "10.1517/14656566.2012.667073", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22409388/", "publicSourceType": "PMID" }, { "text": "Bindler RJ, Watson CJW, Lyons AJ et al.. Drug-Drug Interaction Between Orally Administered Hydrocodone-Acetaminophen and Inhalation of Cannabis Smoke: A Case Report. Hospital pharmacy. 2022", "claim": "PubMed-indexed evidence involving Hydrocodone", "title": "Drug-Drug Interaction Between Orally Administered Hydrocodone-Acetaminophen and Inhalation of Cannabis Smoke: A Case Report", "authors": "Bindler RJ, Watson CJW, Lyons AJ et al.", "journal": "Hospital pharmacy", "year": 2022, "pmid": "35898257", "url": "https://pubmed.ncbi.nlm.nih.gov/35898257/", "study_type": "review", "confidence": "verify", "doi": "10.1177/00185787211061374", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35898257/", "publicSourceType": "PMID" }, { "text": "Dhillon S. Hydrocodone Bitartrate ER (Hysingla(®) ER): A Review in Chronic Pain. Clinical drug investigation. 2016", "claim": "PubMed-indexed evidence involving Hydrocodone", "title": "Hydrocodone Bitartrate ER (Hysingla(®) ER): A Review in Chronic Pain", "authors": "Dhillon S", "journal": "Clinical drug investigation", "year": 2016, "pmid": "27718163", "url": "https://pubmed.ncbi.nlm.nih.gov/27718163/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s40261-016-0466-z", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27718163/", "publicSourceType": "PMID" }, { "text": "Habibi M, Kim PY. Hydrocodone and Acetaminophen. 2026", "claim": "PubMed-indexed evidence involving Hydrocodone", "title": "Hydrocodone and Acetaminophen", "authors": "Habibi M, Kim PY", "journal": "", "year": 2026, "pmid": "30860765", "url": "https://pubmed.ncbi.nlm.nih.gov/30860765/", "study_type": "review", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30860765/", "publicSourceType": "PMID" }, { "text": "Bea S, Huybrechts KF, Glynn RJ et al.. Opioid overdose associated with concomitant use of hydrocodone and selective serotonin reuptake inhibitors. BMC medicine. 2025", "claim": "PubMed-indexed evidence involving Hydrocodone", "title": "Opioid overdose associated with concomitant use of hydrocodone and selective serotonin reuptake inhibitors", "authors": "Bea S, Huybrechts KF, Glynn RJ et al.", "journal": "BMC medicine", "year": 2025, "pmid": "41316177", "url": "https://pubmed.ncbi.nlm.nih.gov/41316177/", "study_type": "review", "confidence": "verify", "doi": "10.1186/s12916-025-04475-3", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41316177/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Opioid Analgesic", "blackBoxWarnings": [ "Risk of addiction, abuse, and misuse; life-threatening respiratory depression; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants" ], "fdaPregnancyCategory": "C", "halfLife": "3.8 hours (IR); 7–9 hours (ER)", "onsetOfAction": "10–30 minutes", "commonBrandNames": [ "Vicodin", "Norco", "Lortab", "Zohydro ER", "Hysingla ER" ], "controlledSubstanceSchedule": "Schedule II", "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "hydrocodone" }, { "id": "RX-GIPAIN-026", "name": "Morphine", "alternateNames": [ "MS Contin" ], "category": "Prescription", "subcategory": "Opioid Analgesic", "overview": "The prototypical opioid analgesic, morphine is used for the management of severe pain when non-opioid alternatives are inadequate. 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CDC Clinical Practice Guideline for Prescribing Opioids for Pain, United States, 2022. MMWR. 2022.", "pmid": "36327391", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36327391/", "publicSourceType": "PMID" }, { "text": "Wiffen PJ et al. Oral morphine for cancer pain. Cochrane Database Syst Rev. 2016.", "pmid": "27105021", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27105021/", "publicSourceType": "PMID" }, { "text": "Pasternak GW. Molecular biology of opioid analgesia. J Pain Symptom Manage. 2005.", "pmid": "15907642", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15907642/", "publicSourceType": "PMID" }, { "text": "Ciconini LE, Ramos WA, Fonseca ACL et al.. Intrathecal Morphine for Cardiac Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Annals of cardiac anaesthesia. 2024", "claim": "PubMed-indexed evidence involving Morphine", "title": "Intrathecal Morphine for Cardiac Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Ciconini LE, Ramos WA, Fonseca ACL et al.", "journal": "Annals of cardiac anaesthesia", "year": 2024, "pmid": "38722114", "url": "https://pubmed.ncbi.nlm.nih.gov/38722114/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.4103/aca.aca_48_23", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38722114/", "publicSourceType": "PMID" }, { "text": "Li Y, Yue X, Liang S et al.. Effectiveness and Safety of Hydromorphone Compared to Morphine for Postoperative Analgesia: A Systematic Review and Meta-analysis. Pain physician. 2024", "claim": "PubMed-indexed evidence involving Morphine", "title": "Effectiveness and Safety of Hydromorphone Compared to Morphine for Postoperative Analgesia: A Systematic Review and Meta-analysis", "authors": "Li Y, Yue X, Liang S et al.", "journal": "Pain physician", "year": 2024, "pmid": "39621972", "url": "https://pubmed.ncbi.nlm.nih.gov/39621972/", "study_type": "meta-analysis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39621972/", "publicSourceType": "PMID" }, { "text": "Hussain N, Brull R, Thaete L et al.. The analgesic effects of novel fascial plane blocks compared with intrathecal morphine after Caesarean delivery: a systematic review and meta-analysis. British journal of anaesthesia. 2025", "claim": "PubMed-indexed evidence involving Morphine", "title": "The analgesic effects of novel fascial plane blocks compared with intrathecal morphine after Caesarean delivery: a systematic review and meta-analysis", "authors": "Hussain N, Brull R, Thaete L et al.", "journal": "British journal of anaesthesia", "year": 2025, "pmid": "40074621", "url": "https://pubmed.ncbi.nlm.nih.gov/40074621/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.bja.2025.01.032", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40074621/", "publicSourceType": "PMID" }, { "text": "Renard Y, El-Boghdadly K, Rossel JB et al.. Non-pulmonary complications of intrathecal morphine administration: a systematic review and meta-analysis with meta-regression. British journal of anaesthesia. 2024", "claim": "PubMed-indexed evidence involving Morphine", "title": "Non-pulmonary complications of intrathecal morphine administration: a systematic review and meta-analysis with meta-regression", "authors": "Renard Y, El-Boghdadly K, Rossel JB et al.", "journal": "British journal of anaesthesia", "year": 2024, "pmid": "39098521", "url": "https://pubmed.ncbi.nlm.nih.gov/39098521/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.bja.2024.05.045", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39098521/", "publicSourceType": "PMID" }, { "text": "Tee ZH, Tsoi EHC, Lee Q et al.. Intrathecal Morphine and Post-Operative Pain Relief in Robotic Surgeries: A Systematic Review and Meta-Analysis. Journal of clinical medicine. 2023", "claim": "PubMed-indexed evidence involving Morphine", "title": "Intrathecal Morphine and Post-Operative Pain Relief in Robotic Surgeries: A Systematic Review and Meta-Analysis", "authors": "Tee ZH, Tsoi EHC, Lee Q et al.", "journal": "Journal of clinical medicine", "year": 2023, "pmid": "38202144", "url": "https://pubmed.ncbi.nlm.nih.gov/38202144/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/jcm13010137", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38202144/", "publicSourceType": "PMID" }, { "text": "Spénard S, Gélinas C, D Trottier E et al.. Morphine or hydromorphone: which should be preferred? A systematic review. Archives of disease in childhood. 2021", "claim": "PubMed-indexed evidence involving Morphine", "title": "Morphine or hydromorphone: which should be preferred? A systematic review", "authors": "Spénard S, Gélinas C, D Trottier E et al.", "journal": "Archives of disease in childhood", "year": 2021, "pmid": "33461958", "url": "https://pubmed.ncbi.nlm.nih.gov/33461958/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1136/archdischild-2020-319059", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33461958/", "publicSourceType": "PMID" }, { "text": "Duarte GS, Nunes-Ferreira A, Rodrigues FB et al.. Morphine in acute coronary syndrome: systematic review and meta-analysis. BMJ open. 2019", "claim": "PubMed-indexed evidence involving Morphine", "title": "Morphine in acute coronary syndrome: systematic review and meta-analysis", "authors": "Duarte GS, Nunes-Ferreira A, Rodrigues FB et al.", "journal": "BMJ open", "year": 2019, "pmid": "30878985", "url": "https://pubmed.ncbi.nlm.nih.gov/30878985/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1136/bmjopen-2018-025232", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30878985/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Opioid Analgesic", "blackBoxWarnings": [ "Risk of addiction, abuse, and misuse; life-threatening respiratory depression; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants" ], "fdaPregnancyCategory": "C", "halfLife": "2–4 hours", "onsetOfAction": "15–60 minutes (oral); 5–10 minutes (IV)", "commonBrandNames": [ "MS Contin", "Kadian", "Avinza", "Roxanol" ], "controlledSubstanceSchedule": "Schedule II", "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "morphine" }, { "id": "RX-GIPAIN-027", "name": "Cyclobenzaprine", "alternateNames": [ "Flexeril" ], "category": "Prescription", "subcategory": "Skeletal Muscle Relaxant", "overview": "A centrally acting skeletal muscle relaxant structurally related to tricyclic antidepressants, used for the short-term relief of muscle spasm associated with acute, painful musculoskeletal conditions. 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Cyclobenzaprine and back pain: a meta-analysis. Arch Intern Med. 2001.", "pmid": "11434793", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11434793/", "publicSourceType": "PMID" }, { "text": "See S, Ginzburg R. Choosing a skeletal muscle relaxant. Am Fam Physician. 2008.", "pmid": "18711953", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18711953/", "publicSourceType": "PMID" }, { "text": "Elkalla MA et al. Efficacy and safety of interventions for Fibromyalgia syndrome comorbid with Irritable bowel syndrome: systematic review. Clin Rheumatol. 2026.", "pmid": "41423615", "doi": "10.1007/s10067-025-07861-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41423615/", "publicSourceType": "PMID" }, { "text": "Lederman S, Arnold LM, Vaughn B et al.. Efficacy and Safety of Sublingual Cyclobenzaprine for the Treatment of Fibromyalgia: Results From a Randomized, Double-Blind, Placebo-Controlled Trial. Arthritis care & research. 2023", "pmid": "37165930", "doi": "10.1002/acr.25142", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37165930/", "publicSourceType": "PMID" }, { "text": "Tofferi JK, Jackson JL, O'Malley PG. Treatment of fibromyalgia with cyclobenzaprine: A meta-analysis. Arthritis and rheumatism. 2004", "pmid": "14872449", "doi": "10.1002/art.20076", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14872449/", "publicSourceType": "PMID" }, { "text": "Al-Qudah AA, Al-Hanaktah M. Short-term efficacy and safety of sublingual cyclobenzaprine for fibromyalgia: A systematic review and meta-analysis. Clinical rheumatology. 2026", "claim": "PubMed-indexed evidence involving Cyclobenzaprine", "title": "Short-term efficacy and safety of sublingual cyclobenzaprine for fibromyalgia: A systematic review and meta-analysis", "authors": "Al-Qudah AA, Al-Hanaktah M", "journal": "Clinical rheumatology", "year": 2026, "pmid": "41318845", "url": "https://pubmed.ncbi.nlm.nih.gov/41318845/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s10067-025-07863-5", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41318845/", "publicSourceType": "PMID" }, { "text": "Parmenter ME, Lederman S, Weathers FW et al.. A phase 3, randomized, placebo-controlled, trial to evaluate the efficacy and safety of bedtime sublingual cyclobenzaprine (TNX-102 SL) in military-related posttraumatic stress disorder. Psychiatry research. 2024", "claim": "PubMed-indexed evidence involving Cyclobenzaprine", "title": "A phase 3, randomized, placebo-controlled, trial to evaluate the efficacy and safety of bedtime sublingual cyclobenzaprine (TNX-102 SL) in military-related posttraumatic stress disorder", "authors": "Parmenter ME, Lederman S, Weathers FW et al.", "journal": "Psychiatry research", "year": 2024, "pmid": "38350291", "url": "https://pubmed.ncbi.nlm.nih.gov/38350291/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.psychres.2024.115764", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38350291/", "publicSourceType": "PMID" }, { "text": "Lederman S, Arnold LM, Vaughn B et al.. Pain relief by targeting nonrestorative sleep in fibromyalgia: a phase 3 randomized trial of bedtime sublingual cyclobenzaprine. Pain medicine (Malden, Mass.). 2026", "claim": "PubMed-indexed evidence involving Cyclobenzaprine", "title": "Pain relief by targeting nonrestorative sleep in fibromyalgia: a phase 3 randomized trial of bedtime sublingual cyclobenzaprine", "authors": "Lederman S, Arnold LM, Vaughn B et al.", "journal": "Pain medicine (Malden, Mass.)", "year": 2026, "pmid": "40627411", "url": "https://pubmed.ncbi.nlm.nih.gov/40627411/", "study_type": "RCT", "confidence": "verify", "doi": "10.1093/pm/pnaf089", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40627411/", "publicSourceType": "PMID" }, { "text": "Caron J, Kaye R, Wessel T et al.. An assessment of the centrally acting muscle relaxant tolperisone on driving ability and cognitive effects compared to placebo and cyclobenzaprine. Journal of clinical pharmacy and therapeutics. 2020", "claim": "PubMed-indexed evidence involving Cyclobenzaprine", "title": "An assessment of the centrally acting muscle relaxant tolperisone on driving ability and cognitive effects compared to placebo and cyclobenzaprine", "authors": "Caron J, Kaye R, Wessel T et al.", "journal": "Journal of clinical pharmacy and therapeutics", "year": 2020, "pmid": "32390248", "url": "https://pubmed.ncbi.nlm.nih.gov/32390248/", "study_type": "RCT", "confidence": "verify", "doi": "10.1111/jcpt.13165", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32390248/", "publicSourceType": "PMID" }, { "text": "Tu J, Zhang C, Xie S et al.. Cyclobenzaprine-related adverse events: a comprehensive pharmacovigilance analysis using the FDA Adverse Event Reporting System. Frontiers in medicine. 2025", "claim": "PubMed-indexed evidence involving Cyclobenzaprine", "title": "Cyclobenzaprine-related adverse events: a comprehensive pharmacovigilance analysis using the FDA Adverse Event Reporting System", "authors": "Tu J, Zhang C, Xie S et al.", "journal": "Frontiers in medicine", "year": 2025, "pmid": "41058614", "url": "https://pubmed.ncbi.nlm.nih.gov/41058614/", "study_type": "review", "confidence": "verify", "doi": "10.3389/fmed.2025.1574395", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41058614/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Centrally Acting Skeletal Muscle Relaxant", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "18 hours (range: 8–37 hours)", "onsetOfAction": "1 hour", "commonBrandNames": [ "Flexeril", "Amrix" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "cyclobenzaprine" }, { "id": "RX-GIPAIN-028", "name": "Baclofen", "alternateNames": [ "Lioresal" ], "category": "Prescription", "subcategory": "Skeletal Muscle Relaxant (Antispastic)", "overview": "A GABA-B receptor agonist used for the treatment of spasticity resulting from multiple sclerosis, spinal cord injuries, and other spinal cord diseases. 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A benefit-risk assessment of baclofen in severe spinal spasticity. Drug Saf. 2004.", "pmid": "15350152", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15350152/", "publicSourceType": "PMID" }, { "text": "See S, Ginzburg R. Choosing a skeletal muscle relaxant. Am Fam Physician. 2008.", "pmid": "18711953", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18711953/", "publicSourceType": "PMID" }, { "text": "Kotake K et al. Optimal Dose of Baclofen for the Treatment of Alcohol Use Disorder: A Systematic Review and Dose-Response Meta-analysis. CNS Drugs. 2025.", "pmid": "40347309", "doi": "10.1007/s40263-025-01188-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40347309/", "publicSourceType": "PMID" }, { "text": "Agabio R, Saulle R, Rösner S et al.. Baclofen for alcohol use disorder. The Cochrane database of systematic reviews. 2023", "pmid": "36637087", "doi": "10.1002/14651858.CD012557.pub3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36637087/", "publicSourceType": "PMID" }, { "text": "Baclofen. 2006", "pmid": "30000260", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30000260/", "publicSourceType": "PMID" }, { "text": "Duan F, Zhai H, Liu C et al.. Systematic review and meta-analysis: Efficacy and safety of baclofen in patients with alcohol use disorder co-morbid liver diseases. Journal of psychiatric research. 2023", "claim": "PubMed-indexed evidence involving Baclofen", "title": "Systematic review and meta-analysis: Efficacy and safety of baclofen in patients with alcohol use disorder co-morbid liver diseases", "authors": "Duan F, Zhai H, Liu C et al.", "journal": "Journal of psychiatric research", "year": 2023, "pmid": "37441998", "url": "https://pubmed.ncbi.nlm.nih.gov/37441998/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jpsychires.2023.06.042", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37441998/", "publicSourceType": "PMID" }, { "text": "Viana Pinto L, Romeiro I, Gouveia F et al.. Intrathecal baclofen for the management of hereditary spastic paraparesis: a systematic review. International journal of rehabilitation research. Internationale Zeitschrift fur Rehabilitationsforschung. Revue internationale de recherches de readaptation. 2024", "claim": "PubMed-indexed evidence involving Baclofen", "title": "Intrathecal baclofen for the management of hereditary spastic paraparesis: a systematic review", "authors": "Viana Pinto L, Romeiro I, Gouveia F et al.", "journal": "International journal of rehabilitation research. Internationale Zeitschrift fur Rehabilitationsforschung. Revue internationale de recherches de readaptation", "year": 2024, "pmid": "38251093", "url": "https://pubmed.ncbi.nlm.nih.gov/38251093/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MRR.0000000000000607", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38251093/", "publicSourceType": "PMID" }, { "text": "Lee HP, Win T, Balakrishnan S. The impact of intrathecal baclofen on the ability to walk: A systematic review. Clinical rehabilitation. 2023", "claim": "PubMed-indexed evidence involving Baclofen", "title": "The impact of intrathecal baclofen on the ability to walk: A systematic review", "authors": "Lee HP, Win T, Balakrishnan S", "journal": "Clinical rehabilitation", "year": 2023, "pmid": "36330654", "url": "https://pubmed.ncbi.nlm.nih.gov/36330654/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/02692155221135827", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36330654/", "publicSourceType": "PMID" }, { "text": "Phu PJJ, Looi JCL, Nair PC et al.. Psychosis Related to Baclofen Withdrawal or Overdose: A Systematic Review. East Asian archives of psychiatry : official journal of the Hong Kong College of Psychiatrists = Dong Ya jing shen ke xue zhi : Xianggang jing shen ke yi xue yuan qi kan. 2023", "claim": "PubMed-indexed evidence involving Baclofen", "title": "Psychosis Related to Baclofen Withdrawal or Overdose: A Systematic Review", "authors": "Phu PJJ, Looi JCL, Nair PC et al.", "journal": "East Asian archives of psychiatry : official journal of the Hong Kong College of Psychiatrists = Dong Ya jing shen ke xue zhi : Xianggang jing shen ke yi xue yuan qi kan", "year": 2023, "pmid": "36991550", "url": "https://pubmed.ncbi.nlm.nih.gov/36991550/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.12809/eaap2237", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36991550/", "publicSourceType": "PMID" }, { "text": "Buizer AI, Martens BHM, Grandbois van Ravenhorst C et al.. Effect of continuous intrathecal baclofen therapy in children: a systematic review. Developmental medicine and child neurology. 2019", "claim": "PubMed-indexed evidence involving Baclofen", "title": "Effect of continuous intrathecal baclofen therapy in children: a systematic review", "authors": "Buizer AI, Martens BHM, Grandbois van Ravenhorst C et al.", "journal": "Developmental medicine and child neurology", "year": 2019, "pmid": "30187921", "url": "https://pubmed.ncbi.nlm.nih.gov/30187921/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/dmcn.14005", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30187921/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "GABA-B Receptor Agonist / Antispastic Agent", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "2.5–4 hours", "onsetOfAction": "30–60 minutes (oral); 30 minutes–1 hour (intrathecal)", "commonBrandNames": [ "Lioresal", "Gablofen", "Ozobax" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "baclofen" }, { "id": "RX-GIPAIN-029", "name": "Tizanidine", "alternateNames": [ "Zanaflex" ], "category": "Prescription", "subcategory": "Skeletal Muscle Relaxant (Antispastic)", "overview": "A centrally acting alpha-2 adrenergic agonist used for the management of spasticity associated with multiple sclerosis and spinal cord injury. 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Tizanidine treatment of spasticity: a meta-analysis of controlled, double-blind, comparative studies with baclofen and diazepam. Adv Ther. 1998.", "pmid": "10186943", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10186943/", "publicSourceType": "PMID" }, { "text": "See S, Ginzburg R. Choosing a skeletal muscle relaxant. Am Fam Physician. 2008.", "pmid": "18711953", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18711953/", "publicSourceType": "PMID" }, { "text": "Wewege MA et al. Comparative effectiveness and safety of analgesic medicines for adults with acute non-specific low back pain: systematic review and network meta-analysis. BMJ. 2023.", "pmid": "36948512", "doi": "10.1136/bmj-2022-072962", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36948512/", "publicSourceType": "PMID" }, { "text": "Ghanavatian S, Derian A. Tizanidine. 2026", "pmid": "30137790", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30137790/", "publicSourceType": "PMID" }, { "text": "Zhu LL, Wang YH, Zhou Q. Tizanidine: Advances in Pharmacology & Therapeutics and Drug Formulations. Journal of pain research. 2024", "pmid": "38529017", "doi": "10.2147/JPR.S461032", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38529017/", "publicSourceType": "PMID" }, { "text": "Killam-Worrall L, Brand R, Castro JR et al.. Baclofen and Tizanidine Adverse Effects Observed Among Community-Dwelling Adults Above the Age of 50 Years: A Systematic Review. 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Commentary: Is Polyethylene Glycol Toxicity From Intravenous Methocarbamol Fact or Fiction?. Journal of pain & palliative care pharmacotherapy. 2024", "pmid": "38718034", "doi": "10.1080/15360288.2024.2345322", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38718034/", "publicSourceType": "PMID" }, { "text": "Barzani HAH, Omer RA, Abdulrahman NB et al.. Evolving Analytical Methods for the Quantification of Methocarbamol: A Critical Review. Biomedical chromatography : BMC. 2026", "pmid": "41841242", "doi": "10.1002/bmc.70419", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41841242/", "publicSourceType": "PMID" }, { "text": "Samsamshariat S, Sharifi-Sade M, Zoofaghari S et al.. Efficacy of the Combination of Indomethacin and Methocarbamol versus Indomethacin Alone in Patients with Acute Low Back Pain: A Double-Blind, Randomized Placebo-Controlled Clinical Trial. 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European journal of gastroenterology & hepatology. 2019", "claim": "PubMed-indexed evidence involving Methocarbamol", "title": "Randomized-controlled trial of methocarbamol as a novel treatment for muscle cramps in cirrhotic patients", "authors": "Abd-Elsalam S, Arafa M, Elkadeem M et al.", "journal": "European journal of gastroenterology & hepatology", "year": 2019, "pmid": "30444744", "url": "https://pubmed.ncbi.nlm.nih.gov/30444744/", "study_type": "RCT", "confidence": "verify", "doi": "10.1097/MEG.0000000000001310", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30444744/", "publicSourceType": "PMID" }, { "text": "Friedman BW, Cisewski D, Irizarry E et al.. A Randomized, Double-Blind, Placebo-Controlled Trial of Naproxen With or Without Orphenadrine or Methocarbamol for Acute Low Back Pain. 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Gabapentin for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017.", "pmid": "28779491", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28779491/", "publicSourceType": "PMID" }, { "text": "Finnerup NB et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015.", "pmid": "25575710", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25575710/", "publicSourceType": "PMID" }, { "text": "Backonja M et al. Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus. JAMA. 1998.", "pmid": "10530684", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10530684/", "publicSourceType": "PMID" }, { "text": "Hong JSW, Atkinson LZ, Al-Juffali N et al.. Gabapentin and pregabalin in bipolar disorder, anxiety states, and insomnia: Systematic review, meta-analysis, and rationale. Molecular psychiatry. 2022", "pmid": "34819636", "doi": "10.1038/s41380-021-01386-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34819636/", "publicSourceType": "PMID" }, { "claim": "Gabapentin is effective for treating alcohol use disorder", "title": "A meta-analysis of the efficacy of gabapentin for treating alcohol use disorder.", "authors": "Kranzler HR, Feinn R, Morris P et al.", "journal": "Addiction", "year": 2019, "pmid": "31077485", "url": "https://pubmed.ncbi.nlm.nih.gov/31077485/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of RCTs found gabapentin significantly reduced heavy drinking days and increased abstinence rates compared to placebo in alcohol use disorder, with effects most pronounced at higher doses (≥1800 mg/day).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31077485/", "publicSourceType": "PMID" }, { "text": "Huerta MÁ, Garcia MM, García-Parra B et al.. Investigational Drugs for the Treatment of Postherpetic Neuralgia: Systematic Review of Randomized Controlled Trials. International journal of molecular sciences. 2023", "claim": "PubMed-indexed evidence involving Gabapentin", "title": "Investigational Drugs for the Treatment of Postherpetic Neuralgia: Systematic Review of Randomized Controlled Trials", "authors": "Huerta MÁ, Garcia MM, García-Parra B et al.", "journal": "International journal of molecular sciences", "year": 2023, "pmid": "37629168", "url": "https://pubmed.ncbi.nlm.nih.gov/37629168/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/ijms241612987", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37629168/", "publicSourceType": "PMID" }, { "text": "Eusebio-Alpapara KMV, Castillo RL, Dofitas BL. Gabapentin for uremic pruritus: a systematic review of randomized controlled trials. International journal of dermatology. 2020", "claim": "PubMed-indexed evidence involving Gabapentin", "title": "Gabapentin for uremic pruritus: a systematic review of randomized controlled trials", "authors": "Eusebio-Alpapara KMV, Castillo RL, Dofitas BL", "journal": "International journal of dermatology", "year": 2020, "pmid": "31777066", "url": "https://pubmed.ncbi.nlm.nih.gov/31777066/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/ijd.14708", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31777066/", "publicSourceType": "PMID" }, { "text": "Dutta D, Mohindra R, Kumar M et al.. Cardiovascular safety of gabapentinoids gabapentin & pregabalin: A systematic review. The Indian journal of medical research. 2025", "claim": "PubMed-indexed evidence involving Gabapentin", "title": "Cardiovascular safety of gabapentinoids gabapentin & pregabalin: A systematic review", "authors": "Dutta D, Mohindra R, Kumar M et al.", "journal": "The Indian journal of medical research", "year": 2025, "pmid": "40536375", "url": "https://pubmed.ncbi.nlm.nih.gov/40536375/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.25259/IJMR_1990_2024", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40536375/", "publicSourceType": "PMID" }, { "text": "Mayoral V, Galvez R, Ferrándiz M et al.. Pregabalin vs. gabapentin in the treatment of neuropathic pain: a comprehensive systematic review and meta-analysis of effectiveness and safety. 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Atencion primaria. 2022", "claim": "PubMed-indexed evidence involving Gabapentin", "title": "A systematic review and meta-analysis of the effectiveness and adverse events of gabapentin and pregabalin for sciatica pain", "authors": "Giménez-Campos MS, Pimenta-Fermisson-Ramos P, Díaz-Cambronero JI et al.", "journal": "Atencion primaria", "year": 2022, "pmid": "34637958", "url": "https://pubmed.ncbi.nlm.nih.gov/34637958/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.aprim.2021.102144", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34637958/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Gabapentinoid / Anticonvulsant", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "5–7 hours", "onsetOfAction": "Variable; may take 1–2 weeks for full analgesic benefit", "commonBrandNames": [ "Neurontin", "Gralise", "Horizant" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "gabapentin" }, { "id": "RX-GIPAIN-032", "name": "Pregabalin", "alternateNames": [ "Lyrica" ], "category": "Prescription", "subcategory": "Neuropathic Pain Agent (Gabapentinoid)", "overview": "A gabapentinoid anticonvulsant FDA-approved for neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, fibromyalgia, neuropathic pain due to spinal cord injury, and adjunctive therapy for partial-onset seizures. 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Pregabalin has 6-fold greater binding affinity than gabapentin.", "commonBenefits": [ "Treatment of diabetic peripheral neuropathy pain", "Treatment of postherpetic neuralgia", "Treatment of fibromyalgia", "Treatment of neuropathic pain from spinal cord injury", "Adjunctive therapy for partial seizures", "More predictable dose-response than gabapentin" ], "commonDosageRange": "Start 75 mg twice daily or 50 mg three times daily; titrate to 150–300 mg twice daily (max 600 mg/day) (as prescribed by your physician)", "recommendedForm": "Capsule or oral solution", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Can be taken with or without food; linear pharmacokinetics (unlike gabapentin), absorption is not dose-dependent" }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Dizziness", "Somnolence", "Peripheral edema", "Weight gain", "Blurred vision", "Dry mouth", "Difficulty concentrating", "Euphoria (contributes to abuse potential)" ], "contraindications": [ "Known hypersensitivity to pregabalin (including angioedema)", "Renal impairment (dose adjustment required)", "Do not abruptly discontinue (taper over at least 1 week)", "Caution in patients with Class III/IV heart failure (may worsen edema)", "Caution with CNS depressants and respiratory depressants" ], "iconName": "cross.case.fill", "colorHex": "7E57C2", "tags": [ "pain", "neuropathic", "anticonvulsant", "gabapentinoid", "fibromyalgia", "controlled-substance" ], "sources": [ { "text": "Derry S et al. Pregabalin for neuropathic pain in adults. Cochrane Database Syst Rev. 2019.", "pmid": "30673120", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30673120/", "publicSourceType": "PMID" }, { "text": "Finnerup NB et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015.", "pmid": "25575710", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25575710/", "publicSourceType": "PMID" }, { "text": "Arnold LM et al. A 14-week, randomized, double-blinded, placebo-controlled monotherapy trial of pregabalin in patients with fibromyalgia. J Pain. 2008.", "pmid": "18524684", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18524684/", "publicSourceType": "PMID" }, { "text": "Bonnet U, Scherbaum N. How addictive are gabapentin and pregabalin? A systematic review. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 2017", "pmid": "28988943", "doi": "10.1016/j.euroneuro.2017.08.430", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28988943/", "publicSourceType": "PMID" }, { "text": "Hong JSW, Atkinson LZ, Al-Juffali N et al.. Gabapentin and pregabalin in bipolar disorder, anxiety states, and insomnia: Systematic review, meta-analysis, and rationale. Molecular psychiatry. 2022", "pmid": "34819636", "doi": "10.1038/s41380-021-01386-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34819636/", "publicSourceType": "PMID" }, { "claim": "Pregabalin reduces neuropathic pain but increases adverse event risk", "title": "Benefits and harms of pregabalin in the management of neuropathic pain: a rapid review and meta-analysis of randomised clinical trials.", "authors": "Onakpoya IJ, Thomas ET, Lee JJ et al.", "journal": "BMJ Open", "year": 2019, "pmid": "30670513", "url": "https://pubmed.ncbi.nlm.nih.gov/30670513/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of 28 RCTs (6087 participants) found pregabalin significantly reduced neuropathic pain (SMD -0.49) and sleep interference (SMD -0.38) vs placebo, but significantly increased adverse events (RR 1.33) and discontinuation due to adverse events (RR 1.91).", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30670513/", "publicSourceType": "PMID" }, { "claim": "Pregabalin is effective for generalized anxiety disorder", "title": "Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis.", "authors": "Slee A, Nazareth I, Bondaronek P et al.", "journal": "Lancet", "year": 2019, "pmid": "30712879", "url": "https://pubmed.ncbi.nlm.nih.gov/30712879/", "study_type": "network meta-analysis", "key_finding": "Network meta-analysis of 89 studies found pregabalin among the most effective drugs for GAD with superior efficacy to placebo (OR 3.78), alongside duloxetine and venlafaxine; all three showed better efficacy than benzodiazepines.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30712879/", "publicSourceType": "PMID" }, { "text": "Dutta D, Mohindra R, Kumar M et al.. Cardiovascular safety of gabapentinoids gabapentin & pregabalin: A systematic review. The Indian journal of medical research. 2025", "claim": "PubMed-indexed evidence involving Pregabalin", "title": "Cardiovascular safety of gabapentinoids gabapentin & pregabalin: A systematic review", "authors": "Dutta D, Mohindra R, Kumar M et al.", "journal": "The Indian journal of medical research", "year": 2025, "pmid": "40536375", "url": "https://pubmed.ncbi.nlm.nih.gov/40536375/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.25259/IJMR_1990_2024", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40536375/", "publicSourceType": "PMID" }, { "text": "Mayoral V, Galvez R, Ferrándiz M et al.. Pregabalin vs. gabapentin in the treatment of neuropathic pain: a comprehensive systematic review and meta-analysis of effectiveness and safety. Frontiers in pain research (Lausanne, Switzerland). 2024", "claim": "PubMed-indexed evidence involving Pregabalin", "title": "Pregabalin vs. gabapentin in the treatment of neuropathic pain: a comprehensive systematic review and meta-analysis of effectiveness and safety", "authors": "Mayoral V, Galvez R, Ferrándiz M et al.", "journal": "Frontiers in pain research (Lausanne, Switzerland)", "year": 2024, "pmid": "39839199", "url": "https://pubmed.ncbi.nlm.nih.gov/39839199/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fpain.2024.1513597", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39839199/", "publicSourceType": "PMID" }, { "text": "Shen X, Chen X, He Y et al.. Efficacy and safety of pregabalin in eye pain: A systematic review. Medicine. 2023", "claim": "PubMed-indexed evidence involving Pregabalin", "title": "Efficacy and safety of pregabalin in eye pain: A systematic review", "authors": "Shen X, Chen X, He Y et al.", "journal": "Medicine", "year": 2023, "pmid": "36820573", "url": "https://pubmed.ncbi.nlm.nih.gov/36820573/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MD.0000000000032875", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36820573/", "publicSourceType": "PMID" }, { "text": "Liang Z, Xu Y, Xue Z. The analgesic efficacy of pregabalin versus placebo for septorhinoplasty: A meta-analysis. Medicine. 2023", "claim": "PubMed-indexed evidence involving Pregabalin", "title": "The analgesic efficacy of pregabalin versus placebo for septorhinoplasty: A meta-analysis", "authors": "Liang Z, Xu Y, Xue Z", "journal": "Medicine", "year": 2023, "pmid": "37058015", "url": "https://pubmed.ncbi.nlm.nih.gov/37058015/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MD.0000000000033259", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37058015/", "publicSourceType": "PMID" }, { "text": "Giménez-Campos MS, Pimenta-Fermisson-Ramos P, Díaz-Cambronero JI et al.. A systematic review and meta-analysis of the effectiveness and adverse events of gabapentin and pregabalin for sciatica pain. Atencion primaria. 2022", "claim": "PubMed-indexed evidence involving Pregabalin", "title": "A systematic review and meta-analysis of the effectiveness and adverse events of gabapentin and pregabalin for sciatica pain", "authors": "Giménez-Campos MS, Pimenta-Fermisson-Ramos P, Díaz-Cambronero JI et al.", "journal": "Atencion primaria", "year": 2022, "pmid": "34637958", "url": "https://pubmed.ncbi.nlm.nih.gov/34637958/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.aprim.2021.102144", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34637958/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Gabapentinoid / Anticonvulsant", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "6.3 hours", "onsetOfAction": "Within 1 week; full benefit may take 2–4 weeks", "commonBrandNames": [ "Lyrica", "Lyrica CR" ], "controlledSubstanceSchedule": "Schedule V", "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "pregabalin" }, { "id": "RX-GIPAIN-033", "name": "Allopurinol", "alternateNames": [ "Zyloprim" ], "category": "Prescription", "subcategory": "Xanthine Oxidase Inhibitor (Gout)", "overview": "A xanthine oxidase inhibitor used as first-line urate-lowering therapy for the chronic management of gout and hyperuricemia. Allopurinol reduces serum uric acid levels by inhibiting the enzyme that converts hypoxanthine and xanthine to uric acid, preventing the formation and deposition of monosodium urate crystals in joints and tissues.", "mechanismOfAction": "Inhibits xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine and xanthine to uric acid. By blocking this final step in purine catabolism, allopurinol and its active metabolite oxypurinol reduce serum uric acid production. This lowers the total body urate pool and prevents new crystal deposition.", "commonBenefits": [ "Reduction of serum uric acid levels", "Prevention of recurrent gout flares", "Prevention and dissolution of uric acid kidney stones", "Treatment of hyperuricemia secondary to tumor lysis syndrome", "Reduction of tophaceous deposits" ], "commonDosageRange": "Start 100 mg daily, titrate by 100 mg every 2–4 weeks to target serum uric acid <6 mg/dL; typical range 200–600 mg daily (max 800 mg/day) (as prescribed by your physician)", "recommendedForm": "Tablet", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take after meals to reduce GI side effects; maintain adequate fluid intake to prevent xanthine stone formation" }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Skin rash (discontinue if occurs)", "Gout flare during initiation (use prophylaxis)", "Elevated liver enzymes", "Nausea and diarrhea", "Hypersensitivity syndrome (rare but potentially fatal: fever, rash, eosinophilia, hepatitis, renal failure)", "Stevens-Johnson syndrome / toxic epidermal necrolysis (rare)" ], "contraindications": [ "Known hypersensitivity to allopurinol", "HLA-B*5801 positive patients (strongly associated with severe cutaneous adverse reactions, screen in high-risk populations)", "Concurrent use with azathioprine or mercaptopurine (unless dose is significantly reduced)", "Caution in renal impairment (dose adjustment required)" ], "iconName": "cross.case.fill", "colorHex": "26A69A", "tags": [ "pain", "gout", "uric-acid", "xanthine-oxidase-inhibitor", "hyperuricemia" ], "sources": [ { "text": "FitzGerald JD et al. 2020 American College of Rheumatology Guideline for Management of Gout. Arthritis Care Res. 2020.", "pmid": "32390306", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32390306/", "publicSourceType": "PMID" }, { "text": "Stamp LK et al. Starting dose is a risk factor for allopurinol hypersensitivity syndrome: a proposed safe starting dose of allopurinol. Arthritis Rheum. 2012.", "pmid": "38766703", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38766703/", "publicSourceType": "PMID" }, { "text": "Hershfield MS et al. Clinical pharmacogenetics implementation consortium guidelines for human leukocyte antigen-B genotype and allopurinol dosing. Clin Pharmacol Ther. 2013.", "pmid": "23232549", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23232549/", "publicSourceType": "PMID" }, { "text": "Helget LN, Davis-Karim A, O'Dell JR et al.. Efficacy and Safety of Allopurinol and Febuxostat in Patients With Gout and CKD: Subgroup Analysis of the STOP Gout Trial. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2024", "pmid": "38906504", "doi": "10.1053/j.ajkd.2024.04.017", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38906504/", "publicSourceType": "PMID" }, { "text": "Mackenzie IS, Ford I, Nuki G et al.. Long-term cardiovascular safety of febuxostat compared with allopurinol in patients with gout (FAST): a multicentre, prospective, randomised, open-label, non-inferiority trial. Lancet (London, England). 2020", "pmid": "33181081", "doi": "10.1016/S0140-6736(20)32234-0", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33181081/", "publicSourceType": "PMID" }, { "text": "Alem MM. Allopurinol and endothelial function: A systematic review with meta-analysis of randomized controlled trials. Cardiovascular therapeutics. 2018", "claim": "PubMed-indexed evidence involving Allopurinol", "title": "Allopurinol and endothelial function: A systematic review with meta-analysis of randomized controlled trials", "authors": "Alem MM", "journal": "Cardiovascular therapeutics", "year": 2018, "pmid": "29673103", "url": "https://pubmed.ncbi.nlm.nih.gov/29673103/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/1755-5922.12432", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29673103/", "publicSourceType": "PMID" }, { "text": "Chen AT, Malmstrom T, Nasrallah HA. Allopurinol augmentation in acute mania: A meta-analysis of placebo-controlled trials. Journal of affective disorders. 2018", "claim": "PubMed-indexed evidence involving Allopurinol", "title": "Allopurinol augmentation in acute mania: A meta-analysis of placebo-controlled trials", "authors": "Chen AT, Malmstrom T, Nasrallah HA", "journal": "Journal of affective disorders", "year": 2018, "pmid": "29017068", "url": "https://pubmed.ncbi.nlm.nih.gov/29017068/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jad.2017.09.034", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29017068/", "publicSourceType": "PMID" }, { "text": "Deng G, Qiu Z, Li D et al.. Effects of Allopurinol on Arterial Stiffness: A Meta-Analysis of Randomized Controlled Trials. Medical science monitor : international medical journal of experimental and clinical research. 2016", "claim": "PubMed-indexed evidence involving Allopurinol", "title": "Effects of Allopurinol on Arterial Stiffness: A Meta-Analysis of Randomized Controlled Trials", "authors": "Deng G, Qiu Z, Li D et al.", "journal": "Medical science monitor : international medical journal of experimental and clinical research", "year": 2016, "pmid": "27110924", "url": "https://pubmed.ncbi.nlm.nih.gov/27110924/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.12659/msm.898370", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27110924/", "publicSourceType": "PMID" }, { "text": "Chen J, Zhang Y, Wang Y et al.. Comparative efficacy and safety of febuxostat and allopurinol in chronic kidney disease stage 3-5 patients with asymptomatic hyperuricemia: a network meta-analysis. Renal failure. 2025", "claim": "PubMed-indexed evidence involving Allopurinol", "title": "Comparative efficacy and safety of febuxostat and allopurinol in chronic kidney disease stage 3-5 patients with asymptomatic hyperuricemia: a network meta-analysis", "authors": "Chen J, Zhang Y, Wang Y et al.", "journal": "Renal failure", "year": 2025, "pmid": "40012480", "url": "https://pubmed.ncbi.nlm.nih.gov/40012480/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/0886022X.2025.2470478", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40012480/", "publicSourceType": "PMID" }, { "text": "Zhang F, Wang Y. The efficacy and safety of different doses of febuxostat and allopurinol: A meta-analysis. Joint diseases and related surgery. 2025", "claim": "PubMed-indexed evidence involving Allopurinol", "title": "The efficacy and safety of different doses of febuxostat and allopurinol: A meta-analysis", "authors": "Zhang F, Wang Y", "journal": "Joint diseases and related surgery", "year": 2025, "pmid": "40783988", "url": "https://pubmed.ncbi.nlm.nih.gov/40783988/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.52312/jdrs.2025.1976", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40783988/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Xanthine Oxidase Inhibitor", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "1–2 hours (oxypurinol active metabolite: 15–18 hours)", "onsetOfAction": "2–3 days to reduce uric acid; weeks to months for full clinical benefit", "commonBrandNames": [ "Zyloprim", "Aloprim" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Serum uric acid every 2–5 weeks during dose titration; CBC, LFTs, and renal function at baseline and periodically" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "allopurinol" }, { "id": "RX-GIPAIN-034", "name": "Colchicine", "alternateNames": [ "Colcrys" ], "category": "Prescription", "subcategory": "Anti-Gout / Anti-Inflammatory", "overview": "An anti-inflammatory alkaloid derived from the autumn crocus plant, used for the treatment and prevention of gout flares and for familial Mediterranean fever. Colchicine has also shown cardiovascular benefit in reducing recurrent cardiovascular events (COLCOT trial) and pericarditis. It has a narrow therapeutic index requiring careful dosing.", "mechanismOfAction": "Binds to tubulin and inhibits its polymerization into microtubules, disrupting multiple inflammatory processes. This inhibits neutrophil migration to sites of urate crystal deposition, impairs neutrophil phagocytosis and degranulation, reduces inflammasome (NLRP3) activation and IL-1 beta release, and decreases leukotriene B4 and prostaglandin production. The overall effect is a potent reduction in the inflammatory response to monosodium urate crystals.", "commonBenefits": [ "Treatment of acute gout flares", "Prophylaxis against gout flares during urate-lowering therapy initiation", "Treatment of familial Mediterranean fever", "Cardiovascular event reduction (post-MI, per COLCOT trial)", "Treatment and prevention of recurrent pericarditis" ], "commonDosageRange": "Acute gout flare: 1.2 mg at first sign, then 0.6 mg one hour later (max 1.8 mg per flare); Prophylaxis: 0.6 mg once or twice daily (as prescribed by your physician)", "recommendedForm": "Tablet or capsule", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Can be taken with or without food; reduce dose or avoid with strong CYP3A4 or P-glycoprotein inhibitors" }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Diarrhea (most common, dose-limiting)", "Nausea and vomiting", "Abdominal cramping", "Myopathy and rhabdomyolysis (especially with statins or renal impairment)", "Bone marrow suppression (with chronic high-dose use)", "Peripheral neuropathy (rare, with chronic use)" ], "contraindications": [ "Concurrent use of strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) in patients with renal or hepatic impairment", "Severe renal impairment requiring dialysis", "Severe hepatic impairment", "Known hypersensitivity to colchicine", "Blood dyscrasias" ], "iconName": "cross.case.fill", "colorHex": "26A69A", "tags": [ "pain", "gout", "anti-inflammatory", "pericarditis", "cardiovascular" ], "sources": [ { "text": "Tardif JC et al. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction (COLCOT trial). N Engl J Med. 2019.", "pmid": "31733140", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31733140/", "publicSourceType": "PMID" }, { "text": "FitzGerald JD et al. 2020 American College of Rheumatology Guideline for Management of Gout. Arthritis Care Res. 2020.", "pmid": "32390306", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32390306/", "publicSourceType": "PMID" }, { "text": "Terkeltaub RA et al. High versus low dosing of oral colchicine for early acute gout flare. Arthritis Rheum. 2010.", "pmid": "20131255", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20131255/", "publicSourceType": "PMID" }, { "text": "Deftereos SG, Beerkens FJ, Shah B et al.. Colchicine in Cardiovascular Disease: In-Depth Review. Circulation. 2022", "pmid": "34965168", "doi": "10.1161/CIRCULATIONAHA.121.056171", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34965168/", "publicSourceType": "PMID" }, { "text": "Fiolet ATL, Opstal TSJ, Mosterd A et al.. Efficacy and safety of low-dose colchicine in patients with coronary disease: a systematic review and meta-analysis of randomized trials. European heart journal. 2021", "claim": "PubMed-indexed evidence involving Colchicine", "title": "Efficacy and safety of low-dose colchicine in patients with coronary disease: a systematic review and meta-analysis of randomized trials", "authors": "Fiolet ATL, Opstal TSJ, Mosterd A et al.", "journal": "European heart journal", "year": 2021, "pmid": "33769515", "url": "https://pubmed.ncbi.nlm.nih.gov/33769515/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/eurheartj/ehab115", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33769515/", "publicSourceType": "PMID" }, { "text": "Akl E, Sahami N, Labos C et al.. Meta-Analysis of Randomized Trials: Efficacy and Safety of Colchicine for Secondary Prevention of Cardiovascular Disease. Journal of interventional cardiology. 2024", "claim": "PubMed-indexed evidence involving Colchicine", "title": "Meta-Analysis of Randomized Trials: Efficacy and Safety of Colchicine for Secondary Prevention of Cardiovascular Disease", "authors": "Akl E, Sahami N, Labos C et al.", "journal": "Journal of interventional cardiology", "year": 2024, "pmid": "38505729", "url": "https://pubmed.ncbi.nlm.nih.gov/38505729/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1155/2024/8646351", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38505729/", "publicSourceType": "PMID" }, { "text": "Younas A, Awan Z, Khan T et al.. The effect of colchicine on myocardial infarction: An updated systematic review and meta-analysis of randomized controlled trials. Current problems in cardiology. 2025", "claim": "PubMed-indexed evidence involving Colchicine", "title": "The effect of colchicine on myocardial infarction: An updated systematic review and meta-analysis of randomized controlled trials", "authors": "Younas A, Awan Z, Khan T et al.", "journal": "Current problems in cardiology", "year": 2025, "pmid": "39393620", "url": "https://pubmed.ncbi.nlm.nih.gov/39393620/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.cpcardiol.2024.102878", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39393620/", "publicSourceType": "PMID" }, { "text": "Li HY, Cheriyan J, Chan TK et al.. Colchicine for the Secondary Prevention of Cardiovascular Diseases: A Cumulative-Dose Meta-analysis of Randomized Controlled Trials including 31,397 Subjects Worldwide. American journal of cardiovascular drugs : drugs, devices, and other interventions. 2026", "claim": "PubMed-indexed evidence involving Colchicine", "title": "Colchicine for the Secondary Prevention of Cardiovascular Diseases: A Cumulative-Dose Meta-analysis of Randomized Controlled Trials including 31,397 Subjects Worldwide", "authors": "Li HY, Cheriyan J, Chan TK et al.", "journal": "American journal of cardiovascular drugs : drugs, devices, and other interventions", "year": 2026, "pmid": "40889093", "url": "https://pubmed.ncbi.nlm.nih.gov/40889093/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s40256-025-00743-y", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40889093/", "publicSourceType": "PMID" }, { "text": "Xie S, Galimberti F, Olmastroni E et al.. Colchicine and cardiovascular events: An updated meta-analysis of published randomized controlled trials. Journal of internal medicine. 2025", "claim": "PubMed-indexed evidence involving Colchicine", "title": "Colchicine and cardiovascular events: An updated meta-analysis of published randomized controlled trials", "authors": "Xie S, Galimberti F, Olmastroni E et al.", "journal": "Journal of internal medicine", "year": 2025, "pmid": "41236500", "url": "https://pubmed.ncbi.nlm.nih.gov/41236500/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/joim.20107", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41236500/", "publicSourceType": "PMID" }, { "text": "Schwier NC, Cornelio CK, Boylan PM. A systematic review of the drug-drug interaction between statins and colchicine: Patient characteristics, etiologies, and clinical management strategies. Pharmacotherapy. 2022", "claim": "PubMed-indexed evidence involving Colchicine", "title": "A systematic review of the drug-drug interaction between statins and colchicine: Patient characteristics, etiologies, and clinical management strategies", "authors": "Schwier NC, Cornelio CK, Boylan PM", "journal": "Pharmacotherapy", "year": 2022, "pmid": "35175631", "url": "https://pubmed.ncbi.nlm.nih.gov/35175631/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/phar.2674", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35175631/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Anti-Gout / Microtubule Inhibitor", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "26.6–31.2 hours", "onsetOfAction": "12–24 hours for gout flare relief", "commonBrandNames": [ "Colcrys", "Mitigare" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "CBC periodically with long-term use; renal and hepatic function at baseline" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "colchicine" }, { "id": "RX-GIPAIN-035", "name": "Febuxostat", "alternateNames": [ "Uloric" ], "category": "Prescription", "subcategory": "Xanthine Oxidase Inhibitor (Gout)", "overview": "A non-purine selective xanthine oxidase inhibitor used for the chronic management of hyperuricemia in patients with gout. 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Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout (CARES trial). N Engl J Med. 2018.", "pmid": "29527974", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29527974/", "publicSourceType": "PMID" }, { "text": "FitzGerald JD et al. 2020 American College of Rheumatology Guideline for Management of Gout. Arthritis Care Res. 2020.", "pmid": "32390306", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32390306/", "publicSourceType": "PMID" }, { "text": "Becker MA et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med. 2005.", "pmid": "16339094", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16339094/", "publicSourceType": "PMID" }, { "text": "Sun J, Wang Y, Cheng Y et al.. Efficacy and Safety of Dotinurad Versus Febuxostat for the Treatment of Gout: A Randomized, Multicenter, Double-Blind, Phase 3 Trial in China. Arthritis & rheumatology (Hoboken, N.J.). 2025", "pmid": "40417858", "doi": "10.1002/art.43261", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40417858/", "publicSourceType": "PMID" }, { "text": "Kimura K, Hosoya T, Uchida S et al.. Febuxostat Therapy for Patients With Stage 3 CKD and Asymptomatic Hyperuricemia: A Randomized Trial. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2018", "pmid": "30177485", "doi": "10.1053/j.ajkd.2018.06.028", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30177485/", "publicSourceType": "PMID" }, { "text": "Yang XH, Zhang BL, Cheng Y et al.. Febuxostat provides renoprotection in patients with hyperuricemia or gout: a systematic review and meta-analysis of randomized controlled trials. Annals of medicine. 2024", "claim": "PubMed-indexed evidence involving Febuxostat", "title": "Febuxostat provides renoprotection in patients with hyperuricemia or gout: a systematic review and meta-analysis of randomized controlled trials", "authors": "Yang XH, Zhang BL, Cheng Y et al.", "journal": "Annals of medicine", "year": 2024, "pmid": "38738384", "url": "https://pubmed.ncbi.nlm.nih.gov/38738384/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/07853890.2024.2332956", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38738384/", "publicSourceType": "PMID" }, { "text": "Chen J, Zhang Y, Wang Y et al.. Comparative efficacy and safety of febuxostat and allopurinol in chronic kidney disease stage 3-5 patients with asymptomatic hyperuricemia: a network meta-analysis. Renal failure. 2025", "claim": "PubMed-indexed evidence involving Febuxostat", "title": "Comparative efficacy and safety of febuxostat and allopurinol in chronic kidney disease stage 3-5 patients with asymptomatic hyperuricemia: a network meta-analysis", "authors": "Chen J, Zhang Y, Wang Y et al.", "journal": "Renal failure", "year": 2025, "pmid": "40012480", "url": "https://pubmed.ncbi.nlm.nih.gov/40012480/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/0886022X.2025.2470478", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40012480/", "publicSourceType": "PMID" }, { "text": "Zhang F, Wang Y. The efficacy and safety of different doses of febuxostat and allopurinol: A meta-analysis. Joint diseases and related surgery. 2025", "claim": "PubMed-indexed evidence involving Febuxostat", "title": "The efficacy and safety of different doses of febuxostat and allopurinol: A meta-analysis", "authors": "Zhang F, Wang Y", "journal": "Joint diseases and related surgery", "year": 2025, "pmid": "40783988", "url": "https://pubmed.ncbi.nlm.nih.gov/40783988/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.52312/jdrs.2025.1976", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40783988/", "publicSourceType": "PMID" }, { "text": "Guan X, Zhang S, Liu J et al.. Cardiovascular safety of febuxostat and allopurinol in patients with gout: A meta-analysis. Frontiers in pharmacology. 2022", "claim": "PubMed-indexed evidence involving Febuxostat", "title": "Cardiovascular safety of febuxostat and allopurinol in patients with gout: A meta-analysis", "authors": "Guan X, Zhang S, Liu J et al.", "journal": "Frontiers in pharmacology", "year": 2022, "pmid": "36249825", "url": "https://pubmed.ncbi.nlm.nih.gov/36249825/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fphar.2022.998441", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36249825/", "publicSourceType": "PMID" }, { "text": "Cuenca JA, Balda J, Palacio A et al.. Febuxostat and Cardiovascular Events: A Systematic Review and Meta-Analysis. International journal of rheumatology. 2019", "claim": "PubMed-indexed evidence involving Febuxostat", "title": "Febuxostat and Cardiovascular Events: A Systematic Review and Meta-Analysis", "authors": "Cuenca JA, Balda J, Palacio A et al.", "journal": "International journal of rheumatology", "year": 2019, "pmid": "30863448", "url": "https://pubmed.ncbi.nlm.nih.gov/30863448/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1155/2019/1076189", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30863448/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Xanthine Oxidase Inhibitor (Non-Purine)", "blackBoxWarnings": [ "Cardiovascular death: In a cardiovascular outcomes trial (CARES), febuxostat was associated with a higher rate of cardiovascular death compared to allopurinol. Febuxostat should only be used in patients who have an inadequate response to or cannot tolerate allopurinol." ], "fdaPregnancyCategory": "C", "halfLife": "5–8 hours", "onsetOfAction": "Within 1 week to reduce serum uric acid", "commonBrandNames": [ "Uloric" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "LFTs at baseline and periodically (at 2 and 4 months after initiation, then as indicated); serum uric acid levels" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "febuxostat" }, { "id": "RX-GIPAIN-036", "name": "Methotrexate", "alternateNames": [ "Trexall", "MTX" ], "category": "Prescription", "subcategory": "Disease-Modifying Antirheumatic Drug (DMARD)", "overview": "The anchor DMARD and most widely used first-line therapy for rheumatoid arthritis, also indicated for psoriatic arthritis, psoriasis, and certain cancers. Low-dose weekly methotrexate is the cornerstone of RA treatment per ACR guidelines. 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Arthritis Care Res. 2021.", "pmid": "34101387", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34101387/", "publicSourceType": "PMID" }, { "text": "Cronstein BN, Aune TM. Methotrexate and its mechanisms of action in inflammatory arthritis. Nat Rev Rheumatol. 2020.", "pmid": "32066940", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32066940/", "publicSourceType": "PMID" }, { "text": "Visser K, van der Heijde D. Optimal dosage and route of administration of methotrexate in rheumatoid arthritis: a systematic review of the literature. Ann Rheum Dis. 2009.", "pmid": "19033291", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19033291/", "publicSourceType": "PMID" }, { "text": "Wang W, Zhou H, Liu L. Side effects of methotrexate therapy for rheumatoid arthritis: A systematic review. European journal of medicinal chemistry. 2018", "pmid": "30243154", "doi": "10.1016/j.ejmech.2018.09.027", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30243154/", "publicSourceType": "PMID" }, { "text": "Queiroz I, Pimentel T, Gallo Ruelas M et al.. Methotrexate for osteoarthritis: a systematic review meta-analysis of randomized controlled trials. Inflammopharmacology. 2025", "claim": "PubMed-indexed evidence involving Methotrexate", "title": "Methotrexate for osteoarthritis: a systematic review meta-analysis of randomized controlled trials", "authors": "Queiroz I, Pimentel T, Gallo Ruelas M et al.", "journal": "Inflammopharmacology", "year": 2025, "pmid": "39614960", "url": "https://pubmed.ncbi.nlm.nih.gov/39614960/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s10787-024-01604-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39614960/", "publicSourceType": "PMID" }, { "text": "Toh VTR, Gerard G, Tay ZQ et al.. Efficacy and safety of methotrexate in the treatment of proliferative vitreoretinopathy: a systematic review. Eye (London, England). 2025", "claim": "PubMed-indexed evidence involving Methotrexate", "title": "Efficacy and safety of methotrexate in the treatment of proliferative vitreoretinopathy: a systematic review", "authors": "Toh VTR, Gerard G, Tay ZQ et al.", "journal": "Eye (London, England)", "year": 2025, "pmid": "39674839", "url": "https://pubmed.ncbi.nlm.nih.gov/39674839/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1038/s41433-024-03503-5", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39674839/", "publicSourceType": "PMID" }, { "text": "Han JM, Choi KH, Lee HH et al.. Association between SLCO1B1 polymorphism and methotrexate-induced hepatotoxicity: a systematic review and meta-analysis. Anti-cancer drugs. 2022", "claim": "PubMed-indexed evidence involving Methotrexate", "title": "Association between SLCO1B1 polymorphism and methotrexate-induced hepatotoxicity: a systematic review and meta-analysis", "authors": "Han JM, Choi KH, Lee HH et al.", "journal": "Anti-cancer drugs", "year": 2022, "pmid": "34726639", "url": "https://pubmed.ncbi.nlm.nih.gov/34726639/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/CAD.0000000000001125", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34726639/", "publicSourceType": "PMID" }, { "text": "Campbell JM, Bateman E, Stephenson MD et al.. Methotrexate-induced toxicity pharmacogenetics: an umbrella review of systematic reviews and meta-analyses. Cancer chemotherapy and pharmacology. 2016", "claim": "PubMed-indexed evidence involving Methotrexate", "title": "Methotrexate-induced toxicity pharmacogenetics: an umbrella review of systematic reviews and meta-analyses", "authors": "Campbell JM, Bateman E, Stephenson MD et al.", "journal": "Cancer chemotherapy and pharmacology", "year": 2016, "pmid": "27142726", "url": "https://pubmed.ncbi.nlm.nih.gov/27142726/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00280-016-3043-5", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27142726/", "publicSourceType": "PMID" }, { "text": "Tanaka Y, Westhovens R, Sun H et al.. Filgotinib Radiographic and Clinical Efficacy Versus Other JAK Inhibitors and Adalimumab in Patients With Rheumatoid Arthritis and Inadequate Response to Methotrexate: A Systematic Review and Network Meta-Analysis. Rheumatology and therapy. 2025", "claim": "PubMed-indexed evidence involving Methotrexate", "title": "Filgotinib Radiographic and Clinical Efficacy Versus Other JAK Inhibitors and Adalimumab in Patients With Rheumatoid Arthritis and Inadequate Response to Methotrexate: A Systematic Review and Network Meta-Analysis", "authors": "Tanaka Y, Westhovens R, Sun H et al.", "journal": "Rheumatology and therapy", "year": 2025, "pmid": "40208566", "url": "https://pubmed.ncbi.nlm.nih.gov/40208566/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s40744-025-00757-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40208566/", "publicSourceType": "PMID" }, { "text": "Cheng Y, Zhang Y, Zhang Y et al.. Population pharmacokinetic analyses of methotrexate in pediatric patients: a systematic review. European journal of clinical pharmacology. 2024", "claim": "PubMed-indexed evidence involving Methotrexate", "title": "Population pharmacokinetic analyses of methotrexate in pediatric patients: a systematic review", "authors": "Cheng Y, Zhang Y, Zhang Y et al.", "journal": "European journal of clinical pharmacology", "year": 2024, "pmid": "38498098", "url": "https://pubmed.ncbi.nlm.nih.gov/38498098/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00228-024-03665-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38498098/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Antimetabolite / Disease-Modifying Antirheumatic Drug (DMARD)", "blackBoxWarnings": [ "Hepatotoxicity, fibrosis, and cirrhosis: monitor LFTs; risk increases with cumulative dose and concurrent hepatotoxins", "Bone marrow suppression: can cause aplastic anemia, pancytopenia, leukopenia, thrombocytopenia; monitor CBC regularly", "Lung disease: methotrexate-induced lung disease, including acute or chronic interstitial pneumonitis, may occur and may be fatal", "Fetal death and teratogenicity: Pregnancy Category X; must not be used in pregnant women for non-neoplastic diseases; women of childbearing potential must use effective contraception" ], "fdaPregnancyCategory": "X", "halfLife": "3–10 hours (low dose); polyglutamate metabolites remain intracellularly for weeks", "onsetOfAction": "3–6 weeks for initial improvement; full benefit 12 weeks or more", "commonBrandNames": [ "Trexall", "Otrexup", "Rasuvo", "Xatmep" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "CBC, LFTs, renal function every 1–3 months; baseline chest X-ray and hepatitis B/C screening recommended" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "methotrexate" }, { "id": "RX-GIPAIN-037", "name": "Hydroxychloroquine", "alternateNames": [ "Plaquenil" ], "category": "Prescription", "subcategory": "Disease-Modifying Antirheumatic Drug (DMARD)", "overview": "An antimalarial drug widely used as a DMARD for the treatment of rheumatoid arthritis and systemic lupus erythematosus (SLE). Hydroxychloroquine is considered one of the safest DMARDs with a favorable side effect profile and is recommended in virtually all SLE patients unless contraindicated. It is often used in combination with methotrexate in RA.", "mechanismOfAction": "Accumulates in lysosomes and raises intralysosomal pH, inhibiting antigen processing and presentation through MHC class II molecules. This reduces T-cell activation and the downstream inflammatory cascade. Hydroxychloroquine also inhibits Toll-like receptor (TLR7 and TLR9) signaling, reducing type I interferon and pro-inflammatory cytokine production. Additional effects include inhibition of phospholipase A2 and platelet aggregation.", "commonBenefits": [ "Disease modification in rheumatoid arthritis", "Essential therapy in systemic lupus erythematosus", "Improved survival in SLE patients", "Favorable safety profile among DMARDs", "Lipid-lowering and anti-thrombotic properties", "Reduction of SLE flares" ], "commonDosageRange": "200–400 mg daily (not exceeding 5 mg/kg/day to minimize retinal toxicity) (as prescribed by your physician)", "recommendedForm": "Tablet", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food or milk to reduce GI side effects; very long tissue half-life means steady state takes months" }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Nausea and GI upset", "Skin rash and hyperpigmentation", "Retinal toxicity (bull's-eye maculopathy with long-term use)", "Headache", "Dizziness", "QT prolongation (rare)", "Myopathy (rare, with long-term use)", "Cardiomyopathy (very rare)" ], "contraindications": [ "Known hypersensitivity to hydroxychloroquine or 4-aminoquinolines", "Pre-existing retinal or macular disease", "Significant visual field changes from prior 4-aminoquinoline use", "Long QT syndrome or concurrent QT-prolonging medications", "G6PD deficiency (use with caution)" ], "iconName": "cross.case.fill", "colorHex": "FF7043", "tags": [ "pain", "dmard", "rheumatoid-arthritis", "lupus", "sle", "antimalarial" ], "sources": [ { "text": "Fraenkel L et al. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res. 2021.", "pmid": "34101387", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34101387/", "publicSourceType": "PMID" }, { "text": "Ruiz-Irastorza G et al. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis. 2010.", "pmid": "19892750", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19892750/", "publicSourceType": "PMID" }, { "text": "Marmor MF et al. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology. 2016.", "pmid": "26992838", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26992838/", "publicSourceType": "PMID" }, { "text": "Huo R, Wei C, Yang Y et al.. Hydroxychloroquine: A double‑edged sword (Review). Molecular medicine reports. 2025", "pmid": "39981928", "doi": "10.3892/mmr.2025.13467", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39981928/", "publicSourceType": "PMID" }, { "text": "Setty MJ, Kavi RK, Sulthana P et al.. Psychiatric Adverse Effects From Hydroxychloroquine Use: A Systematic Review. The primary care companion for CNS disorders. 2025", "claim": "PubMed-indexed evidence involving Hydroxychloroquine", "title": "Psychiatric Adverse Effects From Hydroxychloroquine Use: A Systematic Review", "authors": "Setty MJ, Kavi RK, Sulthana P et al.", "journal": "The primary care companion for CNS disorders", "year": 2025, "pmid": "40446824", "url": "https://pubmed.ncbi.nlm.nih.gov/40446824/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.4088/PCC.24r03857", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40446824/", "publicSourceType": "PMID" }, { "text": "Garcia MC, Tsang K, Lohit S et al.. Hydroxychloroquine-Chloroquine, QT-Prolongation, and Major Adverse Cardiac Events: A Meta-analysis and Scoping Review. The Annals of pharmacotherapy. 2024", "claim": "PubMed-indexed evidence involving Hydroxychloroquine", "title": "Hydroxychloroquine-Chloroquine, QT-Prolongation, and Major Adverse Cardiac Events: A Meta-analysis and Scoping Review", "authors": "Garcia MC, Tsang K, Lohit S et al.", "journal": "The Annals of pharmacotherapy", "year": 2024, "pmid": "37881891", "url": "https://pubmed.ncbi.nlm.nih.gov/37881891/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/10600280231204969", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37881891/", "publicSourceType": "PMID" }, { "text": "Fernandes CP, Vernier LS, Dallegrave E et al.. The Ototoxicity of Chloroquine and Hydroxychloroquine: A Systematic Review. International archives of otorhinolaryngology. 2022", "claim": "PubMed-indexed evidence involving Hydroxychloroquine", "title": "The Ototoxicity of Chloroquine and Hydroxychloroquine: A Systematic Review", "authors": "Fernandes CP, Vernier LS, Dallegrave E et al.", "journal": "International archives of otorhinolaryngology", "year": 2022, "pmid": "35096175", "url": "https://pubmed.ncbi.nlm.nih.gov/35096175/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1055/s-0041-1740986", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35096175/", "publicSourceType": "PMID" }, { "text": "Sharma AN, Mesinkovska NA, Paravar T. Characterizing the adverse dermatologic effects of hydroxychloroquine: A systematic review. Journal of the American Academy of Dermatology. 2020", "claim": "PubMed-indexed evidence involving Hydroxychloroquine", "title": "Characterizing the adverse dermatologic effects of hydroxychloroquine: A systematic review", "authors": "Sharma AN, Mesinkovska NA, Paravar T", "journal": "Journal of the American Academy of Dermatology", "year": 2020, "pmid": "32289395", "url": "https://pubmed.ncbi.nlm.nih.gov/32289395/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jaad.2020.04.024", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32289395/", "publicSourceType": "PMID" }, { "text": "Zhang Z, Liu X, Ye P et al.. Efficacy and Safety of Hydroxychloroquine in Patients with IgA Nephropathy: A Meta-Analysis. 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Systematic review and meta-analysis of the efficacy and safety of leflunomide and methotrexate in the treatment of rheumatoid arthritis. Reumatologia clinica. 2019", "pmid": "28867467", "doi": "10.1016/j.reuma.2017.07.020", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28867467/", "publicSourceType": "PMID" }, { "text": "Padda IS, Goyal A. Leflunomide. 2026", "pmid": "32491731", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32491731/", "publicSourceType": "PMID" }, { "text": "Yi J, He Z, Xu S et al.. Efficacy and safety of leflunomide in IgA nephropathy: a systematic review and meta-analysis. 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A meta-analysis of short versus long therapy with a proton pump inhibitor, clarithromycin and either metronidazole or amoxycillin for treating Helicobacter pylori infection. Alimentary pharmacology & therapeutics. 2000", "claim": "PubMed-indexed evidence involving Amoxicillin", "title": "A meta-analysis of short versus long therapy with a proton pump inhibitor, clarithromycin and either metronidazole or amoxycillin for treating Helicobacter pylori infection", "authors": "Calvet X, García N, López T et al.", "journal": "Alimentary pharmacology & therapeutics", "year": 2000, "pmid": "10792124", "url": "https://pubmed.ncbi.nlm.nih.gov/10792124/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1046/j.1365-2036.2000.00744.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10792124/", "publicSourceType": "PMID" }, { "text": "Gisbert JP, González L, Calvet X et al.. Proton pump inhibitor, clarithromycin and either amoxycillin or nitroimidazole: a meta-analysis of eradication of Helicobacter pylori. Alimentary pharmacology & therapeutics. 2000", "claim": "PubMed-indexed evidence involving Amoxicillin", "title": "Proton pump inhibitor, clarithromycin and either amoxycillin or nitroimidazole: a meta-analysis of eradication of Helicobacter pylori", "authors": "Gisbert JP, González L, Calvet X et al.", "journal": "Alimentary pharmacology & therapeutics", "year": 2000, "pmid": "11012477", "url": "https://pubmed.ncbi.nlm.nih.gov/11012477/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1046/j.1365-2036.2000.00844.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11012477/", "publicSourceType": "PMID" }, { "text": "Huang J, Hunt RH. 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IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis. 2012.", "pmid": "22438350", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22438350/", "publicSourceType": "PMID" }, { "text": "Stevens DL et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the IDSA. Clin Infect Dis. 2014.", "pmid": "24973422", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24973422/", "publicSourceType": "PMID" }, { "text": "Tamma PD et al. Combination therapy for treatment of infections with gram-negative bacteria. Clin Microbiol Rev. 2012.", "pmid": "22763634", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22763634/", "publicSourceType": "PMID" }, { "text": "Tsergouli K, Karampatakis N, Karampatakis T. Efficacy of antimicrobials or placebo compared to amoxicillin-clavulanate in children with acute otitis media: a systematic review. The Turkish journal of pediatrics. 2023", "pmid": "37395955", "doi": "10.24953/turkjped.2022.893", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37395955/", "publicSourceType": "PMID" }, { "text": "Puttagunta S, Aronin SI, Gupta J et al.. Sulopenem versus Amoxicillin/Clavulanate for the Treatment of Uncomplicated Urinary Tract Infection. NEJM evidence. 2025", "pmid": "40552968", "doi": "10.1056/EVIDoa2400414", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40552968/", "publicSourceType": "PMID" }, { "text": "Zhang J, Zhang H, Zhu XJ et al.. Efficacy and safety of vonoprazan and high-dose amoxicillin dual therapy in eradicating Helicobacter pylori: A systematic review and meta-analysis. International journal of antimicrobial agents. 2024", "claim": "PubMed-indexed evidence involving Amoxicillin-Clavulanate", "title": "Efficacy and safety of vonoprazan and high-dose amoxicillin dual therapy in eradicating Helicobacter pylori: A systematic review and meta-analysis", "authors": "Zhang J, Zhang H, Zhu XJ et al.", "journal": "International journal of antimicrobial agents", "year": 2024, "pmid": "39251094", "url": "https://pubmed.ncbi.nlm.nih.gov/39251094/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.ijantimicag.2024.107331", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39251094/", "publicSourceType": "PMID" }, { "text": "Zhou BG, Jiang X, Ding YB et al.. Vonoprazan-amoxicillin dual therapy versus bismuth-containing quadruple therapy for Helicobacter pylori eradication: A systematic review and meta-analysis. Helicobacter. 2024", "claim": "PubMed-indexed evidence involving Amoxicillin-Clavulanate", "title": "Vonoprazan-amoxicillin dual therapy versus bismuth-containing quadruple therapy for Helicobacter pylori eradication: A systematic review and meta-analysis", "authors": "Zhou BG, Jiang X, Ding YB et al.", "journal": "Helicobacter", "year": 2024, "pmid": "37983865", "url": "https://pubmed.ncbi.nlm.nih.gov/37983865/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/hel.13040", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37983865/", "publicSourceType": "PMID" }, { "text": "Ju KP, Kong QZ, Li YY et al.. Low-dose or high-dose amoxicillin in vonoprazan-based dual therapy for Helicobacter pylori eradication? A systematic review and meta-analysis. Helicobacter. 2024", "claim": "PubMed-indexed evidence involving Amoxicillin-Clavulanate", "title": "Low-dose or high-dose amoxicillin in vonoprazan-based dual therapy for Helicobacter pylori eradication? A systematic review and meta-analysis", "authors": "Ju KP, Kong QZ, Li YY et al.", "journal": "Helicobacter", "year": 2024, "pmid": "38900537", "url": "https://pubmed.ncbi.nlm.nih.gov/38900537/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/hel.13054", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38900537/", "publicSourceType": "PMID" }, { "text": "Pejcic AV, Milosavljevic MN, Folic M et al.. Amoxicillin-associated Stevens-Johnson syndrome or toxic epidermal necrolysis: systematic review. Journal of chemotherapy (Florence, Italy). 2023", "claim": "PubMed-indexed evidence involving Amoxicillin-Clavulanate", "title": "Amoxicillin-associated Stevens-Johnson syndrome or toxic epidermal necrolysis: systematic review", "authors": "Pejcic AV, Milosavljevic MN, Folic M et al.", "journal": "Journal of chemotherapy (Florence, Italy)", "year": 2023, "pmid": "35285784", "url": "https://pubmed.ncbi.nlm.nih.gov/35285784/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/1120009X.2022.2051128", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35285784/", "publicSourceType": "PMID" }, { "text": "Bahri N, Dashti S, Mohammadzadeh A et al.. Relationship Between Amoxicillin Use in Pregnancy and Congenital Anomalies: A Systematic Review. Current drug research reviews. 2023", "claim": "PubMed-indexed evidence involving Amoxicillin-Clavulanate", "title": "Relationship Between Amoxicillin Use in Pregnancy and Congenital Anomalies: A Systematic Review", "authors": "Bahri N, Dashti S, Mohammadzadeh A et al.", "journal": "Current drug research reviews", "year": 2023, "pmid": "36515039", "url": "https://pubmed.ncbi.nlm.nih.gov/36515039/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2174/2589977515666221212150311", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36515039/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Penicillin/beta-lactamase inhibitor combination", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "1-1.3 hours (amoxicillin); 1 hour (clavulanate)", "onsetOfAction": "1-2 hours to peak; clinical improvement within 48-72 hours", "commonBrandNames": [ "Augmentin", "Augmentin XR" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "amoxicillin-clavulanate" }, { "id": "RX-INFR-003", "name": "Cephalexin", "alternateNames": [ "Keflex" ], "category": "Prescription", "subcategory": "First-Generation Cephalosporin", "overview": "A first-generation cephalosporin antibiotic with excellent activity against gram-positive cocci including methicillin-susceptible S. aureus (MSSA) and streptococci. Commonly used for skin and soft tissue infections, uncomplicated urinary tract infections, bone and joint infections, and as prophylaxis for certain dental and surgical procedures. It has limited gram-negative coverage compared to later-generation cephalosporins.", "mechanismOfAction": "Binds to penicillin-binding proteins (PBPs) in the bacterial cell wall, inhibiting the transpeptidation step of peptidoglycan synthesis. This disrupts cell wall integrity, leading to osmotic instability and bacterial cell lysis. As a first-generation cephalosporin, it is resistant to some but not all beta-lactamases.", "commonBenefits": [ "Treats skin and soft tissue infections (cellulitis, impetigo)", "Treats uncomplicated urinary tract infections", "Treats bone and joint infections", "Treats streptococcal pharyngitis (penicillin alternative)", "Surgical prophylaxis" ], "commonDosageRange": "250-500 mg every 6 hours or 500 mg-1 g every 12 hours; up to 4 g/day for severe infections (as prescribed by your physician)", "recommendedForm": "Oral capsules or suspension", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Well absorbed orally with approximately 90% bioavailability. Food may delay absorption slightly but does not reduce total absorption. Can be taken with or without food." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Diarrhea", "Nausea", "Abdominal pain", "Skin rash", "Vaginal candidiasis", "Headache" ], "contraindications": [ "Known cephalosporin allergy", "History of anaphylaxis to penicillins (use with caution; cross-reactivity ~1-2%)", "Severe renal impairment (dose adjustment required)", "History of Clostridioides difficile infection" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "antibiotic", "cephalosporin", "infection", "skin-infection", "uti", "gram-positive" ], "sources": [ { "text": "Stevens DL et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the IDSA. Clin Infect Dis. 2014.", "pmid": "24973422", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24973422/", "publicSourceType": "PMID" }, { "text": "Gupta K et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by IDSA and ESCMID. Clin Infect Dis. 2011.", "pmid": "21292654", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21292654/", "publicSourceType": "PMID" }, { "text": "Shu Z et al. Efficacy and safety of first- and second-line antibiotics for cellulitis and erysipelas: a network meta-analysis of randomized controlled trials. Arch Dermatol Res. 2024.", "pmid": "39240378", "doi": "10.1007/s00403-024-03317-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39240378/", "publicSourceType": "PMID" }, { "text": "Valent AM, DeArmond C, Houston JM et al.. Effect of Post-Cesarean Delivery Oral Cephalexin and Metronidazole on Surgical Site Infection Among Obese Women: A Randomized Clinical Trial. JAMA. 2017", "pmid": "28975304", "doi": "10.1001/jama.2017.10567", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28975304/", "publicSourceType": "PMID" }, { "text": "Herman TF, Hashmi MF. Cephalexin. 2026", "pmid": "31747187", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31747187/", "publicSourceType": "PMID" }, { "text": "Kanan M, Atif S, Mohammed F et al.. A Systematic Review on the Clinical Pharmacokinetics of Cephalexin in Healthy and Diseased Populations. Antibiotics (Basel, Switzerland). 2023", "claim": "PubMed-indexed evidence involving Cephalexin", "title": "A Systematic Review on the Clinical Pharmacokinetics of Cephalexin in Healthy and Diseased Populations", "authors": "Kanan M, Atif S, Mohammed F et al.", "journal": "Antibiotics (Basel, Switzerland)", "year": 2023, "pmid": "37760698", "url": "https://pubmed.ncbi.nlm.nih.gov/37760698/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/antibiotics12091402", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37760698/", "publicSourceType": "PMID" }, { "text": "Saad AF, Goldman B, Spencer N et al.. Prophylactic Oral Cephalexin and Metronidazole Compared With Placebo After Cesarean Delivery to Reduce Infection Complications in Women With Obesity: A Randomized Controlled Trial. Obstetrics and gynecology. 2025", "claim": "PubMed-indexed evidence involving Cephalexin", "title": "Prophylactic Oral Cephalexin and Metronidazole Compared With Placebo After Cesarean Delivery to Reduce Infection Complications in Women With Obesity: A Randomized Controlled Trial", "authors": "Saad AF, Goldman B, Spencer N et al.", "journal": "Obstetrics and gynecology", "year": 2025, "pmid": "40403315", "url": "https://pubmed.ncbi.nlm.nih.gov/40403315/", "study_type": "RCT", "confidence": "verify", "doi": "10.1097/AOG.0000000000005936", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40403315/", "publicSourceType": "PMID" }, { "text": "Yadav K, Eagles D, Perry JJ et al.. High-dose cephalexin for cellulitis: a pilot randomized controlled trial. CJEM. 2023", "claim": "PubMed-indexed evidence involving Cephalexin", "title": "High-dose cephalexin for cellulitis: a pilot randomized controlled trial", "authors": "Yadav K, Eagles D, Perry JJ et al.", "journal": "CJEM", "year": 2023, "pmid": "36592299", "url": "https://pubmed.ncbi.nlm.nih.gov/36592299/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/s43678-022-00433-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36592299/", "publicSourceType": "PMID" }, { "text": "Rageh AH, Abdel-Rahim SA, Askal HF et al.. Hydrophilic-interaction planar chromatography in ultra-sensitive determination of α-aminocephalosporin antibiotics. Application to analysis of cefalexin in goat milk samples using modified QuEChERS extraction technique. Journal of pharmaceutical and biomedical analysis. 2019", "claim": "PubMed-indexed evidence involving Cephalexin", "title": "Hydrophilic-interaction planar chromatography in ultra-sensitive determination of α-aminocephalosporin antibiotics. Application to analysis of cefalexin in goat milk samples using modified QuEChERS extraction technique", "authors": "Rageh AH, Abdel-Rahim SA, Askal HF et al.", "journal": "Journal of pharmaceutical and biomedical analysis", "year": 2019, "pmid": "30716654", "url": "https://pubmed.ncbi.nlm.nih.gov/30716654/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.jpba.2019.01.001", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30716654/", "publicSourceType": "PMID" }, { "text": "Fonte E, Ferreira P, Guilhermino L. Temperature rise and microplastics interact with the toxicity of the antibiotic cefalexin to juveniles of the common goby (Pomatoschistus microps): Post-exposure predatory behaviour, acetylcholinesterase activity and lipid peroxidation. Aquatic toxicology (Amsterdam, Netherlands). 2016", "claim": "PubMed-indexed evidence involving Cephalexin", "title": "Temperature rise and microplastics interact with the toxicity of the antibiotic cefalexin to juveniles of the common goby (Pomatoschistus microps): Post-exposure predatory behaviour, acetylcholinesterase activity and lipid peroxidation", "authors": "Fonte E, Ferreira P, Guilhermino L", "journal": "Aquatic toxicology (Amsterdam, Netherlands)", "year": 2016, "pmid": "27721112", "url": "https://pubmed.ncbi.nlm.nih.gov/27721112/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.aquatox.2016.09.015", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27721112/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "First-generation cephalosporin", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "0.5-1.2 hours", "onsetOfAction": "1 hour to peak serum concentration", "commonBrandNames": [ "Keflex" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "cephalexin" }, { "id": "RX-INFR-004", "name": "Ceftriaxone", "alternateNames": [ "Rocephin" ], "category": "Prescription", "subcategory": "Third-Generation Cephalosporin", "overview": "A third-generation cephalosporin with broad-spectrum activity against many gram-negative and gram-positive organisms. Administered parenterally (IM or IV), it is a cornerstone agent for community-acquired pneumonia, bacterial meningitis, gonorrhea, acute bacterial otitis media (when oral therapy fails), pelvic inflammatory disease, intra-abdominal infections, and complicated urinary tract infections. Its long half-life allows once-daily dosing.", "mechanismOfAction": "Binds to penicillin-binding proteins (PBPs), disrupting the transpeptidation step of peptidoglycan cell wall synthesis. Third-generation cephalosporins are highly resistant to many beta-lactamases and have enhanced penetration through gram-negative outer membrane porin channels, resulting in potent gram-negative activity including against N. meningitidis, H. influenzae, and many Enterobacteriaceae. Achieves therapeutic CSF concentrations when meninges are inflamed.", "commonBenefits": [ "Treats community-acquired pneumonia", "Treats bacterial meningitis", "Treats gonorrhea (recommended IM regimen)", "Treats complicated urinary tract infections and pyelonephritis", "Treats intra-abdominal infections (with metronidazole)", "Treats Lyme disease (neuroborreliosis)" ], "commonDosageRange": "1-2 g IV/IM once daily; meningitis: 2 g IV every 12 hours; gonorrhea: 500 mg IM single dose (as prescribed by your physician)", "recommendedForm": "IV or IM injection only", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Administered parenterally (IV or IM). 100% bioavailable by IM route. Not available in oral formulation. Widely distributed including to CSF when meninges are inflamed." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Diarrhea", "Injection site pain (IM)", "Rash", "Eosinophilia", "Biliary sludging/pseudolithiasis (especially in children)", "Elevated liver enzymes", "Clostridioides difficile-associated diarrhea" ], "contraindications": [ "Known cephalosporin or severe penicillin allergy (anaphylaxis)", "Neonates with hyperbilirubinemia (displaces bilirubin from albumin)", "Concomitant IV calcium-containing solutions in neonates (risk of fatal precipitates)", "Premature neonates until corrected age of 41 weeks" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "antibiotic", "cephalosporin", "injection", "meningitis", "pneumonia", "gonorrhea", "hospital" ], "sources": [ { "text": "Tunkel AR et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004.", "pmid": "15494903", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15494903/", "publicSourceType": "PMID" }, { "text": "Mandell LA et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007.", "pmid": "17278083", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17278083/", "publicSourceType": "PMID" }, { "text": "St Cyr S et al. Update to CDC's treatment guidelines for gonococcal infection, 2020. MMWR. 2020.", "pmid": "33332296", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33332296/", "publicSourceType": "PMID" }, { "text": "Richards DM, Heel RC, Brogden RN et al.. Ceftriaxone. A review of its antibacterial activity, pharmacological properties and therapeutic use. Drugs. 1984", "pmid": "6329638", "doi": "10.2165/00003495-198427060-00001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6329638/", "publicSourceType": "PMID" }, { "text": "Bai ZG, Bao XJ, Cheng WD et al.. Efficacy and safety of ceftriaxone for uncomplicated gonorrhoea: a meta-analysis of randomized controlled trials. International journal of STD & AIDS. 2012", "claim": "PubMed-indexed evidence involving Ceftriaxone", "title": "Efficacy and safety of ceftriaxone for uncomplicated gonorrhoea: a meta-analysis of randomized controlled trials", "authors": "Bai ZG, Bao XJ, Cheng WD et al.", "journal": "International journal of STD & AIDS", "year": 2012, "pmid": "22422688", "url": "https://pubmed.ncbi.nlm.nih.gov/22422688/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1258/ijsa.2009.009198", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22422688/", "publicSourceType": "PMID" }, { "text": "Zeng L, Wang C, Jiang M et al.. Safety of ceftriaxone in paediatrics: a systematic review. Archives of disease in childhood. 2020", "claim": "PubMed-indexed evidence involving Ceftriaxone", "title": "Safety of ceftriaxone in paediatrics: a systematic review", "authors": "Zeng L, Wang C, Jiang M et al.", "journal": "Archives of disease in childhood", "year": 2020, "pmid": "32144089", "url": "https://pubmed.ncbi.nlm.nih.gov/32144089/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1136/archdischild-2019-317950", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32144089/", "publicSourceType": "PMID" }, { "text": "Donnelly PC, Sutich RM, Easton R et al.. Ceftriaxone-Associated Biliary and Cardiopulmonary Adverse Events in Neonates: A Systematic Review of the Literature. Paediatric drugs. 2017", "claim": "PubMed-indexed evidence involving Ceftriaxone", "title": "Ceftriaxone-Associated Biliary and Cardiopulmonary Adverse Events in Neonates: A Systematic Review of the Literature", "authors": "Donnelly PC, Sutich RM, Easton R et al.", "journal": "Paediatric drugs", "year": 2017, "pmid": "27718120", "url": "https://pubmed.ncbi.nlm.nih.gov/27718120/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s40272-016-0197-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27718120/", "publicSourceType": "PMID" }, { "text": "Zeng L, Choonara I, Zhang L et al.. Safety of ceftriaxone in paediatrics: a systematic review protocol. BMJ open. 2017", "claim": "PubMed-indexed evidence involving Ceftriaxone", "title": "Safety of ceftriaxone in paediatrics: a systematic review protocol", "authors": "Zeng L, Choonara I, Zhang L et al.", "journal": "BMJ open", "year": 2017, "pmid": "28827252", "url": "https://pubmed.ncbi.nlm.nih.gov/28827252/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1136/bmjopen-2017-016273", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28827252/", "publicSourceType": "PMID" }, { "text": "Maraolo AE, Nobile M, Gentile I. Ceftriaxone for methicillin-susceptible Staphylococcus aureus bloodstream infections is associated with increased short-term mortality: a systematic review and meta-analysis. Annals of medicine. 2026", "claim": "PubMed-indexed evidence involving Ceftriaxone", "title": "Ceftriaxone for methicillin-susceptible Staphylococcus aureus bloodstream infections is associated with increased short-term mortality: a systematic review and meta-analysis", "authors": "Maraolo AE, Nobile M, Gentile I", "journal": "Annals of medicine", "year": 2026, "pmid": "42112603", "url": "https://pubmed.ncbi.nlm.nih.gov/42112603/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/07853890.2026.2667672", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/42112603/", "publicSourceType": "PMID" }, { "text": "Comce MH, Weersink RA, Beuers U et al.. Pharmacokinetics of ceftriaxone, gentamicin, meropenem and vancomycin in liver cirrhosis: a systematic review. The Journal of antimicrobial chemotherapy. 2024", "claim": "PubMed-indexed evidence involving Ceftriaxone", "title": "Pharmacokinetics of ceftriaxone, gentamicin, meropenem and vancomycin in liver cirrhosis: a systematic review", "authors": "Comce MH, Weersink RA, Beuers U et al.", "journal": "The Journal of antimicrobial chemotherapy", "year": 2024, "pmid": "39289819", "url": "https://pubmed.ncbi.nlm.nih.gov/39289819/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/jac/dkae310", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39289819/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Third-generation cephalosporin", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "5.8-8.7 hours", "onsetOfAction": "Peak serum concentration within 2-3 hours (IM); immediate (IV)", "commonBrandNames": [ "Rocephin" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "ceftriaxone" }, { "id": "RX-INFR-005", "name": "Azithromycin", "alternateNames": [ "Zithromax", "Z-Pack", "Zmax" ], "category": "Prescription", "subcategory": "Macrolide Antibiotic", "overview": "A macrolide antibiotic with a broad spectrum of activity against gram-positive, some gram-negative, and atypical organisms (Mycoplasma, Chlamydia, Legionella). The 5-day 'Z-Pack' course is one of the most commonly prescribed antibiotic regimens. Used for community-acquired pneumonia, acute bacterial exacerbations of COPD, sinusitis, pharyngitis (in penicillin-allergic patients), sexually transmitted infections (chlamydia, gonorrhea as adjunct), and traveler's diarrhea.", "mechanismOfAction": "Binds to the 50S ribosomal subunit of susceptible bacteria, specifically the 23S rRNA of the peptidyl transferase center. This blocks translocation of peptides during translation, inhibiting bacterial protein synthesis. Azithromycin is bacteriostatic at usual concentrations but may be bactericidal at high local concentrations. It concentrates extensively in tissues and phagocytes, achieving intracellular concentrations 10-100x higher than plasma.", "commonBenefits": [ "Treats community-acquired pneumonia", "Treats acute bacterial sinusitis", "Treats acute exacerbation of COPD", "Treats Chlamydia trachomatis (single dose)", "Short treatment course (3-5 days)", "Treats pharyngitis in penicillin-allergic patients" ], "commonDosageRange": "Z-Pack: 500 mg day 1, then 250 mg days 2-5; single 1 g dose for chlamydia; 500 mg daily x3 days for COPD exacerbation (as prescribed by your physician)", "recommendedForm": "Oral tablets, suspension, or IV", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Oral bioavailability approximately 37%. Tablets can be taken with or without food. Oral suspension should be taken on an empty stomach (1 hour before or 2 hours after meals). High tissue penetration and prolonged tissue half-life." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Diarrhea", "Nausea", "Abdominal pain", "QT prolongation (rare but clinically significant)", "Headache", "Hepatotoxicity (rare)" ], "contraindications": [ "Known hypersensitivity to azithromycin, erythromycin, or any macrolide/ketolide", "History of cholestatic jaundice/hepatic dysfunction with prior azithromycin use", "Concomitant use with pimozide or ergotamine derivatives", "Patients with known QT prolongation or on QT-prolonging drugs (caution)" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "antibiotic", "macrolide", "infection", "pneumonia", "chlamydia", "respiratory", "z-pack" ], "sources": [ { "text": "Mandell LA et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007.", "pmid": "17278083", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17278083/", "publicSourceType": "PMID" }, { "text": "Ray WA et al. Azithromycin and the risk of cardiovascular death. N Engl J Med. 2012.", "pmid": "22591573", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22591573/", "publicSourceType": "PMID" }, { "text": "Workowski KA et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021.", "pmid": "34292926", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34292926/", "publicSourceType": "PMID" }, { "claim": "Azithromycin is not effective for COVID-19 treatment", "title": "Azithromycin in patients with COVID-19: a systematic review and meta-analysis.", "authors": "Ayerbe L, Risco-Risco C, Forgnone I et al.", "journal": "Journal of Antimicrobial Chemotherapy", "year": 2022, "pmid": "34791330", "url": "https://pubmed.ncbi.nlm.nih.gov/34791330/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of RCTs found azithromycin did not reduce mortality, hospitalization, or symptom resolution in COVID-19 patients compared to standard of care or placebo, and was associated with increased antibiotic resistance.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34791330/", "publicSourceType": "PMID" }, { "claim": "Azithromycin has a favorable safety profile in pediatric populations", "title": "Safety of azithromycin in pediatrics: a systematic review and meta-analysis.", "authors": "Zeng L, Xu P, Choonara I et al.", "journal": "European Journal of Clinical Pharmacology", "year": 2020, "pmid": "32681202", "url": "https://pubmed.ncbi.nlm.nih.gov/32681202/", "study_type": "meta-analysis", "key_finding": "Systematic review found azithromycin had a generally favorable safety profile in children with overall adverse event rates comparable to other antibiotics; gastrointestinal effects (vomiting, diarrhea) were the most common side effects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32681202/", "publicSourceType": "PMID" }, { "text": "Tian BP, Xuan N, Wang Y et al.. The efficacy and safety of azithromycin in asthma: A systematic review. Journal of cellular and molecular medicine. 2019", "claim": "PubMed-indexed evidence involving Azithromycin", "title": "The efficacy and safety of azithromycin in asthma: A systematic review", "authors": "Tian BP, Xuan N, Wang Y et al.", "journal": "Journal of cellular and molecular medicine", "year": 2019, "pmid": "30661297", "url": "https://pubmed.ncbi.nlm.nih.gov/30661297/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/jcmm.13919", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30661297/", "publicSourceType": "PMID" }, { "text": "Smith C, Egunsola O, Choonara I et al.. Use and safety of azithromycin in neonates: a systematic review. BMJ open. 2015", "claim": "PubMed-indexed evidence involving Azithromycin", "title": "Use and safety of azithromycin in neonates: a systematic review", "authors": "Smith C, Egunsola O, Choonara I et al.", "journal": "BMJ open", "year": 2015, "pmid": "26656010", "url": "https://pubmed.ncbi.nlm.nih.gov/26656010/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1136/bmjopen-2015-008194", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26656010/", "publicSourceType": "PMID" }, { "text": "Methaneethorn J, Jiao Z, AlEjielat R et al.. Influential predictors of azithromycin pharmacokinetics: a systematic review of population pharmacokinetics. Annals of medicine. 2025", "claim": "PubMed-indexed evidence involving Azithromycin", "title": "Influential predictors of azithromycin pharmacokinetics: a systematic review of population pharmacokinetics", "authors": "Methaneethorn J, Jiao Z, AlEjielat R et al.", "journal": "Annals of medicine", "year": 2025, "pmid": "40372973", "url": "https://pubmed.ncbi.nlm.nih.gov/40372973/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/07853890.2025.2496792", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40372973/", "publicSourceType": "PMID" }, { "text": "Ukkonen RM, Renko M, Kuitunen I. Azithromycin for acute bronchiolitis and wheezing episodes in children - a systematic review with meta-analysis. Pediatric research. 2024", "claim": "PubMed-indexed evidence involving Azithromycin", "title": "Azithromycin for acute bronchiolitis and wheezing episodes in children - a systematic review with meta-analysis", "authors": "Ukkonen RM, Renko M, Kuitunen I", "journal": "Pediatric research", "year": 2024, "pmid": "38066246", "url": "https://pubmed.ncbi.nlm.nih.gov/38066246/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1038/s41390-023-02953-z", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38066246/", "publicSourceType": "PMID" }, { "text": "Nag K, Tripura K, Datta A et al.. Effect of Hydroxychloroquine and Azithromycin Combination Use in COVID-19 Patients - An Umbrella Review. Indian journal of community medicine : official publication of Indian Association of Preventive & Social Medicine. 2024", "claim": "PubMed-indexed evidence involving Azithromycin", "title": "Effect of Hydroxychloroquine and Azithromycin Combination Use in COVID-19 Patients - An Umbrella Review", "authors": "Nag K, Tripura K, Datta A et al.", "journal": "Indian journal of community medicine : official publication of Indian Association of Preventive & Social Medicine", "year": 2024, "pmid": "38425958", "url": "https://pubmed.ncbi.nlm.nih.gov/38425958/", "study_type": "review", "confidence": "verify", "doi": "10.4103/ijcm.ijcm_983_22", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38425958/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Macrolide antibiotic (azalide subclass)", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "68 hours (terminal; due to extensive tissue distribution)", "onsetOfAction": "2-3 hours to peak serum concentration", "commonBrandNames": [ "Zithromax", "Zmax" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "azithromycin" }, { "id": "RX-INFR-006", "name": "Clarithromycin", "alternateNames": [ "Biaxin", "Biaxin XL" ], "category": "Prescription", "subcategory": "Macrolide Antibiotic", "overview": "A macrolide antibiotic with activity against gram-positive cocci, atypical organisms (Mycoplasma, Chlamydia, Legionella), and Mycobacterium avium complex (MAC). Used for community-acquired pneumonia, acute bacterial sinusitis, pharyngitis, acute exacerbations of chronic bronchitis, skin infections, and as a key component of H. pylori triple therapy. Notable for significant CYP3A4 inhibition, which causes numerous drug interactions.", "mechanismOfAction": "Binds to the 50S ribosomal subunit at the 23S rRNA peptidyl transferase center, blocking peptide chain elongation and inhibiting bacterial protein synthesis. Primarily bacteriostatic. Its active metabolite, 14-hydroxyclarithromycin, also has antibacterial activity and acts synergistically with the parent compound against H. influenzae. Clarithromycin is a potent inhibitor of CYP3A4, CYP2C9, and P-glycoprotein, leading to significant drug-drug interactions.", "commonBenefits": [ "Treats community-acquired pneumonia", "Key component of H. pylori triple/quadruple therapy", "Treats MAC infections in immunocompromised patients", "Treats acute bacterial sinusitis", "Treats acute exacerbations of chronic bronchitis", "Treats pharyngitis and tonsillitis" ], "commonDosageRange": "250-500 mg every 12 hours; XL: 1000 mg once daily; H. pylori: 500 mg BID for 10-14 days as part of combination therapy (as prescribed by your physician)", "recommendedForm": "Oral tablets (immediate-release or extended-release) or suspension", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Bioavailability approximately 50%. Food improves tolerability. Extended-release tablets (Biaxin XL) should be taken with food to optimize absorption. IMPORTANT: Potent CYP3A4 inhibitor, numerous significant drug interactions." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Dysgeusia (metallic taste, very common)", "Diarrhea", "Nausea and vomiting", "Abdominal pain", "Headache", "QT prolongation", "Hepatotoxicity (rare)" ], "contraindications": [ "Known hypersensitivity to clarithromycin or any macrolide", "Concomitant use with colchicine in patients with renal/hepatic impairment", "Concomitant use with pimozide, cisapride, ergotamine, or lovastatin/simvastatin", "History of QT prolongation or ventricular arrhythmia", "History of cholestatic jaundice/hepatic dysfunction with prior clarithromycin use", "Severe hepatic impairment combined with renal impairment" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "antibiotic", "macrolide", "infection", "h-pylori", "respiratory", "cyp3a4-inhibitor", "drug-interactions" ], "sources": [ { "text": "Chey WD et al. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2017.", "pmid": "28071659", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28071659/", "publicSourceType": "PMID" }, { "text": "Mandell LA et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007.", "pmid": "17278083", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17278083/", "publicSourceType": "PMID" }, { "text": "Albert RK et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011.", "pmid": "21864166", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21864166/", "publicSourceType": "PMID" }, { "text": "Clarithromycin. 2006", "pmid": "30000266", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30000266/", "publicSourceType": "PMID" }, { "text": "Dossouvi KM, Bouyo T, Sognonnou S et al.. Clarithromycin-resistant Helicobacter pylori in Africa: a systematic review and meta-analysis. Antimicrobial resistance and infection control. 2025", "claim": "PubMed-indexed evidence involving Clarithromycin", "title": "Clarithromycin-resistant Helicobacter pylori in Africa: a systematic review and meta-analysis", "authors": "Dossouvi KM, Bouyo T, Sognonnou S et al.", "journal": "Antimicrobial resistance and infection control", "year": 2025, "pmid": "40221805", "url": "https://pubmed.ncbi.nlm.nih.gov/40221805/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s13756-025-01533-6", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40221805/", "publicSourceType": "PMID" }, { "text": "Sholeh M, Khoshnood S, Azimi T et al.. The prevalence of clarithromycin-resistant Helicobacter pylori isolates: a systematic review and meta-analysis. PeerJ. 2023", "claim": "PubMed-indexed evidence involving Clarithromycin", "title": "The prevalence of clarithromycin-resistant Helicobacter pylori isolates: a systematic review and meta-analysis", "authors": "Sholeh M, Khoshnood S, Azimi T et al.", "journal": "PeerJ", "year": 2023, "pmid": "37016679", "url": "https://pubmed.ncbi.nlm.nih.gov/37016679/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7717/peerj.15121", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37016679/", "publicSourceType": "PMID" }, { "text": "Bashir NZ, Sharma P. Clarithromycin as an adjunct to periodontal therapy: a systematic review and meta-analysis. International journal of dental hygiene. 2022", "claim": "PubMed-indexed evidence involving Clarithromycin", "title": "Clarithromycin as an adjunct to periodontal therapy: a systematic review and meta-analysis", "authors": "Bashir NZ, Sharma P", "journal": "International journal of dental hygiene", "year": 2022, "pmid": "33773046", "url": "https://pubmed.ncbi.nlm.nih.gov/33773046/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/idh.12498", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33773046/", "publicSourceType": "PMID" }, { "text": "Huang Z, Zhou B. Clarithromycin for the treatment of adult chronic rhinosinusitis: a systematic review and meta-analysis. International forum of allergy & rhinology. 2019", "claim": "PubMed-indexed evidence involving Clarithromycin", "title": "Clarithromycin for the treatment of adult chronic rhinosinusitis: a systematic review and meta-analysis", "authors": "Huang Z, Zhou B", "journal": "International forum of allergy & rhinology", "year": 2019, "pmid": "30629811", "url": "https://pubmed.ncbi.nlm.nih.gov/30629811/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/alr.22281", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30629811/", "publicSourceType": "PMID" }, { "text": "Harb AH, Chalhoub JM, Abou Mrad R et al.. Systematic review and meta-analysis: full- vs. half-dose anti-microbials in clarithromycin-based regimens for Helicobacter pylori eradication. Alimentary pharmacology & therapeutics. 2015", "claim": "PubMed-indexed evidence involving Clarithromycin", "title": "Systematic review and meta-analysis: full- vs. half-dose anti-microbials in clarithromycin-based regimens for Helicobacter pylori eradication", "authors": "Harb AH, Chalhoub JM, Abou Mrad R et al.", "journal": "Alimentary pharmacology & therapeutics", "year": 2015, "pmid": "26011564", "url": "https://pubmed.ncbi.nlm.nih.gov/26011564/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/apt.13259", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26011564/", "publicSourceType": "PMID" }, { "text": "Wood MJ. The tolerance and toxicity of clarithromycin. The Journal of hospital infection. 1991", "claim": "PubMed-indexed evidence involving Clarithromycin", "title": "The tolerance and toxicity of clarithromycin", "authors": "Wood MJ", "journal": "The Journal of hospital infection", "year": 1991, "pmid": "1684982", "url": "https://pubmed.ncbi.nlm.nih.gov/1684982/", "study_type": "review", "confidence": "verify", "doi": "10.1016/0195-6701(91)90216-u", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1684982/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Macrolide antibiotic", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "3-7 hours (dose-dependent); 14-OH metabolite: 5-9 hours", "onsetOfAction": "2 hours to peak serum concentration", "commonBrandNames": [ "Biaxin", "Biaxin XL" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "clarithromycin" }, { "id": "RX-INFR-007", "name": "Ciprofloxacin", "alternateNames": [ "Cipro", "Cipro XR" ], "category": "Prescription", "subcategory": "Fluoroquinolone Antibiotic", "overview": "A second-generation fluoroquinolone with potent gram-negative activity, including Pseudomonas aeruginosa. Used for complicated urinary tract infections, pyelonephritis, infectious diarrhea, intra-abdominal infections (with metronidazole), bone and joint infections, anthrax prophylaxis, and febrile neutropenia. Due to FDA black box warnings regarding serious adverse effects, fluoroquinolones are reserved for infections without safer alternatives.", "mechanismOfAction": "Inhibits bacterial DNA gyrase (topoisomerase II) and topoisomerase IV, enzymes essential for DNA replication, transcription, repair, and recombination. DNA gyrase introduces negative supercoils to relieve torsional strain during replication; topoisomerase IV decatenates daughter chromosomes after replication. By trapping the enzyme-DNA complex, ciprofloxacin causes double-stranded DNA breaks, leading to rapid bactericidal activity.", "commonBenefits": [ "Treats complicated urinary tract infections and pyelonephritis", "Treats Pseudomonas aeruginosa infections", "Treats infectious diarrhea (traveler's diarrhea, Salmonella, Shigella)", "Treats bone and joint infections (oral option for osteomyelitis)", "Anthrax post-exposure prophylaxis", "Treats intra-abdominal infections (combination therapy)" ], "commonDosageRange": "250-750 mg every 12 hours; XR: 500-1000 mg once daily for UTI; IV: 200-400 mg every 8-12 hours (as prescribed by your physician)", "recommendedForm": "Oral tablets, extended-release tablets, suspension, or IV", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Oral bioavailability 70-80%. Do NOT take with calcium, iron, magnesium, zinc, or aluminum-containing antacids, chelation reduces absorption by up to 90%. Separate from dairy products and mineral supplements by at least 2 hours before or 6 hours after. Do not take with enteral feeds." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Nausea and diarrhea", "Tendinitis and tendon rupture (black box warning)", "Peripheral neuropathy (potentially irreversible)", "CNS effects (dizziness, headache, insomnia, seizures)", "QT prolongation", "Photosensitivity", "Clostridioides difficile-associated diarrhea", "Aortic aneurysm/dissection (rare)" ], "contraindications": [ "Known hypersensitivity to ciprofloxacin or any fluoroquinolone", "Concomitant tizanidine use (marked increase in tizanidine levels via CYP1A2 inhibition)", "Myasthenia gravis (may exacerbate muscle weakness)", "History of tendon disorders related to fluoroquinolone use", "Children under 18 (except for specific indications like anthrax, complicated UTI)", "Known aortic aneurysm or high risk for aortic dissection" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "antibiotic", "fluoroquinolone", "infection", "uti", "pseudomonas", "gram-negative", "anthrax" ], "sources": [ { "text": "Gupta K et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by IDSA and ESCMID. Clin Infect Dis. 2011.", "pmid": "21292654", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21292654/", "publicSourceType": "PMID" }, { "text": "FDA Drug Safety Communication: FDA updates warnings for fluoroquinolone antibiotics on risks of mental health and low blood sugar adverse reactions. FDA. 2018.", "pmid": "41790508", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41790508/", "publicSourceType": "PMID" }, { "text": "Pasternak B et al. Fluoroquinolone use and risk of aortic aneurysm and dissection: nationwide cohort study. BMJ. 2018.", "pmid": "29519881", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29519881/", "publicSourceType": "PMID" }, { "claim": "Fluoroquinolones including ciprofloxacin increase risk of tendon injury", "title": "Fluoroquinolones and the risk of tendon injury: a systematic review and meta-analysis.", "authors": "Alves C, Mendes D, Marques FB", "journal": "European Journal of Clinical Pharmacology", "year": 2019, "pmid": "31270563", "url": "https://pubmed.ncbi.nlm.nih.gov/31270563/", "study_type": "meta-analysis", "key_finding": "Meta-analysis confirmed fluoroquinolones including ciprofloxacin significantly increased risk of tendon injury (OR 1.73) and Achilles tendon rupture, with concurrent corticosteroid use substantially amplifying the risk.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31270563/", "publicSourceType": "PMID" }, { "claim": "Ciprofloxacin is effective for treatment of urinary tract infections", "title": "A systematic review and meta-analysis of levofloxacin and ciprofloxacin in the treatment of urinary tract infection.", "authors": "Xue Z, Xiang Y, Li Y et al.", "journal": "Annals of Palliative Medicine", "year": 2021, "pmid": "34628902", "url": "https://pubmed.ncbi.nlm.nih.gov/34628902/", "study_type": "meta-analysis", "key_finding": "Meta-analysis found ciprofloxacin and levofloxacin had comparable efficacy for UTI treatment; ciprofloxacin showed slightly better microbiological eradication rates but also higher resistance rates, with both effective as first-line options in areas with low resistance.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34628902/", "publicSourceType": "PMID" }, { "text": "Kashyap A, Sreenivasan S, Rajan AK et al.. Ciprofloxacin-induced cutaneous adverse drug events: a systematic review of descriptive studies. Journal of basic and clinical physiology and pharmacology. 2021", "claim": "PubMed-indexed evidence involving Ciprofloxacin", "title": "Ciprofloxacin-induced cutaneous adverse drug events: a systematic review of descriptive studies", "authors": "Kashyap A, Sreenivasan S, Rajan AK et al.", "journal": "Journal of basic and clinical physiology and pharmacology", "year": 2021, "pmid": "33725760", "url": "https://pubmed.ncbi.nlm.nih.gov/33725760/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1515/jbcpp-2020-0115", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33725760/", "publicSourceType": "PMID" }, { "text": "Adefurin A, Sammons H, Jacqz-Aigrain E et al.. Ciprofloxacin safety in paediatrics: a systematic review. Archives of disease in childhood. 2011", "claim": "PubMed-indexed evidence involving Ciprofloxacin", "title": "Ciprofloxacin safety in paediatrics: a systematic review", "authors": "Adefurin A, Sammons H, Jacqz-Aigrain E et al.", "journal": "Archives of disease in childhood", "year": 2011, "pmid": "21785119", "url": "https://pubmed.ncbi.nlm.nih.gov/21785119/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1136/adc.2010.208843", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21785119/", "publicSourceType": "PMID" }, { "text": "Wang S, Zhang A, Yao X. Meta-analysis of efficacy and safety of inhaled ciprofloxacin in non-cystic fibrosis bronchiectasis patients. Internal medicine journal. 2021", "claim": "PubMed-indexed evidence involving Ciprofloxacin", "title": "Meta-analysis of efficacy and safety of inhaled ciprofloxacin in non-cystic fibrosis bronchiectasis patients", "authors": "Wang S, Zhang A, Yao X", "journal": "Internal medicine journal", "year": 2021, "pmid": "33469994", "url": "https://pubmed.ncbi.nlm.nih.gov/33469994/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/imj.15210", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33469994/", "publicSourceType": "PMID" }, { "text": "Kaguelidou F, Turner MA, Choonara I et al.. Ciprofloxacin use in neonates: a systematic review of the literature. The Pediatric infectious disease journal. 2011", "claim": "PubMed-indexed evidence involving Ciprofloxacin", "title": "Ciprofloxacin use in neonates: a systematic review of the literature", "authors": "Kaguelidou F, Turner MA, Choonara I et al.", "journal": "The Pediatric infectious disease journal", "year": 2011, "pmid": "21048525", "url": "https://pubmed.ncbi.nlm.nih.gov/21048525/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/INF.0b013e3181fe353d", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21048525/", "publicSourceType": "PMID" }, { "text": "Rahm V, Schacht P. Safety of ciprofloxacin. A review. Scandinavian journal of infectious diseases. Supplementum. 1989", "claim": "PubMed-indexed evidence involving Ciprofloxacin", "title": "Safety of ciprofloxacin. A review", "authors": "Rahm V, Schacht P", "journal": "Scandinavian journal of infectious diseases. Supplementum", "year": 1989, "pmid": "2667105", "url": "https://pubmed.ncbi.nlm.nih.gov/2667105/", "study_type": "RCT", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2667105/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Fluoroquinolone antibiotic (second-generation)", "blackBoxWarnings": [ "Tendinitis and tendon rupture; peripheral neuropathy; CNS effects; exacerbation of myasthenia gravis; risk of aortic aneurysm" ], "fdaPregnancyCategory": "C", "halfLife": "4-6 hours (prolonged in renal impairment)", "onsetOfAction": "1-2 hours to peak serum concentration", "commonBrandNames": [ "Cipro", "Cipro XR", "Proquin XR" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "ciprofloxacin" }, { "id": "RX-INFR-008", "name": "Levofloxacin", "alternateNames": [ "Levaquin" ], "category": "Prescription", "subcategory": "Fluoroquinolone Antibiotic", "overview": "A third-generation (respiratory) fluoroquinolone with broad-spectrum activity against gram-positive (including S. pneumoniae), gram-negative, and atypical organisms. Often called a 'respiratory fluoroquinolone' due to reliable pneumococcal activity. Used for community-acquired pneumonia, hospital-acquired pneumonia, acute bacterial sinusitis, chronic bacterial prostatitis, complicated UTI, and skin infections. Reserved for conditions without safer alternatives due to FDA black box warnings.", "mechanismOfAction": "The L-isomer of ofloxacin, approximately twice as potent. Inhibits bacterial DNA gyrase (topoisomerase II) and topoisomerase IV, trapping the enzyme-DNA complex and causing lethal double-stranded DNA breaks. Has enhanced activity against gram-positive organisms (particularly S. pneumoniae) compared to ciprofloxacin, making it effective for respiratory infections. Exhibits concentration-dependent bactericidal activity.", "commonBenefits": [ "Treats community-acquired pneumonia (including drug-resistant S. pneumoniae)", "Treats acute bacterial sinusitis", "Treats complicated urinary tract infections", "Treats chronic bacterial prostatitis", "Treats hospital-acquired/ventilator-associated pneumonia", "Once-daily dosing" ], "commonDosageRange": "250-750 mg once daily; CAP: 500 mg daily x 7-14 days or 750 mg daily x 5 days; UTI: 250-750 mg daily (as prescribed by your physician)", "recommendedForm": "Oral tablets, oral solution, or IV", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Oral bioavailability approximately 99%. Do NOT take with calcium, iron, magnesium, zinc, or aluminum-containing antacids, chelation reduces absorption by up to 90%. Separate from antacids, sucralfate, and mineral supplements by at least 2 hours before or 2 hours after dosing." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Nausea and diarrhea", "Tendinitis and tendon rupture (black box warning)", "Peripheral neuropathy (potentially irreversible)", "CNS effects (dizziness, insomnia, headache, seizures)", "QT prolongation", "Dysglycemia (hypoglycemia, hyperglycemia)", "Photosensitivity", "Clostridioides difficile-associated diarrhea" ], "contraindications": [ "Known hypersensitivity to levofloxacin or any fluoroquinolone", "Myasthenia gravis (may cause fatal respiratory failure)", "History of tendon disorders related to fluoroquinolone use", "Children under 18 (except for specific indications)", "Known QT prolongation or concurrent use of class IA/III antiarrhythmics", "Known aortic aneurysm or high risk for aortic dissection" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "antibiotic", "fluoroquinolone", "infection", "pneumonia", "respiratory", "uti", "prostatitis" ], "sources": [ { "text": "Mandell LA et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007.", "pmid": "17278083", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17278083/", "publicSourceType": "PMID" }, { "text": "Etminan M et al. Oral fluoroquinolones and the risk of retinal detachment. JAMA. 2012.", "pmid": "22474205", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22474205/", "publicSourceType": "PMID" }, { "text": "FDA Drug Safety Communication: FDA warns about increased risk of ruptures or tears in the aorta blood vessel with fluoroquinolone antibiotics. FDA. 2018.", "pmid": "41790508", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41790508/", "publicSourceType": "PMID" }, { "text": "Hesseling AC, Purchase SE, Martinson NA et al.. Levofloxacin Preventive Treatment in Children Exposed to MDR Tuberculosis. The New England journal of medicine. 2024", "pmid": "39693542", "doi": "10.1056/NEJMoa2314318", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39693542/", "publicSourceType": "PMID" }, { "text": "Ding Y, Zeng X, Zou J et al.. Population pharmacokinetics of levofloxacin: a systematic review. Drug metabolism reviews. 2026", "claim": "PubMed-indexed evidence involving Levofloxacin", "title": "Population pharmacokinetics of levofloxacin: a systematic review", "authors": "Ding Y, Zeng X, Zou J et al.", "journal": "Drug metabolism reviews", "year": 2026, "pmid": "42095354", "url": "https://pubmed.ncbi.nlm.nih.gov/42095354/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/03602532.2026.2670536", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/42095354/", "publicSourceType": "PMID" }, { "text": "Xue Z, Xiang Y, Li Y et al.. A systematic review and meta-analysis of levofloxacin and ciprofloxacin in the treatment of urinary tract infection. Annals of palliative medicine. 2021", "claim": "PubMed-indexed evidence involving Levofloxacin", "title": "A systematic review and meta-analysis of levofloxacin and ciprofloxacin in the treatment of urinary tract infection", "authors": "Xue Z, Xiang Y, Li Y et al.", "journal": "Annals of palliative medicine", "year": 2021, "pmid": "34628902", "url": "https://pubmed.ncbi.nlm.nih.gov/34628902/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.21037/apm-21-2042", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34628902/", "publicSourceType": "PMID" }, { "text": "Duong T, Brigden J, Simon Schaaf H et al.. A Meta-Analysis of Levofloxacin for Contacts of Multidrug-Resistant Tuberculosis. NEJM evidence. 2025", "claim": "PubMed-indexed evidence involving Levofloxacin", "title": "A Meta-Analysis of Levofloxacin for Contacts of Multidrug-Resistant Tuberculosis", "authors": "Duong T, Brigden J, Simon Schaaf H et al.", "journal": "NEJM evidence", "year": 2025, "pmid": "39693627", "url": "https://pubmed.ncbi.nlm.nih.gov/39693627/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1056/EVIDoa2400190", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39693627/", "publicSourceType": "PMID" }, { "text": "Phillips PPJ, Peloquin CA, Sterling TR et al.. Efficacy and Safety of Higher Doses of Levofloxacin for Multidrug-resistant Tuberculosis: A Randomized, Placebo-controlled Phase II Clinical Trial. American journal of respiratory and critical care medicine. 2025", "claim": "PubMed-indexed evidence involving Levofloxacin", "title": "Efficacy and Safety of Higher Doses of Levofloxacin for Multidrug-resistant Tuberculosis: A Randomized, Placebo-controlled Phase II Clinical Trial", "authors": "Phillips PPJ, Peloquin CA, Sterling TR et al.", "journal": "American journal of respiratory and critical care medicine", "year": 2025, "pmid": "40080768", "url": "https://pubmed.ncbi.nlm.nih.gov/40080768/", "study_type": "RCT", "confidence": "verify", "doi": "10.1164/rccm.202407-1354OC", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40080768/", "publicSourceType": "PMID" }, { "text": "Gisbert JP, Morena F. Systematic review and meta-analysis: levofloxacin-based rescue regimens after Helicobacter pylori treatment failure. Alimentary pharmacology & therapeutics. 2006", "claim": "PubMed-indexed evidence involving Levofloxacin", "title": "Systematic review and meta-analysis: levofloxacin-based rescue regimens after Helicobacter pylori treatment failure", "authors": "Gisbert JP, Morena F", "journal": "Alimentary pharmacology & therapeutics", "year": 2006, "pmid": "16393278", "url": "https://pubmed.ncbi.nlm.nih.gov/16393278/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/j.1365-2036.2006.02737.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16393278/", "publicSourceType": "PMID" }, { "text": "Junqi Z, Jie C, Jinglin W et al.. A retrospective study of the efficacy and safety of levofloxacin in children with severe infection. Frontiers in pediatrics. 2024", "claim": "PubMed-indexed evidence involving Levofloxacin", "title": "A retrospective study of the efficacy and safety of levofloxacin in children with severe infection", "authors": "Junqi Z, Jie C, Jinglin W et al.", "journal": "Frontiers in pediatrics", "year": 2024, "pmid": "38646513", "url": "https://pubmed.ncbi.nlm.nih.gov/38646513/", "study_type": "review", "confidence": "verify", "doi": "10.3389/fped.2024.1381742", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38646513/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Fluoroquinolone antibiotic (third-generation/respiratory)", "blackBoxWarnings": [ "Tendinitis and tendon rupture; peripheral neuropathy; CNS effects; exacerbation of myasthenia gravis; risk of aortic aneurysm" ], "fdaPregnancyCategory": "C", "halfLife": "6-8 hours", "onsetOfAction": "1-2 hours to peak serum concentration", "commonBrandNames": [ "Levaquin" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "levofloxacin" }, { "id": "RX-INFR-009", "name": "Doxycycline", "alternateNames": [ "Vibramycin", "Doryx", "Oracea", "Monodox" ], "category": "Prescription", "subcategory": "Tetracycline Antibiotic", "overview": "A broad-spectrum tetracycline antibiotic effective against a wide range of gram-positive, gram-negative, atypical, and intracellular organisms. Used extensively for community-acquired pneumonia, Lyme disease, rickettsial infections (Rocky Mountain spotted fever), chlamydial STIs, acne vulgaris, rosacea, malaria prophylaxis, and periodontal disease. One of the most versatile antibiotics in clinical practice.", "mechanismOfAction": "Binds reversibly to the 30S ribosomal subunit at the A-site (aminoacyl-tRNA site), blocking the attachment of aminoacyl-tRNA to the mRNA-ribosome complex. This prevents the addition of amino acids to the growing peptide chain, inhibiting bacterial protein synthesis. Primarily bacteriostatic. Also has anti-inflammatory and anti-matrix metalloproteinase properties independent of antimicrobial activity, which contribute to its efficacy in acne and rosacea.", "commonBenefits": [ "Treats community-acquired pneumonia (atypical coverage)", "First-line treatment for Lyme disease", "Treats rickettsial infections (Rocky Mountain spotted fever, ehrlichiosis)", "Treats chlamydial infections (C. trachomatis)", "Treats acne vulgaris and rosacea", "Malaria prophylaxis", "Treats periodontal disease" ], "commonDosageRange": "100 mg every 12 hours or 200 mg once daily; acne: 50-100 mg daily; Lyme disease: 100 mg BID x 10-21 days (as prescribed by your physician)", "recommendedForm": "Oral capsules, tablets, delayed-release tablets, or IV", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Bioavailability approximately 90-100%. Do NOT take with calcium, iron, magnesium, zinc, or aluminum-containing antacids, chelation significantly reduces absorption. Separate from dairy products and mineral-containing supplements by at least 2 hours. Take with a full glass of water and remain upright for 30 minutes to avoid esophageal ulceration. Unlike other tetracyclines, food has minimal effect on doxycycline absorption, and taking with food reduces GI upset." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Photosensitivity (common, can be severe)", "Nausea and vomiting", "Esophageal ulceration/erosion", "Diarrhea", "Vaginal candidiasis", "Tooth discoloration (in children under 8)", "Skin hyperpigmentation with prolonged use" ], "contraindications": [ "Known tetracycline hypersensitivity", "Pregnancy (category D, causes permanent tooth discoloration and affects bone growth in fetus)", "Children under 8 years (risk of permanent tooth discoloration, except for life-threatening infections)", "Severe hepatic impairment", "Concomitant use with isotretinoin (risk of pseudotumor cerebri)" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "antibiotic", "tetracycline", "infection", "lyme-disease", "acne", "malaria", "respiratory", "sti" ], "sources": [ { "text": "Wormser GP et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by IDSA. Clin Infect Dis. 2006.", "pmid": "17029130", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17029130/", "publicSourceType": "PMID" }, { "text": "Workowski KA et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021.", "pmid": "34292926", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34292926/", "publicSourceType": "PMID" }, { "text": "Mandell LA et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007.", "pmid": "17278083", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17278083/", "publicSourceType": "PMID" }, { "claim": "Doxycycline is effective for community-acquired pneumonia", "title": "Efficacy of Doxycycline for Mild-to-Moderate Community-Acquired Pneumonia in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.", "authors": "Choi SH, Cesar A, Snow TAC et al.", "journal": "Clinical Infectious Diseases", "year": 2023, "pmid": "35903011", "url": "https://pubmed.ncbi.nlm.nih.gov/35903011/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of RCTs found doxycycline had comparable clinical efficacy to macrolides and fluoroquinolones for mild-to-moderate community-acquired pneumonia, with lower rates of adverse events, supporting its role as first-line therapy.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35903011/", "publicSourceType": "PMID" }, { "claim": "Doxycycline prophylaxis reduces incidence of sexually transmitted infections", "title": "Doxycycline prophylaxis for the prevention of sexually transmitted infections: A systematic review and meta-analysis of randomized controlled trials.", "authors": "Szondy I, Meznerics FA, Lorincz K et al.", "journal": "International Journal of Infectious Diseases", "year": 2024, "pmid": "39122208", "url": "https://pubmed.ncbi.nlm.nih.gov/39122208/", "study_type": "meta-analysis", "key_finding": "Meta-analysis of RCTs found doxycycline post-exposure prophylaxis significantly reduced incidence of syphilis, chlamydia, and gonorrhea by approximately 60-80% in high-risk populations, with greatest benefit in men who have sex with men.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39122208/", "publicSourceType": "PMID" }, { "text": "Goetze S, Hiernickel C, Elsner P. Phototoxicity of Doxycycline: A Systematic Review on Clinical Manifestations, Frequency, Cofactors, and Prevention. Skin pharmacology and physiology. 2017", "claim": "PubMed-indexed evidence involving Doxycycline", "title": "Phototoxicity of Doxycycline: A Systematic Review on Clinical Manifestations, Frequency, Cofactors, and Prevention", "authors": "Goetze S, Hiernickel C, Elsner P", "journal": "Skin pharmacology and physiology", "year": 2017, "pmid": "28291967", "url": "https://pubmed.ncbi.nlm.nih.gov/28291967/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1159/000458761", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28291967/", "publicSourceType": "PMID" }, { "text": "Smith K, Leyden JJ. Safety of doxycycline and minocycline: a systematic review. Clinical therapeutics. 2005", "claim": "PubMed-indexed evidence involving Doxycycline", "title": "Safety of doxycycline and minocycline: a systematic review", "authors": "Smith K, Leyden JJ", "journal": "Clinical therapeutics", "year": 2005, "pmid": "16291409", "url": "https://pubmed.ncbi.nlm.nih.gov/16291409/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.clinthera.2005.09.005", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16291409/", "publicSourceType": "PMID" }, { "text": "Sokoll PR, Migliavaca CB, Döring S et al.. Efficacy of postexposure prophylaxis with doxycycline (Doxy-PEP) in reducing sexually transmitted infections: a systematic review and meta-analysis. Sexually transmitted infections. 2025", "claim": "PubMed-indexed evidence involving Doxycycline", "title": "Efficacy of postexposure prophylaxis with doxycycline (Doxy-PEP) in reducing sexually transmitted infections: a systematic review and meta-analysis", "authors": "Sokoll PR, Migliavaca CB, Döring S et al.", "journal": "Sexually transmitted infections", "year": 2025, "pmid": "39097410", "url": "https://pubmed.ncbi.nlm.nih.gov/39097410/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1136/sextrans-2024-056208", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39097410/", "publicSourceType": "PMID" }, { "text": "Boschiero MN, Sansone NMS, Matos LR et al.. Efficacy of Doxycycline as Preexposure and/or Postexposure Prophylaxis to Prevent Sexually Transmitted Diseases: A Systematic Review and Meta-Analysis. Sexually transmitted diseases. 2025", "claim": "PubMed-indexed evidence involving Doxycycline", "title": "Efficacy of Doxycycline as Preexposure and/or Postexposure Prophylaxis to Prevent Sexually Transmitted Diseases: A Systematic Review and Meta-Analysis", "authors": "Boschiero MN, Sansone NMS, Matos LR et al.", "journal": "Sexually transmitted diseases", "year": 2025, "pmid": "39316078", "url": "https://pubmed.ncbi.nlm.nih.gov/39316078/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/OLQ.0000000000002082", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39316078/", "publicSourceType": "PMID" }, { "text": "Bhagat M, Adusumilli AK, Ghimire A et al.. Comparative efficacy of doxycycline and its analogues with autologous blood patch pleurodesis for persistent air leak following secondary spontaneous pneumothorax in adults-a systematic review. Journal of thoracic disease. 2024", "claim": "PubMed-indexed evidence involving Doxycycline", "title": "Comparative efficacy of doxycycline and its analogues with autologous blood patch pleurodesis for persistent air leak following secondary spontaneous pneumothorax in adults-a systematic review", "authors": "Bhagat M, Adusumilli AK, Ghimire A et al.", "journal": "Journal of thoracic disease", "year": 2024, "pmid": "39552893", "url": "https://pubmed.ncbi.nlm.nih.gov/39552893/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.21037/jtd-24-832", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39552893/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Tetracycline antibiotic", "blackBoxWarnings": [], "fdaPregnancyCategory": "D", "halfLife": "18-22 hours", "onsetOfAction": "1.5-4 hours to peak serum concentration", "commonBrandNames": [ "Vibramycin", "Doryx", "Oracea", "Monodox" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "doxycycline" }, { "id": "RX-INFR-010", "name": "Trimethoprim-Sulfamethoxazole", "alternateNames": [ "Bactrim", "Septra", "TMP-SMX", "Co-trimoxazole" ], "category": "Prescription", "subcategory": "Sulfonamide/Diaminopyrimidine Combination", "overview": "A synergistic combination antibiotic containing trimethoprim and sulfamethoxazole in a 1:5 ratio. Effective against many gram-positive and gram-negative organisms. A first-line agent for uncomplicated urinary tract infections, the drug of choice for Pneumocystis jirovecii pneumonia (PCP) treatment and prophylaxis, and used for MRSA skin infections, Stenotrophomonas, nocardiosis, and toxoplasmosis.", "mechanismOfAction": "Sequentially inhibits two enzymes in the bacterial folate synthesis pathway. Sulfamethoxazole is a structural analog of para-aminobenzoic acid (PABA) that competitively inhibits dihydropteroate synthase, blocking the incorporation of PABA into dihydrofolic acid. Trimethoprim then inhibits dihydrofolate reductase (DHFR), preventing the reduction of dihydrofolic acid to tetrahydrofolic acid. The sequential blockade at two steps produces synergistic bactericidal activity.", "commonBenefits": [ "First-line for uncomplicated urinary tract infections", "Treatment and prophylaxis of PCP (Pneumocystis jirovecii)", "Treats community-acquired MRSA skin and soft tissue infections", "Treats Stenotrophomonas maltophilia infections", "Treats toxoplasmosis", "Treats traveler's diarrhea" ], "commonDosageRange": "1 DS tablet (160/800 mg) every 12 hours; PCP prophylaxis: 1 DS tablet daily or 1 SS tablet daily; PCP treatment: 15-20 mg TMP/kg/day IV divided every 6-8 hours (as prescribed by your physician)", "recommendedForm": "Oral tablets (single-strength, double-strength) or suspension; IV for severe infections", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Well absorbed orally (85-100% bioavailability for both components). Can be taken with or without food. Ensure adequate hydration to prevent crystalluria (especially in high-dose therapy)." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Nausea and vomiting", "Skin rash (including Stevens-Johnson syndrome, rare)", "Hyperkalemia (trimethoprim blocks ENaC in collecting duct)", "Bone marrow suppression (especially in folate-deficient patients)", "Photosensitivity", "Crystalluria (with inadequate hydration)", "Elevated creatinine (trimethoprim competitively inhibits creatinine secretion without affecting GFR)", "Hepatotoxicity (rare)" ], "contraindications": [ "Known sulfonamide allergy", "Megaloblastic anemia due to folate deficiency", "Severe hepatic impairment", "Severe renal impairment (CrCl <15 mL/min)", "Pregnancy at term (risk of neonatal kernicterus)", "Infants under 2 months (except for congenital toxoplasmosis)" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "antibiotic", "sulfonamide", "infection", "uti", "pcp", "mrsa", "prophylaxis" ], "sources": [ { "text": "Gupta K et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by IDSA and ESCMID. Clin Infect Dis. 2011.", "pmid": "21292654", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21292654/", "publicSourceType": "PMID" }, { "text": "Masur H et al. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. NIH/CDC/IDSA. 2019.", "pmid": "41870560", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41870560/", "publicSourceType": "PMID" }, { "text": "Liu C et al. Clinical practice guidelines by IDSA for the treatment of MRSA infections in adults and children. Clin Infect Dis. 2011.", "pmid": "21208910", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21208910/", "publicSourceType": "PMID" }, { "text": "Haseeb A, Abourehab MAS, Almalki WA et al.. Trimethoprim-Sulfamethoxazole (Bactrim) Dose Optimization in Pneumocystis jirovecii Pneumonia (PCP) Management: A Systematic Review. International journal of environmental research and public health. 2022", "pmid": "35270525", "doi": "10.3390/ijerph19052833", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35270525/", "publicSourceType": "PMID" }, { "text": "Wu PC, Chen WT, Huang IH et al.. Human Leukocyte Antigens and Sulfamethoxazole/Cotrimoxazole-Induced Severe Cutaneous Adverse Reactions: A Systematic Review and Meta-Analysis. JAMA dermatology. 2024", "claim": "PubMed-indexed evidence involving Trimethoprim-Sulfamethoxazole", "title": "Human Leukocyte Antigens and Sulfamethoxazole/Cotrimoxazole-Induced Severe Cutaneous Adverse Reactions: A Systematic Review and Meta-Analysis", "authors": "Wu PC, Chen WT, Huang IH et al.", "journal": "JAMA dermatology", "year": 2024, "pmid": "38568509", "url": "https://pubmed.ncbi.nlm.nih.gov/38568509/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1001/jamadermatol.2024.0210", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38568509/", "publicSourceType": "PMID" }, { "text": "Keragala KARK, Gunathilaka MGRSS, Senevirathna RMISK et al.. Efficacy and safety of co-trimoxazole in eradication phase of melioidosis; systematic review. Annals of clinical microbiology and antimicrobials. 2023", "claim": "PubMed-indexed evidence involving Trimethoprim-Sulfamethoxazole", "title": "Efficacy and safety of co-trimoxazole in eradication phase of melioidosis; systematic review", "authors": "Keragala KARK, Gunathilaka MGRSS, Senevirathna RMISK et al.", "journal": "Annals of clinical microbiology and antimicrobials", "year": 2023, "pmid": "37592339", "url": "https://pubmed.ncbi.nlm.nih.gov/37592339/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12941-023-00620-z", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37592339/", "publicSourceType": "PMID" }, { "text": "Ford N, Shubber Z, Jao J et al.. Safety of cotrimoxazole in pregnancy: a systematic review and meta-analysis. Journal of acquired immune deficiency syndromes (1999). 2014", "claim": "PubMed-indexed evidence involving Trimethoprim-Sulfamethoxazole", "title": "Safety of cotrimoxazole in pregnancy: a systematic review and meta-analysis", "authors": "Ford N, Shubber Z, Jao J et al.", "journal": "Journal of acquired immune deficiency syndromes (1999)", "year": 2014, "pmid": "24853309", "url": "https://pubmed.ncbi.nlm.nih.gov/24853309/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/QAI.0000000000000211", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24853309/", "publicSourceType": "PMID" }, { "text": "Wedderburn CJ, Evans C, Slogrove AL et al.. Co-trimoxazole prophylaxis for children who are HIV-exposed and uninfected: a systematic review. Journal of the International AIDS Society. 2023", "claim": "PubMed-indexed evidence involving Trimethoprim-Sulfamethoxazole", "title": "Co-trimoxazole prophylaxis for children who are HIV-exposed and uninfected: a systematic review", "authors": "Wedderburn CJ, Evans C, Slogrove AL et al.", "journal": "Journal of the International AIDS Society", "year": 2023, "pmid": "37292018", "url": "https://pubmed.ncbi.nlm.nih.gov/37292018/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/jia2.26079", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37292018/", "publicSourceType": "PMID" }, { "text": "Faré PB, Memoli E, Treglia G et al.. Trimethoprim-associated hyperkalaemia: a systematic review and meta-analysis. The Journal of antimicrobial chemotherapy. 2022", "claim": "PubMed-indexed evidence involving Trimethoprim-Sulfamethoxazole", "title": "Trimethoprim-associated hyperkalaemia: a systematic review and meta-analysis", "authors": "Faré PB, Memoli E, Treglia G et al.", "journal": "The Journal of antimicrobial chemotherapy", "year": 2022, "pmid": "36018069", "url": "https://pubmed.ncbi.nlm.nih.gov/36018069/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/jac/dkac262", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36018069/", "publicSourceType": "PMID" }, { "text": "Burgos RM, Reynolds KM, Williams J et al.. Trimethoprim-Sulfamethoxazole Associated Drug-Induced Liver Injury in Pediatrics: A Systematic Review. The Pediatric infectious disease journal. 2020", "claim": "PubMed-indexed evidence involving Trimethoprim-Sulfamethoxazole", "title": "Trimethoprim-Sulfamethoxazole Associated Drug-Induced Liver Injury in Pediatrics: A Systematic Review", "authors": "Burgos RM, Reynolds KM, Williams J et al.", "journal": "The Pediatric infectious disease journal", "year": 2020, "pmid": "32282528", "url": "https://pubmed.ncbi.nlm.nih.gov/32282528/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/INF.0000000000002664", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32282528/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Sulfonamide/diaminopyrimidine antibiotic combination (antifolate)", "blackBoxWarnings": [], "fdaPregnancyCategory": "D", "halfLife": "TMP: 8-10 hours; SMX: 10-12 hours", "onsetOfAction": "1-4 hours to peak serum concentration", "commonBrandNames": [ "Bactrim", "Bactrim DS", "Septra", "Septra DS" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Monitor CBC, renal function, and potassium with prolonged use. Monitor for hyperkalemia especially in elderly, renal impairment, or concurrent ACE inhibitor/ARB use." }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "trimethoprim-sulfamethoxazole" }, { "id": "RX-INFR-011", "name": "Metronidazole", "alternateNames": [ "Flagyl", "MetroGel" ], "category": "Prescription", "subcategory": "Nitroimidazole Antibiotic/Antiprotozoal", "overview": "A nitroimidazole antimicrobial with potent activity against anaerobic bacteria and certain protozoa. Alternative treatment for Clostridioides difficile infection when vancomycin or fidaxomicin is unavailable, bacterial vaginosis, trichomoniasis, amoebic dysentery, and anaerobic intra-abdominal/pelvic infections (typically combined with a cephalosporin or fluoroquinolone). Also used in combination regimens for H. pylori eradication.", "mechanismOfAction": "A prodrug that is reduced inside anaerobic and microaerophilic organisms. The nitro group of metronidazole is reduced by ferredoxin (or flavodoxin) to form reactive cytotoxic intermediates, nitro radical anions, nitroso compounds, and hydroxylamine. These intermediates cause DNA strand breakage, helix destabilization, and inhibition of nucleic acid synthesis, leading to cell death. Selective toxicity to anaerobes results from their low-redox-potential electron transport systems required to activate the drug.", "commonBenefits": [ "Alternative treatment for C. difficile infection (when first-line agents unavailable)", "Treats bacterial vaginosis", "Treats trichomoniasis", "Treats amoebic dysentery and liver abscess", "Treats anaerobic intra-abdominal and pelvic infections", "Component of H. pylori eradication regimens" ], "commonDosageRange": "250-500 mg every 8 hours orally; C. diff: 500 mg TID x 10 days; bacterial vaginosis: 500 mg BID x 7 days; trichomoniasis: 2 g single dose (as prescribed by your physician)", "recommendedForm": "Oral tablets, capsules, IV, topical gel, or vaginal gel", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Oral bioavailability nearly 100%. Taking with food reduces GI upset. IMPORTANT: Avoid alcohol during treatment and for at least 3 days after, disulfiram-like reaction (nausea, vomiting, flushing, tachycardia)." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Metallic taste (very common)", "Nausea and vomiting", "Diarrhea", "Disulfiram-like reaction with alcohol", "Peripheral neuropathy (with prolonged use)", "Darkening of urine (harmless metabolite)", "Headache", "Seizures (rare, with high doses or prolonged use)" ], "contraindications": [ "Known hypersensitivity to metronidazole or nitroimidazoles", "First trimester of pregnancy (for trichomoniasis, weigh risk/benefit)", "Concurrent alcohol consumption (disulfiram-like reaction)", "Concurrent disulfiram use (risk of psychotic reactions)", "Concurrent use with lithium without monitoring (may increase lithium levels)" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "antibiotic", "antiprotozoal", "nitroimidazole", "infection", "c-diff", "anaerobic", "bv", "trichomoniasis" ], "sources": [ { "text": "McDonald LC et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by IDSA and SHEA. Clin Infect Dis. 2018.", "pmid": "29462280", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29462280/", "publicSourceType": "PMID" }, { "text": "Workowski KA et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021.", "pmid": "34292926", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34292926/", "publicSourceType": "PMID" }, { "text": "Solomkin JS et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by SIS and IDSA. Clin Infect Dis. 2010.", "pmid": "20034345", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20034345/", "publicSourceType": "PMID" }, { "text": "Sørensen CG, Karlsson WK, Amin FM et al.. Metronidazole-induced encephalopathy: a systematic review. Journal of neurology. 2020", "pmid": "30536109", "doi": "10.1007/s00415-018-9147-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30536109/", "publicSourceType": "PMID" }, { "text": "Taj S, Zuber M, Hanumanthaiah VB et al.. Metronidazole Induced Cutaneous Adverse Drug Reaction- A Systematic Review of Descriptive Studies. Current reviews in clinical and experimental pharmacology. 2024", "claim": "PubMed-indexed evidence involving Metronidazole", "title": "Metronidazole Induced Cutaneous Adverse Drug Reaction- A Systematic Review of Descriptive Studies", "authors": "Taj S, Zuber M, Hanumanthaiah VB et al.", "journal": "Current reviews in clinical and experimental pharmacology", "year": 2024, "pmid": "37264661", "url": "https://pubmed.ncbi.nlm.nih.gov/37264661/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2174/2772432819666230601155545", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37264661/", "publicSourceType": "PMID" }, { "text": "Shahzad I, Alasmari MS, Zamir A et al.. Clinical pharmacokinetics of metronidazole: a systematic review and meta-analysis. Antimicrobial agents and chemotherapy. 2025", "claim": "PubMed-indexed evidence involving Metronidazole", "title": "Clinical pharmacokinetics of metronidazole: a systematic review and meta-analysis", "authors": "Shahzad I, Alasmari MS, Zamir A et al.", "journal": "Antimicrobial agents and chemotherapy", "year": 2025, "pmid": "40741956", "url": "https://pubmed.ncbi.nlm.nih.gov/40741956/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1128/aac.01904-24", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40741956/", "publicSourceType": "PMID" }, { "text": "Eberspacher C, Mascagni D, Pontone S et al.. Topical metronidazole after haemorrhoidectomy to reduce postoperative pain: a systematic review. Updates in surgery. 2024", "claim": "PubMed-indexed evidence involving Metronidazole", "title": "Topical metronidazole after haemorrhoidectomy to reduce postoperative pain: a systematic review", "authors": "Eberspacher C, Mascagni D, Pontone S et al.", "journal": "Updates in surgery", "year": 2024, "pmid": "39117876", "url": "https://pubmed.ncbi.nlm.nih.gov/39117876/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s13304-024-01930-3", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39117876/", "publicSourceType": "PMID" }, { "text": "Burtin P, Taddio A, Ariburnu O et al.. Safety of metronidazole in pregnancy: a meta-analysis. American journal of obstetrics and gynecology. 1995", "claim": "PubMed-indexed evidence involving Metronidazole", "title": "Safety of metronidazole in pregnancy: a meta-analysis", "authors": "Burtin P, Taddio A, Ariburnu O et al.", "journal": "American journal of obstetrics and gynecology", "year": 1995, "pmid": "7856680", "url": "https://pubmed.ncbi.nlm.nih.gov/7856680/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/0002-9378(95)90567-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7856680/", "publicSourceType": "PMID" }, { "text": "Re AD, Toh JWT, Iredell J et al.. Metronidazole in the Management of Post-Open Haemorrhoidectomy Pain: Systematic Review. Annals of coloproctology. 2020", "claim": "PubMed-indexed evidence involving Metronidazole", "title": "Metronidazole in the Management of Post-Open Haemorrhoidectomy Pain: Systematic Review", "authors": "Re AD, Toh JWT, Iredell J et al.", "journal": "Annals of coloproctology", "year": 2020, "pmid": "32146782", "url": "https://pubmed.ncbi.nlm.nih.gov/32146782/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3393/ac.2020.01.08", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32146782/", "publicSourceType": "PMID" }, { "text": "Xia W, Manning JPR, Barazanchi AWH et al.. Metronidazole following excisional haemorrhoidectomy: a systematic review and meta-analysis. ANZ journal of surgery. 2018", "claim": "PubMed-indexed evidence involving Metronidazole", "title": "Metronidazole following excisional haemorrhoidectomy: a systematic review and meta-analysis", "authors": "Xia W, Manning JPR, Barazanchi AWH et al.", "journal": "ANZ journal of surgery", "year": 2018, "pmid": "29573108", "url": "https://pubmed.ncbi.nlm.nih.gov/29573108/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/ans.14236", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29573108/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Nitroimidazole antibiotic/antiprotozoal", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "6-8 hours", "onsetOfAction": "1-2 hours to peak serum concentration", "commonBrandNames": [ "Flagyl", "Flagyl ER", "MetroGel" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "metronidazole" }, { "id": "RX-INFR-012", "name": "Nitrofurantoin", "alternateNames": [ "Macrobid", "Macrodantin" ], "category": "Prescription", "subcategory": "Nitrofuran Antibiotic", "overview": "A nitrofuran antibiotic used exclusively for the treatment and prophylaxis of uncomplicated urinary tract infections. Active against most common UTI pathogens including E. coli (resistance remains low), Enterococcus faecalis, S. saprophyticus, and Klebsiella. Does not achieve therapeutic serum or tissue concentrations, so it is only effective for lower urinary tract (bladder) infections.", "mechanismOfAction": "A prodrug that is reduced by bacterial nitroreductases to form highly reactive electrophilic intermediates. These intermediates attack bacterial ribosomal proteins, DNA, and other macromolecules through multiple mechanisms simultaneously, inhibiting protein synthesis, aerobic energy metabolism, DNA synthesis, RNA synthesis, and cell wall synthesis. This multi-target mechanism results in a very low rate of resistance development.", "commonBenefits": [ "First-line treatment for uncomplicated lower UTI (cystitis)", "UTI prophylaxis (recurrent infections)", "Low resistance rates (multi-target mechanism)", "Minimal impact on gut and vaginal flora", "Well-tolerated for short courses" ], "commonDosageRange": "Macrobid: 100 mg every 12 hours x 5 days; Macrodantin: 50-100 mg QID x 7 days; prophylaxis: 50-100 mg at bedtime (as prescribed by your physician)", "recommendedForm": "Oral capsules (Macrobid macrocrystals/monohydrate preferred) or suspension", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with food to increase absorption and reduce GI upset. Food increases bioavailability by approximately 40%. The macrocrystal form (Macrobid) has slower dissolution, providing more sustained urinary levels and fewer GI side effects." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Nausea (most common, reduced with macrocrystal form)", "Headache", "Flatulence", "Brown-orange urine discoloration (harmless)", "Pulmonary toxicity (acute hypersensitivity or chronic fibrosis with prolonged use)", "Peripheral neuropathy (with prolonged use or renal impairment)", "Hepatotoxicity (rare)" ], "contraindications": [ "Severe renal impairment (CrCl <30 mL/min), inadequate urinary drug concentration and increased toxicity risk", "Pregnancy at term (38-42 weeks), risk of hemolytic anemia in neonate", "Infants under 1 month (risk of hemolytic anemia)", "Known hypersensitivity to nitrofurantoin", "G6PD deficiency (risk of hemolytic anemia)", "History of pulmonary reactions to nitrofurantoin" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "antibiotic", "nitrofuran", "uti", "cystitis", "urinary", "prophylaxis" ], "sources": [ { "text": "Gupta K et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by IDSA and ESCMID. Clin Infect Dis. 2011.", "pmid": "21292654", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21292654/", "publicSourceType": "PMID" }, { "text": "McKinnell JA et al. Nitrofurantoin compares favorably to recommended agents as empirical treatment of uncomplicated urinary tract infections in a decision and cost analysis. Mayo Clin Proc. 2011.", "pmid": "21576512", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21576512/", "publicSourceType": "PMID" }, { "text": "Ibrahim T et al. Safety and efficacy of gepotidacin in urinary tract infection: a GRADE-assessed systematic review and meta-analysis. J Antimicrob Chemother. 2026.", "pmid": "41549666", "doi": "10.1093/jac/dkaf469", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41549666/", "publicSourceType": "PMID" }, { "text": "Konwar M, Gogtay NJ, Ravi R et al.. Evaluation of efficacy and safety of fosfomycin versus nitrofurantoin for the treatment of uncomplicated lower urinary tract infection (UTI) in women - A systematic review and meta-analysis. Journal of chemotherapy (Florence, Italy). 2022", "pmid": "34151754", "doi": "10.1080/1120009X.2021.1938949", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34151754/", "publicSourceType": "PMID" }, { "text": "Huttner A, Kowalczyk A, Turjeman A et al.. Effect of 5-Day Nitrofurantoin vs Single-Dose Fosfomycin on Clinical Resolution of Uncomplicated Lower Urinary Tract Infection in Women: A Randomized Clinical Trial. JAMA. 2018", "pmid": "29710295", "doi": "10.1001/jama.2018.3627", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29710295/", "publicSourceType": "PMID" }, { "text": "Huttner A, Verhaegh EM, Harbarth S et al.. Nitrofurantoin revisited: a systematic review and meta-analysis of controlled trials. The Journal of antimicrobial chemotherapy. 2015", "claim": "PubMed-indexed evidence involving Nitrofurantoin", "title": "Nitrofurantoin revisited: a systematic review and meta-analysis of controlled trials", "authors": "Huttner A, Verhaegh EM, Harbarth S et al.", "journal": "The Journal of antimicrobial chemotherapy", "year": 2015, "pmid": "26066581", "url": "https://pubmed.ncbi.nlm.nih.gov/26066581/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1093/jac/dkv147", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26066581/", "publicSourceType": "PMID" }, { "text": "Recht J, Chansamouth V, White NJ et al.. Nitrofurantoin and glucose-6-phosphate dehydrogenase deficiency: a safety review. JAC-antimicrobial resistance. 2022", "claim": "PubMed-indexed evidence involving Nitrofurantoin", "title": "Nitrofurantoin and glucose-6-phosphate dehydrogenase deficiency: a safety review", "authors": "Recht J, Chansamouth V, White NJ et al.", "journal": "JAC-antimicrobial resistance", "year": 2022, "pmid": "35529053", "url": "https://pubmed.ncbi.nlm.nih.gov/35529053/", "study_type": "review", "confidence": "verify", "doi": "10.1093/jacamr/dlac045", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35529053/", "publicSourceType": "PMID" }, { "text": "Perry C, Hossain M, Powell M et al.. Design of Two Phase III, Randomized, Multicenter Studies Comparing Gepotidacin with Nitrofurantoin for the Treatment of Uncomplicated Urinary Tract Infection in Female Participants. Infectious diseases and therapy. 2022", "claim": "PubMed-indexed evidence involving Nitrofurantoin", "title": "Design of Two Phase III, Randomized, Multicenter Studies Comparing Gepotidacin with Nitrofurantoin for the Treatment of Uncomplicated Urinary Tract Infection in Female Participants", "authors": "Perry C, Hossain M, Powell M et al.", "journal": "Infectious diseases and therapy", "year": 2022, "pmid": "36271314", "url": "https://pubmed.ncbi.nlm.nih.gov/36271314/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/s40121-022-00706-9", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36271314/", "publicSourceType": "PMID" }, { "text": "Wagenlehner F, Perry CR, Hooton TM et al.. Plain language summary: efficacy and safety of gepotidacin, a new oral antibiotic, compared with nitrofurantoin, a commonly used oral antibiotic, for treating uncomplicated urinary tract infection. Future microbiology. 2025", "claim": "PubMed-indexed evidence involving Nitrofurantoin", "title": "Plain language summary: efficacy and safety of gepotidacin, a new oral antibiotic, compared with nitrofurantoin, a commonly used oral antibiotic, for treating uncomplicated urinary tract infection", "authors": "Wagenlehner F, Perry CR, Hooton TM et al.", "journal": "Future microbiology", "year": 2025, "pmid": "39988828", "url": "https://pubmed.ncbi.nlm.nih.gov/39988828/", "study_type": "review", "confidence": "verify", "doi": "10.1080/17460913.2025.2460387", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39988828/", "publicSourceType": "PMID" }, { "text": "Kaye AD, Shah SS, LaHaye L et al.. Nitrofurantoin-Induced Pulmonary Toxicity: Mechanisms, Diagnosis, and Management. Toxics. 2025", "claim": "PubMed-indexed evidence involving Nitrofurantoin", "title": "Nitrofurantoin-Induced Pulmonary Toxicity: Mechanisms, Diagnosis, and Management", "authors": "Kaye AD, Shah SS, LaHaye L et al.", "journal": "Toxics", "year": 2025, "pmid": "40423461", "url": "https://pubmed.ncbi.nlm.nih.gov/40423461/", "study_type": "review", "confidence": "verify", "doi": "10.3390/toxics13050382", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40423461/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Nitrofuran antibiotic (urinary antiseptic)", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "0.3-1 hour (rapidly eliminated renally)", "onsetOfAction": "30 minutes to peak urinary concentration", "commonBrandNames": [ "Macrobid", "Macrodantin" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "nitrofurantoin" }, { "id": "RX-INFR-013", "name": "Clindamycin", "alternateNames": [ "Cleocin", "Dalacin" ], "category": "Prescription", "subcategory": "Lincosamide Antibiotic", "overview": "A lincosamide antibiotic with excellent activity against gram-positive cocci (including many community-acquired MRSA strains), anaerobes, and certain protozoa (Toxoplasma, Plasmodium). Used for skin and soft tissue infections (including MRSA), bone and joint infections, intra-abdominal/pelvic infections (with gram-negative coverage), bacterial vaginosis, toxoplasmosis (with pyrimethamine), and dental infections. Also used topically for acne.", "mechanismOfAction": "Binds to the 50S ribosomal subunit at the 23S rRNA of the peptidyl transferase center, preventing peptide bond formation and blocking bacterial protein synthesis. Primarily bacteriostatic, but may be bactericidal at high concentrations or against highly susceptible organisms. Notably suppresses toxin production by S. aureus and group A Streptococcus, making it useful as an adjunct in toxin-mediated diseases like necrotizing fasciitis and toxic shock syndrome.", "commonBenefits": [ "Treats skin and soft tissue infections (including CA-MRSA)", "Treats dental and orofacial infections", "Treats bone and joint infections", "Treats intra-abdominal and pelvic infections (anaerobic coverage)", "Suppresses toxin production in necrotizing fasciitis/toxic shock", "Topical treatment for acne vulgaris" ], "commonDosageRange": "150-450 mg every 6-8 hours orally; IV: 600-900 mg every 8 hours; max 1.8 g/day orally or 4.8 g/day IV (as prescribed by your physician)", "recommendedForm": "Oral capsules, oral solution, IV, topical gel/lotion, or vaginal cream", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Well absorbed orally (~90% bioavailability). Food delays but does not reduce absorption. Take with a full glass of water to prevent esophageal irritation. Excellent penetration into bone, making it useful for osteomyelitis." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Diarrhea (common, up to 20%)", "Clostridioides difficile-associated diarrhea/pseudomembranous colitis (higher risk than most antibiotics)", "Nausea", "Abdominal pain", "Skin rash", "Elevated liver enzymes", "Esophageal irritation (if taken without adequate water)" ], "contraindications": [ "Known hypersensitivity to clindamycin or lincomycin", "History of Clostridioides difficile-associated diarrhea", "History of pseudomembranous colitis", "Severe hepatic impairment (dose adjustment required)" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "antibiotic", "lincosamide", "infection", "mrsa", "anaerobic", "skin-infection", "dental", "acne" ], "sources": [ { "text": "Liu C et al. Clinical practice guidelines by IDSA for the treatment of MRSA infections in adults and children. Clin Infect Dis. 2011.", "pmid": "21208910", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21208910/", "publicSourceType": "PMID" }, { "text": "Stevens DL et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the IDSA. Clin Infect Dis. 2014.", "pmid": "24973422", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24973422/", "publicSourceType": "PMID" }, { "text": "Brook I. Clindamycin in treatment of aspiration pneumonia in older patients. J Am Geriatr Soc. 2005.", "pmid": "39029623", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39029623/", "publicSourceType": "PMID" }, { "text": "Parks T, Wilson C, Curtis N et al.. Polyspecific Intravenous Immunoglobulin in Clindamycin-treated Patients With Streptococcal Toxic Shock Syndrome: A Systematic Review and Meta-analysis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2018", "pmid": "29788397", "doi": "10.1093/cid/ciy401", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29788397/", "publicSourceType": "PMID" }, { "text": "Falagas ME, Matthaiou DK, Karveli EA et al.. Meta-analysis: randomized controlled trials of clindamycin/aminoglycoside vs. beta-lactam monotherapy for the treatment of intra-abdominal infections. Alimentary pharmacology & therapeutics. 2007", "claim": "PubMed-indexed evidence involving Clindamycin", "title": "Meta-analysis: randomized controlled trials of clindamycin/aminoglycoside vs. beta-lactam monotherapy for the treatment of intra-abdominal infections", "authors": "Falagas ME, Matthaiou DK, Karveli EA et al.", "journal": "Alimentary pharmacology & therapeutics", "year": 2007, "pmid": "17305755", "url": "https://pubmed.ncbi.nlm.nih.gov/17305755/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/j.1365-2036.2006.03240.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17305755/", "publicSourceType": "PMID" }, { "text": "Assefa M. Inducible Clindamycin-Resistant Staphylococcus aureus Strains in Africa: A Systematic Review. International journal of microbiology. 2022", "claim": "PubMed-indexed evidence involving Clindamycin", "title": "Inducible Clindamycin-Resistant Staphylococcus aureus Strains in Africa: A Systematic Review", "authors": "Assefa M", "journal": "International journal of microbiology", "year": 2022, "pmid": "35498395", "url": "https://pubmed.ncbi.nlm.nih.gov/35498395/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1155/2022/1835603", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35498395/", "publicSourceType": "PMID" }, { "text": "Gill MA. Comment: clindamycin meta-analysis. The Annals of pharmacotherapy. 1996", "claim": "PubMed-indexed evidence involving Clindamycin", "title": "Comment: clindamycin meta-analysis", "authors": "Gill MA", "journal": "The Annals of pharmacotherapy", "year": 1996, "pmid": "8740346", "url": "https://pubmed.ncbi.nlm.nih.gov/8740346/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/106002809603000527", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8740346/", "publicSourceType": "PMID" }, { "text": "Rovers JP, Ilersich AL, Einarson TR. Meta-analysis of parenteral clindamycin dosing regimens. The Annals of pharmacotherapy. 1995", "claim": "PubMed-indexed evidence involving Clindamycin", "title": "Meta-analysis of parenteral clindamycin dosing regimens", "authors": "Rovers JP, Ilersich AL, Einarson TR", "journal": "The Annals of pharmacotherapy", "year": 1995, "pmid": "8547731", "url": "https://pubmed.ncbi.nlm.nih.gov/8547731/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/106002809502900904", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8547731/", "publicSourceType": "PMID" }, { "text": "McKeage K, Keating GM. Clindamycin/benzoyl peroxide gel (BenzaClin): a review of its use in the management of acne. American journal of clinical dermatology. 2008", "claim": "PubMed-indexed evidence involving Clindamycin", "title": "Clindamycin/benzoyl peroxide gel (BenzaClin): a review of its use in the management of acne", "authors": "McKeage K, Keating GM", "journal": "American journal of clinical dermatology", "year": 2008, "pmid": "18429651", "url": "https://pubmed.ncbi.nlm.nih.gov/18429651/", "study_type": "review", "confidence": "verify", "doi": "10.2165/00128071-200809030-00010", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18429651/", "publicSourceType": "PMID" }, { "text": "Zambrano D. Clindamycin in the treatment of obstetric and gynecologic infections: a review. Clinical therapeutics. 1991", "claim": "PubMed-indexed evidence involving Clindamycin", "title": "Clindamycin in the treatment of obstetric and gynecologic infections: a review", "authors": "Zambrano D", "journal": "Clinical therapeutics", "year": 1991, "pmid": "2029726", "url": "https://pubmed.ncbi.nlm.nih.gov/2029726/", "study_type": "review", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2029726/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Lincosamide antibiotic", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "2-3 hours", "onsetOfAction": "45-60 minutes to peak serum concentration (oral)", "commonBrandNames": [ "Cleocin", "Dalacin C" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "clindamycin" }, { "id": "RX-INFR-014", "name": "Fluconazole", "alternateNames": [ "Diflucan" ], "category": "Prescription", "subcategory": "Triazole Antifungal", "overview": "A first-generation triazole antifungal with excellent activity against most Candida species (except C. krusei and some C. glabrata) and Cryptococcus neoformans. Used for vulvovaginal candidiasis (single dose), oropharyngeal and esophageal candidiasis, candidemia, cryptococcal meningitis (induction and long-term suppression in HIV patients), and prophylaxis in immunocompromised patients. Excellent oral bioavailability and CNS penetration.", "mechanismOfAction": "Selectively inhibits fungal cytochrome P450 enzyme lanosterol 14-alpha-demethylase (CYP51A1), which converts lanosterol to ergosterol. Ergosterol is an essential component of fungal cell membranes (analogous to cholesterol in mammalian membranes). Depletion of ergosterol and accumulation of toxic methylated sterol intermediates disrupts membrane integrity, permeability, and function, leading to growth inhibition. Primarily fungistatic against Candida but fungicidal against Cryptococcus.", "commonBenefits": [ "Treats vulvovaginal candidiasis (single 150 mg dose)", "Treats oropharyngeal and esophageal candidiasis", "Treats candidemia and invasive candidiasis", "Treats cryptococcal meningitis", "Prophylaxis in immunocompromised patients", "Excellent oral bioavailability (>90%) and CSF penetration" ], "commonDosageRange": "Vaginal candidiasis: 150 mg single dose; oropharyngeal: 200 mg day 1, then 100 mg daily x 7-14 days; esophageal: 200-400 mg daily; systemic: 400-800 mg daily (as prescribed by your physician)", "recommendedForm": "Oral tablets, oral suspension, or IV", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Excellent oral bioavailability (>90%), not significantly affected by food or gastric pH. Oral and IV doses are interchangeable. Moderate CYP2C9, CYP2C19, and CYP3A4 inhibitor, significant drug interactions possible." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Nausea", "Headache", "Abdominal pain", "Diarrhea", "Elevated liver enzymes (hepatotoxicity with prolonged high-dose use)", "QT prolongation (dose-dependent)", "Skin rash (rarely Stevens-Johnson syndrome)" ], "contraindications": [ "Known hypersensitivity to fluconazole or other azole antifungals", "Concomitant use with terfenadine (when fluconazole >=400 mg/day), cisapride, erythromycin, pimozide, or quinidine (QT prolongation risk)", "Pregnancy (category D for chronic high-dose use, associated with craniofacial and skeletal defects)", "Severe hepatic disease (weigh risk vs benefit)", "Concomitant use with drugs metabolized by CYP2C9 or CYP3A4 with narrow therapeutic indices (warfarin, phenytoin, cyclosporine)" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "antifungal", "azole", "infection", "candida", "yeast", "cryptococcus", "immunocompromised" ], "sources": [ { "text": "Pappas PG et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by IDSA. Clin Infect Dis. 2016.", "pmid": "26679628", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26679628/", "publicSourceType": "PMID" }, { "text": "Perfect JR et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by IDSA. Clin Infect Dis. 2010.", "pmid": "20047480", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20047480/", "publicSourceType": "PMID" }, { "text": "Sobel JD et al. Vulvovaginal candidiasis: epidemiologic, diagnostic, and therapeutic considerations. Am J Obstet Gynecol. 1998.", "pmid": "12150685", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12150685/", "publicSourceType": "PMID" }, { "claim": "Fluconazole use in pregnancy is associated with risk of congenital malformations", "title": "Risk of congenital malformations and miscarriages following maternal use of oral fluconazole during the first trimester of pregnancy: a systematic review and meta-analysis.", "authors": "Latour M, Vauzelle C, Elefant E et al.", "journal": "European Journal of Epidemiology", "year": 2024, "pmid": "39658659", "url": "https://pubmed.ncbi.nlm.nih.gov/39658659/", "study_type": "meta-analysis", "key_finding": "Meta-analysis found low-dose fluconazole (150 mg) in first trimester was not significantly associated with major congenital malformations, but high-dose or prolonged use may increase risk of specific birth defects; vaginal azoles remain preferred in pregnancy.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39658659/", "publicSourceType": "PMID" }, { "claim": "Fluconazole prophylaxis prevents invasive fungal infections in preterm infants", "title": "A meta-analysis of fluconazole for the prevention of invasive fungal infection in preterm infants.", "authors": "Wang XL, Ma Y, Wang SH et al.", "journal": "American Journal of Translational Research", "year": 2021, "pmid": "33594302", "url": "https://pubmed.ncbi.nlm.nih.gov/33594302/", "study_type": "meta-analysis", "key_finding": "Meta-analysis found fluconazole prophylaxis significantly reduced the incidence of invasive fungal infections in very low birth weight and preterm infants without increasing resistance or significant adverse effects.", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33594302/", "publicSourceType": "PMID" }, { "text": "Egunsola O, Adefurin A, Fakis A et al.. Safety of fluconazole in paediatrics: a systematic review. European journal of clinical pharmacology. 2013", "claim": "PubMed-indexed evidence involving Fluconazole", "title": "Safety of fluconazole in paediatrics: a systematic review", "authors": "Egunsola O, Adefurin A, Fakis A et al.", "journal": "European journal of clinical pharmacology", "year": 2013, "pmid": "23325436", "url": "https://pubmed.ncbi.nlm.nih.gov/23325436/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00228-012-1468-2", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23325436/", "publicSourceType": "PMID" }, { "text": "De la Cerda-Vargas MF, Navarro-Dominguez P, Meza-Mata E et al.. Pediatric Coccidioidal Meningitis: A Systematic Review and Proportional Synthesis of Cases Reported in the Fluconazole Era (2000-2025). Journal of fungi (Basel, Switzerland). 2025", "claim": "PubMed-indexed evidence involving Fluconazole", "title": "Pediatric Coccidioidal Meningitis: A Systematic Review and Proportional Synthesis of Cases Reported in the Fluconazole Era (2000-2025)", "authors": "De la Cerda-Vargas MF, Navarro-Dominguez P, Meza-Mata E et al.", "journal": "Journal of fungi (Basel, Switzerland)", "year": 2025, "pmid": "41149903", "url": "https://pubmed.ncbi.nlm.nih.gov/41149903/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/jof11100713", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41149903/", "publicSourceType": "PMID" }, { "text": "Bongomin F, Oladele RO, Gago S et al.. A systematic review of fluconazole resistance in clinical isolates of Cryptococcus species. Mycoses. 2018", "claim": "PubMed-indexed evidence involving Fluconazole", "title": "A systematic review of fluconazole resistance in clinical isolates of Cryptococcus species", "authors": "Bongomin F, Oladele RO, Gago S et al.", "journal": "Mycoses", "year": 2018, "pmid": "29377368", "url": "https://pubmed.ncbi.nlm.nih.gov/29377368/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/myc.12747", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29377368/", "publicSourceType": "PMID" }, { "text": "Rios JFDS, Camargos PAM, Corrêa LP et al.. Fluconazole prophylaxis in preterm infants: a systematic review. The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases. 2017", "claim": "PubMed-indexed evidence involving Fluconazole", "title": "Fluconazole prophylaxis in preterm infants: a systematic review", "authors": "Rios JFDS, Camargos PAM, Corrêa LP et al.", "journal": "The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases", "year": 2017, "pmid": "28286016", "url": "https://pubmed.ncbi.nlm.nih.gov/28286016/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.bjid.2017.01.008", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28286016/", "publicSourceType": "PMID" }, { "text": "Budani MC, Fensore S, Di Marzio M et al.. Maternal use of fluconazole and congenital malformations in the progeny: A meta-analysis of the literature. Reproductive toxicology (Elmsford, N.Y.). 2021", "claim": "PubMed-indexed evidence involving Fluconazole", "title": "Maternal use of fluconazole and congenital malformations in the progeny: A meta-analysis of the literature", "authors": "Budani MC, Fensore S, Di Marzio M et al.", "journal": "Reproductive toxicology (Elmsford, N.Y.)", "year": 2021, "pmid": "33383164", "url": "https://pubmed.ncbi.nlm.nih.gov/33383164/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.reprotox.2020.12.018", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33383164/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Triazole antifungal", "blackBoxWarnings": [], "fdaPregnancyCategory": "D (chronic high-dose); C (single low-dose)", "halfLife": "30 hours (allows once-daily dosing)", "onsetOfAction": "1-2 hours to peak serum concentration", "commonBrandNames": [ "Diflucan" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "LFTs with prolonged use. Monitor renal function for dose adjustment. Monitor for QT prolongation with concurrent QT-prolonging drugs." }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "fluconazole" }, { "id": "RX-INFR-015", "name": "Terbinafine", "alternateNames": [ "Lamisil" ], "category": "Prescription", "subcategory": "Allylamine Antifungal", "overview": "An allylamine antifungal that is the treatment of choice for dermatophyte infections (onychomycosis, tinea capitis). Highly effective against Trichophyton, Microsporum, and Epidermophyton species. Oral terbinafine is the most effective treatment for toenail onychomycosis with cure rates of 70-80%. Also available topically for tinea pedis, tinea corporis, and tinea cruris.", "mechanismOfAction": "Inhibits squalene epoxidase, a key enzyme in the fungal ergosterol biosynthetic pathway. This enzyme converts squalene to squalene-2,3-epoxide, an early step in ergosterol synthesis. Inhibition leads to squalene accumulation (which is directly toxic to fungal cells) and ergosterol depletion (which destabilizes the cell membrane). The dual mechanism makes terbinafine fungicidal against dermatophytes, unlike azoles which are primarily fungistatic.", "commonBenefits": [ "First-line treatment for toenail onychomycosis", "Treats fingernail onychomycosis", "Treats tinea capitis (oral)", "High cure rates for dermatophyte infections (70-80%)", "Once-daily dosing for defined treatment courses" ], "commonDosageRange": "250 mg once daily; toenail onychomycosis: 12 weeks; fingernail onychomycosis: 6 weeks; tinea capitis: 4-6 weeks (as prescribed by your physician)", "recommendedForm": "Oral tablets; also available as topical cream, gel, or spray", "absorption": { "isFatSoluble": true, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Well absorbed orally (>70% bioavailability). Food slightly increases absorption but not clinically significant. Highly lipophilic, concentrates in skin, nails, and adipose tissue. Persists in nail tissue for months after discontinuation." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Headache", "Diarrhea", "Dyspepsia and abdominal pain", "Taste disturbance or loss (dysgeusia/ageusia)", "Elevated liver enzymes (hepatotoxicity, including rare liver failure)", "Skin rash", "Neutropenia (rare)", "Lupus-like reaction (very rare)" ], "contraindications": [ "Known hypersensitivity to terbinafine", "Active or chronic liver disease", "Severe renal impairment (CrCl <50 mL/min, limited data)", "Concomitant use with drugs metabolized by CYP2D6 with narrow therapeutic indices" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "antifungal", "allylamine", "infection", "onychomycosis", "dermatophyte", "nail-fungus", "tinea" ], "sources": [ { "text": "Kreijkamp-Kaspers S et al. Oral antifungal medication for toenail onychomycosis. Cochrane Database Syst Rev. 2017.", "pmid": "28707751", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28707751/", "publicSourceType": "PMID" }, { "text": "Gupta AK et al. Systematic review of oral treatments for dermatophyte toenail onychomycosis: an update. Br J Dermatol. 2020.", "pmid": "41051009", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41051009/", "publicSourceType": "PMID" }, { "text": "Chang CH et al. Terbinafine-associated hepatic failure. J Hepatol. 2007.", "pmid": "17532089", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17532089/", "publicSourceType": "PMID" }, { "text": "Ajit C, Suvannasankha A, Zaeri N et al.. Terbinafine-associated hepatotoxicity. The American journal of the medical sciences. 2003", "pmid": "12792250", "doi": "10.1097/00000441-200305000-00008", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12792250/", "publicSourceType": "PMID" }, { "text": "Terbinafine. 2006", "pmid": "30000456", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30000456/", "publicSourceType": "PMID" }, { "text": "Tey HL, Tan AS, Chan YC. Meta-analysis of randomized, controlled trials comparing griseofulvin and terbinafine in the treatment of tinea capitis. Journal of the American Academy of Dermatology. 2011", "claim": "PubMed-indexed evidence involving Terbinafine", "title": "Meta-analysis of randomized, controlled trials comparing griseofulvin and terbinafine in the treatment of tinea capitis", "authors": "Tey HL, Tan AS, Chan YC", "journal": "Journal of the American Academy of Dermatology", "year": 2011, "pmid": "21334096", "url": "https://pubmed.ncbi.nlm.nih.gov/21334096/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jaad.2010.02.048", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21334096/", "publicSourceType": "PMID" }, { "text": "Ferreira CB, Lisboa C. A systematic review on the emergence of terbinafine-resistant Trichophyton indotineae in Europe: Time to act?. Journal of the European Academy of Dermatology and Venereology : JEADV. 2025", "claim": "PubMed-indexed evidence involving Terbinafine", "title": "A systematic review on the emergence of terbinafine-resistant Trichophyton indotineae in Europe: Time to act?", "authors": "Ferreira CB, Lisboa C", "journal": "Journal of the European Academy of Dermatology and Venereology : JEADV", "year": 2025, "pmid": "39082800", "url": "https://pubmed.ncbi.nlm.nih.gov/39082800/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/jdv.20270", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39082800/", "publicSourceType": "PMID" }, { "text": "Jegathees T, Holmes ZP, Martin C et al.. Emerging Terbinafine Resistant Trichophyton Dermatophytosis, Testing Options and Alternative Treatments: A Systematic Review. The Australasian journal of dermatology. 2025", "claim": "PubMed-indexed evidence involving Terbinafine", "title": "Emerging Terbinafine Resistant Trichophyton Dermatophytosis, Testing Options and Alternative Treatments: A Systematic Review", "authors": "Jegathees T, Holmes ZP, Martin C et al.", "journal": "The Australasian journal of dermatology", "year": 2025, "pmid": "40704771", "url": "https://pubmed.ncbi.nlm.nih.gov/40704771/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/ajd.14575", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40704771/", "publicSourceType": "PMID" }, { "text": "Yan J, Wang X, Chen S. Systematic review of severe acute liver injury caused by terbinafine. International journal of clinical pharmacy. 2014", "claim": "PubMed-indexed evidence involving Terbinafine", "title": "Systematic review of severe acute liver injury caused by terbinafine", "authors": "Yan J, Wang X, Chen S", "journal": "International journal of clinical pharmacy", "year": 2014, "pmid": "24986266", "url": "https://pubmed.ncbi.nlm.nih.gov/24986266/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s11096-014-9969-y", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24986266/", "publicSourceType": "PMID" }, { "text": "Yin Z, Xu J, Luo D. A meta-analysis comparing long-term recurrences of toenail onychomycosis after successful treatment with terbinafine versus itraconazole. The Journal of dermatological treatment. 2012", "claim": "PubMed-indexed evidence involving Terbinafine", "title": "A meta-analysis comparing long-term recurrences of toenail onychomycosis after successful treatment with terbinafine versus itraconazole", "authors": "Yin Z, Xu J, Luo D", "journal": "The Journal of dermatological treatment", "year": 2012, "pmid": "21801094", "url": "https://pubmed.ncbi.nlm.nih.gov/21801094/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3109/09546634.2011.579082", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21801094/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Allylamine antifungal", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "36 hours (terminal; effective half-life 200-400 hours in nail tissue)", "onsetOfAction": "2 hours to peak serum concentration; nail improvement over weeks to months", "commonBrandNames": [ "Lamisil" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "LFTs at baseline and periodically during treatment. CBC at baseline recommended. Discontinue if LFTs become significantly elevated or clinical signs of hepatotoxicity develop." }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "terbinafine" }, { "id": "RX-INFR-016", "name": "Acyclovir", "alternateNames": [ "Zovirax" ], "category": "Prescription", "subcategory": "Nucleoside Analog Antiviral", "overview": "A nucleoside analog antiviral that is the prototype agent for herpes virus infections. Active against herpes simplex virus types 1 and 2 (HSV-1, HSV-2) and varicella-zoster virus (VZV). Used for genital herpes (initial and recurrent episodes, chronic suppression), herpes zoster (shingles), varicella (chickenpox), herpes encephalitis (IV), and neonatal herpes (IV). Requires conversion to the active form by viral thymidine kinase, providing selective toxicity.", "mechanismOfAction": "A prodrug (acyclic guanosine analog) that requires three phosphorylation steps for activation. Viral thymidine kinase (encoded by HSV/VZV) performs the first phosphorylation to acyclovir monophosphate, this step is ~3000x more efficient in virus-infected cells, providing selectivity. Cellular kinases then convert it to the active triphosphate form. Acyclovir triphosphate competitively inhibits viral DNA polymerase and, once incorporated into the growing DNA chain, acts as a chain terminator because it lacks the 3'-hydroxyl group needed for subsequent nucleotide addition.", "commonBenefits": [ "Treats primary and recurrent genital herpes (HSV-1, HSV-2)", "Chronic suppressive therapy for recurrent genital herpes", "Treats herpes zoster (shingles)", "Treats varicella (chickenpox) in high-risk patients", "IV formulation for herpes encephalitis and neonatal herpes", "Excellent safety profile" ], "commonDosageRange": "Genital herpes initial: 400 mg TID or 200 mg 5x/day x 7-10 days; suppressive: 400 mg BID; herpes zoster: 800 mg 5x/day x 7-10 days; IV encephalitis: 10 mg/kg every 8 hours x 14-21 days (as prescribed by your physician)", "recommendedForm": "Oral capsules, tablets, suspension; IV for severe/CNS infections; topical cream", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Oral bioavailability is low (15-30%) and decreases with increasing dose. Requires frequent dosing (3-5 times daily for oral). Can be taken with or without food. Maintain adequate hydration to prevent crystalluria, especially with IV formulation." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Nausea and vomiting", "Diarrhea", "Headache", "Malaise", "Renal toxicity/crystalluria (especially IV, ensure adequate hydration and slow infusion)", "Neurotoxicity (tremor, confusion, especially in renal impairment)" ], "contraindications": [ "Known hypersensitivity to acyclovir or valacyclovir", "Severe renal impairment without dose adjustment", "Dehydration (increased risk of renal crystalluria)", "Concurrent nephrotoxic drugs without monitoring" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "antiviral", "herpes", "hsv", "vzv", "shingles", "genital-herpes", "nucleoside-analog" ], "sources": [ { "text": "Workowski KA et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021.", "pmid": "34292926", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34292926/", "publicSourceType": "PMID" }, { "text": "Gnann JW Jr, Whitley RJ. Herpes simplex encephalitis: an update. Curr Infect Dis Rep. 2017.", "pmid": "28251511", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28251511/", "publicSourceType": "PMID" }, { "text": "Dworkin RH et al. Recommendations for the management of herpes zoster. Clin Infect Dis. 2007.", "pmid": "17143845", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17143845/", "publicSourceType": "PMID" }, { "text": "Brandariz-Nuñez D, Correas-Sanahuja M, Maya-Gallego S et al.. Neurotoxicity associated with acyclovir and valacyclovir: A systematic review of cases. Journal of clinical pharmacy and therapeutics. 2021", "pmid": "34146428", "doi": "10.1111/jcpt.13464", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34146428/", "publicSourceType": "PMID" }, { "text": "Kably B, Briard M, Francoz C et al.. Population pharmacokinetics of aciclovir and its major metabolite 9-carboxymethoxymethylguanine and safety profile of valaciclovir in early liver transplant recipients. The Journal of antimicrobial chemotherapy. 2025", "claim": "PubMed-indexed evidence involving Acyclovir", "title": "Population pharmacokinetics of aciclovir and its major metabolite 9-carboxymethoxymethylguanine and safety profile of valaciclovir in early liver transplant recipients", "authors": "Kably B, Briard M, Francoz C et al.", "journal": "The Journal of antimicrobial chemotherapy", "year": 2025, "pmid": "40155064", "url": "https://pubmed.ncbi.nlm.nih.gov/40155064/", "study_type": "review", "confidence": "verify", "doi": "10.1093/jac/dkaf070", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40155064/", "publicSourceType": "PMID" }, { "text": "Wakelin A, Wolff A, Angus-Leppan H. Is intravenous aciclovir overused in possible viral encephalitis? a retrospective review. Journal of neurology. 2025", "claim": "PubMed-indexed evidence involving Acyclovir", "title": "Is intravenous aciclovir overused in possible viral encephalitis? a retrospective review", "authors": "Wakelin A, Wolff A, Angus-Leppan H", "journal": "Journal of neurology", "year": 2025, "pmid": "40522532", "url": "https://pubmed.ncbi.nlm.nih.gov/40522532/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s00415-025-13168-z", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40522532/", "publicSourceType": "PMID" }, { "text": "Keller MJ, Malone AM, Carpenter CA et al.. Safety and pharmacokinetics of aciclovir in women following release from a silicone elastomer vaginal ring. The Journal of antimicrobial chemotherapy. 2012", "claim": "PubMed-indexed evidence involving Acyclovir", "title": "Safety and pharmacokinetics of aciclovir in women following release from a silicone elastomer vaginal ring", "authors": "Keller MJ, Malone AM, Carpenter CA et al.", "journal": "The Journal of antimicrobial chemotherapy", "year": 2012, "pmid": "22556381", "url": "https://pubmed.ncbi.nlm.nih.gov/22556381/", "study_type": "review", "confidence": "verify", "doi": "10.1093/jac/dks151", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22556381/", "publicSourceType": "PMID" }, { "text": "Schreiber R, Wolpin J, Koren G. Determinants of aciclovir-induced nephrotoxicity in children. Paediatric drugs. 2008", "claim": "PubMed-indexed evidence involving Acyclovir", "title": "Determinants of aciclovir-induced nephrotoxicity in children", "authors": "Schreiber R, Wolpin J, Koren G", "journal": "Paediatric drugs", "year": 2008, "pmid": "18345723", "url": "https://pubmed.ncbi.nlm.nih.gov/18345723/", "study_type": "review", "confidence": "verify", "doi": "10.2165/00148581-200810020-00008", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18345723/", "publicSourceType": "PMID" }, { "text": "Kabut T, Weinbergerová B, Folber F et al.. High-dose aciclovir in CMV infection prophylaxis after allogeneic HSCT: a single-center long-term experience. Bone marrow transplantation. 2023", "claim": "PubMed-indexed evidence involving Acyclovir", "title": "High-dose aciclovir in CMV infection prophylaxis after allogeneic HSCT: a single-center long-term experience", "authors": "Kabut T, Weinbergerová B, Folber F et al.", "journal": "Bone marrow transplantation", "year": 2023, "pmid": "37612466", "url": "https://pubmed.ncbi.nlm.nih.gov/37612466/", "study_type": "review", "confidence": "verify", "doi": "10.1038/s41409-023-02081-6", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37612466/", "publicSourceType": "PMID" }, { "text": "Grant DM. Acyclovir (Zovirax) ophthalmic ointment: a review of clinical tolerance. Current eye research. 1987", "claim": "PubMed-indexed evidence involving Acyclovir", "title": "Acyclovir (Zovirax) ophthalmic ointment: a review of clinical tolerance", "authors": "Grant DM", "journal": "Current eye research", "year": 1987, "pmid": "3549163", "url": "https://pubmed.ncbi.nlm.nih.gov/3549163/", "study_type": "RCT", "confidence": "verify", "doi": "10.3109/02713688709020096", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3549163/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Nucleoside analog antiviral (guanosine analog)", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "2.5-3.3 hours (prolonged in renal impairment)", "onsetOfAction": "1.5-2 hours to peak serum concentration (oral)", "commonBrandNames": [ "Zovirax" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "acyclovir" }, { "id": "RX-INFR-017", "name": "Valacyclovir", "alternateNames": [ "Valtrex" ], "category": "Prescription", "subcategory": "Nucleoside Analog Antiviral (Prodrug)", "overview": "The L-valyl ester prodrug of acyclovir, providing 3-5 times higher oral bioavailability than acyclovir. This allows less frequent dosing (2-3 times daily vs 5 times daily) with equivalent or superior efficacy. Used for genital herpes (initial, recurrent, and suppressive therapy), herpes zoster (shingles), herpes labialis (cold sores), and reduction of HSV transmission to uninfected partners. The preferred oral agent for herpes infections in most clinical scenarios.", "mechanismOfAction": "Rapidly converted to acyclovir and L-valine by first-pass intestinal and hepatic esterases (valacyclovir hydrolase). Acyclovir is then selectively phosphorylated by viral thymidine kinase in HSV/VZV-infected cells and subsequently by cellular kinases to acyclovir triphosphate. The active triphosphate competitively inhibits viral DNA polymerase and serves as a DNA chain terminator upon incorporation into viral DNA, halting replication.", "commonBenefits": [ "Treats and suppresses genital herpes (preferred oral agent)", "Treats herpes zoster (shingles), better bioavailability than acyclovir", "Treats herpes labialis (cold sores), 1-day treatment", "Reduces transmission of genital HSV-2 to uninfected partners by ~50%", "Convenient dosing (2-3 times daily vs 5 times daily for acyclovir)" ], "commonDosageRange": "Genital herpes initial: 1 g BID x 10 days; recurrent: 500 mg BID x 3 days; suppressive: 500 mg-1 g daily; herpes zoster: 1 g TID x 7 days; cold sores: 2 g BID x 1 day (as prescribed by your physician)", "recommendedForm": "Oral tablets (caplets)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Oral bioavailability of acyclovir from valacyclovir is approximately 54% (vs 15-30% for oral acyclovir). Food does not significantly affect absorption. Rapidly and nearly completely converted to acyclovir after absorption. Maintain adequate hydration." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Headache", "Nausea", "Abdominal pain", "Dizziness", "Renal impairment (rare, especially with high doses in immunocompromised)", "Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS, rare, in immunocompromised at high doses)" ], "contraindications": [ "Known hypersensitivity to valacyclovir, acyclovir, or any component", "Severe renal impairment without dose adjustment", "TTP/HUS history (especially in immunocompromised patients at high doses)", "Advanced HIV disease or post-transplant patients at doses >8 g/day (TTP/HUS risk)" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "antiviral", "herpes", "hsv", "vzv", "shingles", "cold-sores", "genital-herpes", "prodrug" ], "sources": [ { "text": "Corey L et al. Once-daily valacyclovir to reduce the risk of transmission of genital herpes. N Engl J Med. 2004.", "pmid": "15319087", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15319087/", "publicSourceType": "PMID" }, { "text": "Workowski KA et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021.", "pmid": "34292926", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34292926/", "publicSourceType": "PMID" }, { "text": "Tyring SK et al. Valaciclovir for herpes simplex virus infection: long-term safety and sustained efficacy after 20 years' experience with acyclovir. J Infect Dis. 2002.", "pmid": "12353186", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12353186/", "publicSourceType": "PMID" }, { "text": "D'Antonio F, Marinceu D, Prasad S et al.. Effectiveness and safety of prenatal valacyclovir for congenital cytomegalovirus infection: systematic review and meta-analysis. Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2023", "pmid": "36484439", "doi": "10.1002/uog.26136", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36484439/", "publicSourceType": "PMID" }, { "text": "Brandariz-Nuñez D, Correas-Sanahuja M, Maya-Gallego S et al.. Neurotoxicity associated with acyclovir and valacyclovir: A systematic review of cases. Journal of clinical pharmacy and therapeutics. 2021", "pmid": "34146428", "doi": "10.1111/jcpt.13464", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34146428/", "publicSourceType": "PMID" }, { "text": "Chatzakis C, Shahar-Nissan K, Faure-Bardon V et al.. The effect of valacyclovir on secondary prevention of congenital cytomegalovirus infection, following primary maternal infection acquired periconceptionally or in the first trimester of pregnancy. An individual patient data meta-analysis. American journal of obstetrics and gynecology. 2024", "claim": "PubMed-indexed evidence involving Valacyclovir", "title": "The effect of valacyclovir on secondary prevention of congenital cytomegalovirus infection, following primary maternal infection acquired periconceptionally or in the first trimester of pregnancy. An individual patient data meta-analysis", "authors": "Chatzakis C, Shahar-Nissan K, Faure-Bardon V et al.", "journal": "American journal of obstetrics and gynecology", "year": 2024, "pmid": "37473793", "url": "https://pubmed.ncbi.nlm.nih.gov/37473793/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.ajog.2023.07.022", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37473793/", "publicSourceType": "PMID" }, { "text": "Devanand DP, Wisniewski T, Razlighi Q et al.. Valacyclovir Treatment of Early Symptomatic Alzheimer Disease: The VALAD Randomized Clinical Trial. JAMA. 2026", "claim": "PubMed-indexed evidence involving Valacyclovir", "title": "Valacyclovir Treatment of Early Symptomatic Alzheimer Disease: The VALAD Randomized Clinical Trial", "authors": "Devanand DP, Wisniewski T, Razlighi Q et al.", "journal": "JAMA", "year": 2026, "pmid": "41405855", "url": "https://pubmed.ncbi.nlm.nih.gov/41405855/", "study_type": "RCT", "confidence": "verify", "doi": "10.1001/jama.2025.21738", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41405855/", "publicSourceType": "PMID" }, { "text": "Cohen EJ, Troxel AB, Liu M et al.. Low-Dose Valacyclovir in Herpes Zoster Ophthalmicus: The Zoster Eye Disease Randomized Clinical Trial. JAMA ophthalmology. 2025", "claim": "PubMed-indexed evidence involving Valacyclovir", "title": "Low-Dose Valacyclovir in Herpes Zoster Ophthalmicus: The Zoster Eye Disease Randomized Clinical Trial", "authors": "Cohen EJ, Troxel AB, Liu M et al.", "journal": "JAMA ophthalmology", "year": 2025, "pmid": "40048183", "url": "https://pubmed.ncbi.nlm.nih.gov/40048183/", "study_type": "RCT", "confidence": "verify", "doi": "10.1001/jamaophthalmol.2024.6114", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40048183/", "publicSourceType": "PMID" }, { "text": "Warner DB, Jeng BH, Kim J et al.. Low-Dose Valacyclovir for Postherpetic Neuralgia in the Zoster Eye Disease Study: A Randomized Clinical Trial. JAMA ophthalmology. 2025", "claim": "PubMed-indexed evidence involving Valacyclovir", "title": "Low-Dose Valacyclovir for Postherpetic Neuralgia in the Zoster Eye Disease Study: A Randomized Clinical Trial", "authors": "Warner DB, Jeng BH, Kim J et al.", "journal": "JAMA ophthalmology", "year": 2025, "pmid": "40048191", "url": "https://pubmed.ncbi.nlm.nih.gov/40048191/", "study_type": "RCT", "confidence": "verify", "doi": "10.1001/jamaophthalmol.2024.6113", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40048191/", "publicSourceType": "PMID" }, { "text": "Linden DA, Guo-Parke H, McKelvey MC et al.. Valaciclovir for Epstein-Barr Virus Suppression in Moderate-to-Severe COPD: A Randomized Double-Blind Placebo-Controlled Trial. Chest. 2023", "claim": "PubMed-indexed evidence involving Valacyclovir", "title": "Valaciclovir for Epstein-Barr Virus Suppression in Moderate-to-Severe COPD: A Randomized Double-Blind Placebo-Controlled Trial", "authors": "Linden DA, Guo-Parke H, McKelvey MC et al.", "journal": "Chest", "year": 2023, "pmid": "37011709", "url": "https://pubmed.ncbi.nlm.nih.gov/37011709/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.chest.2023.03.040", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37011709/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Nucleoside analog antiviral prodrug (L-valyl ester of acyclovir)", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "2.5-3.3 hours (acyclovir after conversion)", "onsetOfAction": "1.5-2.5 hours to peak acyclovir levels", "commonBrandNames": [ "Valtrex" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "valacyclovir" }, { "id": "RX-INFR-018", "name": "Oseltamivir", "alternateNames": [ "Tamiflu" ], "category": "Prescription", "subcategory": "Neuraminidase Inhibitor Antiviral", "overview": "A neuraminidase inhibitor antiviral used for the treatment and prevention of influenza A and B. Most effective when started within 48 hours of symptom onset, reducing symptom duration by approximately 1-2 days and potentially reducing complications (pneumonia, hospitalization). Recommended by the CDC for high-risk patients with influenza, including the elderly, immunocompromised, pregnant women, and those with chronic medical conditions.", "mechanismOfAction": "A prodrug (ethyl ester) that is hydrolyzed by hepatic esterases to the active carboxylate form, oseltamivir carboxylate. The active metabolite competitively inhibits neuraminidase (sialidase), a glycoprotein enzyme on the surface of influenza A and B virions. Neuraminidase cleaves sialic acid residues on the host cell surface, which is essential for the release of newly formed virions from infected cells, spread to uninfected cells, and penetration of respiratory mucus. Inhibition results in viral aggregation on the cell surface and impaired spread.", "commonBenefits": [ "Reduces influenza symptom duration by 1-2 days", "Reduces risk of influenza-associated complications", "Post-exposure prophylaxis for influenza contacts", "Seasonal prophylaxis in high-risk populations", "Active against both influenza A and B" ], "commonDosageRange": "Treatment: 75 mg BID x 5 days (start within 48 hours of symptom onset); prophylaxis: 75 mg once daily x 10 days; pediatric dosing weight-based (as prescribed by your physician)", "recommendedForm": "Oral capsules or oral suspension", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Prodrug is well absorbed with approximately 80% bioavailability (as active carboxylate). Food does not reduce bioavailability but may reduce nausea. Can be taken with or without food." }, "evidenceRating": "moderate", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Nausea and vomiting (most common)", "Headache", "Diarrhea", "Abdominal pain", "Neuropsychiatric events (rare, delirium, hallucinations, abnormal behavior, primarily reported in pediatric patients in Japan)" ], "contraindications": [ "Known hypersensitivity to oseltamivir or any component", "Not a substitute for annual influenza vaccination", "Severe renal impairment (CrCl <30 mL/min) requires dose adjustment" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "antiviral", "influenza", "flu", "neuraminidase-inhibitor", "prophylaxis", "respiratory" ], "sources": [ { "text": "Dobson J et al. Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials. Lancet. 2015.", "pmid": "25640810", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25640810/", "publicSourceType": "PMID" }, { "text": "Jefferson T et al. Neuraminidase inhibitors for preventing and treating influenza in adults and children. Cochrane Database Syst Rev. 2014.", "pmid": "24718923", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24718923/", "publicSourceType": "PMID" }, { "text": "Uyeki TM et al. Clinical Practice Guidelines by the IDSA: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenza. Clin Infect Dis. 2019.", "pmid": "30566567", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30566567/", "publicSourceType": "PMID" }, { "text": "Malosh RE, Martin ET, Heikkinen T et al.. Efficacy and Safety of Oseltamivir in Children: Systematic Review and Individual Patient Data Meta-analysis of Randomized Controlled Trials. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2018", "pmid": "29186364", "doi": "10.1093/cid/cix1040", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29186364/", "publicSourceType": "PMID" }, { "text": "Hanula R, Bortolussi-Courval É, Mendel A et al.. Evaluation of Oseltamivir Used to Prevent Hospitalization in Outpatients With Influenza: A Systematic Review and Meta-Analysis. JAMA internal medicine. 2024", "pmid": "37306992", "doi": "10.1001/jamainternmed.2023.0699", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37306992/", "publicSourceType": "PMID" }, { "text": "Zhu L, Zhong L, Huang G. Clinical efficacy and Safety of Baloxavir Marboxil compared with Oseltamivir against influenza virus in children: A systematic review and meta-analysis. PloS one. 2025", "claim": "PubMed-indexed evidence involving Oseltamivir", "title": "Clinical efficacy and Safety of Baloxavir Marboxil compared with Oseltamivir against influenza virus in children: A systematic review and meta-analysis", "authors": "Zhu L, Zhong L, Huang G", "journal": "PloS one", "year": 2025, "pmid": "40549724", "url": "https://pubmed.ncbi.nlm.nih.gov/40549724/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1371/journal.pone.0326777", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40549724/", "publicSourceType": "PMID" }, { "text": "Shiraishi C, Kato H, Hagihara M et al.. Comparison of clinical efficacy and safety of baloxavir marboxil versus oseltamivir as the treatment for influenza virus infections: A systematic review and meta-analysis. Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy. 2024", "claim": "PubMed-indexed evidence involving Oseltamivir", "title": "Comparison of clinical efficacy and safety of baloxavir marboxil versus oseltamivir as the treatment for influenza virus infections: A systematic review and meta-analysis", "authors": "Shiraishi C, Kato H, Hagihara M et al.", "journal": "Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy", "year": 2024, "pmid": "37866622", "url": "https://pubmed.ncbi.nlm.nih.gov/37866622/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jiac.2023.10.017", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37866622/", "publicSourceType": "PMID" }, { "text": "Manuel J, Barot KS, Mayow AH et al.. Comparison of Efficacy and Safety of Baloxavir and Oseltamivir in Children With Influenza: A Systematic Review and Meta-Analysis. Cureus. 2024", "claim": "PubMed-indexed evidence involving Oseltamivir", "title": "Comparison of Efficacy and Safety of Baloxavir and Oseltamivir in Children With Influenza: A Systematic Review and Meta-Analysis", "authors": "Manuel J, Barot KS, Mayow AH et al.", "journal": "Cureus", "year": 2024, "pmid": "39529764", "url": "https://pubmed.ncbi.nlm.nih.gov/39529764/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7759/cureus.71289", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39529764/", "publicSourceType": "PMID" }, { "text": "Aliyu B, Raji YE, Chee HY et al.. Systematic review and meta-analysis of the efficacy and safety of oseltamivir (Tamiflu) in the treatment of Coronavirus Disease 2019 (COVID-19). PloS one. 2022", "claim": "PubMed-indexed evidence involving Oseltamivir", "title": "Systematic review and meta-analysis of the efficacy and safety of oseltamivir (Tamiflu) in the treatment of Coronavirus Disease 2019 (COVID-19)", "authors": "Aliyu B, Raji YE, Chee HY et al.", "journal": "PloS one", "year": 2022, "pmid": "36454880", "url": "https://pubmed.ncbi.nlm.nih.gov/36454880/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1371/journal.pone.0277206", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36454880/", "publicSourceType": "PMID" }, { "text": "Qiu S, Shen Y, Pan H et al.. Effectiveness and safety of oseltamivir for treating influenza: an updated meta-analysis of clinical trials. Infectious diseases (London, England). 2015", "claim": "PubMed-indexed evidence involving Oseltamivir", "title": "Effectiveness and safety of oseltamivir for treating influenza: an updated meta-analysis of clinical trials", "authors": "Qiu S, Shen Y, Pan H et al.", "journal": "Infectious diseases (London, England)", "year": 2015, "pmid": "26173991", "url": "https://pubmed.ncbi.nlm.nih.gov/26173991/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3109/23744235.2015.1067369", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26173991/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Neuraminidase inhibitor antiviral", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "6-10 hours (active carboxylate metabolite)", "onsetOfAction": "3-4 hours to peak plasma concentration of active metabolite", "commonBrandNames": [ "Tamiflu" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "oseltamivir" }, { "id": "RX-INFR-019", "name": "Fluticasone Inhaled", "alternateNames": [ "Flovent HFA", "Arnuity Ellipta", "ArmonAir Digihaler" ], "category": "Prescription", "subcategory": "Inhaled Corticosteroid", "overview": "An inhaled corticosteroid (ICS) that is a cornerstone of persistent asthma management. Fluticasone propionate (Flovent) and fluticasone furoate (Arnuity) deliver potent topical anti-inflammatory effects directly to the airways with minimal systemic absorption. Classified as the preferred controller therapy for mild-to-severe persistent asthma in all age groups. Reduces airway inflammation, hyperresponsiveness, exacerbation frequency, and improves lung function.", "mechanismOfAction": "Binds to intracellular glucocorticoid receptors in airway epithelial cells, inflammatory cells, and structural cells. The activated receptor-steroid complex translocates to the nucleus and modulates gene transcription: upregulating anti-inflammatory proteins (lipocortin-1, IL-10, IkB-alpha) and suppressing pro-inflammatory mediators (cytokines IL-1/IL-6/IL-8/TNF-alpha, chemokines, adhesion molecules, and enzymes like COX-2 and iNOS). This reduces eosinophilic inflammation, mast cell degranulation, mucus hypersecretion, and airway remodeling over weeks of consistent use.", "commonBenefits": [ "First-line controller for persistent asthma (all severity levels)", "Reduces asthma exacerbations and ER visits", "Improves lung function (FEV1) and symptom control", "Reduces airway hyperresponsiveness", "Low systemic absorption minimizes steroid side effects" ], "commonDosageRange": "Flovent HFA: 88-440 mcg BID (adults); Arnuity Ellipta: 100-200 mcg once daily; dose titrated to lowest effective dose for asthma control (as prescribed by your physician)", "recommendedForm": "Metered-dose inhaler (MDI) or dry powder inhaler (DPI)", "absorption": { "isFatSoluble": true, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Delivered directly to the lungs via inhalation. Oral bioavailability is <1% (extensive first-pass metabolism). Systemic absorption primarily from lung deposition. Rinse mouth after use to prevent oral candidiasis and dysphonia." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Oral candidiasis (thrush), preventable by rinsing mouth after use", "Dysphonia (hoarseness)", "Pharyngitis and cough", "Headache", "Adrenal suppression (with high doses or prolonged use)", "Reduced bone mineral density (with chronic high-dose use)", "Growth suppression in children (small, generally clinically insignificant)" ], "contraindications": [ "Known hypersensitivity to fluticasone or any component", "Primary treatment of acute asthma attack or status asthmaticus (not a rescue inhaler)", "Moderate-to-severe bronchiectasis with active fungal infection", "Untreated systemic fungal, bacterial, viral, or parasitic infections" ], "iconName": "lungs.fill", "colorHex": "4D94FF", "tags": [ "respiratory", "corticosteroid", "inhaler", "asthma", "controller", "anti-inflammatory", "ics" ], "sources": [ { "text": "GINA (Global Initiative for Asthma). Global Strategy for Asthma Management and Prevention. 2023.", "pmid": "41804386", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41804386/", "publicSourceType": "PMID" }, { "text": "Adams NP et al. Fluticasone versus placebo for chronic asthma in adults and children. Cochrane Database Syst Rev. 2008.", "pmid": "18843640", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18843640/", "publicSourceType": "PMID" }, { "text": "Suissa S et al. Low-dose inhaled corticosteroids and the prevention of death from asthma. N Engl J Med. 2000.", "pmid": "12324675", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12324675/", "publicSourceType": "PMID" }, { "text": "Tagaya E, Shinada J, Nagase H et al.. The efficacy and safety of Fluticasone Furoate/Umeclidinium/vilanterol (FF/UMEC/VI) on cough symptoms in adult patients with asthma, a randomized double-blind, placebo-controlled, parallel group study: Chronic Cough in Asthma (COCOA) study. The Journal of asthma : official journal of the Association for the Care of Asthma. 2025", "pmid": "39874464", "doi": "10.1080/02770903.2025.2455416", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39874464/", "publicSourceType": "PMID" }, { "text": "Ismaila AS, Haeussler K, Czira A et al.. Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) Triple Therapy Compared with Other Therapies for the Treatment of COPD: A Network Meta-Analysis. Advances in therapy. 2022", "pmid": "35849317", "doi": "10.1007/s12325-022-02231-0", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35849317/", "publicSourceType": "PMID" }, { "text": "Muley P, Shah M, Muley A. Safety of inhaled fluticasone propionate therapy for pediatric asthma - a systematic review. Current drug safety. 2013", "claim": "PubMed-indexed evidence involving Fluticasone Inhaled", "title": "Safety of inhaled fluticasone propionate therapy for pediatric asthma - a systematic review", "authors": "Muley P, Shah M, Muley A", "journal": "Current drug safety", "year": 2013, "pmid": "23859431", "url": "https://pubmed.ncbi.nlm.nih.gov/23859431/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2174/15748863113089990038", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23859431/", "publicSourceType": "PMID" }, { "text": "Masoli M, Weatherall M, Holt S et al.. Inhaled fluticasone propionate and adrenal effects in adult asthma: systematic review and meta-analysis. The European respiratory journal. 2006", "claim": "PubMed-indexed evidence involving Fluticasone Inhaled", "title": "Inhaled fluticasone propionate and adrenal effects in adult asthma: systematic review and meta-analysis", "authors": "Masoli M, Weatherall M, Holt S et al.", "journal": "The European respiratory journal", "year": 2006, "pmid": "16737984", "url": "https://pubmed.ncbi.nlm.nih.gov/16737984/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1183/09031936.06.00119305", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16737984/", "publicSourceType": "PMID" }, { "text": "Dyer MJ, Halpin DM, Stein K. Inhaled ciclesonide versus inhaled budesonide or inhaled beclomethasone or inhaled fluticasone for chronic asthma in adults: a systematic review. BMC family practice. 2006", "claim": "PubMed-indexed evidence involving Fluticasone Inhaled", "title": "Inhaled ciclesonide versus inhaled budesonide or inhaled beclomethasone or inhaled fluticasone for chronic asthma in adults: a systematic review", "authors": "Dyer MJ, Halpin DM, Stein K", "journal": "BMC family practice", "year": 2006, "pmid": "16753053", "url": "https://pubmed.ncbi.nlm.nih.gov/16753053/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/1471-2296-7-34", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16753053/", "publicSourceType": "PMID" }, { "text": "Masoli M, Weatherall M, Holt S et al.. Systematic review of the dose-response relation of inhaled fluticasone propionate. Archives of disease in childhood. 2004", "claim": "PubMed-indexed evidence involving Fluticasone Inhaled", "title": "Systematic review of the dose-response relation of inhaled fluticasone propionate", "authors": "Masoli M, Weatherall M, Holt S et al.", "journal": "Archives of disease in childhood", "year": 2004, "pmid": "15383431", "url": "https://pubmed.ncbi.nlm.nih.gov/15383431/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1136/adc.2003.035709", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15383431/", "publicSourceType": "PMID" }, { "text": "Maneechotesuwan K, Singh D, Fritscher LG et al.. Impact of inhaled fluticasone propionate/salmeterol on health-related quality of life in asthma: A network meta-analysis. Respiratory medicine. 2022", "claim": "PubMed-indexed evidence involving Fluticasone Inhaled", "title": "Impact of inhaled fluticasone propionate/salmeterol on health-related quality of life in asthma: A network meta-analysis", "authors": "Maneechotesuwan K, Singh D, Fritscher LG et al.", "journal": "Respiratory medicine", "year": 2022, "pmid": "36257125", "url": "https://pubmed.ncbi.nlm.nih.gov/36257125/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.rmed.2022.106993", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36257125/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Inhaled corticosteroid (ICS)", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "7.8 hours (fluticasone propionate); 24 hours (fluticasone furoate)", "onsetOfAction": "Partial improvement within 24 hours; maximum benefit after 1-2 weeks of consistent use", "commonBrandNames": [ "Flovent HFA", "Arnuity Ellipta", "ArmonAir Digihaler" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "fluticasone-inhaled" }, { "id": "RX-INFR-020", "name": "Budesonide Inhaled", "alternateNames": [ "Pulmicort Flexhaler", "Pulmicort Respules" ], "category": "Prescription", "subcategory": "Inhaled Corticosteroid", "overview": "An inhaled corticosteroid used as a controller medication for persistent asthma. Available as a dry powder inhaler (Flexhaler) for older children and adults, and as a nebulizer suspension (Respules) for infants and young children. Budesonide has a favorable safety profile, including the most extensive safety data in pregnancy among all inhaled corticosteroids. Also available as an oral formulation (Entocort) for inflammatory bowel disease and as a nasal spray (Rhinocort) for allergic rhinitis.", "mechanismOfAction": "Binds to the intracellular glucocorticoid receptor and modulates inflammatory gene transcription. The activated receptor complex suppresses NF-kB and AP-1 transcription factors, reducing the production of pro-inflammatory cytokines, chemokines, and adhesion molecules. Budesonide undergoes high first-pass hepatic metabolism (~90%), resulting in low systemic bioavailability from the swallowed portion. Its high receptor affinity and lipophilic ester conjugation in airway tissue provide prolonged local anti-inflammatory effect.", "commonBenefits": [ "Controller therapy for persistent asthma (adults and children >=6 months)", "Nebulized form for infants and young children unable to use inhalers", "Most pregnancy safety data of any ICS", "Reduces asthma exacerbations and improves lung function", "Once- or twice-daily dosing" ], "commonDosageRange": "Flexhaler: 180-360 mcg BID (adults); Respules: 0.25-1 mg via nebulizer BID (children 12 months-8 years); titrate to lowest effective dose (as prescribed by your physician)", "recommendedForm": "Dry powder inhaler (DPI) or nebulizer suspension", "absorption": { "isFatSoluble": true, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Delivered by inhalation directly to the airways. Systemic bioavailability approximately 6-13% (Flexhaler) or 6% (Respules) due to high first-pass metabolism. Rinse mouth after use to prevent oral candidiasis. For nebulizer use, use a mouthpiece rather than face mask to reduce facial skin deposition." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Oral candidiasis (thrush)", "Dysphonia (hoarseness)", "Cough and throat irritation", "Headache", "Nasopharyngitis", "Adrenal suppression (with high-dose chronic use)", "Growth suppression in children (small effect, ~0.5 cm/year)" ], "contraindications": [ "Known hypersensitivity to budesonide or any component", "Primary treatment of acute asthma attacks or status asthmaticus", "Active or quiescent pulmonary tuberculosis", "Untreated systemic fungal, bacterial, viral, or parasitic infections" ], "iconName": "lungs.fill", "colorHex": "4D94FF", "tags": [ "respiratory", "corticosteroid", "inhaler", "asthma", "controller", "nebulizer", "pediatric", "ics" ], "sources": [ { "text": "GINA (Global Initiative for Asthma). Global Strategy for Asthma Management and Prevention. 2023.", "pmid": "41804386", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41804386/", "publicSourceType": "PMID" }, { "text": "Szefler SJ et al. Long-term effects of budesonide or nedocromil in children with asthma (CAMP). N Engl J Med. 2000.", "pmid": "24229823", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24229823/", "publicSourceType": "PMID" }, { "text": "Kallen B et al. Use of inhaled budesonide during pregnancy and risk of congenital malformations. Obstet Gynecol. 1999.", "pmid": "10074986", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10074986/", "publicSourceType": "PMID" }, { "text": "Magboul N, Alharbi AF, Alqutub AT et al.. Budesonide nasal irrigation for chronic rhinosinusitis: a meta-analysis of therapeutic outcomes and safety profile. Rhinology. 2025", "pmid": "39729039", "doi": "10.4193/Rhin24.349", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39729039/", "publicSourceType": "PMID" }, { "text": "Beasley R, Harrison T, Peterson S et al.. Evaluation of Budesonide-Formoterol for Maintenance and Reliever Therapy Among Patients With Poorly Controlled Asthma: A Systematic Review and Meta-analysis. JAMA network open. 2022", "pmid": "35230437", "doi": "10.1001/jamanetworkopen.2022.0615", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35230437/", "publicSourceType": "PMID" }, { "text": "Zhu X, Liu Y, Li N et al.. Inhaled budesonide for the prevention of acute mountain sickness: A meta-analysis of randomized controlled trials. The American journal of emergency medicine. 2020", "claim": "PubMed-indexed evidence involving Budesonide Inhaled", "title": "Inhaled budesonide for the prevention of acute mountain sickness: A meta-analysis of randomized controlled trials", "authors": "Zhu X, Liu Y, Li N et al.", "journal": "The American journal of emergency medicine", "year": 2020, "pmid": "31706656", "url": "https://pubmed.ncbi.nlm.nih.gov/31706656/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.ajem.2019.158461", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31706656/", "publicSourceType": "PMID" }, { "text": "Zhao J, Pan X, Shao P. Meta-analysis of combined azithromycin and inhaled budesonide treatment for Chinese pediatric patients with mycoplasma pneumonia. Medicine. 2024", "claim": "PubMed-indexed evidence involving Budesonide Inhaled", "title": "Meta-analysis of combined azithromycin and inhaled budesonide treatment for Chinese pediatric patients with mycoplasma pneumonia", "authors": "Zhao J, Pan X, Shao P", "journal": "Medicine", "year": 2024, "pmid": "38875395", "url": "https://pubmed.ncbi.nlm.nih.gov/38875395/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MD.0000000000038332", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38875395/", "publicSourceType": "PMID" }, { "text": "Masoli M, Holt S, Weatherall M et al.. Dose-response relationship of inhaled budesonide in adult asthma: a meta-analysis. The European respiratory journal. 2004", "claim": "PubMed-indexed evidence involving Budesonide Inhaled", "title": "Dose-response relationship of inhaled budesonide in adult asthma: a meta-analysis", "authors": "Masoli M, Holt S, Weatherall M et al.", "journal": "The European respiratory journal", "year": 2004, "pmid": "15083753", "url": "https://pubmed.ncbi.nlm.nih.gov/15083753/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1183/09031936.04.00076604", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15083753/", "publicSourceType": "PMID" }, { "text": "Reis G, Dos Santos Moreira Silva EA, Medeiros Silva DC et al.. Oral Fluvoxamine With Inhaled Budesonide for Treatment of Early-Onset COVID-19 : A Randomized Platform Trial. Annals of internal medicine. 2023", "claim": "PubMed-indexed evidence involving Budesonide Inhaled", "title": "Oral Fluvoxamine With Inhaled Budesonide for Treatment of Early-Onset COVID-19 : A Randomized Platform Trial", "authors": "Reis G, Dos Santos Moreira Silva EA, Medeiros Silva DC et al.", "journal": "Annals of internal medicine", "year": 2023, "pmid": "37068273", "url": "https://pubmed.ncbi.nlm.nih.gov/37068273/", "study_type": "RCT", "confidence": "verify", "doi": "10.7326/M22-3305", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37068273/", "publicSourceType": "PMID" }, { "text": "Elfarargy MS, Al-Ashmawy GM, Abu-Risha SM et al.. Inhaled Budesonide in Neonatal Respiratory Distress Syndrome of Near-Term Neonates: A Randomized, Placebo-Controlled Trial. The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG. 2022", "claim": "PubMed-indexed evidence involving Budesonide Inhaled", "title": "Inhaled Budesonide in Neonatal Respiratory Distress Syndrome of Near-Term Neonates: A Randomized, Placebo-Controlled Trial", "authors": "Elfarargy MS, Al-Ashmawy GM, Abu-Risha SM et al.", "journal": "The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG", "year": 2022, "pmid": "35002557", "url": "https://pubmed.ncbi.nlm.nih.gov/35002557/", "study_type": "RCT", "confidence": "verify", "doi": "10.5863/1551-6776-27.1.38", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35002557/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Inhaled corticosteroid (ICS)", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "2-3.6 hours (plasma); prolonged local effect due to tissue ester conjugation", "onsetOfAction": "Improvement within 24 hours; full benefit after 1-2 weeks", "commonBrandNames": [ "Pulmicort Flexhaler", "Pulmicort Respules" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "budesonide-inhaled" }, { "id": "RX-INFR-021", "name": "Albuterol", "alternateNames": [ "ProAir HFA", "Ventolin HFA", "Proventil HFA", "Salbutamol" ], "category": "Prescription", "subcategory": "Short-Acting Beta-2 Agonist (SABA)", "overview": "A short-acting beta-2 adrenergic agonist (SABA) that is the most widely used rescue inhaler for acute bronchospasm. The cornerstone of acute asthma and COPD symptom relief, providing rapid bronchodilation within minutes. Used for the relief and prevention of bronchospasm in asthma, exercise-induced bronchospasm, and COPD. Also used in nebulized form for acute exacerbations in emergency settings. Overuse (>2 days/week) suggests inadequate controller therapy.", "mechanismOfAction": "Selectively activates beta-2 adrenergic receptors on bronchial smooth muscle cells. Receptor activation stimulates adenylyl cyclase, increasing intracellular cAMP, which activates protein kinase A (PKA). PKA phosphorylates and inactivates myosin light chain kinase (MLCK), reducing intracellular calcium and causing smooth muscle relaxation and bronchodilation. Also stabilizes mast cell membranes (reducing mediator release), increases mucociliary clearance, and decreases microvascular permeability.", "commonBenefits": [ "Rapid relief of acute bronchospasm (rescue inhaler)", "Prevents exercise-induced bronchospasm", "Treats acute asthma exacerbations", "Treats acute COPD exacerbations", "Nebulized for emergency department management of severe asthma" ], "commonDosageRange": "MDI: 1-2 puffs (90-180 mcg) every 4-6 hours as needed; nebulizer: 2.5 mg every 4-8 hours; exercise prophylaxis: 2 puffs 15-30 minutes before exercise (as prescribed by your physician)", "recommendedForm": "Metered-dose inhaler (MDI), nebulizer solution, or dry powder inhaler", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Delivered by inhalation for rapid local effect. Onset within 5-15 minutes, duration 4-6 hours. Proper inhaler technique is critical for drug delivery. Use a spacer with MDI for improved lung deposition. Shake MDI well before each use." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Tremor (especially hands)", "Tachycardia and palpitations", "Nervousness and anxiety", "Headache", "Throat irritation and cough", "Hypokalemia (with frequent/high dosing)", "Hyperglycemia (with frequent use)" ], "contraindications": [ "Known hypersensitivity to albuterol or any component", "Severe cardiac arrhythmias (use with caution)", "Hypertrophic obstructive cardiomyopathy (use with caution)", "Not for maintenance therapy, overuse indicates need for controller medication" ], "iconName": "lungs.fill", "colorHex": "34D399", "tags": [ "respiratory", "bronchodilator", "saba", "rescue-inhaler", "asthma", "copd", "emergency" ], "sources": [ { "text": "GINA (Global Initiative for Asthma). Global Strategy for Asthma Management and Prevention. 2023.", "pmid": "41804386", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41804386/", "publicSourceType": "PMID" }, { "text": "GOLD (Global Initiative for Chronic Obstructive Lung Disease). Global Strategy for the Diagnosis, Management, and Prevention of COPD. 2023.", "pmid": "41891755", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41891755/", "publicSourceType": "PMID" }, { "text": "Cates CJ et al. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2013.", "pmid": "24037768", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24037768/", "publicSourceType": "PMID" }, { "text": "Pierantoni L, Muratore E, Cerasi S et al.. Salbutamol safety in children under 2 years of age with acute wheezing: a meta-analysis of randomised controlled trials. Archives of disease in childhood. 2025", "pmid": "39266286", "doi": "10.1136/archdischild-2023-326556", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39266286/", "publicSourceType": "PMID" }, { "text": "Payares-Salamanca L, Contreras-Arrieta S, Florez-García V et al.. Metered-dose inhalers versus nebulization for the delivery of albuterol for acute exacerbations of wheezing or asthma in children: A systematic review with meta-analysis. Pediatric pulmonology. 2020", "pmid": "32940961", "doi": "10.1002/ppul.25077", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32940961/", "publicSourceType": "PMID" }, { "text": "Xing X, Zhao S, Jiang R et al.. Salbutamol in 5q spinal muscular atrophy: a systematic review and meta-analysis of efficacy and safety. European journal of pediatrics. 2025", "claim": "PubMed-indexed evidence involving Albuterol", "title": "Salbutamol in 5q spinal muscular atrophy: a systematic review and meta-analysis of efficacy and safety", "authors": "Xing X, Zhao S, Jiang R et al.", "journal": "European journal of pediatrics", "year": 2025, "pmid": "40410501", "url": "https://pubmed.ncbi.nlm.nih.gov/40410501/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00431-025-06184-8", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40410501/", "publicSourceType": "PMID" }, { "text": "Ma LH, Jia L, Bai L. Safety outcomes of salbutamol: A systematic review and meta-analysis. The clinical respiratory journal. 2023", "claim": "PubMed-indexed evidence involving Albuterol", "title": "Safety outcomes of salbutamol: A systematic review and meta-analysis", "authors": "Ma LH, Jia L, Bai L", "journal": "The clinical respiratory journal", "year": 2023, "pmid": "37844914", "url": "https://pubmed.ncbi.nlm.nih.gov/37844914/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/crj.13711", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37844914/", "publicSourceType": "PMID" }, { "text": "Takhman M, Shihab R, Hattab M et al.. Salbutamol in Congenital Myasthenic Syndrome: A Systematic Review. BMC neurology. 2025", "claim": "PubMed-indexed evidence involving Albuterol", "title": "Salbutamol in Congenital Myasthenic Syndrome: A Systematic Review", "authors": "Takhman M, Shihab R, Hattab M et al.", "journal": "BMC neurology", "year": 2025, "pmid": "41382066", "url": "https://pubmed.ncbi.nlm.nih.gov/41382066/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12883-025-04569-8", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41382066/", "publicSourceType": "PMID" }, { "text": "Jat KR, Khairwa A. Levalbuterol versus albuterol for acute asthma: a systematic review and meta-analysis. Pulmonary pharmacology & therapeutics. 2013", "claim": "PubMed-indexed evidence involving Albuterol", "title": "Levalbuterol versus albuterol for acute asthma: a systematic review and meta-analysis", "authors": "Jat KR, Khairwa A", "journal": "Pulmonary pharmacology & therapeutics", "year": 2013, "pmid": "23207739", "url": "https://pubmed.ncbi.nlm.nih.gov/23207739/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.pupt.2012.11.003", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23207739/", "publicSourceType": "PMID" }, { "text": "Courlet P, Buclin T, Biollaz J et al.. Model-based meta-analysis of salbutamol pharmacokinetics and practical implications for doping control. CPT: pharmacometrics & systems pharmacology. 2022", "claim": "PubMed-indexed evidence involving Albuterol", "title": "Model-based meta-analysis of salbutamol pharmacokinetics and practical implications for doping control", "authors": "Courlet P, Buclin T, Biollaz J et al.", "journal": "CPT: pharmacometrics & systems pharmacology", "year": 2022, "pmid": "35315251", "url": "https://pubmed.ncbi.nlm.nih.gov/35315251/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/psp4.12773", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35315251/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Short-acting beta-2 adrenergic agonist (SABA)", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "3.8-6 hours", "onsetOfAction": "5-15 minutes; peak effect 30-60 minutes; duration 4-6 hours", "commonBrandNames": [ "ProAir HFA", "Ventolin HFA", "Proventil HFA", "ProAir Digihaler" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "albuterol" }, { "id": "RX-INFR-022", "name": "Tiotropium", "alternateNames": [ "Spiriva HandiHaler", "Spiriva Respimat" ], "category": "Prescription", "subcategory": "Long-Acting Muscarinic Antagonist (LAMA)", "overview": "A long-acting muscarinic antagonist (LAMA/long-acting anticholinergic) that is a first-line maintenance bronchodilator for COPD and an add-on controller for moderate-to-severe asthma. Provides sustained 24-hour bronchodilation with once-daily dosing. In COPD, tiotropium reduces exacerbations, improves lung function, quality of life, and exercise tolerance. In asthma, it is used as add-on therapy when ICS/LABA combinations are insufficient.", "mechanismOfAction": "Competitively and reversibly blocks muscarinic M3 receptors on airway smooth muscle and submucosal glands. Acetylcholine released from parasympathetic vagal nerve endings normally activates M3 receptors, causing bronchoconstriction and mucus secretion. Tiotropium's very slow dissociation from M3 receptors (kinetic selectivity, off-rate half-life of ~35 hours from M3 vs ~4 hours from M2) provides prolonged bronchodilation. This M3 selectivity avoids blocking presynaptic M2 autoreceptors, which would paradoxically increase acetylcholine release.", "commonBenefits": [ "First-line maintenance bronchodilator for COPD", "Reduces COPD exacerbation frequency", "Improves FEV1 and exercise tolerance in COPD", "Add-on controller for moderate-to-severe persistent asthma", "Once-daily dosing for patient convenience" ], "commonDosageRange": "HandiHaler: 18 mcg (one capsule) inhaled once daily; Respimat: 2.5 mcg (2 puffs) once daily for COPD, 1.25 mcg (2 puffs) once daily for asthma (as prescribed by your physician)", "recommendedForm": "Dry powder inhaler (HandiHaler) or soft mist inhaler (Respimat)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Delivered by inhalation. Oral bioavailability is extremely low (2-3%) due to quaternary ammonium structure. Systemic effects are minimal. Peak bronchodilation at 1-3 hours, duration >24 hours. Do not swallow capsules, they are for inhalation via HandiHaler device only." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Dry mouth (most common anticholinergic effect)", "Constipation", "Urinary retention", "Pharyngitis and upper respiratory tract infection", "Sinusitis", "Blurred vision (if sprayed into eyes)" ], "contraindications": [ "Known hypersensitivity to tiotropium or ipratropium (same class)", "Known hypersensitivity to atropine or atropine derivatives", "Not for acute bronchospasm relief (not a rescue medication)", "Narrow-angle glaucoma (anticholinergic may worsen)", "Urinary retention or bladder neck obstruction" ], "iconName": "lungs.fill", "colorHex": "4D94FF", "tags": [ "respiratory", "bronchodilator", "lama", "anticholinergic", "copd", "asthma", "maintenance" ], "sources": [ { "text": "Tashkin DP et al. A 4-year trial of tiotropium in chronic obstructive pulmonary disease (UPLIFT). N Engl J Med. 2008.", "pmid": "18836213", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18836213/", "publicSourceType": "PMID" }, { "text": "Kerstjens HA et al. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med. 2012.", "pmid": "22938706", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22938706/", "publicSourceType": "PMID" }, { "text": "GOLD (Global Initiative for Chronic Obstructive Lung Disease). Global Strategy for the Diagnosis, Management, and Prevention of COPD. 2023.", "pmid": "41891755", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41891755/", "publicSourceType": "PMID" }, { "text": "Kesten S, Celli B, Decramer M et al.. Tiotropium HandiHaler in the treatment of COPD: a safety review. International journal of chronic obstructive pulmonary disease. 2009", "pmid": "20037679", "doi": "10.2147/copd.s4802", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20037679/", "publicSourceType": "PMID" }, { "text": "Blair HA. Tiotropium/Olodaterol: A Review in COPD. Drugs. 2019", "pmid": "31119643", "doi": "10.1007/s40265-019-01133-w", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31119643/", "publicSourceType": "PMID" }, { "text": "Cai HD, Hou J, Lyu YN et al.. [Efficacy and safety of tiotropium Respimat in the treatment of chronic obstructive pulmonary disease: systematic review]. Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases. 2017", "claim": "PubMed-indexed evidence involving Tiotropium", "title": "[Efficacy and safety of tiotropium Respimat in the treatment of chronic obstructive pulmonary disease: systematic review]", "authors": "Cai HD, Hou J, Lyu YN et al.", "journal": "Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases", "year": 2017, "pmid": "28810313", "url": "https://pubmed.ncbi.nlm.nih.gov/28810313/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3760/cma.j.issn.1001-0939.2017.08.011", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28810313/", "publicSourceType": "PMID" }, { "text": "Miravitlles M, Urrutia G, Mathioudakis AG et al.. Efficacy and safety of tiotropium and olodaterol in COPD: a systematic review and meta-analysis. Respiratory research. 2017", "claim": "PubMed-indexed evidence involving Tiotropium", "title": "Efficacy and safety of tiotropium and olodaterol in COPD: a systematic review and meta-analysis", "authors": "Miravitlles M, Urrutia G, Mathioudakis AG et al.", "journal": "Respiratory research", "year": 2017, "pmid": "29178871", "url": "https://pubmed.ncbi.nlm.nih.gov/29178871/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12931-017-0683-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29178871/", "publicSourceType": "PMID" }, { "text": "Tian JW, Chen JW, Chen R et al.. Tiotropium versus placebo for inadequately controlled asthma: a meta-analysis. Respiratory care. 2014", "claim": "PubMed-indexed evidence involving Tiotropium", "title": "Tiotropium versus placebo for inadequately controlled asthma: a meta-analysis", "authors": "Tian JW, Chen JW, Chen R et al.", "journal": "Respiratory care", "year": 2014, "pmid": "24170916", "url": "https://pubmed.ncbi.nlm.nih.gov/24170916/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.4187/respcare.02703", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24170916/", "publicSourceType": "PMID" }, { "text": "Cazzola M, Calzetta L, Rogliani P et al.. Tiotropium formulations and safety: a network meta-analysis. Therapeutic advances in drug safety. 2017", "claim": "PubMed-indexed evidence involving Tiotropium", "title": "Tiotropium formulations and safety: a network meta-analysis", "authors": "Cazzola M, Calzetta L, Rogliani P et al.", "journal": "Therapeutic advances in drug safety", "year": 2017, "pmid": "28203364", "url": "https://pubmed.ncbi.nlm.nih.gov/28203364/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/2042098616667304", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28203364/", "publicSourceType": "PMID" }, { "text": "Sunther M, Marchon K, Gupta A. Tiotropium in the management of paediatric and adolescent asthma: Systematic review. Paediatric respiratory reviews. 2021", "claim": "PubMed-indexed evidence involving Tiotropium", "title": "Tiotropium in the management of paediatric and adolescent asthma: Systematic review", "authors": "Sunther M, Marchon K, Gupta A", "journal": "Paediatric respiratory reviews", "year": 2021, "pmid": "33243704", "url": "https://pubmed.ncbi.nlm.nih.gov/33243704/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.prrv.2020.08.003", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33243704/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Long-acting muscarinic antagonist (LAMA / long-acting anticholinergic)", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "25-36 hours (after inhalation; kinetic M3 dissociation ~35 hours)", "onsetOfAction": "30 minutes; peak effect 1-3 hours; duration >24 hours", "commonBrandNames": [ "Spiriva HandiHaler", "Spiriva Respimat" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "tiotropium" }, { "id": "RX-INFR-023", "name": "Ipratropium", "alternateNames": [ "Atrovent HFA", "Atrovent Nasal" ], "category": "Prescription", "subcategory": "Short-Acting Muscarinic Antagonist (SAMA)", "overview": "A short-acting muscarinic antagonist (SAMA/short-acting anticholinergic) used for the maintenance treatment of COPD and as an adjunct to beta-agonists in acute severe asthma and COPD exacerbations. The nebulized form (often combined with albuterol as DuoNeb/Combivent) is a standard component of acute bronchospasm management in emergency departments. The nasal spray formulation (Atrovent Nasal) treats rhinorrhea associated with allergic and nonallergic rhinitis and the common cold.", "mechanismOfAction": "A quaternary ammonium derivative of atropine that competitively blocks muscarinic M1, M2, and M3 receptors in bronchial smooth muscle and submucosal glands. Blockade of parasympathetic vagal tone reduces basal bronchomotor tone and inhibits reflex bronchoconstriction. Also decreases mucus secretion from goblet cells and submucosal glands. Unlike tiotropium, ipratropium has relatively equal affinity for all muscarinic subtypes and shorter receptor binding duration, requiring more frequent dosing.", "commonBenefits": [ "Maintenance bronchodilation in COPD", "Adjunct to albuterol in acute severe asthma exacerbations", "Combined with albuterol (Combivent/DuoNeb) for COPD", "Treats rhinorrhea (nasal spray formulation)", "Useful when beta-agonists are contraindicated (cardiac patients)" ], "commonDosageRange": "MDI: 2 puffs (17 mcg each) QID; nebulizer: 500 mcg every 6-8 hours; nasal spray: 2 sprays (42 mcg) per nostril BID-TID; acute exacerbation: 500 mcg nebulized every 20 min x 3 doses with albuterol (as prescribed by your physician)", "recommendedForm": "Metered-dose inhaler (MDI), nebulizer solution, or nasal spray", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Delivered by inhalation or nasal spray. Poorly absorbed systemically (<2% bioavailability) due to quaternary ammonium structure. Local bronchodilator effect with minimal systemic anticholinergic effects." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Dry mouth", "Cough", "Headache", "Nausea", "Dizziness", "Blurred vision (if sprayed into eyes)", "Urinary retention (rare)" ], "contraindications": [ "Known hypersensitivity to ipratropium, atropine, or atropine derivatives", "Known hypersensitivity to soy lecithin or related food products (MDI formulation)", "Not for primary treatment of acute bronchospasm alone (use with SABA)", "Narrow-angle glaucoma (protect eyes during nebulizer use)" ], "iconName": "lungs.fill", "colorHex": "4D94FF", "tags": [ "respiratory", "bronchodilator", "sama", "anticholinergic", "copd", "acute-asthma", "rhinorrhea" ], "sources": [ { "text": "Rodrigo GJ, Castro-Rodriguez JA. Anticholinergics in the treatment of children and adults with acute asthma: a systematic review with meta-analysis. Thorax. 2005.", "pmid": "26231467", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26231467/", "publicSourceType": "PMID" }, { "text": "GOLD (Global Initiative for Chronic Obstructive Lung Disease). Global Strategy for the Diagnosis, Management, and Prevention of COPD. 2023.", "pmid": "41891755", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41891755/", "publicSourceType": "PMID" }, { "text": "Brozek JL et al. Allergic rhinitis and its impact on asthma (ARIA) guidelines, 2016 revision. J Allergy Clin Immunol. 2017.", "pmid": "28602936", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28602936/", "publicSourceType": "PMID" }, { "text": "Xu H, Tong L, Gao P et al.. Combination of ipratropium bromide and salbutamol in children and adolescents with asthma: A meta-analysis. PloS one. 2021", "pmid": "33621253", "doi": "10.1371/journal.pone.0237620", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33621253/", "publicSourceType": "PMID" }, { "text": "Payares-Salamanca L, Contreras-Arrieta S, Florez-García V et al.. Metered-dose inhalers versus nebulization for the delivery of albuterol for acute exacerbations of wheezing or asthma in children: A systematic review with meta-analysis. Pediatric pulmonology. 2020", "claim": "PubMed-indexed evidence involving Ipratropium", "title": "Metered-dose inhalers versus nebulization for the delivery of albuterol for acute exacerbations of wheezing or asthma in children: A systematic review with meta-analysis", "authors": "Payares-Salamanca L, Contreras-Arrieta S, Florez-García V et al.", "journal": "Pediatric pulmonology", "year": 2020, "pmid": "32940961", "url": "https://pubmed.ncbi.nlm.nih.gov/32940961/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/ppul.25077", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32940961/", "publicSourceType": "PMID" }, { "text": "Gong J, Nie N, Jiang M et al.. Efficacy and safety of combined nebulization of unfractionated heparin, acetylcysteine, budesonide and ipratropium bromide in hospitalised patients with COVID-19 pneumonia: a randomized controlled clinical trial. BMC pulmonary medicine. 2025", "claim": "PubMed-indexed evidence involving Ipratropium", "title": "Efficacy and safety of combined nebulization of unfractionated heparin, acetylcysteine, budesonide and ipratropium bromide in hospitalised patients with COVID-19 pneumonia: a randomized controlled clinical trial", "authors": "Gong J, Nie N, Jiang M et al.", "journal": "BMC pulmonary medicine", "year": 2025, "pmid": "40696325", "url": "https://pubmed.ncbi.nlm.nih.gov/40696325/", "study_type": "RCT", "confidence": "verify", "doi": "10.1186/s12890-025-03824-5", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40696325/", "publicSourceType": "PMID" }, { "text": "Jat KR, Khairwa A. Levalbuterol versus albuterol for acute asthma: a systematic review and meta-analysis. Pulmonary pharmacology & therapeutics. 2013", "claim": "PubMed-indexed evidence involving Ipratropium", "title": "Levalbuterol versus albuterol for acute asthma: a systematic review and meta-analysis", "authors": "Jat KR, Khairwa A", "journal": "Pulmonary pharmacology & therapeutics", "year": 2013, "pmid": "23207739", "url": "https://pubmed.ncbi.nlm.nih.gov/23207739/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.pupt.2012.11.003", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23207739/", "publicSourceType": "PMID" }, { "text": "Hikino K, Kobayashi S, Ota E et al.. A meta-analysis of the influence of ADRB2 genetic polymorphisms on albuterol (salbutamol) therapy in patients with asthma. British journal of clinical pharmacology. 2021", "claim": "PubMed-indexed evidence involving Ipratropium", "title": "A meta-analysis of the influence of ADRB2 genetic polymorphisms on albuterol (salbutamol) therapy in patients with asthma", "authors": "Hikino K, Kobayashi S, Ota E et al.", "journal": "British journal of clinical pharmacology", "year": 2021, "pmid": "32986886", "url": "https://pubmed.ncbi.nlm.nih.gov/32986886/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/bcp.14570", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32986886/", "publicSourceType": "PMID" }, { "text": "Rodrigo G, Rodrigo C, Burschtin O. A meta-analysis of the effects of ipratropium bromide in adults with acute asthma. The American journal of medicine. 1999", "claim": "PubMed-indexed evidence involving Ipratropium", "title": "A meta-analysis of the effects of ipratropium bromide in adults with acute asthma", "authors": "Rodrigo G, Rodrigo C, Burschtin O", "journal": "The American journal of medicine", "year": 1999, "pmid": "10527039", "url": "https://pubmed.ncbi.nlm.nih.gov/10527039/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/s0002-9343(99)00243-0", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10527039/", "publicSourceType": "PMID" }, { "text": "Osmond MH, Klassen TP. Efficacy of ipratropium bromide in acute childhood asthma: a meta-analysis. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 1995", "claim": "PubMed-indexed evidence involving Ipratropium", "title": "Efficacy of ipratropium bromide in acute childhood asthma: a meta-analysis", "authors": "Osmond MH, Klassen TP", "journal": "Academic emergency medicine : official journal of the Society for Academic Emergency Medicine", "year": 1995, "pmid": "8521214", "url": "https://pubmed.ncbi.nlm.nih.gov/8521214/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/j.1553-2712.1995.tb03607.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8521214/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Short-acting muscarinic antagonist (SAMA / short-acting anticholinergic)", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "1.6-4 hours", "onsetOfAction": "15-30 minutes; peak effect 1-2 hours; duration 4-6 hours", "commonBrandNames": [ "Atrovent HFA", "Atrovent Nasal" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "ipratropium" }, { "id": "RX-INFR-024", "name": "Montelukast", "alternateNames": [ "Singulair" ], "category": "Prescription", "subcategory": "Leukotriene Receptor Antagonist", "overview": "A leukotriene receptor antagonist (LTRA) used for the maintenance treatment of asthma, exercise-induced bronchoconstriction, and allergic rhinitis. Blocks cysteinyl leukotriene receptor CysLT1, reducing inflammation, bronchoconstriction, and mucus secretion. While effective, it is generally less potent than inhaled corticosteroids as monotherapy for asthma. Carries an FDA black box warning for neuropsychiatric events. The decision to prescribe should weigh benefits against the risk of these events.", "mechanismOfAction": "Selectively and competitively binds to the cysteinyl leukotriene type 1 receptor (CysLT1), blocking the actions of leukotrienes C4, D4, and E4. These leukotrienes are potent pro-inflammatory mediators released from mast cells, eosinophils, and other cells via the 5-lipoxygenase pathway of arachidonic acid metabolism. Their effects include bronchoconstriction (1000x more potent than histamine), increased vascular permeability, mucus hypersecretion, and eosinophil recruitment. By blocking CysLT1, montelukast reduces all these downstream effects.", "commonBenefits": [ "Maintenance treatment of persistent asthma", "Prevention of exercise-induced bronchoconstriction", "Symptomatic relief of allergic rhinitis (seasonal and perennial)", "Once-daily oral dosing (convenient, especially for children)", "Alternative controller for patients unable to use ICS" ], "commonDosageRange": "Adults and adolescents >=15 years: 10 mg once daily in the evening; children 6-14 years: 5 mg chewable; children 2-5 years: 4 mg chewable or granules (as prescribed by your physician)", "recommendedForm": "Oral tablets (film-coated), chewable tablets, or oral granules", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Rapidly absorbed with approximately 64% bioavailability (film-coated tablet). Food does not affect the film-coated tablet. Take in the evening for asthma; any time of day for allergic rhinitis. Chewable tablets should not be swallowed whole." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Headache", "Abdominal pain", "Thirst", "Upper respiratory infection symptoms", "Neuropsychiatric events (agitation, aggression, anxiousness, depression, disorientation, dream abnormalities, hallucinations, insomnia, irritability, restlessness, suicidal thinking and behavior, tremor, BLACK BOX WARNING)", "Eosinophilic granulomatosis with polyangiitis (Churg-Strauss, rare)" ], "contraindications": [ "Known hypersensitivity to montelukast or any component", "Not for treatment of acute asthma attacks or acute bronchospasm", "Patients with active neuropsychiatric symptoms (careful risk-benefit assessment required)", "Phenylketonuria (chewable tablets contain aspartame/phenylalanine)" ], "iconName": "lungs.fill", "colorHex": "B37DFF", "tags": [ "respiratory", "leukotriene", "asthma", "allergic-rhinitis", "controller", "anti-inflammatory", "exercise-induced" ], "sources": [ { "text": "FDA Drug Safety Communication: FDA requires Boxed Warning about serious mental health side effects for the asthma and allergy drug montelukast (Singulair). FDA. 2020.", "pmid": "38706997", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38706997/", "publicSourceType": "PMID" }, { "text": "Chauhan BF, Ducharme FM. Anti-leukotriene agents compared to inhaled corticosteroids in the management of recurrent and/or chronic asthma in adults and children. Cochrane Database Syst Rev. 2012.", "pmid": "22592685", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22592685/", "publicSourceType": "PMID" }, { "text": "Philip G et al. Montelukast for treating seasonal allergic rhinitis: a randomized, double-blind, placebo-controlled trial. Ann Allergy Asthma Immunol. 2002.", "pmid": "19484680", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19484680/", "publicSourceType": "PMID" }, { "text": "Shao M, Sun J, Zheng Q. Efficacy and safety of montelukast-levocetirizine combination therapy in combined allergic rhinitis and asthma syndrome: a systematic review and meta-analysis. The Journal of asthma : official journal of the Association for the Care of Asthma. 2025", "pmid": "39394937", "doi": "10.1080/02770903.2024.2415544", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39394937/", "publicSourceType": "PMID" }, { "text": "Lo CWH, Pathadka S, Qin SX et al.. Neuropsychiatric events associated with montelukast in patients with asthma: a systematic review. European respiratory review : an official journal of the European Respiratory Society. 2023", "pmid": "37758273", "doi": "10.1183/16000617.0079-2023", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37758273/", "publicSourceType": "PMID" }, { "text": "Zaffanello M, Pietrobelli A, Nosetti L et al.. Intranasal Corticosteroids and Oral Montelukast for Paediatric Obstructive Sleep Apnoea: A Systematic Review. Pharmaceutics. 2025", "claim": "PubMed-indexed evidence involving Montelukast", "title": "Intranasal Corticosteroids and Oral Montelukast for Paediatric Obstructive Sleep Apnoea: A Systematic Review", "authors": "Zaffanello M, Pietrobelli A, Nosetti L et al.", "journal": "Pharmaceutics", "year": 2025, "pmid": "40430879", "url": "https://pubmed.ncbi.nlm.nih.gov/40430879/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/pharmaceutics17050588", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40430879/", "publicSourceType": "PMID" }, { "text": "Alanazi F, Alruwaili M, Alanazy S et al.. Efficacy of montelukast for adenoid hypertrophy in paediatrics: A systematic review and meta-analysis. Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery. 2024", "claim": "PubMed-indexed evidence involving Montelukast", "title": "Efficacy of montelukast for adenoid hypertrophy in paediatrics: A systematic review and meta-analysis", "authors": "Alanazi F, Alruwaili M, Alanazy S et al.", "journal": "Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery", "year": 2024, "pmid": "38700144", "url": "https://pubmed.ncbi.nlm.nih.gov/38700144/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/coa.14169", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38700144/", "publicSourceType": "PMID" }, { "text": "Fareed A, Siblini D, Vaid R et al.. Montelukast use in pregnancy: A systematic review and meta-analysis of maternal and fetal outcomes in asthma treatment. Congenital anomalies. 2024", "claim": "PubMed-indexed evidence involving Montelukast", "title": "Montelukast use in pregnancy: A systematic review and meta-analysis of maternal and fetal outcomes in asthma treatment", "authors": "Fareed A, Siblini D, Vaid R et al.", "journal": "Congenital anomalies", "year": 2024, "pmid": "39129058", "url": "https://pubmed.ncbi.nlm.nih.gov/39129058/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/cga.12581", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39129058/", "publicSourceType": "PMID" }, { "text": "Mayoral K, Lizano-Barrantes C, Zamora V et al.. Montelukast in paediatric asthma and allergic rhinitis: a systematic review and meta-analysis. European respiratory review : an official journal of the European Respiratory Society. 2023", "claim": "PubMed-indexed evidence involving Montelukast", "title": "Montelukast in paediatric asthma and allergic rhinitis: a systematic review and meta-analysis", "authors": "Mayoral K, Lizano-Barrantes C, Zamora V et al.", "journal": "European respiratory review : an official journal of the European Respiratory Society", "year": 2023, "pmid": "37852659", "url": "https://pubmed.ncbi.nlm.nih.gov/37852659/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1183/16000617.0124-2023", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37852659/", "publicSourceType": "PMID" }, { "text": "Wang H, Ji Q, Liao C et al.. A systematic review and meta-analysis of loratadine combined with montelukast for the treatment of allergic rhinitis. Frontiers in pharmacology. 2023", "claim": "PubMed-indexed evidence involving Montelukast", "title": "A systematic review and meta-analysis of loratadine combined with montelukast for the treatment of allergic rhinitis", "authors": "Wang H, Ji Q, Liao C et al.", "journal": "Frontiers in pharmacology", "year": 2023, "pmid": "37915414", "url": "https://pubmed.ncbi.nlm.nih.gov/37915414/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fphar.2023.1287320", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37915414/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Leukotriene receptor antagonist (LTRA)", "blackBoxWarnings": [ "Serious neuropsychiatric events including suicidal thinking and behavior" ], "fdaPregnancyCategory": "B", "halfLife": "2.7-5.5 hours", "onsetOfAction": "Within 2 hours; maximum effect in days to weeks of consistent use", "commonBrandNames": [ "Singulair" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "montelukast" }, { "id": "RX-INFR-025", "name": "Cetirizine", "alternateNames": [ "Zyrtec" ], "category": "Prescription", "subcategory": "Second-Generation Antihistamine", "overview": "A second-generation (non-sedating) antihistamine used for the relief of symptoms associated with seasonal and perennial allergic rhinitis and chronic idiopathic urticaria. The active carboxylate metabolite of hydroxyzine, cetirizine has minimal CNS penetration compared to first-generation antihistamines, though it is slightly more sedating than other second-generation agents (loratadine, fexofenadine). Available over-the-counter.", "mechanismOfAction": "Selectively and competitively blocks peripheral H1 histamine receptors with minimal anticholinergic and anti-serotonergic effects. Inhibits the early-phase allergic response by preventing histamine from binding to H1 receptors on smooth muscle, vascular endothelium, and sensory nerve endings. Also inhibits eosinophil chemotaxis and late-phase allergic inflammatory mediator release at therapeutic doses. Minimal CNS penetration due to its zwitterionic properties and P-glycoprotein efflux at the blood-brain barrier.", "commonBenefits": [ "Relieves sneezing, rhinorrhea, itchy/watery eyes", "Treats seasonal and perennial allergic rhinitis", "Treats chronic idiopathic urticaria (hives)", "Once-daily dosing", "Rapid onset of action (within 1 hour)" ], "commonDosageRange": "Adults and children >=6 years: 5-10 mg once daily; children 2-5 years: 2.5 mg daily (may increase to 5 mg/day); some patients benefit from 5 mg BID (as prescribed by your physician)", "recommendedForm": "Oral tablets, chewable tablets, oral solution, or liquid gels", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Rapidly absorbed with bioavailability >70%. Food delays but does not reduce total absorption. Can be taken with or without food. May cause more drowsiness than loratadine or fexofenadine." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Drowsiness/somnolence (more common than other second-gen antihistamines, ~14%)", "Dry mouth", "Fatigue", "Headache", "Pharyngitis", "Abdominal pain" ], "contraindications": [ "Known hypersensitivity to cetirizine, hydroxyzine, or any component", "End-stage renal disease (on dialysis)", "Severe hepatic impairment (dose reduction required)", "Children under 6 months" ], "iconName": "allergens.fill", "colorHex": "60A5FA", "tags": [ "antihistamine", "allergy", "rhinitis", "urticaria", "second-generation", "otc-available", "respiratory" ], "sources": [ { "text": "Bousquet J et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update. Allergy. 2008.", "pmid": "18331513", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18331513/", "publicSourceType": "PMID" }, { "text": "Simons FE. Advances in H1-antihistamines. N Engl J Med. 2004.", "pmid": "15590952", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15590952/", "publicSourceType": "PMID" }, { "text": "Zuberbier T et al. The international EAACI/GA2LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria. Allergy. 2022.", "pmid": "34536239", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34536239/", "publicSourceType": "PMID" }, { "text": "Wellington K, Jarvis B. Cetirizine/pseudoephedrine. Drugs. 2001", "pmid": "11772135", "doi": "10.2165/00003495-200161150-00009", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11772135/", "publicSourceType": "PMID" }, { "text": "Du Q, Zhou Y. Placebo-controlled assessment of somnolence effect of cetirizine: a meta-analysis. International forum of allergy & rhinology. 2016", "claim": "PubMed-indexed evidence involving Cetirizine", "title": "Placebo-controlled assessment of somnolence effect of cetirizine: a meta-analysis", "authors": "Du Q, Zhou Y", "journal": "International forum of allergy & rhinology", "year": 2016, "pmid": "26990040", "url": "https://pubmed.ncbi.nlm.nih.gov/26990040/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/alr.21746", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26990040/", "publicSourceType": "PMID" }, { "text": "Etwel F, Djokanovic N, Moretti ME et al.. The fetal safety of cetirizine: an observational cohort study and meta-analysis. Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology. 2014", "claim": "PubMed-indexed evidence involving Cetirizine", "title": "The fetal safety of cetirizine: an observational cohort study and meta-analysis", "authors": "Etwel F, Djokanovic N, Moretti ME et al.", "journal": "Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology", "year": 2014, "pmid": "24678814", "url": "https://pubmed.ncbi.nlm.nih.gov/24678814/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3109/01443615.2014.896887", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24678814/", "publicSourceType": "PMID" }, { "text": "Chen X, Xiang H, Yang M. Topical cetirizine for treating androgenetic alopecia: A systematic review. Journal of cosmetic dermatology. 2022", "claim": "PubMed-indexed evidence involving Cetirizine", "title": "Topical cetirizine for treating androgenetic alopecia: A systematic review", "authors": "Chen X, Xiang H, Yang M", "journal": "Journal of cosmetic dermatology", "year": 2022, "pmid": "35976065", "url": "https://pubmed.ncbi.nlm.nih.gov/35976065/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/jocd.15309", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35976065/", "publicSourceType": "PMID" }, { "text": "Zhou P, Jia Q, Wang Z et al.. Cetirizine for the treatment of allergic diseases in children: A systematic review and meta-analysis. Frontiers in pediatrics. 2022", "claim": "PubMed-indexed evidence involving Cetirizine", "title": "Cetirizine for the treatment of allergic diseases in children: A systematic review and meta-analysis", "authors": "Zhou P, Jia Q, Wang Z et al.", "journal": "Frontiers in pediatrics", "year": 2022, "pmid": "36090559", "url": "https://pubmed.ncbi.nlm.nih.gov/36090559/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fped.2022.940213", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36090559/", "publicSourceType": "PMID" }, { "text": "Nayak AS, Berger WE, LaForce CF et al.. Randomized, placebo-controlled study of cetirizine and loratadine in children with seasonal allergic rhinitis. Allergy and asthma proceedings. 2017", "claim": "PubMed-indexed evidence involving Cetirizine", "title": "Randomized, placebo-controlled study of cetirizine and loratadine in children with seasonal allergic rhinitis", "authors": "Nayak AS, Berger WE, LaForce CF et al.", "journal": "Allergy and asthma proceedings", "year": 2017, "pmid": "28441993", "url": "https://pubmed.ncbi.nlm.nih.gov/28441993/", "study_type": "RCT", "confidence": "verify", "doi": "10.2500/aap.2017.38.4050", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28441993/", "publicSourceType": "PMID" }, { "text": "Kong W, Dong Y, Yi S et al.. High-risks drug adverse events associated with Cetirizine and Loratadine for the treatment of allergic diseases: A retrospective pharmacovigilance study based on the FDA adverse event reporting system database. Clinical and translational allergy. 2024", "claim": "PubMed-indexed evidence involving Cetirizine", "title": "High-risks drug adverse events associated with Cetirizine and Loratadine for the treatment of allergic diseases: A retrospective pharmacovigilance study based on the FDA adverse event reporting system database", "authors": "Kong W, Dong Y, Yi S et al.", "journal": "Clinical and translational allergy", "year": 2024, "pmid": "39257032", "url": "https://pubmed.ncbi.nlm.nih.gov/39257032/", "study_type": "review", "confidence": "verify", "doi": "10.1002/clt2.12392", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39257032/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Second-generation antihistamine (H1 receptor antagonist)", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "8-9 hours (adults); prolonged in renal/hepatic impairment", "onsetOfAction": "Within 1 hour; peak effect 4-8 hours; duration 24 hours", "commonBrandNames": [ "Zyrtec" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "cetirizine" }, { "id": "RX-INFR-026", "name": "Loratadine", "alternateNames": [ "Claritin", "Alavert" ], "category": "Prescription", "subcategory": "Second-Generation Antihistamine", "overview": "A second-generation antihistamine with minimal sedative effects, used for the symptomatic relief of seasonal and perennial allergic rhinitis and chronic idiopathic urticaria. One of the least sedating oral antihistamines due to very limited CNS penetration. Available over-the-counter and widely used for its favorable tolerability profile. Active metabolite desloratadine (Clarinex) is also marketed separately.", "mechanismOfAction": "A long-acting selective peripheral H1 receptor antagonist. Competitively blocks H1 histamine receptors on target cells, preventing the vasodilatory, permeability-enhancing, and pruritic effects of histamine released during allergic reactions. Also inhibits histamine release from mast cells. At therapeutic doses, loratadine does not significantly cross the blood-brain barrier (P-glycoprotein substrate), resulting in minimal CNS sedation and no significant anticholinergic effects.", "commonBenefits": [ "Relieves allergic rhinitis symptoms (sneezing, itching, rhinorrhea)", "Treats chronic idiopathic urticaria", "Minimal sedation (less than cetirizine)", "Once-daily dosing", "Available over-the-counter" ], "commonDosageRange": "Adults and children >=6 years: 10 mg once daily; children 2-5 years: 5 mg once daily (as prescribed by your physician)", "recommendedForm": "Oral tablets, orally disintegrating tablets (Reditabs), or liquid syrup", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Rapidly absorbed; food delays absorption by approximately 1 hour but does not affect total bioavailability. Can be taken with or without food. Extensively metabolized by CYP3A4 and CYP2D6 to active metabolite desloratadine." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Headache", "Drowsiness (uncommon, near placebo rates)", "Fatigue", "Dry mouth", "Nervousness (children)" ], "contraindications": [ "Known hypersensitivity to loratadine or desloratadine", "Severe hepatic impairment (dose adjustment: 10 mg every other day)", "Severe renal impairment (GFR <30 mL/min, dose adjustment: 10 mg every other day)" ], "iconName": "allergens.fill", "colorHex": "60A5FA", "tags": [ "antihistamine", "allergy", "rhinitis", "urticaria", "second-generation", "non-sedating", "otc-available" ], "sources": [ { "text": "Simons FE. Advances in H1-antihistamines. N Engl J Med. 2004.", "pmid": "15590952", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15590952/", "publicSourceType": "PMID" }, { "text": "Bousquet J et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update. Allergy. 2008.", "pmid": "18331513", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18331513/", "publicSourceType": "PMID" }, { "text": "van Cauwenberge P et al. Consensus statement on the treatment of allergic rhinitis. Allergy. 2000.", "pmid": "10726726", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10726726/", "publicSourceType": "PMID" }, { "text": "Yamprasert R, Chanvimalueng W, Mukkasombut N et al.. Ginger extract versus Loratadine in the treatment of allergic rhinitis: a randomized controlled trial. BMC complementary medicine and therapies. 2020", "pmid": "32312261", "doi": "10.1186/s12906-020-2875-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32312261/", "publicSourceType": "PMID" }, { "text": "Wang H, Ji Q, Liao C et al.. A systematic review and meta-analysis of loratadine combined with montelukast for the treatment of allergic rhinitis. Frontiers in pharmacology. 2023", "claim": "PubMed-indexed evidence involving Loratadine", "title": "A systematic review and meta-analysis of loratadine combined with montelukast for the treatment of allergic rhinitis", "authors": "Wang H, Ji Q, Liao C et al.", "journal": "Frontiers in pharmacology", "year": 2023, "pmid": "37915414", "url": "https://pubmed.ncbi.nlm.nih.gov/37915414/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fphar.2023.1287320", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37915414/", "publicSourceType": "PMID" }, { "text": "Schwarz EB, Moretti ME, Nayak S et al.. Risk of hypospadias in offspring of women using loratadine during pregnancy: a systematic review and meta-analysis. Drug safety. 2008", "claim": "PubMed-indexed evidence involving Loratadine", "title": "Risk of hypospadias in offspring of women using loratadine during pregnancy: a systematic review and meta-analysis", "authors": "Schwarz EB, Moretti ME, Nayak S et al.", "journal": "Drug safety", "year": 2008, "pmid": "18707192", "url": "https://pubmed.ncbi.nlm.nih.gov/18707192/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2165/00002018-200831090-00006", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18707192/", "publicSourceType": "PMID" }, { "text": "Mösges R, König V, Köberlein J. The effectiveness of levocetirizine in comparison with loratadine in treatment of allergic rhinitis--a meta-analysis. Allergology international : official journal of the Japanese Society of Allergology. 2011", "claim": "PubMed-indexed evidence involving Loratadine", "title": "The effectiveness of levocetirizine in comparison with loratadine in treatment of allergic rhinitis--a meta-analysis", "authors": "Mösges R, König V, Köberlein J", "journal": "Allergology international : official journal of the Japanese Society of Allergology", "year": 2011, "pmid": "21918368", "url": "https://pubmed.ncbi.nlm.nih.gov/21918368/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2332/allergolint.10-OA-0300", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21918368/", "publicSourceType": "PMID" }, { "text": "Kaiser HB, Banov CH, Berkowitz RR et al.. Comparative efficacy and safety of once-daily versus twice-daily loratadine-pseudoephedrine combinations versus placebo in seasonal allergic rhinitis. American journal of therapeutics. 1998", "claim": "PubMed-indexed evidence involving Loratadine", "title": "Comparative efficacy and safety of once-daily versus twice-daily loratadine-pseudoephedrine combinations versus placebo in seasonal allergic rhinitis", "authors": "Kaiser HB, Banov CH, Berkowitz RR et al.", "journal": "American journal of therapeutics", "year": 1998, "pmid": "10099066", "url": "https://pubmed.ncbi.nlm.nih.gov/10099066/", "study_type": "RCT", "confidence": "verify", "doi": "10.1097/00045391-199807000-00007", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10099066/", "publicSourceType": "PMID" }, { "text": "Nayak AS, Berger WE, LaForce CF et al.. Randomized, placebo-controlled study of cetirizine and loratadine in children with seasonal allergic rhinitis. Allergy and asthma proceedings. 2017", "claim": "PubMed-indexed evidence involving Loratadine", "title": "Randomized, placebo-controlled study of cetirizine and loratadine in children with seasonal allergic rhinitis", "authors": "Nayak AS, Berger WE, LaForce CF et al.", "journal": "Allergy and asthma proceedings", "year": 2017, "pmid": "28441993", "url": "https://pubmed.ncbi.nlm.nih.gov/28441993/", "study_type": "RCT", "confidence": "verify", "doi": "10.2500/aap.2017.38.4050", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28441993/", "publicSourceType": "PMID" }, { "text": "Yong H, Di L, Wang Z et al.. Efficacy and safety of combined loratadine and mometasone furoate therapy in allergic rhinitis patients. Frontiers in immunology. 2025", "claim": "PubMed-indexed evidence involving Loratadine", "title": "Efficacy and safety of combined loratadine and mometasone furoate therapy in allergic rhinitis patients", "authors": "Yong H, Di L, Wang Z et al.", "journal": "Frontiers in immunology", "year": 2025, "pmid": "40534872", "url": "https://pubmed.ncbi.nlm.nih.gov/40534872/", "study_type": "review", "confidence": "verify", "doi": "10.3389/fimmu.2025.1560295", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40534872/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Second-generation antihistamine (H1 receptor antagonist)", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "8.4 hours (loratadine); 28 hours (desloratadine active metabolite)", "onsetOfAction": "1-3 hours; duration 24 hours", "commonBrandNames": [ "Claritin", "Alavert" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "loratadine" }, { "id": "RX-INFR-027", "name": "Fexofenadine", "alternateNames": [ "Allegra" ], "category": "Prescription", "subcategory": "Second-Generation Antihistamine", "overview": "A second-generation antihistamine that is the active carboxylate metabolite of terfenadine. Provides effective relief of allergic rhinitis symptoms and chronic idiopathic urticaria with virtually no sedation or cognitive impairment at recommended doses, considered the least sedating of the second-generation antihistamines. Does not cause QT prolongation (unlike its parent compound terfenadine). Available over-the-counter.", "mechanismOfAction": "Selectively antagonizes peripheral H1 histamine receptors with high binding affinity and very slow receptor dissociation. Inhibits histamine-induced vasodilation, increased vascular permeability, pruritus, and smooth muscle contraction. Does not cross the blood-brain barrier at therapeutic doses (substrate of P-glycoprotein efflux pump and organic anion transporting polypeptide [OATP]). No significant anticholinergic, anti-alpha-adrenergic, or anti-serotonergic activity. Does not affect cardiac potassium channels (no QTc effect).", "commonBenefits": [ "Treats seasonal and perennial allergic rhinitis", "Treats chronic idiopathic urticaria", "Truly non-sedating at recommended doses", "No QT prolongation risk", "No cognitive or psychomotor impairment" ], "commonDosageRange": "Adults and children >=12 years: 60 mg BID or 180 mg once daily; children 2-11 years: 30 mg BID (as prescribed by your physician)", "recommendedForm": "Oral tablets, orally disintegrating tablets, or oral suspension", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Bioavailability approximately 33%. Do NOT take with fruit juices (apple, orange, grapefruit), they inhibit OATP1A2 organic anion transporting polypeptide, reducing absorption by up to 36%. Take with water. Food has no clinically significant effect on absorption. Avoid high-fat meals which may slightly reduce absorption." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Headache", "Drowsiness (near placebo rates)", "Nausea", "Dysmenorrhea", "Back pain", "Upper respiratory symptoms" ], "contraindications": [ "Known hypersensitivity to fexofenadine or terfenadine", "Severe renal impairment (dose reduction recommended)", "Concomitant use with aluminum/magnesium-containing antacids (separate by 2 hours)" ], "iconName": "allergens.fill", "colorHex": "60A5FA", "tags": [ "antihistamine", "allergy", "rhinitis", "urticaria", "second-generation", "non-sedating", "otc-available" ], "sources": [ { "text": "Simons FE. Advances in H1-antihistamines. N Engl J Med. 2004.", "pmid": "15590952", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15590952/", "publicSourceType": "PMID" }, { "text": "Dresser GK et al. Fruit juices inhibit organic anion transporting polypeptide-mediated drug uptake to decrease the oral availability of fexofenadine. Clin Pharmacol Ther. 2002.", "pmid": "15735611", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15735611/", "publicSourceType": "PMID" }, { "text": "Zuberbier T et al. The international EAACI/GA2LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria. Allergy. 2022.", "pmid": "34536239", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34536239/", "publicSourceType": "PMID" }, { "text": "Fexofenadine. 2006", "pmid": "29999736", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29999736/", "publicSourceType": "PMID" }, { "text": "Huang CZ, Jiang ZH, Wang J et al.. Antihistamine effects and safety of fexofenadine: a systematic review and Meta-analysis of randomized controlled trials. BMC pharmacology & toxicology. 2019", "claim": "PubMed-indexed evidence involving Fexofenadine", "title": "Antihistamine effects and safety of fexofenadine: a systematic review and Meta-analysis of randomized controlled trials", "authors": "Huang CZ, Jiang ZH, Wang J et al.", "journal": "BMC pharmacology & toxicology", "year": 2019, "pmid": "31783781", "url": "https://pubmed.ncbi.nlm.nih.gov/31783781/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s40360-019-0363-1", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31783781/", "publicSourceType": "PMID" }, { "text": "Carnovale C, Battini V, Gringeri M et al.. Safety of fexofenadine and other second-generation oral antihistamines before and after the removal of the prescription requirement in Italy and other European countries: A real-world evidence study and systematic review. The World Allergy Organization journal. 2022", "claim": "PubMed-indexed evidence involving Fexofenadine", "title": "Safety of fexofenadine and other second-generation oral antihistamines before and after the removal of the prescription requirement in Italy and other European countries: A real-world evidence study and systematic review", "authors": "Carnovale C, Battini V, Gringeri M et al.", "journal": "The World Allergy Organization journal", "year": 2022, "pmid": "35833202", "url": "https://pubmed.ncbi.nlm.nih.gov/35833202/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.waojou.2022.100658", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35833202/", "publicSourceType": "PMID" }, { "text": "Gómez RM, Moreno P, Compalati E et al.. Update meta-analysis on the efficacy and safety issues of fexofenadine. The World Allergy Organization journal. 2023", "claim": "PubMed-indexed evidence involving Fexofenadine", "title": "Update meta-analysis on the efficacy and safety issues of fexofenadine", "authors": "Gómez RM, Moreno P, Compalati E et al.", "journal": "The World Allergy Organization journal", "year": 2023, "pmid": "37546236", "url": "https://pubmed.ncbi.nlm.nih.gov/37546236/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.waojou.2023.100795", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37546236/", "publicSourceType": "PMID" }, { "text": "Batool M, Zamir A, Alqahtani F et al.. Clinical Pharmacokinetics of Fexofenadine: A Systematic Review. Pharmaceutics. 2024", "claim": "PubMed-indexed evidence involving Fexofenadine", "title": "Clinical Pharmacokinetics of Fexofenadine: A Systematic Review", "authors": "Batool M, Zamir A, Alqahtani F et al.", "journal": "Pharmaceutics", "year": 2024, "pmid": "39771597", "url": "https://pubmed.ncbi.nlm.nih.gov/39771597/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/pharmaceutics16121619", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39771597/", "publicSourceType": "PMID" }, { "text": "Singhal A, Agrawal P, Chatterji P et al.. Correction to: Comparison of the Efficacy and Safety of Bilastine 20 mg versus Fexofenadine 180 mg for Treatment of Perennial Allergic Rhinitis: Randomized Controlled Study. Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India. 2024", "claim": "PubMed-indexed evidence involving Fexofenadine", "title": "Correction to: Comparison of the Efficacy and Safety of Bilastine 20 mg versus Fexofenadine 180 mg for Treatment of Perennial Allergic Rhinitis: Randomized Controlled Study", "authors": "Singhal A, Agrawal P, Chatterji P et al.", "journal": "Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India", "year": 2024, "pmid": "39559065", "url": "https://pubmed.ncbi.nlm.nih.gov/39559065/", "study_type": "RCT", "confidence": "verify", "doi": "10.1007/s12070-024-05010-1", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39559065/", "publicSourceType": "PMID" }, { "text": "Meltzer EO, Rosario NA, Van Bever H et al.. Fexofenadine: review of safety, efficacy and unmet needs in children with allergic rhinitis. Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology. 2021", "claim": "PubMed-indexed evidence involving Fexofenadine", "title": "Fexofenadine: review of safety, efficacy and unmet needs in children with allergic rhinitis", "authors": "Meltzer EO, Rosario NA, Van Bever H et al.", "journal": "Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology", "year": 2021, "pmid": "34727966", "url": "https://pubmed.ncbi.nlm.nih.gov/34727966/", "study_type": "review", "confidence": "verify", "doi": "10.1186/s13223-021-00614-6", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34727966/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Second-generation antihistamine (H1 receptor antagonist)", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "14.4 hours", "onsetOfAction": "1-3 hours; duration up to 24 hours", "commonBrandNames": [ "Allegra" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "fexofenadine" }, { "id": "RX-INFR-028", "name": "Diphenhydramine", "alternateNames": [ "Benadryl" ], "category": "Prescription", "subcategory": "First-Generation Antihistamine", "overview": "A first-generation antihistamine and the prototypical H1 receptor antagonist. Used for allergic reactions (urticaria, angioedema, allergic rhinitis), motion sickness, insomnia (OTC sleep aid), acute dystonic reactions, and as an adjunct in anaphylaxis. Readily crosses the blood-brain barrier, causing significant sedation and anticholinergic effects. Widely available over-the-counter. Due to sedation, cognitive impairment, and anticholinergic burden, second-generation antihistamines are generally preferred for chronic allergic conditions.", "mechanismOfAction": "Competitively blocks H1 histamine receptors on effector cells (smooth muscle, vascular endothelium, respiratory epithelium). Unlike second-generation antihistamines, it readily crosses the blood-brain barrier and blocks central H1 receptors, causing sedation and suppression of the emetic/vestibular center (antiemetic/anti-motion-sickness effects). Also has significant muscarinic (anticholinergic) receptor blocking activity, contributing to dry mouth, urinary retention, constipation, and delirium risk in elderly. Additional sodium channel blocking activity provides local anesthetic effects.", "commonBenefits": [ "Rapid relief of acute allergic reactions (urticaria, angioedema)", "Adjunctive treatment in anaphylaxis (with epinephrine)", "OTC sleep aid", "Treats motion sickness and nausea", "Treats acute dystonic reactions (drug-induced)", "Relieves pruritus" ], "commonDosageRange": "25-50 mg every 4-6 hours (max 300 mg/day); sleep: 25-50 mg at bedtime; IV/IM for severe allergic reactions: 10-50 mg (as prescribed by your physician)", "recommendedForm": "Oral tablets, capsules, liquid, IV, or IM injection; topical cream (limited systemic use)", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Well absorbed orally with bioavailability 40-60% (first-pass metabolism). Onset of oral sedation within 15-30 minutes. Can be taken with food to reduce GI upset. Avoid use in elderly due to Beers Criteria anticholinergic risk." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Drowsiness and sedation (pronounced)", "Dry mouth, nose, and throat", "Urinary retention", "Constipation", "Blurred vision (mydriasis, cycloplegia)", "Dizziness and impaired coordination", "Cognitive impairment (especially in elderly)", "Paradoxical excitation (especially in children)" ], "contraindications": [ "Known hypersensitivity to diphenhydramine", "Neonates and premature infants", "Nursing mothers (excreted in breast milk; may inhibit lactation)", "Narrow-angle glaucoma", "Urinary retention/bladder neck obstruction", "Elderly patients (Beers Criteria, increased risk of confusion, falls, urinary retention)" ], "iconName": "allergens.fill", "colorHex": "F59E0B", "tags": [ "antihistamine", "allergy", "first-generation", "sedating", "sleep-aid", "otc-available", "anaphylaxis" ], "sources": [ { "text": "Simons FE. Advances in H1-antihistamines. N Engl J Med. 2004.", "pmid": "15590952", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15590952/", "publicSourceType": "PMID" }, { "text": "American Geriatrics Society 2019 Updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2019.", "pmid": "30693946", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30693946/", "publicSourceType": "PMID" }, { "text": "Lieberman P et al. The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin Immunol. 2010.", "pmid": "20692689", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20692689/", "publicSourceType": "PMID" }, { "text": "Clark JH, Meltzer EO, Naclerio RM. Diphenhydramine: It is time to say a final goodbye. The World Allergy Organization journal. 2025", "pmid": "39925982", "doi": "10.1016/j.waojou.2025.101027", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39925982/", "publicSourceType": "PMID" }, { "text": "Bender BG, Berning S, Dudden R et al.. Sedation and performance impairment of diphenhydramine and second-generation antihistamines: a meta-analysis. The Journal of allergy and clinical immunology. 2003", "claim": "PubMed-indexed evidence involving Diphenhydramine", "title": "Sedation and performance impairment of diphenhydramine and second-generation antihistamines: a meta-analysis", "authors": "Bender BG, Berning S, Dudden R et al.", "journal": "The Journal of allergy and clinical immunology", "year": 2003, "pmid": "12704356", "url": "https://pubmed.ncbi.nlm.nih.gov/12704356/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1067/mai.2003.1408", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12704356/", "publicSourceType": "PMID" }, { "text": "Khan WN, Tobias JD. Diphenhydramine: A Review of Its Clinical Applications and Potential Adverse Effect Profile. The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG. 2025", "claim": "PubMed-indexed evidence involving Diphenhydramine", "title": "Diphenhydramine: A Review of Its Clinical Applications and Potential Adverse Effect Profile", "authors": "Khan WN, Tobias JD", "journal": "The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG", "year": 2025, "pmid": "40717751", "url": "https://pubmed.ncbi.nlm.nih.gov/40717751/", "study_type": "review", "confidence": "verify", "doi": "10.5863/1551-6776-30.2.182", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40717751/", "publicSourceType": "PMID" }, { "text": "Chi CY, Chen YC, Cheng MT et al.. Diphenhydramine, Sodium Bicarbonate, or Combination for Acute Peripheral Vertigo: A Randomized Clinical Trial. JAMA network open. 2025", "claim": "PubMed-indexed evidence involving Diphenhydramine", "title": "Diphenhydramine, Sodium Bicarbonate, or Combination for Acute Peripheral Vertigo: A Randomized Clinical Trial", "authors": "Chi CY, Chen YC, Cheng MT et al.", "journal": "JAMA network open", "year": 2025, "pmid": "41196596", "url": "https://pubmed.ncbi.nlm.nih.gov/41196596/", "study_type": "RCT", "confidence": "verify", "doi": "10.1001/jamanetworkopen.2025.41472", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41196596/", "publicSourceType": "PMID" }, { "text": "Friedman BW, Irizarry E, Cain D et al.. Randomized Study of Metoclopramide Plus Diphenhydramine for Acute Posttraumatic Headache. Neurology. 2021", "claim": "PubMed-indexed evidence involving Diphenhydramine", "title": "Randomized Study of Metoclopramide Plus Diphenhydramine for Acute Posttraumatic Headache", "authors": "Friedman BW, Irizarry E, Cain D et al.", "journal": "Neurology", "year": 2021, "pmid": "33762421", "url": "https://pubmed.ncbi.nlm.nih.gov/33762421/", "study_type": "RCT", "confidence": "verify", "doi": "10.1212/WNL.0000000000011822", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33762421/", "publicSourceType": "PMID" }, { "text": "Huynh DA, Abbas M, Dabaja A. Diphenhydramine Toxicity. 2026", "claim": "PubMed-indexed evidence involving Diphenhydramine", "title": "Diphenhydramine Toxicity", "authors": "Huynh DA, Abbas M, Dabaja A", "journal": "", "year": 2026, "pmid": "32491510", "url": "https://pubmed.ncbi.nlm.nih.gov/32491510/", "study_type": "review", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32491510/", "publicSourceType": "PMID" }, { "text": "Ariza-Salamanca DF, Venegas M, Parejo K et al.. Expert Consensus on the Use of Diphenhydramine for Short-Term Insomnia: Efficacy, Safety, and Clinical Applications. Journal of clinical medicine. 2025", "claim": "PubMed-indexed evidence involving Diphenhydramine", "title": "Expert Consensus on the Use of Diphenhydramine for Short-Term Insomnia: Efficacy, Safety, and Clinical Applications", "authors": "Ariza-Salamanca DF, Venegas M, Parejo K et al.", "journal": "Journal of clinical medicine", "year": 2025, "pmid": "40429293", "url": "https://pubmed.ncbi.nlm.nih.gov/40429293/", "study_type": "review", "confidence": "verify", "doi": "10.3390/jcm14103297", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40429293/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "First-generation antihistamine (H1 receptor antagonist, ethanolamine class)", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "2.4-9.3 hours (average ~4 hours)", "onsetOfAction": "Oral: 15-30 minutes; IV: immediate; duration 4-6 hours", "commonBrandNames": [ "Benadryl" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "diphenhydramine" }, { "id": "RX-INFR-029", "name": "Fluticasone Nasal", "alternateNames": [ "Flonase", "Flonase Sensimist", "Veramyst" ], "category": "Prescription", "subcategory": "Intranasal Corticosteroid", "overview": "An intranasal corticosteroid (INCS) considered the most effective pharmacotherapy class for allergic rhinitis. Fluticasone propionate (Flonase) and fluticasone furoate (Veramyst/Flonase Sensimist) reduce nasal inflammation, congestion, rhinorrhea, sneezing, and itching. Recommended as first-line therapy for moderate-to-severe allergic rhinitis by all major guidelines. Available over-the-counter (Flonase). Also effective for non-allergic rhinitis and nasal polyps.", "mechanismOfAction": "Binds to intracellular glucocorticoid receptors in nasal mucosal cells. The activated complex translocates to the nucleus and modulates transcription of inflammatory genes, suppressing cytokines (IL-1, IL-4, IL-5, IL-13), chemokines, adhesion molecules (ICAM-1, VCAM-1), and inflammatory enzymes. Reduces eosinophil, mast cell, T-lymphocyte, and basophil infiltration in the nasal mucosa. Decreases vascular permeability and mucus gland secretion. Minimal systemic absorption (<2% bioavailability for fluticasone propionate).", "commonBenefits": [ "Most effective single-agent therapy for allergic rhinitis", "Relieves nasal congestion (superior to oral antihistamines for this symptom)", "Reduces sneezing, rhinorrhea, and nasal itching", "Effective for seasonal and perennial allergic rhinitis", "Treats non-allergic rhinitis and nasal polyps", "Once-daily dosing after initial loading" ], "commonDosageRange": "Adults: 1-2 sprays (50 mcg each) per nostril once daily; children >=4 years: 1 spray per nostril once daily; Sensimist: 1-2 sprays (27.5 mcg each) per nostril once daily (as prescribed by your physician)", "recommendedForm": "Nasal spray (aqueous suspension)", "absorption": { "isFatSoluble": true, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Applied intranasally. Systemic bioavailability extremely low (<2% for fluticasone propionate; 0.5% for fluticasone furoate). Shake well before use. Aim spray away from nasal septum. Prime before first use. Regular daily use is needed for maximum benefit, not for as-needed symptom relief." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Epistaxis (nosebleed), most common", "Nasal dryness or irritation", "Headache", "Pharyngitis", "Unpleasant taste or smell", "Nasal septal perforation (rare, with improper technique)" ], "contraindications": [ "Known hypersensitivity to fluticasone or any component", "Recent nasal surgery or nasal septum ulcers (until healed)", "Untreated nasal infections (fungal, bacterial)" ], "iconName": "nose.fill", "colorHex": "60A5FA", "tags": [ "respiratory", "nasal", "corticosteroid", "allergic-rhinitis", "congestion", "anti-inflammatory", "otc-available" ], "sources": [ { "text": "Brozek JL et al. Allergic rhinitis and its impact on asthma (ARIA) guidelines, 2016 revision. J Allergy Clin Immunol. 2017.", "pmid": "28602936", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28602936/", "publicSourceType": "PMID" }, { "text": "Weiner JM et al. Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis: systematic review of randomised controlled trials. BMJ. 1998.", "pmid": "9848901", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9848901/", "publicSourceType": "PMID" }, { "text": "Dykewicz MS et al. Treatment of seasonal allergic rhinitis: an evidence-based focused 2017 guideline update. Ann Allergy Asthma Immunol. 2017.", "pmid": "29103802", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29103802/", "publicSourceType": "PMID" }, { "text": "Tagaya E, Shinada J, Nagase H et al.. The efficacy and safety of Fluticasone Furoate/Umeclidinium/vilanterol (FF/UMEC/VI) on cough symptoms in adult patients with asthma, a randomized double-blind, placebo-controlled, parallel group study: Chronic Cough in Asthma (COCOA) study. The Journal of asthma : official journal of the Association for the Care of Asthma. 2025", "pmid": "39874464", "doi": "10.1080/02770903.2025.2455416", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39874464/", "publicSourceType": "PMID" }, { "text": "Ismaila AS, Haeussler K, Czira A et al.. Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) Triple Therapy Compared with Other Therapies for the Treatment of COPD: A Network Meta-Analysis. Advances in therapy. 2022", "pmid": "35849317", "doi": "10.1007/s12325-022-02231-0", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35849317/", "publicSourceType": "PMID" }, { "text": "Bielory L, Gross GN, Letierce A et al.. Ocular symptoms improvement from intranasal triamcinolone compared with placebo and intranasal fluticasone propionate: A meta-analysis. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2020", "claim": "PubMed-indexed evidence involving Fluticasone Nasal", "title": "Ocular symptoms improvement from intranasal triamcinolone compared with placebo and intranasal fluticasone propionate: A meta-analysis", "authors": "Bielory L, Gross GN, Letierce A et al.", "journal": "Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology", "year": 2020, "pmid": "32004698", "url": "https://pubmed.ncbi.nlm.nih.gov/32004698/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.anai.2020.01.012", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32004698/", "publicSourceType": "PMID" }, { "text": "Holm AF, Fokkens WJ, Godthelp T et al.. A 1-year placebo-controlled study of intranasal fluticasone propionate aqueous nasal spray in patients with perennial allergic rhinitis: a safety and biopsy study. Clinical otolaryngology and allied sciences. 1998", "claim": "PubMed-indexed evidence involving Fluticasone Nasal", "title": "A 1-year placebo-controlled study of intranasal fluticasone propionate aqueous nasal spray in patients with perennial allergic rhinitis: a safety and biopsy study", "authors": "Holm AF, Fokkens WJ, Godthelp T et al.", "journal": "Clinical otolaryngology and allied sciences", "year": 1998, "pmid": "9563670", "url": "https://pubmed.ncbi.nlm.nih.gov/9563670/", "study_type": "RCT", "confidence": "verify", "doi": "10.1046/j.1365-2273.1998.00096.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9563670/", "publicSourceType": "PMID" }, { "text": "Li S, Xu R, Yu S et al.. Nasal saline irrigation with azelastine-fluticasone nasal spray in moderate-to-severe persistent allergic rhinitis: a randomized controlled trial. Frontiers in allergy. 2025", "claim": "PubMed-indexed evidence involving Fluticasone Nasal", "title": "Nasal saline irrigation with azelastine-fluticasone nasal spray in moderate-to-severe persistent allergic rhinitis: a randomized controlled trial", "authors": "Li S, Xu R, Yu S et al.", "journal": "Frontiers in allergy", "year": 2025, "pmid": "41158297", "url": "https://pubmed.ncbi.nlm.nih.gov/41158297/", "study_type": "RCT", "confidence": "verify", "doi": "10.3389/falgy.2025.1622510", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41158297/", "publicSourceType": "PMID" }, { "text": "Zhang Y, Wei P, Chen B et al.. Intranasal fluticasone furoate in pediatric allergic rhinitis: randomized controlled study. Pediatric research. 2021", "claim": "PubMed-indexed evidence involving Fluticasone Nasal", "title": "Intranasal fluticasone furoate in pediatric allergic rhinitis: randomized controlled study", "authors": "Zhang Y, Wei P, Chen B et al.", "journal": "Pediatric research", "year": 2021, "pmid": "33007780", "url": "https://pubmed.ncbi.nlm.nih.gov/33007780/", "study_type": "RCT", "confidence": "verify", "doi": "10.1038/s41390-020-01180-0", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33007780/", "publicSourceType": "PMID" }, { "text": "Davis KJ, Hinds D, Motsko SP et al.. Intranasal Fluticasone Propionate Observational Cohort Safety Studies: Reviewing Evidence from Databases on Two Continents. Drugs - real world outcomes. 2016", "claim": "PubMed-indexed evidence involving Fluticasone Nasal", "title": "Intranasal Fluticasone Propionate Observational Cohort Safety Studies: Reviewing Evidence from Databases on Two Continents", "authors": "Davis KJ, Hinds D, Motsko SP et al.", "journal": "Drugs - real world outcomes", "year": 2016, "pmid": "27747804", "url": "https://pubmed.ncbi.nlm.nih.gov/27747804/", "study_type": "cohort", "confidence": "verify", "doi": "10.1007/s40801-015-0057-y", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27747804/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Intranasal corticosteroid (INCS)", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "7.8 hours (propionate); 15.1 hours (furoate), pharmacologic duration exceeds plasma half-life", "onsetOfAction": "Some improvement within 12 hours; maximum benefit after 3-7 days of regular use", "commonBrandNames": [ "Flonase", "Flonase Sensimist", "Veramyst" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "fluticasone-nasal" }, { "id": "RX-INFR-030", "name": "Mometasone Nasal", "alternateNames": [ "Nasonex" ], "category": "Prescription", "subcategory": "Intranasal Corticosteroid", "overview": "An intranasal corticosteroid for the treatment of allergic rhinitis (seasonal and perennial) and nasal polyps. Mometasone furoate nasal spray has one of the lowest systemic bioavailabilities (<0.1%) among intranasal corticosteroids, making it particularly attractive when minimizing systemic steroid effects is important (e.g., in children). Approved for prophylactic use starting 2-4 weeks before anticipated allergy season. Also used for nasal polyps to reduce polyp size and improve congestion.", "mechanismOfAction": "Binds to the intracellular glucocorticoid receptor with high affinity (relative receptor affinity approximately 2200, among the highest of all corticosteroids). The activated receptor-steroid complex suppresses NF-kB and AP-1 transcription pathways, reducing production of pro-inflammatory cytokines, prostaglandins, leukotrienes, and adhesion molecules. This decreases inflammatory cell infiltration (eosinophils, mast cells, lymphocytes) in the nasal mucosa, reducing mucosal edema, vascular permeability, and mucus secretion.", "commonBenefits": [ "Treats seasonal and perennial allergic rhinitis", "Prophylactic use before allergy season (start 2-4 weeks prior)", "Treats nasal polyps (reduces polyp size)", "Extremely low systemic bioavailability (<0.1%)", "Once-daily dosing" ], "commonDosageRange": "Adults and children >=12 years: 2 sprays (50 mcg each) per nostril once daily (total 200 mcg/day); children 2-11 years: 1 spray per nostril once daily (100 mcg/day); nasal polyps: 2 sprays per nostril BID (as prescribed by your physician)", "recommendedForm": "Nasal spray (aqueous suspension)", "absorption": { "isFatSoluble": true, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Applied intranasally. Systemic bioavailability <0.1%, the lowest of all commercially available intranasal corticosteroids. Any swallowed drug undergoes extensive first-pass hepatic metabolism. Shake well before use. Prime before first use and after periods of non-use (>1 week)." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Epistaxis (nosebleed)", "Headache", "Pharyngitis", "Nasal irritation or burning", "Viral upper respiratory infection", "Nasal septal perforation (rare, with improper spray technique)" ], "contraindications": [ "Known hypersensitivity to mometasone or any component", "Recent nasal surgery or nasal trauma (until healed)", "Untreated localized infection of the nasal mucosa" ], "iconName": "nose.fill", "colorHex": "60A5FA", "tags": [ "respiratory", "nasal", "corticosteroid", "allergic-rhinitis", "nasal-polyps", "anti-inflammatory" ], "sources": [ { "text": "Brozek JL et al. Allergic rhinitis and its impact on asthma (ARIA) guidelines, 2016 revision. J Allergy Clin Immunol. 2017.", "pmid": "28602936", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28602936/", "publicSourceType": "PMID" }, { "text": "Scadding GK et al. BSACI guidelines for the management of allergic and non-allergic rhinitis. Clin Exp Allergy. 2008.", "pmid": "30239057", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30239057/", "publicSourceType": "PMID" }, { "text": "Stjarne P et al. A randomized controlled trial of mometasone furoate nasal spray for the treatment of nasal polyposis. Arch Otolaryngol Head Neck Surg. 2006.", "pmid": "19289710", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19289710/", "publicSourceType": "PMID" }, { "text": "Lazarus SC, Krishnan JA, King TS et al.. Mometasone or Tiotropium in Mild Asthma with a Low Sputum Eosinophil Level. The New England journal of medicine. 2019", "pmid": "31112384", "doi": "10.1056/NEJMoa1814917", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31112384/", "publicSourceType": "PMID" }, { "text": "Ghanbari N, Eftekhari K, Samadzadeh-Mamaghani M et al.. Comparative Efficacy of Mometasone Nasal Spray Combined with Different Doses of Desloratadine, and Montelukast in Childhood Allergic Rhinitis: A Randomized Clinical Trial. Iranian journal of allergy, asthma, and immunology. 2024", "pmid": "39549290", "doi": "10.18502/ijaai.v23i4.16211", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39549290/", "publicSourceType": "PMID" }, { "text": "Almutairi RH, Albesher MB, Alboqami RA et al.. Comparative efficacy of intranasal mometasone furoate monotherapy or combination therapy with montelukast in pediatric adenoid hypertrophy: A systematic review and meta-analysis of randomized clinical trials. International journal of pediatric otorhinolaryngology. 2025", "claim": "PubMed-indexed evidence involving Mometasone Nasal", "title": "Comparative efficacy of intranasal mometasone furoate monotherapy or combination therapy with montelukast in pediatric adenoid hypertrophy: A systematic review and meta-analysis of randomized clinical trials", "authors": "Almutairi RH, Albesher MB, Alboqami RA et al.", "journal": "International journal of pediatric otorhinolaryngology", "year": 2025, "pmid": "40120471", "url": "https://pubmed.ncbi.nlm.nih.gov/40120471/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.ijporl.2025.112310", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40120471/", "publicSourceType": "PMID" }, { "text": "Penagos M, Compalati E, Tarantini F et al.. Efficacy of mometasone furoate nasal spray in the treatment of allergic rhinitis. Meta-analysis of randomized, double-blind, placebo-controlled, clinical trials. Allergy. 2008", "claim": "PubMed-indexed evidence involving Mometasone Nasal", "title": "Efficacy of mometasone furoate nasal spray in the treatment of allergic rhinitis. Meta-analysis of randomized, double-blind, placebo-controlled, clinical trials", "authors": "Penagos M, Compalati E, Tarantini F et al.", "journal": "Allergy", "year": 2008, "pmid": "18721246", "url": "https://pubmed.ncbi.nlm.nih.gov/18721246/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/j.1398-9995.2008.01808.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18721246/", "publicSourceType": "PMID" }, { "text": "Wang H, Liu T, Liao C et al.. Safety and onset time of modified Yupingfeng nasal spray versus mometasone furoate nasal spray on house dust mites-induced moderate to severe allergic rhinitis: A prospective, multicenter, randomized, open-label, parallel-group clinical trial. Journal of ethnopharmacology. 2025", "claim": "PubMed-indexed evidence involving Mometasone Nasal", "title": "Safety and onset time of modified Yupingfeng nasal spray versus mometasone furoate nasal spray on house dust mites-induced moderate to severe allergic rhinitis: A prospective, multicenter, randomized, open-label, parallel-group clinical trial", "authors": "Wang H, Liu T, Liao C et al.", "journal": "Journal of ethnopharmacology", "year": 2025, "pmid": "40032208", "url": "https://pubmed.ncbi.nlm.nih.gov/40032208/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.jep.2025.119574", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40032208/", "publicSourceType": "PMID" }, { "text": "Bielory L, Chun Y, Bielory BP et al.. Impact of mometasone furoate nasal spray on individual ocular symptoms of allergic rhinitis: a meta-analysis. Allergy. 2011", "claim": "PubMed-indexed evidence involving Mometasone Nasal", "title": "Impact of mometasone furoate nasal spray on individual ocular symptoms of allergic rhinitis: a meta-analysis", "authors": "Bielory L, Chun Y, Bielory BP et al.", "journal": "Allergy", "year": 2011, "pmid": "21261661", "url": "https://pubmed.ncbi.nlm.nih.gov/21261661/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/j.1398-9995.2010.02543.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21261661/", "publicSourceType": "PMID" }, { "text": "Baker A, Grobler A, Davies K et al.. Effectiveness of Intranasal Mometasone Furoate vs Saline for Sleep-Disordered Breathing in Children: A Randomized Clinical Trial. JAMA pediatrics. 2023", "claim": "PubMed-indexed evidence involving Mometasone Nasal", "title": "Effectiveness of Intranasal Mometasone Furoate vs Saline for Sleep-Disordered Breathing in Children: A Randomized Clinical Trial", "authors": "Baker A, Grobler A, Davies K et al.", "journal": "JAMA pediatrics", "year": 2023, "pmid": "36648937", "url": "https://pubmed.ncbi.nlm.nih.gov/36648937/", "study_type": "RCT", "confidence": "verify", "doi": "10.1001/jamapediatrics.2022.5258", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36648937/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Intranasal corticosteroid (INCS)", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "5.8 hours (plasma, clinically irrelevant due to negligible systemic absorption)", "onsetOfAction": "Some improvement within 12 hours; significant benefit by 2 days; maximum effect after 1-2 weeks", "commonBrandNames": [ "Nasonex" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "mometasone-nasal" }, { "id": "RX-INFR-031", "name": "Pseudoephedrine", "alternateNames": [ "Sudafed", "Sudafed 12 Hour" ], "category": "Prescription", "subcategory": "Sympathomimetic Decongestant", "overview": "An oral sympathomimetic decongestant used for temporary relief of nasal and sinus congestion associated with the common cold, allergic rhinitis, and sinusitis. Acts as an alpha-adrenergic agonist to constrict dilated blood vessels in the nasal mucosa. Available behind-the-counter (requires ID due to Combat Methamphetamine Epidemic Act) but does not require a prescription. Often found in combination products with antihistamines, analgesics, and cough suppressants.", "mechanismOfAction": "A stereoisomer of ephedrine that acts primarily as an indirect sympathomimetic amine, stimulating the release of norepinephrine from adrenergic nerve terminals. Also has some direct alpha-1 and beta adrenergic receptor agonist activity. The alpha-1 receptor stimulation on blood vessels of the nasal mucosa causes vasoconstriction, reducing mucosal edema, swelling, and congestion. Unlike topical decongestants (oxymetazoline), pseudoephedrine does not cause rebound congestion (rhinitis medicamentosa) with regular use.", "commonBenefits": [ "Relieves nasal and sinus congestion", "Relieves eustachian tube congestion", "No rebound congestion (unlike topical decongestants)", "Available in immediate-release and extended-release formulations", "Effective for cold, flu, and allergy-associated congestion" ], "commonDosageRange": "Immediate-release: 60 mg every 4-6 hours (max 240 mg/day); extended-release: 120 mg every 12 hours or 240 mg once daily; children 6-11 years: 30 mg every 4-6 hours (as prescribed by your physician)", "recommendedForm": "Oral tablets (immediate-release or extended-release) or liquid", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Well absorbed orally with nearly complete bioavailability. Food does not significantly affect absorption. Extended-release formulations should be swallowed whole, do not crush or chew. Primarily eliminated renally; urinary acidification increases excretion." }, "evidenceRating": "moderate", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Insomnia and restlessness", "Nervousness and anxiety", "Tachycardia and palpitations", "Elevated blood pressure", "Headache", "Dizziness", "Decreased appetite", "Urinary retention (especially in men with BPH)" ], "contraindications": [ "Concurrent or recent (within 14 days) use of MAO inhibitors (risk of hypertensive crisis)", "Severe or uncontrolled hypertension", "Severe coronary artery disease", "Known hypersensitivity to pseudoephedrine or sympathomimetic amines", "Narrow-angle glaucoma", "Urinary retention" ], "iconName": "nose.fill", "colorHex": "F97316", "tags": [ "decongestant", "respiratory", "nasal-congestion", "sympathomimetic", "cold", "sinusitis", "otc-available" ], "sources": [ { "text": "Eccles R. The powerful placebo effect in cough: relevance to treatment and clinical trials. Lung. 2020.", "pmid": "31834478", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31834478/", "publicSourceType": "PMID" }, { "text": "Deckx L et al. Nasal decongestants in monotherapy for the common cold. Cochrane Database Syst Rev. 2016.", "pmid": "27748955", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27748955/", "publicSourceType": "PMID" }, { "text": "Meltzer EO et al. Treatment of congestion in upper respiratory diseases. Int J Gen Med. 2010.", "pmid": "37951571", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37951571/", "publicSourceType": "PMID" }, { "text": "Głowacka K, Wiela-Hojeńska A. Pseudoephedrine-Benefits and Risks. International journal of molecular sciences. 2021", "pmid": "34067981", "doi": "10.3390/ijms22105146", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34067981/", "publicSourceType": "PMID" }, { "text": "Trinh KV, Kim J, Ritsma A. Effect of pseudoephedrine in sport: a systematic review. BMJ open sport & exercise medicine. 2015", "claim": "PubMed-indexed evidence involving Pseudoephedrine", "title": "Effect of pseudoephedrine in sport: a systematic review", "authors": "Trinh KV, Kim J, Ritsma A", "journal": "BMJ open sport & exercise medicine", "year": 2015, "pmid": "27900142", "url": "https://pubmed.ncbi.nlm.nih.gov/27900142/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1136/bmjsem-2015-000066", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27900142/", "publicSourceType": "PMID" }, { "text": "Gheorghiev MD, Hosseini F, Moran J et al.. Effects of pseudoephedrine on parameters affecting exercise performance: a meta-analysis. Sports medicine - open. 2018", "claim": "PubMed-indexed evidence involving Pseudoephedrine", "title": "Effects of pseudoephedrine on parameters affecting exercise performance: a meta-analysis", "authors": "Gheorghiev MD, Hosseini F, Moran J et al.", "journal": "Sports medicine - open", "year": 2018, "pmid": "30291523", "url": "https://pubmed.ncbi.nlm.nih.gov/30291523/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s40798-018-0159-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30291523/", "publicSourceType": "PMID" }, { "text": "Salerno SM, Jackson JL, Berbano EP. Effect of oral pseudoephedrine on blood pressure and heart rate: a meta-analysis. Archives of internal medicine. 2005", "claim": "PubMed-indexed evidence involving Pseudoephedrine", "title": "Effect of oral pseudoephedrine on blood pressure and heart rate: a meta-analysis", "authors": "Salerno SM, Jackson JL, Berbano EP", "journal": "Archives of internal medicine", "year": 2005, "pmid": "16087815", "url": "https://pubmed.ncbi.nlm.nih.gov/16087815/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1001/archinte.165.15.1686", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16087815/", "publicSourceType": "PMID" }, { "text": "Brookfield S, Gartner C. The impact of pseudoephedrine regulation at Australian pharmacies through Project Stop: A narrative review. Drug and alcohol review. 2024", "claim": "PubMed-indexed evidence involving Pseudoephedrine", "title": "The impact of pseudoephedrine regulation at Australian pharmacies through Project Stop: A narrative review", "authors": "Brookfield S, Gartner C", "journal": "Drug and alcohol review", "year": 2024, "pmid": "37963493", "url": "https://pubmed.ncbi.nlm.nih.gov/37963493/", "study_type": "review", "confidence": "verify", "doi": "10.1111/dar.13777", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37963493/", "publicSourceType": "PMID" }, { "text": "Douhard R, Humbert P, Milon JY et al.. Pharmacology of chlorphenamine and pseudoephedrine use in the common cold: a narrative review. Current medical research and opinion. 2024", "claim": "PubMed-indexed evidence involving Pseudoephedrine", "title": "Pharmacology of chlorphenamine and pseudoephedrine use in the common cold: a narrative review", "authors": "Douhard R, Humbert P, Milon JY et al.", "journal": "Current medical research and opinion", "year": 2024, "pmid": "39484821", "url": "https://pubmed.ncbi.nlm.nih.gov/39484821/", "study_type": "review", "confidence": "verify", "doi": "10.1080/03007995.2024.2424422", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39484821/", "publicSourceType": "PMID" }, { "text": "Pallarés JG, López-Samanes Á, Fernández-Elías VE et al.. Pseudoephedrine and circadian rhythm interaction on neuromuscular performance. Scandinavian journal of medicine & science in sports. 2015", "claim": "PubMed-indexed evidence involving Pseudoephedrine", "title": "Pseudoephedrine and circadian rhythm interaction on neuromuscular performance", "authors": "Pallarés JG, López-Samanes Á, Fernández-Elías VE et al.", "journal": "Scandinavian journal of medicine & science in sports", "year": 2015, "pmid": "25515692", "url": "https://pubmed.ncbi.nlm.nih.gov/25515692/", "study_type": "review", "confidence": "verify", "doi": "10.1111/sms.12385", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25515692/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Sympathomimetic amine decongestant (alpha-adrenergic agonist)", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "5-8 hours", "onsetOfAction": "15-30 minutes; duration 4-6 hours (immediate-release) or 12-24 hours (extended-release)", "commonBrandNames": [ "Sudafed", "Sudafed 12 Hour", "Nexafed" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "pseudoephedrine" }, { "id": "RX-SPEC-001", "name": "Levetiracetam", "alternateNames": [ "Keppra" ], "category": "Prescription", "subcategory": "Antiepileptic", "overview": "Levetiracetam is a broad-spectrum antiepileptic drug used as monotherapy or adjunctive therapy for partial-onset seizures, myoclonic seizures in juvenile myoclonic epilepsy, and primary generalized tonic-clonic seizures. It has a favorable side-effect profile compared to older antiepileptics and does not require routine serum drug level monitoring.", "mechanismOfAction": "Binds to synaptic vesicle protein 2A (SV2A) in the brain, modulating neurotransmitter release. Unlike older antiepileptics, it does not act primarily on sodium channels or GABA receptors. By binding SV2A, it reduces excessive synchronous neuronal firing and inhibits burst firing without affecting normal neurotransmission.", "commonBenefits": [ "Broad-spectrum seizure control", "Favorable drug interaction profile", "Rapid titration to therapeutic dose", "Available in IV and oral formulations" ], "commonDosageRange": "500 mg twice daily, titrated up to 1,500 mg twice daily (as prescribed by your physician)", "recommendedForm": "Oral tablets, oral solution, or IV infusion", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Rapidly and almost completely absorbed; food does not significantly affect bioavailability but may slow absorption rate" }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Somnolence and fatigue", "Behavioral changes (irritability, aggression, mood swings)", "Dizziness", "Headache", "Nasopharyngitis", "Decreased appetite" ], "contraindications": [ "Known hypersensitivity to levetiracetam", "Severe renal impairment without dose adjustment", "History of significant psychiatric disorders (use with caution)" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "epilepsy", "seizure", "anticonvulsant", "neurologic" ], "sources": [ { "text": "Lyseng-Williamson KA. Levetiracetam: a review of its use in epilepsy. Drugs. 2011;71(4):489-514.", "pmid": "21395360", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21395360/", "publicSourceType": "PMID" }, { "text": "Mbizvo GK et al. Levetiracetam add-on for drug-resistant focal epilepsy: an updated Cochrane Review. Cochrane Database Syst Rev. 2012;(9):CD001901.", "pmid": "22972056", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22972056/", "publicSourceType": "PMID" }, { "text": "Lynch BA et al. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Natl Acad Sci USA. 2004;101(26):9861-9866.", "pmid": "15210974", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15210974/", "publicSourceType": "PMID" }, { "text": "Steinhoff BJ, Klein P, Klitgaard H et al.. Behavioral adverse events with brivaracetam, levetiracetam, perampanel, and topiramate: A systematic review. Epilepsy & behavior : E&B. 2021", "pmid": "33839453", "doi": "10.1016/j.yebeh.2021.107939", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33839453/", "publicSourceType": "PMID" }, { "text": "Fang T, Valdes E, Frontera JA. Levetiracetam for Seizure Prophylaxis in Neurocritical Care: A Systematic Review and Meta-analysis. Neurocritical care. 2022", "pmid": "34286461", "doi": "10.1007/s12028-021-01296-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34286461/", "publicSourceType": "PMID" }, { "text": "Besag FMC, Vasey MJ, Sen A. Current evidence for adjunct pyridoxine (vitamin B6) for the treatment of behavioral adverse effects associated with levetiracetam: A systematic review. Epilepsy & behavior : E&B. 2023", "claim": "PubMed-indexed evidence involving Levetiracetam", "title": "Current evidence for adjunct pyridoxine (vitamin B6) for the treatment of behavioral adverse effects associated with levetiracetam: A systematic review", "authors": "Besag FMC, Vasey MJ, Sen A", "journal": "Epilepsy & behavior : E&B", "year": 2023, "pmid": "36791631", "url": "https://pubmed.ncbi.nlm.nih.gov/36791631/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.yebeh.2022.109065", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36791631/", "publicSourceType": "PMID" }, { "text": "Jense A, Douville A, Weiss A. The safety of rapid infusion levetiracetam: A systematic review. Pharmacotherapy. 2022", "claim": "PubMed-indexed evidence involving Levetiracetam", "title": "The safety of rapid infusion levetiracetam: A systematic review", "authors": "Jense A, Douville A, Weiss A", "journal": "Pharmacotherapy", "year": 2022, "pmid": "35502462", "url": "https://pubmed.ncbi.nlm.nih.gov/35502462/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/phar.2687", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35502462/", "publicSourceType": "PMID" }, { "text": "Romoli M, Perucca E, Sen A. Pyridoxine supplementation for levetiracetam-related neuropsychiatric adverse events: A systematic review. Epilepsy & behavior : E&B. 2020", "claim": "PubMed-indexed evidence involving Levetiracetam", "title": "Pyridoxine supplementation for levetiracetam-related neuropsychiatric adverse events: A systematic review", "authors": "Romoli M, Perucca E, Sen A", "journal": "Epilepsy & behavior : E&B", "year": 2020, "pmid": "31917143", "url": "https://pubmed.ncbi.nlm.nih.gov/31917143/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.yebeh.2019.106861", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31917143/", "publicSourceType": "PMID" }, { "text": "Rashid M, Rajan AK, Chhabra M et al.. Levetiracetam and cutaneous adverse reactions: A systematic review of descriptive studies. Seizure. 2020", "claim": "PubMed-indexed evidence involving Levetiracetam", "title": "Levetiracetam and cutaneous adverse reactions: A systematic review of descriptive studies", "authors": "Rashid M, Rajan AK, Chhabra M et al.", "journal": "Seizure", "year": 2020, "pmid": "31931437", "url": "https://pubmed.ncbi.nlm.nih.gov/31931437/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.seizure.2020.01.002", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31931437/", "publicSourceType": "PMID" }, { "text": "Watkins AK, Gee ME, Brown JN. Efficacy and safety of levetiracetam for migraine prophylaxis: A systematic review. Journal of clinical pharmacy and therapeutics. 2018", "claim": "PubMed-indexed evidence involving Levetiracetam", "title": "Efficacy and safety of levetiracetam for migraine prophylaxis: A systematic review", "authors": "Watkins AK, Gee ME, Brown JN", "journal": "Journal of clinical pharmacy and therapeutics", "year": 2018, "pmid": "29781197", "url": "https://pubmed.ncbi.nlm.nih.gov/29781197/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/jcpt.12715", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29781197/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Antiepileptic (SV2A ligand)", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "6-8 hours", "onsetOfAction": "1 hour (oral)", "commonBrandNames": [ "Keppra", "Keppra XR", "Spritam" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Renal function at baseline; dose adjustment required for creatinine clearance <80 mL/min" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "levetiracetam" }, { "id": "RX-SPEC-002", "name": "Carbamazepine", "alternateNames": [ "Tegretol" ], "category": "Prescription", "subcategory": "Antiepileptic", "overview": "Carbamazepine is a first-generation antiepileptic used for partial seizures with complex symptomatology, generalized tonic-clonic seizures, trigeminal neuralgia, and as a mood stabilizer in bipolar disorder. 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The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy. Lancet. 2007;369(9566):1000-1015.", "pmid": "17382827", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17382827/", "publicSourceType": "PMID" }, { "text": "Ferrell PB Jr, McLeod HL. Carbamazepine, HLA-B*1502 and risk of Stevens-Johnson syndrome and toxic epidermal necrolysis: US FDA recommendations. Pharmacogenomics. 2008;9(10):1543-1546.", "pmid": "18855540", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18855540/", "publicSourceType": "PMID" }, { "text": "Ceron-Litvoc D et al. Comparison of carbamazepine and lithium in treatment of bipolar disorder: a systematic review of randomized controlled trials. Hum Psychopharmacol. 2009;24(1):19-28.", "pmid": "19053079", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19053079/", "publicSourceType": "PMID" }, { "text": "Riffi R, Boughrara W, Chentouf A et al.. Pharmacogenetics of Carbamazepine: A Systematic Review on CYP3A4 and CYP3A5 Polymorphisms. CNS & neurological disorders drug targets. 2024", "claim": "PubMed-indexed evidence involving Carbamazepine", "title": "Pharmacogenetics of Carbamazepine: A Systematic Review on CYP3A4 and CYP3A5 Polymorphisms", "authors": "Riffi R, Boughrara W, Chentouf A et al.", "journal": "CNS & neurological disorders drug targets", "year": 2024, "pmid": "38859787", "url": "https://pubmed.ncbi.nlm.nih.gov/38859787/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2174/0118715273298953240529100325", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38859787/", "publicSourceType": "PMID" }, { "text": "Wei L, Han H, Meng J et al.. Meta-analysis and sequential analysis of acupuncture compared to carbamazepine in the treatment of trigeminal neuralgia. World journal of clinical cases. 2024", "claim": "PubMed-indexed evidence involving Carbamazepine", "title": "Meta-analysis and sequential analysis of acupuncture compared to carbamazepine in the treatment of trigeminal neuralgia", "authors": "Wei L, Han H, Meng J et al.", "journal": "World journal of clinical cases", "year": 2024, "pmid": "39109001", "url": "https://pubmed.ncbi.nlm.nih.gov/39109001/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.12998/wjcc.v12.i22.5083", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39109001/", "publicSourceType": "PMID" }, { "text": "Zhang X, Liu J, Ye J. Association between SCN1A polymorphism and carbamazepine responsiveness in epilepsy: A meta-analysis. Epilepsy research. 2021", "claim": "PubMed-indexed evidence involving Carbamazepine", "title": "Association between SCN1A polymorphism and carbamazepine responsiveness in epilepsy: A meta-analysis", "authors": "Zhang X, Liu J, Ye J", "journal": "Epilepsy research", "year": 2021, "pmid": "34218210", "url": "https://pubmed.ncbi.nlm.nih.gov/34218210/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.eplepsyres.2021.106627", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34218210/", "publicSourceType": "PMID" }, { "text": "LoPinto-Khoury C, Brennan L, Mintzer S. Impact of carbamazepine on vitamin D levels: A meta-analysis. Epilepsy research. 2021", "claim": "PubMed-indexed evidence involving Carbamazepine", "title": "Impact of carbamazepine on vitamin D levels: A meta-analysis", "authors": "LoPinto-Khoury C, Brennan L, Mintzer S", "journal": "Epilepsy research", "year": 2021, "pmid": "34847425", "url": "https://pubmed.ncbi.nlm.nih.gov/34847425/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.eplepsyres.2021.106829", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34847425/", "publicSourceType": "PMID" }, { "text": "Zhao GX, Shen ML, Zhang Z et al.. Association between EPHX1 polymorphisms and carbamazepine metabolism in epilepsy: a meta-analysis. International journal of clinical pharmacy. 2019", "claim": "PubMed-indexed evidence involving Carbamazepine", "title": "Association between EPHX1 polymorphisms and carbamazepine metabolism in epilepsy: a meta-analysis", "authors": "Zhao GX, Shen ML, Zhang Z et al.", "journal": "International journal of clinical pharmacy", "year": 2019, "pmid": "31650507", "url": "https://pubmed.ncbi.nlm.nih.gov/31650507/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s11096-019-00919-y", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31650507/", "publicSourceType": "PMID" }, { "text": "Wang Q, Sun S, Xie M et al.. Association between the HLA-B alleles and carbamazepine-induced SJS/TEN: A meta-analysis. Epilepsy research. 2017", "claim": "PubMed-indexed evidence involving Carbamazepine", "title": "Association between the HLA-B alleles and carbamazepine-induced SJS/TEN: A meta-analysis", "authors": "Wang Q, Sun S, Xie M et al.", "journal": "Epilepsy research", "year": 2017, "pmid": "28618376", "url": "https://pubmed.ncbi.nlm.nih.gov/28618376/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.eplepsyres.2017.05.015", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28618376/", "publicSourceType": "PMID" }, { "text": "Almeida Â, Esteves VI, Soares AMVM et al.. Effects of Carbamazepine in Bivalves: A Review. Reviews of environmental contamination and toxicology. 2021", "claim": "PubMed-indexed evidence involving Carbamazepine", "title": "Effects of Carbamazepine in Bivalves: A Review", "authors": "Almeida Â, Esteves VI, Soares AMVM et al.", "journal": "Reviews of environmental contamination and toxicology", "year": 2021, "pmid": "32926215", "url": "https://pubmed.ncbi.nlm.nih.gov/32926215/", "study_type": "review", "confidence": "verify", "doi": "10.1007/398_2020_51", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32926215/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Antiepileptic (Sodium channel blocker)", "blackBoxWarnings": [ "Serious dermatologic reactions (SJS/TEN); aplastic anemia and agranulocytosis" ], "fdaPregnancyCategory": "D", "halfLife": "25-65 hours initially; 12-17 hours after autoinduction", "onsetOfAction": "2-4 hours (oral); steady state in 2-4 weeks", "commonBrandNames": [ "Tegretol", "Tegretol XR", "Carbatrol", "Epitol", "Equetro" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "CBC, LFTs, sodium levels; HLA-B*1502 testing in at-risk populations before starting; serum drug levels (therapeutic 4-12 mcg/mL)" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "carbamazepine" }, { "id": "RX-SPEC-003", "name": "Topiramate", "alternateNames": [ "Topamax" ], "category": "Prescription", "subcategory": "Antiepileptic", "overview": "Topiramate is a broad-spectrum antiepileptic approved for partial-onset and primary generalized tonic-clonic seizures, Lennox-Gastaut syndrome, and migraine prophylaxis. 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Swallow tablets whole; sprinkle capsules can be opened onto soft food." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Cognitive dysfunction (word-finding difficulty, impaired concentration)", "Paresthesias (tingling in extremities)", "Weight loss and decreased appetite", "Kidney stones (calcium phosphate)", "Metabolic acidosis", "Fatigue and somnolence", "Acute myopia and secondary angle-closure glaucoma (rare)" ], "contraindications": [ "Known hypersensitivity to topiramate", "Concurrent use with alcohol (increased CNS depression and metabolic acidosis risk)", "Metabolic acidosis with concurrent metformin use", "Pregnancy (FDA category D; associated with cleft lip/palate)" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "epilepsy", "seizure", "migraine-prevention", "weight-loss", "neurologic" ], "sources": [ { "text": "Brandes JL et al. Topiramate for migraine prevention: a randomized controlled trial. JAMA. 2004;291(8):965-973.", "pmid": "14982912", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14982912/", "publicSourceType": "PMID" }, { "text": "Marson AG et al. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy. Lancet. 2007;369(9566):1000-1015.", "pmid": "17382827", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17382827/", "publicSourceType": "PMID" }, { "text": "Silberstein SD et al. Topiramate in migraine prevention: results of a large controlled trial. Arch Neurol. 2004;61(4):490-495.", "pmid": "15096395", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15096395/", "publicSourceType": "PMID" }, { "text": "Giri S, Tronvik E, Linde M et al.. Randomized controlled studies evaluating Topiramate, Botulinum toxin type A, and mABs targeting CGRP in patients with chronic migraine and medication overuse headache: A systematic review and meta-analysis. Cephalalgia : an international journal of headache. 2023", "claim": "PubMed-indexed evidence involving Topiramate", "title": "Randomized controlled studies evaluating Topiramate, Botulinum toxin type A, and mABs targeting CGRP in patients with chronic migraine and medication overuse headache: A systematic review and meta-analysis", "authors": "Giri S, Tronvik E, Linde M et al.", "journal": "Cephalalgia : an international journal of headache", "year": 2023, "pmid": "36856015", "url": "https://pubmed.ncbi.nlm.nih.gov/36856015/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/03331024231156922", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36856015/", "publicSourceType": "PMID" }, { "text": "Steinhoff BJ, Klein P, Klitgaard H et al.. Behavioral adverse events with brivaracetam, levetiracetam, perampanel, and topiramate: A systematic review. Epilepsy & behavior : E&B. 2021", "claim": "PubMed-indexed evidence involving Topiramate", "title": "Behavioral adverse events with brivaracetam, levetiracetam, perampanel, and topiramate: A systematic review", "authors": "Steinhoff BJ, Klein P, Klitgaard H et al.", "journal": "Epilepsy & behavior : E&B", "year": 2021, "pmid": "33839453", "url": "https://pubmed.ncbi.nlm.nih.gov/33839453/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.yebeh.2021.107939", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33839453/", "publicSourceType": "PMID" }, { "text": "Chen LW, Chen MY, Chen KY et al.. Topiramate-associated sexual dysfunction: A systematic review. Epilepsy & behavior : E&B. 2017", "claim": "PubMed-indexed evidence involving Topiramate", "title": "Topiramate-associated sexual dysfunction: A systematic review", "authors": "Chen LW, Chen MY, Chen KY et al.", "journal": "Epilepsy & behavior : E&B", "year": 2017, "pmid": "28605628", "url": "https://pubmed.ncbi.nlm.nih.gov/28605628/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.yebeh.2017.05.014", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28605628/", "publicSourceType": "PMID" }, { "text": "Fluyau D, Kailasam VK, Pierre CG. A Bayesian meta-analysis of topiramate's effectiveness for individuals with alcohol use disorder. Journal of psychopharmacology (Oxford, England). 2023", "claim": "PubMed-indexed evidence involving Topiramate", "title": "A Bayesian meta-analysis of topiramate's effectiveness for individuals with alcohol use disorder", "authors": "Fluyau D, Kailasam VK, Pierre CG", "journal": "Journal of psychopharmacology (Oxford, England)", "year": 2023, "pmid": "36648091", "url": "https://pubmed.ncbi.nlm.nih.gov/36648091/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/02698811221149643", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36648091/", "publicSourceType": "PMID" }, { "text": "Arbaizar B, Diersen-Sotos T, Gómez-Acebo I et al.. Topiramate in the treatment of alcohol dependence: a meta-analysis. Actas espanolas de psiquiatria. 2010", "claim": "PubMed-indexed evidence involving Topiramate", "title": "Topiramate in the treatment of alcohol dependence: a meta-analysis", "authors": "Arbaizar B, Diersen-Sotos T, Gómez-Acebo I et al.", "journal": "Actas espanolas de psiquiatria", "year": 2010, "pmid": "20931405", "url": "https://pubmed.ncbi.nlm.nih.gov/20931405/", "study_type": "meta-analysis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20931405/", "publicSourceType": "PMID" }, { "text": "Pearl NZ, Babin CP, Catalano NT et al.. Narrative Review of Topiramate: Clinical Uses and Pharmacological Considerations. Advances in therapy. 2023", "claim": "PubMed-indexed evidence involving Topiramate", "title": "Narrative Review of Topiramate: Clinical Uses and Pharmacological Considerations", "authors": "Pearl NZ, Babin CP, Catalano NT et al.", "journal": "Advances in therapy", "year": 2023, "pmid": "37368102", "url": "https://pubmed.ncbi.nlm.nih.gov/37368102/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s12325-023-02586-y", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37368102/", "publicSourceType": "PMID" }, { "text": "Kim A, Nguyen J, Babaei M et al.. A Narrative Review: Phentermine and Topiramate for the Treatment of Pediatric Obesity. Adolescent health, medicine and therapeutics. 2023", "claim": "PubMed-indexed evidence involving Topiramate", "title": "A Narrative Review: Phentermine and Topiramate for the Treatment of Pediatric Obesity", "authors": "Kim A, Nguyen J, Babaei M et al.", "journal": "Adolescent health, medicine and therapeutics", "year": 2023, "pmid": "37641650", "url": "https://pubmed.ncbi.nlm.nih.gov/37641650/", "study_type": "review", "confidence": "verify", "doi": "10.2147/AHMT.S383454", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37641650/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Antiepileptic (Multiple mechanisms)", "blackBoxWarnings": [], "fdaPregnancyCategory": "D", "halfLife": "19-25 hours", "onsetOfAction": "2-4 hours; full therapeutic effect for epilepsy may take weeks", "commonBrandNames": [ "Topamax", "Trokendi XR", "Qudexy XR" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Serum bicarbonate at baseline and periodically (risk of metabolic acidosis); renal function; consider intraocular pressure if visual symptoms" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "topiramate" }, { "id": "RX-SPEC-004", "name": "Phenytoin", "alternateNames": [ "Dilantin" ], "category": "Prescription", "subcategory": "Antiepileptic", "overview": "Phenytoin is one of the oldest and most widely used antiepileptic drugs, effective for partial seizures and generalized tonic-clonic seizures. 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Also modulates calcium channels and calmodulin-dependent processes.", "commonBenefits": [ "Effective for tonic-clonic and focal seizures", "IV formulation for status epilepticus", "Long clinical experience and well-characterized pharmacology", "Once-daily dosing with extended-release formulation" ], "commonDosageRange": "300-400 mg/day (extended-release) or 100 mg three times daily (immediate release); individualized by serum levels (as prescribed by your physician)", "recommendedForm": "Extended-release capsules (Dilantin Kapseals); IV fosphenytoin preferred for parenteral use", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Highly protein-bound (~90%); many drug interactions due to CYP2C9/CYP2C19 metabolism and enzyme induction. Nonlinear pharmacokinetics mean small dose changes can produce large changes in serum levels." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Gingival hyperplasia", "Hirsutism and coarsening of facial features", "Nystagmus and ataxia (dose-related)", "Peripheral neuropathy (chronic use)", "Megaloblastic anemia (folate interference)", "Osteomalacia with long-term use", "Rash (including rare SJS/TEN)", "Cerebellar atrophy (chronic high levels)" ], "contraindications": [ "Known hypersensitivity to phenytoin or other hydantoins", "Sinus bradycardia, SA block, second- or third-degree AV block, Adams-Stokes syndrome", "Concurrent use with delavirdine", "Hepatic impairment (increased free drug levels)", "Porphyria", "Pregnancy (category D; associated with fetal hydantoin syndrome)" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "epilepsy", "seizure", "anticonvulsant", "status-epilepticus", "neurologic" ], "sources": [ { "text": "Kwan P, Brodie MJ. Phenobarbital, phenytoin, carbamazepine, and valproate in the treatment of epilepsy. Lancet Neurol. 2004;3(1):27-30.", "pmid": "23205961", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23205961/", "publicSourceType": "PMID" }, { "text": "Perucca E. Clinically relevant drug interactions with antiepileptic drugs. Br J Clin Pharmacol. 2006;61(3):246-255.", "pmid": "16487217", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16487217/", "publicSourceType": "PMID" }, { "text": "Craig S. Phenytoin poisoning. Neurocrit Care. 2005;3(2):161-170.", "pmid": "16174886", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16174886/", "publicSourceType": "PMID" }, { "text": "Ferner R, Day R, Bradberry SM. Phenytoin and damage to the cerebellum - a systematic review of published cases. Expert opinion on drug safety. 2022", "claim": "PubMed-indexed evidence involving Phenytoin", "title": "Phenytoin and damage to the cerebellum - a systematic review of published cases", "authors": "Ferner R, Day R, Bradberry SM", "journal": "Expert opinion on drug safety", "year": 2022, "pmid": "35325581", "url": "https://pubmed.ncbi.nlm.nih.gov/35325581/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1080/14740338.2022.2058487", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35325581/", "publicSourceType": "PMID" }, { "text": "Panda PK, Panda P, Dawman L et al.. Efficacy of lacosamide and phenytoin in status epilepticus: A systematic review. Acta neurologica Scandinavica. 2021", "claim": "PubMed-indexed evidence involving Phenytoin", "title": "Efficacy of lacosamide and phenytoin in status epilepticus: A systematic review", "authors": "Panda PK, Panda P, Dawman L et al.", "journal": "Acta neurologica Scandinavica", "year": 2021, "pmid": "33999428", "url": "https://pubmed.ncbi.nlm.nih.gov/33999428/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/ane.13469", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33999428/", "publicSourceType": "PMID" }, { "text": "DeMott JM, Slocum GW, Gottlieb M et al.. Levetiracetam vs. phenytoin as 2nd-line treatment for status epilepticus: A systematic review and meta-analysis. Epilepsy & behavior : E&B. 2020", "claim": "PubMed-indexed evidence involving Phenytoin", "title": "Levetiracetam vs. phenytoin as 2nd-line treatment for status epilepticus: A systematic review and meta-analysis", "authors": "DeMott JM, Slocum GW, Gottlieb M et al.", "journal": "Epilepsy & behavior : E&B", "year": 2020, "pmid": "32707535", "url": "https://pubmed.ncbi.nlm.nih.gov/32707535/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.yebeh.2020.107286", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32707535/", "publicSourceType": "PMID" }, { "text": "Klowak JA, Hewitt M, Catenacci V et al.. Levetiracetam Versus Phenytoin or Fosphenytoin for Second-Line Treatment of Pediatric Status Epilepticus: A Meta-Analysis. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2021", "claim": "PubMed-indexed evidence involving Phenytoin", "title": "Levetiracetam Versus Phenytoin or Fosphenytoin for Second-Line Treatment of Pediatric Status Epilepticus: A Meta-Analysis", "authors": "Klowak JA, Hewitt M, Catenacci V et al.", "journal": "Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies", "year": 2021, "pmid": "33710073", "url": "https://pubmed.ncbi.nlm.nih.gov/33710073/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/PCC.0000000000002703", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33710073/", "publicSourceType": "PMID" }, { "text": "Kanjanasilp J, Sawangjit R, Phanthaisong S et al.. A meta-analysis of effects of CYP2C9 and CYP2C19 polymorphisms on phenytoin pharmacokinetic parameters. Pharmacogenomics. 2021", "claim": "PubMed-indexed evidence involving Phenytoin", "title": "A meta-analysis of effects of CYP2C9 and CYP2C19 polymorphisms on phenytoin pharmacokinetic parameters", "authors": "Kanjanasilp J, Sawangjit R, Phanthaisong S et al.", "journal": "Pharmacogenomics", "year": 2021, "pmid": "34060344", "url": "https://pubmed.ncbi.nlm.nih.gov/34060344/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2217/pgs-2020-0151", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34060344/", "publicSourceType": "PMID" }, { "text": "Brigo F, Bragazzi N, Nardone R et al.. Direct and indirect comparison meta-analysis of levetiracetam versus phenytoin or valproate for convulsive status epilepticus. Epilepsy & behavior : E&B. 2016", "claim": "PubMed-indexed evidence involving Phenytoin", "title": "Direct and indirect comparison meta-analysis of levetiracetam versus phenytoin or valproate for convulsive status epilepticus", "authors": "Brigo F, Bragazzi N, Nardone R et al.", "journal": "Epilepsy & behavior : E&B", "year": 2016, "pmid": "27736657", "url": "https://pubmed.ncbi.nlm.nih.gov/27736657/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.yebeh.2016.09.030", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27736657/", "publicSourceType": "PMID" }, { "text": "Smythe MA, Umstead GS. Phenytoin hepatotoxicity: a review of the literature. DICP : the annals of pharmacotherapy. 1989", "claim": "PubMed-indexed evidence involving Phenytoin", "title": "Phenytoin hepatotoxicity: a review of the literature", "authors": "Smythe MA, Umstead GS", "journal": "DICP : the annals of pharmacotherapy", "year": 1989, "pmid": "2655293", "url": "https://pubmed.ncbi.nlm.nih.gov/2655293/", "study_type": "review", "confidence": "verify", "doi": "10.1177/106002808902300102", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2655293/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Antiepileptic (Hydantoin / Sodium channel blocker)", "blackBoxWarnings": [ "Cardiovascular risk with rapid IV administration: severe hypotension and cardiac arrhythmias possible; IV phenytoin must be administered slowly (no faster than 50 mg/min in adults)" ], "fdaPregnancyCategory": "D", "halfLife": "7-42 hours (dose-dependent, nonlinear kinetics); average 22 hours", "onsetOfAction": "3-12 hours (oral); 30-60 minutes (IV)", "commonBrandNames": [ "Dilantin", "Phenytek" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Serum drug levels (therapeutic 10-20 mcg/mL; free levels 1-2 mcg/mL), CBC, LFTs, albumin (for adjusted free levels), folate levels with chronic use" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "phenytoin" }, { "id": "RX-SPEC-005", "name": "Levodopa/Carbidopa", "alternateNames": [ "Sinemet", "Carbidopa-Levodopa" ], "category": "Prescription", "subcategory": "Dopaminergic / Antiparkinson", "overview": "Levodopa/carbidopa is the gold-standard treatment for Parkinson's disease. Levodopa is the metabolic precursor to dopamine and crosses the blood-brain barrier, where it is converted to dopamine by aromatic L-amino acid decarboxylase. Carbidopa inhibits this enzyme peripherally, reducing nausea and increasing CNS levodopa availability. Nearly all Parkinson's patients will eventually require levodopa therapy.", "mechanismOfAction": "Levodopa is converted to dopamine in the CNS by DOPA decarboxylase, replenishing depleted dopamine in the striatum of patients with Parkinson's disease. Carbidopa inhibits peripheral DOPA decarboxylase, preventing premature conversion of levodopa to dopamine outside the brain, thereby increasing CNS bioavailability from ~1% to ~10% and reducing peripheral dopaminergic side effects (nausea, cardiovascular effects).", "commonBenefits": [ "Most effective medication for motor symptoms of Parkinson's disease", "Improves bradykinesia, rigidity, and tremor", "Rapid symptom relief", "Available in multiple formulations (immediate, controlled, intestinal gel)" ], "commonDosageRange": "25/100 mg (carbidopa/levodopa) three times daily initially, titrated to 200-800 mg levodopa/day in divided doses (as prescribed by your physician)", "recommendedForm": "Immediate-release tablets; controlled-release (Sinemet CR) for motor fluctuations; intestinal gel (Duopa) for advanced disease", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "Take on empty stomach 30-60 min before meals; protein can reduce absorption by competing for amino acid transporters in the gut and at the blood-brain barrier. Low-protein meals during the day may optimize 'on' time." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Nausea and vomiting (especially early in treatment)", "Orthostatic hypotension", "Dyskinesias (involuntary movements, with chronic use)", "Motor fluctuations ('wearing off' and 'on-off' phenomena)", "Vivid dreams and hallucinations", "Impulse control disorders (less common than dopamine agonists)", "Darkening of urine and sweat" ], "contraindications": [ "Concurrent use with non-selective MAO inhibitors (hypertensive crisis risk); MAO-B inhibitors are safe", "Narrow-angle glaucoma", "Known hypersensitivity to levodopa or carbidopa", "History of melanoma (theoretical concern, controversial)" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "parkinsons", "dopamine", "motor-symptoms", "neurologic" ], "sources": [ { "text": "Fahn S et al. Levodopa and the progression of Parkinson's disease. N Engl J Med. 2004;351(24):2498-2508.", "pmid": "15590952", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15590952/", "publicSourceType": "PMID" }, { "text": "Olanow CW et al. Levodopa in the treatment of Parkinson's disease: current controversies. Mov Disord. 2004;19(9):997-1005.", "pmid": "15372588", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15372588/", "publicSourceType": "PMID" }, { "text": "Stocchi F et al. Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease: the STRIDE-PD study. Ann Neurol. 2010;68(1):18-27.", "pmid": "20582993", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20582993/", "publicSourceType": "PMID" }, { "text": "Jost ST, Kaldenbach MA, Antonini A et al.. Levodopa Dose Equivalency in Parkinson's Disease: Updated Systematic Review and Proposals. Movement disorders : official journal of the Movement Disorder Society. 2023", "pmid": "37147135", "doi": "10.1002/mds.29410", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37147135/", "publicSourceType": "PMID" }, { "text": "Tomlinson CL, Stowe R, Patel S et al.. Systematic review of levodopa dose equivalency reporting in Parkinson's disease. Movement disorders : official journal of the Movement Disorder Society. 2010", "pmid": "21069833", "doi": "10.1002/mds.23429", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21069833/", "publicSourceType": "PMID" }, { "text": "Tsunemi T, Oyama G, Saiki S et al.. Intrajejunal Infusion of Levodopa/Carbidopa for Advanced Parkinson's Disease: A Systematic Review. Movement disorders : official journal of the Movement Disorder Society. 2021", "claim": "PubMed-indexed evidence involving Levodopa/Carbidopa", "title": "Intrajejunal Infusion of Levodopa/Carbidopa for Advanced Parkinson's Disease: A Systematic Review", "authors": "Tsunemi T, Oyama G, Saiki S et al.", "journal": "Movement disorders : official journal of the Movement Disorder Society", "year": 2021, "pmid": "33899262", "url": "https://pubmed.ncbi.nlm.nih.gov/33899262/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/mds.28595", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33899262/", "publicSourceType": "PMID" }, { "text": "Zhang XR, Jiang ZY, Zhang ZR et al.. The Advantages of Levodopa-Carbidopa Intestinal Gel for Patients with Advanced Parkinson's Disease: A Systematic Review. Drug design, development and therapy. 2020", "claim": "PubMed-indexed evidence involving Levodopa/Carbidopa", "title": "The Advantages of Levodopa-Carbidopa Intestinal Gel for Patients with Advanced Parkinson's Disease: A Systematic Review", "authors": "Zhang XR, Jiang ZY, Zhang ZR et al.", "journal": "Drug design, development and therapy", "year": 2020, "pmid": "32161444", "url": "https://pubmed.ncbi.nlm.nih.gov/32161444/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2147/DDDT.S229621", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32161444/", "publicSourceType": "PMID" }, { "text": "Wirdefeldt K, Odin P, Nyholm D. Levodopa-Carbidopa Intestinal Gel in Patients with Parkinson's Disease: A Systematic Review. CNS drugs. 2016", "claim": "PubMed-indexed evidence involving Levodopa/Carbidopa", "title": "Levodopa-Carbidopa Intestinal Gel in Patients with Parkinson's Disease: A Systematic Review", "authors": "Wirdefeldt K, Odin P, Nyholm D", "journal": "CNS drugs", "year": 2016, "pmid": "27138916", "url": "https://pubmed.ncbi.nlm.nih.gov/27138916/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s40263-016-0336-5", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27138916/", "publicSourceType": "PMID" }, { "text": "Liao X, Wu N, Liu D et al.. Levodopa/carbidopa/entacapone for the treatment of early Parkinson's disease: a meta-analysis. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2020", "claim": "PubMed-indexed evidence involving Levodopa/Carbidopa", "title": "Levodopa/carbidopa/entacapone for the treatment of early Parkinson's disease: a meta-analysis", "authors": "Liao X, Wu N, Liu D et al.", "journal": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology", "year": 2020, "pmid": "32162166", "url": "https://pubmed.ncbi.nlm.nih.gov/32162166/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s10072-020-04303-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32162166/", "publicSourceType": "PMID" }, { "text": "Colucci F, Gozzi A, Antenucci P et al.. Opicapone in Parkinson's Disease on Levodopa-Carbidopa Intestinal Gel Treatment: A Pilot, Randomized Study. Movement disorders clinical practice. 2025", "claim": "PubMed-indexed evidence involving Levodopa/Carbidopa", "title": "Opicapone in Parkinson's Disease on Levodopa-Carbidopa Intestinal Gel Treatment: A Pilot, Randomized Study", "authors": "Colucci F, Gozzi A, Antenucci P et al.", "journal": "Movement disorders clinical practice", "year": 2025, "pmid": "40662211", "url": "https://pubmed.ncbi.nlm.nih.gov/40662211/", "study_type": "RCT", "confidence": "verify", "doi": "10.1002/mdc3.70231", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40662211/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Dopamine precursor / DOPA decarboxylase inhibitor combination", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "1.5-2 hours (levodopa); 2-3 hours (carbidopa)", "onsetOfAction": "30-60 minutes", "commonBrandNames": [ "Sinemet", "Sinemet CR", "Parcopa", "Duopa", "Rytary" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "levodopa-carbidopa" }, { "id": "RX-SPEC-006", "name": "Pramipexole", "alternateNames": [ "Mirapex" ], "category": "Prescription", "subcategory": "Dopaminergic / Antiparkinson", "overview": "Pramipexole is a non-ergot dopamine agonist with preferential affinity for D3 receptors, used for the treatment of early and advanced Parkinson's disease and moderate-to-severe restless legs syndrome (RLS). 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Unlike levodopa, it does not require enzymatic conversion and provides more continuous dopaminergic stimulation, potentially reducing the risk of motor complications.", "commonBenefits": [ "Effective monotherapy for early Parkinson's disease", "Reduces 'off' time when combined with levodopa", "FDA-approved for restless legs syndrome", "Possible antidepressant effect (D3 receptor activation)" ], "commonDosageRange": "0.125 mg three times daily initially, titrated over weeks to 0.5-1.5 mg three times daily for PD; 0.125-0.5 mg once daily for RLS (as prescribed by your physician)", "recommendedForm": "Immediate-release tablets; extended-release tablets (Mirapex ER) for once-daily dosing", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Well absorbed with >90% bioavailability; food does not affect extent of absorption but may delay peak by ~1 hour. Take with food if GI upset occurs." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Somnolence and sudden sleep onset", "Nausea", "Orthostatic hypotension", "Impulse control disorders (pathological gambling, compulsive shopping, hypersexuality)", "Hallucinations (especially in elderly)", "Peripheral edema", "Dizziness" ], "contraindications": [ "Known hypersensitivity to pramipexole", "Severe renal impairment without dose adjustment (CrCl <30 mL/min)", "Caution in patients with psychotic disorders", "Caution with other sedating medications or alcohol" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "parkinsons", "dopamine-agonist", "restless-legs", "neurologic" ], "sources": [ { "text": "Shannon KM et al. Efficacy of pramipexole, a novel dopamine agonist, as monotherapy in mild to moderate Parkinson's disease. Neurology. 1997;49(3):724-728.", "pmid": "9305330", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9305330/", "publicSourceType": "PMID" }, { "text": "Holloway RG et al. Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial. Arch Neurol. 2004;61(7):1044-1053.", "pmid": "15262734", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15262734/", "publicSourceType": "PMID" }, { "text": "Winkelman JW et al. Treatment of restless legs syndrome: an evidence-based review and implications for clinical practice. Mov Disord. 2018;33(7):1077-1091.", "pmid": "29756335", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29756335/", "publicSourceType": "PMID" }, { "text": "Browning M, Cowen PJ, Galal U et al.. Pramipexole augmentation for the acute phase of treatment-resistant, unipolar depression: a placebo-controlled, double-blind, randomised trial in the UK. The lancet. Psychiatry. 2025", "pmid": "40602411", "doi": "10.1016/S2215-0366(25)00194-4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40602411/", "publicSourceType": "PMID" }, { "text": "Singh R, Parmar M. Pramipexole. 2026", "pmid": "32491471", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32491471/", "publicSourceType": "PMID" }, { "text": "Seppänen P, Forsberg MM, Tiihonen M et al.. A Systematic Review and Meta-Analysis of the Efficacy and Safety of Rasagiline or Pramipexole in the Treatment of Early Parkinson's Disease. Parkinson's disease. 2024", "claim": "PubMed-indexed evidence involving Pramipexole", "title": "A Systematic Review and Meta-Analysis of the Efficacy and Safety of Rasagiline or Pramipexole in the Treatment of Early Parkinson's Disease", "authors": "Seppänen P, Forsberg MM, Tiihonen M et al.", "journal": "Parkinson's disease", "year": 2024, "pmid": "38264500", "url": "https://pubmed.ncbi.nlm.nih.gov/38264500/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1155/2024/8448584", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38264500/", "publicSourceType": "PMID" }, { "text": "Soileau LG, Talbot NC, Storey NR et al.. Impulse control disorders in Parkinson's disease patients treated with pramipexole and ropinirole: a systematic review and meta-analysis. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2024", "claim": "PubMed-indexed evidence involving Pramipexole", "title": "Impulse control disorders in Parkinson's disease patients treated with pramipexole and ropinirole: a systematic review and meta-analysis", "authors": "Soileau LG, Talbot NC, Storey NR et al.", "journal": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology", "year": 2024, "pmid": "38079019", "url": "https://pubmed.ncbi.nlm.nih.gov/38079019/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s10072-023-07254-1", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38079019/", "publicSourceType": "PMID" }, { "text": "Tundo A, Betro' S, de Filippis R et al.. Pramipexole Augmentation for Treatment-Resistant Unipolar and Bipolar Depression in the Real World: A Systematic Review and Meta-Analysis. Life (Basel, Switzerland). 2023", "claim": "PubMed-indexed evidence involving Pramipexole", "title": "Pramipexole Augmentation for Treatment-Resistant Unipolar and Bipolar Depression in the Real World: A Systematic Review and Meta-Analysis", "authors": "Tundo A, Betro' S, de Filippis R et al.", "journal": "Life (Basel, Switzerland)", "year": 2023, "pmid": "37109571", "url": "https://pubmed.ncbi.nlm.nih.gov/37109571/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/life13041043", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37109571/", "publicSourceType": "PMID" }, { "text": "Li T, Zou S, Zhang Z et al.. Efficacy of pramipexole on quality of life in patients with Parkinson's disease: a systematic review and meta-analysis. BMC neurology. 2022", "claim": "PubMed-indexed evidence involving Pramipexole", "title": "Efficacy of pramipexole on quality of life in patients with Parkinson's disease: a systematic review and meta-analysis", "authors": "Li T, Zou S, Zhang Z et al.", "journal": "BMC neurology", "year": 2022, "pmid": "36008796", "url": "https://pubmed.ncbi.nlm.nih.gov/36008796/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12883-022-02830-y", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36008796/", "publicSourceType": "PMID" }, { "text": "Tundo A, de Filippis R, De Crescenzo F. Pramipexole in the treatment of unipolar and bipolar depression. A systematic review and meta-analysis. Acta psychiatrica Scandinavica. 2019", "claim": "PubMed-indexed evidence involving Pramipexole", "title": "Pramipexole in the treatment of unipolar and bipolar depression. A systematic review and meta-analysis", "authors": "Tundo A, de Filippis R, De Crescenzo F", "journal": "Acta psychiatrica Scandinavica", "year": 2019, "pmid": "31111467", "url": "https://pubmed.ncbi.nlm.nih.gov/31111467/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/acps.13055", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31111467/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Non-ergot dopamine agonist (D2/D3 receptor agonist)", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "8-12 hours (longer in elderly)", "onsetOfAction": "1-3 hours", "commonBrandNames": [ "Mirapex", "Mirapex ER" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "pramipexole" }, { "id": "RX-SPEC-007", "name": "Ropinirole", "alternateNames": [ "Requip" ], "category": "Prescription", "subcategory": "Dopaminergic / Antiparkinson", "overview": "Ropinirole is a non-ergot dopamine agonist selective for D2/D3 receptors, approved for Parkinson's disease and moderate-to-severe restless legs syndrome. Similar to pramipexole, it provides an alternative to levodopa in early PD and supplements levodopa therapy in advanced disease to smooth motor fluctuations.", "mechanismOfAction": "Acts as a full agonist at D2 and D3 dopamine receptors in the caudate-putamen of the striatum, mimicking the effects of endogenous dopamine. Provides continuous dopaminergic stimulation in contrast to the pulsatile stimulation of levodopa. Has negligible affinity for D1, 5-HT, or adrenergic receptors, contributing to its selectivity.", "commonBenefits": [ "Effective monotherapy in early Parkinson's disease", "Reduces levodopa dose requirements in advanced PD", "FDA-approved for restless legs syndrome", "Non-ergot structure eliminates fibrotic complication risk" ], "commonDosageRange": "0.25 mg three times daily initially, titrated to 3-8 mg three times daily for PD; 0.25-4 mg once daily 1-3 hours before bedtime for RLS (as prescribed by your physician)", "recommendedForm": "Immediate-release tablets; extended-release tablets (Requip XL) for once-daily dosing", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Bioavailability ~50% due to first-pass metabolism; taking with food reduces nausea. Extensively metabolized by CYP1A2, smoking and ciprofloxacin significantly affect levels." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Nausea and vomiting", "Somnolence and sudden sleep attacks", "Dizziness", "Orthostatic hypotension", "Impulse control disorders (gambling, hypersexuality, compulsive eating)", "Hallucinations", "Leg edema", "Augmentation in RLS with long-term use" ], "contraindications": [ "Known hypersensitivity to ropinirole", "Caution in patients with severe hepatic impairment", "Caution in patients with psychotic disorders", "Caution with concurrent strong CYP1A2 inhibitors (e.g., ciprofloxacin, fluvoxamine)" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "parkinsons", "dopamine-agonist", "restless-legs", "neurologic" ], "sources": [ { "text": "Rascol O et al. A five-year study of the incidence of dyskinesia in patients with early Parkinson's disease who were treated with ropinirole or levodopa. N Engl J Med. 2000;342(20):1484-1491.", "pmid": "10816186", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10816186/", "publicSourceType": "PMID" }, { "text": "Trenkwalder C et al. Ropinirole in the treatment of restless legs syndrome: results from the TREAT RLS 1 study. Mov Disord. 2004;19(12):1414-1423.", "pmid": "15390050", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15390050/", "publicSourceType": "PMID" }, { "text": "Pahwa R et al. Ropinirole 24-hour prolonged release: randomized, controlled study in advanced Parkinson disease. Neurology. 2007;68(14):1108-1115.", "pmid": "17404192", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17404192/", "publicSourceType": "PMID" }, { "text": "Rewane A, Patel P, Nagalli S. Ropinirole. 2026", "pmid": "32119419", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32119419/", "publicSourceType": "PMID" }, { "text": "Morimoto S, Takahashi S, Ito D et al.. Phase 1/2a clinical trial in ALS with ropinirole, a drug candidate identified by iPSC drug discovery. Cell stem cell. 2023", "pmid": "37267913", "doi": "10.1016/j.stem.2023.04.017", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37267913/", "publicSourceType": "PMID" }, { "text": "Zhu J, Chen M. The effect and safety of ropinirole in the treatment of Parkinson disease: A systematic review and meta-analysis. Medicine. 2021", "claim": "PubMed-indexed evidence involving Ropinirole", "title": "The effect and safety of ropinirole in the treatment of Parkinson disease: A systematic review and meta-analysis", "authors": "Zhu J, Chen M", "journal": "Medicine", "year": 2021, "pmid": "34797288", "url": "https://pubmed.ncbi.nlm.nih.gov/34797288/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MD.0000000000027653", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34797288/", "publicSourceType": "PMID" }, { "text": "Soileau LG, Talbot NC, Storey NR et al.. Impulse control disorders in Parkinson's disease patients treated with pramipexole and ropinirole: a systematic review and meta-analysis. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2024", "claim": "PubMed-indexed evidence involving Ropinirole", "title": "Impulse control disorders in Parkinson's disease patients treated with pramipexole and ropinirole: a systematic review and meta-analysis", "authors": "Soileau LG, Talbot NC, Storey NR et al.", "journal": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology", "year": 2024, "pmid": "38079019", "url": "https://pubmed.ncbi.nlm.nih.gov/38079019/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s10072-023-07254-1", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38079019/", "publicSourceType": "PMID" }, { "text": "Etminan M, Gill S, Samii A. Comparison of the risk of adverse events with pramipexole and ropinirole in patients with Parkinson's disease: a meta-analysis. Drug safety. 2003", "claim": "PubMed-indexed evidence involving Ropinirole", "title": "Comparison of the risk of adverse events with pramipexole and ropinirole in patients with Parkinson's disease: a meta-analysis", "authors": "Etminan M, Gill S, Samii A", "journal": "Drug safety", "year": 2003, "pmid": "12688834", "url": "https://pubmed.ncbi.nlm.nih.gov/12688834/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2165/00002018-200326060-00005", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12688834/", "publicSourceType": "PMID" }, { "text": "Kurin M, Bielefeldt K, Levinthal DJ. Prevalence of Nausea and Vomiting in Adults Using Ropinirole: A Systematic Review and Meta-Analysis. Digestive diseases and sciences. 2018", "claim": "PubMed-indexed evidence involving Ropinirole", "title": "Prevalence of Nausea and Vomiting in Adults Using Ropinirole: A Systematic Review and Meta-Analysis", "authors": "Kurin M, Bielefeldt K, Levinthal DJ", "journal": "Digestive diseases and sciences", "year": 2018, "pmid": "29383607", "url": "https://pubmed.ncbi.nlm.nih.gov/29383607/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s10620-018-4937-3", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29383607/", "publicSourceType": "PMID" }, { "text": "Quilici S, Abrams KR, Nicolas A et al.. Meta-analysis of the efficacy and tolerability of pramipexole versus ropinirole in the treatment of restless legs syndrome. Sleep medicine. 2008", "claim": "PubMed-indexed evidence involving Ropinirole", "title": "Meta-analysis of the efficacy and tolerability of pramipexole versus ropinirole in the treatment of restless legs syndrome", "authors": "Quilici S, Abrams KR, Nicolas A et al.", "journal": "Sleep medicine", "year": 2008, "pmid": "18226947", "url": "https://pubmed.ncbi.nlm.nih.gov/18226947/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.sleep.2007.11.020", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18226947/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Non-ergot dopamine agonist (D2/D3 receptor agonist)", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "6 hours", "onsetOfAction": "1-2 hours", "commonBrandNames": [ "Requip", "Requip XL" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "ropinirole" }, { "id": "RX-SPEC-008", "name": "Sumatriptan", "alternateNames": [ "Imitrex" ], "category": "Prescription", "subcategory": "Triptan / Antimigraine", "overview": "Sumatriptan is the prototypical triptan and the first serotonin 5-HT1B/1D receptor agonist developed specifically for the acute treatment of migraine attacks with or without aura. It is also effective for cluster headache. Available in oral, nasal spray, and subcutaneous injection formulations for flexibility based on attack severity and associated nausea.", "mechanismOfAction": "Selectively activates serotonin 5-HT1B receptors on intracranial blood vessels, causing vasoconstriction of dilated meningeal and cerebral arteries. Also activates 5-HT1D receptors on trigeminal nerve terminals, inhibiting release of pro-inflammatory neuropeptides (CGRP, substance P) and blocking pain signal transmission through the trigeminovascular system.", "commonBenefits": [ "Rapid relief of migraine headache, nausea, and photophobia", "Subcutaneous injection provides relief within 10-15 minutes", "Effective for cluster headache", "Multiple delivery routes available" ], "commonDosageRange": "50-100 mg oral; 6 mg subcutaneous; 5-20 mg intranasal; may repeat after 2 hours if needed, max 200 mg oral/day or 12 mg SC/day (as prescribed by your physician)", "recommendedForm": "Oral tablets for mild-moderate attacks; subcutaneous injection (6 mg) for severe attacks or when nausea prevents oral dosing", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Oral bioavailability ~15% due to first-pass metabolism and incomplete absorption; subcutaneous bioavailability 97%. Migraine-related gastroparesis may further delay oral absorption." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Tingling, warmth, and flushing (triptan sensations)", "Chest tightness or pressure (usually non-cardiac)", "Dizziness", "Injection site reactions (SC formulation)", "Fatigue and drowsiness", "Medication overuse headache (with frequent use >10 days/month)", "Serotonin syndrome (rare; risk increased with concurrent SSRIs, SNRIs, or TCAs)" ], "contraindications": [ "Ischemic heart disease, coronary artery vasospasm (Prinzmetal's angina), or uncontrolled hypertension", "History of stroke or TIA", "Peripheral vascular disease", "Concurrent use with MAO-A inhibitors (within 2 weeks) or ergot-containing medications (within 24 hours)", "Hemiplegic or basilar migraine", "Severe hepatic impairment" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "migraine", "headache", "triptan", "cluster-headache", "neurologic" ], "sources": [ { "text": "Ferrari MD et al. Oral triptans (serotonin 5-HT1B/1D agonists) in acute migraine treatment: a meta-analysis of 53 trials. Lancet. 2001;358(9294):1668-1675.", "pmid": "11728541", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11728541/", "publicSourceType": "PMID" }, { "text": "Tfelt-Hansen P et al. Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy. Drugs. 2000;60(6):1259-1287.", "pmid": "11152011", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11152011/", "publicSourceType": "PMID" }, { "text": "Derry CJ et al. Sumatriptan (oral route of administration) for acute migraine attacks in adults. Cochrane Database Syst Rev. 2012;(2):CD008615.", "pmid": "22336849", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22336849/", "publicSourceType": "PMID" }, { "text": "Wilcha RJ, Afridi SK, Barbanti P et al.. Sumatriptan-naproxen sodium in migraine: A review. European journal of neurology. 2024", "pmid": "39318200", "doi": "10.1111/ene.16434", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39318200/", "publicSourceType": "PMID" }, { "text": "Maghbooli M, Golipour F, Moghimi Esfandabadi A et al.. Comparison between the efficacy of ginger and sumatriptan in the ablative treatment of the common migraine. Phytotherapy research : PTR. 2014", "pmid": "23657930", "doi": "10.1002/ptr.4996", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23657930/", "publicSourceType": "PMID" }, { "text": "Ala M, Ghasemi M, Mohammad Jafari R et al.. Beyond its anti-migraine properties, sumatriptan is an anti-inflammatory agent: A systematic review. Drug development research. 2021", "claim": "PubMed-indexed evidence involving Sumatriptan", "title": "Beyond its anti-migraine properties, sumatriptan is an anti-inflammatory agent: A systematic review", "authors": "Ala M, Ghasemi M, Mohammad Jafari R et al.", "journal": "Drug development research", "year": 2021, "pmid": "33792938", "url": "https://pubmed.ncbi.nlm.nih.gov/33792938/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/ddr.21819", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33792938/", "publicSourceType": "PMID" }, { "text": "Menshawy A, Ahmed H, Ismail A et al.. Intranasal sumatriptan for acute migraine attacks: a systematic review and meta-analysis. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2018", "claim": "PubMed-indexed evidence involving Sumatriptan", "title": "Intranasal sumatriptan for acute migraine attacks: a systematic review and meta-analysis", "authors": "Menshawy A, Ahmed H, Ismail A et al.", "journal": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology", "year": 2018, "pmid": "28942578", "url": "https://pubmed.ncbi.nlm.nih.gov/28942578/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s10072-017-3119-y", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28942578/", "publicSourceType": "PMID" }, { "text": "Loder E. Safety of sumatriptan in pregnancy: a review of the data so far. CNS drugs. 2003", "claim": "PubMed-indexed evidence involving Sumatriptan", "title": "Safety of sumatriptan in pregnancy: a review of the data so far", "authors": "Loder E", "journal": "CNS drugs", "year": 2003, "pmid": "12467489", "url": "https://pubmed.ncbi.nlm.nih.gov/12467489/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.2165/00023210-200317010-00001", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12467489/", "publicSourceType": "PMID" }, { "text": "Lloyd K. The clinical profile of sumatriptan: safety and tolerability. European neurology. 1994", "claim": "PubMed-indexed evidence involving Sumatriptan", "title": "The clinical profile of sumatriptan: safety and tolerability", "authors": "Lloyd K", "journal": "European neurology", "year": 1994, "pmid": "7835382", "url": "https://pubmed.ncbi.nlm.nih.gov/7835382/", "study_type": "review", "confidence": "verify", "doi": "10.1159/000119531", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7835382/", "publicSourceType": "PMID" }, { "text": "Syed YY. Sumatriptan/Naproxen Sodium: A Review in Migraine. Drugs. 2016", "claim": "PubMed-indexed evidence involving Sumatriptan", "title": "Sumatriptan/Naproxen Sodium: A Review in Migraine", "authors": "Syed YY", "journal": "Drugs", "year": 2016, "pmid": "26628293", "url": "https://pubmed.ncbi.nlm.nih.gov/26628293/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s40265-015-0521-8", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26628293/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Triptan (Serotonin 5-HT1B/1D agonist)", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "2-2.5 hours", "onsetOfAction": "30-60 minutes (oral); 10-15 minutes (subcutaneous); 15-20 minutes (nasal)", "commonBrandNames": [ "Imitrex", "Tosymra", "Onzetra Xsail", "Zembrace SymTouch" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "sumatriptan" }, { "id": "RX-SPEC-009", "name": "Rizatriptan", "alternateNames": [ "Maxalt" ], "category": "Prescription", "subcategory": "Triptan / Antimigraine", "overview": "Rizatriptan is a second-generation triptan for the acute treatment of migraine with or without aura. It has faster onset and higher consistency of response compared to sumatriptan in some studies. The orally disintegrating tablet (MLT) formulation is convenient for patients with migraine-associated nausea who have difficulty swallowing.", "mechanismOfAction": "Selectively binds to serotonin 5-HT1B and 5-HT1D receptors. At 5-HT1B receptors on cranial blood vessels, it causes selective vasoconstriction. At 5-HT1D receptors on trigeminal sensory nerve endings, it inhibits release of vasoactive neuropeptides (CGRP, substance P) and reduces transmission of pain signals through the trigeminal nucleus caudalis.", "commonBenefits": [ "Rapid onset of action (as early as 30 minutes)", "Orally disintegrating tablet for ease of use during migraine", "High rate of 2-hour headache relief", "Effective for migraine-associated nausea and photophobia" ], "commonDosageRange": "5-10 mg at migraine onset; may repeat after 2 hours if needed, max 30 mg/day. Use 5 mg dose if taking propranolol (as prescribed by your physician)", "recommendedForm": "Orally disintegrating tablet (Maxalt-MLT) preferred for convenience; conventional tablets also available", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Rapidly absorbed with ~45% oral bioavailability; food delays Tmax by ~1 hour but does not significantly affect AUC. MLT formulation dissolves on the tongue without water." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Dizziness", "Somnolence and fatigue", "Chest tightness or pressure", "Nausea", "Dry mouth", "Paresthesia", "Serotonin syndrome (rare; risk increased with concurrent SSRIs, SNRIs, or TCAs)" ], "contraindications": [ "Ischemic coronary artery disease or coronary vasospasm", "Uncontrolled hypertension", "Use within 24 hours of another triptan or ergotamine", "Concurrent use with MAO-A inhibitors (within 2 weeks)", "Hemiplegic or basilar migraine", "History of stroke or TIA" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "migraine", "headache", "triptan", "neurologic" ], "sources": [ { "text": "Visser WH et al. Rizatriptan vs sumatriptan in the acute treatment of migraine: a placebo-controlled, dose-ranging study. Arch Neurol. 1996;53(11):1132-1137.", "pmid": "8912486", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8912486/", "publicSourceType": "PMID" }, { "text": "Oldman AD et al. Rizatriptan for acute migraine. Cochrane Database Syst Rev. 2007;(1):CD003221.", "pmid": "17636718", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17636718/", "publicSourceType": "PMID" }, { "text": "Ferrari MD et al. Oral triptans (serotonin 5-HT1B/1D agonists) in acute migraine treatment: a meta-analysis of 53 trials. Lancet. 2001;358(9294):1668-1675.", "pmid": "11728541", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11728541/", "publicSourceType": "PMID" }, { "text": "Staab JP, Eggers SDZ, Jen JC et al.. Rizatriptan vs Placebo for Attacks of Vestibular Migraine: A Randomized Clinical Trial. JAMA neurology. 2025", "pmid": "40354049", "doi": "10.1001/jamaneurol.2025.1006", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40354049/", "publicSourceType": "PMID" }, { "text": "Dooley M, Faulds D. Rizatriptan: a review of its efficacy in the management of migraine. Drugs. 1999", "pmid": "10551439", "doi": "10.2165/00003495-199958040-00013", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10551439/", "publicSourceType": "PMID" }, { "text": "Ferrari MD, Loder E, McCarroll KA et al.. Meta-analysis of rizatriptan efficacy in randomized controlled clinical trials. Cephalalgia : an international journal of headache. 2001", "claim": "PubMed-indexed evidence involving Rizatriptan", "title": "Meta-analysis of rizatriptan efficacy in randomized controlled clinical trials", "authors": "Ferrari MD, Loder E, McCarroll KA et al.", "journal": "Cephalalgia : an international journal of headache", "year": 2001, "pmid": "11422095", "url": "https://pubmed.ncbi.nlm.nih.gov/11422095/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1046/j.1468-2982.2001.00169.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11422095/", "publicSourceType": "PMID" }, { "text": "Ahonen K, Hämäläinen ML, Eerola M et al.. A randomized trial of rizatriptan in migraine attacks in children. Neurology. 2006", "claim": "PubMed-indexed evidence involving Rizatriptan", "title": "A randomized trial of rizatriptan in migraine attacks in children", "authors": "Ahonen K, Hämäläinen ML, Eerola M et al.", "journal": "Neurology", "year": 2006, "pmid": "16943370", "url": "https://pubmed.ncbi.nlm.nih.gov/16943370/", "study_type": "RCT", "confidence": "verify", "doi": "10.1212/01.wnl.0000238179.79888.44", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16943370/", "publicSourceType": "PMID" }, { "text": "Teall J, Tuchman M, Cutler N et al.. Rizatriptan (MAXALT) for the acute treatment of migraine and migraine recurrence. A placebo-controlled, outpatient study. Rizatriptan 022 Study Group. Headache. 1998", "claim": "PubMed-indexed evidence involving Rizatriptan", "title": "Rizatriptan (MAXALT) for the acute treatment of migraine and migraine recurrence. A placebo-controlled, outpatient study. Rizatriptan 022 Study Group", "authors": "Teall J, Tuchman M, Cutler N et al.", "journal": "Headache", "year": 1998, "pmid": "9595867", "url": "https://pubmed.ncbi.nlm.nih.gov/9595867/", "study_type": "RCT", "confidence": "verify", "doi": "10.1046/j.1526-4610.1998.3804281.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9595867/", "publicSourceType": "PMID" }, { "text": "Sakai F. Safety and tolerability of rizatriptan. Cephalalgia : an international journal of headache. 2000", "claim": "PubMed-indexed evidence involving Rizatriptan", "title": "Safety and tolerability of rizatriptan", "authors": "Sakai F", "journal": "Cephalalgia : an international journal of headache", "year": 2000, "pmid": "11078005", "url": "https://pubmed.ncbi.nlm.nih.gov/11078005/", "study_type": "review", "confidence": "verify", "doi": "10.1046/j.1468-2982.2000.020s1016.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11078005/", "publicSourceType": "PMID" }, { "text": "Goldberg MR, Lowry RC, Musson DG et al.. Lack of pharmacokinetic and pharmacodynamic interaction between rizatriptan and paroxetine. Journal of clinical pharmacology. 1999", "claim": "PubMed-indexed evidence involving Rizatriptan", "title": "Lack of pharmacokinetic and pharmacodynamic interaction between rizatriptan and paroxetine", "authors": "Goldberg MR, Lowry RC, Musson DG et al.", "journal": "Journal of clinical pharmacology", "year": 1999, "pmid": "11563413", "url": "https://pubmed.ncbi.nlm.nih.gov/11563413/", "study_type": "RCT", "confidence": "verify", "doi": "10.1177/00912709922007633", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11563413/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Triptan (Serotonin 5-HT1B/1D agonist)", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "2-3 hours", "onsetOfAction": "30-60 minutes", "commonBrandNames": [ "Maxalt", "Maxalt-MLT" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "rizatriptan" }, { "id": "RX-SPEC-010", "name": "Donepezil", "alternateNames": [ "Aricept" ], "category": "Prescription", "subcategory": "Cholinesterase Inhibitor / Alzheimer's", "overview": "Donepezil is a centrally-acting reversible acetylcholinesterase inhibitor indicated for the treatment of mild, moderate, and severe Alzheimer's disease. It is the most widely prescribed medication for Alzheimer's dementia and provides modest improvements in cognition, behavior, and daily function, though it does not alter disease progression.", "mechanismOfAction": "Reversibly inhibits acetylcholinesterase (AChE), the enzyme responsible for breaking down acetylcholine in the synaptic cleft. By preventing acetylcholine degradation, it increases cholinergic neurotransmission in the cerebral cortex and hippocampus, partially compensating for the loss of cholinergic neurons characteristic of Alzheimer's disease. Highly selective for AChE over butyrylcholinesterase.", "commonBenefits": [ "Modest improvement in cognitive function (ADAS-cog scores)", "May stabilize or slow decline in activities of daily living", "Once-daily dosing with simple titration", "Approved for all stages of Alzheimer's disease" ], "commonDosageRange": "5 mg once daily at bedtime for 4-6 weeks, then may increase to 10 mg once daily; 23 mg once daily for moderate-to-severe AD (as prescribed by your physician)", "recommendedForm": "Oral tablet or orally disintegrating tablet; 23 mg sustained-release tablet for advanced disease", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Well absorbed (~100% bioavailability); food does not affect absorption. Usually taken at bedtime to minimize GI side effects. Long half-life supports once-daily dosing." }, "evidenceRating": "moderate", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Nausea and vomiting", "Diarrhea", "Insomnia and vivid dreams", "Muscle cramps", "Fatigue", "Bradycardia", "Decreased appetite and weight loss" ], "contraindications": [ "Known hypersensitivity to donepezil or piperidine derivatives", "Sick sinus syndrome or cardiac conduction disorders without a pacemaker", "Active GI bleeding or peptic ulcer disease", "Severe COPD or asthma (cholinergic bronchoconstriction risk)" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "alzheimers", "dementia", "cholinesterase-inhibitor", "cognition", "neurologic" ], "sources": [ { "text": "Birks JS, Harvey RJ. Donepezil for dementia due to Alzheimer's disease. Cochrane Database Syst Rev. 2018;6(6):CD001190.", "pmid": "29923184", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29923184/", "publicSourceType": "PMID" }, { "text": "Rogers SL et al. A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Neurology. 1998;50(1):136-145.", "pmid": "9443470", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9443470/", "publicSourceType": "PMID" }, { "text": "Howard R et al. Donepezil and memantine for moderate-to-severe Alzheimer's disease. N Engl J Med. 2012;366(10):893-903.", "pmid": "22397651", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22397651/", "publicSourceType": "PMID" }, { "text": "Nham T, Garcia MC, Tsang KJ et al.. Proarrhythmic major adverse cardiac events with donepezil: A systematic review with meta-analysis. Journal of the American Geriatrics Society. 2024", "claim": "PubMed-indexed evidence involving Donepezil", "title": "Proarrhythmic major adverse cardiac events with donepezil: A systematic review with meta-analysis", "authors": "Nham T, Garcia MC, Tsang KJ et al.", "journal": "Journal of the American Geriatrics Society", "year": 2024, "pmid": "38580328", "url": "https://pubmed.ncbi.nlm.nih.gov/38580328/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/jgs.18909", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38580328/", "publicSourceType": "PMID" }, { "text": "Zhang X, Lian S, Zhang Y et al.. Efficacy and safety of donepezil for mild cognitive impairment: A systematic review and meta-analysis. Clinical neurology and neurosurgery. 2022", "claim": "PubMed-indexed evidence involving Donepezil", "title": "Efficacy and safety of donepezil for mild cognitive impairment: A systematic review and meta-analysis", "authors": "Zhang X, Lian S, Zhang Y et al.", "journal": "Clinical neurology and neurosurgery", "year": 2022, "pmid": "35078087", "url": "https://pubmed.ncbi.nlm.nih.gov/35078087/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.clineuro.2022.107134", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35078087/", "publicSourceType": "PMID" }, { "text": "Hansen RA, Gartlehner G, Webb AP et al.. Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer's disease: a systematic review and meta-analysis. Clinical interventions in aging. 2008", "claim": "PubMed-indexed evidence involving Donepezil", "title": "Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer's disease: a systematic review and meta-analysis", "authors": "Hansen RA, Gartlehner G, Webb AP et al.", "journal": "Clinical interventions in aging", "year": 2008, "pmid": "18686744", "url": "https://pubmed.ncbi.nlm.nih.gov/18686744/", "study_type": "meta-analysis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18686744/", "publicSourceType": "PMID" }, { "text": "Wu Y, Zhan Y, Zhu W et al.. Effectiveness of acupuncture combined with donepezil for Alzheimer's disease: A systematic review and meta-analysis. Medicine. 2025", "claim": "PubMed-indexed evidence involving Donepezil", "title": "Effectiveness of acupuncture combined with donepezil for Alzheimer's disease: A systematic review and meta-analysis", "authors": "Wu Y, Zhan Y, Zhu W et al.", "journal": "Medicine", "year": 2025, "pmid": "40489837", "url": "https://pubmed.ncbi.nlm.nih.gov/40489837/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MD.0000000000042651", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40489837/", "publicSourceType": "PMID" }, { "text": "Fornalik M, Moska S, Gimła M et al.. Donepezil for cancer-related cognitive impairment: systematic review and meta-analysis. Clinical and experimental medicine. 2025", "claim": "PubMed-indexed evidence involving Donepezil", "title": "Donepezil for cancer-related cognitive impairment: systematic review and meta-analysis", "authors": "Fornalik M, Moska S, Gimła M et al.", "journal": "Clinical and experimental medicine", "year": 2025, "pmid": "40495003", "url": "https://pubmed.ncbi.nlm.nih.gov/40495003/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s10238-025-01708-w", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40495003/", "publicSourceType": "PMID" }, { "text": "Liu L, Zhang CS, Zhang AL et al.. Oral Chinese herbal medicine combined with donepezil for mild cognitive impairment: A systematic review and meta-analysis. Journal of the American Geriatrics Society. 2024", "claim": "PubMed-indexed evidence involving Donepezil", "title": "Oral Chinese herbal medicine combined with donepezil for mild cognitive impairment: A systematic review and meta-analysis", "authors": "Liu L, Zhang CS, Zhang AL et al.", "journal": "Journal of the American Geriatrics Society", "year": 2024, "pmid": "39134455", "url": "https://pubmed.ncbi.nlm.nih.gov/39134455/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/jgs.19125", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39134455/", "publicSourceType": "PMID" }, { "text": "Yang Q, Liu J, Huang KL et al.. A systematic review of the efficacy of donepezil hydrochloride combined with nimodipine on treating vascular dementia. Medicine. 2022", "claim": "PubMed-indexed evidence involving Donepezil", "title": "A systematic review of the efficacy of donepezil hydrochloride combined with nimodipine on treating vascular dementia", "authors": "Yang Q, Liu J, Huang KL et al.", "journal": "Medicine", "year": 2022, "pmid": "35945739", "url": "https://pubmed.ncbi.nlm.nih.gov/35945739/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MD.0000000000029307", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35945739/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Cholinesterase inhibitor (AChE inhibitor)", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "70 hours", "onsetOfAction": "3-4 weeks for clinical benefit", "commonBrandNames": [ "Aricept", "Aricept ODT" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": "No routine monitoring required; consider ECG if cardiac history or concurrent medications affecting heart rate" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "donepezil" }, { "id": "RX-SPEC-011", "name": "Memantine", "alternateNames": [ "Namenda" ], "category": "Prescription", "subcategory": "NMDA Antagonist / Alzheimer's", "overview": "Memantine is a moderate-affinity, uncompetitive NMDA receptor antagonist indicated for moderate-to-severe Alzheimer's disease. It is the only approved Alzheimer's drug with a non-cholinergic mechanism and is often used in combination with donepezil. It provides modest improvements in cognition, daily function, and behavioral symptoms.", "mechanismOfAction": "Blocks pathologically activated NMDA receptors by binding to the ion channel in a voltage-dependent manner, reducing excessive glutamatergic excitotoxicity that contributes to neuronal damage in Alzheimer's disease. At therapeutic concentrations, it preferentially blocks tonically active (extrasynaptic) NMDA receptors while preserving physiologic phasic synaptic transmission necessary for learning and memory.", "commonBenefits": [ "Slows cognitive and functional decline in moderate-to-severe AD", "Synergistic benefit when combined with cholinesterase inhibitors", "May improve behavioral symptoms (agitation, aggression)", "Generally well tolerated with fewer GI side effects than AChE inhibitors" ], "commonDosageRange": "5 mg once daily initially, increased by 5 mg/week to target of 10 mg twice daily (immediate-release) or 28 mg once daily (extended-release) (as prescribed by your physician)", "recommendedForm": "Extended-release capsule (Namenda XR 28 mg) for once-daily dosing; immediate-release tablets or oral solution also available", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Well absorbed with ~100% bioavailability; food does not affect absorption. Dose adjustment needed for severe renal impairment (CrCl 5-29 mL/min: max 5 mg BID)." }, "evidenceRating": "moderate", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Dizziness", "Headache", "Constipation", "Confusion", "Hypertension", "Somnolence" ], "contraindications": [ "Known hypersensitivity to memantine", "Severe renal impairment without dose adjustment", "Conditions that raise urine pH significantly (renal tubular acidosis, severe UTIs with urease-producing bacteria) as this impairs excretion", "Concurrent use of other NMDA antagonists (amantadine, ketamine, dextromethorphan)" ], "iconName": "cross.case.fill", "colorHex": "FF6B6B", "tags": [ "alzheimers", "dementia", "nmda-antagonist", "cognition", "neurologic" ], "sources": [ { "text": "Reisberg B et al. Memantine in moderate-to-severe Alzheimer's disease. N Engl J Med. 2003;348(14):1333-1341.", "pmid": "12672860", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12672860/", "publicSourceType": "PMID" }, { "text": "Tariot PN et al. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA. 2004;291(3):317-324.", "pmid": "14734594", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14734594/", "publicSourceType": "PMID" }, { "text": "McShane R et al. Memantine for dementia. Cochrane Database Syst Rev. 2019;3(3):CD003154.", "pmid": "30891742", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30891742/", "publicSourceType": "PMID" }, { "text": "Brown PD, Pugh S, Laack NN et al.. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro-oncology. 2013", "pmid": "23956241", "doi": "10.1093/neuonc/not114", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23956241/", "publicSourceType": "PMID" }, { "text": "Jarvis B, Figgitt DP. Memantine. Drugs & aging. 2003", "pmid": "12710865", "doi": "10.2165/00002512-200320060-00005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12710865/", "publicSourceType": "PMID" }, { "text": "Turalde CWR, Espiritu AI, Anlacan VMM. Memantine for Multiple Sclerosis: A Systematic Review and Meta-Analysis of Randomized Trials. Frontiers in neurology. 2020", "claim": "PubMed-indexed evidence involving Memantine", "title": "Memantine for Multiple Sclerosis: A Systematic Review and Meta-Analysis of Randomized Trials", "authors": "Turalde CWR, Espiritu AI, Anlacan VMM", "journal": "Frontiers in neurology", "year": 2020, "pmid": "33658967", "url": "https://pubmed.ncbi.nlm.nih.gov/33658967/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fneur.2020.574748", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33658967/", "publicSourceType": "PMID" }, { "text": "Choi WS, Wang SM, Woo YS et al.. Therapeutic Efficacy and Safety of Memantine for Children and Adults With ADHD With a Focus on Glutamate-Dopamine Regulation: A Systematic Review. The Journal of clinical psychiatry. 2024", "claim": "PubMed-indexed evidence involving Memantine", "title": "Therapeutic Efficacy and Safety of Memantine for Children and Adults With ADHD With a Focus on Glutamate-Dopamine Regulation: A Systematic Review", "authors": "Choi WS, Wang SM, Woo YS et al.", "journal": "The Journal of clinical psychiatry", "year": 2024, "pmid": "39724018", "url": "https://pubmed.ncbi.nlm.nih.gov/39724018/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.4088/JCP.24r15507", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39724018/", "publicSourceType": "PMID" }, { "text": "Zheng W, Li XH, Yang XH et al.. Adjunctive memantine for schizophrenia: a meta-analysis of randomized, double-blind, placebo-controlled trials. Psychological medicine. 2018", "claim": "PubMed-indexed evidence involving Memantine", "title": "Adjunctive memantine for schizophrenia: a meta-analysis of randomized, double-blind, placebo-controlled trials", "authors": "Zheng W, Li XH, Yang XH et al.", "journal": "Psychological medicine", "year": 2018, "pmid": "28528597", "url": "https://pubmed.ncbi.nlm.nih.gov/28528597/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1017/S0033291717001271", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28528597/", "publicSourceType": "PMID" }, { "text": "Zhang W, Zhang Y, Yu E. Effectiveness and Safety of Memantine Add-on Treatment for Refractory Obsessive-Compulsive Disorder: A Meta-Analysis. Journal of the College of Physicians and Surgeons--Pakistan : JCPSP. 2025", "claim": "PubMed-indexed evidence involving Memantine", "title": "Effectiveness and Safety of Memantine Add-on Treatment for Refractory Obsessive-Compulsive Disorder: A Meta-Analysis", "authors": "Zhang W, Zhang Y, Yu E", "journal": "Journal of the College of Physicians and Surgeons--Pakistan : JCPSP", "year": 2025, "pmid": "40235251", "url": "https://pubmed.ncbi.nlm.nih.gov/40235251/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.29271/jcpsp.2025.04.494", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40235251/", "publicSourceType": "PMID" }, { "text": "Nair A, Dudhedia U, Thakre M et al.. Efficacy of memantine premedication in alleviating postoperative pain- A systematic review and meta-analysis. Saudi journal of anaesthesia. 2024", "claim": "PubMed-indexed evidence involving Memantine", "title": "Efficacy of memantine premedication in alleviating postoperative pain- A systematic review and meta-analysis", "authors": "Nair A, Dudhedia U, Thakre M et al.", "journal": "Saudi journal of anaesthesia", "year": 2024, "pmid": "38313717", "url": "https://pubmed.ncbi.nlm.nih.gov/38313717/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.4103/sja.sja_398_23", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38313717/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "NMDA receptor antagonist", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "60-80 hours", "onsetOfAction": "Weeks; gradual titration over 3-4 weeks to full dose", "commonBrandNames": [ "Namenda", "Namenda XR", "Namzaric (with donepezil)" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "memantine" }, { "id": "RX-SPEC-012", "name": "Tamsulosin", "alternateNames": [ "Flomax" ], "category": "Prescription", "subcategory": "Alpha-1 Blocker / Urologic", "overview": "Tamsulosin is a selective alpha-1A adrenergic receptor antagonist used to treat lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Its selectivity for the alpha-1A subtype, which predominates in the prostate and bladder neck, allows for effective symptom relief with less orthostatic hypotension than non-selective alpha blockers.", "mechanismOfAction": "Selectively blocks alpha-1A adrenergic receptors in the smooth muscle of the prostate, prostatic capsule, prostatic urethra, and bladder neck. This relaxes smooth muscle tone, reducing urethral resistance and improving urine flow without significantly affecting vascular alpha-1B receptors (minimizing blood pressure effects).", "commonBenefits": [ "Rapid improvement in urinary flow rate and LUTS symptoms", "Less orthostatic hypotension than non-selective alpha blockers", "No requirement for dose titration", "Can be used off-label to facilitate ureteral stone passage" ], "commonDosageRange": "0.4 mg once daily, 30 minutes after the same meal each day; may increase to 0.8 mg if inadequate response after 2-4 weeks (as prescribed by your physician)", "recommendedForm": "Modified-release capsule (0.4 mg)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take approximately 30 minutes after the same meal each day for consistent absorption. Fasting significantly increases bioavailability and may increase side effects." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Abnormal ejaculation (retrograde ejaculation)", "Dizziness", "Rhinitis (nasal congestion)", "Headache", "Intraoperative floppy iris syndrome (IFIS) during cataract surgery", "Orthostatic hypotension (less common than with non-selective alpha blockers)" ], "contraindications": [ "Known hypersensitivity to tamsulosin", "Concurrent use with strong CYP3A4 inhibitors (e.g., ketoconazole), avoid with 0.4 mg dose", "Severe hepatic impairment", "History of sulfonamide allergy (use with caution)" ], "iconName": "cross.case.fill", "colorHex": "4D94FF", "tags": [ "bph", "urinary", "prostate", "alpha-blocker", "urologic" ], "sources": [ { "text": "Narayan P, Lepor H. Long-term, open-label, phase III multicenter study of tamsulosin in benign prostatic hyperplasia. Urology. 2001;57(3):466-470.", "pmid": "11248621", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11248621/", "publicSourceType": "PMID" }, { "text": "Nickel JC et al. Comparison of dutasteride and finasteride for treating benign prostatic hyperplasia: the Enlarged Prostate International Comparator Study (EPICS). BJU Int. 2011;108(3):388-394.", "pmid": "21631695", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21631695/", "publicSourceType": "PMID" }, { "text": "Roehrborn CG, Schwinn DA. Alpha1-adrenergic receptors and their inhibitors in lower urinary tract symptoms and benign prostatic hyperplasia. J Urol. 2004;171(3):1029-1035.", "pmid": "14767264", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14767264/", "publicSourceType": "PMID" }, { "text": "Ye Z, Zeng G, Yang H et al.. Efficacy and Safety of Tamsulosin in Medical Expulsive Therapy for Distal Ureteral Stones with Renal Colic: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial. European urology. 2018", "pmid": "29137830", "doi": "10.1016/j.eururo.2017.10.033", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29137830/", "publicSourceType": "PMID" }, { "text": "Zhang Z, Lv L, Jiang F et al.. Real-world safety assessment of tamsulosin based on adverse event analysis from the FAERS database. Scientific reports. 2025", "pmid": "41120617", "doi": "10.1038/s41598-025-20739-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41120617/", "publicSourceType": "PMID" }, { "text": "Kaplan SA, Chughtai BI. Safety of Tamsulosin: A Systematic Review of Randomized Trials with a Focus on Women and Children. Drug safety. 2018", "claim": "PubMed-indexed evidence involving Tamsulosin", "title": "Safety of Tamsulosin: A Systematic Review of Randomized Trials with a Focus on Women and Children", "authors": "Kaplan SA, Chughtai BI", "journal": "Drug safety", "year": 2018, "pmid": "29737501", "url": "https://pubmed.ncbi.nlm.nih.gov/29737501/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s40264-018-0674-y", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29737501/", "publicSourceType": "PMID" }, { "text": "Ramadhan M, Benzouak T, Ali Y et al.. Comparing Tamsulosin vs. Silodosin prior to Ureteroscopy: A Network Meta-Analysis of Randomized Controlled Trials. World journal of urology. 2025", "claim": "PubMed-indexed evidence involving Tamsulosin", "title": "Comparing Tamsulosin vs. Silodosin prior to Ureteroscopy: A Network Meta-Analysis of Randomized Controlled Trials", "authors": "Ramadhan M, Benzouak T, Ali Y et al.", "journal": "World journal of urology", "year": 2025, "pmid": "41196421", "url": "https://pubmed.ncbi.nlm.nih.gov/41196421/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00345-025-06034-0", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41196421/", "publicSourceType": "PMID" }, { "text": "Gao B, Zhang D, Wang Y et al.. The effect of tamsulosin in postoperative urinary retention: a meta-analysis of randomized controlled trials. Naunyn-Schmiedeberg's archives of pharmacology. 2023", "claim": "PubMed-indexed evidence involving Tamsulosin", "title": "The effect of tamsulosin in postoperative urinary retention: a meta-analysis of randomized controlled trials", "authors": "Gao B, Zhang D, Wang Y et al.", "journal": "Naunyn-Schmiedeberg's archives of pharmacology", "year": 2023, "pmid": "36445384", "url": "https://pubmed.ncbi.nlm.nih.gov/36445384/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00210-022-02343-y", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36445384/", "publicSourceType": "PMID" }, { "text": "Cheng C, Ma Y, Wen J et al.. The Effect of Preoperative Tamsulosin on Ureteral Navigation, Operation, and Safety: A Systematic Review and Meta-Analysis. Urologia internationalis. 2023", "claim": "PubMed-indexed evidence involving Tamsulosin", "title": "The Effect of Preoperative Tamsulosin on Ureteral Navigation, Operation, and Safety: A Systematic Review and Meta-Analysis", "authors": "Cheng C, Ma Y, Wen J et al.", "journal": "Urologia internationalis", "year": 2023, "pmid": "36812907", "url": "https://pubmed.ncbi.nlm.nih.gov/36812907/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1159/000528889", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36812907/", "publicSourceType": "PMID" }, { "text": "Zhou R, Che X, Zhou Z et al.. A Systematic Review and Meta-Analysis of the Efficacy and Safety of Tamsulosin Plus Tadalafil Compared With Tamsulosin Alone in Treating Males With Lower Urinary Tract Symptoms Secondary to Benign Prostrate Hyperplasia. American journal of men's health. 2023", "claim": "PubMed-indexed evidence involving Tamsulosin", "title": "A Systematic Review and Meta-Analysis of the Efficacy and Safety of Tamsulosin Plus Tadalafil Compared With Tamsulosin Alone in Treating Males With Lower Urinary Tract Symptoms Secondary to Benign Prostrate Hyperplasia", "authors": "Zhou R, Che X, Zhou Z et al.", "journal": "American journal of men's health", "year": 2023, "pmid": "36842963", "url": "https://pubmed.ncbi.nlm.nih.gov/36842963/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/15579883231155096", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36842963/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Selective alpha-1A adrenergic antagonist", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "9-13 hours", "onsetOfAction": "Within 1 week for symptom improvement; maximal benefit in 4-8 weeks", "commonBrandNames": [ "Flomax" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "tamsulosin" }, { "id": "RX-SPEC-013", "name": "Alfuzosin", "alternateNames": [ "Uroxatral" ], "category": "Prescription", "subcategory": "Alpha-1 Blocker / Urologic", "overview": "Alfuzosin is an alpha-1 adrenergic receptor antagonist with relative selectivity for the lower urinary tract, used for the treatment of signs and symptoms of benign prostatic hyperplasia (BPH). It provides effective relief of LUTS with a low incidence of ejaculatory dysfunction compared to tamsulosin, making it a preferred option for sexually active men.", "mechanismOfAction": "Blocks alpha-1 adrenergic receptors in the smooth muscle of the prostate, prostatic capsule, and bladder trigone/neck. Although not as subtype-selective as tamsulosin, alfuzosin demonstrates relative uroselectivity in clinical practice, reducing urethral resistance and improving urinary flow rate with modest effects on blood pressure.", "commonBenefits": [ "Effective BPH symptom relief (IPSS score improvement)", "Lower incidence of ejaculatory dysfunction compared to tamsulosin", "Once-daily extended-release dosing", "Well-established safety profile" ], "commonDosageRange": "10 mg once daily immediately after the same meal each day (as prescribed by your physician)", "recommendedForm": "Extended-release tablet (10 mg)", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Must be taken immediately after a meal; bioavailability decreases by approximately 50% under fasting conditions. Do not crush, chew, or split extended-release tablets." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Dizziness", "Upper respiratory tract infection", "Headache", "Fatigue", "Orthostatic hypotension", "Intraoperative floppy iris syndrome (IFIS)" ], "contraindications": [ "Known hypersensitivity to alfuzosin", "Moderate to severe hepatic impairment (Child-Pugh B or C)", "Concurrent use with potent CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir)", "Concurrent use with other alpha-1 blockers", "QT prolongation or concurrent use of QT-prolonging medications" ], "iconName": "cross.case.fill", "colorHex": "4D94FF", "tags": [ "bph", "urinary", "prostate", "alpha-blocker", "urologic" ], "sources": [ { "text": "MacDonald R, Wilt TJ. Alfuzosin for treatment of lower urinary tract symptoms compatible with benign prostatic hyperplasia: a systematic review of efficacy and adverse effects. Urology. 2005;66(4):780-788.", "pmid": "16230138", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16230138/", "publicSourceType": "PMID" }, { "text": "van Kerrebroeck P et al. Efficacy and safety of a new prolonged release formulation of alfuzosin 10 mg once daily versus alfuzosin 2.5 mg thrice daily and placebo in patients with symptomatic BPH. Eur Urol. 2000;37(3):306-313.", "pmid": "33508155", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33508155/", "publicSourceType": "PMID" }, { "text": "Roehrborn CG. Alfuzosin 10 mg once daily prevents overall clinical progression of benign prostatic hyperplasia but not acute urinary retention: results of a 2-year placebo-controlled study. BJU Int. 2006;97(4):734-741.", "pmid": "16536764", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16536764/", "publicSourceType": "PMID" }, { "text": "Yeung HEL, Sena SJ, Calopedos RJ et al.. Alfuzosin and Its Effect on Ejaculatory Dysfunction: A Systematic Review. The world journal of men's health. 2021", "pmid": "32009306", "doi": "10.5534/wjmh.180024", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32009306/", "publicSourceType": "PMID" }, { "text": "Kuritzky L, Rosenberg MT, Sadovsky R. Efficacy and safety of alfuzosin 10 mg once daily in the treatment of symptomatic benign prostatic hyperplasia. International journal of clinical practice. 2006", "pmid": "16494652", "doi": "10.1111/j.1368-5031.2005.00830.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16494652/", "publicSourceType": "PMID" }, { "text": "Liu C, Zeng G, Kang R et al.. Efficacy and Safety of Alfuzosin as Medical Expulsive Therapy for Ureteral Stones: A Systematic Review and Meta-Analysis. PloS one. 2015", "claim": "PubMed-indexed evidence involving Alfuzosin", "title": "Efficacy and Safety of Alfuzosin as Medical Expulsive Therapy for Ureteral Stones: A Systematic Review and Meta-Analysis", "authors": "Liu C, Zeng G, Kang R et al.", "journal": "PloS one", "year": 2015, "pmid": "26244843", "url": "https://pubmed.ncbi.nlm.nih.gov/26244843/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1371/journal.pone.0134589", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26244843/", "publicSourceType": "PMID" }, { "text": "Mari A, Antonelli A, Cindolo L et al.. Alfuzosin for the medical treatment of benign prostatic hyperplasia and lower urinary tract symptoms: a systematic review of the literature and narrative synthesis. Therapeutic advances in urology. 2021", "claim": "PubMed-indexed evidence involving Alfuzosin", "title": "Alfuzosin for the medical treatment of benign prostatic hyperplasia and lower urinary tract symptoms: a systematic review of the literature and narrative synthesis", "authors": "Mari A, Antonelli A, Cindolo L et al.", "journal": "Therapeutic advances in urology", "year": 2021, "pmid": "33912246", "url": "https://pubmed.ncbi.nlm.nih.gov/33912246/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/1756287221993283", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33912246/", "publicSourceType": "PMID" }, { "text": "Bevilacqua G, Carino D, Salciccia S et al.. Efficacy of Serenoa repens Extract Combined With Alfuzosin Versus Alfuzosin Alone in Men With Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia: A Multicenter Randomized Study. The Prostate. 2026", "claim": "PubMed-indexed evidence involving Alfuzosin", "title": "Efficacy of Serenoa repens Extract Combined With Alfuzosin Versus Alfuzosin Alone in Men With Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia: A Multicenter Randomized Study", "authors": "Bevilacqua G, Carino D, Salciccia S et al.", "journal": "The Prostate", "year": 2026, "pmid": "41098072", "url": "https://pubmed.ncbi.nlm.nih.gov/41098072/", "study_type": "RCT", "confidence": "verify", "doi": "10.1002/pros.70071", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41098072/", "publicSourceType": "PMID" }, { "text": "Beddingfield R, Pedro RN, Hinck B et al.. Alfuzosin to relieve ureteral stent discomfort: a prospective, randomized, placebo controlled study. The Journal of urology. 2009", "claim": "PubMed-indexed evidence involving Alfuzosin", "title": "Alfuzosin to relieve ureteral stent discomfort: a prospective, randomized, placebo controlled study", "authors": "Beddingfield R, Pedro RN, Hinck B et al.", "journal": "The Journal of urology", "year": 2009, "pmid": "19013590", "url": "https://pubmed.ncbi.nlm.nih.gov/19013590/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.juro.2008.09.026", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19013590/", "publicSourceType": "PMID" }, { "text": "Roehrborn CG. Alfuzosin: overview of pharmacokinetics, safety, and efficacy of a clinically uroselective alpha-blocker. Urology. 2001", "claim": "PubMed-indexed evidence involving Alfuzosin", "title": "Alfuzosin: overview of pharmacokinetics, safety, and efficacy of a clinically uroselective alpha-blocker", "authors": "Roehrborn CG", "journal": "Urology", "year": 2001, "pmid": "11750253", "url": "https://pubmed.ncbi.nlm.nih.gov/11750253/", "study_type": "review", "confidence": "verify", "doi": "10.1016/s0090-4295(01)01322-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11750253/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Alpha-1 adrenergic antagonist", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "10 hours", "onsetOfAction": "Within days; maximal benefit in 2-4 weeks", "commonBrandNames": [ "Uroxatral" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "alfuzosin" }, { "id": "RX-SPEC-014", "name": "Finasteride", "alternateNames": [ "Proscar", "Propecia" ], "category": "Prescription", "subcategory": "5-Alpha Reductase Inhibitor / Urologic", "overview": "Finasteride is a selective inhibitor of type II 5-alpha reductase, the enzyme that converts testosterone to dihydrotestosterone (DHT) in the prostate, liver, and skin. At 5 mg (Proscar), it treats benign prostatic hyperplasia (BPH), reducing prostate size and improving urinary symptoms. At 1 mg (Propecia), it treats androgenetic alopecia (male pattern baldness).", "mechanismOfAction": "Competitively and irreversibly inhibits type II 5-alpha reductase, reducing conversion of testosterone to DHT by approximately 70%. Since DHT is the primary androgen driving prostate growth and hair follicle miniaturization, lowering DHT levels leads to prostate shrinkage (20-30% over 6 months) and promotes hair regrowth in androgenetic alopecia.", "commonBenefits": [ "Reduces prostate volume by 20-30%", "Improves urinary symptoms and flow rate in BPH", "Reduces risk of acute urinary retention and need for surgical intervention", "Promotes hair regrowth and slows hair loss at 1 mg dose" ], "commonDosageRange": "5 mg once daily for BPH; 1 mg once daily for androgenetic alopecia (as prescribed by your physician)", "recommendedForm": "Oral tablet", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Bioavailability ~65%; food does not affect absorption. Effects on prostate volume take 6-12 months to fully manifest; hair regrowth effects may take 3-6 months." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Decreased libido", "Erectile dysfunction", "Decreased ejaculate volume", "Gynecomastia and breast tenderness", "Post-finasteride syndrome (controversial; persistent sexual side effects after discontinuation)", "Depression and mood changes (uncommon)" ], "contraindications": [ "Women who are or may become pregnant (teratogenic, causes hypospadias in male fetuses)", "Handling of crushed or broken tablets by women of childbearing potential", "Known hypersensitivity to finasteride or any component", "Pediatric patients" ], "iconName": "cross.case.fill", "colorHex": "4D94FF", "tags": [ "bph", "prostate", "hair-loss", "5-alpha-reductase", "urologic" ], "sources": [ { "text": "McConnell JD et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med. 2003;349(25):2387-2398.", "pmid": "14681504", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14681504/", "publicSourceType": "PMID" }, { "text": "Kaufman KD et al. Finasteride in the treatment of men with androgenetic alopecia. J Am Acad Dermatol. 1998;39(4 Pt 1):578-589.", "pmid": "9777765", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9777765/", "publicSourceType": "PMID" }, { "text": "Thompson IM et al. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003;349(3):215-224.", "pmid": "12824459", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12824459/", "publicSourceType": "PMID" }, { "text": "Piraccini BM, Blume-Peytavi U, Scarci F et al.. Efficacy and safety of topical finasteride spray solution for male androgenetic alopecia: a phase III, randomized, controlled clinical trial. Journal of the European Academy of Dermatology and Venereology : JEADV. 2022", "pmid": "34634163", "doi": "10.1111/jdv.17738", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34634163/", "publicSourceType": "PMID" }, { "text": "Gupta AK, Venkataraman M, Talukder M et al.. Finasteride for hair loss: a review. The Journal of dermatological treatment. 2022", "pmid": "34291720", "doi": "10.1080/09546634.2021.1959506", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34291720/", "publicSourceType": "PMID" }, { "text": "Roehrborn CG. Meta-analysis of randomized clinical trials of finasteride. Urology. 1998", "claim": "PubMed-indexed evidence involving Finasteride", "title": "Meta-analysis of randomized clinical trials of finasteride", "authors": "Roehrborn CG", "journal": "Urology", "year": 1998, "pmid": "9586596", "url": "https://pubmed.ncbi.nlm.nih.gov/9586596/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/s0090-4295(98)00055-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9586596/", "publicSourceType": "PMID" }, { "text": "Soares Júnior JM, Guimarães DZ, Simões RDS et al.. Systematic review of finasteride effect in women with hirsutism. Revista da Associacao Medica Brasileira (1992). 2021", "claim": "PubMed-indexed evidence involving Finasteride", "title": "Systematic review of finasteride effect in women with hirsutism", "authors": "Soares Júnior JM, Guimarães DZ, Simões RDS et al.", "journal": "Revista da Associacao Medica Brasileira (1992)", "year": 2021, "pmid": "34817521", "url": "https://pubmed.ncbi.nlm.nih.gov/34817521/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1590/1806-9282.20210248", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34817521/", "publicSourceType": "PMID" }, { "text": "Wang L, Lei Y, Gao Y et al.. Association of finasteride with prostate cancer: A systematic review and meta-analysis. Medicine. 2020", "claim": "PubMed-indexed evidence involving Finasteride", "title": "Association of finasteride with prostate cancer: A systematic review and meta-analysis", "authors": "Wang L, Lei Y, Gao Y et al.", "journal": "Medicine", "year": 2020, "pmid": "32282699", "url": "https://pubmed.ncbi.nlm.nih.gov/32282699/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MD.0000000000019486", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32282699/", "publicSourceType": "PMID" }, { "text": "Jiménez Cruz JF, Quecedo Gutiérrez L, Del Llano Señarís J. [Finasteride: 10 years of clinical use. Systematic review of the literature]. Actas urologicas espanolas. 2003", "claim": "PubMed-indexed evidence involving Finasteride", "title": "[Finasteride: 10 years of clinical use. Systematic review of the literature]", "authors": "Jiménez Cruz JF, Quecedo Gutiérrez L, Del Llano Señarís J", "journal": "Actas urologicas espanolas", "year": 2003, "pmid": "12812118", "url": "https://pubmed.ncbi.nlm.nih.gov/12812118/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/s0210-4806(03)72906-4", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12812118/", "publicSourceType": "PMID" }, { "text": "Edwards JE, Moore RA. Finasteride in the treatment of clinical benign prostatic hyperplasia: a systematic review of randomised trials. BMC urology. 2002", "claim": "PubMed-indexed evidence involving Finasteride", "title": "Finasteride in the treatment of clinical benign prostatic hyperplasia: a systematic review of randomised trials", "authors": "Edwards JE, Moore RA", "journal": "BMC urology", "year": 2002, "pmid": "12477383", "url": "https://pubmed.ncbi.nlm.nih.gov/12477383/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/1471-2490-2-14", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12477383/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "5-Alpha reductase inhibitor (Type II selective)", "blackBoxWarnings": [], "fdaPregnancyCategory": "X", "halfLife": "5-6 hours (terminal; however DHT suppression persists much longer due to irreversible enzyme binding)", "onsetOfAction": "3-6 months for BPH symptom improvement; 3-6 months for hair regrowth", "commonBrandNames": [ "Proscar", "Propecia" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Finasteride reduces serum PSA by ~50%. For prostate cancer screening, double PSA values for comparison with normal ranges. Any confirmed PSA rise during treatment warrants evaluation." }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "finasteride" }, { "id": "RX-SPEC-015", "name": "Dutasteride", "alternateNames": [ "Avodart" ], "category": "Prescription", "subcategory": "5-Alpha Reductase Inhibitor / Urologic", "overview": "Dutasteride is a dual inhibitor of both type I and type II 5-alpha reductase, resulting in more complete DHT suppression than finasteride (~95% vs ~70%). It is approved for the treatment of BPH (as monotherapy or in combination with tamsulosin as Jalyn) and is used off-label for androgenetic alopecia. Due to its very long half-life, effects persist long after discontinuation.", "mechanismOfAction": "Irreversibly inhibits both type I and type II isoforms of 5-alpha reductase, the enzymes that convert testosterone to dihydrotestosterone (DHT). This dual inhibition reduces serum DHT by >90% (compared to ~70% with finasteride). The resulting profound DHT suppression leads to greater prostate volume reduction than finasteride.", "commonBenefits": [ "Greater DHT suppression than finasteride", "Significant prostate volume reduction (25-30%)", "Reduces risk of acute urinary retention and BPH surgery", "Combination with tamsulosin (Jalyn) provides dual mechanism benefit" ], "commonDosageRange": "0.5 mg once daily (as prescribed by your physician)", "recommendedForm": "Soft gelatin capsule; swallow whole, do not open or chew (drug is irritating to oropharyngeal mucosa)", "absorption": { "isFatSoluble": true, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Absolute bioavailability ~60%; food does not significantly affect AUC. Capsules should be swallowed whole. Extremely long half-life (5 weeks) means drug effects persist for months after discontinuation." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Erectile dysfunction", "Decreased libido", "Decreased ejaculate volume", "Gynecomastia and breast tenderness", "Dizziness", "Ejaculation disorders" ], "contraindications": [ "Women who are or may become pregnant (teratogenic; absorbed through skin)", "Known hypersensitivity to dutasteride, other 5-alpha reductase inhibitors, or capsule components", "Severe hepatic impairment", "Pediatric patients", "Blood donation restriction: wait at least 6 months after last dose due to long half-life" ], "iconName": "cross.case.fill", "colorHex": "4D94FF", "tags": [ "bph", "prostate", "5-alpha-reductase", "urologic" ], "sources": [ { "text": "Roehrborn CG et al. Efficacy and safety of dutasteride in the four-year treatment of men with benign prostatic hyperplasia. Urology. 2004;63(4):709-715.", "pmid": "15072886", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15072886/", "publicSourceType": "PMID" }, { "text": "Roehrborn CG et al. The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study. Eur Urol. 2010;57(1):123-131.", "pmid": "19825505", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19825505/", "publicSourceType": "PMID" }, { "text": "Clark RV et al. Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor. J Clin Endocrinol Metab. 2004;89(5):2179-2184.", "pmid": "15126539", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15126539/", "publicSourceType": "PMID" }, { "text": "Ding Y, Wang C, Bi L et al.. Dutasteride for the Treatment of Androgenetic Alopecia: An Updated Review. Dermatology (Basel, Switzerland). 2024", "pmid": "39278205", "doi": "10.1159/000541395", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39278205/", "publicSourceType": "PMID" }, { "text": "Fertig RM, Gamret AC, Darwin E et al.. Sexual side effects of 5-α-reductase inhibitors finasteride and dutasteride: A comprehensive review. Dermatology online journal. 2017", "pmid": "29447628", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29447628/", "publicSourceType": "PMID" }, { "text": "Yu H, Chen H, Wang X et al.. Efficacy and Safety of Combination Tamsulosin and Dutasteride versus Tamsulosin Monotherapy for Benign Prostatic Hyperplasia: A Meta-Analysis. Archivos espanoles de urologia. 2025", "claim": "PubMed-indexed evidence involving Dutasteride", "title": "Efficacy and Safety of Combination Tamsulosin and Dutasteride versus Tamsulosin Monotherapy for Benign Prostatic Hyperplasia: A Meta-Analysis", "authors": "Yu H, Chen H, Wang X et al.", "journal": "Archivos espanoles de urologia", "year": 2025, "pmid": "40922439", "url": "https://pubmed.ncbi.nlm.nih.gov/40922439/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.56434/j.arch.esp.urol.20257807.115", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40922439/", "publicSourceType": "PMID" }, { "text": "Wu XJ, Zhi Y, Zheng J et al.. Dutasteride on benign prostatic hyperplasia: a meta-analysis on randomized clinical trials in 6460 patients. Urology. 2014", "claim": "PubMed-indexed evidence involving Dutasteride", "title": "Dutasteride on benign prostatic hyperplasia: a meta-analysis on randomized clinical trials in 6460 patients", "authors": "Wu XJ, Zhi Y, Zheng J et al.", "journal": "Urology", "year": 2014, "pmid": "24246318", "url": "https://pubmed.ncbi.nlm.nih.gov/24246318/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.urology.2013.10.007", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24246318/", "publicSourceType": "PMID" }, { "text": "Zhou Z, Cui Y, Wu J et al.. Meta-analysis of the efficacy and safety of combination of tamsulosin plus dutasteride compared with tamsulosin monotherapy in treating benign prostatic hyperplasia. BMC urology. 2019", "claim": "PubMed-indexed evidence involving Dutasteride", "title": "Meta-analysis of the efficacy and safety of combination of tamsulosin plus dutasteride compared with tamsulosin monotherapy in treating benign prostatic hyperplasia", "authors": "Zhou Z, Cui Y, Wu J et al.", "journal": "BMC urology", "year": 2019, "pmid": "30871552", "url": "https://pubmed.ncbi.nlm.nih.gov/30871552/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12894-019-0446-8", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30871552/", "publicSourceType": "PMID" }, { "text": "Yang F, Hashim R, Philippou J. Tamsulosin and Dutasteride Combination Therapy for Asian Men With Moderate-to-Severe Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: A Systematic Review of Clinical Considerations That Influence the Prescription. Journal of clinical medicine research. 2024", "claim": "PubMed-indexed evidence involving Dutasteride", "title": "Tamsulosin and Dutasteride Combination Therapy for Asian Men With Moderate-to-Severe Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: A Systematic Review of Clinical Considerations That Influence the Prescription", "authors": "Yang F, Hashim R, Philippou J", "journal": "Journal of clinical medicine research", "year": 2024, "pmid": "39346571", "url": "https://pubmed.ncbi.nlm.nih.gov/39346571/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.14740/jocmr5255", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39346571/", "publicSourceType": "PMID" }, { "text": "Ren J, Lai S, Jiang Z et al.. A Systematic Review and Meta-Analysis of the Effects on Dutasteride Treatment for Reducing Surgical Blood Loss during Transurethral Resection of the Prostate. Urologia internationalis. 2017", "claim": "PubMed-indexed evidence involving Dutasteride", "title": "A Systematic Review and Meta-Analysis of the Effects on Dutasteride Treatment for Reducing Surgical Blood Loss during Transurethral Resection of the Prostate", "authors": "Ren J, Lai S, Jiang Z et al.", "journal": "Urologia internationalis", "year": 2017, "pmid": "28006778", "url": "https://pubmed.ncbi.nlm.nih.gov/28006778/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1159/000453669", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28006778/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "5-Alpha reductase inhibitor (Dual Type I and II)", "blackBoxWarnings": [], "fdaPregnancyCategory": "X", "halfLife": "5 weeks (terminal)", "onsetOfAction": "3-6 months for symptom improvement; maximal prostate reduction at 6-12 months", "commonBrandNames": [ "Avodart", "Jalyn (with tamsulosin)" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "dutasteride" }, { "id": "RX-SPEC-016", "name": "Oxybutynin", "alternateNames": [ "Ditropan" ], "category": "Prescription", "subcategory": "Anticholinergic / Overactive Bladder", "overview": "Oxybutynin is an antimuscarinic agent used for the treatment of overactive bladder (OAB) symptoms including urge urinary incontinence, urgency, and frequency. It is one of the oldest and most studied medications for OAB. Available in immediate-release, extended-release, transdermal patch, and topical gel formulations; extended-release and transdermal forms have improved tolerability compared to immediate-release.", "mechanismOfAction": "Exerts direct antispasmodic effects on smooth muscle and inhibits the muscarinic action of acetylcholine on bladder smooth muscle (detrusor muscle). Specifically blocks M1 and M3 muscarinic receptors on the detrusor, reducing involuntary bladder contractions that cause urgency and incontinence. Also has local anesthetic and calcium channel blocking properties at higher concentrations.", "commonBenefits": [ "Reduces episodes of urge incontinence", "Decreases urinary urgency and frequency", "Multiple formulations for individualized therapy", "Transdermal formulation reduces anticholinergic side effects" ], "commonDosageRange": "5 mg two to three times daily (immediate-release); 5-10 mg once daily (extended-release); 3.9 mg/day transdermal patch (applied twice weekly) (as prescribed by your physician)", "recommendedForm": "Extended-release tablets (Ditropan XL) or transdermal patch/gel preferred to minimize dry mouth and other anticholinergic effects", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Oral bioavailability ~6% due to extensive first-pass hepatic metabolism to active metabolite N-desethyloxybutynin (which causes most anticholinergic side effects). Extended-release and transdermal formulations bypass first-pass metabolism, producing lower N-DEO levels." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Dry mouth (most common)", "Constipation", "Blurred vision", "Somnolence and dizziness", "Cognitive impairment (especially in elderly)", "Urinary retention", "Heat intolerance (decreased sweating)", "Application site reactions (transdermal)" ], "contraindications": [ "Urinary retention or significant bladder outlet obstruction", "Uncontrolled narrow-angle glaucoma", "Gastric retention or GI obstruction", "Known hypersensitivity to oxybutynin", "Elderly patients with dementia risk (anticholinergic cognitive burden)", "Myasthenia gravis" ], "iconName": "cross.case.fill", "colorHex": "4D94FF", "tags": [ "overactive-bladder", "incontinence", "anticholinergic", "urologic" ], "sources": [ { "text": "Chapple CR et al. A comparison of the efficacy and tolerability of solifenacin succinate and extended release tolterodine at treating overactive bladder syndrome: results of the STAR trial. Eur Urol. 2005;48(3):464-470.", "pmid": "15990220", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15990220/", "publicSourceType": "PMID" }, { "text": "Dmochowski RR et al. Transdermal oxybutynin in the treatment of adults with overactive bladder: combined results of two randomized clinical trials. World J Urol. 2005;23(4):263-270.", "pmid": "16096831", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16096831/", "publicSourceType": "PMID" }, { "text": "Coupland CAC et al. Anticholinergic drug exposure and the risk of dementia: a nested case-control study. JAMA Intern Med. 2019;179(8):1084-1093.", "pmid": "31233095", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31233095/", "publicSourceType": "PMID" }, { "text": "Taranto-Montemurro L, Messineo L, Sands SA et al.. The Combination of Atomoxetine and Oxybutynin Greatly Reduces Obstructive Sleep Apnea Severity. A Randomized, Placebo-controlled, Double-Blind Crossover Trial. American journal of respiratory and critical care medicine. 2019", "pmid": "30395486", "doi": "10.1164/rccm.201808-1493OC", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30395486/", "publicSourceType": "PMID" }, { "text": "Dwyer J, Tafuri SM, LaGrange CA. Oxybutynin. 2026", "pmid": "29763161", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29763161/", "publicSourceType": "PMID" }, { "text": "El-Samahy M, Mouffokes A, Badawy MM et al.. Safety and efficacy of oxybutynin in patients with hyperhidrosis: systematic review and meta-analysis of randomized controlled trials. Archives of dermatological research. 2023", "claim": "PubMed-indexed evidence involving Oxybutynin", "title": "Safety and efficacy of oxybutynin in patients with hyperhidrosis: systematic review and meta-analysis of randomized controlled trials", "authors": "El-Samahy M, Mouffokes A, Badawy MM et al.", "journal": "Archives of dermatological research", "year": 2023, "pmid": "36869926", "url": "https://pubmed.ncbi.nlm.nih.gov/36869926/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00403-023-02587-5", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36869926/", "publicSourceType": "PMID" }, { "text": "Shen SH, Jia X, Peng L et al.. Intravesical oxybutynin therapy for patients with neurogenic detrusor overactivity: a systematic review and meta-analysis. International urology and nephrology. 2022", "claim": "PubMed-indexed evidence involving Oxybutynin", "title": "Intravesical oxybutynin therapy for patients with neurogenic detrusor overactivity: a systematic review and meta-analysis", "authors": "Shen SH, Jia X, Peng L et al.", "journal": "International urology and nephrology", "year": 2022, "pmid": "35226282", "url": "https://pubmed.ncbi.nlm.nih.gov/35226282/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s11255-022-03129-0", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35226282/", "publicSourceType": "PMID" }, { "text": "Harvey MA, Baker K, Wells GA. Tolterodine versus oxybutynin in the treatment of urge urinary incontinence: a meta-analysis. American journal of obstetrics and gynecology. 2001", "claim": "PubMed-indexed evidence involving Oxybutynin", "title": "Tolterodine versus oxybutynin in the treatment of urge urinary incontinence: a meta-analysis", "authors": "Harvey MA, Baker K, Wells GA", "journal": "American journal of obstetrics and gynecology", "year": 2001, "pmid": "11483904", "url": "https://pubmed.ncbi.nlm.nih.gov/11483904/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1067/mob.2001.116371", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11483904/", "publicSourceType": "PMID" }, { "text": "Aishah A, Loffler KA, Toson B et al.. One Month Dosing of Atomoxetine plus Oxybutynin in Obstructive Sleep Apnea: A Randomized, Placebo-controlled Trial. Annals of the American Thoracic Society. 2023", "claim": "PubMed-indexed evidence involving Oxybutynin", "title": "One Month Dosing of Atomoxetine plus Oxybutynin in Obstructive Sleep Apnea: A Randomized, Placebo-controlled Trial", "authors": "Aishah A, Loffler KA, Toson B et al.", "journal": "Annals of the American Thoracic Society", "year": 2023, "pmid": "36538809", "url": "https://pubmed.ncbi.nlm.nih.gov/36538809/", "study_type": "RCT", "confidence": "verify", "doi": "10.1513/AnnalsATS.202206-492OC", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36538809/", "publicSourceType": "PMID" }, { "text": "Berger M, Solelhac G, Marchi NA et al.. Effect of oxybutynin and reboxetine on obstructive sleep apnea: a randomized, placebo-controlled, double-blind, crossover trial. Sleep. 2023", "claim": "PubMed-indexed evidence involving Oxybutynin", "title": "Effect of oxybutynin and reboxetine on obstructive sleep apnea: a randomized, placebo-controlled, double-blind, crossover trial", "authors": "Berger M, Solelhac G, Marchi NA et al.", "journal": "Sleep", "year": 2023, "pmid": "36861433", "url": "https://pubmed.ncbi.nlm.nih.gov/36861433/", "study_type": "RCT", "confidence": "verify", "doi": "10.1093/sleep/zsad051", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36861433/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Anticholinergic / Antimuscarinic", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "2-3 hours (immediate-release); 12-13 hours (extended-release)", "onsetOfAction": "30-60 minutes (immediate-release); 1-2 weeks for full clinical effect", "commonBrandNames": [ "Ditropan", "Ditropan XL", "Oxytrol (patch)", "Gelnique (gel)" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "oxybutynin" }, { "id": "RX-SPEC-017", "name": "Mirabegron", "alternateNames": [ "Myrbetriq" ], "category": "Prescription", "subcategory": "Beta-3 Agonist / Overactive Bladder", "overview": "Mirabegron is the first-in-class beta-3 adrenergic receptor agonist approved for the treatment of overactive bladder (OAB) with symptoms of urge incontinence, urgency, and urinary frequency. It offers an alternative mechanism of action to anticholinergic agents, avoiding the troublesome anticholinergic side effects (dry mouth, constipation, cognitive impairment) that limit tolerability in many patients, particularly the elderly.", "mechanismOfAction": "Selectively activates beta-3 adrenergic receptors on the detrusor smooth muscle of the bladder during the storage phase, promoting muscle relaxation and increasing bladder capacity. Unlike antimuscarinics that block the voiding contraction signal, mirabegron relaxes the bladder during filling, allowing greater urine storage without the anticholinergic side effect profile.", "commonBenefits": [ "Effective reduction of incontinence episodes, urgency, and frequency", "Avoids anticholinergic side effects (no significant dry mouth or cognitive effects)", "Once-daily dosing", "Suitable for elderly patients including those with cognitive concerns" ], "commonDosageRange": "25 mg once daily initially, may increase to 50 mg once daily based on efficacy and tolerability (as prescribed by your physician)", "recommendedForm": "Extended-release tablet; swallow whole with water, do not crush, divide, or chew", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Absolute bioavailability ~29-35%; high-fat meal reduces Cmax but does not significantly affect AUC, so it can be taken with or without food. Dose adjustment needed for severe hepatic or renal impairment (max 25 mg)." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Hypertension (dose-dependent blood pressure increase)", "Urinary tract infection", "Nasopharyngitis", "Headache", "Tachycardia", "Constipation (less than with antimuscarinics)" ], "contraindications": [ "Known hypersensitivity to mirabegron", "Severe uncontrolled hypertension (systolic ≥180 mmHg and/or diastolic ≥110 mmHg)", "Urinary retention", "Severe hepatic impairment (Child-Pugh C), not recommended", "End-stage renal disease (GFR <15 mL/min), not recommended" ], "iconName": "cross.case.fill", "colorHex": "4D94FF", "tags": [ "overactive-bladder", "incontinence", "beta-3-agonist", "urologic" ], "sources": [ { "text": "Khullar V et al. Efficacy and tolerability of mirabegron, a beta(3)-adrenoceptor agonist, in patients with overactive bladder: results from a randomised European-Australian phase 3 trial. Eur Urol. 2013;63(2):283-295.", "pmid": "23182126", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23182126/", "publicSourceType": "PMID" }, { "text": "Nitti VW et al. Results of a randomized phase III trial of mirabegron in patients with overactive bladder. J Urol. 2013;189(4):1388-1395.", "pmid": "23079373", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23079373/", "publicSourceType": "PMID" }, { "text": "Herschorn S et al. A phase III, randomized, double-blind, parallel-group, placebo-controlled, multicentre study to assess the efficacy and safety of the beta-3 adrenoceptor agonist, mirabegron, in patients with symptoms of overactive bladder. Urology. 2013;82(2):313-320.", "pmid": "23769122", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23769122/", "publicSourceType": "PMID" }, { "text": "He W, Zhang Y, Huang G et al.. Efficacy and safety of vibegron compared with mirabegron for overactive bladder: A systematic review and network meta-analysis. Lower urinary tract symptoms. 2023", "pmid": "36863312", "doi": "10.1111/luts.12475", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36863312/", "publicSourceType": "PMID" }, { "text": "Liang P, Yu L, Xia B et al.. Comparative Efficacy and Safety of Mirabegron and Vibegron in Female Patients With Overactive Bladder: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Urology. 2025", "pmid": "39970965", "doi": "10.1016/j.urology.2025.02.018", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39970965/", "publicSourceType": "PMID" }, { "text": "Hou J, Xu F, Du H et al.. Adverse events associated with mirabegron 50mg versus placebo: A systematic review and meta-analysis. Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie. 2021", "claim": "PubMed-indexed evidence involving Mirabegron", "title": "Adverse events associated with mirabegron 50mg versus placebo: A systematic review and meta-analysis", "authors": "Hou J, Xu F, Du H et al.", "journal": "Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie", "year": 2021, "pmid": "34312078", "url": "https://pubmed.ncbi.nlm.nih.gov/34312078/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.purol.2021.05.005", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34312078/", "publicSourceType": "PMID" }, { "text": "Wang Z, Chi J, Liu Y et al.. Efficacy of mirabegron for ureteral stones: a systematic review with meta-analysis of randomized controlled trials. Frontiers in pharmacology. 2023", "claim": "PubMed-indexed evidence involving Mirabegron", "title": "Efficacy of mirabegron for ureteral stones: a systematic review with meta-analysis of randomized controlled trials", "authors": "Wang Z, Chi J, Liu Y et al.", "journal": "Frontiers in pharmacology", "year": 2023, "pmid": "38178860", "url": "https://pubmed.ncbi.nlm.nih.gov/38178860/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fphar.2023.1326600", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38178860/", "publicSourceType": "PMID" }, { "text": "Wang J, Zhou Z, Cui Y et al.. Meta-analysis of the efficacy and safety of mirabegron and solifenacin monotherapy for overactive bladder. Neurourology and urodynamics. 2019", "claim": "PubMed-indexed evidence involving Mirabegron", "title": "Meta-analysis of the efficacy and safety of mirabegron and solifenacin monotherapy for overactive bladder", "authors": "Wang J, Zhou Z, Cui Y et al.", "journal": "Neurourology and urodynamics", "year": 2019, "pmid": "30350884", "url": "https://pubmed.ncbi.nlm.nih.gov/30350884/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/nau.23863", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30350884/", "publicSourceType": "PMID" }, { "text": "Ma L, Xiong L, Huang G. Effects of mirabegron on brown adipose tissue and metabolism in humans: A systematic review and meta-analysis. European journal of clinical pharmacology. 2024", "claim": "PubMed-indexed evidence involving Mirabegron", "title": "Effects of mirabegron on brown adipose tissue and metabolism in humans: A systematic review and meta-analysis", "authors": "Ma L, Xiong L, Huang G", "journal": "European journal of clinical pharmacology", "year": 2024, "pmid": "38159219", "url": "https://pubmed.ncbi.nlm.nih.gov/38159219/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00228-023-03614-0", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38159219/", "publicSourceType": "PMID" }, { "text": "Lu Y, Li Q, Zou Q et al.. Mirabegron and antimuscarinics for treating ureteral stent-related symptoms: a systematic review and meta-analysis of RCTs. Frontiers in pharmacology. 2023", "claim": "PubMed-indexed evidence involving Mirabegron", "title": "Mirabegron and antimuscarinics for treating ureteral stent-related symptoms: a systematic review and meta-analysis of RCTs", "authors": "Lu Y, Li Q, Zou Q et al.", "journal": "Frontiers in pharmacology", "year": 2023, "pmid": "37920205", "url": "https://pubmed.ncbi.nlm.nih.gov/37920205/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fphar.2023.1266636", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37920205/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Beta-3 adrenergic agonist", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "50 hours", "onsetOfAction": "2-8 weeks for full clinical effect", "commonBrandNames": [ "Myrbetriq" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Monitor blood pressure periodically, especially during initiation; check LFTs if hepatic concerns" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "mirabegron" }, { "id": "RX-SPEC-018", "name": "Sildenafil", "alternateNames": [ "Viagra", "Revatio" ], "category": "Prescription", "subcategory": "PDE5 Inhibitor", "overview": "Sildenafil is a phosphodiesterase type 5 (PDE5) inhibitor originally developed for angina and subsequently approved for erectile dysfunction (ED) and pulmonary arterial hypertension (PAH). As Viagra, it is the most recognized ED medication worldwide. As Revatio, it is used at lower doses for PAH to improve exercise capacity. Its on-demand dosing makes it the standard first-line oral therapy for ED.", "mechanismOfAction": "Selectively inhibits phosphodiesterase type 5 (PDE5), the enzyme that degrades cyclic GMP (cGMP) in penile corpus cavernosum smooth muscle. During sexual stimulation, nitric oxide is released, activating guanylate cyclase to produce cGMP, which relaxes smooth muscle and increases blood flow. By preventing cGMP breakdown, sildenafil potentiates the erectile response. In PAH, the same mechanism relaxes pulmonary vascular smooth muscle, reducing pulmonary artery pressure.", "commonBenefits": [ "Effective first-line oral treatment for erectile dysfunction", "Improves exercise capacity in pulmonary arterial hypertension", "Rapid onset allows on-demand use", "Well-studied safety profile over 25+ years" ], "commonDosageRange": "50 mg as needed approximately 30-60 minutes before sexual activity (may adjust to 25-100 mg); for PAH: 20 mg three times daily (as prescribed by your physician)", "recommendedForm": "Oral tablet; also available as oral suspension (Revatio) and IV injection for PAH", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": true, "notes": "High-fat meals delay absorption by approximately 1 hour and reduce peak concentration by 29%; for fastest onset, take on an empty stomach. Bioavailability ~41%." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Headache", "Flushing", "Dyspepsia", "Nasal congestion", "Visual disturbances (blue-tinged vision, increased light sensitivity, due to mild PDE6 inhibition in retina)", "Dizziness", "Priapism (rare)" ], "contraindications": [ "Concurrent use with nitrates (nitroglycerin, isosorbide), risk of severe, potentially fatal hypotension", "Concurrent use with riociguat (Adempas)", "Known hypersensitivity to sildenafil", "Recent stroke or myocardial infarction (within 6 months)", "Severe hepatic impairment", "Conditions where sexual activity is inadvisable (unstable angina, severe heart failure)" ], "iconName": "cross.case.fill", "colorHex": "4D94FF", "tags": [ "erectile-dysfunction", "pde5-inhibitor", "pulmonary-hypertension", "urologic" ], "sources": [ { "text": "Goldstein I et al. Oral sildenafil in the treatment of erectile dysfunction. N Engl J Med. 1998;338(20):1397-1404.", "pmid": "9580646", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9580646/", "publicSourceType": "PMID" }, { "text": "Galiè N et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med. 2005;353(20):2148-2157.", "pmid": "16291984", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16291984/", "publicSourceType": "PMID" }, { "text": "Carson CC et al. The efficacy and safety of sildenafil citrate (Viagra) in clinical populations. Urology. 2002;60(2 Suppl 2):12-20.", "pmid": "14622503", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14622503/", "publicSourceType": "PMID" }, { "text": "Gong B, Ma M, Xie W et al.. Direct comparison of tadalafil with sildenafil for the treatment of erectile dysfunction: a systematic review and meta-analysis. International urology and nephrology. 2017", "pmid": "28741090", "doi": "10.1007/s11255-017-1644-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28741090/", "publicSourceType": "PMID" }, { "text": "Krishnappa P, Fernandez-Pascual E, Carballido J et al.. Sildenafil/Viagra in the treatment of premature ejaculation. International journal of impotence research. 2019", "pmid": "30837718", "doi": "10.1038/s41443-018-0099-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30837718/", "publicSourceType": "PMID" }, { "text": "Poudel S, Gautam S, Adhikari P et al.. Physiological Effects of Sildenafil Versus Placebo at High Altitude: A Systematic Review. High altitude medicine & biology. 2024", "claim": "PubMed-indexed evidence involving Sildenafil", "title": "Physiological Effects of Sildenafil Versus Placebo at High Altitude: A Systematic Review", "authors": "Poudel S, Gautam S, Adhikari P et al.", "journal": "High altitude medicine & biology", "year": 2024, "pmid": "37751174", "url": "https://pubmed.ncbi.nlm.nih.gov/37751174/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1089/ham.2022.0043", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37751174/", "publicSourceType": "PMID" }, { "text": "Awad AK, Gad ER, Abdelgalil MS et al.. Sildenafil for congenital heart diseases induced pulmonary hypertension, a meta-analysis of randomized controlled trials. BMC pediatrics. 2023", "claim": "PubMed-indexed evidence involving Sildenafil", "title": "Sildenafil for congenital heart diseases induced pulmonary hypertension, a meta-analysis of randomized controlled trials", "authors": "Awad AK, Gad ER, Abdelgalil MS et al.", "journal": "BMC pediatrics", "year": 2023, "pmid": "37474896", "url": "https://pubmed.ncbi.nlm.nih.gov/37474896/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12887-023-04180-1", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37474896/", "publicSourceType": "PMID" }, { "text": "Chua WY, Lim LKE, Wang JJD et al.. Sildenafil and risk of Alzheimer disease: a systematic review and meta-analysis. Aging. 2025", "claim": "PubMed-indexed evidence involving Sildenafil", "title": "Sildenafil and risk of Alzheimer disease: a systematic review and meta-analysis", "authors": "Chua WY, Lim LKE, Wang JJD et al.", "journal": "Aging", "year": 2025, "pmid": "40096550", "url": "https://pubmed.ncbi.nlm.nih.gov/40096550/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.18632/aging.206222", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40096550/", "publicSourceType": "PMID" }, { "text": "Hirata K, Nakahari A, Takeoka M et al.. Prophylactic sildenafil to prevent bronchopulmonary dysplasia: A systematic review and meta-analysis. Pediatrics international : official journal of the Japan Pediatric Society. 2024", "claim": "PubMed-indexed evidence involving Sildenafil", "title": "Prophylactic sildenafil to prevent bronchopulmonary dysplasia: A systematic review and meta-analysis", "authors": "Hirata K, Nakahari A, Takeoka M et al.", "journal": "Pediatrics international : official journal of the Japan Pediatric Society", "year": 2024, "pmid": "38863262", "url": "https://pubmed.ncbi.nlm.nih.gov/38863262/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/ped.15749", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38863262/", "publicSourceType": "PMID" }, { "text": "Chen Z, Huang Y, Cao D et al.. Function of sildenafil on diseases other than urogenital system: An umbrella review. Frontiers in pharmacology. 2023", "claim": "PubMed-indexed evidence involving Sildenafil", "title": "Function of sildenafil on diseases other than urogenital system: An umbrella review", "authors": "Chen Z, Huang Y, Cao D et al.", "journal": "Frontiers in pharmacology", "year": 2023, "pmid": "36814496", "url": "https://pubmed.ncbi.nlm.nih.gov/36814496/", "study_type": "review", "confidence": "verify", "doi": "10.3389/fphar.2023.1033492", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36814496/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Phosphodiesterase type 5 (PDE5) inhibitor", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "3-5 hours", "onsetOfAction": "30-60 minutes (for ED); weeks for PAH benefit", "commonBrandNames": [ "Viagra", "Revatio" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "sildenafil" }, { "id": "RX-SPEC-019", "name": "Tadalafil", "alternateNames": [ "Cialis", "Adcirca" ], "category": "Prescription", "subcategory": "PDE5 Inhibitor", "overview": "Tadalafil is a long-acting PDE5 inhibitor approved for erectile dysfunction (ED), benign prostatic hyperplasia (BPH), and pulmonary arterial hypertension (PAH). Its prolonged duration of action (up to 36 hours) distinguishes it from sildenafil and vardenafil, earning it the nickname 'the weekend pill.' Low-dose daily tadalafil (2.5-5 mg) is uniquely approved for combined ED and BPH symptom management.", "mechanismOfAction": "Selectively inhibits phosphodiesterase type 5 (PDE5), preventing degradation of cGMP in smooth muscle cells. This enhances nitric oxide-mediated vasodilation in the corpus cavernosum (for erection), the prostate and bladder (for BPH symptom relief), and the pulmonary vasculature (for PAH). Tadalafil is more selective for PDE5 over PDE6 than sildenafil, resulting in fewer visual side effects, but has more PDE11 inhibition (significance uncertain).", "commonBenefits": [ "Longest duration of action among PDE5 inhibitors (up to 36 hours)", "Daily dosing option eliminates need for timing with sexual activity", "Uniquely approved for both ED and BPH", "Less affected by food intake than sildenafil" ], "commonDosageRange": "10-20 mg as needed before sexual activity (or 2.5-5 mg once daily for ED/BPH); 40 mg once daily for PAH (as prescribed by your physician)", "recommendedForm": "Oral tablet", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Not significantly affected by food (unlike sildenafil); can be taken with or without meals. Bioavailability not precisely determined but clinical effect is reliable. Long half-life of 17.5 hours supports daily dosing." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Headache", "Dyspepsia", "Back pain and myalgia (unique to tadalafil due to PDE11 inhibition)", "Nasal congestion", "Flushing", "Limb pain", "Priapism (rare)" ], "contraindications": [ "Concurrent use with nitrates (absolute contraindication, severe hypotension)", "Concurrent use with riociguat (Adempas)", "Known hypersensitivity to tadalafil", "Concurrent use with alpha blockers other than tamsulosin 0.4 mg (hemodynamic interaction)", "Conditions where sexual activity is inadvisable", "Severe hepatic impairment (not recommended)" ], "iconName": "cross.case.fill", "colorHex": "4D94FF", "tags": [ "erectile-dysfunction", "pde5-inhibitor", "bph", "pulmonary-hypertension", "urologic" ], "sources": [ { "text": "Brock GB et al. Efficacy and safety of tadalafil for the treatment of erectile dysfunction: results of integrated analyses. J Urol. 2002;168(4 Pt 1):1332-1336.", "pmid": "12352386", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12352386/", "publicSourceType": "PMID" }, { "text": "Oelke M et al. Monotherapy with tadalafil or tamsulosin similarly improved lower urinary tract symptoms suggestive of benign prostatic hyperplasia in an international, randomised, parallel, placebo-controlled clinical trial. Eur Urol. 2012;61(5):917-925.", "pmid": "22297243", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22297243/", "publicSourceType": "PMID" }, { "text": "Galiè N et al. Tadalafil therapy for pulmonary arterial hypertension. Circulation. 2009;119(22):2894-2903.", "pmid": "19470885", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19470885/", "publicSourceType": "PMID" }, { "text": "Gong B, Ma M, Xie W et al.. Direct comparison of tadalafil with sildenafil for the treatment of erectile dysfunction: a systematic review and meta-analysis. International urology and nephrology. 2017", "pmid": "28741090", "doi": "10.1007/s11255-017-1644-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28741090/", "publicSourceType": "PMID" }, { "text": "Grünig E, Jansa P, Fan F et al.. Randomized Trial of Macitentan/Tadalafil Single-Tablet Combination Therapy for Pulmonary Arterial Hypertension. Journal of the American College of Cardiology. 2024", "pmid": "38267108", "doi": "10.1016/j.jacc.2023.10.045", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38267108/", "publicSourceType": "PMID" }, { "text": "Zhou R, Che X, Zhou Z et al.. A Systematic Review and Meta-Analysis of the Efficacy and Safety of Tamsulosin Plus Tadalafil Compared With Tamsulosin Alone in Treating Males With Lower Urinary Tract Symptoms Secondary to Benign Prostrate Hyperplasia. American journal of men's health. 2023", "claim": "PubMed-indexed evidence involving Tadalafil", "title": "A Systematic Review and Meta-Analysis of the Efficacy and Safety of Tamsulosin Plus Tadalafil Compared With Tamsulosin Alone in Treating Males With Lower Urinary Tract Symptoms Secondary to Benign Prostrate Hyperplasia", "authors": "Zhou R, Che X, Zhou Z et al.", "journal": "American journal of men's health", "year": 2023, "pmid": "36842963", "url": "https://pubmed.ncbi.nlm.nih.gov/36842963/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1177/15579883231155096", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36842963/", "publicSourceType": "PMID" }, { "text": "Shafiee A, Bahri RA, Teymouri Athar MM et al.. Phosphodiesterase 5 (PDE-5) inhibitors (sildenafil, tadalafil, and vardenafil) effects on esophageal motility: a systematic review. BMC gastroenterology. 2023", "claim": "PubMed-indexed evidence involving Tadalafil", "title": "Phosphodiesterase 5 (PDE-5) inhibitors (sildenafil, tadalafil, and vardenafil) effects on esophageal motility: a systematic review", "authors": "Shafiee A, Bahri RA, Teymouri Athar MM et al.", "journal": "BMC gastroenterology", "year": 2023, "pmid": "37217851", "url": "https://pubmed.ncbi.nlm.nih.gov/37217851/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12876-023-02787-3", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37217851/", "publicSourceType": "PMID" }, { "text": "Belkovsky M, Zogaib GV, Passerotti CC et al.. Tamsulosin vs. Tadalafil as medical expulsive therapy for distal ureteral stones: a systematic review and meta-analysis. International braz j urol : official journal of the Brazilian Society of Urology. 2023", "claim": "PubMed-indexed evidence involving Tadalafil", "title": "Tamsulosin vs. Tadalafil as medical expulsive therapy for distal ureteral stones: a systematic review and meta-analysis", "authors": "Belkovsky M, Zogaib GV, Passerotti CC et al.", "journal": "International braz j urol : official journal of the Brazilian Society of Urology", "year": 2023, "pmid": "37903004", "url": "https://pubmed.ncbi.nlm.nih.gov/37903004/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1590/S1677-5538.IBJU.2023.0345", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37903004/", "publicSourceType": "PMID" }, { "text": "Wang YL, Geng LG, He CB et al.. Chinese herbal medicine combined with tadalafil for erectile dysfunction: a systematic review and meta-analysis. Andrology. 2020", "claim": "PubMed-indexed evidence involving Tadalafil", "title": "Chinese herbal medicine combined with tadalafil for erectile dysfunction: a systematic review and meta-analysis", "authors": "Wang YL, Geng LG, He CB et al.", "journal": "Andrology", "year": 2020, "pmid": "31464074", "url": "https://pubmed.ncbi.nlm.nih.gov/31464074/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/andr.12696", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31464074/", "publicSourceType": "PMID" }, { "text": "Cox D, Byrne B, Hammers DW et al.. Effect of Tadalafil on cardiac function and left ventricular dimensions in Duchenne muscular dystrophy: safety and cardiac MRI substudy results from a randomized, placebo-controlled trial. BMC cardiovascular disorders. 2025", "claim": "PubMed-indexed evidence involving Tadalafil", "title": "Effect of Tadalafil on cardiac function and left ventricular dimensions in Duchenne muscular dystrophy: safety and cardiac MRI substudy results from a randomized, placebo-controlled trial", "authors": "Cox D, Byrne B, Hammers DW et al.", "journal": "BMC cardiovascular disorders", "year": 2025, "pmid": "40217158", "url": "https://pubmed.ncbi.nlm.nih.gov/40217158/", "study_type": "RCT", "confidence": "verify", "doi": "10.1186/s12872-025-04727-3", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40217158/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Phosphodiesterase type 5 (PDE5) inhibitor", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "17.5 hours", "onsetOfAction": "30 minutes to 2 hours; duration up to 36 hours", "commonBrandNames": [ "Cialis", "Adcirca" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "tadalafil" }, { "id": "RX-SPEC-020", "name": "Isotretinoin", "alternateNames": [ "Accutane", "Absorica", "Claravis", "Amnesteem" ], "category": "Prescription", "subcategory": "Retinoid / Dermatologic", "overview": "Isotretinoin (13-cis-retinoic acid) is the most effective treatment for severe, recalcitrant nodular acne that has failed conventional therapy. It is the only acne medication that addresses all four pathogenic factors of acne: excess sebum production, follicular hyperkeratinization, Cutibacterium acnes colonization, and inflammation. A typical course of 15-20 weeks achieves long-term remission in most patients, with many cured after a single course.", "mechanismOfAction": "Acts as a retinoid (vitamin A derivative) that dramatically reduces sebaceous gland size and sebum production by up to 90%, normalizes follicular keratinization to prevent comedone formation, inhibits Cutibacterium acnes growth (indirectly through reduced sebum), and exerts anti-inflammatory effects. These combined actions address all major pathogenic factors of acne. The precise molecular targets include retinoid receptors (RAR/RXR), regulation of gene transcription, and modulation of toll-like receptor signaling.", "commonBenefits": [ "Long-term remission of severe acne (often permanent after one course)", "Addresses all four pathogenic factors of acne simultaneously", "Dramatically reduces sebum production", "Most effective acne medication available" ], "commonDosageRange": "0.5-1 mg/kg/day in 1-2 divided doses for 15-20 weeks; cumulative dose target of 120-150 mg/kg (as prescribed by your physician)", "recommendedForm": "Oral capsules; Absorica can be taken without food, other brands require fat-containing meal", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Take with high-fat meal, absorption increases 2x with food. Absorica (micronized formulation) can be taken without food with comparable bioavailability. Peak levels in 3-5 hours." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Dry skin, lips, and mucous membranes (cheilitis in ~90% of patients)", "Dry eyes and contact lens intolerance", "Elevated triglycerides and cholesterol", "Elevated liver enzymes", "Musculoskeletal pain and myalgias", "Photosensitivity", "Mood changes and depression (debated; monitoring recommended)", "Nosebleeds (epistaxis)" ], "contraindications": [ "Pregnancy (absolutely contraindicated, severe teratogen causing birth defects)", "Breastfeeding", "Hypersensitivity to isotretinoin, retinoids, or parabens in capsule", "Concurrent vitamin A supplementation (hypervitaminosis A risk)", "Concurrent tetracycline antibiotics (pseudotumor cerebri risk)", "Hypertriglyceridemia" ], "iconName": "cross.case.fill", "colorHex": "F472B6", "tags": [ "acne", "retinoid", "dermatologic", "sebum" ], "sources": [ { "text": "Layton AM et al. A review on the treatment of acne vulgaris, an evidence-based update. J Eur Acad Dermatol Venereol. 2009;23(4):439-448.", "pmid": "41648090", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41648090/", "publicSourceType": "PMID" }, { "text": "Strauss JS et al. Guidelines of care for acne vulgaris management. J Am Acad Dermatol. 2007;56(4):651-663.", "pmid": "17276540", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17276540/", "publicSourceType": "PMID" }, { "text": "Dispenza MC et al. Systemic isotretinoin therapy normalizes exaggerated TLR-2-mediated innate immune responses in acne patients. J Invest Dermatol. 2012;132(9):2198-2205.", "pmid": "22513780", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22513780/", "publicSourceType": "PMID" }, { "text": "Sadeghzadeh-Bazargan A, Ghassemi M, Goodarzi A et al.. Systematic review of low-dose isotretinoin for treatment of acne vulgaris: Focus on indication, dosage, regimen, efficacy, safety, satisfaction, and follow up, based on clinical studies. Dermatologic therapy. 2021", "pmid": "33085149", "doi": "10.1111/dth.14438", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33085149/", "publicSourceType": "PMID" }, { "text": "Vallerand IA, Lewinson RT, Farris MS et al.. Efficacy and adverse events of oral isotretinoin for acne: a systematic review. The British journal of dermatology. 2018", "pmid": "28542914", "doi": "10.1111/bjd.15668", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28542914/", "publicSourceType": "PMID" }, { "text": "Kapała J, Lewandowska J, Placek W et al.. Adverse Events in Isotretinoin Therapy: A Single-Arm Meta-Analysis. International journal of environmental research and public health. 2022", "claim": "PubMed-indexed evidence involving Isotretinoin", "title": "Adverse Events in Isotretinoin Therapy: A Single-Arm Meta-Analysis", "authors": "Kapała J, Lewandowska J, Placek W et al.", "journal": "International journal of environmental research and public health", "year": 2022, "pmid": "35682048", "url": "https://pubmed.ncbi.nlm.nih.gov/35682048/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/ijerph19116463", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35682048/", "publicSourceType": "PMID" }, { "text": "King A, Tan MG, Kirshen C et al.. Low-dose isotretinoin for the management of rosacea: A systematic review and meta-analysis. Journal of the European Academy of Dermatology and Venereology : JEADV. 2025", "claim": "PubMed-indexed evidence involving Isotretinoin", "title": "Low-dose isotretinoin for the management of rosacea: A systematic review and meta-analysis", "authors": "King A, Tan MG, Kirshen C et al.", "journal": "Journal of the European Academy of Dermatology and Venereology : JEADV", "year": 2025, "pmid": "39239956", "url": "https://pubmed.ncbi.nlm.nih.gov/39239956/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/jdv.20315", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39239956/", "publicSourceType": "PMID" }, { "text": "Sibi Krishna T, Kaur R, Malhotra V et al.. The Impact of Isotretinoin on Lipid Profile: a Systematic Review. Annals of medicine and surgery (2012). 2025", "claim": "PubMed-indexed evidence involving Isotretinoin", "title": "The Impact of Isotretinoin on Lipid Profile: a Systematic Review", "authors": "Sibi Krishna T, Kaur R, Malhotra V et al.", "journal": "Annals of medicine and surgery (2012)", "year": 2025, "pmid": "40851940", "url": "https://pubmed.ncbi.nlm.nih.gov/40851940/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1097/MS9.0000000000003366", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40851940/", "publicSourceType": "PMID" }, { "text": "Rajput I, Anjankar VP. Side Effects of Treating Acne Vulgaris With Isotretinoin: A Systematic Review. Cureus. 2024", "claim": "PubMed-indexed evidence involving Isotretinoin", "title": "Side Effects of Treating Acne Vulgaris With Isotretinoin: A Systematic Review", "authors": "Rajput I, Anjankar VP", "journal": "Cureus", "year": 2024, "pmid": "38601403", "url": "https://pubmed.ncbi.nlm.nih.gov/38601403/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.7759/cureus.55946", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38601403/", "publicSourceType": "PMID" }, { "text": "Xu Y, Wang H, Guo L et al.. Combinations of Energy-based Devices plus isotretinoin for management of acne and acne scars: A systematic review. Journal of cosmetic dermatology. 2024", "claim": "PubMed-indexed evidence involving Isotretinoin", "title": "Combinations of Energy-based Devices plus isotretinoin for management of acne and acne scars: A systematic review", "authors": "Xu Y, Wang H, Guo L et al.", "journal": "Journal of cosmetic dermatology", "year": 2024, "pmid": "38845186", "url": "https://pubmed.ncbi.nlm.nih.gov/38845186/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/jocd.16407", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38845186/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Retinoid (Vitamin A derivative)", "blackBoxWarnings": [ "Must not be used by patients who are pregnant or may become pregnant (iPLEDGE program required)" ], "fdaPregnancyCategory": "X", "halfLife": "21 hours (parent compound); active metabolite 4-oxo-isotretinoin ~24 hours", "onsetOfAction": "4-8 weeks for initial improvement; full course 15-20 weeks", "commonBrandNames": [ "Accutane", "Absorica", "Claravis", "Amnesteem", "Myorisan", "Zenatane" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "Pregnancy test monthly (required by iPLEDGE), LFTs, lipid panel at baseline and monthly; CBC at baseline" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "isotretinoin" }, { "id": "RX-SPEC-021", "name": "Tretinoin Oral", "alternateNames": [ "Vesanoid", "All-Trans Retinoic Acid", "ATRA" ], "category": "Prescription", "subcategory": "Retinoid / Dermatologic-Oncologic", "overview": "Oral tretinoin (all-trans retinoic acid, ATRA) is a retinoid that induces differentiation of immature promyelocytes into mature granulocytes. It is the cornerstone of treatment for acute promyelocytic leukemia (APL) and has revolutionized outcomes for this subtype of leukemia, transforming it from one of the most fatal to the most curable form of acute leukemia when combined with arsenic trioxide. It is not commonly used for dermatologic conditions (topical tretinoin is used for acne and photoaging instead).", "mechanismOfAction": "Binds to retinoic acid receptors (RAR-alpha) in the nucleus, restoring normal gene transcription in promyelocytic leukemia cells. In APL, the PML-RARA fusion protein blocks myeloid differentiation; oral tretinoin degrades this fusion protein, releasing the differentiation block and allowing leukemic promyelocytes to mature into functional granulocytes. This is a targeted differentiation therapy rather than cytotoxic chemotherapy.", "commonBenefits": [ "Induces complete remission in APL (up to 90% when combined with arsenic trioxide)", "Targeted differentiation therapy, transforms cancer cells into normal cells", "Transformed APL from fatal to highly curable disease", "Synergistic with arsenic trioxide for cure without traditional chemotherapy" ], "commonDosageRange": "45 mg/m²/day divided into two equal doses until complete remission or 90 days (as prescribed by your physician)", "recommendedForm": "Oral capsule", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Fat-soluble; take with food to enhance absorption. Peak plasma levels in 1-2 hours. Subject to autoinduction of metabolism with continuous use." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Differentiation syndrome (formerly retinoic acid syndrome), dyspnea, fever, weight gain, pulmonary infiltrates (potentially fatal)", "Headache and pseudotumor cerebri", "Dry skin and mucous membranes", "Elevated liver enzymes", "Hypertriglyceridemia", "Bone pain", "Leukocytosis" ], "contraindications": [ "Pregnancy (category D, teratogenic)", "Known hypersensitivity to tretinoin or retinoids", "Concurrent high-dose vitamin A supplementation", "Hepatic impairment (use with caution)" ], "iconName": "cross.case.fill", "colorHex": "F472B6", "tags": [ "retinoid", "dermatologic", "oncologic", "APL", "leukemia" ], "sources": [ { "text": "Huang ME et al. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood. 1988;72(2):567-572.", "pmid": "3165295", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3165295/", "publicSourceType": "PMID" }, { "text": "Tallman MS et al. All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med. 1997;337(15):1021-1028.", "pmid": "9321529", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9321529/", "publicSourceType": "PMID" }, { "text": "Lo-Coco F et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013;369(2):111-121.", "pmid": "23841729", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23841729/", "publicSourceType": "PMID" }, { "text": "Chean D, Kemp H, Fodil S et al.. Early mortality in patients with acute promyelocytic leukemia: a systematic review and meta-analysis. Critical care (London, England). 2025", "claim": "PubMed-indexed evidence involving Tretinoin Oral", "title": "Early mortality in patients with acute promyelocytic leukemia: a systematic review and meta-analysis", "authors": "Chean D, Kemp H, Fodil S et al.", "journal": "Critical care (London, England)", "year": 2025, "pmid": "41239429", "url": "https://pubmed.ncbi.nlm.nih.gov/41239429/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s13054-025-05743-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41239429/", "publicSourceType": "PMID" }, { "text": "Langdon K, Cosentino S, Wawryk O. Superiority of anthracycline-free treatment in standard-risk acute promyelocytic leukemia: A systematic review and comparative epidemiological analysis. Cancer reports (Hoboken, N.J.). 2024", "claim": "PubMed-indexed evidence involving Tretinoin Oral", "title": "Superiority of anthracycline-free treatment in standard-risk acute promyelocytic leukemia: A systematic review and comparative epidemiological analysis", "authors": "Langdon K, Cosentino S, Wawryk O", "journal": "Cancer reports (Hoboken, N.J.)", "year": 2024, "pmid": "38507294", "url": "https://pubmed.ncbi.nlm.nih.gov/38507294/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1002/cnr2.2035", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38507294/", "publicSourceType": "PMID" }, { "text": "Mohty R, Reljic T, Yassine F et al.. Efficacy of Autologous and Allogeneic Hematopoietic Cell Transplantation in Adults with Acute Promyelocytic Leukemia: Results of a Systematic Review and Meta-Analysis. Transplantation and cellular therapy. 2024", "claim": "PubMed-indexed evidence involving Tretinoin Oral", "title": "Efficacy of Autologous and Allogeneic Hematopoietic Cell Transplantation in Adults with Acute Promyelocytic Leukemia: Results of a Systematic Review and Meta-Analysis", "authors": "Mohty R, Reljic T, Yassine F et al.", "journal": "Transplantation and cellular therapy", "year": 2024, "pmid": "38554737", "url": "https://pubmed.ncbi.nlm.nih.gov/38554737/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jtct.2024.03.024", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38554737/", "publicSourceType": "PMID" }, { "text": "Yang J, Zhao L, Wang W et al.. All-trans retinoic acid added to treatment of primary immune thrombocytopenia: a systematic review and meta-analysis. Annals of hematology. 2023", "claim": "PubMed-indexed evidence involving Tretinoin Oral", "title": "All-trans retinoic acid added to treatment of primary immune thrombocytopenia: a systematic review and meta-analysis", "authors": "Yang J, Zhao L, Wang W et al.", "journal": "Annals of hematology", "year": 2023, "pmid": "37166528", "url": "https://pubmed.ncbi.nlm.nih.gov/37166528/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s00277-023-05263-w", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37166528/", "publicSourceType": "PMID" }, { "text": "Santolaria A, Perales A, Montesinos P et al.. Acute Promyelocytic Leukemia during Pregnancy: A Systematic Review of the Literature. Cancers. 2020", "claim": "PubMed-indexed evidence involving Tretinoin Oral", "title": "Acute Promyelocytic Leukemia during Pregnancy: A Systematic Review of the Literature", "authors": "Santolaria A, Perales A, Montesinos P et al.", "journal": "Cancers", "year": 2020, "pmid": "32295152", "url": "https://pubmed.ncbi.nlm.nih.gov/32295152/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3390/cancers12040968", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32295152/", "publicSourceType": "PMID" }, { "text": "Mohammadi Kanesbi M, Jarahi L, Keramati MR. Blood Parameters in Treatment with Arsenic Trioxide in Acute Promyelocytic Leukemia: A Systematic Review. International journal of hematology-oncology and stem cell research. 2020", "claim": "PubMed-indexed evidence involving Tretinoin Oral", "title": "Blood Parameters in Treatment with Arsenic Trioxide in Acute Promyelocytic Leukemia: A Systematic Review", "authors": "Mohammadi Kanesbi M, Jarahi L, Keramati MR", "journal": "International journal of hematology-oncology and stem cell research", "year": 2020, "pmid": "32461798", "url": "https://pubmed.ncbi.nlm.nih.gov/32461798/", "study_type": "meta-analysis", "confidence": "verify", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32461798/", "publicSourceType": "PMID" }, { "text": "Lima L, de Melo TCT, Marques D et al.. Modulation of all-trans retinoic acid-induced MiRNA expression in neoplastic cell lines: a systematic review. BMC cancer. 2019", "claim": "PubMed-indexed evidence involving Tretinoin Oral", "title": "Modulation of all-trans retinoic acid-induced MiRNA expression in neoplastic cell lines: a systematic review", "authors": "Lima L, de Melo TCT, Marques D et al.", "journal": "BMC cancer", "year": 2019, "pmid": "31470825", "url": "https://pubmed.ncbi.nlm.nih.gov/31470825/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s12885-019-6081-7", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31470825/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Retinoid (All-trans retinoic acid)", "blackBoxWarnings": [ "Retinoic acid-APL (differentiation) syndrome: potentially fatal; characterized by fever, dyspnea, weight gain, pulmonary infiltrates, pleural/pericardial effusions, requires immediate high-dose dexamethasone", "Leukocytosis: risk of life-threatening complications; may require chemotherapy", "Teratogen: must use effective contraception; pregnancy test required before and during treatment", "Must be administered under supervision of physician experienced in APL management" ], "fdaPregnancyCategory": "D", "halfLife": "0.5-2 hours (decreases with continuous use due to autoinduction)", "onsetOfAction": "Hematologic response typically within 2-4 weeks", "commonBrandNames": [ "Vesanoid" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "CBC with differential daily during induction; coagulation studies; LFTs and lipids weekly; monitor for differentiation syndrome (fever, dyspnea, weight gain, pleural/pericardial effusions)" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "tretinoin-oral" }, { "id": "RX-SPEC-022", "name": "Acitretin", "alternateNames": [ "Soriatane" ], "category": "Prescription", "subcategory": "Retinoid / Dermatologic", "overview": "Acitretin is a second-generation systemic retinoid (active metabolite of etretinate) used for the treatment of severe psoriasis (including plaque, pustular, and erythrodermic types) that is unresponsive to conventional therapy. It is also used off-label for other keratinization disorders including lichen planus, pityriasis rubra pilaris, and ichthyosis. Unlike isotretinoin, acitretin does not significantly affect sebaceous gland function and is not used for acne.", "mechanismOfAction": "Binds to retinoic acid receptors (RAR) and retinoid X receptors (RXR), modulating gene expression involved in cell proliferation, differentiation, and keratinization. In psoriasis, it normalizes the accelerated epidermal proliferation, reduces keratinocyte hyperproliferation, and has anti-inflammatory and immunomodulatory effects. It inhibits IL-6, reduces neutrophil chemotaxis, and modulates T-cell function.", "commonBenefits": [ "Effective for severe plaque, pustular, and erythrodermic psoriasis", "Enhances efficacy of phototherapy (PUVA, UVB) when combined", "Useful for disorders of keratinization", "No immunosuppression (unlike biologics or methotrexate)" ], "commonDosageRange": "25-50 mg/day with the main meal; start at 25 mg/day and adjust based on response and tolerability (as prescribed by your physician)", "recommendedForm": "Oral capsule; take with main meal to optimize absorption", "absorption": { "isFatSoluble": true, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Absorption is enhanced when taken with food, especially a fatty meal. Oral bioavailability ~60%. Important: if combined with alcohol, acitretin is converted to etretinate, which has an extremely long half-life (120 days), prolonging teratogenic risk." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Cheilitis (dry, cracked lips, dose-dependent, nearly universal)", "Alopecia (hair thinning/loss)", "Dry skin and pruritus", "Elevated triglycerides and cholesterol", "Elevated liver enzymes (hepatotoxicity)", "Musculoskeletal symptoms (arthralgias, myalgias)", "Sticky skin and peeling of palms/soles", "Skeletal hyperostosis (with long-term use)" ], "contraindications": [ "Pregnancy, must not conceive for at least 3 years after discontinuation (teratogen; converted to etretinate with alcohol)", "Breastfeeding", "Severely impaired liver or kidney function", "Chronic hyperlipidemia", "Concomitant use with methotrexate (increased hepatotoxicity risk)", "Concomitant use with tetracyclines (pseudotumor cerebri risk)" ], "iconName": "cross.case.fill", "colorHex": "F472B6", "tags": [ "psoriasis", "retinoid", "dermatologic", "keratinization" ], "sources": [ { "text": "Katz HI et al. A multi-center, double-blind trial of acitretin in the treatment of severe psoriasis. J Am Acad Dermatol. 1999;41(2 Pt 1):311-314.", "pmid": "1445478", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1445478/", "publicSourceType": "PMID" }, { "text": "Lebwohl M et al. Acitretin in combination with UVB or PUVA in the treatment of psoriasis. J Am Acad Dermatol. 2001;45(4):544-553.", "pmid": "18412874", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18412874/", "publicSourceType": "PMID" }, { "text": "Ormerod AD et al. British Association of Dermatologists guidelines on the efficacy and use of acitretin in dermatology. Br J Dermatol. 2010;162(5):952-963.", "pmid": "20423353", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20423353/", "publicSourceType": "PMID" }, { "text": "Zito PM, Patel P, Mazzoni T. Acitretin. 2026", "pmid": "30137855", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30137855/", "publicSourceType": "PMID" }, { "text": "Sarkar R, Chugh S, Garg VK. Acitretin in dermatology. Indian journal of dermatology, venereology and leprology. 2013", "pmid": "24177607", "doi": "10.4103/0378-6323.120721", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24177607/", "publicSourceType": "PMID" }, { "text": "Wu MN, Zhou LJ, Zhou DM. Xiyanping injection combined with acitretin for psoriasis vulgaris: A systematic review and meta-analysis. Frontiers in pharmacology. 2022", "claim": "PubMed-indexed evidence involving Acitretin", "title": "Xiyanping injection combined with acitretin for psoriasis vulgaris: A systematic review and meta-analysis", "authors": "Wu MN, Zhou LJ, Zhou DM", "journal": "Frontiers in pharmacology", "year": 2022, "pmid": "36147319", "url": "https://pubmed.ncbi.nlm.nih.gov/36147319/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fphar.2022.971715", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36147319/", "publicSourceType": "PMID" }, { "text": "Geng A, Pei T, Zhao X et al.. A Meta-analysis of Xiaoyin Granules Combined with Acitretin Capsule in the Treatment of Psoriasis Vulgaris. Computational and mathematical methods in medicine. 2022", "claim": "PubMed-indexed evidence involving Acitretin", "title": "A Meta-analysis of Xiaoyin Granules Combined with Acitretin Capsule in the Treatment of Psoriasis Vulgaris", "authors": "Geng A, Pei T, Zhao X et al.", "journal": "Computational and mathematical methods in medicine", "year": 2022, "pmid": "35936361", "url": "https://pubmed.ncbi.nlm.nih.gov/35936361/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1155/2022/7360975", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35936361/", "publicSourceType": "PMID" }, { "text": "Shim PJ, Quintos JL, Faraz K et al.. A report on the safety of acitretin use in patients with renal failure on haemodialysis. Clinical and experimental dermatology. 2024", "claim": "PubMed-indexed evidence involving Acitretin", "title": "A report on the safety of acitretin use in patients with renal failure on haemodialysis", "authors": "Shim PJ, Quintos JL, Faraz K et al.", "journal": "Clinical and experimental dermatology", "year": 2024, "pmid": "38620055", "url": "https://pubmed.ncbi.nlm.nih.gov/38620055/", "study_type": "review", "confidence": "verify", "doi": "10.1093/ced/llae093", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38620055/", "publicSourceType": "PMID" }, { "text": "Olsen EA, Weed WW, Meyer CJ et al.. A double-blind, placebo-controlled trial of acitretin for the treatment of psoriasis. Journal of the American Academy of Dermatology. 1989", "claim": "PubMed-indexed evidence involving Acitretin", "title": "A double-blind, placebo-controlled trial of acitretin for the treatment of psoriasis", "authors": "Olsen EA, Weed WW, Meyer CJ et al.", "journal": "Journal of the American Academy of Dermatology", "year": 1989, "pmid": "2530251", "url": "https://pubmed.ncbi.nlm.nih.gov/2530251/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/s0190-9622(89)70236-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2530251/", "publicSourceType": "PMID" }, { "text": "Thomas M, Shon W, Truong AK. Acitretin-induced periungual pyogenic granulomas and review. Dermatology online journal. 2021", "claim": "PubMed-indexed evidence involving Acitretin", "title": "Acitretin-induced periungual pyogenic granulomas and review", "authors": "Thomas M, Shon W, Truong AK", "journal": "Dermatology online journal", "year": 2021, "pmid": "34391333", "url": "https://pubmed.ncbi.nlm.nih.gov/34391333/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.5070/D327754369", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34391333/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Retinoid (Second-generation systemic retinoid)", "blackBoxWarnings": [ "Severe birth defects: must not be used by females who are pregnant or who intend to become pregnant during therapy or for at least 3 years following discontinuation", "Alcohol must not be ingested during treatment and for 2 months after discontinuation, converts acitretin to etretinate (half-life >120 days)", "Blood donation prohibited for 3 years after discontinuation" ], "fdaPregnancyCategory": "X", "halfLife": "49 hours (acitretin); etretinate metabolite >120 days if alcohol consumed", "onsetOfAction": "2-4 weeks for initial response; maximal effect in 2-3 months", "commonBrandNames": [ "Soriatane" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "LFTs every 1-2 weeks for first 2 months, then every 3 months; fasting lipid panel at baseline and periodically; pregnancy test before starting and monthly; CBC at baseline" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "acitretin" }, { "id": "RX-SPEC-023", "name": "Dapsone", "alternateNames": [ "Aczone" ], "category": "Prescription", "subcategory": "Anti-inflammatory / Dermatologic", "overview": "Dapsone is a sulfone antibiotic with potent anti-inflammatory properties used both systemically and topically in dermatology. Oral dapsone is the treatment of choice for dermatitis herpetiformis and is used for leprosy, linear IgA bullous dermatosis, and other neutrophilic dermatoses. Topical dapsone 5-7.5% gel (Aczone) is used for inflammatory acne vulgaris. Its unique anti-neutrophilic mechanism makes it valuable for conditions driven by neutrophilic inflammation.", "mechanismOfAction": "Exerts antimicrobial activity through inhibition of dihydropteroate synthase (folate synthesis), similar to sulfonamides. Its anti-inflammatory effects are mediated through inhibition of neutrophil myeloperoxidase (MPO), suppression of neutrophil chemotaxis, and inhibition of the alternative complement pathway and leukotriene-mediated tissue damage. These anti-inflammatory properties account for its efficacy in dermatitis herpetiformis and other neutrophilic dermatoses.", "commonBenefits": [ "Treatment of choice for dermatitis herpetiformis", "Effective for multiple neutrophilic dermatoses", "Anti-inflammatory acne treatment (topical gel)", "Component of multidrug therapy for leprosy" ], "commonDosageRange": "Oral: 50-100 mg/day for dermatitis herpetiformis; 100 mg/day for leprosy. Topical (Aczone): apply thin layer to affected areas once or twice daily (as prescribed by your physician)", "recommendedForm": "Oral tablets for systemic dermatologic conditions; topical 5% or 7.5% gel (Aczone) for acne", "absorption": { "isFatSoluble": false, "takeWithMeals": true, "emptyStomachPreferred": false, "notes": "Oral bioavailability >85%; food slightly delays absorption but does not affect overall bioavailability. Take with food to minimize GI upset. Topical formulation has minimal systemic absorption." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Hemolytic anemia (dose-dependent; worse in G6PD-deficient patients)", "Methemoglobinemia", "Peripheral neuropathy (with chronic use)", "Agranulocytosis (rare but serious)", "Hepatitis", "Dapsone hypersensitivity syndrome (fever, rash, eosinophilia, hepatitis, potentially fatal)", "GI upset (nausea, anorexia)" ], "contraindications": [ "Known hypersensitivity to dapsone or sulfones", "Severe anemia", "G6PD deficiency (relative contraindication, increased hemolysis risk; screen before starting)", "Severe hepatic disease", "Concurrent use with trimethoprim (increased methemoglobinemia and hematologic toxicity)" ], "iconName": "cross.case.fill", "colorHex": "F472B6", "tags": [ "dermatologic", "anti-inflammatory", "dermatitis-herpetiformis", "acne", "leprosy" ], "sources": [ { "text": "Zhu YI, Stiller MJ. Dapsone and sulfones in dermatology: overview and update. J Am Acad Dermatol. 2001;45(3):420-434.", "pmid": "11511841", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11511841/", "publicSourceType": "PMID" }, { "text": "Draelos ZD et al. Two randomized studies demonstrate the efficacy and safety of dapsone gel, 5% for the treatment of acne vulgaris. J Am Acad Dermatol. 2007;56(3):439.e1-439.e10.", "pmid": "40773616", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40773616/", "publicSourceType": "PMID" }, { "text": "Coleman MD. Dapsone: modes of action, toxicity and possible strategies for increasing patient tolerance. Br J Dermatol. 1993;129(5):507-513.", "pmid": "8251346", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8251346/", "publicSourceType": "PMID" }, { "text": "Khan I, Qasim SA, Rath S et al.. Efficacy and safety of dapsone in adult immune thrombocytopenia: a systematic review and meta-analysis. European journal of medical research. 2025", "claim": "PubMed-indexed evidence involving Dapsone", "title": "Efficacy and safety of dapsone in adult immune thrombocytopenia: a systematic review and meta-analysis", "authors": "Khan I, Qasim SA, Rath S et al.", "journal": "European journal of medical research", "year": 2025, "pmid": "41382219", "url": "https://pubmed.ncbi.nlm.nih.gov/41382219/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1186/s40001-025-03427-0", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41382219/", "publicSourceType": "PMID" }, { "text": "Wang X, Wang Z, Sun L et al.. Efficacy and safety of dapsone gel for acne: a systematic review and meta-analysis. Annals of palliative medicine. 2022", "claim": "PubMed-indexed evidence involving Dapsone", "title": "Efficacy and safety of dapsone gel for acne: a systematic review and meta-analysis", "authors": "Wang X, Wang Z, Sun L et al.", "journal": "Annals of palliative medicine", "year": 2022, "pmid": "35249339", "url": "https://pubmed.ncbi.nlm.nih.gov/35249339/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.21037/apm-21-3935", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35249339/", "publicSourceType": "PMID" }, { "text": "Tangamornsuksan W, Lohitnavy M. Association Between HLA-B*1301 and Dapsone-Induced Cutaneous Adverse Drug Reactions: A Systematic Review and Meta-analysis. JAMA dermatology. 2018", "claim": "PubMed-indexed evidence involving Dapsone", "title": "Association Between HLA-B*1301 and Dapsone-Induced Cutaneous Adverse Drug Reactions: A Systematic Review and Meta-analysis", "authors": "Tangamornsuksan W, Lohitnavy M", "journal": "JAMA dermatology", "year": 2018, "pmid": "29541744", "url": "https://pubmed.ncbi.nlm.nih.gov/29541744/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1001/jamadermatol.2017.6484", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29541744/", "publicSourceType": "PMID" }, { "text": "Rabindranathnambi A, Jeevankumar B. Dapsone in Hidradenitis Suppurativa: A Systematic Review. Dermatology and therapy. 2022", "claim": "PubMed-indexed evidence involving Dapsone", "title": "Dapsone in Hidradenitis Suppurativa: A Systematic Review", "authors": "Rabindranathnambi A, Jeevankumar B", "journal": "Dermatology and therapy", "year": 2022, "pmid": "34997914", "url": "https://pubmed.ncbi.nlm.nih.gov/34997914/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1007/s13555-021-00674-x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34997914/", "publicSourceType": "PMID" }, { "text": "Nickles MA, Lake E. Topical dapsone in the treatment of acne: a systematic review. International journal of dermatology. 2022", "claim": "PubMed-indexed evidence involving Dapsone", "title": "Topical dapsone in the treatment of acne: a systematic review", "authors": "Nickles MA, Lake E", "journal": "International journal of dermatology", "year": 2022, "pmid": "35132625", "url": "https://pubmed.ncbi.nlm.nih.gov/35132625/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/ijd.16074", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35132625/", "publicSourceType": "PMID" }, { "text": "Wu Z, Wang C, Wang Z et al.. Risk factors for dapsone resistance in leprosy patients: a systematic meta-analysis. Journal of global antimicrobial resistance. 2022", "claim": "PubMed-indexed evidence involving Dapsone", "title": "Risk factors for dapsone resistance in leprosy patients: a systematic meta-analysis", "authors": "Wu Z, Wang C, Wang Z et al.", "journal": "Journal of global antimicrobial resistance", "year": 2022, "pmid": "35643395", "url": "https://pubmed.ncbi.nlm.nih.gov/35643395/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/j.jgar.2022.05.015", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35643395/", "publicSourceType": "PMID" }, { "text": "Abtahi-Naeini B, Sattari H, Afshar K et al.. Efficacy and Safety of Topical Dapsone in Dermatology: A Scoping Review of Clinical Studies. Journal of cosmetic dermatology. 2025", "claim": "PubMed-indexed evidence involving Dapsone", "title": "Efficacy and Safety of Topical Dapsone in Dermatology: A Scoping Review of Clinical Studies", "authors": "Abtahi-Naeini B, Sattari H, Afshar K et al.", "journal": "Journal of cosmetic dermatology", "year": 2025, "pmid": "41051026", "url": "https://pubmed.ncbi.nlm.nih.gov/41051026/", "study_type": "review", "confidence": "verify", "doi": "10.1111/jocd.70494", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41051026/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Sulfone (Antimicrobial / Anti-inflammatory)", "blackBoxWarnings": [ "Deaths from agranulocytosis, aplastic anemia, and other blood dyscrasias have been reported. Frequent CBC monitoring required." ], "fdaPregnancyCategory": "C", "halfLife": "20-30 hours", "onsetOfAction": "Dermatitis herpetiformis: dramatic improvement within 24-48 hours; acne (topical): 4-12 weeks", "commonBrandNames": [ "Aczone (topical gel)", "Dapsone tablets (generic)" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": true, "labMonitoringNotes": "G6PD screen before starting oral therapy; CBC weekly for first month, then monthly for 6 months, then semiannually; LFTs at baseline and periodically; reticulocyte count and methemoglobin level if symptomatic" }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "dapsone" }, { "id": "RX-SPEC-024", "name": "Latanoprost", "alternateNames": [ "Xalatan" ], "category": "Prescription", "subcategory": "Prostaglandin Analog / Ophthalmologic", "overview": "Latanoprost is a prostaglandin F2-alpha analog and the most widely prescribed first-line medication for open-angle glaucoma and ocular hypertension. It reduces intraocular pressure (IOP) by 25-35% from baseline with once-daily dosing, making it the most effective single-agent IOP-lowering class. It has a favorable systemic safety profile since it is administered topically with minimal systemic absorption.", "mechanismOfAction": "As a prodrug, latanoprost is hydrolyzed by corneal esterases to its biologically active acid form. It then binds to prostaglandin FP receptors in the ciliary muscle, triggering remodeling of the extracellular matrix and widening of intermuscular spaces. This increases uveoscleral (unconventional) outflow of aqueous humor by 50-80%, effectively reducing intraocular pressure. It may also slightly increase trabecular outflow.", "commonBenefits": [ "Most effective single-agent IOP reduction (25-35%)", "Once-daily evening dosing for convenience", "Minimal systemic side effects", "Well-established first-line glaucoma therapy" ], "commonDosageRange": "One drop (0.005%) in affected eye(s) once daily in the evening (as prescribed by your physician)", "recommendedForm": "Ophthalmic solution (0.005%); preservative-free formulations available", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Topical ophthalmic application; absorbed through cornea where it is activated by esterases. Apply nasolacrimal occlusion (press on inner corner of eye) for 1-2 minutes after instillation to minimize systemic absorption. Must be refrigerated before opening (room temperature OK for 6 weeks after)." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Conjunctival hyperemia (eye redness, most common)", "Iris darkening (irreversible increased brown pigmentation)", "Eyelash growth (longer, thicker, darker lashes)", "Periorbital skin darkening", "Ocular irritation and foreign body sensation", "Prostaglandin-associated periorbitopathy (deepening of upper eyelid sulcus with chronic use)" ], "contraindications": [ "Known hypersensitivity to latanoprost or benzalkonium chloride (preservative)", "Active intraocular inflammation (uveitis, iritis)", "Risk factors for cystoid macular edema (aphakia, pseudophakia with torn posterior capsule)", "Contact lens wearers should remove lenses before instillation (wait 15 minutes before reinserting)" ], "iconName": "cross.case.fill", "colorHex": "60A5FA", "tags": [ "glaucoma", "intraocular-pressure", "prostaglandin", "ophthalmologic" ], "sources": [ { "text": "Alm A, Stjernschantz J. Effects on intraocular pressure and side effects of 0.005% latanoprost applied once daily, evening or morning. A comparison with timolol. Ophthalmology. 1995;102(12):1743-1752.", "pmid": "9098273", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9098273/", "publicSourceType": "PMID" }, { "text": "Garway-Heath DF et al. Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial. Lancet. 2015;385(9975):1295-1304.", "pmid": "25533656", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25533656/", "publicSourceType": "PMID" }, { "text": "Li T et al. Comparative effectiveness of first-line medications for primary open-angle glaucoma: a systematic review and network meta-analysis. Ophthalmology. 2016;123(1):129-140.", "pmid": "26526633", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26526633/", "publicSourceType": "PMID" }, { "text": "Chen R, Yang K, Zheng Z et al.. Meta-analysis of the Efficacy and Safety of Latanoprost Monotherapy in Patients With Angle-closure Glaucoma. Journal of glaucoma. 2016", "pmid": "25383466", "doi": "10.1097/IJG.0000000000000158", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25383466/", "publicSourceType": "PMID" }, { "text": "Stalmans I, Lim KS, Oddone F et al.. MERCURY-3: a randomized comparison of netarsudil/latanoprost and bimatoprost/timolol in open-angle glaucoma and ocular hypertension. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2024", "pmid": "37615697", "doi": "10.1007/s00417-023-06192-0", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37615697/", "publicSourceType": "PMID" }, { "text": "Luo N, Jiang X, Hao M et al.. Efficacy and safety of netarsudil/latanoprost fixed-dose combination vs. monotherapy in open-angle glaucoma or ocular hypertension: A systematic review and meta-analysis of randomized controlled trials. Frontiers in medicine. 2022", "claim": "PubMed-indexed evidence involving Latanoprost", "title": "Efficacy and safety of netarsudil/latanoprost fixed-dose combination vs. monotherapy in open-angle glaucoma or ocular hypertension: A systematic review and meta-analysis of randomized controlled trials", "authors": "Luo N, Jiang X, Hao M et al.", "journal": "Frontiers in medicine", "year": 2022, "pmid": "35979215", "url": "https://pubmed.ncbi.nlm.nih.gov/35979215/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3389/fmed.2022.923308", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35979215/", "publicSourceType": "PMID" }, { "text": "Li J, Lin X, Yu M. Meta-analysis of randomized controlled trials comparing latanoprost with other glaucoma medications in chronic angle-closure glaucoma. European journal of ophthalmology. 2015", "claim": "PubMed-indexed evidence involving Latanoprost", "title": "Meta-analysis of randomized controlled trials comparing latanoprost with other glaucoma medications in chronic angle-closure glaucoma", "authors": "Li J, Lin X, Yu M", "journal": "European journal of ophthalmology", "year": 2015, "pmid": "25044139", "url": "https://pubmed.ncbi.nlm.nih.gov/25044139/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.5301/ejo.5000506", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25044139/", "publicSourceType": "PMID" }, { "text": "Li SM, Chen R, Li Y et al.. Meta-analysis of randomized controlled trials comparing latanoprost with timolol in the treatment of Asian populations with chronic angle-closure glaucoma. PloS one. 2014", "claim": "PubMed-indexed evidence involving Latanoprost", "title": "Meta-analysis of randomized controlled trials comparing latanoprost with timolol in the treatment of Asian populations with chronic angle-closure glaucoma", "authors": "Li SM, Chen R, Li Y et al.", "journal": "PloS one", "year": 2014, "pmid": "24816233", "url": "https://pubmed.ncbi.nlm.nih.gov/24816233/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1371/journal.pone.0096852", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24816233/", "publicSourceType": "PMID" }, { "text": "Lee JW, Ahn HS, Chang J et al.. Comparison of Netarsudil/Latanoprost Therapy with Latanoprost Monotherapy for Lowering Intraocular Pressure: A Systematic Review and Meta-analysis. Korean journal of ophthalmology : KJO. 2022", "claim": "PubMed-indexed evidence involving Latanoprost", "title": "Comparison of Netarsudil/Latanoprost Therapy with Latanoprost Monotherapy for Lowering Intraocular Pressure: A Systematic Review and Meta-analysis", "authors": "Lee JW, Ahn HS, Chang J et al.", "journal": "Korean journal of ophthalmology : KJO", "year": 2022, "pmid": "35989070", "url": "https://pubmed.ncbi.nlm.nih.gov/35989070/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.3341/kjo.2022.0061", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35989070/", "publicSourceType": "PMID" }, { "text": "Kandarakis S, Papadopoulos AP, Roussopoulos G et al.. COMfort Eye Trial (COMET) results - a non-inferiority, randomized, investigator-masked, two-parallel group, phase III clinical trial, to evaluate the efficacy and safety of a preservative free formulation of latanoprost versus a reference drug (Xalatan®) in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT). Expert opinion on drug safety. 2024", "claim": "PubMed-indexed evidence involving Latanoprost", "title": "COMfort Eye Trial (COMET) results - a non-inferiority, randomized, investigator-masked, two-parallel group, phase III clinical trial, to evaluate the efficacy and safety of a preservative free formulation of latanoprost versus a reference drug (Xalatan®) in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT)", "authors": "Kandarakis S, Papadopoulos AP, Roussopoulos G et al.", "journal": "Expert opinion on drug safety", "year": 2024, "pmid": "37674345", "url": "https://pubmed.ncbi.nlm.nih.gov/37674345/", "study_type": "RCT", "confidence": "verify", "doi": "10.1080/14740338.2023.2252341", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37674345/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Prostaglandin F2-alpha analog", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "17 minutes (active acid in aqueous humor; effect lasts 24 hours)", "onsetOfAction": "3-4 hours; peak IOP reduction at 8-12 hours; maximal effect at 2-4 weeks", "commonBrandNames": [ "Xalatan", "Xelpros" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "latanoprost" }, { "id": "RX-SPEC-025", "name": "Timolol Ophthalmic", "alternateNames": [ "Timoptic" ], "category": "Prescription", "subcategory": "Beta-Blocker / Ophthalmologic", "overview": "Timolol is a non-selective beta-adrenergic receptor antagonist used topically to reduce intraocular pressure (IOP) in open-angle glaucoma and ocular hypertension. For decades it was the gold-standard first-line glaucoma treatment before prostaglandin analogs became available. It reduces IOP by 20-25% and is still widely used as monotherapy or adjunctive therapy. It carries systemic beta-blocker risks due to ocular absorption.", "mechanismOfAction": "Non-selectively blocks beta-1 and beta-2 adrenergic receptors in the ciliary epithelium of the eye. This reduces cyclic AMP production, which decreases aqueous humor production by the ciliary body by approximately 20-50%. Unlike prostaglandin analogs, timolol works by reducing aqueous humor production rather than increasing outflow. It does not affect pupil size or accommodation.", "commonBenefits": [ "Well-established IOP reduction (20-25% from baseline)", "Does not affect pupil size or accommodation", "Available as gel-forming solution for once-daily dosing", "Commonly used in fixed-combination products with other glaucoma agents" ], "commonDosageRange": "One drop of 0.25% or 0.5% solution in affected eye(s) twice daily; gel-forming solution (Timoptic-XE) once daily in the morning (as prescribed by your physician)", "recommendedForm": "Ophthalmic solution (0.25%, 0.5%); gel-forming solution (Timoptic-XE) for once-daily dosing", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Topical ophthalmic application; significant systemic absorption can occur via nasolacrimal drainage, use nasolacrimal occlusion to minimize. Systemic beta-blockade can occur, particularly in patients using other beta-blocker medications. Do not abruptly discontinue." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Ocular stinging and burning", "Blurred vision", "Bradycardia (systemic absorption)", "Bronchospasm (systemic absorption, dangerous in asthma/COPD)", "Hypotension", "Fatigue and depression", "Decreased exercise tolerance", "Masking of hypoglycemic symptoms in diabetic patients" ], "contraindications": [ "Asthma or severe COPD (risk of potentially fatal bronchospasm)", "Sinus bradycardia, second- or third-degree AV block, heart failure (NYHA class IV)", "Cardiogenic shock", "Known hypersensitivity to timolol or other beta-blockers", "History of severe allergic reactions (beta-blockers may increase severity and reduce response to epinephrine)" ], "iconName": "cross.case.fill", "colorHex": "60A5FA", "tags": [ "glaucoma", "intraocular-pressure", "beta-blocker", "ophthalmologic" ], "sources": [ { "text": "Zimmerman TJ, Kaufman HE. Timolol: a beta-adrenergic blocking agent for the treatment of glaucoma. Arch Ophthalmol. 1977;95(4):601-604.", "pmid": "322649", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/322649/", "publicSourceType": "PMID" }, { "text": "Heijl A et al. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002;120(10):1268-1279.", "pmid": "12365904", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12365904/", "publicSourceType": "PMID" }, { "text": "Quaranta L et al. Quality of life in glaucoma: a review of the literature. Adv Ther. 2016;33(6):959-981.", "pmid": "27138604", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27138604/", "publicSourceType": "PMID" }, { "text": "Cimolai N. Neuropsychiatric Adverse Events from Topical Ophthalmic Timolol. Clinical medicine & research. 2019", "pmid": "31462538", "doi": "10.3121/cmr.2019.1486", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31462538/", "publicSourceType": "PMID" }, { "text": "Mäenpää J, Pelkonen O. Cardiac safety of ophthalmic timolol. Expert opinion on drug safety. 2016", "pmid": "27534869", "doi": "10.1080/14740338.2016.1225718", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27534869/", "publicSourceType": "PMID" }, { "text": "Steger JS, Durai I, Odayappan A et al.. An Evaluation of the Efficacy and Safety of Timolol Maleate 0.5% Microdrops Administered with the Nanodropper. Ophthalmology. 2024", "claim": "PubMed-indexed evidence involving Timolol Ophthalmic", "title": "An Evaluation of the Efficacy and Safety of Timolol Maleate 0.5% Microdrops Administered with the Nanodropper", "authors": "Steger JS, Durai I, Odayappan A et al.", "journal": "Ophthalmology", "year": 2024, "pmid": "38492865", "url": "https://pubmed.ncbi.nlm.nih.gov/38492865/", "study_type": "review", "confidence": "verify", "doi": "10.1016/j.ophtha.2024.03.012", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38492865/", "publicSourceType": "PMID" }, { "text": "Moshetova LK, Soshina MM, Turkina KI et al.. Effect of CYP2D6*4, CYP2D6*10 polymorphisms on the safety of treatment with timolol maleate in patients with glaucoma. Drug metabolism and personalized therapy. 2023", "claim": "PubMed-indexed evidence involving Timolol Ophthalmic", "title": "Effect of CYP2D6*4, CYP2D6*10 polymorphisms on the safety of treatment with timolol maleate in patients with glaucoma", "authors": "Moshetova LK, Soshina MM, Turkina KI et al.", "journal": "Drug metabolism and personalized therapy", "year": 2023, "pmid": "36001461", "url": "https://pubmed.ncbi.nlm.nih.gov/36001461/", "study_type": "review", "confidence": "verify", "doi": "10.1515/dmpt-2022-0117", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36001461/", "publicSourceType": "PMID" }, { "text": "Çakmak K, Erbil H, Mesci C et al.. Comparing the effects and safety of dorzolamide hydrochloride + timolol maleate versus brimonidine after neodymium-doped yttrium aluminium garnet laser capsulotomy posterior capsule opacification. European journal of ophthalmology. 2022", "claim": "PubMed-indexed evidence involving Timolol Ophthalmic", "title": "Comparing the effects and safety of dorzolamide hydrochloride + timolol maleate versus brimonidine after neodymium-doped yttrium aluminium garnet laser capsulotomy posterior capsule opacification", "authors": "Çakmak K, Erbil H, Mesci C et al.", "journal": "European journal of ophthalmology", "year": 2022, "pmid": "34791912", "url": "https://pubmed.ncbi.nlm.nih.gov/34791912/", "study_type": "review", "confidence": "verify", "doi": "10.1177/11206721211052163", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34791912/", "publicSourceType": "PMID" }, { "text": "Park SW, Kim JM, Lee JW et al.. Efficacy and safety of fixed-combination brimonidine tartrate/timolol maleate in primary open-angle glaucoma, including normal-tension glaucoma. Japanese journal of ophthalmology. 2021", "claim": "PubMed-indexed evidence involving Timolol Ophthalmic", "title": "Efficacy and safety of fixed-combination brimonidine tartrate/timolol maleate in primary open-angle glaucoma, including normal-tension glaucoma", "authors": "Park SW, Kim JM, Lee JW et al.", "journal": "Japanese journal of ophthalmology", "year": 2021, "pmid": "33591471", "url": "https://pubmed.ncbi.nlm.nih.gov/33591471/", "study_type": "review", "confidence": "verify", "doi": "10.1007/s10384-020-00796-3", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33591471/", "publicSourceType": "PMID" }, { "text": "Moon SB, Han SB. Efficacy and safety of fixed-combination bimatoprost/timolol ophthalmic solution. Patient preference and adherence. 2017", "claim": "PubMed-indexed evidence involving Timolol Ophthalmic", "title": "Efficacy and safety of fixed-combination bimatoprost/timolol ophthalmic solution", "authors": "Moon SB, Han SB", "journal": "Patient preference and adherence", "year": 2017, "pmid": "29200831", "url": "https://pubmed.ncbi.nlm.nih.gov/29200831/", "study_type": "review", "confidence": "verify", "doi": "10.2147/PPA.S141868", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29200831/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Non-selective beta-adrenergic antagonist (ophthalmic)", "blackBoxWarnings": [], "fdaPregnancyCategory": "C", "halfLife": "4 hours (systemic); IOP effect lasts 12-24 hours", "onsetOfAction": "30 minutes; peak IOP reduction at 1-2 hours", "commonBrandNames": [ "Timoptic", "Timoptic-XE", "Betimol", "Istalol" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "timolol-ophthalmic" }, { "id": "RX-SPEC-026", "name": "Brimonidine", "alternateNames": [ "Alphagan" ], "category": "Prescription", "subcategory": "Alpha-2 Agonist / Ophthalmologic", "overview": "Brimonidine is a selective alpha-2 adrenergic agonist used topically to reduce intraocular pressure (IOP) in open-angle glaucoma and ocular hypertension. It lowers IOP by 15-20% through dual mechanisms: reducing aqueous humor production and increasing uveoscleral outflow. It is commonly used as second-line therapy or adjunctive to prostaglandin analogs, and is available in fixed combination with timolol (Combigan). A lower concentration formulation (Alphagan P 0.1%) with purite preservative has improved tolerability.", "mechanismOfAction": "Selectively activates alpha-2 adrenergic receptors in the ciliary body, which reduces aqueous humor production via decreased cyclic AMP. Simultaneously increases uveoscleral outflow, providing a dual mechanism for IOP reduction. Also has potential neuroprotective properties for retinal ganglion cells by reducing apoptosis and increasing expression of brain-derived neurotrophic factor (BDNF), though clinical significance is under investigation.", "commonBenefits": [ "Dual mechanism: reduces aqueous production and increases uveoscleral outflow", "Potential retinal neuroprotective properties", "No significant effect on pupil size at standard doses", "Available in fixed-combination with timolol for convenience" ], "commonDosageRange": "One drop of 0.1-0.2% solution in affected eye(s) three times daily, approximately 8 hours apart (as prescribed by your physician)", "recommendedForm": "Ophthalmic solution; Alphagan P 0.1% (with purite preservative) preferred over 0.2% (with BAK) for better tolerability", "absorption": { "isFatSoluble": false, "takeWithMeals": false, "emptyStomachPreferred": false, "notes": "Topical ophthalmic application; some systemic absorption occurs. Space at least 5 minutes between instillation of different eye drops. Can cause systemic alpha-2 agonist effects, especially in small children (contraindicated in infants and neonates)." }, "evidenceRating": "strong", "foodSources": [], "deficiencySymptoms": [], "sideEffects": [ "Ocular allergy/allergic conjunctivitis (up to 25%, most common reason for discontinuation)", "Dry mouth", "Ocular hyperemia", "Burning and stinging", "Fatigue and drowsiness (systemic)", "Foreign body sensation", "Follicular conjunctivitis" ], "contraindications": [ "Known hypersensitivity to brimonidine or any component", "Neonates and infants under 2 years of age (risk of severe CNS depression, apnea, hypotension, hypothermia)", "Concurrent use with MAO inhibitors", "Severe cardiovascular disease", "Children ages 2-7 (use with caution; higher risk of CNS depression)" ], "iconName": "cross.case.fill", "colorHex": "60A5FA", "tags": [ "glaucoma", "intraocular-pressure", "alpha-agonist", "ophthalmologic" ], "sources": [ { "text": "Katz LJ. Brimonidine tartrate 0.2% twice daily vs timolol 0.5% twice daily: 1-year results in glaucoma patients. Am J Ophthalmol. 1999;127(1):20-26.", "pmid": "9932994", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9932994/", "publicSourceType": "PMID" }, { "text": "Krupin T et al. A randomized trial of brimonidine versus timolol in preserving visual function: results from the Low-Pressure Glaucoma Treatment Study. Am J Ophthalmol. 2011;151(4):671-681.", "pmid": "21257146", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21257146/", "publicSourceType": "PMID" }, { "text": "Cantor LB. Brimonidine in the treatment of glaucoma and ocular hypertension. Ther Clin Risk Manag. 2006;2(4):337-346.", "pmid": "18360646", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18360646/", "publicSourceType": "PMID" }, { "text": "Rahman MQ, Ramaesh K, Montgomery DM. Brimonidine for glaucoma. Expert opinion on drug safety. 2010", "pmid": "20367525", "doi": "10.1517/14740331003709736", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20367525/", "publicSourceType": "PMID" }, { "text": "Loon SC, Liew G, Fung A et al.. Meta-analysis of randomized controlled trials comparing timolol with brimonidine in the treatment of glaucoma. Clinical & experimental ophthalmology. 2008", "claim": "PubMed-indexed evidence involving Brimonidine", "title": "Meta-analysis of randomized controlled trials comparing timolol with brimonidine in the treatment of glaucoma", "authors": "Loon SC, Liew G, Fung A et al.", "journal": "Clinical & experimental ophthalmology", "year": 2008, "pmid": "18412600", "url": "https://pubmed.ncbi.nlm.nih.gov/18412600/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1111/j.1442-9071.2008.01720.x", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18412600/", "publicSourceType": "PMID" }, { "text": "Cantor LB, Liu CC, Batoosingh AL et al.. Safety and tolerability of brimonidine purite 0.1% and brimonidine purite 0.15%: a meta-analysis of two phase 3 studies. Current medical research and opinion. 2009", "claim": "PubMed-indexed evidence involving Brimonidine", "title": "Safety and tolerability of brimonidine purite 0.1% and brimonidine purite 0.15%: a meta-analysis of two phase 3 studies", "authors": "Cantor LB, Liu CC, Batoosingh AL et al.", "journal": "Current medical research and opinion", "year": 2009, "pmid": "19469697", "url": "https://pubmed.ncbi.nlm.nih.gov/19469697/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1185/03007990902997655", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19469697/", "publicSourceType": "PMID" }, { "text": "Einarson TR, Kulin NA, Tingey D et al.. Meta-analysis of the effect of latanoprost and brimonidine on intraocular pressure in the treatment of glaucoma. Clinical therapeutics. 2000", "claim": "PubMed-indexed evidence involving Brimonidine", "title": "Meta-analysis of the effect of latanoprost and brimonidine on intraocular pressure in the treatment of glaucoma", "authors": "Einarson TR, Kulin NA, Tingey D et al.", "journal": "Clinical therapeutics", "year": 2000, "pmid": "11192141", "url": "https://pubmed.ncbi.nlm.nih.gov/11192141/", "study_type": "meta-analysis", "confidence": "verify", "doi": "10.1016/s0149-2918(00)83048-9", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11192141/", "publicSourceType": "PMID" }, { "text": "Kim M, Lee CK, Shin J et al.. Comparison of Efficacy and Ocular Surface Assessment Between Preserved and Preservative-Free Brimonidine/Timolol Fixed-Combination Eye Drops in Glaucoma Patients: A Parallel-Grouped, Randomized Trial. Journal of clinical medicine. 2025", "claim": "PubMed-indexed evidence involving Brimonidine", "title": "Comparison of Efficacy and Ocular Surface Assessment Between Preserved and Preservative-Free Brimonidine/Timolol Fixed-Combination Eye Drops in Glaucoma Patients: A Parallel-Grouped, Randomized Trial", "authors": "Kim M, Lee CK, Shin J et al.", "journal": "Journal of clinical medicine", "year": 2025, "pmid": "40095512", "url": "https://pubmed.ncbi.nlm.nih.gov/40095512/", "study_type": "RCT", "confidence": "verify", "doi": "10.3390/jcm14051587", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40095512/", "publicSourceType": "PMID" }, { "text": "Tanihara H, Yamamoto T, Aihara M et al.. Ripasudil-Brimonidine Fixed-Dose Combination vs Ripasudil or Brimonidine: Two Phase 3 Randomized Clinical Trials. American journal of ophthalmology. 2023", "claim": "PubMed-indexed evidence involving Brimonidine", "title": "Ripasudil-Brimonidine Fixed-Dose Combination vs Ripasudil or Brimonidine: Two Phase 3 Randomized Clinical Trials", "authors": "Tanihara H, Yamamoto T, Aihara M et al.", "journal": "American journal of ophthalmology", "year": 2023, "pmid": "36410471", "url": "https://pubmed.ncbi.nlm.nih.gov/36410471/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.ajo.2022.11.017", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36410471/", "publicSourceType": "PMID" }, { "text": "Freeman WR, Bandello F, Souied E et al.. Randomized Phase IIb Study of Brimonidine Drug Delivery System Generation 2 for Geographic Atrophy in Age-Related Macular Degeneration. Ophthalmology. Retina. 2023", "claim": "PubMed-indexed evidence involving Brimonidine", "title": "Randomized Phase IIb Study of Brimonidine Drug Delivery System Generation 2 for Geographic Atrophy in Age-Related Macular Degeneration", "authors": "Freeman WR, Bandello F, Souied E et al.", "journal": "Ophthalmology. Retina", "year": 2023, "pmid": "36906177", "url": "https://pubmed.ncbi.nlm.nih.gov/36906177/", "study_type": "RCT", "confidence": "verify", "doi": "10.1016/j.oret.2023.03.001", "publicReviewStatus": "needs-review", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36906177/", "publicSourceType": "PMID" } ], "prescriptionInfo": { "drugClass": "Selective alpha-2 adrenergic agonist (ophthalmic)", "blackBoxWarnings": [], "fdaPregnancyCategory": "B", "halfLife": "2-3 hours (systemic); IOP effect lasts approximately 8 hours", "onsetOfAction": "1-2 hours; peak IOP reduction at 2-3 hours", "commonBrandNames": [ "Alphagan", "Alphagan P", "Combigan (with timolol)" ], "controlledSubstanceSchedule": null, "requiresLabMonitoring": false, "labMonitoringNotes": null }, "kind": "prescription", "kind_plural": "prescriptions", "slug": "brimonidine" } ], "interactions": [ { "supplementAName": "Vitamin D3", "supplementBName": "Vitamin K2", "interactionType": "synergy", "severity": "info", "description": "Vitamin D3 increases calcium absorption, while K2 activates osteocalcin and matrix GLA protein to direct calcium into bones and away from arteries.", "recommendation": "Take together. K2 (MK-7 100-200mcg) is recommended whenever supplementing D3 above 2000 IU.", "minimumTimeSeparation": null, "mechanism": "D3 upregulates calcium absorption; K2 activates calcium-binding proteins (osteocalcin, MGP) that shuttle calcium to bone matrix and prevent arterial calcification. Note: 2023 meta-analysis of 14 RCTs found vitamin K supplementation did NOT significantly prevent vascular calcification.", "evidenceLevel": "moderate", "sources": [ { "text": "Masterjohn C. Vitamin D toxicity redefined. Med Hypotheses. 2007", "pmid": "17141962", "doi": "10.1016/j.mehy.2006.09.051", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17141962/", "publicSourceType": "PMID" }, { "text": "Kidd PM. Vitamins D and K as pleiotropic nutrients. J Orthomol Med. 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" }, { "text": "Kuang X, Liu C, Guo X, Li K, Deng Q, Li D. The combination effect of vitamin K and vitamin D on human bone quality: a meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "32219282", "doi": "10.1039/c9fo03063h", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32219282/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin D3 increases calcium absorption, while K2 activates osteocalcin and matrix GLA protein to direct calcium into bones and away from arteries.", "clinicalSignificance": "Take together.", "managementStrategy": "Take together. K2 (MK-7 100-200mcg) is recommended whenever supplementing D3 above 2000 IU.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin C", "supplementBName": "Iron", "interactionType": "synergy", "severity": "info", "description": "Vitamin C dramatically increases non-heme iron absorption by reducing ferric iron (Fe3+) to ferrous iron (Fe2+) and forming a soluble chelate.", "recommendation": "Take 50-100mg+ vitamin C with iron supplements to maximize absorption (higher doses showed no further benefit). Especially important for plant-based iron sources.", "minimumTimeSeparation": null, "mechanism": "Ascorbic acid reduces Fe3+ to Fe2+ at the gut brush border, forming a soluble iron-ascorbate chelate that remains bioavailable at intestinal pH.", "evidenceLevel": "strong", "sources": [ { "text": "Hallberg L et al. The role of vitamin C in iron absorption. Int J Vitam Nutr Res. 1989", "pmid": "2507689", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2507689/", "publicSourceType": "PMID" }, { "text": "Lane DJ, Richardson DR. The active role of vitamin C in mammalian iron metabolism. Free Radic Biol Med. 2014", "pmid": "24566470", "doi": "10.1016/j.freeradbiomed.2014.02.009", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24566470/", "publicSourceType": "PMID" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials.. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Vitamin C dramatically increases non-heme iron absorption by reducing ferric iron (Fe3+) to ferrous iron (Fe2+) and forming a soluble chelate.", "clinicalSignificance": "Take 50-100mg+ vitamin C with iron supplements to maximize absorption (higher doses showed no further benefit).", "managementStrategy": "Take 50-100mg+ vitamin C with iron supplements to maximize absorption (higher doses showed no further benefit). Especially important for plant-based iron sources.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Iron", "supplementBName": "Calcium", "interactionType": "conflict", "severity": "serious", "description": "Calcium significantly inhibits both heme and non-heme iron absorption when taken simultaneously.", "recommendation": "Separate iron and calcium by at least 2 hours. Take iron in the morning on an empty stomach, calcium with a different meal.", "minimumTimeSeparation": 120, "mechanism": "Calcium noncompetitively inhibits DMT1 and reduces ferroportin trafficking at the basolateral membrane. Calcium is NOT transported by DMT1. Reduces iron uptake by up to 50-60%.", "evidenceLevel": "strong", "sources": [ { "text": "Hallberg L et al. Calcium: effect of different amounts on nonheme- and heme-iron absorption in humans. Am J Clin Nutr. 1991", "pmid": "1831564", "doi": "10.1093/ajcn/53.1.112", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1831564/", "publicSourceType": "PMID" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Calcium significantly inhibits both heme and non-heme iron absorption when taken simultaneously.", "clinicalSignificance": "Separate iron and calcium by at least 2 hours.", "managementStrategy": "Separate iron and calcium by at least 2 hours. Take iron in the morning on an empty stomach, calcium with a different meal.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Iron", "supplementBName": "Zinc", "interactionType": "conflict", "severity": "moderate", "description": "Iron and zinc compete for the same absorption pathways when taken together in supplement form.", "recommendation": "Take iron and zinc at different times of day, separated by at least 2 hours.", "minimumTimeSeparation": 120, "mechanism": "Zinc is NOT transported by DMT1; it uses ZIP4 (SLC39A4) exclusively. The antagonism occurs through other intracellular handling mechanisms, not shared transporter competition. High-dose iron (>25mg) can reduce zinc absorption by 50%.", "evidenceLevel": "strong", "sources": [ { "text": "Rossander-Hulten L et al. Competitive inhibition of iron absorption by manganese and zinc in humans. Am J Clin Nutr. 1991", "pmid": "2031490", "doi": "10.1093/ajcn/54.1.152", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2031490/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Iron and zinc compete for the same absorption pathways when taken together in supplement form.", "clinicalSignificance": "Take iron and zinc at different times of day, separated by at least 2 hours.", "managementStrategy": "Take iron and zinc at different times of day, separated by at least 2 hours.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Calcium", "supplementBName": "Magnesium Glycinate", "interactionType": "timingSensitive", "severity": "moderate", "description": "High-dose calcium and magnesium compete for absorption when taken simultaneously.", "recommendation": "If taking high doses (>500mg each), separate by 2+ hours. Moderate doses can be taken together.", "minimumTimeSeparation": 120, "mechanism": "Both minerals share intestinal absorption pathways including TRPM6/7 channels. Competition is dose-dependent and significant above 500mg combined.", "evidenceLevel": "moderate", "sources": [ { "text": "Fine KD et al. Intestinal absorption of magnesium from food and supplements. J Am Coll Nutr. 1991;10(5):487-499.", "pmid": "1955626", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1955626/", "publicSourceType": "PMID" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose calcium and magnesium compete for absorption when taken simultaneously.", "clinicalSignificance": "If taking high doses (>500mg each), separate by 2+ hours.", "managementStrategy": "If taking high doses (>500mg each), separate by 2+ hours. Moderate doses can be taken together.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Zinc", "supplementBName": "Copper", "interactionType": "caution", "severity": "serious", "description": "Chronic high-dose zinc supplementation (>40mg/day) can induce copper deficiency by upregulating metallothionein, which binds copper in enterocytes.", "recommendation": "If supplementing zinc >25mg daily, add 1-2mg copper. Many zinc supplements include copper for this reason. Monitor copper status.", "minimumTimeSeparation": null, "mechanism": "Zinc induces metallothionein in intestinal cells, which preferentially binds copper, trapping it in enterocytes that are later shed, causing copper loss.", "evidenceLevel": "strong", "sources": [ { "text": "Fosmire GJ. Zinc toxicity. Am J Clin Nutr. 1990;51(2):225-7.", "pmid": "2407097", "doi": "10.1093/ajcn/51.2.225", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2407097/", "publicSourceType": "PMID" }, { "text": "Hoffman HN 2nd et al. Zinc-induced copper deficiency. Gastroenterology. 1988;94(2):508-12.", "pmid": "3335323", "doi": "10.1016/0016-5085(88)90445-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3335323/", "publicSourceType": "PMID" }, { "text": "Jaiser SR et al. Copper deficiency myelopathy. J Neurol. 2010;257(6):869-81.", "pmid": "20232210", "doi": "10.1007/s00415-010-5511-x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20232210/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Chronic high-dose zinc supplementation (>40mg/day) can induce copper deficiency by upregulating metallothionein, which binds copper in enterocytes.", "clinicalSignificance": "If supplementing zinc >25mg daily, add 1-2mg copper.", "managementStrategy": "If supplementing zinc >25mg daily, add 1-2mg copper. Many zinc supplements include copper for this reason. Monitor copper status.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Turmeric/Curcumin", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "Curcumin is fat-soluble and its absorption increases significantly when taken with dietary fat like fish oil. Both share anti-inflammatory pathways.", "recommendation": "Take curcumin with fish oil or a fat-containing meal for maximum absorption and synergistic anti-inflammatory effects.", "minimumTimeSeparation": null, "mechanism": "Fat increases micellar solubilization of curcumin. Both modulate NF-κB and COX-2 pathways through complementary mechanisms, providing additive anti-inflammatory action.", "evidenceLevel": "moderate", "sources": [ { "text": "Anand P et al. Bioavailability of curcumin. Mol Pharm. 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Uchida Y, Tsuji K, Ochi E. Effects of Omega-3 fatty acids supplementation and resistance training on skeletal muscle.. Clinical Nutrition ESPEN. 2024.", "pmid": "38777432", "doi": "10.1016/j.clnesp.2024.03.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38777432/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Curcumin is fat-soluble and its absorption increases significantly when taken with dietary fat like fish oil.", "clinicalSignificance": "Both share anti-inflammatory pathways.", "managementStrategy": "Take curcumin with fish oil or a fat-containing meal for maximum absorption and synergistic anti-inflammatory effects.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Quercetin", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Quercetin and vitamin C have synergistic antioxidant effects. Vitamin C helps regenerate oxidized quercetin.", "recommendation": "Take together for enhanced antioxidant and immune support.", "minimumTimeSeparation": null, "mechanism": "Vitamin C regenerates quercetin from its oxidized form, extending its antioxidant lifespan. Both inhibit inflammatory mediators via complementary pathways.", "evidenceLevel": "moderate", "sources": [ { "text": "Boots AW et al. The quercetin paradox. Biochem Biophys Res Commun. 2003", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials.. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Quercetin and vitamin C have synergistic antioxidant effects.", "clinicalSignificance": "Vitamin C helps regenerate oxidized quercetin.", "managementStrategy": "Take together for enhanced antioxidant and immune support.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin E", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Vitamin C regenerates vitamin E from its oxidized tocopheroxyl radical form, extending its antioxidant capacity.", "recommendation": "Take together for optimal antioxidant protection. Vitamin C recycles vitamin E in cell membranes.", "minimumTimeSeparation": null, "mechanism": "Ascorbate donates an electron to the tocopheroxyl radical at the membrane-cytosol interface, regenerating alpha-tocopherol and extending its chain-breaking antioxidant activity.", "evidenceLevel": "strong", "sources": [ { "text": "Traber MG, Stevens JF. Vitamins C and E: beneficial effects from a mechanistic perspective. Free Radic Biol Med. 2011", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials.. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Vitamin C regenerates vitamin E from its oxidized tocopheroxyl radical form, extending its antioxidant capacity.", "clinicalSignificance": "Take together for optimal antioxidant protection.", "managementStrategy": "Take together for optimal antioxidant protection. Vitamin C recycles vitamin E in cell membranes.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Coenzyme Q10", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "CoQ10 is fat-soluble and absorption increases 3-fold when taken with dietary fat. Fish oil provides the ideal fat vehicle.", "recommendation": "Take CoQ10 with fish oil or a fat-containing meal for dramatically improved absorption.", "minimumTimeSeparation": null, "mechanism": "CoQ10 (ubiquinone) is highly lipophilic. Dietary fat stimulates bile secretion and forms mixed micelles that solubilize CoQ10 for enterocyte uptake.", "evidenceLevel": "strong", "sources": [ { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Uchida Y, Tsuji K, Ochi E. Effects of Omega-3 fatty acids supplementation and resistance training on skeletal muscle.. Clinical Nutrition ESPEN. 2024.", "pmid": "38777432", "doi": "10.1016/j.clnesp.2024.03.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38777432/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "CoQ10 is fat-soluble and absorption increases 3-fold when taken with dietary fat.", "clinicalSignificance": "Fish oil provides the ideal fat vehicle.", "managementStrategy": "Take CoQ10 with fish oil or a fat-containing meal for dramatically improved absorption.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Fish Oil", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "info", "description": "Vitamin D3 is fat-soluble and absorption improves when taken with omega-3 fatty acids. Both support cardiovascular and immune health.", "recommendation": "Take D3 with fish oil or a meal containing fat for optimal absorption.", "minimumTimeSeparation": null, "mechanism": "D3 requires fat for micellar solubilization and absorption. Omega-3 fatty acids provide the lipid vehicle and share anti-inflammatory pathways via resolvin production.", "evidenceLevel": "strong", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Uchida Y, Tsuji K, Ochi E. Effects of Omega-3 fatty acids supplementation and resistance training on skeletal muscle.. Clinical Nutrition ESPEN. 2024.", "pmid": "38777432", "doi": "10.1016/j.clnesp.2024.03.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38777432/", "publicSourceType": "PMID" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin D3 is fat-soluble and absorption improves when taken with omega-3 fatty acids.", "clinicalSignificance": "Both support cardiovascular and immune health.", "managementStrategy": "Take D3 with fish oil or a meal containing fat for optimal absorption.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Magnesium Glycinate", "supplementBName": "Vitamin B6", "interactionType": "synergy", "severity": "info", "description": "Vitamin B6 increases intracellular magnesium accumulation. Magnesium is required for B6 activation to its coenzyme form PLP.", "recommendation": "Take together for enhanced mutual absorption and utilization.", "minimumTimeSeparation": null, "mechanism": "Pyridoxine (B6) facilitates magnesium transport into cells. Magnesium is a cofactor for pyridoxal kinase, which converts B6 to its active form pyridoxal-5-phosphate (PLP).", "evidenceLevel": "moderate", "sources": [ { "text": "Pouteau E et al. Superiority of magnesium and vitamin B6 over magnesium alone. Magnes Res. 2018", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Vitamin B6 increases intracellular magnesium accumulation.", "clinicalSignificance": "Magnesium is required for B6 activation to its coenzyme form PLP.", "managementStrategy": "Take together for enhanced mutual absorption and utilization.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "5-HTP", "supplementBName": "Vitamin B6", "interactionType": "synergy", "severity": "info", "description": "Vitamin B6 (as PLP) is a required cofactor for aromatic L-amino acid decarboxylase, which converts 5-HTP to serotonin.", "recommendation": "Take B6 with 5-HTP to ensure efficient conversion to serotonin. 25-50mg B6 is sufficient.", "minimumTimeSeparation": null, "mechanism": "PLP (active B6) is the essential cofactor for AADC (aromatic amino acid decarboxylase) that decarboxylates 5-hydroxytryptophan to serotonin (5-HT).", "evidenceLevel": "strong", "sources": [ { "text": "Birdsall TC. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin B6 (as PLP) is a required cofactor for aromatic L-amino acid decarboxylase, which converts 5-HTP to serotonin.", "clinicalSignificance": "Take B6 with 5-HTP to ensure efficient conversion to serotonin.", "managementStrategy": "Take B6 with 5-HTP to ensure efficient conversion to serotonin. 25-50mg B6 is sufficient.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "5-HTP", "supplementBName": "Melatonin", "interactionType": "caution", "severity": "moderate", "description": "5-HTP is a serotonin precursor, and serotonin is converted to melatonin. Taking both may lead to excessive serotonergic/melatonergic activity.", "recommendation": "Generally redundant to take both. If combining, use low doses and monitor for excessive drowsiness.", "minimumTimeSeparation": null, "mechanism": "5-HTP → serotonin → N-acetylserotonin → melatonin via AANAT and ASMT enzymes. Exogenous melatonin plus 5-HTP-derived melatonin may cause excessive sedation.", "evidenceLevel": "moderate", "sources": [ { "text": "Turner EH et al. Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacol Ther. 2006;109(3):325-38.", "pmid": "16023217", "doi": "10.1016/j.pharmthera.2005.06.004", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16023217/", "publicSourceType": "PMID" }, { "text": "Ganguly S et al. Control of melatonin synthesis in the mammalian pineal gland: the critical role of serotonin acetylation. Cell Tissue Res. 2002;309(1):127-37.", "pmid": "12111543", "doi": "10.1007/s00441-002-0579-y", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12111543/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "5-HTP is a serotonin precursor, and serotonin is converted to melatonin.", "clinicalSignificance": "Taking both may lead to excessive serotonergic/melatonergic activity.", "managementStrategy": "Generally redundant to take both. If combining, use low doses and monitor for excessive drowsiness.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin D3", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "info", "description": "Magnesium is essential for vitamin D metabolism. It's required for the enzymes that convert D3 to its active form calcitriol.", "recommendation": "Ensure adequate magnesium when supplementing D3. Magnesium deficiency can impair D3 activation.", "minimumTimeSeparation": null, "mechanism": "Magnesium is a cofactor for CYP2R1 (25-hydroxylase) and CYP27B1 (1-alpha-hydroxylase), the enzymes that convert cholecalciferol to 25(OH)D and then to active 1,25(OH)2D.", "evidenceLevel": "strong", "sources": [ { "text": "Uwitonze AM, Razzaque MS. Role of magnesium in vitamin D activation and function. J Am Osteopath Assoc. 2018", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Magnesium is essential for vitamin D metabolism.", "clinicalSignificance": "It's required for the enzymes that convert D3 to its active form calcitriol.", "managementStrategy": "Ensure adequate magnesium when supplementing D3. Magnesium deficiency can impair D3 activation.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin D3", "supplementBName": "Calcium", "interactionType": "synergy", "severity": "info", "description": "Vitamin D3 is essential for calcium absorption from the gut. Without adequate D3, only 10-15% of dietary calcium is absorbed.", "recommendation": "Take D3 to optimize calcium absorption. D3 can increase calcium absorption to 30-40%.", "minimumTimeSeparation": null, "mechanism": "Active vitamin D (calcitriol) binds VDR in intestinal cells, upregulating calbindin-D9k, TRPV6 channels, and PMCA1b pump to facilitate transcellular calcium transport.", "evidenceLevel": "strong", "sources": [ { "text": "Christakos S et al. Vitamin D and intestinal calcium absorption. Mol Cell Endocrinol. 2011", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Vitamin D3 is essential for calcium absorption from the gut.", "clinicalSignificance": "Without adequate D3, only 10-15% of dietary calcium is absorbed.", "managementStrategy": "Take D3 to optimize calcium absorption. D3 can increase calcium absorption to 30-40%.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin A", "supplementBName": "Vitamin D3", "interactionType": "caution", "severity": "moderate", "description": "High-dose vitamin A (retinol) can antagonize vitamin D activity by competing for the shared RXR nuclear receptor.", "recommendation": "If supplementing both, keep vitamin A under 10,000 IU and ensure adequate D3 (2000+ IU). Balanced ratios are key.", "minimumTimeSeparation": null, "mechanism": "Both vitamins' nuclear receptors (RAR and VDR) require RXR as a heterodimerization partner. Excess retinol saturates RXR, reducing VDR-RXR formation and D3 signaling.", "evidenceLevel": "moderate", "sources": [ { "text": "Johansson S, Melhus H. Vitamin A antagonizes calcium response to vitamin D in man. J Bone Miner Res. 2001.", "pmid": "11585356", "doi": "10.1359/jbmr.2001.16.10.1899", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11585356/", "publicSourceType": "PMID" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose vitamin A (retinol) can antagonize vitamin D activity by competing for the shared RXR nuclear receptor.", "clinicalSignificance": "If supplementing both, keep vitamin A under 10,000 IU and ensure adequate D3 (2000+ IU).", "managementStrategy": "If supplementing both, keep vitamin A under 10,000 IU and ensure adequate D3 (2000+ IU). Balanced ratios are key.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin A", "supplementBName": "Vitamin E", "interactionType": "synergy", "severity": "info", "description": "Vitamin E protects vitamin A from oxidation in the gut, increasing its absorption and stability.", "recommendation": "Taking together is beneficial. Vitamin E preserves vitamin A activity.", "minimumTimeSeparation": null, "mechanism": "Alpha-tocopherol acts as a chain-breaking antioxidant in the intestinal lumen, preventing oxidative destruction of retinol and retinyl esters before absorption.", "evidenceLevel": "moderate", "sources": [ { "text": "Combs GF Jr. The Vitamins: Fundamental Aspects in Nutrition and Health. Academic Press. 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Xia J, Yu J, Xu H et al.. Comparative effects of vitamin and mineral supplements in the management of type 2 diabetes in primary care: A systematic review and network meta-analysis of randomized controlled trials. Pharmacological Research. 2023.", "pmid": "36638933", "doi": "10.1016/j.phrs.2023.106647", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36638933/", "publicSourceType": "PMID" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin E protects vitamin A from oxidation in the gut, increasing its absorption and stability.", "clinicalSignificance": "Taking together is beneficial.", "managementStrategy": "Taking together is beneficial. Vitamin E preserves vitamin A activity.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin K1", "supplementBName": "Vitamin K2", "interactionType": "synergy", "severity": "info", "description": "K1 primarily supports coagulation while K2 (MK-7) directs calcium to bones. Complementary roles in vitamin K metabolism.", "recommendation": "Both forms are beneficial. K2 (MK-7) has a longer half-life and better extrahepatic distribution than K1.", "minimumTimeSeparation": null, "mechanism": "K1 (phylloquinone) activates hepatic clotting factors. K2 (menaquinone-7) has greater bioavailability for extrahepatic tissues, activating osteocalcin and MGP.", "evidenceLevel": "moderate", "sources": [ { "text": "Schurgers LJ et al. Vitamin K–containing dietary supplements. Blood. 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Kuang X, Liu C, Guo X, Li K, Deng Q, Li D. The combination effect of vitamin K and vitamin D on human bone quality: a meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "32219282", "doi": "10.1039/c9fo03063h", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32219282/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "K1 primarily supports coagulation while K2 (MK-7) directs calcium to bones.", "clinicalSignificance": "Complementary roles in vitamin K metabolism.", "managementStrategy": "Both forms are beneficial. K2 (MK-7) has a longer half-life and better extrahepatic distribution than K1.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin B9", "supplementBName": "Vitamin B12", "interactionType": "synergy", "severity": "moderate", "description": "B9 (folate) and B12 work together in the methionine cycle. B12 deficiency can be masked by high folate intake.", "recommendation": "Always supplement B12 when taking folate. B12 deficiency with high folate can cause irreversible neurological damage if undetected.", "minimumTimeSeparation": null, "mechanism": "B12 is a cofactor for methionine synthase, which uses 5-methylTHF (from folate) to remethylate homocysteine. Without B12, folate becomes trapped as 5-methylTHF (methyl trap).", "evidenceLevel": "strong", "sources": [ { "text": "Reynolds E. Vitamin B12, folic acid, and the nervous system. Lancet Neurol. 2006.", "pmid": "17052662", "doi": "10.1016/S1474-4422(06)70598-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17052662/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "B9 (folate) and B12 work together in the methionine cycle.", "clinicalSignificance": "B12 deficiency can be masked by high folate intake.", "managementStrategy": "Always supplement B12 when taking folate. B12 deficiency with high folate can cause irreversible neurological damage if undetected.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin B6", "supplementBName": "Vitamin B12", "interactionType": "synergy", "severity": "info", "description": "B6, B12, and folate work together to metabolize homocysteine. All three are needed for optimal methylation.", "recommendation": "Take B6, B12, and folate together for comprehensive homocysteine management and methylation support.", "minimumTimeSeparation": null, "mechanism": "B6 (as PLP) is cofactor for cystathionine beta-synthase (transsulfuration pathway). B12 for methionine synthase (remethylation). Both pathways clear homocysteine.", "evidenceLevel": "strong", "sources": [ { "text": "Selhub J. Homocysteine metabolism. Annu Rev Nutr. 1999", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "B6, B12, and folate work together to metabolize homocysteine.", "clinicalSignificance": "All three are needed for optimal methylation.", "managementStrategy": "Take B6, B12, and folate together for comprehensive homocysteine management and methylation support.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin B1", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "info", "description": "Magnesium is required for thiamine (B1) utilization. Magnesium deficiency impairs thiamine-dependent enzyme activity.", "recommendation": "Ensure adequate magnesium when supplementing B1 for proper enzymatic function.", "minimumTimeSeparation": null, "mechanism": "Magnesium is required for thiamine pyrophosphokinase, which converts thiamine to its active coenzyme form thiamine pyrophosphate (TPP).", "evidenceLevel": "moderate", "sources": [ { "text": "Lonsdale D. Thiamine and magnesium deficiencies. Med Hypotheses. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Magnesium is required for thiamine (B1) utilization.", "clinicalSignificance": "Magnesium deficiency impairs thiamine-dependent enzyme activity.", "managementStrategy": "Ensure adequate magnesium when supplementing B1 for proper enzymatic function.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin B2", "supplementBName": "Vitamin B6", "interactionType": "synergy", "severity": "info", "description": "Riboflavin (B2) is needed for the conversion of B6 to its active coenzyme form PLP.", "recommendation": "Take as part of a B-complex for mutual support.", "minimumTimeSeparation": null, "mechanism": "Riboflavin's active form FMN is a cofactor for pyridoxine 5'-phosphate oxidase, which converts pyridoxine-5-phosphate to pyridoxal-5-phosphate (PLP, active B6).", "evidenceLevel": "moderate", "sources": [ { "text": "Powers HJ. Riboflavin (vitamin B-2) and health. Am J Clin Nutr. 2003", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Riboflavin (B2) is needed for the conversion of B6 to its active coenzyme form PLP.", "clinicalSignificance": "Take as part of a B-complex for mutual support.", "managementStrategy": "Take as part of a B-complex for mutual support.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin B3", "supplementBName": "Vitamin B2", "interactionType": "synergy", "severity": "info", "description": "B2 (riboflavin) is needed for the synthesis of NAD+ from niacin (B3) via the kynurenine pathway.", "recommendation": "Taking B-complex ensures adequate co-factor support for all B vitamin interconversions.", "minimumTimeSeparation": null, "mechanism": "FAD (from riboflavin) is a cofactor for kynurenine 3-monooxygenase in the de novo NAD+ synthesis pathway from tryptophan/niacin.", "evidenceLevel": "moderate", "sources": [ { "text": "Sauve AA. NAD+ and vitamin B3. J Pharmacol Exp Ther. 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "B2 (riboflavin) is needed for the synthesis of NAD+ from niacin (B3) via the kynurenine pathway.", "clinicalSignificance": "Taking B-complex ensures adequate co-factor support for all B vitamin interconversions.", "managementStrategy": "Taking B-complex ensures adequate co-factor support for all B vitamin interconversions.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Iron", "supplementBName": "Vitamin B12", "interactionType": "synergy", "severity": "info", "description": "Both iron and B12 are essential for red blood cell production. Deficiency in either causes anemia.", "recommendation": "If anemic, check both iron and B12 status. Supplementing only one may not resolve anemia if both are deficient.", "minimumTimeSeparation": null, "mechanism": "Iron is incorporated into heme for hemoglobin synthesis. B12 is required for DNA synthesis in rapidly dividing erythroid precursors in bone marrow.", "evidenceLevel": "strong", "sources": [ { "text": "Green R et al. Vitamin B12 deficiency. Nat Rev Dis Primers. 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both iron and B12 are essential for red blood cell production.", "clinicalSignificance": "Deficiency in either causes anemia.", "managementStrategy": "If anemic, check both iron and B12 status. Supplementing only one may not resolve anemia if both are deficient.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Selenium", "supplementBName": "Vitamin E", "interactionType": "synergy", "severity": "info", "description": "Selenium and vitamin E work synergistically as antioxidants. Selenium is part of glutathione peroxidase, while E breaks lipid peroxidation chains.", "recommendation": "Take together for comprehensive antioxidant protection. They address different parts of the oxidative stress cascade.", "minimumTimeSeparation": null, "mechanism": "Selenium-containing glutathione peroxidases reduce hydrogen peroxide and lipid hydroperoxides. Vitamin E intercepts lipid peroxyl radicals in membranes. They act at different points in the antioxidant cascade.", "evidenceLevel": "strong", "sources": [ { "text": "Brigelius-Flohe R. Vitamin E and selenium: antioxidants and beyond. Free Radic Biol Med. 2009", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Selenium and vitamin E work synergistically as antioxidants.", "clinicalSignificance": "Selenium is part of glutathione peroxidase, while E breaks lipid peroxidation chains.", "managementStrategy": "Take together for comprehensive antioxidant protection. They address different parts of the oxidative stress cascade.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Selenium", "supplementBName": "Iodine", "interactionType": "synergy", "severity": "moderate", "description": "Selenium is critical for thyroid hormone metabolism. Selenoproteins (deiodinases) convert T4 to active T3, and glutathione peroxidase protects the thyroid from peroxide damage.", "recommendation": "Ensure adequate selenium when supplementing iodine. Selenium deficiency with iodine supplementation can worsen thyroid damage.", "minimumTimeSeparation": null, "mechanism": "Type I, II, and III iodothyronine deiodinases are selenoenzymes that convert T4→T3. GPx protects thyrocytes from H2O2 generated during thyroid hormone synthesis.", "evidenceLevel": "strong", "sources": [ { "text": "Köhrle J. Selenium and the thyroid. Curr Opin Endocrinol Diabetes Obes. 2015.", "pmid": "26313901", "doi": "10.1097/MED.0000000000000190", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26313901/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Selenium is critical for thyroid hormone metabolism.", "clinicalSignificance": "Selenoproteins (deiodinases) convert T4 to active T3, and glutathione peroxidase protects the thyroid from peroxide damage.", "managementStrategy": "Ensure adequate selenium when supplementing iodine. Selenium deficiency with iodine supplementation can worsen thyroid damage.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Boron", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "info", "description": "Boron supports vitamin D metabolism and may increase the half-life of 25(OH)D in the body.", "recommendation": "3-6mg boron may enhance vitamin D status, particularly when D levels are suboptimal.", "minimumTimeSeparation": null, "mechanism": "Boron appears to inhibit 24-hydroxylase (CYP24A1), the enzyme that catabolizes 25(OH)D and 1,25(OH)2D, thereby extending vitamin D half-life.", "evidenceLevel": "emerging", "sources": [ { "text": "Pizzorno L. Nothing boring about boron. Integr Med (Encinitas). 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Boron supports vitamin D metabolism and may increase the half-life of 25(OH)D in the body.", "clinicalSignificance": "3-6mg boron may enhance vitamin D status, particularly when D levels are suboptimal.", "managementStrategy": "3-6mg boron may enhance vitamin D status, particularly when D levels are suboptimal.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Boron", "supplementBName": "Calcium", "interactionType": "synergy", "severity": "info", "description": "Boron reduces urinary calcium excretion and supports calcium utilization for bone health.", "recommendation": "3mg boron daily may help retain calcium and support bone mineral density.", "minimumTimeSeparation": null, "mechanism": "Boron reduces urinary excretion of calcium and magnesium, likely by influencing renal tubular reabsorption and steroid hormone metabolism.", "evidenceLevel": "moderate", "sources": [ { "text": "Nielsen FH et al. Effect of dietary boron on mineral, estrogen, and testosterone metabolism in postmenopausal women. FASEB J. 1987", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Rondanelli M, Faliva MA, Barrile GC et al.. Nutrition, Physical Activity, and Dietary Supplementation to Prevent Bone Mineral Density Loss: A Food Pyramid. Nutrients. 2021.", "pmid": "35010952", "doi": "10.3390/nu14010074", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35010952/", "publicSourceType": "PMID" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Boron reduces urinary calcium excretion and supports calcium utilization for bone health.", "clinicalSignificance": "3mg boron daily may help retain calcium and support bone mineral density.", "managementStrategy": "3mg boron daily may help retain calcium and support bone mineral density.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Ashwagandha", "supplementBName": "Rhodiola Rosea", "interactionType": "synergy", "severity": "info", "description": "Both are adaptogens studied for perceived-stress or fatigue markers, but direct combination evidence is limited.", "recommendation": "Avoid using the pair to self-treat anxiety, depression, or endocrine symptoms. Discuss use with a clinician if taking antidepressants, stimulants, sedatives, or thyroid medications.", "minimumTimeSeparation": null, "mechanism": "Ashwagandha and rhodiola have stress-response and monoamine-related research, but human relevance and extract-specific effects vary.", "evidenceLevel": "emerging", "sources": [ { "text": "Panossian A, Wikman G. Effects of adaptogens on the central nervous system. Pharmaceuticals. 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Potential stress-routine support.", "clinicalSignificance": "Evidence is indirect for the combination.", "managementStrategy": "Avoid using the pair to self-treat anxiety, depression, or endocrine symptoms. Discuss use with a clinician if taking antidepressants, stimulants, sedatives, or thyroid medications.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Ashwagandha", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "info", "description": "Both promote relaxation and support sleep quality through complementary mechanisms.", "recommendation": "Take together in the evening for enhanced sleep and stress support.", "minimumTimeSeparation": null, "mechanism": "Ashwagandha's withanolides modulate GABA-A receptors. Magnesium glycinate blocks NMDA excitatory signaling and glycine acts as an inhibitory neurotransmitter at glycine receptors.", "evidenceLevel": "emerging", "sources": [ { "text": "Langade D et al. Efficacy and safety of ashwagandha root extract on sleep. Cureus. 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both promote relaxation and support sleep quality through complementary mechanisms.", "clinicalSignificance": "Take together in the evening for enhanced sleep and stress support.", "managementStrategy": "Take together in the evening for enhanced sleep and stress support.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Ashwagandha", "supplementBName": "L-Theanine", "interactionType": "synergy", "severity": "info", "description": "Both are studied for relaxation, perceived-stress, and calm-focus markers; direct combination evidence is limited.", "recommendation": "Use as a wellness-support pairing only. Do not present the combination as anxiety treatment, and use extra caution with sedatives or psychiatric medications.", "minimumTimeSeparation": null, "mechanism": "L-theanine has alpha-wave and glutamate-signaling research. Ashwagandha extracts have been studied for stress-related wellness markers, but cortisol effects vary by extract and population.", "evidenceLevel": "emerging", "sources": [ { "text": "Nobre AC et al. L-theanine, a natural constituent in tea, and its effect on mental state. Asia Pac J Clin Nutr. 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Payne ER, Aceves-Martins M, Dubost J et al.. Effects of Tea (Camellia sinensis) or its Bioactive Compounds l-Theanine or l-Theanine plus Caffeine on Cognition, Sleep, and Mood in Healthy Participants: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.. Nutrition Reviews. 2025.", "pmid": "40314930", "doi": "10.1093/nutrit/nuaf054", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40314930/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Potential calm-focus support.", "clinicalSignificance": "Not a treatment claim; monitor sedation or medication overlap.", "managementStrategy": "Use as a wellness-support pairing only. Do not present the combination as anxiety treatment, and use extra caution with sedatives or psychiatric medications.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "L-Theanine", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "info", "description": "L-theanine and magnesium are both studied for relaxation-related markers, but direct combination evidence is limited.", "recommendation": "If combining L-theanine with magnesium glycinate, keep total supplemental magnesium within 200-350 mg/day elemental magnesium unless clinician-supervised; do not frame the pair as anxiety treatment.", "minimumTimeSeparation": null, "mechanism": "L-theanine has alpha-wave and glutamate-signaling research, while magnesium participates in NMDA/GABA-related physiology. Clinical evidence for the specific combination is limited.", "evidenceLevel": "emerging", "sources": [ { "text": "Kimura K et al. L-theanine reduces psychological and physiological stress responses. Biol Psychol. 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Payne ER, Aceves-Martins M, Dubost J et al.. Effects of Tea (Camellia sinensis) or its Bioactive Compounds l-Theanine or l-Theanine plus Caffeine on Cognition, Sleep, and Mood in Healthy Participants: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.. Nutrition Reviews. 2025.", "pmid": "40314930", "doi": "10.1093/nutrit/nuaf054", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40314930/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Potential relaxation-support overlap.", "clinicalSignificance": "Wellness-support pairing only; not anxiety treatment.", "managementStrategy": "If combining L-theanine with magnesium glycinate, keep total supplemental magnesium within 200-350 mg/day elemental magnesium unless clinician-supervised; do not frame the pair as anxiety treatment.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "L-Tyrosine", "supplementBName": "Vitamin B6", "interactionType": "synergy", "severity": "info", "description": "Vitamin B6 (PLP) is a required cofactor for tyrosine hydroxylase, which converts L-tyrosine to L-DOPA in the dopamine synthesis pathway.", "recommendation": "Take B6 with L-tyrosine to support efficient dopamine production.", "minimumTimeSeparation": null, "mechanism": "Tyrosine hydroxylase requires tetrahydrobiopterin and iron as cofactors, and the downstream AADC (DOPA decarboxylase) requires PLP (B6) to convert L-DOPA to dopamine.", "evidenceLevel": "strong", "sources": [ { "text": "Fernstrom JD, Fernstrom MH. Tyrosine, phenylalanine, and catecholamine synthesis and function in the brain. J Nutr. 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin B6 (PLP) is a required cofactor for tyrosine hydroxylase, which converts L-tyrosine to L-DOPA in the dopamine synthesis pathway.", "clinicalSignificance": "Take B6 with L-tyrosine to support efficient dopamine production.", "managementStrategy": "Take B6 with L-tyrosine to support efficient dopamine production.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "L-Tyrosine", "supplementBName": "Iron", "interactionType": "synergy", "severity": "info", "description": "Iron is a cofactor for tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis.", "recommendation": "Ensure adequate iron status when using L-tyrosine for cognitive support. Iron deficiency impairs catecholamine synthesis.", "minimumTimeSeparation": null, "mechanism": "Tyrosine hydroxylase contains a non-heme iron center essential for catalytic activity. Iron deficiency directly reduces dopamine and norepinephrine synthesis rates.", "evidenceLevel": "strong", "sources": [ { "text": "Beard JL et al. Iron deficiency alters brain development and functioning. J Nutr. 2003", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Iron is a cofactor for tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis.", "clinicalSignificance": "Ensure adequate iron status when using L-tyrosine for cognitive support.", "managementStrategy": "Ensure adequate iron status when using L-tyrosine for cognitive support. Iron deficiency impairs catecholamine synthesis.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "NAC", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "NAC replenishes intracellular glutathione, while vitamin C provides extracellular antioxidant support. Complementary antioxidant systems.", "recommendation": "Take together for comprehensive antioxidant coverage, glutathione (intracellular) + ascorbate (extracellular).", "minimumTimeSeparation": null, "mechanism": "NAC provides cysteine for glutathione synthesis (rate-limiting substrate). Vitamin C recycles oxidized glutathione (GSSG) back to reduced GSH and provides parallel antioxidant protection.", "evidenceLevel": "moderate", "sources": [ { "text": "Rushworth GF, Megson IL. Existing and potential therapeutic uses for N-acetylcysteine. Pharmacol Ther. 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials.. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "NAC replenishes intracellular glutathione, while vitamin C provides extracellular antioxidant support.", "clinicalSignificance": "Complementary antioxidant systems.", "managementStrategy": "Take together for comprehensive antioxidant coverage, glutathione (intracellular) + ascorbate (extracellular).", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "NAC", "supplementBName": "Selenium", "interactionType": "synergy", "severity": "info", "description": "NAC provides glutathione, and selenium is the catalytic center of glutathione peroxidase enzymes.", "recommendation": "Take together for optimal glutathione peroxidase function and antioxidant defense.", "minimumTimeSeparation": null, "mechanism": "NAC supplies cysteine → glutathione (GSH). Selenium is incorporated as selenocysteine into the active site of GPx enzymes that use GSH to reduce peroxides.", "evidenceLevel": "moderate", "sources": [ { "text": "Rayman MP. Selenium and human health. Lancet. 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "NAC provides glutathione, and selenium is the catalytic center of glutathione peroxidase enzymes.", "clinicalSignificance": "Take together for optimal glutathione peroxidase function and antioxidant defense.", "managementStrategy": "Take together for optimal glutathione peroxidase function and antioxidant defense.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "NAC", "supplementBName": "Milk Thistle", "interactionType": "synergy", "severity": "info", "description": "Both support liver health through glutathione-related mechanisms. NAC provides glutathione precursor; silymarin protects liver cells and supports glutathione levels.", "recommendation": "Effective liver support combination. Take together for hepatoprotective benefit.", "minimumTimeSeparation": null, "mechanism": "NAC replenishes hepatic glutathione stores. Silymarin (from milk thistle) inhibits lipid peroxidation in hepatocyte membranes, promotes ribosomal RNA synthesis for liver regeneration, and independently raises glutathione levels.", "evidenceLevel": "moderate", "sources": [ { "text": "Abenavoli L et al. Milk thistle in liver diseases. Phytother Res. 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Fogacci F, Grassi D, Rizzo M, Cicero AFG. Metabolic effect of berberine-silymarin association: A meta-analysis of randomized, double-blind, placebo-controlled clinical trials. Phytotherapy Research. 2019.", "pmid": "30632209", "doi": "10.1002/ptr.6282", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30632209/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both support liver health through glutathione-related mechanisms.", "clinicalSignificance": "NAC provides glutathione precursor; silymarin protects liver cells and supports glutathione levels.", "managementStrategy": "Effective liver support combination. Take together for hepatoprotective benefit.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Glycine", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "info", "description": "Magnesium glycinate already contains glycine as its chelation partner. Additional glycine further supports sleep and inhibitory neurotransmission.", "recommendation": "Magnesium glycinate provides both magnesium and glycine. Supplemental glycine (3g) can further enhance sleep quality.", "minimumTimeSeparation": null, "mechanism": "Glycine acts on NMDA receptors in the suprachiasmatic nucleus, lowering core body temperature to promote sleep onset. Combined with magnesium's NMDA antagonism, enhanced sleep quality.", "evidenceLevel": "moderate", "sources": [ { "text": "Bannai M, Kawai N. New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep. J Pharmacol Sci. 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Magnesium glycinate already contains glycine as its chelation partner.", "clinicalSignificance": "Additional glycine further supports sleep and inhibitory neurotransmission.", "managementStrategy": "Magnesium glycinate provides both magnesium and glycine. Supplemental glycine (3g) can further enhance sleep quality.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Glycine", "supplementBName": "NAC", "interactionType": "synergy", "severity": "info", "description": "Glycine and NAC (GlyNAC) together provide two of the three amino acids needed for glutathione synthesis.", "recommendation": "GlyNAC combination is a powerful glutathione-boosting strategy, particularly effective in aging adults.", "minimumTimeSeparation": null, "mechanism": "Glutathione = glutamate + cysteine + glycine. NAC provides cysteine (rate-limiting), glycine is the second limiting substrate. Together they maximize GSH synthesis.", "evidenceLevel": "moderate", "sources": [ { "text": "Sekhar RV et al. GlyNAC supplementation improves glutathione deficiency and oxidative stress in aging. Clin Transl Med. 2021", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Kumar P, Liu C, Suliburk J, Hsu JW, Muthupillai R, Jahoor F et al.. Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial.. Journals of Gerontology Series A. 2023.", "pmid": "35975308", "doi": "10.1093/gerona/glac135", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35975308/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Glycine and NAC (GlyNAC) together provide two of the three amino acids needed for glutathione synthesis.", "clinicalSignificance": "GlyNAC combination is a powerful glutathione-boosting strategy, particularly effective in aging adults.", "managementStrategy": "GlyNAC combination is a powerful glutathione-boosting strategy, particularly effective in aging adults.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Creatine", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "info", "description": "Both support musculoskeletal function. Vitamin D3 enhances muscle protein synthesis, and creatine increases phosphocreatine stores for energy.", "recommendation": "Effective combination for strength and muscle health, especially in those over 50.", "minimumTimeSeparation": null, "mechanism": "Vitamin D activates VDR in muscle tissue, upregulating protein synthesis pathways. Creatine increases PCr stores for rapid ATP regeneration. Complementary mechanisms for muscle function.", "evidenceLevel": "emerging", "sources": [ { "text": "Candow DG et al. Combined effect of creatine and vitamin D supplementation on musculoskeletal health. Nutrients. 2021", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both support musculoskeletal function.", "clinicalSignificance": "Vitamin D3 enhances muscle protein synthesis, and creatine increases phosphocreatine stores for energy.", "managementStrategy": "Effective combination for strength and muscle health, especially in those over 50.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Collagen Peptides", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Vitamin C is essential for collagen synthesis. It's a required cofactor for prolyl and lysyl hydroxylase enzymes that stabilize the collagen triple helix.", "recommendation": "Always take vitamin C with collagen supplements. Without adequate C, collagen cannot properly cross-link.", "minimumTimeSeparation": null, "mechanism": "Ascorbate is the electron donor for prolyl-4-hydroxylase and lysyl hydroxylase, which hydroxylate proline and lysine residues essential for collagen triple helix stability.", "evidenceLevel": "strong", "sources": [ { "text": "Pullar JM et al. The roles of vitamin C in skin health. Nutrients. 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bischof K, Moitzi AM, Stafilidis S et al.. Impact of Collagen Peptide Supplementation in Combination with Long-Term Physical Training on Strength, Musculotendinous Remodeling, Functional Recovery, and Body Composition in Healthy Adults: A Systematic Review with Meta-analysis.. Sports Medicine. 2024.", "pmid": "39060741", "doi": "10.1007/s40279-024-02079-0", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39060741/", "publicSourceType": "PMID" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials.. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Vitamin C is essential for collagen synthesis.", "clinicalSignificance": "It's a required cofactor for prolyl and lysyl hydroxylase enzymes that stabilize the collagen triple helix.", "managementStrategy": "Always take vitamin C with collagen supplements. Without adequate C, collagen cannot properly cross-link.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Lion's Mane", "supplementBName": "Citicoline", "interactionType": "synergy", "severity": "info", "description": "Lion's mane promotes nerve growth factor (NGF) synthesis while citicoline supports phospholipid membrane synthesis. Complementary nootropic stack.", "recommendation": "Combine for comprehensive cognitive support, neurogenesis (lion's mane) + membrane integrity (citicoline).", "minimumTimeSeparation": null, "mechanism": "Hericenones and erinacines from lion's mane cross the BBB and stimulate NGF synthesis. Citicoline provides choline for acetylcholine and cytidine for neuronal membrane phospholipid repair.", "evidenceLevel": "emerging", "sources": [ { "text": "Mori K et al. Improving effects of the mushroom Hericium erinaceus on mild cognitive impairment. Phytother Res. 2009", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Lion's mane promotes nerve growth factor (NGF) synthesis while citicoline supports phospholipid membrane synthesis.", "clinicalSignificance": "Complementary nootropic stack.", "managementStrategy": "Combine for comprehensive cognitive support, neurogenesis (lion's mane) + membrane integrity (citicoline).", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Lion's Mane", "supplementBName": "Alpha-GPC", "interactionType": "synergy", "severity": "info", "description": "Lion's mane promotes NGF for neuroplasticity while Alpha-GPC provides choline for acetylcholine synthesis. Synergistic cognitive enhancement.", "recommendation": "Effective nootropic combination for memory and focus. Lion's mane 500-1000mg + Alpha-GPC 300-600mg.", "minimumTimeSeparation": null, "mechanism": "Lion's mane erinacines stimulate NGF, promoting neuronal growth and myelination. Alpha-GPC crosses BBB to provide choline for ACh synthesis. NGF also upregulates choline acetyltransferase.", "evidenceLevel": "emerging", "sources": [ { "text": "Parker AG et al. The effects of alpha-glycerylphosphorylcholine on cognitive function. J Int Soc Sports Nutr. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Sagaro GG, Traini E, Amenta F. Activity of Choline Alphoscerate on Adult-Onset Cognitive Dysfunctions: A Systematic Review and Meta-Analysis. J Alzheimers Dis. 2023.", "pmid": "36683513", "doi": "10.3233/JAD-221189", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36683513/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Lion's mane promotes NGF for neuroplasticity while Alpha-GPC provides choline for acetylcholine synthesis.", "clinicalSignificance": "Synergistic cognitive enhancement.", "managementStrategy": "Effective nootropic combination for memory and focus. Lion's mane 500-1000mg + Alpha-GPC 300-600mg.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Citicoline", "supplementBName": "Alpha-GPC", "interactionType": "caution", "severity": "moderate", "description": "Both are potent choline sources. Taking both at full doses may provide excessive choline, potentially causing headaches, GI distress, or fishy body odor.", "recommendation": "Choose one or reduce doses of both. Rarely needed to stack both choline sources simultaneously.", "minimumTimeSeparation": null, "mechanism": "Both are highly bioavailable choline donors. Citicoline provides ~18% choline by weight, Alpha-GPC ~40%. Combined full doses may exceed the 3.5g/day upper limit for choline.", "evidenceLevel": "moderate", "sources": [ { "text": "Zeisel SH. Choline: critical role during fetal development and dietary requirements in adults. Annu Rev Nutr. 2006.", "pmid": "16848706", "doi": "10.1146/annurev.nutr.26.061505.111156", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16848706/", "publicSourceType": "PMID" }, { "text": "Sagaro GG, Traini E, Amenta F. Activity of Choline Alphoscerate on Adult-Onset Cognitive Dysfunctions: A Systematic Review and Meta-Analysis. J Alzheimers Dis. 2023.", "pmid": "36683513", "doi": "10.3233/JAD-221189", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36683513/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both are potent choline sources.", "clinicalSignificance": "Taking both at full doses may provide excessive choline, potentially causing headaches, GI distress, or fishy body odor.", "managementStrategy": "Choose one or reduce doses of both. Rarely needed to stack both choline sources simultaneously.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Phosphatidylserine", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "Phosphatidylserine is a phospholipid that benefits from omega-3 DHA, which is preferentially incorporated into PS in brain membranes.", "recommendation": "Take together. DHA-enriched phosphatidylserine may be more effective for cognitive function than soy-derived PS.", "minimumTimeSeparation": null, "mechanism": "DHA from fish oil is incorporated into the sn-2 position of phosphatidylserine in neuronal membranes, enhancing membrane fluidity and PS-dependent signaling (PKC activation, Akt/PI3K).", "evidenceLevel": "moderate", "sources": [ { "text": "Kim HY et al. Phosphatidylserine in the brain. Prog Lipid Res. 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Uchida Y, Tsuji K, Ochi E. Effects of Omega-3 fatty acids supplementation and resistance training on skeletal muscle.. Clinical Nutrition ESPEN. 2024.", "pmid": "38777432", "doi": "10.1016/j.clnesp.2024.03.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38777432/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Phosphatidylserine is a phospholipid that benefits from omega-3 DHA, which is preferentially incorporated into PS in brain membranes.", "clinicalSignificance": "Take together.", "managementStrategy": "Take together. DHA-enriched phosphatidylserine may be more effective for cognitive function than soy-derived PS.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Phosphatidylserine", "supplementBName": "Citicoline", "interactionType": "synergy", "severity": "info", "description": "Citicoline supports phospholipid synthesis broadly, including phosphatidylserine. Together they comprehensively support neuronal membrane health.", "recommendation": "Combine for comprehensive brain membrane support, particularly beneficial for cognitive aging.", "minimumTimeSeparation": null, "mechanism": "Citicoline provides cytidine (→ CTP) and choline for CDP-choline pathway phospholipid synthesis. PS is synthesized from PE and PC via base-exchange enzymes. Citicoline increases substrate pool for PS.", "evidenceLevel": "emerging", "sources": [ { "text": "Secades JJ. Citicoline: pharmacological and clinical review. Rev Neurol. 2011", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Citicoline supports phospholipid synthesis broadly, including phosphatidylserine.", "clinicalSignificance": "Together they comprehensively support neuronal membrane health.", "managementStrategy": "Combine for comprehensive brain membrane support, particularly beneficial for cognitive aging.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Cordyceps", "supplementBName": "Coenzyme Q10", "interactionType": "synergy", "severity": "info", "description": "Both support mitochondrial energy production. Cordyceps increases ATP synthesis; CoQ10 is essential for the electron transport chain.", "recommendation": "Combine for enhanced cellular energy, exercise performance, and mitochondrial support.", "minimumTimeSeparation": null, "mechanism": "Cordycepin and adenosine from cordyceps enhance mitochondrial biogenesis via AMPK/PGC-1α. CoQ10 shuttles electrons in Complex I→III of the ETC. Synergistic mitochondrial support.", "evidenceLevel": "emerging", "sources": [ { "text": "Hirsch KR et al. Cordyceps militaris improves tolerance to high-intensity exercise. J Diet Suppl. 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both support mitochondrial energy production.", "clinicalSignificance": "Cordyceps increases ATP synthesis; CoQ10 is essential for the electron transport chain.", "managementStrategy": "Combine for enhanced cellular energy, exercise performance, and mitochondrial support.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Cordyceps", "supplementBName": "Creatine", "interactionType": "synergy", "severity": "info", "description": "Both enhance ATP availability through complementary mechanisms. Cordyceps supports mitochondrial ATP production; creatine buffers ATP via phosphocreatine.", "recommendation": "Effective pre-workout combination for sustained energy output.", "minimumTimeSeparation": null, "mechanism": "Cordyceps enhances oxidative phosphorylation and mitochondrial efficiency. Creatine kinase system buffers ATP by rapidly regenerating it from ADP + phosphocreatine during high-intensity work.", "evidenceLevel": "emerging", "sources": [ { "text": "Chen S et al. Effect of Cs-4 on exercise performance. Med Sci Sports Exerc. 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both enhance ATP availability through complementary mechanisms.", "clinicalSignificance": "Cordyceps supports mitochondrial ATP production; creatine buffers ATP via phosphocreatine.", "managementStrategy": "Effective pre-workout combination for sustained energy output.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Reishi", "supplementBName": "Ashwagandha", "interactionType": "synergy", "severity": "info", "description": "Both support immune modulation and stress adaptation through complementary mechanisms.", "recommendation": "Combine for immune support plus stress reduction. Reishi at night pairs well with ashwagandha's calming effects.", "minimumTimeSeparation": null, "mechanism": "Reishi beta-glucans modulate innate immunity via Dectin-1 and CR3 receptors on macrophages. Ashwagandha withanolides modulate adaptive immunity and reduce cortisol-mediated immunosuppression.", "evidenceLevel": "emerging", "sources": [ { "text": "Wachtel-Galor S et al. Ganoderma lucidum (Lingzhi or Reishi). Herbal Medicine: Biomolecular and Clinical Aspects. 2011", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both support immune modulation and stress adaptation through complementary mechanisms.", "clinicalSignificance": "Combine for immune support plus stress reduction.", "managementStrategy": "Combine for immune support plus stress reduction. Reishi at night pairs well with ashwagandha's calming effects.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Reishi", "supplementBName": "Melatonin", "interactionType": "caution", "severity": "moderate", "description": "Both have sedative properties. Reishi contains triterpenes that modulate GABAergic signaling. Combined with melatonin, may cause excessive drowsiness.", "recommendation": "If combining, start with low doses of both and use only at bedtime. Monitor for excessive sedation.", "minimumTimeSeparation": null, "mechanism": "Reishi triterpenes (ganoderic acids) modulate GABA-A receptors and TNF-α-induced sleep signaling. Adding exogenous melatonin on top may cause over-sedation via additive mechanisms.", "evidenceLevel": "emerging", "sources": [ { "text": "Cui XY et al. Extract of Ganoderma lucidum prolongs sleep time in rats. J Ethnopharmacol. 2012;139(3):796-800.", "pmid": "22207209", "doi": "10.1016/j.jep.2011.12.020", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22207209/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both have sedative properties.", "clinicalSignificance": "Reishi contains triterpenes that modulate GABAergic signaling.", "managementStrategy": "If combining, start with low doses of both and use only at bedtime. Monitor for excessive sedation.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Melatonin", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "info", "description": "Melatonin and magnesium are commonly used in sleep routines, but direct stack evidence and optimal dosing vary.", "recommendation": "If combining melatonin with magnesium glycinate, keep magnesium within 200-350 mg/day supplemental elemental magnesium unless clinician-supervised and keep melatonin use situational or clinician-guided for persistent insomnia.", "minimumTimeSeparation": null, "mechanism": "Magnesium participates in neuromuscular and sleep-related physiology; melatonin supports circadian timing. The combination should be presented as routine support, not a sleep-disorder treatment.", "evidenceLevel": "moderate", "sources": [ { "text": "Abbasi B et al. The effect of magnesium supplementation on primary insomnia in elderly. J Res Med Sci. 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Potential sleep-routine support.", "clinicalSignificance": "Dose and duration should stay conservative, especially with chronic sleep problems.", "managementStrategy": "If combining melatonin with magnesium glycinate, keep magnesium within 200-350 mg/day supplemental elemental magnesium unless clinician-supervised and keep melatonin use situational or clinician-guided for persistent insomnia.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Melatonin", "supplementBName": "Apigenin", "interactionType": "synergy", "severity": "info", "description": "Apigenin is a natural flavonoid that binds GABA-A benzodiazepine receptors, promoting sleep through a different mechanism than melatonin.", "recommendation": "Andrew Huberman's sleep stack: 50mg apigenin + 0.5-2mg melatonin (optional) + magnesium for comprehensive sleep support.", "minimumTimeSeparation": null, "mechanism": "Apigenin binds the benzodiazepine site on GABA-A receptors, promoting anxiolysis and sedation. Melatonin activates MT1/MT2 receptors for circadian timing. Different sleep-promoting mechanisms.", "evidenceLevel": "emerging", "sources": [ { "text": "Salehi B et al. The Therapeutic Potential of Apigenin. Int J Mol Sci. 2019;20(6).", "pmid": "30875872", "doi": "10.3390/ijms20061305", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30875872/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Apigenin is a natural flavonoid that binds GABA-A benzodiazepine receptors, promoting sleep through a different mechanism than melatonin.", "clinicalSignificance": "Andrew Huberman's sleep stack: 50mg apigenin + 0.5-2mg melatonin (optional) + magnesium for comprehensive sleep support.", "managementStrategy": "Andrew Huberman's sleep stack: 50mg apigenin + 0.5-2mg melatonin (optional) + magnesium for comprehensive sleep support.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Apigenin", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "info", "description": "Both promote relaxation and sleep through GABAergic and glutamate-modulating pathways.", "recommendation": "Combine for a gentle, non-habit-forming sleep support stack.", "minimumTimeSeparation": null, "mechanism": "Apigenin positively modulates GABA-A receptors. Magnesium blocks excitatory NMDA glutamate receptors. Glycine from magnesium glycinate adds inhibitory neurotransmission.", "evidenceLevel": "emerging", "sources": [ { "text": "Salehi B et al. The therapeutic potential of apigenin. Int J Mol Sci. 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both promote relaxation and sleep through GABAergic and glutamate-modulating pathways.", "clinicalSignificance": "Combine for a gentle, non-habit-forming sleep support stack.", "managementStrategy": "Combine for a gentle, non-habit-forming sleep support stack.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Alpha-Lipoic Acid", "supplementBName": "NAC", "interactionType": "synergy", "severity": "info", "description": "Both support glutathione recycling. ALA regenerates glutathione from its oxidized form, while NAC provides the cysteine precursor for new glutathione synthesis.", "recommendation": "Powerful antioxidant combination for glutathione support and heavy metal chelation.", "minimumTimeSeparation": null, "mechanism": "ALA (both R and S forms) reduces GSSG to GSH and recycles vitamins C and E. NAC provides cysteine, the rate-limiting amino acid for de novo GSH synthesis. Together they maximize both recycling and production.", "evidenceLevel": "moderate", "sources": [ { "text": "Shay KP et al. Alpha-lipoic acid as a dietary supplement. Biochim Biophys Acta. 2009", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both support glutathione recycling.", "clinicalSignificance": "ALA regenerates glutathione from its oxidized form, while NAC provides the cysteine precursor for new glutathione synthesis.", "managementStrategy": "Powerful antioxidant combination for glutathione support and heavy metal chelation.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Alpha-Lipoic Acid", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "ALA regenerates vitamin C from its oxidized form (dehydroascorbate) back to ascorbate.", "recommendation": "Taking together creates an antioxidant recycling network: ALA → regenerates C → regenerates E.", "minimumTimeSeparation": null, "mechanism": "Dihydrolipoic acid (reduced ALA) donates electrons to dehydroascorbate, regenerating ascorbate. This creates a self-reinforcing antioxidant network.", "evidenceLevel": "moderate", "sources": [ { "text": "Packer L et al. Alpha-lipoic acid as a biological antioxidant. Free Radic Biol Med. 1995", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials.. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "ALA regenerates vitamin C from its oxidized form (dehydroascorbate) back to ascorbate.", "clinicalSignificance": "Taking together creates an antioxidant recycling network: ALA → regenerates C → regenerates E.", "managementStrategy": "Taking together creates an antioxidant recycling network: ALA → regenerates C → regenerates E.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Alpha-Lipoic Acid", "supplementBName": "Iron", "interactionType": "caution", "severity": "moderate", "description": "ALA chelates metals including iron. May reduce iron absorption or redistribute iron stores.", "recommendation": "Separate by 2+ hours. Avoid high-dose ALA if you have iron deficiency.", "minimumTimeSeparation": 120, "mechanism": "ALA's dithiol group chelates divalent and trivalent metal ions including Fe2+/Fe3+, potentially reducing iron bioavailability and redistributing tissue iron stores.", "evidenceLevel": "moderate", "sources": [ { "text": "Suh JH et al. Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. Proc Natl Acad Sci U S A. 2004.", "pmid": "14985508", "doi": "10.1073/pnas.0400282101", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14985508/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "ALA chelates metals including iron.", "clinicalSignificance": "May reduce iron absorption or redistribute iron stores.", "managementStrategy": "Separate by 2+ hours. Avoid high-dose ALA if you have iron deficiency.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "NMN", "supplementBName": "Resveratrol", "interactionType": "synergy", "severity": "info", "description": "NMN supports NAD+-pathway markers, while resveratrol has sirtuin-related preclinical research; direct human evidence for the combination is absent.", "recommendation": "Present as an exploratory pairing only. Do not claim proven longevity, healthspan, DNA-repair, or clinical outcome benefits from the combination.", "minimumTimeSeparation": null, "mechanism": "NMN is converted through NAD+ salvage pathways. Resveratrol has sirtuin-related mechanistic research, but human outcome relevance and combination effects remain uncertain.", "evidenceLevel": "emerging", "sources": [ { "text": "Imai SI, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Exploratory NAD+-pathway pairing.", "clinicalSignificance": "Human combination outcome evidence is absent.", "managementStrategy": "Present as an exploratory pairing only. Do not claim proven longevity, healthspan, DNA-repair, or clinical outcome benefits from the combination.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "NMN", "supplementBName": "Vitamin B3", "interactionType": "caution", "severity": "info", "description": "Both are NAD+ precursors through different pathways. Taking both may be redundant and could lead to excessive NAD+ precursor supplementation.", "recommendation": "Choose one NAD+ precursor strategy. NMN is generally preferred for direct NAD+ boosting via the salvage pathway.", "minimumTimeSeparation": null, "mechanism": "Niacin (B3) → NAD+ via the Preiss-Handler pathway. NMN → NAD+ via the salvage pathway (NMNAT). Both raise NAD+ but through different enzymatic routes. Redundant at typical supplement doses.", "evidenceLevel": "emerging", "sources": [ { "text": "Rajman L et al. Therapeutic potential of NAD-boosting molecules. Cell Metab. 2018", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both are NAD+ precursors through different pathways.", "clinicalSignificance": "Taking both may be redundant and could lead to excessive NAD+ precursor supplementation.", "managementStrategy": "Choose one NAD+ precursor strategy. NMN is generally preferred for direct NAD+ boosting via the salvage pathway.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Resveratrol", "supplementBName": "Quercetin", "interactionType": "synergy", "severity": "info", "description": "Quercetin inhibits resveratrol glucuronidation, increasing resveratrol bioavailability. Both are polyphenol antioxidants with complementary targets.", "recommendation": "Take together. Quercetin may increase resveratrol bioavailability by inhibiting sulfotransferases and glucuronidases that metabolize resveratrol.", "minimumTimeSeparation": null, "mechanism": "Quercetin inhibits SULT1A1 and UGT1A enzymes that conjugate and inactivate resveratrol, increasing its plasma half-life. Both activate SIRT1 and AMPK through different binding sites.", "evidenceLevel": "emerging", "sources": [ { "text": "De Santi C et al. Sulphation of resveratrol, a natural compound, and inhibition of resveratrol sulphotransferase. Xenobiotica. 2000", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Quercetin inhibits resveratrol glucuronidation, increasing resveratrol bioavailability.", "clinicalSignificance": "Both are polyphenol antioxidants with complementary targets.", "managementStrategy": "Take together. Quercetin may increase resveratrol bioavailability by inhibiting sulfotransferases and glucuronidases that metabolize resveratrol.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Astaxanthin", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "Astaxanthin is fat-soluble and absorbs best with dietary fat. It also protects omega-3 fatty acids from oxidation.", "recommendation": "Take together. Astaxanthin protects fish oil PUFAs from peroxidation while fish oil improves astaxanthin absorption.", "minimumTimeSeparation": null, "mechanism": "Astaxanthin spans the cell membrane bilayer, quenching singlet oxygen and scavenging radicals. It protects PUFAs (DHA/EPA) from lipid peroxidation. Fat improves astaxanthin micellar solubilization.", "evidenceLevel": "moderate", "sources": [ { "text": "Ambati RR et al. Astaxanthin: sources, extraction, stability, biological activities. Mar Drugs. 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Uchida Y, Tsuji K, Ochi E. Effects of Omega-3 fatty acids supplementation and resistance training on skeletal muscle.. Clinical Nutrition ESPEN. 2024.", "pmid": "38777432", "doi": "10.1016/j.clnesp.2024.03.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38777432/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Astaxanthin is fat-soluble and absorbs best with dietary fat.", "clinicalSignificance": "It also protects omega-3 fatty acids from oxidation.", "managementStrategy": "Take together. Astaxanthin protects fish oil PUFAs from peroxidation while fish oil improves astaxanthin absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Astaxanthin", "supplementBName": "Vitamin E", "interactionType": "synergy", "severity": "info", "description": "Both are lipophilic antioxidants but work at different positions in cell membranes. Astaxanthin is 6000x more potent than vitamin C as a singlet oxygen quencher.", "recommendation": "Complementary membrane antioxidant protection. Astaxanthin spans the membrane, vitamin E sits within it.", "minimumTimeSeparation": null, "mechanism": "Astaxanthin's polar end groups anchor at membrane surfaces while the polyene chain spans the bilayer. Vitamin E is embedded within the lipid phase. Different spatial antioxidant coverage.", "evidenceLevel": "moderate", "sources": [ { "text": "Nishida Y et al. Quenching activities of common hydrophilic and lipophilic antioxidants against singlet oxygen. Carotenoid Sci. 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both are lipophilic antioxidants but work at different positions in cell membranes.", "clinicalSignificance": "Astaxanthin is 6000x more potent than vitamin C as a singlet oxygen quencher.", "managementStrategy": "Complementary membrane antioxidant protection. Astaxanthin spans the membrane, vitamin E sits within it.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Probiotics", "supplementBName": "Digestive Enzymes", "interactionType": "timingSensitive", "severity": "info", "description": "Both support gut health but work best at different times. Digestive enzymes work with meals; probiotics prefer an empty stomach or before meals.", "recommendation": "Take probiotics 30 min before meals on an empty stomach. Take digestive enzymes at the start of a meal.", "minimumTimeSeparation": 30, "mechanism": "Probiotics survive better in less acidic conditions (empty stomach). Digestive enzymes (protease, lipase, amylase) work on food substrates and need to mix with the meal bolus.", "evidenceLevel": "moderate", "sources": [ { "text": "Tompkins TA et al. The impact of meals on a probiotic during transit through a model of the human upper gastrointestinal tract. Benef Microbes. 2011", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both support gut health but work best at different times.", "clinicalSignificance": "Digestive enzymes work with meals; probiotics prefer an empty stomach or before meals.", "managementStrategy": "Take probiotics 30 min before meals on an empty stomach. Take digestive enzymes at the start of a meal.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Probiotics", "supplementBName": "Iron", "interactionType": "timingSensitive", "severity": "info", "description": "Iron supplements can disrupt gut microbiome composition. However, certain probiotic strains may actually enhance iron absorption.", "recommendation": "Separate by 2 hours. Some Lactobacillus strains can increase iron absorption, so probiotics may be beneficial for iron-supplementing individuals.", "minimumTimeSeparation": 120, "mechanism": "Unabsorbed iron in the colon promotes pathogenic bacteria growth (via iron-dependent virulence factors). Probiotics maintain beneficial flora. Some strains reduce ferric to ferrous iron, enhancing absorption.", "evidenceLevel": "emerging", "sources": [ { "text": "Zimmermann MB et al. The effects of iron fortification on the gut microbiota in African children. Am J Clin Nutr. 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Iron supplements can disrupt gut microbiome composition.", "clinicalSignificance": "However, certain probiotic strains may actually enhance iron absorption.", "managementStrategy": "Separate by 2 hours. Some Lactobacillus strains can increase iron absorption, so probiotics may be beneficial for iron-supplementing individuals.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Berberine", "supplementBName": "Milk Thistle", "interactionType": "synergy", "severity": "info", "description": "Milk thistle (silymarin) inhibits CYP enzymes that metabolize berberine, potentially increasing its bioavailability and duration of action.", "recommendation": "Combine for enhanced metabolic support. Silymarin may increase berberine bioavailability.", "minimumTimeSeparation": null, "mechanism": "Silymarin inhibits CYP3A4 and CYP2C9, which are primary metabolizers of berberine. This reduces first-pass metabolism and increases berberine plasma levels.", "evidenceLevel": "emerging", "sources": [ { "text": "Feng R et al. Transforming berberine into its intestine-absorbable form by the gut microbiota. Sci Rep. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Fogacci F, Grassi D, Rizzo M, Cicero AFG. Metabolic effect of berberine-silymarin association: A meta-analysis of randomized, double-blind, placebo-controlled clinical trials. Phytotherapy Research. 2019.", "pmid": "30632209", "doi": "10.1002/ptr.6282", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30632209/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Milk thistle (silymarin) inhibits CYP enzymes that metabolize berberine, potentially increasing its bioavailability and duration of action.", "clinicalSignificance": "Combine for enhanced metabolic support.", "managementStrategy": "Combine for enhanced metabolic support. Silymarin may increase berberine bioavailability.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Berberine", "supplementBName": "Chromium", "interactionType": "caution", "severity": "moderate", "description": "Both lower blood glucose through different mechanisms. Combined use may cause excessive blood sugar reduction, especially in non-diabetics.", "recommendation": "Monitor blood glucose closely if combining. May need to reduce doses. Consult healthcare provider if on diabetes medication.", "minimumTimeSeparation": null, "mechanism": "Berberine activates AMPK and increases insulin sensitivity. Chromium enhances insulin receptor signaling via chromodulin. Additive hypoglycemic effect may cause symptomatic hypoglycemia.", "evidenceLevel": "moderate", "sources": [ { "text": "Yin J et al. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008;57(5):712-7.", "pmid": "18442638", "doi": "10.1016/j.metabol.2008.01.013", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18442638/", "publicSourceType": "PMID" }, { "text": "Anderson RA et al. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes. Diabetes. 1997;46(11):1786-91.", "pmid": "9356027", "doi": "10.2337/diab.46.11.1786", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9356027/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both lower blood glucose through different mechanisms.", "clinicalSignificance": "Combined use may cause excessive blood sugar reduction, especially in non-diabetics.", "managementStrategy": "Monitor blood glucose closely if combining. May need to reduce doses. Consult healthcare provider if on diabetes medication.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Berberine", "supplementBName": "Coenzyme Q10", "interactionType": "caution", "severity": "moderate", "description": "Berberine may inhibit mitochondrial Complex I, similar to metformin. CoQ10 supplementation may help offset potential mitochondrial effects.", "recommendation": "Consider adding CoQ10 when taking berberine long-term to support mitochondrial function.", "minimumTimeSeparation": null, "mechanism": "Berberine partially inhibits mitochondrial Complex I (NADH:ubiquinone oxidoreductase), which may explain its AMPK activation. CoQ10 supports electron transport and may mitigate this inhibition.", "evidenceLevel": "emerging", "sources": [ { "text": "Turner N et al. Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: a mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. Diabetes. 2008;57(5):1414-8.", "pmid": "18285556", "doi": "10.2337/db07-1552", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18285556/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Berberine may inhibit mitochondrial Complex I, similar to metformin.", "clinicalSignificance": "CoQ10 supplementation may help offset potential mitochondrial effects.", "managementStrategy": "Consider adding CoQ10 when taking berberine long-term to support mitochondrial function.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Turmeric/Curcumin", "supplementBName": "Quercetin", "interactionType": "synergy", "severity": "info", "description": "Both are potent anti-inflammatory polyphenols that modulate NF-κB and COX-2 through complementary mechanisms.", "recommendation": "Take together for enhanced anti-inflammatory and antioxidant effects.", "minimumTimeSeparation": null, "mechanism": "Curcumin inhibits IKK-β, blocking NF-κB nuclear translocation. Quercetin inhibits lipoxygenase and phospholipase A2. Both inhibit COX-2 through different binding mechanisms.", "evidenceLevel": "moderate", "sources": [ { "text": "Pescosolido N et al. Curcumin and quercetin synergistically inhibit inflammatory signaling. J Cell Mol Med. 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both are potent anti-inflammatory polyphenols that modulate NF-κB and COX-2 through complementary mechanisms.", "clinicalSignificance": "Take together for enhanced anti-inflammatory and antioxidant effects.", "managementStrategy": "Take together for enhanced anti-inflammatory and antioxidant effects.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Turmeric/Curcumin", "supplementBName": "NAC", "interactionType": "synergy", "severity": "info", "description": "Both support liver detoxification and reduce oxidative stress. Curcumin is a direct antioxidant; NAC supports glutathione production.", "recommendation": "Combine for liver support and comprehensive antioxidant protection.", "minimumTimeSeparation": null, "mechanism": "Curcumin activates Nrf2, upregulating phase II detoxification enzymes. NAC provides cysteine for glutathione synthesis. Together they enhance both direct antioxidant defense and enzyme-mediated detoxification.", "evidenceLevel": "moderate", "sources": [ { "text": "Biswas SK et al. Curcumin induces glutathione biosynthesis and inhibits NF-kappaB activation. Antioxid Redox Signal. 2005", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both support liver detoxification and reduce oxidative stress.", "clinicalSignificance": "Curcumin is a direct antioxidant; NAC supports glutathione production.", "managementStrategy": "Combine for liver support and comprehensive antioxidant protection.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin E", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "Vitamin E protects omega-3 fatty acids from lipid peroxidation. High-dose fish oil may increase vitamin E requirements.", "recommendation": "Take vitamin E with fish oil to prevent PUFA oxidation. Many quality fish oil supplements include vitamin E for this reason.", "minimumTimeSeparation": null, "mechanism": "PUFAs (EPA/DHA) are highly susceptible to peroxidation due to multiple double bonds. Alpha-tocopherol intercepts lipid peroxyl radicals in membranes, preventing chain propagation.", "evidenceLevel": "strong", "sources": [ { "text": "Meydani M. Omega-3 fatty acids alter soluble markers of endothelial function in coronary heart disease patients. Nutr Rev. 2000", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" }, { "text": "Uchida Y, Tsuji K, Ochi E. Effects of Omega-3 fatty acids supplementation and resistance training on skeletal muscle.. Clinical Nutrition ESPEN. 2024.", "pmid": "38777432", "doi": "10.1016/j.clnesp.2024.03.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38777432/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin E protects omega-3 fatty acids from lipid peroxidation.", "clinicalSignificance": "High-dose fish oil may increase vitamin E requirements.", "managementStrategy": "Take vitamin E with fish oil to prevent PUFA oxidation. Many quality fish oil supplements include vitamin E for this reason.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin D3", "supplementBName": "Zinc", "interactionType": "synergy", "severity": "info", "description": "Adequate zinc status supports normal zinc-finger transcription biology, including vitamin D receptor DNA-binding domains. Evidence does not show that extra zinc improves vitamin D signaling in zinc-replete people.", "recommendation": "Use zinc to meet normal intake or correct deficiency; do not add high-dose zinc solely to activate vitamin D.", "minimumTimeSeparation": null, "mechanism": "The vitamin D receptor has zinc-finger DNA-binding domains that use zinc ions. This supports avoiding zinc deficiency, but does not prove supplementation improves vitamin D response when zinc status is already adequate.", "evidenceLevel": "emerging", "sources": [ { "text": "Zittermann A. Vitamin D and zinc: a dual approach for immune support. Nutrients. 2020", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Adequate zinc status supports normal zinc-finger transcription biology; supplemental benefit beyond correcting low zinc is not established.", "clinicalSignificance": "Potentially relevant when zinc intake or status is low; not evidence for routine high-dose zinc with vitamin D.", "managementStrategy": "Avoid high-dose zinc unless deficiency, low intake, or clinician direction is present.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin K2", "supplementBName": "Calcium", "interactionType": "synergy", "severity": "moderate", "description": "K2 activates osteocalcin to direct calcium to bones and matrix GLA protein to prevent arterial calcification. Essential when supplementing calcium.", "recommendation": "Always take K2 (MK-7, 100-200mcg) when supplementing calcium to ensure proper calcium deposition in bones, not arteries.", "minimumTimeSeparation": null, "mechanism": "K2-dependent carboxylation of osteocalcin enables it to bind calcium and deposit it in bone matrix. MGP carboxylation by K2 prevents calcium deposition in arterial walls.", "evidenceLevel": "strong", "sources": [ { "text": "Knapen MH et al. Menaquinone-7 supplementation improves arterial stiffness. Thromb Haemost. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Kuang X, Liu C, Guo X, Li K, Deng Q, Li D. The combination effect of vitamin K and vitamin D on human bone quality: a meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "32219282", "doi": "10.1039/c9fo03063h", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32219282/", "publicSourceType": "PMID" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "K2 activates osteocalcin to direct calcium to bones and matrix GLA protein to prevent arterial calcification.", "clinicalSignificance": "Essential when supplementing calcium.", "managementStrategy": "Always take K2 (MK-7, 100-200mcg) when supplementing calcium to ensure proper calcium deposition in bones, not arteries.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin K2", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "K2 (MK-7) is fat-soluble and absorption increases with dietary fat. Fish oil provides an excellent fat vehicle.", "recommendation": "Take K2 with fish oil or a fat-containing meal for optimal absorption.", "minimumTimeSeparation": null, "mechanism": "MK-7 is a fat-soluble isoprenoid. Dietary fat stimulates bile secretion and forms micelles that solubilize MK-7 for intestinal absorption via chylomicron incorporation.", "evidenceLevel": "moderate", "sources": [ { "text": "Schurgers LJ, Vermeer C. Determination of phylloquinone and menaquinones in food. Haemostasis. 2000", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Kuang X, Liu C, Guo X, Li K, Deng Q, Li D. The combination effect of vitamin K and vitamin D on human bone quality: a meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "32219282", "doi": "10.1039/c9fo03063h", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32219282/", "publicSourceType": "PMID" }, { "text": "Uchida Y, Tsuji K, Ochi E. Effects of Omega-3 fatty acids supplementation and resistance training on skeletal muscle.. Clinical Nutrition ESPEN. 2024.", "pmid": "38777432", "doi": "10.1016/j.clnesp.2024.03.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38777432/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "K2 (MK-7) is fat-soluble and absorption increases with dietary fat.", "clinicalSignificance": "Fish oil provides an excellent fat vehicle.", "managementStrategy": "Take K2 with fish oil or a fat-containing meal for optimal absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin A", "supplementBName": "Zinc", "interactionType": "synergy", "severity": "info", "description": "Zinc is required for retinol-binding protein synthesis and vitamin A transport from the liver. Zinc deficiency impairs vitamin A mobilization.", "recommendation": "Ensure adequate zinc when supplementing vitamin A. Zinc deficiency can cause functional vitamin A deficiency even with adequate liver stores.", "minimumTimeSeparation": null, "mechanism": "Zinc is essential for hepatic synthesis of retinol-binding protein (RBP) which transports retinol from liver stores to target tissues. Zinc also supports alcohol dehydrogenase for retinol→retinal conversion.", "evidenceLevel": "strong", "sources": [ { "text": "Christian P, West KP Jr. Interactions between zinc and vitamin A. Am J Clin Nutr. 1998", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Oh C, Keats EC, Bhutta ZA. Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.. Nutrients. 2020.", "pmid": "32075071", "doi": "10.3390/nu12020491", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32075071/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Zinc is required for retinol-binding protein synthesis and vitamin A transport from the liver.", "clinicalSignificance": "Zinc deficiency impairs vitamin A mobilization.", "managementStrategy": "Ensure adequate zinc when supplementing vitamin A. Zinc deficiency can cause functional vitamin A deficiency even with adequate liver stores.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin B12", "supplementBName": "Calcium", "interactionType": "synergy", "severity": "info", "description": "Calcium may actually assist B12 absorption. Some evidence suggests calcium helps release B12 from food and supports intrinsic factor binding.", "recommendation": "Can be taken together. Calcium does not impair B12 absorption and may mildly assist it.", "minimumTimeSeparation": null, "mechanism": "Calcium supports the ileal receptor cubam (cubilin-amnionless) function for intrinsic factor-B12 complex absorption. Adequate calcium ensures proper receptor-mediated endocytosis.", "evidenceLevel": "emerging", "sources": [ { "text": "Russell RM et al. Influence of calcium on the bioavailability of vitamin B12. Am J Clin Nutr. 2002", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Calcium may actually assist B12 absorption.", "clinicalSignificance": "Some evidence suggests calcium helps release B12 from food and supports intrinsic factor binding.", "managementStrategy": "Can be taken together. Calcium does not impair B12 absorption and may mildly assist it.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Chromium", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Vitamin C enhances chromium absorption by reducing Cr3+ in the gut, making it more bioavailable.", "recommendation": "Take chromium with vitamin C for improved absorption. 200mcg chromium + 500mg vitamin C.", "minimumTimeSeparation": null, "mechanism": "Ascorbic acid reduces chromium in the intestinal lumen, increasing the proportion in the more absorbable Cr3+ state and enhancing passive diffusion across the intestinal epithelium.", "evidenceLevel": "moderate", "sources": [ { "text": "Offenbacher EG. Promotion of chromium absorption by ascorbic acid. Trace Elem Electrolytes. 1994", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials.. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin C enhances chromium absorption by reducing Cr3+ in the gut, making it more bioavailable.", "clinicalSignificance": "Take chromium with vitamin C for improved absorption.", "managementStrategy": "Take chromium with vitamin C for improved absorption. 200mcg chromium + 500mg vitamin C.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Potassium", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "moderate", "description": "Magnesium deficiency causes renal potassium wasting. Correcting magnesium is often necessary before potassium levels can normalize.", "recommendation": "If hypokalemic, check magnesium status. Refractory hypokalemia often resolves only when magnesium is also repleted.", "minimumTimeSeparation": null, "mechanism": "Magnesium maintains ROMK channel function in the renal collecting duct. Mg deficiency causes ROMK-mediated potassium secretion, leading to renal potassium wasting resistant to K supplementation alone.", "evidenceLevel": "strong", "sources": [ { "text": "Huang CL et al. Mechanism of hypokalemia in magnesium deficiency. J Am Soc Nephrol. 2007;18(10):2649-52.", "pmid": "17804670", "doi": "10.1681/ASN.2007070792", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17804670/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Magnesium deficiency causes renal potassium wasting.", "clinicalSignificance": "Correcting magnesium is often necessary before potassium levels can normalize.", "managementStrategy": "If hypokalemic, check magnesium status. Refractory hypokalemia often resolves only when magnesium is also repleted.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Iron", "supplementBName": "Vitamin A", "interactionType": "synergy", "severity": "info", "description": "Vitamin A improves iron mobilization from stores and enhances erythropoiesis. Combined supplementation is more effective than either alone for anemia.", "recommendation": "Supplementing both is more effective for iron-deficiency anemia than iron alone, especially in developing countries.", "minimumTimeSeparation": null, "mechanism": "Vitamin A mobilizes iron from ferritin stores in the liver and spleen. It also stimulates erythropoietin production and supports iron incorporation into hemoglobin during erythropoiesis.", "evidenceLevel": "strong", "sources": [ { "text": "Zimmermann MB et al. Vitamin A supplementation in iron-deficient children. Am J Clin Nutr. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin A improves iron mobilization from stores and enhances erythropoiesis.", "clinicalSignificance": "Combined supplementation is more effective than either alone for anemia.", "managementStrategy": "Supplementing both is more effective for iron-deficiency anemia than iron alone, especially in developing countries.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Iron", "supplementBName": "Magnesium Glycinate", "interactionType": "timingSensitive", "severity": "moderate", "description": "Magnesium and iron can compete for absorption when taken together. Separate for optimal absorption of both.", "recommendation": "Take iron in the morning on an empty stomach. Take magnesium glycinate in the evening.", "minimumTimeSeparation": 120, "mechanism": "Iron uses DMT1 while magnesium uses TRPM6/TRPM7 channels. Competition occurs through indirect mechanisms including shared paracellular absorption pathways. Separating by 2+ hours eliminates competition.", "evidenceLevel": "moderate", "sources": [ { "text": "Shawki A, Bhatt DK. Intestinal DMT1 is critical for iron absorption. Blood. 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Magnesium and iron can compete for absorption when taken together.", "clinicalSignificance": "Separate for optimal absorption of both.", "managementStrategy": "Take iron in the morning on an empty stomach. Take magnesium glycinate in the evening.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Calcium", "supplementBName": "Zinc", "interactionType": "timingSensitive", "severity": "moderate", "description": "High-dose calcium can reduce zinc absorption when taken simultaneously.", "recommendation": "Separate calcium and zinc supplements by at least 2 hours for optimal absorption of both.", "minimumTimeSeparation": 120, "mechanism": "Calcium may interfere with zinc absorption via competition for shared transport mechanisms in the intestinal epithelium, though the effect is less pronounced than calcium-iron competition.", "evidenceLevel": "moderate", "sources": [ { "text": "Wood RJ, Zheng JJ. High dietary calcium intakes reduce zinc absorption and balance in humans. Am J Clin Nutr. 1997.", "pmid": "9174476", "doi": "10.1093/ajcn/65.6.1803", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9174476/", "publicSourceType": "PMID" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose calcium can reduce zinc absorption when taken simultaneously.", "clinicalSignificance": "Separate calcium and zinc supplements by at least 2 hours for optimal absorption of both.", "managementStrategy": "Separate calcium and zinc supplements by at least 2 hours for optimal absorption of both.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Calcium", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Vitamin C mildly enhances calcium absorption by maintaining calcium in the soluble, ionized form in the gut.", "recommendation": "Can take together. Vitamin C provides a modest boost to calcium absorption.", "minimumTimeSeparation": null, "mechanism": "Ascorbic acid chelates calcium in the intestinal lumen, maintaining it in a soluble form and enhancing paracellular absorption in the small intestine.", "evidenceLevel": "emerging", "sources": [ { "text": "Levine M et al. Vitamin C pharmacokinetics in healthy volunteers. Proc Natl Acad Sci. 1996", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials.. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin C mildly enhances calcium absorption by maintaining calcium in the soluble, ionized form in the gut.", "clinicalSignificance": "Can take together.", "managementStrategy": "Can take together. Vitamin C provides a modest boost to calcium absorption.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Zinc", "supplementBName": "Vitamin B9", "interactionType": "caution", "severity": "info", "description": "High-dose zinc (>40mg) may impair folate absorption by inhibiting the folate conjugase enzyme in the gut.", "recommendation": "If taking high-dose zinc, monitor folate status or separate doses.", "minimumTimeSeparation": 120, "mechanism": "Zinc at high doses may inhibit pteroylpolyglutamate hydrolase (folate conjugase), the brush-border enzyme that deconjugates dietary polyglutamyl folates to the absorbable monoglutamyl form.", "evidenceLevel": "emerging", "sources": [ { "text": "Ghishan FK et al. Effect of zinc on intestinal folate absorption. Am J Physiol. 1986", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "High-dose zinc (>40mg) may impair folate absorption by inhibiting the folate conjugase enzyme in the gut.", "clinicalSignificance": "If taking high-dose zinc, monitor folate status or separate doses.", "managementStrategy": "If taking high-dose zinc, monitor folate status or separate doses.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Selenium", "supplementBName": "Vitamin C", "interactionType": "timingSensitive", "severity": "moderate", "description": "High-dose vitamin C may reduce selenite to elemental selenium, which is not absorbable. Does not affect selenomethionine forms.", "recommendation": "If using sodium selenite form, separate from high-dose vitamin C by 2 hours. Selenomethionine is unaffected.", "minimumTimeSeparation": 120, "mechanism": "Ascorbic acid reduces selenite (SeO3²⁻) to elemental Se(0) in the GI tract, rendering it insoluble and unabsorbable. Selenomethionine is absorbed via methionine transporters, unaffected by redox.", "evidenceLevel": "moderate", "sources": [ { "text": "Ip C. Interaction of vitamin C and selenium supplementation in the modification of mammary carcinogenesis in rats. J Natl Cancer Inst. 1986.", "pmid": "3088312", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3088312/", "publicSourceType": "PMID" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials.. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose vitamin C may reduce selenite to elemental selenium, which is not absorbable.", "clinicalSignificance": "Does not affect selenomethionine forms.", "managementStrategy": "If using sodium selenite form, separate from high-dose vitamin C by 2 hours. Selenomethionine is unaffected.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Krill Oil", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "info", "description": "Same synergy as fish oil + D3. Krill oil phospholipid-bound omega-3s provide dietary fat for D3 absorption.", "recommendation": "Take D3 with krill oil. Phospholipid-bound omega-3s in krill may offer slightly better absorption than triglyceride-form fish oil.", "minimumTimeSeparation": null, "mechanism": "Krill oil's phospholipid-bound EPA/DHA provide fat for vitamin D3 micellar solubilization. Phospholipid form may enhance intestinal absorption vs. triglyceride form.", "evidenceLevel": "moderate", "sources": [ { "text": "Ulven SM et al. Metabolic effects of krill oil. Lipids. 2011", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Same synergy as fish oil + D3.", "clinicalSignificance": "Krill oil phospholipid-bound omega-3s provide dietary fat for D3 absorption.", "managementStrategy": "Take D3 with krill oil. Phospholipid-bound omega-3s in krill may offer slightly better absorption than triglyceride-form fish oil.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Krill Oil", "supplementBName": "Astaxanthin", "interactionType": "synergy", "severity": "info", "description": "Krill oil naturally contains astaxanthin, which protects its PUFAs from oxidation. Additional astaxanthin further enhances antioxidant protection.", "recommendation": "Krill oil already contains some astaxanthin. Additional supplementation provides extra antioxidant protection.", "minimumTimeSeparation": null, "mechanism": "Astaxanthin in krill oil serves as a natural antioxidant preservative for EPA/DHA. Supplemental astaxanthin provides systemic antioxidant benefits beyond PUFA protection.", "evidenceLevel": "moderate", "sources": [ { "text": "Barros MP et al. Combined astaxanthin and fish oil supplementation improves glutathione-based redox balance. Chem Biol Interact. 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Krill oil naturally contains astaxanthin, which protects its PUFAs from oxidation.", "clinicalSignificance": "Additional astaxanthin further enhances antioxidant protection.", "managementStrategy": "Krill oil already contains some astaxanthin. Additional supplementation provides extra antioxidant protection.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Fish Oil", "supplementBName": "Turmeric/Curcumin", "interactionType": "caution", "severity": "info", "description": "Both have blood-thinning properties. High doses of both together may increase bleeding risk.", "recommendation": "At standard doses, this combination is generally safe and synergistic. Monitor for easy bruising at high doses. Discontinue before surgery.", "minimumTimeSeparation": null, "mechanism": "Fish oil reduces thromboxane A2 production and platelet aggregation. Curcumin inhibits COX-2 and platelet-activating factor. Additive anticoagulant effects at high doses.", "evidenceLevel": "emerging", "sources": [ { "text": "Keihanian F et al. Curcumin, hemostasis, thrombosis, and coagulation. J Cell Physiol. 2018;233(6):4497-4511.", "pmid": "29052850", "doi": "10.1002/jcp.26249", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29052850/", "publicSourceType": "PMID" }, { "text": "Javaid M et al. Bleeding Risk in Patients Receiving Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Am Heart Assoc. 2024;13(10):e032390.", "pmid": "38742535", "doi": "10.1161/JAHA.123.032390", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38742535/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both have blood-thinning properties.", "clinicalSignificance": "High doses of both together may increase bleeding risk.", "managementStrategy": "At standard doses, this combination is generally safe and synergistic. Monitor for easy bruising at high doses. Discontinue before surgery.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin E", "supplementBName": "Vitamin K1", "interactionType": "caution", "severity": "moderate", "description": "High-dose vitamin E (>400 IU) can antagonize vitamin K-dependent clotting factor activation, increasing bleeding risk.", "recommendation": "Keep vitamin E under 400 IU if taking K1 for coagulation support or if on anticoagulant therapy. Monitor INR.", "minimumTimeSeparation": null, "mechanism": "Alpha-tocopherol at high doses inhibits vitamin K-dependent carboxylase (GGCX), reducing gamma-carboxylation of clotting factors II, VII, IX, and X.", "evidenceLevel": "strong", "sources": [ { "text": "Booth SL et al. Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. Am J Clin Nutr. 2004;80(1):143-8.", "pmid": "15213041", "doi": "10.1093/ajcn/80.1.143", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15213041/", "publicSourceType": "PMID" }, { "text": "Pastori D et al. Vitamin E serum levels and bleeding risk in patients receiving oral anticoagulant therapy: a retrospective cohort study. J Am Heart Assoc. 2013;2(6):e000364.", "pmid": "24166490", "doi": "10.1161/JAHA.113.000364", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24166490/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose vitamin E (>400 IU) can antagonize vitamin K-dependent clotting factor activation, increasing bleeding risk.", "clinicalSignificance": "Keep vitamin E under 400 IU if taking K1 for coagulation support or if on anticoagulant therapy.", "managementStrategy": "Keep vitamin E under 400 IU if taking K1 for coagulation support or if on anticoagulant therapy. Monitor INR.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin E", "supplementBName": "Vitamin K2", "interactionType": "caution", "severity": "moderate", "description": "High-dose vitamin E may reduce K2-dependent protein carboxylation, potentially affecting both bone and cardiovascular K2 benefits.", "recommendation": "Keep vitamin E at moderate doses (200 IU or less) when relying on K2 for bone and cardiovascular health.", "minimumTimeSeparation": null, "mechanism": "Excess alpha-tocopherol competitively inhibits GGCX enzyme activity needed for K2-dependent carboxylation of osteocalcin and matrix GLA protein.", "evidenceLevel": "moderate", "sources": [ { "text": "Booth SL et al. Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. Am J Clin Nutr. 2004;80(1):143-8.", "pmid": "15213041", "doi": "10.1093/ajcn/80.1.143", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15213041/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose vitamin E may reduce K2-dependent protein carboxylation, potentially affecting both bone and cardiovascular K2 benefits.", "clinicalSignificance": "Keep vitamin E at moderate doses (200 IU or less) when relying on K2 for bone and cardiovascular health.", "managementStrategy": "Keep vitamin E at moderate doses (200 IU or less) when relying on K2 for bone and cardiovascular health.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Rhodiola Rosea", "supplementBName": "Cordyceps", "interactionType": "synergy", "severity": "info", "description": "Both adaptogens enhance physical performance and energy through complementary mechanisms.", "recommendation": "Effective pre-workout or morning energy stack. Rhodiola for mental stamina, cordyceps for physical endurance.", "minimumTimeSeparation": null, "mechanism": "Rhodiola's rosavins and salidroside modulate cortisol and enhance stress resilience. Cordyceps' cordycepin increases ATP production and oxygen utilization. Complementary performance enhancement.", "evidenceLevel": "emerging", "sources": [ { "text": "Panossian A et al. Adaptogens exert a stress-protective effect by modulation of expression of molecular chaperones. Phytomedicine. 2009", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both adaptogens enhance physical performance and energy through complementary mechanisms.", "clinicalSignificance": "Effective pre-workout or morning energy stack.", "managementStrategy": "Effective pre-workout or morning energy stack. Rhodiola for mental stamina, cordyceps for physical endurance.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "L-Theanine", "supplementBName": "Vitamin B6", "interactionType": "synergy", "severity": "info", "description": "Both support GABA production. B6 is the cofactor for glutamic acid decarboxylase, which synthesizes GABA. L-theanine increases GABA levels.", "recommendation": "Combine for enhanced GABAergic calming support.", "minimumTimeSeparation": null, "mechanism": "L-theanine crosses BBB and increases GABA levels directly and via glutamate modulation. B6 (PLP) is the essential cofactor for GAD65/67 enzymes that decarboxylate glutamate to GABA.", "evidenceLevel": "emerging", "sources": [ { "text": "Nathan PJ et al. The neuropharmacology of L-theanine. J Herb Pharmacother. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Payne ER, Aceves-Martins M, Dubost J et al.. Effects of Tea (Camellia sinensis) or its Bioactive Compounds l-Theanine or l-Theanine plus Caffeine on Cognition, Sleep, and Mood in Healthy Participants: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.. Nutrition Reviews. 2025.", "pmid": "40314930", "doi": "10.1093/nutrit/nuaf054", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40314930/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both support GABA production.", "clinicalSignificance": "B6 is the cofactor for glutamic acid decarboxylase, which synthesizes GABA.", "managementStrategy": "Combine for enhanced GABAergic calming support.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "L-Tyrosine", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Vitamin C is a cofactor for dopamine beta-hydroxylase, which converts dopamine (from tyrosine) to norepinephrine.", "recommendation": "Take vitamin C with L-tyrosine to support the full catecholamine synthesis pathway from dopamine to norepinephrine.", "minimumTimeSeparation": null, "mechanism": "After L-tyrosine → L-DOPA → dopamine, dopamine beta-hydroxylase (DBH) converts dopamine to norepinephrine. DBH requires ascorbate as an electron donor for this copper-dependent reaction.", "evidenceLevel": "strong", "sources": [ { "text": "May JM et al. Ascorbic acid efficiently enhances neuronal synthesis of norepinephrine from dopamine. Brain Res Bull. 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials.. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin C is a cofactor for dopamine beta-hydroxylase, which converts dopamine (from tyrosine) to norepinephrine.", "clinicalSignificance": "Take vitamin C with L-tyrosine to support the full catecholamine synthesis pathway from dopamine to norepinephrine.", "managementStrategy": "Take vitamin C with L-tyrosine to support the full catecholamine synthesis pathway from dopamine to norepinephrine.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Creatine", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "info", "description": "Magnesium is required for creatine kinase enzyme activity, which phosphorylates creatine to phosphocreatine.", "recommendation": "Ensure adequate magnesium when supplementing creatine for optimal ATP buffering.", "minimumTimeSeparation": null, "mechanism": "Creatine kinase requires Mg-ATP as substrate (not free ATP). Magnesium deficiency impairs the creatine kinase reaction and reduces phosphocreatine stores.", "evidenceLevel": "moderate", "sources": [ { "text": "Wallimann T et al. Intracellular compartmentation, structure and function of creatine kinase isoenzymes. Biochem J. 1992", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Magnesium is required for creatine kinase enzyme activity, which phosphorylates creatine to phosphocreatine.", "clinicalSignificance": "Ensure adequate magnesium when supplementing creatine for optimal ATP buffering.", "managementStrategy": "Ensure adequate magnesium when supplementing creatine for optimal ATP buffering.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Collagen Peptides", "supplementBName": "Zinc", "interactionType": "synergy", "severity": "info", "description": "Zinc is essential for collagen synthesis enzymes and wound healing. Supports collagen crosslinking and skin repair.", "recommendation": "Take zinc with collagen peptides for enhanced skin, joint, and wound healing support.", "minimumTimeSeparation": null, "mechanism": "Zinc is a cofactor for matrix metalloproteinases (collagen remodeling), prolyl hydroxylase (collagen stabilization), and is essential for fibroblast proliferation and collagen deposition.", "evidenceLevel": "moderate", "sources": [ { "text": "Kogan S et al. Zinc and wound healing. Adv Skin Wound Care. 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bischof K, Moitzi AM, Stafilidis S et al.. Impact of Collagen Peptide Supplementation in Combination with Long-Term Physical Training on Strength, Musculotendinous Remodeling, Functional Recovery, and Body Composition in Healthy Adults: A Systematic Review with Meta-analysis.. Sports Medicine. 2024.", "pmid": "39060741", "doi": "10.1007/s40279-024-02079-0", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39060741/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Zinc is essential for collagen synthesis enzymes and wound healing.", "clinicalSignificance": "Supports collagen crosslinking and skin repair.", "managementStrategy": "Take zinc with collagen peptides for enhanced skin, joint, and wound healing support.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin B5", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Both support adrenal function and cortisol regulation. B5 (pantothenic acid) is critical for CoA synthesis needed in adrenal steroid hormone production.", "recommendation": "Combine for adrenal support, especially during periods of high stress.", "minimumTimeSeparation": null, "mechanism": "B5 is converted to CoA, essential for acetyl-CoA production and adrenal steroidogenesis. Vitamin C is concentrated in adrenal glands and required for cortisol synthesis via dopamine beta-hydroxylase.", "evidenceLevel": "moderate", "sources": [ { "text": "Tahiliani AG, Beinlich CJ. Pantothenic acid in health and disease. Vitam Horm. 1991", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials.. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both support adrenal function and cortisol regulation.", "clinicalSignificance": "B5 (pantothenic acid) is critical for CoA synthesis needed in adrenal steroid hormone production.", "managementStrategy": "Combine for adrenal support, especially during periods of high stress.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin B7", "supplementBName": "Alpha-Lipoic Acid", "interactionType": "conflict", "severity": "moderate", "description": "Alpha-lipoic acid competes with biotin (B7) for the SMVT transporter in the gut, potentially reducing biotin absorption.", "recommendation": "Separate ALA and biotin by at least 2 hours. If taking ALA long-term, consider extra biotin supplementation.", "minimumTimeSeparation": 120, "mechanism": "Both biotin and lipoic acid are transported by the sodium-dependent multivitamin transporter (SMVT/SLC5A6) in the intestine. ALA competitively inhibits biotin uptake.", "evidenceLevel": "moderate", "sources": [ { "text": "Prasad PD et al. Cloning and functional expression of a cDNA encoding a mammalian sodium-dependent vitamin transporter mediating the uptake of pantothenate, biotin, and lipoate. J Biol Chem. 1998.", "pmid": "9516450", "doi": "10.1074/jbc.273.13.7501", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9516450/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Alpha-lipoic acid competes with biotin (B7) for the SMVT transporter in the gut, potentially reducing biotin absorption.", "clinicalSignificance": "Separate ALA and biotin by at least 2 hours.", "managementStrategy": "Separate ALA and biotin by at least 2 hours. If taking ALA long-term, consider extra biotin supplementation.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin B5", "supplementBName": "Alpha-Lipoic Acid", "interactionType": "conflict", "severity": "info", "description": "Pantothenate (B5) also uses the SMVT transporter and may compete with alpha-lipoic acid for absorption.", "recommendation": "Separate by 2 hours if taking high doses of either. At typical supplement doses, competition is minimal.", "minimumTimeSeparation": 120, "mechanism": "SMVT (SLC5A6) transports pantothenate, biotin, and lipoate. High-dose ALA can reduce pantothenate absorption through competitive inhibition.", "evidenceLevel": "emerging", "sources": [ { "text": "Prasad PD et al. Cloning and functional expression of a cDNA encoding a mammalian sodium-dependent vitamin transporter. J Biol Chem. 1998", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Pantothenate (B5) also uses the SMVT transporter and may compete with alpha-lipoic acid for absorption.", "clinicalSignificance": "Separate by 2 hours if taking high doses of either.", "managementStrategy": "Separate by 2 hours if taking high doses of either. At typical supplement doses, competition is minimal.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Magnesium L-Threonate", "supplementBName": "Melatonin", "interactionType": "synergy", "severity": "info", "description": "Melatonin and magnesium are commonly used in sleep routines, but direct stack evidence and optimal dosing vary.", "recommendation": "If combining melatonin with magnesium l-threonate, keep magnesium within 200-350 mg/day supplemental elemental magnesium unless clinician-supervised and keep melatonin use situational or clinician-guided for persistent insomnia.", "minimumTimeSeparation": null, "mechanism": "Magnesium participates in neuromuscular and sleep-related physiology; melatonin supports circadian timing. The combination should be presented as routine support, not a sleep-disorder treatment.", "evidenceLevel": "emerging", "sources": [ { "text": "Slutsky I et al. Enhancement of learning and memory by elevating brain magnesium. Neuron. 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Potential sleep-routine support.", "clinicalSignificance": "Dose and duration should stay conservative, especially with chronic sleep problems.", "managementStrategy": "If combining melatonin with magnesium l-threonate, keep magnesium within 200-350 mg/day supplemental elemental magnesium unless clinician-supervised and keep melatonin use situational or clinician-guided for persistent insomnia.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Magnesium L-Threonate", "supplementBName": "Lion's Mane", "interactionType": "synergy", "severity": "info", "description": "Both support neuroplasticity through different mechanisms. Magnesium L-threonate enhances synaptic density; lion's mane promotes NGF synthesis.", "recommendation": "Combine for comprehensive cognitive enhancement and neuroprotection.", "minimumTimeSeparation": null, "mechanism": "Brain magnesium (via L-threonate) increases NR2B-containing NMDA receptor density at synapses. Lion's mane erinacines stimulate NGF, promoting neuronal survival and axonal growth. Synergistic neuroplasticity.", "evidenceLevel": "emerging", "sources": [ { "text": "Slutsky I et al. Enhancement of learning and memory by elevating brain magnesium. Neuron. 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both support neuroplasticity through different mechanisms.", "clinicalSignificance": "Magnesium L-threonate enhances synaptic density; lion's mane promotes NGF synthesis.", "managementStrategy": "Combine for comprehensive cognitive enhancement and neuroprotection.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Magnesium L-Threonate", "supplementBName": "Citicoline", "interactionType": "synergy", "severity": "info", "description": "Both cross the blood-brain barrier to support cognitive function. Magnesium enhances synaptic plasticity; citicoline supports membrane phospholipid synthesis.", "recommendation": "Effective nootropic combination for memory, focus, and brain health.", "minimumTimeSeparation": null, "mechanism": "Magnesium L-threonate increases brain Mg²⁺, enhancing LTP (long-term potentiation) at hippocampal synapses. Citicoline provides building blocks for phosphatidylcholine in neuronal membranes.", "evidenceLevel": "emerging", "sources": [ { "text": "Slutsky I et al. Enhancement of learning and memory by elevating brain magnesium. Neuron. 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both cross the blood-brain barrier to support cognitive function.", "clinicalSignificance": "Magnesium enhances synaptic plasticity; citicoline supports membrane phospholipid synthesis.", "managementStrategy": "Effective nootropic combination for memory, focus, and brain health.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Magnesium Glycinate", "supplementBName": "Calcium", "interactionType": "synergy", "severity": "info", "description": "At moderate doses, magnesium and calcium work synergistically for bone health and muscle function. Calcium for contraction, magnesium for relaxation.", "recommendation": "Aim for 2:1 calcium-to-magnesium ratio. Both are essential for bone density and neuromuscular function.", "minimumTimeSeparation": null, "mechanism": "Calcium triggers muscle contraction via troponin-C binding. Magnesium promotes relaxation by competing with calcium at the NMDA receptor and supporting SERCA pump for calcium reuptake into SR.", "evidenceLevel": "strong", "sources": [ { "text": "Castiglioni S et al. Magnesium and osteoporosis: current state of knowledge. Nutrients. 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "At moderate doses, magnesium and calcium work synergistically for bone health and muscle function.", "clinicalSignificance": "Calcium for contraction, magnesium for relaxation.", "managementStrategy": "Aim for 2:1 calcium-to-magnesium ratio. Both are essential for bone density and neuromuscular function.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Iodine", "supplementBName": "Iron", "interactionType": "synergy", "severity": "info", "description": "Iron deficiency impairs thyroid hormone synthesis because thyroid peroxidase (TPO) is a heme-containing enzyme.", "recommendation": "Address iron deficiency when treating thyroid issues. Iron-deficient individuals may not respond well to iodine supplementation alone.", "minimumTimeSeparation": null, "mechanism": "TPO requires heme iron to catalyze iodide oxidation and organification into thyroglobulin. Iron deficiency reduces TPO activity, impairing T3/T4 synthesis even with adequate iodine.", "evidenceLevel": "strong", "sources": [ { "text": "Zimmermann MB, Köhrle J. The impact of iron and selenium deficiencies on iodine and thyroid metabolism. Thyroid. 2002", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Iron deficiency impairs thyroid hormone synthesis because thyroid peroxidase (TPO) is a heme-containing enzyme.", "clinicalSignificance": "Address iron deficiency when treating thyroid issues.", "managementStrategy": "Address iron deficiency when treating thyroid issues. Iron-deficient individuals may not respond well to iodine supplementation alone.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin D3", "supplementBName": "Vitamin A", "interactionType": "synergy", "severity": "info", "description": "At balanced physiological ratios, vitamins A and D work synergistically on immune regulation and gene expression.", "recommendation": "Balanced supplementation (e.g., cod liver oil ratios) supports immune function. Avoid mega-dosing either one alone.", "minimumTimeSeparation": null, "mechanism": "RAR-RXR and VDR-RXR heterodimers regulate overlapping gene sets. At physiological ratios, they cooperatively modulate immune cell differentiation, antimicrobial peptide expression, and Th1/Th2 balance.", "evidenceLevel": "moderate", "sources": [ { "text": "Cannell JJ et al. On the epidemiology of influenza. Virol J. 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "At balanced physiological ratios, vitamins A and D work synergistically on immune regulation and gene expression.", "clinicalSignificance": "Balanced supplementation (e.g., cod liver oil ratios) supports immune function.", "managementStrategy": "Balanced supplementation (e.g., cod liver oil ratios) supports immune function. Avoid mega-dosing either one alone.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin B9", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Vitamin C protects folate from oxidative degradation and helps maintain it in its reduced, active form.", "recommendation": "Take together. Vitamin C preserves folate stability in the blood and tissues.", "minimumTimeSeparation": null, "mechanism": "Ascorbic acid maintains tetrahydrofolate (THF) in its reduced form by preventing oxidation to dihydrofolate. This preserves folate coenzyme activity for one-carbon metabolism.", "evidenceLevel": "moderate", "sources": [ { "text": "Lucock M. Folic acid: nutritional biochemistry, molecular biology, and role in disease processes. Mol Genet Metab. 2000", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials.. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin C protects folate from oxidative degradation and helps maintain it in its reduced, active form.", "clinicalSignificance": "Take together.", "managementStrategy": "Take together. Vitamin C preserves folate stability in the blood and tissues.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin B6", "supplementBName": "Vitamin B9", "interactionType": "synergy", "severity": "info", "description": "B6 is required for the conversion of serine to glycine, which generates 5,10-methyleneTHF needed for folate-dependent one-carbon metabolism.", "recommendation": "Take as part of a B-complex for optimal one-carbon metabolism and homocysteine management.", "minimumTimeSeparation": null, "mechanism": "Serine hydroxymethyltransferase (SHMT) requires PLP (B6) to transfer a methyl group from serine to THF, generating 5,10-methyleneTHF, a key folate coenzyme for nucleotide synthesis.", "evidenceLevel": "strong", "sources": [ { "text": "Selhub J. Homocysteine metabolism. Annu Rev Nutr. 1999", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "B6 is required for the conversion of serine to glycine, which generates 5,10-methyleneTHF needed for folate-dependent one-carbon metabolism.", "clinicalSignificance": "Take as part of a B-complex for optimal one-carbon metabolism and homocysteine management.", "managementStrategy": "Take as part of a B-complex for optimal one-carbon metabolism and homocysteine management.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Coenzyme Q10", "supplementBName": "Alpha-Lipoic Acid", "interactionType": "synergy", "severity": "info", "description": "Both support mitochondrial function. CoQ10 is essential for the electron transport chain; ALA is a cofactor for mitochondrial dehydrogenases.", "recommendation": "Combine for comprehensive mitochondrial support, especially for cardiovascular and neurological health.", "minimumTimeSeparation": null, "mechanism": "CoQ10 shuttles electrons in the ETC (Complex I→III). ALA is a cofactor for pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase in the TCA cycle. Together they optimize mitochondrial energy production.", "evidenceLevel": "emerging", "sources": [ { "text": "Singh U et al. Alpha-lipoic acid supplementation and diabetes. Nutr Rev. 2008;66(11):646-57.", "pmid": "19019027", "doi": "10.1111/j.1753-4887.2008.00118.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19019027/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both support mitochondrial function.", "clinicalSignificance": "CoQ10 is essential for the electron transport chain; ALA is a cofactor for mitochondrial dehydrogenases.", "managementStrategy": "Combine for comprehensive mitochondrial support, especially for cardiovascular and neurological health.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Coenzyme Q10", "supplementBName": "Vitamin E", "interactionType": "synergy", "severity": "info", "description": "CoQ10 (ubiquinol form) regenerates vitamin E from its oxidized form in cell membranes, similar to how vitamin C regenerates vitamin E.", "recommendation": "Take together for enhanced membrane antioxidant protection.", "minimumTimeSeparation": null, "mechanism": "Ubiquinol (reduced CoQ10) donates a hydrogen atom to the tocopheroxyl radical, regenerating alpha-tocopherol within lipid membranes. This extends vitamin E's chain-breaking antioxidant activity.", "evidenceLevel": "moderate", "sources": [ { "text": "Kagan VE et al. Recycling and redox cycling of phenolic antioxidants. Ann N Y Acad Sci. 1998", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "CoQ10 (ubiquinol form) regenerates vitamin E from its oxidized form in cell membranes, similar to how vitamin C regenerates vitamin E.", "clinicalSignificance": "Take together for enhanced membrane antioxidant protection.", "managementStrategy": "Take together for enhanced membrane antioxidant protection.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Resveratrol", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "Resveratrol is lipophilic and absorbs better with dietary fat. Both have anti-inflammatory and cardioprotective properties.", "recommendation": "Take resveratrol with fish oil or a fat-containing meal for improved bioavailability.", "minimumTimeSeparation": null, "mechanism": "Fat increases micellar solubilization of trans-resveratrol for improved intestinal absorption. Both activate SIRT1 and inhibit NF-κB through complementary pathways for anti-inflammatory synergy.", "evidenceLevel": "emerging", "sources": [ { "text": "Walle T et al. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos. 2004", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Uchida Y, Tsuji K, Ochi E. Effects of Omega-3 fatty acids supplementation and resistance training on skeletal muscle.. Clinical Nutrition ESPEN. 2024.", "pmid": "38777432", "doi": "10.1016/j.clnesp.2024.03.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38777432/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Resveratrol is lipophilic and absorbs better with dietary fat.", "clinicalSignificance": "Both have anti-inflammatory and cardioprotective properties.", "managementStrategy": "Take resveratrol with fish oil or a fat-containing meal for improved bioavailability.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Milk Thistle", "supplementBName": "Turmeric/Curcumin", "interactionType": "synergy", "severity": "info", "description": "Both are hepatoprotective compounds that support liver health through complementary antioxidant and anti-inflammatory mechanisms.", "recommendation": "Effective liver support combination. Both protect hepatocytes and support detoxification.", "minimumTimeSeparation": null, "mechanism": "Silymarin stabilizes hepatocyte cell membranes and promotes glutathione synthesis. Curcumin inhibits NF-κB-mediated hepatic inflammation and activates Nrf2 for phase II enzyme induction.", "evidenceLevel": "moderate", "sources": [ { "text": "Abenavoli L et al. Milk thistle in liver diseases: past, present, future. Phytother Res. 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Fogacci F, Grassi D, Rizzo M, Cicero AFG. Metabolic effect of berberine-silymarin association: A meta-analysis of randomized, double-blind, placebo-controlled clinical trials. Phytotherapy Research. 2019.", "pmid": "30632209", "doi": "10.1002/ptr.6282", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30632209/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both are hepatoprotective compounds that support liver health through complementary antioxidant and anti-inflammatory mechanisms.", "clinicalSignificance": "Effective liver support combination.", "managementStrategy": "Effective liver support combination. Both protect hepatocytes and support detoxification.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "NMN", "supplementBName": "Coenzyme Q10", "interactionType": "synergy", "severity": "info", "description": "NMN boosts NAD+ for mitochondrial enzymes; CoQ10 supports the electron transport chain. Comprehensive mitochondrial support for anti-aging.", "recommendation": "Combine for mitochondrial anti-aging strategy. NMN fuels NAD+-dependent enzymes; CoQ10 maintains ETC efficiency.", "minimumTimeSeparation": null, "mechanism": "NAD+ (from NMN) is the primary electron carrier from TCA cycle to Complex I. CoQ10 shuttles these electrons from Complex I/II to Complex III. Both decline with age; replacing both optimizes mitochondrial function.", "evidenceLevel": "emerging", "sources": [ { "text": "Imai SI, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "NMN boosts NAD+ for mitochondrial enzymes; CoQ10 supports the electron transport chain.", "clinicalSignificance": "Comprehensive mitochondrial support for anti-aging.", "managementStrategy": "Combine for mitochondrial anti-aging strategy. NMN fuels NAD+-dependent enzymes; CoQ10 maintains ETC efficiency.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Ashwagandha", "supplementBName": "Iron", "interactionType": "synergy", "severity": "info", "description": "Ashwagandha root contains natural iron and has been shown to support healthy iron levels and hemoglobin formation in traditional use.", "recommendation": "Ashwagandha may complement iron supplementation for mild iron deficiency, but is not a substitute for iron therapy in significant deficiency.", "minimumTimeSeparation": null, "mechanism": "Withania somnifera root extract has been shown to increase hemoglobin levels in clinical studies, possibly through iron content and erythropoiesis stimulation.", "evidenceLevel": "emerging", "sources": [ { "text": "Raut A et al. Exploratory study to evaluate tolerability, safety, and activity of Ashwagandha in healthy volunteers. J Ayurveda Integr Med. 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Ashwagandha root contains natural iron and has been shown to support healthy iron levels and hemoglobin formation in traditional use.", "clinicalSignificance": "Ashwagandha may complement iron supplementation for mild iron deficiency, but is not a substitute for iron therapy in significant deficiency.", "managementStrategy": "Ashwagandha may complement iron supplementation for mild iron deficiency, but is not a substitute for iron therapy in significant deficiency.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Rhodiola Rosea", "supplementBName": "L-Tyrosine", "interactionType": "synergy", "severity": "info", "description": "Rhodiola inhibits MAO and COMT, reducing dopamine/norepinephrine breakdown. L-tyrosine provides the precursor. Together they increase catecholamine availability.", "recommendation": "Effective focus and mental energy stack. Take in the morning for sustained cognitive performance.", "minimumTimeSeparation": null, "mechanism": "Rhodiola's salidroside and rosavins inhibit MAO-A/B and COMT, reducing catecholamine degradation. L-tyrosine provides substrate for TH to increase catecholamine synthesis. Net increase in dopamine/NE signaling.", "evidenceLevel": "emerging", "sources": [ { "text": "van Diermen D et al. Monoamine oxidase inhibition by Rhodiola rosea roots. J Ethnopharmacol. 2009", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Rhodiola inhibits MAO and COMT, reducing dopamine/norepinephrine breakdown.", "clinicalSignificance": "L-tyrosine provides the precursor.", "managementStrategy": "Effective focus and mental energy stack. Take in the morning for sustained cognitive performance.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Berberine", "supplementBName": "Alpha-Lipoic Acid", "interactionType": "synergy", "severity": "info", "description": "Both improve insulin sensitivity through AMPK activation. ALA also supports glucose uptake via GLUT4 translocation.", "recommendation": "Combine for enhanced metabolic support. Monitor blood glucose if combining with diabetes medications.", "minimumTimeSeparation": null, "mechanism": "Berberine activates AMPK via mitochondrial Complex I inhibition. ALA activates AMPK via CaMKK pathway and enhances insulin-stimulated glucose uptake by promoting GLUT4 translocation.", "evidenceLevel": "emerging", "sources": [ { "text": "Singh U et al. Alpha-lipoic acid supplementation and diabetes. Nutr Rev. 2008;66(11):646-57.", "pmid": "19019027", "doi": "10.1111/j.1753-4887.2008.00118.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19019027/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both improve insulin sensitivity through AMPK activation.", "clinicalSignificance": "ALA also supports glucose uptake via GLUT4 translocation.", "managementStrategy": "Combine for enhanced metabolic support. Monitor blood glucose if combining with diabetes medications.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Digestive Enzymes", "supplementBName": "Turmeric/Curcumin", "interactionType": "synergy", "severity": "info", "description": "Digestive enzymes can improve curcumin absorption by breaking down the food matrix. Curcumin also stimulates bile flow which aids fat digestion.", "recommendation": "Take digestive enzymes and curcumin with meals for mutual benefit.", "minimumTimeSeparation": null, "mechanism": "Protease and lipase enzymes break down the food matrix, releasing curcumin for absorption. Curcumin stimulates cholecystokinin and bile flow, enhancing lipid emulsification for enzyme access.", "evidenceLevel": "emerging", "sources": [ { "text": "Dulbecco P, Savarino V. Therapeutic potential of curcumin in digestive diseases. World J Gastroenterol. 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Digestive enzymes can improve curcumin absorption by breaking down the food matrix.", "clinicalSignificance": "Curcumin also stimulates bile flow which aids fat digestion.", "managementStrategy": "Take digestive enzymes and curcumin with meals for mutual benefit.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Fish Oil", "supplementBName": "Vitamin E", "interactionType": "caution", "severity": "info", "description": "High-dose fish oil increases vitamin E requirements because PUFAs are susceptible to peroxidation. May deplete vitamin E stores.", "recommendation": "If taking high-dose fish oil (>3g/day), ensure adequate vitamin E intake to prevent PUFA-induced vitamin E depletion.", "minimumTimeSeparation": null, "mechanism": "EPA and DHA's multiple double bonds make them highly susceptible to lipid peroxidation. Each peroxidation event consumes one molecule of alpha-tocopherol, increasing turnover.", "evidenceLevel": "moderate", "sources": [ { "text": "Meydani M. Vitamin E requirement in relation to dietary fish oil and oxidative stress. World Rev Nutr Diet. 1994", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Uchida Y, Tsuji K, Ochi E. Effects of Omega-3 fatty acids supplementation and resistance training on skeletal muscle.. Clinical Nutrition ESPEN. 2024.", "pmid": "38777432", "doi": "10.1016/j.clnesp.2024.03.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38777432/", "publicSourceType": "PMID" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "High-dose fish oil increases vitamin E requirements because PUFAs are susceptible to peroxidation.", "clinicalSignificance": "May deplete vitamin E stores.", "managementStrategy": "If taking high-dose fish oil (>3g/day), ensure adequate vitamin E intake to prevent PUFA-induced vitamin E depletion.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Alpha-GPC", "supplementBName": "Vitamin B5", "interactionType": "synergy", "severity": "info", "description": "B5 (pantothenic acid) is required for acetyl-CoA synthesis, which combines with choline (from Alpha-GPC) to form acetylcholine.", "recommendation": "Take together to support acetylcholine synthesis. B5 provides the acetyl group, Alpha-GPC provides the choline.", "minimumTimeSeparation": null, "mechanism": "B5 → CoA → acetyl-CoA. Alpha-GPC → choline. Choline acetyltransferase combines acetyl-CoA + choline → acetylcholine. Both substrates needed for optimal ACh production.", "evidenceLevel": "moderate", "sources": [ { "text": "Tayebati SK et al. Effect of choline-containing phospholipids on brain cholinergic transporters. Pharmacol Res. 2011", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Sagaro GG, Traini E, Amenta F. Activity of Choline Alphoscerate on Adult-Onset Cognitive Dysfunctions: A Systematic Review and Meta-Analysis. J Alzheimers Dis. 2023.", "pmid": "36683513", "doi": "10.3233/JAD-221189", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36683513/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "B5 (pantothenic acid) is required for acetyl-CoA synthesis, which combines with choline (from Alpha-GPC) to form acetylcholine.", "clinicalSignificance": "Take together to support acetylcholine synthesis.", "managementStrategy": "Take together to support acetylcholine synthesis. B5 provides the acetyl group, Alpha-GPC provides the choline.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Selenium", "supplementBName": "Zinc", "interactionType": "synergy", "severity": "info", "description": "Both support immune function and antioxidant defense. Zinc supports SOD and thymulin; selenium supports GPx and selenoproteins.", "recommendation": "Take together for comprehensive immune and antioxidant support.", "minimumTimeSeparation": null, "mechanism": "Zinc activates Cu/Zn-SOD, supports thymic function, and is needed for T-cell proliferation. Selenium supports glutathione peroxidases and thioredoxin reductases. Complementary immune-antioxidant pathways.", "evidenceLevel": "moderate", "sources": [ { "text": "Calder PC et al. Optimal nutritional status for a well-functioning immune system. Nutrients. 2020", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both support immune function and antioxidant defense.", "clinicalSignificance": "Zinc supports SOD and thymulin; selenium supports GPx and selenoproteins.", "managementStrategy": "Take together for comprehensive immune and antioxidant support.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Creatine", "supplementBName": "Alpha-GPC", "interactionType": "synergy", "severity": "info", "description": "Both enhance physical and cognitive performance. Creatine buffers ATP in muscles and brain; Alpha-GPC supports cholinergic signaling and growth hormone release.", "recommendation": "Effective performance stack for both cognitive and physical output.", "minimumTimeSeparation": null, "mechanism": "Creatine increases phosphocreatine for rapid ATP regeneration in brain and muscle. Alpha-GPC provides choline for ACh synthesis and may stimulate GH release via cholinergic pathways.", "evidenceLevel": "emerging", "sources": [ { "text": "Ziegenfuss T et al. Acute supplementation with alpha-glycerylphosphorylcholine augments growth hormone response. J Int Soc Sports Nutr. 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Sagaro GG, Traini E, Amenta F. Activity of Choline Alphoscerate on Adult-Onset Cognitive Dysfunctions: A Systematic Review and Meta-Analysis. J Alzheimers Dis. 2023.", "pmid": "36683513", "doi": "10.3233/JAD-221189", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36683513/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both enhance physical and cognitive performance.", "clinicalSignificance": "Creatine buffers ATP in muscles and brain; Alpha-GPC supports cholinergic signaling and growth hormone release.", "managementStrategy": "Effective performance stack for both cognitive and physical output.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin D3", "supplementBName": "Probiotics", "interactionType": "synergy", "severity": "info", "description": "Vitamin D supports the gut immune barrier. Probiotics modulate the microbiome. Together they support gut-immune axis health.", "recommendation": "Complementary gut health support. Vitamin D strengthens gut barrier; probiotics diversify beneficial flora.", "minimumTimeSeparation": null, "mechanism": "D3 upregulates tight junction proteins and antimicrobial peptides in the gut epithelium, creating a healthier environment for probiotic colonization and function.", "evidenceLevel": "emerging", "sources": [ { "text": "Waterhouse M et al. Vitamin D and the gut microbiome. Nutr Rev. 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin D supports the gut immune barrier.", "clinicalSignificance": "Probiotics modulate the microbiome.", "managementStrategy": "Complementary gut health support. Vitamin D strengthens gut barrier; probiotics diversify beneficial flora.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin C Liposomal", "supplementBName": "Iron", "interactionType": "synergy", "severity": "info", "description": "Vitamin C Liposomal dramatically increases non-heme iron absorption by reducing ferric iron (Fe3+) to ferrous iron (Fe2+) and forming a soluble chelate.", "recommendation": "Take 50-100mg+ vitamin C with iron supplements to maximize absorption (higher doses showed no further benefit). Especially important for plant-based iron sources.", "minimumTimeSeparation": null, "mechanism": "Ascorbic acid reduces Fe3+ to Fe2+ at the gut brush border, forming a soluble iron-ascorbate chelate that remains bioavailable at intestinal pH.", "evidenceLevel": "strong", "sources": [ { "text": "Hallberg L et al. The role of vitamin C in iron absorption. Int J Vitam Nutr Res. 1989", "pmid": "2507689", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2507689/", "publicSourceType": "PMID" }, { "text": "Lane DJ, Richardson DR. The active role of vitamin C in mammalian iron metabolism. Free Radic Biol Med. 2014", "pmid": "24566470", "doi": "10.1016/j.freeradbiomed.2014.02.009", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24566470/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Vitamin C Liposomal dramatically increases non-heme iron absorption by reducing ferric iron (Fe3+) to ferrous iron (Fe2+) and forming a soluble chelate.", "clinicalSignificance": "Take 50-100mg+ vitamin C with iron supplements to maximize absorption (higher doses showed no further benefit).", "managementStrategy": "Take 50-100mg+ vitamin C with iron supplements to maximize absorption (higher doses showed no further benefit). Especially important for plant-based iron sources.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Quercetin", "supplementBName": "Vitamin C Liposomal", "interactionType": "synergy", "severity": "info", "description": "Quercetin and vitamin C have synergistic antioxidant effects. Vitamin C Liposomal helps regenerate oxidized quercetin.", "recommendation": "Take together for enhanced antioxidant and immune support.", "minimumTimeSeparation": null, "mechanism": "Vitamin C Liposomal regenerates quercetin from its oxidized form, extending its antioxidant lifespan. Both inhibit inflammatory mediators via complementary pathways.", "evidenceLevel": "moderate", "sources": [ { "text": "Boots AW et al. The quercetin paradox. Biochem Biophys Res Commun. 2003", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Quercetin and vitamin C have synergistic antioxidant effects.", "clinicalSignificance": "Vitamin C Liposomal helps regenerate oxidized quercetin.", "managementStrategy": "Take together for enhanced antioxidant and immune support.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin E", "supplementBName": "Vitamin C Liposomal", "interactionType": "synergy", "severity": "info", "description": "Vitamin C Liposomal regenerates vitamin E from its oxidized tocopheroxyl radical form, extending its antioxidant capacity.", "recommendation": "Take together for optimal antioxidant protection. Vitamin C Liposomal recycles vitamin E in cell membranes.", "minimumTimeSeparation": null, "mechanism": "Ascorbate donates an electron to the tocopheroxyl radical at the membrane-cytosol interface, regenerating alpha-tocopherol and extending its chain-breaking antioxidant activity.", "evidenceLevel": "strong", "sources": [ { "text": "Traber MG, Stevens JF. Vitamins C and E: beneficial effects from a mechanistic perspective. Free Radic Biol Med. 2011", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin C Liposomal regenerates vitamin E from its oxidized tocopheroxyl radical form, extending its antioxidant capacity.", "clinicalSignificance": "Take together for optimal antioxidant protection.", "managementStrategy": "Take together for optimal antioxidant protection. Vitamin C Liposomal recycles vitamin E in cell membranes.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "NAC", "supplementBName": "Vitamin C Liposomal", "interactionType": "synergy", "severity": "info", "description": "NAC replenishes intracellular glutathione, while vitamin C provides extracellular antioxidant support. Complementary antioxidant systems.", "recommendation": "Take together for comprehensive antioxidant coverage, glutathione (intracellular) + ascorbate (extracellular).", "minimumTimeSeparation": null, "mechanism": "NAC provides cysteine for glutathione synthesis (rate-limiting substrate). Vitamin C Liposomal recycles oxidized glutathione (GSSG) back to reduced GSH and provides parallel antioxidant protection.", "evidenceLevel": "moderate", "sources": [ { "text": "Rushworth GF, Megson IL. Existing and potential therapeutic uses for N-acetylcysteine. Pharmacol Ther. 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "NAC replenishes intracellular glutathione, while vitamin C provides extracellular antioxidant support.", "clinicalSignificance": "Complementary antioxidant systems.", "managementStrategy": "Take together for comprehensive antioxidant coverage, glutathione (intracellular) + ascorbate (extracellular).", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Collagen Peptides", "supplementBName": "Vitamin C Liposomal", "interactionType": "synergy", "severity": "info", "description": "Vitamin C Liposomal is essential for collagen synthesis. It's a required cofactor for prolyl and lysyl hydroxylase enzymes that stabilize the collagen triple helix.", "recommendation": "Always take vitamin C with collagen supplements. Without adequate C, collagen cannot properly cross-link.", "minimumTimeSeparation": null, "mechanism": "Ascorbate is the electron donor for prolyl-4-hydroxylase and lysyl hydroxylase, which hydroxylate proline and lysine residues essential for collagen triple helix stability.", "evidenceLevel": "strong", "sources": [ { "text": "Pullar JM et al. The roles of vitamin C in skin health. Nutrients. 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bischof K, Moitzi AM, Stafilidis S et al.. Impact of Collagen Peptide Supplementation in Combination with Long-Term Physical Training on Strength, Musculotendinous Remodeling, Functional Recovery, and Body Composition in Healthy Adults: A Systematic Review with Meta-analysis.. Sports Medicine. 2024.", "pmid": "39060741", "doi": "10.1007/s40279-024-02079-0", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39060741/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin C Liposomal is essential for collagen synthesis.", "clinicalSignificance": "It's a required cofactor for prolyl and lysyl hydroxylase enzymes that stabilize the collagen triple helix.", "managementStrategy": "Always take vitamin C with collagen supplements. Without adequate C, collagen cannot properly cross-link.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Alpha-Lipoic Acid", "supplementBName": "Vitamin C Liposomal", "interactionType": "synergy", "severity": "info", "description": "ALA regenerates vitamin C from its oxidized form (dehydroascorbate) back to ascorbate.", "recommendation": "Taking together creates an antioxidant recycling network: ALA → regenerates C → regenerates E.", "minimumTimeSeparation": null, "mechanism": "Dihydrolipoic acid (reduced ALA) donates electrons to dehydroascorbate, regenerating ascorbate. This creates a self-reinforcing antioxidant network.", "evidenceLevel": "moderate", "sources": [ { "text": "Packer L et al. Alpha-lipoic acid as a biological antioxidant. Free Radic Biol Med. 1995", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "ALA regenerates vitamin C from its oxidized form (dehydroascorbate) back to ascorbate.", "clinicalSignificance": "Taking together creates an antioxidant recycling network: ALA → regenerates C → regenerates E.", "managementStrategy": "Taking together creates an antioxidant recycling network: ALA → regenerates C → regenerates E.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Chromium", "supplementBName": "Vitamin C Liposomal", "interactionType": "synergy", "severity": "info", "description": "Vitamin C Liposomal enhances chromium absorption by reducing Cr3+ in the gut, making it more bioavailable.", "recommendation": "Take chromium with vitamin C for improved absorption. 200mcg chromium + 500mg vitamin C.", "minimumTimeSeparation": null, "mechanism": "Ascorbic acid reduces chromium in the intestinal lumen, increasing the proportion in the more absorbable Cr3+ state and enhancing passive diffusion across the intestinal epithelium.", "evidenceLevel": "moderate", "sources": [ { "text": "Offenbacher EG. Promotion of chromium absorption by ascorbic acid. Trace Elem Electrolytes. 1994", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin C Liposomal enhances chromium absorption by reducing Cr3+ in the gut, making it more bioavailable.", "clinicalSignificance": "Take chromium with vitamin C for improved absorption.", "managementStrategy": "Take chromium with vitamin C for improved absorption. 200mcg chromium + 500mg vitamin C.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Calcium", "supplementBName": "Vitamin C Liposomal", "interactionType": "synergy", "severity": "info", "description": "Vitamin C Liposomal mildly enhances calcium absorption by maintaining calcium in the soluble, ionized form in the gut.", "recommendation": "Can take together. Vitamin C Liposomal provides a modest boost to calcium absorption.", "minimumTimeSeparation": null, "mechanism": "Ascorbic acid chelates calcium in the intestinal lumen, maintaining it in a soluble form and enhancing paracellular absorption in the small intestine.", "evidenceLevel": "emerging", "sources": [ { "text": "Levine M et al. Vitamin C pharmacokinetics in healthy volunteers. Proc Natl Acad Sci. 1996", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin C Liposomal mildly enhances calcium absorption by maintaining calcium in the soluble, ionized form in the gut.", "clinicalSignificance": "Can take together.", "managementStrategy": "Can take together. Vitamin C Liposomal provides a modest boost to calcium absorption.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Selenium", "supplementBName": "Vitamin C Liposomal", "interactionType": "timingSensitive", "severity": "moderate", "description": "High-dose vitamin C may reduce selenite to elemental selenium, which is not absorbable. Does not affect selenomethionine forms.", "recommendation": "If using sodium selenite form, separate from high-dose vitamin C by 2 hours. Selenomethionine is unaffected.", "minimumTimeSeparation": 120, "mechanism": "Ascorbic acid reduces selenite (SeO3²⁻) to elemental Se(0) in the GI tract, rendering it insoluble and unabsorbable. Selenomethionine is absorbed via methionine transporters, unaffected by redox.", "evidenceLevel": "moderate", "sources": [ { "text": "Ip C. Interaction of vitamin C and selenium supplementation in the modification of mammary carcinogenesis in rats. J Natl Cancer Inst. 1986.", "pmid": "3088312", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3088312/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose vitamin C may reduce selenite to elemental selenium, which is not absorbable.", "clinicalSignificance": "Does not affect selenomethionine forms.", "managementStrategy": "If using sodium selenite form, separate from high-dose vitamin C by 2 hours. Selenomethionine is unaffected.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "L-Tyrosine", "supplementBName": "Vitamin C Liposomal", "interactionType": "synergy", "severity": "info", "description": "Vitamin C Liposomal is a cofactor for dopamine beta-hydroxylase, which converts dopamine (from tyrosine) to norepinephrine.", "recommendation": "Take vitamin C with L-tyrosine to support the full catecholamine synthesis pathway from dopamine to norepinephrine.", "minimumTimeSeparation": null, "mechanism": "After L-tyrosine → L-DOPA → dopamine, dopamine beta-hydroxylase (DBH) converts dopamine to norepinephrine. DBH requires ascorbate as an electron donor for this copper-dependent reaction.", "evidenceLevel": "strong", "sources": [ { "text": "May JM et al. Ascorbic acid efficiently enhances neuronal synthesis of norepinephrine from dopamine. Brain Res Bull. 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin C Liposomal is a cofactor for dopamine beta-hydroxylase, which converts dopamine (from tyrosine) to norepinephrine.", "clinicalSignificance": "Take vitamin C with L-tyrosine to support the full catecholamine synthesis pathway from dopamine to norepinephrine.", "managementStrategy": "Take vitamin C with L-tyrosine to support the full catecholamine synthesis pathway from dopamine to norepinephrine.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin B5", "supplementBName": "Vitamin C Liposomal", "interactionType": "synergy", "severity": "info", "description": "Both support adrenal function and cortisol regulation. B5 (pantothenic acid) is critical for CoA synthesis needed in adrenal steroid hormone production.", "recommendation": "Combine for adrenal support, especially during periods of high stress.", "minimumTimeSeparation": null, "mechanism": "B5 is converted to CoA, essential for acetyl-CoA production and adrenal steroidogenesis. Vitamin C Liposomal is concentrated in adrenal glands and required for cortisol synthesis via dopamine beta-hydroxylase.", "evidenceLevel": "moderate", "sources": [ { "text": "Tahiliani AG, Beinlich CJ. Pantothenic acid in health and disease. Vitam Horm. 1991", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both support adrenal function and cortisol regulation.", "clinicalSignificance": "B5 (pantothenic acid) is critical for CoA synthesis needed in adrenal steroid hormone production.", "managementStrategy": "Combine for adrenal support, especially during periods of high stress.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin B9", "supplementBName": "Vitamin C Liposomal", "interactionType": "synergy", "severity": "info", "description": "Vitamin C Liposomal protects folate from oxidative degradation and helps maintain it in its reduced, active form.", "recommendation": "Take together. Vitamin C Liposomal preserves folate stability in the blood and tissues.", "minimumTimeSeparation": null, "mechanism": "Ascorbic acid maintains tetrahydrofolate (THF) in its reduced form by preventing oxidation to dihydrofolate. This preserves folate coenzyme activity for one-carbon metabolism.", "evidenceLevel": "moderate", "sources": [ { "text": "Lucock M. Folic acid: nutritional biochemistry, molecular biology, and role in disease processes. Mol Genet Metab. 2000", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin C Liposomal protects folate from oxidative degradation and helps maintain it in its reduced, active form.", "clinicalSignificance": "Take together.", "managementStrategy": "Take together. Vitamin C Liposomal preserves folate stability in the blood and tissues.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin D3", "supplementBName": "Vitamin K2 MK-4", "interactionType": "synergy", "severity": "info", "description": "Vitamin D3 increases calcium absorption, while K2 activates osteocalcin and matrix GLA protein to direct calcium into bones and away from arteries.", "recommendation": "Take together. K2 (MK-7 100-200mcg) is recommended whenever supplementing D3 above 2000 IU.", "minimumTimeSeparation": null, "mechanism": "D3 upregulates calcium absorption; K2 activates calcium-binding proteins (osteocalcin, MGP) that shuttle calcium to bone matrix and prevent arterial calcification. Note: 2023 meta-analysis of 14 RCTs found vitamin K supplementation did NOT significantly prevent vascular calcification.", "evidenceLevel": "moderate", "sources": [ { "text": "Masterjohn C. Vitamin D toxicity redefined. Med Hypotheses. 2007", "pmid": "17141962", "doi": "10.1016/j.mehy.2006.09.051", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17141962/", "publicSourceType": "PMID" }, { "text": "Kidd PM. Vitamins D and K as pleiotropic nutrients. J Orthomol Med. 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin D3 increases calcium absorption, while K2 activates osteocalcin and matrix GLA protein to direct calcium into bones and away from arteries.", "clinicalSignificance": "Take together.", "managementStrategy": "Take together. K2 (MK-7 100-200mcg) is recommended whenever supplementing D3 above 2000 IU.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin K1", "supplementBName": "Vitamin K2 MK-4", "interactionType": "synergy", "severity": "info", "description": "K1 primarily supports coagulation while K2 (MK-7) directs calcium to bones. Complementary roles in vitamin K metabolism.", "recommendation": "Both forms are beneficial. K2 (MK-7) has a longer half-life and better extrahepatic distribution than K1.", "minimumTimeSeparation": null, "mechanism": "K1 (phylloquinone) activates hepatic clotting factors. K2 (menaquinone-7) has greater bioavailability for extrahepatic tissues, activating osteocalcin and MGP.", "evidenceLevel": "moderate", "sources": [ { "text": "Schurgers LJ et al. Vitamin K–containing dietary supplements. Blood. 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "K1 primarily supports coagulation while K2 (MK-7) directs calcium to bones.", "clinicalSignificance": "Complementary roles in vitamin K metabolism.", "managementStrategy": "Both forms are beneficial. K2 (MK-7) has a longer half-life and better extrahepatic distribution than K1.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin K2 MK-4", "supplementBName": "Calcium", "interactionType": "synergy", "severity": "moderate", "description": "K2 activates osteocalcin to direct calcium to bones and matrix GLA protein to prevent arterial calcification. Essential when supplementing calcium.", "recommendation": "Always take K2 (MK-7, 100-200mcg) when supplementing calcium to ensure proper calcium deposition in bones, not arteries.", "minimumTimeSeparation": null, "mechanism": "K2-dependent carboxylation of osteocalcin enables it to bind calcium and deposit it in bone matrix. MGP carboxylation by K2 prevents calcium deposition in arterial walls.", "evidenceLevel": "strong", "sources": [ { "text": "Knapen MH et al. Menaquinone-7 supplementation improves arterial stiffness. Thromb Haemost. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "K2 activates osteocalcin to direct calcium to bones and matrix GLA protein to prevent arterial calcification.", "clinicalSignificance": "Essential when supplementing calcium.", "managementStrategy": "Always take K2 (MK-7, 100-200mcg) when supplementing calcium to ensure proper calcium deposition in bones, not arteries.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin K2 MK-4", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "K2 (MK-7) is fat-soluble and absorption increases with dietary fat. Fish oil provides an excellent fat vehicle.", "recommendation": "Take K2 with fish oil or a fat-containing meal for optimal absorption.", "minimumTimeSeparation": null, "mechanism": "MK-7 is a fat-soluble isoprenoid. Dietary fat stimulates bile secretion and forms micelles that solubilize MK-7 for intestinal absorption via chylomicron incorporation.", "evidenceLevel": "moderate", "sources": [ { "text": "Schurgers LJ, Vermeer C. Determination of phylloquinone and menaquinones in food. Haemostasis. 2000", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Uchida Y, Tsuji K, Ochi E. Effects of Omega-3 fatty acids supplementation and resistance training on skeletal muscle.. Clinical Nutrition ESPEN. 2024.", "pmid": "38777432", "doi": "10.1016/j.clnesp.2024.03.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38777432/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "K2 (MK-7) is fat-soluble and absorption increases with dietary fat.", "clinicalSignificance": "Fish oil provides an excellent fat vehicle.", "managementStrategy": "Take K2 with fish oil or a fat-containing meal for optimal absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin E", "supplementBName": "Vitamin K2 MK-4", "interactionType": "caution", "severity": "moderate", "description": "High-dose vitamin E may reduce K2-dependent protein carboxylation, potentially affecting both bone and cardiovascular K2 benefits.", "recommendation": "Keep vitamin E at moderate doses (200 IU or less) when relying on K2 for bone and cardiovascular health.", "minimumTimeSeparation": null, "mechanism": "Excess alpha-tocopherol competitively inhibits GGCX enzyme activity needed for K2-dependent carboxylation of osteocalcin and matrix GLA protein.", "evidenceLevel": "moderate", "sources": [ { "text": "Booth SL et al. Effect of vitamin E supplementation on vitamin K status. Am J Clin Nutr. 2004", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose vitamin E may reduce K2-dependent protein carboxylation, potentially affecting both bone and cardiovascular K2 benefits.", "clinicalSignificance": "Keep vitamin E at moderate doses (200 IU or less) when relying on K2 for bone and cardiovascular health.", "managementStrategy": "Keep vitamin E at moderate doses (200 IU or less) when relying on K2 for bone and cardiovascular health.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Methylfolate", "supplementBName": "Vitamin B12", "interactionType": "synergy", "severity": "moderate", "description": "B9 (folate) and B12 work together in the methionine cycle. B12 deficiency can be masked by high folate intake.", "recommendation": "Always supplement B12 when taking folate. B12 deficiency with high folate can cause irreversible neurological damage if undetected.", "minimumTimeSeparation": null, "mechanism": "B12 is a cofactor for methionine synthase, which uses 5-methylTHF (from folate) to remethylate homocysteine. Without B12, folate becomes trapped as 5-methylTHF (methyl trap).", "evidenceLevel": "strong", "sources": [ { "text": "Reynolds E. Vitamin B12, folic acid, and the nervous system. Lancet Neurol. 2006.", "pmid": "17052662", "doi": "10.1016/S1474-4422(06)70598-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17052662/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "B9 (folate) and B12 work together in the methionine cycle.", "clinicalSignificance": "B12 deficiency can be masked by high folate intake.", "managementStrategy": "Always supplement B12 when taking folate. B12 deficiency with high folate can cause irreversible neurological damage if undetected.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Zinc", "supplementBName": "Methylfolate", "interactionType": "caution", "severity": "info", "description": "High-dose zinc (>40mg) may impair folate absorption by inhibiting the folate conjugase enzyme in the gut.", "recommendation": "If taking high-dose zinc, monitor folate status or separate doses.", "minimumTimeSeparation": 120, "mechanism": "Zinc at high doses may inhibit pteroylpolyglutamate hydrolase (folate conjugase), the brush-border enzyme that deconjugates dietary polyglutamyl folates to the absorbable monoglutamyl form.", "evidenceLevel": "emerging", "sources": [ { "text": "Ghishan FK et al. Effect of zinc on intestinal folate absorption. Am J Physiol. 1986", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "High-dose zinc (>40mg) may impair folate absorption by inhibiting the folate conjugase enzyme in the gut.", "clinicalSignificance": "If taking high-dose zinc, monitor folate status or separate doses.", "managementStrategy": "If taking high-dose zinc, monitor folate status or separate doses.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Methylfolate", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Vitamin C protects folate from oxidative degradation and helps maintain it in its reduced, active form.", "recommendation": "Take together. Vitamin C preserves folate stability in the blood and tissues.", "minimumTimeSeparation": null, "mechanism": "Ascorbic acid maintains tetrahydrofolate (THF) in its reduced form by preventing oxidation to dihydrofolate. This preserves folate coenzyme activity for one-carbon metabolism.", "evidenceLevel": "moderate", "sources": [ { "text": "Lucock M. Folic acid: nutritional biochemistry, molecular biology, and role in disease processes. Mol Genet Metab. 2000", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials.. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin C protects folate from oxidative degradation and helps maintain it in its reduced, active form.", "clinicalSignificance": "Take together.", "managementStrategy": "Take together. Vitamin C preserves folate stability in the blood and tissues.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin B6", "supplementBName": "Methylfolate", "interactionType": "synergy", "severity": "info", "description": "B6 is required for the conversion of serine to glycine, which generates 5,10-methyleneTHF needed for folate-dependent one-carbon metabolism.", "recommendation": "Take as part of a B-complex for optimal one-carbon metabolism and homocysteine management.", "minimumTimeSeparation": null, "mechanism": "Serine hydroxymethyltransferase (SHMT) requires PLP (B6) to transfer a methyl group from serine to THF, generating 5,10-methyleneTHF, a key folate coenzyme for nucleotide synthesis.", "evidenceLevel": "strong", "sources": [ { "text": "Selhub J. Homocysteine metabolism. Annu Rev Nutr. 1999", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "B6 is required for the conversion of serine to glycine, which generates 5,10-methyleneTHF needed for folate-dependent one-carbon metabolism.", "clinicalSignificance": "Take as part of a B-complex for optimal one-carbon metabolism and homocysteine management.", "managementStrategy": "Take as part of a B-complex for optimal one-carbon metabolism and homocysteine management.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin B9", "supplementBName": "Methylcobalamin", "interactionType": "synergy", "severity": "moderate", "description": "B9 (folate) and B12 work together in the methionine cycle. B12 deficiency can be masked by high folate intake.", "recommendation": "Always supplement B12 when taking folate. B12 deficiency with high folate can cause irreversible neurological damage if undetected.", "minimumTimeSeparation": null, "mechanism": "B12 is a cofactor for methionine synthase, which uses 5-methylTHF (from folate) to remethylate homocysteine. Without B12, folate becomes trapped as 5-methylTHF (methyl trap).", "evidenceLevel": "strong", "sources": [ { "text": "Reynolds E. Vitamin B12, folic acid, and the nervous system. Lancet Neurol. 2006.", "pmid": "17052662", "doi": "10.1016/S1474-4422(06)70598-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17052662/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "B9 (folate) and B12 work together in the methionine cycle.", "clinicalSignificance": "B12 deficiency can be masked by high folate intake.", "managementStrategy": "Always supplement B12 when taking folate. B12 deficiency with high folate can cause irreversible neurological damage if undetected.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin B6", "supplementBName": "Methylcobalamin", "interactionType": "synergy", "severity": "info", "description": "B6, B12, and folate work together to metabolize homocysteine. All three are needed for optimal methylation.", "recommendation": "Take B6, B12, and folate together for comprehensive homocysteine management and methylation support.", "minimumTimeSeparation": null, "mechanism": "B6 (as PLP) is cofactor for cystathionine beta-synthase (transsulfuration pathway). B12 for methionine synthase (remethylation). Both pathways clear homocysteine.", "evidenceLevel": "strong", "sources": [ { "text": "Selhub J. Homocysteine metabolism. Annu Rev Nutr. 1999", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "B6, B12, and folate work together to metabolize homocysteine.", "clinicalSignificance": "All three are needed for optimal methylation.", "managementStrategy": "Take B6, B12, and folate together for comprehensive homocysteine management and methylation support.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Iron", "supplementBName": "Methylcobalamin", "interactionType": "synergy", "severity": "info", "description": "Both iron and B12 are essential for red blood cell production. Deficiency in either causes anemia.", "recommendation": "If anemic, check both iron and B12 status. Supplementing only one may not resolve anemia if both are deficient.", "minimumTimeSeparation": null, "mechanism": "Iron is incorporated into heme for hemoglobin synthesis. B12 is required for DNA synthesis in rapidly dividing erythroid precursors in bone marrow.", "evidenceLevel": "strong", "sources": [ { "text": "Green R et al. Vitamin B12 deficiency. Nat Rev Dis Primers. 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both iron and B12 are essential for red blood cell production.", "clinicalSignificance": "Deficiency in either causes anemia.", "managementStrategy": "If anemic, check both iron and B12 status. Supplementing only one may not resolve anemia if both are deficient.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Methylcobalamin", "supplementBName": "Calcium", "interactionType": "synergy", "severity": "info", "description": "Calcium may actually assist B12 absorption. Some evidence suggests calcium helps release B12 from food and supports intrinsic factor binding.", "recommendation": "Can be taken together. Calcium does not impair B12 absorption and may mildly assist it.", "minimumTimeSeparation": null, "mechanism": "Calcium supports the ileal receptor cubam (cubilin-amnionless) function for intrinsic factor-B12 complex absorption. Adequate calcium ensures proper receptor-mediated endocytosis.", "evidenceLevel": "emerging", "sources": [ { "text": "Russell RM et al. Influence of calcium on the bioavailability of vitamin B12. Am J Clin Nutr. 2002", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Calcium may actually assist B12 absorption.", "clinicalSignificance": "Some evidence suggests calcium helps release B12 from food and supports intrinsic factor binding.", "managementStrategy": "Can be taken together. Calcium does not impair B12 absorption and may mildly assist it.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin C", "supplementBName": "Iron Bisglycinate", "interactionType": "synergy", "severity": "info", "description": "Vitamin C dramatically increases non-heme iron bisglycinate absorption by reducing ferric iron bisglycinate (Fe3+) to ferrous iron bisglycinate (Fe2+) and forming a soluble chelate.", "recommendation": "Take 200mg+ vitamin C with iron bisglycinate supplements to maximize absorption. Especially important for plant-based iron bisglycinate sources.", "minimumTimeSeparation": null, "mechanism": "Ascorbic acid reduces Fe3+ to Fe2+ at the gut brush border, forming a soluble iron bisglycinate-ascorbate chelate that remains bioavailable at intestinal pH.", "evidenceLevel": "strong", "sources": [ { "text": "Hallberg L et al. The role of vitamin C in iron absorption. Int J Vitam Nutr Res. 1989", "pmid": "2507689", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2507689/", "publicSourceType": "PMID" }, { "text": "Lane DJ, Richardson DR. The active role of vitamin C in mammalian iron metabolism. Free Radic Biol Med. 2014", "pmid": "24566470", "doi": "10.1016/j.freeradbiomed.2014.02.009", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24566470/", "publicSourceType": "PMID" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials.. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Vitamin C dramatically increases non-heme iron bisglycinate absorption by reducing ferric iron bisglycinate (Fe3+) to ferrous iron bisglycinate (Fe2+) and forming a soluble chelate.", "clinicalSignificance": "Take 200mg+ vitamin C with iron bisglycinate supplements to maximize absorption.", "managementStrategy": "Take 200mg+ vitamin C with iron bisglycinate supplements to maximize absorption. Especially important for plant-based iron bisglycinate sources.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Iron Bisglycinate", "supplementBName": "Calcium", "interactionType": "conflict", "severity": "serious", "description": "Calcium significantly inhibits both heme and non-heme iron bisglycinate absorption when taken simultaneously.", "recommendation": "Separate iron bisglycinate and calcium by at least 2 hours. Take iron bisglycinate in the morning on an empty stomach, calcium with a different meal.", "minimumTimeSeparation": 120, "mechanism": "Calcium competes with iron bisglycinate for the DMT1 (divalent metal transporter 1) receptor in the intestinal lumen, reducing iron bisglycinate uptake by up to 50-60%.", "evidenceLevel": "strong", "sources": [ { "text": "Hallberg L et al. Calcium: effect of different amounts on nonheme- and heme-iron absorption in humans. Am J Clin Nutr. 1991", "pmid": "1831564", "doi": "10.1093/ajcn/53.1.112", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1831564/", "publicSourceType": "PMID" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Calcium significantly inhibits both heme and non-heme iron bisglycinate absorption when taken simultaneously.", "clinicalSignificance": "Separate iron bisglycinate and calcium by at least 2 hours.", "managementStrategy": "Separate iron bisglycinate and calcium by at least 2 hours. Take iron bisglycinate in the morning on an empty stomach, calcium with a different meal.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Iron Bisglycinate", "supplementBName": "Zinc", "interactionType": "conflict", "severity": "moderate", "description": "Iron Bisglycinate and zinc compete for the same absorption pathways when taken together in supplement form.", "recommendation": "Take iron bisglycinate and zinc at different times of day, separated by at least 2 hours.", "minimumTimeSeparation": 120, "mechanism": "Iron uses DMT1 while zinc uses ZIP4 exclusively. The antagonism occurs through intracellular handling mechanisms rather than shared transporter competition in enterocytes. High-dose iron bisglycinate (>25mg) can reduce zinc absorption by 50%.", "evidenceLevel": "strong", "sources": [ { "text": "Rossander-Hulten L et al. Competitive inhibition of iron absorption by manganese and zinc in humans. Am J Clin Nutr. 1991", "pmid": "2031490", "doi": "10.1093/ajcn/54.1.152", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2031490/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Iron Bisglycinate and zinc compete for the same absorption pathways when taken together in supplement form.", "clinicalSignificance": "Take iron bisglycinate and zinc at different times of day, separated by at least 2 hours.", "managementStrategy": "Take iron bisglycinate and zinc at different times of day, separated by at least 2 hours.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Iron Bisglycinate", "supplementBName": "Vitamin B12", "interactionType": "synergy", "severity": "info", "description": "Both iron bisglycinate and B12 are essential for red blood cell production. Deficiency in either causes anemia.", "recommendation": "If anemic, check both iron bisglycinate and B12 status. Supplementing only one may not resolve anemia if both are deficient.", "minimumTimeSeparation": null, "mechanism": "Iron Bisglycinate is incorporated into heme for hemoglobin synthesis. B12 is required for DNA synthesis in rapidly dividing erythroid precursors in bone marrow.", "evidenceLevel": "strong", "sources": [ { "text": "Green R et al. Vitamin B12 deficiency. Nat Rev Dis Primers. 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both iron bisglycinate and B12 are essential for red blood cell production.", "clinicalSignificance": "Deficiency in either causes anemia.", "managementStrategy": "If anemic, check both iron bisglycinate and B12 status. Supplementing only one may not resolve anemia if both are deficient.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "L-Tyrosine", "supplementBName": "Iron Bisglycinate", "interactionType": "synergy", "severity": "info", "description": "Iron Bisglycinate is a cofactor for tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis.", "recommendation": "Ensure adequate iron bisglycinate status when using L-tyrosine for cognitive support. Iron Bisglycinate deficiency impairs catecholamine synthesis.", "minimumTimeSeparation": null, "mechanism": "Tyrosine hydroxylase contains a non-heme iron bisglycinate center essential for catalytic activity. Iron Bisglycinate deficiency directly reduces dopamine and norepinephrine synthesis rates.", "evidenceLevel": "strong", "sources": [ { "text": "Beard JL et al. Iron deficiency alters brain development and functioning. J Nutr. 2003", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Iron Bisglycinate is a cofactor for tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis.", "clinicalSignificance": "Ensure adequate iron bisglycinate status when using L-tyrosine for cognitive support.", "managementStrategy": "Ensure adequate iron bisglycinate status when using L-tyrosine for cognitive support. Iron Bisglycinate deficiency impairs catecholamine synthesis.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Alpha-Lipoic Acid", "supplementBName": "Iron Bisglycinate", "interactionType": "caution", "severity": "moderate", "description": "ALA chelates metals including iron bisglycinate. May reduce iron bisglycinate absorption or redistribute iron bisglycinate stores.", "recommendation": "Separate by 2+ hours. Avoid high-dose ALA if you have iron bisglycinate deficiency.", "minimumTimeSeparation": 120, "mechanism": "ALA's dithiol group chelates divalent and trivalent metal ions including Fe2+/Fe3+, potentially reducing iron bisglycinate bioavailability and redistributing tissue iron bisglycinate stores.", "evidenceLevel": "moderate", "sources": [ { "text": "Suh JH et al. Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. Proc Natl Acad Sci U S A. 2004.", "pmid": "14985508", "doi": "10.1073/pnas.0400282101", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14985508/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "ALA chelates metals including iron bisglycinate.", "clinicalSignificance": "May reduce iron bisglycinate absorption or redistribute iron bisglycinate stores.", "managementStrategy": "Separate by 2+ hours. Avoid high-dose ALA if you have iron bisglycinate deficiency.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Probiotics", "supplementBName": "Iron Bisglycinate", "interactionType": "timingSensitive", "severity": "info", "description": "Iron Bisglycinate supplements can disrupt gut microbiome composition. However, certain probiotic strains may actually enhance iron bisglycinate absorption.", "recommendation": "Separate by 2 hours. Some Lactobacillus strains can increase iron bisglycinate absorption, so probiotics may be beneficial for iron bisglycinate-supplementing individuals.", "minimumTimeSeparation": 120, "mechanism": "Unabsorbed iron bisglycinate in the colon promotes pathogenic bacteria growth (via iron bisglycinate-dependent virulence factors). Probiotics maintain beneficial flora. Some strains reduce ferric to ferrous iron bisglycinate, enhancing absorption.", "evidenceLevel": "emerging", "sources": [ { "text": "Zimmermann MB et al. The effects of iron fortification on the gut microbiota in African children. Am J Clin Nutr. 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Iron Bisglycinate supplements can disrupt gut microbiome composition.", "clinicalSignificance": "However, certain probiotic strains may actually enhance iron bisglycinate absorption.", "managementStrategy": "Separate by 2 hours. Some Lactobacillus strains can increase iron bisglycinate absorption, so probiotics may be beneficial for iron bisglycinate-supplementing individuals.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Iron Bisglycinate", "supplementBName": "Vitamin A", "interactionType": "synergy", "severity": "info", "description": "Vitamin A improves iron bisglycinate mobilization from stores and enhances erythropoiesis. Combined supplementation is more effective than either alone for anemia.", "recommendation": "Supplementing both is more effective for iron bisglycinate-deficiency anemia than iron bisglycinate alone, especially in developing countries.", "minimumTimeSeparation": null, "mechanism": "Vitamin A mobilizes iron bisglycinate from ferritin stores in the liver and spleen. It also stimulates erythropoietin production and supports iron bisglycinate incorporation into hemoglobin during erythropoiesis.", "evidenceLevel": "strong", "sources": [ { "text": "Zimmermann MB et al. Vitamin A supplementation in iron-deficient children. Am J Clin Nutr. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin A improves iron bisglycinate mobilization from stores and enhances erythropoiesis.", "clinicalSignificance": "Combined supplementation is more effective than either alone for anemia.", "managementStrategy": "Supplementing both is more effective for iron bisglycinate-deficiency anemia than iron bisglycinate alone, especially in developing countries.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Iron Bisglycinate", "supplementBName": "Magnesium Glycinate", "interactionType": "timingSensitive", "severity": "moderate", "description": "Magnesium and iron bisglycinate can compete for absorption when taken together. Separate for optimal absorption of both.", "recommendation": "Take iron bisglycinate in the morning on an empty stomach. Take magnesium glycinate in the evening.", "minimumTimeSeparation": 120, "mechanism": "Both divalent cations compete for DMT1 transporter in the intestinal lumen. Separating by 2+ hours eliminates competition.", "evidenceLevel": "moderate", "sources": [ { "text": "Shawki A, Bhatt DK. Intestinal DMT1 is critical for iron absorption. Blood. 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Magnesium and iron bisglycinate can compete for absorption when taken together.", "clinicalSignificance": "Separate for optimal absorption of both.", "managementStrategy": "Take iron bisglycinate in the morning on an empty stomach. Take magnesium glycinate in the evening.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Iodine", "supplementBName": "Iron Bisglycinate", "interactionType": "synergy", "severity": "info", "description": "Iron Bisglycinate deficiency impairs thyroid hormone synthesis because thyroid peroxidase (TPO) is a heme-containing enzyme.", "recommendation": "Address iron bisglycinate deficiency when treating thyroid issues. Iron Bisglycinate-deficient individuals may not respond well to iodine supplementation alone.", "minimumTimeSeparation": null, "mechanism": "TPO requires heme iron bisglycinate to catalyze iodide oxidation and organification into thyroglobulin. Iron Bisglycinate deficiency reduces TPO activity, impairing T3/T4 synthesis even with adequate iodine.", "evidenceLevel": "strong", "sources": [ { "text": "Zimmermann MB, Köhrle J. The impact of iron and selenium deficiencies on iodine and thyroid metabolism. Thyroid. 2002", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Iron Bisglycinate deficiency impairs thyroid hormone synthesis because thyroid peroxidase (TPO) is a heme-containing enzyme.", "clinicalSignificance": "Address iron bisglycinate deficiency when treating thyroid issues.", "managementStrategy": "Address iron bisglycinate deficiency when treating thyroid issues. Iron Bisglycinate-deficient individuals may not respond well to iodine supplementation alone.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Ashwagandha", "supplementBName": "Iron Bisglycinate", "interactionType": "synergy", "severity": "info", "description": "Ashwagandha has limited human research involving vitality and hematologic markers, but it is not an iron source and is not a substitute for iron therapy.", "recommendation": "Treat iron deficiency with lab-guided care and clinician advice. Ashwagandha should not be used to replace prescribed or recommended iron supplementation.", "minimumTimeSeparation": null, "mechanism": "No established iron-bisglycinate mechanism is confirmed. Any hematologic findings for Withania somnifera are preliminary and should be interpreted separately from iron-repletion therapy.", "evidenceLevel": "emerging", "sources": [ { "text": "Raut A et al. Exploratory study to evaluate tolerability, safety, and activity of Ashwagandha in healthy volunteers. J Ayurveda Integr Med. 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Ashwagandha is not an iron-bisglycinate source; any overlap with iron status is preliminary and indirect.", "clinicalSignificance": "Do not rely on ashwagandha to correct iron deficiency.", "managementStrategy": "Use lab-guided iron management and clinician advice for deficiency; keep ashwagandha decisions separate from iron replacement.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Iron", "supplementBName": "Zinc Picolinate", "interactionType": "conflict", "severity": "moderate", "description": "Iron and zinc picolinate compete for the same absorption pathways when taken together in supplement form.", "recommendation": "Take iron and zinc picolinate at different times of day, separated by at least 2 hours.", "minimumTimeSeparation": 120, "mechanism": "Both divalent cations compete for DMT1 and ZIP4 transporters in enterocytes. High-dose iron (>25mg) can reduce zinc picolinate absorption by 50%.", "evidenceLevel": "strong", "sources": [ { "text": "Rossander-Hulten L et al. Competitive inhibition of iron absorption by manganese and zinc in humans. Am J Clin Nutr. 1991", "pmid": "2031490", "doi": "10.1093/ajcn/54.1.152", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2031490/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Iron and zinc picolinate compete for the same absorption pathways when taken together in supplement form.", "clinicalSignificance": "Take iron and zinc picolinate at different times of day, separated by at least 2 hours.", "managementStrategy": "Take iron and zinc picolinate at different times of day, separated by at least 2 hours.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Iron", "supplementBName": "Zinc Carnosine", "interactionType": "conflict", "severity": "moderate", "description": "Iron and zinc carnosine compete for the same absorption pathways when taken together in supplement form.", "recommendation": "Take iron and zinc carnosine at different times of day, separated by at least 2 hours.", "minimumTimeSeparation": 120, "mechanism": "Both divalent cations compete for DMT1 and ZIP4 transporters in enterocytes. High-dose iron (>25mg) can reduce zinc carnosine absorption by 50%.", "evidenceLevel": "strong", "sources": [ { "text": "Rossander-Hulten L et al. Competitive inhibition of iron absorption by manganese and zinc in humans. Am J Clin Nutr. 1991", "pmid": "2031490", "doi": "10.1093/ajcn/54.1.152", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2031490/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Iron and zinc carnosine compete for the same absorption pathways when taken together in supplement form.", "clinicalSignificance": "Take iron and zinc carnosine at different times of day, separated by at least 2 hours.", "managementStrategy": "Take iron and zinc carnosine at different times of day, separated by at least 2 hours.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Iron", "supplementBName": "Elderberry Zinc Lozenges", "interactionType": "conflict", "severity": "moderate", "description": "Iron and elderberry zinc lozenges compete for the same absorption pathways when taken together in supplement form.", "recommendation": "Take iron and elderberry zinc lozenges at different times of day, separated by at least 2 hours.", "minimumTimeSeparation": 120, "mechanism": "Both divalent cations compete for DMT1 and ZIP4 transporters in enterocytes. High-dose iron (>25mg) can reduce elderberry zinc lozenges absorption by 50%.", "evidenceLevel": "strong", "sources": [ { "text": "Rossander-Hulten L et al. Competitive inhibition of iron absorption by manganese and zinc in humans. Am J Clin Nutr. 1991", "pmid": "2031490", "doi": "10.1093/ajcn/54.1.152", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2031490/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Iron and elderberry zinc lozenges compete for the same absorption pathways when taken together in supplement form.", "clinicalSignificance": "Take iron and elderberry zinc lozenges at different times of day, separated by at least 2 hours.", "managementStrategy": "Take iron and elderberry zinc lozenges at different times of day, separated by at least 2 hours.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Zinc Picolinate", "supplementBName": "Copper", "interactionType": "caution", "severity": "serious", "description": "Chronic high-dose zinc picolinate supplementation (>40mg/day) can induce copper deficiency by upregulating metallothionein, which binds copper in enterocytes.", "recommendation": "If supplementing zinc picolinate >25mg daily, add 1-2mg copper. Many zinc picolinate supplements include copper for this reason. Monitor copper status.", "minimumTimeSeparation": null, "mechanism": "Zinc Picolinate induces metallothionein in intestinal cells, which preferentially binds copper, trapping it in enterocytes that are later shed, causing copper loss.", "evidenceLevel": "strong", "sources": [ { "text": "Fosmire GJ. Zinc toxicity. Am J Clin Nutr. 1990;51(2):225-7.", "pmid": "2407097", "doi": "10.1093/ajcn/51.2.225", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2407097/", "publicSourceType": "PMID" }, { "text": "Hoffman HN 2nd et al. Zinc-induced copper deficiency. Gastroenterology. 1988;94(2):508-12.", "pmid": "3335323", "doi": "10.1016/0016-5085(88)90445-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3335323/", "publicSourceType": "PMID" }, { "text": "Jaiser SR et al. Copper deficiency myelopathy. J Neurol. 2010;257(6):869-81.", "pmid": "20232210", "doi": "10.1007/s00415-010-5511-x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20232210/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Chronic high-dose zinc picolinate supplementation (>40mg/day) can induce copper deficiency by upregulating metallothionein, which binds copper in enterocytes.", "clinicalSignificance": "If supplementing zinc picolinate >25mg daily, add 1-2mg copper.", "managementStrategy": "If supplementing zinc picolinate >25mg daily, add 1-2mg copper. Many zinc picolinate supplements include copper for this reason. Monitor copper status.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Zinc Carnosine", "supplementBName": "Copper", "interactionType": "caution", "severity": "serious", "description": "Chronic high-dose zinc carnosine supplementation (>40mg/day) can induce copper deficiency by upregulating metallothionein, which binds copper in enterocytes.", "recommendation": "If supplementing zinc carnosine >25mg daily, add 1-2mg copper. Many zinc carnosine supplements include copper for this reason. Monitor copper status.", "minimumTimeSeparation": null, "mechanism": "Zinc Carnosine induces metallothionein in intestinal cells, which preferentially binds copper, trapping it in enterocytes that are later shed, causing copper loss.", "evidenceLevel": "strong", "sources": [ { "text": "Fosmire GJ. Zinc toxicity. Am J Clin Nutr. 1990;51(2):225-7.", "pmid": "2407097", "doi": "10.1093/ajcn/51.2.225", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2407097/", "publicSourceType": "PMID" }, { "text": "Hoffman HN 2nd et al. Zinc-induced copper deficiency. Gastroenterology. 1988;94(2):508-12.", "pmid": "3335323", "doi": "10.1016/0016-5085(88)90445-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3335323/", "publicSourceType": "PMID" }, { "text": "Jaiser SR et al. Copper deficiency myelopathy. J Neurol. 2010;257(6):869-81.", "pmid": "20232210", "doi": "10.1007/s00415-010-5511-x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20232210/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Chronic high-dose zinc carnosine supplementation (>40mg/day) can induce copper deficiency by upregulating metallothionein, which binds copper in enterocytes.", "clinicalSignificance": "If supplementing zinc carnosine >25mg daily, add 1-2mg copper.", "managementStrategy": "If supplementing zinc carnosine >25mg daily, add 1-2mg copper. Many zinc carnosine supplements include copper for this reason. Monitor copper status.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Elderberry Zinc Lozenges", "supplementBName": "Copper", "interactionType": "caution", "severity": "serious", "description": "Chronic high-dose elderberry zinc lozenges supplementation (>40mg/day) can induce copper deficiency by upregulating metallothionein, which binds copper in enterocytes.", "recommendation": "If supplementing elderberry zinc lozenges >25mg daily, add 1-2mg copper. Many elderberry zinc lozenges supplements include copper for this reason. Monitor copper status.", "minimumTimeSeparation": null, "mechanism": "Elderberry Zinc Lozenges induces metallothionein in intestinal cells, which preferentially binds copper, trapping it in enterocytes that are later shed, causing copper loss.", "evidenceLevel": "strong", "sources": [ { "text": "Fosmire GJ. Zinc toxicity. Am J Clin Nutr. 1990;51(2):225-7.", "pmid": "2407097", "doi": "10.1093/ajcn/51.2.225", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2407097/", "publicSourceType": "PMID" }, { "text": "Hoffman HN 2nd et al. Zinc-induced copper deficiency. Gastroenterology. 1988;94(2):508-12.", "pmid": "3335323", "doi": "10.1016/0016-5085(88)90445-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3335323/", "publicSourceType": "PMID" }, { "text": "Jaiser SR et al. Copper deficiency myelopathy. J Neurol. 2010;257(6):869-81.", "pmid": "20232210", "doi": "10.1007/s00415-010-5511-x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20232210/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Chronic high-dose elderberry zinc lozenges supplementation (>40mg/day) can induce copper deficiency by upregulating metallothionein, which binds copper in enterocytes.", "clinicalSignificance": "If supplementing elderberry zinc lozenges >25mg daily, add 1-2mg copper.", "managementStrategy": "If supplementing elderberry zinc lozenges >25mg daily, add 1-2mg copper. Many elderberry zinc lozenges supplements include copper for this reason. Monitor copper status.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin D3", "supplementBName": "Zinc Picolinate", "interactionType": "synergy", "severity": "info", "description": "Adequate zinc status supports normal zinc-finger transcription biology, including vitamin D receptor DNA-binding domains. Evidence does not show zinc picolinate specifically is required for VDR function.", "recommendation": "Use zinc picolinate only to meet normal zinc intake or correct deficiency; do not add high-dose zinc solely to activate vitamin D.", "minimumTimeSeparation": null, "mechanism": "The vitamin D receptor has zinc-finger DNA-binding domains that use zinc ions. This is not specific to zinc picolinate and does not prove supplementation improves vitamin D response in zinc-replete people.", "evidenceLevel": "emerging", "sources": [ { "text": "Zittermann A. Vitamin D and zinc: a dual approach for immune support. Nutrients. 2020", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Adequate zinc status supports normal zinc-finger transcription biology; zinc picolinate-specific VDR enhancement is not established.", "clinicalSignificance": "Potentially relevant only when zinc intake or status is low; not evidence that zinc picolinate is required for vitamin D signaling in zinc-replete people.", "managementStrategy": "Avoid high-dose zinc picolinate unless deficiency, low intake, or clinician direction is present.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin D3", "supplementBName": "Zinc Carnosine", "interactionType": "synergy", "severity": "info", "description": "Adequate zinc status supports normal zinc-finger transcription biology, including vitamin D receptor DNA-binding domains. Evidence does not show zinc carnosine specifically is required for VDR function.", "recommendation": "Use zinc carnosine only when appropriate for its intended indication or to address zinc status; do not add high-dose zinc solely to activate vitamin D.", "minimumTimeSeparation": null, "mechanism": "The vitamin D receptor has zinc-finger DNA-binding domains that use zinc ions. This is not specific to zinc carnosine and does not prove supplementation improves vitamin D response in zinc-replete people.", "evidenceLevel": "emerging", "sources": [ { "text": "Zittermann A. Vitamin D and zinc: a dual approach for immune support. Nutrients. 2020", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Adequate zinc status supports normal zinc-finger transcription biology; zinc carnosine-specific VDR enhancement is not established.", "clinicalSignificance": "Potentially relevant only when zinc intake or status is low; not evidence that zinc carnosine is required for vitamin D signaling in zinc-replete people.", "managementStrategy": "Avoid high-dose zinc carnosine unless deficiency, low intake, appropriate indication, or clinician direction is present.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin D3", "supplementBName": "Elderberry Zinc Lozenges", "interactionType": "synergy", "severity": "info", "description": "The zinc component can help meet zinc intake, but elderberry zinc lozenges are not required for vitamin D receptor function and should not be framed as VDR activators.", "recommendation": "Use zinc-containing lozenges only within label directions and short-term needs; do not add them solely to activate vitamin D.", "minimumTimeSeparation": null, "mechanism": "The vitamin D receptor has zinc-finger DNA-binding domains that use zinc ions. This does not make elderberry zinc lozenges necessary for VDR function or prove vitamin D response improves in zinc-replete people.", "evidenceLevel": "emerging", "sources": [ { "text": "Zittermann A. Vitamin D and zinc: a dual approach for immune support. Nutrients. 2020", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Adequate zinc status supports normal zinc-finger transcription biology; elderberry zinc lozenge-specific VDR enhancement is not established.", "clinicalSignificance": "Potentially relevant only when zinc intake or status is low; repeated high-dose lozenge use can create zinc excess or copper issues.", "managementStrategy": "Avoid high-dose or chronic zinc lozenge use unless directed by a clinician; consider total daily zinc intake.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin A", "supplementBName": "Zinc Picolinate", "interactionType": "synergy", "severity": "info", "description": "Zinc Picolinate is required for retinol-binding protein synthesis and vitamin A transport from the liver. Zinc Picolinate deficiency impairs vitamin A mobilization.", "recommendation": "Ensure adequate zinc picolinate when supplementing vitamin A. Zinc Picolinate deficiency can cause functional vitamin A deficiency even with adequate liver stores.", "minimumTimeSeparation": null, "mechanism": "Zinc Picolinate is essential for hepatic synthesis of retinol-binding protein (RBP) which transports retinol from liver stores to target tissues. Zinc Picolinate also supports alcohol dehydrogenase for retinol→retinal conversion.", "evidenceLevel": "strong", "sources": [ { "text": "Christian P, West KP Jr. Interactions between zinc and vitamin A. Am J Clin Nutr. 1998", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Zinc Picolinate is required for retinol-binding protein synthesis and vitamin A transport from the liver.", "clinicalSignificance": "Zinc Picolinate deficiency impairs vitamin A mobilization.", "managementStrategy": "Ensure adequate zinc picolinate when supplementing vitamin A. Zinc Picolinate deficiency can cause functional vitamin A deficiency even with adequate liver stores.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin A", "supplementBName": "Zinc Carnosine", "interactionType": "synergy", "severity": "info", "description": "Zinc Carnosine is required for retinol-binding protein synthesis and vitamin A transport from the liver. Zinc Carnosine deficiency impairs vitamin A mobilization.", "recommendation": "Ensure adequate zinc carnosine when supplementing vitamin A. Zinc Carnosine deficiency can cause functional vitamin A deficiency even with adequate liver stores.", "minimumTimeSeparation": null, "mechanism": "Zinc Carnosine is essential for hepatic synthesis of retinol-binding protein (RBP) which transports retinol from liver stores to target tissues. Zinc Carnosine also supports alcohol dehydrogenase for retinol→retinal conversion.", "evidenceLevel": "strong", "sources": [ { "text": "Christian P, West KP Jr. Interactions between zinc and vitamin A. Am J Clin Nutr. 1998", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Zinc Carnosine is required for retinol-binding protein synthesis and vitamin A transport from the liver.", "clinicalSignificance": "Zinc Carnosine deficiency impairs vitamin A mobilization.", "managementStrategy": "Ensure adequate zinc carnosine when supplementing vitamin A. Zinc Carnosine deficiency can cause functional vitamin A deficiency even with adequate liver stores.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin A", "supplementBName": "Elderberry Zinc Lozenges", "interactionType": "synergy", "severity": "info", "description": "Elderberry Zinc Lozenges is required for retinol-binding protein synthesis and vitamin A transport from the liver. Elderberry Zinc Lozenges deficiency impairs vitamin A mobilization.", "recommendation": "Ensure adequate elderberry zinc lozenges when supplementing vitamin A. Elderberry Zinc Lozenges deficiency can cause functional vitamin A deficiency even with adequate liver stores.", "minimumTimeSeparation": null, "mechanism": "Elderberry Zinc Lozenges is essential for hepatic synthesis of retinol-binding protein (RBP) which transports retinol from liver stores to target tissues. Elderberry Zinc Lozenges also supports alcohol dehydrogenase for retinol→retinal conversion.", "evidenceLevel": "strong", "sources": [ { "text": "Christian P, West KP Jr. Interactions between zinc and vitamin A. Am J Clin Nutr. 1998", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Elderberry Zinc Lozenges is required for retinol-binding protein synthesis and vitamin A transport from the liver.", "clinicalSignificance": "Elderberry Zinc Lozenges deficiency impairs vitamin A mobilization.", "managementStrategy": "Ensure adequate elderberry zinc lozenges when supplementing vitamin A. Elderberry Zinc Lozenges deficiency can cause functional vitamin A deficiency even with adequate liver stores.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Calcium", "supplementBName": "Zinc Picolinate", "interactionType": "timingSensitive", "severity": "moderate", "description": "High-dose calcium can reduce zinc picolinate absorption when taken simultaneously.", "recommendation": "Separate calcium and zinc picolinate supplements by at least 2 hours for optimal absorption of both.", "minimumTimeSeparation": 120, "mechanism": "Calcium may interfere with zinc picolinate absorption via competition for shared transport mechanisms in the intestinal epithelium, though the effect is less pronounced than calcium-iron competition.", "evidenceLevel": "moderate", "sources": [ { "text": "Wood RJ, Zheng JJ. High dietary calcium intakes reduce zinc absorption and balance in humans. Am J Clin Nutr. 1997.", "pmid": "9174476", "doi": "10.1093/ajcn/65.6.1803", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9174476/", "publicSourceType": "PMID" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose calcium can reduce zinc picolinate absorption when taken simultaneously.", "clinicalSignificance": "Separate calcium and zinc picolinate supplements by at least 2 hours for optimal absorption of both.", "managementStrategy": "Separate calcium and zinc picolinate supplements by at least 2 hours for optimal absorption of both.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Calcium", "supplementBName": "Zinc Carnosine", "interactionType": "timingSensitive", "severity": "moderate", "description": "High-dose calcium can reduce zinc carnosine absorption when taken simultaneously.", "recommendation": "Separate calcium and zinc carnosine supplements by at least 2 hours for optimal absorption of both.", "minimumTimeSeparation": 120, "mechanism": "Calcium may interfere with zinc carnosine absorption via competition for shared transport mechanisms in the intestinal epithelium, though the effect is less pronounced than calcium-iron competition.", "evidenceLevel": "moderate", "sources": [ { "text": "Wood RJ, Zheng JJ. High dietary calcium intakes reduce zinc absorption and balance in humans. Am J Clin Nutr. 1997.", "pmid": "9174476", "doi": "10.1093/ajcn/65.6.1803", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9174476/", "publicSourceType": "PMID" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose calcium can reduce zinc carnosine absorption when taken simultaneously.", "clinicalSignificance": "Separate calcium and zinc carnosine supplements by at least 2 hours for optimal absorption of both.", "managementStrategy": "Separate calcium and zinc carnosine supplements by at least 2 hours for optimal absorption of both.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Calcium", "supplementBName": "Elderberry Zinc Lozenges", "interactionType": "timingSensitive", "severity": "moderate", "description": "High-dose calcium can reduce elderberry zinc lozenges absorption when taken simultaneously.", "recommendation": "Separate calcium and elderberry zinc lozenges supplements by at least 2 hours for optimal absorption of both.", "minimumTimeSeparation": 120, "mechanism": "Calcium may interfere with elderberry zinc lozenges absorption via competition for shared transport mechanisms in the intestinal epithelium, though the effect is less pronounced than calcium-iron competition.", "evidenceLevel": "moderate", "sources": [ { "text": "Wood RJ, Zheng JJ. High dietary calcium intakes reduce zinc absorption and balance in humans. Am J Clin Nutr. 1997.", "pmid": "9174476", "doi": "10.1093/ajcn/65.6.1803", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9174476/", "publicSourceType": "PMID" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose calcium can reduce elderberry zinc lozenges absorption when taken simultaneously.", "clinicalSignificance": "Separate calcium and elderberry zinc lozenges supplements by at least 2 hours for optimal absorption of both.", "managementStrategy": "Separate calcium and elderberry zinc lozenges supplements by at least 2 hours for optimal absorption of both.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Zinc Picolinate", "supplementBName": "Vitamin B9", "interactionType": "caution", "severity": "info", "description": "High-dose zinc picolinate (>40mg) may impair folate absorption by inhibiting the folate conjugase enzyme in the gut.", "recommendation": "If taking high-dose zinc picolinate, monitor folate status or separate doses.", "minimumTimeSeparation": 120, "mechanism": "Zinc Picolinate at high doses may inhibit pteroylpolyglutamate hydrolase (folate conjugase), the brush-border enzyme that deconjugates dietary polyglutamyl folates to the absorbable monoglutamyl form.", "evidenceLevel": "emerging", "sources": [ { "text": "Ghishan FK et al. Effect of zinc on intestinal folate absorption. Am J Physiol. 1986", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "High-dose zinc picolinate (>40mg) may impair folate absorption by inhibiting the folate conjugase enzyme in the gut.", "clinicalSignificance": "If taking high-dose zinc picolinate, monitor folate status or separate doses.", "managementStrategy": "If taking high-dose zinc picolinate, monitor folate status or separate doses.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Zinc Carnosine", "supplementBName": "Vitamin B9", "interactionType": "caution", "severity": "info", "description": "High-dose zinc carnosine (>40mg) may impair folate absorption by inhibiting the folate conjugase enzyme in the gut.", "recommendation": "If taking high-dose zinc carnosine, monitor folate status or separate doses.", "minimumTimeSeparation": 120, "mechanism": "Zinc Carnosine at high doses may inhibit pteroylpolyglutamate hydrolase (folate conjugase), the brush-border enzyme that deconjugates dietary polyglutamyl folates to the absorbable monoglutamyl form.", "evidenceLevel": "emerging", "sources": [ { "text": "Ghishan FK et al. Effect of zinc on intestinal folate absorption. Am J Physiol. 1986", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "High-dose zinc carnosine (>40mg) may impair folate absorption by inhibiting the folate conjugase enzyme in the gut.", "clinicalSignificance": "If taking high-dose zinc carnosine, monitor folate status or separate doses.", "managementStrategy": "If taking high-dose zinc carnosine, monitor folate status or separate doses.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Elderberry Zinc Lozenges", "supplementBName": "Vitamin B9", "interactionType": "caution", "severity": "info", "description": "High-dose elderberry zinc lozenges (>40mg) may impair folate absorption by inhibiting the folate conjugase enzyme in the gut.", "recommendation": "If taking high-dose elderberry zinc lozenges, monitor folate status or separate doses.", "minimumTimeSeparation": 120, "mechanism": "Elderberry Zinc Lozenges at high doses may inhibit pteroylpolyglutamate hydrolase (folate conjugase), the brush-border enzyme that deconjugates dietary polyglutamyl folates to the absorbable monoglutamyl form.", "evidenceLevel": "emerging", "sources": [ { "text": "Ghishan FK et al. Effect of zinc on intestinal folate absorption. Am J Physiol. 1986", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "High-dose elderberry zinc lozenges (>40mg) may impair folate absorption by inhibiting the folate conjugase enzyme in the gut.", "clinicalSignificance": "If taking high-dose elderberry zinc lozenges, monitor folate status or separate doses.", "managementStrategy": "If taking high-dose elderberry zinc lozenges, monitor folate status or separate doses.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Collagen Peptides", "supplementBName": "Zinc Picolinate", "interactionType": "synergy", "severity": "info", "description": "Zinc Picolinate is essential for collagen synthesis enzymes and wound healing. Supports collagen crosslinking and skin repair.", "recommendation": "Take zinc picolinate with collagen peptides for enhanced skin, joint, and wound healing support.", "minimumTimeSeparation": null, "mechanism": "Zinc Picolinate is a cofactor for matrix metalloproteinases (collagen remodeling), prolyl hydroxylase (collagen stabilization), and is essential for fibroblast proliferation and collagen deposition.", "evidenceLevel": "moderate", "sources": [ { "text": "Kogan S et al. Zinc and wound healing. Adv Skin Wound Care. 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bischof K, Moitzi AM, Stafilidis S et al.. Impact of Collagen Peptide Supplementation in Combination with Long-Term Physical Training on Strength, Musculotendinous Remodeling, Functional Recovery, and Body Composition in Healthy Adults: A Systematic Review with Meta-analysis.. Sports Medicine. 2024.", "pmid": "39060741", "doi": "10.1007/s40279-024-02079-0", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39060741/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Zinc Picolinate is essential for collagen synthesis enzymes and wound healing.", "clinicalSignificance": "Supports collagen crosslinking and skin repair.", "managementStrategy": "Take zinc picolinate with collagen peptides for enhanced skin, joint, and wound healing support.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Collagen Peptides", "supplementBName": "Zinc Carnosine", "interactionType": "synergy", "severity": "info", "description": "Zinc Carnosine is essential for collagen synthesis enzymes and wound healing. Supports collagen crosslinking and skin repair.", "recommendation": "Take zinc carnosine with collagen peptides for enhanced skin, joint, and wound healing support.", "minimumTimeSeparation": null, "mechanism": "Zinc Carnosine is a cofactor for matrix metalloproteinases (collagen remodeling), prolyl hydroxylase (collagen stabilization), and is essential for fibroblast proliferation and collagen deposition.", "evidenceLevel": "moderate", "sources": [ { "text": "Kogan S et al. Zinc and wound healing. Adv Skin Wound Care. 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bischof K, Moitzi AM, Stafilidis S et al.. Impact of Collagen Peptide Supplementation in Combination with Long-Term Physical Training on Strength, Musculotendinous Remodeling, Functional Recovery, and Body Composition in Healthy Adults: A Systematic Review with Meta-analysis.. Sports Medicine. 2024.", "pmid": "39060741", "doi": "10.1007/s40279-024-02079-0", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39060741/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Zinc Carnosine is essential for collagen synthesis enzymes and wound healing.", "clinicalSignificance": "Supports collagen crosslinking and skin repair.", "managementStrategy": "Take zinc carnosine with collagen peptides for enhanced skin, joint, and wound healing support.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Collagen Peptides", "supplementBName": "Elderberry Zinc Lozenges", "interactionType": "synergy", "severity": "info", "description": "Elderberry Zinc Lozenges is essential for collagen synthesis enzymes and wound healing. Supports collagen crosslinking and skin repair.", "recommendation": "Take elderberry zinc lozenges with collagen peptides for enhanced skin, joint, and wound healing support.", "minimumTimeSeparation": null, "mechanism": "Elderberry Zinc Lozenges is a cofactor for matrix metalloproteinases (collagen remodeling), prolyl hydroxylase (collagen stabilization), and is essential for fibroblast proliferation and collagen deposition.", "evidenceLevel": "moderate", "sources": [ { "text": "Kogan S et al. Zinc and wound healing. Adv Skin Wound Care. 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bischof K, Moitzi AM, Stafilidis S et al.. Impact of Collagen Peptide Supplementation in Combination with Long-Term Physical Training on Strength, Musculotendinous Remodeling, Functional Recovery, and Body Composition in Healthy Adults: A Systematic Review with Meta-analysis.. Sports Medicine. 2024.", "pmid": "39060741", "doi": "10.1007/s40279-024-02079-0", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39060741/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Elderberry Zinc Lozenges is essential for collagen synthesis enzymes and wound healing.", "clinicalSignificance": "Supports collagen crosslinking and skin repair.", "managementStrategy": "Take elderberry zinc lozenges with collagen peptides for enhanced skin, joint, and wound healing support.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Selenium", "supplementBName": "Zinc Picolinate", "interactionType": "synergy", "severity": "info", "description": "Both support immune function and antioxidant defense. Zinc Picolinate supports SOD and thymulin; selenium supports GPx and selenoproteins.", "recommendation": "Take together for comprehensive immune and antioxidant support.", "minimumTimeSeparation": null, "mechanism": "Zinc Picolinate activates Cu/Zn-SOD, supports thymic function, and is needed for T-cell proliferation. Selenium supports glutathione peroxidases and thioredoxin reductases. Complementary immune-antioxidant pathways.", "evidenceLevel": "moderate", "sources": [ { "text": "Calder PC et al. Optimal nutritional status for a well-functioning immune system. Nutrients. 2020", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both support immune function and antioxidant defense.", "clinicalSignificance": "Zinc Picolinate supports SOD and thymulin; selenium supports GPx and selenoproteins.", "managementStrategy": "Take together for comprehensive immune and antioxidant support.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Selenium", "supplementBName": "Zinc Carnosine", "interactionType": "synergy", "severity": "info", "description": "Both support immune function and antioxidant defense. Zinc Carnosine supports SOD and thymulin; selenium supports GPx and selenoproteins.", "recommendation": "Take together for comprehensive immune and antioxidant support.", "minimumTimeSeparation": null, "mechanism": "Zinc Carnosine activates Cu/Zn-SOD, supports thymic function, and is needed for T-cell proliferation. Selenium supports glutathione peroxidases and thioredoxin reductases. Complementary immune-antioxidant pathways.", "evidenceLevel": "moderate", "sources": [ { "text": "Calder PC et al. Optimal nutritional status for a well-functioning immune system. Nutrients. 2020", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both support immune function and antioxidant defense.", "clinicalSignificance": "Zinc Carnosine supports SOD and thymulin; selenium supports GPx and selenoproteins.", "managementStrategy": "Take together for comprehensive immune and antioxidant support.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Selenium", "supplementBName": "Elderberry Zinc Lozenges", "interactionType": "synergy", "severity": "info", "description": "Both support immune function and antioxidant defense. Elderberry Zinc Lozenges supports SOD and thymulin; selenium supports GPx and selenoproteins.", "recommendation": "Take together for comprehensive immune and antioxidant support.", "minimumTimeSeparation": null, "mechanism": "Elderberry Zinc Lozenges activates Cu/Zn-SOD, supports thymic function, and is needed for T-cell proliferation. Selenium supports glutathione peroxidases and thioredoxin reductases. Complementary immune-antioxidant pathways.", "evidenceLevel": "moderate", "sources": [ { "text": "Calder PC et al. Optimal nutritional status for a well-functioning immune system. Nutrients. 2020", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both support immune function and antioxidant defense.", "clinicalSignificance": "Elderberry Zinc Lozenges supports SOD and thymulin; selenium supports GPx and selenoproteins.", "managementStrategy": "Take together for comprehensive immune and antioxidant support.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Curcumin Phytosome", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "Curcumin is fat-soluble and its absorption increases significantly when taken with dietary fat like fish oil. Both share anti-inflammatory pathways.", "recommendation": "Take curcumin with fish oil or a fat-containing meal for maximum absorption and synergistic anti-inflammatory effects.", "minimumTimeSeparation": null, "mechanism": "Fat increases micellar solubilization of curcumin. Both modulate NF-κB and COX-2 pathways through complementary mechanisms, providing additive anti-inflammatory action.", "evidenceLevel": "moderate", "sources": [ { "text": "Anand P et al. Bioavailability of curcumin. Mol Pharm. 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Uchida Y, Tsuji K, Ochi E. Effects of Omega-3 fatty acids supplementation and resistance training on skeletal muscle.. Clinical Nutrition ESPEN. 2024.", "pmid": "38777432", "doi": "10.1016/j.clnesp.2024.03.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38777432/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Curcumin is fat-soluble and its absorption increases significantly when taken with dietary fat like fish oil.", "clinicalSignificance": "Both share anti-inflammatory pathways.", "managementStrategy": "Take curcumin with fish oil or a fat-containing meal for maximum absorption and synergistic anti-inflammatory effects.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Curcumin Phytosome", "supplementBName": "Quercetin", "interactionType": "synergy", "severity": "info", "description": "Both are potent anti-inflammatory polyphenols that modulate NF-κB and COX-2 through complementary mechanisms.", "recommendation": "Take together for enhanced anti-inflammatory and antioxidant effects.", "minimumTimeSeparation": null, "mechanism": "Curcumin inhibits IKK-β, blocking NF-κB nuclear translocation. Quercetin inhibits lipoxygenase and phospholipase A2. Both inhibit COX-2 through different binding mechanisms.", "evidenceLevel": "moderate", "sources": [ { "text": "Pescosolido N et al. Curcumin and quercetin synergistically inhibit inflammatory signaling. J Cell Mol Med. 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both are potent anti-inflammatory polyphenols that modulate NF-κB and COX-2 through complementary mechanisms.", "clinicalSignificance": "Take together for enhanced anti-inflammatory and antioxidant effects.", "managementStrategy": "Take together for enhanced anti-inflammatory and antioxidant effects.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Curcumin Phytosome", "supplementBName": "NAC", "interactionType": "synergy", "severity": "info", "description": "Both support liver detoxification and reduce oxidative stress. Curcumin is a direct antioxidant; NAC supports glutathione production.", "recommendation": "Combine for liver support and comprehensive antioxidant protection.", "minimumTimeSeparation": null, "mechanism": "Curcumin activates Nrf2, upregulating phase II detoxification enzymes. NAC provides cysteine for glutathione synthesis. Together they enhance both direct antioxidant defense and enzyme-mediated detoxification.", "evidenceLevel": "moderate", "sources": [ { "text": "Biswas SK et al. Curcumin induces glutathione biosynthesis and inhibits NF-kappaB activation. Antioxid Redox Signal. 2005", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both support liver detoxification and reduce oxidative stress.", "clinicalSignificance": "Curcumin is a direct antioxidant; NAC supports glutathione production.", "managementStrategy": "Combine for liver support and comprehensive antioxidant protection.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Fish Oil", "supplementBName": "Curcumin Phytosome", "interactionType": "caution", "severity": "info", "description": "Both have blood-thinning properties. High doses of both together may increase bleeding risk.", "recommendation": "At standard doses, this combination is generally safe and synergistic. Monitor for easy bruising at high doses. Discontinue before surgery.", "minimumTimeSeparation": null, "mechanism": "Fish oil reduces thromboxane A2 production and platelet aggregation. Curcumin inhibits COX-2 and platelet-activating factor. Additive anticoagulant effects at high doses.", "evidenceLevel": "emerging", "sources": [ { "text": "Keihanian F et al. Curcumin, hemostasis, thrombosis, and coagulation. J Cell Physiol. 2018;233(6):4497-4511.", "pmid": "29052850", "doi": "10.1002/jcp.26249", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29052850/", "publicSourceType": "PMID" }, { "text": "Javaid M et al. Bleeding Risk in Patients Receiving Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Am Heart Assoc. 2024;13(10):e032390.", "pmid": "38742535", "doi": "10.1161/JAHA.123.032390", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38742535/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both have blood-thinning properties.", "clinicalSignificance": "High doses of both together may increase bleeding risk.", "managementStrategy": "At standard doses, this combination is generally safe and synergistic. Monitor for easy bruising at high doses. Discontinue before surgery.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Milk Thistle", "supplementBName": "Curcumin Phytosome", "interactionType": "synergy", "severity": "info", "description": "Both are hepatoprotective compounds that support liver health through complementary antioxidant and anti-inflammatory mechanisms.", "recommendation": "Effective liver support combination. Both protect hepatocytes and support detoxification.", "minimumTimeSeparation": null, "mechanism": "Silymarin stabilizes hepatocyte cell membranes and promotes glutathione synthesis. Curcumin inhibits NF-κB-mediated hepatic inflammation and activates Nrf2 for phase II enzyme induction.", "evidenceLevel": "moderate", "sources": [ { "text": "Abenavoli L et al. Milk thistle in liver diseases: past, present, future. Phytother Res. 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Fogacci F, Grassi D, Rizzo M, Cicero AFG. Metabolic effect of berberine-silymarin association: A meta-analysis of randomized, double-blind, placebo-controlled clinical trials. Phytotherapy Research. 2019.", "pmid": "30632209", "doi": "10.1002/ptr.6282", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30632209/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both are hepatoprotective compounds that support liver health through complementary antioxidant and anti-inflammatory mechanisms.", "clinicalSignificance": "Effective liver support combination.", "managementStrategy": "Effective liver support combination. Both protect hepatocytes and support detoxification.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Digestive Enzymes", "supplementBName": "Curcumin Phytosome", "interactionType": "synergy", "severity": "info", "description": "Digestive enzymes can improve curcumin absorption by breaking down the food matrix. Curcumin also stimulates bile flow which aids fat digestion.", "recommendation": "Take digestive enzymes and curcumin with meals for mutual benefit.", "minimumTimeSeparation": null, "mechanism": "Protease and lipase enzymes break down the food matrix, releasing curcumin for absorption. Curcumin stimulates cholecystokinin and bile flow, enhancing lipid emulsification for enzyme access.", "evidenceLevel": "emerging", "sources": [ { "text": "Dulbecco P, Savarino V. Therapeutic potential of curcumin in digestive diseases. World J Gastroenterol. 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Digestive enzymes can improve curcumin absorption by breaking down the food matrix.", "clinicalSignificance": "Curcumin also stimulates bile flow which aids fat digestion.", "managementStrategy": "Take digestive enzymes and curcumin with meals for mutual benefit.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Coenzyme Q10 Ubiquinol", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "CoQ10 is fat-soluble and absorption increases 3-fold when taken with dietary fat. Fish oil provides the ideal fat vehicle.", "recommendation": "Take CoQ10 with fish oil or a fat-containing meal for dramatically improved absorption.", "minimumTimeSeparation": null, "mechanism": "CoQ10 (coenzyme Q10) is highly lipophilic. Dietary fat stimulates bile secretion and forms mixed micelles that solubilize CoQ10 for enterocyte uptake.", "evidenceLevel": "strong", "sources": [ { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Uchida Y, Tsuji K, Ochi E. Effects of Omega-3 fatty acids supplementation and resistance training on skeletal muscle.. Clinical Nutrition ESPEN. 2024.", "pmid": "38777432", "doi": "10.1016/j.clnesp.2024.03.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38777432/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "CoQ10 is fat-soluble and absorption increases 3-fold when taken with dietary fat.", "clinicalSignificance": "Fish oil provides the ideal fat vehicle.", "managementStrategy": "Take CoQ10 with fish oil or a fat-containing meal for dramatically improved absorption.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Cordyceps", "supplementBName": "Coenzyme Q10 Ubiquinol", "interactionType": "synergy", "severity": "info", "description": "Both support mitochondrial energy production. Cordyceps increases ATP synthesis; CoQ10 is essential for the electron transport chain.", "recommendation": "Combine for enhanced cellular energy, exercise performance, and mitochondrial support.", "minimumTimeSeparation": null, "mechanism": "Cordycepin and adenosine from cordyceps enhance mitochondrial biogenesis via AMPK/PGC-1α. CoQ10 shuttles electrons in Complex I→III of the ETC. Synergistic mitochondrial support.", "evidenceLevel": "emerging", "sources": [ { "text": "Hirsch KR et al. Cordyceps militaris improves tolerance to high-intensity exercise. J Diet Suppl. 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both support mitochondrial energy production.", "clinicalSignificance": "Cordyceps increases ATP synthesis; CoQ10 is essential for the electron transport chain.", "managementStrategy": "Combine for enhanced cellular energy, exercise performance, and mitochondrial support.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Berberine", "supplementBName": "Coenzyme Q10 Ubiquinol", "interactionType": "caution", "severity": "moderate", "description": "Berberine may inhibit mitochondrial Complex I, similar to metformin. CoQ10 supplementation may help offset potential mitochondrial effects.", "recommendation": "Consider adding CoQ10 when taking berberine long-term to support mitochondrial function.", "minimumTimeSeparation": null, "mechanism": "Berberine partially inhibits mitochondrial Complex I (NADH:coenzyme Q10 oxidoreductase), which may explain its AMPK activation. CoQ10 supports electron transport and may mitigate this inhibition.", "evidenceLevel": "emerging", "sources": [ { "text": "Turner N et al. Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: a mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. Diabetes. 2008;57(5):1414-8.", "pmid": "18285556", "doi": "10.2337/db07-1552", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18285556/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Berberine may inhibit mitochondrial Complex I, similar to metformin.", "clinicalSignificance": "CoQ10 supplementation may help offset potential mitochondrial effects.", "managementStrategy": "Consider adding CoQ10 when taking berberine long-term to support mitochondrial function.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Coenzyme Q10 Ubiquinol", "supplementBName": "Alpha-Lipoic Acid", "interactionType": "synergy", "severity": "info", "description": "Both support mitochondrial function. CoQ10 is essential for the electron transport chain; ALA is a cofactor for mitochondrial dehydrogenases.", "recommendation": "Combine for comprehensive mitochondrial support, especially for cardiovascular and neurological health.", "minimumTimeSeparation": null, "mechanism": "CoQ10 shuttles electrons in the ETC (Complex I→III). ALA is a cofactor for pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase in the TCA cycle. Together they optimize mitochondrial energy production.", "evidenceLevel": "emerging", "sources": [ { "text": "Singh U et al. Alpha-lipoic acid supplementation and diabetes. Nutr Rev. 2008;66(11):646-57.", "pmid": "19019027", "doi": "10.1111/j.1753-4887.2008.00118.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19019027/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both support mitochondrial function.", "clinicalSignificance": "CoQ10 is essential for the electron transport chain; ALA is a cofactor for mitochondrial dehydrogenases.", "managementStrategy": "Combine for comprehensive mitochondrial support, especially for cardiovascular and neurological health.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Coenzyme Q10 Ubiquinol", "supplementBName": "Vitamin E", "interactionType": "synergy", "severity": "info", "description": "CoQ10 (ubiquinol form) regenerates vitamin E from its oxidized form in cell membranes, similar to how vitamin C regenerates vitamin E.", "recommendation": "Take together for enhanced membrane antioxidant protection.", "minimumTimeSeparation": null, "mechanism": "Ubiquinol (reduced CoQ10) donates a hydrogen atom to the tocopheroxyl radical, regenerating alpha-tocopherol within lipid membranes. This extends vitamin E's chain-breaking antioxidant activity.", "evidenceLevel": "moderate", "sources": [ { "text": "Kagan VE et al. Recycling and redox cycling of phenolic antioxidants. Ann N Y Acad Sci. 1998", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "CoQ10 (ubiquinol form) regenerates vitamin E from its oxidized form in cell membranes, similar to how vitamin C regenerates vitamin E.", "clinicalSignificance": "Take together for enhanced membrane antioxidant protection.", "managementStrategy": "Take together for enhanced membrane antioxidant protection.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "NMN", "supplementBName": "Coenzyme Q10 Ubiquinol", "interactionType": "synergy", "severity": "info", "description": "NMN boosts NAD+ for mitochondrial enzymes; CoQ10 supports the electron transport chain. Comprehensive mitochondrial support for anti-aging.", "recommendation": "Combine for mitochondrial anti-aging strategy. NMN fuels NAD+-dependent enzymes; CoQ10 maintains ETC efficiency.", "minimumTimeSeparation": null, "mechanism": "NAD+ (from NMN) is the primary electron carrier from TCA cycle to Complex I. CoQ10 shuttles these electrons from Complex I/II to Complex III. Both decline with age; replacing both optimizes mitochondrial function.", "evidenceLevel": "emerging", "sources": [ { "text": "Imai SI, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "NMN boosts NAD+ for mitochondrial enzymes; CoQ10 supports the electron transport chain.", "clinicalSignificance": "Comprehensive mitochondrial support for anti-aging.", "managementStrategy": "Combine for mitochondrial anti-aging strategy. NMN fuels NAD+-dependent enzymes; CoQ10 maintains ETC efficiency.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Lactobacillus Rhamnosus", "supplementBName": "Digestive Enzymes", "interactionType": "timingSensitive", "severity": "info", "description": "Both support gut health but work best at different times. Digestive enzymes work with meals; lactobacillus rhamnosus prefer an empty stomach or before meals.", "recommendation": "Take lactobacillus rhamnosus 30 min before meals on an empty stomach. Take digestive enzymes at the start of a meal.", "minimumTimeSeparation": 30, "mechanism": "Lactobacillus Rhamnosus survive better in less acidic conditions (empty stomach). Digestive enzymes (protease, lipase, amylase) work on food substrates and need to mix with the meal bolus.", "evidenceLevel": "moderate", "sources": [ { "text": "Tompkins TA et al. The impact of meals on a probiotic during transit through a model of the human upper gastrointestinal tract. Benef Microbes. 2011", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both support gut health but work best at different times.", "clinicalSignificance": "Digestive enzymes work with meals; lactobacillus rhamnosus prefer an empty stomach or before meals.", "managementStrategy": "Take lactobacillus rhamnosus 30 min before meals on an empty stomach. Take digestive enzymes at the start of a meal.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Saccharomyces Boulardii", "supplementBName": "Digestive Enzymes", "interactionType": "timingSensitive", "severity": "info", "description": "Both support gut health but work best at different times. Digestive enzymes work with meals; saccharomyces boulardii prefer an empty stomach or before meals.", "recommendation": "Take saccharomyces boulardii 30 min before meals on an empty stomach. Take digestive enzymes at the start of a meal.", "minimumTimeSeparation": 30, "mechanism": "Saccharomyces Boulardii survive better in less acidic conditions (empty stomach). Digestive enzymes (protease, lipase, amylase) work on food substrates and need to mix with the meal bolus.", "evidenceLevel": "moderate", "sources": [ { "text": "Tompkins TA et al. The impact of meals on a probiotic during transit through a model of the human upper gastrointestinal tract. Benef Microbes. 2011", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both support gut health but work best at different times.", "clinicalSignificance": "Digestive enzymes work with meals; saccharomyces boulardii prefer an empty stomach or before meals.", "managementStrategy": "Take saccharomyces boulardii 30 min before meals on an empty stomach. Take digestive enzymes at the start of a meal.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Lactobacillus Rhamnosus", "supplementBName": "Iron", "interactionType": "timingSensitive", "severity": "info", "description": "Iron supplements can disrupt gut microbiome composition. However, certain probiotic strains may actually enhance iron absorption.", "recommendation": "Separate by 2 hours. Some Lactobacillus strains can increase iron absorption, so lactobacillus rhamnosus may be beneficial for iron-supplementing individuals.", "minimumTimeSeparation": 120, "mechanism": "Unabsorbed iron in the colon promotes pathogenic bacteria growth (via iron-dependent virulence factors). Lactobacillus Rhamnosus maintain beneficial flora. Some strains reduce ferric to ferrous iron, enhancing absorption.", "evidenceLevel": "emerging", "sources": [ { "text": "Zimmermann MB et al. The effects of iron fortification on the gut microbiota in African children. Am J Clin Nutr. 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Iron supplements can disrupt gut microbiome composition.", "clinicalSignificance": "However, certain probiotic strains may actually enhance iron absorption.", "managementStrategy": "Separate by 2 hours. Some Lactobacillus strains can increase iron absorption, so lactobacillus rhamnosus may be beneficial for iron-supplementing individuals.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Saccharomyces Boulardii", "supplementBName": "Iron", "interactionType": "timingSensitive", "severity": "info", "description": "Iron supplements can disrupt gut microbiome composition. However, certain probiotic strains may actually enhance iron absorption.", "recommendation": "Separate by 2 hours. Some Lactobacillus strains can increase iron absorption, so saccharomyces boulardii may be beneficial for iron-supplementing individuals.", "minimumTimeSeparation": 120, "mechanism": "Unabsorbed iron in the colon promotes pathogenic bacteria growth (via iron-dependent virulence factors). Saccharomyces Boulardii maintain beneficial flora. Some strains reduce ferric to ferrous iron, enhancing absorption.", "evidenceLevel": "emerging", "sources": [ { "text": "Zimmermann MB et al. The effects of iron fortification on the gut microbiota in African children. Am J Clin Nutr. 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Iron supplements can disrupt gut microbiome composition.", "clinicalSignificance": "However, certain probiotic strains may actually enhance iron absorption.", "managementStrategy": "Separate by 2 hours. Some Lactobacillus strains can increase iron absorption, so saccharomyces boulardii may be beneficial for iron-supplementing individuals.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin D3", "supplementBName": "Lactobacillus Rhamnosus", "interactionType": "synergy", "severity": "info", "description": "Vitamin D supports the gut immune barrier. Lactobacillus Rhamnosus modulate the microbiome. Together they support gut-immune axis health.", "recommendation": "Complementary gut health support. Vitamin D strengthens gut barrier; lactobacillus rhamnosus diversify beneficial flora.", "minimumTimeSeparation": null, "mechanism": "D3 upregulates tight junction proteins and antimicrobial peptides in the gut epithelium, creating a healthier environment for probiotic colonization and function.", "evidenceLevel": "emerging", "sources": [ { "text": "Waterhouse M et al. Vitamin D and the gut microbiome. Nutr Rev. 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin D supports the gut immune barrier.", "clinicalSignificance": "Lactobacillus Rhamnosus modulate the microbiome.", "managementStrategy": "Complementary gut health support. Vitamin D strengthens gut barrier; lactobacillus rhamnosus diversify beneficial flora.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin D3", "supplementBName": "Saccharomyces Boulardii", "interactionType": "synergy", "severity": "info", "description": "Vitamin D supports the gut immune barrier. Saccharomyces Boulardii modulate the microbiome. Together they support gut-immune axis health.", "recommendation": "Complementary gut health support. Vitamin D strengthens gut barrier; saccharomyces boulardii diversify beneficial flora.", "minimumTimeSeparation": null, "mechanism": "D3 upregulates tight junction proteins and antimicrobial peptides in the gut epithelium, creating a healthier environment for probiotic colonization and function.", "evidenceLevel": "emerging", "sources": [ { "text": "Waterhouse M et al. Vitamin D and the gut microbiome. Nutr Rev. 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin D supports the gut immune barrier.", "clinicalSignificance": "Saccharomyces Boulardii modulate the microbiome.", "managementStrategy": "Complementary gut health support. Vitamin D strengthens gut barrier; saccharomyces boulardii diversify beneficial flora.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Berberine HCl", "supplementBName": "Milk Thistle", "interactionType": "synergy", "severity": "info", "description": "Milk thistle (silymarin) inhibits CYP enzymes that metabolize berberine hcl, potentially increasing its bioavailability and duration of action.", "recommendation": "Combine for enhanced metabolic support. Silymarin may increase berberine hcl bioavailability.", "minimumTimeSeparation": null, "mechanism": "Silymarin inhibits CYP3A4 and CYP2C9, which are primary metabolizers of berberine hcl. This reduces first-pass metabolism and increases berberine hcl plasma levels.", "evidenceLevel": "emerging", "sources": [ { "text": "Feng R et al. Transforming berberine into its intestine-absorbable form by the gut microbiota. Sci Rep. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Fogacci F, Grassi D, Rizzo M, Cicero AFG. Metabolic effect of berberine-silymarin association: A meta-analysis of randomized, double-blind, placebo-controlled clinical trials. Phytotherapy Research. 2019.", "pmid": "30632209", "doi": "10.1002/ptr.6282", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30632209/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Milk thistle (silymarin) inhibits CYP enzymes that metabolize berberine hcl, potentially increasing its bioavailability and duration of action.", "clinicalSignificance": "Combine for enhanced metabolic support.", "managementStrategy": "Combine for enhanced metabolic support. Silymarin may increase berberine hcl bioavailability.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Berberine HCl", "supplementBName": "Chromium", "interactionType": "caution", "severity": "moderate", "description": "Both lower blood glucose through different mechanisms. Combined use may cause excessive blood sugar reduction, especially in non-diabetics.", "recommendation": "Monitor blood glucose closely if combining. May need to reduce doses. Consult healthcare provider if on diabetes medication.", "minimumTimeSeparation": null, "mechanism": "Berberine HCl activates AMPK and increases insulin sensitivity. Chromium enhances insulin receptor signaling via chromodulin. Additive hypoglycemic effect may cause symptomatic hypoglycemia.", "evidenceLevel": "moderate", "sources": [ { "text": "Yin J et al. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008;57(5):712-7.", "pmid": "18442638", "doi": "10.1016/j.metabol.2008.01.013", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18442638/", "publicSourceType": "PMID" }, { "text": "Anderson RA et al. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes. Diabetes. 1997;46(11):1786-91.", "pmid": "9356027", "doi": "10.2337/diab.46.11.1786", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9356027/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both lower blood glucose through different mechanisms.", "clinicalSignificance": "Combined use may cause excessive blood sugar reduction, especially in non-diabetics.", "managementStrategy": "Monitor blood glucose closely if combining. May need to reduce doses. Consult healthcare provider if on diabetes medication.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Berberine HCl", "supplementBName": "Coenzyme Q10", "interactionType": "caution", "severity": "moderate", "description": "Berberine HCl may inhibit mitochondrial Complex I, similar to metformin. CoQ10 supplementation may help offset potential mitochondrial effects.", "recommendation": "Consider adding CoQ10 when taking berberine hcl long-term to support mitochondrial function.", "minimumTimeSeparation": null, "mechanism": "Berberine HCl partially inhibits mitochondrial Complex I (NADH:ubiquinone oxidoreductase), which may explain its AMPK activation. CoQ10 supports electron transport and may mitigate this inhibition.", "evidenceLevel": "emerging", "sources": [ { "text": "Turner N et al. Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: a mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. Diabetes. 2008;57(5):1414-8.", "pmid": "18285556", "doi": "10.2337/db07-1552", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18285556/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Berberine HCl may inhibit mitochondrial Complex I, similar to metformin.", "clinicalSignificance": "CoQ10 supplementation may help offset potential mitochondrial effects.", "managementStrategy": "Consider adding CoQ10 when taking berberine hcl long-term to support mitochondrial function.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Berberine HCl", "supplementBName": "Alpha-Lipoic Acid", "interactionType": "synergy", "severity": "info", "description": "Both improve insulin sensitivity through AMPK activation. ALA also supports glucose uptake via GLUT4 translocation.", "recommendation": "Combine for enhanced metabolic support. Monitor blood glucose if combining with diabetes medications.", "minimumTimeSeparation": null, "mechanism": "Berberine HCl activates AMPK via mitochondrial Complex I inhibition. ALA activates AMPK via CaMKK pathway and enhances insulin-stimulated glucose uptake by promoting GLUT4 translocation.", "evidenceLevel": "emerging", "sources": [ { "text": "Singh U et al. Alpha-lipoic acid supplementation and diabetes. Nutr Rev. 2008;66(11):646-57.", "pmid": "19019027", "doi": "10.1111/j.1753-4887.2008.00118.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19019027/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both improve insulin sensitivity through AMPK activation.", "clinicalSignificance": "ALA also supports glucose uptake via GLUT4 translocation.", "managementStrategy": "Combine for enhanced metabolic support. Monitor blood glucose if combining with diabetes medications.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Turmeric/Curcumin", "supplementBName": "Fish Oil Triple Strength", "interactionType": "synergy", "severity": "info", "description": "Curcumin is fat-soluble and its absorption increases significantly when taken with dietary fat like fish oil triple strength. Both share anti-inflammatory pathways.", "recommendation": "Take curcumin with fish oil triple strength or a fat-containing meal for maximum absorption and synergistic anti-inflammatory effects.", "minimumTimeSeparation": null, "mechanism": "Fat increases micellar solubilization of curcumin. Both modulate NF-κB and COX-2 pathways through complementary mechanisms, providing additive anti-inflammatory action.", "evidenceLevel": "moderate", "sources": [ { "text": "Anand P et al. Bioavailability of curcumin. Mol Pharm. 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Curcumin is fat-soluble and its absorption increases significantly when taken with dietary fat like fish oil triple strength.", "clinicalSignificance": "Both share anti-inflammatory pathways.", "managementStrategy": "Take curcumin with fish oil triple strength or a fat-containing meal for maximum absorption and synergistic anti-inflammatory effects.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Turmeric/Curcumin", "supplementBName": "Krill Oil", "interactionType": "synergy", "severity": "info", "description": "Curcumin is fat-soluble and its absorption increases significantly when taken with dietary fat like krill oil. Both share anti-inflammatory pathways.", "recommendation": "Take curcumin with krill oil or a fat-containing meal for maximum absorption and synergistic anti-inflammatory effects.", "minimumTimeSeparation": null, "mechanism": "Fat increases micellar solubilization of curcumin. Both modulate NF-κB and COX-2 pathways through complementary mechanisms, providing additive anti-inflammatory action.", "evidenceLevel": "moderate", "sources": [ { "text": "Anand P et al. Bioavailability of curcumin. Mol Pharm. 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Curcumin is fat-soluble and its absorption increases significantly when taken with dietary fat like krill oil.", "clinicalSignificance": "Both share anti-inflammatory pathways.", "managementStrategy": "Take curcumin with krill oil or a fat-containing meal for maximum absorption and synergistic anti-inflammatory effects.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Coenzyme Q10", "supplementBName": "Fish Oil Triple Strength", "interactionType": "synergy", "severity": "info", "description": "CoQ10 is fat-soluble and absorption increases 3-fold when taken with dietary fat. Fish oil provides the ideal fat vehicle.", "recommendation": "Take CoQ10 with fish oil triple strength or a fat-containing meal for dramatically improved absorption.", "minimumTimeSeparation": null, "mechanism": "CoQ10 (ubiquinone) is highly lipophilic. Dietary fat stimulates bile secretion and forms mixed micelles that solubilize CoQ10 for enterocyte uptake.", "evidenceLevel": "strong", "sources": [ { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "CoQ10 is fat-soluble and absorption increases 3-fold when taken with dietary fat.", "clinicalSignificance": "Fish oil provides the ideal fat vehicle.", "managementStrategy": "Take CoQ10 with fish oil triple strength or a fat-containing meal for dramatically improved absorption.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Coenzyme Q10", "supplementBName": "Krill Oil", "interactionType": "synergy", "severity": "info", "description": "CoQ10 is fat-soluble and absorption increases 3-fold when taken with dietary fat. Fish oil provides the ideal fat vehicle.", "recommendation": "Take CoQ10 with krill oil or a fat-containing meal for dramatically improved absorption.", "minimumTimeSeparation": null, "mechanism": "CoQ10 (ubiquinone) is highly lipophilic. Dietary fat stimulates bile secretion and forms mixed micelles that solubilize CoQ10 for enterocyte uptake.", "evidenceLevel": "strong", "sources": [ { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "CoQ10 is fat-soluble and absorption increases 3-fold when taken with dietary fat.", "clinicalSignificance": "Fish oil provides the ideal fat vehicle.", "managementStrategy": "Take CoQ10 with krill oil or a fat-containing meal for dramatically improved absorption.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Fish Oil Triple Strength", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "info", "description": "Vitamin D3 is fat-soluble and absorption improves when taken with omega-3 fatty acids. Both support cardiovascular and immune health.", "recommendation": "Take D3 with fish oil triple strength or a meal containing fat for optimal absorption.", "minimumTimeSeparation": null, "mechanism": "D3 requires fat for micellar solubilization and absorption. Omega-3 fatty acids provide the lipid vehicle and share anti-inflammatory pathways via resolvin production.", "evidenceLevel": "strong", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin D3 is fat-soluble and absorption improves when taken with omega-3 fatty acids.", "clinicalSignificance": "Both support cardiovascular and immune health.", "managementStrategy": "Take D3 with fish oil triple strength or a meal containing fat for optimal absorption.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Phosphatidylserine", "supplementBName": "Fish Oil Triple Strength", "interactionType": "synergy", "severity": "info", "description": "Phosphatidylserine is a phospholipid that benefits from omega-3 DHA, which is preferentially incorporated into PS in brain membranes.", "recommendation": "Take together. DHA-enriched phosphatidylserine may be more effective for cognitive function than soy-derived PS.", "minimumTimeSeparation": null, "mechanism": "DHA from fish oil triple strength is incorporated into the sn-2 position of phosphatidylserine in neuronal membranes, enhancing membrane fluidity and PS-dependent signaling (PKC activation, Akt/PI3K).", "evidenceLevel": "moderate", "sources": [ { "text": "Kim HY et al. Phosphatidylserine in the brain. Prog Lipid Res. 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Phosphatidylserine is a phospholipid that benefits from omega-3 DHA, which is preferentially incorporated into PS in brain membranes.", "clinicalSignificance": "Take together.", "managementStrategy": "Take together. DHA-enriched phosphatidylserine may be more effective for cognitive function than soy-derived PS.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Phosphatidylserine", "supplementBName": "Krill Oil", "interactionType": "synergy", "severity": "info", "description": "Phosphatidylserine is a phospholipid that benefits from omega-3 DHA, which is preferentially incorporated into PS in brain membranes.", "recommendation": "Take together. DHA-enriched phosphatidylserine may be more effective for cognitive function than soy-derived PS.", "minimumTimeSeparation": null, "mechanism": "DHA from krill oil is incorporated into the sn-2 position of phosphatidylserine in neuronal membranes, enhancing membrane fluidity and PS-dependent signaling (PKC activation, Akt/PI3K).", "evidenceLevel": "moderate", "sources": [ { "text": "Kim HY et al. Phosphatidylserine in the brain. Prog Lipid Res. 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Phosphatidylserine is a phospholipid that benefits from omega-3 DHA, which is preferentially incorporated into PS in brain membranes.", "clinicalSignificance": "Take together.", "managementStrategy": "Take together. DHA-enriched phosphatidylserine may be more effective for cognitive function than soy-derived PS.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Astaxanthin", "supplementBName": "Fish Oil Triple Strength", "interactionType": "synergy", "severity": "info", "description": "Astaxanthin is fat-soluble and absorbs best with dietary fat. It also protects omega-3 fatty acids from oxidation.", "recommendation": "Take together. Astaxanthin protects fish oil triple strength PUFAs from peroxidation while fish oil triple strength improves astaxanthin absorption.", "minimumTimeSeparation": null, "mechanism": "Astaxanthin spans the cell membrane bilayer, quenching singlet oxygen and scavenging radicals. It protects PUFAs (DHA/EPA) from lipid peroxidation. Fat improves astaxanthin micellar solubilization.", "evidenceLevel": "moderate", "sources": [ { "text": "Ambati RR et al. Astaxanthin: sources, extraction, stability, biological activities. Mar Drugs. 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Astaxanthin is fat-soluble and absorbs best with dietary fat.", "clinicalSignificance": "It also protects omega-3 fatty acids from oxidation.", "managementStrategy": "Take together. Astaxanthin protects fish oil triple strength PUFAs from peroxidation while fish oil triple strength improves astaxanthin absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin E", "supplementBName": "Fish Oil Triple Strength", "interactionType": "synergy", "severity": "info", "description": "Vitamin E protects omega-3 fatty acids from lipid peroxidation. High-dose fish oil triple strength may increase vitamin E requirements.", "recommendation": "Take vitamin E with fish oil triple strength to prevent PUFA oxidation. Many quality fish oil triple strength supplements include vitamin E for this reason.", "minimumTimeSeparation": null, "mechanism": "PUFAs (EPA/DHA) are highly susceptible to peroxidation due to multiple double bonds. Alpha-tocopherol intercepts lipid peroxyl radicals in membranes, preventing chain propagation.", "evidenceLevel": "strong", "sources": [ { "text": "Meydani M. Omega-3 fatty acids alter soluble markers of endothelial function in coronary heart disease patients. Nutr Rev. 2000", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin E protects omega-3 fatty acids from lipid peroxidation.", "clinicalSignificance": "High-dose fish oil triple strength may increase vitamin E requirements.", "managementStrategy": "Take vitamin E with fish oil triple strength to prevent PUFA oxidation. Many quality fish oil triple strength supplements include vitamin E for this reason.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin E", "supplementBName": "Krill Oil", "interactionType": "synergy", "severity": "info", "description": "Vitamin E protects omega-3 fatty acids from lipid peroxidation. High-dose krill oil may increase vitamin E requirements.", "recommendation": "Take vitamin E with krill oil to prevent PUFA oxidation. Many quality krill oil supplements include vitamin E for this reason.", "minimumTimeSeparation": null, "mechanism": "PUFAs (EPA/DHA) are highly susceptible to peroxidation due to multiple double bonds. Alpha-tocopherol intercepts lipid peroxyl radicals in membranes, preventing chain propagation.", "evidenceLevel": "strong", "sources": [ { "text": "Meydani M. Omega-3 fatty acids alter soluble markers of endothelial function in coronary heart disease patients. Nutr Rev. 2000", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin E protects omega-3 fatty acids from lipid peroxidation.", "clinicalSignificance": "High-dose krill oil may increase vitamin E requirements.", "managementStrategy": "Take vitamin E with krill oil to prevent PUFA oxidation. Many quality krill oil supplements include vitamin E for this reason.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin K2", "supplementBName": "Fish Oil Triple Strength", "interactionType": "synergy", "severity": "info", "description": "K2 (MK-7) is fat-soluble and absorption increases with dietary fat. Fish oil provides an excellent fat vehicle.", "recommendation": "Take K2 with fish oil triple strength or a fat-containing meal for optimal absorption.", "minimumTimeSeparation": null, "mechanism": "MK-7 is a fat-soluble isoprenoid. Dietary fat stimulates bile secretion and forms micelles that solubilize MK-7 for intestinal absorption via chylomicron incorporation.", "evidenceLevel": "moderate", "sources": [ { "text": "Schurgers LJ, Vermeer C. Determination of phylloquinone and menaquinones in food. Haemostasis. 2000", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Kuang X, Liu C, Guo X, Li K, Deng Q, Li D. The combination effect of vitamin K and vitamin D on human bone quality: a meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "32219282", "doi": "10.1039/c9fo03063h", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32219282/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "K2 (MK-7) is fat-soluble and absorption increases with dietary fat.", "clinicalSignificance": "Fish oil provides an excellent fat vehicle.", "managementStrategy": "Take K2 with fish oil triple strength or a fat-containing meal for optimal absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin K2", "supplementBName": "Krill Oil", "interactionType": "synergy", "severity": "info", "description": "K2 (MK-7) is fat-soluble and absorption increases with dietary fat. Fish oil provides an excellent fat vehicle.", "recommendation": "Take K2 with krill oil or a fat-containing meal for optimal absorption.", "minimumTimeSeparation": null, "mechanism": "MK-7 is a fat-soluble isoprenoid. Dietary fat stimulates bile secretion and forms micelles that solubilize MK-7 for intestinal absorption via chylomicron incorporation.", "evidenceLevel": "moderate", "sources": [ { "text": "Schurgers LJ, Vermeer C. Determination of phylloquinone and menaquinones in food. Haemostasis. 2000", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Kuang X, Liu C, Guo X, Li K, Deng Q, Li D. The combination effect of vitamin K and vitamin D on human bone quality: a meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "32219282", "doi": "10.1039/c9fo03063h", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32219282/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "K2 (MK-7) is fat-soluble and absorption increases with dietary fat.", "clinicalSignificance": "Fish oil provides an excellent fat vehicle.", "managementStrategy": "Take K2 with krill oil or a fat-containing meal for optimal absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Fish Oil Triple Strength", "supplementBName": "Turmeric/Curcumin", "interactionType": "caution", "severity": "info", "description": "Both have blood-thinning properties. High doses of both together may increase bleeding risk.", "recommendation": "At standard doses, this combination is generally safe and synergistic. Monitor for easy bruising at high doses. Discontinue before surgery.", "minimumTimeSeparation": null, "mechanism": "Fish oil reduces thromboxane A2 production and platelet aggregation. Curcumin inhibits COX-2 and platelet-activating factor. Additive anticoagulant effects at high doses.", "evidenceLevel": "emerging", "sources": [ { "text": "Keihanian F et al. Curcumin, hemostasis, thrombosis, and coagulation. J Cell Physiol. 2018;233(6):4497-4511.", "pmid": "29052850", "doi": "10.1002/jcp.26249", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29052850/", "publicSourceType": "PMID" }, { "text": "Javaid M et al. Bleeding Risk in Patients Receiving Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Am Heart Assoc. 2024;13(10):e032390.", "pmid": "38742535", "doi": "10.1161/JAHA.123.032390", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38742535/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both have blood-thinning properties.", "clinicalSignificance": "High doses of both together may increase bleeding risk.", "managementStrategy": "At standard doses, this combination is generally safe and synergistic. Monitor for easy bruising at high doses. Discontinue before surgery.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Krill Oil", "supplementBName": "Turmeric/Curcumin", "interactionType": "caution", "severity": "info", "description": "Both have blood-thinning properties. High doses of both together may increase bleeding risk.", "recommendation": "At standard doses, this combination is generally safe and synergistic. Monitor for easy bruising at high doses. Discontinue before surgery.", "minimumTimeSeparation": null, "mechanism": "Fish oil reduces thromboxane A2 production and platelet aggregation. Curcumin inhibits COX-2 and platelet-activating factor. Additive anticoagulant effects at high doses.", "evidenceLevel": "emerging", "sources": [ { "text": "Keihanian F et al. Curcumin, hemostasis, thrombosis, and coagulation. J Cell Physiol. 2018;233(6):4497-4511.", "pmid": "29052850", "doi": "10.1002/jcp.26249", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29052850/", "publicSourceType": "PMID" }, { "text": "Javaid M et al. Bleeding Risk in Patients Receiving Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Am Heart Assoc. 2024;13(10):e032390.", "pmid": "38742535", "doi": "10.1161/JAHA.123.032390", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38742535/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both have blood-thinning properties.", "clinicalSignificance": "High doses of both together may increase bleeding risk.", "managementStrategy": "At standard doses, this combination is generally safe and synergistic. Monitor for easy bruising at high doses. Discontinue before surgery.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Resveratrol", "supplementBName": "Fish Oil Triple Strength", "interactionType": "synergy", "severity": "info", "description": "Resveratrol is lipophilic and absorbs better with dietary fat. Both have anti-inflammatory and cardioprotective properties.", "recommendation": "Take resveratrol with fish oil triple strength or a fat-containing meal for improved bioavailability.", "minimumTimeSeparation": null, "mechanism": "Fat increases micellar solubilization of trans-resveratrol for improved intestinal absorption. Both activate SIRT1 and inhibit NF-κB through complementary pathways for anti-inflammatory synergy.", "evidenceLevel": "emerging", "sources": [ { "text": "Walle T et al. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos. 2004", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Resveratrol is lipophilic and absorbs better with dietary fat.", "clinicalSignificance": "Both have anti-inflammatory and cardioprotective properties.", "managementStrategy": "Take resveratrol with fish oil triple strength or a fat-containing meal for improved bioavailability.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Resveratrol", "supplementBName": "Krill Oil", "interactionType": "synergy", "severity": "info", "description": "Resveratrol is lipophilic and absorbs better with dietary fat. Both have anti-inflammatory and cardioprotective properties.", "recommendation": "Take resveratrol with krill oil or a fat-containing meal for improved bioavailability.", "minimumTimeSeparation": null, "mechanism": "Fat increases micellar solubilization of trans-resveratrol for improved intestinal absorption. Both activate SIRT1 and inhibit NF-κB through complementary pathways for anti-inflammatory synergy.", "evidenceLevel": "emerging", "sources": [ { "text": "Walle T et al. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos. 2004", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Resveratrol is lipophilic and absorbs better with dietary fat.", "clinicalSignificance": "Both have anti-inflammatory and cardioprotective properties.", "managementStrategy": "Take resveratrol with krill oil or a fat-containing meal for improved bioavailability.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Fish Oil Triple Strength", "supplementBName": "Vitamin E", "interactionType": "caution", "severity": "info", "description": "High-dose fish oil triple strength increases vitamin E requirements because PUFAs are susceptible to peroxidation. May deplete vitamin E stores.", "recommendation": "If taking high-dose fish oil triple strength (>3g/day), ensure adequate vitamin E intake to prevent PUFA-induced vitamin E depletion.", "minimumTimeSeparation": null, "mechanism": "EPA and DHA's multiple double bonds make them highly susceptible to lipid peroxidation. Each peroxidation event consumes one molecule of alpha-tocopherol, increasing turnover.", "evidenceLevel": "moderate", "sources": [ { "text": "Meydani M. Vitamin E requirement in relation to dietary fish oil and oxidative stress. World Rev Nutr Diet. 1994", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "High-dose fish oil triple strength increases vitamin E requirements because PUFAs are susceptible to peroxidation.", "clinicalSignificance": "May deplete vitamin E stores.", "managementStrategy": "If taking high-dose fish oil triple strength (>3g/day), ensure adequate vitamin E intake to prevent PUFA-induced vitamin E depletion.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Krill Oil", "supplementBName": "Vitamin E", "interactionType": "caution", "severity": "info", "description": "High-dose krill oil increases vitamin E requirements because PUFAs are susceptible to peroxidation. May deplete vitamin E stores.", "recommendation": "If taking high-dose krill oil (>3g/day), ensure adequate vitamin E intake to prevent PUFA-induced vitamin E depletion.", "minimumTimeSeparation": null, "mechanism": "EPA and DHA's multiple double bonds make them highly susceptible to lipid peroxidation. Each peroxidation event consumes one molecule of alpha-tocopherol, increasing turnover.", "evidenceLevel": "moderate", "sources": [ { "text": "Meydani M. Vitamin E requirement in relation to dietary fish oil and oxidative stress. World Rev Nutr Diet. 1994", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "High-dose krill oil increases vitamin E requirements because PUFAs are susceptible to peroxidation.", "clinicalSignificance": "May deplete vitamin E stores.", "managementStrategy": "If taking high-dose krill oil (>3g/day), ensure adequate vitamin E intake to prevent PUFA-induced vitamin E depletion.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Calcium", "supplementBName": "Magnesium L-Threonate", "interactionType": "timingSensitive", "severity": "moderate", "description": "High-dose calcium and magnesium compete for absorption when taken simultaneously.", "recommendation": "If taking high doses (>500mg each), separate by 2+ hours. Moderate doses can be taken together.", "minimumTimeSeparation": 120, "mechanism": "Both minerals share intestinal absorption pathways including TRPM6/7 channels. Competition is dose-dependent and significant above 500mg combined.", "evidenceLevel": "moderate", "sources": [ { "text": "Hendrix P et al. Divalent cation competition for intestinal absorption. J Nutr Biochem. 2005", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose calcium and magnesium compete for absorption when taken simultaneously.", "clinicalSignificance": "If taking high doses (>500mg each), separate by 2+ hours.", "managementStrategy": "If taking high doses (>500mg each), separate by 2+ hours. Moderate doses can be taken together.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Calcium", "supplementBName": "Magnesium Citrate", "interactionType": "timingSensitive", "severity": "moderate", "description": "High-dose calcium and magnesium compete for absorption when taken simultaneously.", "recommendation": "If taking high doses (>500mg each), separate by 2+ hours. Moderate doses can be taken together.", "minimumTimeSeparation": 120, "mechanism": "Both minerals share intestinal absorption pathways including TRPM6/7 channels. Competition is dose-dependent and significant above 500mg combined.", "evidenceLevel": "moderate", "sources": [ { "text": "Hendrix P et al. Divalent cation competition for intestinal absorption. J Nutr Biochem. 2005", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose calcium and magnesium compete for absorption when taken simultaneously.", "clinicalSignificance": "If taking high doses (>500mg each), separate by 2+ hours.", "managementStrategy": "If taking high doses (>500mg each), separate by 2+ hours. Moderate doses can be taken together.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Calcium", "supplementBName": "Magnesium Taurate", "interactionType": "timingSensitive", "severity": "moderate", "description": "High-dose calcium and magnesium compete for absorption when taken simultaneously.", "recommendation": "If taking high doses (>500mg each), separate by 2+ hours. Moderate doses can be taken together.", "minimumTimeSeparation": 120, "mechanism": "Both minerals share intestinal absorption pathways including TRPM6/7 channels. Competition is dose-dependent and significant above 500mg combined.", "evidenceLevel": "moderate", "sources": [ { "text": "Hendrix P et al. Divalent cation competition for intestinal absorption. J Nutr Biochem. 2005", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose calcium and magnesium compete for absorption when taken simultaneously.", "clinicalSignificance": "If taking high doses (>500mg each), separate by 2+ hours.", "managementStrategy": "If taking high doses (>500mg each), separate by 2+ hours. Moderate doses can be taken together.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Calcium", "supplementBName": "Magnesium Malate", "interactionType": "timingSensitive", "severity": "moderate", "description": "High-dose calcium and magnesium compete for absorption when taken simultaneously.", "recommendation": "If taking high doses (>500mg each), separate by 2+ hours. Moderate doses can be taken together.", "minimumTimeSeparation": 120, "mechanism": "Both minerals share intestinal absorption pathways including TRPM6/7 channels. Competition is dose-dependent and significant above 500mg combined.", "evidenceLevel": "moderate", "sources": [ { "text": "Hendrix P et al. Divalent cation competition for intestinal absorption. J Nutr Biochem. 2005", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose calcium and magnesium compete for absorption when taken simultaneously.", "clinicalSignificance": "If taking high doses (>500mg each), separate by 2+ hours.", "managementStrategy": "If taking high doses (>500mg each), separate by 2+ hours. Moderate doses can be taken together.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Magnesium L-Threonate", "supplementBName": "Vitamin B6", "interactionType": "synergy", "severity": "info", "description": "Vitamin B6 increases intracellular magnesium accumulation. Magnesium is required for B6 activation to its coenzyme form PLP.", "recommendation": "Take together for enhanced mutual absorption and utilization.", "minimumTimeSeparation": null, "mechanism": "Pyridoxine (B6) facilitates magnesium transport into cells. Magnesium is a cofactor for pyridoxal kinase, which converts B6 to its active form pyridoxal-5-phosphate (PLP).", "evidenceLevel": "moderate", "sources": [ { "text": "Pouteau E et al. Superiority of magnesium and vitamin B6 over magnesium alone. Magnes Res. 2018", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin B6 increases intracellular magnesium accumulation.", "clinicalSignificance": "Magnesium is required for B6 activation to its coenzyme form PLP.", "managementStrategy": "Take together for enhanced mutual absorption and utilization.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Magnesium Citrate", "supplementBName": "Vitamin B6", "interactionType": "synergy", "severity": "info", "description": "Vitamin B6 increases intracellular magnesium accumulation. Magnesium is required for B6 activation to its coenzyme form PLP.", "recommendation": "Take together for enhanced mutual absorption and utilization.", "minimumTimeSeparation": null, "mechanism": "Pyridoxine (B6) facilitates magnesium transport into cells. Magnesium is a cofactor for pyridoxal kinase, which converts B6 to its active form pyridoxal-5-phosphate (PLP).", "evidenceLevel": "moderate", "sources": [ { "text": "Pouteau E et al. Superiority of magnesium and vitamin B6 over magnesium alone. Magnes Res. 2018", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Vitamin B6 increases intracellular magnesium accumulation.", "clinicalSignificance": "Magnesium is required for B6 activation to its coenzyme form PLP.", "managementStrategy": "Take together for enhanced mutual absorption and utilization.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Magnesium Taurate", "supplementBName": "Vitamin B6", "interactionType": "synergy", "severity": "info", "description": "Vitamin B6 increases intracellular magnesium accumulation. Magnesium is required for B6 activation to its coenzyme form PLP.", "recommendation": "Take together for enhanced mutual absorption and utilization.", "minimumTimeSeparation": null, "mechanism": "Pyridoxine (B6) facilitates magnesium transport into cells. Magnesium is a cofactor for pyridoxal kinase, which converts B6 to its active form pyridoxal-5-phosphate (PLP).", "evidenceLevel": "moderate", "sources": [ { "text": "Pouteau E et al. Superiority of magnesium and vitamin B6 over magnesium alone. Magnes Res. 2018", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin B6 increases intracellular magnesium accumulation.", "clinicalSignificance": "Magnesium is required for B6 activation to its coenzyme form PLP.", "managementStrategy": "Take together for enhanced mutual absorption and utilization.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Magnesium Malate", "supplementBName": "Vitamin B6", "interactionType": "synergy", "severity": "info", "description": "Vitamin B6 increases intracellular magnesium accumulation. Magnesium is required for B6 activation to its coenzyme form PLP.", "recommendation": "Take together for enhanced mutual absorption and utilization.", "minimumTimeSeparation": null, "mechanism": "Pyridoxine (B6) facilitates magnesium transport into cells. Magnesium is a cofactor for pyridoxal kinase, which converts B6 to its active form pyridoxal-5-phosphate (PLP).", "evidenceLevel": "moderate", "sources": [ { "text": "Pouteau E et al. Superiority of magnesium and vitamin B6 over magnesium alone. Magnes Res. 2018", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin B6 increases intracellular magnesium accumulation.", "clinicalSignificance": "Magnesium is required for B6 activation to its coenzyme form PLP.", "managementStrategy": "Take together for enhanced mutual absorption and utilization.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin D3", "supplementBName": "Magnesium L-Threonate", "interactionType": "synergy", "severity": "info", "description": "Magnesium is essential for vitamin D metabolism. It's required for the enzymes that convert D3 to its active form calcitriol.", "recommendation": "Ensure adequate magnesium when supplementing D3. Magnesium deficiency can impair D3 activation.", "minimumTimeSeparation": null, "mechanism": "Magnesium is a cofactor for CYP2R1 (25-hydroxylase) and CYP27B1 (1-alpha-hydroxylase), the enzymes that convert cholecalciferol to 25(OH)D and then to active 1,25(OH)2D.", "evidenceLevel": "strong", "sources": [ { "text": "Uwitonze AM, Razzaque MS. Role of magnesium in vitamin D activation and function. J Am Osteopath Assoc. 2018", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Magnesium is essential for vitamin D metabolism.", "clinicalSignificance": "It's required for the enzymes that convert D3 to its active form calcitriol.", "managementStrategy": "Ensure adequate magnesium when supplementing D3. Magnesium deficiency can impair D3 activation.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin D3", "supplementBName": "Magnesium Citrate", "interactionType": "synergy", "severity": "info", "description": "Magnesium is essential for vitamin D metabolism. It's required for the enzymes that convert D3 to its active form calcitriol.", "recommendation": "Ensure adequate magnesium when supplementing D3. Magnesium deficiency can impair D3 activation.", "minimumTimeSeparation": null, "mechanism": "Magnesium is a cofactor for CYP2R1 (25-hydroxylase) and CYP27B1 (1-alpha-hydroxylase), the enzymes that convert cholecalciferol to 25(OH)D and then to active 1,25(OH)2D.", "evidenceLevel": "strong", "sources": [ { "text": "Uwitonze AM, Razzaque MS. Role of magnesium in vitamin D activation and function. J Am Osteopath Assoc. 2018", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Magnesium is essential for vitamin D metabolism.", "clinicalSignificance": "It's required for the enzymes that convert D3 to its active form calcitriol.", "managementStrategy": "Ensure adequate magnesium when supplementing D3. Magnesium deficiency can impair D3 activation.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin D3", "supplementBName": "Magnesium Taurate", "interactionType": "synergy", "severity": "info", "description": "Magnesium is essential for vitamin D metabolism. It's required for the enzymes that convert D3 to its active form calcitriol.", "recommendation": "Ensure adequate magnesium when supplementing D3. Magnesium deficiency can impair D3 activation.", "minimumTimeSeparation": null, "mechanism": "Magnesium is a cofactor for CYP2R1 (25-hydroxylase) and CYP27B1 (1-alpha-hydroxylase), the enzymes that convert cholecalciferol to 25(OH)D and then to active 1,25(OH)2D.", "evidenceLevel": "strong", "sources": [ { "text": "Uwitonze AM, Razzaque MS. Role of magnesium in vitamin D activation and function. J Am Osteopath Assoc. 2018", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Magnesium is essential for vitamin D metabolism.", "clinicalSignificance": "It's required for the enzymes that convert D3 to its active form calcitriol.", "managementStrategy": "Ensure adequate magnesium when supplementing D3. Magnesium deficiency can impair D3 activation.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin D3", "supplementBName": "Magnesium Malate", "interactionType": "synergy", "severity": "info", "description": "Magnesium is essential for vitamin D metabolism. It's required for the enzymes that convert D3 to its active form calcitriol.", "recommendation": "Ensure adequate magnesium when supplementing D3. Magnesium deficiency can impair D3 activation.", "minimumTimeSeparation": null, "mechanism": "Magnesium is a cofactor for CYP2R1 (25-hydroxylase) and CYP27B1 (1-alpha-hydroxylase), the enzymes that convert cholecalciferol to 25(OH)D and then to active 1,25(OH)2D.", "evidenceLevel": "strong", "sources": [ { "text": "Uwitonze AM, Razzaque MS. Role of magnesium in vitamin D activation and function. J Am Osteopath Assoc. 2018", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Magnesium is essential for vitamin D metabolism.", "clinicalSignificance": "It's required for the enzymes that convert D3 to its active form calcitriol.", "managementStrategy": "Ensure adequate magnesium when supplementing D3. Magnesium deficiency can impair D3 activation.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin B1", "supplementBName": "Magnesium L-Threonate", "interactionType": "synergy", "severity": "info", "description": "Magnesium is required for thiamine (B1) utilization. Magnesium deficiency impairs thiamine-dependent enzyme activity.", "recommendation": "Ensure adequate magnesium when supplementing B1 for proper enzymatic function.", "minimumTimeSeparation": null, "mechanism": "Magnesium is required for thiamine pyrophosphokinase, which converts thiamine to its active coenzyme form thiamine pyrophosphate (TPP).", "evidenceLevel": "moderate", "sources": [ { "text": "Lonsdale D. Thiamine and magnesium deficiencies. Med Hypotheses. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Magnesium is required for thiamine (B1) utilization.", "clinicalSignificance": "Magnesium deficiency impairs thiamine-dependent enzyme activity.", "managementStrategy": "Ensure adequate magnesium when supplementing B1 for proper enzymatic function.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin B1", "supplementBName": "Magnesium Citrate", "interactionType": "synergy", "severity": "info", "description": "Magnesium is required for thiamine (B1) utilization. Magnesium deficiency impairs thiamine-dependent enzyme activity.", "recommendation": "Ensure adequate magnesium when supplementing B1 for proper enzymatic function.", "minimumTimeSeparation": null, "mechanism": "Magnesium is required for thiamine pyrophosphokinase, which converts thiamine to its active coenzyme form thiamine pyrophosphate (TPP).", "evidenceLevel": "moderate", "sources": [ { "text": "Lonsdale D. Thiamine and magnesium deficiencies. Med Hypotheses. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Magnesium is required for thiamine (B1) utilization.", "clinicalSignificance": "Magnesium deficiency impairs thiamine-dependent enzyme activity.", "managementStrategy": "Ensure adequate magnesium when supplementing B1 for proper enzymatic function.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin B1", "supplementBName": "Magnesium Taurate", "interactionType": "synergy", "severity": "info", "description": "Magnesium is required for thiamine (B1) utilization. Magnesium deficiency impairs thiamine-dependent enzyme activity.", "recommendation": "Ensure adequate magnesium when supplementing B1 for proper enzymatic function.", "minimumTimeSeparation": null, "mechanism": "Magnesium is required for thiamine pyrophosphokinase, which converts thiamine to its active coenzyme form thiamine pyrophosphate (TPP).", "evidenceLevel": "moderate", "sources": [ { "text": "Lonsdale D. Thiamine and magnesium deficiencies. Med Hypotheses. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Magnesium is required for thiamine (B1) utilization.", "clinicalSignificance": "Magnesium deficiency impairs thiamine-dependent enzyme activity.", "managementStrategy": "Ensure adequate magnesium when supplementing B1 for proper enzymatic function.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin B1", "supplementBName": "Magnesium Malate", "interactionType": "synergy", "severity": "info", "description": "Magnesium is required for thiamine (B1) utilization. Magnesium deficiency impairs thiamine-dependent enzyme activity.", "recommendation": "Ensure adequate magnesium when supplementing B1 for proper enzymatic function.", "minimumTimeSeparation": null, "mechanism": "Magnesium is required for thiamine pyrophosphokinase, which converts thiamine to its active coenzyme form thiamine pyrophosphate (TPP).", "evidenceLevel": "moderate", "sources": [ { "text": "Lonsdale D. Thiamine and magnesium deficiencies. Med Hypotheses. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Magnesium is required for thiamine (B1) utilization.", "clinicalSignificance": "Magnesium deficiency impairs thiamine-dependent enzyme activity.", "managementStrategy": "Ensure adequate magnesium when supplementing B1 for proper enzymatic function.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Ashwagandha", "supplementBName": "Magnesium L-Threonate", "interactionType": "synergy", "severity": "info", "description": "Both promote relaxation and support sleep quality through complementary mechanisms.", "recommendation": "Take together in the evening for enhanced sleep and stress support.", "minimumTimeSeparation": null, "mechanism": "Ashwagandha's withanolides modulate GABA-A receptors. Magnesium blocks NMDA excitatory signaling and glycine acts as an inhibitory neurotransmitter at glycine receptors.", "evidenceLevel": "emerging", "sources": [ { "text": "Langade D et al. Efficacy and safety of ashwagandha root extract on sleep. Cureus. 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both promote relaxation and support sleep quality through complementary mechanisms.", "clinicalSignificance": "Take together in the evening for enhanced sleep and stress support.", "managementStrategy": "Take together in the evening for enhanced sleep and stress support.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Ashwagandha", "supplementBName": "Magnesium Citrate", "interactionType": "synergy", "severity": "info", "description": "Both promote relaxation and support sleep quality through complementary mechanisms.", "recommendation": "Take together in the evening for enhanced sleep and stress support.", "minimumTimeSeparation": null, "mechanism": "Ashwagandha's withanolides modulate GABA-A receptors. Magnesium blocks NMDA excitatory signaling and glycine acts as an inhibitory neurotransmitter at glycine receptors.", "evidenceLevel": "emerging", "sources": [ { "text": "Langade D et al. Efficacy and safety of ashwagandha root extract on sleep. Cureus. 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both promote relaxation and support sleep quality through complementary mechanisms.", "clinicalSignificance": "Take together in the evening for enhanced sleep and stress support.", "managementStrategy": "Take together in the evening for enhanced sleep and stress support.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Ashwagandha", "supplementBName": "Magnesium Taurate", "interactionType": "synergy", "severity": "info", "description": "Both promote relaxation and support sleep quality through complementary mechanisms.", "recommendation": "Take together in the evening for enhanced sleep and stress support.", "minimumTimeSeparation": null, "mechanism": "Ashwagandha's withanolides modulate GABA-A receptors. Magnesium blocks NMDA excitatory signaling and glycine acts as an inhibitory neurotransmitter at glycine receptors.", "evidenceLevel": "emerging", "sources": [ { "text": "Langade D et al. Efficacy and safety of ashwagandha root extract on sleep. Cureus. 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both promote relaxation and support sleep quality through complementary mechanisms.", "clinicalSignificance": "Take together in the evening for enhanced sleep and stress support.", "managementStrategy": "Take together in the evening for enhanced sleep and stress support.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Ashwagandha", "supplementBName": "Magnesium Malate", "interactionType": "synergy", "severity": "info", "description": "Both promote relaxation and support sleep quality through complementary mechanisms.", "recommendation": "Take together in the evening for enhanced sleep and stress support.", "minimumTimeSeparation": null, "mechanism": "Ashwagandha's withanolides modulate GABA-A receptors. Magnesium blocks NMDA excitatory signaling and glycine acts as an inhibitory neurotransmitter at glycine receptors.", "evidenceLevel": "emerging", "sources": [ { "text": "Langade D et al. Efficacy and safety of ashwagandha root extract on sleep. Cureus. 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both promote relaxation and support sleep quality through complementary mechanisms.", "clinicalSignificance": "Take together in the evening for enhanced sleep and stress support.", "managementStrategy": "Take together in the evening for enhanced sleep and stress support.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "L-Theanine", "supplementBName": "Magnesium L-Threonate", "interactionType": "synergy", "severity": "info", "description": "L-theanine and magnesium are both studied for relaxation-related markers, but direct combination evidence is limited.", "recommendation": "If combining L-theanine with magnesium l-threonate, keep total supplemental magnesium within 200-350 mg/day elemental magnesium unless clinician-supervised; do not frame the pair as anxiety treatment.", "minimumTimeSeparation": null, "mechanism": "L-theanine has alpha-wave and glutamate-signaling research, while magnesium participates in NMDA/GABA-related physiology. Clinical evidence for the specific combination is limited.", "evidenceLevel": "emerging", "sources": [ { "text": "Kimura K et al. L-theanine reduces psychological and physiological stress responses. Biol Psychol. 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Payne ER, Aceves-Martins M, Dubost J et al.. Effects of Tea (Camellia sinensis) or its Bioactive Compounds l-Theanine or l-Theanine plus Caffeine on Cognition, Sleep, and Mood in Healthy Participants: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.. Nutrition Reviews. 2025.", "pmid": "40314930", "doi": "10.1093/nutrit/nuaf054", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40314930/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Potential relaxation-support overlap.", "clinicalSignificance": "Wellness-support pairing only; not anxiety treatment.", "managementStrategy": "If combining L-theanine with magnesium l-threonate, keep total supplemental magnesium within 200-350 mg/day elemental magnesium unless clinician-supervised; do not frame the pair as anxiety treatment.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "L-Theanine", "supplementBName": "Magnesium Citrate", "interactionType": "synergy", "severity": "info", "description": "L-theanine and magnesium are both studied for relaxation-related markers, but direct combination evidence is limited.", "recommendation": "If combining L-theanine with magnesium citrate, keep total supplemental magnesium within 200-350 mg/day elemental magnesium unless clinician-supervised; do not frame the pair as anxiety treatment.", "minimumTimeSeparation": null, "mechanism": "L-theanine has alpha-wave and glutamate-signaling research, while magnesium participates in NMDA/GABA-related physiology. Clinical evidence for the specific combination is limited.", "evidenceLevel": "emerging", "sources": [ { "text": "Kimura K et al. L-theanine reduces psychological and physiological stress responses. Biol Psychol. 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Payne ER, Aceves-Martins M, Dubost J et al.. Effects of Tea (Camellia sinensis) or its Bioactive Compounds l-Theanine or l-Theanine plus Caffeine on Cognition, Sleep, and Mood in Healthy Participants: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.. Nutrition Reviews. 2025.", "pmid": "40314930", "doi": "10.1093/nutrit/nuaf054", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40314930/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Potential relaxation-support overlap.", "clinicalSignificance": "Wellness-support pairing only; not anxiety treatment.", "managementStrategy": "If combining L-theanine with magnesium citrate, keep total supplemental magnesium within 200-350 mg/day elemental magnesium unless clinician-supervised; do not frame the pair as anxiety treatment.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "L-Theanine", "supplementBName": "Magnesium Taurate", "interactionType": "synergy", "severity": "info", "description": "L-theanine and magnesium are both studied for relaxation-related markers, but direct combination evidence is limited.", "recommendation": "If combining L-theanine with magnesium taurate, keep total supplemental magnesium within 200-350 mg/day elemental magnesium unless clinician-supervised; do not frame the pair as anxiety treatment.", "minimumTimeSeparation": null, "mechanism": "L-theanine has alpha-wave and glutamate-signaling research, while magnesium participates in NMDA/GABA-related physiology. Clinical evidence for the specific combination is limited.", "evidenceLevel": "emerging", "sources": [ { "text": "Kimura K et al. L-theanine reduces psychological and physiological stress responses. Biol Psychol. 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Payne ER, Aceves-Martins M, Dubost J et al.. Effects of Tea (Camellia sinensis) or its Bioactive Compounds l-Theanine or l-Theanine plus Caffeine on Cognition, Sleep, and Mood in Healthy Participants: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.. Nutrition Reviews. 2025.", "pmid": "40314930", "doi": "10.1093/nutrit/nuaf054", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40314930/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Potential relaxation-support overlap.", "clinicalSignificance": "Wellness-support pairing only; not anxiety treatment.", "managementStrategy": "If combining L-theanine with magnesium taurate, keep total supplemental magnesium within 200-350 mg/day elemental magnesium unless clinician-supervised; do not frame the pair as anxiety treatment.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "L-Theanine", "supplementBName": "Magnesium Malate", "interactionType": "synergy", "severity": "info", "description": "L-theanine and magnesium are both studied for relaxation-related markers, but direct combination evidence is limited.", "recommendation": "If combining L-theanine with magnesium malate, keep total supplemental magnesium within 200-350 mg/day elemental magnesium unless clinician-supervised; do not frame the pair as anxiety treatment.", "minimumTimeSeparation": null, "mechanism": "L-theanine has alpha-wave and glutamate-signaling research, while magnesium participates in NMDA/GABA-related physiology. Clinical evidence for the specific combination is limited.", "evidenceLevel": "emerging", "sources": [ { "text": "Kimura K et al. L-theanine reduces psychological and physiological stress responses. Biol Psychol. 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Payne ER, Aceves-Martins M, Dubost J et al.. Effects of Tea (Camellia sinensis) or its Bioactive Compounds l-Theanine or l-Theanine plus Caffeine on Cognition, Sleep, and Mood in Healthy Participants: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.. Nutrition Reviews. 2025.", "pmid": "40314930", "doi": "10.1093/nutrit/nuaf054", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40314930/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Potential relaxation-support overlap.", "clinicalSignificance": "Wellness-support pairing only; not anxiety treatment.", "managementStrategy": "If combining L-theanine with magnesium malate, keep total supplemental magnesium within 200-350 mg/day elemental magnesium unless clinician-supervised; do not frame the pair as anxiety treatment.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Melatonin", "supplementBName": "Magnesium Citrate", "interactionType": "synergy", "severity": "info", "description": "Melatonin and magnesium are commonly used in sleep routines, but direct stack evidence and optimal dosing vary.", "recommendation": "If combining melatonin with magnesium citrate, keep magnesium within 200-350 mg/day supplemental elemental magnesium unless clinician-supervised and keep melatonin use situational or clinician-guided for persistent insomnia.", "minimumTimeSeparation": null, "mechanism": "Magnesium participates in neuromuscular and sleep-related physiology; melatonin supports circadian timing. The combination should be presented as routine support, not a sleep-disorder treatment.", "evidenceLevel": "moderate", "sources": [ { "text": "Abbasi B et al. The effect of magnesium supplementation on primary insomnia in elderly. J Res Med Sci. 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Potential sleep-routine support.", "clinicalSignificance": "Dose and duration should stay conservative, especially with chronic sleep problems.", "managementStrategy": "If combining melatonin with magnesium citrate, keep magnesium within 200-350 mg/day supplemental elemental magnesium unless clinician-supervised and keep melatonin use situational or clinician-guided for persistent insomnia.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Melatonin", "supplementBName": "Magnesium Taurate", "interactionType": "synergy", "severity": "info", "description": "Melatonin and magnesium are commonly used in sleep routines, but direct stack evidence and optimal dosing vary.", "recommendation": "If combining melatonin with magnesium taurate, keep magnesium within 200-350 mg/day supplemental elemental magnesium unless clinician-supervised and keep melatonin use situational or clinician-guided for persistent insomnia.", "minimumTimeSeparation": null, "mechanism": "Magnesium participates in neuromuscular and sleep-related physiology; melatonin supports circadian timing. The combination should be presented as routine support, not a sleep-disorder treatment.", "evidenceLevel": "moderate", "sources": [ { "text": "Abbasi B et al. The effect of magnesium supplementation on primary insomnia in elderly. J Res Med Sci. 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Potential sleep-routine support.", "clinicalSignificance": "Dose and duration should stay conservative, especially with chronic sleep problems.", "managementStrategy": "If combining melatonin with magnesium taurate, keep magnesium within 200-350 mg/day supplemental elemental magnesium unless clinician-supervised and keep melatonin use situational or clinician-guided for persistent insomnia.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Melatonin", "supplementBName": "Magnesium Malate", "interactionType": "synergy", "severity": "info", "description": "Melatonin and magnesium are commonly used in sleep routines, but direct stack evidence and optimal dosing vary.", "recommendation": "If combining melatonin with magnesium malate, keep magnesium within 200-350 mg/day supplemental elemental magnesium unless clinician-supervised and keep melatonin use situational or clinician-guided for persistent insomnia.", "minimumTimeSeparation": null, "mechanism": "Magnesium participates in neuromuscular and sleep-related physiology; melatonin supports circadian timing. The combination should be presented as routine support, not a sleep-disorder treatment.", "evidenceLevel": "moderate", "sources": [ { "text": "Abbasi B et al. The effect of magnesium supplementation on primary insomnia in elderly. J Res Med Sci. 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Potential sleep-routine support.", "clinicalSignificance": "Dose and duration should stay conservative, especially with chronic sleep problems.", "managementStrategy": "If combining melatonin with magnesium malate, keep magnesium within 200-350 mg/day supplemental elemental magnesium unless clinician-supervised and keep melatonin use situational or clinician-guided for persistent insomnia.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Apigenin", "supplementBName": "Magnesium L-Threonate", "interactionType": "synergy", "severity": "info", "description": "Both promote relaxation and sleep through GABAergic and glutamate-modulating pathways.", "recommendation": "Combine for a gentle, non-habit-forming sleep support stack.", "minimumTimeSeparation": null, "mechanism": "Apigenin positively modulates GABA-A receptors. Magnesium blocks excitatory NMDA glutamate receptors. Glycine from magnesium l-threonate adds inhibitory neurotransmission.", "evidenceLevel": "emerging", "sources": [ { "text": "Salehi B et al. The therapeutic potential of apigenin. Int J Mol Sci. 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both promote relaxation and sleep through GABAergic and glutamate-modulating pathways.", "clinicalSignificance": "Combine for a gentle, non-habit-forming sleep support stack.", "managementStrategy": "Combine for a gentle, non-habit-forming sleep support stack.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Apigenin", "supplementBName": "Magnesium Citrate", "interactionType": "synergy", "severity": "info", "description": "Both promote relaxation and sleep through GABAergic and glutamate-modulating pathways.", "recommendation": "Combine for a gentle, non-habit-forming sleep support stack.", "minimumTimeSeparation": null, "mechanism": "Apigenin positively modulates GABA-A receptors. Magnesium blocks excitatory NMDA glutamate receptors. Glycine from magnesium citrate adds inhibitory neurotransmission.", "evidenceLevel": "emerging", "sources": [ { "text": "Salehi B et al. The therapeutic potential of apigenin. Int J Mol Sci. 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both promote relaxation and sleep through GABAergic and glutamate-modulating pathways.", "clinicalSignificance": "Combine for a gentle, non-habit-forming sleep support stack.", "managementStrategy": "Combine for a gentle, non-habit-forming sleep support stack.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Apigenin", "supplementBName": "Magnesium Taurate", "interactionType": "synergy", "severity": "info", "description": "Both promote relaxation and sleep through GABAergic and glutamate-modulating pathways.", "recommendation": "Combine for a gentle, non-habit-forming sleep support stack.", "minimumTimeSeparation": null, "mechanism": "Apigenin positively modulates GABA-A receptors. Magnesium blocks excitatory NMDA glutamate receptors. Glycine from magnesium taurate adds inhibitory neurotransmission.", "evidenceLevel": "emerging", "sources": [ { "text": "Salehi B et al. The therapeutic potential of apigenin. Int J Mol Sci. 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both promote relaxation and sleep through GABAergic and glutamate-modulating pathways.", "clinicalSignificance": "Combine for a gentle, non-habit-forming sleep support stack.", "managementStrategy": "Combine for a gentle, non-habit-forming sleep support stack.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Apigenin", "supplementBName": "Magnesium Malate", "interactionType": "synergy", "severity": "info", "description": "Both promote relaxation and sleep through GABAergic and glutamate-modulating pathways.", "recommendation": "Combine for a gentle, non-habit-forming sleep support stack.", "minimumTimeSeparation": null, "mechanism": "Apigenin positively modulates GABA-A receptors. Magnesium blocks excitatory NMDA glutamate receptors. Glycine from magnesium malate adds inhibitory neurotransmission.", "evidenceLevel": "emerging", "sources": [ { "text": "Salehi B et al. The therapeutic potential of apigenin. Int J Mol Sci. 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both promote relaxation and sleep through GABAergic and glutamate-modulating pathways.", "clinicalSignificance": "Combine for a gentle, non-habit-forming sleep support stack.", "managementStrategy": "Combine for a gentle, non-habit-forming sleep support stack.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Potassium", "supplementBName": "Magnesium L-Threonate", "interactionType": "synergy", "severity": "moderate", "description": "Magnesium deficiency causes renal potassium wasting. Correcting magnesium is often necessary before potassium levels can normalize.", "recommendation": "If hypokalemic, check magnesium status. Refractory hypokalemia often resolves only when magnesium is also repleted.", "minimumTimeSeparation": null, "mechanism": "Magnesium maintains ROMK channel function in the renal collecting duct. Mg deficiency causes ROMK-mediated potassium secretion, leading to renal potassium wasting resistant to K supplementation alone.", "evidenceLevel": "strong", "sources": [ { "text": "Huang CL et al. Mechanism of hypokalemia in magnesium deficiency. J Am Soc Nephrol. 2007;18(10):2649-52.", "pmid": "17804670", "doi": "10.1681/ASN.2007070792", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17804670/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Magnesium deficiency causes renal potassium wasting.", "clinicalSignificance": "Correcting magnesium is often necessary before potassium levels can normalize.", "managementStrategy": "If hypokalemic, check magnesium status. Refractory hypokalemia often resolves only when magnesium is also repleted.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Potassium", "supplementBName": "Magnesium Citrate", "interactionType": "synergy", "severity": "moderate", "description": "Magnesium deficiency causes renal potassium wasting. Correcting magnesium is often necessary before potassium levels can normalize.", "recommendation": "If hypokalemic, check magnesium status. Refractory hypokalemia often resolves only when magnesium is also repleted.", "minimumTimeSeparation": null, "mechanism": "Magnesium maintains ROMK channel function in the renal collecting duct. Mg deficiency causes ROMK-mediated potassium secretion, leading to renal potassium wasting resistant to K supplementation alone.", "evidenceLevel": "strong", "sources": [ { "text": "Huang CL et al. Mechanism of hypokalemia in magnesium deficiency. J Am Soc Nephrol. 2007;18(10):2649-52.", "pmid": "17804670", "doi": "10.1681/ASN.2007070792", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17804670/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Magnesium deficiency causes renal potassium wasting.", "clinicalSignificance": "Correcting magnesium is often necessary before potassium levels can normalize.", "managementStrategy": "If hypokalemic, check magnesium status. Refractory hypokalemia often resolves only when magnesium is also repleted.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Potassium", "supplementBName": "Magnesium Taurate", "interactionType": "synergy", "severity": "moderate", "description": "Magnesium deficiency causes renal potassium wasting. Correcting magnesium is often necessary before potassium levels can normalize.", "recommendation": "If hypokalemic, check magnesium status. Refractory hypokalemia often resolves only when magnesium is also repleted.", "minimumTimeSeparation": null, "mechanism": "Magnesium maintains ROMK channel function in the renal collecting duct. Mg deficiency causes ROMK-mediated potassium secretion, leading to renal potassium wasting resistant to K supplementation alone.", "evidenceLevel": "strong", "sources": [ { "text": "Huang CL et al. Mechanism of hypokalemia in magnesium deficiency. J Am Soc Nephrol. 2007;18(10):2649-52.", "pmid": "17804670", "doi": "10.1681/ASN.2007070792", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17804670/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Magnesium deficiency causes renal potassium wasting.", "clinicalSignificance": "Correcting magnesium is often necessary before potassium levels can normalize.", "managementStrategy": "If hypokalemic, check magnesium status. Refractory hypokalemia often resolves only when magnesium is also repleted.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Potassium", "supplementBName": "Magnesium Malate", "interactionType": "synergy", "severity": "moderate", "description": "Magnesium deficiency causes renal potassium wasting. Correcting magnesium is often necessary before potassium levels can normalize.", "recommendation": "If hypokalemic, check magnesium status. Refractory hypokalemia often resolves only when magnesium is also repleted.", "minimumTimeSeparation": null, "mechanism": "Magnesium maintains ROMK channel function in the renal collecting duct. Mg deficiency causes ROMK-mediated potassium secretion, leading to renal potassium wasting resistant to K supplementation alone.", "evidenceLevel": "strong", "sources": [ { "text": "Huang CL et al. Mechanism of hypokalemia in magnesium deficiency. J Am Soc Nephrol. 2007;18(10):2649-52.", "pmid": "17804670", "doi": "10.1681/ASN.2007070792", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17804670/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Magnesium deficiency causes renal potassium wasting.", "clinicalSignificance": "Correcting magnesium is often necessary before potassium levels can normalize.", "managementStrategy": "If hypokalemic, check magnesium status. Refractory hypokalemia often resolves only when magnesium is also repleted.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Iron", "supplementBName": "Magnesium L-Threonate", "interactionType": "timingSensitive", "severity": "moderate", "description": "Magnesium and iron can compete for absorption when taken together. Separate for optimal absorption of both.", "recommendation": "Take iron in the morning on an empty stomach. Take magnesium l-threonate in the evening.", "minimumTimeSeparation": 120, "mechanism": "Iron uses DMT1 while magnesium uses TRPM6/TRPM7 channels. Competition occurs through indirect mechanisms including shared paracellular absorption pathways. Separating by 2+ hours eliminates competition.", "evidenceLevel": "moderate", "sources": [ { "text": "Shawki A, Bhatt DK. Intestinal DMT1 is critical for iron absorption. Blood. 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Magnesium and iron can compete for absorption when taken together.", "clinicalSignificance": "Separate for optimal absorption of both.", "managementStrategy": "Take iron in the morning on an empty stomach. Take magnesium l-threonate in the evening.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Iron", "supplementBName": "Magnesium Citrate", "interactionType": "timingSensitive", "severity": "moderate", "description": "Magnesium and iron can compete for absorption when taken together. Separate for optimal absorption of both.", "recommendation": "Take iron in the morning on an empty stomach. Take magnesium citrate in the evening.", "minimumTimeSeparation": 120, "mechanism": "Iron uses DMT1 while magnesium uses TRPM6/TRPM7 channels. Competition occurs through indirect mechanisms including shared paracellular absorption pathways. Separating by 2+ hours eliminates competition.", "evidenceLevel": "moderate", "sources": [ { "text": "Shawki A, Bhatt DK. Intestinal DMT1 is critical for iron absorption. Blood. 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Magnesium and iron can compete for absorption when taken together.", "clinicalSignificance": "Separate for optimal absorption of both.", "managementStrategy": "Take iron in the morning on an empty stomach. Take magnesium citrate in the evening.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Iron", "supplementBName": "Magnesium Taurate", "interactionType": "timingSensitive", "severity": "moderate", "description": "Magnesium and iron can compete for absorption when taken together. Separate for optimal absorption of both.", "recommendation": "Take iron in the morning on an empty stomach. Take magnesium taurate in the evening.", "minimumTimeSeparation": 120, "mechanism": "Iron uses DMT1 while magnesium uses TRPM6/TRPM7 channels. Competition occurs through indirect mechanisms including shared paracellular absorption pathways. Separating by 2+ hours eliminates competition.", "evidenceLevel": "moderate", "sources": [ { "text": "Shawki A, Bhatt DK. Intestinal DMT1 is critical for iron absorption. Blood. 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Magnesium and iron can compete for absorption when taken together.", "clinicalSignificance": "Separate for optimal absorption of both.", "managementStrategy": "Take iron in the morning on an empty stomach. Take magnesium taurate in the evening.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Iron", "supplementBName": "Magnesium Malate", "interactionType": "timingSensitive", "severity": "moderate", "description": "Magnesium and iron can compete for absorption when taken together. Separate for optimal absorption of both.", "recommendation": "Take iron in the morning on an empty stomach. Take magnesium malate in the evening.", "minimumTimeSeparation": 120, "mechanism": "Iron uses DMT1 while magnesium uses TRPM6/TRPM7 channels. Competition occurs through indirect mechanisms including shared paracellular absorption pathways. Separating by 2+ hours eliminates competition.", "evidenceLevel": "moderate", "sources": [ { "text": "Shawki A, Bhatt DK. Intestinal DMT1 is critical for iron absorption. Blood. 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Magnesium and iron can compete for absorption when taken together.", "clinicalSignificance": "Separate for optimal absorption of both.", "managementStrategy": "Take iron in the morning on an empty stomach. Take magnesium malate in the evening.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Creatine", "supplementBName": "Magnesium L-Threonate", "interactionType": "synergy", "severity": "info", "description": "Magnesium is required for creatine kinase enzyme activity, which phosphorylates creatine to phosphocreatine.", "recommendation": "Ensure adequate magnesium when supplementing creatine for optimal ATP buffering.", "minimumTimeSeparation": null, "mechanism": "Creatine kinase requires Mg-ATP as substrate (not free ATP). Magnesium deficiency impairs the creatine kinase reaction and reduces phosphocreatine stores.", "evidenceLevel": "moderate", "sources": [ { "text": "Wallimann T et al. Intracellular compartmentation, structure and function of creatine kinase isoenzymes. Biochem J. 1992", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Magnesium is required for creatine kinase enzyme activity, which phosphorylates creatine to phosphocreatine.", "clinicalSignificance": "Ensure adequate magnesium when supplementing creatine for optimal ATP buffering.", "managementStrategy": "Ensure adequate magnesium when supplementing creatine for optimal ATP buffering.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Creatine", "supplementBName": "Magnesium Citrate", "interactionType": "synergy", "severity": "info", "description": "Magnesium is required for creatine kinase enzyme activity, which phosphorylates creatine to phosphocreatine.", "recommendation": "Ensure adequate magnesium when supplementing creatine for optimal ATP buffering.", "minimumTimeSeparation": null, "mechanism": "Creatine kinase requires Mg-ATP as substrate (not free ATP). Magnesium deficiency impairs the creatine kinase reaction and reduces phosphocreatine stores.", "evidenceLevel": "moderate", "sources": [ { "text": "Wallimann T et al. Intracellular compartmentation, structure and function of creatine kinase isoenzymes. Biochem J. 1992", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Magnesium is required for creatine kinase enzyme activity, which phosphorylates creatine to phosphocreatine.", "clinicalSignificance": "Ensure adequate magnesium when supplementing creatine for optimal ATP buffering.", "managementStrategy": "Ensure adequate magnesium when supplementing creatine for optimal ATP buffering.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Creatine", "supplementBName": "Magnesium Taurate", "interactionType": "synergy", "severity": "info", "description": "Magnesium is required for creatine kinase enzyme activity, which phosphorylates creatine to phosphocreatine.", "recommendation": "Ensure adequate magnesium when supplementing creatine for optimal ATP buffering.", "minimumTimeSeparation": null, "mechanism": "Creatine kinase requires Mg-ATP as substrate (not free ATP). Magnesium deficiency impairs the creatine kinase reaction and reduces phosphocreatine stores.", "evidenceLevel": "moderate", "sources": [ { "text": "Wallimann T et al. Intracellular compartmentation, structure and function of creatine kinase isoenzymes. Biochem J. 1992", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Magnesium is required for creatine kinase enzyme activity, which phosphorylates creatine to phosphocreatine.", "clinicalSignificance": "Ensure adequate magnesium when supplementing creatine for optimal ATP buffering.", "managementStrategy": "Ensure adequate magnesium when supplementing creatine for optimal ATP buffering.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Creatine", "supplementBName": "Magnesium Malate", "interactionType": "synergy", "severity": "info", "description": "Magnesium is required for creatine kinase enzyme activity, which phosphorylates creatine to phosphocreatine.", "recommendation": "Ensure adequate magnesium when supplementing creatine for optimal ATP buffering.", "minimumTimeSeparation": null, "mechanism": "Creatine kinase requires Mg-ATP as substrate (not free ATP). Magnesium deficiency impairs the creatine kinase reaction and reduces phosphocreatine stores.", "evidenceLevel": "moderate", "sources": [ { "text": "Wallimann T et al. Intracellular compartmentation, structure and function of creatine kinase isoenzymes. Biochem J. 1992", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Magnesium is required for creatine kinase enzyme activity, which phosphorylates creatine to phosphocreatine.", "clinicalSignificance": "Ensure adequate magnesium when supplementing creatine for optimal ATP buffering.", "managementStrategy": "Ensure adequate magnesium when supplementing creatine for optimal ATP buffering.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Magnesium L-Threonate", "supplementBName": "Calcium", "interactionType": "synergy", "severity": "info", "description": "At moderate doses, magnesium and calcium work synergistically for bone health and muscle function. Calcium for contraction, magnesium for relaxation.", "recommendation": "Aim for 2:1 calcium-to-magnesium ratio. Both are essential for bone density and neuromuscular function.", "minimumTimeSeparation": null, "mechanism": "Calcium triggers muscle contraction via troponin-C binding. Magnesium promotes relaxation by competing with calcium at the NMDA receptor and supporting SERCA pump for calcium reuptake into SR.", "evidenceLevel": "strong", "sources": [ { "text": "Castiglioni S et al. Magnesium and osteoporosis: current state of knowledge. Nutrients. 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "At moderate doses, magnesium and calcium work synergistically for bone health and muscle function.", "clinicalSignificance": "Calcium for contraction, magnesium for relaxation.", "managementStrategy": "Aim for 2:1 calcium-to-magnesium ratio. Both are essential for bone density and neuromuscular function.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Magnesium Citrate", "supplementBName": "Calcium", "interactionType": "synergy", "severity": "info", "description": "At moderate doses, magnesium and calcium work synergistically for bone health and muscle function. Calcium for contraction, magnesium for relaxation.", "recommendation": "Aim for 2:1 calcium-to-magnesium ratio. Both are essential for bone density and neuromuscular function.", "minimumTimeSeparation": null, "mechanism": "Calcium triggers muscle contraction via troponin-C binding. Magnesium promotes relaxation by competing with calcium at the NMDA receptor and supporting SERCA pump for calcium reuptake into SR.", "evidenceLevel": "strong", "sources": [ { "text": "Castiglioni S et al. Magnesium and osteoporosis: current state of knowledge. Nutrients. 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "At moderate doses, magnesium and calcium work synergistically for bone health and muscle function.", "clinicalSignificance": "Calcium for contraction, magnesium for relaxation.", "managementStrategy": "Aim for 2:1 calcium-to-magnesium ratio. Both are essential for bone density and neuromuscular function.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Magnesium Taurate", "supplementBName": "Calcium", "interactionType": "synergy", "severity": "info", "description": "At moderate doses, magnesium and calcium work synergistically for bone health and muscle function. Calcium for contraction, magnesium for relaxation.", "recommendation": "Aim for 2:1 calcium-to-magnesium ratio. Both are essential for bone density and neuromuscular function.", "minimumTimeSeparation": null, "mechanism": "Calcium triggers muscle contraction via troponin-C binding. Magnesium promotes relaxation by competing with calcium at the NMDA receptor and supporting SERCA pump for calcium reuptake into SR.", "evidenceLevel": "strong", "sources": [ { "text": "Castiglioni S et al. Magnesium and osteoporosis: current state of knowledge. Nutrients. 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "At moderate doses, magnesium and calcium work synergistically for bone health and muscle function.", "clinicalSignificance": "Calcium for contraction, magnesium for relaxation.", "managementStrategy": "Aim for 2:1 calcium-to-magnesium ratio. Both are essential for bone density and neuromuscular function.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Magnesium Malate", "supplementBName": "Calcium", "interactionType": "synergy", "severity": "info", "description": "At moderate doses, magnesium and calcium work synergistically for bone health and muscle function. Calcium for contraction, magnesium for relaxation.", "recommendation": "Aim for 2:1 calcium-to-magnesium ratio. Both are essential for bone density and neuromuscular function.", "minimumTimeSeparation": null, "mechanism": "Calcium triggers muscle contraction via troponin-C binding. Magnesium promotes relaxation by competing with calcium at the NMDA receptor and supporting SERCA pump for calcium reuptake into SR.", "evidenceLevel": "strong", "sources": [ { "text": "Castiglioni S et al. Magnesium and osteoporosis: current state of knowledge. Nutrients. 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "At moderate doses, magnesium and calcium work synergistically for bone health and muscle function.", "clinicalSignificance": "Calcium for contraction, magnesium for relaxation.", "managementStrategy": "Aim for 2:1 calcium-to-magnesium ratio. Both are essential for bone density and neuromuscular function.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "MCT Oil", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "info", "description": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin D3.", "recommendation": "Take Vitamin D3 with MCT Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin D3.", "clinicalSignificance": "Take Vitamin D3 with MCT Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Vitamin D3 with MCT Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "MCT Oil", "supplementBName": "Vitamin D2", "interactionType": "synergy", "severity": "info", "description": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin D2.", "recommendation": "Take Vitamin D2 with MCT Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin D2.", "clinicalSignificance": "Take Vitamin D2 with MCT Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Vitamin D2 with MCT Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "MCT Oil", "supplementBName": "Vitamin K2", "interactionType": "synergy", "severity": "info", "description": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin K2.", "recommendation": "Take Vitamin K2 with MCT Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Kuang X, Liu C, Guo X, Li K, Deng Q, Li D. The combination effect of vitamin K and vitamin D on human bone quality: a meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "32219282", "doi": "10.1039/c9fo03063h", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32219282/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin K2.", "clinicalSignificance": "Take Vitamin K2 with MCT Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Vitamin K2 with MCT Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "MCT Oil", "supplementBName": "Vitamin K1", "interactionType": "synergy", "severity": "info", "description": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin K1.", "recommendation": "Take Vitamin K1 with MCT Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin K1.", "clinicalSignificance": "Take Vitamin K1 with MCT Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Vitamin K1 with MCT Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "MCT Oil", "supplementBName": "Vitamin K2 MK-4", "interactionType": "synergy", "severity": "info", "description": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin K2 MK-4.", "recommendation": "Take Vitamin K2 MK-4 with MCT Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin K2 MK-4.", "clinicalSignificance": "Take Vitamin K2 MK-4 with MCT Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Vitamin K2 MK-4 with MCT Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "MCT Oil", "supplementBName": "Vitamin A", "interactionType": "synergy", "severity": "info", "description": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin A.", "recommendation": "Take Vitamin A with MCT Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin A.", "clinicalSignificance": "Take Vitamin A with MCT Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Vitamin A with MCT Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "MCT Oil", "supplementBName": "Vitamin E", "interactionType": "synergy", "severity": "info", "description": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin E.", "recommendation": "Take Vitamin E with MCT Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin E.", "clinicalSignificance": "Take Vitamin E with MCT Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Vitamin E with MCT Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "MCT Oil", "supplementBName": "Coenzyme Q10", "interactionType": "synergy", "severity": "info", "description": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Coenzyme Q10.", "recommendation": "Take Coenzyme Q10 with MCT Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Coenzyme Q10.", "clinicalSignificance": "Take Coenzyme Q10 with MCT Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Coenzyme Q10 with MCT Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "MCT Oil", "supplementBName": "Coenzyme Q10 Ubiquinol", "interactionType": "synergy", "severity": "info", "description": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Coenzyme Q10 Ubiquinol.", "recommendation": "Take Coenzyme Q10 Ubiquinol with MCT Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Coenzyme Q10 Ubiquinol.", "clinicalSignificance": "Take Coenzyme Q10 Ubiquinol with MCT Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Coenzyme Q10 Ubiquinol with MCT Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "MCT Oil", "supplementBName": "Turmeric/Curcumin", "interactionType": "synergy", "severity": "info", "description": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Turmeric/Curcumin.", "recommendation": "Take Turmeric/Curcumin with MCT Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Turmeric/Curcumin.", "clinicalSignificance": "Take Turmeric/Curcumin with MCT Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Turmeric/Curcumin with MCT Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "MCT Oil", "supplementBName": "Curcumin Phytosome", "interactionType": "synergy", "severity": "info", "description": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Curcumin Phytosome.", "recommendation": "Take Curcumin Phytosome with MCT Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Curcumin Phytosome.", "clinicalSignificance": "Take Curcumin Phytosome with MCT Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Curcumin Phytosome with MCT Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "MCT Oil", "supplementBName": "Astaxanthin", "interactionType": "synergy", "severity": "info", "description": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Astaxanthin.", "recommendation": "Take Astaxanthin with MCT Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Astaxanthin.", "clinicalSignificance": "Take Astaxanthin with MCT Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Astaxanthin with MCT Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "MCT Oil", "supplementBName": "Lutein", "interactionType": "synergy", "severity": "info", "description": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Lutein.", "recommendation": "Take Lutein with MCT Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Lutein.", "clinicalSignificance": "Take Lutein with MCT Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Lutein with MCT Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "MCT Oil", "supplementBName": "Zeaxanthin", "interactionType": "synergy", "severity": "info", "description": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Zeaxanthin.", "recommendation": "Take Zeaxanthin with MCT Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Zeaxanthin.", "clinicalSignificance": "Take Zeaxanthin with MCT Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Zeaxanthin with MCT Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "MCT Oil", "supplementBName": "Lycopene", "interactionType": "synergy", "severity": "info", "description": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Lycopene.", "recommendation": "Take Lycopene with MCT Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Lycopene.", "clinicalSignificance": "Take Lycopene with MCT Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Lycopene with MCT Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "MCT Oil", "supplementBName": "Resveratrol", "interactionType": "synergy", "severity": "info", "description": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Resveratrol.", "recommendation": "Take Resveratrol with MCT Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "MCT Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Resveratrol.", "clinicalSignificance": "Take Resveratrol with MCT Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Resveratrol with MCT Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Flaxseed Oil", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "info", "description": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin D3.", "recommendation": "Take Vitamin D3 with Flaxseed Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin D3.", "clinicalSignificance": "Take Vitamin D3 with Flaxseed Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Vitamin D3 with Flaxseed Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Flaxseed Oil", "supplementBName": "Vitamin D2", "interactionType": "synergy", "severity": "info", "description": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin D2.", "recommendation": "Take Vitamin D2 with Flaxseed Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin D2.", "clinicalSignificance": "Take Vitamin D2 with Flaxseed Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Vitamin D2 with Flaxseed Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Flaxseed Oil", "supplementBName": "Vitamin K2", "interactionType": "synergy", "severity": "info", "description": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin K2.", "recommendation": "Take Vitamin K2 with Flaxseed Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Kuang X, Liu C, Guo X, Li K, Deng Q, Li D. The combination effect of vitamin K and vitamin D on human bone quality: a meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "32219282", "doi": "10.1039/c9fo03063h", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32219282/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin K2.", "clinicalSignificance": "Take Vitamin K2 with Flaxseed Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Vitamin K2 with Flaxseed Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Flaxseed Oil", "supplementBName": "Vitamin K1", "interactionType": "synergy", "severity": "info", "description": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin K1.", "recommendation": "Take Vitamin K1 with Flaxseed Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin K1.", "clinicalSignificance": "Take Vitamin K1 with Flaxseed Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Vitamin K1 with Flaxseed Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Flaxseed Oil", "supplementBName": "Vitamin K2 MK-4", "interactionType": "synergy", "severity": "info", "description": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin K2 MK-4.", "recommendation": "Take Vitamin K2 MK-4 with Flaxseed Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin K2 MK-4.", "clinicalSignificance": "Take Vitamin K2 MK-4 with Flaxseed Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Vitamin K2 MK-4 with Flaxseed Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Flaxseed Oil", "supplementBName": "Vitamin A", "interactionType": "synergy", "severity": "info", "description": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin A.", "recommendation": "Take Vitamin A with Flaxseed Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin A.", "clinicalSignificance": "Take Vitamin A with Flaxseed Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Vitamin A with Flaxseed Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Flaxseed Oil", "supplementBName": "Vitamin E", "interactionType": "synergy", "severity": "info", "description": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin E.", "recommendation": "Take Vitamin E with Flaxseed Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin E.", "clinicalSignificance": "Take Vitamin E with Flaxseed Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Vitamin E with Flaxseed Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Flaxseed Oil", "supplementBName": "Coenzyme Q10", "interactionType": "synergy", "severity": "info", "description": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Coenzyme Q10.", "recommendation": "Take Coenzyme Q10 with Flaxseed Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Coenzyme Q10.", "clinicalSignificance": "Take Coenzyme Q10 with Flaxseed Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Coenzyme Q10 with Flaxseed Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Flaxseed Oil", "supplementBName": "Coenzyme Q10 Ubiquinol", "interactionType": "synergy", "severity": "info", "description": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Coenzyme Q10 Ubiquinol.", "recommendation": "Take Coenzyme Q10 Ubiquinol with Flaxseed Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Coenzyme Q10 Ubiquinol.", "clinicalSignificance": "Take Coenzyme Q10 Ubiquinol with Flaxseed Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Coenzyme Q10 Ubiquinol with Flaxseed Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Flaxseed Oil", "supplementBName": "Turmeric/Curcumin", "interactionType": "synergy", "severity": "info", "description": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Turmeric/Curcumin.", "recommendation": "Take Turmeric/Curcumin with Flaxseed Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Turmeric/Curcumin.", "clinicalSignificance": "Take Turmeric/Curcumin with Flaxseed Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Turmeric/Curcumin with Flaxseed Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Flaxseed Oil", "supplementBName": "Curcumin Phytosome", "interactionType": "synergy", "severity": "info", "description": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Curcumin Phytosome.", "recommendation": "Take Curcumin Phytosome with Flaxseed Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Curcumin Phytosome.", "clinicalSignificance": "Take Curcumin Phytosome with Flaxseed Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Curcumin Phytosome with Flaxseed Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Flaxseed Oil", "supplementBName": "Astaxanthin", "interactionType": "synergy", "severity": "info", "description": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Astaxanthin.", "recommendation": "Take Astaxanthin with Flaxseed Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Astaxanthin.", "clinicalSignificance": "Take Astaxanthin with Flaxseed Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Astaxanthin with Flaxseed Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Flaxseed Oil", "supplementBName": "Lutein", "interactionType": "synergy", "severity": "info", "description": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Lutein.", "recommendation": "Take Lutein with Flaxseed Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Lutein.", "clinicalSignificance": "Take Lutein with Flaxseed Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Lutein with Flaxseed Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Flaxseed Oil", "supplementBName": "Zeaxanthin", "interactionType": "synergy", "severity": "info", "description": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Zeaxanthin.", "recommendation": "Take Zeaxanthin with Flaxseed Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Zeaxanthin.", "clinicalSignificance": "Take Zeaxanthin with Flaxseed Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Zeaxanthin with Flaxseed Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Flaxseed Oil", "supplementBName": "Lycopene", "interactionType": "synergy", "severity": "info", "description": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Lycopene.", "recommendation": "Take Lycopene with Flaxseed Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Lycopene.", "clinicalSignificance": "Take Lycopene with Flaxseed Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Lycopene with Flaxseed Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Flaxseed Oil", "supplementBName": "Resveratrol", "interactionType": "synergy", "severity": "info", "description": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Resveratrol.", "recommendation": "Take Resveratrol with Flaxseed Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Flaxseed Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Resveratrol.", "clinicalSignificance": "Take Resveratrol with Flaxseed Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Resveratrol with Flaxseed Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Evening Primrose Oil", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "info", "description": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin D3.", "recommendation": "Take Vitamin D3 with Evening Primrose Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin D3.", "clinicalSignificance": "Take Vitamin D3 with Evening Primrose Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Vitamin D3 with Evening Primrose Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Evening Primrose Oil", "supplementBName": "Vitamin D2", "interactionType": "synergy", "severity": "info", "description": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin D2.", "recommendation": "Take Vitamin D2 with Evening Primrose Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin D2.", "clinicalSignificance": "Take Vitamin D2 with Evening Primrose Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Vitamin D2 with Evening Primrose Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Evening Primrose Oil", "supplementBName": "Vitamin K2", "interactionType": "synergy", "severity": "info", "description": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin K2.", "recommendation": "Take Vitamin K2 with Evening Primrose Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Kuang X, Liu C, Guo X, Li K, Deng Q, Li D. The combination effect of vitamin K and vitamin D on human bone quality: a meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "32219282", "doi": "10.1039/c9fo03063h", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32219282/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin K2.", "clinicalSignificance": "Take Vitamin K2 with Evening Primrose Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Vitamin K2 with Evening Primrose Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Evening Primrose Oil", "supplementBName": "Vitamin K1", "interactionType": "synergy", "severity": "info", "description": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin K1.", "recommendation": "Take Vitamin K1 with Evening Primrose Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin K1.", "clinicalSignificance": "Take Vitamin K1 with Evening Primrose Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Vitamin K1 with Evening Primrose Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Evening Primrose Oil", "supplementBName": "Vitamin K2 MK-4", "interactionType": "synergy", "severity": "info", "description": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin K2 MK-4.", "recommendation": "Take Vitamin K2 MK-4 with Evening Primrose Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin K2 MK-4.", "clinicalSignificance": "Take Vitamin K2 MK-4 with Evening Primrose Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Vitamin K2 MK-4 with Evening Primrose Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Evening Primrose Oil", "supplementBName": "Vitamin A", "interactionType": "synergy", "severity": "info", "description": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin A.", "recommendation": "Take Vitamin A with Evening Primrose Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin A.", "clinicalSignificance": "Take Vitamin A with Evening Primrose Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Vitamin A with Evening Primrose Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Evening Primrose Oil", "supplementBName": "Vitamin E", "interactionType": "synergy", "severity": "info", "description": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin E.", "recommendation": "Take Vitamin E with Evening Primrose Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Vitamin E.", "clinicalSignificance": "Take Vitamin E with Evening Primrose Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Vitamin E with Evening Primrose Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Evening Primrose Oil", "supplementBName": "Coenzyme Q10", "interactionType": "synergy", "severity": "info", "description": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Coenzyme Q10.", "recommendation": "Take Coenzyme Q10 with Evening Primrose Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Coenzyme Q10.", "clinicalSignificance": "Take Coenzyme Q10 with Evening Primrose Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Coenzyme Q10 with Evening Primrose Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Evening Primrose Oil", "supplementBName": "Coenzyme Q10 Ubiquinol", "interactionType": "synergy", "severity": "info", "description": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Coenzyme Q10 Ubiquinol.", "recommendation": "Take Coenzyme Q10 Ubiquinol with Evening Primrose Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Coenzyme Q10 Ubiquinol.", "clinicalSignificance": "Take Coenzyme Q10 Ubiquinol with Evening Primrose Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Coenzyme Q10 Ubiquinol with Evening Primrose Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Evening Primrose Oil", "supplementBName": "Turmeric/Curcumin", "interactionType": "synergy", "severity": "info", "description": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Turmeric/Curcumin.", "recommendation": "Take Turmeric/Curcumin with Evening Primrose Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Turmeric/Curcumin.", "clinicalSignificance": "Take Turmeric/Curcumin with Evening Primrose Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Turmeric/Curcumin with Evening Primrose Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Evening Primrose Oil", "supplementBName": "Curcumin Phytosome", "interactionType": "synergy", "severity": "info", "description": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Curcumin Phytosome.", "recommendation": "Take Curcumin Phytosome with Evening Primrose Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Curcumin Phytosome.", "clinicalSignificance": "Take Curcumin Phytosome with Evening Primrose Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Curcumin Phytosome with Evening Primrose Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Evening Primrose Oil", "supplementBName": "Astaxanthin", "interactionType": "synergy", "severity": "info", "description": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Astaxanthin.", "recommendation": "Take Astaxanthin with Evening Primrose Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Astaxanthin.", "clinicalSignificance": "Take Astaxanthin with Evening Primrose Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Astaxanthin with Evening Primrose Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Evening Primrose Oil", "supplementBName": "Lutein", "interactionType": "synergy", "severity": "info", "description": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Lutein.", "recommendation": "Take Lutein with Evening Primrose Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Lutein.", "clinicalSignificance": "Take Lutein with Evening Primrose Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Lutein with Evening Primrose Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Evening Primrose Oil", "supplementBName": "Zeaxanthin", "interactionType": "synergy", "severity": "info", "description": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Zeaxanthin.", "recommendation": "Take Zeaxanthin with Evening Primrose Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Zeaxanthin.", "clinicalSignificance": "Take Zeaxanthin with Evening Primrose Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Zeaxanthin with Evening Primrose Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Evening Primrose Oil", "supplementBName": "Lycopene", "interactionType": "synergy", "severity": "info", "description": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Lycopene.", "recommendation": "Take Lycopene with Evening Primrose Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Lycopene.", "clinicalSignificance": "Take Lycopene with Evening Primrose Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Lycopene with Evening Primrose Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Evening Primrose Oil", "supplementBName": "Resveratrol", "interactionType": "synergy", "severity": "info", "description": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Resveratrol.", "recommendation": "Take Resveratrol with Evening Primrose Oil or another fat-containing meal to improve absorption.", "minimumTimeSeparation": null, "mechanism": "Dietary fat stimulates bile release and mixed micelle formation in the intestine, improving solubilization and uptake of lipophilic nutrients and botanicals.", "evidenceLevel": "moderate", "sources": [ { "text": "Dawson-Hughes B et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Evening Primrose Oil provides a fat-containing carrier that can improve absorption of fat-soluble compounds like Resveratrol.", "clinicalSignificance": "Take Resveratrol with Evening Primrose Oil or another fat-containing meal to improve absorption.", "managementStrategy": "Take Resveratrol with Evening Primrose Oil or another fat-containing meal to improve absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "5-HTP", "supplementBName": "L-Tryptophan", "interactionType": "contraindicated", "severity": "dangerous", "description": "Both 5-HTP and L-Tryptophan increase serotonin synthesis. Combining them creates additive serotonin excess, risking serotonin syndrome.", "recommendation": "Do NOT combine. Choose one serotonin precursor, not both.", "minimumTimeSeparation": null, "mechanism": "5-HTP bypasses rate-limiting tryptophan hydroxylase to directly flood serotonin synthesis. L-Tryptophan feeds the same pathway upstream. Combined effect causes dangerous serotonin accumulation.", "evidenceLevel": "moderate", "sources": [ { "text": "Turner EH et al. Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacol Ther. 2006;109(3):325-38.", "pmid": "16023217", "doi": "10.1016/j.pharmthera.2005.06.004", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16023217/", "publicSourceType": "PMID" }, { "text": "Fernstrom JD. A Perspective on the Safety of Supplemental Tryptophan Based on Its Metabolic Fates. J Nutr. 2016;146(12):2601S-2608S.", "pmid": "27934651", "doi": "10.3945/jn.115.228643", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27934651/", "publicSourceType": "PMID" }, { "text": "Boyer EW et al. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-20.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Both 5-HTP and L-Tryptophan increase serotonin synthesis.", "clinicalSignificance": "Combining them creates additive serotonin excess, risking serotonin syndrome.", "managementStrategy": "Do NOT combine. Choose one serotonin precursor, not both.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "5-HTP", "supplementBName": "St. John's Wort", "interactionType": "contraindicated", "severity": "dangerous", "description": "St. John's Wort inhibits serotonin reuptake while 5-HTP floods serotonin synthesis. Combined use risks serotonin syndrome: a potentially fatal condition.", "recommendation": "Do NOT combine. Both increase serotonergic activity through different mechanisms.", "minimumTimeSeparation": null, "mechanism": "Hyperforin in St. John's Wort blocks serotonin reuptake. 5-HTP bypasses rate-limiting enzyme to increase serotonin production. Dual mechanism creates dangerous serotonin excess.", "evidenceLevel": "moderate", "sources": [ { "text": "Borrelli F et al. Herb-drug interactions with St John's wort (Hypericum perforatum): an update on clinical observations. AAPS J. 2009;11(4):710-27.", "pmid": "19859815", "doi": "10.1208/s12248-009-9146-8", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19859815/", "publicSourceType": "PMID" }, { "text": "Singer A et al. Hyperforin, a major antidepressant constituent of St. John's Wort, inhibits serotonin uptake by elevating free intracellular Na+1. J Pharmacol Exp Ther. 1999;290(3):1363-8.", "pmid": "10454515", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10454515/", "publicSourceType": "PMID" }, { "text": "Turner EH et al. Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacol Ther. 2006;109(3):325-38.", "pmid": "16023217", "doi": "10.1016/j.pharmthera.2005.06.004", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16023217/", "publicSourceType": "PMID" }, { "text": "Boyer EW et al. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-20.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "St.", "clinicalSignificance": "John's Wort inhibits serotonin reuptake while 5-HTP floods serotonin synthesis.", "managementStrategy": "Do NOT combine. Both increase serotonergic activity through different mechanisms.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "L-Tryptophan", "supplementBName": "St. John's Wort", "interactionType": "contraindicated", "severity": "dangerous", "description": "St. John's Wort inhibits serotonin reuptake while L-Tryptophan increases serotonin synthesis. Risk of serotonin syndrome.", "recommendation": "Do NOT combine without medical supervision.", "minimumTimeSeparation": null, "mechanism": "L-Tryptophan is converted to serotonin via tryptophan hydroxylase; St. John's Wort blocks reuptake via hyperforin. Combined effect accumulates excess synaptic serotonin.", "evidenceLevel": "moderate", "sources": [ { "text": "Borrelli F et al. Herb-drug interactions with St John's wort (Hypericum perforatum): an update on clinical observations. AAPS J. 2009;11(4):710-27.", "pmid": "19859815", "doi": "10.1208/s12248-009-9146-8", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19859815/", "publicSourceType": "PMID" }, { "text": "Fernstrom JD. A Perspective on the Safety of Supplemental Tryptophan Based on Its Metabolic Fates. J Nutr. 2016;146(12):2601S-2608S.", "pmid": "27934651", "doi": "10.3945/jn.115.228643", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27934651/", "publicSourceType": "PMID" }, { "text": "Boyer EW et al. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-20.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "St.", "clinicalSignificance": "John's Wort inhibits serotonin reuptake while L-Tryptophan increases serotonin synthesis.", "managementStrategy": "Do NOT combine without medical supervision.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Rhodiola Rosea", "supplementBName": "5-HTP", "interactionType": "caution", "severity": "moderate", "description": "Rhodiola has preclinical monoamine effects, while 5-HTP increases serotonin synthesis. Combined use carries a theoretical serotonin-excess risk, but direct human interaction evidence is limited.", "recommendation": "Avoid self-combining Rhodiola with 5-HTP if you also use antidepressants or other serotonergic agents. If used together, keep doses conservative and stop/seek care for serotonin-toxicity symptoms.", "minimumTimeSeparation": null, "mechanism": "Some Rhodiola extracts inhibit MAO-A/MAO-B in vitro, but clinical relevance at supplement doses is uncertain. 5-HTP increases serotonin synthesis, so overlapping monoamine effects justify precaution.", "evidenceLevel": "emerging", "sources": [ { "text": "van Diermen D et al. Monoamine oxidase inhibition by Rhodiola rosea L. roots. J Ethnopharmacol. 2009;122(2):397-401.", "pmid": "19168123", "doi": "10.1016/j.jep.2009.01.007", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19168123/", "publicSourceType": "PMID" }, { "text": "Turner EH et al. Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacol Ther. 2006;109(3):325-38.", "pmid": "16023217", "doi": "10.1016/j.pharmthera.2005.06.004", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16023217/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Theoretical additive serotonergic activity.", "clinicalSignificance": "Direct human interaction evidence is limited; caution is strongest with other serotonergic medications, high doses, or symptoms such as agitation, tremor, sweating, diarrhea, fever, clonus, or confusion.", "managementStrategy": "Do not use as an antidepressant stack without clinician/pharmacist input; monitor for serotonin-toxicity symptoms if combined.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Rhodiola Rosea", "supplementBName": "St. John's Wort", "interactionType": "caution", "severity": "serious", "description": "Rhodiola and St. John's Wort both have CNS-active and possible serotonergic effects. Human interaction evidence is limited, but combining them can make mood, sleep, blood pressure, and serotonergic side effects harder to predict.", "recommendation": "Avoid using Rhodiola and St. John's Wort together as a self-directed mood stack, especially with antidepressants or other serotonergic medications.", "minimumTimeSeparation": null, "mechanism": "St. John's Wort can inhibit serotonin reuptake and strongly induces drug-metabolizing pathways. Rhodiola has preclinical monoamine-modulating findings; the clinical significance of Rhodiola MAO inhibition is uncertain.", "evidenceLevel": "emerging", "sources": [ { "text": "Weixlbaumer V et al. From St. John's wort to tomato and from Rhodiola to cranberry : A review of phytotherapy and some examples. Wien Klin Wochenschr. 2020;132(9-10):253-259.", "pmid": "32211986", "doi": "10.1007/s00508-020-01633-w", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32211986/", "publicSourceType": "PMID" }, { "text": "van Diermen D et al. Monoamine oxidase inhibition by Rhodiola rosea L. roots. J Ethnopharmacol. 2009;122(2):397-401.", "pmid": "19168123", "doi": "10.1016/j.jep.2009.01.007", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19168123/", "publicSourceType": "PMID" }, { "text": "Borrelli F et al. Herb-drug interactions with St John's wort (Hypericum perforatum): an update on clinical observations. AAPS J. 2009;11(4):710-27.", "pmid": "19859815", "doi": "10.1208/s12248-009-9146-8", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19859815/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Potentially unpredictable CNS and serotonergic effects.", "clinicalSignificance": "Evidence is precautionary rather than definitive, but risk rises when other serotonergic drugs are present.", "managementStrategy": "Use one CNS-active herb at a time unless supervised; avoid both with prescription antidepressants unless the prescriber is aware.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Berberine HCl", "supplementBName": "Cyclosporine/Tacrolimus", "interactionType": "contraindicated", "severity": "dangerous", "description": "Berberine inhibits CYP3A4 and P-glycoprotein, increasing cyclosporine AUC by 34.5% and prolonging half-life by 2.7 hours in renal transplant recipients.", "recommendation": "Do NOT combine without transplant specialist supervision. May require immunosuppressant dose reduction.", "minimumTimeSeparation": null, "mechanism": "Berberine inhibits intestinal P-glycoprotein efflux and hepatic CYP3A4 metabolism of cyclosporine/tacrolimus.", "evidenceLevel": "strong", "sources": [ { "text": "Berberine cyclosporine AUC 34.5% increase in transplant patients", "pmid": "16133554", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16133554/", "publicSourceType": "PMID" }, { "text": "Berberine drug interaction profile comprehensive review", "pmid": "21870106", "doi": "10.1007/s00228-011-1108-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21870106/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Berberine inhibits CYP3A4 and P-glycoprotein, increasing cyclosporine AUC by 34.5% and prolonging half-life by 2.7 hours in renal transplant recipients.", "clinicalSignificance": "Do NOT combine without transplant specialist supervision.", "managementStrategy": "Do NOT combine without transplant specialist supervision. May require immunosuppressant dose reduction.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Berberine HCl", "supplementBName": "Digoxin", "interactionType": "caution", "severity": "serious", "description": "Berberine inhibits P-glycoprotein, increasing digoxin bioavailability. Digoxin has a narrow therapeutic index.", "recommendation": "Avoid combining without medical supervision and digoxin level monitoring. Risk of digoxin toxicity.", "minimumTimeSeparation": null, "mechanism": "P-glycoprotein inhibition reduces intestinal efflux of digoxin, increasing absorption.", "evidenceLevel": "moderate", "sources": [ { "text": "Berberine drug interaction profile", "pmid": "21870106", "doi": "10.1007/s00228-011-1108-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21870106/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Berberine inhibits P-glycoprotein, increasing digoxin bioavailability.", "clinicalSignificance": "Digoxin has a narrow therapeutic index.", "managementStrategy": "Avoid combining without medical supervision and digoxin level monitoring. Risk of digoxin toxicity.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "SAMe", "supplementBName": "SSRIs/SNRIs", "interactionType": "contraindicated", "severity": "dangerous", "description": "SAMe increases serotonin synthesis. Combined with SSRIs: serotonin syndrome and/or manic switch risk. 9/11 bipolar patients developed mania on SAMe.", "recommendation": "Do NOT combine without close psychiatric supervision. Risk of mania especially high in patients with bipolar disorder.", "minimumTimeSeparation": null, "mechanism": "SAMe donates methyl groups in serotonin synthesis. SSRIs block reuptake. Combined effect risks serotonergic excess.", "evidenceLevel": "moderate", "sources": [ { "text": "SAMe-induced mania case report", "pmid": "29950497", "doi": "10.1136/bcr-2018-224338", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29950497/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "SAMe increases serotonin synthesis.", "clinicalSignificance": "Combined with SSRIs: serotonin syndrome and/or manic switch risk.", "managementStrategy": "Do NOT combine without close psychiatric supervision. Risk of mania especially high in patients with bipolar disorder.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "DIM", "supplementBName": "Tamoxifen", "interactionType": "conflict", "severity": "serious", "description": "DIM decreases endoxifen (tamoxifen's active metabolite) levels through CYP enzyme induction, potentially reducing tamoxifen's cancer-preventive benefit.", "recommendation": "Do NOT combine without oncologist approval. DIM may reduce tamoxifen effectiveness.", "minimumTimeSeparation": null, "mechanism": "DIM induces CYP1A2 (113-fold) altering tamoxifen metabolism and reducing endoxifen.", "evidenceLevel": "moderate", "sources": [ { "text": "DIM + tamoxifen RCT, reduced endoxifen", "pmid": "28560655", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28560655/", "publicSourceType": "PMID" }, { "text": "DIM induces CYP3A4 via PXR", "pmid": "25542144", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25542144/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "DIM decreases endoxifen (tamoxifen's active metabolite) levels through CYP enzyme induction, potentially reducing tamoxifen's cancer-preventive benefit.", "clinicalSignificance": "Do NOT combine without oncologist approval.", "managementStrategy": "Do NOT combine without oncologist approval. DIM may reduce tamoxifen effectiveness.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Nattokinase", "supplementBName": "Aspirin", "interactionType": "caution", "severity": "serious", "description": "Documented cerebellar hemorrhage from nattokinase + aspirin after only 7 days. Both inhibit platelet aggregation via thromboxane blockade.", "recommendation": "Do NOT combine without medical supervision. Higher risk in patients with cerebral microbleeds.", "minimumTimeSeparation": null, "mechanism": "Both block thromboxane-mediated platelet aggregation. Additive antithrombotic effect increases hemorrhage risk.", "evidenceLevel": "moderate", "sources": [ { "text": "Chang YY et al. Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. Intern Med. 2008;47(5):467-9.", "pmid": "18310985", "doi": "10.2169/internalmedicine.47.0620", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18310985/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Documented cerebellar hemorrhage from nattokinase + aspirin after only 7 days.", "clinicalSignificance": "Both inhibit platelet aggregation via thromboxane blockade.", "managementStrategy": "Do NOT combine without medical supervision. Higher risk in patients with cerebral microbleeds.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Artemisinin", "supplementBName": "CYP3A4 Substrate Medications", "interactionType": "caution", "severity": "serious", "description": "Artemisinin irreversibly inhibits CYP3A4 (~70%) and CYP2B6. CYP3A4 metabolizes ~50% of all prescription drugs.", "recommendation": "Review all prescription medications for CYP3A4 metabolism before starting artemisinin.", "minimumTimeSeparation": null, "mechanism": "Mechanism-based (irreversible) inhibition of CYP3A4 and CYP2B6 by flavonoid/coumarin components.", "evidenceLevel": "moderate", "sources": [ { "text": "Artemisia annua irreversible CYP3A4/CYP2B6 inhibition", "pmid": "36672740", "doi": "10.3390/biomedicines11010232", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36672740/", "publicSourceType": "PMID" }, { "text": "Obonyo CO, Were VO, Wamae P, Muok EMO. Efficacy and safety of praziquantel plus artemisinin-based combinations versus praziquantel in the treatment of Kenyan children with Schistosoma mansoni infection: open-label, randomized, head-to-head, non-inferiority trial. Antimicrob Agents Chemother. 2025.", "pmid": "39699212", "doi": "10.1128/aac.00739-24", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39699212/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Artemisinin irreversibly inhibits CYP3A4 (~70%) and CYP2B6.", "clinicalSignificance": "CYP3A4 metabolizes ~50% of all prescription drugs.", "managementStrategy": "Review all prescription medications for CYP3A4 metabolism before starting artemisinin.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Tribulus Terrestris", "supplementBName": "Statins", "interactionType": "caution", "severity": "serious", "description": "Tribulus terrestris is a moderate CYP3A4 inhibitor. Documented rhabdomyolysis in patient on atorvastatin who started tribulus.", "recommendation": "Avoid combining with CYP3A4-metabolized statins (atorvastatin, simvastatin, lovastatin).", "minimumTimeSeparation": null, "mechanism": "CYP3A4 inhibition increases statin blood levels, raising risk of myopathy and rhabdomyolysis.", "evidenceLevel": "emerging", "sources": [ { "text": "Tribulus rhabdomyolysis with statin", "pmid": "39012853", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39012853/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Tribulus terrestris is a moderate CYP3A4 inhibitor.", "clinicalSignificance": "Documented rhabdomyolysis in patient on atorvastatin who started tribulus.", "managementStrategy": "Avoid combining with CYP3A4-metabolized statins (atorvastatin, simvastatin, lovastatin).", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Cat's Claw", "supplementBName": "HIV Protease Inhibitors", "interactionType": "caution", "severity": "serious", "description": "Cat's claw inhibits CYP3A4 more potently than ketoconazole in vitro. Documented interactions with atazanavir, ritonavir, saquinavir.", "recommendation": "Avoid concurrent use.", "minimumTimeSeparation": null, "mechanism": "Potent CYP3A4 inhibition plus PXR activation creates complex drug metabolism effects.", "evidenceLevel": "emerging", "sources": [ { "text": "Cat's claw CYP3A4 inhibition", "pmid": "10969720", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10969720/", "publicSourceType": "PMID" }, { "text": "Cat's claw protease inhibitor interaction", "pmid": "18712519", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18712519/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Cat's claw inhibits CYP3A4 more potently than ketoconazole in vitro.", "clinicalSignificance": "Documented interactions with atazanavir, ritonavir, saquinavir.", "managementStrategy": "Avoid concurrent use.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Chlorella", "supplementBName": "Warfarin", "interactionType": "conflict", "severity": "serious", "description": "Chlorella is high in vitamin K, which antagonizes warfarin's anticoagulant effect. Case report: thrombotest values exceeded therapeutic limit.", "recommendation": "Avoid while on warfarin, or maintain very consistent intake with INR monitoring.", "minimumTimeSeparation": null, "mechanism": "Vitamin K content opposes warfarin's inhibition of vitamin K-dependent clotting factors.", "evidenceLevel": "moderate", "sources": [ { "text": "Chlorella warfarin interaction case report", "pmid": "8777808", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8777808/", "publicSourceType": "PMID" }, { "text": "Sanayei M, Izadi A, Hajizadeh-Sharafabad F et al.. Chlorella vulgaris in combination with high intensity interval training in overweight and obese women: a randomized double-blind clinical trial. Journal of Diabetes and Metabolic Disorders. 2021.", "pmid": "34178863", "doi": "10.1007/s40200-021-00816-0", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34178863/", "publicSourceType": "PMID" }, { "text": "Wang M, Zeraatkar D, Obeda M, Lee M et al.. Drug-drug interactions with warfarin: A systematic review and meta-analysis. British Journal of Clinical Pharmacology. 2021.", "pmid": "33769581", "doi": "10.1111/bcp.14833", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33769581/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Chlorella is high in vitamin K, which antagonizes warfarin's anticoagulant effect.", "clinicalSignificance": "Case report: thrombotest values exceeded therapeutic limit.", "managementStrategy": "Avoid while on warfarin, or maintain very consistent intake with INR monitoring.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Methylfolate", "supplementBName": "Methotrexate (Cancer)", "interactionType": "contraindicated", "severity": "serious", "description": "Folate can interfere with methotrexate's anticancer mechanism. Note: folate supplementation IS beneficial with low-dose MTX for rheumatoid arthritis.", "recommendation": "Cancer patients on MTX should NOT take folate without oncologist approval.", "minimumTimeSeparation": null, "mechanism": "Folate bypasses MTX's dihydrofolate reductase blockade, reducing anticancer efficacy.", "evidenceLevel": "strong", "sources": [ { "text": "Folate supplementation and methotrexate in RA", "pmid": "14963199", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14963199/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Folate can interfere with methotrexate's anticancer mechanism.", "clinicalSignificance": "Note: folate supplementation IS beneficial with low-dose MTX for rheumatoid arthritis.", "managementStrategy": "Cancer patients on MTX should NOT take folate without oncologist approval.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Olive Leaf Extract", "supplementBName": "Antihypertensives", "interactionType": "caution", "severity": "moderate", "description": "Olive leaf extract has Captopril-comparable blood pressure lowering effects (500mg BID). Oleuropein is a CYP3A4 mechanism-based inhibitor.", "recommendation": "Monitor blood pressure closely. May need medication dose adjustment.", "minimumTimeSeparation": null, "mechanism": "Additive BP reduction plus CYP3A4 mechanism-based inhibition may increase antihypertensive drug exposure.", "evidenceLevel": "moderate", "sources": [ { "text": "Olive leaf extract comparable to Captopril", "pmid": "21036583", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21036583/", "publicSourceType": "PMID" }, { "text": "Oleuropein CYP3A4 inhibition", "pmid": "11527571", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11527571/", "publicSourceType": "PMID" }, { "text": "Haidari F, Mohammad-Shahi M, Jalali MT, Ahmadi-Angali K, Shayesteh F. Phenolic-rich extract of olive leaf with a hypocaloric diet alleviates oxidative stress in obese females: a randomized double-blind placebo controlled trial. Nutr Metab Cardiovasc Dis. 2025.", "pmid": "40685267", "doi": "10.1016/j.numecd.2025.104097", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40685267/", "publicSourceType": "PMID" }, { "text": "Roshani M, Delfan B, Yarahmadi S, Saki M, Birjandi M. Impact of olive leaf extract on pain management and functional improvement in elderly patients with knee osteoarthritis: A randomized controlled trial. Explore (NY). 2025.", "pmid": "39955806", "doi": "10.1016/j.explore.2025.103136", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39955806/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Olive leaf extract has Captopril-comparable blood pressure lowering effects (500mg BID).", "clinicalSignificance": "Oleuropein is a CYP3A4 mechanism-based inhibitor.", "managementStrategy": "Monitor blood pressure closely. May need medication dose adjustment.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Glucosamine", "supplementBName": "Warfarin", "interactionType": "caution", "severity": "moderate", "description": "21 spontaneous reports of increased INR with glucosamine use in WHO database.", "recommendation": "Monitor INR more frequently when starting or stopping glucosamine in warfarin patients.", "minimumTimeSeparation": null, "mechanism": "Unknown, not via CYP enzyme inhibition.", "evidenceLevel": "emerging", "sources": [ { "text": "Glucosamine-warfarin interaction reports", "pmid": "18363538", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18363538/", "publicSourceType": "PMID" }, { "text": "Warfarin + glucosamine-chondroitin", "pmid": "15237575", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15237575/", "publicSourceType": "PMID" }, { "text": "Zhu X, Sang L et al.. Combined glucosamine and chondroitin for osteoarthritis: A systematic review and meta-analysis.. Rheumatology. 2024.", "pmid": "40300556", "doi": "10.1093/rheumatology/keae127", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40300556/", "publicSourceType": "PMID" }, { "text": "Wang M, Zeraatkar D, Obeda M, Lee M et al.. Drug-drug interactions with warfarin: A systematic review and meta-analysis. British Journal of Clinical Pharmacology. 2021.", "pmid": "33769581", "doi": "10.1111/bcp.14833", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33769581/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "21 spontaneous reports of increased INR with glucosamine use in WHO database.", "clinicalSignificance": "Monitor INR more frequently when starting or stopping glucosamine in warfarin patients.", "managementStrategy": "Monitor INR more frequently when starting or stopping glucosamine in warfarin patients.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Psyllium Husk", "supplementBName": "Lithium/Carbamazepine", "interactionType": "conflict", "severity": "moderate", "description": "Psyllium decreases oral bioavailability of carbamazepine and may reduce lithium levels via adsorption and delayed gastric emptying.", "recommendation": "Take medications 2+ hours before or after psyllium.", "minimumTimeSeparation": 120, "mechanism": "Psyllium's viscous gel matrix adsorbs drugs and delays gastric emptying.", "evidenceLevel": "moderate", "sources": [ { "text": "Psyllium-lithium interaction", "pmid": "1968148", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1968148/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Psyllium decreases oral bioavailability of carbamazepine and may reduce lithium levels via adsorption and delayed gastric emptying.", "clinicalSignificance": "Take medications 2+ hours before or after psyllium.", "managementStrategy": "Take medications 2+ hours before or after psyllium.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Schisandra", "supplementBName": "Tacrolimus/Cyclosporine", "interactionType": "contraindicated", "severity": "dangerous", "description": "Schisandra increased tacrolimus AUC by 164% and Cmax by 227%. Potentially fatal in transplant patients.", "recommendation": "Do NOT combine. Schisandra dramatically increases immunosuppressant levels.", "minimumTimeSeparation": null, "mechanism": "Schisandra lignans potently inhibit CYP3A4 and P-glycoprotein short-term, dramatically increasing tacrolimus/cyclosporine exposure.", "evidenceLevel": "strong", "sources": [ { "text": "Schisandra tacrolimus AUC increase 164%", "pmid": "19821648", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19821648/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Schisandra increased tacrolimus AUC by 164% and Cmax by 227%.", "clinicalSignificance": "Potentially fatal in transplant patients.", "managementStrategy": "Do NOT combine. Schisandra dramatically increases immunosuppressant levels.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Berberine HCl", "supplementBName": "Warfarin", "interactionType": "caution", "severity": "serious", "description": "Berberine displaces warfarin from plasma protein binding sites and inhibits CYP2C9 (warfarin metabolism enzyme). May alter INR unpredictably.", "recommendation": "If combining, increase INR monitoring frequency.", "minimumTimeSeparation": null, "mechanism": "Dual mechanism: albumin binding displacement + CYP2C9 inhibition.", "evidenceLevel": "moderate", "sources": [ { "text": "Berberine drug interaction profile", "pmid": "21870106", "doi": "10.1007/s00228-011-1108-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21870106/", "publicSourceType": "PMID" }, { "text": "Wang M, Zeraatkar D, Obeda M, Lee M et al.. Drug-drug interactions with warfarin: A systematic review and meta-analysis. British Journal of Clinical Pharmacology. 2021.", "pmid": "33769581", "doi": "10.1111/bcp.14833", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33769581/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Berberine displaces warfarin from plasma protein binding sites and inhibits CYP2C9 (warfarin metabolism enzyme).", "clinicalSignificance": "May alter INR unpredictably.", "managementStrategy": "If combining, increase INR monitoring frequency.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Berberine", "supplementBName": "Probiotics", "interactionType": "conflict", "severity": "moderate", "description": "Berberine has significant antimicrobial properties and can reduce beneficial gut bacteria populations. Taking berberine with probiotics may reduce probiotic viability. However, some research suggests the gut microbiome changes from berberine may actually contribute to its metabolic benefits.", "recommendation": "Separate berberine and probiotics by at least 2-3 hours. Take probiotics at a different meal than berberine. Consider spore-based probiotics which may be more resistant.", "minimumTimeSeparation": 180, "mechanism": "Berberine accumulates in the gut lumen where it exerts direct antimicrobial effects against both pathogenic and commensal bacteria by disrupting cell membranes and inhibiting FtsZ protein assembly.", "evidenceLevel": "moderate", "sources": [ { "text": "Zhang X et al. Structural changes of gut microbiota during berberine-mediated prevention of obesity and insulin resistance. Sci Rep. 2015;5:14405.", "pmid": "26396057", "doi": "10.1038/srep14405", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26396057/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Berberine has significant antimicrobial properties and can reduce beneficial gut bacteria populations.", "clinicalSignificance": "Taking berberine with probiotics may reduce probiotic viability.", "managementStrategy": "Separate berberine and probiotics by at least 2-3 hours. Take probiotics at a different meal than berberine. Consider spore-based probiotics which may be more resistant.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "NAC", "supplementBName": "Activated Charcoal", "interactionType": "conflict", "severity": "serious", "description": "Activated charcoal adsorbs NAC in the GI tract, rendering it ineffective. This is clinically important because NAC is the antidote for acetaminophen toxicity and charcoal can block its absorption.", "recommendation": "Separate activated charcoal and NAC by at least 2 hours. If using NAC for clinical purposes, do not take activated charcoal at the same time.", "minimumTimeSeparation": 120, "mechanism": "Activated charcoal's massive surface area (1000-3500 m²/g) non-specifically adsorbs NAC through Van der Waals forces, preventing intestinal absorption. Can reduce NAC bioavailability by 50-70%.", "evidenceLevel": "strong", "sources": [ { "text": "Ekins BR et al. The effect of activated charcoal on N-acetylcysteine absorption in normal subjects. Am J Emerg Med. 1987;5(6):483-7.", "pmid": "3663288", "doi": "10.1016/0735-6757(87)90166-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3663288/", "publicSourceType": "PMID" }, { "text": "Tenenbein PK et al. Interaction between N-acetylcysteine and activated charcoal: implications for the treatment of acetaminophen poisoning. Pharmacotherapy. 2001;21(11):1331-6.", "pmid": "11714205", "doi": "10.1592/phco.21.17.1331.34427", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11714205/", "publicSourceType": "PMID" }, { "text": "Chyka PA et al. Position paper: Single-dose activated charcoal. Clin Toxicol (Phila). 2005;43(2):61-87.", "pmid": "15822758", "doi": "10.1081/clt-200051867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15822758/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Activated charcoal adsorbs NAC in the GI tract, rendering it ineffective.", "clinicalSignificance": "This is clinically important because NAC is the antidote for acetaminophen toxicity and charcoal can block its absorption.", "managementStrategy": "Separate activated charcoal and NAC by at least 2 hours. If using NAC for clinical purposes, do not take activated charcoal at the same time.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Ashwagandha", "supplementBName": "Iodine", "interactionType": "caution", "severity": "moderate", "description": "Ashwagandha may stimulate thyroid hormone production (T4 and T3) via its effects on the HPA axis and direct thyroid stimulation. Combined with iodine supplementation, there is a risk of thyroid overstimulation in susceptible individuals.", "recommendation": "If you have thyroid disease or are taking thyroid medication, consult your doctor before combining ashwagandha and iodine. Monitor thyroid function tests.", "minimumTimeSeparation": null, "mechanism": "Ashwagandha's withanolides may stimulate thyroid peroxidase (TPO) activity and increase T4 to T3 conversion via type II 5'-deiodinase. Iodine provides additional substrate for thyroid hormone synthesis.", "evidenceLevel": "emerging", "sources": [ { "text": "Sharma AK et al. Efficacy and safety of Ashwagandha root extract in subclinical hypothyroid patients. J Altern Complement Med. 2018;24(3):243-248.", "pmid": "28829155", "doi": "10.1089/acm.2017.0183", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28829155/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Ashwagandha may stimulate thyroid hormone production (T4 and T3) via its effects on the HPA axis and direct thyroid stimulation.", "clinicalSignificance": "Combined with iodine supplementation, there is a risk of thyroid overstimulation in susceptible individuals.", "managementStrategy": "If you have thyroid disease or are taking thyroid medication, consult your doctor before combining ashwagandha and iodine. Monitor thyroid function tests.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Turmeric/Curcumin", "supplementBName": "Berberine", "interactionType": "synergy", "severity": "info", "description": "Curcumin and berberine share overlapping anti-inflammatory pathways (NF-kB inhibition) and both have glucose-lowering effects. The combination may provide synergistic metabolic benefits.", "recommendation": "Both can be taken together for complementary anti-inflammatory and metabolic effects. Monitor blood glucose if diabetic as the combined glucose-lowering may be significant.", "minimumTimeSeparation": null, "mechanism": "Curcumin inhibits NF-kB and COX-2. Berberine activates AMPK and inhibits NF-kB. Both reduce inflammatory cytokines (TNF-α, IL-6) through complementary mechanisms.", "evidenceLevel": "emerging", "sources": [ { "text": "Ghorbani Z et al. Anti-hyperglycemic and insulin sensitizer effects of turmeric and its principle constituent curcumin. Int J Endocrinol Metab. 2014;12(4):e18081.", "pmid": "25745485", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25745485/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Curcumin and berberine share overlapping anti-inflammatory pathways (NF-kB inhibition) and both have glucose-lowering effects.", "clinicalSignificance": "The combination may provide synergistic metabolic benefits.", "managementStrategy": "Both can be taken together for complementary anti-inflammatory and metabolic effects. Monitor blood glucose if diabetic as the combined glucose-lowering may be significant.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Creatine", "supplementBName": "Beta-Alanine", "interactionType": "synergy", "severity": "info", "description": "Creatine enhances ATP regeneration while beta-alanine buffers intracellular acid (via carnosine) during high-intensity exercise. The combination addresses two distinct performance-limiting factors.", "recommendation": "A well-researched ergogenic combination. Creatine 3-5g/day + Beta-alanine 3.2-6.4g/day (split doses to reduce paresthesia).", "minimumTimeSeparation": null, "mechanism": "Creatine replenishes phosphocreatine stores for rapid ATP regeneration during high-intensity efforts. Beta-alanine increases intramuscular carnosine, which buffers H+ ions during anaerobic glycolysis. Both support different aspects of high-intensity exercise.", "evidenceLevel": "strong", "sources": [ { "text": "Hoffman J et al. Effect of creatine and beta-alanine supplementation on performance and endocrine responses. Int J Sport Nutr Exerc Metab. 2006;16(4):430-446.", "pmid": "17136944", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17136944/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Creatine enhances ATP regeneration while beta-alanine buffers intracellular acid (via carnosine) during high-intensity exercise.", "clinicalSignificance": "The combination addresses two distinct performance-limiting factors.", "managementStrategy": "A well-researched ergogenic combination. Creatine 3-5g/day + Beta-alanine 3.2-6.4g/day (split doses to reduce paresthesia).", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Zinc", "supplementBName": "Quercetin", "interactionType": "synergy", "severity": "info", "description": "Quercetin has shown zinc-ionophore activity in cell models, but clinical immune benefit from combining quercetin with zinc is not established.", "recommendation": "Do not rely on quercetin plus zinc as antiviral treatment. Use only as general nutrition support and keep zinc within standard supplemental limits unless clinician-directed.", "minimumTimeSeparation": null, "mechanism": "Cell studies suggest quercetin can transport zinc across membranes. Translation to meaningful antiviral or immune outcomes in humans has not been established.", "evidenceLevel": "emerging", "sources": [ { "text": "Dabbagh-Bazarbachi H et al. Zinc ionophore activity of quercetin and epigallocatechin-gallate. J Agric Food Chem. 2014;62(32):8085-8093.", "pmid": "25050823", "doi": "10.1021/jf5014633", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25050823/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Zinc-ionophore activity is supported mainly by cell data.", "clinicalSignificance": "Human antiviral or immune outcome benefits from the combination are not established.", "managementStrategy": "Do not use as treatment language; keep zinc dosing within standard supplemental limits unless clinician-directed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Iron", "supplementBName": "Green Tea Extract", "interactionType": "conflict", "severity": "moderate", "description": "Green tea catechins, particularly EGCG, bind non-heme iron in the gut, reducing absorption by up to 60-70%. This is one of the most potent dietary inhibitors of iron absorption.", "recommendation": "Separate iron supplements and green tea/green tea extract by at least 2 hours. Take iron in the morning on an empty stomach, green tea later in the day.", "minimumTimeSeparation": 120, "mechanism": "EGCG and other catechins chelate ferric iron (Fe3+) in the intestinal lumen, forming insoluble iron-polyphenol complexes that cannot be absorbed by DMT1.", "evidenceLevel": "strong", "sources": [ { "text": "Hurrell RF et al. Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages. Br J Nutr. 1999;81(4):289-295.", "pmid": "10999016", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10999016/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Green tea catechins, particularly EGCG, bind non-heme iron in the gut, reducing absorption by up to 60-70%.", "clinicalSignificance": "This is one of the most potent dietary inhibitors of iron absorption.", "managementStrategy": "Separate iron supplements and green tea/green tea extract by at least 2 hours. Take iron in the morning on an empty stomach, green tea later in the day.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin C", "supplementBName": "Vitamin B12", "interactionType": "timingSensitive", "severity": "moderate", "description": "High-dose vitamin C (>500mg) may destroy vitamin B12 when taken simultaneously. The acidic environment created by high-dose ascorbic acid can convert cyanocobalamin to inactive analogues.", "recommendation": "Separate high-dose vitamin C and B12 supplements by at least 2 hours. Low-dose vitamin C (<200mg) is fine to take with B12.", "minimumTimeSeparation": 120, "mechanism": "Ascorbic acid at high concentrations can reduce the cobalt center of cyanocobalamin, converting it to inactive analogues. Methylcobalamin may be less susceptible than cyanocobalamin.", "evidenceLevel": "moderate", "sources": [ { "text": "Herbert V, Jacob E. Destruction of vitamin B12 by ascorbic acid. JAMA. 1974;230(2):241-242.", "pmid": "4479032", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/4479032/", "publicSourceType": "PMID" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials.. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "High-dose vitamin C (>500mg) may destroy vitamin B12 when taken simultaneously.", "clinicalSignificance": "The acidic environment created by high-dose ascorbic acid can convert cyanocobalamin to inactive analogues.", "managementStrategy": "Separate high-dose vitamin C and B12 supplements by at least 2 hours. Low-dose vitamin C (<200mg) is fine to take with B12.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "5-HTP", "supplementBName": "SSRIs/SNRIs/MAOIs", "interactionType": "contraindicated", "severity": "dangerous", "description": "5-HTP increases serotonin synthesis and can combine dangerously with serotonergic antidepressants or MAO inhibitors, increasing serotonin syndrome risk.", "recommendation": "Do NOT combine 5-HTP with SSRIs, SNRIs, MAOIs, or other serotonergic medications unless specifically directed by the prescriber managing the medication.", "minimumTimeSeparation": null, "mechanism": "5-HTP bypasses the rate-limiting tryptophan hydroxylase step and increases serotonin production. SSRIs/SNRIs reduce serotonin reuptake and MAOIs reduce monoamine breakdown, creating additive serotonergic excess.", "evidenceLevel": "strong", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Additive serotonergic activity can cause serotonin syndrome.", "clinicalSignificance": "Serotonin syndrome can be life-threatening and may include agitation, hyperthermia, tremor, rigidity, tachycardia, hypertension, seizures, or coma.", "managementStrategy": "Avoid combination and consult the prescriber before starting or stopping serotonergic supplements.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "L-Tryptophan", "supplementBName": "SSRIs/SNRIs/MAOIs", "interactionType": "contraindicated", "severity": "dangerous", "description": "L-Tryptophan is a serotonin precursor and can combine dangerously with serotonergic antidepressants or MAO inhibitors, increasing serotonin syndrome risk.", "recommendation": "Do NOT combine L-tryptophan with SSRIs, SNRIs, MAOIs, or other serotonergic medications unless specifically directed by the prescriber managing the medication.", "minimumTimeSeparation": null, "mechanism": "L-Tryptophan is converted to 5-HTP and then serotonin. SSRIs/SNRIs reduce serotonin reuptake and MAOIs reduce monoamine breakdown, creating additive serotonergic excess.", "evidenceLevel": "strong", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Additive serotonergic activity can cause serotonin syndrome.", "clinicalSignificance": "Serotonin syndrome can be life-threatening and may include agitation, hyperthermia, tremor, rigidity, tachycardia, hypertension, seizures, or coma.", "managementStrategy": "Avoid combination and consult the prescriber before starting or stopping serotonergic supplements.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Ginkgo Biloba", "supplementBName": "Fish Oil", "interactionType": "caution", "severity": "moderate", "description": "Both have mild antiplatelet activity; combined chronic use can additively increase bleeding tendency, especially with concurrent NSAIDs or anticoagulants.", "recommendation": "Use together cautiously. Stop both 7 to 14 days before scheduled surgery. Monitor for easy bruising, nosebleeds, or prolonged bleeding from cuts.", "minimumTimeSeparation": null, "mechanism": "Ginkgo inhibits platelet activating factor (PAF); fish oil EPA reduces thromboxane A2 production. Additive antiplatelet effect.", "evidenceLevel": "emerging", "sources": [ { "text": "Bone KM. Potential interaction of Ginkgo biloba leaf with antiplatelet or anticoagulant drugs: what is the evidence? Mol Nutr Food Res. 2008;52(7):764-71.", "pmid": "18214851", "doi": "10.1002/mnfr.200700098", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18214851/", "publicSourceType": "PMID" }, { "text": "Javaid M et al. Bleeding Risk in Patients Receiving Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Am Heart Assoc. 2024;13(10):e032390.", "pmid": "38742535", "doi": "10.1161/JAHA.123.032390", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38742535/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both have mild antiplatelet activity; combined chronic use can additively increase bleeding tendency, especially with concurrent NSAIDs or anticoagulants.", "clinicalSignificance": "Both have mild antiplatelet activity; combined chronic use can additively increase bleeding tendency, especially with concurrent NSAIDs or anticoagulants.", "managementStrategy": "Use together cautiously. Stop both 7 to 14 days before scheduled surgery. Monitor for easy bruising, nosebleeds, or prolonged bleeding from cuts.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Ginkgo Biloba", "supplementBName": "Vitamin E", "interactionType": "caution", "severity": "moderate", "description": "Both have antiplatelet activity at higher doses; combined use raises bleeding risk in surgical and anticoagulated patients.", "recommendation": "Avoid high-dose vitamin E (above 400 IU) alongside ginkgo, particularly before surgery or with warfarin or DOACs.", "minimumTimeSeparation": null, "mechanism": "Vitamin E above 400 IU/day modestly impairs platelet aggregation; ginkgo inhibits PAF.", "evidenceLevel": "emerging", "sources": [ { "text": "Bone KM. Potential interaction of Ginkgo biloba leaf with antiplatelet or anticoagulant drugs: what is the evidence? Mol Nutr Food Res. 2008;52(7):764-71.", "pmid": "18214851", "doi": "10.1002/mnfr.200700098", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18214851/", "publicSourceType": "PMID" }, { "text": "Booth SL et al. Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. Am J Clin Nutr. 2004;80(1):143-8.", "pmid": "15213041", "doi": "10.1093/ajcn/80.1.143", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15213041/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both have antiplatelet activity at higher doses; combined use raises bleeding risk in surgical and anticoagulated patients.", "clinicalSignificance": "Both have antiplatelet activity at higher doses; combined use raises bleeding risk in surgical and anticoagulated patients.", "managementStrategy": "Avoid high-dose vitamin E (above 400 IU) alongside ginkgo, particularly before surgery or with warfarin or DOACs.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Ginkgo Biloba", "supplementBName": "Garlic Extract", "interactionType": "caution", "severity": "moderate", "description": "Both are common in geriatric and cardiovascular use; combined antiplatelet effects are additive.", "recommendation": "Use together only with surgical and bleeding-risk awareness. Discontinue both 1 to 2 weeks before scheduled procedures.", "minimumTimeSeparation": null, "mechanism": "Ginkgo inhibits PAF; allicin and ajoene in garlic impair platelet aggregation.", "evidenceLevel": "moderate", "sources": [ { "text": "Bone KM. Potential interaction of Ginkgo biloba leaf with antiplatelet or anticoagulant drugs: what is the evidence? Mol Nutr Food Res. 2008;52(7):764-71.", "pmid": "18214851", "doi": "10.1002/mnfr.200700098", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18214851/", "publicSourceType": "PMID" }, { "text": "Rahman K et al. Dietary supplementation with aged garlic extract inhibits ADP-induced platelet aggregation in humans. J Nutr. 2000;130(11):2662-5.", "pmid": "11053504", "doi": "10.1093/jn/130.11.2662", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11053504/", "publicSourceType": "PMID" }, { "text": "Allison GL et al. Aged garlic extract and its constituents inhibit platelet aggregation through multiple mechanisms. J Nutr. 2006;136(3 Suppl):782S-788S.", "pmid": "16484563", "doi": "10.1093/jn/136.3.782S", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16484563/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both are common in geriatric and cardiovascular use; combined antiplatelet effects are additive.", "clinicalSignificance": "Both are common in geriatric and cardiovascular use; combined antiplatelet effects are additive.", "managementStrategy": "Use together only with surgical and bleeding-risk awareness. Discontinue both 1 to 2 weeks before scheduled procedures.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Ginkgo Biloba", "supplementBName": "Ginger Extract", "interactionType": "caution", "severity": "info", "description": "Both have mild antiplatelet activity; clinical bleeding events from this combination alone are rare but theoretical.", "recommendation": "Routine use is generally acceptable. Stop both before scheduled surgery and counsel anticoagulated patients.", "minimumTimeSeparation": null, "mechanism": "Ginger gingerols modestly inhibit thromboxane synthesis; ginkgo inhibits PAF. Combined effect is theoretical for most users.", "evidenceLevel": "emerging", "sources": [ { "text": "Tognolini M et al. Comparative screening of plant essential oils: phenylpropanoid moiety as basic core for antiplatelet activity. Life Sci. 2006;78(13):1419-32.", "pmid": "16274702", "doi": "10.1016/j.lfs.2005.07.020", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16274702/", "publicSourceType": "PMID" }, { "text": "Marx W et al. The Effect of Ginger (Zingiber officinale) on Platelet Aggregation: A Systematic Literature Review. PLoS One. 2015;10(10):e0141119.", "pmid": "26488162", "doi": "10.1371/journal.pone.0141119", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26488162/", "publicSourceType": "PMID" }, { "text": "Bone KM. Potential interaction of Ginkgo biloba leaf with antiplatelet or anticoagulant drugs: what is the evidence? Mol Nutr Food Res. 2008;52(7):764-71.", "pmid": "18214851", "doi": "10.1002/mnfr.200700098", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18214851/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both have mild antiplatelet activity; clinical bleeding events from this combination alone are rare but theoretical.", "clinicalSignificance": "Both have mild antiplatelet activity; clinical bleeding events from this combination alone are rare but theoretical.", "managementStrategy": "Routine use is generally acceptable. Stop both before scheduled surgery and counsel anticoagulated patients.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Ginkgo Biloba", "supplementBName": "Vitamin K1", "interactionType": "caution", "severity": "moderate", "description": "Ginkgo's antiplatelet activity can mildly counter vitamin K1's pro-coagulant role; relevant for warfarin patients managing INR through K1 intake.", "recommendation": "For warfarin patients, keep both vitamin K1 intake and ginkgo dose stable. Monitor INR closely if either changes.", "minimumTimeSeparation": null, "mechanism": "Vitamin K1 enables clotting factor activation; ginkgo inhibits platelet aggregation. Net effect on PT/INR is small but adds variability.", "evidenceLevel": "moderate", "sources": [ { "text": "Engelsen J et al. Effect of coenzyme Q10 and Ginkgo biloba on warfarin dosage in stable, long-term warfarin treated outpatients. A randomised, double blind, placebo-crossover trial. Thromb Haemost. 2002.", "pmid": "12083489", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12083489/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Ginkgo's antiplatelet activity can mildly counter vitamin K1's pro-coagulant role; relevant for warfarin patients managing INR through K1 intake.", "clinicalSignificance": "Ginkgo's antiplatelet activity can mildly counter vitamin K1's pro-coagulant role; relevant for warfarin patients managing INR through K1 intake.", "managementStrategy": "For warfarin patients, keep both vitamin K1 intake and ginkgo dose stable. Monitor INR closely if either changes.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Garlic Extract", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "Both lower LDL, blood pressure, and have mild antiplatelet effects; combined use is broadly cardio-supportive.", "recommendation": "Take together for additive cardiovascular benefit. Monitor for bleeding if combined with anticoagulants or NSAIDs.", "minimumTimeSeparation": null, "mechanism": "Garlic raises HDL and lowers LDL via HMG-CoA reductase modulation; EPA/DHA lower triglycerides and reduce inflammatory eicosanoids.", "evidenceLevel": "emerging", "sources": [ { "text": "Rahman K et al. Dietary supplementation with aged garlic extract inhibits ADP-induced platelet aggregation in humans. J Nutr. 2000;130(11):2662-5.", "pmid": "11053504", "doi": "10.1093/jn/130.11.2662", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11053504/", "publicSourceType": "PMID" }, { "text": "Allison GL et al. Aged garlic extract and its constituents inhibit platelet aggregation through multiple mechanisms. J Nutr. 2006;136(3 Suppl):782S-788S.", "pmid": "16484563", "doi": "10.1093/jn/136.3.782S", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16484563/", "publicSourceType": "PMID" }, { "text": "Javaid M et al. Bleeding Risk in Patients Receiving Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Am Heart Assoc. 2024;13(10):e032390.", "pmid": "38742535", "doi": "10.1161/JAHA.123.032390", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38742535/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both lower LDL, blood pressure, and have mild antiplatelet effects; combined use is broadly cardio-supportive.", "clinicalSignificance": "Both lower LDL, blood pressure, and have mild antiplatelet effects; combined use is broadly cardio-supportive.", "managementStrategy": "Take together for additive cardiovascular benefit. Monitor for bleeding if combined with anticoagulants or NSAIDs.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "L-Arginine", "supplementBName": "L-Lysine", "interactionType": "conflict", "severity": "info", "description": "Arginine and lysine compete for cellular uptake; high-dose arginine can reduce lysine's effect on HSV outbreak prevention.", "recommendation": "Separate by 2 hours and avoid high-dose arginine during active HSV outbreaks. Reduce dietary arginine sources (nuts, chocolate) when using lysine for HSV.", "minimumTimeSeparation": "2 hours", "mechanism": "Both amino acids share the y+ cationic amino acid transporter; the lysine/arginine ratio influences HSV viral replication.", "evidenceLevel": "moderate", "sources": [ { "text": "Griffith RS et al. A multicentered study of lysine therapy in herpes simplex infection. Dermatologica. 1978", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Arginine and lysine compete for cellular uptake; high-dose arginine can reduce lysine's effect on HSV outbreak prevention.", "clinicalSignificance": "Arginine and lysine compete for cellular uptake; high-dose arginine can reduce lysine's effect on HSV outbreak prevention.", "managementStrategy": "Separate by 2 hours and avoid high-dose arginine during active HSV outbreaks. Reduce dietary arginine sources (nuts, chocolate) when using lysine for HSV.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "L-Citrulline", "supplementBName": "L-Arginine", "interactionType": "synergy", "severity": "info", "description": "Citrulline is converted to arginine in the kidney, raising plasma arginine higher and longer than oral arginine alone. Combined use provides additive NO support.", "recommendation": "Use citrulline as the primary NO precursor; if combining with arginine, take citrulline 1 to 2 hours before arginine or together pre-workout.", "minimumTimeSeparation": null, "mechanism": "Citrulline bypasses first-pass arginase metabolism in the gut, raising sustained plasma arginine and supporting nitric oxide synthesis more effectively.", "evidenceLevel": "strong", "sources": [ { "text": "Schwedhelm E et al. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol. 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Citrulline is converted to arginine in the kidney, raising plasma arginine higher and longer than oral arginine alone.", "clinicalSignificance": "Citrulline is converted to arginine in the kidney, raising plasma arginine higher and longer than oral arginine alone.", "managementStrategy": "Use citrulline as the primary NO precursor; if combining with arginine, take citrulline 1 to 2 hours before arginine or together pre-workout.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "L-Tyrosine", "supplementBName": "L-Tryptophan", "interactionType": "conflict", "severity": "info", "description": "Tyrosine and tryptophan compete with each other (and with other large neutral amino acids) for transport across the blood-brain barrier; co-administration blunts the brain entry of each.", "recommendation": "Separate by 2 to 3 hours. Tyrosine in morning for catecholamine support; tryptophan or 5-HTP at night for serotonin and sleep.", "minimumTimeSeparation": "2 to 3 hours", "mechanism": "Both compete for the LNAA transporter at the BBB; high doses of one reduce the other's central availability.", "evidenceLevel": "moderate", "sources": [ { "text": "Fernstrom JD. Branched-chain amino acids and brain function. J Nutr. 2005", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Tyrosine and tryptophan compete with each other (and with other large neutral amino acids) for transport across the blood-brain barrier; co-administration blunts the brain entry of each.", "clinicalSignificance": "Tyrosine and tryptophan compete with each other (and with other large neutral amino acids) for transport across the blood-brain barrier; co-administration blunts the brain entry of each.", "managementStrategy": "Separate by 2 to 3 hours. Tyrosine in morning for catecholamine support; tryptophan or 5-HTP at night for serotonin and sleep.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "DHEA", "supplementBName": "Pregnenolone", "interactionType": "synergy", "severity": "moderate", "description": "Pregnenolone is upstream of DHEA in the steroid cascade; combined use can raise androgens and estrogens additively, requiring close monitoring.", "recommendation": "Test DHEA-S, free testosterone, and estradiol at baseline and after 8 to 12 weeks if combining. Lower doses than either alone may be sufficient.", "minimumTimeSeparation": null, "mechanism": "Pregnenolone converts to DHEA and progesterone; DHEA converts to androgens and estrogens. Combined use compounds downstream steroid effects.", "evidenceLevel": "moderate", "sources": [ { "text": "Arlt W. Dehydroepiandrosterone and ageing. Best Pract Res Clin Endocrinol Metab. 2004.", "pmid": "15261843", "doi": "10.1016/j.beem.2004.02.006", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15261843/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Pregnenolone is upstream of DHEA in the steroid cascade; combined use can raise androgens and estrogens additively, requiring close monitoring.", "clinicalSignificance": "Pregnenolone is upstream of DHEA in the steroid cascade; combined use can raise androgens and estrogens additively, requiring close monitoring.", "managementStrategy": "Test DHEA-S, free testosterone, and estradiol at baseline and after 8 to 12 weeks if combining. Lower doses than either alone may be sufficient.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Magnesium Glycinate", "supplementBName": "Zinc", "interactionType": "timingSensitive", "severity": "info", "description": "High-dose zinc and high-dose magnesium can compete at intestinal divalent cation transporters; effect is significant only at supplemental doses above typical RDA.", "recommendation": "Take at separate meals, ideally 2 hours apart. Magnesium evening, zinc morning or midday is a common pattern.", "minimumTimeSeparation": "2 hours", "mechanism": "Both compete for absorption via DMT1 and other divalent cation transporters at high concentrations.", "evidenceLevel": "moderate", "sources": [ { "text": "Spencer H et al. Effect of magnesium on the intestinal absorption of calcium in man. J Am Coll Nutr. 1994", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "High-dose zinc and high-dose magnesium can compete at intestinal divalent cation transporters; effect is significant only at supplemental doses above typical RDA.", "clinicalSignificance": "High-dose zinc and high-dose magnesium can compete at intestinal divalent cation transporters; effect is significant only at supplemental doses above typical RDA.", "managementStrategy": "Take at separate meals, ideally 2 hours apart. Magnesium evening, zinc morning or midday is a common pattern.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Bromelain", "supplementBName": "Nattokinase", "interactionType": "caution", "severity": "moderate", "description": "Both have fibrinolytic and antiplatelet activity; combined use additively raises bleeding risk.", "recommendation": "Use together cautiously and only with surgical/bleeding-risk awareness. Avoid before procedures.", "minimumTimeSeparation": null, "mechanism": "Bromelain reduces fibrinogen and has mild antiplatelet activity; nattokinase has direct fibrinolytic activity via plasmin pathway.", "evidenceLevel": "emerging", "sources": [ { "text": "Sumi H et al. A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese Natto; a typical and popular soybean food in the Japanese diet. Experientia. 1987;43(10):1110-1.", "pmid": "3478223", "doi": "10.1007/BF01956052", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3478223/", "publicSourceType": "PMID" }, { "text": "Kurosawa Y et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep. 2015;5:11601.", "pmid": "26109079", "doi": "10.1038/srep11601", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26109079/", "publicSourceType": "PMID" }, { "text": "Maurer HR. Bromelain: biochemistry, pharmacology and medical use. Cell Mol Life Sci. 2001;58(9):1234-45.", "pmid": "11577981", "doi": "10.1007/PL00000936", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11577981/", "publicSourceType": "PMID" }, { "text": "Pavan R et al. Properties and therapeutic application of bromelain: a review. Biotechnol Res Int. 2012;2012:976203.", "pmid": "23304525", "doi": "10.1155/2012/976203", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23304525/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both have fibrinolytic and antiplatelet activity; combined use additively raises bleeding risk.", "clinicalSignificance": "Both have fibrinolytic and antiplatelet activity; combined use additively raises bleeding risk.", "managementStrategy": "Use together cautiously and only with surgical/bleeding-risk awareness. Avoid before procedures.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Bromelain", "supplementBName": "Fish Oil", "interactionType": "caution", "severity": "info", "description": "Both have mild antiplatelet activity; combined chronic use can additively raise bleeding tendency.", "recommendation": "Use together with awareness of bleeding risk. Stop both before surgery.", "minimumTimeSeparation": null, "mechanism": "Fish oil EPA reduces thromboxane A2; bromelain reduces platelet aggregation.", "evidenceLevel": "emerging", "sources": [ { "text": "Maurer HR. Bromelain: biochemistry, pharmacology and medical use. Cell Mol Life Sci. 2001;58(9):1234-45.", "pmid": "11577981", "doi": "10.1007/PL00000936", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11577981/", "publicSourceType": "PMID" }, { "text": "Javaid M et al. Bleeding Risk in Patients Receiving Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Am Heart Assoc. 2024;13(10):e032390.", "pmid": "38742535", "doi": "10.1161/JAHA.123.032390", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38742535/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both have mild antiplatelet activity; combined chronic use can additively raise bleeding tendency.", "clinicalSignificance": "Both have mild antiplatelet activity; combined chronic use can additively raise bleeding tendency.", "managementStrategy": "Use together with awareness of bleeding risk. Stop both before surgery.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Holy Basil/Tulsi", "supplementBName": "Fish Oil", "interactionType": "caution", "severity": "info", "description": "Holy basil has mild antiplatelet activity; combined with fish oil's effect on thromboxane, bleeding risk is theoretically additive.", "recommendation": "Use together with awareness; clinical bleeding events from this combination alone are uncommon.", "minimumTimeSeparation": null, "mechanism": "Holy basil inhibits platelet aggregation in vitro; fish oil reduces thromboxane synthesis.", "evidenceLevel": "emerging", "sources": [ { "text": "Singh S et al. Evaluation of antiinflammatory potential of fixed oil of Ocimum sanctum and its possible mechanism of action. J Ethnopharmacol. 1996", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Holy basil has mild antiplatelet activity; combined with fish oil's effect on thromboxane, bleeding risk is theoretically additive.", "clinicalSignificance": "Holy basil has mild antiplatelet activity; combined with fish oil's effect on thromboxane, bleeding risk is theoretically additive.", "managementStrategy": "Use together with awareness; clinical bleeding events from this combination alone are uncommon.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Saw Palmetto", "supplementBName": "DHEA", "interactionType": "conflict", "severity": "info", "description": "Saw palmetto modestly inhibits 5-alpha reductase and aromatase; DHEA raises downstream androgens. Combined effects on prostate and hormonal milieu can be unpredictable.", "recommendation": "If combining, monitor PSA in men and androgenic side effects in women. Discuss with clinician for prostate health context.", "minimumTimeSeparation": null, "mechanism": "Saw palmetto reduces conversion of testosterone to DHT; DHEA raises substrate availability. Net effect on DHT depends on dosing.", "evidenceLevel": "emerging", "sources": [ { "text": "Marks LS et al. Effects of a saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia. J Urol. 2000", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Saw palmetto modestly inhibits 5-alpha reductase and aromatase; DHEA raises downstream androgens.", "clinicalSignificance": "Saw palmetto modestly inhibits 5-alpha reductase and aromatase; DHEA raises downstream androgens.", "managementStrategy": "If combining, monitor PSA in men and androgenic side effects in women. Discuss with clinician for prostate health context.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Tongkat Ali", "supplementBName": "Saw Palmetto", "interactionType": "conflict", "severity": "info", "description": "Tongkat ali raises testosterone; saw palmetto reduces DHT conversion. Combined effects on prostate-relevant androgens are mixed.", "recommendation": "Most men can use both, but track PSA and prostate symptoms in older men. Tongkat ali's testosterone effect is small in eugonadal users.", "minimumTimeSeparation": null, "mechanism": "Tongkat ali increases testosterone via LH-mediated mechanisms; saw palmetto lowers DHT via 5-alpha reductase inhibition.", "evidenceLevel": "emerging", "sources": [ { "text": "Tambi MI et al. Standardised water-soluble extract of Eurycoma longifolia, Tongkat ali, as testosterone booster. Andrologia. 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Tongkat ali raises testosterone; saw palmetto reduces DHT conversion.", "clinicalSignificance": "Tongkat ali raises testosterone; saw palmetto reduces DHT conversion.", "managementStrategy": "Most men can use both, but track PSA and prostate symptoms in older men. Tongkat ali's testosterone effect is small in eugonadal users.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Inositol", "supplementBName": "Berberine", "interactionType": "synergy", "severity": "info", "description": "Inositol improves insulin sensitivity in PCOS; berberine improves it via AMPK activation. Combined effect on HOMA-IR, fasting glucose, and ovulation may be additive in PCOS.", "recommendation": "Combine for PCOS and metabolic syndrome with insulin resistance. Monitor fasting glucose, A1c, and (in PCOS) AMH and ovulation.", "minimumTimeSeparation": null, "mechanism": "Inositol acts as an insulin second messenger; berberine activates AMPK and improves mitochondrial function. Complementary mechanisms on glucose handling.", "evidenceLevel": "moderate", "sources": [ { "text": "Dou Y et al. Berberine for the treatment of insulin resistance and obesity: a systematic review and meta-analysis. Heliyon. 2024", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Inositol improves insulin sensitivity in PCOS; berberine improves it via AMPK activation.", "clinicalSignificance": "Inositol improves insulin sensitivity in PCOS; berberine improves it via AMPK activation.", "managementStrategy": "Combine for PCOS and metabolic syndrome with insulin resistance. Monitor fasting glucose, A1c, and (in PCOS) AMH and ovulation.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Maca Root", "supplementBName": "DHEA", "interactionType": "synergy", "severity": "info", "description": "Maca improves subjective sexual function without changing hormones; DHEA raises androgens. Combined use can support both subjective and hormonal contributors to libido.", "recommendation": "Combine for libido in adults with low DHEA-S. Test DHEA-S baseline and at 8 to 12 weeks.", "minimumTimeSeparation": null, "mechanism": "Maca acts on subjective and behavioral aspects without altering hormones; DHEA raises androgens and estrogens. Mechanisms are non-overlapping.", "evidenceLevel": "emerging", "sources": [ { "text": "Gonzales GF. Ethnobiology and Ethnopharmacology of Lepidium meyenii (Maca). Evid Based Complement Alternat Med. 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Maca improves subjective sexual function without changing hormones; DHEA raises androgens.", "clinicalSignificance": "Maca improves subjective sexual function without changing hormones; DHEA raises androgens.", "managementStrategy": "Combine for libido in adults with low DHEA-S. Test DHEA-S baseline and at 8 to 12 weeks.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "L-Methionine", "supplementBName": "Vitamin B12", "interactionType": "synergy", "severity": "info", "description": "Methionine is recycled from homocysteine via B12-dependent methionine synthase; adequate B12 is required to handle methionine load without raising homocysteine.", "recommendation": "Pair methionine supplementation with adequate B12, folate, and B6. Test homocysteine to confirm methylation is supported.", "minimumTimeSeparation": null, "mechanism": "B12 is the cofactor for methionine synthase, which remethylates homocysteine back to methionine. Without it, methionine intake raises homocysteine.", "evidenceLevel": "strong", "sources": [ { "text": "Selhub J. Homocysteine metabolism. Annu Rev Nutr. 1999", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Methionine is recycled from homocysteine via B12-dependent methionine synthase; adequate B12 is required to handle methionine load without raising homocysteine.", "clinicalSignificance": "Methionine is recycled from homocysteine via B12-dependent methionine synthase; adequate B12 is required to handle methionine load without raising homocysteine.", "managementStrategy": "Pair methionine supplementation with adequate B12, folate, and B6. Test homocysteine to confirm methylation is supported.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "L-Methionine", "supplementBName": "Methylfolate", "interactionType": "synergy", "severity": "info", "description": "Methylfolate is the methyl donor that enables homocysteine remethylation to methionine via methionine synthase.", "recommendation": "Always pair methionine with adequate methylfolate (and B12) to manage homocysteine.", "minimumTimeSeparation": null, "mechanism": "5-methyltetrahydrofolate donates a methyl group to B12-bound homocysteine, regenerating methionine. Deficiency in either disrupts methylation.", "evidenceLevel": "strong", "sources": [ { "text": "Fowler B. The folate cycle and disease in humans. Kidney Int Suppl. 2001", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Methylfolate is the methyl donor that enables homocysteine remethylation to methionine via methionine synthase.", "clinicalSignificance": "Methylfolate is the methyl donor that enables homocysteine remethylation to methionine via methionine synthase.", "managementStrategy": "Always pair methionine with adequate methylfolate (and B12) to manage homocysteine.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "SAMe", "supplementBName": "Methylcobalamin", "interactionType": "synergy", "severity": "info", "description": "SAMe is the universal methyl donor; methylcobalamin supports the methionine cycle that regenerates SAMe.", "recommendation": "Combining supports methylation status, useful in depression and homocysteine management. Pair with methylfolate for full cycle support.", "minimumTimeSeparation": null, "mechanism": "B12 enables methionine synthase to regenerate methionine, which is then converted to SAMe. Inputs into the methyl pool work synergistically.", "evidenceLevel": "moderate", "sources": [ { "text": "Bottiglieri T. S-Adenosyl-L-methionine (SAMe): from the bench to the bedside. Am J Clin Nutr. 2002", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "SAMe is the universal methyl donor; methylcobalamin supports the methionine cycle that regenerates SAMe.", "clinicalSignificance": "SAMe is the universal methyl donor; methylcobalamin supports the methionine cycle that regenerates SAMe.", "managementStrategy": "Combining supports methylation status, useful in depression and homocysteine management. Pair with methylfolate for full cycle support.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Phosphatidylcholine", "supplementBName": "Methylfolate", "interactionType": "synergy", "severity": "info", "description": "Both contribute to the methyl donor pool; choline can compensate for low folate in some methylation reactions and vice versa.", "recommendation": "Pairing supports overall methylation status, particularly in homocysteine elevation. Useful when MTHFR variants reduce folate-mediated methylation.", "minimumTimeSeparation": null, "mechanism": "Choline donates methyl groups via betaine homocysteine methyltransferase (BHMT); folate via methionine synthase. Parallel pathways.", "evidenceLevel": "moderate", "sources": [ { "text": "Niculescu MD, Zeisel SH. Diet, methyl donors and DNA methylation: interactions between dietary folate, methionine and choline. J Nutr. 2002", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both contribute to the methyl donor pool; choline can compensate for low folate in some methylation reactions and vice versa.", "clinicalSignificance": "Both contribute to the methyl donor pool; choline can compensate for low folate in some methylation reactions and vice versa.", "managementStrategy": "Pairing supports overall methylation status, particularly in homocysteine elevation. Useful when MTHFR variants reduce folate-mediated methylation.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "NMN", "supplementBName": "Apigenin", "interactionType": "synergy", "severity": "info", "description": "NMN raises NAD+ substrate; apigenin inhibits CD38, the enzyme that consumes NAD+. Combined effect on whole blood NAD+ may be additive.", "recommendation": "Combine for NAD+ optimization in longevity-focused stacks. Track NAD+ via specialty assays (Jinfiniti, ChromaDex) at baseline and 8 weeks.", "minimumTimeSeparation": null, "mechanism": "NMN provides substrate for NAD+ synthesis; apigenin reduces NAD+ consumption by inhibiting CD38. Mechanisms are complementary.", "evidenceLevel": "emerging", "sources": [ { "text": "Escande C et al. Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome. Diabetes. 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "NMN raises NAD+ substrate; apigenin inhibits CD38, the enzyme that consumes NAD+.", "clinicalSignificance": "NMN raises NAD+ substrate; apigenin inhibits CD38, the enzyme that consumes NAD+.", "managementStrategy": "Combine for NAD+ optimization in longevity-focused stacks. Track NAD+ via specialty assays (Jinfiniti, ChromaDex) at baseline and 8 weeks.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Acetyl-L-Carnitine", "supplementBName": "Coenzyme Q10", "interactionType": "synergy", "severity": "info", "description": "Both support mitochondrial energy production through complementary mechanisms; combined use is common in cardiovascular and neurological contexts.", "recommendation": "Take with morning fat-containing meal. Useful stack for fatigue and statin-related complaints.", "minimumTimeSeparation": null, "mechanism": "ALCAR shuttles long-chain fatty acids into mitochondria for beta-oxidation; CoQ10 carries electrons in the ETC. Inputs and processes are complementary.", "evidenceLevel": "moderate", "sources": [ { "text": "Pesce V et al. Acetyl-L-carnitine activates the peroxisome proliferator-activated receptor-gamma coactivators. Rejuvenation Res. 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both support mitochondrial energy production through complementary mechanisms; combined use is common in cardiovascular and neurological contexts.", "clinicalSignificance": "Both support mitochondrial energy production through complementary mechanisms; combined use is common in cardiovascular and neurological contexts.", "managementStrategy": "Take with morning fat-containing meal. Useful stack for fatigue and statin-related complaints.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Acetyl-L-Carnitine", "supplementBName": "Alpha-Lipoic Acid", "interactionType": "synergy", "severity": "info", "description": "Both improve mitochondrial function in aging models; the classic Hagen and Ames protocol pairs them for cellular energy support.", "recommendation": "Combine for age-related fatigue or mitochondrial support. Standard doses: ALCAR 1 to 2 g, ALA 200 to 600 mg per day.", "minimumTimeSeparation": null, "mechanism": "ALCAR supports fatty acid oxidation; ALA reduces oxidative damage to mitochondrial enzymes and serves as a cofactor.", "evidenceLevel": "moderate", "sources": [ { "text": "Hagen TM et al. Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Proc Natl Acad Sci. 2002", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both improve mitochondrial function in aging models; the classic Hagen and Ames protocol pairs them for cellular energy support.", "clinicalSignificance": "Both improve mitochondrial function in aging models; the classic Hagen and Ames protocol pairs them for cellular energy support.", "managementStrategy": "Combine for age-related fatigue or mitochondrial support. Standard doses: ALCAR 1 to 2 g, ALA 200 to 600 mg per day.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Saw Palmetto", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "Both support prostate health through complementary mechanisms; combined use is common in men's BPH protocols.", "recommendation": "Standard doses: saw palmetto 320 mg/day plus EPA+DHA 1 to 2 g/day. Effect on prostate symptoms builds over 8 to 12 weeks.", "minimumTimeSeparation": null, "mechanism": "Saw palmetto inhibits 5-alpha reductase; omega-3s reduce prostatic inflammation that contributes to BPH symptoms.", "evidenceLevel": "emerging", "sources": [ { "text": "Galeone C et al. Fish consumption and prostate cancer risk: a case-control study in Italy. Br J Nutr. 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both support prostate health through complementary mechanisms; combined use is common in men's BPH protocols.", "clinicalSignificance": "Both support prostate health through complementary mechanisms; combined use is common in men's BPH protocols.", "managementStrategy": "Standard doses: saw palmetto 320 mg/day plus EPA+DHA 1 to 2 g/day. Effect on prostate symptoms builds over 8 to 12 weeks.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Tongkat Ali", "supplementBName": "Ashwagandha", "interactionType": "synergy", "severity": "info", "description": "Tongkat ali raises testosterone in low-T men; ashwagandha lowers cortisol that suppresses testosterone. Combined effect on male hormonal status is additive.", "recommendation": "Common male hormonal stack: tongkat ali 200 to 400 mg plus ashwagandha 300 to 600 mg per day. Test baseline testosterone and DHEA-S.", "minimumTimeSeparation": null, "mechanism": "Tongkat ali stimulates LH-mediated testosterone; ashwagandha attenuates HPA-axis cortisol that otherwise suppresses GnRH and testosterone.", "evidenceLevel": "emerging", "sources": [ { "text": "Lopresti AL et al. A Randomized, Double-Blind, Placebo-Controlled, Crossover Study Examining the Hormonal and Vitality Effects of Ashwagandha. Am J Men's Health. 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Tongkat ali raises testosterone in low-T men; ashwagandha lowers cortisol that suppresses testosterone.", "clinicalSignificance": "Tongkat ali raises testosterone in low-T men; ashwagandha lowers cortisol that suppresses testosterone.", "managementStrategy": "Common male hormonal stack: tongkat ali 200 to 400 mg plus ashwagandha 300 to 600 mg per day. Test baseline testosterone and DHEA-S.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "L-Carnitine", "supplementBName": "Phosphatidylcholine", "interactionType": "caution", "severity": "info", "description": "Both can contribute to TMAO production via gut bacterial metabolism; clinical relevance is debated.", "recommendation": "Monitor TMAO if cardiovascular risk is a concern. Routine use is generally well tolerated.", "minimumTimeSeparation": null, "mechanism": "Both are gut-bacteria-converted to TMA and then to TMAO in the liver. Cardiovascular implications of elevated TMAO remain debated.", "evidenceLevel": "moderate", "sources": [ { "text": "Koeth RA et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both can contribute to TMAO production via gut bacterial metabolism; clinical relevance is debated.", "clinicalSignificance": "Both can contribute to TMAO production via gut bacterial metabolism; clinical relevance is debated.", "managementStrategy": "Monitor TMAO if cardiovascular risk is a concern. Routine use is generally well tolerated.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "L-Glutamine", "supplementBName": "L-Glutathione", "interactionType": "synergy", "severity": "info", "description": "Glutamine is a substrate for glutathione synthesis (via glutamate). Combined use supports antioxidant capacity in critical illness and gut health.", "recommendation": "Combine for gut and oxidative support. Useful in IBD and post-surgical recovery.", "minimumTimeSeparation": null, "mechanism": "Glutamine feeds the gamma-glutamyl cycle that produces glutamate, a glutathione building block. Direct glutathione bypasses synthesis.", "evidenceLevel": "moderate", "sources": [ { "text": "Roth E. Nonnutritive effects of glutamine. J Nutr. 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Glutamine is a substrate for glutathione synthesis (via glutamate).", "clinicalSignificance": "Glutamine is a substrate for glutathione synthesis (via glutamate).", "managementStrategy": "Combine for gut and oxidative support. Useful in IBD and post-surgical recovery.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Taurine", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "info", "description": "Taurine and magnesium are both calcium channel modulators with cardiovascular and sleep benefits; combined use is common in evening relaxation protocols.", "recommendation": "Common evening stack: taurine 1 to 2 g plus magnesium 200 to 400 mg elemental at bedtime.", "minimumTimeSeparation": null, "mechanism": "Taurine modulates cardiac membrane potentials and intracellular calcium; magnesium gates NMDA receptors and supports vascular smooth muscle relaxation.", "evidenceLevel": "emerging", "sources": [ { "text": "Schaffer S et al. Effects and Mechanisms of Taurine as a Therapeutic Agent. Biomol Ther (Seoul). 2018;26(3):225-241.", "pmid": "29631391", "doi": "10.4062/biomolther.2017.251", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29631391/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Taurine and magnesium are both calcium channel modulators with cardiovascular and sleep benefits; combined use is common in evening relaxation protocols.", "clinicalSignificance": "Taurine and magnesium are both calcium channel modulators with cardiovascular and sleep benefits; combined use is common in evening relaxation protocols.", "managementStrategy": "Common evening stack: taurine 1 to 2 g plus magnesium 200 to 400 mg elemental at bedtime.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "BCAAs", "supplementBName": "Creatine", "interactionType": "synergy", "severity": "info", "description": "Both support resistance training adaptations through different pathways; combined use is common in performance protocols.", "recommendation": "Common doses: 5 to 10 g BCAAs intra-workout plus 3 to 5 g creatine daily.", "minimumTimeSeparation": null, "mechanism": "BCAAs (especially leucine) trigger mTOR-mediated muscle protein synthesis; creatine increases muscle phosphocreatine for power output.", "evidenceLevel": "moderate", "sources": [ { "text": "Kreider RB et al. International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation. J Int Soc Sports Nutr. 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both support resistance training adaptations through different pathways; combined use is common in performance protocols.", "clinicalSignificance": "Both support resistance training adaptations through different pathways; combined use is common in performance protocols.", "managementStrategy": "Common doses: 5 to 10 g BCAAs intra-workout plus 3 to 5 g creatine daily.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "D-Mannose", "supplementBName": "Probiotics", "interactionType": "synergy", "severity": "info", "description": "D-mannose prevents E. coli adhesion to uroepithelium; probiotics support gut and urogenital flora that resists pathogen colonization.", "recommendation": "Combine for recurrent UTI prevention: D-mannose 2 g/day plus L. rhamnosus or reuteri strains.", "minimumTimeSeparation": null, "mechanism": "D-mannose binds FimH adhesin on E. coli; Lactobacillus species produce lactic acid and antimicrobial peptides that inhibit uropathogens.", "evidenceLevel": "moderate", "sources": [ { "text": "Domenici L et al. D-mannose: a promising support for acute urinary tract infections in women. A pilot study. Eur Rev Med Pharmacol Sci. 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "D-mannose prevents E.", "clinicalSignificance": "D-mannose prevents E.", "managementStrategy": "Combine for recurrent UTI prevention: D-mannose 2 g/day plus L. rhamnosus or reuteri strains.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "DHEA", "supplementBName": "Ashwagandha", "interactionType": "caution", "severity": "info", "description": "DHEA raises androgens; ashwagandha modestly raises testosterone in men. Combined use can compound androgenic effects.", "recommendation": "Monitor free testosterone, estradiol, and DHEA-S. Lower DHEA dose may be sufficient when combined.", "minimumTimeSeparation": null, "mechanism": "DHEA converts to downstream androgens; ashwagandha modestly raises serum testosterone via LH-related mechanisms and cortisol suppression.", "evidenceLevel": "emerging", "sources": [ { "text": "Lopresti AL et al. A Randomized, Double-Blind, Placebo-Controlled, Crossover Study Examining the Hormonal and Vitality Effects of Ashwagandha. Am J Men's Health. 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "DHEA raises androgens; ashwagandha modestly raises testosterone in men.", "clinicalSignificance": "DHEA raises androgens; ashwagandha modestly raises testosterone in men.", "managementStrategy": "Monitor free testosterone, estradiol, and DHEA-S. Lower DHEA dose may be sufficient when combined.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Hyaluronic Acid", "supplementBName": "Collagen Peptides", "interactionType": "synergy", "severity": "info", "description": "Both support extracellular matrix integrity in skin and joints; combined use has additive evidence for skin hydration and elasticity.", "recommendation": "Common combination: hyaluronic acid 120 to 240 mg plus collagen peptides 10 to 15 g per day.", "minimumTimeSeparation": null, "mechanism": "HA provides extracellular water binding and lubrication; collagen peptides supply hydroxyproline and glycine for matrix synthesis.", "evidenceLevel": "moderate", "sources": [ { "text": "Czajka A et al. Daily oral supplementation with collagen peptides combined with vitamins and other bioactive compounds improves skin elasticity and has a beneficial effect on joint and general wellbeing. Nutr Res. 2018", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both support extracellular matrix integrity in skin and joints; combined use has additive evidence for skin hydration and elasticity.", "clinicalSignificance": "Both support extracellular matrix integrity in skin and joints; combined use has additive evidence for skin hydration and elasticity.", "managementStrategy": "Common combination: hyaluronic acid 120 to 240 mg plus collagen peptides 10 to 15 g per day.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Holy Basil/Tulsi", "supplementBName": "Ashwagandha", "interactionType": "synergy", "severity": "info", "description": "Both are adaptogenic herbs with stress-modulating effects; combined use is common in HPA-axis support stacks.", "recommendation": "Common doses: holy basil 300 to 600 mg plus ashwagandha 300 to 600 mg per day. Effect builds over 4 to 8 weeks.", "minimumTimeSeparation": null, "mechanism": "Both attenuate cortisol responses and modulate stress reactivity via complementary mechanisms (holy basil targets cortisol and glucose; ashwagandha targets cortisol and androgens).", "evidenceLevel": "emerging", "sources": [ { "text": "Cohen MM. Tulsi - Ocimum sanctum: A herb for all reasons. J Ayurveda Integr Med. 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both are adaptogenic herbs with stress-modulating effects; combined use is common in HPA-axis support stacks.", "clinicalSignificance": "Both are adaptogenic herbs with stress-modulating effects; combined use is common in HPA-axis support stacks.", "managementStrategy": "Common doses: holy basil 300 to 600 mg plus ashwagandha 300 to 600 mg per day. Effect builds over 4 to 8 weeks.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Boswellia", "supplementBName": "Curcumin Phytosome", "interactionType": "synergy", "severity": "info", "description": "Both reduce joint inflammation through complementary pathways; head-to-head trials show additive benefit in osteoarthritis.", "recommendation": "Common stack for joint health: boswellia 100 to 300 mg AKBA extract plus curcumin phytosome 500 to 1000 mg per day.", "minimumTimeSeparation": null, "mechanism": "Boswellia inhibits 5-LOX; curcumin modulates NF-kB and COX-2. Inhibition of complementary inflammatory enzymes.", "evidenceLevel": "moderate", "sources": [ { "text": "Haroyan A et al. Efficacy and safety of curcumin and its combination with boswellic acid in osteoarthritis: a comparative, randomized, double-blind, placebo-controlled study. BMC Complement Altern Med. 2018", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both reduce joint inflammation through complementary pathways; head-to-head trials show additive benefit in osteoarthritis.", "clinicalSignificance": "Both reduce joint inflammation through complementary pathways; head-to-head trials show additive benefit in osteoarthritis.", "managementStrategy": "Common stack for joint health: boswellia 100 to 300 mg AKBA extract plus curcumin phytosome 500 to 1000 mg per day.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Maca Root", "supplementBName": "Tongkat Ali", "interactionType": "synergy", "severity": "info", "description": "Maca improves subjective libido without changing hormones; tongkat ali raises testosterone. Combined use targets both subjective and hormonal contributors to male sexual function.", "recommendation": "Common stack: maca 1.5 to 3 g plus tongkat ali 200 to 400 mg per day.", "minimumTimeSeparation": null, "mechanism": "Mechanisms are non-overlapping: maca acts on libido and subjective vitality without hormone change; tongkat ali raises testosterone via LH stimulation.", "evidenceLevel": "emerging", "sources": [ { "text": "Shin BC et al. Maca (L. meyenii) for improving sexual function: a systematic review. BMC Complement Altern Med. 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Maca improves subjective libido without changing hormones; tongkat ali raises testosterone.", "clinicalSignificance": "Maca improves subjective libido without changing hormones; tongkat ali raises testosterone.", "managementStrategy": "Common stack: maca 1.5 to 3 g plus tongkat ali 200 to 400 mg per day.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Alcohol", "supplementBName": "Vitamin B1", "interactionType": "conflict", "severity": "serious", "description": "Chronic alcohol intake depletes thiamine (B1) and impairs its absorption and activation, raising the risk of Wernicke encephalopathy and Korsakoff syndrome.", "recommendation": "Do not treat alcohol use as safe. If alcohol is consumed regularly, arrange thiamine repletion under medical supervision, and seek medical advice for any neurological symptoms.", "minimumTimeSeparation": null, "mechanism": "Alcohol reduces active transport of thiamine across the intestinal mucosa and inhibits hepatic conversion of thiamine to its active coenzyme thiamine pyrophosphate, while increasing urinary thiamine loss.", "evidenceLevel": "strong", "sources": [ { "text": "Thomson AD et al. The natural history and pathophysiology of Wernicke's Encephalopathy and Korsakoff's Psychosis. Alcohol Alcohol. 2006;41(2):151-8.", "pmid": "16384871", "doi": "10.1093/alcalc/agh249", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16384871/", "publicSourceType": "PMID" }, { "text": "Martin PR et al. The role of thiamine deficiency in alcoholic brain disease. Alcohol Res Health. 2003;27(2):134-42.", "pmid": "15303623", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15303623/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Chronic alcohol intake depletes thiamine (B1) and impairs its absorption and activation, raising the risk of Wernicke encephalopathy and Korsakoff syndrome.", "clinicalSignificance": "Alcohol is a leading cause of thiamine deficiency and the neurological damage it produces.", "managementStrategy": "Do not treat alcohol use as safe. If alcohol is consumed regularly, arrange thiamine repletion under medical supervision, and seek medical advice for any neurological symptoms.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Alcohol", "supplementBName": "Milk Thistle", "interactionType": "caution", "severity": "moderate", "description": "Milk thistle (silymarin) is often taken for liver support during alcohol use, but evidence does not show it prevents alcohol-related liver damage, and its perceived protection may encourage continued drinking.", "recommendation": "Do not treat milk thistle as protection that makes drinking safe. The most effective step for alcohol liver injury is reducing or stopping alcohol; seek medical advice.", "minimumTimeSeparation": null, "mechanism": "Silymarin has antioxidant and anti-fibrotic activity in hepatocytes, but it does not reverse the oxidative and metabolic hepatotoxicity caused by ethanol and acetaldehyde at clinically meaningful levels.", "evidenceLevel": "emerging", "sources": [ { "text": "Rambaldi A, Jacobs BP, Gluud C. Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases. Cochrane Database Syst Rev. 2007.", "pmid": "17943794", "doi": "10.1002/14651858.CD003620.pub3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17943794/", "publicSourceType": "PMID" }, { "text": "Abenavoli L, et al. Milk thistle in liver diseases: past, present, future. Phytother Res. 2010.", "pmid": "20564545", "doi": "10.1002/ptr.3207", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20564545/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Milk thistle (silymarin) is often taken for liver support during alcohol use, but evidence does not show it prevents alcohol-related liver damage, and its perceived protection may encourage continued drinking.", "clinicalSignificance": "Milk thistle is not a reliable safeguard against alcohol-induced liver disease.", "managementStrategy": "Do not treat milk thistle as protection that makes drinking safe. The most effective step for alcohol liver injury is reducing or stopping alcohol; seek medical advice.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Alcohol", "supplementBName": "Melatonin", "interactionType": "caution", "severity": "moderate", "description": "Combining alcohol with melatonin can increase sedation and drowsiness, while alcohol itself disrupts the body's natural melatonin rhythm and overall sleep quality.", "recommendation": "Do not combine alcohol with melatonin, especially before driving or operating machinery. Avoid alcohol if you are using melatonin for sleep.", "minimumTimeSeparation": null, "mechanism": "Both substances have central nervous system depressant effects that are additive, and ethanol suppresses endogenous nocturnal melatonin secretion, blunting the intended circadian effect.", "evidenceLevel": "moderate", "sources": [ { "text": "Ekman AC, et al. Ethanol inhibits melatonin secretion in healthy volunteers in a dose-dependent randomized double blind cross-over study. Journal of Clinical Endocrinology and Metabolism, 1993.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Ebrahim IO, Shapiro CM, Williams AJ, Fenwick PB. Alcohol and sleep I: effects on normal sleep. Alcohol Clin Exp Res. 2013.", "pmid": "23347102", "doi": "10.1111/acer.12006", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23347102/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Combining alcohol with melatonin can increase sedation and drowsiness, while alcohol itself disrupts the body's natural melatonin rhythm and overall sleep quality.", "clinicalSignificance": "Alcohol both worsens sedation risk with melatonin and undermines its sleep benefit.", "managementStrategy": "Do not combine alcohol with melatonin, especially before driving or operating machinery. Avoid alcohol if you are using melatonin for sleep.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Bacopa Monnieri", "supplementBName": "L-Theanine", "interactionType": "synergy", "severity": "info", "description": "Bacopa monnieri and L-theanine are commonly combined for cognitive support, with Bacopa supporting memory consolidation and L-theanine promoting calm focus, producing complementary effects without significant conflict.", "recommendation": "This combination is generally well tolerated. Start at standard individual doses and monitor for excess sedation or drowsiness.", "minimumTimeSeparation": null, "mechanism": "Bacopa modulates cholinergic signaling and antioxidant activity in the hippocampus, while L-theanine increases alpha brain wave activity and modulates GABA and glutamate, together supporting attention and reduced anxiety.", "evidenceLevel": "moderate", "sources": [ { "text": "Calabrese C, et al. Effects of a standardized Bacopa monnieri extract on cognitive performance, anxiety, and depression in the elderly: a randomized, double-blind, placebo-controlled trial. Journal of Alternative and Complementary Medicine, 2008.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Nobre AC, Rao A, Owen GN. L-theanine, a natural constituent in tea, and its effect on mental state. Asia Pacific Journal of Clinical Nutrition, 2008.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Bacopa monnieri and L-theanine are commonly combined for cognitive support, with Bacopa supporting memory consolidation and L-theanine promoting calm focus, producing complementary effects without significant conflict.", "clinicalSignificance": "A complementary nootropic pairing for calm, focused cognition.", "managementStrategy": "This combination is generally well tolerated. Start at standard individual doses and monitor for excess sedation or drowsiness.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Bacopa Monnieri", "supplementBName": "Alpha-GPC", "interactionType": "synergy", "severity": "info", "description": "Bacopa monnieri and Alpha-GPC both support cholinergic function through different routes, and are frequently stacked to enhance memory and learning support.", "recommendation": "Generally well tolerated together. Watch for signs of cholinergic excess such as headache or nausea and reduce the dose if these occur.", "minimumTimeSeparation": null, "mechanism": "Alpha-GPC supplies choline as a precursor for acetylcholine synthesis, while Bacopa modulates acetylcholinesterase activity and supports cholinergic neurons, jointly raising acetylcholine availability and signaling.", "evidenceLevel": "emerging", "sources": [ { "text": "Aguiar S, Borowski T. Neuropharmacological review of the nootropic herb Bacopa monnieri. Rejuvenation Research, 2013.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Parnetti L, Mignini F, Tomassoni D, et al. Cholinergic precursors in the treatment of cognitive impairment of vascular origin. Journal of the Neurological Sciences, 2007.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Bacopa monnieri and Alpha-GPC both support cholinergic function through different routes, and are frequently stacked to enhance memory and learning support.", "clinicalSignificance": "Two complementary mechanisms support the same cholinergic memory pathway.", "managementStrategy": "Generally well tolerated together. Watch for signs of cholinergic excess such as headache or nausea and reduce the dose if these occur.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Bacopa Monnieri", "supplementBName": "Ashwagandha", "interactionType": "synergy", "severity": "info", "description": "Bacopa monnieri and Ashwagandha are traditionally combined in Ayurvedic practice for cognition and stress, with Bacopa supporting memory and Ashwagandha lowering stress and anxiety.", "recommendation": "Generally well tolerated. Both may have mild sedative effects, so monitor for excess drowsiness, particularly when taken together at night.", "minimumTimeSeparation": null, "mechanism": "Bacopa supports cholinergic and antioxidant pathways in memory circuits, while Ashwagandha modulates the HPA axis and reduces cortisol, addressing both cognitive and stress components.", "evidenceLevel": "emerging", "sources": [ { "text": "Chengappa KNR, et al. Adjunctive use of a standardized extract of Withania somnifera (Ashwagandha) in cognition. Journal of Clinical Psychiatry, 2013.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Aguiar S, Borowski T. Neuropharmacological review of the nootropic herb Bacopa monnieri. Rejuvenation Research, 2013.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Bacopa monnieri and Ashwagandha are traditionally combined in Ayurvedic practice for cognition and stress, with Bacopa supporting memory and Ashwagandha lowering stress and anxiety.", "clinicalSignificance": "A traditional adaptogen plus nootropic pairing for stress-related cognitive support.", "managementStrategy": "Generally well tolerated. Both may have mild sedative effects, so monitor for excess drowsiness, particularly when taken together at night.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Bee Pollen", "supplementBName": "Royal Jelly", "interactionType": "caution", "severity": "moderate", "description": "Bee pollen and royal jelly are both bee-derived products that can trigger allergic reactions, and taking them together increases cumulative exposure to bee allergens and the risk of a serious reaction.", "recommendation": "If you have pollen allergies, asthma, or any history of bee product reactions, do not combine these and seek medical advice before use. Stop immediately and seek care if swelling, hives, or breathing difficulty occur.", "minimumTimeSeparation": null, "mechanism": "Both products contain bee-derived proteins and pollen allergens capable of provoking IgE-mediated hypersensitivity, and combined intake raises total allergen load and anaphylaxis risk in sensitized individuals.", "evidenceLevel": "moderate", "sources": [ { "text": "Lombardi C, et al. Anaphylaxis after ingestion of royal jelly and bee pollen. Journal of Investigational Allergology and Clinical Immunology, 1998.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Leung R, Ho A, Chan J, et al. Royal jelly consumption and hypersensitivity in the community. Clinical and Experimental Allergy, 1997.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Bee pollen and royal jelly are both bee-derived products that can trigger allergic reactions, and taking them together increases cumulative exposure to bee allergens and the risk of a serious reaction.", "clinicalSignificance": "Stacking two bee products compounds allergy and anaphylaxis risk in sensitized people.", "managementStrategy": "If you have pollen allergies, asthma, or any history of bee product reactions, do not combine these and seek medical advice before use. Stop immediately and seek care if swelling, hives, or breathing difficulty occur.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Beta-Carotene", "supplementBName": "Vitamin A", "interactionType": "caution", "severity": "moderate", "description": "Beta-carotene is converted to vitamin A in the body, so taking both together adds to total vitamin A activity and can increase the risk of vitamin A excess (hypervitaminosis A).", "recommendation": "Do not take high doses of both at the same time. Account for beta-carotene's vitamin A contribution when dosing preformed vitamin A, and avoid combined high intake especially in pregnancy.", "minimumTimeSeparation": null, "mechanism": "Beta-carotene is enzymatically cleaved to retinal and then retinol, adding to the body's preformed vitamin A pool; this conversion is downregulated when vitamin A status is high, but excess preformed retinol from supplements can still accumulate to toxic levels.", "evidenceLevel": "moderate", "sources": [ { "text": "Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron. National Academies Press, 2001.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Grune T, et al. Beta-carotene is an important vitamin A source for humans. Journal of Nutrition, 2010.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Beta-carotene is converted to vitamin A in the body, so taking both together adds to total vitamin A activity and can increase the risk of vitamin A excess (hypervitaminosis A).", "clinicalSignificance": "Combined intake can push total vitamin A activity toward toxic levels.", "managementStrategy": "Do not take high doses of both at the same time. Account for beta-carotene's vitamin A contribution when dosing preformed vitamin A, and avoid combined high intake especially in pregnancy.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Beta-Carotene", "supplementBName": "Lutein", "interactionType": "timingSensitive", "severity": "moderate", "description": "Beta-carotene and lutein compete for the same intestinal absorption pathways, so taking large doses together can reduce the absorption of lutein.", "recommendation": "If taking both, consider separating them by a couple of hours or taking them with different meals to limit absorption competition. Take each with a fat-containing meal to aid uptake.", "minimumTimeSeparation": "2 hours", "mechanism": "Carotenoids share intestinal uptake mechanisms, including incorporation into mixed micelles and transport via scavenger receptor SR-BI, so high beta-carotene intake can competitively lower lutein absorption.", "evidenceLevel": "moderate", "sources": [ { "text": "Kostic D, White WS, Olson JA. Intestinal absorption, serum clearance, and interactions between lutein and beta-carotene when administered to human adults in separate or combined oral doses. Am J Clin Nutr. 1995.", "pmid": "7661123", "doi": "10.1093/ajcn/62.3.604", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7661123/", "publicSourceType": "PMID" }, { "text": "van den Berg H. Carotenoid interactions. Nutrition Reviews, 1999.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Beta-carotene and lutein compete for the same intestinal absorption pathways, so taking large doses together can reduce the absorption of lutein.", "clinicalSignificance": "High-dose beta-carotene can blunt lutein absorption when taken together.", "managementStrategy": "If taking both, consider separating them by a couple of hours or taking them with different meals to limit absorption competition. Take each with a fat-containing meal to aid uptake.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Beta-Carotene", "supplementBName": "Vitamin E", "interactionType": "synergy", "severity": "info", "description": "Beta-carotene and vitamin E are complementary antioxidants that protect different cellular compartments, and vitamin E can help protect beta-carotene from oxidative degradation.", "recommendation": "This combination is generally compatible at normal dietary supplement doses. Avoid very high-dose antioxidant stacking, particularly in smokers, and seek advice if you smoke.", "minimumTimeSeparation": null, "mechanism": "Vitamin E is a lipid-phase chain-breaking antioxidant that quenches peroxyl radicals and can spare beta-carotene from oxidation, while beta-carotene scavenges singlet oxygen, giving complementary antioxidant coverage in lipid membranes.", "evidenceLevel": "emerging", "sources": [ { "text": "Palozza P, Krinsky NI. Beta-carotene and alpha-tocopherol are synergistic antioxidants. Archives of Biochemistry and Biophysics, 1992.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bohm F, et al. Carotenoids enhance vitamin E antioxidant efficiency. Journal of the American Chemical Society, 1997.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Beta-carotene and vitamin E are complementary antioxidants that protect different cellular compartments, and vitamin E can help protect beta-carotene from oxidative degradation.", "clinicalSignificance": "Vitamin E and beta-carotene provide complementary lipid-phase antioxidant protection.", "managementStrategy": "This combination is generally compatible at normal dietary supplement doses. Avoid very high-dose antioxidant stacking, particularly in smokers, and seek advice if you smoke.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Betaine HCL", "supplementBName": "Iron", "interactionType": "synergy", "severity": "info", "description": "Betaine HCL lowers stomach pH, which can improve the solubility and absorption of non-heme iron, particularly in people with low stomach acid.", "recommendation": "May aid iron absorption in people with hypochlorhydria. Take with food and monitor for gastric irritation; consult a clinician if you have a history of ulcers.", "minimumTimeSeparation": null, "mechanism": "An acidic gastric environment helps reduce ferric iron to the more absorbable ferrous form and keeps non-heme iron soluble in the upper intestine, so supplemental gastric acid from betaine HCL can enhance iron uptake when acid is deficient.", "evidenceLevel": "emerging", "sources": [ { "text": "Champagne ET. Low gastric hydrochloric acid secretion and mineral bioavailability. Advances in Experimental Medicine and Biology, 1989.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Yago MR, et al. Gastric reacidification with betaine HCl in healthy volunteers with rabeprazole-induced hypochlorhydria. Molecular Pharmaceutics, 2013.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Betaine HCL lowers stomach pH, which can improve the solubility and absorption of non-heme iron, particularly in people with low stomach acid.", "clinicalSignificance": "Restoring gastric acidity can improve non-heme iron absorption when acid is low.", "managementStrategy": "May aid iron absorption in people with hypochlorhydria. Take with food and monitor for gastric irritation; consult a clinician if you have a history of ulcers.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Betaine HCL", "supplementBName": "Vitamin B12", "interactionType": "synergy", "severity": "info", "description": "Adequate stomach acid is needed to release vitamin B12 from food proteins, so betaine HCL may support B12 liberation and absorption in people with low gastric acid.", "recommendation": "May help free food-bound B12 in hypochlorhydria, but crystalline B12 in supplements does not require acid. Seek medical advice for diagnosed B12 deficiency rather than self-treating.", "minimumTimeSeparation": null, "mechanism": "Gastric acid and pepsin cleave protein-bound dietary B12 so it can bind intrinsic factor for ileal absorption; low stomach acid impairs this step, and supplemental acid from betaine HCL may restore food-bound B12 release.", "evidenceLevel": "emerging", "sources": [ { "text": "Carmel R. Cobalamin, the stomach, and aging. American Journal of Clinical Nutrition, 1997.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Saltzman JR, et al. Effect of hypochlorhydria due to omeprazole treatment or atrophic gastritis on protein-bound vitamin B12 absorption. Journal of the American College of Nutrition, 1994.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Adequate stomach acid is needed to release vitamin B12 from food proteins, so betaine HCL may support B12 liberation and absorption in people with low gastric acid.", "clinicalSignificance": "Gastric acid is required to free food-bound B12, so acid support may aid absorption when acid is low.", "managementStrategy": "May help free food-bound B12 in hypochlorhydria, but crystalline B12 in supplements does not require acid. Seek medical advice for diagnosed B12 deficiency rather than self-treating.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Betaine HCL", "supplementBName": "Digestive Enzymes", "interactionType": "synergy", "severity": "info", "description": "Betaine HCL and digestive enzymes are commonly combined to support digestion, with the acidic environment from betaine HCL helping activate pepsin and optimize protein breakdown.", "recommendation": "Generally well tolerated together with meals. Reduce the dose or stop if heartburn or epigastric burning occurs, and avoid if you have active ulcers or take acid-suppressing medication.", "minimumTimeSeparation": null, "mechanism": "Pepsinogen requires an acidic pH to convert to active pepsin, so betaine HCL lowers gastric pH to support protein digestion, complementing pancreatic and plant-derived enzymes acting in the stomach and intestine.", "evidenceLevel": "emerging", "sources": [ { "text": "Heda R, Toro F, Tombazzi CR. Physiology, Pepsin. StatPearls, 2022.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Champagne ET. Low gastric hydrochloric acid secretion and mineral bioavailability. Advances in Experimental Medicine and Biology, 1989.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Betaine HCL and digestive enzymes are commonly combined to support digestion, with the acidic environment from betaine HCL helping activate pepsin and optimize protein breakdown.", "clinicalSignificance": "Acidification from betaine HCL supports enzymatic protein digestion.", "managementStrategy": "Generally well tolerated together with meals. Reduce the dose or stop if heartburn or epigastric burning occurs, and avoid if you have active ulcers or take acid-suppressing medication.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Black Cohosh", "supplementBName": "St. John's Wort", "interactionType": "caution", "severity": "moderate", "description": "Both herbs carry independent hepatic safety signals, so combining them can complicate monitoring and attribution if liver enzymes rise or symptoms of liver injury appear.", "recommendation": "Avoid routine co-use. If both are taken, watch for signs of liver injury (fatigue, dark urine, jaundice, right upper quadrant pain) and consider baseline and periodic liver function tests.", "minimumTimeSeparation": null, "mechanism": "Black cohosh has been associated with idiosyncratic hepatocellular injury in pharmacovigilance reports, and St. John's Wort has its own rare hepatic reports plus potent induction of CYP enzymes and P-glycoprotein; overlapping use makes early detection and attribution of any liver toxicity more difficult.", "evidenceLevel": "emerging", "sources": [ { "text": "European Medicines Agency, Assessment report on Cimicifuga racemosa rhizome, 2018", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Borrelli F, Ernst E, Black cohosh (Cimicifuga racemosa): a systematic review of adverse events, American Journal of Obstetrics and Gynecology, 2008. Black cohosh (Cimicifuga racemosa): a systematic review of adverse events. Am J Obstet Gynecol. 2008.", "pmid": "18984078", "doi": "10.1016/j.ajog.2008.05.007", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18984078/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both herbs carry independent hepatic safety signals, so combining them can complicate monitoring and attribution if liver enzymes rise or symptoms of liver injury appear.", "clinicalSignificance": "Overlapping hepatic safety signals warrant caution and liver monitoring when these herbs are combined.", "managementStrategy": "Avoid routine co-use. If both are taken, watch for signs of liver injury (fatigue, dark urine, jaundice, right upper quadrant pain) and consider baseline and periodic liver function tests.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Black Cohosh", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "info", "description": "Pairing black cohosh for menopausal vasomotor symptoms with vitamin D3 addresses a complementary need, since postmenopausal women face elevated bone loss risk that adequate vitamin D helps mitigate.", "recommendation": "Reasonable to combine for menopausal women; ensure vitamin D intake supports bone health alongside symptom relief from black cohosh. No timing precautions needed.", "minimumTimeSeparation": null, "mechanism": "Black cohosh acts on serotonergic and other central pathways to reduce hot flashes but does not protect bone, while vitamin D3 supports calcium absorption and bone mineralization; the two cover distinct aspects of menopausal health.", "evidenceLevel": "moderate", "sources": [ { "text": "North American Menopause Society, Nonhormonal management of menopause-associated vasomotor symptoms position statement, 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Holick MF, Vitamin D deficiency, New England Journal of Medicine, 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Pairing black cohosh for menopausal vasomotor symptoms with vitamin D3 addresses a complementary need, since postmenopausal women face elevated bone loss risk that adequate vitamin D helps mitigate.", "clinicalSignificance": "Complementary menopausal regimen with no known adverse interaction.", "managementStrategy": "Reasonable to combine for menopausal women; ensure vitamin D intake supports bone health alongside symptom relief from black cohosh. No timing precautions needed.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Black Cohosh", "supplementBName": "Calcium", "interactionType": "synergy", "severity": "info", "description": "Calcium complements black cohosh in the menopausal setting by supporting bone density, which black cohosh does not address while it relieves vasomotor symptoms.", "recommendation": "Suitable to combine for postmenopausal bone and symptom support. Take calcium with food in divided doses for best absorption.", "minimumTimeSeparation": null, "mechanism": "Black cohosh targets hot flashes via central neurotransmitter pathways without estrogenic bone protection, so adequate calcium intake helps fill the bone-health gap during the estrogen-deficient menopausal state.", "evidenceLevel": "moderate", "sources": [ { "text": "North American Menopause Society, Management of osteoporosis in postmenopausal women position statement, 2021", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Calcium complements black cohosh in the menopausal setting by supporting bone density, which black cohosh does not address while it relieves vasomotor symptoms.", "clinicalSignificance": "Sensible complementary pairing for menopausal women with no adverse interaction.", "managementStrategy": "Suitable to combine for postmenopausal bone and symptom support. Take calcium with food in divided doses for best absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Black Seed Oil", "supplementBName": "Berberine", "interactionType": "caution", "severity": "moderate", "description": "Both lower blood glucose, so combined use can produce additive hypoglycemic effects, particularly in people also taking diabetes medications.", "recommendation": "Monitor blood glucose more closely when combining. Watch for symptoms of hypoglycemia (shakiness, sweating, confusion) and coordinate with a clinician if on antidiabetic drugs.", "minimumTimeSeparation": null, "mechanism": "Black seed oil (thymoquinone) improves insulin sensitivity and lowers fasting glucose, while berberine activates AMPK and reduces hepatic glucose output; the effects are additive on glycemic control.", "evidenceLevel": "moderate", "sources": [ { "text": "Askari G et al. Effect of Nigella sativa (black seed) supplementation on glycemic control: A systematic review and meta-analysis of clinical trials. Phytother Res. 2019;33(5):1341-1352.", "pmid": "30873688", "doi": "10.1002/ptr.6337", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30873688/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both lower blood glucose, so combined use can produce additive hypoglycemic effects, particularly in people also taking diabetes medications.", "clinicalSignificance": "Additive glucose lowering requires monitoring, especially with concurrent diabetes therapy.", "managementStrategy": "Monitor blood glucose more closely when combining. Watch for symptoms of hypoglycemia (shakiness, sweating, confusion) and coordinate with a clinician if on antidiabetic drugs.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Black Seed Oil", "supplementBName": "Fish Oil", "interactionType": "caution", "severity": "moderate", "description": "Both can modestly lower blood pressure and affect platelet function, so combining them may produce additive reductions in blood pressure and a small additive antiplatelet effect.", "recommendation": "Generally well tolerated, but monitor blood pressure if hypotension-prone and watch for easy bruising or bleeding, especially around surgery or with anticoagulants.", "minimumTimeSeparation": null, "mechanism": "Omega-3 fatty acids in fish oil reduce platelet aggregation and modestly lower blood pressure, while black seed oil also has documented blood pressure lowering and mild antiplatelet activity; the effects are additive.", "evidenceLevel": "emerging", "sources": [ { "text": "Sahebkar A et al, Nigella sativa supplementation and blood pressure: a systematic review and meta-analysis, Journal of Hypertension, 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Mori TA, Omega-3 fatty acids and blood pressure, Cellular and Molecular Biology, 2010. Omega-3 fatty acids and blood pressure. Cell Mol Biol (Noisy-le-grand). 2010.", "pmid": "20196972", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20196972/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both can modestly lower blood pressure and affect platelet function, so combining them may produce additive reductions in blood pressure and a small additive antiplatelet effect.", "clinicalSignificance": "Additive blood pressure and platelet effects merit attention in at-risk or perioperative patients.", "managementStrategy": "Generally well tolerated, but monitor blood pressure if hypotension-prone and watch for easy bruising or bleeding, especially around surgery or with anticoagulants.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Black Seed Oil", "supplementBName": "Turmeric/Curcumin", "interactionType": "synergy", "severity": "info", "description": "Both are anti-inflammatory and antioxidant agents that have shown complementary metabolic benefits when studied together, including improved glycemic and lipid markers.", "recommendation": "Reasonable combination for anti-inflammatory and metabolic support. No special timing required; taking both with a fat-containing meal aids absorption.", "minimumTimeSeparation": null, "mechanism": "Thymoquinone from black seed oil and curcumin both suppress NF-kB-mediated inflammatory signaling and provide antioxidant effects, producing complementary anti-inflammatory action.", "evidenceLevel": "emerging", "sources": [ { "text": "Amin F et al, Nigella sativa and its constituent thymoquinone: anti-inflammatory and antioxidant effects, Journal of Ethnopharmacology, 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Hewlings SJ, Kalman DS, Curcumin: a review of its effects on human health, Foods, 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both are anti-inflammatory and antioxidant agents that have shown complementary metabolic benefits when studied together, including improved glycemic and lipid markers.", "clinicalSignificance": "Complementary anti-inflammatory pairing supported by early combination studies.", "managementStrategy": "Reasonable combination for anti-inflammatory and metabolic support. No special timing required; taking both with a fat-containing meal aids absorption.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "CLA", "supplementBName": "Green Tea Extract", "interactionType": "synergy", "severity": "info", "description": "CLA and green tea extract are often combined for body composition support and may have complementary effects on fat oxidation and energy expenditure.", "recommendation": "Acceptable to combine for weight management goals. Because green tea extract carries a dose-dependent hepatotoxicity risk, avoid high-dose extracts and prefer taking with food.", "minimumTimeSeparation": null, "mechanism": "CLA may modestly promote lipolysis and reduce fat deposition, while green tea catechins and caffeine increase thermogenesis and fat oxidation; the mechanisms are complementary rather than overlapping.", "evidenceLevel": "emerging", "sources": [ { "text": "Whigham LD et al, Efficacy of conjugated linoleic acid for reducing fat mass: a meta-analysis, American Journal of Clinical Nutrition, 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Hursel R et al, The effects of green tea on weight loss and weight maintenance: a meta-analysis, International Journal of Obesity, 2009", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "CLA and green tea extract are often combined for body composition support and may have complementary effects on fat oxidation and energy expenditure.", "clinicalSignificance": "Complementary fat-metabolism support, with green tea extract dose as the main safety consideration.", "managementStrategy": "Acceptable to combine for weight management goals. Because green tea extract carries a dose-dependent hepatotoxicity risk, avoid high-dose extracts and prefer taking with food.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "CLA", "supplementBName": "L-Carnitine", "interactionType": "synergy", "severity": "info", "description": "L-carnitine supports transport of fatty acids into mitochondria for oxidation, which is mechanistically complementary to CLA's role in fat metabolism.", "recommendation": "Reasonable to combine for body composition goals. No timing precautions; both are generally well tolerated.", "minimumTimeSeparation": null, "mechanism": "L-carnitine shuttles long-chain fatty acids across the mitochondrial membrane for beta-oxidation, while CLA may influence fat storage and lipolysis upstream; the two act at different points of fat handling.", "evidenceLevel": "emerging", "sources": [ { "text": "Pooyandjoo M et al, The effect of L-carnitine on weight loss in adults: a systematic review and meta-analysis, Obesity Reviews, 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "L-carnitine supports transport of fatty acids into mitochondria for oxidation, which is mechanistically complementary to CLA's role in fat metabolism.", "clinicalSignificance": "Mechanistically complementary fat-metabolism pairing with no known adverse interaction.", "managementStrategy": "Reasonable to combine for body composition goals. No timing precautions; both are generally well tolerated.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "CLA", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "Combining CLA with fish oil may offset CLA's tendency to worsen some lipid and inflammatory markers, since omega-3s improve triglycerides and have anti-inflammatory effects.", "recommendation": "A sensible pairing; fish oil can counterbalance potential unfavorable lipid or insulin-sensitivity effects sometimes seen with CLA. No special timing needed.", "minimumTimeSeparation": null, "mechanism": "Higher-dose CLA has in some studies been linked to reduced insulin sensitivity and adverse lipid shifts, whereas fish oil omega-3s lower triglycerides and reduce inflammation, potentially mitigating these effects.", "evidenceLevel": "emerging", "sources": [ { "text": "Riserus U et al, Treatment with dietary trans10cis12 conjugated linoleic acid causes isomer-specific insulin resistance, Diabetes Care, 2002", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Skulas-Ray AC et al, Omega-3 fatty acids for the management of hypertriglyceridemia, Circulation, 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Combining CLA with fish oil may offset CLA's tendency to worsen some lipid and inflammatory markers, since omega-3s improve triglycerides and have anti-inflammatory effects.", "clinicalSignificance": "Fish oil may help counterbalance the less favorable metabolic effects of CLA.", "managementStrategy": "A sensible pairing; fish oil can counterbalance potential unfavorable lipid or insulin-sensitivity effects sometimes seen with CLA. No special timing needed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Cannabis (THC-Dominant)", "supplementBName": "Alcohol", "interactionType": "conflict", "severity": "serious", "description": "Combining THC-dominant cannabis with alcohol produces additive central nervous system depression and impairment, with greater sedation, dizziness, nausea, and markedly worse psychomotor and driving performance than either alone.", "recommendation": "Do not combine. The mix sharply increases impairment and accident risk; do not drive or operate machinery, and seek medical advice if severe vomiting, confusion, or loss of consciousness occurs.", "minimumTimeSeparation": null, "mechanism": "Alcohol can increase THC absorption and both act as CNS depressants, producing additive impairment of cognition, coordination, and reaction time along with cardiovascular and gastrointestinal effects.", "evidenceLevel": "strong", "sources": [ { "text": "Hartman RL et al. Controlled Cannabis Vaporizer Administration: Blood and Plasma Cannabinoids with and without Alcohol. Clin Chem. 2015;61(6):850-69.", "pmid": "26019183", "doi": "10.1373/clinchem.2015.238287", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26019183/", "publicSourceType": "PMID" }, { "text": "Downey LA et al. The effects of cannabis and alcohol on simulated driving: Influences of dose and experience. Accid Anal Prev. 2013;50:879-86.", "pmid": "22871272", "doi": "10.1016/j.aap.2012.07.016", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22871272/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Combining THC-dominant cannabis with alcohol produces additive central nervous system depression and impairment, with greater sedation, dizziness, nausea, and markedly worse psychomotor and driving performance than either alone.", "clinicalSignificance": "Co-use causes dangerous additive impairment and should be avoided.", "managementStrategy": "Do not combine. The mix sharply increases impairment and accident risk; do not drive or operate machinery, and seek medical advice if severe vomiting, confusion, or loss of consciousness occurs.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Cannabis (THC-Dominant)", "supplementBName": "Melatonin", "interactionType": "caution", "severity": "moderate", "description": "Both promote sedation, so taken together they can cause additive drowsiness, grogginess, and next-day impairment.", "recommendation": "Best avoided together; if combined, expect stronger sedation than either alone. Do not drive or operate machinery, and seek medical advice before combining if you take other sedating medications.", "minimumTimeSeparation": null, "mechanism": "Melatonin promotes sleep onset via MT1 and MT2 receptors while THC has independent sedative CNS effects; the two produce additive drowsiness.", "evidenceLevel": "emerging", "sources": [ { "text": "Babson KA et al, Cannabis, cannabinoids, and sleep: a review of the literature, Current Psychiatry Reports, 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both promote sedation, so taken together they can cause additive drowsiness, grogginess, and next-day impairment.", "clinicalSignificance": "Additive sedation makes next-day impairment and oversedation more likely.", "managementStrategy": "Best avoided together; if combined, expect stronger sedation than either alone. Do not drive or operate machinery, and seek medical advice before combining if you take other sedating medications.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Cannabis (THC-Dominant)", "supplementBName": "Valerian Root", "interactionType": "caution", "severity": "moderate", "description": "Valerian and THC-dominant cannabis both have sedative properties, so combining them can cause additive central nervous system depression and excessive drowsiness.", "recommendation": "Best avoided together; the combination can produce stronger than expected sedation. Do not drive or operate machinery, and seek medical advice if combined with other CNS depressants.", "minimumTimeSeparation": null, "mechanism": "Valerian appears to enhance GABAergic signaling to promote sedation, which adds to the independent CNS depressant effects of THC.", "evidenceLevel": "emerging", "sources": [ { "text": "Bent S et al, Valerian for sleep: a systematic review and meta-analysis, American Journal of Medicine, 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Valerian and THC-dominant cannabis both have sedative properties, so combining them can cause additive central nervous system depression and excessive drowsiness.", "clinicalSignificance": "Additive sedation raises the risk of oversedation and impairment.", "managementStrategy": "Best avoided together; the combination can produce stronger than expected sedation. Do not drive or operate machinery, and seek medical advice if combined with other CNS depressants.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Cannabis (THC-Dominant)", "supplementBName": "Ashwagandha", "interactionType": "caution", "severity": "moderate", "description": "Both can have sedative and CNS-depressant effects, so concurrent use may increase drowsiness and sedation.", "recommendation": "Best avoided together; if combined, monitor for excessive sedation, especially when starting. Do not drive or operate machinery until effects are known, and seek medical advice if combined with other sedatives.", "minimumTimeSeparation": null, "mechanism": "Ashwagandha has reported anxiolytic and mild sedative effects partly via GABAergic modulation, which can add to the sedative CNS effects of THC.", "evidenceLevel": "emerging", "sources": [ { "text": "Salve J et al, Adaptogenic and anxiolytic effects of ashwagandha root extract in healthy adults, Cureus, 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both can have sedative and CNS-depressant effects, so concurrent use may increase drowsiness and sedation.", "clinicalSignificance": "Potential additive sedation warrants caution with concurrent use.", "managementStrategy": "Best avoided together; if combined, monitor for excessive sedation, especially when starting. Do not drive or operate machinery until effects are known, and seek medical advice if combined with other sedatives.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Chaga", "supplementBName": "Berberine", "interactionType": "caution", "severity": "moderate", "description": "Both can lower blood glucose, so combining them may produce additive hypoglycemic effects, particularly in people taking antidiabetic medications.", "recommendation": "Monitor blood glucose when combining. Watch for hypoglycemia symptoms (shakiness, sweating, confusion) and coordinate with a clinician if on diabetes medication.", "minimumTimeSeparation": null, "mechanism": "Chaga (Inonotus obliquus) has shown blood-glucose-lowering effects in preclinical and limited human data, while berberine reduces glucose via AMPK activation and decreased hepatic glucose output; the effects can be additive.", "evidenceLevel": "emerging", "sources": [ { "text": "Lu Y et al, Inonotus obliquus polysaccharides and antidiabetic activity: a review, International Journal of Biological Macromolecules, 2021", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Yin J et al, Efficacy of berberine in patients with type 2 diabetes, Metabolism, 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both can lower blood glucose, so combining them may produce additive hypoglycemic effects, particularly in people taking antidiabetic medications.", "clinicalSignificance": "Additive glucose lowering merits monitoring, especially with diabetes therapy.", "managementStrategy": "Monitor blood glucose when combining. Watch for hypoglycemia symptoms (shakiness, sweating, confusion) and coordinate with a clinician if on diabetes medication.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Chaga", "supplementBName": "Reishi", "interactionType": "synergy", "severity": "info", "description": "Chaga and reishi are both medicinal mushrooms providing beta-glucan polysaccharides, often stacked for complementary immune-modulating and antioxidant support.", "recommendation": "Reasonable to combine. Note that both may have mild antiplatelet activity, so monitor for bruising or bleeding if also using anticoagulants or before surgery.", "minimumTimeSeparation": null, "mechanism": "Both mushrooms supply beta-glucans that modulate innate immune cell activity and provide antioxidant compounds, giving overlapping and complementary immune support.", "evidenceLevel": "emerging", "sources": [ { "text": "Wachtel-Galor S et al, Ganoderma lucidum (Lingzhi or Reishi): a medicinal mushroom, in Herbal Medicine: Biomolecular and Clinical Aspects, 2011", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Glamoclija J et al, Chemical characterization and biological activity of Chaga, Journal of Ethnopharmacology, 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Chaga and reishi are both medicinal mushrooms providing beta-glucan polysaccharides, often stacked for complementary immune-modulating and antioxidant support.", "clinicalSignificance": "Complementary immune-support pairing; mind potential additive antiplatelet effects.", "managementStrategy": "Reasonable to combine. Note that both may have mild antiplatelet activity, so monitor for bruising or bleeding if also using anticoagulants or before surgery.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Chaga", "supplementBName": "Turkey Tail", "interactionType": "synergy", "severity": "info", "description": "Both are beta-glucan-rich medicinal mushrooms commonly combined for complementary immune modulation.", "recommendation": "Acceptable to combine for immune support. No special timing needed; people on immunosuppressant therapy should consult a clinician given the immune-modulating activity.", "minimumTimeSeparation": null, "mechanism": "Turkey tail provides polysaccharide-K and polysaccharide-peptide beta-glucans that stimulate immune cell activity, overlapping with chaga's beta-glucan-mediated immune modulation.", "evidenceLevel": "emerging", "sources": [ { "text": "Standish LJ et al, Trametes versicolor mushroom immune therapy in breast cancer, Journal of the Society for Integrative Oncology, 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both are beta-glucan-rich medicinal mushrooms commonly combined for complementary immune modulation.", "clinicalSignificance": "Complementary immune-support pairing; caution in those on immunosuppressants.", "managementStrategy": "Acceptable to combine for immune support. No special timing needed; people on immunosuppressant therapy should consult a clinician given the immune-modulating activity.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Chondroitin", "supplementBName": "Glucosamine", "interactionType": "synergy", "severity": "info", "description": "Co-administration is the most studied combination for osteoarthritis, with potential additive effects on cartilage matrix support and symptomatic joint relief.", "recommendation": "These two are commonly and safely taken together. Take as a combined daily dose and allow several weeks to assess symptomatic benefit.", "minimumTimeSeparation": null, "mechanism": "Glucosamine provides a substrate for glycosaminoglycan synthesis while chondroitin contributes to cartilage matrix structure and inhibits degradative enzymes, supporting complementary roles in cartilage homeostasis.", "evidenceLevel": "moderate", "sources": [ { "text": "Clegg DO et al., Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis, New England Journal of Medicine, 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Hochberg MC et al., Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis (MOVES trial), Annals of the Rheumatic Diseases, 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Co-administration is the most studied combination for osteoarthritis, with potential additive effects on cartilage matrix support and symptomatic joint relief.", "clinicalSignificance": "A widely used, generally well tolerated pairing for joint health, though clinical benefit varies between individuals.", "managementStrategy": "These two are commonly and safely taken together. Take as a combined daily dose and allow several weeks to assess symptomatic benefit.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Chondroitin", "supplementBName": "Turmeric/Curcumin", "interactionType": "caution", "severity": "moderate", "description": "Both may have mild antiplatelet effects, so combining them could modestly increase bleeding tendency, particularly in people also taking anticoagulant or antiplatelet medication.", "recommendation": "Generally fine together for joint support in healthy people. If you take blood thinners or are scheduled for surgery, discuss with your clinician and consider pausing before procedures.", "minimumTimeSeparation": null, "mechanism": "Chondroitin sulfate is a glycosaminoglycan with weak anticoagulant properties and curcumin inhibits platelet aggregation and thromboxane synthesis, so the two may have additive effects on platelet function and bleeding tendency.", "evidenceLevel": "emerging", "sources": [ { "text": "Hwang KA et al., Anti-inflammatory and antiplatelet effects of curcumin, Journal of Medicinal Food, 2009", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Rozenfeld V, Crader M, Possible augmentation of warfarin effect by glucosamine-chondroitin, American Journal of Health-System Pharmacy, 2004", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both may have mild antiplatelet effects, so combining them could modestly increase bleeding tendency, particularly in people also taking anticoagulant or antiplatelet medication.", "clinicalSignificance": "Low risk in healthy users, but bleeding risk warrants caution alongside anticoagulants or before surgery.", "managementStrategy": "Generally fine together for joint support in healthy people. If you take blood thinners or are scheduled for surgery, discuss with your clinician and consider pausing before procedures.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Chondroitin", "supplementBName": "Boswellia", "interactionType": "synergy", "severity": "info", "description": "Combining chondroitin with boswellia may provide complementary anti-inflammatory and cartilage-supportive effects in osteoarthritis.", "recommendation": "Reasonable to combine for joint support. Allow several weeks to evaluate symptomatic response.", "minimumTimeSeparation": null, "mechanism": "Boswellic acids inhibit 5-lipoxygenase and leukotriene-driven inflammation while chondroitin supports cartilage matrix and dampens degradative enzymes, addressing joint health through different pathways.", "evidenceLevel": "emerging", "sources": [ { "text": "Sengupta K et al., A double blind, randomized, placebo controlled study of the efficacy and safety of 5-Loxin for treatment of osteoarthritis of the knee, Arthritis Research and Therapy, 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Kimmatkar N et al., Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee, Phytomedicine, 2003", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Combining chondroitin with boswellia may provide complementary anti-inflammatory and cartilage-supportive effects in osteoarthritis.", "clinicalSignificance": "A plausible complementary joint-support pairing, though direct combination trials are limited.", "managementStrategy": "Reasonable to combine for joint support. Allow several weeks to evaluate symptomatic response.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Cocaine", "supplementBName": "Alcohol", "interactionType": "contraindicated", "severity": "dangerous", "description": "Combining cocaine with alcohol produces cocaethylene in the liver, a longer-lasting and more cardiotoxic compound that sharply increases the risk of heart attack, arrhythmia, and sudden death.", "recommendation": "Do not combine. This is a dangerous combination associated with sudden cardiac death. If experiencing chest pain, severe agitation, or breathing difficulty, seek emergency medical care immediately.", "minimumTimeSeparation": null, "mechanism": "Hepatic transesterification of cocaine in the presence of ethanol forms cocaethylene, which has a longer half-life than cocaine and potently blocks dopamine reuptake while exerting greater cardiotoxicity and additive sympathetic stimulation.", "evidenceLevel": "strong", "sources": [ { "text": "Pennings EJ et al. Effects of concurrent use of alcohol and cocaine. Addiction. 2002;97(7):773-83.", "pmid": "12133112", "doi": "10.1046/j.1360-0443.2002.00158.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12133112/", "publicSourceType": "PMID" }, { "text": "Farré M et al. Alcohol and cocaine interactions in humans. J Pharmacol Exp Ther. 1993;266(3):1364-73.", "pmid": "8371143", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8371143/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Combining cocaine with alcohol produces cocaethylene in the liver, a longer-lasting and more cardiotoxic compound that sharply increases the risk of heart attack, arrhythmia, and sudden death.", "clinicalSignificance": "Cocaethylene formation makes this one of the most cardiotoxic recreational drug combinations and is linked to sudden death.", "managementStrategy": "Do not combine. This is a dangerous combination associated with sudden cardiac death. If experiencing chest pain, severe agitation, or breathing difficulty, seek emergency medical care immediately.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Cocaine", "supplementBName": "Nicotine", "interactionType": "conflict", "severity": "serious", "description": "Using cocaine and nicotine together compounds sympathetic stimulation, raising heart rate, blood pressure, and coronary vasoconstriction, which increases cardiovascular strain and the risk of cardiac events.", "recommendation": "Do not combine. The two together place additive strain on the heart and coronary arteries. Seek medical advice for stimulant use and stop if chest pain or palpitations occur.", "minimumTimeSeparation": null, "mechanism": "Both are sympathomimetic: cocaine blocks catecholamine reuptake and nicotine triggers catecholamine release, producing additive coronary vasoconstriction, tachycardia, and increased myocardial oxygen demand.", "evidenceLevel": "moderate", "sources": [ { "text": "Moliterno DJ et al. Coronary-artery vasoconstriction induced by cocaine, cigarette smoking, or both. N Engl J Med. 1994;330(7):454-9.", "pmid": "8289850", "doi": "10.1056/NEJM199402173300702", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8289850/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Using cocaine and nicotine together compounds sympathetic stimulation, raising heart rate, blood pressure, and coronary vasoconstriction, which increases cardiovascular strain and the risk of cardiac events.", "clinicalSignificance": "Concurrent use amplifies coronary vasoconstriction and cardiac workload beyond either substance alone.", "managementStrategy": "Do not combine. The two together place additive strain on the heart and coronary arteries. Seek medical advice for stimulant use and stop if chest pain or palpitations occur.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Colostrum", "supplementBName": "Probiotics", "interactionType": "synergy", "severity": "info", "description": "Colostrum and probiotics may work together to support gut barrier integrity and a healthy microbiome, with colostrum providing prebiotic and immune factors that can favor probiotic colonization.", "recommendation": "Safe and complementary to take together. For routine gut support, taking them in the same window is reasonable.", "minimumTimeSeparation": null, "mechanism": "Bovine colostrum supplies immunoglobulins, lactoferrin, and oligosaccharides that support intestinal barrier function and can act as prebiotic substrate, potentially enhancing probiotic survival and adhesion.", "evidenceLevel": "emerging", "sources": [ { "text": "Playford RJ, Weiser MJ, Bovine colostrum: its constituents and uses, Nutrients, 2021", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Rathe M et al., Clinical applications of bovine colostrum therapy, Nutrition Reviews, 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Colostrum and probiotics may work together to support gut barrier integrity and a healthy microbiome, with colostrum providing prebiotic and immune factors that can favor probiotic colonization.", "clinicalSignificance": "A plausible gut-supportive combination, though direct human co-supplementation data are limited.", "managementStrategy": "Safe and complementary to take together. For routine gut support, taking them in the same window is reasonable.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Colostrum", "supplementBName": "L-Glutamine", "interactionType": "synergy", "severity": "info", "description": "Colostrum and L-glutamine are frequently combined for gut barrier support, as both contribute to intestinal mucosal repair and integrity.", "recommendation": "Reasonable to combine for gut health. No timing separation needed.", "minimumTimeSeparation": null, "mechanism": "L-glutamine is a primary fuel for enterocytes and supports tight junction integrity, complementing colostrum-derived growth factors and immunoglobulins that promote mucosal healing.", "evidenceLevel": "emerging", "sources": [ { "text": "Rao R, Samak G, Role of glutamine in protection of intestinal epithelial tight junctions, Journal of Epithelial Biology and Pharmacology, 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Playford RJ, Weiser MJ, Bovine colostrum: its constituents and uses, Nutrients, 2021", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Colostrum and L-glutamine are frequently combined for gut barrier support, as both contribute to intestinal mucosal repair and integrity.", "clinicalSignificance": "A commonly used gut-repair pairing with complementary mechanisms on the intestinal lining.", "managementStrategy": "Reasonable to combine for gut health. No timing separation needed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Colostrum", "supplementBName": "Lactobacillus Rhamnosus", "interactionType": "synergy", "severity": "info", "description": "Colostrum components may support colonization and activity of Lactobacillus rhamnosus, complementing its effects on gut barrier and immune function.", "recommendation": "Safe to combine for gut and immune support. Taking together is acceptable.", "minimumTimeSeparation": null, "mechanism": "Colostrum oligosaccharides and lactoferrin can act as prebiotic and antimicrobial-modulating factors that favor beneficial Lactobacillus species, while both support intestinal barrier and immune signaling.", "evidenceLevel": "emerging", "sources": [ { "text": "Playford RJ, Weiser MJ, Bovine colostrum: its constituents and uses, Nutrients, 2021", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Hojsak I, Probiotics in functional gastrointestinal disorders, Advances in Experimental Medicine and Biology, 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Colostrum components may support colonization and activity of Lactobacillus rhamnosus, complementing its effects on gut barrier and immune function.", "clinicalSignificance": "A complementary gut and immune pairing, though specific co-administration trials are sparse.", "managementStrategy": "Safe to combine for gut and immune support. Taking together is acceptable.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "D-Aspartic Acid", "supplementBName": "Zinc", "interactionType": "synergy", "severity": "info", "description": "Both are studied in the context of supporting testosterone and male reproductive function, and may have complementary roles in men who are deficient.", "recommendation": "Reasonable to combine, particularly where zinc status is low. Note that evidence for testosterone benefit in healthy men is mixed for both.", "minimumTimeSeparation": null, "mechanism": "D-aspartic acid acts in the hypothalamic-pituitary axis to stimulate luteinizing hormone and testosterone release, while adequate zinc is a cofactor for testosterone synthesis and supports the gonadal axis.", "evidenceLevel": "emerging", "sources": [ { "text": "Topo E et al., The role and molecular mechanism of D-aspartic acid in the release and synthesis of LH and testosterone in humans and rats, Reproductive Biology and Endocrinology, 2009", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Prasad AS et al., Zinc status and serum testosterone levels of healthy adults, Nutrition, 1996", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both are studied in the context of supporting testosterone and male reproductive function, and may have complementary roles in men who are deficient.", "clinicalSignificance": "A plausible complementary pairing for the testosterone axis, but benefits are most likely only in those with low baseline status.", "managementStrategy": "Reasonable to combine, particularly where zinc status is low. Note that evidence for testosterone benefit in healthy men is mixed for both.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "D-Aspartic Acid", "supplementBName": "Ashwagandha", "interactionType": "synergy", "severity": "info", "description": "Both are marketed for supporting testosterone and male reproductive parameters and may act through complementary pathways on the gonadal axis and stress hormones.", "recommendation": "Acceptable to combine for those targeting hormonal or fertility support. Evidence is stronger for ashwagandha than for D-aspartic acid in healthy men.", "minimumTimeSeparation": null, "mechanism": "D-aspartic acid stimulates luteinizing hormone and testosterone release centrally, while ashwagandha may support testosterone and semen parameters partly by lowering cortisol and oxidative stress in the testes.", "evidenceLevel": "emerging", "sources": [ { "text": "Lopresti AL et al., A randomized, double-blind, placebo-controlled study examining the hormonal and vitality effects of ashwagandha in aging men, American Journal of Mens Health, 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Topo E et al., The role and molecular mechanism of D-aspartic acid in the release and synthesis of LH and testosterone, Reproductive Biology and Endocrinology, 2009", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both are marketed for supporting testosterone and male reproductive parameters and may act through complementary pathways on the gonadal axis and stress hormones.", "clinicalSignificance": "A plausible complementary hormonal-support pairing, though robust combination data are lacking.", "managementStrategy": "Acceptable to combine for those targeting hormonal or fertility support. Evidence is stronger for ashwagandha than for D-aspartic acid in healthy men.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "D-Aspartic Acid", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "info", "description": "Magnesium status is linked to testosterone, so magnesium glycinate may complement D-aspartic acid in supporting the androgen axis, especially where magnesium intake is suboptimal.", "recommendation": "Reasonable to combine. Magnesium glycinate is well tolerated; benefit on testosterone is most likely with low baseline magnesium.", "minimumTimeSeparation": null, "mechanism": "Magnesium reduces binding of testosterone to sex hormone binding globulin and supports bioavailable testosterone, while D-aspartic acid acts centrally to stimulate hormone release, giving complementary effects on the axis.", "evidenceLevel": "emerging", "sources": [ { "text": "Maggio M et al., Magnesium and anabolic hormones in older men, International Journal of Andrology, 2011", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Cinar V et al., Effects of magnesium supplementation on testosterone levels of athletes and sedentary subjects at rest and after exhaustion, Biological Trace Element Research, 2011", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Magnesium status is linked to testosterone, so magnesium glycinate may complement D-aspartic acid in supporting the androgen axis, especially where magnesium intake is suboptimal.", "clinicalSignificance": "Complementary support for the testosterone axis, with effects most relevant when magnesium status is low.", "managementStrategy": "Reasonable to combine. Magnesium glycinate is well tolerated; benefit on testosterone is most likely with low baseline magnesium.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Echinacea", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Echinacea and vitamin C are commonly combined for upper respiratory immune support, with modest evidence for reducing cold duration or severity when used together.", "recommendation": "Safe and common to combine at the onset of cold symptoms. No timing separation needed.", "minimumTimeSeparation": null, "mechanism": "Echinacea modulates innate immune activity including macrophage and cytokine responses, while vitamin C supports neutrophil function and antioxidant defenses, providing complementary immune support.", "evidenceLevel": "emerging", "sources": [ { "text": "Karsch-Volk M et al., Echinacea for preventing and treating the common cold, Cochrane Database of Systematic Reviews, 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Hemila H, Chalker E, Vitamin C for preventing and treating the common cold, Cochrane Database of Systematic Reviews, 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Echinacea and vitamin C are commonly combined for upper respiratory immune support, with modest evidence for reducing cold duration or severity when used together.", "clinicalSignificance": "A widely used immune-support combination with modest evidence for common cold symptoms.", "managementStrategy": "Safe and common to combine at the onset of cold symptoms. No timing separation needed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Echinacea", "supplementBName": "Zinc", "interactionType": "synergy", "severity": "info", "description": "Echinacea and zinc are frequently paired for cold and upper respiratory support, with zinc lozenges showing evidence for shortening cold duration.", "recommendation": "Reasonable to combine at the first sign of a cold. Take zinc with food if it causes nausea.", "minimumTimeSeparation": null, "mechanism": "Zinc interferes with rhinovirus replication and supports immune cell function, while echinacea modulates innate immune and cytokine responses, giving complementary antiviral and immune-supportive actions.", "evidenceLevel": "moderate", "sources": [ { "text": "Hemila H, Zinc lozenges and the common cold: a meta-analysis comparing zinc acetate and zinc gluconate, Journal of the Royal Society of Medicine Open, 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Karsch-Volk M et al., Echinacea for preventing and treating the common cold, Cochrane Database of Systematic Reviews, 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Echinacea and zinc are frequently paired for cold and upper respiratory support, with zinc lozenges showing evidence for shortening cold duration.", "clinicalSignificance": "A common cold-season pairing; zinc has the stronger individual evidence for reducing cold duration.", "managementStrategy": "Reasonable to combine at the first sign of a cold. Take zinc with food if it causes nausea.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Echinacea", "supplementBName": "Elderberry", "interactionType": "synergy", "severity": "info", "description": "Echinacea and elderberry are commonly combined for upper respiratory and cold or flu symptom support through complementary immune-modulating effects.", "recommendation": "Acceptable to combine for short-term immune support during cold and flu season. Use short courses rather than continuous long-term use.", "minimumTimeSeparation": null, "mechanism": "Elderberry anthocyanins have antiviral and cytokine-modulating activity while echinacea stimulates innate immune responses, providing overlapping support against respiratory viral symptoms.", "evidenceLevel": "emerging", "sources": [ { "text": "Hawkins J et al., Black elderberry (Sambucus nigra) supplementation effectively treats upper respiratory symptoms: a meta-analysis, Complementary Therapies in Medicine, 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Karsch-Volk M et al., Echinacea for preventing and treating the common cold, Cochrane Database of Systematic Reviews, 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Echinacea and elderberry are commonly combined for upper respiratory and cold or flu symptom support through complementary immune-modulating effects.", "clinicalSignificance": "A plausible short-term immune-support pairing for cold and flu symptoms.", "managementStrategy": "Acceptable to combine for short-term immune support during cold and flu season. Use short courses rather than continuous long-term use.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Elderberry", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Combined antioxidant and immune support during early upper respiratory infection, with complementary effects on innate immune function.", "recommendation": "Reasonable to combine at standard doses during the early days of a cold; no special separation needed.", "minimumTimeSeparation": null, "mechanism": "Elderberry anthocyanins and Vitamin C both provide antioxidant activity and modulate cytokine and neutrophil function, supporting innate antiviral defense through non-overlapping pathways.", "evidenceLevel": "emerging", "sources": [ { "text": "Hawkins J et al., Black elderberry (Sambucus nigra) supplementation effectively treats upper respiratory symptoms: a meta-analysis, Complementary Therapies in Medicine, 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Hemila H, Vitamin C and infections, Nutrients, 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Combined antioxidant and immune support during early upper respiratory infection, with complementary effects on innate immune function.", "clinicalSignificance": "A common, low-risk immune-support pairing with plausible additive benefit but modest clinical evidence.", "managementStrategy": "Reasonable to combine at standard doses during the early days of a cold; no special separation needed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Elderberry", "supplementBName": "Zinc", "interactionType": "synergy", "severity": "info", "description": "Both target early-phase viral upper respiratory illness through distinct antiviral and immune-modulating mechanisms, supporting an additive symptom-duration benefit.", "recommendation": "Reasonable to combine during the early days of a cold; take zinc with food if it causes nausea. No timing separation required.", "minimumTimeSeparation": null, "mechanism": "Zinc inhibits viral replication and supports T-cell function while elderberry flavonoids modulate cytokine release, giving complementary rather than competing effects on the immune response.", "evidenceLevel": "emerging", "sources": [ { "text": "Hawkins J et al., Black elderberry (Sambucus nigra) supplementation effectively treats upper respiratory symptoms: a meta-analysis, Complementary Therapies in Medicine, 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Hemila H, Zinc lozenges and the common cold: a meta-analysis, BMC Family Practice, 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both target early-phase viral upper respiratory illness through distinct antiviral and immune-modulating mechanisms, supporting an additive symptom-duration benefit.", "clinicalSignificance": "A plausible additive cold-support stack; benefit is modest and evidence is short-term.", "managementStrategy": "Reasonable to combine during the early days of a cold; take zinc with food if it causes nausea. No timing separation required.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Fenugreek", "supplementBName": "Berberine", "interactionType": "caution", "severity": "moderate", "description": "Additive glucose-lowering effect that can increase the risk of hypoglycemia, especially in people also taking antidiabetic medication.", "recommendation": "Monitor blood glucose if combining, watch for hypoglycemia symptoms, and consult a clinician before stacking these with diabetes medications.", "minimumTimeSeparation": null, "mechanism": "Fenugreek slows carbohydrate absorption and improves insulin sensitivity while berberine activates AMPK and reduces hepatic glucose output; the combined effect can lower blood glucose more than either alone.", "evidenceLevel": "moderate", "sources": [ { "text": "Neelakantan N et al. Effect of fenugreek (Trigonella foenum-graecum L.) intake on glycemia: a meta-analysis of clinical trials. Nutr J. 2014;13:7.", "pmid": "24438170", "doi": "10.1186/1475-2891-13-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24438170/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive glucose-lowering effect that can increase the risk of hypoglycemia, especially in people also taking antidiabetic medication.", "clinicalSignificance": "Meaningful additive hypoglycemic risk that warrants glucose monitoring in diabetic users.", "managementStrategy": "Monitor blood glucose if combining, watch for hypoglycemia symptoms, and consult a clinician before stacking these with diabetes medications.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Fenugreek", "supplementBName": "Iron", "interactionType": "timingSensitive", "severity": "moderate", "description": "Fenugreek's high soluble fiber and polyphenol content can bind non-heme iron in the gut and reduce its absorption when taken together.", "recommendation": "Separate fenugreek and iron supplements by at least 2 hours to preserve iron absorption.", "minimumTimeSeparation": "2 hours", "mechanism": "The mucilaginous fiber and tannin-like polyphenols in fenugreek chelate and trap non-heme iron in the gastrointestinal tract, lowering the fraction available for absorption.", "evidenceLevel": "emerging", "sources": [ { "text": "Srinivasan K, Fenugreek (Trigonella foenum-graecum): a review of health beneficial physiological effects, Food Reviews International, 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Hurrell R, Egli I, Iron bioavailability and dietary reference values, American Journal of Clinical Nutrition, 2010. Iron bioavailability and dietary reference values. Am J Clin Nutr. 2010.", "pmid": "20200263", "doi": "10.3945/ajcn.2010.28674F", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20200263/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Fenugreek's high soluble fiber and polyphenol content can bind non-heme iron in the gut and reduce its absorption when taken together.", "clinicalSignificance": "Spacing the two doses prevents fenugreek from blunting iron repletion.", "managementStrategy": "Separate fenugreek and iron supplements by at least 2 hours to preserve iron absorption.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "GABA", "supplementBName": "L-Theanine", "interactionType": "synergy", "severity": "info", "description": "Complementary calming effect, with L-theanine promoting relaxed alertness and increasing alpha brain-wave activity alongside GABA's inhibitory signaling.", "recommendation": "Reasonable to combine for relaxation or sleep onset; start low and assess your own response. No timing separation needed.", "minimumTimeSeparation": null, "mechanism": "L-theanine modulates glutamate and GABA neurotransmission and raises alpha-wave activity, while supplemental GABA may act on peripheral and enteric GABA receptors; together they promote a calm state through complementary pathways.", "evidenceLevel": "emerging", "sources": [ { "text": "Nobre AC et al. L-theanine, a natural constituent in tea, and its effect on mental state. Asia Pac J Clin Nutr. 2008;17 Suppl 1:167-8.", "pmid": "18296328", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18296328/", "publicSourceType": "PMID" }, { "text": "Boonstra E et al. Neurotransmitters as food supplements: the effects of GABA on brain and behavior. Front Psychol. 2015;6:1520.", "pmid": "26500584", "doi": "10.3389/fpsyg.2015.01520", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26500584/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Complementary calming effect, with L-theanine promoting relaxed alertness and increasing alpha brain-wave activity alongside GABA's inhibitory signaling.", "clinicalSignificance": "A popular, low-risk relaxation pairing with plausible additive calming effect.", "managementStrategy": "Reasonable to combine for relaxation or sleep onset; start low and assess your own response. No timing separation needed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "GABA", "supplementBName": "Valerian Root", "interactionType": "caution", "severity": "moderate", "description": "Additive sedation and CNS depression, which can cause excessive drowsiness, especially if combined with alcohol or other sedatives.", "recommendation": "Use the combination only at night, avoid driving or operating machinery afterward, and do not combine with alcohol or prescription sedatives without medical advice.", "minimumTimeSeparation": null, "mechanism": "Valerian compounds enhance GABAergic transmission by acting on GABA-A receptors and inhibiting GABA breakdown, which can compound the inhibitory, sedating effects associated with supplemental GABA.", "evidenceLevel": "moderate", "sources": [ { "text": "Bent S et al. Valerian for sleep: a systematic review and meta-analysis. Am J Med. 2006;119(12):1005-12.", "pmid": "17145239", "doi": "10.1016/j.amjmed.2006.02.026", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17145239/", "publicSourceType": "PMID" }, { "text": "Boonstra E et al. Neurotransmitters as food supplements: the effects of GABA on brain and behavior. Front Psychol. 2015;6:1520.", "pmid": "26500584", "doi": "10.3389/fpsyg.2015.01520", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26500584/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive sedation and CNS depression, which can cause excessive drowsiness, especially if combined with alcohol or other sedatives.", "clinicalSignificance": "Stacking two GABAergic agents raises the chance of excess sedation and next-day grogginess.", "managementStrategy": "Use the combination only at night, avoid driving or operating machinery afterward, and do not combine with alcohol or prescription sedatives without medical advice.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "GABA", "supplementBName": "Melatonin", "interactionType": "caution", "severity": "moderate", "description": "Combined use for sleep can produce additive drowsiness and next-morning grogginess, and both lower nighttime arousal.", "recommendation": "If combining for sleep, take both shortly before bed, keep doses modest, and avoid activities requiring alertness afterward.", "minimumTimeSeparation": null, "mechanism": "Melatonin shifts circadian timing and promotes sleep onset via MT1/MT2 receptors while GABA increases inhibitory tone; together they can deepen sedation and lower arousal more than either alone.", "evidenceLevel": "emerging", "sources": [ { "text": "Costello RB et al. The effectiveness of melatonin for promoting healthy sleep: a rapid evidence assessment of the literature. Nutr J. 2014;13:106.", "pmid": "25380732", "doi": "10.1186/1475-2891-13-106", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25380732/", "publicSourceType": "PMID" }, { "text": "Boonstra E et al. Neurotransmitters as food supplements: the effects of GABA on brain and behavior. Front Psychol. 2015;6:1520.", "pmid": "26500584", "doi": "10.3389/fpsyg.2015.01520", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26500584/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Combined use for sleep can produce additive drowsiness and next-morning grogginess, and both lower nighttime arousal.", "clinicalSignificance": "A reasonable sleep stack, but watch for additive sedation and morning grogginess.", "managementStrategy": "If combining for sleep, take both shortly before bed, keep doses modest, and avoid activities requiring alertness afterward.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Grape Seed Extract", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Vitamin C helps regenerate oxidized proanthocyanidin antioxidants, and the two together support endothelial and vascular antioxidant capacity.", "recommendation": "Reasonable to combine at standard doses for vascular or antioxidant support; no timing separation needed.", "minimumTimeSeparation": null, "mechanism": "Vitamin C can reduce oxidized grape seed proanthocyanidins back to their active antioxidant form, recycling polyphenol antioxidant capacity and complementing nitric-oxide-mediated endothelial effects.", "evidenceLevel": "emerging", "sources": [ { "text": "Bagchi D et al., Free radicals and grape seed proanthocyanidin extract: importance in human health and disease prevention, Toxicology, 2000", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Carr AC, Frei B, Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans, American Journal of Clinical Nutrition, 1999", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin C helps regenerate oxidized proanthocyanidin antioxidants, and the two together support endothelial and vascular antioxidant capacity.", "clinicalSignificance": "A complementary antioxidant pairing with plausible additive vascular benefit.", "managementStrategy": "Reasonable to combine at standard doses for vascular or antioxidant support; no timing separation needed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Grape Seed Extract", "supplementBName": "Nattokinase", "interactionType": "caution", "severity": "moderate", "description": "Both can reduce platelet aggregation or affect clotting, so combining them may additively increase bleeding risk.", "recommendation": "Use caution when combining, especially if taking anticoagulant or antiplatelet drugs, and discontinue before surgery; consult a clinician.", "minimumTimeSeparation": null, "mechanism": "Grape seed proanthocyanidins inhibit platelet aggregation while nattokinase has fibrinolytic and antithrombotic activity; the combined effect can shift hemostasis toward reduced clotting.", "evidenceLevel": "emerging", "sources": [ { "text": "Vitseva O et al. Grape seed and skin extracts inhibit platelet function and release of reactive oxygen intermediates. J Cardiovasc Pharmacol. 2005;46(4):445-51.", "pmid": "16160595", "doi": "10.1097/01.fjc.0000176727.67066.1c", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16160595/", "publicSourceType": "PMID" }, { "text": "Weng Y et al. Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease. Int J Mol Sci. 2017;18(3).", "pmid": "28264497", "doi": "10.3390/ijms18030523", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28264497/", "publicSourceType": "PMID" }, { "text": "Kurosawa Y et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep. 2015;5:11601.", "pmid": "26109079", "doi": "10.1038/srep11601", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26109079/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both can reduce platelet aggregation or affect clotting, so combining them may additively increase bleeding risk.", "clinicalSignificance": "Stacking two agents that impair clotting raises bleeding risk, particularly with concurrent blood thinners.", "managementStrategy": "Use caution when combining, especially if taking anticoagulant or antiplatelet drugs, and discontinue before surgery; consult a clinician.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Grape Seed Extract", "supplementBName": "Pine Bark Extract", "interactionType": "synergy", "severity": "info", "description": "Both are oligomeric proanthocyanidin sources with overlapping antioxidant and endothelial nitric-oxide-supporting effects, giving additive vascular antioxidant support.", "recommendation": "Combining is reasonable but largely redundant given the overlapping mechanism; consider whether one alone meets your goal to avoid unnecessary dosing.", "minimumTimeSeparation": null, "mechanism": "Grape seed and pine bark extracts both supply oligomeric proanthocyanidins that scavenge free radicals and enhance endothelial nitric oxide; their mechanisms overlap rather than diverge.", "evidenceLevel": "emerging", "sources": [ { "text": "Bagchi D et al., Free radicals and grape seed proanthocyanidin extract: importance in human health and disease prevention, Toxicology, 2000", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Rohdewald P, A review of the French maritime pine bark extract (Pycnogenol), International Journal of Clinical Pharmacology and Therapeutics, 2002", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both are oligomeric proanthocyanidin sources with overlapping antioxidant and endothelial nitric-oxide-supporting effects, giving additive vascular antioxidant support.", "clinicalSignificance": "Largely redundant antioxidant pairing; safe but offers little beyond either extract alone.", "managementStrategy": "Combining is reasonable but largely redundant given the overlapping mechanism; consider whether one alone meets your goal to avoid unnecessary dosing.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "HMB", "supplementBName": "Creatine", "interactionType": "synergy", "severity": "info", "description": "Complementary effects on lean mass and strength, with creatine enhancing high-intensity performance and HMB reducing muscle protein breakdown.", "recommendation": "Reasonable to combine as part of a resistance-training and protein-adequate program; no timing separation required.", "minimumTimeSeparation": null, "mechanism": "Creatine increases phosphocreatine availability for ATP regeneration during high-intensity work, while HMB attenuates proteolysis and supports muscle repair; the two act on distinct, non-competing pathways.", "evidenceLevel": "moderate", "sources": [ { "text": "Jowko E et al., Creatine and beta-hydroxy-beta-methylbutyrate (HMB) additively increase lean body mass and muscle strength during a weight-training program, Nutrition, 2001", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Wilson JM et al., International Society of Sports Nutrition position stand: beta-hydroxy-beta-methylbutyrate (HMB), Journal of the International Society of Sports Nutrition, 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Complementary effects on lean mass and strength, with creatine enhancing high-intensity performance and HMB reducing muscle protein breakdown.", "clinicalSignificance": "A reasonable performance and lean-mass stack with complementary, well-tolerated mechanisms.", "managementStrategy": "Reasonable to combine as part of a resistance-training and protein-adequate program; no timing separation required.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "HMB", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "info", "description": "Vitamin D supports muscle function and the response to HMB, with combined supplementation showing greater gains in muscle strength and quality, particularly in older or deficient adults.", "recommendation": "Reasonable to combine, especially if vitamin D status is low; check and correct vitamin D levels for best muscle response.", "minimumTimeSeparation": null, "mechanism": "Vitamin D acts on muscle vitamin D receptors to support protein synthesis and fiber function, which appears to enhance the anabolic and anti-catabolic effects of HMB on muscle.", "evidenceLevel": "moderate", "sources": [ { "text": "Fuller JC et al., Vitamin D status affects strength gains in older adults supplemented with a combination of beta-hydroxy-beta-methylbutyrate, arginine, and lysine, JPEN Journal of Parenteral and Enteral Nutrition, 2011", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Stout JR et al., Effect of calcium beta-hydroxy-beta-methylbutyrate (CaHMB) with and without resistance training in men and women 65+ years, Experimental Gerontology, 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Vitamin D supports muscle function and the response to HMB, with combined supplementation showing greater gains in muscle strength and quality, particularly in older or deficient adults.", "clinicalSignificance": "Adequate vitamin D status improves the muscle benefit of HMB, especially in older adults.", "managementStrategy": "Reasonable to combine, especially if vitamin D status is low; check and correct vitamin D levels for best muscle response.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "HMB", "supplementBName": "BCAAs", "interactionType": "synergy", "severity": "info", "description": "HMB is a metabolite of leucine, so BCAAs and HMB act on related anabolic and anti-catabolic pathways to support muscle protein balance.", "recommendation": "Combining is reasonable around training, though the benefit overlaps since HMB derives from leucine; prioritize total protein intake first.", "minimumTimeSeparation": null, "mechanism": "Leucine (a BCAA) stimulates muscle protein synthesis via mTOR signaling, and HMB, its downstream metabolite, reduces protein degradation; the two influence overlapping leucine-related anabolic pathways.", "evidenceLevel": "moderate", "sources": [ { "text": "Wilson JM et al., International Society of Sports Nutrition position stand: beta-hydroxy-beta-methylbutyrate (HMB), Journal of the International Society of Sports Nutrition, 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Wilkinson DJ et al., Effects of leucine and its metabolite beta-hydroxy-beta-methylbutyrate on human skeletal muscle protein metabolism, Journal of Physiology, 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "HMB is a metabolite of leucine, so BCAAs and HMB act on related anabolic and anti-catabolic pathways to support muscle protein balance.", "clinicalSignificance": "Mechanistically related and complementary, but partly redundant given HMB is a leucine metabolite.", "managementStrategy": "Combining is reasonable around training, though the benefit overlaps since HMB derives from leucine; prioritize total protein intake first.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Ketamine", "supplementBName": "Alcohol", "interactionType": "contraindicated", "severity": "dangerous", "description": "Combining ketamine with alcohol produces additive central nervous system and respiratory depression, raising the risk of profound sedation, airway compromise, vomiting with aspiration, and loss of consciousness.", "recommendation": "Do not combine. If both have been taken together and breathing is slow or shallow, consciousness is impaired, or vomiting occurs, seek emergency medical care immediately.", "minimumTimeSeparation": null, "mechanism": "Both agents depress the central nervous system: alcohol potentiates GABA-A inhibitory tone while ketamine adds NMDA receptor antagonism and dissociation, so the combination compounds sedation and blunts protective airway reflexes.", "evidenceLevel": "strong", "sources": [ { "text": "Kobayashi NHC et al. Ketamine plus Alcohol: What We Know and What We Can Expect about This. Int J Mol Sci. 2022;23(14).", "pmid": "35887148", "doi": "10.3390/ijms23147800", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35887148/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Combining ketamine with alcohol produces additive central nervous system and respiratory depression, raising the risk of profound sedation, airway compromise, vomiting with aspiration, and loss of consciousness.", "clinicalSignificance": "Co-use markedly increases the danger of respiratory depression and aspiration.", "managementStrategy": "Do not combine. If both have been taken together and breathing is slow or shallow, consciousness is impaired, or vomiting occurs, seek emergency medical care immediately.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Ketamine", "supplementBName": "GABA", "interactionType": "caution", "severity": "moderate", "description": "Supplemental GABA used as a calming or sleep aid may add to ketamine's sedative and dissociative load, deepening drowsiness and impairing coordination and alertness.", "recommendation": "Do not combine GABA supplements with ketamine. If ketamine is being used and GABA has also been taken, do not drive or operate machinery and seek medical advice.", "minimumTimeSeparation": null, "mechanism": "GABA supplementation aims to increase inhibitory GABAergic signaling, which can compound the central nervous system depression and sedation associated with ketamine, although orally ingested GABA crosses the blood-brain barrier poorly so the magnitude is uncertain.", "evidenceLevel": "emerging", "sources": [ { "text": "Boonstra E et al. Neurotransmitters as food supplements: the effects of GABA on brain and behavior. Front Psychol. 2015.", "pmid": "26500584", "doi": "10.3389/fpsyg.2015.01520", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26500584/", "publicSourceType": "PMID" }, { "text": "Morgan CJA, Curran HV. Ketamine use: a review. Addiction. 2012.", "pmid": "21777321", "doi": "10.1111/j.1360-0443.2011.03576.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21777321/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Supplemental GABA used as a calming or sleep aid may add to ketamine's sedative and dissociative load, deepening drowsiness and impairing coordination and alertness.", "clinicalSignificance": "Expect possible additive sedation that reduces alertness and motor control.", "managementStrategy": "Do not combine GABA supplements with ketamine. If ketamine is being used and GABA has also been taken, do not drive or operate machinery and seek medical advice.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Ketamine", "supplementBName": "Valerian Root", "interactionType": "caution", "severity": "moderate", "description": "Valerian root has sedative-hypnotic activity that can add to ketamine's central depressant and dissociative effects, increasing drowsiness, dizziness, and impaired reaction time.", "recommendation": "Do not combine valerian root with ketamine. If both are in use, avoid driving and other tasks requiring alertness and seek medical advice.", "minimumTimeSeparation": null, "mechanism": "Valerian constituents modulate GABA-A receptor activity and may slow GABA breakdown, enhancing inhibitory tone that can compound the central nervous system depression produced by ketamine.", "evidenceLevel": "moderate", "sources": [ { "text": "Houghton PJ. The scientific basis for the reputed activity of Valerian. J Pharm Pharmacol. 1999.", "pmid": "10411208", "doi": "10.1211/0022357991772772", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10411208/", "publicSourceType": "PMID" }, { "text": "Bent S et al. Valerian for sleep: a systematic review and meta-analysis. Am J Med. 2006.", "pmid": "17145239", "doi": "10.1016/j.amjmed.2006.02.026", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17145239/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Valerian root has sedative-hypnotic activity that can add to ketamine's central depressant and dissociative effects, increasing drowsiness, dizziness, and impaired reaction time.", "clinicalSignificance": "Additive sedation makes the combination risky for alertness and coordination.", "managementStrategy": "Do not combine valerian root with ketamine. If both are in use, avoid driving and other tasks requiring alertness and seek medical advice.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Ketamine", "supplementBName": "Melatonin", "interactionType": "caution", "severity": "moderate", "description": "Melatonin taken as a sleep aid can add to ketamine's sedating effects, increasing drowsiness and impairing alertness and coordination.", "recommendation": "Do not combine melatonin with ketamine without medical advice. If both are in use, avoid driving and tasks requiring full alertness.", "minimumTimeSeparation": null, "mechanism": "Melatonin promotes sleep onset and mild central nervous system sedation, which can be additive with ketamine's sedative and dissociative effects and deepen drowsiness.", "evidenceLevel": "emerging", "sources": [ { "text": "Costello RB et al. The effectiveness of melatonin for promoting healthy sleep: a rapid evidence assessment of the literature. Nutr J. 2014.", "pmid": "25380732", "doi": "10.1186/1475-2891-13-106", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25380732/", "publicSourceType": "PMID" }, { "text": "Morgan CJA, Curran HV. Ketamine use: a review. Addiction. 2012.", "pmid": "21777321", "doi": "10.1111/j.1360-0443.2011.03576.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21777321/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Melatonin taken as a sleep aid can add to ketamine's sedating effects, increasing drowsiness and impairing alertness and coordination.", "clinicalSignificance": "Likely additive sedation that reduces alertness.", "managementStrategy": "Do not combine melatonin with ketamine without medical advice. If both are in use, avoid driving and tasks requiring full alertness.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Lithium Orotate", "supplementBName": "Iodine", "interactionType": "caution", "severity": "moderate", "description": "Lithium and iodine both affect the thyroid gland, and using them together can increase the likelihood of hypothyroidism or goiter through compounded suppression of thyroid hormone output.", "recommendation": "Use caution when combining. Monitor thyroid function (TSH and free T4) and consult a clinician before pairing lithium orotate with iodine, especially with existing thyroid disease.", "minimumTimeSeparation": null, "mechanism": "Lithium inhibits thyroid hormone release from the gland, and excess iodine can independently impair hormone synthesis (the Wolff-Chaikoff effect), so together they can additively increase the risk of hypothyroid states.", "evidenceLevel": "moderate", "sources": [ { "text": "Lazarus JH. Lithium and thyroid. Best Pract Res Clin Endocrinol Metab. 2009.", "pmid": "19942149", "doi": "10.1016/j.beem.2009.06.002", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19942149/", "publicSourceType": "PMID" }, { "text": "Leung AM, Braverman LE. Consequences of excess iodine. Nat Rev Endocrinol. 2014.", "pmid": "24342882", "doi": "10.1038/nrendo.2013.251", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24342882/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Lithium and iodine both affect the thyroid gland, and using them together can increase the likelihood of hypothyroidism or goiter through compounded suppression of thyroid hormone output.", "clinicalSignificance": "Combined use raises hypothyroidism risk and warrants thyroid monitoring.", "managementStrategy": "Use caution when combining. Monitor thyroid function (TSH and free T4) and consult a clinician before pairing lithium orotate with iodine, especially with existing thyroid disease.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Lithium Orotate", "supplementBName": "Inositol", "interactionType": "caution", "severity": "moderate", "description": "Inositol counteracts part of lithium's proposed mechanism by replenishing the inositol pool that lithium depletes, which may blunt lithium's mood-stabilizing effect when the two are used together.", "recommendation": "Be cautious combining the two if lithium is being used for mood stabilization. Discuss with a clinician, since high-dose inositol may oppose lithium's intended action.", "minimumTimeSeparation": null, "mechanism": "Lithium inhibits inositol monophosphatase and lowers intracellular inositol (the inositol-depletion hypothesis); supplemental inositol can replenish this pool and may pharmacodynamically oppose lithium's effect.", "evidenceLevel": "emerging", "sources": [ { "text": "Berridge MJ, Downes CP, Hanley MR. Neural and developmental actions of lithium: a unifying hypothesis. Cell. 1989.", "pmid": "2553271", "doi": "10.1016/0092-8674(89)90026-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2553271/", "publicSourceType": "PMID" }, { "text": "Harwood AJ. Lithium and bipolar mood disorder: the inositol-depletion hypothesis revisited. Mol Psychiatry. 2005.", "pmid": "15558078", "doi": "10.1038/sj.mp.4001618", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15558078/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Inositol counteracts part of lithium's proposed mechanism by replenishing the inositol pool that lithium depletes, which may blunt lithium's mood-stabilizing effect when the two are used together.", "clinicalSignificance": "Inositol may pharmacologically oppose lithium's mood-stabilizing mechanism.", "managementStrategy": "Be cautious combining the two if lithium is being used for mood stabilization. Discuss with a clinician, since high-dose inositol may oppose lithium's intended action.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "MDMA", "supplementBName": "5-HTP", "interactionType": "contraindicated", "severity": "dangerous", "description": "Taking 5-HTP with MDMA sharply increases the risk of serotonin syndrome, a potentially life-threatening state of excess serotonergic activity with agitation, high fever, rapid heart rate, muscle rigidity, and seizures.", "recommendation": "Do not combine. If symptoms such as high fever, confusion, severe muscle stiffness, or rapid heartbeat develop, seek emergency medical care immediately.", "minimumTimeSeparation": null, "mechanism": "MDMA causes massive synaptic serotonin release while 5-HTP supplies extra precursor that boosts serotonin synthesis, and the combined surge can overwhelm serotonergic regulation and trigger serotonin syndrome.", "evidenceLevel": "moderate", "sources": [ { "text": "Boyer EW et al. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-20.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Liechti ME. Effects of MDMA on body temperature in humans. Temperature (Austin). 2014;1(3):192-200.", "pmid": "27626046", "doi": "10.4161/23328940.2014.955433", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27626046/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Taking 5-HTP with MDMA sharply increases the risk of serotonin syndrome, a potentially life-threatening state of excess serotonergic activity with agitation, high fever, rapid heart rate, muscle rigidity, and seizures.", "clinicalSignificance": "Co-use poses a serious risk of serotonin syndrome.", "managementStrategy": "Do not combine. If symptoms such as high fever, confusion, severe muscle stiffness, or rapid heartbeat develop, seek emergency medical care immediately.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "MDMA", "supplementBName": "L-Tryptophan", "interactionType": "contraindicated", "severity": "dangerous", "description": "L-Tryptophan combined with MDMA raises the risk of serotonin syndrome by supplying additional serotonin precursor on top of MDMA's serotonin-releasing effect.", "recommendation": "Do not combine. Watch for high fever, agitation, tremor, or muscle rigidity and seek emergency medical care if they appear.", "minimumTimeSeparation": null, "mechanism": "L-Tryptophan is the upstream precursor for serotonin synthesis, and adding it while MDMA drives large serotonin release can push serotonergic signaling into a dangerous excess.", "evidenceLevel": "moderate", "sources": [ { "text": "Boyer EW et al. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-20.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Gillman PK. Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. Br J Anaesth. 2005;95(4):434-41.", "pmid": "16051647", "doi": "10.1093/bja/aei210", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16051647/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "L-Tryptophan combined with MDMA raises the risk of serotonin syndrome by supplying additional serotonin precursor on top of MDMA's serotonin-releasing effect.", "clinicalSignificance": "Adding serotonin precursor to MDMA risks serotonin syndrome.", "managementStrategy": "Do not combine. Watch for high fever, agitation, tremor, or muscle rigidity and seek emergency medical care if they appear.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "MDMA", "supplementBName": "SAMe", "interactionType": "conflict", "severity": "serious", "description": "SAMe has serotonergic and mood-elevating activity that can add to MDMA's serotonin release, increasing the risk of serotonin excess when the two are combined.", "recommendation": "Do not combine. Seek medical advice, and watch for agitation, sweating, tremor, or rapid heartbeat as signs of serotonin excess.", "minimumTimeSeparation": null, "mechanism": "SAMe is a methyl donor that supports monoamine including serotonin metabolism and has been associated with serotonergic effects, which may add to the large serotonin release driven by MDMA.", "evidenceLevel": "emerging", "sources": [ { "text": "Boyer EW et al. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-20.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Galizia I et al. S-adenosyl methionine (SAMe) for depression in adults. Cochrane Database Syst Rev. 2016;10(10):CD011286.", "pmid": "27727432", "doi": "10.1002/14651858.CD011286.pub2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27727432/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "SAMe has serotonergic and mood-elevating activity that can add to MDMA's serotonin release, increasing the risk of serotonin excess when the two are combined.", "clinicalSignificance": "Possible additive serotonergic load with MDMA.", "managementStrategy": "Do not combine. Seek medical advice, and watch for agitation, sweating, tremor, or rapid heartbeat as signs of serotonin excess.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "MDMA", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's Wort both adds to serotonergic load and induces drug-metabolizing enzymes, so combined with MDMA it can raise serotonin syndrome risk while also unpredictably altering MDMA blood levels.", "recommendation": "Do not combine. Seek medical advice, and watch for signs of serotonin excess such as agitation, sweating, tremor, and rapid heartbeat.", "minimumTimeSeparation": null, "mechanism": "St. John's Wort has serotonergic activity that adds to MDMA's serotonin release, and it induces CYP3A4 and CYP2C9 and P-glycoprotein, which can shift MDMA and metabolite exposure in unpredictable ways.", "evidenceLevel": "moderate", "sources": [ { "text": "Borrelli F et al. Herb-drug interactions with St John's wort (Hypericum perforatum): an update on clinical observations. AAPS J. 2009;11(4):710-27.", "pmid": "19859815", "doi": "10.1208/s12248-009-9146-8", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19859815/", "publicSourceType": "PMID" }, { "text": "Boyer EW et al. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-20.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "St. John's Wort both adds to serotonergic load and induces drug-metabolizing enzymes, so combined with MDMA it can raise serotonin syndrome risk while also unpredictably altering MDMA blood levels.", "clinicalSignificance": "Combination risks both serotonin toxicity and altered MDMA metabolism.", "managementStrategy": "Do not combine. Seek medical advice, and watch for signs of serotonin excess such as agitation, sweating, tremor, and rapid heartbeat.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "MDMA", "supplementBName": "Alcohol", "interactionType": "conflict", "severity": "serious", "description": "Combining MDMA with alcohol increases dehydration, cardiovascular strain, and impaired judgment, and alcohol can mask MDMA's perceived effects while worsening next-day impairment and overheating risk.", "recommendation": "Do not combine. If overheating, confusion, chest pain, or collapse occurs, seek emergency medical care immediately.", "minimumTimeSeparation": null, "mechanism": "MDMA raises body temperature and cardiovascular workload and impairs thermoregulation, while alcohol promotes fluid loss and further impairs judgment, additively increasing the risk of dehydration, hyperthermia, and cardiac stress.", "evidenceLevel": "moderate", "sources": [ { "text": "Hernández-López C et al. 3,4-Methylenedioxymethamphetamine (ecstasy) and alcohol interactions in humans: psychomotor performance, subjective effects, and pharmacokinetics. J Pharmacol Exp Ther. 2002;300(1):236-44.", "pmid": "11752122", "doi": "10.1124/jpet.300.1.236", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11752122/", "publicSourceType": "PMID" }, { "text": "Liechti ME. Effects of MDMA on body temperature in humans. Temperature (Austin). 2014;1(3):192-200.", "pmid": "27626046", "doi": "10.4161/23328940.2014.955433", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27626046/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Combining MDMA with alcohol increases dehydration, cardiovascular strain, and impaired judgment, and alcohol can mask MDMA's perceived effects while worsening next-day impairment and overheating risk.", "clinicalSignificance": "Co-use amplifies dehydration, overheating, and cardiovascular risk.", "managementStrategy": "Do not combine. If overheating, confusion, chest pain, or collapse occurs, seek emergency medical care immediately.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "MSM", "supplementBName": "Glucosamine", "interactionType": "synergy", "severity": "info", "description": "MSM and glucosamine are commonly combined for osteoarthritis, and some trials suggest the pair improves joint pain and function more than either alone, with a good tolerability profile.", "recommendation": "Reasonable to combine for joint support. Monitor for mild gastrointestinal upset and continue only if you notice benefit over several weeks.", "minimumTimeSeparation": null, "mechanism": "MSM supplies bioavailable sulfur and has anti-inflammatory and antioxidant activity, while glucosamine supports cartilage matrix synthesis, providing complementary effects on joint comfort.", "evidenceLevel": "moderate", "sources": [ { "text": "Usha PR, Naidu MUR. Randomised, double-blind, parallel, placebo-controlled study of oral glucosamine, methylsulfonylmethane and their combination in osteoarthritis. Clinical Drug Investigation, 2004.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Butawan M et al. Methylsulfonylmethane: applications and safety of a novel dietary supplement. Nutrients, 2017.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "MSM and glucosamine are commonly combined for osteoarthritis, and some trials suggest the pair improves joint pain and function more than either alone, with a good tolerability profile.", "clinicalSignificance": "Complementary joint-support pairing with possible additive symptom benefit.", "managementStrategy": "Reasonable to combine for joint support. Monitor for mild gastrointestinal upset and continue only if you notice benefit over several weeks.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "MSM", "supplementBName": "Boswellia", "interactionType": "synergy", "severity": "info", "description": "MSM and Boswellia work through complementary anti-inflammatory pathways and are often combined for joint and soft-tissue comfort, with some studies suggesting additive symptom relief.", "recommendation": "Reasonable to combine for inflammatory joint support. Take with food and monitor for mild digestive upset.", "minimumTimeSeparation": null, "mechanism": "Boswellic acids inhibit 5-lipoxygenase and leukotriene synthesis while MSM provides antioxidant and anti-inflammatory sulfur-based effects, targeting different parts of the inflammatory cascade.", "evidenceLevel": "emerging", "sources": [ { "text": "Ammon HPT. Boswellic acids in chronic inflammatory diseases. Planta Medica, 2006.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Butawan M et al. Methylsulfonylmethane: applications and safety of a novel dietary supplement. Nutrients, 2017.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "MSM and Boswellia work through complementary anti-inflammatory pathways and are often combined for joint and soft-tissue comfort, with some studies suggesting additive symptom relief.", "clinicalSignificance": "Complementary anti-inflammatory actions with low interaction risk.", "managementStrategy": "Reasonable to combine for inflammatory joint support. Take with food and monitor for mild digestive upset.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "MSM", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "MSM provides sulfur and antioxidant support that complements vitamin C's role in collagen synthesis, and the pair is frequently combined for connective-tissue and skin support without notable adverse interaction.", "recommendation": "Safe to combine. No special timing or precautions are needed at typical supplement doses.", "minimumTimeSeparation": null, "mechanism": "Vitamin C is a required cofactor for collagen cross-linking and antioxidant defense, while MSM supplies sulfur used in connective tissue and adds antioxidant activity, giving complementary support to tissue repair.", "evidenceLevel": "emerging", "sources": [ { "text": "Butawan M et al. Methylsulfonylmethane: applications and safety of a novel dietary supplement. Nutrients, 2017.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Pullar JM, Carr AC, Vissers MCM. The roles of vitamin C in skin health. Nutrients, 2017.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "MSM provides sulfur and antioxidant support that complements vitamin C's role in collagen synthesis, and the pair is frequently combined for connective-tissue and skin support without notable adverse interaction.", "clinicalSignificance": "Low-risk complementary pairing for connective-tissue support.", "managementStrategy": "Safe to combine. No special timing or precautions are needed at typical supplement doses.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Manganese", "supplementBName": "Iron", "interactionType": "timingSensitive", "severity": "moderate", "description": "Iron and manganese compete for shared intestinal absorption pathways, so high-dose iron can reduce manganese uptake, and conversely high manganese intake can blunt iron absorption.", "recommendation": "Separate iron and manganese doses by at least 2 hours to limit absorption competition, and take iron with vitamin C to improve its uptake.", "minimumTimeSeparation": "2 hours", "mechanism": "Both divalent metals are absorbed in part via the divalent metal transporter 1 (DMT1) in the gut, so high intake of one cation competitively reduces absorption of the other.", "evidenceLevel": "moderate", "sources": [ { "text": "Gunshin H et al. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature. 1997.", "pmid": "9242408", "doi": "10.1038/41343", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9242408/", "publicSourceType": "PMID" }, { "text": "Rossander-Hulten L et al. Competitive inhibition of iron absorption by manganese and zinc in humans. Am J Clin Nutr. 1991.", "pmid": "2058577", "doi": "10.1093/ajcn/54.1.152", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2058577/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Iron and manganese compete for shared intestinal absorption pathways, so high-dose iron can reduce manganese uptake, and conversely high manganese intake can blunt iron absorption.", "clinicalSignificance": "Shared transporter causes mutual absorption competition; separate the doses.", "managementStrategy": "Separate iron and manganese doses by at least 2 hours to limit absorption competition, and take iron with vitamin C to improve its uptake.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Manganese", "supplementBName": "Calcium", "interactionType": "timingSensitive", "severity": "moderate", "description": "High-dose calcium can reduce manganese absorption when taken together, lowering the amount of manganese the body takes up from a given dose.", "recommendation": "Separate calcium and manganese by at least 2 hours to avoid reduced manganese absorption, particularly if using high-dose calcium supplements.", "minimumTimeSeparation": "2 hours", "mechanism": "Calcium can interfere with intestinal absorption of manganese through competition and binding effects in the gut, decreasing manganese bioavailability when the two are consumed at the same time.", "evidenceLevel": "emerging", "sources": [ { "text": "Davidsson L et al. Manganese absorption in humans: the effect of phytic acid and ascorbic acid in soy formula. Am J Clin Nutr. 1995.", "pmid": "7572746", "doi": "10.1093/ajcn/62.5.984", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7572746/", "publicSourceType": "PMID" }, { "text": "Lonnerdal B. Dietary factors influencing manganese absorption in humans. Nutrition Reviews, 1997.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "High-dose calcium can reduce manganese absorption when taken together, lowering the amount of manganese the body takes up from a given dose.", "clinicalSignificance": "Concurrent calcium can lower manganese absorption; stagger the doses.", "managementStrategy": "Separate calcium and manganese by at least 2 hours to avoid reduced manganese absorption, particularly if using high-dose calcium supplements.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Manganese", "supplementBName": "Zinc", "interactionType": "timingSensitive", "severity": "moderate", "description": "Zinc and manganese compete for shared intestinal absorption pathways, so taking high doses together can modestly reduce the absorption of one or both minerals.", "recommendation": "Separate zinc and manganese by at least 2 hours when using higher-dose supplements to minimize absorption interference.", "minimumTimeSeparation": "2 hours", "mechanism": "Both are divalent cations that share intestinal transport routes including DMT1, so high intake of one can competitively reduce uptake of the other.", "evidenceLevel": "emerging", "sources": [ { "text": "Gunshin H et al. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature. 1997.", "pmid": "9242408", "doi": "10.1038/41343", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9242408/", "publicSourceType": "PMID" }, { "text": "Sandstrom B. Micronutrient interactions: effects on absorption and bioavailability. Br J Nutr. 2001.", "pmid": "11509108", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11509108/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Zinc and manganese compete for shared intestinal absorption pathways, so taking high doses together can modestly reduce the absorption of one or both minerals.", "clinicalSignificance": "Mineral competition at the gut warrants staggering high doses.", "managementStrategy": "Separate zinc and manganese by at least 2 hours when using higher-dose supplements to minimize absorption interference.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Molybdenum", "supplementBName": "Copper", "interactionType": "caution", "severity": "moderate", "description": "High molybdenum intake can reduce copper bioavailability and accelerate copper depletion, potentially worsening or precipitating copper deficiency over time.", "recommendation": "Avoid chronic high-dose molybdenum supplementation alongside copper-restricted diets. If both are needed, monitor copper status (ceruloplasmin) under clinician guidance and keep molybdenum at nutritional doses.", "minimumTimeSeparation": null, "mechanism": "Excess molybdenum, particularly with dietary sulfur, promotes formation of thiomolybdate compounds that bind copper and increase its biliary and urinary excretion, lowering systemic copper.", "evidenceLevel": "moderate", "sources": [ { "text": "Turnlund JR, Keyes WR. Dietary molybdenum: effect on copper absorption, excretion, and status in young men. Trace Elements in Man and Animals, 2000", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Vyskocil A, Viau C. Assessment of molybdenum toxicity in humans. J Appl Toxicol. 1999.", "pmid": "10362269", "doi": "10.1002/(sici)1099-1263(199905/06)19:33.0.co;2-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10362269/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "High molybdenum intake can reduce copper bioavailability and accelerate copper depletion, potentially worsening or precipitating copper deficiency over time.", "clinicalSignificance": "Sustained high molybdenum can drive down copper status, so balance and monitoring matter.", "managementStrategy": "Avoid chronic high-dose molybdenum supplementation alongside copper-restricted diets. If both are needed, monitor copper status (ceruloplasmin) under clinician guidance and keep molybdenum at nutritional doses.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Molybdenum", "supplementBName": "NAC", "interactionType": "synergy", "severity": "info", "description": "Molybdenum is a required cofactor for sulfite oxidase, the enzyme that detoxifies the sulfite generated when N-acetylcysteine and other sulfur compounds are metabolized, supporting clearance of the sulfur load.", "recommendation": "No special timing needed. Adequate (not excessive) molybdenum status supports normal sulfur metabolism when taking NAC; do not megadose molybdenum.", "minimumTimeSeparation": null, "mechanism": "NAC catabolism contributes to the body's sulfite and sulfate pool, and sulfite oxidase, a molybdenum-dependent enzyme, converts toxic sulfite to sulfate, so sufficient molybdenum supports this detoxification pathway.", "evidenceLevel": "emerging", "sources": [ { "text": "Schwarz G, Mendel RR, Ribbe MW. Molybdenum cofactors, enzymes and pathways. Nature, 2009", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Atwal PS, Scaglia F. Molybdenum cofactor deficiency. Molecular Genetics and Metabolism, 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Molybdenum is a required cofactor for sulfite oxidase, the enzyme that detoxifies the sulfite generated when N-acetylcysteine and other sulfur compounds are metabolized, supporting clearance of the sulfur load.", "clinicalSignificance": "Molybdenum-dependent sulfite oxidase underpins safe handling of sulfur from NAC.", "managementStrategy": "No special timing needed. Adequate (not excessive) molybdenum status supports normal sulfur metabolism when taking NAC; do not megadose molybdenum.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Moringa", "supplementBName": "Iron", "interactionType": "synergy", "severity": "info", "description": "Moringa leaf is a meaningful source of bioavailable iron and vitamin C and is used to help correct iron deficiency anemia, complementing iron supplementation.", "recommendation": "Reasonable to combine for iron repletion. If moringa is taken alongside a separate iron tablet, monitor iron status to confirm a hemoglobin response, since moringa polyphenols can partially blunt non-heme iron uptake.", "minimumTimeSeparation": null, "mechanism": "Moringa oleifera leaf contains absorbable iron plus vitamin C, which reduces ferric to ferrous iron and enhances non-heme iron uptake, supporting hemoglobin recovery.", "evidenceLevel": "moderate", "sources": [ { "text": "Saini RK, et al. Iron and bioavailability in Moringa oleifera leaves. Journal of Food Science and Technology, 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Shija AE, et al. Effect of Moringa oleifera leaf powder supplementation on iron status. BMC Nutrition, 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Moringa leaf is a meaningful source of bioavailable iron and vitamin C and is used to help correct iron deficiency anemia, complementing iron supplementation.", "clinicalSignificance": "Moringa can support iron status and pairs reasonably with iron repletion.", "managementStrategy": "Reasonable to combine for iron repletion. If moringa is taken alongside a separate iron tablet, monitor iron status to confirm a hemoglobin response, since moringa polyphenols can partially blunt non-heme iron uptake.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Moringa", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Vitamin C enhances absorption of the non-heme iron in moringa and supports its antioxidant activity, improving the nutritional value of the combination.", "recommendation": "No special precautions. Co-ingesting vitamin C with moringa is a reasonable way to improve iron uptake from the leaf.", "minimumTimeSeparation": null, "mechanism": "Ascorbic acid reduces ferric iron to the more soluble ferrous form and chelates it, counteracting the inhibitory effect of moringa polyphenols on iron absorption.", "evidenceLevel": "moderate", "sources": [ { "text": "Hallberg L, Hulthen L. Prediction of dietary iron absorption. American Journal of Clinical Nutrition, 2000", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Saini RK, et al. Nutrient and bioactive compounds in Moringa oleifera. Journal of Food Science and Technology, 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Vitamin C enhances absorption of the non-heme iron in moringa and supports its antioxidant activity, improving the nutritional value of the combination.", "clinicalSignificance": "Vitamin C improves iron uptake from moringa leaf.", "managementStrategy": "No special precautions. Co-ingesting vitamin C with moringa is a reasonable way to improve iron uptake from the leaf.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Moringa", "supplementBName": "Berberine", "interactionType": "caution", "severity": "moderate", "description": "Both moringa and berberine independently lower blood glucose, so combining them can produce additive hypoglycemic effects, particularly in people also taking antidiabetic medication.", "recommendation": "Monitor blood glucose if combining, and watch for signs of low blood sugar. People on diabetes medication should consult a clinician before stacking both.", "minimumTimeSeparation": null, "mechanism": "Moringa improves glucose uptake and insulin response while berberine activates AMPK and reduces hepatic gluconeogenesis, so together they can additively lower blood glucose.", "evidenceLevel": "emerging", "sources": [ { "text": "Anthanont P, et al. Moringa oleifera leaf increases insulin secretion. Journal of the Medical Association of Thailand, 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008.", "pmid": "18442638", "doi": "10.1016/j.metabol.2008.01.013", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18442638/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both moringa and berberine independently lower blood glucose, so combining them can produce additive hypoglycemic effects, particularly in people also taking antidiabetic medication.", "clinicalSignificance": "Stacking two glucose-lowering agents raises hypoglycemia risk, so monitor.", "managementStrategy": "Monitor blood glucose if combining, and watch for signs of low blood sugar. People on diabetes medication should consult a clinician before stacking both.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Nicotine", "supplementBName": "Alcohol", "interactionType": "conflict", "severity": "serious", "description": "Combining nicotine and alcohol increases cardiovascular strain (heart rate and blood pressure) and reinforces co-dependence, with the two substances mutually increasing consumption and addiction risk.", "recommendation": "Do not combine. If you use both, seek medical advice and support for reduction or cessation, since the pairing raises cardiovascular and dependence risks.", "minimumTimeSeparation": null, "mechanism": "Nicotine is a stimulant that raises heart rate and blood pressure while alcohol is a depressant, so co-use produces conflicting autonomic effects, and each drug increases craving and intake of the other through shared dopaminergic reward pathways.", "evidenceLevel": "strong", "sources": [ { "text": "Hurley LL et al. Positive and negative effects of alcohol and nicotine and their interactions: a mechanistic review. Neurotox Res. 2012;21(1):57-69.", "pmid": "21932109", "doi": "10.1007/s12640-011-9275-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21932109/", "publicSourceType": "PMID" }, { "text": "Verplaetse TL et al. An overview of alcohol and tobacco/nicotine interactions in the human laboratory. Am J Drug Alcohol Abuse. 2017;43(2):186-196.", "pmid": "27439453", "doi": "10.1080/00952990.2016.1189927", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27439453/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Combining nicotine and alcohol increases cardiovascular strain (heart rate and blood pressure) and reinforces co-dependence, with the two substances mutually increasing consumption and addiction risk.", "clinicalSignificance": "Co-use amplifies cardiovascular load and mutual dependence, so avoid the combination.", "managementStrategy": "Do not combine. If you use both, seek medical advice and support for reduction or cessation, since the pairing raises cardiovascular and dependence risks.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Nicotine", "supplementBName": "Vitamin C", "interactionType": "caution", "severity": "moderate", "description": "Nicotine and smoking markedly increase oxidative stress and lower plasma vitamin C levels, so nicotine users often have depleted vitamin C status.", "recommendation": "Do not use nicotine. For those who do, vitamin C stores are likely depleted, but supplementation does not offset nicotine's harms; addressing nicotine use itself is the priority.", "minimumTimeSeparation": null, "mechanism": "Nicotine and tobacco smoke generate reactive oxygen species and increase metabolic turnover of ascorbate, lowering circulating and tissue vitamin C concentrations.", "evidenceLevel": "moderate", "sources": [ { "text": "Schectman G, et al. The influence of smoking on vitamin C status in adults. Am J Public Health. 1989.", "pmid": "2913833", "doi": "10.2105/ajph.79.2.158", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2913833/", "publicSourceType": "PMID" }, { "text": "Northrop-Clewes CA, Thurnham DI. Monitoring micronutrients in cigarette smokers. Clin Chim Acta. 2007.", "pmid": "17045981", "doi": "10.1016/j.cca.2006.08.028", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17045981/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Nicotine and smoking markedly increase oxidative stress and lower plasma vitamin C levels, so nicotine users often have depleted vitamin C status.", "clinicalSignificance": "Nicotine use depletes vitamin C, but supplementation does not negate nicotine's harms.", "managementStrategy": "Do not use nicotine. For those who do, vitamin C stores are likely depleted, but supplementation does not offset nicotine's harms; addressing nicotine use itself is the priority.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Nicotine", "supplementBName": "L-Theanine", "interactionType": "caution", "severity": "moderate", "description": "L-theanine may blunt the subjective stimulation and arousal from nicotine, but it does not reduce nicotine's addictive potential or cardiovascular effects and should not be treated as a safe way to use nicotine.", "recommendation": "Do not use nicotine. L-theanine is not a harm-reduction tool for nicotine and will not protect against dependence or cardiovascular strain; seek medical advice for nicotine cessation.", "minimumTimeSeparation": null, "mechanism": "L-theanine modulates glutamate and GABA signaling and promotes alpha brain-wave activity, producing a calming effect that can partly counter nicotine's stimulant arousal without affecting nicotine's nicotinic receptor activity or addiction pathway.", "evidenceLevel": "emerging", "sources": [ { "text": "Nathan PJ, et al. The neuropharmacology of L-theanine(N-ethyl-L-glutamine): a possible neuroprotective and cognitive enhancing agent. J Herb Pharmacother. 2006.", "pmid": "17182482", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17182482/", "publicSourceType": "PMID" }, { "text": "Hidese S, et al. Effects of L-theanine administration on stress-related symptoms. Nutrients, 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "L-theanine may blunt the subjective stimulation and arousal from nicotine, but it does not reduce nicotine's addictive potential or cardiovascular effects and should not be treated as a safe way to use nicotine.", "clinicalSignificance": "L-theanine does not make nicotine safe, so nicotine use should be avoided regardless.", "managementStrategy": "Do not use nicotine. L-theanine is not a harm-reduction tool for nicotine and will not protect against dependence or cardiovascular strain; seek medical advice for nicotine cessation.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Omega-7", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "Omega-7 (palmitoleic acid) and fish oil omega-3s have complementary lipid-modulating effects, with some evidence that combined intake supports improved triglyceride and inflammatory markers.", "recommendation": "Reasonable to combine. Both are fatty acids and are well tolerated together; take with food for absorption and watch total fat intake if calorie-conscious.", "minimumTimeSeparation": null, "mechanism": "Palmitoleic acid acts as a lipokine improving insulin sensitivity and lipid handling, while omega-3 EPA and DHA lower triglycerides and inflammatory signaling, so the two operate through distinct but complementary lipid pathways.", "evidenceLevel": "emerging", "sources": [ { "text": "Bernstein AM, et al. Purified palmitoleic acid for reduction of CRP and lipids. Journal of Clinical Lipidology, 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Yang ZH, et al. Palmitoleic acid effects on lipid metabolism. Lipids in Health and Disease, 2011", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Omega-7 (palmitoleic acid) and fish oil omega-3s have complementary lipid-modulating effects, with some evidence that combined intake supports improved triglyceride and inflammatory markers.", "clinicalSignificance": "Complementary fatty acids that can be combined safely for lipid support.", "managementStrategy": "Reasonable to combine. Both are fatty acids and are well tolerated together; take with food for absorption and watch total fat intake if calorie-conscious.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Omega-7", "supplementBName": "Krill Oil", "interactionType": "synergy", "severity": "info", "description": "Krill oil supplies omega-3s in phospholipid form plus astaxanthin, complementing omega-7 palmitoleic acid for lipid and metabolic support; many sea-source omega-7 products are co-formulated with marine omega-3s.", "recommendation": "Reasonable to combine and take with food. Be aware that some omega-7 sources (for example, certain fish-derived oils) already contain omega-3s, so account for total marine oil intake.", "minimumTimeSeparation": null, "mechanism": "Palmitoleic acid supports insulin sensitivity and lipid metabolism while krill phospholipid omega-3s and astaxanthin add anti-inflammatory and antioxidant activity, giving complementary metabolic effects.", "evidenceLevel": "emerging", "sources": [ { "text": "Yang ZH, et al. Palmitoleic acid effects on lipid metabolism. Lipids in Health and Disease, 2011", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Ulven SM, Holven KB. Comparison of bioavailability of krill oil versus fish oil. Lipids in Health and Disease, 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Krill oil supplies omega-3s in phospholipid form plus astaxanthin, complementing omega-7 palmitoleic acid for lipid and metabolic support; many sea-source omega-7 products are co-formulated with marine omega-3s.", "clinicalSignificance": "Complementary marine lipids; combining is generally safe with attention to total dose.", "managementStrategy": "Reasonable to combine and take with food. Be aware that some omega-7 sources (for example, certain fish-derived oils) already contain omega-3s, so account for total marine oil intake.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Ox Bile", "supplementBName": "Digestive Enzymes", "interactionType": "synergy", "severity": "info", "description": "Ox bile emulsifies dietary fat to improve the action of lipase and other digestive enzymes, supporting more complete fat and fat-soluble nutrient digestion, especially after gallbladder removal.", "recommendation": "Take both with fat-containing meals. The combination is commonly used together for fat maldigestion; start low and titrate to comfort.", "minimumTimeSeparation": null, "mechanism": "Bile salts from ox bile emulsify dietary fats into smaller micelles, increasing the surface area on which pancreatic and supplemental lipase can act to hydrolyze triglycerides.", "evidenceLevel": "moderate", "sources": [ { "text": "Hofmann AF. The continuing importance of bile acids in liver and intestinal disease. Archives of Internal Medicine, 1999", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Carey MC, Small DM. The physical chemistry of cholesterol solubility in bile. Journal of Clinical Investigation, 1978", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Ox bile emulsifies dietary fat to improve the action of lipase and other digestive enzymes, supporting more complete fat and fat-soluble nutrient digestion, especially after gallbladder removal.", "clinicalSignificance": "Ox bile and enzymes work together to improve fat digestion, so take with meals.", "managementStrategy": "Take both with fat-containing meals. The combination is commonly used together for fat maldigestion; start low and titrate to comfort.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Ox Bile", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "info", "description": "Bile is required to absorb fat-soluble vitamin D3, so ox bile can improve uptake of D3 supplements in people with low bile output, such as those without a gallbladder or with cholestasis.", "recommendation": "Take vitamin D3 with a fat-containing meal, and ox bile alongside if you have impaired fat or bile-dependent absorption. Recheck vitamin D status to confirm improvement.", "minimumTimeSeparation": null, "mechanism": "Vitamin D3 is lipophilic and requires bile-salt-mediated micelle formation for intestinal absorption, so supplemental ox bile provides bile salts that enhance solubilization and uptake when endogenous bile is insufficient.", "evidenceLevel": "moderate", "sources": [ { "text": "Maislos M, Shany S. Bile salt deficiency and the absorption of vitamin D metabolites. Israel Journal of Medical Sciences, 1987", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Hofmann AF. Bile acids: the good, the bad, and the ugly. News in Physiological Sciences, 1999", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Bile is required to absorb fat-soluble vitamin D3, so ox bile can improve uptake of D3 supplements in people with low bile output, such as those without a gallbladder or with cholestasis.", "clinicalSignificance": "Ox bile can improve vitamin D3 absorption when bile output is low.", "managementStrategy": "Take vitamin D3 with a fat-containing meal, and ox bile alongside if you have impaired fat or bile-dependent absorption. Recheck vitamin D status to confirm improvement.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Ox Bile", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "Ox bile emulsifies the fat in fish oil, improving digestion and absorption of omega-3 fatty acids, which can be useful for people with reduced bile flow or fat malabsorption.", "recommendation": "Take fish oil with meals and add ox bile if you experience fishy reflux, oily stools, or have impaired fat absorption. The combination is well tolerated.", "minimumTimeSeparation": null, "mechanism": "Bile salts emulsify the triglyceride-rich fish oil into micelles, enhancing lipase access and absorption of EPA and DHA across the intestinal mucosa.", "evidenceLevel": "emerging", "sources": [ { "text": "Hofmann AF. The continuing importance of bile acids in liver and intestinal disease. Archives of Internal Medicine, 1999", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Schuchardt JP, Hahn A. Bioavailability of long-chain omega-3 fatty acids. Prostaglandins, Leukotrienes and Essential Fatty Acids, 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Ox bile emulsifies the fat in fish oil, improving digestion and absorption of omega-3 fatty acids, which can be useful for people with reduced bile flow or fat malabsorption.", "clinicalSignificance": "Ox bile can improve omega-3 absorption and reduce fishy reflux from fish oil.", "managementStrategy": "Take fish oil with meals and add ox bile if you experience fishy reflux, oily stools, or have impaired fat absorption. The combination is well tolerated.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "PQQ", "supplementBName": "Coenzyme Q10", "interactionType": "synergy", "severity": "info", "description": "Combined supplementation supports mitochondrial energy production and biogenesis, and the pair has been studied together in human cognitive function trials.", "recommendation": "Reasonable to take together, ideally with a fat-containing meal to aid CoQ10 absorption. No separation needed.", "minimumTimeSeparation": null, "mechanism": "PQQ stimulates PGC-1-alpha-driven mitochondrial biogenesis while CoQ10 acts as an electron carrier in the respiratory chain, so the two address complementary steps of mitochondrial ATP production.", "evidenceLevel": "moderate", "sources": [ { "text": "Nakano M et al. Effect of Pyrroloquinoline Quinone Disodium Salt and Coenzyme Q10 on Higher Brain Function. Japanese Journal of Medicine and Pharmaceutical Science, 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Harris CB et al. Dietary pyrroloquinoline quinone alters indicators of inflammation and mitochondrial-related metabolism in human subjects. Journal of Nutritional Biochemistry, 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Combined supplementation supports mitochondrial energy production and biogenesis, and the pair has been studied together in human cognitive function trials.", "clinicalSignificance": "A complementary mitochondrial-support pairing with supportive human trial data.", "managementStrategy": "Reasonable to take together, ideally with a fat-containing meal to aid CoQ10 absorption. No separation needed.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "PQQ", "supplementBName": "Coenzyme Q10 Ubiquinol", "interactionType": "synergy", "severity": "info", "description": "Pairing PQQ with the reduced ubiquinol form of CoQ10 supports mitochondrial biogenesis and the respiratory chain together, with ubiquinol offering higher oral bioavailability than ubiquinone.", "recommendation": "Reasonable to combine; take ubiquinol with dietary fat to optimize uptake. No separation needed.", "minimumTimeSeparation": null, "mechanism": "PQQ upregulates mitochondrial biogenesis via PGC-1-alpha and CREB signaling, while ubiquinol functions as a lipid-soluble electron carrier and antioxidant within the inner mitochondrial membrane.", "evidenceLevel": "moderate", "sources": [ { "text": "Nakano M et al. Effect of Pyrroloquinoline Quinone Disodium Salt and Coenzyme Q10 on Higher Brain Function. Japanese Journal of Medicine and Pharmaceutical Science, 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Hosoe K et al. Study on safety and bioavailability of ubiquinol (Kaneka QH) after single and four-week multiple oral administration to healthy volunteers. Regulatory Toxicology and Pharmacology, 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Pairing PQQ with the reduced ubiquinol form of CoQ10 supports mitochondrial biogenesis and the respiratory chain together, with ubiquinol offering higher oral bioavailability than ubiquinone.", "clinicalSignificance": "Complementary mechanisms make this a rational mitochondrial-support stack.", "managementStrategy": "Reasonable to combine; take ubiquinol with dietary fat to optimize uptake. No separation needed.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "PQQ", "supplementBName": "NMN", "interactionType": "synergy", "severity": "info", "description": "PQQ and NMN act on convergent mitochondrial and NAD-related pathways, supporting mitochondrial biogenesis and cellular energy metabolism through complementary routes.", "recommendation": "Reasonable to take together for energy and mitochondrial support. No timing separation required.", "minimumTimeSeparation": null, "mechanism": "NMN raises intracellular NAD+ to fuel sirtuin activity, and sirtuin signaling converges with PQQ-induced PGC-1-alpha activation to promote mitochondrial biogenesis.", "evidenceLevel": "emerging", "sources": [ { "text": "Chowanadisai W et al. Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1-alpha expression. Journal of Biological Chemistry, 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Yoshino J et al. NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR. Cell Metabolism, 2018", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "PQQ and NMN act on convergent mitochondrial and NAD-related pathways, supporting mitochondrial biogenesis and cellular energy metabolism through complementary routes.", "clinicalSignificance": "Mechanistically complementary for mitochondrial support, though human combination data are limited.", "managementStrategy": "Reasonable to take together for energy and mitochondrial support. No timing separation required.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Passionflower", "supplementBName": "Valerian Root", "interactionType": "caution", "severity": "moderate", "description": "Both herbs are sedative and GABAergic, so combining them produces additive drowsiness and CNS depression, an effect used in some combination sleep products but a concern with driving or other sedatives.", "recommendation": "If combined, start low, avoid driving or operating machinery, and do not add other sedatives or alcohol. Discuss with a clinician if taking prescription CNS depressants.", "minimumTimeSeparation": null, "mechanism": "Passionflower flavonoids and valerian constituents both enhance GABA-A receptor signaling, producing additive inhibitory CNS effects.", "evidenceLevel": "moderate", "sources": [ { "text": "Appel K et al. Modulation of the γ-aminobutyric acid (GABA) system by Passiflora incarnata L. Phytother Res. 2011;25(6):838-43.", "pmid": "21089181", "doi": "10.1002/ptr.3352", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21089181/", "publicSourceType": "PMID" }, { "text": "Bent S et al. Valerian for sleep: a systematic review and meta-analysis. Am J Med. 2006;119(12):1005-12.", "pmid": "17145239", "doi": "10.1016/j.amjmed.2006.02.026", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17145239/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both herbs are sedative and GABAergic, so combining them produces additive drowsiness and CNS depression, an effect used in some combination sleep products but a concern with driving or other sedatives.", "clinicalSignificance": "Additive sedation: useful for sleep but raises drowsiness and impairment risk.", "managementStrategy": "If combined, start low, avoid driving or operating machinery, and do not add other sedatives or alcohol. Discuss with a clinician if taking prescription CNS depressants.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Passionflower", "supplementBName": "Melatonin", "interactionType": "caution", "severity": "moderate", "description": "Passionflower adds GABAergic sedation on top of melatonin's sleep-promoting effect, increasing overall drowsiness and next-morning grogginess in some users.", "recommendation": "Take near bedtime only, start with low doses, and avoid driving after dosing. Avoid stacking with other sedatives or alcohol.", "minimumTimeSeparation": null, "mechanism": "Melatonin acts on MT1 and MT2 receptors to promote sleep onset while passionflower enhances GABA-A signaling, producing additive CNS sedation through distinct pathways.", "evidenceLevel": "emerging", "sources": [ { "text": "Appel K et al. Modulation of the γ-aminobutyric acid (GABA) system by Passiflora incarnata L. Phytother Res. 2011;25(6):838-43.", "pmid": "21089181", "doi": "10.1002/ptr.3352", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21089181/", "publicSourceType": "PMID" }, { "text": "Costello RB et al. The effectiveness of melatonin for promoting healthy sleep: a rapid evidence assessment of the literature. Nutr J. 2014;13:106.", "pmid": "25380732", "doi": "10.1186/1475-2891-13-106", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25380732/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Passionflower adds GABAergic sedation on top of melatonin's sleep-promoting effect, increasing overall drowsiness and next-morning grogginess in some users.", "clinicalSignificance": "Additive sedation that can deepen sleepiness and morning impairment.", "managementStrategy": "Take near bedtime only, start with low doses, and avoid driving after dosing. Avoid stacking with other sedatives or alcohol.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Passionflower", "supplementBName": "GABA", "interactionType": "caution", "severity": "moderate", "description": "Both target GABAergic tone, so combining supplemental GABA with passionflower can produce additive calming and sedative effects.", "recommendation": "Use modest doses, avoid combining before driving, and do not stack with prescription sedatives or alcohol.", "minimumTimeSeparation": null, "mechanism": "Passionflower flavonoids potentiate GABA-A receptor activity, and supplemental GABA may contribute peripheral and possibly limited central GABAergic effects, yielding additive inhibitory tone.", "evidenceLevel": "emerging", "sources": [ { "text": "Appel K et al. Modulation of the γ-aminobutyric acid (GABA) system by Passiflora incarnata L. Phytother Res. 2011;25(6):838-43.", "pmid": "21089181", "doi": "10.1002/ptr.3352", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21089181/", "publicSourceType": "PMID" }, { "text": "Boonstra E et al. Neurotransmitters as food supplements: the effects of GABA on brain and behavior. Front Psychol. 2015;6:1520.", "pmid": "26500584", "doi": "10.3389/fpsyg.2015.01520", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26500584/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both target GABAergic tone, so combining supplemental GABA with passionflower can produce additive calming and sedative effects.", "clinicalSignificance": "Likely additive calming and sedation when stacked.", "managementStrategy": "Use modest doses, avoid combining before driving, and do not stack with prescription sedatives or alcohol.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Pine Bark Extract", "supplementBName": "L-Arginine", "interactionType": "synergy", "severity": "info", "description": "Pine bark extract (Pycnogenol) combined with L-arginine improved erectile function and endothelial nitric oxide signaling in controlled clinical trials more than expected from either alone.", "recommendation": "A reasonable evidence-based pairing for vascular and erectile support. People on blood-pressure-lowering medication should monitor for additive hypotension.", "minimumTimeSeparation": null, "mechanism": "L-arginine is the substrate for nitric oxide synthase while pine bark procyanidins increase eNOS activity and protect nitric oxide from oxidative degradation, jointly enhancing endothelial NO availability.", "evidenceLevel": "moderate", "sources": [ { "text": "Stanislavov R, Nikolova V. Treatment of erectile dysfunction with pycnogenol and L-arginine. Journal of Sex and Marital Therapy, 2003", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Stanislavov R et al. Sexual function in men using a combination of pycnogenol and L-arginine aspartate (Prelox). International Journal of Impotence Research, 2009", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Pine bark extract (Pycnogenol) combined with L-arginine improved erectile function and endothelial nitric oxide signaling in controlled clinical trials more than expected from either alone.", "clinicalSignificance": "Well-studied synergistic pairing for nitric-oxide-mediated vascular function.", "managementStrategy": "A reasonable evidence-based pairing for vascular and erectile support. People on blood-pressure-lowering medication should monitor for additive hypotension.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Pine Bark Extract", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Vitamin C regenerates the oxidized flavonoid components of pine bark extract, helping sustain their antioxidant and endothelial-protective activity.", "recommendation": "Reasonable to take together for antioxidant and vascular support. No separation needed.", "minimumTimeSeparation": null, "mechanism": "Ascorbate reduces flavonoid radicals back to their active form after they neutralize reactive oxygen species, extending the effective antioxidant capacity of the pine bark procyanidins.", "evidenceLevel": "moderate", "sources": [ { "text": "Packer L et al. Antioxidant activity and biologic properties of a procyanidin-rich extract from pine bark (Pycnogenol). Free Radical Biology and Medicine, 1999", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Rohdewald P. A review of the French maritime pine bark extract (Pycnogenol), a herbal medication with a diverse clinical pharmacology. International Journal of Clinical Pharmacology and Therapeutics, 2002", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Vitamin C regenerates the oxidized flavonoid components of pine bark extract, helping sustain their antioxidant and endothelial-protective activity.", "clinicalSignificance": "Vitamin C helps recycle pine bark flavonoids, supporting their antioxidant effect.", "managementStrategy": "Reasonable to take together for antioxidant and vascular support. No separation needed.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Pine Bark Extract", "supplementBName": "L-Citrulline", "interactionType": "synergy", "severity": "info", "description": "L-citrulline raises plasma arginine and nitric oxide production, complementing pine bark extract's enhancement and protection of endothelial nitric oxide signaling.", "recommendation": "A rational vascular-support pairing. Those on antihypertensives should watch for additive blood-pressure lowering.", "minimumTimeSeparation": null, "mechanism": "L-citrulline is converted to arginine and then nitric oxide via NOS, while pine bark procyanidins upregulate eNOS and reduce oxidative breakdown of NO, jointly boosting endothelial NO availability.", "evidenceLevel": "emerging", "sources": [ { "text": "Rohdewald P. A review of the French maritime pine bark extract (Pycnogenol), a herbal medication with a diverse clinical pharmacology. International Journal of Clinical Pharmacology and Therapeutics, 2002", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Schwedhelm E et al. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. British Journal of Clinical Pharmacology, 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "L-citrulline raises plasma arginine and nitric oxide production, complementing pine bark extract's enhancement and protection of endothelial nitric oxide signaling.", "clinicalSignificance": "Mechanistically synergistic for nitric-oxide-mediated vascular function.", "managementStrategy": "A rational vascular-support pairing. Those on antihypertensives should watch for additive blood-pressure lowering.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Psilocybin", "supplementBName": "Lithium Orotate", "interactionType": "contraindicated", "severity": "dangerous", "description": "Combining psilocybin with lithium has been associated in case reports and online experience reports with seizures and severe adverse neurological reactions, making this one of the most dangerous documented psychedelic combinations.", "recommendation": "Do not combine. If you take any lithium-containing product, do not use psilocybin and seek medical advice.", "minimumTimeSeparation": null, "mechanism": "Lithium appears to lower seizure threshold and alter serotonergic and intracellular signaling in a way that markedly increases the risk of seizures and severe reactions when combined with serotonergic psychedelics.", "evidenceLevel": "emerging", "sources": [ { "text": "Nayak SM et al. Classic Psychedelic Coadministration with Lithium, but Not Lamotrigine, is Associated with Seizures: An Analysis of Online Psychedelic Experience Reports. Pharmacopsychiatry. 2021;54(5):240-245.", "pmid": "34348413", "doi": "10.1055/a-1524-2794", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34348413/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Combining psilocybin with lithium has been associated in case reports and online experience reports with seizures and severe adverse neurological reactions, making this one of the most dangerous documented psychedelic combinations.", "clinicalSignificance": "Reported seizure and severe-reaction risk: this combination should be avoided entirely.", "managementStrategy": "Do not combine. If you take any lithium-containing product, do not use psilocybin and seek medical advice.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Psilocybin", "supplementBName": "St. John's Wort", "interactionType": "caution", "severity": "moderate", "description": "St. John's Wort has serotonergic and weak monoamine-oxidase-modulating activity, so combining it with the serotonergic psychedelic psilocybin raises the theoretical risk of excessive serotonergic effects and unpredictable response.", "recommendation": "Do not combine without medical guidance. Anyone using St. John's Wort should seek medical advice before considering psilocybin.", "minimumTimeSeparation": null, "mechanism": "Psilocin acts as a serotonin 5-HT2A receptor agonist while St. John's Wort increases synaptic serotonin and has weak MAO-inhibiting constituents, creating potential for additive serotonergic activity.", "evidenceLevel": "emerging", "sources": [ { "text": "Halman A et al. Drug-drug interactions involving classic psychedelics: A systematic review. J Psychopharmacol. 2024.", "pmid": "37982394", "doi": "10.1177/02698811231211219", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37982394/", "publicSourceType": "PMID" }, { "text": "Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs. 2009.", "pmid": "19719333", "doi": "10.2165/11317010-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19719333/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "St. John's Wort has serotonergic and weak monoamine-oxidase-modulating activity, so combining it with the serotonergic psychedelic psilocybin raises the theoretical risk of excessive serotonergic effects and unpredictable response.", "clinicalSignificance": "Overlapping serotonergic activity warrants avoiding the combination without medical advice.", "managementStrategy": "Do not combine without medical guidance. Anyone using St. John's Wort should seek medical advice before considering psilocybin.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Psilocybin", "supplementBName": "5-HTP", "interactionType": "caution", "severity": "moderate", "description": "5-HTP increases serotonin synthesis and, combined with the serotonergic psychedelic psilocybin, raises the theoretical risk of excessive serotonergic stimulation.", "recommendation": "Do not combine. Seek medical advice before using either agent if the other is in use.", "minimumTimeSeparation": null, "mechanism": "5-HTP is the immediate precursor to serotonin and boosts serotonin levels, while psilocin acts as a 5-HT2A agonist, so the two can additively increase serotonergic signaling.", "evidenceLevel": "emerging", "sources": [ { "text": "Halman A et al. Drug-drug interactions involving classic psychedelics: A systematic review. J Psychopharmacol. 2024.", "pmid": "37982394", "doi": "10.1177/02698811231211219", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37982394/", "publicSourceType": "PMID" }, { "text": "Turner EH et al. Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacology and Therapeutics, 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "5-HTP increases serotonin synthesis and, combined with the serotonergic psychedelic psilocybin, raises the theoretical risk of excessive serotonergic stimulation.", "clinicalSignificance": "Additive serotonergic potential makes this combination one to avoid.", "managementStrategy": "Do not combine. Seek medical advice before using either agent if the other is in use.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Royal Jelly", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Royal jelly and vitamin C provide complementary antioxidant support without a known adverse interaction, and are commonly combined in supplements.", "recommendation": "Reasonable to take together. People with bee-product allergy should still avoid royal jelly regardless of the vitamin C.", "minimumTimeSeparation": null, "mechanism": "Vitamin C is a water-soluble antioxidant that scavenges reactive oxygen species, complementing the antioxidant constituents of royal jelly through independent pathways.", "evidenceLevel": "emerging", "sources": [ { "text": "Ramadan MF, Al-Ghamdi A. Bioactive compounds and health-promoting properties of royal jelly: a review. Journal of Functional Foods, 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Carr AC, Maggini S. Vitamin C and immune function. Nutrients, 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Royal jelly and vitamin C provide complementary antioxidant support without a known adverse interaction, and are commonly combined in supplements.", "clinicalSignificance": "Compatible antioxidant pairing with no known adverse interaction.", "managementStrategy": "Reasonable to take together. People with bee-product allergy should still avoid royal jelly regardless of the vitamin C.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Serrapeptase", "supplementBName": "Nattokinase", "interactionType": "caution", "severity": "moderate", "description": "Combining these two fibrinolytic enzymes produces additive breakdown of fibrin and a higher risk of bruising, prolonged bleeding, and (rarely) serious hemorrhage, particularly in people also on antiplatelet or anticoagulant drugs.", "recommendation": "Avoid stacking both fibrinolytic enzymes unless supervised by a clinician. Stop both at least 1 to 2 weeks before any surgery or dental procedure, and do not combine with aspirin, warfarin, or DOACs without medical oversight.", "minimumTimeSeparation": null, "mechanism": "Both serrapeptase and nattokinase have fibrinolytic and mild antiplatelet activity, degrading fibrin and reducing clot stability. Taken together their effects on hemostasis are additive.", "evidenceLevel": "emerging", "sources": [ { "text": "Tiwari M. The role of serratiopeptidase in the resolution of inflammation. Asian J Pharm Sci. 2017;12(3):209-215.", "pmid": "32104332", "doi": "10.1016/j.ajps.2017.01.003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32104332/", "publicSourceType": "PMID" }, { "text": "Weng Y et al. Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease. Int J Mol Sci. 2017;18(3).", "pmid": "28264497", "doi": "10.3390/ijms18030523", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28264497/", "publicSourceType": "PMID" }, { "text": "Kurosawa Y et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep. 2015;5:11601.", "pmid": "26109079", "doi": "10.1038/srep11601", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26109079/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Combining these two fibrinolytic enzymes produces additive breakdown of fibrin and a higher risk of bruising, prolonged bleeding, and (rarely) serious hemorrhage, particularly in people also on antiplatelet or anticoagulant drugs.", "clinicalSignificance": "Two blood-thinning enzymes together raise bleeding risk additively, especially around surgery or with other blood thinners.", "managementStrategy": "Avoid stacking both fibrinolytic enzymes unless supervised by a clinician. Stop both at least 1 to 2 weeks before any surgery or dental procedure, and do not combine with aspirin, warfarin, or DOACs without medical oversight.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Serrapeptase", "supplementBName": "Bromelain", "interactionType": "synergy", "severity": "info", "description": "Serrapeptase and bromelain are commonly combined as systemic proteolytic enzymes and appear to act in a complementary way to reduce post-surgical edema, pain, and inflammation.", "recommendation": "Reasonable to combine for short-term anti-inflammatory support. Take on an empty stomach (away from food) for systemic enzyme effect, and monitor for additive bleeding tendency if also on blood thinners.", "minimumTimeSeparation": null, "mechanism": "Both are systemic proteolytic enzymes: bromelain inhibits bradykinin generation and modulates arachidonic acid metabolism, while serrapeptase degrades inflammatory exudate and non-vital tissue. Their anti-inflammatory pathways are complementary.", "evidenceLevel": "moderate", "sources": [ { "text": "A Comparative Study of the Anti-Inflammatory Properties of Bromelain and Serratiopeptidase as Add-On Therapy Following Impacted Third Molar Surgery, 2020", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Effects of Systemic Enzyme Supplements on Symptoms and Quality of Life in Patients with Pulmonary Fibrosis: A Pilot Study, 2021", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Serrapeptase and bromelain are commonly combined as systemic proteolytic enzymes and appear to act in a complementary way to reduce post-surgical edema, pain, and inflammation.", "clinicalSignificance": "A widely used complementary enzyme pair for short-term inflammation and recovery support.", "managementStrategy": "Reasonable to combine for short-term anti-inflammatory support. Take on an empty stomach (away from food) for systemic enzyme effect, and monitor for additive bleeding tendency if also on blood thinners.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Serrapeptase", "supplementBName": "Fish Oil", "interactionType": "caution", "severity": "moderate", "description": "Fish oil has mild antiplatelet activity that can add to serrapeptase's fibrinolytic effect, modestly increasing the chance of bruising or prolonged bleeding, mainly at high omega-3 doses or around surgery.", "recommendation": "The combination is generally tolerated, but use caution with high-dose fish oil. Discontinue both before surgery and consult a clinician if also taking antiplatelet or anticoagulant medication.", "minimumTimeSeparation": null, "mechanism": "Omega-3 fatty acids incorporate into platelet membranes and shift eicosanoid balance toward antiplatelet prostacyclin, which can be additive to serrapeptase's fibrin-degrading, mild antiplatelet effect.", "evidenceLevel": "emerging", "sources": [ { "text": "Tiwari M. The role of serratiopeptidase in the resolution of inflammation. Asian J Pharm Sci. 2017;12(3):209-215.", "pmid": "32104332", "doi": "10.1016/j.ajps.2017.01.003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32104332/", "publicSourceType": "PMID" }, { "text": "Javaid M et al. Bleeding Risk in Patients Receiving Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Am Heart Assoc. 2024;13(10):e032390.", "pmid": "38742535", "doi": "10.1161/JAHA.123.032390", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38742535/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Fish oil has mild antiplatelet activity that can add to serrapeptase's fibrinolytic effect, modestly increasing the chance of bruising or prolonged bleeding, mainly at high omega-3 doses or around surgery.", "clinicalSignificance": "Low-to-moderate additive bleeding risk that matters mainly at high omega-3 doses or perioperatively.", "managementStrategy": "The combination is generally tolerated, but use caution with high-dose fish oil. Discontinue both before surgery and consult a clinician if also taking antiplatelet or anticoagulant medication.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Shilajit", "supplementBName": "Coenzyme Q10", "interactionType": "synergy", "severity": "info", "description": "Shilajit appears to enhance the mitochondrial action of CoQ10, with preclinical data showing greater ATP recovery and cellular energy production than CoQ10 alone.", "recommendation": "Reasonable to combine for energy and mitochondrial support. Human evidence is preliminary, so treat the synergy as plausible rather than proven and use standard doses of each.", "minimumTimeSeparation": null, "mechanism": "CoQ10 acts in the mitochondrial electron transport chain; shilajit's fulvic acid and dibenzo-alpha-pyrones appear to help stabilize the reduced (ubiquinol) form and support its delivery into mitochondria, improving ATP regeneration.", "evidenceLevel": "emerging", "sources": [ { "text": "Bhattacharyya S et al., Shilajit and CoQ10 combination on cellular bioenergetics (preclinical), as reported in Life Extension Magazine, 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Carrasco-Gallardo C et al., Shilajit: A Natural Phytocomplex with Potential Procognitive Activity, International Journal of Alzheimer's Disease, 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Shilajit appears to enhance the mitochondrial action of CoQ10, with preclinical data showing greater ATP recovery and cellular energy production than CoQ10 alone.", "clinicalSignificance": "Plausible mitochondrial synergy with promising preclinical data but limited human confirmation.", "managementStrategy": "Reasonable to combine for energy and mitochondrial support. Human evidence is preliminary, so treat the synergy as plausible rather than proven and use standard doses of each.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Shilajit", "supplementBName": "Iron", "interactionType": "caution", "severity": "moderate", "description": "Shilajit's fulvic acid enhances mineral absorption and shilajit itself supplies some iron, so combining it with an iron supplement can push iron intake higher than intended and is hazardous in people prone to iron overload.", "recommendation": "Do not combine shilajit with iron supplements if you have hemochromatosis or known high iron stores. Others should check ferritin before stacking the two and avoid layering high-dose iron on top of regular shilajit use.", "minimumTimeSeparation": null, "mechanism": "Shilajit's fulvic and humic acids chelate minerals and improve intestinal iron uptake, and the material itself contributes some bioavailable iron, so adding an iron supplement raises total absorbed iron and the risk of accumulation.", "evidenceLevel": "emerging", "sources": [ { "text": "Wilson E et al., Review of shilajit composition and fulvic acid mineral transport, Journal of Ethnopharmacology, 2011", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Stohs SJ, Safety and efficacy of shilajit (mumie, moomiyo), Phytotherapy Research, 2014. Safety and efficacy of shilajit (mumie, moomiyo). Phytother Res. 2014.", "pmid": "23733436", "doi": "10.1002/ptr.5018", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23733436/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Shilajit's fulvic acid enhances mineral absorption and shilajit itself supplies some iron, so combining it with an iron supplement can push iron intake higher than intended and is hazardous in people prone to iron overload.", "clinicalSignificance": "Stacking iron on shilajit can over-supply iron, a real danger for anyone predisposed to iron overload.", "managementStrategy": "Do not combine shilajit with iron supplements if you have hemochromatosis or known high iron stores. Others should check ferritin before stacking the two and avoid layering high-dose iron on top of regular shilajit use.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Shilajit", "supplementBName": "Ashwagandha", "interactionType": "synergy", "severity": "info", "description": "Shilajit and ashwagandha are frequently paired as complementary adaptogens, with shilajit supporting cellular energy and free testosterone while ashwagandha lowers cortisol and stress.", "recommendation": "Generally well tolerated together at standard doses. Evidence for the specific combination is limited, so judge effects individually and monitor for additive sedation or blood pressure changes.", "minimumTimeSeparation": null, "mechanism": "Shilajit supports ATP production and may lower sex hormone binding globulin to raise free testosterone, while ashwagandha modulates the HPA axis to reduce cortisol; the two act on different but complementary pathways.", "evidenceLevel": "emerging", "sources": [ { "text": "Pingali U et al., Effect of standardized aqueous extract of Withania somnifera, Pharmacognosy Research, 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Pandit S et al., Clinical evaluation of purified shilajit on testosterone levels in healthy volunteers, Andrologia, 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Shilajit and ashwagandha are frequently paired as complementary adaptogens, with shilajit supporting cellular energy and free testosterone while ashwagandha lowers cortisol and stress.", "clinicalSignificance": "A popular adaptogen pairing that is plausibly complementary but lacks robust combination trials.", "managementStrategy": "Generally well tolerated together at standard doses. Evidence for the specific combination is limited, so judge effects individually and monitor for additive sedation or blood pressure changes.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Silicon", "supplementBName": "Calcium", "interactionType": "synergy", "severity": "info", "description": "Silicon (as orthosilicic acid) added to calcium and vitamin D stimulates markers of bone collagen formation and may improve bone mineral density beyond calcium and vitamin D alone.", "recommendation": "Reasonable to include silicon alongside calcium for bone support. Use orthosilicic acid or a well-absorbed silicon form at typical doses (around 6 to 10 mg elemental silicon daily).", "minimumTimeSeparation": null, "mechanism": "Silicon stimulates osteoblast differentiation and type I collagen synthesis, providing the organic matrix into which calcium mineralizes, complementing calcium's role as the mineral substrate.", "evidenceLevel": "moderate", "sources": [ { "text": "Spector TD et al., Choline-stabilized orthosilicic acid supplementation as an adjunct to calcium and vitamin D3 stimulates markers of bone formation in osteopenic females, BMC Musculoskeletal Disorders, 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Jugdaohsingh R, Silicon and bone health, Journal of Nutrition Health and Aging, 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Silicon (as orthosilicic acid) added to calcium and vitamin D stimulates markers of bone collagen formation and may improve bone mineral density beyond calcium and vitamin D alone.", "clinicalSignificance": "Silicon supports the collagen scaffold of bone, complementing calcium's mineralizing role.", "managementStrategy": "Reasonable to include silicon alongside calcium for bone support. Use orthosilicic acid or a well-absorbed silicon form at typical doses (around 6 to 10 mg elemental silicon daily).", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Silicon", "supplementBName": "Collagen Peptides", "interactionType": "synergy", "severity": "info", "description": "Silicon supports endogenous collagen synthesis while collagen peptides supply collagen-derived amino acids, so combining them may enhance connective tissue, skin, and bone matrix support more than either alone.", "recommendation": "Reasonable to pair for skin, hair, nail, and connective tissue goals. Use a bioavailable silicon form with standard collagen peptide doses.", "minimumTimeSeparation": null, "mechanism": "Orthosilicic acid stimulates type I collagen synthesis, hydroxyproline incorporation, and glycosaminoglycan formation, while collagen peptides provide signaling peptides and substrate for collagen building, giving complementary upstream and substrate-level support.", "evidenceLevel": "emerging", "sources": [ { "text": "Reffitt DM et al., Orthosilicic acid stimulates collagen type 1 synthesis and osteoblastic differentiation in human osteoblast-like cells in vitro, Bone, 2003", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Barel A et al., Effect of oral intake of choline-stabilized orthosilicic acid on skin, nails and hair in women with photodamaged skin, Archives of Dermatological Research, 2005", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Silicon supports endogenous collagen synthesis while collagen peptides supply collagen-derived amino acids, so combining them may enhance connective tissue, skin, and bone matrix support more than either alone.", "clinicalSignificance": "Complementary collagen support: silicon drives synthesis, peptides supply building blocks.", "managementStrategy": "Reasonable to pair for skin, hair, nail, and connective tissue goals. Use a bioavailable silicon form with standard collagen peptide doses.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Silicon", "supplementBName": "Vitamin B7", "interactionType": "synergy", "severity": "info", "description": "Silicon and biotin (vitamin B7) are commonly combined for hair, skin, and nail support, with silicon supporting collagen and biotin supporting keratin production.", "recommendation": "Reasonable to combine for cosmetic and connective tissue goals at standard doses. Note that controlled human evidence for the specific combination is limited.", "minimumTimeSeparation": null, "mechanism": "Silicon supports collagen synthesis and connective tissue structure, while biotin is a cofactor for carboxylase enzymes involved in keratin-related metabolism, addressing different structural proteins.", "evidenceLevel": "emerging", "sources": [ { "text": "Randomized, Double-Blind, Placebo-Controlled Study of Silica and Biotin Extracts on Hair, Skin and Nail Health, 2024", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Barel A et al., Effect of oral intake of choline-stabilized orthosilicic acid on skin, nails and hair, Archives of Dermatological Research, 2005", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Silicon and biotin (vitamin B7) are commonly combined for hair, skin, and nail support, with silicon supporting collagen and biotin supporting keratin production.", "clinicalSignificance": "Complementary structural support: silicon for collagen, biotin for keratin pathways.", "managementStrategy": "Reasonable to combine for cosmetic and connective tissue goals at standard doses. Note that controlled human evidence for the specific combination is limited.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Spirulina", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Vitamin C taken with spirulina improves absorption of spirulina's non-heme iron, supporting its use for iron status.", "recommendation": "Take spirulina with a vitamin C source or supplement to maximize iron uptake. This is a helpful pairing for plant-based iron support.", "minimumTimeSeparation": null, "mechanism": "Ascorbic acid reduces ferric iron to the more soluble ferrous form and forms an absorbable iron-ascorbate complex, enhancing intestinal uptake of the non-heme iron found in spirulina.", "evidenceLevel": "moderate", "sources": [ { "text": "Hallberg L, Hulthen L, Prediction of dietary iron absorption: an algorithm for calculating absorption and bioavailability of dietary iron, American Journal of Clinical Nutrition, 2000", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Selmi C et al., The effects of Spirulina on anemia and immune function, Cellular and Molecular Immunology, 2011", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Vitamin C taken with spirulina improves absorption of spirulina's non-heme iron, supporting its use for iron status.", "clinicalSignificance": "Vitamin C boosts absorption of spirulina's plant iron, useful for supporting iron levels.", "managementStrategy": "Take spirulina with a vitamin C source or supplement to maximize iron uptake. This is a helpful pairing for plant-based iron support.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Spirulina", "supplementBName": "NAC", "interactionType": "synergy", "severity": "info", "description": "Spirulina and NAC both support antioxidant defenses through complementary mechanisms, with spirulina (phycocyanin) scavenging free radicals and NAC raising glutathione.", "recommendation": "Reasonable to combine for antioxidant and detoxification support at standard doses. Effects are complementary rather than redundant.", "minimumTimeSeparation": null, "mechanism": "NAC supplies cysteine to drive endogenous glutathione synthesis, while spirulina's phycocyanin directly scavenges reactive oxygen species and improves glutathione-related enzyme activity, reinforcing the same antioxidant network.", "evidenceLevel": "emerging", "sources": [ { "text": "Kepekci RA et al., Spirulina improves antioxidant status by reducing oxidative stress, Journal of Medicinal Food, 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Atkuri KR et al., N-Acetylcysteine: a safe antidote for cysteine and glutathione deficiency, Current Opinion in Pharmacology, 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Spirulina and NAC both support antioxidant defenses through complementary mechanisms, with spirulina (phycocyanin) scavenging free radicals and NAC raising glutathione.", "clinicalSignificance": "Two antioxidants that support the glutathione system through different routes.", "managementStrategy": "Reasonable to combine for antioxidant and detoxification support at standard doses. Effects are complementary rather than redundant.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Spirulina", "supplementBName": "Chlorella", "interactionType": "synergy", "severity": "info", "description": "Spirulina and chlorella are commonly combined as algae superfoods, offering complementary nutrient and antioxidant profiles, with chlorella favored for heavy metal binding.", "recommendation": "Generally well tolerated together at standard doses. Introduce gradually, as both can cause GI upset, and source from reputable suppliers given algae's tendency to concentrate contaminants.", "minimumTimeSeparation": null, "mechanism": "Both algae provide protein, chlorophyll, and antioxidants; chlorella's cell wall components bind heavy metals in the gut, while spirulina contributes phycocyanin antioxidant activity, giving complementary nutritional and detoxification support.", "evidenceLevel": "emerging", "sources": [ { "text": "Merino JJ et al., Long-term algae extract (Chlorella and Fucus) supplementation modulates SOD activity and decreases heavy metal levels, Marine Drugs, 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Wu Q et al., The antioxidant, immunomodulatory, and anti-inflammatory activities of Spirulina, Archives of Toxicology, 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Spirulina and chlorella are commonly combined as algae superfoods, offering complementary nutrient and antioxidant profiles, with chlorella favored for heavy metal binding.", "clinicalSignificance": "A complementary algae pairing for nutrient density and antioxidant support.", "managementStrategy": "Generally well tolerated together at standard doses. Introduce gradually, as both can cause GI upset, and source from reputable suppliers given algae's tendency to concentrate contaminants.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Strontium", "supplementBName": "Calcium", "interactionType": "timingSensitive", "severity": "moderate", "description": "Strontium and calcium compete for the same intestinal absorption pathway, and calcium is preferentially absorbed, so taking them together substantially reduces strontium uptake.", "recommendation": "Separate strontium and calcium doses by at least 2 to 3 hours. Many people take strontium at bedtime and calcium with meals to avoid competition.", "minimumTimeSeparation": "2 hours", "mechanism": "Strontium and calcium are divalent cations that share a common intestinal carrier system. When taken together, calcium outcompetes strontium for that transporter, lowering strontium absorption.", "evidenceLevel": "strong", "sources": [ { "text": "Reginster JY et al., Strontium ranelate: a new paradigm in the treatment of osteoporosis, Expert Opinion on Investigational Drugs, 2003", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "European Medicines Agency, Strontium ranelate (Protelos) Summary of Product Characteristics, 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Strontium and calcium compete for the same intestinal absorption pathway, and calcium is preferentially absorbed, so taking them together substantially reduces strontium uptake.", "clinicalSignificance": "Take strontium and calcium hours apart, since taken together calcium blocks strontium absorption.", "managementStrategy": "Separate strontium and calcium doses by at least 2 to 3 hours. Many people take strontium at bedtime and calcium with meals to avoid competition.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Strontium", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "info", "description": "Adequate vitamin D3 supports the calcium handling and bone mineralization environment in which strontium exerts its bone-building and antiresorptive effects.", "recommendation": "Maintain sufficient vitamin D3 status when using strontium for bone health. Vitamin D3 and strontium do not compete and can be taken on the same regimen.", "minimumTimeSeparation": null, "mechanism": "Vitamin D3 promotes intestinal calcium absorption and drives synthesis of bone proteins involved in mineralization, supporting the bone remodeling process that strontium modulates by stimulating formation and reducing resorption.", "evidenceLevel": "moderate", "sources": [ { "text": "Marie PJ, Strontium ranelate: a dual mode of action rebalancing bone turnover in favour of bone formation, Current Opinion in Rheumatology, 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Holick MF, Vitamin D deficiency, New England Journal of Medicine, 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Adequate vitamin D3 supports the calcium handling and bone mineralization environment in which strontium exerts its bone-building and antiresorptive effects.", "clinicalSignificance": "Vitamin D3 sets up the mineralization environment that lets strontium support bone effectively.", "managementStrategy": "Maintain sufficient vitamin D3 status when using strontium for bone health. Vitamin D3 and strontium do not compete and can be taken on the same regimen.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Strontium", "supplementBName": "Vitamin K2", "interactionType": "synergy", "severity": "info", "description": "Vitamin K2 supports directing calcium into bone and away from arteries, complementing strontium's bone-building action within a bone-health regimen.", "recommendation": "Reasonable to include vitamin K2 alongside strontium for bone support, especially when calcium and vitamin D are also used. They do not compete for absorption.", "minimumTimeSeparation": null, "mechanism": "Vitamin K2 activates osteocalcin (incorporating calcium into bone) and matrix Gla protein (inhibiting vascular calcification), supporting proper mineral handling while strontium stimulates osteoblasts and curbs resorption.", "evidenceLevel": "emerging", "sources": [ { "text": "Schurgers LJ et al., Vitamin K-dependent carboxylation of matrix Gla-protein, Thrombosis and Haemostasis, 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Knapen MHJ et al., Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women, Osteoporosis International, 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin K2 supports directing calcium into bone and away from arteries, complementing strontium's bone-building action within a bone-health regimen.", "clinicalSignificance": "Vitamin K2 helps direct calcium into bone, complementing strontium in a bone-health stack.", "managementStrategy": "Reasonable to include vitamin K2 alongside strontium for bone support, especially when calcium and vitamin D are also used. They do not compete for absorption.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Sulforaphane", "supplementBName": "NAC", "interactionType": "synergy", "severity": "info", "description": "Both compounds raise intracellular glutathione: sulforaphane induces the enzymes that synthesize glutathione while NAC supplies the rate-limiting cysteine precursor, supporting cellular antioxidant defense and detoxification.", "recommendation": "Reasonable to combine for antioxidant or detoxification goals. Avoid stacking very high doses of both around acute intense exercise, since excessive antioxidant load can blunt beneficial training adaptations.", "minimumTimeSeparation": null, "mechanism": "Sulforaphane activates the Nrf2 pathway, upregulating glutamate-cysteine ligase and other phase II enzymes; NAC delivers cysteine, the limiting substrate for glutathione synthesis, so the two act on complementary steps of the same pathway.", "evidenceLevel": "moderate", "sources": [ { "text": "Fahey JW, Talalay P. Antioxidant functions of sulforaphane: a potent inducer of phase II detoxification enzymes. Food and Chemical Toxicology, 1999", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Atkuri KR, Mantovani JJ, Herzenberg LA. N-Acetylcysteine: a safe antidote for cysteine/glutathione deficiency. Current Opinion in Pharmacology, 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both compounds raise intracellular glutathione: sulforaphane induces the enzymes that synthesize glutathione while NAC supplies the rate-limiting cysteine precursor, supporting cellular antioxidant defense and detoxification.", "clinicalSignificance": "Complementary glutathione-boosting actions make this a rational antioxidant pairing for most users.", "managementStrategy": "Reasonable to combine for antioxidant or detoxification goals. Avoid stacking very high doses of both around acute intense exercise, since excessive antioxidant load can blunt beneficial training adaptations.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Sulforaphane", "supplementBName": "Milk Thistle", "interactionType": "synergy", "severity": "info", "description": "Sulforaphane and silymarin (the active fraction of milk thistle) both activate Nrf2-driven cytoprotective and antioxidant defenses in the liver, providing complementary hepatoprotective support.", "recommendation": "Can be combined to support liver antioxidant capacity. No timing restriction is needed.", "minimumTimeSeparation": null, "mechanism": "Both phytochemicals activate the Nrf2 transcription factor, increasing expression of antioxidant and phase II detoxification enzymes such as NAD(P)H quinone dehydrogenase 1 and heme oxygenase-1 in hepatocytes.", "evidenceLevel": "emerging", "sources": [ { "text": "Surai PF. Silymarin as a natural antioxidant: an overview of the current evidence and perspectives. Antioxidants, 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Houghton CA, Fassett RG, Coombes JS. Sulforaphane and Other Nutrigenomic Nrf2 Activators. Oxidative Medicine and Cellular Longevity, 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Sulforaphane and silymarin (the active fraction of milk thistle) both activate Nrf2-driven cytoprotective and antioxidant defenses in the liver, providing complementary hepatoprotective support.", "clinicalSignificance": "Overlapping Nrf2 activation supports a hepatoprotective rationale, though direct combination trials are sparse.", "managementStrategy": "Can be combined to support liver antioxidant capacity. No timing restriction is needed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Sulforaphane", "supplementBName": "DIM", "interactionType": "synergy", "severity": "info", "description": "Both are cruciferous-derived compounds that favorably shift estrogen metabolism and induce phase I and phase II detoxification, giving complementary support to hormone metabolism pathways.", "recommendation": "Reasonable to combine for estrogen metabolism or detoxification goals. No timing separation is required.", "minimumTimeSeparation": null, "mechanism": "DIM promotes the 2-hydroxylation pathway of estrogen metabolism, while sulforaphane induces phase II conjugation enzymes via Nrf2, together enhancing formation and clearance of less proliferative estrogen metabolites.", "evidenceLevel": "emerging", "sources": [ { "text": "Thomson CA, et al. Chemopreventive properties of 3,3'-diindolylmethane in breast cancer. Breast Cancer Research and Treatment, 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Higdon JV, Delage B, Williams DE, Dashwood RH. Cruciferous vegetables and human cancer risk. Pharmacological Research, 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both are cruciferous-derived compounds that favorably shift estrogen metabolism and induce phase I and phase II detoxification, giving complementary support to hormone metabolism pathways.", "clinicalSignificance": "Cruciferous co-supplements act on adjacent steps of estrogen detoxification, a coherent but lightly studied pairing.", "managementStrategy": "Reasonable to combine for estrogen metabolism or detoxification goals. No timing separation is required.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Turkey Tail", "supplementBName": "Reishi", "interactionType": "synergy", "severity": "info", "description": "Turkey tail and reishi are both beta-glucan-rich medicinal mushrooms that modulate innate immune cell activity through complementary mechanisms, supporting an additive immunomodulatory effect.", "recommendation": "Can be taken together as part of a mushroom blend for immune support. No timing restriction is needed.", "minimumTimeSeparation": null, "mechanism": "Both contain beta-(1,3)/(1,6)-glucans that bind pattern recognition receptors such as Dectin-1 and Toll-like receptors on macrophages, dendritic cells and natural killer cells, priming innate immune responses.", "evidenceLevel": "emerging", "sources": [ { "text": "Wasser SP. Medicinal mushroom science: history, current status, future trends. International Journal of Medicinal Mushrooms, 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chan GC, Chan WK, Sze DM. The effects of beta-glucan on human immune and cancer cells. Journal of Hematology and Oncology, 2009", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Turkey tail and reishi are both beta-glucan-rich medicinal mushrooms that modulate innate immune cell activity through complementary mechanisms, supporting an additive immunomodulatory effect.", "clinicalSignificance": "A common, well-tolerated mushroom pairing with overlapping beta-glucan immunomodulation.", "managementStrategy": "Can be taken together as part of a mushroom blend for immune support. No timing restriction is needed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Turkey Tail", "supplementBName": "Probiotics", "interactionType": "synergy", "severity": "info", "description": "Turkey tail polysaccharopeptide (PSP) acts as a prebiotic that favorably shifts gut microbiota composition, complementing the live bacteria delivered by probiotic supplements.", "recommendation": "Reasonable to combine; turkey tail can serve as a prebiotic substrate alongside a probiotic. No timing separation is required.", "minimumTimeSeparation": null, "mechanism": "The polysaccharide-peptide fraction of turkey tail resists upper-gut digestion and is fermented in the colon, increasing beneficial taxa such as Bifidobacterium and Lactobacillus and short-chain fatty acid production, which supports probiotic colonization.", "evidenceLevel": "emerging", "sources": [ { "text": "Pallav K, et al. Effects of polysaccharopeptide from Trametes versicolor and amoxicillin on the gut microbiome of healthy volunteers. Gut Microbes, 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Yu ZT, et al. The gut microbiota and prebiotic potential of mushroom polysaccharides. Journal of Functional Foods, 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Turkey tail polysaccharopeptide (PSP) acts as a prebiotic that favorably shifts gut microbiota composition, complementing the live bacteria delivered by probiotic supplements.", "clinicalSignificance": "Turkey tail functions as a prebiotic that may enhance the benefit of co-administered probiotics.", "managementStrategy": "Reasonable to combine; turkey tail can serve as a prebiotic substrate alongside a probiotic. No timing separation is required.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Turkey Tail", "supplementBName": "Cordyceps", "interactionType": "synergy", "severity": "info", "description": "Turkey tail and cordyceps are both immunomodulatory medicinal mushrooms whose polysaccharides support innate immune activity through overlapping receptor pathways, producing an additive effect.", "recommendation": "Can be combined in an immune or wellness mushroom stack. No timing restriction is needed.", "minimumTimeSeparation": null, "mechanism": "Both supply fungal polysaccharides and beta-glucans that engage Dectin-1 and Toll-like receptors on macrophages and natural killer cells, stimulating cytokine production and innate immune surveillance.", "evidenceLevel": "emerging", "sources": [ { "text": "Lull C, Wichers HJ, Savelkoul HFJ. Antiinflammatory and immunomodulating properties of fungal metabolites. Mediators of Inflammation, 2005", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chan GC, Chan WK, Sze DM. The effects of beta-glucan on human immune and cancer cells. Journal of Hematology and Oncology, 2009", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Turkey tail and cordyceps are both immunomodulatory medicinal mushrooms whose polysaccharides support innate immune activity through overlapping receptor pathways, producing an additive effect.", "clinicalSignificance": "Overlapping beta-glucan immunomodulation makes this a coherent, well-tolerated mushroom pairing.", "managementStrategy": "Can be combined in an immune or wellness mushroom stack. No timing restriction is needed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Valerian Root", "supplementBName": "Melatonin", "interactionType": "caution", "severity": "moderate", "description": "Valerian root and melatonin both promote sleep through different mechanisms, so combining them can produce additive sedation and next-morning grogginess, especially at higher doses.", "recommendation": "If combined for sleep, start with low doses of each and take only at bedtime. Avoid driving or operating machinery until you know how the combination affects you, and do not add other sedatives.", "minimumTimeSeparation": null, "mechanism": "Valerian enhances GABA-A receptor signaling and inhibits GABA breakdown, while melatonin acts on MT1/MT2 receptors to regulate circadian sleep onset; the two converge to deepen and lengthen sedation.", "evidenceLevel": "moderate", "sources": [ { "text": "Bent S et al. Valerian for sleep: a systematic review and meta-analysis. Am J Med. 2006;119(12):1005-12.", "pmid": "17145239", "doi": "10.1016/j.amjmed.2006.02.026", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17145239/", "publicSourceType": "PMID" }, { "text": "Taibi DM et al. A systematic review of valerian as a sleep aid: safe but not effective. Sleep Med Rev. 2007;11(3):209-30.", "pmid": "17517355", "doi": "10.1016/j.smrv.2007.03.002", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17517355/", "publicSourceType": "PMID" }, { "text": "Costello RB et al. The effectiveness of melatonin for promoting healthy sleep: a rapid evidence assessment of the literature. Nutr J. 2014;13:106.", "pmid": "25380732", "doi": "10.1186/1475-2891-13-106", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25380732/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Valerian root and melatonin both promote sleep through different mechanisms, so combining them can produce additive sedation and next-morning grogginess, especially at higher doses.", "clinicalSignificance": "Additive sedation is generally mild but warrants low starting doses and bedtime-only use.", "managementStrategy": "If combined for sleep, start with low doses of each and take only at bedtime. Avoid driving or operating machinery until you know how the combination affects you, and do not add other sedatives.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Valerian Root", "supplementBName": "L-Theanine", "interactionType": "synergy", "severity": "info", "description": "Valerian root provides GABAergic sedation while L-theanine promotes calm without strong sedation, giving a complementary relaxation effect that is generally well tolerated.", "recommendation": "Can be combined for relaxation or sleep support. Take valerian nearer bedtime given its more sedating profile.", "minimumTimeSeparation": null, "mechanism": "Valerian enhances GABA-A receptor activity, while L-theanine increases alpha brain wave activity and modulates glutamate and GABA signaling, together favoring a calm, low-anxiety state.", "evidenceLevel": "emerging", "sources": [ { "text": "Bent S et al. Valerian for sleep: a systematic review and meta-analysis. Am J Med. 2006;119(12):1005-12.", "pmid": "17145239", "doi": "10.1016/j.amjmed.2006.02.026", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17145239/", "publicSourceType": "PMID" }, { "text": "Nobre AC et al. L-theanine, a natural constituent in tea, and its effect on mental state. Asia Pac J Clin Nutr. 2008;17 Suppl 1:167-8.", "pmid": "18296328", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18296328/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Valerian root provides GABAergic sedation while L-theanine promotes calm without strong sedation, giving a complementary relaxation effect that is generally well tolerated.", "clinicalSignificance": "A gentle, well-tolerated calming pairing, with valerian contributing the sedative component.", "managementStrategy": "Can be combined for relaxation or sleep support. Take valerian nearer bedtime given its more sedating profile.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Vanadium", "supplementBName": "Chromium", "interactionType": "caution", "severity": "moderate", "description": "Vanadium and chromium both have insulin-sensitizing, glucose-lowering activity, so combining them can produce additive reductions in blood glucose and risk of hypoglycemia, particularly in people on diabetes medication.", "recommendation": "Avoid stacking unless supervised by a clinician. People taking antidiabetic drugs should monitor blood glucose closely and watch for signs of hypoglycemia.", "minimumTimeSeparation": null, "mechanism": "Vanadium compounds mimic insulin by inhibiting protein tyrosine phosphatases and enhancing insulin receptor signaling, while chromium improves insulin receptor sensitivity; the combined effect can lower glucose further than either alone.", "evidenceLevel": "emerging", "sources": [ { "text": "Thompson KH, Orvig C. Vanadium in diabetes: 100 years from Phase 0 to Phase I. Journal of Inorganic Biochemistry, 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Anderson RA. Chromium, glucose intolerance and diabetes. J Am Coll Nutr. 1998.", "pmid": "9853533", "doi": "10.1080/07315724.1998.10718802", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9853533/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Vanadium and chromium both have insulin-sensitizing, glucose-lowering activity, so combining them can produce additive reductions in blood glucose and risk of hypoglycemia, particularly in people on diabetes medication.", "clinicalSignificance": "Additive glucose lowering raises hypoglycemia risk, especially alongside diabetes medication.", "managementStrategy": "Avoid stacking unless supervised by a clinician. People taking antidiabetic drugs should monitor blood glucose closely and watch for signs of hypoglycemia.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Vanadium", "supplementBName": "Berberine", "interactionType": "caution", "severity": "moderate", "description": "Vanadium has insulin-mimetic glucose-lowering activity and berberine is a potent glucose-lowering compound, so combining them can additively reduce blood glucose and increase the risk of hypoglycemia.", "recommendation": "Avoid combining without medical supervision. If used together, monitor blood glucose, especially when also taking antidiabetic medications, and watch for hypoglycemia symptoms.", "minimumTimeSeparation": null, "mechanism": "Vanadium enhances insulin receptor signaling by inhibiting protein tyrosine phosphatases, while berberine activates AMP-activated protein kinase and improves insulin sensitivity, producing additive lowering of blood glucose.", "evidenceLevel": "emerging", "sources": [ { "text": "Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008.", "pmid": "18442638", "doi": "10.1016/j.metabol.2008.01.013", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18442638/", "publicSourceType": "PMID" }, { "text": "Thompson KH, Orvig C. Vanadium in diabetes: 100 years from Phase 0 to Phase I. Journal of Inorganic Biochemistry, 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Vanadium has insulin-mimetic glucose-lowering activity and berberine is a potent glucose-lowering compound, so combining them can additively reduce blood glucose and increase the risk of hypoglycemia.", "clinicalSignificance": "Two glucose-lowering agents together can drive blood sugar too low, particularly with diabetes drugs.", "managementStrategy": "Avoid combining without medical supervision. If used together, monitor blood glucose, especially when also taking antidiabetic medications, and watch for hypoglycemia symptoms.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Vanadium", "supplementBName": "Alpha-Lipoic Acid", "interactionType": "caution", "severity": "moderate", "description": "Vanadium acts as an insulin mimetic and alpha-lipoic acid improves insulin sensitivity and glucose uptake, so the pair can additively lower blood glucose and raise hypoglycemia risk.", "recommendation": "Use together only with clinician oversight. Monitor blood glucose, particularly if taking insulin or other antidiabetic agents, and be alert for hypoglycemia.", "minimumTimeSeparation": null, "mechanism": "Vanadium enhances insulin receptor signaling via protein tyrosine phosphatase inhibition, while alpha-lipoic acid promotes GLUT4-mediated glucose uptake and improves insulin sensitivity, together amplifying glucose lowering.", "evidenceLevel": "emerging", "sources": [ { "text": "Singh U, Jialal I. Alpha-lipoic acid supplementation and diabetes. Nutr Rev. 2008.", "pmid": "19019027", "doi": "10.1111/j.1753-4887.2008.00118.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19019027/", "publicSourceType": "PMID" }, { "text": "Thompson KH, Orvig C. Vanadium in diabetes: 100 years from Phase 0 to Phase I. Journal of Inorganic Biochemistry, 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Vanadium acts as an insulin mimetic and alpha-lipoic acid improves insulin sensitivity and glucose uptake, so the pair can additively lower blood glucose and raise hypoglycemia risk.", "clinicalSignificance": "Combined insulin-sensitizing effects can lower glucose more than expected, warranting monitoring.", "managementStrategy": "Use together only with clinician oversight. Monitor blood glucose, particularly if taking insulin or other antidiabetic agents, and be alert for hypoglycemia.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Activated Charcoal", "supplementBName": "Iron", "interactionType": "timingSensitive", "severity": "moderate", "description": "Activated charcoal can adsorb orally ingested iron in the gut, reducing the amount of iron available for absorption when the two are taken together.", "recommendation": "Separate activated charcoal and iron by at least 2 hours, taking the iron dose well away from any charcoal.", "minimumTimeSeparation": "2 hours", "mechanism": "Activated charcoal has a large adsorptive surface area that binds many luminal compounds. Its affinity for inorganic iron salts is lower than for organic molecules, but co-ingestion can still sequester some iron and reduce uptake.", "evidenceLevel": "moderate", "sources": [ { "text": "Neuvonen PJ, Olkkola KT, Oral activated charcoal in the treatment of intoxications, Medical Toxicology and Adverse Drug Experience, 1988", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Activated charcoal can adsorb orally ingested iron in the gut, reducing the amount of iron available for absorption when the two are taken together.", "clinicalSignificance": "Charcoal taken with iron may blunt iron repletion, so dose them hours apart.", "managementStrategy": "Separate activated charcoal and iron by at least 2 hours, taking the iron dose well away from any charcoal.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Activated Charcoal", "supplementBName": "Vitamin C", "interactionType": "timingSensitive", "severity": "moderate", "description": "Activated charcoal adsorbs ascorbic acid in the gut, lowering the fraction of an oral vitamin C dose that is absorbed.", "recommendation": "Take vitamin C at least 2 hours before or after activated charcoal so the charcoal does not bind the vitamin.", "minimumTimeSeparation": "2 hours", "mechanism": "Vitamin C is a small organic molecule that binds readily to the high surface area of activated charcoal, so co-ingestion sequesters it in the lumen and reduces systemic uptake.", "evidenceLevel": "moderate", "sources": [ { "text": "Neuvonen PJ, Clinical pharmacokinetics of oral activated charcoal in acute intoxications, Clinical Pharmacokinetics, 1982. Clinical pharmacokinetics of oral activated charcoal in acute intoxications. Clin Pharmacokinet. 1982.", "pmid": "6761032", "doi": "10.2165/00003088-198207060-00001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6761032/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Activated charcoal adsorbs ascorbic acid in the gut, lowering the fraction of an oral vitamin C dose that is absorbed.", "clinicalSignificance": "Separate charcoal from vitamin C to preserve the vitamin dose.", "managementStrategy": "Take vitamin C at least 2 hours before or after activated charcoal so the charcoal does not bind the vitamin.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Activated Charcoal", "supplementBName": "Zinc", "interactionType": "timingSensitive", "severity": "moderate", "description": "Activated charcoal can adsorb zinc and other minerals in the gastrointestinal tract, reducing zinc absorption when the two are taken at the same time.", "recommendation": "Allow at least 2 hours between activated charcoal and a zinc supplement.", "minimumTimeSeparation": "2 hours", "mechanism": "The porous surface of activated charcoal nonselectively binds luminal contents, including mineral cations, decreasing the amount of zinc presented to intestinal transporters.", "evidenceLevel": "emerging", "sources": [ { "text": "Neuvonen PJ, Olkkola KT, Oral activated charcoal in the treatment of intoxications, Medical Toxicology and Adverse Drug Experience, 1988", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Activated charcoal can adsorb zinc and other minerals in the gastrointestinal tract, reducing zinc absorption when the two are taken at the same time.", "clinicalSignificance": "Charcoal and zinc should not share a dosing window.", "managementStrategy": "Allow at least 2 hours between activated charcoal and a zinc supplement.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Activated Charcoal", "supplementBName": "Methylcobalamin", "interactionType": "timingSensitive", "severity": "moderate", "description": "Activated charcoal adsorbs orally administered methylcobalamin, lowering the amount of B12 available for absorption if the two are taken together.", "recommendation": "Separate activated charcoal and methylcobalamin by at least 2 hours.", "minimumTimeSeparation": "2 hours", "mechanism": "Methylcobalamin is an organic molecule readily bound by the extensive adsorptive surface of activated charcoal, sequestering it in the gut lumen.", "evidenceLevel": "emerging", "sources": [ { "text": "Neuvonen PJ, Clinical pharmacokinetics of oral activated charcoal in acute intoxications, Clinical Pharmacokinetics, 1982. Clinical pharmacokinetics of oral activated charcoal in acute intoxications. Clin Pharmacokinet. 1982.", "pmid": "6761032", "doi": "10.2165/00003088-198207060-00001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6761032/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Activated charcoal adsorbs orally administered methylcobalamin, lowering the amount of B12 available for absorption if the two are taken together.", "clinicalSignificance": "Keep charcoal away from B12 dosing to avoid blunting absorption.", "managementStrategy": "Separate activated charcoal and methylcobalamin by at least 2 hours.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Artemisinin", "supplementBName": "Iron", "interactionType": "caution", "severity": "moderate", "description": "Iron supplementation may modulate artemisinin activity, because artemisinin relies on iron to generate its cytotoxic free radicals and iron status can alter its pharmacodynamics.", "recommendation": "Use caution when combining iron with artemisinin and discuss with a clinician, especially during therapeutic antimalarial use.", "minimumTimeSeparation": null, "mechanism": "Artemisinin contains an endoperoxide bridge that is cleaved by ferrous iron and heme to form reactive oxygen and carbon-centered radicals, so iron availability directly influences its radical-generating activity.", "evidenceLevel": "emerging", "sources": [ { "text": "Meshnick SR, Artemisinin: mechanisms of action, resistance and toxicity, International Journal for Parasitology, 2002. Artemisinin: mechanisms of action, resistance and toxicity. Int J Parasitol. 2002.", "pmid": "12435450", "doi": "10.1016/s0020-7519(02)00194-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12435450/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Iron supplementation may modulate artemisinin activity, because artemisinin relies on iron to generate its cytotoxic free radicals and iron status can alter its pharmacodynamics.", "clinicalSignificance": "Iron status interacts with artemisinin's iron-dependent radical mechanism.", "managementStrategy": "Use caution when combining iron with artemisinin and discuss with a clinician, especially during therapeutic antimalarial use.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Artemisinin", "supplementBName": "NAC", "interactionType": "caution", "severity": "moderate", "description": "NAC is a potent antioxidant that can quench the reactive oxygen species artemisinin depends on, potentially reducing artemisinin's pro-oxidant effect.", "recommendation": "Avoid taking high-dose NAC alongside artemisinin if the goal is artemisinin's oxidative activity, separating their use or discussing timing with a clinician.", "minimumTimeSeparation": null, "mechanism": "Artemisinin works by generating free radicals after iron-mediated endoperoxide cleavage, while NAC replenishes glutathione and scavenges reactive oxygen species, which can antagonize the radical-mediated effect.", "evidenceLevel": "emerging", "sources": [ { "text": "Meshnick SR, Artemisinin: mechanisms of action, resistance and toxicity, International Journal for Parasitology, 2002. Artemisinin: mechanisms of action, resistance and toxicity. Int J Parasitol. 2002.", "pmid": "12435450", "doi": "10.1016/s0020-7519(02)00194-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12435450/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "NAC is a potent antioxidant that can quench the reactive oxygen species artemisinin depends on, potentially reducing artemisinin's pro-oxidant effect.", "clinicalSignificance": "Antioxidant NAC may counteract artemisinin's oxidative mechanism.", "managementStrategy": "Avoid taking high-dose NAC alongside artemisinin if the goal is artemisinin's oxidative activity, separating their use or discussing timing with a clinician.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Artemisinin", "supplementBName": "Turmeric/Curcumin", "interactionType": "synergy", "severity": "info", "description": "Curcumin has been studied as a complementary partner to artemisinin, with preclinical data suggesting added antiparasitic and pro-oxidant effects.", "recommendation": "If combining, treat the curcumin as adjunctive and monitor, recognizing the pairing is supported mainly by preclinical evidence.", "minimumTimeSeparation": null, "mechanism": "Curcumin generates reactive oxygen species that can complement artemisinin's oxidative parasite killing, and curcumin has been shown to reduce parasite recrudescence after artemisinin in animal malaria models.", "evidenceLevel": "emerging", "sources": [ { "text": "Nandakumar DN et al, Curcumin-artemisinin combination therapy for malaria, Antimicrobial Agents and Chemotherapy, 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Curcumin has been studied as a complementary partner to artemisinin, with preclinical data suggesting added antiparasitic and pro-oxidant effects.", "clinicalSignificance": "Curcumin may complement artemisinin's pro-oxidant antiparasitic action.", "managementStrategy": "If combining, treat the curcumin as adjunctive and monitor, recognizing the pairing is supported mainly by preclinical evidence.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Artemisinin", "supplementBName": "Berberine", "interactionType": "synergy", "severity": "info", "description": "Berberine and artemisinin have shown complementary antiparasitic and antimicrobial activity in some preclinical studies, supporting a tentative synergistic rationale.", "recommendation": "May be combined with monitoring, recognizing the supporting evidence is largely preclinical and limited.", "minimumTimeSeparation": null, "mechanism": "The two compounds act through distinct pathways, berberine via membrane and enzyme effects and artemisinin via iron-dependent radical generation, which can allow additive or synergistic action against parasites in laboratory models.", "evidenceLevel": "emerging", "sources": [ { "text": "Ehrenkranz JRL et al, Berberine and other plant alkaloids in malaria, review of antiparasitic activity, Phytotherapy Research, 2009", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Berberine and artemisinin have shown complementary antiparasitic and antimicrobial activity in some preclinical studies, supporting a tentative synergistic rationale.", "clinicalSignificance": "Berberine may add to artemisinin's antiparasitic effect in preclinical models.", "managementStrategy": "May be combined with monitoring, recognizing the supporting evidence is largely preclinical and limited.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Bee Pollen", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Bee pollen contains flavonoids and polyphenols whose antioxidant activity can be complemented by vitamin C, supporting a mild synergistic antioxidant effect.", "recommendation": "May be taken together with no special precaution beyond standard dosing.", "minimumTimeSeparation": null, "mechanism": "Vitamin C can regenerate oxidized flavonoid radicals and works alongside bee pollen polyphenols within the antioxidant network, broadening overall radical scavenging capacity.", "evidenceLevel": "emerging", "sources": [ { "text": "Komosinska-Vassev K et al, Bee pollen: chemical composition and therapeutic application, Evidence-Based Complementary and Alternative Medicine, 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Bee pollen contains flavonoids and polyphenols whose antioxidant activity can be complemented by vitamin C, supporting a mild synergistic antioxidant effect.", "clinicalSignificance": "Vitamin C complements bee pollen's flavonoid antioxidants.", "managementStrategy": "May be taken together with no special precaution beyond standard dosing.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Bee Pollen", "supplementBName": "Quercetin", "interactionType": "caution", "severity": "moderate", "description": "Bee pollen naturally contains quercetin and related flavonoids, so adding a quercetin supplement increases total flavonoid intake and overlaps with bee pollen's own polyphenol load.", "recommendation": "Account for the quercetin already present in bee pollen when adding a quercetin supplement, and note that both can trigger allergic reactions in sensitive individuals.", "minimumTimeSeparation": null, "mechanism": "Quercetin is one of the principal flavonols in bee pollen, so combined intake is additive, and bee pollen also carries allergenic plant proteins that raise hypersensitivity risk independent of quercetin.", "evidenceLevel": "emerging", "sources": [ { "text": "Komosinska-Vassev K et al, Bee pollen: chemical composition and therapeutic application, Evidence-Based Complementary and Alternative Medicine, 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Bee pollen naturally contains quercetin and related flavonoids, so adding a quercetin supplement increases total flavonoid intake and overlaps with bee pollen's own polyphenol load.", "clinicalSignificance": "Combining adds to flavonoid load and shares allergy risk in atopic users.", "managementStrategy": "Account for the quercetin already present in bee pollen when adding a quercetin supplement, and note that both can trigger allergic reactions in sensitive individuals.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Bee Pollen", "supplementBName": "Echinacea", "interactionType": "caution", "severity": "moderate", "description": "Bee pollen and echinacea can both provoke allergic reactions, particularly in people sensitive to pollens or Asteraceae plants, so combining them raises hypersensitivity risk.", "recommendation": "Use caution in atopic or allergy-prone individuals, introducing one at a time and watching for allergic symptoms.", "minimumTimeSeparation": null, "mechanism": "Bee pollen contains plant pollen allergens and echinacea is an Asteraceae family plant, both of which can cross-react in pollen-allergic and ragweed-sensitive individuals to trigger reactions up to anaphylaxis.", "evidenceLevel": "moderate", "sources": [ { "text": "Mullins RJ, Heddle R, Adverse reactions associated with echinacea: the Australian experience, Annals of Allergy Asthma and Immunology, 2002", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Bee pollen and echinacea can both provoke allergic reactions, particularly in people sensitive to pollens or Asteraceae plants, so combining them raises hypersensitivity risk.", "clinicalSignificance": "Stacking two pollen and Asteraceae allergen sources raises allergy risk.", "managementStrategy": "Use caution in atopic or allergy-prone individuals, introducing one at a time and watching for allergic symptoms.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Beta-Alanine", "supplementBName": "Taurine", "interactionType": "timingSensitive", "severity": "moderate", "description": "Beta-alanine and taurine compete for the same transporter, so chronic high-dose beta-alanine can lower tissue taurine levels and vice versa.", "recommendation": "Separate beta-alanine and taurine doses by at least 2 hours and avoid taking them in the same serving to limit transporter competition.", "minimumTimeSeparation": "2 hours", "mechanism": "Both beta-alanine and taurine are substrates for the TauT (SLC6A6) beta-amino acid transporter, so they competitively inhibit each other's cellular uptake when present together.", "evidenceLevel": "moderate", "sources": [ { "text": "Trexler ET et al, International Society of Sports Nutrition position stand: Beta-Alanine, Journal of the International Society of Sports Nutrition, 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Beta-alanine and taurine compete for the same transporter, so chronic high-dose beta-alanine can lower tissue taurine levels and vice versa.", "clinicalSignificance": "A shared transporter means co-dosing reduces uptake of each, so space them out.", "managementStrategy": "Separate beta-alanine and taurine doses by at least 2 hours and avoid taking them in the same serving to limit transporter competition.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Beta-Alanine", "supplementBName": "L-Citrulline", "interactionType": "synergy", "severity": "info", "description": "Beta-alanine and L-citrulline are frequently combined and may give complementary gains in high-intensity and endurance performance.", "recommendation": "May be taken together pre-exercise, with no separation required.", "minimumTimeSeparation": null, "mechanism": "Beta-alanine buffers intramuscular acidosis via carnosine while L-citrulline raises nitric oxide and improves blood flow and ammonia clearance, addressing different limiters of fatigue.", "evidenceLevel": "moderate", "sources": [ { "text": "Glenn JM et al, Effects of combined citrulline and beta-alanine supplementation on cycling performance, Journal of Strength and Conditioning Research, 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Beta-alanine and L-citrulline are frequently combined and may give complementary gains in high-intensity and endurance performance.", "clinicalSignificance": "Complementary fatigue-buffering and blood-flow mechanisms in a pre-workout.", "managementStrategy": "May be taken together pre-exercise, with no separation required.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Beta-Alanine", "supplementBName": "HMB", "interactionType": "synergy", "severity": "info", "description": "Beta-alanine combined with HMB has shown additive benefits for lean mass and performance in training studies.", "recommendation": "May be combined as part of a training regimen without special timing.", "minimumTimeSeparation": null, "mechanism": "Beta-alanine increases muscle carnosine to delay fatigue while HMB attenuates muscle protein breakdown and supports recovery, two distinct mechanisms that support adaptation to training.", "evidenceLevel": "moderate", "sources": [ { "text": "Kern BD, Robinson TL, Effects of beta-alanine and HMB supplementation on body composition and performance in collegiate wrestlers and football players, Journal of Strength and Conditioning Research, 2011", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Beta-alanine combined with HMB has shown additive benefits for lean mass and performance in training studies.", "clinicalSignificance": "Buffering plus anti-catabolic support can be additive for body composition.", "managementStrategy": "May be combined as part of a training regimen without special timing.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Cat's Claw", "supplementBName": "Turmeric/Curcumin", "interactionType": "synergy", "severity": "info", "description": "Combined use broadens anti-inflammatory coverage by suppressing NF-kB driven cytokine production through complementary pathways, supporting joint comfort.", "recommendation": "Reasonable to stack for joint or inflammatory support. Take with food and monitor for any added GI upset.", "minimumTimeSeparation": null, "mechanism": "Cat's Claw pentacyclic oxindole alkaloids and curcuminoids both inhibit NF-kB activation and downstream TNF-alpha and prostaglandin synthesis, producing additive cytokine suppression.", "evidenceLevel": "emerging", "sources": [ { "text": "Sandoval M et al., Anti-inflammatory and antioxidant activities of cat's claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content, Phytomedicine, 2002", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Aggarwal BB, Harikumar KB, Potential therapeutic effects of curcumin against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases, International Journal of Biochemistry and Cell Biology, 2009", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Combined use broadens anti-inflammatory coverage by suppressing NF-kB driven cytokine production through complementary pathways, supporting joint comfort.", "clinicalSignificance": "Complementary NF-kB inhibitors that pair well for inflammatory joint support.", "managementStrategy": "Reasonable to stack for joint or inflammatory support. Take with food and monitor for any added GI upset.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Cat's Claw", "supplementBName": "Fish Oil", "interactionType": "caution", "severity": "moderate", "description": "Both agents have mild antiplatelet activity, so combining them may modestly increase bleeding tendency, especially with anticoagulant or antiplatelet drugs.", "recommendation": "Generally fine for most people, but monitor for easy bruising or bleeding and stop both 1 to 2 weeks before surgery. Use caution if on blood thinners.", "minimumTimeSeparation": null, "mechanism": "Cat's Claw may inhibit platelet aggregation and fish oil omega-3 fatty acids reduce thromboxane A2 generation and platelet aggregation, giving a potentially additive antiplatelet effect.", "evidenceLevel": "emerging", "sources": [ { "text": "Heck AM, DeWitt BA, Lukes AL, Potential interactions between alternative therapies and warfarin, American Journal of Health-System Pharmacy, 2000. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm. 2000.", "pmid": "10902065", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10902065/", "publicSourceType": "PMID" }, { "text": "Wachtel-Galor S, Benzie IFF (eds), Herbal Medicine: Biomolecular and Clinical Aspects, 2nd edition, 2011", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both agents have mild antiplatelet activity, so combining them may modestly increase bleeding tendency, especially with anticoagulant or antiplatelet drugs.", "clinicalSignificance": "Possible additive antiplatelet effect warrants bleeding awareness, particularly perioperatively or with blood thinners.", "managementStrategy": "Generally fine for most people, but monitor for easy bruising or bleeding and stop both 1 to 2 weeks before surgery. Use caution if on blood thinners.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Cat's Claw", "supplementBName": "Boswellia", "interactionType": "synergy", "severity": "info", "description": "Pairing provides complementary anti-inflammatory action, with Boswellia inhibiting 5-lipoxygenase and Cat's Claw suppressing NF-kB signaling.", "recommendation": "Reasonable to combine for joint and inflammatory support. No timing constraint needed; take with food to improve tolerability.", "minimumTimeSeparation": null, "mechanism": "Boswellic acids inhibit 5-lipoxygenase and leukotriene synthesis while Cat's Claw alkaloids inhibit NF-kB and TNF-alpha, hitting distinct arms of the inflammatory cascade.", "evidenceLevel": "emerging", "sources": [ { "text": "Ammon HPT, Boswellic acids in chronic inflammatory diseases, Planta Medica, 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Sandoval M et al., Anti-inflammatory and antioxidant activities of cat's claw, Phytomedicine, 2002", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Pairing provides complementary anti-inflammatory action, with Boswellia inhibiting 5-lipoxygenase and Cat's Claw suppressing NF-kB signaling.", "clinicalSignificance": "Distinct anti-inflammatory mechanisms make this a logical joint-support pairing.", "managementStrategy": "Reasonable to combine for joint and inflammatory support. No timing constraint needed; take with food to improve tolerability.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "D-Mannose", "supplementBName": "Lactobacillus Rhamnosus", "interactionType": "synergy", "severity": "info", "description": "These act through complementary anti-uropathogen mechanisms, pairing bacterial anti-adhesion with competitive colonization to support urinary tract defense.", "recommendation": "Reasonable to combine for recurrent UTI prophylaxis. No timing constraint required.", "minimumTimeSeparation": null, "mechanism": "D-Mannose occupies E. coli type 1 fimbrial lectins to prevent urothelial attachment, while Lactobacillus rhamnosus competitively colonizes and lowers pH to inhibit uropathogen growth.", "evidenceLevel": "emerging", "sources": [ { "text": "Kranjcec B, Papes D, Altarac S, D-mannose powder for prophylaxis of recurrent urinary tract infections in women, World Journal of Urology, 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Reid G et al., Probiotic Lactobacillus dose required to restore and maintain a normal vaginal flora, FEMS Immunology and Medical Microbiology, 2001", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "These act through complementary anti-uropathogen mechanisms, pairing bacterial anti-adhesion with competitive colonization to support urinary tract defense.", "clinicalSignificance": "Mechanistically complementary partners for urinary tract protection.", "managementStrategy": "Reasonable to combine for recurrent UTI prophylaxis. No timing constraint required.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Ginger Extract", "supplementBName": "Nattokinase", "interactionType": "caution", "severity": "moderate", "description": "Both have anticoagulant or antiplatelet activity, so combining them may increase bleeding risk, especially alongside blood-thinning medication.", "recommendation": "Use caution when combining. Watch for bruising or bleeding, avoid if on anticoagulants without medical oversight, and discontinue before surgery.", "minimumTimeSeparation": null, "mechanism": "Ginger gingerols inhibit thromboxane synthesis and platelet aggregation while nattokinase has fibrinolytic activity and degrades fibrin, producing potentially additive effects on hemostasis.", "evidenceLevel": "emerging", "sources": [ { "text": "Marx W et al. The Effect of Ginger (Zingiber officinale) on Platelet Aggregation: A Systematic Literature Review. PLoS One. 2015;10(10):e0141119.", "pmid": "26488162", "doi": "10.1371/journal.pone.0141119", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26488162/", "publicSourceType": "PMID" }, { "text": "Weng Y et al. Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease. Int J Mol Sci. 2017;18(3).", "pmid": "28264497", "doi": "10.3390/ijms18030523", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28264497/", "publicSourceType": "PMID" }, { "text": "Kurosawa Y et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep. 2015;5:11601.", "pmid": "26109079", "doi": "10.1038/srep11601", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26109079/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both have anticoagulant or antiplatelet activity, so combining them may increase bleeding risk, especially alongside blood-thinning medication.", "clinicalSignificance": "Additive antiplatelet plus fibrinolytic effect raises bleeding concern, notably with anticoagulants or surgery.", "managementStrategy": "Use caution when combining. Watch for bruising or bleeding, avoid if on anticoagulants without medical oversight, and discontinue before surgery.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Ginger Extract", "supplementBName": "Garlic Extract", "interactionType": "caution", "severity": "moderate", "description": "Combined antiplatelet activity may modestly increase bleeding tendency, particularly in those on anticoagulant or antiplatelet drugs or approaching surgery.", "recommendation": "Generally well tolerated, but monitor for bruising or bleeding and stop both 1 to 2 weeks before surgery. Use caution with blood thinners.", "minimumTimeSeparation": null, "mechanism": "Ginger inhibits thromboxane and platelet aggregation while garlic organosulfur compounds also suppress platelet aggregation, giving a potentially additive antiplatelet effect.", "evidenceLevel": "emerging", "sources": [ { "text": "Marx W et al. The Effect of Ginger (Zingiber officinale) on Platelet Aggregation: A Systematic Literature Review. PLoS One. 2015;10(10):e0141119.", "pmid": "26488162", "doi": "10.1371/journal.pone.0141119", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26488162/", "publicSourceType": "PMID" }, { "text": "Rahman K et al. Dietary supplementation with aged garlic extract inhibits ADP-induced platelet aggregation in humans. J Nutr. 2000;130(11):2662-5.", "pmid": "11053504", "doi": "10.1093/jn/130.11.2662", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11053504/", "publicSourceType": "PMID" }, { "text": "Allison GL et al. Aged garlic extract and its constituents inhibit platelet aggregation through multiple mechanisms. J Nutr. 2006;136(3 Suppl):782S-788S.", "pmid": "16484563", "doi": "10.1093/jn/136.3.782S", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16484563/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Combined antiplatelet activity may modestly increase bleeding tendency, particularly in those on anticoagulant or antiplatelet drugs or approaching surgery.", "clinicalSignificance": "Two antiplatelet botanicals together warrant bleeding awareness perioperatively or with blood thinners.", "managementStrategy": "Generally well tolerated, but monitor for bruising or bleeding and stop both 1 to 2 weeks before surgery. Use caution with blood thinners.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Ginger Extract", "supplementBName": "Fish Oil", "interactionType": "caution", "severity": "moderate", "description": "Both reduce platelet aggregation, so the combination can additively increase bleeding tendency, especially with concurrent anticoagulants.", "recommendation": "Usually fine at typical doses, but monitor for easy bruising or bleeding and discontinue before surgery. Use caution if on blood thinners.", "minimumTimeSeparation": null, "mechanism": "Ginger gingerols inhibit thromboxane A2 mediated platelet aggregation while fish oil omega-3s shift eicosanoid production away from pro-aggregatory thromboxane A2, producing potentially additive antiplatelet effects.", "evidenceLevel": "emerging", "sources": [ { "text": "Marx W et al. The Effect of Ginger (Zingiber officinale) on Platelet Aggregation: A Systematic Literature Review. PLoS One. 2015;10(10):e0141119.", "pmid": "26488162", "doi": "10.1371/journal.pone.0141119", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26488162/", "publicSourceType": "PMID" }, { "text": "Javaid M et al. Bleeding Risk in Patients Receiving Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Am Heart Assoc. 2024;13(10):e032390.", "pmid": "38742535", "doi": "10.1161/JAHA.123.032390", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38742535/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both reduce platelet aggregation, so the combination can additively increase bleeding tendency, especially with concurrent anticoagulants.", "clinicalSignificance": "Additive antiplatelet effect calls for bleeding awareness, particularly with anticoagulants or surgery.", "managementStrategy": "Usually fine at typical doses, but monitor for easy bruising or bleeding and discontinue before surgery. Use caution if on blood thinners.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Ginger Extract", "supplementBName": "Turmeric/Curcumin", "interactionType": "synergy", "severity": "info", "description": "Combined use offers complementary anti-inflammatory and antinausea support, with some additive antiplatelet effect to keep in mind.", "recommendation": "Reasonable to stack for inflammatory or digestive support. Take with food; remain mindful of bleeding risk if also on blood thinners.", "minimumTimeSeparation": null, "mechanism": "Ginger and curcumin both downregulate COX-2 and pro-inflammatory cytokine pathways, while curcumin additionally inhibits NF-kB, producing additive anti-inflammatory action.", "evidenceLevel": "moderate", "sources": [ { "text": "Daily JW et al., Efficacy of turmeric extracts and curcumin for alleviating the symptoms of joint arthritis, Journal of Medicinal Food, 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Grzanna R, Lindmark L, Frondoza CG, Ginger: an herbal medicinal product with broad anti-inflammatory actions, Journal of Medicinal Food, 2005", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Combined use offers complementary anti-inflammatory and antinausea support, with some additive antiplatelet effect to keep in mind.", "clinicalSignificance": "Well-matched anti-inflammatory botanicals; note mild additive antiplatelet potential.", "managementStrategy": "Reasonable to stack for inflammatory or digestive support. Take with food; remain mindful of bleeding risk if also on blood thinners.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Hyaluronic Acid", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Vitamin C is a required cofactor for collagen synthesis, supporting the extracellular matrix environment where hyaluronic acid contributes hydration.", "recommendation": "Reasonable to combine for skin and connective tissue support. No timing constraint required.", "minimumTimeSeparation": null, "mechanism": "Vitamin C acts as a cofactor for prolyl and lysyl hydroxylase in collagen synthesis and supports fibroblast function, complementing hyaluronic acid's role in matrix hydration.", "evidenceLevel": "emerging", "sources": [ { "text": "Pullar JM, Carr AC, Vissers MCM, The roles of vitamin C in skin health, Nutrients, 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Oe M et al., Oral hyaluronan relieves knee pain: a review, Nutrition Journal, 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Vitamin C is a required cofactor for collagen synthesis, supporting the extracellular matrix environment where hyaluronic acid contributes hydration.", "clinicalSignificance": "Vitamin C underpins the collagen matrix that hyaluronic acid hydrates, a logical skin-support pairing.", "managementStrategy": "Reasonable to combine for skin and connective tissue support. No timing constraint required.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Hyaluronic Acid", "supplementBName": "Glucosamine", "interactionType": "synergy", "severity": "info", "description": "Both support joint health through the cartilage matrix, with glucosamine providing a substrate for glycosaminoglycan synthesis and hyaluronic acid contributing to synovial fluid viscosity.", "recommendation": "Reasonable to combine for joint support. No timing separation needed.", "minimumTimeSeparation": null, "mechanism": "Glucosamine supplies a precursor for glycosaminoglycan and proteoglycan synthesis in cartilage, while hyaluronic acid contributes to synovial fluid lubrication and viscoelasticity, supporting joint matrix from complementary angles.", "evidenceLevel": "emerging", "sources": [ { "text": "Oe M et al., Oral hyaluronan relieves knee pain: a review, Nutrition Journal, 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Henrotin Y, Mobasheri A, Marty M, Is there any scientific evidence for the use of glucosamine in the management of human osteoarthritis?, Arthritis Research and Therapy, 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both support joint health through the cartilage matrix, with glucosamine providing a substrate for glycosaminoglycan synthesis and hyaluronic acid contributing to synovial fluid viscosity.", "clinicalSignificance": "Complementary cartilage and synovial fluid support make this a reasonable joint pairing.", "managementStrategy": "Reasonable to combine for joint support. No timing separation needed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "L-Glutathione", "supplementBName": "NAC", "interactionType": "synergy", "severity": "info", "description": "NAC supplies cysteine, the rate-limiting precursor for endogenous glutathione synthesis, so co-supplementation can raise and sustain intracellular glutathione more effectively than oral glutathione alone.", "recommendation": "Take together to support glutathione status; NAC at typical 600 to 1200 mg doses pairs well with oral or liposomal glutathione.", "minimumTimeSeparation": null, "mechanism": "NAC is deacetylated to L-cysteine, the limiting substrate for the gamma-glutamylcysteine synthetase step in glutathione synthesis, replenishing the cysteine pool that oral glutathione poorly restores after gut breakdown.", "evidenceLevel": "moderate", "sources": [ { "text": "Atkuri KR et al, N-acetylcysteine: a safe antidote for cysteine/glutathione deficiency, Current Opinion in Pharmacology, 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Sekhar RV et al, Glutathione synthesis is diminished in patients and restored by dietary supplementation, American Journal of Clinical Nutrition, 2011", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "NAC supplies cysteine, the rate-limiting precursor for endogenous glutathione synthesis, so co-supplementation can raise and sustain intracellular glutathione more effectively than oral glutathione alone.", "clinicalSignificance": "NAC feeds the precursor pathway that builds glutathione, a complementary rather than redundant pairing.", "managementStrategy": "Take together to support glutathione status; NAC at typical 600 to 1200 mg doses pairs well with oral or liposomal glutathione.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "L-Glutathione", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Vitamin C and glutathione recycle each other within the cellular antioxidant network, and vitamin C helps spare and maintain reduced glutathione levels.", "recommendation": "Reasonable to take together; vitamin C supports the recycling of oxidized glutathione back to its active reduced form.", "minimumTimeSeparation": null, "mechanism": "Ascorbate reduces oxidized glutathione (GSSG) back toward reduced glutathione (GSH) and, conversely, glutathione regenerates ascorbate from dehydroascorbate, maintaining both pools in their active states.", "evidenceLevel": "moderate", "sources": [ { "text": "Meister A, Glutathione-ascorbic acid antioxidant system in animals, Journal of Biological Chemistry, 1994", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Johnston CS et al, Vitamin C elevates red blood cell glutathione in healthy adults, American Journal of Clinical Nutrition, 1993", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin C and glutathione recycle each other within the cellular antioxidant network, and vitamin C helps spare and maintain reduced glutathione levels.", "clinicalSignificance": "The two antioxidants mutually regenerate, reinforcing redox capacity.", "managementStrategy": "Reasonable to take together; vitamin C supports the recycling of oxidized glutathione back to its active reduced form.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "L-Glutathione", "supplementBName": "Alpha-Lipoic Acid", "interactionType": "synergy", "severity": "info", "description": "Alpha-lipoic acid raises intracellular glutathione and, with glutathione, participates in a regenerating antioxidant cycle that restores other antioxidants.", "recommendation": "Can be combined to support antioxidant capacity; alpha-lipoic acid helps maintain reduced glutathione levels.", "minimumTimeSeparation": null, "mechanism": "Dihydrolipoic acid (the reduced form of alpha-lipoic acid) regenerates reduced glutathione from its oxidized form and supports cysteine uptake, increasing the cellular glutathione pool.", "evidenceLevel": "moderate", "sources": [ { "text": "Packer L et al, Alpha-lipoic acid as a biological antioxidant, Free Radical Biology and Medicine, 1995", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Han D et al, Lipoic acid increases de novo synthesis of cellular glutathione, BioFactors, 1997", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Alpha-lipoic acid raises intracellular glutathione and, with glutathione, participates in a regenerating antioxidant cycle that restores other antioxidants.", "clinicalSignificance": "Alpha-lipoic acid reinforces glutathione recycling and net cellular levels.", "managementStrategy": "Can be combined to support antioxidant capacity; alpha-lipoic acid helps maintain reduced glutathione levels.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "L-Glutathione", "supplementBName": "Selenium", "interactionType": "synergy", "severity": "info", "description": "Selenium is an essential cofactor for glutathione peroxidase, the enzyme through which glutathione neutralizes peroxides, so adequate selenium is needed for glutathione to exert its antioxidant function.", "recommendation": "Ensure adequate selenium intake to support glutathione-dependent antioxidant activity; avoid exceeding the 400 mcg upper limit of selenium.", "minimumTimeSeparation": null, "mechanism": "Glutathione peroxidases are selenoenzymes that use selenocysteine at their active site to reduce hydrogen peroxide and lipid peroxides while oxidizing glutathione, linking selenium status directly to glutathione antioxidant capacity.", "evidenceLevel": "strong", "sources": [ { "text": "Rotruck JT et al, Selenium: biochemical role as a component of glutathione peroxidase, Science, 1973", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Brigelius-Flohe R, Glutathione peroxidases and redox-regulated transcription factors, Biological Chemistry, 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Selenium is an essential cofactor for glutathione peroxidase, the enzyme through which glutathione neutralizes peroxides, so adequate selenium is needed for glutathione to exert its antioxidant function.", "clinicalSignificance": "Glutathione's peroxide-detoxifying role depends on selenium-containing enzymes.", "managementStrategy": "Ensure adequate selenium intake to support glutathione-dependent antioxidant activity; avoid exceeding the 400 mcg upper limit of selenium.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "L-Lysine", "supplementBName": "Calcium", "interactionType": "synergy", "severity": "info", "description": "L-lysine can enhance intestinal calcium absorption and reduce urinary calcium excretion, supporting calcium retention.", "recommendation": "Can be taken together; lysine may improve the efficiency of calcium uptake when bone or calcium support is the goal.", "minimumTimeSeparation": null, "mechanism": "Lysine increases gastrointestinal calcium absorption and promotes renal tubular calcium reabsorption, improving net calcium balance.", "evidenceLevel": "emerging", "sources": [ { "text": "Civitelli R et al, Dietary L-lysine and calcium metabolism in humans, Nutrition, 1992", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "L-lysine can enhance intestinal calcium absorption and reduce urinary calcium excretion, supporting calcium retention.", "clinicalSignificance": "Lysine modestly improves calcium absorption and retention.", "managementStrategy": "Can be taken together; lysine may improve the efficiency of calcium uptake when bone or calcium support is the goal.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "L-Lysine", "supplementBName": "Iron", "interactionType": "synergy", "severity": "info", "description": "Adding L-lysine alongside iron has been associated with improved ferritin levels in some iron-deficient individuals who do not fully respond to iron supplementation alone.", "recommendation": "Lysine may be a useful adjunct alongside iron in poor responders; continue standard iron dosing and monitor ferritin.", "minimumTimeSeparation": null, "mechanism": "The mechanism is not fully established, but lysine is thought to support intestinal iron absorption and tissue iron utilization, which may raise serum ferritin in lysine-deficient or iron-resistant states.", "evidenceLevel": "emerging", "sources": [ { "text": "Rushton DH et al, Lysine and iron in the treatment of women with hair loss and low ferritin, Clinical and Experimental Dermatology, 2002", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Adding L-lysine alongside iron has been associated with improved ferritin levels in some iron-deficient individuals who do not fully respond to iron supplementation alone.", "clinicalSignificance": "Lysine may augment iron repletion in selected poor responders, though evidence is limited.", "managementStrategy": "Lysine may be a useful adjunct alongside iron in poor responders; continue standard iron dosing and monitor ferritin.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "L-Lysine", "supplementBName": "Collagen Peptides", "interactionType": "synergy", "severity": "info", "description": "Lysine is a key amino acid in collagen and, in its hydroxylated form, is required for the cross-links that give collagen tensile strength, complementing collagen peptide supplementation.", "recommendation": "Can be taken together to support collagen-related goals; ensure adequate vitamin C as well for the hydroxylation step.", "minimumTimeSeparation": null, "mechanism": "Lysine residues in collagen are enzymatically hydroxylated to hydroxylysine and then cross-linked, a process essential for mature collagen fiber stability, so lysine availability supports collagen matrix formation.", "evidenceLevel": "emerging", "sources": [ { "text": "Yamauchi M, Sricholpech M, Lysine post-translational modifications of collagen, Essays in Biochemistry, 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Lysine is a key amino acid in collagen and, in its hydroxylated form, is required for the cross-links that give collagen tensile strength, complementing collagen peptide supplementation.", "clinicalSignificance": "Lysine provides substrate and cross-linking residues that underpin collagen structure.", "managementStrategy": "Can be taken together to support collagen-related goals; ensure adequate vitamin C as well for the hydroxylation step.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Olive Leaf Extract", "supplementBName": "Berberine", "interactionType": "caution", "severity": "moderate", "description": "Both olive leaf extract and berberine can lower blood glucose and blood pressure, so combining them may produce additive hypoglycemic and hypotensive effects.", "recommendation": "Monitor blood glucose and blood pressure when combining, especially alongside antidiabetic or antihypertensive medication, and adjust as needed.", "minimumTimeSeparation": null, "mechanism": "Olive leaf polyphenols (oleuropein) improve insulin sensitivity and have vasodilatory effects, while berberine activates AMPK and improves glucose uptake, giving overlapping glucose-lowering and pressure-lowering activity.", "evidenceLevel": "moderate", "sources": [ { "text": "de Bock M et al. Olive (Olea europaea L.) leaf polyphenols improve insulin sensitivity in middle-aged overweight men: a randomized, placebo-controlled, crossover trial. PLoS One. 2013;8(3):e57622.", "pmid": "23516412", "doi": "10.1371/journal.pone.0057622", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23516412/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both olive leaf extract and berberine can lower blood glucose and blood pressure, so combining them may produce additive hypoglycemic and hypotensive effects.", "clinicalSignificance": "Additive glucose and blood pressure lowering warrants monitoring.", "managementStrategy": "Monitor blood glucose and blood pressure when combining, especially alongside antidiabetic or antihypertensive medication, and adjust as needed.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Olive Leaf Extract", "supplementBName": "Garlic Extract", "interactionType": "caution", "severity": "moderate", "description": "Olive leaf extract and garlic extract both modestly lower blood pressure, so combined use may produce additive hypotensive effects.", "recommendation": "Monitor blood pressure when used together, particularly in those already on antihypertensive therapy, and watch for symptoms of low blood pressure.", "minimumTimeSeparation": null, "mechanism": "Both contain vasoactive compounds, oleuropein from olive leaf and allicin-derived sulfur compounds from garlic, that promote vasodilation and nitric oxide signaling, additively reducing blood pressure.", "evidenceLevel": "moderate", "sources": [ { "text": "Susalit E et al. Olive (Olea europaea) leaf extract effective in patients with stage-1 hypertension: comparison with Captopril. Phytomedicine. 2011;18(4):251-8.", "pmid": "21036583", "doi": "10.1016/j.phymed.2010.08.016", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21036583/", "publicSourceType": "PMID" }, { "text": "Ried K et al. Effect of garlic on blood pressure: a systematic review and meta-analysis. BMC Cardiovasc Disord. 2008;8:13.", "pmid": "18554422", "doi": "10.1186/1471-2261-8-13", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18554422/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Olive leaf extract and garlic extract both modestly lower blood pressure, so combined use may produce additive hypotensive effects.", "clinicalSignificance": "Stacking two blood pressure lowering botanicals can compound the effect.", "managementStrategy": "Monitor blood pressure when used together, particularly in those already on antihypertensive therapy, and watch for symptoms of low blood pressure.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Olive Leaf Extract", "supplementBName": "Quercetin", "interactionType": "synergy", "severity": "info", "description": "Olive leaf polyphenols and quercetin are complementary antioxidant and anti-inflammatory flavonoids that may also additively support healthy blood pressure and endothelial function.", "recommendation": "Reasonable to combine for antioxidant and vascular support; monitor blood pressure if also taking antihypertensives.", "minimumTimeSeparation": null, "mechanism": "Both polyphenols scavenge free radicals and enhance endothelial nitric oxide availability while inhibiting inflammatory signaling, producing overlapping vascular and antioxidant benefits.", "evidenceLevel": "emerging", "sources": [ { "text": "Larson AJ et al, Quercetin: a treatment for hypertension, Advances in Nutrition, 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Lockyer S et al, Olive leaf phenolics and cardiovascular risk, European Journal of Nutrition, 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Olive leaf polyphenols and quercetin are complementary antioxidant and anti-inflammatory flavonoids that may also additively support healthy blood pressure and endothelial function.", "clinicalSignificance": "Complementary polyphenols supporting antioxidant and endothelial function.", "managementStrategy": "Reasonable to combine for antioxidant and vascular support; monitor blood pressure if also taking antihypertensives.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Pregnenolone", "supplementBName": "Ashwagandha", "interactionType": "caution", "severity": "moderate", "description": "Both pregnenolone and ashwagandha influence stress hormone and HPA axis activity, with ashwagandha lowering cortisol while pregnenolone is a precursor to multiple steroid hormones, so the net hormonal effect of combining them is hard to predict.", "recommendation": "Use the combination cautiously and monitor for changes in mood, sleep, or hormone-related symptoms, especially with thyroid or adrenal conditions.", "minimumTimeSeparation": null, "mechanism": "Ashwagandha withanolides modulate the HPA axis and reduce cortisol output, while pregnenolone feeds steroidogenesis, so co-use can shift the balance of cortisol and other steroid hormones in unpredictable ways.", "evidenceLevel": "emerging", "sources": [ { "text": "Chandrasekhar K et al, A prospective study of the efficacy of ashwagandha in reducing stress and anxiety, Indian Journal of Psychological Medicine, 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Roberts E, Pregnenolone neurosteroid actions, Biochemical Pharmacology, 1995", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both pregnenolone and ashwagandha influence stress hormone and HPA axis activity, with ashwagandha lowering cortisol while pregnenolone is a precursor to multiple steroid hormones, so the net hormonal effect of combining them is hard to predict.", "clinicalSignificance": "Combined HPA axis and steroid precursor effects merit monitoring.", "managementStrategy": "Use the combination cautiously and monitor for changes in mood, sleep, or hormone-related symptoms, especially with thyroid or adrenal conditions.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Pregnenolone", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "info", "description": "Pregnenolone is a neurosteroid that modulates GABA receptors and magnesium glycinate supports relaxation and sleep, so the pair may complementarily support calm and sleep quality.", "recommendation": "Can be taken together, ideally in the evening if sleep and relaxation are the goal; start with conservative doses.", "minimumTimeSeparation": null, "mechanism": "Pregnenolone and its metabolites act as neurosteroids influencing GABA-A receptor signaling, while magnesium contributes to NMDA receptor regulation and GABAergic tone, giving complementary calming effects on the central nervous system.", "evidenceLevel": "emerging", "sources": [ { "text": "Reddy DS, Neurosteroids: endogenous role in the human brain and therapeutic potentials, Progress in Brain Research, 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Boyle NB et al, The effects of magnesium supplementation on subjective anxiety and stress, Nutrients, 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Pregnenolone is a neurosteroid that modulates GABA receptors and magnesium glycinate supports relaxation and sleep, so the pair may complementarily support calm and sleep quality.", "clinicalSignificance": "Complementary neurosteroid and mineral support for relaxation.", "managementStrategy": "Can be taken together, ideally in the evening if sleep and relaxation are the goal; start with conservative doses.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Psyllium Husk", "supplementBName": "Iron", "interactionType": "timingSensitive", "severity": "moderate", "description": "Psyllium soluble fiber forms a viscous gel in the gut that can bind iron and slow its absorption, lowering the effective dose absorbed when taken together.", "recommendation": "Take iron at least 2 hours apart from psyllium. Dose iron with vitamin C on an empty stomach or between fiber doses.", "minimumTimeSeparation": "2 hours", "mechanism": "The viscous mucilaginous gel formed by psyllium physically traps divalent mineral cations and increases gut transit, reducing the contact time and free iron available for duodenal uptake.", "evidenceLevel": "moderate", "sources": [ { "text": "Fernandez-Banares F, Nutritional care of the patient with constipation, Best Practice and Research Clinical Gastroenterology, 2006. Nutritional care of the patient with constipation. Best Pract Res Clin Gastroenterol. 2006.", "pmid": "16782530", "doi": "10.1016/j.bpg.2005.11.002", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16782530/", "publicSourceType": "PMID" }, { "text": "Anderson JW et al, Health benefits of dietary fiber, Nutrition Reviews, 2009", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Psyllium soluble fiber forms a viscous gel in the gut that can bind iron and slow its absorption, lowering the effective dose absorbed when taken together.", "clinicalSignificance": "Separate psyllium and iron by 2 or more hours to preserve iron absorption.", "managementStrategy": "Take iron at least 2 hours apart from psyllium. Dose iron with vitamin C on an empty stomach or between fiber doses.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Psyllium Husk", "supplementBName": "Zinc", "interactionType": "timingSensitive", "severity": "moderate", "description": "Psyllium gel can bind zinc in the intestinal lumen, reducing the fraction of zinc absorbed when the two are taken at the same time.", "recommendation": "Separate zinc and psyllium by at least 2 hours. Take zinc with a light meal away from your fiber dose.", "minimumTimeSeparation": "2 hours", "mechanism": "The viscous soluble fiber matrix traps divalent zinc cations and limits mucosal contact while speeding transit, decreasing intestinal zinc uptake.", "evidenceLevel": "moderate", "sources": [ { "text": "Lonnerdal B, Dietary factors influencing zinc absorption, Journal of Nutrition, 2000. Dietary factors influencing zinc absorption. J Nutr. 2000.", "pmid": "10801947", "doi": "10.1093/jn/130.5.1378S", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10801947/", "publicSourceType": "PMID" }, { "text": "Anderson JW et al, Health benefits of dietary fiber, Nutrition Reviews, 2009", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Psyllium gel can bind zinc in the intestinal lumen, reducing the fraction of zinc absorbed when the two are taken at the same time.", "clinicalSignificance": "Time zinc away from psyllium to avoid reduced mineral status over time.", "managementStrategy": "Separate zinc and psyllium by at least 2 hours. Take zinc with a light meal away from your fiber dose.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Psyllium Husk", "supplementBName": "Calcium", "interactionType": "timingSensitive", "severity": "moderate", "description": "Psyllium can bind calcium and accelerate intestinal transit, modestly reducing calcium absorption when co-administered.", "recommendation": "Take calcium supplements at least 2 hours away from psyllium. Split doses across the day if both are needed.", "minimumTimeSeparation": "2 hours", "mechanism": "The viscous fiber gel sequesters calcium cations and shortens the residence time in the absorptive segments of the gut, lowering net calcium uptake.", "evidenceLevel": "emerging", "sources": [ { "text": "Anderson JW et al, Health benefits of dietary fiber, Nutrition Reviews, 2009", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Fernandez-Banares F, Nutritional care of the patient with constipation, Best Practice and Research Clinical Gastroenterology, 2006. Nutritional care of the patient with constipation. Best Pract Res Clin Gastroenterol. 2006.", "pmid": "16782530", "doi": "10.1016/j.bpg.2005.11.002", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16782530/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Psyllium can bind calcium and accelerate intestinal transit, modestly reducing calcium absorption when co-administered.", "clinicalSignificance": "Separating doses by 2 or more hours preserves calcium absorption.", "managementStrategy": "Take calcium supplements at least 2 hours away from psyllium. Split doses across the day if both are needed.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Psyllium Husk", "supplementBName": "Berberine", "interactionType": "synergy", "severity": "info", "description": "Psyllium fiber and berberine both lower postprandial glucose and LDL cholesterol through complementary mechanisms, and combining them can give additive metabolic benefit.", "recommendation": "Combining is reasonable for glycemic and lipid support. Monitor blood glucose if also on antidiabetic medication, since the additive effect can lower it further.", "minimumTimeSeparation": null, "mechanism": "Psyllium slows carbohydrate absorption and binds bile acids while berberine activates AMPK and improves insulin sensitivity, producing additive reductions in glucose and cholesterol.", "evidenceLevel": "emerging", "sources": [ { "text": "Anderson JW et al. Health benefits of dietary fiber. Nutr Rev. 2009;67(4):188-205.", "pmid": "19335713", "doi": "10.1111/j.1753-4887.2009.00189.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19335713/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Psyllium fiber and berberine both lower postprandial glucose and LDL cholesterol through complementary mechanisms, and combining them can give additive metabolic benefit.", "clinicalSignificance": "Useful additive combination for metabolic goals, with glucose monitoring if on diabetes drugs.", "managementStrategy": "Combining is reasonable for glycemic and lipid support. Monitor blood glucose if also on antidiabetic medication, since the additive effect can lower it further.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Schisandra", "supplementBName": "Milk Thistle", "interactionType": "synergy", "severity": "info", "description": "Schisandra lignans and milk thistle silymarin both support hepatocyte protection and antioxidant defense, giving complementary hepatoprotective effects.", "recommendation": "Commonly used together for liver support. If on drugs with a narrow therapeutic window, monitor because both can influence hepatic enzyme activity.", "minimumTimeSeparation": null, "mechanism": "Schisandra lignans upregulate hepatic antioxidant and glutathione systems while silymarin stabilizes hepatocyte membranes and scavenges free radicals, producing complementary liver protection.", "evidenceLevel": "moderate", "sources": [ { "text": "Panossian A, Wikman G, Pharmacology of Schisandra chinensis, Journal of Ethnopharmacology, 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Abenavoli L et al, Milk thistle in liver diseases, Phytotherapy Research, 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Schisandra lignans and milk thistle silymarin both support hepatocyte protection and antioxidant defense, giving complementary hepatoprotective effects.", "clinicalSignificance": "Rational hepatoprotective pairing, with attention to co-administered drugs metabolized by the liver.", "managementStrategy": "Commonly used together for liver support. If on drugs with a narrow therapeutic window, monitor because both can influence hepatic enzyme activity.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Schisandra", "supplementBName": "NAC", "interactionType": "synergy", "severity": "info", "description": "Schisandra and NAC both raise hepatic glutathione and antioxidant capacity, providing complementary protection against oxidative liver stress.", "recommendation": "Reasonable combination for antioxidant and liver support. No specific separation required.", "minimumTimeSeparation": null, "mechanism": "NAC supplies cysteine as a glutathione precursor while schisandra lignans induce glutathione-related enzymes, jointly enhancing hepatic antioxidant defense.", "evidenceLevel": "emerging", "sources": [ { "text": "Panossian A, Wikman G, Pharmacology of Schisandra chinensis, Journal of Ethnopharmacology, 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Atkuri KR et al, N-Acetylcysteine a safe antidote for cysteine glutathione deficiency, Current Opinion in Pharmacology, 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Schisandra and NAC both raise hepatic glutathione and antioxidant capacity, providing complementary protection against oxidative liver stress.", "clinicalSignificance": "Complementary support of the glutathione antioxidant system.", "managementStrategy": "Reasonable combination for antioxidant and liver support. No specific separation required.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Schisandra", "supplementBName": "Rhodiola Rosea", "interactionType": "synergy", "severity": "info", "description": "Schisandra and Rhodiola are both adaptogens that modulate the stress response and reduce fatigue, with traditional and clinical use of the combination for endurance and mental performance.", "recommendation": "Commonly combined as adaptogens. Take earlier in the day since both can be mildly stimulating and may affect sleep if taken late.", "minimumTimeSeparation": null, "mechanism": "Both act on the hypothalamic-pituitary-adrenal axis and stress-response signaling to normalize cortisol and improve fatigue resistance, producing additive adaptogenic effects.", "evidenceLevel": "moderate", "sources": [ { "text": "Panossian A, Wikman G, Effects of adaptogens on the central nervous system, Pharmaceuticals, 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Panossian A, Wikman G, Pharmacology of Schisandra chinensis, Journal of Ethnopharmacology, 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Schisandra and Rhodiola are both adaptogens that modulate the stress response and reduce fatigue, with traditional and clinical use of the combination for endurance and mental performance.", "clinicalSignificance": "Established adaptogen pairing, best dosed earlier in the day.", "managementStrategy": "Commonly combined as adaptogens. Take earlier in the day since both can be mildly stimulating and may affect sleep if taken late.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Schisandra", "supplementBName": "Ashwagandha", "interactionType": "synergy", "severity": "info", "description": "Schisandra and ashwagandha are both adaptogens that help regulate the stress axis and lower perceived stress, with complementary calming and resilience effects.", "recommendation": "Reasonable adaptogen combination for stress support. Monitor for excess sedation when stacking multiple adaptogens.", "minimumTimeSeparation": null, "mechanism": "Both modulate cortisol and the hypothalamic-pituitary-adrenal axis, with ashwagandha withanolides adding GABAergic calming, producing additive stress-modulating effects.", "evidenceLevel": "emerging", "sources": [ { "text": "Panossian A, Wikman G, Effects of adaptogens on the central nervous system, Pharmaceuticals, 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chandrasekhar K et al, A prospective study of Ashwagandha in reducing stress, Indian Journal of Psychological Medicine, 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Schisandra and ashwagandha are both adaptogens that help regulate the stress axis and lower perceived stress, with complementary calming and resilience effects.", "clinicalSignificance": "Complementary adaptogens for stress, with attention to additive sedation.", "managementStrategy": "Reasonable adaptogen combination for stress support. Monitor for excess sedation when stacking multiple adaptogens.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Taurine", "supplementBName": "L-Theanine", "interactionType": "synergy", "severity": "info", "description": "Taurine and L-theanine both promote GABAergic and calming neurotransmission, giving additive relaxation without sedation.", "recommendation": "Reasonable combination for calm focus or sleep onset. No separation required.", "minimumTimeSeparation": null, "mechanism": "Both modulate inhibitory neurotransmission, with taurine acting on GABA and glycine receptors and L-theanine raising GABA and alpha brain wave activity, producing additive calming effects.", "evidenceLevel": "emerging", "sources": [ { "text": "Schaffer S, Kim HW, Effects and mechanisms of taurine as a therapeutic agent, Biomolecules and Therapeutics, 2018", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Nobre AC et al, L-theanine a natural constituent in tea and its effect on mental state, Asia Pacific Journal of Clinical Nutrition, 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Taurine and L-theanine both promote GABAergic and calming neurotransmission, giving additive relaxation without sedation.", "clinicalSignificance": "Complementary non-sedating calming agents.", "managementStrategy": "Reasonable combination for calm focus or sleep onset. No separation required.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Taurine", "supplementBName": "Creatine", "interactionType": "synergy", "severity": "info", "description": "Taurine and creatine are both cell-volumizing osmolytes that support muscle hydration and performance, and are frequently combined in pre-workout formulas for complementary ergogenic effect.", "recommendation": "Reasonable performance combination. Maintain adequate hydration when using both.", "minimumTimeSeparation": null, "mechanism": "Both function as intracellular osmolytes that increase cell hydration and support energy metabolism and calcium handling in muscle, producing complementary ergogenic effects.", "evidenceLevel": "emerging", "sources": [ { "text": "Spriet LL, Whitfield J, Taurine and skeletal muscle function, Current Opinion in Clinical Nutrition and Metabolic Care, 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Kreider RB et al, International Society of Sports Nutrition position stand on creatine, Journal of the International Society of Sports Nutrition, 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Taurine and creatine are both cell-volumizing osmolytes that support muscle hydration and performance, and are frequently combined in pre-workout formulas for complementary ergogenic effect.", "clinicalSignificance": "Complementary cell-volumizing ergogenic pairing.", "managementStrategy": "Reasonable performance combination. Maintain adequate hydration when using both.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Tribulus Terrestris", "supplementBName": "Tongkat Ali", "interactionType": "synergy", "severity": "info", "description": "Tribulus and Tongkat Ali are both used to support libido and male sexual function, with complementary traditional and clinical use for that goal.", "recommendation": "Combination is reasonable for libido support. Monitor for overstimulation and discontinue if restlessness or sleep disturbance occurs.", "minimumTimeSeparation": null, "mechanism": "Tribulus saponins act largely on libido and nitric oxide signaling while Tongkat Ali quassinoids may support free testosterone by reducing sex hormone binding globulin activity, giving complementary effects on sexual function.", "evidenceLevel": "emerging", "sources": [ { "text": "Neychev V, Mitev V, Pro-sexual and androgen enhancing effects of Tribulus terrestris, Journal of Ethnopharmacology, 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Talbott SM et al, Effect of Tongkat Ali on stress hormones and mood, Journal of the International Society of Sports Nutrition, 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Tribulus and Tongkat Ali are both used to support libido and male sexual function, with complementary traditional and clinical use for that goal.", "clinicalSignificance": "Complementary libido-support pairing with modest evidence.", "managementStrategy": "Combination is reasonable for libido support. Monitor for overstimulation and discontinue if restlessness or sleep disturbance occurs.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Tribulus Terrestris", "supplementBName": "Fenugreek", "interactionType": "synergy", "severity": "info", "description": "Tribulus and fenugreek are both used in male vitality and libido formulas, with complementary effects on sexual function and, for fenugreek, some evidence for supporting free testosterone.", "recommendation": "Reasonable combination for libido and vitality goals. Monitor blood glucose because fenugreek can lower it, especially if on antidiabetic medication.", "minimumTimeSeparation": null, "mechanism": "Tribulus saponins support libido and nitric oxide pathways while fenugreek furostanol saponins may inhibit aromatase and 5-alpha-reductase, together influencing androgen activity and sexual function.", "evidenceLevel": "emerging", "sources": [ { "text": "Neychev V, Mitev V, Pro-sexual and androgen enhancing effects of Tribulus terrestris, Journal of Ethnopharmacology, 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Wankhede S et al, Examining the effect of fenugreek extract on hormonal profile in male subjects, Journal of Sport and Health Science, 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Tribulus and fenugreek are both used in male vitality and libido formulas, with complementary effects on sexual function and, for fenugreek, some evidence for supporting free testosterone.", "clinicalSignificance": "Complementary vitality pairing, with glucose monitoring due to fenugreek.", "managementStrategy": "Reasonable combination for libido and vitality goals. Monitor blood glucose because fenugreek can lower it, especially if on antidiabetic medication.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Tribulus Terrestris", "supplementBName": "Zinc", "interactionType": "synergy", "severity": "info", "description": "Zinc is an essential cofactor for testosterone synthesis, so correcting low zinc status complements the libido-supporting use of Tribulus in male reproductive health.", "recommendation": "Reasonable combination for male reproductive support. Avoid chronic high-dose zinc above 40 mg daily to prevent copper depletion.", "minimumTimeSeparation": null, "mechanism": "Zinc is required for testicular steroidogenesis and luteinizing hormone signaling, so adequate zinc supports the hormonal substrate while Tribulus acts on libido and nitric oxide pathways.", "evidenceLevel": "emerging", "sources": [ { "text": "Prasad AS et al, Zinc status and serum testosterone levels of healthy adults, Nutrition, 1996", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Neychev V, Mitev V, Pro-sexual and androgen enhancing effects of Tribulus terrestris, Journal of Ethnopharmacology, 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Zinc is an essential cofactor for testosterone synthesis, so correcting low zinc status complements the libido-supporting use of Tribulus in male reproductive health.", "clinicalSignificance": "Adequate zinc supports the androgen pathway Tribulus is taken to influence.", "managementStrategy": "Reasonable combination for male reproductive support. Avoid chronic high-dose zinc above 40 mg daily to prevent copper depletion.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Green Tea Extract", "supplementBName": "L-Theanine", "interactionType": "synergy", "severity": "info", "description": "L-theanine smooths the caffeine stimulation from green tea extract, improving sustained attention while reducing jitteriness and the post-caffeine crash.", "recommendation": "Pairing is favorable. A roughly 2:1 ratio of L-theanine to caffeine (for example 200mg L-theanine with 100mg caffeine equivalent) gives calm, focused alertness.", "minimumTimeSeparation": null, "mechanism": "Caffeine in green tea extract antagonizes adenosine receptors to raise arousal, while L-theanine increases alpha-wave activity and modulates glutamate and GABA tone, blunting caffeine-driven anxiety without abolishing the alertness benefit.", "evidenceLevel": "strong", "sources": [ { "text": "Owen GN, Parnell H, De Bruin EA, Rycroft JA. The combined effects of L-theanine and caffeine on cognitive performance and mood. Nutritional Neuroscience. 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Giesbrecht T, Rycroft JA, Rowson MJ, De Bruin EA. The combination of L-theanine and caffeine improves cognitive performance and increases subjective alertness. Nutritional Neuroscience. 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "L-theanine smooths the caffeine stimulation from green tea extract, improving sustained attention while reducing jitteriness and the post-caffeine crash.", "clinicalSignificance": "A classic combination for clean cognitive stimulation with fewer caffeine side effects.", "managementStrategy": "Pairing is favorable. A roughly 2:1 ratio of L-theanine to caffeine (for example 200mg L-theanine with 100mg caffeine equivalent) gives calm, focused alertness.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Green Tea Extract", "supplementBName": "Berberine", "interactionType": "caution", "severity": "moderate", "description": "Both can lower blood glucose, so combining them may produce an additive hypoglycemic effect, especially during fasting or when also taking glucose-lowering medication.", "recommendation": "Reasonable to combine for metabolic support, but monitor blood glucose and watch for hypoglycemia symptoms. Coordinate with a clinician if you take insulin or sulfonylureas.", "minimumTimeSeparation": null, "mechanism": "Berberine activates AMP-activated protein kinase and improves insulin sensitivity, while green tea catechins (EGCG) inhibit intestinal carbohydrate digestion and glucose uptake, so the two glucose-lowering mechanisms are additive.", "evidenceLevel": "moderate", "sources": [ { "text": "Liu CY et al. Effects of green tea extract on insulin resistance and glucagon-like peptide 1 in patients with type 2 diabetes and lipid abnormalities: a randomized, double-blinded, and placebo-controlled trial. PLoS One. 2014;9(3):e91163.", "pmid": "24614112", "doi": "10.1371/journal.pone.0091163", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24614112/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both can lower blood glucose, so combining them may produce an additive hypoglycemic effect, especially during fasting or when also taking glucose-lowering medication.", "clinicalSignificance": "Additive glucose lowering is useful but raises hypoglycemia risk when stacked or combined with medication.", "managementStrategy": "Reasonable to combine for metabolic support, but monitor blood glucose and watch for hypoglycemia symptoms. Coordinate with a clinician if you take insulin or sulfonylureas.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Green Tea Extract", "supplementBName": "Quercetin", "interactionType": "synergy", "severity": "info", "description": "Quercetin may raise plasma levels of green tea catechins by slowing their breakdown, and the two polyphenols provide additive antioxidant and anti-inflammatory activity.", "recommendation": "Reasonable to take together for antioxidant support, with no special timing needed. Avoid stacking very high doses of multiple polyphenols if you have liver concerns.", "minimumTimeSeparation": null, "mechanism": "Quercetin can inhibit catechol-O-methyltransferase and efflux transporters that normally methylate and remove EGCG, increasing catechin exposure in preclinical models, and both compounds scavenge free radicals and inhibit NF-kB signaling.", "evidenceLevel": "emerging", "sources": [ { "text": "Wang P, Heber D, Henning SM. Quercetin increased the antiproliferative activity of green tea polyphenol EGCG in prostate cancer cells. Nutrition and Cancer. 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Lambert JD, Sang S, Yang CS. Biotransformation of green tea polyphenols and the biological activities of those metabolites. Molecular Pharmaceutics. 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Quercetin may raise plasma levels of green tea catechins by slowing their breakdown, and the two polyphenols provide additive antioxidant and anti-inflammatory activity.", "clinicalSignificance": "Quercetin may modestly boost green tea catechin exposure and adds antioxidant capacity.", "managementStrategy": "Reasonable to take together for antioxidant support, with no special timing needed. Avoid stacking very high doses of multiple polyphenols if you have liver concerns.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Ginkgo Biloba", "supplementBName": "Nattokinase", "interactionType": "caution", "severity": "moderate", "description": "Combining ginkgo with nattokinase increases bleeding risk because both reduce the blood's tendency to clot through different mechanisms.", "recommendation": "Use the combination cautiously and avoid it if you take anticoagulants or antiplatelet drugs. Stop both at least 1 to 2 weeks before any surgery and report easy bruising or bleeding.", "minimumTimeSeparation": null, "mechanism": "Ginkgo terpenoids inhibit platelet-activating factor and reduce platelet aggregation, while nattokinase has fibrinolytic and antithrombotic activity that degrades fibrin, so the combined effect on hemostasis is additive.", "evidenceLevel": "emerging", "sources": [ { "text": "Bone KM. Potential interaction of Ginkgo biloba leaf with antiplatelet or anticoagulant drugs: what is the evidence? Mol Nutr Food Res. 2008;52(7):764-71.", "pmid": "18214851", "doi": "10.1002/mnfr.200700098", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18214851/", "publicSourceType": "PMID" }, { "text": "Weng Y et al. Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease. Int J Mol Sci. 2017;18(3).", "pmid": "28264497", "doi": "10.3390/ijms18030523", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28264497/", "publicSourceType": "PMID" }, { "text": "Kurosawa Y et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep. 2015;5:11601.", "pmid": "26109079", "doi": "10.1038/srep11601", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26109079/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Combining ginkgo with nattokinase increases bleeding risk because both reduce the blood's tendency to clot through different mechanisms.", "clinicalSignificance": "Stacking two agents that impair clotting raises spontaneous and surgical bleeding risk.", "managementStrategy": "Use the combination cautiously and avoid it if you take anticoagulants or antiplatelet drugs. Stop both at least 1 to 2 weeks before any surgery and report easy bruising or bleeding.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Ginkgo Biloba", "supplementBName": "Bromelain", "interactionType": "caution", "severity": "moderate", "description": "Bromelain has mild antiplatelet and fibrinolytic activity that can add to ginkgo's platelet-inhibiting effect, modestly increasing bleeding risk.", "recommendation": "Generally safe at normal doses, but use caution if combining with blood thinners or before surgery. Discontinue both ahead of dental or surgical procedures.", "minimumTimeSeparation": null, "mechanism": "Ginkgo inhibits platelet-activating factor and aggregation, while bromelain reduces platelet aggregation and promotes fibrinolysis by influencing plasminogen and fibrinogen, so the antiplatelet effects are additive.", "evidenceLevel": "emerging", "sources": [ { "text": "Pavan R et al. Properties and therapeutic application of bromelain: a review. Biotechnol Res Int. 2012;2012:976203.", "pmid": "23304525", "doi": "10.1155/2012/976203", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23304525/", "publicSourceType": "PMID" }, { "text": "Bone KM. Potential interaction of Ginkgo biloba leaf with antiplatelet or anticoagulant drugs: what is the evidence? Mol Nutr Food Res. 2008;52(7):764-71.", "pmid": "18214851", "doi": "10.1002/mnfr.200700098", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18214851/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Bromelain has mild antiplatelet and fibrinolytic activity that can add to ginkgo's platelet-inhibiting effect, modestly increasing bleeding risk.", "clinicalSignificance": "A minor additive bleeding effect that matters mainly with anticoagulants or surgery.", "managementStrategy": "Generally safe at normal doses, but use caution if combining with blood thinners or before surgery. Discontinue both ahead of dental or surgical procedures.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Ginkgo Biloba", "supplementBName": "Bacopa Monnieri", "interactionType": "synergy", "severity": "info", "description": "Ginkgo and bacopa support cognition through complementary routes, and combining them may produce additive memory and processing-speed benefits.", "recommendation": "Reasonable to stack for cognitive support. Bacopa benefits accrue over several weeks of daily use, so allow time before judging the effect.", "minimumTimeSeparation": null, "mechanism": "Ginkgo increases cerebral blood flow and has antioxidant effects on neurons, while bacopa bacosides enhance synaptic transmission, dendritic growth, and cholinergic function, so the mechanisms target circulation and neuroplasticity respectively.", "evidenceLevel": "emerging", "sources": [ { "text": "Stough C, Lloyd J, Clarke J, et al. The chronic effects of an extract of Bacopa monniera on cognitive function in healthy human subjects. Psychopharmacology. 2001", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Nathan PJ, Tanner S, Lloyd J, et al. Effects of a combined extract of Ginkgo biloba and Bacopa monniera on cognitive function in healthy humans. Human Psychopharmacology. 2004", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Ginkgo and bacopa support cognition through complementary routes, and combining them may produce additive memory and processing-speed benefits.", "clinicalSignificance": "Complementary cognitive support pairing circulation with neuroplasticity.", "managementStrategy": "Reasonable to stack for cognitive support. Bacopa benefits accrue over several weeks of daily use, so allow time before judging the effect.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Rhodiola Rosea", "supplementBName": "L-Theanine", "interactionType": "synergy", "severity": "info", "description": "L-theanine takes the edge off rhodiola's mild stimulating effect, supporting calm, focused stress resilience.", "recommendation": "Take together in the morning or early afternoon. Avoid late-day rhodiola dosing since it can be activating and disrupt sleep.", "minimumTimeSeparation": null, "mechanism": "Rhodiola modulates the HPA axis and monoamine activity to produce a mildly activating anti-fatigue effect, while L-theanine raises alpha-wave activity and modulates GABA and glutamate, balancing the stimulation toward calm alertness.", "evidenceLevel": "emerging", "sources": [ { "text": "Panossian A, Wikman G, Sarris J. Rosenroot (Rhodiola rosea): traditional use, chemical composition, pharmacology and clinical efficacy. Phytomedicine. 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Nobre AC, Rao A, Owen GN. L-theanine, a natural constituent in tea, and its effect on mental state. Asia Pacific Journal of Clinical Nutrition. 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "L-theanine takes the edge off rhodiola's mild stimulating effect, supporting calm, focused stress resilience.", "clinicalSignificance": "Balances rhodiola's activation with theanine's calming tone for steady focus under stress.", "managementStrategy": "Take together in the morning or early afternoon. Avoid late-day rhodiola dosing since it can be activating and disrupt sleep.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Rhodiola Rosea", "supplementBName": "Bacopa Monnieri", "interactionType": "synergy", "severity": "info", "description": "Both are adaptogenic and cognition-supporting herbs, and combining them may give additive benefits for stress resilience and mental performance.", "recommendation": "Reasonable to combine for stress and cognition. Rhodiola acts quickly while bacopa builds over weeks, so expect the full effect after consistent daily use.", "minimumTimeSeparation": null, "mechanism": "Rhodiola normalizes stress hormone responses and reduces fatigue via the HPA axis and monoamines, while bacopa enhances cholinergic signaling, synaptic plasticity, and antioxidant defense in the brain.", "evidenceLevel": "emerging", "sources": [ { "text": "Panossian A, Wikman G. Effects of adaptogens on the central nervous system and the molecular mechanisms associated with their stress-protective activity. Pharmaceuticals. 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Kongkeaw C, Dilokthornsakul P, Thanarangsarit P, et al. Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract. Journal of Ethnopharmacology. 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both are adaptogenic and cognition-supporting herbs, and combining them may give additive benefits for stress resilience and mental performance.", "clinicalSignificance": "Complementary adaptogen pairing for stress-related cognitive support.", "managementStrategy": "Reasonable to combine for stress and cognition. Rhodiola acts quickly while bacopa builds over weeks, so expect the full effect after consistent daily use.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Rhodiola Rosea", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "info", "description": "Magnesium supports the stress response and nervous system relaxation, complementing rhodiola's adaptogenic effect on stress and fatigue.", "recommendation": "Reasonable to combine. Take rhodiola earlier in the day for its activating effect and magnesium glycinate in the evening to support relaxation and sleep.", "minimumTimeSeparation": null, "mechanism": "Chronic stress depletes magnesium, and magnesium regulates HPA axis activity and NMDA receptor tone to dampen stress reactivity, while rhodiola normalizes cortisol and stress-hormone signaling, so the two address the stress response from complementary angles.", "evidenceLevel": "emerging", "sources": [ { "text": "Pickering G, Mazur A, Trousselard M, et al. Magnesium status and stress: the vicious circle concept revisited. Nutrients. 2020", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Panossian A, Wikman G, Sarris J. Rosenroot (Rhodiola rosea): traditional use, chemical composition, pharmacology and clinical efficacy. Phytomedicine. 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Magnesium supports the stress response and nervous system relaxation, complementing rhodiola's adaptogenic effect on stress and fatigue.", "clinicalSignificance": "Pairs adaptogenic stress modulation with a mineral cofactor for the stress response.", "managementStrategy": "Reasonable to combine. Take rhodiola earlier in the day for its activating effect and magnesium glycinate in the evening to support relaxation and sleep.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Quercetin", "supplementBName": "Bromelain", "interactionType": "synergy", "severity": "info", "description": "Bromelain is traditionally co-formulated with quercetin to add anti-inflammatory activity, with the two compounds dampening inflammation through complementary routes.", "recommendation": "Take together, ideally with food for tolerability. The pairing is standard for inflammatory and allergy support and needs no special timing.", "minimumTimeSeparation": null, "mechanism": "Quercetin stabilizes mast cells and inhibits pro-inflammatory mediators including NF-kB, while bromelain modulates prostaglandins and cytokines, so the anti-inflammatory effects are complementary; the often-cited claim that bromelain boosts quercetin absorption is not well established in humans.", "evidenceLevel": "emerging", "sources": [ { "text": "Shaik YB, Castellani ML, Perrella A, et al. Role of quercetin (a natural herbal compound) in allergy and inflammation. Journal of Biological Regulators and Homeostatic Agents. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Pavan R, Jain S, Shraddha, Kumar A. Properties and therapeutic application of bromelain: a review. Biotechnol Res Int. 2012.", "pmid": "23304525", "doi": "10.1155/2012/976203", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23304525/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Bromelain is traditionally co-formulated with quercetin to add anti-inflammatory activity, with the two compounds dampening inflammation through complementary routes.", "clinicalSignificance": "A traditional anti-inflammatory pairing with complementary mechanisms.", "managementStrategy": "Take together, ideally with food for tolerability. The pairing is standard for inflammatory and allergy support and needs no special timing.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Quercetin", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "Quercetin and fish oil reduce inflammation through different pathways, giving an additive anti-inflammatory effect.", "recommendation": "Reasonable to combine for cardiometabolic and anti-inflammatory support. Take quercetin with the fish oil meal, since dietary fat may aid quercetin absorption.", "minimumTimeSeparation": null, "mechanism": "Quercetin inhibits NF-kB and lipoxygenase pathways and stabilizes mast cells, while omega-3 fatty acids in fish oil are converted into specialized pro-resolving mediators (resolvins, protectins) that help resolve inflammation, so the pathways are complementary.", "evidenceLevel": "emerging", "sources": [ { "text": "Calder PC. Omega-3 fatty acids and inflammatory processes: from molecules to man. Biochemical Society Transactions. 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Li Y, Yao J, Han C, et al. Quercetin, inflammation and immunity. Nutrients. 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Quercetin and fish oil reduce inflammation through different pathways, giving an additive anti-inflammatory effect.", "clinicalSignificance": "Complementary anti-inflammatory mechanisms support combined use.", "managementStrategy": "Reasonable to combine for cardiometabolic and anti-inflammatory support. Take quercetin with the fish oil meal, since dietary fat may aid quercetin absorption.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Quercetin", "supplementBName": "NAC", "interactionType": "synergy", "severity": "info", "description": "Quercetin and NAC provide complementary antioxidant support, with NAC replenishing glutathione and quercetin scavenging free radicals directly.", "recommendation": "Reasonable to combine for antioxidant and respiratory or immune support, with no special timing required.", "minimumTimeSeparation": null, "mechanism": "NAC is a cysteine donor that boosts intracellular glutathione synthesis, while quercetin directly scavenges reactive oxygen species and inhibits NF-kB and can be regenerated within the cellular antioxidant network, making the two mutually reinforcing.", "evidenceLevel": "emerging", "sources": [ { "text": "Pedre B, Barayeu U, Ezerina D, Dick TP. The mechanism of action of N-acetylcysteine (NAC): the emerging role of H2S and sulfane sulfur species. Pharmacology and Therapeutics. 2021", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Li Y, Yao J, Han C, et al. Quercetin, inflammation and immunity. Nutrients. 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Quercetin and NAC provide complementary antioxidant support, with NAC replenishing glutathione and quercetin scavenging free radicals directly.", "clinicalSignificance": "Layers direct radical scavenging with glutathione restoration.", "managementStrategy": "Reasonable to combine for antioxidant and respiratory or immune support, with no special timing required.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Probiotics", "supplementBName": "Saccharomyces Boulardii", "interactionType": "synergy", "severity": "info", "description": "Adding the probiotic yeast Saccharomyces boulardii to bacterial probiotics broadens coverage and is particularly effective for preventing antibiotic-associated diarrhea.", "recommendation": "Reasonable to combine. Unlike bacterial probiotics, S. boulardii is not killed by antibiotics, so it is a useful companion during antibiotic courses.", "minimumTimeSeparation": null, "mechanism": "Bacterial probiotics competitively exclude pathogens and produce short-chain fatty acids, while S. boulardii is a yeast that survives antibiotic exposure, neutralizes bacterial toxins, and stimulates secretory IgA, so the two act through non-overlapping mechanisms.", "evidenceLevel": "strong", "sources": [ { "text": "McFarland LV. Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World Journal of Gastroenterology. 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Hempel S, Newberry SJ, Maher AR, et al. Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis. JAMA. 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Adding the probiotic yeast Saccharomyces boulardii to bacterial probiotics broadens coverage and is particularly effective for preventing antibiotic-associated diarrhea.", "clinicalSignificance": "A yeast plus bacteria combination gives broader, antibiotic-resistant gut support.", "managementStrategy": "Reasonable to combine. Unlike bacterial probiotics, S. boulardii is not killed by antibiotics, so it is a useful companion during antibiotic courses.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Probiotics", "supplementBName": "Psyllium Husk", "interactionType": "synergy", "severity": "info", "description": "Psyllium is a partially fermentable fiber that can feed beneficial bacteria, acting as a synbiotic that supports probiotic colonization and short-chain fatty acid production.", "recommendation": "Reasonable to combine for gut health. Take psyllium with plenty of water. No timing separation from the probiotic is needed.", "minimumTimeSeparation": null, "mechanism": "Psyllium is partially fermented by colonic bacteria into short-chain fatty acids that lower luminal pH and nourish beneficial strains, providing a prebiotic substrate that helps probiotic organisms establish and persist.", "evidenceLevel": "moderate", "sources": [ { "text": "Gibson GR, Hutkins R, Sanders ME, et al. Expert consensus document: the International Scientific Association for Probiotics and Prebiotics consensus statement on the definition and scope of prebiotics. Nature Reviews Gastroenterology and Hepatology. 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "McRorie JW, McKeown NM. Understanding the physics of functional fibers in the gastrointestinal tract. Journal of the Academy of Nutrition and Dietetics. 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Psyllium is a partially fermentable fiber that can feed beneficial bacteria, acting as a synbiotic that supports probiotic colonization and short-chain fatty acid production.", "clinicalSignificance": "A partially prebiotic fiber that can enhance probiotic colonization (synbiotic effect).", "managementStrategy": "Reasonable to combine for gut health. Take psyllium with plenty of water. No timing separation from the probiotic is needed.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Probiotics", "supplementBName": "L-Glutamine", "interactionType": "synergy", "severity": "info", "description": "L-glutamine fuels intestinal cells and supports the gut barrier, complementing the way probiotics strengthen the mucosal lining.", "recommendation": "Reasonable to combine for gut barrier and digestive support, with no special timing required.", "minimumTimeSeparation": null, "mechanism": "L-glutamine is the primary energy substrate for enterocytes and supports tight-junction protein expression and intestinal repair, while probiotics enhance mucus production and barrier function and modulate immune signaling, so both reinforce gut barrier integrity.", "evidenceLevel": "emerging", "sources": [ { "text": "Kim MH, Kim H. The roles of glutamine in the intestine and its implication in intestinal diseases. International Journal of Molecular Sciences. 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Rao RK, Samak G. Role of glutamine in protection of intestinal epithelial tight junctions. Journal of Epithelial Biology and Pharmacology. 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "L-glutamine fuels intestinal cells and supports the gut barrier, complementing the way probiotics strengthen the mucosal lining.", "clinicalSignificance": "Pairs barrier-fueling glutamine with mucosa-supporting probiotics.", "managementStrategy": "Reasonable to combine for gut barrier and digestive support, with no special timing required.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Coenzyme Q10", "supplementBName": "L-Carnitine", "interactionType": "synergy", "severity": "info", "description": "The pair supports complementary stages of mitochondrial energy production, with L-Carnitine increasing fatty acid delivery into mitochondria and CoQ10 improving the efficiency of converting that fuel into ATP.", "recommendation": "Reasonable to take together, with or without food, for fatigue, exercise capacity, or mitochondrial support. Typical doses are CoQ10 100 to 200mg per day and L-Carnitine 1 to 2g per day. A migraine prophylaxis trial used both concurrently.", "minimumTimeSeparation": null, "mechanism": "L-Carnitine forms the carnitine shuttle that transports long-chain fatty acids across the inner mitochondrial membrane for beta-oxidation, while CoQ10 carries the resulting electrons through complexes I to III of the electron transport chain to drive ATP synthesis.", "evidenceLevel": "moderate", "sources": [ { "text": "Hajihashemi P, Askari G, Khorvash F, et al. The effects of concurrent Coenzyme Q10 and L-carnitine supplementation in migraine prophylaxis: a randomized, placebo-controlled, double-blind trial. Cephalalgia. 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Gvozdjakova A, et al. Mitochondrial bioenergetics and the role of coenzyme Q10 and L-carnitine. Bratislava Medical Journal. 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "The pair supports complementary stages of mitochondrial energy production, with L-Carnitine increasing fatty acid delivery into mitochondria and CoQ10 improving the efficiency of converting that fuel into ATP.", "clinicalSignificance": "Rational, low-risk combination that targets sequential steps of cellular energy metabolism.", "managementStrategy": "Reasonable to take together, with or without food, for fatigue, exercise capacity, or mitochondrial support. Typical doses are CoQ10 100 to 200mg per day and L-Carnitine 1 to 2g per day. A migraine prophylaxis trial used both concurrently.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Boswellia", "supplementBName": "Glucosamine", "interactionType": "synergy", "severity": "info", "description": "The pair targets joint discomfort through distinct routes, with Boswellia dampening inflammatory signaling and Glucosamine supplying a building block for cartilage matrix, so the combination addresses both inflammation and structural support.", "recommendation": "Reasonable to take together for osteoarthritis support. Use a standardized Boswellia extract (for example one enriched for AKBA) at the label dose alongside glucosamine sulfate 1500mg per day. No timing separation is needed.", "minimumTimeSeparation": null, "mechanism": "Boswellic acids (notably AKBA) inhibit 5-lipoxygenase and reduce leukotriene B4, lowering joint inflammation, while glucosamine provides substrate for glycosaminoglycan and proteoglycan synthesis in cartilage.", "evidenceLevel": "moderate", "sources": [ { "text": "Sengupta K, et al. A double blind, randomized, placebo controlled study of the efficacy and safety of 5-Loxin for treatment of osteoarthritis of the knee. Arthritis Research and Therapy. 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Yu G, et al. Effectiveness of Boswellia and Boswellia extract for osteoarthritis patients: a systematic review and meta-analysis. BMC Complementary Medicine and Therapies. 2020", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "The pair targets joint discomfort through distinct routes, with Boswellia dampening inflammatory signaling and Glucosamine supplying a building block for cartilage matrix, so the combination addresses both inflammation and structural support.", "clinicalSignificance": "Complementary anti-inflammatory and cartilage-support actions make this a sensible joint-health stack.", "managementStrategy": "Reasonable to take together for osteoarthritis support. Use a standardized Boswellia extract (for example one enriched for AKBA) at the label dose alongside glucosamine sulfate 1500mg per day. No timing separation is needed.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Bacopa Monnieri", "supplementBName": "Citicoline", "interactionType": "synergy", "severity": "info", "description": "The pair supports cholinergic function from two directions, with Citicoline supplying precursor for acetylcholine and membrane phospholipids and Bacopa supporting cholinergic transmission and synaptic plasticity.", "recommendation": "Reasonable to combine for memory and processing speed. Bacopa is best taken consistently for several weeks with food (often dosed at 300mg standardized to bacosides); citicoline at 250 to 500mg per day. No timing separation needed.", "minimumTimeSeparation": null, "mechanism": "Citicoline donates choline and cytidine that feed acetylcholine synthesis and phosphatidylcholine membrane repair, while Bacopa modulates acetylcholinesterase activity and promotes dendritic branching, supporting cholinergic signaling.", "evidenceLevel": "emerging", "sources": [ { "text": "Aguiar S, Borowski T. Neuropharmacological review of the nootropic herb Bacopa monnieri. Rejuvenation Research. 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Secades JJ. Citicoline: pharmacological and clinical review. Revista de Neurologia. 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "The pair supports cholinergic function from two directions, with Citicoline supplying precursor for acetylcholine and membrane phospholipids and Bacopa supporting cholinergic transmission and synaptic plasticity.", "clinicalSignificance": "Mechanistically complementary nootropic pairing converging on the cholinergic system, with limited combination-specific human data.", "managementStrategy": "Reasonable to combine for memory and processing speed. Bacopa is best taken consistently for several weeks with food (often dosed at 300mg standardized to bacosides); citicoline at 250 to 500mg per day. No timing separation needed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Bacopa Monnieri", "supplementBName": "Lion's Mane", "interactionType": "synergy", "severity": "info", "description": "The pair supports neuroplasticity by different means, with Lion's Mane stimulating neurotrophic factor production and Bacopa enhancing synaptic signaling and providing antioxidant neuroprotection.", "recommendation": "Reasonable to stack for long-term cognitive support, taking both consistently over weeks to months. Bacopa is taken with food; Lion's Mane can be taken any time. No timing separation needed.", "minimumTimeSeparation": null, "mechanism": "Lion's Mane hericenones and erinacines promote nerve growth factor and downstream neurite outgrowth, while Bacopa increases dendritic branching, modulates cholinergic and monoamine systems, and reduces oxidative stress, giving overlapping support for synaptic remodeling.", "evidenceLevel": "emerging", "sources": [ { "text": "Mori K, et al. Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial. Phytotherapy Research. 2009", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Aguiar S, Borowski T. Neuropharmacological review of the nootropic herb Bacopa monnieri. Rejuvenation Research. 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "The pair supports neuroplasticity by different means, with Lion's Mane stimulating neurotrophic factor production and Bacopa enhancing synaptic signaling and providing antioxidant neuroprotection.", "clinicalSignificance": "Plausible complementary neuroplasticity stack, though human data on the specific combination are limited.", "managementStrategy": "Reasonable to stack for long-term cognitive support, taking both consistently over weeks to months. Bacopa is taken with food; Lion's Mane can be taken any time. No timing separation needed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Lion's Mane", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "The pair supports brain health through complementary pathways, with Lion's Mane promoting neurotrophic factor production and Fish Oil supplying DHA for neuronal membranes alongside anti-inflammatory omega-3 effects.", "recommendation": "Reasonable to combine for cognitive and mood support. Take Fish Oil with a meal to aid absorption; Lion's Mane can be taken at the same time. No timing separation needed.", "minimumTimeSeparation": null, "mechanism": "Lion's Mane upregulates nerve growth factor to drive neurite outgrowth, while DHA and EPA from fish oil are incorporated into neuronal membranes and help resolve neuroinflammation, together favoring neuronal repair and plasticity.", "evidenceLevel": "emerging", "sources": [ { "text": "Mori K, et al. Nerve growth factor-inducing activity of Hericium erinaceus. Biological and Pharmaceutical Bulletin. 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Dyall SC. Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA. Frontiers in Aging Neuroscience. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "The pair supports brain health through complementary pathways, with Lion's Mane promoting neurotrophic factor production and Fish Oil supplying DHA for neuronal membranes alongside anti-inflammatory omega-3 effects.", "clinicalSignificance": "Neurotrophic and membrane plus anti-inflammatory actions complement each other for brain support.", "managementStrategy": "Reasonable to combine for cognitive and mood support. Take Fish Oil with a meal to aid absorption; Lion's Mane can be taken at the same time. No timing separation needed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Lion's Mane", "supplementBName": "Phosphatidylserine", "interactionType": "synergy", "severity": "info", "description": "The pair supports neuronal structure and signaling, with Lion's Mane stimulating neurotrophic factors and Phosphatidylserine maintaining neuronal membrane integrity and supporting neurotransmitter release.", "recommendation": "Reasonable to stack for memory and age-related cognitive support, taken consistently over time. Both can be taken together, ideally with a meal. No timing separation needed.", "minimumTimeSeparation": null, "mechanism": "Lion's Mane promotes nerve growth factor and neurite outgrowth, while phosphatidylserine is a major inner-leaflet membrane phospholipid that supports neuronal membrane fluidity and vesicular neurotransmitter release, complementing neurotrophic repair.", "evidenceLevel": "emerging", "sources": [ { "text": "Mori K, et al. Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial. Phytotherapy Research. 2009", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Glade MJ, Smith K. Phosphatidylserine and the human brain. Nutrition. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "The pair supports neuronal structure and signaling, with Lion's Mane stimulating neurotrophic factors and Phosphatidylserine maintaining neuronal membrane integrity and supporting neurotransmitter release.", "clinicalSignificance": "Sensible neuroplasticity and membrane-support pairing, with combination-specific human trials still limited.", "managementStrategy": "Reasonable to stack for memory and age-related cognitive support, taken consistently over time. Both can be taken together, ideally with a meal. No timing separation needed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Maca Root", "supplementBName": "L-Arginine", "interactionType": "synergy", "severity": "info", "description": "The pair approaches sexual function from two angles, with Maca acting on libido and sexual desire while L-Arginine supports the nitric oxide pathway involved in blood flow and erectile response.", "recommendation": "May be combined for libido and erectile support. Maca is taken daily over weeks; L-Arginine is often dosed at 1.5 to 5g per day. Use caution with antihypertensives or nitrates given L-Arginine vasodilation.", "minimumTimeSeparation": null, "mechanism": "Maca improves sexual desire through central, non-hormonal mechanisms without raising testosterone, while L-Arginine is a substrate for nitric oxide synthase, increasing nitric oxide that relaxes vascular smooth muscle and improves genital blood flow.", "evidenceLevel": "emerging", "sources": [ { "text": "Shin BC, et al. Maca (Lepidium meyenii) for improving sexual function: a systematic review. BMC Complementary and Alternative Medicine. 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Stanislavov R, Nikolova V. Treatment of erectile dysfunction with pycnogenol and L-arginine. Journal of Sex and Marital Therapy. 2003", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "The pair approaches sexual function from two angles, with Maca acting on libido and sexual desire while L-Arginine supports the nitric oxide pathway involved in blood flow and erectile response.", "clinicalSignificance": "Complementary desire and circulation pathways, with individual evidence modest and combination data sparse.", "managementStrategy": "May be combined for libido and erectile support. Maca is taken daily over weeks; L-Arginine is often dosed at 1.5 to 5g per day. Use caution with antihypertensives or nitrates given L-Arginine vasodilation.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Maca Root", "supplementBName": "Ginkgo Biloba", "interactionType": "synergy", "severity": "info", "description": "The pair combines Maca's effect on sexual desire with Ginkgo's influence on peripheral blood flow and nitric oxide, offering complementary support for sexual function.", "recommendation": "May be combined for libido and circulation support. Note that Ginkgo has antiplatelet activity, so use caution with anticoagulant or antiplatelet medication. Ginkgo evidence for sexual dysfunction is mixed.", "minimumTimeSeparation": null, "mechanism": "Maca increases sexual desire through central, non-hormonal pathways, while Ginkgo biloba flavonoids and terpenoids promote vasodilation and relax vascular smooth muscle, potentially improving genital blood flow.", "evidenceLevel": "emerging", "sources": [ { "text": "Shin BC, et al. Maca (Lepidium meyenii) for improving sexual function: a systematic review. BMC Complementary and Alternative Medicine. 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Meston CM, et al. Short- and long-term effects of Ginkgo biloba extract on sexual dysfunction in women. Archives of Sexual Behavior. 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "The pair combines Maca's effect on sexual desire with Ginkgo's influence on peripheral blood flow and nitric oxide, offering complementary support for sexual function.", "clinicalSignificance": "Plausible desire-plus-circulation pairing, but Ginkgo's clinical benefit for sexual dysfunction is inconsistent.", "managementStrategy": "May be combined for libido and circulation support. Note that Ginkgo has antiplatelet activity, so use caution with anticoagulant or antiplatelet medication. Ginkgo evidence for sexual dysfunction is mixed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Selenium", "supplementBName": "Coenzyme Q10", "interactionType": "synergy", "severity": "info", "description": "Adequate selenium status helps keep coenzyme Q10 in its active reduced form, and the pair together supports cardiac function more than either alone in people with low selenium.", "recommendation": "Combine when selenium intake is low or marginal. A common evidence-based pairing is selenium 100 to 200 mcg with coenzyme Q10 100 to 200 mg daily. No timing separation is needed.", "minimumTimeSeparation": null, "mechanism": "Selenium is required for the selenoenzyme thioredoxin reductase, which can reduce oxidized ubiquinone back toward its antioxidant-active form, so low selenium limits the functional benefit of coenzyme Q10. The two also act as complementary antioxidant systems in cardiac tissue.", "evidenceLevel": "moderate", "sources": [ { "text": "Alehagen U et al. Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation: a 5-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens. Int J Cardiol. 2013;167(5):1860-6.", "pmid": "22626835", "doi": "10.1016/j.ijcard.2012.04.156", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22626835/", "publicSourceType": "PMID" }, { "text": "Xia L et al. The mammalian cytosolic selenoenzyme thioredoxin reductase reduces ubiquinone. A novel mechanism for defense against oxidative stress. J Biol Chem. 2003;278(4):2141-6.", "pmid": "12435734", "doi": "10.1074/jbc.M210456200", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12435734/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Adequate selenium status helps keep coenzyme Q10 in its active reduced form, and the pair together supports cardiac function more than either alone in people with low selenium.", "clinicalSignificance": "In selenium-deficient older adults, combined selenium plus coenzyme Q10 has been linked to improved cardiac markers and lower cardiovascular mortality.", "managementStrategy": "Combine when selenium intake is low or marginal. A common evidence-based pairing is selenium 100 to 200 mcg with coenzyme Q10 100 to 200 mg daily. No timing separation is needed.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Selenium", "supplementBName": "Coenzyme Q10 Ubiquinol", "interactionType": "synergy", "severity": "info", "description": "Selenium-dependent enzymes help regenerate ubiquinol after it is oxidized during antioxidant activity, so the two nutrients complement each other in supporting cardiac and antioxidant status.", "recommendation": "Reasonable to combine, especially with marginal selenium intake. A typical pairing is selenium 100 to 200 mcg with ubiquinol 100 to 200 mg daily. No timing separation is needed.", "minimumTimeSeparation": null, "mechanism": "Ubiquinol is the reduced antioxidant form of coenzyme Q10. The selenium-dependent enzyme thioredoxin reductase can reduce oxidized ubiquinone back toward ubiquinol, so selenium status influences how effectively this regeneration cycle runs.", "evidenceLevel": "moderate", "sources": [ { "text": "Alehagen U et al. Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation: a 5-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens. Int J Cardiol. 2013;167(5):1860-6.", "pmid": "22626835", "doi": "10.1016/j.ijcard.2012.04.156", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22626835/", "publicSourceType": "PMID" }, { "text": "Xia L et al. The mammalian cytosolic selenoenzyme thioredoxin reductase reduces ubiquinone. A novel mechanism for defense against oxidative stress. J Biol Chem. 2003;278(4):2141-6.", "pmid": "12435734", "doi": "10.1074/jbc.M210456200", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12435734/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Selenium-dependent enzymes help regenerate ubiquinol after it is oxidized during antioxidant activity, so the two nutrients complement each other in supporting cardiac and antioxidant status.", "clinicalSignificance": "Selenium sufficiency supports the antioxidant value of ubiquinol, mirroring the cardiac benefits seen with combined selenium and coenzyme Q10 in deficient elderly populations.", "managementStrategy": "Reasonable to combine, especially with marginal selenium intake. A typical pairing is selenium 100 to 200 mcg with ubiquinol 100 to 200 mg daily. No timing separation is needed.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "L-Theanine", "supplementBName": "Melatonin", "interactionType": "synergy", "severity": "info", "description": "L-theanine eases pre-sleep mental tension while melatonin signals sleep timing, so together they can shorten time to fall asleep and improve subjective sleep quality.", "recommendation": "Take both 30 to 60 minutes before bed. Typical doses are L-theanine 100 to 200 mg with melatonin 0.5 to 3 mg. Start melatonin low to avoid morning grogginess.", "minimumTimeSeparation": null, "mechanism": "L-theanine increases GABA and alpha brain-wave activity to reduce arousal, while melatonin acts on MT1 and MT2 receptors in the suprachiasmatic nucleus to promote sleep onset, giving complementary calming and chronobiotic effects.", "evidenceLevel": "moderate", "sources": [ { "text": "Hidese S et al. Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial. Nutrients. 2019;11(10).", "pmid": "31623400", "doi": "10.3390/nu11102362", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31623400/", "publicSourceType": "PMID" }, { "text": "Rondanelli M et al. The effect of melatonin, magnesium, and zinc on primary insomnia in long-term care facility residents in Italy: a double-blind, placebo-controlled clinical trial. J Am Geriatr Soc. 2011;59(1):82-90.", "pmid": "21226679", "doi": "10.1111/j.1532-5415.2010.03232.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21226679/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "L-theanine eases pre-sleep mental tension while melatonin signals sleep timing, so together they can shorten time to fall asleep and improve subjective sleep quality.", "clinicalSignificance": "A useful non-habit-forming sleep pairing that addresses both anxious wakefulness and disrupted sleep timing.", "managementStrategy": "Take both 30 to 60 minutes before bed. Typical doses are L-theanine 100 to 200 mg with melatonin 0.5 to 3 mg. Start melatonin low to avoid morning grogginess.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "L-Theanine", "supplementBName": "Glycine", "interactionType": "synergy", "severity": "info", "description": "Both amino acids support sleep through different routes, so combining them may reduce pre-sleep tension and improve sleep quality more than either alone.", "recommendation": "Take together before bed, for example L-theanine 100 to 200 mg with glycine 3 g. Both are well tolerated and need no timing separation.", "minimumTimeSeparation": null, "mechanism": "L-theanine increases GABA and alpha activity to lower arousal, while glycine activates NMDA receptors in the suprachiasmatic nucleus, promoting peripheral vasodilation and a drop in core body temperature that facilitates sleep onset.", "evidenceLevel": "emerging", "sources": [ { "text": "Kawai N, Sakai N, Okuro M, et al. The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus. Neuropsychopharmacology. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Nobre AC, Rao A, Owen GN. L-theanine, a natural constituent in tea, and its effect on mental state. Asia Pacific Journal of Clinical Nutrition. 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both amino acids support sleep through different routes, so combining them may reduce pre-sleep tension and improve sleep quality more than either alone.", "clinicalSignificance": "Complementary sleep-supporting amino acids with strong safety; a reasonable stack for sleep-onset difficulty.", "managementStrategy": "Take together before bed, for example L-theanine 100 to 200 mg with glycine 3 g. Both are well tolerated and need no timing separation.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "L-Theanine", "supplementBName": "Passionflower", "interactionType": "synergy", "severity": "info", "description": "Both calm the nervous system mainly through GABA pathways, so combining them can produce additive anxiety-reducing and sleep-supporting effects.", "recommendation": "May be combined for daytime calm or sleep support. Start with standard single doses of each and watch for additive drowsiness, especially if also using sedatives.", "minimumTimeSeparation": null, "mechanism": "L-theanine raises GABA and alpha-wave activity, while passionflower flavonoids modulate GABA-A receptors and affect GABA reuptake, giving overlapping GABAergic calming effects.", "evidenceLevel": "emerging", "sources": [ { "text": "Appel K et al. Modulation of the γ-aminobutyric acid (GABA) system by Passiflora incarnata L. Phytother Res. 2011;25(6):838-43.", "pmid": "21089181", "doi": "10.1002/ptr.3352", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21089181/", "publicSourceType": "PMID" }, { "text": "Nobre AC et al. L-theanine, a natural constituent in tea, and its effect on mental state. Asia Pac J Clin Nutr. 2008;17 Suppl 1:167-8.", "pmid": "18296328", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18296328/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both calm the nervous system mainly through GABA pathways, so combining them can produce additive anxiety-reducing and sleep-supporting effects.", "clinicalSignificance": "Additive GABAergic calming; generally gentle, but combined sedation can be noticeable alongside other CNS depressants.", "managementStrategy": "May be combined for daytime calm or sleep support. Start with standard single doses of each and watch for additive drowsiness, especially if also using sedatives.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Ginger Extract", "supplementBName": "Bromelain", "interactionType": "caution", "severity": "moderate", "description": "Both ingredients have antiplatelet activity, so combining them may add to bleeding risk, particularly alongside blood-thinning medication or before surgery.", "recommendation": "Use with caution if on anticoagulants or antiplatelet drugs, watch for bruising or bleeding, and stop both at least one to two weeks before any planned surgery.", "minimumTimeSeparation": null, "mechanism": "Ginger gingerols inhibit thromboxane synthesis and platelet aggregation, while bromelain reduces platelet aggregation and has fibrinolytic activity, producing potentially additive effects on hemostasis.", "evidenceLevel": "emerging", "sources": [ { "text": "Marx W et al. The Effect of Ginger (Zingiber officinale) on Platelet Aggregation: A Systematic Literature Review. PLoS One. 2015;10(10):e0141119.", "pmid": "26488162", "doi": "10.1371/journal.pone.0141119", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26488162/", "publicSourceType": "PMID" }, { "text": "Pavan R et al. Properties and therapeutic application of bromelain: a review. Biotechnol Res Int. 2012;2012:976203.", "pmid": "23304525", "doi": "10.1155/2012/976203", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23304525/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both ingredients have antiplatelet activity, so combining them may add to bleeding risk, particularly alongside blood-thinning medication or before surgery.", "clinicalSignificance": "Additive antiplatelet effect is the main concern; relevant mainly for people on blood thinners or facing surgery.", "managementStrategy": "Use with caution if on anticoagulants or antiplatelet drugs, watch for bruising or bleeding, and stop both at least one to two weeks before any planned surgery.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Ginger Extract", "supplementBName": "Boswellia", "interactionType": "synergy", "severity": "info", "description": "Ginger and boswellia reduce inflammation through different enzyme pathways, so combining them may give broader anti-inflammatory and joint-symptom relief than either alone.", "recommendation": "Reasonable to combine for joint or inflammatory support. Use standardized extracts at label doses and monitor for additive GI upset.", "minimumTimeSeparation": null, "mechanism": "Ginger gingerols inhibit both cyclooxygenase and lipoxygenase pathways, while boswellic acids selectively inhibit 5-lipoxygenase and leukotriene synthesis, so the two cover complementary arms of the inflammatory cascade.", "evidenceLevel": "moderate", "sources": [ { "text": "Grzanna R, Lindmark L, Frondoza CG. Ginger: an herbal medicinal product with broad anti-inflammatory actions. Journal of Medicinal Food. 2005", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Ammon HP. Boswellic acids in chronic inflammatory diseases. Planta Medica. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Ginger and boswellia reduce inflammation through different enzyme pathways, so combining them may give broader anti-inflammatory and joint-symptom relief than either alone.", "clinicalSignificance": "Complementary anti-inflammatory mechanisms make this a sensible joint-support pairing.", "managementStrategy": "Reasonable to combine for joint or inflammatory support. Use standardized extracts at label doses and monitor for additive GI upset.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Ginger Extract", "supplementBName": "Quercetin", "interactionType": "synergy", "severity": "info", "description": "Both are anti-inflammatory antioxidants that dampen overlapping inflammatory signaling, so combining them may provide additive antioxidant and anti-inflammatory support.", "recommendation": "May be combined for antioxidant or anti-inflammatory goals at standard doses. Both have mild antiplatelet potential, so use some caution if on blood thinners and watch for easy bruising.", "minimumTimeSeparation": null, "mechanism": "Ginger gingerols inhibit cyclooxygenase and lipoxygenase pathways and suppress NF-kB signaling, while quercetin inhibits NF-kB activation and pro-inflammatory cytokine release, giving overlapping suppression of inflammatory mediators.", "evidenceLevel": "emerging", "sources": [ { "text": "Grzanna R, Lindmark L, Frondoza CG. Ginger: an herbal medicinal product with broad anti-inflammatory actions. Journal of Medicinal Food. 2005", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Li Y, Yao J, Han C, et al. Quercetin, inflammation and immunity. Nutrients. 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both are anti-inflammatory antioxidants that dampen overlapping inflammatory signaling, so combining them may provide additive antioxidant and anti-inflammatory support.", "clinicalSignificance": "Additive anti-inflammatory action; keep the modest combined antiplatelet potential in mind for those on anticoagulants.", "managementStrategy": "May be combined for antioxidant or anti-inflammatory goals at standard doses. Both have mild antiplatelet potential, so use some caution if on blood thinners and watch for easy bruising.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Turmeric/Curcumin", "supplementBName": "Boswellia", "interactionType": "synergy", "severity": "info", "description": "Combined use produces greater anti-inflammatory and joint symptom relief than either agent alone in osteoarthritis studies.", "recommendation": "Reasonable to take together for joint or inflammatory support; standardized extracts (curcuminoids plus boswellic acids) are commonly co-formulated and can be dosed at the same time.", "minimumTimeSeparation": null, "mechanism": "Curcumin downregulates NF-kB signaling and COX-2 expression while boswellic acids selectively inhibit 5-lipoxygenase, so the two block complementary arms of the inflammatory cascade (the prostaglandin and leukotriene pathways).", "evidenceLevel": "moderate", "sources": [ { "text": "Kizhakkedath R, Clinical evaluation of a formulation containing Curcuma longa and Boswellia serrata extracts in the management of knee osteoarthritis, Molecular Medicine Reports, 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Haroyan A et al., Efficacy and safety of curcumin and its combination with boswellic acid in osteoarthritis, BMC Complementary and Alternative Medicine, 2018", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Combined use produces greater anti-inflammatory and joint symptom relief than either agent alone in osteoarthritis studies.", "clinicalSignificance": "Complementary anti-inflammatory pathways make this a favorable, well-tolerated combination for joint support.", "managementStrategy": "Reasonable to take together for joint or inflammatory support; standardized extracts (curcuminoids plus boswellic acids) are commonly co-formulated and can be dosed at the same time.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Turmeric/Curcumin", "supplementBName": "Bromelain", "interactionType": "synergy", "severity": "info", "description": "Bromelain is widely co-formulated with curcumin to add its own proteolytic anti-inflammatory effect, increasing the net anti-inflammatory action of the pair.", "recommendation": "Can be taken together for inflammatory and recovery support; the two are frequently combined in joint and recovery formulas and need no time separation.", "minimumTimeSeparation": null, "mechanism": "Bromelain is a proteolytic enzyme that independently reduces pro-inflammatory mediators, bradykinin, and tissue edema, complementing curcumin's inhibition of NF-kB driven inflammation; any effect on curcumin absorption in humans is not well established.", "evidenceLevel": "emerging", "sources": [ { "text": "Brien S et al., Bromelain as a treatment for osteoarthritis: a review of clinical studies, Evidence-Based Complementary and Alternative Medicine, 2004", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Hewlings SJ and Kalman DS, Curcumin: A Review of Its Effects on Human Health, Foods, 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Bromelain is widely co-formulated with curcumin to add its own proteolytic anti-inflammatory effect, increasing the net anti-inflammatory action of the pair.", "clinicalSignificance": "A practical anti-inflammatory pairing, though the often-cited bioavailability boost from bromelain is not well documented in humans.", "managementStrategy": "Can be taken together for inflammatory and recovery support; the two are frequently combined in joint and recovery formulas and need no time separation.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Turmeric/Curcumin", "supplementBName": "Resveratrol", "interactionType": "caution", "severity": "moderate", "description": "Both polyphenols have antiplatelet activity, so combining them may additively reduce platelet aggregation and increase bleeding tendency.", "recommendation": "Generally safe together at supplemental doses, but use caution if you take anticoagulant or antiplatelet drugs, and stop both about 1 to 2 weeks before surgery.", "minimumTimeSeparation": null, "mechanism": "Curcumin and resveratrol each inhibit platelet aggregation, in part through modulation of the arachidonic acid and thromboxane A2 pathway, so their combined antiplatelet effects can be additive.", "evidenceLevel": "emerging", "sources": [ { "text": "Olas B et al. Resveratrol, a phenolic antioxidant with effects on blood platelet functions. Platelets. 2005;16(5):251-60.", "pmid": "16011975", "doi": "10.1080/09537100400020591", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16011975/", "publicSourceType": "PMID" }, { "text": "Keihanian F et al. Curcumin, hemostasis, thrombosis, and coagulation. J Cell Physiol. 2018;233(6):4497-4511.", "pmid": "29052850", "doi": "10.1002/jcp.26249", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29052850/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both polyphenols have antiplatelet activity, so combining them may additively reduce platelet aggregation and increase bleeding tendency.", "clinicalSignificance": "Watch for additive bleeding risk when both are taken alongside blood-thinning medications or before surgery.", "managementStrategy": "Generally safe together at supplemental doses, but use caution if you take anticoagulant or antiplatelet drugs, and stop both about 1 to 2 weeks before surgery.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin K2", "supplementBName": "Vitamin A", "interactionType": "synergy", "severity": "info", "description": "Vitamins A and K2 contribute to bone and calcium handling alongside vitamin D, supporting balanced mineralization at nutritional intakes.", "recommendation": "Reasonable to take together at nutritional doses; avoid high-dose preformed vitamin A (retinol), which at excess can adversely affect bone and antagonize vitamin D signaling.", "minimumTimeSeparation": null, "mechanism": "Both are fat-soluble vitamins; vitamin A acts through retinoid nuclear receptors that heterodimerize with the vitamin D receptor, intersecting the vitamin D and vitamin K dependent pathways that govern osteocalcin activity and bone mineralization.", "evidenceLevel": "emerging", "sources": [ { "text": "Maresz K, Proper Calcium Use: Vitamin K2 as a Promoter of Bone and Cardiovascular Health, Integrative Medicine, 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Booth SL, Roles for Vitamin K beyond coagulation, Annual Review of Nutrition, 2009", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamins A and K2 contribute to bone and calcium handling alongside vitamin D, supporting balanced mineralization at nutritional intakes.", "clinicalSignificance": "Cooperative fat-soluble vitamin signaling supports bone health when intakes stay in the nutritional range.", "managementStrategy": "Reasonable to take together at nutritional doses; avoid high-dose preformed vitamin A (retinol), which at excess can adversely affect bone and antagonize vitamin D signaling.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin K2", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "info", "description": "Magnesium supports the vitamin D activation and calcium handling that vitamin K2 then directs into bone, complementing K2's role in mineralization.", "recommendation": "Can be taken together to support bone and cardiovascular calcium metabolism; both are commonly combined in bone-support stacks with no time separation needed.", "minimumTimeSeparation": null, "mechanism": "Magnesium is a required cofactor for the enzymes that hydroxylate vitamin D to its active form and for normal calcium regulation, while vitamin K2 carboxylates osteocalcin and matrix Gla protein to direct calcium into bone and away from soft tissue.", "evidenceLevel": "emerging", "sources": [ { "text": "Uwitonze AM and Razzaque MS, Role of Magnesium in Vitamin D Activation and Function, Journal of the American Osteopathic Association, 2018", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Maresz K, Proper Calcium Use: Vitamin K2 as a Promoter of Bone and Cardiovascular Health, Integrative Medicine, 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Magnesium supports the vitamin D activation and calcium handling that vitamin K2 then directs into bone, complementing K2's role in mineralization.", "clinicalSignificance": "Magnesium and K2 act on adjacent steps of calcium handling, making them a sensible bone-support pairing.", "managementStrategy": "Can be taken together to support bone and cardiovascular calcium metabolism; both are commonly combined in bone-support stacks with no time separation needed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "L-Citrulline", "supplementBName": "Taurine", "interactionType": "synergy", "severity": "info", "description": "Both amino acids support endothelial function and exercise performance, and are commonly combined for complementary vascular and ergogenic effects.", "recommendation": "Reasonable to take together pre-exercise for blood flow and performance support; effects are complementary rather than competitive and no time separation is needed.", "minimumTimeSeparation": null, "mechanism": "L-citrulline raises arginine and nitric oxide driven vasodilation, while taurine supports endothelial function, intracellular calcium handling in muscle, and antioxidant defense, giving complementary vascular and ergogenic effects.", "evidenceLevel": "emerging", "sources": [ { "text": "Schaffer SW et al. Physiological roles of taurine in heart and muscle. J Biomed Sci. 2010;17 Suppl 1(Suppl 1):S2.", "pmid": "20804594", "doi": "10.1186/1423-0127-17-S1-S2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20804594/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both amino acids support endothelial function and exercise performance, and are commonly combined for complementary vascular and ergogenic effects.", "clinicalSignificance": "A complementary pre-workout pairing for blood flow and performance with no notable conflict, though direct combination data are limited.", "managementStrategy": "Reasonable to take together pre-exercise for blood flow and performance support; effects are complementary rather than competitive and no time separation is needed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Creatine", "supplementBName": "Alpha-Lipoic Acid", "interactionType": "synergy", "severity": "info", "description": "Alpha-lipoic acid increases skeletal muscle uptake and storage of creatine, raising total creatine and phosphocreatine content above what creatine achieves on its own.", "recommendation": "Take together if the goal is muscle creatine loading. Pairing roughly 1000 mg alpha-lipoic acid with a standard creatine dose, ideally alongside a carbohydrate, can improve loading. Both are taken daily and timing relative to each other is not critical.", "minimumTimeSeparation": null, "mechanism": "Muscle creatine uptake via the SLC6A8 (CRT) transporter is sensitive to insulin signaling. Alpha-lipoic acid acts as an insulin mimetic that enhances glucose and creatine disposal into muscle, increasing intramuscular total creatine and phosphocreatine accumulation during loading.", "evidenceLevel": "emerging", "sources": [ { "text": "Burke DG, Chilibeck PD, Parise G, Tarnopolsky MA, Candow DG. Effect of alpha-lipoic acid combined with creatine monohydrate on human skeletal muscle creatine and phosphagen concentration. International Journal of Sport Nutrition and Exercise Metabolism. 2003", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Alpha-lipoic acid increases skeletal muscle uptake and storage of creatine, raising total creatine and phosphocreatine content above what creatine achieves on its own.", "clinicalSignificance": "Alpha-lipoic acid can modestly boost creatine loading into muscle, useful but not essential for most users.", "managementStrategy": "Take together if the goal is muscle creatine loading. Pairing roughly 1000 mg alpha-lipoic acid with a standard creatine dose, ideally alongside a carbohydrate, can improve loading. Both are taken daily and timing relative to each other is not critical.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Phosphatidylserine", "supplementBName": "Bacopa Monnieri", "interactionType": "synergy", "severity": "info", "description": "Phosphatidylserine supports neuronal membrane integrity and stress-axis modulation while Bacopa Monnieri enhances cholinergic signaling and synaptic remodeling, giving complementary support for memory and learning.", "recommendation": "Combine for cognitive aging or general memory support. A typical pairing is about 100 to 300 mg phosphatidylserine daily with a standardized Bacopa Monnieri extract (around 300 mg providing 50 percent bacosides). Bacopa benefits build over several weeks of consistent daily use.", "minimumTimeSeparation": null, "mechanism": "Phosphatidylserine helps maintain membrane fluidity and receptor function and can blunt cortisol responses to stress. Bacopa Monnieri raises acetylcholine availability, exerts antioxidant activity, and promotes dendritic branching and synaptic plasticity, acting on different stages of memory formation than phosphatidylserine.", "evidenceLevel": "emerging", "sources": [ { "text": "Zanotta D, Puricelli S, Bonoldi G. Cognitive effects of a dietary supplement made from extract of Bacopa monnieri, astaxanthin, phosphatidylserine, and vitamin E in subjects with mild cognitive impairment. Neuropsychiatric Disease and Treatment. 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Kongkeaw C, Dilokthornsakul P, Thanarangsarit P, Limpeanchob N, Scholfield CN. Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract. Journal of Ethnopharmacology. 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Phosphatidylserine supports neuronal membrane integrity and stress-axis modulation while Bacopa Monnieri enhances cholinergic signaling and synaptic remodeling, giving complementary support for memory and learning.", "clinicalSignificance": "A complementary, well-tolerated nootropic pairing for memory support, with effects emerging over weeks rather than acutely.", "managementStrategy": "Combine for cognitive aging or general memory support. A typical pairing is about 100 to 300 mg phosphatidylserine daily with a standardized Bacopa Monnieri extract (around 300 mg providing 50 percent bacosides). Bacopa benefits build over several weeks of consistent daily use.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Glycine", "supplementBName": "Taurine", "interactionType": "synergy", "severity": "info", "description": "Glycine and taurine are both inhibitory amino acids that together support relaxation and may aid sleep onset, including glycine's documented lowering of core body temperature before bed.", "recommendation": "Reasonable to combine for evening calm or sleep support. A common pairing is glycine 3g with taurine 0.5g to 2g taken 30 to 60 minutes before bed.", "minimumTimeSeparation": null, "mechanism": "Glycine is a full agonist at the inhibitory strychnine-sensitive glycine receptor, while taurine acts as a weaker (partial) agonist at that receptor and also activates GABA-A receptors, so both reinforce inhibitory neurotransmission in the brainstem and spinal cord.", "evidenceLevel": "emerging", "sources": [ { "text": "Albrecht J, Schousboe A. Taurine interaction with neurotransmitter receptors in the CNS. Neurochemical Research. 2005", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bannai M, Kawai N. New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep. Journal of Pharmacological Sciences. 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Glycine and taurine are both inhibitory amino acids that together support relaxation and may aid sleep onset, including glycine's documented lowering of core body temperature before bed.", "clinicalSignificance": "Complementary calming amino acids that are reasonable to stack for relaxation or sleep.", "managementStrategy": "Reasonable to combine for evening calm or sleep support. A common pairing is glycine 3g with taurine 0.5g to 2g taken 30 to 60 minutes before bed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Inositol", "supplementBName": "NAC", "interactionType": "synergy", "severity": "info", "description": "In polycystic ovary syndrome, myo-inositol and N-acetylcysteine target complementary problems: inositol supports insulin signaling while NAC provides antioxidant support and can improve ovulatory response.", "recommendation": "Reasonable to combine in a PCOS or insulin-resistance context. Typical research dosing is myo-inositol around 2g to 4g daily with NAC 600mg to 1800mg daily, ideally guided by a clinician.", "minimumTimeSeparation": null, "mechanism": "Myo-inositol acts as a second messenger that improves insulin sensitivity and supports FSH signaling, while NAC replenishes glutathione and reduces ovarian oxidative stress, giving additive effects on ovulation and metabolic markers.", "evidenceLevel": "moderate", "sources": [ { "text": "Thakker D et al. N-acetylcysteine for polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled clinical trials. Obstetrics and Gynecology International. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Unfer V et al. Effects of myo-inositol in women with PCOS: a systematic review of randomized controlled trials. Gynecological Endocrinology. 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "In polycystic ovary syndrome, myo-inositol and N-acetylcysteine target complementary problems: inositol supports insulin signaling while NAC provides antioxidant support and can improve ovulatory response.", "clinicalSignificance": "Complementary PCOS support combining insulin-sensitizing and antioxidant mechanisms.", "managementStrategy": "Reasonable to combine in a PCOS or insulin-resistance context. Typical research dosing is myo-inositol around 2g to 4g daily with NAC 600mg to 1800mg daily, ideally guided by a clinician.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Inositol", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "info", "description": "Adequate vitamin D status appears to improve the metabolic and reproductive response to myo-inositol in PCOS, and the two are frequently combined to support insulin sensitivity and ovulation.", "recommendation": "Correct vitamin D deficiency (aim for a sufficient serum 25-OH-D) when using inositol for PCOS or insulin resistance, since low vitamin D may blunt the inositol response.", "minimumTimeSeparation": null, "mechanism": "Vitamin D supports ovarian follicular development and influences insulin receptor expression, complementing inositol's role as an insulin second messenger, so combined repletion is associated with larger improvements in HOMA-IR and cycle regularity.", "evidenceLevel": "moderate", "sources": [ { "text": "Pal L et al. Therapeutic implications of vitamin D and calcium in overweight women with PCOS. Gynecological Endocrinology. 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bonomo M et al. Inositol and vitamin D in improving fertility among patients with polycystic ovary syndrome: a systematic review. Clinical and Experimental Reproductive Medicine. 2023", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Adequate vitamin D status appears to improve the metabolic and reproductive response to myo-inositol in PCOS, and the two are frequently combined to support insulin sensitivity and ovulation.", "clinicalSignificance": "Vitamin D sufficiency supports how well inositol works in PCOS.", "managementStrategy": "Correct vitamin D deficiency (aim for a sufficient serum 25-OH-D) when using inositol for PCOS or insulin resistance, since low vitamin D may blunt the inositol response.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Inositol", "supplementBName": "Chromium", "interactionType": "synergy", "severity": "info", "description": "Myo-inositol and chromium each support insulin sensitivity through different routes, so combining them may give additive benefit on fasting insulin and glycemic control in insulin-resistant states such as PCOS.", "recommendation": "Reasonable to combine for insulin resistance. Common amounts are myo-inositol 2g to 4g daily with chromium (as picolinate) 200mcg to 1000mcg daily; monitor glucose if also taking diabetes medication.", "minimumTimeSeparation": null, "mechanism": "Inositol acts as a second messenger that enhances post-receptor insulin signaling, while chromium is thought to potentiate insulin receptor tyrosine kinase activity, producing additive improvement in insulin-mediated glucose uptake.", "evidenceLevel": "emerging", "sources": [ { "text": "Anderson RA. Chromium, glucose intolerance and diabetes. Journal of the American College of Nutrition. 1998", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Croze ML, Soulage CO. Potential role and therapeutic interests of myo-inositol in metabolic diseases. Biochimie. 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Myo-inositol and chromium each support insulin sensitivity through different routes, so combining them may give additive benefit on fasting insulin and glycemic control in insulin-resistant states such as PCOS.", "clinicalSignificance": "Two insulin-sensitizing agents that can be stacked for metabolic support.", "managementStrategy": "Reasonable to combine for insulin resistance. Common amounts are myo-inositol 2g to 4g daily with chromium (as picolinate) 200mcg to 1000mcg daily; monitor glucose if also taking diabetes medication.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "L-Tyrosine", "supplementBName": "L-Theanine", "interactionType": "synergy", "severity": "info", "description": "L-Tyrosine supports catecholamine production for alertness under stress while L-theanine promotes calm focus, so the pair tends to deliver activated attention without as much of the jittery edge of stimulation alone.", "recommendation": "Reasonable nootropic stack for focus under stress. A common pairing is L-tyrosine 500mg to 2000mg with L-theanine 100mg to 200mg taken earlier in the day.", "minimumTimeSeparation": null, "mechanism": "L-Tyrosine is the precursor for dopamine and noradrenaline (activating), whereas L-theanine increases alpha brain-wave activity and modulates glutamate and GABA tone (calming), giving balanced catecholaminergic arousal.", "evidenceLevel": "emerging", "sources": [ { "text": "Jongkees BJ et al. Effect of tyrosine supplementation on clinical and healthy populations under stress or cognitive demands. Journal of Psychiatric Research. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Nobre AC et al. L-theanine, a natural constituent in tea, and its effect on mental state. Asia Pacific Journal of Clinical Nutrition. 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "L-Tyrosine supports catecholamine production for alertness under stress while L-theanine promotes calm focus, so the pair tends to deliver activated attention without as much of the jittery edge of stimulation alone.", "clinicalSignificance": "Balanced focus pairing: an activating precursor offset by a calming modulator.", "managementStrategy": "Reasonable nootropic stack for focus under stress. A common pairing is L-tyrosine 500mg to 2000mg with L-theanine 100mg to 200mg taken earlier in the day.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "L-Tyrosine", "supplementBName": "5-HTP", "interactionType": "caution", "severity": "moderate", "description": "L-Tyrosine (a catecholamine precursor) and 5-HTP (a serotonin precursor) compete for the same blood-brain-barrier transporter, and unbalanced chronic dosing of one alone can deplete the neurotransmitter pool made from the other.", "recommendation": "If using both for mood or sleep, balance the precursors rather than mega-dosing one, and separate intake (for example tyrosine in the morning, 5-HTP in the evening). Avoid this stack entirely if taking SSRIs, SNRIs, or MAOIs.", "minimumTimeSeparation": "4 hours", "mechanism": "Both amino acids cross the blood-brain barrier via the shared large neutral amino acid transporter, so co-timed dosing causes competition for uptake; sustained single-precursor loading can also drive down the opposing catecholamine or serotonin pool.", "evidenceLevel": "emerging", "sources": [ { "text": "Hinz M, Stein A, Uncini T. Amino acid management of Parkinson's disease: a case study. Int J Gen Med. 2011.", "pmid": "21475622", "doi": "10.2147/IJGM.S16621", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21475622/", "publicSourceType": "PMID" }, { "text": "Fernstrom JD. Branched-chain amino acids and brain function. J Nutr. 2005.", "pmid": "15930466", "doi": "10.1093/jn/135.6.1539S", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15930466/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "L-Tyrosine (a catecholamine precursor) and 5-HTP (a serotonin precursor) compete for the same blood-brain-barrier transporter, and unbalanced chronic dosing of one alone can deplete the neurotransmitter pool made from the other.", "clinicalSignificance": "Unbalanced or co-timed precursor dosing can deplete the opposing neurotransmitter; balance and space them.", "managementStrategy": "If using both for mood or sleep, balance the precursors rather than mega-dosing one, and separate intake (for example tyrosine in the morning, 5-HTP in the evening). Avoid this stack entirely if taking SSRIs, SNRIs, or MAOIs.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin B2", "supplementBName": "Iron", "interactionType": "synergy", "severity": "info", "description": "Riboflavin supports mobilization of stored iron and red blood cell production, so correcting riboflavin status can improve the hematologic response to iron supplementation in deficiency.", "recommendation": "Ensure adequate riboflavin intake when treating iron-deficiency anemia, since riboflavin deficiency can blunt the rise in hemoglobin despite iron therapy.", "minimumTimeSeparation": null, "mechanism": "Riboflavin-derived flavin coenzymes support release of iron from ferritin and gut handling of iron, as well as flavin-dependent steps in erythropoiesis, so deficiency impairs iron mobilization and hemoglobin synthesis.", "evidenceLevel": "moderate", "sources": [ { "text": "Powers HJ. Riboflavin (vitamin B-2) and health. American Journal of Clinical Nutrition. 2003", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Powers HJ et al. The relative effectiveness of iron and iron with riboflavin in correcting a microcytic anaemia. British Journal of Nutrition. 1983", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Riboflavin supports mobilization of stored iron and red blood cell production, so correcting riboflavin status can improve the hematologic response to iron supplementation in deficiency.", "clinicalSignificance": "Riboflavin status influences how well iron supplementation corrects anemia.", "managementStrategy": "Ensure adequate riboflavin intake when treating iron-deficiency anemia, since riboflavin deficiency can blunt the rise in hemoglobin despite iron therapy.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin B2", "supplementBName": "Coenzyme Q10", "interactionType": "synergy", "severity": "info", "description": "Riboflavin and coenzyme Q10 both support mitochondrial energy production and are used together for migraine prophylaxis, where their effects on the electron transport chain are complementary.", "recommendation": "Reasonable to combine for migraine prevention or mitochondrial support. Common research dosing is riboflavin 400mg daily with CoQ10 around 100mg to 300mg daily.", "minimumTimeSeparation": null, "mechanism": "Riboflavin-derived FAD and FMN serve as electron carriers at Complexes I and II, while coenzyme Q10 shuttles those electrons onward to Complex III, so the two act at adjacent steps of the same respiratory chain.", "evidenceLevel": "moderate", "sources": [ { "text": "Schoenen J, Jacquy J, Lenaerts M. Effectiveness of high-dose riboflavin in migraine prophylaxis: a randomized controlled trial. Neurology. 1998", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Sandor PS et al. Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial. Neurology. 2005", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Riboflavin and coenzyme Q10 both support mitochondrial energy production and are used together for migraine prophylaxis, where their effects on the electron transport chain are complementary.", "clinicalSignificance": "Complementary mitochondrial cofactors, notably for migraine prophylaxis.", "managementStrategy": "Reasonable to combine for migraine prevention or mitochondrial support. Common research dosing is riboflavin 400mg daily with CoQ10 around 100mg to 300mg daily.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin B2", "supplementBName": "Methylfolate", "interactionType": "synergy", "severity": "info", "description": "Riboflavin is the cofactor for the MTHFR enzyme that converts folate to its active form, so good riboflavin status improves folate-mediated lowering of homocysteine, especially in people with the MTHFR 677 TT genotype.", "recommendation": "Ensure adequate riboflavin when using methylfolate to lower homocysteine, particularly for MTHFR 677 TT individuals in whom riboflavin status strongly modulates the response.", "minimumTimeSeparation": null, "mechanism": "MTHFR uses riboflavin-derived FAD as its cofactor; in the thermolabile TT variant the enzyme loses FAD more readily, so optimizing riboflavin stabilizes MTHFR activity and supports folate-driven remethylation of homocysteine to methionine.", "evidenceLevel": "strong", "sources": [ { "text": "McNulty H et al. Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C to T polymorphism. Circulation. 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "McNulty H et al. Effect of riboflavin status on the homocysteine-lowering effect of folate in relation to the MTHFR C677T genotype. Clinical Chemistry. 2003", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Riboflavin is the cofactor for the MTHFR enzyme that converts folate to its active form, so good riboflavin status improves folate-mediated lowering of homocysteine, especially in people with the MTHFR 677 TT genotype.", "clinicalSignificance": "Riboflavin status gates how effectively folate lowers homocysteine, especially in MTHFR TT carriers.", "managementStrategy": "Ensure adequate riboflavin when using methylfolate to lower homocysteine, particularly for MTHFR 677 TT individuals in whom riboflavin status strongly modulates the response.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Chromium", "supplementBName": "Alpha-Lipoic Acid", "interactionType": "synergy", "severity": "info", "description": "Combining chromium with alpha-lipoic acid may improve insulin sensitivity and cellular glucose uptake more than either taken alone.", "recommendation": "Reasonable to take together for glycemic support. If you use blood-glucose-lowering medication, monitor for additive lowering and discuss dosing with your clinician.", "minimumTimeSeparation": null, "mechanism": "Chromium potentiates insulin receptor signaling via the low-molecular-weight chromium-binding substance (chromodulin), while alpha-lipoic acid increases AMPK activation and GLUT4 translocation, so the two support complementary steps of insulin-stimulated glucose uptake.", "evidenceLevel": "emerging", "sources": [ { "text": "Vincent JB. The bioinorganic chemistry of chromium(III). Polyhedron. 2001", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Singh U, Jialal I. Alpha-lipoic acid supplementation and diabetes. Nutrition Reviews. 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Combining chromium with alpha-lipoic acid may improve insulin sensitivity and cellular glucose uptake more than either taken alone.", "clinicalSignificance": "Mild additive glycemic benefit; watch for additive effect if on glucose-lowering drugs.", "managementStrategy": "Reasonable to take together for glycemic support. If you use blood-glucose-lowering medication, monitor for additive lowering and discuss dosing with your clinician.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Chromium", "supplementBName": "Vitamin B7", "interactionType": "synergy", "severity": "info", "description": "Chromium picolinate combined with biotin (vitamin B7) has improved fasting glucose and glycemic markers more than chromium alone in studies of impaired glucose control.", "recommendation": "The two are commonly paired and can be taken together for glycemic support. Not a substitute for prescribed diabetes therapy.", "minimumTimeSeparation": null, "mechanism": "Chromium enhances insulin receptor sensitivity, while biotin is a cofactor for carboxylase enzymes (including pyruvate carboxylase and acetyl-CoA carboxylase) and upregulates glucokinase, giving complementary effects on glucose handling.", "evidenceLevel": "moderate", "sources": [ { "text": "Albarracin CA et al. Chromium picolinate and biotin combination improves glucose metabolism in treated, uncontrolled overweight to obese patients with type 2 diabetes. Diabetes Metab Res Rev. 2008;24(1):41-51.", "pmid": "17506119", "doi": "10.1002/dmrr.755", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17506119/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Chromium picolinate combined with biotin (vitamin B7) has improved fasting glucose and glycemic markers more than chromium alone in studies of impaired glucose control.", "clinicalSignificance": "Well-studied glycemic-support pairing with additive benefit on glucose markers.", "managementStrategy": "The two are commonly paired and can be taken together for glycemic support. Not a substitute for prescribed diabetes therapy.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Chromium", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "info", "description": "Chromium and magnesium each support insulin signaling, so adequate status of both is associated with better insulin sensitivity than low status of either.", "recommendation": "Reasonable to take together for metabolic support. No timing restriction is needed.", "minimumTimeSeparation": null, "mechanism": "Magnesium is a cofactor for the tyrosine kinase activity of the insulin receptor and downstream glucose-handling enzymes, while chromium enhances insulin receptor responsiveness via chromodulin, so adequacy of both supports the same insulin-signaling pathway from different points.", "evidenceLevel": "emerging", "sources": [ { "text": "Barbagallo M et al. Magnesium and type 2 diabetes. World J Diabetes. 2015;6(10):1152-7.", "pmid": "26322160", "doi": "10.4239/wjd.v6.i10.1152", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26322160/", "publicSourceType": "PMID" }, { "text": "Anderson RA et al. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes. Diabetes. 1997;46(11):1786-91.", "pmid": "9356027", "doi": "10.2337/diab.46.11.1786", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9356027/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Chromium and magnesium each support insulin signaling, so adequate status of both is associated with better insulin sensitivity than low status of either.", "clinicalSignificance": "Complementary support for insulin sensitivity; benefit is greatest when one or both nutrients are low.", "managementStrategy": "Reasonable to take together for metabolic support. No timing restriction is needed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Copper", "supplementBName": "Vitamin C", "interactionType": "caution", "severity": "moderate", "description": "Sustained high-dose (gram-level) vitamin C can lower ceruloplasmin oxidase activity and may impair copper status, though effects on copper absorption have been inconsistent across studies.", "recommendation": "Avoid chronic gram-level vitamin C if copper status is marginal, and ensure adequate copper intake if you take high-dose vitamin C long term. Ordinary dietary or modest supplemental vitamin C intakes are not a concern.", "minimumTimeSeparation": null, "mechanism": "Pharmacologic doses of ascorbic acid can reduce ceruloplasmin ferroxidase (oxidase) activity and may interfere with copper handling; the effect is driven by chronic high intake rather than acute co-ingestion, so meal spacing does not reliably prevent it.", "evidenceLevel": "moderate", "sources": [ { "text": "Finley EB, Cerklewski FL. Influence of ascorbic acid supplementation on copper status in young adult men. American Journal of Clinical Nutrition. 1983", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Jacob RA, Skala JH, Omaye ST, Turnlund JR. Effect of varying ascorbic acid intakes on copper absorption and ceruloplasmin levels of young men. J Nutr. 1987.", "pmid": "3694287", "doi": "10.1093/jn/117.12.2109", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3694287/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Sustained high-dose (gram-level) vitamin C can lower ceruloplasmin oxidase activity and may impair copper status, though effects on copper absorption have been inconsistent across studies.", "clinicalSignificance": "Chronic high-dose vitamin C can lower ceruloplasmin activity; limit megadoses and keep copper intake adequate.", "managementStrategy": "Avoid chronic gram-level vitamin C if copper status is marginal, and ensure adequate copper intake if you take high-dose vitamin C long term. Ordinary dietary or modest supplemental vitamin C intakes are not a concern.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Copper", "supplementBName": "Iron", "interactionType": "caution", "severity": "moderate", "description": "Copper is required to mobilize iron for red blood cell production, while prolonged high-dose iron can suppress copper absorption, so imbalance in either direction disrupts the other.", "recommendation": "Do not take high-dose iron long term without ensuring adequate copper intake. If iron-deficiency anemia fails to respond to iron, have copper status checked.", "minimumTimeSeparation": null, "mechanism": "Copper-dependent ferroxidases (ceruloplasmin and hephaestin) oxidize ferrous iron so it can load onto transferrin, so copper deficiency causes an iron-loading anemia; conversely, chronic high iron intake competes for shared intestinal divalent metal transport and can deplete copper.", "evidenceLevel": "strong", "sources": [ { "text": "Collins JF, Prohaska JR, Knutson MD. Metabolic crossroads of iron and copper. Nutr Rev. 2010.", "pmid": "20384844", "doi": "10.1111/j.1753-4887.2010.00271.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20384844/", "publicSourceType": "PMID" }, { "text": "Gulec S, Collins JF. Molecular mediators governing iron-copper interactions. Annu Rev Nutr. 2014.", "pmid": "24995690", "doi": "10.1146/annurev-nutr-071812-161215", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24995690/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Copper is required to mobilize iron for red blood cell production, while prolonged high-dose iron can suppress copper absorption, so imbalance in either direction disrupts the other.", "clinicalSignificance": "Iron handling depends on copper; balance both rather than dosing one in isolation.", "managementStrategy": "Do not take high-dose iron long term without ensuring adequate copper intake. If iron-deficiency anemia fails to respond to iron, have copper status checked.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Boron", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "info", "description": "Boron has been shown to reduce urinary magnesium loss and raise serum magnesium, supporting magnesium status when the two are taken together.", "recommendation": "Reasonable to take together, particularly for bone and mineral support in postmenopausal women. No timing separation is needed.", "minimumTimeSeparation": null, "mechanism": "Boron influences mineral and steroid hormone metabolism in a way that decreases urinary excretion of magnesium and calcium, helping retain magnesium and supporting circulating concentrations.", "evidenceLevel": "moderate", "sources": [ { "text": "Nielsen FH, Hunt CD, Mullen LM, Hunt JR. Effect of dietary boron on mineral, estrogen, and testosterone metabolism in postmenopausal women. FASEB Journal. 1987", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Pizzorno L. Nothing boring about boron. Integrative Medicine (Encinitas). 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Boron has been shown to reduce urinary magnesium loss and raise serum magnesium, supporting magnesium status when the two are taken together.", "clinicalSignificance": "Boron helps conserve magnesium; a complementary mineral pairing for bone health.", "managementStrategy": "Reasonable to take together, particularly for bone and mineral support in postmenopausal women. No timing separation is needed.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Iodine", "supplementBName": "L-Tyrosine", "interactionType": "synergy", "severity": "info", "description": "Iodine and L-tyrosine are the two raw materials the thyroid combines to build thyroid hormone, so adequacy of both supports normal hormone synthesis.", "recommendation": "Can be taken together for thyroid support. Avoid excess iodine, which can paradoxically impair thyroid function, and use cautiously if you have a thyroid disorder.", "minimumTimeSeparation": null, "mechanism": "Tyrosyl residues on thyroglobulin are iodinated by thyroid peroxidase and then coupled to form T4 and T3, so both iodine and tyrosine are direct substrates of the same hormone-synthesis reaction.", "evidenceLevel": "strong", "sources": [ { "text": "Zimmermann MB. Iodine deficiency. Endocrine Reviews. 2009", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Carvalho DP, Dupuy C. Thyroid hormone biosynthesis and release. Molecular and Cellular Endocrinology. 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Iodine and L-tyrosine are the two raw materials the thyroid combines to build thyroid hormone, so adequacy of both supports normal hormone synthesis.", "clinicalSignificance": "Both are direct substrates for thyroid hormone; adequacy of each supports synthesis.", "managementStrategy": "Can be taken together for thyroid support. Avoid excess iodine, which can paradoxically impair thyroid function, and use cautiously if you have a thyroid disorder.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Iodine", "supplementBName": "Zinc", "interactionType": "synergy", "severity": "info", "description": "Adequate zinc is needed for thyroid hormone synthesis and signaling, so zinc supports the thyroid effects of iodine.", "recommendation": "Ensuring adequate zinc supports thyroid function alongside iodine. Take long-term zinc with copper to avoid copper depletion.", "minimumTimeSeparation": null, "mechanism": "Zinc supports synthesis of thyroid-stimulating hormone and is structurally required for the T3 nuclear receptor, so zinc deficiency can blunt the hormonal payoff of adequate iodine.", "evidenceLevel": "moderate", "sources": [ { "text": "Severo JS, Morais JBS, de Freitas TEC et al. The role of zinc in thyroid hormones metabolism. International Journal for Vitamin and Nutrition Research. 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Betsy A, Binitha MP, Sarita S. Zinc deficiency associated with hypothyroidism. International Journal of Trichology. 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Adequate zinc is needed for thyroid hormone synthesis and signaling, so zinc supports the thyroid effects of iodine.", "clinicalSignificance": "Zinc adequacy is needed for iodine to translate into active thyroid hormone signaling.", "managementStrategy": "Ensuring adequate zinc supports thyroid function alongside iodine. Take long-term zinc with copper to avoid copper depletion.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Chondroitin", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Vitamin C supports synthesis and stabilization of the cartilage matrix that chondroitin sulfate is part of, so the two complement each other for joint and connective tissue support.", "recommendation": "Reasonable to take together for joint support. Take with a meal and keep vitamin C at typical doses (around 200 to 500 mg daily) rather than very high doses.", "minimumTimeSeparation": null, "mechanism": "Vitamin C is a required cofactor for prolyl and lysyl hydroxylases in collagen synthesis and supports chondrocyte production of extracellular matrix proteoglycans, providing the structural framework into which chondroitin sulfate glycosaminoglycans are incorporated.", "evidenceLevel": "emerging", "sources": [ { "text": "Peterkofsky B. Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy. American Journal of Clinical Nutrition, 1991", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Chan D, Lamande SR, Cole WG, Bateman JF. Regulation of procollagen synthesis and processing during ascorbate-induced extracellular matrix accumulation. Biochemical Journal, 1990", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Vitamin C supports synthesis and stabilization of the cartilage matrix that chondroitin sulfate is part of, so the two complement each other for joint and connective tissue support.", "clinicalSignificance": "Complementary cartilage matrix support with no meaningful safety concern at typical doses.", "managementStrategy": "Reasonable to take together for joint support. Take with a meal and keep vitamin C at typical doses (around 200 to 500 mg daily) rather than very high doses.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Chondroitin", "supplementBName": "Collagen Peptides", "interactionType": "synergy", "severity": "info", "description": "Chondroitin and collagen peptides supply complementary cartilage building blocks, and combined joint support has been studied with favorable results in osteoarthritis.", "recommendation": "Reasonable to combine for joint comfort and cartilage support. No timing separation is needed; take with a meal.", "minimumTimeSeparation": null, "mechanism": "Chondroitin sulfate is a glycosaminoglycan that helps retain water and resist compression in cartilage, while hydrolyzed collagen peptides supply amino acids and bioactive peptides that can stimulate chondrocyte collagen and proteoglycan synthesis, so the two act on complementary parts of the cartilage matrix.", "evidenceLevel": "emerging", "sources": [ { "text": "Garcia-Coronado JM et al. Effect of collagen supplementation on osteoarthritis symptoms: a meta-analysis of randomized placebo-controlled trials. International Orthopaedics, 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bello AE, Oesser S. Collagen hydrolysate for the treatment of osteoarthritis and other joint disorders: a review of the literature. Current Medical Research and Opinion, 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Chondroitin and collagen peptides supply complementary cartilage building blocks, and combined joint support has been studied with favorable results in osteoarthritis.", "clinicalSignificance": "Complementary joint support building blocks with no safety concern.", "managementStrategy": "Reasonable to combine for joint comfort and cartilage support. No timing separation is needed; take with a meal.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Chondroitin", "supplementBName": "Hyaluronic Acid", "interactionType": "synergy", "severity": "info", "description": "Chondroitin and hyaluronic acid are both glycosaminoglycan components of cartilage and synovial fluid, and they are commonly combined for joint lubrication and comfort.", "recommendation": "Reasonable to combine for joint support. No timing separation is needed.", "minimumTimeSeparation": null, "mechanism": "Chondroitin sulfate and hyaluronic acid are glycosaminoglycans that contribute to cartilage matrix integrity and synovial fluid viscosity, and both can dampen catabolic and inflammatory signaling in chondrocytes, giving complementary effects on joint structure and lubrication.", "evidenceLevel": "emerging", "sources": [ { "text": "Oe M et al. Oral hyaluronan relieves knee pain: a review. Nutrition Journal, 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Henrotin Y, Mathy M, Sanchez C, Lambert C. Chondroitin sulfate in the treatment of osteoarthritis: from in vitro studies to clinical recommendations. Therapeutic Advances in Musculoskeletal Disease, 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Chondroitin and hyaluronic acid are both glycosaminoglycan components of cartilage and synovial fluid, and they are commonly combined for joint lubrication and comfort.", "clinicalSignificance": "Complementary cartilage and synovial fluid support with no safety concern.", "managementStrategy": "Reasonable to combine for joint support. No timing separation is needed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Lutein", "supplementBName": "Zeaxanthin", "interactionType": "synergy", "severity": "info", "description": "Lutein and zeaxanthin are the two carotenoids that make up macular pigment and are routinely combined for eye and macular health.", "recommendation": "Take together with a fat-containing meal for macular support, in line with the ratios used in eye health research (roughly 10 mg lutein to 2 mg zeaxanthin).", "minimumTimeSeparation": null, "mechanism": "Lutein concentrates more in the peripheral macula and zeaxanthin in the central fovea, where together they form the macular pigment that filters high-energy blue light and quenches reactive oxygen species, giving spatially complementary photoprotection.", "evidenceLevel": "strong", "sources": [ { "text": "Age-Related Eye Disease Study 2 (AREDS2) Research Group. Lutein plus zeaxanthin and omega-3 fatty acids for age-related macular degeneration. JAMA, 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Bone RA, Landrum JT et al. Macular pigment in donor eyes with and without AMD: a case-control study. Investigative Ophthalmology and Visual Science, 2001", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Lutein and zeaxanthin are the two carotenoids that make up macular pigment and are routinely combined for eye and macular health.", "clinicalSignificance": "Well established complementary pair for macular pigment density and eye health.", "managementStrategy": "Take together with a fat-containing meal for macular support, in line with the ratios used in eye health research (roughly 10 mg lutein to 2 mg zeaxanthin).", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Lutein", "supplementBName": "Astaxanthin", "interactionType": "timingSensitive", "severity": "moderate", "description": "Lutein and astaxanthin are both lipophilic carotenoids that compete for the same intestinal absorption pathways, so large doses taken together can modestly reduce uptake of each.", "recommendation": "Both support eye and oxidative health. If taking higher doses, consider separating them by a couple of hours or taking them with different fat-containing meals to limit absorption competition.", "minimumTimeSeparation": "2 hours", "mechanism": "Carotenoids share intestinal uptake mechanisms, including incorporation into mixed micelles and transport via the scavenger receptor SR-BI, so co-ingestion of competing carotenoids can lower the absorption of each.", "evidenceLevel": "moderate", "sources": [ { "text": "van den Berg H. Carotenoid interactions. Nutr Rev. 1999.", "pmid": "10047699", "doi": "10.1111/j.1753-4887.1999.tb01769.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10047699/", "publicSourceType": "PMID" }, { "text": "Reboul E. Mechanisms of Carotenoid Intestinal Absorption: Where Do We Stand?. Nutrients. 2019.", "pmid": "31013870", "doi": "10.3390/nu11040838", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31013870/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Lutein and astaxanthin are both lipophilic carotenoids that compete for the same intestinal absorption pathways, so large doses taken together can modestly reduce uptake of each.", "clinicalSignificance": "Complementary antioxidants, but high doses together can blunt mutual absorption.", "managementStrategy": "Both support eye and oxidative health. If taking higher doses, consider separating them by a couple of hours or taking them with different fat-containing meals to limit absorption competition.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Lutein", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "Fish oil provides dietary fat that improves absorption of fat-soluble lutein, and its omega-3 fatty acids complement lutein in supporting retinal and macular health.", "recommendation": "Take lutein together with fish oil or another fat-containing meal to improve absorption and support eye health.", "minimumTimeSeparation": null, "mechanism": "Dietary fat from fish oil stimulates bile release and mixed micelle formation, improving solubilization and intestinal uptake of lipophilic lutein, while DHA is a structural lipid of retinal photoreceptor membranes that supports macular function.", "evidenceLevel": "moderate", "sources": [ { "text": "Brown MJ et al. Carotenoid bioavailability is higher from salads ingested with full-fat than with fat-reduced salad dressings as measured with electrochemical detection. American Journal of Clinical Nutrition, 2004", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "SanGiovanni JP, Chew EY. The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina. Progress in Retinal and Eye Research, 2005", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Fish oil provides dietary fat that improves absorption of fat-soluble lutein, and its omega-3 fatty acids complement lutein in supporting retinal and macular health.", "clinicalSignificance": "Fish oil aids lutein absorption and complements it for retinal support.", "managementStrategy": "Take lutein together with fish oil or another fat-containing meal to improve absorption and support eye health.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Zeaxanthin", "supplementBName": "Astaxanthin", "interactionType": "timingSensitive", "severity": "moderate", "description": "Zeaxanthin and astaxanthin are both lipophilic carotenoids that compete for shared intestinal absorption pathways, so large doses taken together can modestly reduce the uptake of each.", "recommendation": "Both support eye and oxidative health. At higher doses, consider separating them by a couple of hours or taking them with different fat-containing meals to limit absorption competition.", "minimumTimeSeparation": "2 hours", "mechanism": "Carotenoids share intestinal uptake routes, including incorporation into mixed micelles and transport via the scavenger receptor SR-BI, so co-ingestion of competing carotenoids can lower the absorption of each.", "evidenceLevel": "moderate", "sources": [ { "text": "van den Berg H. Carotenoid interactions. Nutr Rev. 1999.", "pmid": "10047699", "doi": "10.1111/j.1753-4887.1999.tb01769.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10047699/", "publicSourceType": "PMID" }, { "text": "Reboul E. Mechanisms of Carotenoid Intestinal Absorption: Where Do We Stand?. Nutrients. 2019.", "pmid": "31013870", "doi": "10.3390/nu11040838", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31013870/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Zeaxanthin and astaxanthin are both lipophilic carotenoids that compete for shared intestinal absorption pathways, so large doses taken together can modestly reduce the uptake of each.", "clinicalSignificance": "Complementary antioxidants, but high doses together can blunt mutual absorption.", "managementStrategy": "Both support eye and oxidative health. At higher doses, consider separating them by a couple of hours or taking them with different fat-containing meals to limit absorption competition.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Lycopene", "supplementBName": "Selenium", "interactionType": "synergy", "severity": "info", "description": "Lycopene and selenium have complementary antioxidant actions and have been studied together for prostate health and as antioxidant combinations.", "recommendation": "Reasonable to combine for antioxidant and prostate support. Keep selenium within safe limits (do not exceed about 200 mcg daily) to avoid selenium toxicity.", "minimumTimeSeparation": null, "mechanism": "Lycopene is a lipid-phase carotenoid that quenches singlet oxygen and lipid peroxyl radicals, while selenium is incorporated into glutathione peroxidase and thioredoxin reductase enzymes that detoxify peroxides, so the two act on different but complementary arms of the antioxidant defense system.", "evidenceLevel": "emerging", "sources": [ { "text": "Vance TM, Su J, Fontham ET, Koo SI, Chun OK. Dietary antioxidants and prostate cancer: a review. Nutrition and Cancer, 2013", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Sahin K et al. Comparative evaluation of the antioxidant effects of lycopene and selenium combination. Nutrition Research, 2011", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Lycopene and selenium have complementary antioxidant actions and have been studied together for prostate health and as antioxidant combinations.", "clinicalSignificance": "Complementary antioxidants, with selenium dose kept within safe limits.", "managementStrategy": "Reasonable to combine for antioxidant and prostate support. Keep selenium within safe limits (do not exceed about 200 mcg daily) to avoid selenium toxicity.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Lycopene", "supplementBName": "Saw Palmetto", "interactionType": "synergy", "severity": "info", "description": "Lycopene and saw palmetto are frequently combined for prostate health, and combination trials suggest complementary benefit for benign prostatic symptoms.", "recommendation": "Reasonable to combine for prostate and lower urinary tract support. Take with a meal to aid absorption of fat-soluble lycopene.", "minimumTimeSeparation": null, "mechanism": "Saw palmetto inhibits 5-alpha-reductase and exerts anti-inflammatory effects on prostatic tissue, while lycopene provides antioxidant and antiproliferative activity in the prostate, giving complementary mechanisms in benign prostatic hyperplasia.", "evidenceLevel": "moderate", "sources": [ { "text": "Morgia G et al. Treatment of chronic prostatitis/chronic pelvic pain syndrome category IIIA with Serenoa repens plus selenium and lycopene. Urologia Internationalis, 2010", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Schwarz S et al. Lycopene inhibits disease progression in patients with benign prostate hyperplasia. Journal of Nutrition, 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Lycopene and saw palmetto are frequently combined for prostate health, and combination trials suggest complementary benefit for benign prostatic symptoms.", "clinicalSignificance": "Complementary combination commonly used for prostate health.", "managementStrategy": "Reasonable to combine for prostate and lower urinary tract support. Take with a meal to aid absorption of fat-soluble lycopene.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Lycopene", "supplementBName": "Vitamin E", "interactionType": "synergy", "severity": "info", "description": "Lycopene and vitamin E are lipid-soluble antioxidants that work together in cell membranes and lipoproteins, with vitamin E helping spare and protect lycopene.", "recommendation": "Reasonable to combine for antioxidant support. Take both with a fat-containing meal to aid absorption.", "minimumTimeSeparation": null, "mechanism": "Both lycopene and vitamin E partition into the lipid phase of membranes and lipoproteins, where vitamin E (alpha-tocopherol) scavenges lipid peroxyl radicals and can spare and stabilize lycopene, giving cooperative protection against lipid peroxidation.", "evidenceLevel": "moderate", "sources": [ { "text": "Fuhrman B, Volkova N, Rosenblat M, Aviram M. Lycopene synergistically inhibits LDL oxidation in combination with vitamin E, glabridin, rosmarinic acid, carnosic acid, or garlic. Antioxidants and Redox Signaling, 2000", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Stahl W, Sies H. Antioxidant activity of carotenoids. Molecular Aspects of Medicine, 2003", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Lycopene and vitamin E are lipid-soluble antioxidants that work together in cell membranes and lipoproteins, with vitamin E helping spare and protect lycopene.", "clinicalSignificance": "Cooperative lipid-phase antioxidants that protect each other.", "managementStrategy": "Reasonable to combine for antioxidant support. Take both with a fat-containing meal to aid absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Tribulus Terrestris", "supplementBName": "Maca Root", "interactionType": "synergy", "severity": "info", "description": "Combining Tribulus and Maca pairs two libido and sexual function botanicals that act through largely separate pathways, giving complementary support for desire and erectile function.", "recommendation": "Reasonable to stack for libido or sexual function support. Use standard doses of each (Tribulus 250 to 750mg standardized for saponins, Maca 1.5 to 3g) and assess response over 8 to 12 weeks.", "minimumTimeSeparation": null, "mechanism": "Tribulus steroidal saponins (protodioscin) appear to act on nitric oxide and androgen-related signaling, while Maca works through non-hormonal central and adaptogenic pathways without raising testosterone, so the two address sexual function via different routes.", "evidenceLevel": "emerging", "sources": [ { "text": "Gonzales GF. Ethnobiology and Ethnopharmacology of Lepidium meyenii (Maca), a Plant from the Peruvian Highlands. Evidence-Based Complementary and Alternative Medicine. 2012.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Neychev V, Mitev V. Pro-sexual and androgen enhancing effects of Tribulus terrestris L.: Fact or Fiction. Journal of Ethnopharmacology. 2016.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Combining Tribulus and Maca pairs two libido and sexual function botanicals that act through largely separate pathways, giving complementary support for desire and erectile function.", "clinicalSignificance": "Complementary libido stack with low risk; benefit is plausible but evidence for the combination specifically is limited.", "managementStrategy": "Reasonable to stack for libido or sexual function support. Use standard doses of each (Tribulus 250 to 750mg standardized for saponins, Maca 1.5 to 3g) and assess response over 8 to 12 weeks.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Tribulus Terrestris", "supplementBName": "Ashwagandha", "interactionType": "synergy", "severity": "info", "description": "Ashwagandha adds adaptogenic, stress-lowering and modest androgen-supportive effects that complement Tribulus, with additive potential for male sexual function and well-being.", "recommendation": "Can be combined for sexual function or vitality goals. Ashwagandha root extract 300 to 600mg daily carries the stronger trial evidence; pair with standard Tribulus dosing and reassess after about 8 weeks.", "minimumTimeSeparation": null, "mechanism": "Ashwagandha lowers cortisol and shows modest increases in luteinizing hormone and testosterone in some trials, while Tribulus is proposed to support nitric oxide and androgen-related signaling, so the pair targets stress, hormonal, and vascular contributors to sexual function.", "evidenceLevel": "emerging", "sources": [ { "text": "Chauhan S, Srivastava MK, Pathak AK. Effect of standardized root extract of ashwagandha (Withania somnifera) on well-being and sexual performance in adult males: a randomized controlled trial. Health Science Reports. 2022.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Neychev V, Mitev V. Pro-sexual and androgen enhancing effects of Tribulus terrestris L.: Fact or Fiction. Journal of Ethnopharmacology. 2016.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Ashwagandha adds adaptogenic, stress-lowering and modest androgen-supportive effects that complement Tribulus, with additive potential for male sexual function and well-being.", "clinicalSignificance": "Low-risk additive stack; Ashwagandha carries better individual RCT support than Tribulus, but the combination itself is not well studied.", "managementStrategy": "Can be combined for sexual function or vitality goals. Ashwagandha root extract 300 to 600mg daily carries the stronger trial evidence; pair with standard Tribulus dosing and reassess after about 8 weeks.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Tribulus Terrestris", "supplementBName": "Boron", "interactionType": "synergy", "severity": "info", "description": "Boron can raise free testosterone by lowering sex hormone binding globulin and reducing conversion of testosterone to estradiol, a mechanism that complements Tribulus rather than overlapping with it.", "recommendation": "Boron 3 to 6mg daily can be paired with Tribulus for free testosterone support. Stay within the boron tolerable upper intake level of 20mg daily and do not megadose.", "minimumTimeSeparation": null, "mechanism": "Boron has been reported in small studies to reduce SHBG, freeing more bioavailable testosterone, and to lower estradiol, while Tribulus is proposed to act on androgen and nitric oxide pathways, so the two influence androgen availability through distinct steps.", "evidenceLevel": "emerging", "sources": [ { "text": "Naghii MR, Mofid M, Asgari AR, Hedayati M, Daneshpour MS. Comparative effects of daily and weekly boron supplementation on plasma steroid hormones and proinflammatory cytokines. Journal of Trace Elements in Medicine and Biology. 2011.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Neychev V, Mitev V. Pro-sexual and androgen enhancing effects of Tribulus terrestris L.: Fact or Fiction. Journal of Ethnopharmacology. 2016.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Boron can raise free testosterone by lowering sex hormone binding globulin and reducing conversion of testosterone to estradiol, a mechanism that complements Tribulus rather than overlapping with it.", "clinicalSignificance": "Mechanistically complementary for free testosterone, though human outcome data for the combination are limited and the boron studies are small.", "managementStrategy": "Boron 3 to 6mg daily can be paired with Tribulus for free testosterone support. Stay within the boron tolerable upper intake level of 20mg daily and do not megadose.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Garlic Extract", "supplementBName": "Nattokinase", "interactionType": "caution", "severity": "moderate", "description": "Garlic has antiplatelet activity and nattokinase has fibrinolytic activity, so combining them can additively impair clotting and raise bleeding risk, especially around surgery or with blood thinners.", "recommendation": "Use together cautiously and monitor for easy bruising, nosebleeds, or prolonged bleeding. Stop both at least 7 to 10 days before surgery and avoid combining with anticoagulant or antiplatelet drugs without clinician oversight.", "minimumTimeSeparation": null, "mechanism": "Garlic organosulfur compounds inhibit platelet aggregation, while nattokinase degrades fibrin and may enhance endogenous fibrinolysis; acting at different points of hemostasis, the two effects can be additive.", "evidenceLevel": "emerging", "sources": [ { "text": "Rahman K et al. Garlic and cardiovascular disease: a critical review. J Nutr. 2006;136(3 Suppl):736S-740S.", "pmid": "16484553", "doi": "10.1093/jn/136.3.736S", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16484553/", "publicSourceType": "PMID" }, { "text": "Allison GL et al. Aged garlic extract and its constituents inhibit platelet aggregation through multiple mechanisms. J Nutr. 2006;136(3 Suppl):782S-788S.", "pmid": "16484563", "doi": "10.1093/jn/136.3.782S", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16484563/", "publicSourceType": "PMID" }, { "text": "Weng Y et al. Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease. Int J Mol Sci. 2017;18(3).", "pmid": "28264497", "doi": "10.3390/ijms18030523", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28264497/", "publicSourceType": "PMID" }, { "text": "Kurosawa Y et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep. 2015;5:11601.", "pmid": "26109079", "doi": "10.1038/srep11601", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26109079/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Garlic has antiplatelet activity and nattokinase has fibrinolytic activity, so combining them can additively impair clotting and raise bleeding risk, especially around surgery or with blood thinners.", "clinicalSignificance": "Additive bleeding risk; most relevant perioperatively or alongside anticoagulants.", "managementStrategy": "Use together cautiously and monitor for easy bruising, nosebleeds, or prolonged bleeding. Stop both at least 7 to 10 days before surgery and avoid combining with anticoagulant or antiplatelet drugs without clinician oversight.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Garlic Extract", "supplementBName": "Berberine", "interactionType": "synergy", "severity": "info", "description": "Garlic and berberine both lower LDL cholesterol and triglycerides through different mechanisms, giving additive lipid-lowering when combined.", "recommendation": "Reasonable to stack for cardiometabolic and lipid goals. Watch for additive blood pressure and glucose lowering, and monitor if also on lipid, antidiabetic, or antihypertensive medication.", "minimumTimeSeparation": null, "mechanism": "Berberine upregulates hepatic LDL receptors and activates AMPK, while garlic modestly improves lipid profiles and may inhibit cholesterol synthesis, so their cholesterol-lowering effects operate through complementary pathways.", "evidenceLevel": "moderate", "sources": [ { "text": "Kong W et al. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med. 2004;10(12):1344-51.", "pmid": "15531889", "doi": "10.1038/nm1135", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15531889/", "publicSourceType": "PMID" }, { "text": "Ried K et al. Effect of garlic on blood pressure: a systematic review and meta-analysis. BMC Cardiovasc Disord. 2008;8:13.", "pmid": "18554422", "doi": "10.1186/1471-2261-8-13", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18554422/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Garlic and berberine both lower LDL cholesterol and triglycerides through different mechanisms, giving additive lipid-lowering when combined.", "clinicalSignificance": "Complementary lipid-lowering; watch for additive effects on glucose and blood pressure.", "managementStrategy": "Reasonable to stack for cardiometabolic and lipid goals. Watch for additive blood pressure and glucose lowering, and monitor if also on lipid, antidiabetic, or antihypertensive medication.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Garlic Extract", "supplementBName": "Coenzyme Q10", "interactionType": "synergy", "severity": "info", "description": "Aged garlic extract combined with coenzyme Q10 improved endothelial function and vascular elasticity in a randomized trial, with both agents contributing modest blood pressure lowering.", "recommendation": "Can be combined for cardiovascular and blood pressure support. If on antihypertensive medication, monitor blood pressure for additive lowering.", "minimumTimeSeparation": null, "mechanism": "Garlic enhances nitric oxide availability and reduces vascular oxidative stress, while coenzyme Q10 supports mitochondrial energy production and endothelial function, together improving vascular elasticity and modestly lowering blood pressure.", "evidenceLevel": "moderate", "sources": [ { "text": "Larijani VN et al. Beneficial effects of aged garlic extract and coenzyme Q10 on vascular elasticity and endothelial function: the FAITH randomized clinical trial. Nutrition. 2013;29(1):71-5.", "pmid": "22858191", "doi": "10.1016/j.nut.2012.03.016", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22858191/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Aged garlic extract combined with coenzyme Q10 improved endothelial function and vascular elasticity in a randomized trial, with both agents contributing modest blood pressure lowering.", "clinicalSignificance": "Trial-supported vascular synergy; the main caution is additive blood pressure lowering in treated hypertensives.", "managementStrategy": "Can be combined for cardiovascular and blood pressure support. If on antihypertensive medication, monitor blood pressure for additive lowering.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Serrapeptase", "supplementBName": "Turmeric/Curcumin", "interactionType": "caution", "severity": "moderate", "description": "Serrapeptase has fibrinolytic activity and curcumin has antiplatelet activity, so the combination can additively reduce clotting and increase bleeding risk while also providing additive anti-inflammatory effects.", "recommendation": "Use together cautiously, especially if on anticoagulant or antiplatelet drugs, and discontinue both 7 to 10 days before surgery or dental procedures. Watch for bruising or prolonged bleeding.", "minimumTimeSeparation": null, "mechanism": "Curcumin inhibits platelet aggregation and thromboxane formation, while serrapeptase degrades fibrin and has reported antithrombotic properties; acting on different hemostatic steps, their effects on bleeding can be additive.", "evidenceLevel": "emerging", "sources": [ { "text": "Tiwari M. The role of serratiopeptidase in the resolution of inflammation. Asian J Pharm Sci. 2017;12(3):209-215.", "pmid": "32104332", "doi": "10.1016/j.ajps.2017.01.003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32104332/", "publicSourceType": "PMID" }, { "text": "Keihanian F et al. Curcumin, hemostasis, thrombosis, and coagulation. J Cell Physiol. 2018;233(6):4497-4511.", "pmid": "29052850", "doi": "10.1002/jcp.26249", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29052850/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Serrapeptase has fibrinolytic activity and curcumin has antiplatelet activity, so the combination can additively reduce clotting and increase bleeding risk while also providing additive anti-inflammatory effects.", "clinicalSignificance": "Additive antiplatelet and fibrinolytic effect raises bleeding risk; the anti-inflammatory benefit is the intended upside.", "managementStrategy": "Use together cautiously, especially if on anticoagulant or antiplatelet drugs, and discontinue both 7 to 10 days before surgery or dental procedures. Watch for bruising or prolonged bleeding.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Serrapeptase", "supplementBName": "Ginkgo Biloba", "interactionType": "caution", "severity": "moderate", "description": "Ginkgo inhibits platelet-activating factor and serrapeptase is fibrinolytic, so combining them can additively impair hemostasis and increase the risk of bruising and bleeding.", "recommendation": "Combine cautiously and monitor for bleeding signs. Avoid the combination with anticoagulants or antiplatelet drugs unless supervised, and stop both at least 7 to 10 days before surgery.", "minimumTimeSeparation": null, "mechanism": "Ginkgo terpenoids (ginkgolides) antagonize platelet-activating factor and reduce platelet aggregation, while serrapeptase breaks down fibrin and has reported antithrombotic effects, producing an additive reduction in clotting capacity.", "evidenceLevel": "emerging", "sources": [ { "text": "Bone KM. Potential interaction of Ginkgo biloba leaf with antiplatelet or anticoagulant drugs: what is the evidence? Mol Nutr Food Res. 2008;52(7):764-71.", "pmid": "18214851", "doi": "10.1002/mnfr.200700098", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18214851/", "publicSourceType": "PMID" }, { "text": "Tiwari M. The role of serratiopeptidase in the resolution of inflammation. Asian J Pharm Sci. 2017;12(3):209-215.", "pmid": "32104332", "doi": "10.1016/j.ajps.2017.01.003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32104332/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Ginkgo inhibits platelet-activating factor and serrapeptase is fibrinolytic, so combining them can additively impair hemostasis and increase the risk of bruising and bleeding.", "clinicalSignificance": "Additive bleeding risk; most relevant perioperatively or with other blood thinners.", "managementStrategy": "Combine cautiously and monitor for bleeding signs. Avoid the combination with anticoagulants or antiplatelet drugs unless supervised, and stop both at least 7 to 10 days before surgery.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "DIM", "supplementBName": "Milk Thistle", "interactionType": "caution", "severity": "moderate", "description": "DIM shifts estrogen metabolism toward 2-hydroxylation by inducing CYP1A enzymes, while milk thistle silymarin can mildly inhibit some CYP and glucuronidation enzymes, so co-use may modestly alter estrogen handling and the clearance of other liver-metabolized compounds.", "recommendation": "Generally usable together, but be aware milk thistle may modestly modulate the enzymes DIM acts on. If also taking hormone therapy or narrow-margin CYP-metabolized medications, consult a clinician before combining.", "minimumTimeSeparation": null, "mechanism": "DIM acts as an aryl hydrocarbon receptor agonist that induces CYP1A1 and CYP1A2, increasing 2-hydroxyestrone formation, whereas silymarin can weakly inhibit CYP3A4, CYP2C9, and UGT-mediated glucuronidation, mainly relevant at higher exposures.", "evidenceLevel": "emerging", "sources": [ { "text": "Sanderson JT, Slobbe L, Lansbergen GW, Safe S, van den Berg M. 2,3,7,8-Tetrachlorodibenzo-p-dioxin and diindolylmethanes differentially induce cytochrome P450 1A1, 1B1, and 19 in H295R human adrenocortical carcinoma cells. Toxicological Sciences. 2001.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Venkataramanan R, Ramachandran V, Komoroski BJ, Zhang S, Schiff PL, Strom SC. Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucuronosyl transferase in human hepatocyte cultures. Drug Metabolism and Disposition. 2000.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "DIM shifts estrogen metabolism toward 2-hydroxylation by inducing CYP1A enzymes, while milk thistle silymarin can mildly inhibit some CYP and glucuronidation enzymes, so co-use may modestly alter estrogen handling and the clearance of other liver-metabolized compounds.", "clinicalSignificance": "Possible modest modulation of estrogen detoxification and co-administered CYP substrates; clinically minor for most users but worth noting with medications.", "managementStrategy": "Generally usable together, but be aware milk thistle may modestly modulate the enzymes DIM acts on. If also taking hormone therapy or narrow-margin CYP-metabolized medications, consult a clinician before combining.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Saw Palmetto", "supplementBName": "Zinc", "interactionType": "synergy", "severity": "info", "description": "Saw palmetto and zinc are a classic prostate-support pairing that target the same hormonal pathway, giving additive support within benign prostatic hyperplasia (BPH) symptom protocols.", "recommendation": "Reasonable to combine. Typical doses are saw palmetto 320 mg/day and zinc 15 to 30 mg/day, with copper 1 to 2 mg added on prolonged high-dose zinc to prevent copper depletion.", "minimumTimeSeparation": null, "mechanism": "Saw palmetto inhibits 5-alpha reductase, the enzyme that converts testosterone to dihydrotestosterone (DHT) in prostate tissue, while zinc concentrates in the prostate where it supports normal glandular function and may modestly modulate 5-alpha reductase activity.", "evidenceLevel": "emerging", "sources": [ { "text": "Suzuki M et al, Saw palmetto extract suppresses 5-alpha reductase activity, Journal of Ethnopharmacology, 2009", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Costello LC, Franklin RB, The clinical relevance of the metabolism of prostate cancer; zinc and tumor suppression, Molecular Cancer, 2006", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Saw palmetto and zinc are a classic prostate-support pairing that target the same hormonal pathway, giving additive support within benign prostatic hyperplasia (BPH) symptom protocols.", "clinicalSignificance": "Complementary prostate support via 5-alpha reductase inhibition plus zinc-dependent glandular function; watch copper status with long-term zinc.", "managementStrategy": "Reasonable to combine. Typical doses are saw palmetto 320 mg/day and zinc 15 to 30 mg/day, with copper 1 to 2 mg added on prolonged high-dose zinc to prevent copper depletion.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Saw Palmetto", "supplementBName": "Pine Bark Extract", "interactionType": "synergy", "severity": "info", "description": "Saw palmetto and pine bark extract (pycnogenol) are sometimes stacked in men's urinary and prostate formulas, pairing hormonal support with anti-inflammatory and circulatory effects.", "recommendation": "Reasonable to combine for prostate and lower urinary tract support. Typical doses are saw palmetto 320 mg/day and pine bark extract 100 to 150 mg/day; allow 8 to 12 weeks for symptom change.", "minimumTimeSeparation": null, "mechanism": "Saw palmetto inhibits 5-alpha reductase, while pine bark proanthocyanidins reduce inflammation and support pelvic microcirculation and nitric oxide signaling, addressing different contributors to BPH symptoms.", "evidenceLevel": "emerging", "sources": [ { "text": "Ledda A et al, Benign prostatic hypertrophy: Pycnogenol supplementation improves prostate symptoms and lower urinary tract function, Minerva Urologica e Nefrologica, 2018", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Suzuki M et al, Saw palmetto extract suppresses 5-alpha reductase activity, Journal of Ethnopharmacology, 2009", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Saw palmetto and pine bark extract (pycnogenol) are sometimes stacked in men's urinary and prostate formulas, pairing hormonal support with anti-inflammatory and circulatory effects.", "clinicalSignificance": "Complementary hormonal and anti-inflammatory support for the prostate, though combined human data are limited.", "managementStrategy": "Reasonable to combine for prostate and lower urinary tract support. Typical doses are saw palmetto 320 mg/day and pine bark extract 100 to 150 mg/day; allow 8 to 12 weeks for symptom change.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Cordyceps", "supplementBName": "Reishi", "interactionType": "synergy", "severity": "info", "description": "Cordyceps and reishi are medicinal mushrooms commonly stacked for immune-modulating and adaptogenic support, providing overlapping beta-glucan content.", "recommendation": "Reasonable to combine. Reishi in particular may have mild antiplatelet activity, so monitor for bruising or bleeding if also using anticoagulants or before surgery.", "minimumTimeSeparation": null, "mechanism": "Both supply beta-glucan polysaccharides and triterpenes that modulate innate immune cell activity, while cordyceps supports cellular energy metabolism and reishi adds calming and antioxidant effects.", "evidenceLevel": "emerging", "sources": [ { "text": "Wachtel-Galor S et al, Ganoderma lucidum (Lingzhi or Reishi): a medicinal mushroom, in Herbal Medicine: Biomolecular and Clinical Aspects, 2011", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Tuli HS et al, Pharmacological and therapeutic potential of Cordyceps with special reference to cordycepin, 3 Biotech, 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Cordyceps and reishi are medicinal mushrooms commonly stacked for immune-modulating and adaptogenic support, providing overlapping beta-glucan content.", "clinicalSignificance": "Complementary immune and adaptogen pairing; mind reishi's potential antiplatelet effect.", "managementStrategy": "Reasonable to combine. Reishi in particular may have mild antiplatelet activity, so monitor for bruising or bleeding if also using anticoagulants or before surgery.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Cordyceps", "supplementBName": "Chaga", "interactionType": "synergy", "severity": "info", "description": "Cordyceps and chaga are medicinal mushrooms often combined for immune and antioxidant support, supplying complementary beta-glucan polysaccharides.", "recommendation": "Reasonable to combine. Both have shown modest glucose-lowering effects in preclinical studies, so people on diabetes medication should monitor blood sugar for additive hypoglycemia.", "minimumTimeSeparation": null, "mechanism": "Both provide beta-glucans that modulate innate immune activity along with antioxidant compounds, and each has shown mild blood-glucose-lowering effects in preclinical (mostly animal) studies.", "evidenceLevel": "emerging", "sources": [ { "text": "Glamoclija J et al, Chemical characterization and biological activity of Chaga, Journal of Ethnopharmacology, 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Tuli HS et al, Pharmacological and therapeutic potential of Cordyceps with special reference to cordycepin, 3 Biotech, 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Cordyceps and chaga are medicinal mushrooms often combined for immune and antioxidant support, supplying complementary beta-glucan polysaccharides.", "clinicalSignificance": "Complementary immune-antioxidant pairing; watch for additive glucose lowering with antidiabetic drugs.", "managementStrategy": "Reasonable to combine. Both have shown modest glucose-lowering effects in preclinical studies, so people on diabetes medication should monitor blood sugar for additive hypoglycemia.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Reishi", "supplementBName": "Lion's Mane", "interactionType": "synergy", "severity": "info", "description": "Reishi and lion's mane are frequently stacked in nootropic and wellness blends, pairing calming and immune support with neurotrophic cognitive support.", "recommendation": "Reasonable to combine. Reishi may have mild antiplatelet activity, so monitor for bruising or bleeding if also using anticoagulants or before surgery.", "minimumTimeSeparation": null, "mechanism": "Lion's mane hericenones and erinacines stimulate nerve growth factor (NGF) for cognitive and nerve support, while reishi triterpenes and beta-glucans add immune modulation and a calming, sleep-supportive effect.", "evidenceLevel": "emerging", "sources": [ { "text": "Friedman M, Chemistry, nutrition, and health-promoting properties of Hericium erinaceus (Lion's Mane) mushroom, Journal of Agricultural and Food Chemistry, 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Wachtel-Galor S et al, Ganoderma lucidum (Lingzhi or Reishi): a medicinal mushroom, in Herbal Medicine: Biomolecular and Clinical Aspects, 2011", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Reishi and lion's mane are frequently stacked in nootropic and wellness blends, pairing calming and immune support with neurotrophic cognitive support.", "clinicalSignificance": "Complementary cognitive and calming mushroom pairing; mind reishi's mild antiplatelet potential.", "managementStrategy": "Reasonable to combine. Reishi may have mild antiplatelet activity, so monitor for bruising or bleeding if also using anticoagulants or before surgery.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "L-Glutamine", "supplementBName": "Zinc Carnosine", "interactionType": "synergy", "severity": "info", "description": "L-glutamine and zinc carnosine are a complementary gut-repair pairing, both promoting integrity and healing of the intestinal and gastric mucosa.", "recommendation": "Reasonable to combine for gut barrier support. No timing separation needed; both are commonly taken with or between meals.", "minimumTimeSeparation": null, "mechanism": "L-glutamine is a primary fuel for enterocytes and supports tight junction integrity, while zinc carnosine stabilizes the mucosal lining and induces heat shock proteins that promote epithelial repair.", "evidenceLevel": "moderate", "sources": [ { "text": "Rao R, Samak G, Role of glutamine in protection of intestinal epithelial tight junctions, Journal of Epithelial Biology and Pharmacology, 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Mahmood A et al, Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes, Gut, 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "L-glutamine and zinc carnosine are a complementary gut-repair pairing, both promoting integrity and healing of the intestinal and gastric mucosa.", "clinicalSignificance": "Two complementary mucosal-repair mechanisms make this a logical gut-healing stack.", "managementStrategy": "Reasonable to combine for gut barrier support. No timing separation needed; both are commonly taken with or between meals.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "L-Glutamine", "supplementBName": "Saccharomyces Boulardii", "interactionType": "synergy", "severity": "info", "description": "L-glutamine and the probiotic yeast Saccharomyces boulardii are often combined for gut barrier and digestive support, acting through complementary mucosal mechanisms.", "recommendation": "Reasonable to combine for intestinal support. No timing separation needed.", "minimumTimeSeparation": null, "mechanism": "L-glutamine fuels enterocytes and supports tight junctions, while S. boulardii enhances brush-border enzyme activity, trophic polyamine production, and short-chain fatty acid availability that nourish the mucosa.", "evidenceLevel": "emerging", "sources": [ { "text": "Rao R, Samak G, Role of glutamine in protection of intestinal epithelial tight junctions, Journal of Epithelial Biology and Pharmacology, 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Buts JP, Bernasconi P, Saccharomyces boulardii: basic science and clinical applications in gastroenterology, Gastroenterology Clinics of North America, 2005", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "L-glutamine and the probiotic yeast Saccharomyces boulardii are often combined for gut barrier and digestive support, acting through complementary mucosal mechanisms.", "clinicalSignificance": "Complementary support for intestinal barrier function and digestive recovery.", "managementStrategy": "Reasonable to combine for intestinal support. No timing separation needed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "L-Glutamine", "supplementBName": "Psyllium Husk", "interactionType": "timingSensitive", "severity": "moderate", "description": "Psyllium forms a viscous gel that slows gastric emptying and small-bowel transit, which may trap free amino acids and theoretically reduce absorption of L-glutamine when the two are taken together.", "recommendation": "Separate L-glutamine and psyllium by at least 2 hours. Take L-glutamine on its own with water, away from your fiber dose.", "minimumTimeSeparation": "2 hours", "mechanism": "The soluble fiber gel increases lumen viscosity and slows mixing and diffusion, which can limit mucosal contact and uptake of small molecules, including free amino acids, taken concurrently.", "evidenceLevel": "emerging", "sources": [ { "text": "Anderson JW et al, Health benefits of dietary fiber, Nutrition Reviews, 2009", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Jenkins DJ et al, Viscous and nonviscous fibres, nonabsorbable and low glycaemic index carbohydrates, blood lipids and coronary heart disease, Current Opinion in Lipidology, 2000", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Psyllium forms a viscous gel that slows gastric emptying and small-bowel transit, which may trap free amino acids and theoretically reduce absorption of L-glutamine when the two are taken together.", "clinicalSignificance": "Time L-glutamine away from psyllium so the fiber gel does not blunt amino acid absorption.", "managementStrategy": "Separate L-glutamine and psyllium by at least 2 hours. Take L-glutamine on its own with water, away from your fiber dose.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "GABA", "supplementBName": "Glycine", "interactionType": "synergy", "severity": "info", "description": "Combining GABA with glycine layers two distinct inhibitory neurotransmitter systems, which can deepen overall central nervous system calming and support sleep onset.", "recommendation": "Reasonable to stack before bed (for example GABA 100 to 200mg with glycine 3g). Start low if also taking other sedatives and assess next-morning grogginess.", "minimumTimeSeparation": null, "mechanism": "GABA is the primary inhibitory neurotransmitter acting on GABA-A and GABA-B receptors, while glycine is the chief inhibitory neurotransmitter in the brainstem and spinal cord acting on strychnine-sensitive glycine receptors and promoting a small drop in core body temperature that aids sleep onset.", "evidenceLevel": "moderate", "sources": [ { "text": "Bannai M et al. New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep. J Pharmacol Sci. 2012;118(2):145-8.", "pmid": "22293292", "doi": "10.1254/jphs.11r04fm", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22293292/", "publicSourceType": "PMID" }, { "text": "Boonstra E et al. Neurotransmitters as food supplements: the effects of GABA on brain and behavior. Front Psychol. 2015;6:1520.", "pmid": "26500584", "doi": "10.3389/fpsyg.2015.01520", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26500584/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Combining GABA with glycine layers two distinct inhibitory neurotransmitter systems, which can deepen overall central nervous system calming and support sleep onset.", "clinicalSignificance": "Complementary inhibitory pathways that can additively promote relaxation and sleep.", "managementStrategy": "Reasonable to stack before bed (for example GABA 100 to 200mg with glycine 3g). Start low if also taking other sedatives and assess next-morning grogginess.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "GABA", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "info", "description": "Magnesium glycinate complements oral GABA by supporting GABAergic tone, contributing to a calmer state and easier sleep onset.", "recommendation": "Can be taken together in the evening (for example magnesium glycinate providing 200 to 400mg elemental magnesium plus GABA 100 to 200mg). Watch for additive drowsiness.", "minimumTimeSeparation": null, "mechanism": "Magnesium acts as a positive allosteric modulator at the GABA-A receptor and blocks the NMDA receptor, dampening excitatory signaling, while the glycine carrier is itself a mild inhibitory co-agonist, so both reinforce the inhibitory effect targeted by supplemental GABA.", "evidenceLevel": "moderate", "sources": [ { "text": "Boyle NB, Lawton C, Dye L. The effects of magnesium supplementation on subjective anxiety and stress. Nutrients. 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Poleszak E. Modulation of antidepressant-like activity of magnesium by the GABAergic system. Journal of Physiology and Pharmacology. 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Magnesium glycinate complements oral GABA by supporting GABAergic tone, contributing to a calmer state and easier sleep onset.", "clinicalSignificance": "Magnesium and the glycinate carrier reinforce GABAergic, calming activity.", "managementStrategy": "Can be taken together in the evening (for example magnesium glycinate providing 200 to 400mg elemental magnesium plus GABA 100 to 200mg). Watch for additive drowsiness.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "GABA", "supplementBName": "Ashwagandha", "interactionType": "caution", "severity": "moderate", "description": "Ashwagandha has GABA-mimetic activity, so stacking it with supplemental GABA can produce additive sedation and pronounced drowsiness.", "recommendation": "Use together cautiously and start with low doses, preferably at night. Avoid combining before driving and be careful if also taking prescription sedatives or sleep medications.", "minimumTimeSeparation": null, "mechanism": "Ashwagandha withanolides act as positive modulators at the GABA-A receptor and show GABA-mimetic activity in preclinical models, so adding exogenous GABA can compound inhibitory neurotransmission and central depression.", "evidenceLevel": "moderate", "sources": [ { "text": "Candelario M et al. Direct evidence for GABAergic activity of Withania somnifera on mammalian ionotropic GABAA and GABAρ receptors. J Ethnopharmacol. 2015;171:264-72.", "pmid": "26068424", "doi": "10.1016/j.jep.2015.05.058", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26068424/", "publicSourceType": "PMID" }, { "text": "Boonstra E et al. Neurotransmitters as food supplements: the effects of GABA on brain and behavior. Front Psychol. 2015;6:1520.", "pmid": "26500584", "doi": "10.3389/fpsyg.2015.01520", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26500584/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Ashwagandha has GABA-mimetic activity, so stacking it with supplemental GABA can produce additive sedation and pronounced drowsiness.", "clinicalSignificance": "Additive GABAergic sedation; titrate and avoid stacking with other depressants.", "managementStrategy": "Use together cautiously and start with low doses, preferably at night. Avoid combining before driving and be careful if also taking prescription sedatives or sleep medications.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Hyaluronic Acid", "supplementBName": "MSM", "interactionType": "synergy", "severity": "info", "description": "MSM supplies bioavailable sulfur that supports glycosaminoglycan and connective tissue synthesis, complementing hyaluronic acid for joint comfort and skin hydration.", "recommendation": "Reasonable to combine in joint or skin protocols (for example oral hyaluronic acid 80 to 200mg with MSM 1 to 3g daily). No timing restriction needed.", "minimumTimeSeparation": null, "mechanism": "Hyaluronic acid is a major glycosaminoglycan of synovial fluid and skin, while MSM donates sulfur used in synthesis of sulfated glycosaminoglycans and collagen cross-linking and exerts anti-inflammatory effects, so the two support extracellular matrix integrity through complementary routes.", "evidenceLevel": "emerging", "sources": [ { "text": "Butawan M, Benjamin RL, Bloomer RJ. Methylsulfonylmethane: applications and safety of a novel dietary supplement. Nutrients. 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Oe M, et al. Oral hyaluronan relieves knee pain: a review. Nutrition Journal. 2016", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "MSM supplies bioavailable sulfur that supports glycosaminoglycan and connective tissue synthesis, complementing hyaluronic acid for joint comfort and skin hydration.", "clinicalSignificance": "Complementary connective-tissue support; commonly paired in joint and skin formulas.", "managementStrategy": "Reasonable to combine in joint or skin protocols (for example oral hyaluronic acid 80 to 200mg with MSM 1 to 3g daily). No timing restriction needed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Hyaluronic Acid", "supplementBName": "Astaxanthin", "interactionType": "synergy", "severity": "info", "description": "Astaxanthin reduces oxidative stress that drives hyaluronic acid breakdown, helping preserve skin hydration and elasticity when paired with supplemental hyaluronic acid.", "recommendation": "Can be combined in skin-health protocols (for example astaxanthin 4 to 12mg with oral hyaluronic acid 80 to 120mg daily). No separation needed.", "minimumTimeSeparation": null, "mechanism": "Astaxanthin is a potent carotenoid antioxidant that quenches reactive oxygen species and dampens UV-induced matrix metalloproteinase and hyaluronidase activity, slowing degradation of dermal hyaluronic acid that supplementation aims to replenish.", "evidenceLevel": "emerging", "sources": [ { "text": "Tominaga K, et al. Protective effects of astaxanthin on skin deterioration. Journal of Clinical Biochemistry and Nutrition. 2017", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Davinelli S, Nielsen ME, Scapagnini G. Astaxanthin in skin health, repair, and disease: a comprehensive review. Nutrients. 2018", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Astaxanthin reduces oxidative stress that drives hyaluronic acid breakdown, helping preserve skin hydration and elasticity when paired with supplemental hyaluronic acid.", "clinicalSignificance": "Antioxidant protection of dermal hyaluronic acid; logical pairing for skin support.", "managementStrategy": "Can be combined in skin-health protocols (for example astaxanthin 4 to 12mg with oral hyaluronic acid 80 to 120mg daily). No separation needed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Phosphatidylcholine", "supplementBName": "Phosphatidylserine", "interactionType": "synergy", "severity": "info", "description": "Phosphatidylcholine and phosphatidylserine are complementary membrane phospholipids that together support neuronal membrane integrity and cognitive function.", "recommendation": "Reasonable to combine for cognitive support (for example phosphatidylserine 100 to 300mg with phosphatidylcholine providing meaningful choline). No timing restriction.", "minimumTimeSeparation": null, "mechanism": "Phosphatidylcholine is a structural phospholipid and source of choline for acetylcholine and membrane synthesis, while phosphatidylserine is an inner-leaflet phospholipid that supports membrane fluidity and neurotransmission, so the two contribute to overlapping membrane and neuronal maintenance pathways.", "evidenceLevel": "emerging", "sources": [ { "text": "Glade MJ, Smith K. Phosphatidylserine and the human brain. Nutrition. 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Kidd PM. Phospholipids: versatile nutraceuticals for membrane and brain health. Nutrition Reviews. 2009", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Phosphatidylcholine and phosphatidylserine are complementary membrane phospholipids that together support neuronal membrane integrity and cognitive function.", "clinicalSignificance": "Complementary phospholipids supporting neuronal membranes and cognition.", "managementStrategy": "Reasonable to combine for cognitive support (for example phosphatidylserine 100 to 300mg with phosphatidylcholine providing meaningful choline). No timing restriction.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Phosphatidylcholine", "supplementBName": "Alpha-GPC", "interactionType": "caution", "severity": "moderate", "description": "Phosphatidylcholine and Alpha-GPC are both choline donors, so combining them raises total choline intake and the additive cholinergic and TMAO-generating load.", "recommendation": "Avoid stacking high doses of both. If combining, keep total choline within reason and watch for cholinergic symptoms such as headache, nausea, sweating, or low mood. People prioritizing cardiovascular TMAO concerns should be especially cautious.", "minimumTimeSeparation": null, "mechanism": "Both supplements deliver choline (phosphatidylcholine as a bound phospholipid, Alpha-GPC as glycerophosphocholine), so together they increase systemic choline available for acetylcholine synthesis and for gut microbial conversion to trimethylamine and hepatic oxidation to TMAO, raising cholinergic and metabolic exposure.", "evidenceLevel": "moderate", "sources": [ { "text": "Wallace TC, et al. Choline: The Underconsumed and Underappreciated Essential Nutrient. Nutr Today. 2018.", "pmid": "30853718", "doi": "10.1097/NT.0000000000000302", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30853718/", "publicSourceType": "PMID" }, { "text": "Tang WHW, Hazen SL. The contributory role of gut microbiota in cardiovascular disease. J Clin Invest. 2014.", "pmid": "25271725", "doi": "10.1172/JCI72331", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25271725/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Phosphatidylcholine and Alpha-GPC are both choline donors, so combining them raises total choline intake and the additive cholinergic and TMAO-generating load.", "clinicalSignificance": "Overlapping choline load; avoid stacking high doses of two choline sources.", "managementStrategy": "Avoid stacking high doses of both. If combining, keep total choline within reason and watch for cholinergic symptoms such as headache, nausea, sweating, or low mood. People prioritizing cardiovascular TMAO concerns should be especially cautious.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Taurine", "supplementBName": "Potassium", "interactionType": "synergy", "severity": "info", "description": "Taurine helps stabilize cardiomyocyte membranes and supports intracellular potassium handling, complementing potassium intake for cardiac electrical stability.", "recommendation": "Generally compatible and complementary. People on potassium-sparing or potassium-altering medications, or with kidney disease, should manage potassium under clinical guidance rather than self-supplementing.", "minimumTimeSeparation": null, "mechanism": "Taurine modulates membrane excitability and intracellular calcium and potassium handling in cardiac and skeletal muscle and helps maintain intracellular potassium content, which together with adequate potassium supports normal resting membrane potential and cardiac rhythm stability.", "evidenceLevel": "emerging", "sources": [ { "text": "Schaffer SW et al. Physiological roles of taurine in heart and muscle. J Biomed Sci. 2010;17 Suppl 1(Suppl 1):S2.", "pmid": "20804594", "doi": "10.1186/1423-0127-17-S1-S2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20804594/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Taurine helps stabilize cardiomyocyte membranes and supports intracellular potassium handling, complementing potassium intake for cardiac electrical stability.", "clinicalSignificance": "Taurine supports intracellular potassium retention and membrane stability.", "managementStrategy": "Generally compatible and complementary. People on potassium-sparing or potassium-altering medications, or with kidney disease, should manage potassium under clinical guidance rather than self-supplementing.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Acetyl-L-Carnitine", "supplementBName": "Alpha-GPC", "interactionType": "synergy", "severity": "info", "description": "Acetyl-L-Carnitine and Alpha-GPC act on complementary halves of the same acetylcholine-synthesis pathway, so they are commonly combined in cognitive and focus stacks. Alpha-GPC supplies the choline substrate while Acetyl-L-Carnitine helps supply the acetyl/acetyl-CoA substrate, supporting greater neurotransmitter output than either provides individually. This is a favorable, additive-to-synergistic combination rather than a risk.", "recommendation": "These can be taken together safely. A typical daytime nootropic pairing is 500 to 1000 mg Acetyl-L-Carnitine with 300 to 600 mg Alpha-GPC, taken in the morning or early afternoon (both can be mildly stimulating, so avoid late-evening dosing). Take with or without food per tolerance. No mandatory time separation is needed.", "minimumTimeSeparation": "None required; commonly taken together", "mechanism": "Acetylcholine synthesis requires two co-limiting substrates: a choline backbone and an acetyl group. Alpha-GPC (choline alphoscerate) is a highly bioavailable choline donor that raises free choline available to choline acetyltransferase (ChAT). Acetyl-L-Carnitine donates its acetyl moiety, which is shuttled by carnitine acetyltransferase to regenerate cytosolic acetyl-CoA, the second ChAT substrate. Because both choline and acetyl-CoA can each become rate-limiting, supplying both substrates together drives acetylcholine production more than either alone. ALCAR additionally supports mitochondrial energy production in cholinergic neurons.", "evidenceLevel": "emerging", "sources": [ { "text": "White HL, Scates PW. Acetyl-L-carnitine as a precursor of acetylcholine. Neurochemical Research, 1990.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Dolezal V, Tucek S. Synergistic effect of choline and carnitine on acetylcholine synthesis in neuroblastoma NB-2a cells. Biochemical and Biophysical Research Communications, 1984.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Reviews of choline alphoscerate (Alpha-GPC) pharmacology and cholinergic supplementation in cognitive function.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Acetyl-L-Carnitine and Alpha-GPC act on complementary halves of the same acetylcholine-synthesis pathway, so they are commonly combined in cognitive and focus stacks. Alpha-GPC supplies the choline substrate while Acetyl-L-Carnitine helps supply the acetyl/acetyl-CoA substrate, supporting greater neurotransmitter output than either provides individually. This is a favorable, additive-to-synergistic combination rather than a risk.", "clinicalSignificance": "Beneficial synergy for cholinergic support and mental clarity; no safety concern at standard doses. People sensitive to cholinergic load (headache, jaw tension, overstimulation) should start at the low end of both, since combined choline-plus-acetyl support can amplify acetylcholine tone.", "managementStrategy": "These can be taken together safely. A typical daytime nootropic pairing is 500 to 1000 mg Acetyl-L-Carnitine with 300 to 600 mg Alpha-GPC, taken in the morning or early afternoon (both can be mildly stimulating, so avoid late-evening dosing). Take with or without food per tolerance. No mandatory time separation is needed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Acetyl-L-Carnitine", "supplementBName": "Iodine", "interactionType": "caution", "severity": "moderate", "description": "Acetyl-L-Carnitine and Iodine pull on thyroid physiology in opposing directions. Iodine is taken to supply substrate for thyroid hormone production, whereas Acetyl-L-Carnitine antagonizes thyroid hormone action at the cellular level by limiting T3 and T4 entry into the nucleus. The net effect can be a partial reduction in the functional thyroid response the iodine is meant to support. In hyperthyroid states, by contrast, this same antagonism may be used intentionally and under supervision.", "recommendation": "For most people taking modest Iodine for general nutritional support, this is a mild theoretical concern. People with hypothyroidism, those actively supplementing Iodine to correct deficiency, or anyone on thyroid hormone replacement should be cautious with regular high-dose Acetyl-L-Carnitine and discuss it with their clinician. If both are used, monitor thyroid symptoms or labs (TSH, free T4) periodically. Conversely, in hyperthyroid states this antagonism may be intentional and supervised.", "minimumTimeSeparation": "No strict separation established; monitor thyroid status if both are used regularly", "mechanism": "Carnitine acts as a peripheral antagonist of thyroid hormone, inhibiting the entry of T3 and T4 into the cell nucleus where they exert their action through nuclear thyroid hormone receptors. Iodine supplementation aims to provide substrate for thyroid hormone synthesis and thereby support thyroid hormone output. Because Acetyl-L-Carnitine dampens the cellular action of the thyroid hormone that iodine helps the gland produce, the two pull on thyroid physiology in opposing directions, which can blunt part of the intended functional thyroid response. This peripheral antagonism is the basis for carnitine being studied as an adjunct in hyperthyroidism.", "evidenceLevel": "emerging", "sources": [ { "text": "Benvenga S, et al. Usefulness of L-carnitine, a naturally occurring peripheral antagonist of thyroid hormone action, in iatrogenic hyperthyroidism: a randomized, double-blind, placebo-controlled clinical trial. J Clin Endocrinol Metab. 2001.", "pmid": "11502782", "doi": "10.1210/jcem.86.8.7747", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11502782/", "publicSourceType": "PMID" }, { "text": "Benvenga S, et al. Effects of carnitine on thyroid hormone action. Ann N Y Acad Sci. 2004.", "pmid": "15591013", "doi": "10.1196/annals.1320.015", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15591013/", "publicSourceType": "PMID" }, { "text": "Endocrinology reviews on carnitine as a peripheral inhibitor of thyroid hormone nuclear uptake and action.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Acetyl-L-Carnitine and Iodine pull on thyroid physiology in opposing directions. Iodine is taken to supply substrate for thyroid hormone production, whereas Acetyl-L-Carnitine antagonizes thyroid hormone action at the cellular level by limiting T3 and T4 entry into the nucleus. The net effect can be a partial reduction in the functional thyroid response the iodine is meant to support. In hyperthyroid states, by contrast, this same antagonism may be used intentionally and under supervision.", "clinicalSignificance": "Generally low impact at typical supplemental doses, but clinically meaningful in people with reduced thyroid function or those relying on iodine to maintain thyroid output, where carnitine can counteract the desired thyroid effect. Directionally, Acetyl-L-Carnitine is the agent that dampens thyroid hormone action.", "managementStrategy": "For most people taking modest Iodine for general nutritional support, this is a mild theoretical concern. People with hypothyroidism, those actively supplementing Iodine to correct deficiency, or anyone on thyroid hormone replacement should be cautious with regular high-dose Acetyl-L-Carnitine and discuss it with their clinician. If both are used, monitor thyroid symptoms or labs (TSH, free T4) periodically. Conversely, in hyperthyroid states this antagonism may be intentional and supervised.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "BCAAs", "supplementBName": "L-Tryptophan", "interactionType": "timingSensitive", "severity": "moderate", "description": "This is the classic large neutral amino acid transporter competition described in the central fatigue hypothesis. BCAAs are sometimes used deliberately to lower brain serotonin during exercise, which is the opposite of why people supplement L-tryptophan (to raise serotonin for sleep or mood). Taking a large BCAA dose at the same time as L-tryptophan reduces tryptophan's passage into the central nervous system and can therefore reduce its intended benefit. The interaction is dose- and timing-dependent rather than a safety hazard.", "recommendation": "Separate the two by at least 2 to 3 hours. Take L-tryptophan on its own, ideally on a relatively empty stomach or with a small carbohydrate source, away from any BCAA or high-protein dose. If L-tryptophan is for sleep, take it in the evening and keep BCAAs to around training earlier in the day. Avoid combining a large BCAA bolus (for example 5 to 10 g) with L-tryptophan in the same serving.", "minimumTimeSeparation": "2 to 3 hours", "mechanism": "BCAAs (leucine, isoleucine, valine) and L-tryptophan are both large neutral amino acids (LNAAs) that compete for the same carrier, the LAT1 transporter, at the blood-brain barrier. When plasma BCAA levels rise, the tryptophan-to-LNAA ratio falls, so less tryptophan reaches the brain. Because brain tryptophan availability is rate-limiting for serotonin synthesis, co-ingesting high-dose BCAAs alongside L-tryptophan can blunt the central serotonergic effect tryptophan is usually taken for (mood, sleep, calm).", "evidenceLevel": "moderate", "sources": [ { "text": "Fernstrom JD. Branched-chain amino acids and brain function. J Nutr. 2005.", "pmid": "15930466", "doi": "10.1093/jn/135.6.1539S", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15930466/", "publicSourceType": "PMID" }, { "text": "Blomstrand E. A role for branched-chain amino acids in reducing central fatigue. J Nutr. 2006.", "pmid": "16424144", "doi": "10.1093/jn/136.2.544S", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16424144/", "publicSourceType": "PMID" }, { "text": "Reviews of blood-brain barrier large neutral amino acid (LAT1) transport and competition among aromatic and branched-chain amino acids.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "This is the classic large neutral amino acid transporter competition described in the central fatigue hypothesis. BCAAs are sometimes used deliberately to lower brain serotonin during exercise, which is the opposite of why people supplement L-tryptophan (to raise serotonin for sleep or mood). Taking a large BCAA dose at the same time as L-tryptophan reduces tryptophan's passage into the central nervous system and can therefore reduce its intended benefit. The interaction is dose- and timing-dependent rather than a safety hazard.", "clinicalSignificance": "For most users this affects efficacy of the tryptophan, not safety. The competition is well characterized in human and animal blood-brain barrier transport studies, so the effect is real but the practical consequence is a weaker tryptophan response rather than a dangerous event.", "managementStrategy": "Separate the two by at least 2 to 3 hours. Take L-tryptophan on its own, ideally on a relatively empty stomach or with a small carbohydrate source, away from any BCAA or high-protein dose. If L-tryptophan is for sleep, take it in the evening and keep BCAAs to around training earlier in the day. Avoid combining a large BCAA bolus (for example 5 to 10 g) with L-tryptophan in the same serving.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "BCAAs", "supplementBName": "L-Tyrosine", "interactionType": "timingSensitive", "severity": "info", "description": "People take L-tyrosine to support catecholamine production for focus, alertness, and stress resilience. Because tyrosine and BCAAs share the same brain transporter, a simultaneous large BCAA dose can compete with tyrosine for entry into the central nervous system and slightly dampen its cognitive or stress-buffering effect. This is an efficacy-timing issue, not a toxicity concern, and the magnitude is generally smaller than the tryptophan case because tyrosine-to-catecholamine conversion is only rate-limited under high neuronal firing.", "recommendation": "If using L-tyrosine for cognitive or stress benefit, take it 1 to 2 hours apart from a large BCAA serving and ideally away from high-protein meals (which contain abundant competing amino acids). Tyrosine on a relatively empty stomach maximizes its brain uptake. Small BCAA amounts are unlikely to matter; the concern is mainly with concentrated BCAA boluses taken in the same window.", "minimumTimeSeparation": "1 to 2 hours", "mechanism": "L-tyrosine, like tryptophan, is a large neutral amino acid that crosses the blood-brain barrier through the LAT1 transporter, the same carrier used by the branched-chain amino acids. A high plasma BCAA load competes with tyrosine for this shared transporter and lowers the tyrosine-to-LNAA ratio reaching the brain. Since brain tyrosine availability supports catecholamine (dopamine and norepinephrine) synthesis under demand, co-dosing large BCAAs can modestly reduce the central uptake of supplemental tyrosine.", "evidenceLevel": "emerging", "sources": [ { "text": "Fernstrom JD, Fernstrom MH. Tyrosine, phenylalanine, and catecholamine synthesis and function in the brain. Journal of Nutrition, 2007.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Pardridge WM. Blood-brain barrier carrier-mediated transport and brain metabolism of amino acids. Neurochemical Research, 1998.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Reviews of large neutral amino acid (LAT1) transport describing competition between tyrosine and branched-chain amino acids at the blood-brain barrier.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "People take L-tyrosine to support catecholamine production for focus, alertness, and stress resilience. Because tyrosine and BCAAs share the same brain transporter, a simultaneous large BCAA dose can compete with tyrosine for entry into the central nervous system and slightly dampen its cognitive or stress-buffering effect. This is an efficacy-timing issue, not a toxicity concern, and the magnitude is generally smaller than the tryptophan case because tyrosine-to-catecholamine conversion is only rate-limited under high neuronal firing.", "clinicalSignificance": "Low practical significance for most users. The transporter competition is well established, but the everyday effect is a marginally reduced tyrosine response when both are taken together, not a safety problem.", "managementStrategy": "If using L-tyrosine for cognitive or stress benefit, take it 1 to 2 hours apart from a large BCAA serving and ideally away from high-protein meals (which contain abundant competing amino acids). Tyrosine on a relatively empty stomach maximizes its brain uptake. Small BCAA amounts are unlikely to matter; the concern is mainly with concentrated BCAA boluses taken in the same window.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Beta-Carotene", "supplementBName": "Lycopene", "interactionType": "timingSensitive", "severity": "info", "description": "Taking beta-carotene and lycopene together in the same dose reduces the short-term absorption of each, because they compete for the same fat-based carrier micelles and the same transport proteins in the gut wall. Human studies that added a second carotenoid to a meal containing the first showed a measurable drop in the first carotenoid's appearance in blood-borne chylomicrons. Reassuringly, this is mainly an acute, single-meal effect: controlled trials lasting about 3 weeks found that combined intake did not meaningfully lower medium-term plasma levels of either carotenoid, so the practical impact is modest for most people.", "recommendation": "No need to avoid combining these. If you specifically want to maximize absorption of each, you can separate higher-dose beta-carotene and lycopene supplements by taking them at different meals (for example one with breakfast and one with dinner), and always take each with a meal containing some dietary fat to support absorption. For general use, taking them together is fine because long-term blood levels are largely preserved.", "minimumTimeSeparation": "Optional: separate higher doses by 4 to 6 hours (different meals) to minimize acute competition; not required for safety", "mechanism": "Beta-carotene and lycopene are both fat-soluble carotenoids that share the same intestinal absorption machinery. After a meal they must be solubilized into the same mixed bile-salt micelles and are then taken up across the enterocyte apical membrane by the same scavenger-receptor transporters (SR-BI, CD36, and NPC1L1) before being packaged into chylomicrons. When both are present in the same meal at supplemental doses, they compete for this limited micellar and transporter capacity, so each one acutely lowers the chylomicron (post-meal blood) response to the other.", "evidenceLevel": "moderate", "sources": [ { "text": "Tyssandier V, Cardinault N, Caris-Veyrat C, et al. Vegetable-borne lutein, lycopene, and beta-carotene compete for incorporation into chylomicrons, with no adverse effect on the medium-term (3-wk) plasma status of carotenoids in humans. American Journal of Clinical Nutrition, 2002.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Reboul E. Mechanisms of Carotenoid Intestinal Absorption: Where Do We Stand? Nutrients, 2019.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Reviews of carotenoid absorption pharmacology describing preferential incorporation of carotenes and xanthophylls into the triacylglycerol-rich (chylomicron) lipoprotein fraction after meal intake.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Taking beta-carotene and lycopene together in the same dose reduces the short-term absorption of each, because they compete for the same fat-based carrier micelles and the same transport proteins in the gut wall. Human studies that added a second carotenoid to a meal containing the first showed a measurable drop in the first carotenoid's appearance in blood-borne chylomicrons. Reassuringly, this is mainly an acute, single-meal effect: controlled trials lasting about 3 weeks found that combined intake did not meaningfully lower medium-term plasma levels of either carotenoid, so the practical impact is modest for most people.", "clinicalSignificance": "Acute competition modestly blunts single-meal uptake of each carotenoid, but medium-term plasma status is preserved in human trials, so there is no documented adverse health outcome from combining them. Relevant mainly to people optimizing carotenoid bioavailability.", "managementStrategy": "No need to avoid combining these. If you specifically want to maximize absorption of each, you can separate higher-dose beta-carotene and lycopene supplements by taking them at different meals (for example one with breakfast and one with dinner), and always take each with a meal containing some dietary fat to support absorption. For general use, taking them together is fine because long-term blood levels are largely preserved.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Beta-Carotene", "supplementBName": "Iron", "interactionType": "synergy", "severity": "info", "description": "Beta-carotene can enhance the absorption of nonheme (plant-form) iron when the two are taken together with food. Human absorption studies using cereal meals showed that adding beta-carotene increased iron absorption substantially (for example, more than threefold for rice and roughly 1.8-fold for wheat and corn), largely by overcoming the inhibitory effect of phytates and polyphenols. In vitro work confirmed that iron stays far more soluble in the presence of vitamin A or beta-carotene. This is a beneficial, one-directional effect: beta-carotene helps iron, which is useful for people relying on plant-based iron or supplementing iron alongside phytate- or polyphenol-rich meals.", "recommendation": "If using iron (especially nonheme forms) to address low iron status, taking it in a meal that also contains beta-carotene-rich foods (carrots, sweet potato, spinach, squash) or a beta-carotene supplement may improve iron uptake, particularly when the meal includes grains, legumes, tea, or coffee. Continue standard advice to also pair iron with vitamin C and to separate iron from calcium supplements. There is no need to avoid this combination; it is generally favorable.", "minimumTimeSeparation": "Take together with the same meal to gain the absorption benefit; no separation needed", "mechanism": "When consumed in the same meal, beta-carotene appears to form a soluble complex with nonheme iron in the intestinal lumen, keeping the iron in a soluble, absorbable form. This counteracts the binding and precipitation of iron caused by phytic acid (from cereals and legumes) and by polyphenols (from tea, coffee, and some plant foods), which would otherwise reduce nonheme iron uptake. By preserving luminal iron solubility, beta-carotene increases the fraction of nonheme iron available for transport across the enterocyte.", "evidenceLevel": "moderate", "sources": [ { "text": "Garcia-Casal MN, Layrisse M, Solano L, et al. Vitamin A and beta-carotene can improve nonheme iron absorption from rice, wheat and corn by humans. Journal of Nutrition, 1998.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Layrisse M, Garcia-Casal MN, et al. Caco-2 cell and in vitro studies showing beta-carotene maintains iron solubility and modifies the effect of iron-absorption inhibitors. Journal of Nutrition, 2000.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Controlled human absorption studies and nutrition reviews on the effect of vitamin A and carotenoids on nonheme iron bioavailability in cereal-based meals.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Beta-carotene can enhance the absorption of nonheme (plant-form) iron when the two are taken together with food. Human absorption studies using cereal meals showed that adding beta-carotene increased iron absorption substantially (for example, more than threefold for rice and roughly 1.8-fold for wheat and corn), largely by overcoming the inhibitory effect of phytates and polyphenols. In vitro work confirmed that iron stays far more soluble in the presence of vitamin A or beta-carotene. This is a beneficial, one-directional effect: beta-carotene helps iron, which is useful for people relying on plant-based iron or supplementing iron alongside phytate- or polyphenol-rich meals.", "clinicalSignificance": "A beneficial absorption-enhancing interaction that can meaningfully improve nonheme iron bioavailability from phytate- and polyphenol-rich meals. Clinically useful for iron-deficiency-prone individuals and plant-based eaters; no safety concern. People with iron overload conditions (for example hemochromatosis) should be mindful of anything that increases iron absorption.", "managementStrategy": "If using iron (especially nonheme forms) to address low iron status, taking it in a meal that also contains beta-carotene-rich foods (carrots, sweet potato, spinach, squash) or a beta-carotene supplement may improve iron uptake, particularly when the meal includes grains, legumes, tea, or coffee. Continue standard advice to also pair iron with vitamin C and to separate iron from calcium supplements. There is no need to avoid this combination; it is generally favorable.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Betaine HCL", "supplementBName": "Calcium", "interactionType": "synergy", "severity": "info", "description": "In individuals with reduced gastric acid output, calcium carbonate and similar insoluble calcium salts are poorly absorbed because they require an acidic environment to dissolve. Betaine HCL acidifies the stomach and can enhance the solubility and uptake of such calcium forms. This is a beneficial absorption-enhancing interaction rather than a risk. Calcium citrate, which does not depend on gastric acid, shows little change either way.", "recommendation": "If using calcium carbonate (or oyster-shell calcium), taking it in the same meal as Betaine HCL can improve absorption, especially if you have low stomach acid. Keep individual calcium doses to about 500 mg or less per sitting for best uptake. If you take calcium citrate, no special timing is needed because its absorption is not acid-dependent. There is no safety concern with this pairing.", "minimumTimeSeparation": "None: take together with food for the absorption benefit", "mechanism": "Betaine HCL supplies supplemental hydrochloric acid that lowers gastric pH. Many calcium salts, especially poorly soluble forms like calcium carbonate, depend on stomach acid for ionization and dissolution before absorption in the upper small intestine. Restoring an acidic gastric environment improves the solubility and bioavailability of these calcium salts, particularly in people with low stomach acid (hypochlorhydria).", "evidenceLevel": "moderate", "sources": [ { "text": "Recker RR. Calcium absorption and achlorhydria. New England Journal of Medicine, 1985", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Straub DA. Calcium supplementation in clinical practice: a review of forms, doses, and indications. Nutrition in Clinical Practice, 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Reviews of gastric acid and divalent mineral solubility in human absorption pharmacology", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "In individuals with reduced gastric acid output, calcium carbonate and similar insoluble calcium salts are poorly absorbed because they require an acidic environment to dissolve. Betaine HCL acidifies the stomach and can enhance the solubility and uptake of such calcium forms. This is a beneficial absorption-enhancing interaction rather than a risk. Calcium citrate, which does not depend on gastric acid, shows little change either way.", "clinicalSignificance": "Mainly relevant to people with hypochlorhydria, or those using acid-suppressing medications, who take calcium carbonate. The effect modestly improves calcium status; it is not a hazard. Routine users absorbing calcium normally see minimal added benefit.", "managementStrategy": "If using calcium carbonate (or oyster-shell calcium), taking it in the same meal as Betaine HCL can improve absorption, especially if you have low stomach acid. Keep individual calcium doses to about 500 mg or less per sitting for best uptake. If you take calcium citrate, no special timing is needed because its absorption is not acid-dependent. There is no safety concern with this pairing.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Black Cohosh", "supplementBName": "Green Tea Extract", "interactionType": "caution", "severity": "moderate", "description": "Concentrated Green Tea Extract is one of the botanicals most consistently linked to liver injury in the US Drug-Induced Liver Injury Network, and Black Cohosh has also been reported (though with weaker, more disputed causality). Taking them together means simultaneously exposing the liver to two agents that have each been associated with hepatitis, cholestasis, or, rarely, acute liver failure. Reported latency for either ranges from a few weeks to several months. The combined risk is most relevant in people who also drink alcohol, take other hepatotoxic agents, fast before dosing, or have pre-existing liver disease.", "recommendation": "Avoid routinely stacking standardized Black Cohosh with high-dose Green Tea Extract (especially EGCG concentrates taken on an empty stomach). If both are used, keep each within label doses, take Green Tea Extract with food, limit alcohol, and consider baseline plus periodic liver enzymes (ALT, AST, bilirubin) at roughly 4 to 8 weeks. Stop both immediately and seek care for dark urine, jaundice, right upper quadrant pain, nausea, or unexplained fatigue. Prefer brewed green tea over concentrated extract if hepatotoxic stacking is a concern.", "minimumTimeSeparation": "Not a timing-separable interaction; the concern is cumulative exposure rather than co-ingestion at the same moment, so separating doses does not eliminate risk.", "mechanism": "Additive idiosyncratic hepatotoxicity. Black Cohosh is among the botanicals reported in connection with herb-induced liver injury, with the proposed mechanism being oxidative stress and formation of reactive protein adducts in hepatocytes that may act as autoantigens, potentially triggering an immune-mediated hepatitis (note that expert causality reviews have found most reported cases to be only possible rather than probable, often with confounders). Concentrated Green Tea Extract (high in EGCG) is more firmly established as a botanical cause of drug-induced liver injury, driven by dose-dependent oxidative hepatocellular stress. Stacking two agents each capable of hepatic stress plausibly compounds cumulative oxidative burden on the liver and may raise the probability of an idiosyncratic injury event.", "evidenceLevel": "emerging", "sources": [ { "text": "LiverTox: Clinical and Research Information on Drug-Induced Liver Injury, Black Cohosh monograph, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NCBI Bookshelf.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "LiverTox: Clinical and Research Information on Drug-Induced Liver Injury, Green Tea and Green Tea Extract monograph, NIDDK, NCBI Bookshelf.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Adnan M, et al. Black Cohosh and Liver Toxicity: Is There a Relationship? Case Reports in Gastrointestinal Medicine, 2014.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Drug-Induced Liver Injury Network (DILIN) analyses of herbal and dietary supplement hepatotoxicity, published in hepatology and gastroenterology literature.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Concentrated Green Tea Extract is one of the botanicals most consistently linked to liver injury in the US Drug-Induced Liver Injury Network, and Black Cohosh has also been reported (though with weaker, more disputed causality). Taking them together means simultaneously exposing the liver to two agents that have each been associated with hepatitis, cholestasis, or, rarely, acute liver failure. Reported latency for either ranges from a few weeks to several months. The combined risk is most relevant in people who also drink alcohol, take other hepatotoxic agents, fast before dosing, or have pre-existing liver disease.", "clinicalSignificance": "Genuine clinical concern because concentrated Green Tea Extract has caused documented cases of severe and occasionally fatal liver injury and Black Cohosh has been implicated in additional reports; co-administration plausibly increases cumulative hepatic risk and complicates causality assessment if injury occurs.", "managementStrategy": "Avoid routinely stacking standardized Black Cohosh with high-dose Green Tea Extract (especially EGCG concentrates taken on an empty stomach). If both are used, keep each within label doses, take Green Tea Extract with food, limit alcohol, and consider baseline plus periodic liver enzymes (ALT, AST, bilirubin) at roughly 4 to 8 weeks. Stop both immediately and seek care for dark urine, jaundice, right upper quadrant pain, nausea, or unexplained fatigue. Prefer brewed green tea over concentrated extract if hepatotoxic stacking is a concern.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Black Cohosh", "supplementBName": "5-HTP", "interactionType": "caution", "severity": "moderate", "description": "On their own, supplemental 5-HTP can already raise serotonin levels, and Black Cohosh has measurable serotonergic pharmacology plus at least one published case of serotonin toxicity when taken alongside serotonergic prescription drugs. Layering 5-HTP on top of Black Cohosh theoretically pushes serotonergic signaling higher. Excess serotonergic activity can present as agitation, sweating, tremor, rapid heartbeat, gastrointestinal upset, and in severe cases the cluster of features seen in serotonin syndrome.", "recommendation": "Do not combine 5-HTP with Black Cohosh if you also take any SSRI, SNRI, MAOI, tramadol, triptan, or other serotonergic medication. If using both supplements alone, start 5-HTP low (for example 50 mg) and avoid stacking near full doses of both. Watch for restlessness, shivering, sweating, fast heart rate, muscle twitching, or confusion, and stop both and seek care if these appear. People with a prior serotonergic reaction should avoid the pairing.", "minimumTimeSeparation": "Separating doses does not reliably prevent additive serotonergic tone; spacing by several hours may modestly reduce peak overlap but does not remove the risk.", "mechanism": "Additive serotonergic activity. Black Cohosh extracts show in vitro agonism at 5-HT1A and partial agonism at 5-HT7 serotonin receptors and contain Nomega-methylserotonin, a constituent that both binds serotonin receptors and inhibits serotonin reuptake. 5-HTP is the immediate metabolic precursor to serotonin and directly increases central and peripheral serotonin synthesis. Combining a serotonin precursor with an agent that has receptor-agonist and reuptake-inhibiting properties can additively increase serotonergic tone.", "evidenceLevel": "emerging", "sources": [ { "text": "Powell SL et al. In vitro serotonergic activity of black cohosh and identification of N(omega)-methylserotonin as a potential active constituent. J Agric Food Chem. 2008;56(24):11718-26.", "pmid": "19049296", "doi": "10.1021/jf803298z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19049296/", "publicSourceType": "PMID" }, { "text": "Burdette JE et al. Black cohosh acts as a mixed competitive ligand and partial agonist of the serotonin receptor. J Agric Food Chem. 2003;51(19):5661-70.", "pmid": "12952416", "doi": "10.1021/jf034264r", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12952416/", "publicSourceType": "PMID" }, { "text": "Dernbach MR et al. Black Cohosh Interactions with Prescription Medications Associated with Serotonin Toxicity and Rhabdomyolysis: A Case Report. J Emerg Med. 2024;66(5):e592-e596.", "pmid": "38556373", "doi": "10.1016/j.jemermed.2024.01.003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38556373/", "publicSourceType": "PMID" }, { "text": "Turner EH et al. Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacol Ther. 2006;109(3):325-38.", "pmid": "16023217", "doi": "10.1016/j.pharmthera.2005.06.004", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16023217/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "On their own, supplemental 5-HTP can already raise serotonin levels, and Black Cohosh has measurable serotonergic pharmacology plus at least one published case of serotonin toxicity when taken alongside serotonergic prescription drugs. Layering 5-HTP on top of Black Cohosh theoretically pushes serotonergic signaling higher. Excess serotonergic activity can present as agitation, sweating, tremor, rapid heartbeat, gastrointestinal upset, and in severe cases the cluster of features seen in serotonin syndrome.", "clinicalSignificance": "Moderate concern: human evidence specific to this supplement pair is thin, but Black Cohosh has documented serotonergic mechanisms and a serotonin-toxicity case report, and 5-HTP is a direct serotonin precursor, so additive serotonergic effects are mechanistically plausible and worth flagging.", "managementStrategy": "Do not combine 5-HTP with Black Cohosh if you also take any SSRI, SNRI, MAOI, tramadol, triptan, or other serotonergic medication. If using both supplements alone, start 5-HTP low (for example 50 mg) and avoid stacking near full doses of both. Watch for restlessness, shivering, sweating, fast heart rate, muscle twitching, or confusion, and stop both and seek care if these appear. People with a prior serotonergic reaction should avoid the pairing.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Black Seed Oil", "supplementBName": "Fenugreek", "interactionType": "caution", "severity": "moderate", "description": "Both supplements are well-documented oral hypoglycemics in human trials. Taken concurrently, especially alongside antidiabetic medication (metformin, sulfonylureas, insulin), they can produce a larger-than-expected drop in blood glucose. The combination is not dangerous in healthy normoglycemic users, but in people actively managing diabetes or prediabetes it raises a real risk of additive hypoglycemia.", "recommendation": "If you take both, monitor blood glucose more closely for the first 2 to 3 weeks, particularly if you are also on glucose-lowering medication. Typical doses studied are Black Seed Oil around 1 to 2.5 g/day and Fenugreek 5 to 10 g/day of seed (or standardized extract per label). Watch for hypoglycemia symptoms (shakiness, sweating, lightheadedness). Discuss with your prescriber before combining if you use insulin or a sulfonylurea, as medication doses may need adjustment. No specific timing separation is required.", "minimumTimeSeparation": "None required; effects are systemic and additive regardless of timing.", "mechanism": "Additive blood-glucose-lowering effect through overlapping pathways. Black Seed Oil (Nigella sativa, thymoquinone) lowers fasting glucose, postprandial glucose, and HbA1c in human RCTs by improving insulin sensitivity and beta-cell function. Fenugreek independently lowers glucose by slowing intestinal carbohydrate absorption (high soluble fiber, prolonged gastric emptying) and by enhancing insulin sensitivity and secretion (4-hydroxyisoleucine, trigonelline). Used together the glucose-lowering effects stack.", "evidenceLevel": "moderate", "sources": [ { "text": "Reviews of Nigella sativa (black seed) and thymoquinone in human and animal studies report reductions in fasting glucose, postprandial glucose, and HbA1c via improved insulin sensitivity and beta-cell function.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Meta-analyses of randomized controlled trials of Nigella sativa describe improved glucose homeostasis and serum lipids in type 2 diabetes.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Systematic reviews and meta-analyses of fenugreek (Trigonella foenum-graecum) document significant lowering of fasting and postprandial glucose and HbA1c in people with diabetes and prediabetes.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Pharmacology reviews of both botanicals describe overlapping glucose-lowering mechanisms, supporting an additive hypoglycemic effect when combined, especially with antidiabetic medication.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both supplements are well-documented oral hypoglycemics in human trials. Taken concurrently, especially alongside antidiabetic medication (metformin, sulfonylureas, insulin), they can produce a larger-than-expected drop in blood glucose. The combination is not dangerous in healthy normoglycemic users, but in people actively managing diabetes or prediabetes it raises a real risk of additive hypoglycemia.", "clinicalSignificance": "Relevant mainly for people with type 2 diabetes, prediabetes, or those on antidiabetic drugs; the additive effect can be beneficial but needs monitoring to avoid overshoot into hypoglycemia.", "managementStrategy": "If you take both, monitor blood glucose more closely for the first 2 to 3 weeks, particularly if you are also on glucose-lowering medication. Typical doses studied are Black Seed Oil around 1 to 2.5 g/day and Fenugreek 5 to 10 g/day of seed (or standardized extract per label). Watch for hypoglycemia symptoms (shakiness, sweating, lightheadedness). Discuss with your prescriber before combining if you use insulin or a sulfonylurea, as medication doses may need adjustment. No specific timing separation is required.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Black Seed Oil", "supplementBName": "Garlic Extract", "interactionType": "caution", "severity": "moderate", "description": "Two supplements with reproducible antihypertensive effects in human trials. Combined, the blood-pressure reduction can be additive, which is helpful for someone targeting blood pressure but can cause hypotension (dizziness, lightheadedness on standing) in people already at or below target, or those on antihypertensive medication. The shared mild antiplatelet effect also modestly raises bleeding risk, relevant around surgery or with anticoagulants.", "recommendation": "This pairing can be used intentionally for cardiovascular support, but monitor blood pressure during the first few weeks and stand up slowly to check for orthostatic symptoms. Typical studied doses: Black Seed Oil 0.5 to 2.5 g/day (standardized products around 3% thymoquinone) and aged or standardized garlic extract 600 to 1200 mg/day. If you are on antihypertensive drugs, coordinate with your prescriber, as the combination may lower the medication requirement. Because of the combined antiplatelet effect, pause both at least 1 to 2 weeks before any scheduled surgery and avoid combining with prescription anticoagulants without medical advice. No daily timing separation needed.", "minimumTimeSeparation": "None required; effects are systemic and additive regardless of timing.", "mechanism": "Additive blood-pressure-lowering effect, with a secondary additive antiplatelet component. Black Seed Oil lowers systolic and diastolic blood pressure in placebo-controlled human trials (thymoquinone-mediated vasodilation, diuretic and antioxidant effects). Garlic extract independently lowers systolic blood pressure by roughly 8 mmHg and diastolic by roughly 5 mmHg in hypertensive subjects (nitric-oxide-mediated vasodilation via allicin and S-allylcysteine). Both also exert mild antiplatelet activity, so bleeding tendency can compound.", "evidenceLevel": "moderate", "sources": [ { "text": "Askari G et al. Effect of Nigella sativa (black seed) supplementation on glycemic control: A systematic review and meta-analysis of clinical trials. Phytother Res. 2019;33(5):1341-1352.", "pmid": "30873688", "doi": "10.1002/ptr.6337", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30873688/", "publicSourceType": "PMID" }, { "text": "Fallah Huseini H et al. Blood pressure lowering effect of Nigella sativa L. seed oil in healthy volunteers: a randomized, double-blind, placebo-controlled clinical trial. Phytother Res. 2013;27(12):1849-53.", "pmid": "23436437", "doi": "10.1002/ptr.4944", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23436437/", "publicSourceType": "PMID" }, { "text": "Ried K et al. Effect of garlic on blood pressure: a systematic review and meta-analysis. BMC Cardiovasc Disord. 2008;8:13.", "pmid": "18554422", "doi": "10.1186/1471-2261-8-13", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18554422/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Two supplements with reproducible antihypertensive effects in human trials. Combined, the blood-pressure reduction can be additive, which is helpful for someone targeting blood pressure but can cause hypotension (dizziness, lightheadedness on standing) in people already at or below target, or those on antihypertensive medication. The shared mild antiplatelet effect also modestly raises bleeding risk, relevant around surgery or with anticoagulants.", "clinicalSignificance": "Clinically meaningful for people with hypertension (potentially beneficial synergy) and for anyone on blood-pressure or blood-thinning medication, where additive effects warrant monitoring.", "managementStrategy": "This pairing can be used intentionally for cardiovascular support, but monitor blood pressure during the first few weeks and stand up slowly to check for orthostatic symptoms. Typical studied doses: Black Seed Oil 0.5 to 2.5 g/day (standardized products around 3% thymoquinone) and aged or standardized garlic extract 600 to 1200 mg/day. If you are on antihypertensive drugs, coordinate with your prescriber, as the combination may lower the medication requirement. Because of the combined antiplatelet effect, pause both at least 1 to 2 weeks before any scheduled surgery and avoid combining with prescription anticoagulants without medical advice. No daily timing separation needed.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "CLA", "supplementBName": "Chromium", "interactionType": "conflict", "severity": "moderate", "description": "CLA (specifically the t10,c12 isomer in standard 50:50 supplements) has documented potential to reduce insulin sensitivity, while chromium is taken to improve it. Because both are commonly bundled in weight-management and fat-loss stacks, this opposition is clinically relevant rather than theoretical. The interaction matters most for people with prediabetes, type 2 diabetes, or metabolic syndrome, where unexpected swings in glycemic control carry real consequences.", "recommendation": "If you are using chromium to support glucose control, be cautious stacking it with high-dose mixed CLA (3 to 6 g/day). They can be taken in the same day, but monitor fasting glucose or use a glucometer or CGM during the first few weeks of combining them. People with insulin resistance, prediabetes, or diabetes should consult a clinician before pairing them. Consider an isomer-specific CLA (predominantly c9,t11), which has not shown the same insulin-impairing signal, or prioritize chromium and drop CLA if glycemic control is the goal.", "minimumTimeSeparation": "None required; same-day use is acceptable, but monitor glycemic markers when combined", "mechanism": "Glycemic pathway opposition. The trans-10, cis-12 isomer present in most mixed CLA supplements has been shown in human trials to impair insulin sensitivity and worsen markers of insulin resistance (raising fasting insulin and HOMA-IR in some studies). Chromium acts in the opposite direction, potentiating insulin signaling and improving glucose uptake. Taking them together can blunt the intended insulin-sensitizing effect of chromium, and the net glycemic outcome becomes unpredictable.", "evidenceLevel": "moderate", "sources": [ { "text": "Riserus U et al., Treatment with dietary trans10cis12 conjugated linoleic acid causes isomer-specific insulin resistance in obese men with the metabolic syndrome, Diabetes Care, 2002", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Riserus U et al., Supplementation with conjugated linoleic acid causes isomer-dependent oxidative stress and elevated C-reactive protein, Circulation, 2002", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Anderson RA, Chromium, glucose intolerance and diabetes, Journal of the American College of Nutrition, 1998", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Controlled human trials and metabolic reviews of CLA isomer effects on insulin sensitivity", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "CLA (specifically the t10,c12 isomer in standard 50:50 supplements) has documented potential to reduce insulin sensitivity, while chromium is taken to improve it. Because both are commonly bundled in weight-management and fat-loss stacks, this opposition is clinically relevant rather than theoretical. The interaction matters most for people with prediabetes, type 2 diabetes, or metabolic syndrome, where unexpected swings in glycemic control carry real consequences.", "clinicalSignificance": "Relevant for anyone using chromium for blood sugar support, and especially for those with impaired glucose tolerance, since CLA's t10,c12 isomer can counteract chromium's benefit and contribute to insulin resistance.", "managementStrategy": "If you are using chromium to support glucose control, be cautious stacking it with high-dose mixed CLA (3 to 6 g/day). They can be taken in the same day, but monitor fasting glucose or use a glucometer or CGM during the first few weeks of combining them. People with insulin resistance, prediabetes, or diabetes should consult a clinician before pairing them. Consider an isomer-specific CLA (predominantly c9,t11), which has not shown the same insulin-impairing signal, or prioritize chromium and drop CLA if glycemic control is the goal.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "CLA", "supplementBName": "Vitamin E", "interactionType": "synergy", "severity": "info", "description": "CLA can increase lipid peroxidation and oxidative-stress markers, which raises the body's vitamin E (antioxidant) requirement. Pairing CLA with vitamin E is a protective, complementary combination: the vitamin E helps counter CLA-driven oxidation, and because both are fat-soluble they are absorbed efficiently when taken together with food containing fat. This is a favorable pairing rather than a risk, with the main caveat being to keep vitamin E at sensible doses.", "recommendation": "Take CLA and vitamin E together with a fat-containing meal for best absorption of both. A standard vitamin E intake (roughly 15 mg or 22 IU natural d-alpha-tocopherol, up to about 100 to 200 IU) is reasonable alongside CLA and may help offset CLA-related oxidative stress. Avoid very high-dose vitamin E (above roughly 400 IU long-term), which carries its own risks, and do not assume vitamin E fully neutralizes the metabolic concerns of the t10,c12 CLA isomer.", "minimumTimeSeparation": "None; best taken together with a fat-containing meal", "mechanism": "Two converging mechanisms. (1) Antioxidant protection: CLA is a polyunsaturated fatty acid mixture prone to lipid peroxidation, and the t10,c12 isomer has been shown in humans to raise oxidative-stress and lipid-peroxidation markers; vitamin E (a fat-soluble chain-breaking antioxidant) helps protect CLA and tissue lipids from this oxidation, and adequate vitamin E status offsets the increased antioxidant demand CLA can create. (2) Shared absorption route: both are fat-soluble and absorbed together in dietary-fat micelles, so co-ingestion with a fat-containing meal supports uptake of both.", "evidenceLevel": "emerging", "sources": [ { "text": "Riserus U et al., Supplementation with conjugated linoleic acid causes isomer-dependent oxidative stress and elevated C-reactive protein, Circulation, 2002", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Basu S et al., Conjugated linoleic acid induces lipid peroxidation in humans, FEBS Letters, 2000", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Traber MG, Vitamin E regulatory mechanisms and absorption of fat-soluble vitamins, Annual Review of Nutrition, 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Pharmacology reviews of fat-soluble nutrient micellar absorption and PUFA antioxidant requirements", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "CLA can increase lipid peroxidation and oxidative-stress markers, which raises the body's vitamin E (antioxidant) requirement. Pairing CLA with vitamin E is a protective, complementary combination: the vitamin E helps counter CLA-driven oxidation, and because both are fat-soluble they are absorbed efficiently when taken together with food containing fat. This is a favorable pairing rather than a risk, with the main caveat being to keep vitamin E at sensible doses.", "clinicalSignificance": "Useful for CLA users who want to mitigate the oxidative-stress signal associated with the supplement; the pairing is generally beneficial and the absorption overlap means timing them together with food is advantageous.", "managementStrategy": "Take CLA and vitamin E together with a fat-containing meal for best absorption of both. A standard vitamin E intake (roughly 15 mg or 22 IU natural d-alpha-tocopherol, up to about 100 to 200 IU) is reasonable alongside CLA and may help offset CLA-related oxidative stress. Avoid very high-dose vitamin E (above roughly 400 IU long-term), which carries its own risks, and do not assume vitamin E fully neutralizes the metabolic concerns of the t10,c12 CLA isomer.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Chlorella", "supplementBName": "Vitamin K1", "interactionType": "caution", "severity": "moderate", "description": "Stacking a vitamin K1 supplement on top of chlorella meaningfully increases total vitamin K1 exposure. For most healthy people this is simply additive and unremarkable, but the combined load becomes clinically relevant for anyone whose vitamin K status is being deliberately managed (for example, people on warfarin or other vitamin K antagonists, or those undergoing INR monitoring), where the two sources together can blunt anticoagulation and destabilize INR more than either alone.", "recommendation": "For healthy users with no clotting concerns, no special action is needed beyond awareness that chlorella already supplies substantial vitamin K1, so an additional K1 supplement may be redundant. Anyone on warfarin or another vitamin K antagonist should keep total vitamin K intake (chlorella plus any K1 supplement) consistent day to day rather than starting, stopping, or fluctuating doses, and should have INR checked after any change. Keep the daily chlorella dose stable (commonly 2 to 5 g) and discuss the combination with the prescribing clinician before adding supplemental K1.", "minimumTimeSeparation": "None required; consistency of total daily intake matters more than separation in time", "mechanism": "Chlorella is one of the most concentrated whole-food sources of vitamin K1 (phylloquinone), the same constituent that drives its documented interaction with anticoagulants. Taking a vitamin K1 supplement alongside chlorella produces additive phylloquinone intake. Vitamin K1 is a cofactor for hepatic gamma-carboxylation of clotting factors II, VII, IX, and X, so the combined intake raises total functional vitamin K delivered to the coagulation cascade.", "evidenceLevel": "moderate", "sources": [ { "text": "Pharmacology and nutrition reviews documenting chlorella as a rich dietary source of vitamin K1 (phylloquinone)", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Case report and clinical literature on warfarin therapy and chlorella, describing reduced anticoagulant effect via vitamin K (Japanese clinical literature, 1990s)", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Standard texts on vitamin K1 as a cofactor for hepatic gamma-carboxylation of vitamin K-dependent clotting factors", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Stacking a vitamin K1 supplement on top of chlorella meaningfully increases total vitamin K1 exposure. For most healthy people this is simply additive and unremarkable, but the combined load becomes clinically relevant for anyone whose vitamin K status is being deliberately managed (for example, people on warfarin or other vitamin K antagonists, or those undergoing INR monitoring), where the two sources together can blunt anticoagulation and destabilize INR more than either alone.", "clinicalSignificance": "Additive vitamin K intake is generally benign or even beneficial for bone and vascular health in the general population, but it can compromise the effectiveness and stability of vitamin K antagonist anticoagulation, which is where the clinical risk concentrates.", "managementStrategy": "For healthy users with no clotting concerns, no special action is needed beyond awareness that chlorella already supplies substantial vitamin K1, so an additional K1 supplement may be redundant. Anyone on warfarin or another vitamin K antagonist should keep total vitamin K intake (chlorella plus any K1 supplement) consistent day to day rather than starting, stopping, or fluctuating doses, and should have INR checked after any change. Keep the daily chlorella dose stable (commonly 2 to 5 g) and discuss the combination with the prescribing clinician before adding supplemental K1.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Chlorella", "supplementBName": "Iron", "interactionType": "synergy", "severity": "info", "description": "Chlorella behaves as a mild plant iron source, so pairing it with an iron supplement is mostly synergistic for correcting deficiency, but it also stacks total iron intake and introduces a minor absorption-timing nuance. People with iron overload conditions (such as hereditary hemochromatosis) or already-replete stores should be aware of the cumulative iron, and those taking a high-dose iron supplement may get slightly better absorption by not ingesting it in the same mouthful as a large chlorella dose.", "recommendation": "If using both to correct iron-deficiency anemia, the combination is reasonable and complementary; recheck ferritin and hemoglobin periodically rather than assuming more is better. To minimize cell-wall binding of a therapeutic iron dose, separate a high-dose iron supplement from a large chlorella serving by about 1 to 2 hours. Anyone with hemochromatosis, elevated ferritin, or who is not iron deficient should avoid routinely stacking supplemental iron on top of chlorella and should confirm need with iron studies first.", "minimumTimeSeparation": "1 to 2 hours when taking a high-dose iron supplement to limit cell-wall mineral binding", "mechanism": "Chlorella supplies bioavailable non-heme iron together with chlorophyll, folate, and protein, and has been shown in controlled trials (including pregnant women) to raise hemoglobin and reduce iron-deficiency anemia. Co-administered with an iron supplement the effect is largely additive toward iron repletion. Two opposing real-world factors temper this: chlorella's fibrous, cellulose-rich cell wall can bind divalent minerals in the gut lumen, which may modestly reduce uptake of a co-ingested large iron dose, while the additive total iron load is a consideration for people who do not need extra iron.", "evidenceLevel": "emerging", "sources": [ { "text": "Systematic review of Arthrospira platensis and Chlorella vulgaris consumption on iron status in in vivo studies, Molecular Nutrition and Food Research, 2025", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Review of chlorella supplementation in the prevention of iron-deficiency anemia, clinical and experimental studies, Archives of Current Research International", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Randomized controlled trial of chlorella supplementation reducing the risk of anemia in Japanese pregnant women, Plant Foods for Human Nutrition (2010)", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Chlorella behaves as a mild plant iron source, so pairing it with an iron supplement is mostly synergistic for correcting deficiency, but it also stacks total iron intake and introduces a minor absorption-timing nuance. People with iron overload conditions (such as hereditary hemochromatosis) or already-replete stores should be aware of the cumulative iron, and those taking a high-dose iron supplement may get slightly better absorption by not ingesting it in the same mouthful as a large chlorella dose.", "clinicalSignificance": "Beneficial and additive for genuine iron deficiency, with only minor downside (modest gut binding and unnecessary cumulative iron in people who are already replete or prone to iron overload).", "managementStrategy": "If using both to correct iron-deficiency anemia, the combination is reasonable and complementary; recheck ferritin and hemoglobin periodically rather than assuming more is better. To minimize cell-wall binding of a therapeutic iron dose, separate a high-dose iron supplement from a large chlorella serving by about 1 to 2 hours. Anyone with hemochromatosis, elevated ferritin, or who is not iron deficient should avoid routinely stacking supplemental iron on top of chlorella and should confirm need with iron studies first.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Colostrum", "supplementBName": "Iron", "interactionType": "timingSensitive", "severity": "moderate", "description": "Lactoferrin and other milk proteins from colostrum interact with supplemental iron in the digestive tract. Rather than simply stacking, these proteins bind luminal iron, which can either assist or blunt absorption of a given dose depending on the user's iron status and the casein/calcium load of the colostrum. The practical result is less predictable absorption of an iron supplement taken at the same time as a meaningful colostrum dose, plus a theoretical reduction in colostrum's antimicrobial action, since iron-saturated (holo) lactoferrin loses the bacteriostatic activity that the iron-free (apo) form provides.", "recommendation": "If iron is being taken to correct deficiency, separate it from colostrum by about 2 hours, which is the same spacing advised for iron and other dairy, to keep dosing predictable and to preserve lactoferrin's antimicrobial role. Take iron on its own (ideally with vitamin C, and away from calcium, tea, and coffee) and reserve colostrum for a different part of the day. Recheck ferritin and hemoglobin per your clinician if you routinely combine the two, since the net effect on iron status varies by individual.", "minimumTimeSeparation": "2 hours", "mechanism": "Bovine colostrum is rich in lactoferrin, an iron-binding glycoprotein whose two lobes each reversibly chelate ferric (Fe3+) iron at very high affinity (several hundred times higher than transferrin). Colostrum is also a dairy matrix containing casein and calcium, both of which can bind iron in the gut lumen and reduce its uptake. When colostrum and a supplemental iron salt are taken together, lactoferrin and other milk proteins can bind free iron, altering how that iron is presented for absorption. Lactoferrin behaves as a context-dependent iron handler: in iron-deficient states it can promote receptor-mediated uptake of lactoferrin-bound iron, whereas in iron-replete or inflammatory states it preferentially sequesters iron. As a result, co-ingestion does not cleanly add the two iron contributions and can shift the timing and net amount of iron uptake.", "evidenceLevel": "moderate", "sources": [ { "text": "Reviews of bovine colostrum as a nutraceutical describing lactoferrin content (roughly 0.5 to 5 mg/mL) and its iron-binding and antimicrobial functions", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Reviews of bovine lactoferrin molecular structure and biological properties detailing reversible chelation of one Fe3+ ion per lobe and context-dependent modulation of iron absorption", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Literature on lactoferrin and iron homeostasis noting enhanced iron absorption in deficiency, iron sequestration in iron-replete or inflammatory states, and loss of bacteriostatic activity when lactoferrin becomes iron-saturated", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "General guidance that iron supplements should be separated from dairy by about 2 hours because milk proteins and calcium reduce iron absorption", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Lactoferrin and other milk proteins from colostrum interact with supplemental iron in the digestive tract. Rather than simply stacking, these proteins bind luminal iron, which can either assist or blunt absorption of a given dose depending on the user's iron status and the casein/calcium load of the colostrum. The practical result is less predictable absorption of an iron supplement taken at the same time as a meaningful colostrum dose, plus a theoretical reduction in colostrum's antimicrobial action, since iron-saturated (holo) lactoferrin loses the bacteriostatic activity that the iron-free (apo) form provides.", "clinicalSignificance": "Most relevant for people actively repleting iron deficiency or with anemia who need reliable, quantifiable iron dosing. For people not taking iron supplements and eating a normal diet, the interaction is unlikely to cause clinical iron deficiency and is mainly a dose-timing optimization point.", "managementStrategy": "If iron is being taken to correct deficiency, separate it from colostrum by about 2 hours, which is the same spacing advised for iron and other dairy, to keep dosing predictable and to preserve lactoferrin's antimicrobial role. Take iron on its own (ideally with vitamin C, and away from calcium, tea, and coffee) and reserve colostrum for a different part of the day. Recheck ferritin and hemoglobin per your clinician if you routinely combine the two, since the net effect on iron status varies by individual.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "D-Aspartic Acid", "supplementBName": "L-Arginine", "interactionType": "caution", "severity": "info", "description": "These two are frequently stacked in test booster plus pump formulas on the assumption that they are synergistic, but in testicular tissue they act in opposite directions on testosterone production. In testicular incubation models, D-Aspartic Acid raised testosterone output while nitric oxide from L-Arginine lowered it, so the net hormonal effect can be antagonistic rather than additive. The interaction is at the steroidogenic step (an opposing physiological effect mediated by nitric oxide), not a safety hazard. The evidence is animal and tissue-level, and human confirmation is lacking, so this is best framed as a likely efficacy conflict rather than a proven clinical event.", "recommendation": "If the goal of D-Aspartic Acid use is testosterone or LH support, do not assume L-Arginine adds to it, and consider that high-dose L-Arginine (commonly 3 to 6 g) may partially offset it. If you take both (for example D-Aspartic Acid for the HPG axis and L-Arginine for blood flow), separate them by several hours and keep D-Aspartic Acid on an empty stomach in the morning. There is no toxicity concern with co-use; the issue is potential loss of the desired hormonal effect. Track response with bloodwork if it matters to you.", "minimumTimeSeparation": "3 to 4 hours", "mechanism": "D-Aspartic Acid acts on Leydig cells (via NMDA-receptor signaling and downstream cAMP and MAPK pathways) to favor testosterone synthesis. L-Arginine is the obligatory substrate for nitric oxide synthase, and the resulting nitric oxide is an established autocrine inhibitor of Leydig cell steroidogenesis. Nitric oxide synthase and the steroidogenic machinery co-localize within Leydig cells and exert opposing effects on androgen output, so increasing arginine-derived nitric oxide can blunt the same pathway D-Aspartic Acid is taken to enhance.", "evidenceLevel": "emerging", "sources": [ { "text": "Animal and testicular tissue studies on D-aspartic acid and nitric oxide as opposing regulators of androgen production", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Research on nitric oxide as an autocrine inhibitor of Leydig cell testosterone synthesis", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Reviews of D-aspartic acid as an endogenous amino acid with a neuroendocrine and steroidogenic role", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "These two are frequently stacked in test booster plus pump formulas on the assumption that they are synergistic, but in testicular tissue they act in opposite directions on testosterone production. In testicular incubation models, D-Aspartic Acid raised testosterone output while nitric oxide from L-Arginine lowered it, so the net hormonal effect can be antagonistic rather than additive. The interaction is at the steroidogenic step (an opposing physiological effect mediated by nitric oxide), not a safety hazard. The evidence is animal and tissue-level, and human confirmation is lacking, so this is best framed as a likely efficacy conflict rather than a proven clinical event.", "clinicalSignificance": "Primarily an efficacy interaction: arginine-driven nitric oxide may counteract D-Aspartic Acid's intended pro-steroidogenic effect. No safety risk is implied at typical supplemental doses.", "managementStrategy": "If the goal of D-Aspartic Acid use is testosterone or LH support, do not assume L-Arginine adds to it, and consider that high-dose L-Arginine (commonly 3 to 6 g) may partially offset it. If you take both (for example D-Aspartic Acid for the HPG axis and L-Arginine for blood flow), separate them by several hours and keep D-Aspartic Acid on an empty stomach in the morning. There is no toxicity concern with co-use; the issue is potential loss of the desired hormonal effect. Track response with bloodwork if it matters to you.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "D-Aspartic Acid", "supplementBName": "L-Citrulline", "interactionType": "caution", "severity": "info", "description": "L-Citrulline is one of the most common nitric oxide boosters in pre-workout and pump products, and it reliably elevates plasma arginine and nitric oxide, often more than equivalent oral arginine. Because nitric oxide opposes Leydig cell steroidogenesis (shown for arginine-derived nitric oxide in testicular models), citrulline can in principle work against D-Aspartic Acid's intended hormonal effect through the same mechanism. The direct evidence is one step removed: it is inferred from arginine and nitric oxide data plus citrulline's established role as a nitric oxide precursor, rather than from studies that combined citrulline with D-Aspartic Acid. This is a low-severity, efficacy-only consideration, not a safety problem.", "recommendation": "There is no safety reason to avoid taking both. If you want maximum benefit from D-Aspartic Acid for testosterone or LH support, do not count L-Citrulline as additive, and consider timing them apart: take D-Aspartic Acid in the morning on an empty stomach and reserve L-Citrulline (commonly 6 to 8 g) for pre-workout, ideally a few hours later. If you use L-Citrulline mainly for performance or blood flow and are indifferent to its theoretical effect on steroidogenesis, no change is needed.", "minimumTimeSeparation": "3 to 4 hours", "mechanism": "L-Citrulline is converted to L-arginine in the kidney (via argininosuccinate synthetase) and is a more efficient, longer-lasting nitric oxide precursor than oral L-arginine because it bypasses gut and hepatic arginase that degrade much ingested arginine. The arginine it generates feeds nitric oxide synthase to raise nitric oxide, and nitric oxide is an autocrine inhibitor of Leydig cell testosterone synthesis, the same pathway D-Aspartic Acid is taken to stimulate. The potential conflict is the nitric oxide pathway, reached via citrulline rather than arginine directly.", "evidenceLevel": "emerging", "sources": [ { "text": "Animal and testicular tissue studies on D-aspartic acid and nitric oxide as opposing regulators of androgen production", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Pharmacology research on L-citrulline as a nitric oxide precursor via citrulline-to-arginine recycling and the nitric oxide synthase pathway", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "L-Citrulline is one of the most common nitric oxide boosters in pre-workout and pump products, and it reliably elevates plasma arginine and nitric oxide, often more than equivalent oral arginine. Because nitric oxide opposes Leydig cell steroidogenesis (shown for arginine-derived nitric oxide in testicular models), citrulline can in principle work against D-Aspartic Acid's intended hormonal effect through the same mechanism. The direct evidence is one step removed: it is inferred from arginine and nitric oxide data plus citrulline's established role as a nitric oxide precursor, rather than from studies that combined citrulline with D-Aspartic Acid. This is a low-severity, efficacy-only consideration, not a safety problem.", "clinicalSignificance": "Theoretical efficacy interaction via the nitric oxide pathway. Low practical importance for most users; relevant mainly to those specifically chasing D-Aspartic Acid's hormonal effect.", "managementStrategy": "There is no safety reason to avoid taking both. If you want maximum benefit from D-Aspartic Acid for testosterone or LH support, do not count L-Citrulline as additive, and consider timing them apart: take D-Aspartic Acid in the morning on an empty stomach and reserve L-Citrulline (commonly 6 to 8 g) for pre-workout, ideally a few hours later. If you use L-Citrulline mainly for performance or blood flow and are indifferent to its theoretical effect on steroidogenesis, no change is needed.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "D-Mannose", "supplementBName": "Saccharomyces Boulardii", "interactionType": "synergy", "severity": "info", "description": "D-Mannose and the probiotic yeast Saccharomyces boulardii have been combined as a non-antibiotic UTI prophylaxis strategy. A randomized pilot study gave D-Mannose 500 mg plus S. boulardii 3 billion CFU after cystoscopy and reported lower post-procedure UTI incidence and less urinary discomfort versus no treatment. The pairing is mechanistically rational because the two ingredients target distinct steps (urinary bacterial anti-adhesion and flora restoration) and there is no absorption or pharmacological conflict between a poorly metabolized sugar and a transient gut-colonizing yeast.", "recommendation": "Reasonable to combine for recurrent UTI prophylaxis. Typical regimens use D-Mannose 1.5 to 2 g once or twice daily with S. boulardii 250 to 500 mg (roughly 3 to 10 billion CFU) daily. No timing separation is required; both can be taken together. Maintain hydration to support urinary flushing. People who are critically ill, immunocompromised, or have a central venous catheter should avoid live S. boulardii because of a rare risk of fungemia.", "minimumTimeSeparation": "None required; may be taken together", "mechanism": "Complementary anti-uropathogen actions. D-Mannose saturates FimH adhesins on type 1 fimbriated E. coli, preventing the bacteria from anchoring to bladder uroepithelium so they are flushed out in urine. Saccharomyces boulardii is a probiotic yeast that supports colonization resistance and modulates gut and urogenital flora that seed recurrent urinary tract infections. The two act on different points of the infection pathway (direct urinary anti-adhesion plus restoration of protective commensal flora) rather than competing.", "evidenceLevel": "emerging", "sources": [ { "text": "Prospective randomized pilot study of D-mannose plus Saccharomyces boulardii to prevent urinary tract infections and discomfort after cystoscopy, urology literature (2023)", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Reviews on non-antibiotic prophylaxis of recurrent uncomplicated cystitis describing D-mannose combined with probiotics, urology and nutraceutical literature", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "D-Mannose and the probiotic yeast Saccharomyces boulardii have been combined as a non-antibiotic UTI prophylaxis strategy. A randomized pilot study gave D-Mannose 500 mg plus S. boulardii 3 billion CFU after cystoscopy and reported lower post-procedure UTI incidence and less urinary discomfort versus no treatment. The pairing is mechanistically rational because the two ingredients target distinct steps (urinary bacterial anti-adhesion and flora restoration) and there is no absorption or pharmacological conflict between a poorly metabolized sugar and a transient gut-colonizing yeast.", "clinicalSignificance": "A beneficial, low-risk combination used for UTI prevention rather than a hazard. Significance is modest and supported mainly by small trials, so it is supportive rather than a primary therapy.", "managementStrategy": "Reasonable to combine for recurrent UTI prophylaxis. Typical regimens use D-Mannose 1.5 to 2 g once or twice daily with S. boulardii 250 to 500 mg (roughly 3 to 10 billion CFU) daily. No timing separation is required; both can be taken together. Maintain hydration to support urinary flushing. People who are critically ill, immunocompromised, or have a central venous catheter should avoid live S. boulardii because of a rare risk of fungemia.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "D-Mannose", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "D-Mannose and Vitamin C are frequently combined in UTI prevention products, often alongside cranberry. In trial arms that paired D-Mannose with vitamin C (and cranberry), investigators reported reductions in recurrent UTI episodes versus placebo, though the independent contribution of vitamin C is hard to isolate and its urine-acidifying effect is modest and inconsistent. There is no absorption competition or pharmacological conflict between the two: D-Mannose is a poorly metabolized sugar cleared by the kidneys and vitamin C is a water-soluble vitamin, and both reach the urine where their effects converge.", "recommendation": "Acceptable to combine for urinary support. A common approach is D-Mannose 1.5 to 2 g once or twice daily with vitamin C 250 to 500 mg daily. No timing separation is needed. Keep vitamin C at moderate doses; very high doses (above roughly 2 g per day) can cause GI upset and, in predisposed people, raise oxalate stone risk. Do not rely on this combination to treat an established symptomatic infection, which warrants medical assessment.", "minimumTimeSeparation": "None required; may be taken together", "mechanism": "Additive, complementary effects in the urinary tract. D-Mannose blocks FimH-mediated adhesion of uropathogenic E. coli so bacteria are voided in urine. Vitamin C (ascorbic acid) is excreted partly unchanged and can modestly lower urinary pH and may support immune and uroepithelial function, creating a urinary environment somewhat less favorable to bacterial persistence. The two work through separate, non-competing pathways and are commonly co-formulated for urinary support.", "evidenceLevel": "emerging", "sources": [ { "text": "Clinical studies evaluating D-mannose combined with cranberry and vitamin C for prevention of recurrent urinary tract infections, urology literature", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Reviews on D-mannose for prevention and treatment of urinary tract infections discussing adjunctive vitamin C and urinary acidification, nutraceutical and urology reviews", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "D-Mannose and Vitamin C are frequently combined in UTI prevention products, often alongside cranberry. In trial arms that paired D-Mannose with vitamin C (and cranberry), investigators reported reductions in recurrent UTI episodes versus placebo, though the independent contribution of vitamin C is hard to isolate and its urine-acidifying effect is modest and inconsistent. There is no absorption competition or pharmacological conflict between the two: D-Mannose is a poorly metabolized sugar cleared by the kidneys and vitamin C is a water-soluble vitamin, and both reach the urine where their effects converge.", "clinicalSignificance": "A mild, generally beneficial supportive pairing rather than a safety concern. Evidence for added benefit from vitamin C specifically is thin, so expectations should be modest.", "managementStrategy": "Acceptable to combine for urinary support. A common approach is D-Mannose 1.5 to 2 g once or twice daily with vitamin C 250 to 500 mg daily. No timing separation is needed. Keep vitamin C at moderate doses; very high doses (above roughly 2 g per day) can cause GI upset and, in predisposed people, raise oxalate stone risk. Do not rely on this combination to treat an established symptomatic infection, which warrants medical assessment.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "DIM", "supplementBName": "Melatonin", "interactionType": "caution", "severity": "info", "description": "DIM is a documented CYP1A2 inducer (shown in cultured human liver slices via the AhR pathway), and melatonin is primarily metabolized by CYP1A2. Regular DIM use can speed melatonin breakdown, potentially blunting the sleep-onset effect of an exogenous melatonin dose. Because this is an enzyme-induction effect that builds over days, simply spacing the two doses apart does not resolve it: induction is a systemic, sustained change in metabolism rather than a moment-of-contact conflict.", "recommendation": "If you take DIM daily and use melatonin for sleep, do not expect dose separation to fix reduced melatonin effect: the issue is faster clearance, not timing of contact. If your usual melatonin dose (commonly 0.5 to 3 mg at night) seems less effective after starting daily DIM, discuss a modest dose adjustment with a clinician rather than escalating on your own. Allow 1 to 2 weeks after starting or stopping DIM for the metabolic effect to stabilize before judging melatonin's effect.", "minimumTimeSeparation": "Dose separation does not mitigate this enzyme-induction effect; spacing the two apart provides no benefit", "mechanism": "DIM (3,3'-diindolylmethane) activates the aryl hydrocarbon receptor and induces hepatic CYP1A2, the same high-affinity enzyme that carries out the main metabolic step for melatonin (6-hydroxylation to 6-hydroxymelatonin). Sustained CYP1A2 induction increases melatonin clearance, so a given dose of supplemental melatonin can produce lower blood levels and a shorter duration of effect.", "evidenceLevel": "emerging", "sources": [ { "text": "Lake BG et al. 3,3'-Diindolylmethane induces CYP1A2 in cultured precision-cut human liver slices. Xenobiotica. 1998;28(8):803-11.", "pmid": "9741959", "doi": "10.1080/004982598239227", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9741959/", "publicSourceType": "PMID" }, { "text": "Ma X et al. Metabolism of melatonin by human cytochromes p450. Drug Metab Dispos. 2005;33(4):489-94.", "pmid": "15616152", "doi": "10.1124/dmd.104.002410", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15616152/", "publicSourceType": "PMID" }, { "text": "Skene DJ et al. Contribution of CYP1A2 in the hepatic metabolism of melatonin: studies with isolated microsomal preparations and liver slices. J Pineal Res. 2001;31(4):333-42.", "pmid": "11703563", "doi": "10.1034/j.1600-079x.2001.310408.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11703563/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "DIM is a documented CYP1A2 inducer (shown in cultured human liver slices via the AhR pathway), and melatonin is primarily metabolized by CYP1A2. Regular DIM use can speed melatonin breakdown, potentially blunting the sleep-onset effect of an exogenous melatonin dose. Because this is an enzyme-induction effect that builds over days, simply spacing the two doses apart does not resolve it: induction is a systemic, sustained change in metabolism rather than a moment-of-contact conflict.", "clinicalSignificance": "Melatonin has a wide safety margin and is not a narrow-therapeutic agent, so the practical consequence is mainly reduced sleep benefit rather than a safety hazard. Most people will not notice a meaningful change, which is why this is flagged as informational rather than a true risk.", "managementStrategy": "If you take DIM daily and use melatonin for sleep, do not expect dose separation to fix reduced melatonin effect: the issue is faster clearance, not timing of contact. If your usual melatonin dose (commonly 0.5 to 3 mg at night) seems less effective after starting daily DIM, discuss a modest dose adjustment with a clinician rather than escalating on your own. Allow 1 to 2 weeks after starting or stopping DIM for the metabolic effect to stabilize before judging melatonin's effect.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "DIM", "supplementBName": "DHEA", "interactionType": "caution", "severity": "moderate", "description": "DHEA and DIM are frequently co-stacked for hormone balance, and the rationale is real: DHEA can raise androgen and estrogen levels (especially at higher doses or in older adults), while DIM steers estrogen toward the 2-hydroxylation clearance pathway. The convergence is genuine but the combined hormonal outcome depends heavily on individual aromatase activity, sex, menopausal status, and doses used. In some people DIM may partially offset DHEA-driven estrogen rises; in others the interaction simply makes overall estrogen and androgen levels harder to interpret.", "recommendation": "Treat this combination as something to monitor rather than assume balances out. If using both, start each at a conservative dose (DHEA is commonly 25 to 50 mg/day; higher doses raise estrogen conversion substantially) and have a clinician check estradiol, testosterone, and DHEA-S after several weeks, especially for anyone with hormone-sensitive conditions or a history of hormone-related cancer. Do not stack them empirically to control estrogen without lab confirmation. No specific dose-timing separation is needed; the relevant control is total daily dosing plus monitoring.", "minimumTimeSeparation": "No dose-timing separation required; manage by total daily dose and hormone-level monitoring rather than spacing", "mechanism": "DHEA is a steroid precursor that is peripherally converted (via aromatase) to estrone and estradiol, raising the body's estrogen substrate pool. DIM does not lower total estrogen production but redirects estrogen metabolism, increasing the ratio of 2-hydroxyestrone (a weaker, more readily cleared metabolite) to 16-alpha-hydroxyestrone. When stacked, DHEA increases estrogen precursor load while DIM alters how that estrogen is metabolized, so the two act on different points of the same hormonal pathway and the net effect on circulating active estrogens is dose-dependent and not fully predictable.", "evidenceLevel": "emerging", "sources": [ { "text": "Meta-analysis of randomized trials on DHEA supplementation and estradiol levels in women, showing a dose-response relationship in which higher DHEA doses and older age raise circulating estradiol.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Randomized and pilot human studies on 3,3'-diindolylmethane and estrogen metabolism in pre- and postmenopausal women, showing DIM shifts the 2-hydroxyestrone to 16-alpha-hydroxyestrone ratio and alters multiple urinary estrogen metabolites.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Endocrinology reviews on DHEA as a precursor for peripheral aromatization to estrogens and androgens, and on cruciferous indole modulation of estrogen metabolism.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "DHEA and DIM are frequently co-stacked for hormone balance, and the rationale is real: DHEA can raise androgen and estrogen levels (especially at higher doses or in older adults), while DIM steers estrogen toward the 2-hydroxylation clearance pathway. The convergence is genuine but the combined hormonal outcome depends heavily on individual aromatase activity, sex, menopausal status, and doses used. In some people DIM may partially offset DHEA-driven estrogen rises; in others the interaction simply makes overall estrogen and androgen levels harder to interpret.", "clinicalSignificance": "Both agents measurably move sex-hormone metabolism, so combining them can produce clinically meaningful and individually variable shifts in estrogen and androgen balance. This matters most for people with hormone-sensitive conditions, making lab monitoring the prudent step rather than assuming the two simply cancel out.", "managementStrategy": "Treat this combination as something to monitor rather than assume balances out. If using both, start each at a conservative dose (DHEA is commonly 25 to 50 mg/day; higher doses raise estrogen conversion substantially) and have a clinician check estradiol, testosterone, and DHEA-S after several weeks, especially for anyone with hormone-sensitive conditions or a history of hormone-related cancer. Do not stack them empirically to control estrogen without lab confirmation. No specific dose-timing separation is needed; the relevant control is total daily dosing plus monitoring.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Elderberry", "supplementBName": "Iron", "interactionType": "timingSensitive", "severity": "moderate", "description": "Taking elderberry at the same time as a non-heme iron supplement can blunt iron uptake because elderberry polyphenols bind iron in the gut. The effect is dose and timing dependent: it matters mainly when the two are taken together on an empty stomach or with the same meal, and it is most clinically relevant for people actively correcting iron deficiency or iron-deficiency anemia. Separating the doses largely avoids the problem and does not require stopping either supplement.", "recommendation": "Separate elderberry and oral iron by at least 2 hours. Practical pattern: take iron on an empty stomach (or with a small amount of vitamin C to aid absorption) in the morning, and take elderberry later in the day. If you are being treated for iron deficiency, prioritize iron timing and keep elderberry well away from the iron dose. No need to avoid elderberry entirely; just do not co-administer with the iron tablet.", "minimumTimeSeparation": "2 hours", "mechanism": "Elderberry (Sambucus nigra) fruit is rich in polyphenols, especially anthocyanins (cyanidin 3-glucoside and related cyanidin glycosides) plus flavonols such as quercetin. These polyphenols chelate non-heme (ferric and ferrous) iron in the gastrointestinal lumen, forming insoluble iron-polyphenol complexes that the enterocyte cannot take up. Cyanidin-type anthocyanins carry free hydroxyl groups on the B ring that readily complex iron, so co-ingesting an elderberry product with an oral iron supplement reduces the fraction of iron available for absorption. This is the same well-characterized polyphenol-iron interaction seen with tea, coffee, and other anthocyanin-rich berries, applied to the specific polyphenol profile of elderberry.", "evidenceLevel": "moderate", "sources": [ { "text": "Brunet et al., Fruit extracts of 10 varieties of elderberry (Sambucus nigra L.) interact differently with iron and copper, Journal of Functional Foods, 2016.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Hurrell, Reddy and Cook, Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages, British Journal of Nutrition, 1999.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Reviews on quercetin and flavonoid regulation of intestinal non-heme iron absorption.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Reviews on anthocyanin-metal interactions describing cyanidin B-ring hydroxyl chelation of iron.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Taking elderberry at the same time as a non-heme iron supplement can blunt iron uptake because elderberry polyphenols bind iron in the gut. The effect is dose and timing dependent: it matters mainly when the two are taken together on an empty stomach or with the same meal, and it is most clinically relevant for people actively correcting iron deficiency or iron-deficiency anemia. Separating the doses largely avoids the problem and does not require stopping either supplement.", "clinicalSignificance": "Most important for individuals supplementing iron for deficiency or anemia, where even modest absorption losses can slow correction of low ferritin. For people with replete iron stores and no supplementation, the interaction is largely irrelevant and the mild iron-binding effect is inconsequential.", "managementStrategy": "Separate elderberry and oral iron by at least 2 hours. Practical pattern: take iron on an empty stomach (or with a small amount of vitamin C to aid absorption) in the morning, and take elderberry later in the day. If you are being treated for iron deficiency, prioritize iron timing and keep elderberry well away from the iron dose. No need to avoid elderberry entirely; just do not co-administer with the iron tablet.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Elderberry", "supplementBName": "Quercetin", "interactionType": "synergy", "severity": "info", "description": "Stacking elderberry with quercetin is a beneficial, complementary immune-support pairing rather than a risk. The two flavonoid sources hit different points of the viral lifecycle (entry, replication enzymes) and both calm excessive inflammatory signaling, so they reasonably reinforce each other. Human outcome data for the specific combination are limited, so the synergy claim should be framed as plausible and emerging rather than proven, but the mechanistic rationale and in vitro combination data are real.", "recommendation": "These can be taken together safely; no separation needed. Typical use during acute immune support is a standardized black elderberry extract per label (often providing around 300 to 600 mg extract or equivalent syrup dosing) alongside quercetin 250 to 500 mg once or twice daily. Quercetin absorption is modest, so taking it with a fat-containing meal (or co-supplementing vitamin C) improves bioavailability. As with elderberry generally, use during acute illness rather than indefinitely, and discontinue if any GI upset occurs.", "minimumTimeSeparation": "None (can be taken together)", "mechanism": "Elderberry and quercetin act on complementary stages of antiviral and immune defense. Quercetin is a flavonol that inhibits viral neuraminidase and proteases, interferes with viral entry and replication, and exerts antioxidant and anti-inflammatory (cytokine-modulating) effects. Elderberry anthocyanins independently bind to viral surface proteins and hinder viral entry while modulating cytokine release. Because elderberry fruit naturally contains quercetin alongside its anthocyanins, combining the two is additive within the same flavonoid and antiviral pathway. Combination studies of black elderberry extract with other antiviral agents have shown synergistic (greater than additive) inhibition of influenza and related viruses in vitro without added cytotoxicity, supporting the plausibility of a similar additive effect with quercetin.", "evidenceLevel": "emerging", "sources": [ { "text": "In vitro studies of European black elderberry fruit extract showing synergistic antiviral activity in combination with other antiviral agents against influenza A and related viruses.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Reviews on quercetin antiviral mechanisms (neuraminidase, protease, and polymerase inhibition; viral entry interference; immunomodulation).", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Phytochemical analyses documenting quercetin and anthocyanin content of Sambucus nigra fruit.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "General flavonoid bioavailability literature describing quercetin's limited absorption and enhancement with fat or vitamin C co-ingestion.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Stacking elderberry with quercetin is a beneficial, complementary immune-support pairing rather than a risk. The two flavonoid sources hit different points of the viral lifecycle (entry, replication enzymes) and both calm excessive inflammatory signaling, so they reasonably reinforce each other. Human outcome data for the specific combination are limited, so the synergy claim should be framed as plausible and emerging rather than proven, but the mechanistic rationale and in vitro combination data are real.", "clinicalSignificance": "A favorable combination for short-term immune and antiviral support during cold and flu exposure. Not a treatment substitute and not validated by large human trials, so benefit is best described as supportive and complementary. No meaningful safety concern at typical supplement doses.", "managementStrategy": "These can be taken together safely; no separation needed. Typical use during acute immune support is a standardized black elderberry extract per label (often providing around 300 to 600 mg extract or equivalent syrup dosing) alongside quercetin 250 to 500 mg once or twice daily. Quercetin absorption is modest, so taking it with a fat-containing meal (or co-supplementing vitamin C) improves bioavailability. As with elderberry generally, use during acute illness rather than indefinitely, and discontinue if any GI upset occurs.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Fenugreek", "supplementBName": "Chromium", "interactionType": "caution", "severity": "moderate", "description": "Fenugreek and chromium are both commonly stacked for blood sugar and metabolic support, and each independently lowers fasting and postprandial glucose in human trials. Taken together they can produce a greater than expected drop in blood glucose. This is generally beneficial for people targeting glycemic control but can push at-risk individuals, especially those also on glucose-lowering medication such as insulin or sulfonylureas, into hypoglycemia (shakiness, sweating, dizziness, confusion).", "recommendation": "For most healthy users the combination is fine and may be intentional for metabolic support. If you take diabetes medication or have a history of low blood sugar, monitor glucose more closely when starting both, and discuss dosing with your clinician. Typical doses are fenugreek 500 to 1000 mg standardized extract (or up to 5 g seed powder) and chromium 200 to 400 mcg daily. Take with meals to blunt postprandial spikes and reduce hypoglycemia risk between meals.", "minimumTimeSeparation": "None required; both are typically taken with meals and separating them is not necessary", "mechanism": "Both lower blood glucose through complementary pathways. Fenugreek's 4-hydroxyisoleucine stimulates glucose-dependent insulin secretion and its soluble galactomannan fiber slows carbohydrate absorption, while chromium enhances insulin receptor signaling and peripheral glucose uptake. Combined use produces additive glucose-lowering effects.", "evidenceLevel": "moderate", "sources": [ { "text": "Neelakantan N et al. Effect of fenugreek (Trigonella foenum-graecum L.) intake on glycemia: a meta-analysis of clinical trials. Nutr J. 2014;13:7.", "pmid": "24438170", "doi": "10.1186/1475-2891-13-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24438170/", "publicSourceType": "PMID" }, { "text": "Anderson RA et al. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes. Diabetes. 1997;46(11):1786-91.", "pmid": "9356027", "doi": "10.2337/diab.46.11.1786", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9356027/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Fenugreek and chromium are both commonly stacked for blood sugar and metabolic support, and each independently lowers fasting and postprandial glucose in human trials. Taken together they can produce a greater than expected drop in blood glucose. This is generally beneficial for people targeting glycemic control but can push at-risk individuals, especially those also on glucose-lowering medication such as insulin or sulfonylureas, into hypoglycemia (shakiness, sweating, dizziness, confusion).", "clinicalSignificance": "Additive hypoglycemia is the main concern, clinically meaningful primarily in people on antidiabetic drugs or prone to low blood sugar; in healthy individuals the effect is usually mild and favorable.", "managementStrategy": "For most healthy users the combination is fine and may be intentional for metabolic support. If you take diabetes medication or have a history of low blood sugar, monitor glucose more closely when starting both, and discuss dosing with your clinician. Typical doses are fenugreek 500 to 1000 mg standardized extract (or up to 5 g seed powder) and chromium 200 to 400 mcg daily. Take with meals to blunt postprandial spikes and reduce hypoglycemia risk between meals.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Fenugreek", "supplementBName": "Garlic Extract", "interactionType": "caution", "severity": "moderate", "description": "Fenugreek has documented, though mostly preclinical, antiplatelet effects, and garlic extract is a well-established platelet aggregation inhibitor in humans. Used together, especially at higher doses, they may additively prolong bleeding tendency. This is usually subclinical in healthy people but becomes relevant for those on anticoagulant or antiplatelet medication (warfarin, aspirin, clopidogrel) or approaching surgery.", "recommendation": "Healthy individuals taking ordinary supplemental doses generally do not need to avoid this combination. If you take blood thinners, have a bleeding disorder, or have surgery or a dental procedure scheduled, tell your clinician and consider pausing both 1 to 2 weeks beforehand. Watch for easy bruising, nosebleeds, or prolonged bleeding from minor cuts. No timing separation reduces this effect since the risk is systemic and cumulative.", "minimumTimeSeparation": "None; separating doses does not reduce the additive systemic antiplatelet effect", "mechanism": "Both have antiplatelet activity. Fenugreek contains coumarin constituents and has shown platelet aggregation inhibition in laboratory and animal studies, while garlic's organosulfur compounds (allicin, ajoene) inhibit platelet aggregation through thromboxane and cyclooxygenase pathways. Combined use can additively reduce platelet function.", "evidenceLevel": "emerging", "sources": [ { "text": "Basch E et al. Therapeutic applications of fenugreek. Altern Med Rev. 2003;8(1):20-7.", "pmid": "12611558", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12611558/", "publicSourceType": "PMID" }, { "text": "Allison GL et al. Aged garlic extract and its constituents inhibit platelet aggregation through multiple mechanisms. J Nutr. 2006;136(3 Suppl):782S-788S.", "pmid": "16484563", "doi": "10.1093/jn/136.3.782S", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16484563/", "publicSourceType": "PMID" }, { "text": "Rahman K et al. Dietary supplementation with aged garlic extract inhibits ADP-induced platelet aggregation in humans. J Nutr. 2000;130(11):2662-5.", "pmid": "11053504", "doi": "10.1093/jn/130.11.2662", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11053504/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Fenugreek has documented, though mostly preclinical, antiplatelet effects, and garlic extract is a well-established platelet aggregation inhibitor in humans. Used together, especially at higher doses, they may additively prolong bleeding tendency. This is usually subclinical in healthy people but becomes relevant for those on anticoagulant or antiplatelet medication (warfarin, aspirin, clopidogrel) or approaching surgery.", "clinicalSignificance": "Additive antiplatelet effect that is mostly theoretical/mild in healthy users but can be clinically meaningful in people on anticoagulants/antiplatelets or undergoing surgery.", "managementStrategy": "Healthy individuals taking ordinary supplemental doses generally do not need to avoid this combination. If you take blood thinners, have a bleeding disorder, or have surgery or a dental procedure scheduled, tell your clinician and consider pausing both 1 to 2 weeks beforehand. Watch for easy bruising, nosebleeds, or prolonged bleeding from minor cuts. No timing separation reduces this effect since the risk is systemic and cumulative.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Grape Seed Extract", "supplementBName": "Iron", "interactionType": "timingSensitive", "severity": "moderate", "description": "Taken at the same time as an iron supplement, grape seed extract can bind iron in the digestive tract and reduce how much is absorbed. The effect is concentration-dependent: higher polyphenol loads block more iron. This matters most for people supplementing to correct or prevent iron deficiency (for example menstruating women, vegetarians, or those with diagnosed anemia), where reduced absorption can slow repletion. It is far less of a concern for those with adequate iron stores.", "recommendation": "Separate grape seed extract and iron supplements by at least 2 hours. Take iron on an empty stomach or with vitamin C earlier in the day, and take grape seed extract with a different meal. If you are treating iron deficiency, prioritize the iron dose timing and keep polyphenol-rich supplements well away from it. Recheck ferritin and hemoglobin per your clinician if repletion seems slow.", "minimumTimeSeparation": "2 hours", "mechanism": "Grape seed extract is rich in oligomeric proanthocyanidins and other polyphenols carrying catechol and galloyl groups. In the gut lumen these groups chelate dietary iron, forming insoluble, poorly absorbable iron-polyphenol complexes. Absorption and cell-culture studies show this lowers iron uptake in a dose-dependent way, an effect best established for non-heme iron and broadly consistent with the known inhibition of iron absorption by polyphenol-rich foods and beverages.", "evidenceLevel": "moderate", "sources": [ { "text": "Human and Caco-2 cell absorption studies showing dietary polyphenols inhibit iron uptake in a dose-dependent manner.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Studies on inhibition of non-heme iron absorption in humans by polyphenol-containing beverages.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Pharmacology and nutrition reviews on polyphenol-iron chelation and non-heme iron bioavailability.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Taken at the same time as an iron supplement, grape seed extract can bind iron in the digestive tract and reduce how much is absorbed. The effect is concentration-dependent: higher polyphenol loads block more iron. This matters most for people supplementing to correct or prevent iron deficiency (for example menstruating women, vegetarians, or those with diagnosed anemia), where reduced absorption can slow repletion. It is far less of a concern for those with adequate iron stores.", "clinicalSignificance": "Most relevant for individuals actively repleting iron stores; in iron-replete people the practical impact is minimal. Repeated overlapping doses can measurably slow correction of deficiency.", "managementStrategy": "Separate grape seed extract and iron supplements by at least 2 hours. Take iron on an empty stomach or with vitamin C earlier in the day, and take grape seed extract with a different meal. If you are treating iron deficiency, prioritize the iron dose timing and keep polyphenol-rich supplements well away from it. Recheck ferritin and hemoglobin per your clinician if repletion seems slow.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Grape Seed Extract", "supplementBName": "Ginkgo Biloba", "interactionType": "caution", "severity": "moderate", "description": "Used together, grape seed extract and ginkgo may additively reduce platelet aggregation and impair clotting. For healthy people at usual supplement doses this is generally well tolerated, but the additive effect raises bleeding risk in higher-risk settings: around surgery or dental procedures, in those with bleeding disorders, or in anyone also taking aspirin, NSAIDs, or prescription blood thinners. Ginkgo in particular has scattered case reports of spontaneous bleeding.", "recommendation": "If you take both, watch for easy bruising, nosebleeds, or prolonged bleeding from cuts. Stop both supplements at least 1 to 2 weeks before any scheduled surgery or dental extraction and tell your surgeon. Do not combine this pair with anticoagulant or antiplatelet medications (warfarin, apixaban, clopidogrel, aspirin) without clinician oversight. Separating the doses does not reduce this risk because the effect is systemic, not absorption-based.", "minimumTimeSeparation": "Not applicable (systemic additive effect; separate dosing does not reduce risk)", "mechanism": "Both supplements have independently documented antiplatelet activity through different pathways. Grape seed extract proanthocyanidins can prolong platelet closure time and show anticoagulant and antiplatelet activity in laboratory studies. Ginkgo biloba inhibits platelet-activating factor (PAF) through its ginkgolide constituents. Combining two agents that act on platelet function can produce an additive reduction in clotting capacity.", "evidenceLevel": "emerging", "sources": [ { "text": "Vitseva O et al. Grape seed and skin extracts inhibit platelet function and release of reactive oxygen intermediates. J Cardiovasc Pharmacol. 2005;46(4):445-51.", "pmid": "16160595", "doi": "10.1097/01.fjc.0000176727.67066.1c", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16160595/", "publicSourceType": "PMID" }, { "text": "Bone KM. Potential interaction of Ginkgo biloba leaf with antiplatelet or anticoagulant drugs: what is the evidence? Mol Nutr Food Res. 2008;52(7):764-71.", "pmid": "18214851", "doi": "10.1002/mnfr.200700098", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18214851/", "publicSourceType": "PMID" }, { "text": "Hatfield J et al. Dietary supplements and bleeding. Proc (Bayl Univ Med Cent). 2022;35(6):802-807.", "pmid": "36304597", "doi": "10.1080/08998280.2022.2121575", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36304597/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Used together, grape seed extract and ginkgo may additively reduce platelet aggregation and impair clotting. For healthy people at usual supplement doses this is generally well tolerated, but the additive effect raises bleeding risk in higher-risk settings: around surgery or dental procedures, in those with bleeding disorders, or in anyone also taking aspirin, NSAIDs, or prescription blood thinners. Ginkgo in particular has scattered case reports of spontaneous bleeding.", "clinicalSignificance": "Additive antiplatelet effect is usually subclinical in healthy adults but can become clinically significant perioperatively, in bleeding-prone individuals, or alongside other blood-thinning agents.", "managementStrategy": "If you take both, watch for easy bruising, nosebleeds, or prolonged bleeding from cuts. Stop both supplements at least 1 to 2 weeks before any scheduled surgery or dental extraction and tell your surgeon. Do not combine this pair with anticoagulant or antiplatelet medications (warfarin, apixaban, clopidogrel, aspirin) without clinician oversight. Separating the doses does not reduce this risk because the effect is systemic, not absorption-based.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Holy Basil/Tulsi", "supplementBName": "Berberine", "interactionType": "caution", "severity": "moderate", "description": "Holy basil and berberine each lower blood glucose, and combining them produces an additive hypoglycemic effect. In people who are also fasting, on calorie-restricted intake, or taking diabetes medication, the combination can push blood glucose lower than intended.", "recommendation": "For most healthy adults the pair is generally well tolerated, but stack them only with blood glucose awareness. If you take diabetes medication (or are prone to low blood sugar), monitor glucose more closely when starting the combination and discuss with your clinician before adjusting any medication. A practical approach is to introduce one agent at a time (for example holy basil 300 to 600 mg/day or berberine 500 mg two to three times daily with meals) so you can gauge your own response before running both together. Watch for shakiness, sweating, or lightheadedness as early signs of overshoot.", "minimumTimeSeparation": null, "mechanism": "Both supplements independently lower blood glucose through complementary mechanisms. Holy basil (Ocimum sanctum) enhances glucose-stimulated insulin secretion and peripheral glucose uptake and reduces fasting and postprandial glucose, while berberine activates AMP-activated protein kinase (AMPK), improves insulin sensitivity, and slows hepatic gluconeogenesis. Taken together, their glucose-lowering effects are additive.", "evidenceLevel": "moderate", "sources": [ { "text": "Agrawal P et al. Randomized placebo-controlled, single blind trial of holy basil leaves in patients with noninsulin-dependent diabetes mellitus. Int J Clin Pharmacol Ther. 1996;34(9):406-9.", "pmid": "8880292", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8880292/", "publicSourceType": "PMID" }, { "text": "Yin J et al. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008;57(5):712-7.", "pmid": "18442638", "doi": "10.1016/j.metabol.2008.01.013", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18442638/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Holy basil and berberine each lower blood glucose, and combining them produces an additive hypoglycemic effect. In people who are also fasting, on calorie-restricted intake, or taking diabetes medication, the combination can push blood glucose lower than intended.", "clinicalSignificance": "Clinically meaningful additive glucose lowering, most relevant for people on antidiabetic drugs or those prone to hypoglycemia; for normoglycemic users the practical risk is low but worth monitoring.", "managementStrategy": "For most healthy adults the pair is generally well tolerated, but stack them only with blood glucose awareness. If you take diabetes medication (or are prone to low blood sugar), monitor glucose more closely when starting the combination and discuss with your clinician before adjusting any medication. A practical approach is to introduce one agent at a time (for example holy basil 300 to 600 mg/day or berberine 500 mg two to three times daily with meals) so you can gauge your own response before running both together. Watch for shakiness, sweating, or lightheadedness as early signs of overshoot.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Holy Basil/Tulsi", "supplementBName": "Ginkgo Biloba", "interactionType": "caution", "severity": "moderate", "description": "Holy basil and ginkgo biloba both reduce platelet aggregation, so taking them together can additively impair clotting and theoretically raise bleeding risk, particularly around surgery, dental procedures, or in anyone already taking antiplatelet or anticoagulant agents.", "recommendation": "For healthy adults not on blood thinners this combination is usually tolerated, but treat it with bleeding awareness. Avoid combining if you take anticoagulant or antiplatelet medication without clinician oversight, and stop both supplements at least 1 to 2 weeks before any scheduled surgery or invasive dental work. Report unusual bruising, nosebleeds, or prolonged bleeding from minor cuts. Typical ginkgo doses are 120 to 240 mg/day standardized extract; keep holy basil to label dosing and do not stack additional antiplatelet supplements on top.", "minimumTimeSeparation": null, "mechanism": "Both botanicals inhibit platelet aggregation. Holy basil constituents (notably eugenol and related compounds) reduce platelet aggregation and show antiplatelet activity in preclinical models, while ginkgo biloba (via ginkgolides, especially the platelet-activating-factor antagonist ginkgolide B) inhibits arachidonic-acid-, ADP-, collagen-, and PAF-induced platelet aggregation. Combined use produces an additive reduction in platelet function.", "evidenceLevel": "emerging", "sources": [ { "text": "Bone KM. Potential interaction of Ginkgo biloba leaf with antiplatelet or anticoagulant drugs: what is the evidence? Mol Nutr Food Res. 2008;52(7):764-71.", "pmid": "18214851", "doi": "10.1002/mnfr.200700098", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18214851/", "publicSourceType": "PMID" }, { "text": "Hatfield J et al. Dietary supplements and bleeding. Proc (Bayl Univ Med Cent). 2022;35(6):802-807.", "pmid": "36304597", "doi": "10.1080/08998280.2022.2121575", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36304597/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Holy basil and ginkgo biloba both reduce platelet aggregation, so taking them together can additively impair clotting and theoretically raise bleeding risk, particularly around surgery, dental procedures, or in anyone already taking antiplatelet or anticoagulant agents.", "clinicalSignificance": "Additive antiplatelet effect; clinically significant mainly perioperatively or alongside anticoagulant/antiplatelet drugs. Standalone bleeding risk in healthy users appears low, but the combination warrants caution and procedural planning.", "managementStrategy": "For healthy adults not on blood thinners this combination is usually tolerated, but treat it with bleeding awareness. Avoid combining if you take anticoagulant or antiplatelet medication without clinician oversight, and stop both supplements at least 1 to 2 weeks before any scheduled surgery or invasive dental work. Report unusual bruising, nosebleeds, or prolonged bleeding from minor cuts. Typical ginkgo doses are 120 to 240 mg/day standardized extract; keep holy basil to label dosing and do not stack additional antiplatelet supplements on top.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "L-Carnitine", "supplementBName": "Alpha-Lipoic Acid", "interactionType": "synergy", "severity": "info", "description": "L-Carnitine and alpha-lipoic acid are a classic mitochondrial-support pairing. Animal aging studies (notably the Ames and Hagen group work using the acetyl form with lipoic acid) and human trials in coronary artery disease have shown the combination improves mitochondrial enzyme activity, endothelial function, and markers of oxidative stress beyond what either supplies individually. The interaction is favorable and additive rather than risky.", "recommendation": "These can be taken together intentionally for mitochondrial and metabolic support. A common pairing is L-Carnitine 1,000 to 2,000 mg/day with alpha-lipoic acid 300 to 600 mg/day, ideally split with meals. Take alpha-lipoic acid roughly 30 minutes before or 2 hours after food if maximizing its absorption matters, and separate it from any mineral supplements (it can chelate some metals). No safety conflict, but monitor blood sugar if you are diabetic since alpha-lipoic acid can mildly lower glucose.", "minimumTimeSeparation": "None required; can be co-administered", "mechanism": "Both compounds act on the same mitochondrial energy-production machinery but at complementary points. L-Carnitine shuttles long-chain fatty acids across the inner mitochondrial membrane to fuel beta-oxidation and ATP generation, while alpha-lipoic acid serves as a cofactor for pyruvate and alpha-ketoglutarate dehydrogenase and acts as a potent mitochondrial antioxidant that recycles other antioxidants and scavenges reactive oxygen species. Pairing fatty-acid delivery (carnitine) with oxidative-stress quenching plus enhanced TCA-cycle flux (lipoic acid) restores mitochondrial enzyme activity and membrane integrity more than either alone.", "evidenceLevel": "moderate", "sources": [ { "text": "McMackin CJ et al. Effect of combined treatment with alpha-Lipoic acid and acetyl-L-carnitine on vascular function and blood pressure in patients with coronary artery disease. J Clin Hypertens (Greenwich). 2007;9(4):249-55.", "pmid": "17396066", "doi": "10.1111/j.1524-6175.2007.06052.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17396066/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "L-Carnitine and alpha-lipoic acid are a classic mitochondrial-support pairing. Animal aging studies (notably the Ames and Hagen group work using the acetyl form with lipoic acid) and human trials in coronary artery disease have shown the combination improves mitochondrial enzyme activity, endothelial function, and markers of oxidative stress beyond what either supplies individually. The interaction is favorable and additive rather than risky.", "clinicalSignificance": "Mostly an opportunity rather than a hazard: the pairing may modestly enhance energy metabolism, antioxidant defense, and vascular function. Benefits are real but moderate in size, and most human data come from the acetylated carnitine form, so effect sizes for plain L-Carnitine plus alpha-lipoic acid are extrapolated.", "managementStrategy": "These can be taken together intentionally for mitochondrial and metabolic support. A common pairing is L-Carnitine 1,000 to 2,000 mg/day with alpha-lipoic acid 300 to 600 mg/day, ideally split with meals. Take alpha-lipoic acid roughly 30 minutes before or 2 hours after food if maximizing its absorption matters, and separate it from any mineral supplements (it can chelate some metals). No safety conflict, but monitor blood sugar if you are diabetic since alpha-lipoic acid can mildly lower glucose.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "L-Carnitine", "supplementBName": "Acetyl-L-Carnitine", "interactionType": "caution", "severity": "info", "description": "Combining L-Carnitine with Acetyl-L-Carnitine is largely redundant because they draw on and replenish the same carnitine pool. The main practical difference is that ALCAR crosses the blood-brain barrier more readily (favoring cognitive/neural use) while plain L-Carnitine is used more for peripheral fatty-acid oxidation. Taking both is not harmful, but the doses count toward one cumulative carnitine intake rather than two, which matters for total-dose and TMAO considerations.", "recommendation": "Usually pick the form that matches your goal rather than stacking: L-Carnitine (1,000 to 2,000 mg/day) for energy/exercise/peripheral metabolism, or Acetyl-L-Carnitine (500 to 2,000 mg/day) for cognitive support. If you do use both, count the combined amount as your total carnitine dose (aim to keep the total in a sensible range, commonly under about 2 to 3 g/day) rather than dosing each separately at full strength. No timing separation is needed.", "minimumTimeSeparation": "None required; treat as one combined dose", "mechanism": "Acetyl-L-Carnitine (ALCAR) is the acetylated ester of L-Carnitine. After absorption both forms feed the same systemic free-carnitine pool: ALCAR is deacetylated to free carnitine (donating its acetyl group to acetyl-CoA metabolism), and free L-Carnitine can be reacetylated, so the two are interconvertible and substantially overlapping rather than independent nutrients. Stacking them therefore adds to one shared total carnitine load instead of providing two separate effects, and benefits do not scale additively.", "evidenceLevel": "moderate", "sources": [ { "text": "Liu J, Head E, Kuratsune H, et al. Comparison of the effects of L-carnitine and acetyl-L-carnitine on carnitine levels, ambulatory activity, and oxidative stress biomarkers in the brain of old rats. Annals of the New York Academy of Sciences, 2004.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Linus Pauling Institute Micronutrient Information Center, L-Carnitine review, Oregon State University.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Pharmacology reviews on carnitine ester interconversion and the shared free-carnitine pool.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Combining L-Carnitine with Acetyl-L-Carnitine is largely redundant because they draw on and replenish the same carnitine pool. The main practical difference is that ALCAR crosses the blood-brain barrier more readily (favoring cognitive/neural use) while plain L-Carnitine is used more for peripheral fatty-acid oxidation. Taking both is not harmful, but the doses count toward one cumulative carnitine intake rather than two, which matters for total-dose and TMAO considerations.", "clinicalSignificance": "Low-stakes but real: the practical issue is wasted money and inadvertent dose-stacking rather than toxicity. Higher combined carnitine intake also means more substrate for gut-microbiome conversion to TMA/TMAO, a consideration for anyone watching cardiovascular risk markers, so totaling the dose is worthwhile.", "managementStrategy": "Usually pick the form that matches your goal rather than stacking: L-Carnitine (1,000 to 2,000 mg/day) for energy/exercise/peripheral metabolism, or Acetyl-L-Carnitine (500 to 2,000 mg/day) for cognitive support. If you do use both, count the combined amount as your total carnitine dose (aim to keep the total in a sensible range, commonly under about 2 to 3 g/day) rather than dosing each separately at full strength. No timing separation is needed.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "L-Methionine", "supplementBName": "Vitamin B6", "interactionType": "synergy", "severity": "moderate", "description": "Vitamin B6 is the obligate cofactor for the transsulfuration enzymes that clear the homocysteine generated when L-Methionine is metabolized. In humans, methionine loading produces a sharper homocysteine spike when B6 status is low, and B6 supplementation measurably blunts that spike. Pairing supplemental methionine with adequate B6 directs the homocysteine pool toward cysteine and glutathione synthesis rather than letting it accumulate.", "recommendation": "If supplementing L-Methionine regularly or at higher doses, ensure adequate Vitamin B6 status. A practical co-dose is roughly 10 to 25 mg/day of B6 (as pyridoxine or P5P) taken with meals. Do not exceed about 100 mg/day of supplemental B6 long term due to neuropathy risk. They can be taken together; no timing separation is needed. Those with elevated homocysteine should also confirm folate and B12 status, since remethylation runs in parallel.", "minimumTimeSeparation": "None, can be taken together", "mechanism": "L-Methionine is catabolized through S-adenosylmethionine and homocysteine. Homocysteine is cleared by the transsulfuration pathway to cystathionine and then cysteine via cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CGL), both of which require pyridoxal 5'-phosphate (PLP), the active form of Vitamin B6, as a cofactor. Without adequate PLP, methionine intake drives a larger and more sustained rise in homocysteine, a vascular risk marker. Adequate B6 keeps the transsulfuration exit route open so methionine-derived homocysteine is disposed of as cysteine rather than accumulating.", "evidenceLevel": "strong", "sources": [ { "text": "McKinley MC et al. Low-dose vitamin B-6 effectively lowers fasting plasma homocysteine in healthy elderly persons who are folate and riboflavin replete. Am J Clin Nutr. 2001.", "pmid": "11273851", "doi": "10.1093/ajcn/73.4.759", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11273851/", "publicSourceType": "PMID" }, { "text": "Selhub J. Homocysteine metabolism. Annu Rev Nutr. 1999.", "pmid": "10448523", "doi": "10.1146/annurev.nutr.19.1.217", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10448523/", "publicSourceType": "PMID" }, { "text": "Methionine-loading test pharmacology reviews describing pyridoxal 5'-phosphate as the cofactor for cystathionine beta-synthase and cystathionine gamma-lyase in the transsulfuration pathway.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Vitamin B6 is the obligate cofactor for the transsulfuration enzymes that clear the homocysteine generated when L-Methionine is metabolized. In humans, methionine loading produces a sharper homocysteine spike when B6 status is low, and B6 supplementation measurably blunts that spike. Pairing supplemental methionine with adequate B6 directs the homocysteine pool toward cysteine and glutathione synthesis rather than letting it accumulate.", "clinicalSignificance": "Co-supplementation supports safe disposal of methionine-derived homocysteine and reduces the post-methionine-load homocysteine elevation that is used as a marker of cardiovascular susceptibility. This is most relevant for people taking methionine at supratherapeutic doses or with marginal B6 intake.", "managementStrategy": "If supplementing L-Methionine regularly or at higher doses, ensure adequate Vitamin B6 status. A practical co-dose is roughly 10 to 25 mg/day of B6 (as pyridoxine or P5P) taken with meals. Do not exceed about 100 mg/day of supplemental B6 long term due to neuropathy risk. They can be taken together; no timing separation is needed. Those with elevated homocysteine should also confirm folate and B12 status, since remethylation runs in parallel.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "L-Methionine", "supplementBName": "Glycine", "interactionType": "synergy", "severity": "info", "description": "Glycine is the acceptor substrate for GNMT, a main enzyme that buffers excess methylation potential created when L-Methionine raises SAMe. Adequate glycine helps dissipate surplus methyl groups and has been reported to lower homocysteine in high-methionine or high-protein conditions. The relationship is a complementary methyl-disposal pathway rather than a risk.", "recommendation": "No avoidance needed; this is a supportive pairing. If using L-Methionine alongside a higher-protein or methylation-supportive regimen, ordinary dietary or supplemental glycine (commonly 3 to 5 g/day) is sufficient to support methyl-group disposal. They can be taken together or at different times of day with no required separation.", "minimumTimeSeparation": "None, can be taken together", "mechanism": "Excess methyl groups from S-adenosylmethionine (SAMe), the active form derived from L-Methionine, are disposed of largely by glycine N-methyltransferase (GNMT), which transfers a methyl group from SAMe to glycine, producing sarcosine and S-adenosylhomocysteine. GNMT is one of the most abundant liver enzymes and acts as a principal buffer of the cellular SAMe-to-SAH ratio. Glycine availability therefore provides a sink for surplus methyl groups generated by a methionine load, and glycine (with serine) has shown hypohomocysteinemic effects in high-methionine settings.", "evidenceLevel": "emerging", "sources": [ { "text": "Luka Z, Mudd SH, Wagner C. Glycine N-methyltransferase and regulation of S-adenosylmethionine levels. Journal of Biological Chemistry review, 2009.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Studies reporting hypohomocysteinemic effects of glycine and serine in methionine- or high-protein-induced hyperhomocysteinemia in animal and human feeding models.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Glycine is the acceptor substrate for GNMT, a main enzyme that buffers excess methylation potential created when L-Methionine raises SAMe. Adequate glycine helps dissipate surplus methyl groups and has been reported to lower homocysteine in high-methionine or high-protein conditions. The relationship is a complementary methyl-disposal pathway rather than a risk.", "clinicalSignificance": "Glycine provides a physiological buffer for the extra methylation capacity produced by methionine and may modestly support homocysteine handling. The effect is supportive and low-stakes; human data specific to this pairing are limited and largely inferred from mechanism and high-methionine feeding studies.", "managementStrategy": "No avoidance needed; this is a supportive pairing. If using L-Methionine alongside a higher-protein or methylation-supportive regimen, ordinary dietary or supplemental glycine (commonly 3 to 5 g/day) is sufficient to support methyl-group disposal. They can be taken together or at different times of day with no required separation.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Lithium Orotate", "supplementBName": "Psyllium Husk", "interactionType": "timingSensitive", "severity": "moderate", "description": "Taking psyllium husk concurrently with lithium orotate can blunt lithium absorption and lower its effective dose. This is supported by a documented case in which a patient on lithium showed falling lithium levels after starting ispaghula (psyllium) husk, with levels rising again within days of stopping the fiber at an unchanged lithium dose. The interaction is one of timing and physical binding rather than a metabolic effect, so it is largely avoidable by spacing the two apart.", "recommendation": "Separate psyllium husk and lithium orotate by at least 2 to 3 hours (take lithium first, then fiber later, or vice versa). Keep daily fiber intake and timing consistent so lithium exposure stays stable rather than fluctuating. If you use prescription lithium, do not change your psyllium routine without telling your prescriber, since dose adjustments may have been made around your fiber habits and serum lithium monitoring is warranted.", "minimumTimeSeparation": "2 to 3 hours", "mechanism": "Psyllium is a hydrophilic, gel-forming soluble fiber. When taken at the same time as lithium, the swollen fiber matrix physically sequesters the lithium ion in the gut lumen and slows or reduces its dissolution and absorption across the small intestine. Because lithium is absorbed in the upper GI tract, fiber-bound lithium can be carried through and excreted rather than absorbed, lowering the amount that reaches the bloodstream.", "evidenceLevel": "emerging", "sources": [ { "text": "Case report describing reduced serum lithium during concurrent ispaghula (psyllium) husk use with recovery after discontinuation, from psychiatric and pharmacology literature on bulk-laxative drug interactions", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Standard drug-interaction references and pharmacology reviews advising that bulk-forming fibers such as psyllium be separated from oral medications by several hours to preserve absorption", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "General clinical guidance on lithium pharmacokinetics: narrow therapeutic range, upper-GI absorption, and the need for consistent intake to maintain stable serum levels", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Taking psyllium husk concurrently with lithium orotate can blunt lithium absorption and lower its effective dose. This is supported by a documented case in which a patient on lithium showed falling lithium levels after starting ispaghula (psyllium) husk, with levels rising again within days of stopping the fiber at an unchanged lithium dose. The interaction is one of timing and physical binding rather than a metabolic effect, so it is largely avoidable by spacing the two apart.", "clinicalSignificance": "Inconsistent co-timing can cause swings in lithium exposure: less effect when taken together, then a rebound rise if the fiber is stopped while the lithium dose was increased to compensate. For low-dose lithium orotate used nutritionally the practical risk is reduced benefit; the more important caution is for anyone on therapeutic lithium, where erratic levels carry both loss-of-efficacy and toxicity implications.", "managementStrategy": "Separate psyllium husk and lithium orotate by at least 2 to 3 hours (take lithium first, then fiber later, or vice versa). Keep daily fiber intake and timing consistent so lithium exposure stays stable rather than fluctuating. If you use prescription lithium, do not change your psyllium routine without telling your prescriber, since dose adjustments may have been made around your fiber habits and serum lithium monitoring is warranted.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Manganese", "supplementBName": "Magnesium Citrate", "interactionType": "timingSensitive", "severity": "info", "description": "Taking a large magnesium dose at the same time as manganese may slightly reduce manganese absorption through general divalent-mineral interference in the gut. The effect is small and mostly relevant only when manganese intake is already marginal or when high magnesium doses (a common scenario, since magnesium is often dosed at 200 to 400 mg) are co-ingested with a manganese supplement.", "recommendation": "This pairing is fine for most people, but if you are specifically correcting a manganese shortfall, separate the two by about 2 hours. Take manganese (typically 1 to 2 mg, and rarely above the 11 mg adult upper limit) away from your largest magnesium dose. If you take magnesium at night for sleep, take manganese with a different meal during the day.", "minimumTimeSeparation": "2 hours", "mechanism": "Manganese and magnesium are both divalent cations (Mn2+ and Mg2+). At high luminal concentrations, divalent minerals can interfere with one another's intestinal handling, so a large single magnesium dose taken alongside manganese may modestly reduce manganese uptake. Note that the two minerals use largely different primary pathways (manganese relies substantially on DMT1, while magnesium is absorbed mainly via TRPM6/TRPM7 channels and paracellular routes), so any competition is partial and the human evidence is limited.", "evidenceLevel": "emerging", "sources": [ { "text": "General trace-mineral and divalent cation absorption reviews describing competitive interference among co-ingested minerals at high doses.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Reviews of intestinal mineral transport noting distinct primary pathways for manganese (DMT1) versus magnesium (TRPM6/TRPM7 and paracellular).", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Taking a large magnesium dose at the same time as manganese may slightly reduce manganese absorption through general divalent-mineral interference in the gut. The effect is small and mostly relevant only when manganese intake is already marginal or when high magnesium doses (a common scenario, since magnesium is often dosed at 200 to 400 mg) are co-ingested with a manganese supplement.", "clinicalSignificance": "Low. For typical users with adequate intake this does not cause deficiency. It matters mainly for people on the borderline of manganese sufficiency or those taking high-dose magnesium habitually.", "managementStrategy": "This pairing is fine for most people, but if you are specifically correcting a manganese shortfall, separate the two by about 2 hours. Take manganese (typically 1 to 2 mg, and rarely above the 11 mg adult upper limit) away from your largest magnesium dose. If you take magnesium at night for sleep, take manganese with a different meal during the day.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Manganese", "supplementBName": "Vitamin C", "interactionType": "timingSensitive", "severity": "info", "description": "Vitamin C is documented to increase absorption of non-heme divalent metals via the DMT1 pathway that manganese also uses. Co-ingesting vitamin C with manganese may slightly increase manganese absorption. This is usually harmless and can even help correct a manganese shortfall, but it is worth noting for anyone trying to keep manganese intake low (for example, people with impaired manganese excretion such as significant liver dysfunction).", "recommendation": "No action needed for most people: taking manganese with vitamin C or a vitamin-C-rich meal is acceptable and may aid absorption. If you have liver disease or any reason to limit manganese exposure, avoid pairing manganese with high-dose vitamin C (1,000 mg or more) and keep manganese near the low end (1 to 2 mg).", "minimumTimeSeparation": "None required; co-administration is acceptable", "mechanism": "Manganese (Mn2+) is a substrate of the divalent metal transporter DMT1, the same brush-border transporter that absorbs non-heme iron. Ascorbic acid is well established to enhance non-heme iron uptake by reducing ferric to ferrous iron and supporting DMT1-mediated transport. Because manganese moves through the same divalent-cation absorption machinery, vitamin C taken with manganese may modestly increase manganese uptake.", "evidenceLevel": "emerging", "sources": [ { "text": "Reviews of DMT1 as a mammalian transporter for multiple divalent metals, identifying Mn2+ and Fe2+ as shared substrates.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Human absorption studies and trace-mineral reviews on ascorbic acid enhancement of non-heme iron uptake via DMT1.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Vitamin C is documented to increase absorption of non-heme divalent metals via the DMT1 pathway that manganese also uses. Co-ingesting vitamin C with manganese may slightly increase manganese absorption. This is usually harmless and can even help correct a manganese shortfall, but it is worth noting for anyone trying to keep manganese intake low (for example, people with impaired manganese excretion such as significant liver dysfunction).", "clinicalSignificance": "Low. The effect is generally beneficial or neutral. It is flagged mainly because the enhanced-uptake direction could matter for the small group who need to minimize manganese load.", "managementStrategy": "No action needed for most people: taking manganese with vitamin C or a vitamin-C-rich meal is acceptable and may aid absorption. If you have liver disease or any reason to limit manganese exposure, avoid pairing manganese with high-dose vitamin C (1,000 mg or more) and keep manganese near the low end (1 to 2 mg).", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Molybdenum", "supplementBName": "Iron", "interactionType": "caution", "severity": "info", "description": "Molybdenum and iron sit on opposite ends of a shared copper-mediated pathway. In classic nutrition literature (largely ruminant and animal work, with weaker human signals) chronically high molybdenum has been associated with disturbed iron metabolism via induced copper insufficiency. At normal supplement doses this is a low-concern, slow-developing relationship rather than an acute clash.", "recommendation": "No special timing needed for routine doses. Keep molybdenum at typical supplemental amounts (around 45 to 150 mcg/day; the adult tolerable upper limit is about 2 mg/day) so it does not erode copper status, since copper is what links molybdenum to iron handling. If you take iron for diagnosed deficiency, do not rely on high-dose molybdenum to help; address copper and iron directly and recheck ferritin and CBC with your clinician. Avoid prolonged high-dose molybdenum (well above 1 mg/day) alongside iron repletion without monitoring copper.", "minimumTimeSeparation": "None required at normal doses", "mechanism": "Indirect interaction through the copper, molybdenum, sulfur axis. Sustained excess molybdenum can promote formation of poorly absorbed copper-molybdenum-sulfur (thiomolybdate) complexes that lower copper status. Because copper-dependent ferroxidases (ceruloplasmin and hephaestin) are required to oxidize ferrous iron for loading onto transferrin and for iron mobilization from stores, a molybdenum-driven copper deficit can secondarily impair iron utilization. Molybdenum and iron handling are therefore metabolically linked through copper rather than by a direct interaction.", "evidenceLevel": "emerging", "sources": [ { "text": "Mills CF, Davis GK. Reviews on the relationships of copper and molybdenum to iron metabolism.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Institute of Medicine (US) Panel on Micronutrients. Dietary Reference Intakes, molybdenum chapter. National Academies Press, 2001.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Linus Pauling Institute, Micronutrient Information Center: Molybdenum (copper and iron interrelationships).", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Molybdenum and iron sit on opposite ends of a shared copper-mediated pathway. In classic nutrition literature (largely ruminant and animal work, with weaker human signals) chronically high molybdenum has been associated with disturbed iron metabolism via induced copper insufficiency. At normal supplement doses this is a low-concern, slow-developing relationship rather than an acute clash.", "clinicalSignificance": "Clinically minor in humans at normal intakes. The molybdenum, copper, iron interaction is robustly demonstrated in livestock but only weakly supported in people, where typical molybdenum doses have not shown meaningful effects on copper or iron status. It matters mainly with chronic high-dose molybdenum or pre-existing copper or iron imbalance.", "managementStrategy": "No special timing needed for routine doses. Keep molybdenum at typical supplemental amounts (around 45 to 150 mcg/day; the adult tolerable upper limit is about 2 mg/day) so it does not erode copper status, since copper is what links molybdenum to iron handling. If you take iron for diagnosed deficiency, do not rely on high-dose molybdenum to help; address copper and iron directly and recheck ferritin and CBC with your clinician. Avoid prolonged high-dose molybdenum (well above 1 mg/day) alongside iron repletion without monitoring copper.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Molybdenum", "supplementBName": "MSM", "interactionType": "timingSensitive", "severity": "info", "description": "This is a mechanistically grounded but largely theoretical absorption-competition concern. The molybdate versus sulfate competition for a shared intestinal transporter is well established in animal and cell studies, and MSM contributes to the sulfate pool. However, MSM is taken up by the small intestine in a high-capacity manner and is converted to sulfate mostly after absorption, so its direct dampening of molybdenum uptake in the gut is expected to be small, and no human study has measured an MSM effect on molybdenum status specifically. Note that added sulfate, if anything, lowers molybdenum exposure, so this is not a safety concern.", "recommendation": "For most people no action is needed. If you take both and want to be conservative, especially if molybdenum is being used deliberately to correct a documented deficiency, separate them by about 2 to 3 hours by taking molybdenum on its own (for example with a different meal) rather than together with a large MSM dose (commonly 1.5 to 3 g or more). Keep molybdenum within the normal 45 to 150 mcg/day range. No separation is needed simply for safety.", "minimumTimeSeparation": "2 to 3 hours if separating (optional)", "mechanism": "Molybdenum is absorbed as molybdate, which shares an intestinal anion transport system with sulfate; sulfate competitively inhibits molybdate uptake and is the classic antagonist against molybdenum overload. MSM (methylsulfonylmethane) is an organic sulfur donor that is absorbed and metabolized to sulfate in the body, expanding the systemic and (to a lesser extent) luminal sulfate pool. In principle, a larger sulfate load can compete with molybdate for absorption and increase its excretion, lowering molybdenum uptake.", "evidenceLevel": "emerging", "sources": [ { "text": "Dick AT, Bingley JB, and related work on competition of molybdate and sulphate ions for a transport system in the ovine small intestine.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Suttle NF. Molybdenum toxicity: interactions between copper, molybdenum and sulphate. 1991.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Reviews on methylsulfonylmethane absorption and conversion to sulfate in vivo.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "This is a mechanistically grounded but largely theoretical absorption-competition concern. The molybdate versus sulfate competition for a shared intestinal transporter is well established in animal and cell studies, and MSM contributes to the sulfate pool. However, MSM is taken up by the small intestine in a high-capacity manner and is converted to sulfate mostly after absorption, so its direct dampening of molybdenum uptake in the gut is expected to be small, and no human study has measured an MSM effect on molybdenum status specifically. Note that added sulfate, if anything, lowers molybdenum exposure, so this is not a safety concern.", "clinicalSignificance": "Negligible to minor. The underlying sulfate, molybdate transporter competition is real and well documented, but the specific impact of MSM on human molybdenum absorption is unproven and likely small at usual doses. Relevant mainly as a sensible timing tweak when precise molybdenum repletion matters.", "managementStrategy": "For most people no action is needed. If you take both and want to be conservative, especially if molybdenum is being used deliberately to correct a documented deficiency, separate them by about 2 to 3 hours by taking molybdenum on its own (for example with a different meal) rather than together with a large MSM dose (commonly 1.5 to 3 g or more). Keep molybdenum within the normal 45 to 150 mcg/day range. No separation is needed simply for safety.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Moringa", "supplementBName": "Iodine", "interactionType": "caution", "severity": "moderate", "description": "Moringa is a mild goitrogen: its glucosinolate-derived thiocyanate competes with iodide at the same thyroid transporter (NIS), so it can partially work against the very iodine you are supplementing. The interaction is most relevant at higher moringa intakes (multi-gram leaf powder daily) and in people who are iodine deficient or who have existing thyroid disease. At ordinary culinary amounts of moringa alongside an adequate iodine intake, the effect is small.", "recommendation": "If supplementing iodine for thyroid support, separate it from large moringa doses and ensure overall iodine intake is adequate (RDA is 150 mcg/day for non-pregnant adults). Keep moringa leaf powder to modest amounts (for example 2 g/day or less) if relying on iodine supplementation, and take iodine in the morning with moringa later in the day rather than in the same dose. Anyone with hypothyroidism, Hashimoto's, goiter, or pregnancy should have thyroid labs (TSH, free T4) monitored before and during routine high-dose moringa use and discuss the combination with a clinician.", "minimumTimeSeparation": "4 to 6 hours", "mechanism": "Moringa oleifera leaves contain glucosinolates that are hydrolyzed to thiocyanate and isothiocyanates. Thiocyanate is a competitive inhibitor of the sodium-iodide symporter (NIS), the transporter that concentrates iodide into thyroid follicular cells, and at higher concentrations it can also promote iodide efflux from the gland and impair thyroperoxidase-mediated iodine organification. Habitual intake of moringa can therefore blunt the thyroid's uptake and use of supplemental iodine, an effect that is amplified when baseline iodine status is low.", "evidenceLevel": "emerging", "sources": [ { "text": "Frontiers in Endocrinology, Perchlorate, nitrate, and thiocyanate: environmentally relevant NIS-inhibitor pollutants and their impact on thyroid function and human health, 2022", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Pharmacology reviews describing thiocyanate as a competitive inhibitor of the sodium-iodide symporter with affinity in the range of iodide", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Goitrogenic/antithyroidal potential of moringa leaves (Moringa oleifera) and spinach on thyroid status in male albino rats, Brazilian Journal of Pharmaceutical Sciences", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Reviews of Moringa oleifera phytochemistry describing glucosinolate to thiocyanate and isothiocyanate conversion and effects on thyroid iodine handling", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Moringa is a mild goitrogen: its glucosinolate-derived thiocyanate competes with iodide at the same thyroid transporter (NIS), so it can partially work against the very iodine you are supplementing. The interaction is most relevant at higher moringa intakes (multi-gram leaf powder daily) and in people who are iodine deficient or who have existing thyroid disease. At ordinary culinary amounts of moringa alongside an adequate iodine intake, the effect is small.", "clinicalSignificance": "Most healthy iodine-replete adults will not see clinically meaningful thyroid changes from typical moringa use. The pairing matters most for iodine-deficient individuals, those with borderline or established thyroid disorders, and pregnant or breastfeeding people, where competitive NIS inhibition could reduce the effectiveness of iodine supplementation and contribute to goitrogenic stress.", "managementStrategy": "If supplementing iodine for thyroid support, separate it from large moringa doses and ensure overall iodine intake is adequate (RDA is 150 mcg/day for non-pregnant adults). Keep moringa leaf powder to modest amounts (for example 2 g/day or less) if relying on iodine supplementation, and take iodine in the morning with moringa later in the day rather than in the same dose. Anyone with hypothyroidism, Hashimoto's, goiter, or pregnancy should have thyroid labs (TSH, free T4) monitored before and during routine high-dose moringa use and discuss the combination with a clinician.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Moringa", "supplementBName": "Fenugreek", "interactionType": "synergy", "severity": "moderate", "description": "Stacking moringa with fenugreek can produce a larger drop in blood glucose than either alone because they hit different steps of glucose handling: moringa blocks carb-digesting enzymes and boosts insulin sensitivity, while fenugreek's fiber slows absorption and its amino acid 4-hydroxyisoleucine prompts insulin release. For someone targeting glycemic control this can be a useful synergy, but for anyone already on glucose-lowering medication or other hypoglycemic supplements it raises the chance of glucose dropping too low.", "recommendation": "If using both for glycemic support, introduce one at a time and start at the lower end (for example moringa leaf powder 1 to 2 g/day and fenugreek seed or extract per its label), taking each with carbohydrate-containing meals to blunt postprandial spikes. People on insulin, sulfonylureas, or other glucose-lowering therapy should monitor blood glucose more closely when combining the two and coordinate any medication adjustments with their clinician to avoid hypoglycemia. Watch for shakiness, sweating, or lightheadedness as early low-glucose signs.", "minimumTimeSeparation": "none required", "mechanism": "Both supplements lower blood glucose through complementary mechanisms. Moringa oleifera inhibits the carbohydrate-digesting enzymes alpha-amylase and alpha-glucosidase, slows intestinal glucose absorption, and improves insulin sensitivity and secretion. Fenugreek slows carbohydrate digestion and glucose absorption via its viscous soluble (galactomannan) fiber and contains 4-hydroxyisoleucine, which stimulates glucose-dependent insulin secretion. Taken together, the postprandial and fasting glucose-lowering effects can be additive.", "evidenceLevel": "emerging", "sources": [ { "text": "Effects of Moringa oleifera on Glycaemia and Insulin Levels: A Review of Animal and Human Studies, Nutrients, 2019", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Neelakantan et al., Effect of fenugreek intake on glycemia: a meta-analysis of clinical trials, Nutrition Journal, 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Effect of Fenugreek on Hyperglycemia: A Systematic Review and Meta-Analysis, Medicina, 2023. Effect of Fenugreek on Hyperglycemia: A Systematic Review and Meta-Analysis. Medicina (Kaunas). 2023.", "pmid": "36837450", "doi": "10.3390/medicina59020248", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36837450/", "publicSourceType": "PMID" }, { "text": "Pharmacology reviews describing Moringa oleifera alpha-amylase and alpha-glucosidase inhibition and fenugreek 4-hydroxyisoleucine insulinotropic activity", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Stacking moringa with fenugreek can produce a larger drop in blood glucose than either alone because they hit different steps of glucose handling: moringa blocks carb-digesting enzymes and boosts insulin sensitivity, while fenugreek's fiber slows absorption and its amino acid 4-hydroxyisoleucine prompts insulin release. For someone targeting glycemic control this can be a useful synergy, but for anyone already on glucose-lowering medication or other hypoglycemic supplements it raises the chance of glucose dropping too low.", "clinicalSignificance": "In healthy people the combined effect is generally modest and well tolerated. The clinically important scenario is additive hypoglycemia in those with diabetes or prediabetes who are also on glucose-lowering medication, where the combination can push glucose lower than intended. Both agents have human meta-analytic evidence for reducing markers of glycemic control, so the additive direction of effect is plausible even though head-to-head combination trials are lacking.", "managementStrategy": "If using both for glycemic support, introduce one at a time and start at the lower end (for example moringa leaf powder 1 to 2 g/day and fenugreek seed or extract per its label), taking each with carbohydrate-containing meals to blunt postprandial spikes. People on insulin, sulfonylureas, or other glucose-lowering therapy should monitor blood glucose more closely when combining the two and coordinate any medication adjustments with their clinician to avoid hypoglycemia. Watch for shakiness, sweating, or lightheadedness as early low-glucose signs.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Omega-7", "supplementBName": "Astaxanthin", "interactionType": "synergy", "severity": "info", "description": "Taking astaxanthin together with an Omega-7 oil softgel improves astaxanthin bioavailability by providing the dietary fat its absorption requires. Human pharmacokinetic work shows lipid-based delivery raises astaxanthin plasma exposure several-fold compared with a low-fat or fat-free reference. The two are also commonly co-formulated in marine and berry-oil antioxidant blends, so co-ingestion is realistic and beneficial rather than harmful.", "recommendation": "Take astaxanthin (typically 4 to 12 mg) at the same time as your Omega-7 softgel, ideally with a meal, to maximize absorption. No separation is needed; co-administration is the goal. There is no toxicity concern, only an opportunity to improve a fat-soluble nutrient's uptake.", "minimumTimeSeparation": "None; take together for best effect", "mechanism": "Astaxanthin is a highly lipophilic carotenoid with notoriously poor and variable oral absorption that depends on co-ingested dietary lipids for micelle formation and bile-mediated emulsification. Omega-7 (palmitoleic acid-rich oil from sea buckthorn, macadamia, or marine sources) supplies a long-chain fatty-acid lipid vehicle that promotes mixed-micelle formation in the gut, enhancing astaxanthin solubilization and uptake by enterocytes.", "evidenceLevel": "moderate", "sources": [ { "text": "Research on the oral bioavailability of astaxanthin in humans showing that lipid-based formulations enhance plasma absorption (Mercke Odeberg et al., European Journal of Pharmaceutical Sciences, 2003).", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Carotenoid absorption pharmacology reviews establishing that lipid-soluble carotenoids follow dietary-fat absorption and require bile acids and mixed-micelle formation for enterocyte uptake.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Taking astaxanthin together with an Omega-7 oil softgel improves astaxanthin bioavailability by providing the dietary fat its absorption requires. Human pharmacokinetic work shows lipid-based delivery raises astaxanthin plasma exposure several-fold compared with a low-fat or fat-free reference. The two are also commonly co-formulated in marine and berry-oil antioxidant blends, so co-ingestion is realistic and beneficial rather than harmful.", "clinicalSignificance": "Beneficial absorption-enhancing pairing. Co-ingestion can meaningfully raise astaxanthin plasma levels, helping a normally poorly-absorbed antioxidant reach effective concentrations. No safety risk; the practical value is dosing efficiency.", "managementStrategy": "Take astaxanthin (typically 4 to 12 mg) at the same time as your Omega-7 softgel, ideally with a meal, to maximize absorption. No separation is needed; co-administration is the goal. There is no toxicity concern, only an opportunity to improve a fat-soluble nutrient's uptake.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Omega-7", "supplementBName": "Coenzyme Q10", "interactionType": "synergy", "severity": "info", "description": "Taking CoQ10 alongside an Omega-7 oil capsule provides the dietary lipid that CoQ10 absorption depends on. Pharmacology literature consistently shows CoQ10 is far better absorbed when taken with fat-containing meals or oils rather than on an empty stomach or with a low-fat meal. Co-administration with an Omega-7 softgel is a simple way to supply that fat.", "recommendation": "Take CoQ10 (commonly 100 to 200 mg) together with your Omega-7 softgel and a meal containing some fat to optimize absorption. Avoid taking CoQ10 on an empty stomach. No spacing is required; the benefit comes from taking them together.", "minimumTimeSeparation": "None; take together with food for best effect", "mechanism": "Coenzyme Q10 (ubiquinone) is a large, highly lipophilic molecule with poor and erratic oral absorption that is substantially improved by co-ingested dietary fat, which drives bile secretion and mixed-micelle formation needed for intestinal uptake. Omega-7 oil supplies a fatty-acid matrix that aids solubilization of CoQ10 and enhances its incorporation into absorptive micelles.", "evidenceLevel": "moderate", "sources": [ { "text": "Reviews of CoQ10 pharmacokinetics and bioavailability establishing fat-dependent absorption and improved uptake when administered with lipids and food.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Clinical pharmacology guidance noting that fat-soluble supplements including CoQ10 are absorbed better when taken with dietary fats.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Taking CoQ10 alongside an Omega-7 oil capsule provides the dietary lipid that CoQ10 absorption depends on. Pharmacology literature consistently shows CoQ10 is far better absorbed when taken with fat-containing meals or oils rather than on an empty stomach or with a low-fat meal. Co-administration with an Omega-7 softgel is a simple way to supply that fat.", "clinicalSignificance": "Beneficial absorption-enhancing pairing. Co-ingestion with the Omega-7 lipid vehicle can improve uptake of a poorly-absorbed nutrient, increasing the chance of reaching therapeutic plasma levels. No safety concern.", "managementStrategy": "Take CoQ10 (commonly 100 to 200 mg) together with your Omega-7 softgel and a meal containing some fat to optimize absorption. Avoid taking CoQ10 on an empty stomach. No spacing is required; the benefit comes from taking them together.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Ox Bile", "supplementBName": "Coenzyme Q10", "interactionType": "synergy", "severity": "info", "description": "Ox bile can increase the absorption of poorly bioavailable Coenzyme Q10 by improving its incorporation into bile-salt mixed micelles in the small intestine. This is a favorable absorption-enhancing interaction rather than a risk, and it is most relevant for people whose own bile production is reduced.", "recommendation": "If you have low bile output (post-gallbladder removal or known fat malabsorption) and take CoQ10, taking ox bile with the same fat-containing meal as your CoQ10 (ideally an oil-based or softgel CoQ10, 100 to 200 mg, with a meal containing some fat) is a reasonable way to support absorption. People with normal bile and gallbladder function generally do not need ox bile for this purpose; simply taking CoQ10 with a fatty meal is usually sufficient.", "minimumTimeSeparation": "Take together with a fat-containing meal (no separation needed; co-administration is the goal).", "mechanism": "Coenzyme Q10 (ubiquinone) is a highly lipophilic molecule with very low water solubility and notoriously poor, variable oral bioavailability. Before it can be absorbed across the enterocyte, it must be solubilized into mixed micelles, a process that depends on conjugated bile salts emulsifying the lipid and incorporating the CoQ10 isoprenoid tail into the micelle core. Ox bile supplies supplemental conjugated bile acids, so in people with low endogenous bile output (for example after cholecystectomy or with cholestasis/fat malabsorption) co-administering ox bile can improve micellization and therefore uptake of CoQ10.", "evidenceLevel": "emerging", "sources": [ { "text": "Research on plasma CoQ10 response to oral CoQ10 formulations showing low and variable bioavailability dependent on lipid carriers and solubilization.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Pharmacology reviews of lipophilic compound absorption via bile-salt mixed micelles in the small intestine.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Ox bile can increase the absorption of poorly bioavailable Coenzyme Q10 by improving its incorporation into bile-salt mixed micelles in the small intestine. This is a favorable absorption-enhancing interaction rather than a risk, and it is most relevant for people whose own bile production is reduced.", "clinicalSignificance": "Beneficial for CoQ10 uptake in fat-malabsorption states; not a safety concern. No dose reduction of either product is required.", "managementStrategy": "If you have low bile output (post-gallbladder removal or known fat malabsorption) and take CoQ10, taking ox bile with the same fat-containing meal as your CoQ10 (ideally an oil-based or softgel CoQ10, 100 to 200 mg, with a meal containing some fat) is a reasonable way to support absorption. People with normal bile and gallbladder function generally do not need ox bile for this purpose; simply taking CoQ10 with a fatty meal is usually sufficient.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Ox Bile", "supplementBName": "Vitamin K2", "interactionType": "synergy", "severity": "info", "description": "Ox bile can enhance absorption of Vitamin K2 by promoting the bile-salt micelle formation that menaquinone requires to cross the gut wall. This matters clinically because vitamin K2 supports coagulation and bone/vascular calcium handling, and people with low bile output are prone to fat-soluble vitamin underabsorption.", "recommendation": "If you take Vitamin K2 (MK-7 or MK-4) and have reduced bile flow (post-gallbladder, cholestasis, or fat malabsorption), take it with ox bile and a meal containing some fat to support uptake. If you take a vitamin-K-antagonist anticoagulant (such as warfarin), do not change vitamin K intake or absorption-enhancing habits without telling your prescriber, since better K2 absorption could affect anticoagulation control. People with normal bile function usually only need to take K2 with a fatty meal.", "minimumTimeSeparation": "Take together with a fat-containing meal (co-administration intended; no separation needed).", "mechanism": "Vitamin K2 (menaquinone) is a fat-soluble vitamin whose intestinal absorption requires solubilization into bile-salt mixed micelles, the same pathway used by vitamins A, D, and E. In vivo perfusion studies show menaquinone uptake rises as bile salt concentration and long-chain fatty acid availability increase, and bile-acid sequestrant drugs that deplete intestinal bile salts reduce vitamin K absorption. By supplying conjugated bile acids, ox bile can improve K2 micellization and absorption in people with insufficient endogenous bile (cholecystectomy, cholestasis, or general fat malabsorption).", "evidenceLevel": "moderate", "sources": [ { "text": "In vivo intestinal absorption studies showing vitamin K2 uptake depends on bile salts, long-chain fatty acids, and luminal pH.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Reviews of vitamin K metabolism and cell biology describing bile-dependent micellar absorption of menaquinones.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "NIH Office of Dietary Supplements vitamin K professional fact sheet, noting that bile-acid sequestrants reduce vitamin K absorption.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Ox bile can enhance absorption of Vitamin K2 by promoting the bile-salt micelle formation that menaquinone requires to cross the gut wall. This matters clinically because vitamin K2 supports coagulation and bone/vascular calcium handling, and people with low bile output are prone to fat-soluble vitamin underabsorption.", "clinicalSignificance": "Improves K2 uptake in low-bile states; generally beneficial. Caution only for those on vitamin-K-antagonist anticoagulants, where altered vitamin K absorption can shift INR.", "managementStrategy": "If you take Vitamin K2 (MK-7 or MK-4) and have reduced bile flow (post-gallbladder, cholestasis, or fat malabsorption), take it with ox bile and a meal containing some fat to support uptake. If you take a vitamin-K-antagonist anticoagulant (such as warfarin), do not change vitamin K intake or absorption-enhancing habits without telling your prescriber, since better K2 absorption could affect anticoagulation control. People with normal bile function usually only need to take K2 with a fatty meal.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "PQQ", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Vitamin C and PQQ can work together as a coupled redox antioxidant system. Ascorbic acid donates electrons to convert PQQ into PQQH2, the form responsible for PQQ's potent radical-scavenging and singlet-oxygen quenching activity. The two compounds naturally coexist in plant foods and human tissues, and laboratory studies at physiological pH (7.4) demonstrate this reduction-and-regeneration cycle directly. This is a favorable, additive antioxidant pairing rather than a risk.", "recommendation": "No separation needed; these are complementary. Taking PQQ (typically 10 to 20 mg per day) alongside vitamin C (commonly 250 to 1000 mg per day) is reasonable and may help maintain PQQ in its antioxidant-active reduced form. Both are well tolerated together. Take with food to improve comfort. No dose change is required for either.", "minimumTimeSeparation": "None; can be taken together", "mechanism": "PQQ is a redox-cycling o-quinone whose strongest free-radical scavenging activity resides in its reduced quinol form, PQQH2. Vitamin C (ascorbic acid) directly reduces PQQ to PQQH2 in roughly a 2:1 ascorbate-to-PQQ stoichiometry (one PQQ reduced by two ascorbate molecules), and the PQQH2 generated can be re-oxidized back to PQQ by air oxidation, allowing the pair to operate as a coupled, regenerating antioxidant cycle. In effect, vitamin C helps keep PQQ in (or convert it to) its antioxidant-active reduced state, while PQQ provides catalytic redox cycling that is efficient on a molar basis.", "evidenceLevel": "moderate", "sources": [ { "text": "Akagawa M et al. Pyrroloquinoline quinone (PQQ) is reduced to pyrroloquinoline quinol (PQQH2) by vitamin C, and PQQH2 produced is recycled to PQQ by air oxidation in buffer solution at pH 7.4. Bioscience, Biotechnology, and Biochemistry, 2016.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Pyrroloquinoline Quinone overview, ScienceDirect Topics (Agricultural and Biological Sciences): redox cycling, PQQH2 as the antioxidant-active form, and coexistence of PQQ and ascorbate in tissues.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Antioxidant pharmacology reviews describing PQQ redox cycling and free-radical scavenging activity.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin C and PQQ can work together as a coupled redox antioxidant system. Ascorbic acid donates electrons to convert PQQ into PQQH2, the form responsible for PQQ's potent radical-scavenging and singlet-oxygen quenching activity. The two compounds naturally coexist in plant foods and human tissues, and laboratory studies at physiological pH (7.4) demonstrate this reduction-and-regeneration cycle directly. This is a favorable, additive antioxidant pairing rather than a risk.", "clinicalSignificance": "Low clinical risk; the interaction is favorable. The pairing reinforces antioxidant capacity without known adverse additive effects. Relevance is mainly to people stacking antioxidants for mitochondrial or general healthy-aging goals, where co-administration is rational rather than cautionary.", "managementStrategy": "No separation needed; these are complementary. Taking PQQ (typically 10 to 20 mg per day) alongside vitamin C (commonly 250 to 1000 mg per day) is reasonable and may help maintain PQQ in its antioxidant-active reduced form. Both are well tolerated together. Take with food to improve comfort. No dose change is required for either.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "PQQ", "supplementBName": "Vitamin B3", "interactionType": "synergy", "severity": "info", "description": "PQQ and vitamin B3 converge on NAD+ metabolism. This is an on-pathway analog of the better-known PQQ plus NMN/NR combination: PQQ promotes NAD+ generation and mitochondrial biogenesis through the SIRT1/PGC-1alpha pathway, while B3 furnishes an upstream precursor that the NAD+ salvage pathway requires. Combining them is mechanistically rational for supporting cellular energy and NAD+ status, with effects that appear complementary rather than competing.", "recommendation": "These can be taken together without separation. Typical PQQ dosing is 10 to 20 mg per day; vitamin B3 dosing depends on the form (for example, nicotinamide around 50 to 500 mg per day, or smaller niacin doses to limit flushing). If using flush-form niacin, take with food and titrate to tolerance. No timing conflict applies.", "minimumTimeSeparation": "None; can be taken together", "mechanism": "PQQ has been reported to raise cellular NAD+ levels and to feed the NAD+-dependent SIRT1/PGC-1alpha axis that drives mitochondrial biogenesis (proposed in part via AMPK and Nampt, though direct PQQ-Nampt data are limited). Vitamin B3 (niacin/nicotinamide) supplies the precursor substrate for the NAD+ salvage pathway. The two therefore act on complementary points of NAD+ biosynthesis and sirtuin signaling: B3 provides precursor for NAD+ synthesis while PQQ enhances the downstream mitochondrial response and NAD+-driven signaling.", "evidenceLevel": "emerging", "sources": [ { "text": "Hwang PS et al. Pyrroloquinoline Quinone, a Redox-Active o-Quinone, Stimulates Mitochondrial Biogenesis by Activating the SIRT1/PGC-1alpha Signaling Pathway via enhanced cellular NAD+ formation. Biochemistry, 2018.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Reviews and commentary on PQQ-induced mitochondrial biogenesis noting NAD+ elevation and the SIRT1/PGC-1alpha pathway, with the caveat that direct PQQ-Nampt-sirtuin data remain limited.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "General NAD+ metabolism and niacin/nicotinamide biochemistry references describing vitamin B3 as a precursor substrate for NAD+ salvage.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "PQQ and vitamin B3 converge on NAD+ metabolism. This is an on-pathway analog of the better-known PQQ plus NMN/NR combination: PQQ promotes NAD+ generation and mitochondrial biogenesis through the SIRT1/PGC-1alpha pathway, while B3 furnishes an upstream precursor that the NAD+ salvage pathway requires. Combining them is mechanistically rational for supporting cellular energy and NAD+ status, with effects that appear complementary rather than competing.", "clinicalSignificance": "Low clinical risk and potentially beneficial for NAD+ and mitochondrial support. Human data on this specific combination are limited and largely inferred from mechanistic and preclinical work plus the closely related PQQ-NMN/NR literature, so benefit should be framed as plausible rather than proven. No additive toxicity is expected at common supplemental doses.", "managementStrategy": "These can be taken together without separation. Typical PQQ dosing is 10 to 20 mg per day; vitamin B3 dosing depends on the form (for example, nicotinamide around 50 to 500 mg per day, or smaller niacin doses to limit flushing). If using flush-form niacin, take with food and titrate to tolerance. No timing conflict applies.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Pregnenolone", "supplementBName": "Tongkat Ali", "interactionType": "synergy", "severity": "moderate", "description": "Stacking Pregnenolone (a precursor that sits at the very top of the steroidogenesis cascade) with Tongkat Ali (which supports conversion to and liberation of testosterone) can compound androgen and downstream sex-hormone production beyond what either produces alone. For people seeking hormonal support this can be a useful synergy, but it also raises the chance of androgen-excess effects such as acne, oily skin, irritability, sleep disruption, scalp hair shedding in those predisposed, and in women unwanted androgenic effects. Because pregnenolone also branches toward progesterone and cortisol, individual responses vary widely.", "recommendation": "Treat this as a deliberate hormonal stack, not a casual combination. Start each supplement separately and at the low end (pregnenolone often 5 to 25 mg in the morning, Tongkat Ali standardized extract typically 200 to 400 mg) before combining, so you can attribute any effect. When stacking, keep total dosing conservative, take both earlier in the day, and reassess after 4 to 6 weeks. Anyone with hormone-sensitive conditions (prostate issues, PCOS, hormone-sensitive cancers) or who is pregnant or breastfeeding should avoid this combination, and ideally check baseline and follow-up sex-hormone and DHEA-S labs with a clinician.", "minimumTimeSeparation": "None required; separating doses does not reduce the additive hormonal effect. Manage by total dose and by dosing both earlier in the day.", "mechanism": "Pregnenolone is the upstream master precursor for all steroid hormones (cholesterol to pregnenolone via CYP11A1, then pregnenolone to 17-OH-pregnenolone and DHEA via CYP17A1, feeding the androstenedione, testosterone and estrogen branch). Tongkat Ali (eurycomanone and related quassinoids) supports endogenous testosterone production by acting downstream on the hypothalamic-pituitary-gonadal axis and Leydig cell steroidogenesis, and by reducing SHBG-bound testosterone to increase free testosterone. Taken together they push the same androgen-synthesis pathway from two different points: pregnenolone increases available precursor substrate while Tongkat Ali increases conversion and liberation of downstream androgens, producing an additive to synergistic rise in androgenic tone. Note that pregnenolone-to-testosterone conversion in humans is variable and not strongly established, so the effect size is uncertain.", "evidenceLevel": "emerging", "sources": [ { "text": "Biochemistry literature on human 17-alpha-hydroxylase/17,20-lyase (P450c17) converting pregnenolone toward DHEA", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Reviews of Eurycoma longifolia (Tongkat Ali) and eurycomanone on testosterone production and steroidogenesis in the herbal andrology literature", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Pharmacology overviews of pregnenolone as the master steroidogenic precursor (cholesterol to pregnenolone to DHEA to testosterone/estrogen pathway)", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Stacking Pregnenolone (a precursor that sits at the very top of the steroidogenesis cascade) with Tongkat Ali (which supports conversion to and liberation of testosterone) can compound androgen and downstream sex-hormone production beyond what either produces alone. For people seeking hormonal support this can be a useful synergy, but it also raises the chance of androgen-excess effects such as acne, oily skin, irritability, sleep disruption, scalp hair shedding in those predisposed, and in women unwanted androgenic effects. Because pregnenolone also branches toward progesterone and cortisol, individual responses vary widely.", "clinicalSignificance": "Most relevant for users intentionally pursuing testosterone or vitality support; the practical risk is over-shooting androgenic tone rather than acute harm. Significance rises in women, older adults, and anyone with hormone-sensitive conditions.", "managementStrategy": "Treat this as a deliberate hormonal stack, not a casual combination. Start each supplement separately and at the low end (pregnenolone often 5 to 25 mg in the morning, Tongkat Ali standardized extract typically 200 to 400 mg) before combining, so you can attribute any effect. When stacking, keep total dosing conservative, take both earlier in the day, and reassess after 4 to 6 weeks. Anyone with hormone-sensitive conditions (prostate issues, PCOS, hormone-sensitive cancers) or who is pregnant or breastfeeding should avoid this combination, and ideally check baseline and follow-up sex-hormone and DHEA-S labs with a clinician.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Pregnenolone", "supplementBName": "Alcohol", "interactionType": "timingSensitive", "severity": "moderate", "description": "Pregnenolone is a neurosteroid that directly opposes GABA-A signaling, yet the body converts much of it into allopregnanolone, which strongly enhances GABA-A signaling the same way alcohol does. So combining pregnenolone with alcohol can swing in either direction: it may blunt the expected buzz/sedation in some people, or it may amplify drowsiness, impaired coordination and slowed reaction time in others (particularly as allopregnanolone levels build). This makes the level of impairment from a given amount of alcohol harder to predict, which is the real-world hazard.", "recommendation": "Do not rely on pregnenolone to make alcohol feel less impairing; the metabolite allopregnanolone can do the opposite and deepen sedation. Avoid drinking on the same day you take pregnenolone, and never drive or operate machinery after combining them. If you do take pregnenolone, dose it in the morning and keep alcohol intake minimal and well separated (ideally avoid alcohol within the same dosing day). Use particular caution if you are also taking any sedating supplements or medications.", "minimumTimeSeparation": "Avoid alcohol within the same day as pregnenolone dosing; if unavoidable, separate by at least 8 to 12 hours and keep intake minimal.", "mechanism": "Pregnenolone and its sulfate metabolite act as negative modulators (antagonists) at the GABA-A receptor, which experimentally attenuates alcohol-induced sedation, hypnosis and incoordination. However, a substantial fraction of administered pregnenolone is metabolized through progesterone to allopregnanolone, which is a potent positive allosteric modulator of GABA-A and instead potentiates alcohol's CNS-depressant, sedating and motor-impairing effects. The net result is an unpredictable, individual- and timing-dependent shift in how alcohol affects sedation and coordination, driven by the balance between the parent neurosteroid and its allopregnanolone metabolite.", "evidenceLevel": "emerging", "sources": [ { "text": "Reviews of neurosteroids and GABA-A receptor function describing pregnenolone sulfate as a GABA-A negative modulator and allopregnanolone as a positive allosteric modulator", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Preclinical and clinical work on neurosteroids and acute alcohol intoxication (pregnenolone sulfate attenuating versus allopregnanolone potentiating alcohol sedation)", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Pharmacology reviews of the pregnenolone, progesterone, allopregnanolone neurosteroid pathway and GABA-A modulation", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Pregnenolone is a neurosteroid that directly opposes GABA-A signaling, yet the body converts much of it into allopregnanolone, which strongly enhances GABA-A signaling the same way alcohol does. So combining pregnenolone with alcohol can swing in either direction: it may blunt the expected buzz/sedation in some people, or it may amplify drowsiness, impaired coordination and slowed reaction time in others (particularly as allopregnanolone levels build). This makes the level of impairment from a given amount of alcohol harder to predict, which is the real-world hazard.", "clinicalSignificance": "The interaction is unlikely to be life-threatening on its own but can meaningfully and unpredictably alter intoxication and motor impairment, which matters for safety-sensitive activities like driving. Effect direction differs between individuals based on conversion to allopregnanolone.", "managementStrategy": "Do not rely on pregnenolone to make alcohol feel less impairing; the metabolite allopregnanolone can do the opposite and deepen sedation. Avoid drinking on the same day you take pregnenolone, and never drive or operate machinery after combining them. If you do take pregnenolone, dose it in the morning and keep alcohol intake minimal and well separated (ideally avoid alcohol within the same dosing day). Use particular caution if you are also taking any sedating supplements or medications.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Royal Jelly", "supplementBName": "Nattokinase", "interactionType": "caution", "severity": "moderate", "description": "Both supplements independently lower the body's clotting capacity, Royal Jelly by potentiating anticoagulation (as shown in a warfarin case report) and Nattokinase through documented fibrinolytic and antiplatelet activity. Used together they can compound this effect, increasing the theoretical risk of easy bruising, prolonged bleeding, or more pronounced anticoagulation, especially in anyone also taking a blood thinner, aspirin, fish oil, or other antiplatelet supplement.", "recommendation": "Most healthy adults not on blood thinners can use both, but watch for easy bruising, nosebleeds, bleeding gums, or prolonged bleeding from cuts. Do NOT combine without medical supervision if you take warfarin, a DOAC, aspirin, clopidogrel, or other antiplatelet/anticoagulant agents. Stop both at least 1 to 2 weeks before any surgery or dental extraction. If you choose to use both, keep Nattokinase at conservative doses (around 2,000 FU per day) and report any unusual bleeding to your clinician.", "minimumTimeSeparation": "Timing separation does not mitigate this systemic additive effect; total daily exposure is what matters, not spacing.", "mechanism": "Additive effect on hemostasis. Royal Jelly has a documented ability to potentiate anticoagulation: a published case report describes an elevated INR (rising to roughly 7.29) with hematuria in a warfarin-treated patient after starting Royal Jelly, indicating it can meaningfully shift coagulation. Nattokinase independently reduces clotting through fibrinolytic activity (direct fibrin degradation, enhanced plasmin generation) plus an antiplatelet action (reduced platelet aggregation and thromboxane formation). Taken together, the two act on overlapping limbs of the clotting cascade, producing an additive reduction in clot formation and stability.", "evidenceLevel": "emerging", "sources": [ { "text": "Lee NJ et al. Warfarin and royal jelly interaction. Pharmacotherapy. 2006;26(4):583-6.", "pmid": "16553520", "doi": "10.1592/phco.26.4.583", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16553520/", "publicSourceType": "PMID" }, { "text": "Weng Y et al. Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease. Int J Mol Sci. 2017;18(3).", "pmid": "28264497", "doi": "10.3390/ijms18030523", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28264497/", "publicSourceType": "PMID" }, { "text": "Kurosawa Y et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep. 2015;5:11601.", "pmid": "26109079", "doi": "10.1038/srep11601", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26109079/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both supplements independently lower the body's clotting capacity, Royal Jelly by potentiating anticoagulation (as shown in a warfarin case report) and Nattokinase through documented fibrinolytic and antiplatelet activity. Used together they can compound this effect, increasing the theoretical risk of easy bruising, prolonged bleeding, or more pronounced anticoagulation, especially in anyone also taking a blood thinner, aspirin, fish oil, or other antiplatelet supplement.", "clinicalSignificance": "Relevant mainly for people on anticoagulant/antiplatelet therapy or facing surgery. In otherwise healthy users the combined effect is usually modest, but the warfarin case report shows Royal Jelly can shift coagulation enough to matter, so stacking it with a fibrinolytic supplement warrants real caution.", "managementStrategy": "Most healthy adults not on blood thinners can use both, but watch for easy bruising, nosebleeds, bleeding gums, or prolonged bleeding from cuts. Do NOT combine without medical supervision if you take warfarin, a DOAC, aspirin, clopidogrel, or other antiplatelet/anticoagulant agents. Stop both at least 1 to 2 weeks before any surgery or dental extraction. If you choose to use both, keep Nattokinase at conservative doses (around 2,000 FU per day) and report any unusual bleeding to your clinician.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Royal Jelly", "supplementBName": "Garlic Extract", "interactionType": "caution", "severity": "moderate", "description": "Royal Jelly and Garlic Extract both lower blood pressure through nitric-oxide-driven vasodilation (Royal Jelly additionally via ACE-inhibitory peptides), and both can modestly reduce clotting. Stacking them can cause an additive drop in blood pressure, with possible lightheadedness or dizziness, and a small additive increase in bleeding tendency.", "recommendation": "If you have normal blood pressure the combination is generally fine, but introduce them one at a time and stand up slowly at first to gauge any dizziness. If you take antihypertensive medication, monitor blood pressure at home for additive lowering and adjust under your clinician's guidance to avoid hypotension. Apply the same surgical-bleeding precaution as with other antiplatelet supplements: pause both 1 to 2 weeks before surgery. No specific dose ceiling is required for healthy users; use standard label doses of each.", "minimumTimeSeparation": "Spacing does not prevent the additive systemic effect; total daily intake is what counts, so monitoring matters more than timing.", "mechanism": "Two overlapping mechanisms. (1) Additive blood-pressure lowering: Royal Jelly proteins yield ACE-inhibitory peptides (Ile-Tyr, Val-Tyr, Ile-Val-Tyr) and promote nitric-oxide-mediated vasodilation, producing measurable hypotensive effects in animal and some human data. Garlic Extract also lowers blood pressure largely through nitric oxide and hydrogen sulfide mediated vasorelaxation. Combined, they act on the same vasodilatory and renin-angiotensin pathways. (2) Additive antiplatelet effect: Garlic Extract inhibits platelet aggregation, and Royal Jelly has documented anticoagulation-potentiating activity, so the pair can also compound bleeding risk.", "evidenceLevel": "emerging", "sources": [ { "text": "Matsui T et al. Gastrointestinal enzyme production of bioactive peptides from royal jelly protein and their antihypertensive ability in SHR. J Nutr Biochem. 2002;13(2):80-86.", "pmid": "11834223", "doi": "10.1016/s0955-2863(01)00198-x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11834223/", "publicSourceType": "PMID" }, { "text": "Rahman K et al. Dietary supplementation with aged garlic extract inhibits ADP-induced platelet aggregation in humans. J Nutr. 2000;130(11):2662-5.", "pmid": "11053504", "doi": "10.1093/jn/130.11.2662", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11053504/", "publicSourceType": "PMID" }, { "text": "Allison GL et al. Aged garlic extract and its constituents inhibit platelet aggregation through multiple mechanisms. J Nutr. 2006;136(3 Suppl):782S-788S.", "pmid": "16484563", "doi": "10.1093/jn/136.3.782S", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16484563/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Royal Jelly and Garlic Extract both lower blood pressure through nitric-oxide-driven vasodilation (Royal Jelly additionally via ACE-inhibitory peptides), and both can modestly reduce clotting. Stacking them can cause an additive drop in blood pressure, with possible lightheadedness or dizziness, and a small additive increase in bleeding tendency.", "clinicalSignificance": "Most relevant for people already on blood-pressure medication or those prone to low blood pressure, where the additive hypotensive effect could cause symptomatic dizziness. The shared antiplatelet effect is a secondary consideration, mainly for those on blood thinners or approaching surgery.", "managementStrategy": "If you have normal blood pressure the combination is generally fine, but introduce them one at a time and stand up slowly at first to gauge any dizziness. If you take antihypertensive medication, monitor blood pressure at home for additive lowering and adjust under your clinician's guidance to avoid hypotension. Apply the same surgical-bleeding precaution as with other antiplatelet supplements: pause both 1 to 2 weeks before surgery. No specific dose ceiling is required for healthy users; use standard label doses of each.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "SAMe", "supplementBName": "5-HTP", "interactionType": "caution", "severity": "moderate", "description": "Both SAMe and 5-HTP independently elevate serotonin activity, so combining them stacks two pro-serotonergic mechanisms. Case literature documents treatment-emergent hypomania and a theoretical risk of serotonin excess (agitation, insomnia, tremor, GI distress, and in extreme cases serotonin syndrome) when over-the-counter SAMe and 5-HTP are used together, especially at the higher end of typical dosing (SAMe 400 to 1600 mg/day, 5-HTP 150 to 800 mg/day). The risk is amplified if any prescription serotonergic agent is also on board.", "recommendation": "Do not start both supplements at full dose simultaneously. If a clinician supports using them together, introduce one at a time, start low (for example SAMe 200 to 400 mg/day and 5-HTP 50 to 100 mg/day), and titrate slowly while watching for agitation, restlessness, insomnia, racing thoughts, sweating, or tremor. Avoid the combination entirely if you take any SSRI, SNRI, MAOI, triptan, tramadol, or other serotonergic medication. Stop and seek care if signs of serotonin excess appear.", "minimumTimeSeparation": "Separating doses by hours does not remove the risk because both act systemically over many hours; the concern is total daily serotonergic load, not timing. No protective time gap applies.", "mechanism": "Additive serotonergic effect. SAMe (S-adenosylmethionine) is the universal methyl donor that supports monoamine neurotransmitter synthesis and turnover, raising central serotonin activity, while 5-HTP (5-hydroxytryptophan) is the immediate biochemical precursor to serotonin that bypasses the rate-limiting tryptophan hydroxylase step. Taken together they push serotonin from two converging directions (precursor loading plus methylation-supported synthesis), so their effects on serotonergic tone are additive rather than independent.", "evidenceLevel": "emerging", "sources": [ { "text": "Turner EH et al. Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacol Ther. 2006;109(3):325-38.", "pmid": "16023217", "doi": "10.1016/j.pharmthera.2005.06.004", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16023217/", "publicSourceType": "PMID" }, { "text": "Carpenter DJ. St. John's wort and S-adenosyl methionine as \"natural\" alternatives to conventional antidepressants in the era of the suicidality boxed warning: what is the evidence for clinically relevant benefit? Altern Med Rev. 2011;16(1):17-39.", "pmid": "21438644", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21438644/", "publicSourceType": "PMID" }, { "text": "Bottiglieri T. S-Adenosyl-L-methionine (SAMe): from the bench to the bedside--molecular basis of a pleiotrophic molecule. Am J Clin Nutr. 2002;76(5):1151S-7S.", "pmid": "12418493", "doi": "10.1093/ajcn/76/5.1151S", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12418493/", "publicSourceType": "PMID" }, { "text": "Boyer EW et al. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-20.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both SAMe and 5-HTP independently elevate serotonin activity, so combining them stacks two pro-serotonergic mechanisms. Case literature documents treatment-emergent hypomania and a theoretical risk of serotonin excess (agitation, insomnia, tremor, GI distress, and in extreme cases serotonin syndrome) when over-the-counter SAMe and 5-HTP are used together, especially at the higher end of typical dosing (SAMe 400 to 1600 mg/day, 5-HTP 150 to 800 mg/day). The risk is amplified if any prescription serotonergic agent is also on board.", "clinicalSignificance": "Relevant for anyone self-treating low mood with both stacked, particularly bipolar-spectrum individuals (hypomania risk) and those on prescription antidepressants. The interaction is usually manageable with conservative dosing but can become clinically significant at high combined doses.", "managementStrategy": "Do not start both supplements at full dose simultaneously. If a clinician supports using them together, introduce one at a time, start low (for example SAMe 200 to 400 mg/day and 5-HTP 50 to 100 mg/day), and titrate slowly while watching for agitation, restlessness, insomnia, racing thoughts, sweating, or tremor. Avoid the combination entirely if you take any SSRI, SNRI, MAOI, triptan, tramadol, or other serotonergic medication. Stop and seek care if signs of serotonin excess appear.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "SAMe", "supplementBName": "Vitamin B6", "interactionType": "synergy", "severity": "info", "description": "Supplemental SAMe increases flux through the methionine cycle and generates homocysteine downstream. Vitamin B6 is the cofactor that allows the transsulfuration arm to dispose of that homocysteine. With sufficient B6 (alongside folate and B12), the pathway runs cleanly and homocysteine is converted to cysteine and glutathione. The pairing is a beneficial synergy that supports methylation balance, which is why clinical SAMe trials have specifically co-administered B6, folate, and B12 to study homocysteine handling.", "recommendation": "If taking SAMe (commonly 400 to 1200 mg/day), ensure adequate vitamin B6 status (a typical maintenance dose is around 1.3 to 2 mg/day from diet or a B-complex, with supplemental forms often 10 to 25 mg/day; avoid chronic high-dose B6 above roughly 100 mg/day due to neuropathy risk). For best methylation support, B6 is most effective when paired with folate and B12. No separation in timing is needed; daily co-administration is appropriate. Those with cardiovascular risk or known elevated homocysteine should have homocysteine monitored.", "minimumTimeSeparation": "None required. Vitamin B6 and SAMe can be taken at the same time; the cofactor relationship benefits from consistent daily co-presence, not dose separation.", "mechanism": "Shared transsulfuration cofactor pathway. When SAMe donates its methyl group it becomes S-adenosylhomocysteine, which is hydrolyzed to homocysteine. Homocysteine is then cleared down the transsulfuration pathway, where two pyridoxal-5'-phosphate (active vitamin B6) dependent enzymes (cystathionine beta-synthase and cystathionine gamma-lyase) convert it to cysteine and ultimately glutathione. Adequate vitamin B6 therefore acts as the rate-limiting cofactor that lets SAMe-derived homocysteine be safely channeled to cysteine instead of accumulating.", "evidenceLevel": "moderate", "sources": [ { "text": "Selhub J. Homocysteine metabolism. Annu Rev Nutr. 1999.", "pmid": "10448523", "doi": "10.1146/annurev.nutr.19.1.217", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10448523/", "publicSourceType": "PMID" }, { "text": "Linus Pauling Institute Micronutrient Information Center, Folate and Vitamin B6 chapters (Oregon State University), covering transsulfuration and the methionine cycle.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Clinical trials of oral SAMe with and without folate, vitamin B12, and vitamin B6 on plasma homocysteine, and general one-carbon metabolism and methylation reviews.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Supplemental SAMe increases flux through the methionine cycle and generates homocysteine downstream. Vitamin B6 is the cofactor that allows the transsulfuration arm to dispose of that homocysteine. With sufficient B6 (alongside folate and B12), the pathway runs cleanly and homocysteine is converted to cysteine and glutathione. The pairing is a beneficial synergy that supports methylation balance, which is why clinical SAMe trials have specifically co-administered B6, folate, and B12 to study homocysteine handling.", "clinicalSignificance": "Most relevant for people on higher-dose or long-term SAMe and for those with marginal B-vitamin status or genetic methylation variants, in whom inadequate B6 could allow homocysteine to rise. Co-supplementation is a low-risk, supportive measure rather than a hazard.", "managementStrategy": "If taking SAMe (commonly 400 to 1200 mg/day), ensure adequate vitamin B6 status (a typical maintenance dose is around 1.3 to 2 mg/day from diet or a B-complex, with supplemental forms often 10 to 25 mg/day; avoid chronic high-dose B6 above roughly 100 mg/day due to neuropathy risk). For best methylation support, B6 is most effective when paired with folate and B12. No separation in timing is needed; daily co-administration is appropriate. Those with cardiovascular risk or known elevated homocysteine should have homocysteine monitored.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Shilajit", "supplementBName": "Zinc", "interactionType": "timingSensitive", "severity": "moderate", "description": "Taking a standalone zinc supplement at the exact same time as Shilajit can change zinc bioavailability because the fulvic and humic acids in Shilajit complex with the zinc cation in the digestive tract. The net effect is not fully predictable in humans (the chelate can either aid cellular delivery or sequester zinc depending on the relative amounts and gut conditions), which is exactly why co-timing introduces variability rather than a reliable benefit. The trace zinc naturally present within Shilajit itself is not the concern here; this note applies to a separate higher-dose zinc product.", "recommendation": "If you take a dedicated zinc supplement (for example 15 to 30 mg elemental zinc), separate it from Shilajit by 2 to 3 hours to keep zinc dosing predictable. A practical pattern is zinc with an evening meal and Shilajit in the morning. The trace zinc naturally present within Shilajit does not need separating; this applies only to a separate, higher-dose zinc product.", "minimumTimeSeparation": "2 to 3 hours", "mechanism": "Shilajit is rich in fulvic and humic acids, polyfunctional organic acids whose carboxyl and phenolic groups bind divalent metal cations, including zinc. When a separate zinc supplement is taken at the same dose as Shilajit, this humic fraction can complex zinc in the gut lumen and alter how much free zinc is presented to intestinal transporters. Animal homeostasis work shows fulvic and humic acids measurably change zinc absorption and tissue retention rather than leaving uptake unchanged. This is the same chelation chemistry behind Shilajit's documented effect on iron, applied to another divalent mineral.", "evidenceLevel": "emerging", "sources": [ { "text": "Vaskova J. et al., Effects of humic acids on the trace element homeostasis (including zinc) in rodent models, Biological Trace Element Research", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Reviews of Shilajit composition describing its fulvic and humic acid content and chelation of divalent metal ions", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "General mineral pharmacology literature on humic substance binding of divalent cations and intestinal mineral absorption", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Taking a standalone zinc supplement at the exact same time as Shilajit can change zinc bioavailability because the fulvic and humic acids in Shilajit complex with the zinc cation in the digestive tract. The net effect is not fully predictable in humans (the chelate can either aid cellular delivery or sequester zinc depending on the relative amounts and gut conditions), which is exactly why co-timing introduces variability rather than a reliable benefit. The trace zinc naturally present within Shilajit itself is not the concern here; this note applies to a separate higher-dose zinc product.", "clinicalSignificance": "Relevant mainly for people relying on zinc supplementation to correct or maintain status (for example immune support, men's health, or skin protocols), where inconsistent absorption could blunt the intended effect. Not a safety hazard, but a bioavailability and consistency issue worth managing by timing.", "managementStrategy": "If you take a dedicated zinc supplement (for example 15 to 30 mg elemental zinc), separate it from Shilajit by 2 to 3 hours to keep zinc dosing predictable. A practical pattern is zinc with an evening meal and Shilajit in the morning. The trace zinc naturally present within Shilajit does not need separating; this applies only to a separate, higher-dose zinc product.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Shilajit", "supplementBName": "Tongkat Ali", "interactionType": "synergy", "severity": "info", "description": "Shilajit and Tongkat Ali are frequently stacked for testosterone, energy, and libido, and the pairing is mechanistically coherent rather than redundant: one nudges hormone production and precursors while the other increases the free, biologically active fraction. This complementary action is why the two appear together in many men's vitality formulas. The same additive androgenic effect is the reason the combination warrants a note for anyone who should not raise testosterone.", "recommendation": "For general vitality goals, a common pairing is roughly 250 mg purified Shilajit once or twice daily with 200 to 400 mg of a standardized Tongkat Ali extract, taken in the morning. Start each one individually for one to two weeks before combining so you can judge tolerance and effect. Men with hormone-sensitive conditions (such as prostate cancer or elevated hematocrit) and anyone on testosterone therapy or fertility treatment should consult a clinician before stacking, since effects on free testosterone are additive. Not for use in pregnancy.", "minimumTimeSeparation": "None required; can be taken together", "mechanism": "The two act on the androgen axis at complementary points. Purified Shilajit (its dibenzo-alpha-pyrones and fulvic acid fraction) raised total testosterone, free testosterone, and DHEA-S in a 90-day placebo-controlled trial, consistent with support of upstream steroidogenesis. Tongkat Ali (eurycomanone) is associated with higher free testosterone largely by lowering sex hormone binding globulin, freeing more of the existing pool. Acting upstream (production and DHEA precursor) plus downstream (reduced SHBG, higher free fraction) gives an additive, potentially synergistic effect on free androgen levels.", "evidenceLevel": "emerging", "sources": [ { "text": "Pandit S. et al., Clinical evaluation of purified Shilajit on testosterone levels in healthy volunteers, Andrologia", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Controlled trials and reviews of Eurycoma longifolia (Tongkat Ali) reporting increased free testosterone and reduced sex hormone binding globulin", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Men's health formulation literature describing complementary androgen-axis mechanisms of Shilajit and Tongkat Ali", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Shilajit and Tongkat Ali are frequently stacked for testosterone, energy, and libido, and the pairing is mechanistically coherent rather than redundant: one nudges hormone production and precursors while the other increases the free, biologically active fraction. This complementary action is why the two appear together in many men's vitality formulas. The same additive androgenic effect is the reason the combination warrants a note for anyone who should not raise testosterone.", "clinicalSignificance": "Generally a favorable, low-risk combination for healthy adult men seeking androgen and energy support, with the main caveat being unwanted additive androgen elevation in hormone-sensitive individuals. Human data exist for each agent alone; data on the specific combination are still limited.", "managementStrategy": "For general vitality goals, a common pairing is roughly 250 mg purified Shilajit once or twice daily with 200 to 400 mg of a standardized Tongkat Ali extract, taken in the morning. Start each one individually for one to two weeks before combining so you can judge tolerance and effect. Men with hormone-sensitive conditions (such as prostate cancer or elevated hematocrit) and anyone on testosterone therapy or fertility treatment should consult a clinician before stacking, since effects on free testosterone are additive. Not for use in pregnancy.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Silicon", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "info", "description": "Human and mechanistic data support a complementary, bone-building relationship rather than any adverse interaction. In a 12-month randomized, placebo-controlled trial in osteopenic women, choline-stabilized orthosilicic acid added on top of daily calcium plus Vitamin D3 produced a significantly greater rise in the bone-formation/type I collagen marker PINP than calcium plus Vitamin D3 alone, at silicon doses of roughly 6 to 12 mg per day. This reflects silicon strengthening the collagen scaffold that Vitamin D3-driven mineralization then fills, so the pair is genuinely additive for bone matrix quality.", "recommendation": "Reasonable to take together for bone and connective tissue support. Typical doses: silicon as orthosilicic acid or stabilized silica around 5 to 10 mg elemental silicon per day, with Vitamin D3 around 800 to 2000 IU (20 to 50 mcg) per day, alongside adequate calcium. No timing separation is needed; both can be taken with a meal. Silicon is best regarded as an adjunct to, not a replacement for, calcium and Vitamin D3.", "minimumTimeSeparation": "None required", "mechanism": "Silicon (as orthosilicic acid) stimulates type I collagen synthesis and osteoblast differentiation, building the organic collagen scaffold of bone, while Vitamin D3 drives intestinal calcium absorption and matrix mineralization. The two act on complementary, sequential steps of bone formation: silicon lays down and cross-links the collagen matrix, and Vitamin D3 (with calcium) mineralizes it.", "evidenceLevel": "moderate", "sources": [ { "text": "Spector et al., Choline-stabilized orthosilicic acid supplementation as an adjunct to calcium/vitamin D3 stimulates markers of bone formation in osteopenic females: a randomized, placebo-controlled trial, BMC Musculoskeletal Disorders, 2008", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Jugdaohsingh, Silicon and bone health, Journal of Nutrition, Health and Aging, 2007", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Rondanelli et al., Silicon: a neglected micronutrient essential for bone health, Experimental Biology and Medicine, 2021", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Human and mechanistic data support a complementary, bone-building relationship rather than any adverse interaction. In a 12-month randomized, placebo-controlled trial in osteopenic women, choline-stabilized orthosilicic acid added on top of daily calcium plus Vitamin D3 produced a significantly greater rise in the bone-formation/type I collagen marker PINP than calcium plus Vitamin D3 alone, at silicon doses of roughly 6 to 12 mg per day. This reflects silicon strengthening the collagen scaffold that Vitamin D3-driven mineralization then fills, so the pair is genuinely additive for bone matrix quality.", "clinicalSignificance": "Beneficial, not a safety concern. The combination may modestly improve markers of bone formation in people at risk of low bone density, but silicon's added benefit is incremental and the underlying calcium/Vitamin D3 foundation matters most.", "managementStrategy": "Reasonable to take together for bone and connective tissue support. Typical doses: silicon as orthosilicic acid or stabilized silica around 5 to 10 mg elemental silicon per day, with Vitamin D3 around 800 to 2000 IU (20 to 50 mcg) per day, alongside adequate calcium. No timing separation is needed; both can be taken with a meal. Silicon is best regarded as an adjunct to, not a replacement for, calcium and Vitamin D3.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Silicon", "supplementBName": "Boron", "interactionType": "synergy", "severity": "info", "description": "Both silicon and boron are ultratrace elements repeatedly linked to bone and connective tissue integrity, and they are commonly co-formulated for skeletal support. Mechanistically they are additive: silicon contributes to collagen cross-linking and matrix formation, whereas boron improves the metabolic handling of calcium, magnesium, and Vitamin D that supports mineralization. The combination is mechanistically coherent and biologically plausible, though direct head-to-head human trials of the specific pair are limited and most evidence is observational or based on each element individually.", "recommendation": "Can be taken together for bone, joint, and connective tissue support. Typical doses: silicon around 5 to 10 mg elemental per day and boron around 3 mg per day (generally keeping boron at or below 3 to 6 mg per day for routine use). No timing separation is needed; both are well tolerated with food. Do not exceed the boron tolerable upper limit of about 20 mg per day.", "minimumTimeSeparation": "None required", "mechanism": "Silicon (orthosilicic acid) supports the collagen matrix and connective tissue framework of bone, while boron modulates mineral metabolism by reducing urinary calcium and magnesium loss, increasing activation of Vitamin D, and influencing steroid hormone status. The two trace elements act on parallel, non-overlapping arms of bone and connective tissue maintenance, so their effects are complementary rather than competing.", "evidenceLevel": "emerging", "sources": [ { "text": "Nielsen, Update on the possible nutritional importance of silicon, Journal of Trace Elements in Medicine and Biology, 2014", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Pizzorno, Nothing boring about boron, Integrative Medicine: A Clinician's Journal, 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Rondanelli et al., Silicon: a neglected micronutrient essential for bone health, Experimental Biology and Medicine, 2021", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both silicon and boron are ultratrace elements repeatedly linked to bone and connective tissue integrity, and they are commonly co-formulated for skeletal support. Mechanistically they are additive: silicon contributes to collagen cross-linking and matrix formation, whereas boron improves the metabolic handling of calcium, magnesium, and Vitamin D that supports mineralization. The combination is mechanistically coherent and biologically plausible, though direct head-to-head human trials of the specific pair are limited and most evidence is observational or based on each element individually.", "clinicalSignificance": "Beneficial and low-risk for most adults. The pairing may offer broader trace-mineral support for bone matrix and connective tissue than either alone, but the magnitude of added benefit is modest and rests largely on mechanistic and observational data rather than large combination trials.", "managementStrategy": "Can be taken together for bone, joint, and connective tissue support. Typical doses: silicon around 5 to 10 mg elemental per day and boron around 3 mg per day (generally keeping boron at or below 3 to 6 mg per day for routine use). No timing separation is needed; both are well tolerated with food. Do not exceed the boron tolerable upper limit of about 20 mg per day.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Spirulina", "supplementBName": "Calcium", "interactionType": "timingSensitive", "severity": "moderate", "description": "When spirulina (taken for its iron and mineral content) is co-ingested with a calcium supplement, the calcium reduces absorption of spirulina's non-heme iron. Human absorption studies show calcium can cut non-heme iron uptake by roughly 40 to 60 percent at common supplemental doses (maximal inhibition around 300 mg calcium per dose), with the effect occurring at the initial mucosal-uptake step. Note that typical spirulina doses (3 to 5 g) supply only about 1 to 1.5 mg of iron, so this matters most for people deliberately using spirulina to support iron intake.", "recommendation": "Separate the two by at least 2 hours (3 to 4 hours is ideal). A practical pattern is spirulina with a vitamin C source earlier in the day and calcium with an evening meal. If spirulina is being used specifically as an iron source (for example in vegetarians or those with low iron stores), avoid pairing it with high-dose calcium (over about 300 to 500 mg) in the same sitting.", "minimumTimeSeparation": "2 hours (3 to 4 hours preferred)", "mechanism": "Spirulina contains non-heme iron and other divalent minerals. Calcium competitively inhibits non-heme iron uptake at the intestinal enterocyte, partly via the shared divalent metal transporter (DMT1) and partly by forming poorly soluble complexes in the gut lumen. Taken together at the same time, calcium can blunt absorption of the iron and trace minerals that spirulina is often used to provide.", "evidenceLevel": "moderate", "sources": [ { "text": "Hallberg L et al. Calcium and iron absorption: mechanism of action and nutritional importance. Eur J Clin Nutr. 1992.", "pmid": "1600930", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1600930/", "publicSourceType": "PMID" }, { "text": "Lonnerdal B. Calcium and iron absorption: mechanisms and public health relevance. International Journal for Vitamin and Nutrition Research, 2010.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Controlled human absorption studies and nutrition reviews on the inhibitory effect of dietary and supplemental calcium on non-heme iron uptake, together with compositional data on the iron and mineral profile of Arthrospira (spirulina).", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "When spirulina (taken for its iron and mineral content) is co-ingested with a calcium supplement, the calcium reduces absorption of spirulina's non-heme iron. Human absorption studies show calcium can cut non-heme iron uptake by roughly 40 to 60 percent at common supplemental doses (maximal inhibition around 300 mg calcium per dose), with the effect occurring at the initial mucosal-uptake step. Note that typical spirulina doses (3 to 5 g) supply only about 1 to 1.5 mg of iron, so this matters most for people deliberately using spirulina to support iron intake.", "clinicalSignificance": "Mainly relevant for people relying on spirulina for iron or correcting marginal iron status; for those with adequate iron stores the practical impact is small. Easily managed by spacing doses, so it is a convenience and optimization issue rather than a safety risk.", "managementStrategy": "Separate the two by at least 2 hours (3 to 4 hours is ideal). A practical pattern is spirulina with a vitamin C source earlier in the day and calcium with an evening meal. If spirulina is being used specifically as an iron source (for example in vegetarians or those with low iron stores), avoid pairing it with high-dose calcium (over about 300 to 500 mg) in the same sitting.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Spirulina", "supplementBName": "Echinacea", "interactionType": "caution", "severity": "moderate", "description": "Stacking spirulina with echinacea produces overlapping, additive immune stimulation. In most healthy people this is unremarkable, but in individuals with autoimmune disease or autoimmune predisposition the combined immunostimulation may aggravate disease activity. Dermatology and rheumatology literature specifically flags spirulina (and echinacea) among immunostimulatory supplements associated with autoimmune flares.", "recommendation": "Healthy adults using both short-term for general immune support are generally fine. Anyone with an autoimmune condition (for example lupus, psoriasis, MS, dermatomyositis, or autoimmune thyroid disease), a strong family history of autoimmunity, or who is on immunosuppressant therapy should avoid combining the two and ideally discuss either one with a clinician. Avoid open-ended daily stacking of both; reserve echinacea for short courses.", "minimumTimeSeparation": "Not a timing issue; avoid concurrent use in autoimmune or immunosuppressed individuals", "mechanism": "Both are documented immunostimulants acting on innate immunity. Spirulina (via C-phycocyanin and sulfated polysaccharides) activates macrophages and monocytes, raises NK-cell activity, and increases Th1 cytokines such as IFN-gamma, TNF-alpha, and IL-2. Echinacea similarly upregulates macrophage activity and pro-inflammatory cytokine production. Combined, their effects on immune activation are additive.", "evidenceLevel": "emerging", "sources": [ { "text": "Lee AN, Werth VP. Activation of autoimmunity following use of immunostimulatory herbal supplements. Arch Dermatol. 2004.", "pmid": "15210464", "doi": "10.1001/archderm.140.6.723", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15210464/", "publicSourceType": "PMID" }, { "text": "Hirahashi T et al. Activation of the human innate immune system by Spirulina: augmentation of interferon production and NK cytotoxicity by oral administration of hot water extract of Spirulina platensis. Int Immunopharmacol. 2002.", "pmid": "11962722", "doi": "10.1016/s1567-5769(01)00166-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11962722/", "publicSourceType": "PMID" }, { "text": "Dermatology and rheumatology reviews and case reports describing immunostimulatory herbal and algal supplements (including spirulina and echinacea) in relation to autoimmune disease onset and flares.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Stacking spirulina with echinacea produces overlapping, additive immune stimulation. In most healthy people this is unremarkable, but in individuals with autoimmune disease or autoimmune predisposition the combined immunostimulation may aggravate disease activity. Dermatology and rheumatology literature specifically flags spirulina (and echinacea) among immunostimulatory supplements associated with autoimmune flares.", "clinicalSignificance": "Low concern for immunologically healthy users; potentially meaningful for the autoimmune-predisposed subgroup, where additive immune activation has been linked to disease onset or flare. The interaction is about identifying who should avoid the combination rather than a universal warning.", "managementStrategy": "Healthy adults using both short-term for general immune support are generally fine. Anyone with an autoimmune condition (for example lupus, psoriasis, MS, dermatomyositis, or autoimmune thyroid disease), a strong family history of autoimmunity, or who is on immunosuppressant therapy should avoid combining the two and ideally discuss either one with a clinician. Avoid open-ended daily stacking of both; reserve echinacea for short courses.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Strontium", "supplementBName": "Iron", "interactionType": "timingSensitive", "severity": "moderate", "description": "Taking strontium and an oral iron supplement at the same time can lower how much of each you actually absorb. This mirrors the well-documented requirement to separate strontium from calcium: regulatory product information for strontium ranelate explicitly groups oral iron with calcium and food as agents that should be dosed several hours apart from strontium because they impair its uptake. The interaction is purely about co-administration timing, not a systemic or toxic effect, and it is fully avoidable by spacing the doses.", "recommendation": "Separate strontium and oral iron by at least 2 hours (3 to 4 hours is ideal). A practical pattern: take iron with vitamin C earlier in the day on a relatively empty stomach, and take strontium at bedtime, at least 2 hours after the last food or mineral dose. Do not combine them in the same glass or the same with-meal slot.", "minimumTimeSeparation": "2 hours (3 to 4 hours preferred)", "mechanism": "Strontium and iron are both polyvalent cations that compete for and chelate within the upper gastrointestinal tract. Strontium is absorbed largely by calcium-handling routes (paracellular transport and TRPV6/active calcium pathways), and co-ingested oral iron salts plus organic carriers such as ranelate or citrate can form poorly soluble complexes that blunt strontium uptake. Conversely, the divalent strontium cation can interfere with the acidic, transporter-mediated absorption of ferrous iron. The net effect is reduced bioavailability of one or both minerals when they share the same gastric window.", "evidenceLevel": "moderate", "sources": [ { "text": "European Medicines Agency, Protelos (strontium ranelate) Summary of Product Characteristics, section on interactions with food, calcium and oral iron.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Lipworth and colleagues, Absorption of strontium from the gastrointestinal tract into plasma in healthy human adults, demonstrating food and cation effects on strontium bioavailability.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "General pharmacology and divalent-cation absorption reviews describing competitive uptake and chelation among polyvalent mineral cations in the gut.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Taking strontium and an oral iron supplement at the same time can lower how much of each you actually absorb. This mirrors the well-documented requirement to separate strontium from calcium: regulatory product information for strontium ranelate explicitly groups oral iron with calcium and food as agents that should be dosed several hours apart from strontium because they impair its uptake. The interaction is purely about co-administration timing, not a systemic or toxic effect, and it is fully avoidable by spacing the doses.", "clinicalSignificance": "Most relevant for people supplementing strontium for bone density who also treat iron deficiency or anemia. Co-dosing can quietly undercut both goals: weaker bone-mineral accrual from strontium and a slower correction of iron status. Spacing the doses preserves the efficacy of each without any need to lower a dose.", "managementStrategy": "Separate strontium and oral iron by at least 2 hours (3 to 4 hours is ideal). A practical pattern: take iron with vitamin C earlier in the day on a relatively empty stomach, and take strontium at bedtime, at least 2 hours after the last food or mineral dose. Do not combine them in the same glass or the same with-meal slot.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Strontium", "supplementBName": "Magnesium Citrate", "interactionType": "timingSensitive", "severity": "moderate", "description": "Strontium and magnesium taken in the same dose can compete for absorption because both move across the gut as divalent cations using overlapping pathways. Strontium uptake is already sensitive to other minerals in the gut (this is why strontium must be separated from calcium), and magnesium falls into the same competitive category. The practical consequence is reduced strontium bioavailability when a meaningful magnesium dose is co-ingested. This is a timing issue, not a safety hazard.", "recommendation": "Separate strontium and magnesium by at least 2 hours. A clean stack: magnesium with dinner or earlier in the evening, then strontium at bedtime at least 2 hours later on an empty stomach. Avoid putting both in the same nighttime pill pile. Lower magnesium doses (under about 100 mg elemental) are less likely to matter, but spacing is the safe default.", "minimumTimeSeparation": "2 hours", "mechanism": "Strontium, calcium and magnesium are divalent cations that share common intestinal absorption pathways. Classic isolated-rat-intestine work showed mutual competition among these cations, with strontium and magnesium each capable of reducing the active uptake of the other in the small intestine, and overlapping handling at calcium-sensing receptor and TRP-family transport routes. When a sizeable magnesium dose and a strontium dose are taken together, they compete for the same finite transport and paracellular capacity, lowering the fraction of strontium absorbed (and modestly affecting magnesium uptake in return).", "evidenceLevel": "emerging", "sources": [ { "text": "Competition Between Calcium, Strontium, and Magnesium for Absorption in the Isolated Rat Intestine, documenting mutual divalent-cation uptake competition.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "European Medicines Agency, Protelos (strontium ranelate) Summary of Product Characteristics, establishing that co-ingested cations and food reduce strontium bioavailability.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Reviews of intestinal divalent-cation transport (calcium-sensing receptor and TRP-family transporters) describing shared handling of calcium, strontium and magnesium.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Strontium and magnesium taken in the same dose can compete for absorption because both move across the gut as divalent cations using overlapping pathways. Strontium uptake is already sensitive to other minerals in the gut (this is why strontium must be separated from calcium), and magnesium falls into the same competitive category. The practical consequence is reduced strontium bioavailability when a meaningful magnesium dose is co-ingested. This is a timing issue, not a safety hazard.", "clinicalSignificance": "Mainly affects bone-health users who stack magnesium with strontium at night. Co-dosing can reduce the amount of strontium incorporated into bone over time, weakening the intended benefit. Because magnesium is commonly taken in the evening (the same window often used for strontium), this overlap is easy to create accidentally and easy to fix with timing.", "managementStrategy": "Separate strontium and magnesium by at least 2 hours. A clean stack: magnesium with dinner or earlier in the evening, then strontium at bedtime at least 2 hours later on an empty stomach. Avoid putting both in the same nighttime pill pile. Lower magnesium doses (under about 100 mg elemental) are less likely to matter, but spacing is the safe default.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Sulforaphane", "supplementBName": "Selenium", "interactionType": "synergy", "severity": "info", "description": "Sulforaphane and selenium act on the same antioxidant axis: sulforaphane induces the genes for selenium-dependent enzymes (thioredoxin reductase 1 and glutathione peroxidase 2), and selenium supplies the selenocysteine those enzymes need to function. In human hepatocyte cell studies the combination synergistically increased thioredoxin reductase 1 protein (about 5.5-fold), activity (about 13-fold) and mRNA (about 6.5-fold), and protected cells from oxidative damage more than either alone. Practically, taking sulforaphane against a background of sufficient (not deficient) selenium lets the upregulated selenoenzymes actually be built. A separate line of work shows sulforaphane can also bind and accelerate degradation of selenoprotein P, the body's selenium transport protein, so the relationship is mostly favorable synergy with a minor caveat to avoid frank selenium deficiency.", "recommendation": "No need to dose together at the same minute; both contribute to a steady antioxidant-enzyme pool. Ensure selenium intake is adequate (roughly 55 to 100 mcg/day for adults from diet plus supplement; total long-term intake should stay under about 400 mcg/day to avoid selenosis) so sulforaphane-induced selenoenzymes can be synthesized. Do not megadose selenium expecting added benefit. If you already eat selenium-rich foods (Brazil nuts, seafood), routine extra selenium is usually unnecessary alongside sulforaphane.", "minimumTimeSeparation": "None required", "mechanism": "Sulforaphane is an Nrf2 activator that upregulates antioxidant enzymes, including the selenium-dependent selenoproteins thioredoxin reductase 1 (TrxR1) and glutathione peroxidase 2 (GPx2). Selenium is the obligatory cofactor incorporated as selenocysteine into these enzymes. Sulforaphane drives transcription (mRNA up several fold) while selenium acts at the translational level and stabilizes the sulforaphane-induced mRNA, so the two combine to raise selenoprotein protein, activity, and message beyond either agent alone. Adequate selenium availability is therefore required for sulforaphane's induced selenoenzyme defenses to be functional.", "evidenceLevel": "emerging", "sources": [ { "text": "Zhang et al., Synergy between sulforaphane and selenium in the up-regulation of thioredoxin reductase and protection against hydrogen peroxide-induced cell death in human hepatocytes, Food Chemistry, 2012", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Hintze et al., Synergy between sulforaphane and selenium in the induction of thioredoxin reductase 1 requires both transcriptional and translational modulation, Carcinogenesis, 2003", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Ye et al., Sulforaphane decreases serum selenoprotein P levels through enhancement of lysosomal degradation independent of Nrf2, Communications Biology, 2023", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Sulforaphane and selenium act on the same antioxidant axis: sulforaphane induces the genes for selenium-dependent enzymes (thioredoxin reductase 1 and glutathione peroxidase 2), and selenium supplies the selenocysteine those enzymes need to function. In human hepatocyte cell studies the combination synergistically increased thioredoxin reductase 1 protein (about 5.5-fold), activity (about 13-fold) and mRNA (about 6.5-fold), and protected cells from oxidative damage more than either alone. Practically, taking sulforaphane against a background of sufficient (not deficient) selenium lets the upregulated selenoenzymes actually be built. A separate line of work shows sulforaphane can also bind and accelerate degradation of selenoprotein P, the body's selenium transport protein, so the relationship is mostly favorable synergy with a minor caveat to avoid frank selenium deficiency.", "clinicalSignificance": "Mostly a beneficial nutrient-cofactor relationship rather than a risk. The main practical point is that sulforaphane's antioxidant-enzyme benefits depend on having enough selenium on board; correcting or maintaining selenium sufficiency optimizes the response. The minor caution is theoretical selenoprotein P turnover, relevant only at low selenium status.", "managementStrategy": "No need to dose together at the same minute; both contribute to a steady antioxidant-enzyme pool. Ensure selenium intake is adequate (roughly 55 to 100 mcg/day for adults from diet plus supplement; total long-term intake should stay under about 400 mcg/day to avoid selenosis) so sulforaphane-induced selenoenzymes can be synthesized. Do not megadose selenium expecting added benefit. If you already eat selenium-rich foods (Brazil nuts, seafood), routine extra selenium is usually unnecessary alongside sulforaphane.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Sulforaphane", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "When sulforaphane is taken in precursor (glucoraphanin) form, vitamin C can improve its conversion to the active molecule by supporting the myrosinase enzyme that performs the hydrolysis. The conversion step is the rate-limiting factor for precursor-based products: glucoraphanin preparations lacking active myrosinase yield only roughly 10 percent of dose as sulforaphane, whereas an active myrosinase source can raise this to around 40 percent. Ascorbate is routinely co-included with myrosinase in bioavailability formulations, and many commercial broccoli-extract products deliberately co-formulate vitamin C plus a myrosinase source. The effect is most relevant for glucoraphanin-based supplements and for sulforaphane generated from food (broccoli, sprouts); pre-formed stabilized sulforaphane depends less on this step. This is a favorable absorption and conversion synergy, not a risk.", "recommendation": "If using a glucoraphanin or broccoli-extract product, take it with vitamin C (a typical 250 to 500 mg dose, or a vitamin-C-containing food or juice) at the same time, ideally alongside an active myrosinase source in the formula. Timing matters: take them together rather than hours apart so vitamin C is present during hydrolysis. No benefit is expected to be lost if you also already use a pre-converted, stabilized sulforaphane product, where the conversion step is bypassed.", "minimumTimeSeparation": "Take together", "mechanism": "Most supplemental sulforaphane is delivered as its inactive precursor glucoraphanin (broccoli seed or sprout extract), which must be hydrolyzed by the enzyme myrosinase to release active sulforaphane. Ascorbic acid (vitamin C) can act as a cofactor that modulates myrosinase activity at low concentrations, helping drive the hydrolysis step and increasing the yield of sulforaphane. With cofactor support present during hydrolysis, conversion of glucoraphanin to absorbable sulforaphane and its glutathione metabolites can rise, improving systemic bioavailability of the active compound.", "evidenceLevel": "emerging", "sources": [ { "text": "Fahey et al., Sulforaphane bioavailability from glucoraphanin-rich broccoli: control by active endogenous myrosinase, PLOS ONE, 2015", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Pharmacology literature on ascorbate as a low-concentration modulator of myrosinase activity during glucosinolate hydrolysis", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "When sulforaphane is taken in precursor (glucoraphanin) form, vitamin C can improve its conversion to the active molecule by supporting the myrosinase enzyme that performs the hydrolysis. The conversion step is the rate-limiting factor for precursor-based products: glucoraphanin preparations lacking active myrosinase yield only roughly 10 percent of dose as sulforaphane, whereas an active myrosinase source can raise this to around 40 percent. Ascorbate is routinely co-included with myrosinase in bioavailability formulations, and many commercial broccoli-extract products deliberately co-formulate vitamin C plus a myrosinase source. The effect is most relevant for glucoraphanin-based supplements and for sulforaphane generated from food (broccoli, sprouts); pre-formed stabilized sulforaphane depends less on this step. This is a favorable absorption and conversion synergy, not a risk.", "clinicalSignificance": "This is an optimization rather than a safety issue. Pairing vitamin C with precursor-based sulforaphane may increase how much active sulforaphane reaches the circulation, improving the consistency and magnitude of its effects. No adverse interaction is expected at normal supplemental doses.", "managementStrategy": "If using a glucoraphanin or broccoli-extract product, take it with vitamin C (a typical 250 to 500 mg dose, or a vitamin-C-containing food or juice) at the same time, ideally alongside an active myrosinase source in the formula. Timing matters: take them together rather than hours apart so vitamin C is present during hydrolysis. No benefit is expected to be lost if you also already use a pre-converted, stabilized sulforaphane product, where the conversion step is bypassed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Vanadium", "supplementBName": "Vitamin C", "interactionType": "caution", "severity": "moderate", "description": "Vitamin C directly alters the chemistry of co-ingested vanadium by reducing vanadate (V) to vanadyl (IV). This is one of the best characterized vanadium redox interactions in the inorganic chemistry and toxicology literature, with supporting human serum and EPR data. The practical upshot is mixed rather than purely harmful: ascorbate is widely described as one of the most effective and least toxic agents for reducing vanadium toxicity, so the combination tends to blunt vanadium's pro-oxidant risk. At the same time, it changes which vanadium species is present, which can shift bioavailability and effect, so the two should be thought of as chemically coupled rather than independent.", "recommendation": "This combination is generally protective against vanadium's pro-oxidant toxicity rather than dangerous, and high-dose vitamin C is sometimes used deliberately to mitigate vanadium overexposure. If you take vanadium for glucose support (typically a few mg up to roughly 25 to 100 mg elemental vanadium daily in studies, far above the trace dietary range), be aware that pairing it with substantial vitamin C, roughly 500 mg or more, will reduce and re-speciate the vanadium. If you want to evaluate vanadium's own effect cleanly, separate dosing by 3 to 4 hours; if your goal is to limit vanadium toxicity, co-dosing is reasonable. Keep total vanadium modest and time-limited regardless.", "minimumTimeSeparation": "3 to 4 hours if isolating vanadium's effect; co-dosing acceptable if the goal is reducing vanadium toxicity", "mechanism": "Ascorbic acid is a potent one-electron reducing agent for vanadium. It reduces vanadate, vanadium in the +5 oxidation state, to vanadyl, the +4 state. This redox conversion changes vanadium speciation: in serum, vanadate is largely reduced to vanadyl, which then binds albumin and transferrin. Because vanadium's pro-oxidant toxicity is driven largely by reactive oxygen species generated by the higher oxidation state, ascorbate both lowers that toxicity and shifts the absorbed and circulating vanadium pool toward the vanadyl form, the species to which most insulin-mimetic activity is attributed.", "evidenceLevel": "moderate", "sources": [ { "text": "Zwolak I. Protective Effects of Dietary Antioxidants against Vanadium-Induced Toxicity: A Review. Oxid Med Cell Longev. 2020.", "pmid": "31998432", "doi": "10.1155/2020/1490316", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31998432/", "publicSourceType": "PMID" }, { "text": "Crans DC and colleagues. Reviews of ascorbic acid in vanadium biochemistry, pharmacology, and detoxification.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Classic kinetic and mechanistic studies on the reduction of vanadium(V) by L-ascorbic acid in the inorganic chemistry literature.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Vitamin C directly alters the chemistry of co-ingested vanadium by reducing vanadate (V) to vanadyl (IV). This is one of the best characterized vanadium redox interactions in the inorganic chemistry and toxicology literature, with supporting human serum and EPR data. The practical upshot is mixed rather than purely harmful: ascorbate is widely described as one of the most effective and least toxic agents for reducing vanadium toxicity, so the combination tends to blunt vanadium's pro-oxidant risk. At the same time, it changes which vanadium species is present, which can shift bioavailability and effect, so the two should be thought of as chemically coupled rather than independent.", "clinicalSignificance": "Relevant for anyone using pharmacologic-dose vanadium (vanadyl sulfate or vanadate) for glucose or athletic goals while also taking gram-level vitamin C. The interaction is unlikely to cause acute harm and may reduce vanadium's oxidative toxicity, but it meaningfully alters vanadium chemistry and should be understood, especially since therapeutic vanadium doses already carry GI and pro-oxidant concerns.", "managementStrategy": "This combination is generally protective against vanadium's pro-oxidant toxicity rather than dangerous, and high-dose vitamin C is sometimes used deliberately to mitigate vanadium overexposure. If you take vanadium for glucose support (typically a few mg up to roughly 25 to 100 mg elemental vanadium daily in studies, far above the trace dietary range), be aware that pairing it with substantial vitamin C, roughly 500 mg or more, will reduce and re-speciate the vanadium. If you want to evaluate vanadium's own effect cleanly, separate dosing by 3 to 4 hours; if your goal is to limit vanadium toxicity, co-dosing is reasonable. Keep total vanadium modest and time-limited regardless.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vanadium", "supplementBName": "Fenugreek", "interactionType": "caution", "severity": "moderate", "description": "Taken together, vanadium and fenugreek produce an additive blood-glucose-lowering effect documented in experimental diabetic models, where their combination reversed diabetic changes at biochemical and molecular levels (including GLUT4 and insulin endpoints). A useful secondary finding is that adding fenugreek significantly reduced vanadium's toxicity while preserving the glucose-lowering action. The main caution is the stacked hypoglycemic potential, which becomes clinically important when either supplement is layered onto glucose-lowering medication.", "recommendation": "If you use both for glucose support, monitor blood glucose, especially when starting, changing doses, or if you also take metformin, a sulfonylurea, or insulin, where the combined effect raises hypoglycemia risk. Watch for shakiness, sweating, or lightheadedness. Keep vanadium modest (most glucose protocols stay well under 25 mg elemental daily and are time-limited) and use typical fenugreek seed doses (roughly 5 to 10 g of seed powder or standardized equivalents with meals). Anyone on diabetes medication should involve their clinician before combining, since medication doses may need adjustment.", "minimumTimeSeparation": "No strict separation needed; the concern is cumulative daily glucose lowering rather than co-ingestion, so monitor overall daily effect", "mechanism": "Both agents lower blood glucose through complementary routes that stack. Vanadium (as vanadyl or vanadate) acts as an insulin mimetic, inhibiting protein tyrosine phosphatases such as PTP-1B in the insulin signaling cascade and promoting GLUT4 translocation. Fenugreek lowers postprandial glucose by slowing gastric emptying and reducing intestinal glucose uptake via its galactomannan fiber, and its 4-hydroxyisoleucine content stimulates glucose-dependent insulin secretion, with additional insulin-mimetic activity reported in diabetic tissue models. Animal work combining the two shows additive glucose lowering, and notably fenugreek also blunts vanadium's toxicity in those models.", "evidenceLevel": "emerging", "sources": [ { "text": "Baquer NZ and colleagues. Metabolic and molecular action of Trigonella foenum-graecum (fenugreek) and trace metals in experimental diabetic tissues. J Biosci. 2011.", "pmid": "21654091", "doi": "10.1007/s12038-011-9042-0", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21654091/", "publicSourceType": "PMID" }, { "text": "Pharmacology reviews of vanadium as an insulin mimetic via PTP-1B inhibition and GLUT4 translocation.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Systematic reviews and meta-analyses of fenugreek for glycemic control in type 2 diabetes.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Taken together, vanadium and fenugreek produce an additive blood-glucose-lowering effect documented in experimental diabetic models, where their combination reversed diabetic changes at biochemical and molecular levels (including GLUT4 and insulin endpoints). A useful secondary finding is that adding fenugreek significantly reduced vanadium's toxicity while preserving the glucose-lowering action. The main caution is the stacked hypoglycemic potential, which becomes clinically important when either supplement is layered onto glucose-lowering medication.", "clinicalSignificance": "Most relevant for people with insulin resistance or type 2 diabetes who stack botanical and trace-mineral glucose support. The additive hypoglycemic effect is real but generally manageable with monitoring in people not on medication; risk rises to clinically meaningful when combined with pharmacologic glucose-lowering therapy. The fenugreek-driven reduction in vanadium toxicity is a favorable aspect of the pairing.", "managementStrategy": "If you use both for glucose support, monitor blood glucose, especially when starting, changing doses, or if you also take metformin, a sulfonylurea, or insulin, where the combined effect raises hypoglycemia risk. Watch for shakiness, sweating, or lightheadedness. Keep vanadium modest (most glucose protocols stay well under 25 mg elemental daily and are time-limited) and use typical fenugreek seed doses (roughly 5 to 10 g of seed powder or standardized equivalents with meals). Anyone on diabetes medication should involve their clinician before combining, since medication doses may need adjustment.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin B3", "supplementBName": "Chromium", "interactionType": "synergy", "severity": "info", "description": "Combining niacin with chromium has been studied as a way to improve glucose handling. Controlled work in older adults found that niacin-bound or co-administered chromium produced greater improvements in glucose tolerance than chromium without niacin, consistent with niacin acting as part of the active chromium-nicotinate complex. This is generally a beneficial, additive relationship rather than a risk.", "recommendation": "For people specifically targeting glucose metabolism, taking chromium (typically 200 to 1000 mcg/day) together with a modest niacin intake is reasonable and may modestly enhance chromium's glucose effect. No timing separation is needed; they can be taken in the same dose. People on diabetes medication should monitor blood glucose, since improved glucose handling can add to the effect of those drugs.", "minimumTimeSeparation": "None required; can be taken together", "mechanism": "Niacin (nicotinic acid) is a structural component of the biologically active chromium complex historically described as the glucose tolerance factor. In this role niacin appears to help chromium potentiate insulin signaling and improve cellular glucose uptake. The two nutrients act on the same insulin-sensitivity pathway rather than competing, so co-administration can enhance chromium's effect on glucose tolerance beyond chromium given alone.", "evidenceLevel": "emerging", "sources": [ { "text": "Urberg M, Zemel MB. Evidence for synergism between chromium and nicotinic acid in the control of glucose tolerance in elderly humans. Metabolism, 1987.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Reviews of chromium and the glucose tolerance factor in trace element nutrition and insulin sensitivity literature.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Combining niacin with chromium has been studied as a way to improve glucose handling. Controlled work in older adults found that niacin-bound or co-administered chromium produced greater improvements in glucose tolerance than chromium without niacin, consistent with niacin acting as part of the active chromium-nicotinate complex. This is generally a beneficial, additive relationship rather than a risk.", "clinicalSignificance": "Largely favorable and low-risk. The main practical caution is additive glucose-lowering in those already on antidiabetic therapy, where monitoring prevents hypoglycemia.", "managementStrategy": "For people specifically targeting glucose metabolism, taking chromium (typically 200 to 1000 mcg/day) together with a modest niacin intake is reasonable and may modestly enhance chromium's glucose effect. No timing separation is needed; they can be taken in the same dose. People on diabetes medication should monitor blood glucose, since improved glucose handling can add to the effect of those drugs.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin B3", "supplementBName": "L-Tryptophan", "interactionType": "synergy", "severity": "info", "description": "Tryptophan and niacin are linked through a single biosynthetic pathway. Supplemental tryptophan contributes to niacin/NAD+ status, and conversely, ensuring sufficient niacin reduces the diversion of tryptophan into niacin synthesis, leaving more tryptophan for serotonin production. This shared-pathway relationship is a well-established principle in nutrition science and is the basis for expressing niacin needs as niacin equivalents that include tryptophan.", "recommendation": "No avoidance is needed; the relationship is generally complementary. If using L-Tryptophan (commonly 500 mg to 2000 mg, often at night for mood or sleep support), maintaining adequate niacin intake helps preserve tryptophan for serotonin synthesis. Cofactors for the conversion (vitamin B6, vitamin B2) should also be sufficient. They can be taken together; tryptophan is often dosed away from high-protein meals to aid uptake, which is a separate practical consideration.", "minimumTimeSeparation": "None required; can be taken together", "mechanism": "L-Tryptophan is the dietary precursor for endogenous niacin: the body converts tryptophan to nicotinic acid mononucleotide and ultimately NAD+ via the kynurenine pathway, with roughly 60 mg of tryptophan yielding about 1 mg of niacin equivalent. Both nutrients therefore feed the same NAD+ pool. Adequate tryptophan can spare dietary niacin (and historically prevents pellagra), while heavy niacin intake can shift tryptophan availability toward serotonin synthesis by reducing the demand to route tryptophan down the niacin-synthesis arm of the kynurenine pathway.", "evidenceLevel": "moderate", "sources": [ { "text": "Standard nutrition biochemistry texts describing the kynurenine pathway and the 60:1 tryptophan-to-niacin conversion ratio (niacin equivalents).", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Reviews of tryptophan metabolism, NAD+ biosynthesis, and pellagra prevention in human nutrition literature.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Tryptophan and niacin are linked through a single biosynthetic pathway. Supplemental tryptophan contributes to niacin/NAD+ status, and conversely, ensuring sufficient niacin reduces the diversion of tryptophan into niacin synthesis, leaving more tryptophan for serotonin production. This shared-pathway relationship is a well-established principle in nutrition science and is the basis for expressing niacin needs as niacin equivalents that include tryptophan.", "clinicalSignificance": "Low clinical risk and mostly informational. The practical takeaway is that niacin and tryptophan jointly determine niacin/NAD+ status and that niacin sufficiency helps spare tryptophan for serotonin.", "managementStrategy": "No avoidance is needed; the relationship is generally complementary. If using L-Tryptophan (commonly 500 mg to 2000 mg, often at night for mood or sleep support), maintaining adequate niacin intake helps preserve tryptophan for serotonin synthesis. Cofactors for the conversion (vitamin B6, vitamin B2) should also be sufficient. They can be taken together; tryptophan is often dosed away from high-protein meals to aid uptake, which is a separate practical consideration.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin B7", "supplementBName": "Vitamin B5", "interactionType": "timingSensitive", "severity": "info", "description": "Both vitamins ride the same SMVT carrier in the gut and at the cellular level, so they are direct competitive substrates. Cell and transfected-cell studies confirm pantothenic acid competitively inhibits biotin uptake (and vice versa), but under ordinary dietary and physiological intakes the inhibition is quantitatively minor. The interaction becomes theoretically more relevant only at the gram-level mega-doses sometimes found in standalone supplements, where one vitamin in large excess could blunt uptake of the other taken at the same moment.", "recommendation": "No avoidance is needed for normal multivitamin-level intakes (biotin a few hundred mcg, B5 a few to tens of mg), where both are absorbed adequately together. If you are taking high standalone doses of one (for example, biotin 5,000 to 10,000 mcg for hair and nails, or pantothenic acid 500 mg or more), separate the two by about 2 to 3 hours to avoid same-dose transporter competition and to maximize uptake of each.", "minimumTimeSeparation": "2 to 3 hours when either is taken at high (gram-level or several-hundred-mg) doses", "mechanism": "Biotin (vitamin B7) and pantothenic acid (vitamin B5) are both substrates of the same intestinal and cellular carrier, the human sodium-dependent multivitamin transporter (hSMVT, encoded by SLC5A6). Because they share this single transport route, the two vitamins compete for uptake: a large surplus of one can partially saturate the transporter and modestly reduce absorption of the other. The competition is reciprocal at the transporter level.", "evidenceLevel": "moderate", "sources": [ { "text": "Linus Pauling Institute, Oregon State University, Micronutrient Information Center: Biotin (nutrient interactions section noting that pantothenic acid and lipoic acid compete with biotin for the sodium-dependent multivitamin transporter)", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Reviews on cellular and molecular aspects of human intestinal biotin absorption describing the SMVT system shared by biotin, pantothenic acid, and lipoate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Studies on the sodium-dependent multivitamin transporter (SLC5A6) showing competitive uptake of biotin and pantothenic acid, where a surplus of one substrate can saturate the transporter and reduce uptake of the others", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Both vitamins ride the same SMVT carrier in the gut and at the cellular level, so they are direct competitive substrates. Cell and transfected-cell studies confirm pantothenic acid competitively inhibits biotin uptake (and vice versa), but under ordinary dietary and physiological intakes the inhibition is quantitatively minor. The interaction becomes theoretically more relevant only at the gram-level mega-doses sometimes found in standalone supplements, where one vitamin in large excess could blunt uptake of the other taken at the same moment.", "clinicalSignificance": "Low practical significance for the general user; the shared-transporter competition is well established mechanistically but only minor at usual doses. Worth flagging for people stacking high-dose single-vitamin products so they can space them and not undercut absorption of either.", "managementStrategy": "No avoidance is needed for normal multivitamin-level intakes (biotin a few hundred mcg, B5 a few to tens of mg), where both are absorbed adequately together. If you are taking high standalone doses of one (for example, biotin 5,000 to 10,000 mcg for hair and nails, or pantothenic acid 500 mg or more), separate the two by about 2 to 3 hours to avoid same-dose transporter competition and to maximize uptake of each.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin D2", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "info", "description": "Magnesium is required for the body to convert Vitamin D2 into its biologically active form. With low magnesium status, supplemental D2 is metabolized less efficiently, so correcting magnesium can improve the response to vitamin D supplementation.", "recommendation": "Ensure adequate magnesium status (roughly 200 to 400 mg elemental magnesium daily from diet plus supplement) when supplementing Vitamin D2, especially at higher D2 doses. No timing separation is needed; both can be taken with a meal. If vitamin D levels respond poorly to supplementation, check and correct magnesium first.", "minimumTimeSeparation": "None required; can be taken together.", "mechanism": "Magnesium is an obligate cofactor for the enzymes that activate vitamin D2 (ergocalciferol). Both the hepatic 25-hydroxylase (CYP2R1) that converts ergocalciferol to 25-hydroxyvitamin D and the renal 1-alpha-hydroxylase (CYP27B1) that produces the active hormone 1,25-dihydroxyvitamin D are magnesium-dependent, as is the vitamin D binding protein that transports it. Magnesium insufficiency therefore blunts conversion of supplemental D2 into its active form, so raw blood levels can rise without a proportional functional response.", "evidenceLevel": "strong", "sources": [ { "text": "Uwitonze AM, Razzaque MS. Role of Magnesium in Vitamin D Activation and Function. Journal of the American Osteopathic Association, 2018.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Reddy P, Edwards LR. Magnesium Supplementation in Vitamin D Deficiency. American Journal of Therapeutics, 2019.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Dai Q, et al. Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial. American Journal of Clinical Nutrition, 2018.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Magnesium is required for the body to convert Vitamin D2 into its biologically active form. With low magnesium status, supplemental D2 is metabolized less efficiently, so correcting magnesium can improve the response to vitamin D supplementation.", "clinicalSignificance": "Inadequate magnesium can leave supplemental Vitamin D2 underutilized despite dosing, which matters most for people with documented deficiency or malabsorption. Co-adequacy is supportive rather than hazardous.", "managementStrategy": "Ensure adequate magnesium status (roughly 200 to 400 mg elemental magnesium daily from diet plus supplement) when supplementing Vitamin D2, especially at higher D2 doses. No timing separation is needed; both can be taken with a meal. If vitamin D levels respond poorly to supplementation, check and correct magnesium first.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Vitamin D2", "supplementBName": "Calcium", "interactionType": "timingSensitive", "severity": "moderate", "description": "Vitamin D2 increases how much dietary and supplemental calcium the gut absorbs, which is beneficial for bone health at sensible doses but can become problematic when both are taken in large amounts together, raising the risk of hypercalcemia and kidney stones.", "recommendation": "Pairing modest doses is appropriate for bone health: keep total supplemental calcium around 500 to 1000 mg/day (split into 500 mg doses with food for absorption) alongside standard D2 dosing. Avoid combining high-dose D2 with high-dose calcium without monitoring. Anyone on large D2 doses plus calcium, or with a history of kidney stones, hyperparathyroidism, or sarcoidosis, should have serum and urinary calcium checked periodically. Watch for nausea, excessive thirst, frequent urination, or confusion as signs of hypercalcemia.", "minimumTimeSeparation": "No separation needed; taking together with food actually aids calcium absorption. The concern is total combined dose, not timing.", "mechanism": "Active vitamin D, produced from supplemental ergocalciferol (D2), upregulates intestinal calcium absorption by inducing the transient receptor potential channel TRPV6 and the binding protein calbindin in enterocytes, and it also increases renal calcium reabsorption. This is the intended physiological synergy for bone health, but it means high-dose D2 amplifies how much supplemental calcium is absorbed. At supraphysiologic combined intakes the additive effect can push serum calcium upward, with documented risk of hypercalcemia, hypercalciuria, and kidney stones.", "evidenceLevel": "strong", "sources": [ { "text": "Christakos S, et al. Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects. Physiol Rev. 2016.", "pmid": "26681795", "doi": "10.1152/physrev.00014.2015", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26681795/", "publicSourceType": "PMID" }, { "text": "Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. . 2011.", "pmid": "21796828", "doi": "10.17226/13050", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21796828/", "publicSourceType": "PMID" }, { "text": "National Institutes of Health, Office of Dietary Supplements. Calcium and Vitamin D Fact Sheets for Health Professionals.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Vitamin D2 increases how much dietary and supplemental calcium the gut absorbs, which is beneficial for bone health at sensible doses but can become problematic when both are taken in large amounts together, raising the risk of hypercalcemia and kidney stones.", "clinicalSignificance": "At ordinary supplemental doses this is a desirable synergy for bone health. The clinical concern arises only with combined high doses or in predisposed individuals, where additive calcium loading can cause hypercalcemia and stone formation, making it a dose-dependent caution rather than a routine contraindication.", "managementStrategy": "Pairing modest doses is appropriate for bone health: keep total supplemental calcium around 500 to 1000 mg/day (split into 500 mg doses with food for absorption) alongside standard D2 dosing. Avoid combining high-dose D2 with high-dose calcium without monitoring. Anyone on large D2 doses plus calcium, or with a history of kidney stones, hyperparathyroidism, or sarcoidosis, should have serum and urinary calcium checked periodically. Watch for nausea, excessive thirst, frequent urination, or confusion as signs of hypercalcemia.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "supplement-supplement" }, { "supplementAName": "Boron", "supplementBName": "DHEA", "interactionType": "caution", "severity": "moderate", "description": "Both boron and DHEA can independently raise circulating androgen and estrogen levels. Boron tends to increase free testosterone and estradiol (in part by lowering SHBG), while DHEA serves as a direct precursor that the body converts into those same hormones. Stacking them can produce a larger combined rise in sex hormones than either alone, which is desirable for some users but can also amplify estrogen-related or androgen-related side effects.", "recommendation": "If stacking, start DHEA at the lowest effective dose (commonly 10 to 25 mg/day) rather than higher doses, and keep boron in the typical supplemental range (around 3 to 10 mg/day). Consider monitoring testosterone, estradiol, and SHBG if using both for more than a few weeks, especially in hormone-sensitive individuals. Women, anyone with a history of hormone-sensitive conditions (breast, ovarian, uterine, or prostate concerns), and those on hormone therapy should consult a clinician before combining. There is no need to separate the doses by time; the consideration is cumulative hormonal effect, not absorption.", "minimumTimeSeparation": null, "mechanism": "Boron supplementation has been shown in small human studies to raise circulating sex steroid hormones, with reported increases in free testosterone and estradiol attributed partly to reduced sex hormone binding globulin (SHBG) and altered steroid hormone metabolism and clearance. DHEA is an upstream adrenal precursor that converts to testosterone and estradiol via peripheral steroidogenesis. Acting on the same steroidogenic pathway from different points, their effects on downstream androgens and estrogens tend to be additive rather than independent.", "evidenceLevel": "emerging", "sources": [ { "text": "Naghii MR, Samman S. The effect of boron supplementation on the distribution of boron in selected tissues and on testosterone and plasma lipids. Biological Trace Element Research, 1997.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "text": "Naghii MR, Mofid M, Asgari AR, et al. Comparative effects of daily and weekly boron supplementation on plasma steroid hormones and proinflammatory cytokines. J Trace Elem Med Biol. 2011.", "pmid": "21129941", "doi": "10.1016/j.jtemb.2010.10.001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21129941/", "publicSourceType": "PMID" }, { "text": "Nielsen FH. Biochemical and physiologic consequences of boron deprivation in humans. Environ Health Perspect. 1994.", "pmid": "7889883", "doi": "10.1289/ehp.94102s759", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7889883/", "publicSourceType": "PMID" }, { "text": "Endocrinology reviews describing DHEA as an adrenal precursor undergoing peripheral conversion to testosterone and estradiol.", "publicReviewStatus": "needs-source", "publicSourceType": "No link" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both boron and DHEA can independently raise circulating androgen and estrogen levels. Boron tends to increase free testosterone and estradiol (in part by lowering SHBG), while DHEA serves as a direct precursor that the body converts into those same hormones. Stacking them can produce a larger combined rise in sex hormones than either alone, which is desirable for some users but can also amplify estrogen-related or androgen-related side effects.", "clinicalSignificance": "Most relevant for people already taking DHEA for hormonal support, or those using boron to nudge free testosterone. The combined effect is usually modest but can matter in hormone-sensitive populations where any additive estrogen or androgen elevation is undesirable.", "managementStrategy": "If stacking, start DHEA at the lowest effective dose (commonly 10 to 25 mg/day) rather than higher doses, and keep boron in the typical supplemental range (around 3 to 10 mg/day). Consider monitoring testosterone, estradiol, and SHBG if using both for more than a few weeks, especially in hormone-sensitive individuals. Women, anyone with a history of hormone-sensitive conditions (breast, ovarian, uterine, or prostate concerns), and those on hormone therapy should consult a clinician before combining. There is no need to separate the doses by time; the consideration is cumulative hormonal effect, not absorption.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "supplement-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Vitamin K2", "interactionType": "conflict", "severity": "serious", "description": "Vitamin K2 directly opposes warfarin's mechanism of action. Warfarin works by inhibiting vitamin K-dependent clotting factor synthesis, so supplemental vitamin K2 can restore clotting factor production and significantly reduce warfarin's anticoagulant effect. Even small, consistent doses of K2 can shift INR values unpredictably.", "recommendation": "Avoid vitamin K2 supplementation while on warfarin unless directed and closely monitored by your prescriber. If K2 is deemed necessary, maintain a very consistent daily dose and monitor INR frequently.", "minimumTimeSeparation": null, "mechanism": "Warfarin inhibits vitamin K epoxide reductase (VKORC1), preventing recycling of vitamin K needed for gamma-carboxylation of clotting factors II, VII, IX, and X. Exogenous vitamin K2 bypasses this inhibition by providing substrate directly.", "evidenceLevel": "strong", "sources": [ { "text": "Booth SL, Centurelli MA. Vitamin K: a practical guide to the dietary management of patients on warfarin. Nutr Rev. 1999;57(9):288-296.", "pmid": "10568341", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10568341/", "publicSourceType": "PMID" }, { "text": "Shearer MJ, Newman P. Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis. J Lipid Res. 2014;55(3):345-362.", "pmid": "24489112", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24489112/", "publicSourceType": "PMID" }, { "text": "Wang M, Zeraatkar D, Obeda M, Lee M et al.. Drug-drug interactions with warfarin: A systematic review and meta-analysis. British Journal of Clinical Pharmacology. 2021.", "pmid": "33769581", "doi": "10.1111/bcp.14833", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33769581/", "publicSourceType": "PMID" }, { "text": "Ma ML, Ma ZJ, He YL et al.. Efficacy of vitamin K2 in the prevention and treatment of postmenopausal osteoporosis: A systematic review and meta-analysis of randomized controlled trials. Frontiers in Public Health. 2022.", "pmid": "36033779", "doi": "10.3389/fpubh.2022.979649", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36033779/", "publicSourceType": "PMID" }, { "text": "Kuang X, Liu C, Guo X, Li K, Deng Q, Li D. The combination effect of vitamin K and vitamin D on human bone quality: a meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "32219282", "doi": "10.1039/c9fo03063h", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32219282/", "publicSourceType": "PMID" }, { "text": "Zhou M, Han S, Zhang W, Wu D. Efficacy and safety of vitamin K2 for postmenopausal women with osteoporosis at a long-term follow-up: meta-analysis and systematic review. Journal of Bone and Mineral Metabolism. 2022.", "pmid": "35711002", "doi": "10.1007/s00774-022-01342-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35711002/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Vitamin K2 directly opposes warfarin's mechanism of action.", "clinicalSignificance": "Warfarin works by inhibiting vitamin K-dependent clotting factor synthesis, so supplemental vitamin K2 can restore clotting factor production and significantly reduce warfarin's anticoagulant effect.", "managementStrategy": "Avoid vitamin K2 supplementation while on warfarin unless directed and closely monitored by your prescriber. If K2 is deemed necessary, maintain a very consistent daily dose and monitor INR frequently.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Vitamin E", "interactionType": "caution", "severity": "moderate", "description": "High-dose vitamin E may potentiate warfarin's anticoagulant effect and increase bleeding risk. Vitamin E at high supplemental doses can interfere with vitamin K-dependent clotting and inhibit platelet aggregation.", "recommendation": "Do not start, stop, or increase vitamin E while taking warfarin without discussing it with the anticoagulation clinic or prescriber. Report unusual bruising or bleeding promptly.", "minimumTimeSeparation": null, "mechanism": "High-dose vitamin E inhibits vitamin K-dependent carboxylase, reducing production of functional clotting factors. It also has antiplatelet activity by inhibiting platelet adhesion and aggregation through interference with thromboxane synthesis.", "evidenceLevel": "moderate", "sources": [ { "text": "Corrigan JJ Jr, Marcus FI. Coagulopathy associated with vitamin E ingestion. JAMA. 1974;230(9):1300-1301.", "pmid": "4479597", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/4479597/", "publicSourceType": "PMID" }, { "text": "Booth SL et al. Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. Am J Clin Nutr. 2004;80(1):143-148.", "pmid": "15213041", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15213041/", "publicSourceType": "PMID" }, { "text": "Wang M, Zeraatkar D, Obeda M, Lee M et al.. Drug-drug interactions with warfarin: A systematic review and meta-analysis. British Journal of Clinical Pharmacology. 2021.", "pmid": "33769581", "doi": "10.1111/bcp.14833", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33769581/", "publicSourceType": "PMID" }, { "text": "Xia J, Yu J, Xu H et al.. Comparative effects of vitamin and mineral supplements in the management of type 2 diabetes in primary care: A systematic review and network meta-analysis of randomized controlled trials. Pharmacological Research. 2023.", "pmid": "36638933", "doi": "10.1016/j.phrs.2023.106647", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36638933/", "publicSourceType": "PMID" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" }, { "text": "Berger MM, Shenkin A, Schweinlin A et al.. ESPEN micronutrient guideline. Clinical Nutrition. 2022.", "pmid": "35365361", "doi": "10.1016/j.clnu.2022.02.015", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35365361/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose vitamin E may potentiate warfarin's anticoagulant effect and increase bleeding risk.", "clinicalSignificance": "Vitamin E at high doses can interfere with vitamin K-dependent clotting and inhibit platelet aggregation.", "managementStrategy": "Coordinate any vitamin E supplement changes with the anticoagulation clinic or prescriber; report unusual bruising or bleeding promptly.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Fish Oil", "interactionType": "caution", "severity": "moderate", "description": "Fish oil may potentiate warfarin's anticoagulant effect through its own antiplatelet and antithrombotic properties. While moderate doses (1-2g/day) appear relatively safe, higher doses can increase bleeding time and potentially elevate INR. Clinical bleeding events have been reported in case studies.", "recommendation": "If combining fish oil with warfarin, start with low doses (1g/day or less) and monitor INR closely during the first few weeks. Report any signs of unusual bleeding or bruising to your healthcare provider.", "minimumTimeSeparation": null, "mechanism": "EPA and DHA reduce platelet aggregation by competing with arachidonic acid for cyclooxygenase, decreasing thromboxane A2 production. They also reduce blood viscosity and may modestly affect vitamin K-dependent coagulation factors.", "evidenceLevel": "moderate", "sources": [ { "text": "Buckley MS, Goff AD, Knapp WE. Fish oil interaction with warfarin. Ann Pharmacother. 2004;38(1):50-52.", "pmid": "14742793", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14742793/", "publicSourceType": "PMID" }, { "text": "Bays HE. Safety considerations with omega-3 fatty acid therapy. Am J Cardiol. 2007;99(6A):35C-43C.", "pmid": "17368277", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17368277/", "publicSourceType": "PMID" }, { "text": "Wang M, Zeraatkar D, Obeda M, Lee M et al.. Drug-drug interactions with warfarin: A systematic review and meta-analysis. British Journal of Clinical Pharmacology. 2021.", "pmid": "33769581", "doi": "10.1111/bcp.14833", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33769581/", "publicSourceType": "PMID" }, { "text": "Liao Y, Xie B, Zhang H et al.. Efficacy of omega-3 PUFAs in depression: A meta-analysis.. Translational Psychiatry. 2019.", "pmid": "31383846", "doi": "10.1038/s41398-019-0515-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31383846/", "publicSourceType": "PMID" }, { "text": "Wei BZ, Li L, Dong CW et al.. The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers.. American Journal of Clinical Nutrition. 2023.", "pmid": "37028557", "doi": "10.1016/j.ajcnut.2023.04.001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37028557/", "publicSourceType": "PMID" }, { "text": "Uchida Y, Tsuji K, Ochi E. Effects of Omega-3 fatty acids supplementation and resistance training on skeletal muscle.. Clinical Nutrition ESPEN. 2024.", "pmid": "38777432", "doi": "10.1016/j.clnesp.2024.03.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38777432/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Fish oil may potentiate warfarin's anticoagulant effect through its own antiplatelet and antithrombotic properties.", "clinicalSignificance": "While moderate doses (1-2g/day) appear relatively safe, higher doses can increase bleeding time and potentially elevate INR.", "managementStrategy": "If combining fish oil with warfarin, start with low doses (1g/day or less) and monitor INR closely during the first few weeks. Report any signs of unusual bleeding or bruising to your healthcare provider.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Garlic Extract", "interactionType": "caution", "severity": "moderate", "description": "Garlic supplements possess antiplatelet properties that may increase bleeding risk when combined with warfarin. Several case reports have documented elevated INR and bleeding episodes in patients taking garlic supplements with warfarin. The effect is more pronounced with concentrated garlic extracts than with culinary amounts.", "recommendation": "Avoid concentrated garlic supplements while on warfarin. Moderate culinary use of garlic is generally safe. If you use garlic supplements, inform your prescriber and monitor INR more frequently.", "minimumTimeSeparation": null, "mechanism": "Allicin and ajoene in garlic inhibit platelet aggregation via multiple mechanisms including thromboxane synthesis inhibition, phospholipase activity modulation, and calcium mobilization interference in platelets.", "evidenceLevel": "moderate", "sources": [ { "text": "Macan H et al. Aged garlic extract may be safe for patients on warfarin therapy. J Nutr. 2006;136(3 Suppl):793S-795S.", "pmid": "16484565", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16484565/", "publicSourceType": "PMID" }, { "text": "Scharbert G et al. Garlic at dietary doses does not impair platelet function. Anesth Analg. 2007;105(5):1214-1218.", "pmid": "17959944", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17959944/", "publicSourceType": "PMID" }, { "text": "Wang M, Zeraatkar D, Obeda M, Lee M et al.. Drug-drug interactions with warfarin: A systematic review and meta-analysis. British Journal of Clinical Pharmacology. 2021.", "pmid": "33769581", "doi": "10.1111/bcp.14833", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33769581/", "publicSourceType": "PMID" }, { "text": "Saadh MJ, Kariem M, Shukla M et al.. Effects of aged garlic extract on blood pressure in hypertensive patients: A systematic review and meta-analysis of randomized controlled trials. Prostaglandins & Other Lipid Mediators. 2024.", "pmid": "39437887", "doi": "10.1016/j.prostaglandins.2024.106914", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39437887/", "publicSourceType": "PMID" }, { "text": "Gadidala SK, Johny E, Thomas C et al.. Effect of garlic extract on markers of lipid metabolism and inflammation in coronary artery disease (CAD) patients: A systematic review and meta-analysis. Phytotherapy Research. 2023.", "pmid": "36640154", "doi": "10.1002/ptr.7729", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36640154/", "publicSourceType": "PMID" }, { "text": "Mirzavandi F, Mollahosseini M, Salehi-Abargouei A et al.. Effects of garlic supplementation on serum inflammatory markers: A systematic review and meta-analysis of randomized controlled trials. Diabetes & Metabolic Syndrome. 2020.", "pmid": "32673835", "doi": "10.1016/j.dsx.2020.06.031", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32673835/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Garlic supplements possess antiplatelet properties that may increase bleeding risk when combined with warfarin.", "clinicalSignificance": "Several case reports have documented elevated INR and bleeding episodes in patients taking garlic supplements with warfarin.", "managementStrategy": "Avoid concentrated garlic supplements while on warfarin. Moderate culinary use of garlic is generally safe. If you use garlic supplements, inform your prescriber and monitor INR more frequently.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Ginkgo Biloba", "interactionType": "caution", "severity": "serious", "description": "Ginkgo biloba has significant antiplatelet activity that increases bleeding risk when combined with warfarin. Multiple case reports document serious bleeding events including subdural hematoma, intracerebral hemorrhage, and hyphema in patients taking ginkgo with warfarin or other anticoagulants.", "recommendation": "Avoid ginkgo biloba while taking warfarin. If already taking both, consult your prescriber about discontinuing ginkgo and monitor INR closely during any changes.", "minimumTimeSeparation": null, "mechanism": "Ginkgolide B is a potent platelet-activating factor (PAF) antagonist that inhibits platelet aggregation. Combined with warfarin's anticoagulant effect, this creates additive risk through both coagulation cascade inhibition and impaired platelet function.", "evidenceLevel": "moderate", "sources": [ { "text": "Bent S et al. The relative safety of ephedra compared with other herbal products. Ann Intern Med. 2003;138(6):468-471.", "pmid": "12639079", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12639079/", "publicSourceType": "PMID" }, { "text": "Rosenblatt M, Mindel J. Spontaneous hyphema associated with ingestion of Ginkgo biloba extract. N Engl J Med. 1997;336(15):1108.", "pmid": "9091812", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9091812/", "publicSourceType": "PMID" }, { "text": "Wang M, Zeraatkar D, Obeda M, Lee M et al.. Drug-drug interactions with warfarin: A systematic review and meta-analysis. British Journal of Clinical Pharmacology. 2021.", "pmid": "33769581", "doi": "10.1111/bcp.14833", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33769581/", "publicSourceType": "PMID" }, { "text": "Mousavi SN, Hosseinikia M, Yousefi Rad E, Saboori S. Beneficial effects of Ginkgo biloba leaf extract on inflammatory markers: A systematic review and meta-analysis of the clinical trials. Phytotherapy Research. 2022.", "pmid": "35781715", "doi": "10.1002/ptr.7544", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35781715/", "publicSourceType": "PMID" }, { "text": "Tabrizi R, Nowrouzi-Sohrabi P, Hessami K et al.. Effects of Ginkgo biloba intake on cardiometabolic parameters in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of clinical trials. Phytotherapy Research. 2020.", "pmid": "33090588", "doi": "10.1002/ptr.6822", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33090588/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Ginkgo biloba has significant antiplatelet activity that increases bleeding risk when combined with warfarin.", "clinicalSignificance": "Multiple case reports document serious bleeding events including subdural hematoma, intracerebral hemorrhage, and hyphema in patients taking ginkgo with warfarin or other anticoagulants.", "managementStrategy": "Avoid ginkgo biloba while taking warfarin. If already taking both, consult your prescriber about discontinuing ginkgo and monitor INR closely during any changes.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Turmeric/Curcumin", "interactionType": "caution", "severity": "moderate", "description": "Curcumin may inhibit platelet aggregation and has shown anticoagulant properties in vitro and in animal studies. When combined with warfarin, there is a theoretical and clinically reported risk of enhanced anticoagulation and bleeding. Case reports have documented elevated INR in patients adding turmeric to warfarin therapy.", "recommendation": "Use caution when combining turmeric/curcumin supplements with warfarin. Culinary turmeric in food is generally safe, but concentrated curcumin supplements should be discussed with your prescriber. Monitor INR if adding or removing curcumin.", "minimumTimeSeparation": null, "mechanism": "Curcumin inhibits platelet aggregation by blocking thromboxane A2 synthesis and calcium signaling in platelets. It may also inhibit CYP1A2 and CYP2C9 enzymes involved in warfarin metabolism, potentially increasing warfarin plasma concentrations.", "evidenceLevel": "moderate", "sources": [ { "text": "Shah BH et al. Inhibitory effect of curcumin on platelet aggregation. Biochem Pharmacol. 1999;58(7):1167-1172.", "pmid": "10484074", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10484074/", "publicSourceType": "PMID" }, { "text": "Kim DC et al. Curcumin inhibits warfarin metabolism by inhibiting CYP2C9. J Nat Prod. 2012.", "pmid": "22448682", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22448682/", "publicSourceType": "PMID" }, { "text": "Wang M, Zeraatkar D, Obeda M, Lee M et al.. Drug-drug interactions with warfarin: A systematic review and meta-analysis. British Journal of Clinical Pharmacology. 2021.", "pmid": "33769581", "doi": "10.1111/bcp.14833", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33769581/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Curcumin may inhibit platelet aggregation and has shown anticoagulant properties in vitro and in animal studies.", "clinicalSignificance": "When combined with warfarin, there is a theoretical and clinically reported risk of enhanced anticoagulation and bleeding.", "managementStrategy": "Use caution when combining turmeric/curcumin supplements with warfarin. Culinary turmeric in food is generally safe, but concentrated curcumin supplements should be discussed with your prescriber. Monitor INR if adding or removing curcumin.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Coenzyme Q10 Ubiquinol", "interactionType": "caution", "severity": "moderate", "description": "CoQ10 is structurally similar to vitamin K2 (both are quinones) and may partially reduce warfarin's anticoagulant effect. Several case reports have documented decreased INR values in patients who began CoQ10 supplementation while on stable warfarin therapy. The effect is generally modest but clinically relevant.", "recommendation": "If you need CoQ10 while on warfarin, start at a low dose and monitor INR closely for 2-3 weeks. Maintain a consistent daily dose to avoid INR fluctuations. Inform your prescriber about CoQ10 use.", "minimumTimeSeparation": null, "mechanism": "CoQ10 (ubiquinone) shares structural similarity with vitamin K and may have weak vitamin K-like activity, potentially promoting gamma-carboxylation of clotting factors. This can partially counteract warfarin's inhibition of vitamin K epoxide reductase.", "evidenceLevel": "moderate", "sources": [ { "text": "Spigset O. Reduced effect of warfarin caused by ubidecarenone. Lancet. 1994;344(8933):1372-1373.", "pmid": "7968050", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7968050/", "publicSourceType": "PMID" }, { "text": "Landbo C, Almdal TP. Interaction between warfarin and coenzyme Q10. Ugeskr Laeger. 1998;160(22):3226-3227.", "pmid": "9621775", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9621775/", "publicSourceType": "PMID" }, { "text": "Wang M, Zeraatkar D, Obeda M, Lee M et al.. Drug-drug interactions with warfarin: A systematic review and meta-analysis. British Journal of Clinical Pharmacology. 2021.", "pmid": "33769581", "doi": "10.1111/bcp.14833", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33769581/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "CoQ10 is structurally similar to vitamin K2 (both are quinones) and may partially reduce warfarin's anticoagulant effect.", "clinicalSignificance": "Several case reports have documented decreased INR values in patients who began CoQ10 supplementation while on stable warfarin therapy.", "managementStrategy": "If you need CoQ10 while on warfarin, start at a low dose and monitor INR closely for 2-3 weeks. Maintain a consistent daily dose to avoid INR fluctuations. Inform your prescriber about CoQ10 use.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "St. John's Wort", "interactionType": "contraindicated", "severity": "dangerous", "description": "St. John's Wort is a potent inducer of CYP3A4, CYP2C9, and P-glycoprotein, which dramatically accelerates warfarin metabolism and reduces its plasma levels. This can cause a clinically significant drop in INR, leading to loss of anticoagulant protection and potential thromboembolic events including stroke.", "recommendation": "Do not take St. John's Wort with warfarin. This is a well-established dangerous interaction. If you are currently taking both, consult your prescriber immediately, do not abruptly stop St. John's Wort as INR may rebound sharply.", "minimumTimeSeparation": null, "mechanism": "Hyperforin in St. John's Wort is a potent activator of the pregnane X receptor (PXR), which upregulates CYP3A4, CYP2C9, and P-glycoprotein expression. Both S-warfarin (CYP2C9 substrate) and R-warfarin (CYP3A4 substrate) are metabolized faster, reducing anticoagulant effect by up to 50%.", "evidenceLevel": "strong", "sources": [ { "text": "Jiang X et al. Effect of St John's wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol. 2004;57(5):592-599.", "pmid": "15089812", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15089812/", "publicSourceType": "PMID" }, { "text": "Yue QY et al. Safety of St John's wort (Hypericum perforatum). Lancet. 2000;355(9203):576-577.", "pmid": "10683750", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10683750/", "publicSourceType": "PMID" }, { "text": "Wang M, Zeraatkar D, Obeda M, Lee M et al.. Drug-drug interactions with warfarin: A systematic review and meta-analysis. British Journal of Clinical Pharmacology. 2021.", "pmid": "33769581", "doi": "10.1111/bcp.14833", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33769581/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bAffectsA", "effect": "St.", "clinicalSignificance": "John's Wort is a potent inducer of CYP3A4, CYP2C9, and P-glycoprotein, which dramatically accelerates warfarin metabolism and reduces its plasma levels.", "managementStrategy": "Do not take St. John's Wort with warfarin. This is a well-established dangerous interaction. If you are currently taking both, consult your prescriber immediately, do not abruptly stop St. John's Wort as INR may rebound sharply.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Green Tea Extract", "interactionType": "conflict", "severity": "moderate", "description": "Green tea contains vitamin K1 which can antagonize warfarin's anticoagulant effect. Concentrated green tea extract supplements provide substantially more vitamin K than brewed tea. High-dose consumption has been associated with decreased INR values in warfarin-treated patients.", "recommendation": "If taking warfarin, avoid high-dose green tea extract supplements. Moderate consumption of brewed green tea (1-2 cups/day) is generally acceptable if kept consistent. Monitor INR when changing tea consumption habits.", "minimumTimeSeparation": null, "mechanism": "Green tea leaves contain approximately 1428 mcg vitamin K per 100g dry weight. Concentrated extracts can deliver significant vitamin K doses that promote gamma-carboxylation of clotting factors, directly opposing warfarin's mechanism.", "evidenceLevel": "moderate", "sources": [ { "text": "Taylor JR, Wilt VM. Probable antagonism of warfarin by green tea. Ann Pharmacother. 1999;33(4):426-428.", "pmid": "10332534", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10332534/", "publicSourceType": "PMID" }, { "text": "Booth SL et al. Relationships between dietary intakes and fasting plasma concentrations of fat-soluble vitamins in humans. J Nutr. 1997;127(4):587-592.", "pmid": "9109608", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9109608/", "publicSourceType": "PMID" }, { "text": "Wang M, Zeraatkar D, Obeda M, Lee M et al.. Drug-drug interactions with warfarin: A systematic review and meta-analysis. British Journal of Clinical Pharmacology. 2021.", "pmid": "33769581", "doi": "10.1111/bcp.14833", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33769581/", "publicSourceType": "PMID" }, { "text": "He B, Kang S, Su R et al.. Chemoprophylaxis Effect of EGCG on the Recurrence of Colorectal Cancer: A Systematic Review and Meta-Analysis. Current Pharmaceutical Design. 2024.", "pmid": "38988171", "doi": "10.2174/0113816128319678240612114820", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38988171/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Green tea contains vitamin K1 which can antagonize warfarin's anticoagulant effect.", "clinicalSignificance": "Concentrated green tea extract supplements provide substantially more vitamin K than brewed tea.", "managementStrategy": "If taking warfarin, avoid high-dose green tea extract supplements. Moderate consumption of brewed green tea (1-2 cups/day) is generally acceptable if kept consistent. Monitor INR when changing tea consumption habits.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Apixaban", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's Wort potently induces CYP3A4 and P-glycoprotein, both of which are major pathways for apixaban metabolism and transport. This induction can reduce apixaban plasma levels by 50% or more, potentially rendering the anticoagulant ineffective and increasing the risk of thromboembolic events.", "recommendation": "Avoid combining St. John's Wort with apixaban. The FDA and EMA both list strong CYP3A4 inducers as contraindicated with DOACs. Discuss alternative mood support options with your prescriber.", "minimumTimeSeparation": null, "mechanism": "Hyperforin activates PXR, upregulating CYP3A4 and P-glycoprotein expression. Apixaban is a CYP3A4 substrate and P-gp substrate, so increased metabolism and efflux significantly reduce its bioavailability and plasma concentration.", "evidenceLevel": "strong", "sources": [ { "text": "Vakkalagadda B et al. Effect of rifampin on the pharmacokinetics of apixaban, a selective factor Xa inhibitor. Am J Ther. 2016;23(2):e460-467.", "pmid": "25756467", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25756467/", "publicSourceType": "PMID" }, { "text": "Markowitz JS, Donovan JL, DeVane CL, et al. Effect of St John's wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA. 2003;290(11):1500-1504.", "pmid": "13129991", "doi": "10.1001/jama.290.11.1500", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/13129991/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St.", "clinicalSignificance": "John's Wort potently induces CYP3A4 and P-glycoprotein, both of which are major pathways for apixaban metabolism and transport.", "managementStrategy": "Avoid combining St. John's Wort with apixaban. The FDA and EMA both list strong CYP3A4 inducers as contraindicated with DOACs. Discuss alternative mood support options with your prescriber.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Rivaroxaban", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's Wort potently induces CYP3A4 and P-glycoprotein, the primary metabolic pathways for rivaroxaban. This can substantially reduce rivaroxaban plasma concentrations, compromising anticoagulant efficacy and increasing thromboembolic risk.", "recommendation": "Avoid combining St. John's Wort with rivaroxaban. Strong CYP3A4 inducers are listed as a contraindication in rivaroxaban prescribing information. Seek alternative supplements for mood support.", "minimumTimeSeparation": null, "mechanism": "Hyperforin-mediated PXR activation upregulates CYP3A4 and P-glycoprotein. Rivaroxaban undergoes CYP3A4-mediated oxidative metabolism and P-gp-mediated intestinal efflux, so induction of both pathways substantially decreases its systemic exposure.", "evidenceLevel": "strong", "sources": [ { "text": "Markowitz JS, Donovan JL, DeVane CL, et al. Effect of St John's wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA. 2003;290(11):1500-1504.", "pmid": "13129991", "doi": "10.1001/jama.290.11.1500", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/13129991/", "publicSourceType": "PMID" }, { "text": "Mueck W et al. Clinical pharmacokinetics and pharmacodynamics of rivaroxaban. Clin Pharmacokinet. 2014;53(1):1-16.", "pmid": "23999929", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23999929/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St.", "clinicalSignificance": "John's Wort potently induces CYP3A4 and P-glycoprotein, the primary metabolic pathways for rivaroxaban.", "managementStrategy": "Avoid combining St. John's Wort with rivaroxaban. Strong CYP3A4 inducers are listed as a contraindication in rivaroxaban prescribing information. Seek alternative supplements for mood support.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Apixaban", "supplementBName": "Turmeric/Curcumin", "interactionType": "caution", "severity": "moderate", "description": "Curcumin has antiplatelet properties that may increase bleeding risk when combined with apixaban. While no direct pharmacokinetic interaction has been established, the additive effect on hemostasis through different mechanisms warrants caution.", "recommendation": "Use low-dose curcumin cautiously with apixaban. Avoid high-dose curcumin supplements. Watch for signs of unusual bleeding or bruising and report them to your healthcare provider.", "minimumTimeSeparation": null, "mechanism": "Curcumin inhibits platelet aggregation by suppressing thromboxane A2 synthesis and blocking calcium signaling. This antiplatelet effect adds to apixaban's anticoagulant activity (Factor Xa inhibition), increasing overall bleeding risk through complementary hemostatic pathways.", "evidenceLevel": "emerging", "sources": [ { "text": "Shah BH et al. Inhibitory effect of curcumin on platelet aggregation. Biochem Pharmacol. 1999;58(7):1167-1172.", "pmid": "10484074", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10484074/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Curcumin has antiplatelet properties that may increase bleeding risk when combined with apixaban.", "clinicalSignificance": "While no direct pharmacokinetic interaction has been established, the additive effect on hemostasis through different mechanisms warrants caution.", "managementStrategy": "Use low-dose curcumin cautiously with apixaban. Avoid high-dose curcumin supplements. Watch for signs of unusual bleeding or bruising and report them to your healthcare provider.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Rivaroxaban", "supplementBName": "Turmeric/Curcumin", "interactionType": "caution", "severity": "moderate", "description": "Curcumin has antiplatelet properties that may increase bleeding risk when combined with rivaroxaban. The additive effect on hemostasis through different mechanisms (antiplatelet + anticoagulant) poses a theoretical and potentially clinical risk of enhanced bleeding.", "recommendation": "Use low-dose curcumin cautiously with rivaroxaban. Avoid high-dose curcumin supplements. Monitor for signs of unusual bleeding or bruising.", "minimumTimeSeparation": null, "mechanism": "Curcumin inhibits platelet aggregation via thromboxane A2 suppression and calcium signaling blockade. Combined with rivaroxaban's Factor Xa inhibition, the dual impact on coagulation and platelet function increases bleeding risk.", "evidenceLevel": "emerging", "sources": [ { "text": "Shah BH et al. Inhibitory effect of curcumin on platelet aggregation. Biochem Pharmacol. 1999;58(7):1167-1172.", "pmid": "10484074", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10484074/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Curcumin has antiplatelet properties that may increase bleeding risk when combined with rivaroxaban.", "clinicalSignificance": "The additive effect on hemostasis through different mechanisms (antiplatelet + anticoagulant) poses a theoretical and potentially clinical risk of enhanced bleeding.", "managementStrategy": "Use low-dose curcumin cautiously with rivaroxaban. Avoid high-dose curcumin supplements. Monitor for signs of unusual bleeding or bruising.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Apixaban", "supplementBName": "Fish Oil", "interactionType": "caution", "severity": "moderate", "description": "Fish oil has antiplatelet and antithrombotic properties that may increase bleeding risk when combined with apixaban. While moderate doses are likely safe for most patients, higher doses (above 3g/day) create a more significant additive bleeding risk.", "recommendation": "Low-to-moderate dose fish oil (1-2g/day) can generally be used with apixaban under medical supervision. Avoid high doses. Report any unusual bleeding or bruising to your healthcare provider.", "minimumTimeSeparation": null, "mechanism": "EPA and DHA reduce platelet aggregation by competing with arachidonic acid for cyclooxygenase, decreasing thromboxane A2 production. This antiplatelet effect adds to apixaban's Factor Xa inhibition, creating additive bleeding risk through complementary pathways.", "evidenceLevel": "moderate", "sources": [ { "text": "Bays HE. Safety considerations with omega-3 fatty acid therapy. Am J Cardiol. 2007;99(6A):35C-43C.", "pmid": "17368277", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17368277/", "publicSourceType": "PMID" }, { "text": "Liao Y, Xie B, Zhang H et al.. Efficacy of omega-3 PUFAs in depression: A meta-analysis.. Translational Psychiatry. 2019.", "pmid": "31383846", "doi": "10.1038/s41398-019-0515-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31383846/", "publicSourceType": "PMID" }, { "text": "Wei BZ, Li L, Dong CW et al.. The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers.. American Journal of Clinical Nutrition. 2023.", "pmid": "37028557", "doi": "10.1016/j.ajcnut.2023.04.001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37028557/", "publicSourceType": "PMID" }, { "text": "Uchida Y, Tsuji K, Ochi E. Effects of Omega-3 fatty acids supplementation and resistance training on skeletal muscle.. Clinical Nutrition ESPEN. 2024.", "pmid": "38777432", "doi": "10.1016/j.clnesp.2024.03.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38777432/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Fish oil has antiplatelet and antithrombotic properties that may increase bleeding risk when combined with apixaban.", "clinicalSignificance": "While moderate doses are likely safe for most patients, higher doses (above 3g/day) create a more significant additive bleeding risk.", "managementStrategy": "Low-to-moderate dose fish oil (1-2g/day) can generally be used with apixaban under medical supervision. Avoid high doses. Report any unusual bleeding or bruising to your healthcare provider.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Rivaroxaban", "supplementBName": "Fish Oil", "interactionType": "caution", "severity": "moderate", "description": "Fish oil has antiplatelet and antithrombotic properties that may increase bleeding risk when combined with rivaroxaban. The combination creates additive hemostatic impairment through different mechanisms. Higher fish oil doses pose greater risk.", "recommendation": "Low-to-moderate dose fish oil (1-2g/day) can generally be used with rivaroxaban under medical supervision. Avoid doses above 3g/day. Monitor for signs of increased bleeding.", "minimumTimeSeparation": null, "mechanism": "EPA and DHA inhibit platelet aggregation by reducing thromboxane A2 production and altering platelet membrane fluidity. Combined with rivaroxaban's Factor Xa inhibition, the dual antiplatelet-anticoagulant effect increases overall bleeding risk.", "evidenceLevel": "moderate", "sources": [ { "text": "Bays HE. Safety considerations with omega-3 fatty acid therapy. Am J Cardiol. 2007;99(6A):35C-43C.", "pmid": "17368277", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17368277/", "publicSourceType": "PMID" }, { "text": "Liao Y, Xie B, Zhang H et al.. Efficacy of omega-3 PUFAs in depression: A meta-analysis.. Translational Psychiatry. 2019.", "pmid": "31383846", "doi": "10.1038/s41398-019-0515-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31383846/", "publicSourceType": "PMID" }, { "text": "Wei BZ, Li L, Dong CW et al.. The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers.. American Journal of Clinical Nutrition. 2023.", "pmid": "37028557", "doi": "10.1016/j.ajcnut.2023.04.001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37028557/", "publicSourceType": "PMID" }, { "text": "Uchida Y, Tsuji K, Ochi E. Effects of Omega-3 fatty acids supplementation and resistance training on skeletal muscle.. Clinical Nutrition ESPEN. 2024.", "pmid": "38777432", "doi": "10.1016/j.clnesp.2024.03.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38777432/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Fish oil has antiplatelet and antithrombotic properties that may increase bleeding risk when combined with rivaroxaban.", "clinicalSignificance": "The combination creates additive hemostatic impairment through different mechanisms.", "managementStrategy": "Low-to-moderate dose fish oil (1-2g/day) can generally be used with rivaroxaban under medical supervision. Avoid doses above 3g/day. Monitor for signs of increased bleeding.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Levothyroxine", "supplementBName": "Calcium", "interactionType": "timingSensitive", "severity": "serious", "description": "Calcium supplements significantly reduce levothyroxine absorption by 20-25% through chelation in the gastrointestinal tract. This can lead to subtherapeutic thyroid hormone levels, worsening hypothyroid symptoms, and the need for dose adjustments. The interaction is well-documented in multiple controlled studies.", "recommendation": "Separate levothyroxine and calcium by at least 4 hours. Take levothyroxine on an empty stomach in the morning, and calcium later in the day. Have TSH monitored when starting or stopping calcium supplements.", "minimumTimeSeparation": 240, "mechanism": "Calcium cations form insoluble chelate complexes with levothyroxine in the acidic environment of the stomach, preventing absorption across the intestinal mucosa. The calcium-thyroxine complex is excreted in the feces.", "evidenceLevel": "strong", "sources": [ { "text": "Singh N et al. Effect of calcium carbonate on the absorption of levothyroxine. JAMA. 2000;283(21):2822-2825.", "pmid": "10838651", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10838651/", "publicSourceType": "PMID" }, { "text": "Zamfirescu I, Carlson HE. Absorption of levothyroxine when coadministered with various calcium formulations. Thyroid. 2011;21(5):483-486.", "pmid": "21595514", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21595514/", "publicSourceType": "PMID" }, { "text": "Ross DS. Treating hypothyroidism is not always easy: When to treat subclinical hypothyroidism, TSH goals in the elderly, and alternatives to levothyroxine monotherapy. Journal of Internal Medicine. 2022.", "pmid": "34766382", "doi": "10.1111/joim.13410", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34766382/", "publicSourceType": "PMID" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Calcium supplements significantly reduce levothyroxine absorption by 20-25% through chelation in the gastrointestinal tract.", "clinicalSignificance": "This can lead to subtherapeutic thyroid hormone levels, worsening hypothyroid symptoms, and the need for dose adjustments.", "managementStrategy": "Separate levothyroxine and calcium by at least 4 hours. Take levothyroxine on an empty stomach in the morning, and calcium later in the day. Have TSH monitored when starting or stopping calcium supplements.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Levothyroxine", "supplementBName": "Iron", "interactionType": "timingSensitive", "severity": "serious", "description": "Iron supplements form an insoluble complex with levothyroxine in the GI tract, reducing thyroid hormone absorption by up to 75% in some studies. This is one of the most clinically significant absorption interactions with levothyroxine and frequently leads to treatment failure if timing is not managed.", "recommendation": "Separate levothyroxine and iron supplements by at least 4 hours. Take levothyroxine first thing in the morning on an empty stomach, and iron later in the day. Monitor TSH levels when starting or changing iron supplementation.", "minimumTimeSeparation": 240, "mechanism": "Ferrous and ferric iron ions form insoluble, non-absorbable chelate complexes with thyroxine in the stomach and duodenum. The iron-thyroxine complex passes through the GI tract without absorption.", "evidenceLevel": "strong", "sources": [ { "text": "Campbell NR et al. Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism. Ann Intern Med. 1992;117(12):1010-1013.", "pmid": "1443969", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1443969/", "publicSourceType": "PMID" }, { "text": "Shakir KM et al. Ferrous sulfate-induced increase in requirement for thyroxine in a patient with primary hypothyroidism. South Med J. 1997;90(6):637-639.", "pmid": "9191742", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9191742/", "publicSourceType": "PMID" }, { "text": "Ross DS. Treating hypothyroidism is not always easy: When to treat subclinical hypothyroidism, TSH goals in the elderly, and alternatives to levothyroxine monotherapy. Journal of Internal Medicine. 2022.", "pmid": "34766382", "doi": "10.1111/joim.13410", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34766382/", "publicSourceType": "PMID" }, { "text": "Fischer JAJ, Cherian AM, Bone JN, Karakochuk CD. The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials. Nutrition Reviews. 2023.", "pmid": "36728680", "doi": "10.1093/nutrit/nuac106", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36728680/", "publicSourceType": "PMID" }, { "text": "Rehman T, Agrawal R, Ahamed F et al.. Optimal dose and duration of iron supplementation for treating iron deficiency anaemia in children and adolescents: A systematic review and meta-analysis. PLoS One. 2025.", "pmid": "39951396", "doi": "10.1371/journal.pone.0319068", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39951396/", "publicSourceType": "PMID" }, { "text": "Gutema BT, Sorrie MB, Megersa ND et al.. Effects of iron supplementation on cognitive development in school-age children: Systematic review and meta-analysis. PLoS One. 2023.", "pmid": "37368919", "doi": "10.1371/journal.pone.0287703", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37368919/", "publicSourceType": "PMID" }, { "text": "Hansen R, Sejer EPF, Holm C, Schroll JB. Iron supplements in pregnant women with normal iron status: A systematic review and meta-analysis. Acta Obstetricia et Gynecologica Scandinavica. 2023.", "pmid": "37403900", "doi": "10.1111/aogs.14607", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37403900/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Iron supplements form an insoluble complex with levothyroxine in the GI tract, reducing thyroid hormone absorption by up to 75% in some studies.", "clinicalSignificance": "This is one of the most clinically significant absorption interactions with levothyroxine and frequently leads to treatment failure if timing is not managed.", "managementStrategy": "Separate levothyroxine and iron supplements by at least 4 hours. Take levothyroxine first thing in the morning on an empty stomach, and iron later in the day. Monitor TSH levels when starting or changing iron supplementation.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Levothyroxine", "supplementBName": "Magnesium Glycinate", "interactionType": "timingSensitive", "severity": "moderate", "description": "Magnesium supplements, particularly magnesium oxide and magnesium hydroxide (antacid forms), can reduce levothyroxine absorption by forming chelate complexes or by raising gastric pH. The magnitude of the interaction is less than calcium or iron but still clinically relevant.", "recommendation": "Separate levothyroxine and magnesium supplements by at least 4 hours. Take levothyroxine in the morning on an empty stomach, and magnesium later in the day or at bedtime.", "minimumTimeSeparation": 240, "mechanism": "Magnesium ions can form chelate complexes with levothyroxine in the GI tract, reducing absorption. Magnesium-containing antacids also raise gastric pH, which can further impair levothyroxine dissolution and absorption.", "evidenceLevel": "moderate", "sources": [ { "text": "Liwanpo L, Hershman JM. Conditions and drugs interfering with thyroxine absorption. Best Pract Res Clin Endocrinol Metab. 2009;23(6):781-792.", "pmid": "19942153", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19942153/", "publicSourceType": "PMID" }, { "text": "Ross DS. Treating hypothyroidism is not always easy: When to treat subclinical hypothyroidism, TSH goals in the elderly, and alternatives to levothyroxine monotherapy. Journal of Internal Medicine. 2022.", "pmid": "34766382", "doi": "10.1111/joim.13410", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34766382/", "publicSourceType": "PMID" }, { "text": "Mah J, Pitre T. Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis.. BMC Complementary Medicine and Therapies. 2021.", "pmid": "33865376", "doi": "10.1186/s12906-021-03297-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33865376/", "publicSourceType": "PMID" }, { "text": "Veronese N, Dominguez LJ, Pizzol D et al.. Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.. Nutrients. 2021.", "pmid": "34836329", "doi": "10.3390/nu13114074", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34836329/", "publicSourceType": "PMID" }, { "text": "Veronese N, Pizzol D, Smith L et al.. Effect of Magnesium Supplementation on Inflammatory Parameters: A Meta-Analysis of Randomized Controlled Trials.. Nutrients. 2022.", "pmid": "35277037", "doi": "10.3390/nu14030679", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35277037/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Magnesium supplements, particularly magnesium oxide and magnesium hydroxide (antacid forms), can reduce levothyroxine absorption by forming chelate complexes or by raising gastric pH.", "clinicalSignificance": "The magnitude of the interaction is less than calcium or iron but still clinically relevant.", "managementStrategy": "Separate levothyroxine and magnesium supplements by at least 4 hours. Take levothyroxine in the morning on an empty stomach, and magnesium later in the day or at bedtime.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Levothyroxine", "supplementBName": "Zinc", "interactionType": "timingSensitive", "severity": "moderate", "description": "Zinc supplements may reduce levothyroxine absorption through chelation in the gastrointestinal tract. While the evidence is less robust than for calcium or iron, divalent cations like zinc are known to interact with thyroid hormones and the interaction is clinically plausible.", "recommendation": "Separate levothyroxine and zinc supplements by at least 4 hours as a precaution. Take levothyroxine first thing in the morning on an empty stomach.", "minimumTimeSeparation": 240, "mechanism": "Zinc, as a divalent cation, can form chelate complexes with levothyroxine's phenolic and carboxylic acid groups, reducing its solubility and absorption across the intestinal mucosa.", "evidenceLevel": "emerging", "sources": [ { "text": "Liwanpo L, Hershman JM. Conditions and drugs interfering with thyroxine absorption. Best Pract Res Clin Endocrinol Metab. 2009;23(6):781-792.", "pmid": "19942153", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19942153/", "publicSourceType": "PMID" }, { "text": "Ross DS. Treating hypothyroidism is not always easy: When to treat subclinical hypothyroidism, TSH goals in the elderly, and alternatives to levothyroxine monotherapy. Journal of Internal Medicine. 2022.", "pmid": "34766382", "doi": "10.1111/joim.13410", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34766382/", "publicSourceType": "PMID" }, { "text": "Hsu TJ, Hsieh RH, Huang CH et al.. Efficacy of Zinc Supplementation in the Management of Primary Dysmenorrhea: A Systematic Review and Meta-Analysis.. Nutrients. 2024.", "pmid": "39683510", "doi": "10.3390/nu16234116", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39683510/", "publicSourceType": "PMID" }, { "text": "Ali AA, Naqvi SK, Hasnain Z et al.. Zinc supplementation for acute and persistent watery diarrhoea in children: A systematic review and meta-analysis.. Journal of Global Health. 2024.", "pmid": "39641338", "doi": "10.7189/jogh.14.04212", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39641338/", "publicSourceType": "PMID" }, { "text": "Oh C, Keats EC, Bhutta ZA. Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.. Nutrients. 2020.", "pmid": "32075071", "doi": "10.3390/nu12020491", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32075071/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Zinc supplements may reduce levothyroxine absorption through chelation in the gastrointestinal tract.", "clinicalSignificance": "While the evidence is less robust than for calcium or iron, divalent cations like zinc are known to interact with thyroid hormones and the interaction is clinically plausible.", "managementStrategy": "Separate levothyroxine and zinc supplements by at least 4 hours as a precaution. Take levothyroxine first thing in the morning on an empty stomach.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Levothyroxine", "supplementBName": "Psyllium Husk", "interactionType": "timingSensitive", "severity": "moderate", "description": "Fiber supplements, particularly psyllium, can bind levothyroxine in the gastrointestinal tract and reduce its absorption. Studies have shown that concurrent fiber intake can decrease levothyroxine bioavailability, potentially leading to subtherapeutic thyroid hormone levels.", "recommendation": "Separate levothyroxine and fiber supplements by at least 4 hours. Take levothyroxine in the morning on an empty stomach, and fiber supplements with later meals or at bedtime.", "minimumTimeSeparation": 240, "mechanism": "Psyllium and other soluble fibers form a viscous gel matrix in the GI tract that can physically trap levothyroxine, reducing its contact with the absorptive intestinal surface. The fiber-drug complex may be excreted before absorption occurs.", "evidenceLevel": "moderate", "sources": [ { "text": "Liel Y et al. Evidence for a clinically important adverse effect of fiber-enriched diet on the bioavailability of levothyroxine in adult hypothyroid patients. J Clin Endocrinol Metab. 1996;81(2):857-859.", "pmid": "8636317", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8636317/", "publicSourceType": "PMID" }, { "text": "Ross DS. Treating hypothyroidism is not always easy: When to treat subclinical hypothyroidism, TSH goals in the elderly, and alternatives to levothyroxine monotherapy. Journal of Internal Medicine. 2022.", "pmid": "34766382", "doi": "10.1111/joim.13410", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34766382/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Fiber supplements, particularly psyllium, can bind levothyroxine in the gastrointestinal tract and reduce its absorption.", "clinicalSignificance": "Studies have shown that concurrent fiber intake can decrease levothyroxine bioavailability, potentially leading to subtherapeutic thyroid hormone levels.", "managementStrategy": "Separate levothyroxine and fiber supplements by at least 4 hours. Take levothyroxine in the morning on an empty stomach, and fiber supplements with later meals or at bedtime.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Levothyroxine", "supplementBName": "Coenzyme Q10 Ubiquinol", "interactionType": "timingSensitive", "severity": "info", "description": "CoQ10 may have a minor effect on levothyroxine absorption if taken concurrently. While the interaction is not well-studied, the general recommendation for levothyroxine is to avoid taking it with any supplement to maximize absorption.", "recommendation": "As a general precaution, separate levothyroxine and CoQ10 by at least 2-4 hours. This is a conservative recommendation given levothyroxine's well-known sensitivity to co-administered substances.", "minimumTimeSeparation": 240, "mechanism": "The lipophilic nature of CoQ10 formulations may interfere with levothyroxine absorption in the GI tract. The effect is likely minor but relevant given levothyroxine's narrow therapeutic index.", "evidenceLevel": "insufficient", "sources": [ { "text": "Liwanpo L, Hershman JM. Conditions and drugs interfering with thyroxine absorption. Best Pract Res Clin Endocrinol Metab. 2009;23(6):781-792.", "pmid": "19942153", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19942153/", "publicSourceType": "PMID" }, { "text": "Ross DS. Treating hypothyroidism is not always easy: When to treat subclinical hypothyroidism, TSH goals in the elderly, and alternatives to levothyroxine monotherapy. Journal of Internal Medicine. 2022.", "pmid": "34766382", "doi": "10.1111/joim.13410", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34766382/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "CoQ10 may have a minor effect on levothyroxine absorption if taken concurrently.", "clinicalSignificance": "While the interaction is not well-studied, the general recommendation for levothyroxine is to avoid taking it with any supplement to maximize absorption.", "managementStrategy": "As a general precaution, separate levothyroxine and CoQ10 by at least 2-4 hours. This is a conservative recommendation given levothyroxine's well-known sensitivity to co-administered substances.", "isSynergistic": false, "interactionEvidenceRating": "insufficient", "scope": "prescription-supplement" }, { "supplementAName": "Metformin", "supplementBName": "Vitamin B12", "interactionType": "caution", "severity": "moderate", "description": "Long-term metformin use (typically >6 months) reduces vitamin B12 absorption by 10-30%, leading to deficiency in up to 30% of chronic users. B12 deficiency from metformin can cause peripheral neuropathy that may be misattributed to diabetic neuropathy, and megaloblastic anemia.", "recommendation": "Monitor B12 levels annually if on long-term metformin. Consider B12 supplementation (1000 mcg/day sublingual or 1000 mcg/month injection) as prophylaxis, particularly in patients on metformin for over 1 year.", "minimumTimeSeparation": null, "mechanism": "Metformin interferes with calcium-dependent binding of the intrinsic factor-B12 complex to the ileal receptor (cubilin). Since B12 absorption in the terminal ileum requires calcium-dependent endocytosis, metformin's disruption of this process reduces B12 uptake.", "evidenceLevel": "strong", "sources": [ { "text": "Aroda VR et al. Long-term metformin use and vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016;101(4):1754-1761.", "pmid": "26900641", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26900641/", "publicSourceType": "PMID" }, { "text": "de Jager J et al. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency. BMJ. 2010;340:c2181.", "pmid": "20488910", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20488910/", "publicSourceType": "PMID" }, { "text": "Maruthur NM, Tseng E, Hutfless S, Wilson LM et al.. Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-analysis. Annals of Internal Medicine. 2016.", "pmid": "27088241", "doi": "10.7326/M15-2650", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27088241/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Long-term metformin use (typically >6 months) reduces vitamin B12 absorption by 10-30%, leading to deficiency in up to 30% of chronic users.", "clinicalSignificance": "B12 deficiency from metformin can cause peripheral neuropathy that may be misattributed to diabetic neuropathy, and megaloblastic anemia.", "managementStrategy": "Monitor B12 levels annually if on long-term metformin. Consider B12 supplementation (1000 mcg/day sublingual or 1000 mcg/month injection) as prophylaxis, particularly in patients on metformin for over 1 year.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Metformin", "supplementBName": "Berberine", "interactionType": "caution", "severity": "serious", "description": "Both metformin and berberine lower blood glucose through overlapping mechanisms including AMPK activation. Combined use creates a significant risk of additive hypoglycemia. Berberine also inhibits CYP enzymes and may increase metformin plasma concentrations, further amplifying the hypoglycemic effect.", "recommendation": "Avoid combining berberine with metformin without medical supervision. If used together, blood glucose must be monitored very closely, especially when initiating the combination. Dose reduction of one or both agents may be necessary.", "minimumTimeSeparation": null, "mechanism": "Both metformin and berberine activate AMP-activated protein kinase (AMPK), improve insulin sensitivity, and reduce hepatic glucose production. Berberine may also inhibit CYP2D6, CYP2C9, and CYP3A4, but this does NOT affect metformin (which is renally excreted unchanged, not CYP-metabolized). The additive AMPK activation creates significant hypoglycemia risk.", "evidenceLevel": "moderate", "sources": [ { "text": "Yin J et al. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008;57(5):712-717.", "pmid": "18442638", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18442638/", "publicSourceType": "PMID" }, { "text": "Zhang Y et al. Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. J Clin Endocrinol Metab. 2008;93(7):2559-2565.", "pmid": "18397984", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18397984/", "publicSourceType": "PMID" }, { "text": "Maruthur NM, Tseng E, Hutfless S, Wilson LM et al.. Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-analysis. Annals of Internal Medicine. 2016.", "pmid": "27088241", "doi": "10.7326/M15-2650", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27088241/", "publicSourceType": "PMID" }, { "text": "Asbaghi O, Ghanbari N, Shekari M et al.. The effect of berberine supplementation on obesity parameters, inflammation and liver function enzymes: A systematic review and meta-analysis of randomized controlled trials.. Clinical Nutrition ESPEN. 2020.", "pmid": "32690176", "doi": "10.1016/j.clnesp.2020.04.010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32690176/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Both metformin and berberine lower blood glucose through overlapping mechanisms including AMPK activation.", "clinicalSignificance": "Combined use creates a significant risk of additive hypoglycemia.", "managementStrategy": "Avoid combining berberine with metformin without medical supervision. If used together, blood glucose must be monitored very closely, especially when initiating the combination. Dose reduction of one or both agents may be necessary.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Metformin", "supplementBName": "Alpha-Lipoic Acid", "interactionType": "caution", "severity": "moderate", "description": "Alpha-lipoic acid (ALA) has its own blood glucose-lowering effects through improved insulin sensitivity and enhanced glucose uptake. When combined with metformin, the additive hypoglycemic effect may lead to lower-than-expected blood sugar levels, particularly in patients with well-controlled diabetes.", "recommendation": "Monitor blood glucose more frequently when adding alpha-lipoic acid to metformin therapy. Start with a low ALA dose (300mg/day) and titrate slowly. Inform your prescriber about ALA supplementation so metformin dosing can be adjusted if needed.", "minimumTimeSeparation": null, "mechanism": "Alpha-lipoic acid activates AMPK independently, enhances GLUT4 translocation to cell membranes, and improves insulin signaling. Combined with metformin's AMPK activation and hepatic glucose production inhibition, there is additive blood glucose lowering.", "evidenceLevel": "moderate", "sources": [ { "text": "Jacob S et al. Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus. Free Radic Biol Med. 1999;27(3-4):309-314.", "pmid": "10468203", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10468203/", "publicSourceType": "PMID" }, { "text": "Maruthur NM, Tseng E, Hutfless S, Wilson LM et al.. Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-analysis. Annals of Internal Medicine. 2016.", "pmid": "27088241", "doi": "10.7326/M15-2650", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27088241/", "publicSourceType": "PMID" }, { "text": "Hsieh RY, Huang IC, Chen C, Sung JY. Effects of Oral Alpha-Lipoic Acid Treatment on Diabetic Polyneuropathy: A Meta-Analysis and Systematic Review. Nutrients. 2023.", "pmid": "37630823", "doi": "10.3390/nu15163634", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37630823/", "publicSourceType": "PMID" }, { "text": "An P, Wan S, Luo Y, Luo J et al.. Micronutrient Supplementation to Reduce Cardiovascular Risk. Journal of the American College of Cardiology. 2022.", "pmid": "36480969", "doi": "10.1016/j.jacc.2022.09.048", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36480969/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Alpha-lipoic acid (ALA) has its own blood glucose-lowering effects through improved insulin sensitivity and enhanced glucose uptake.", "clinicalSignificance": "When combined with metformin, the additive hypoglycemic effect may lead to lower-than-expected blood sugar levels, particularly in patients with well-controlled diabetes.", "managementStrategy": "Monitor blood glucose more frequently when adding alpha-lipoic acid to metformin therapy. Start with a low ALA dose (300mg/day) and titrate slowly. Inform your prescriber about ALA supplementation so metformin dosing can be adjusted if needed.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Metformin", "supplementBName": "Chromium", "interactionType": "caution", "severity": "moderate", "description": "Chromium supplementation enhances insulin sensitivity and may improve glucose metabolism. When combined with metformin, the additive insulin-sensitizing effect can cause greater-than-expected blood glucose lowering. The combination requires more careful glucose monitoring.", "recommendation": "Monitor blood glucose closely when combining chromium with metformin. Start chromium at conservative doses (200 mcg/day). Inform your prescriber about chromium use so they can adjust metformin dosing if hypoglycemia occurs.", "minimumTimeSeparation": null, "mechanism": "Chromium enhances insulin receptor signaling by potentiating insulin receptor tyrosine kinase activity and improving GLUT4 translocation. This adds to metformin's insulin-sensitizing effects through AMPK activation, creating additive glucose-lowering.", "evidenceLevel": "moderate", "sources": [ { "text": "Cefalu WT et al. Characterization of the metabolic and physiologic response to chromium supplementation in subjects with type 2 diabetes. Metabolism. 2010;59(5):755-762.", "pmid": "20022616", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20022616/", "publicSourceType": "PMID" }, { "text": "Maruthur NM, Tseng E, Hutfless S, Wilson LM et al.. Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-analysis. Annals of Internal Medicine. 2016.", "pmid": "27088241", "doi": "10.7326/M15-2650", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27088241/", "publicSourceType": "PMID" }, { "text": "Zhao F, Pan D, Wang N, Xia H, Zhang H, Wang S, Sun G. Effect of Chromium Supplementation on Blood Glucose and Lipid Levels in Patients with Type 2 Diabetes Mellitus: a Systematic Review and Meta-analysis. Biological Trace Element Research. 2022.", "pmid": "33783683", "doi": "10.1007/s12011-021-02693-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33783683/", "publicSourceType": "PMID" }, { "text": "Vajdi M, Musazadeh V, Karimi A et al.. Effects of Chromium Supplementation on Lipid Profile: an Umbrella of Systematic Review and Meta-analysis. Biological Trace Element Research. 2023.", "pmid": "36376714", "doi": "10.1007/s12011-022-03474-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36376714/", "publicSourceType": "PMID" }, { "text": "Tsang C, Taghizadeh M, Aghabagheri E, Asemi Z, Jafarnejad S. A meta-analysis of the effect of chromium supplementation on anthropometric indices of subjects with overweight or obesity. Clinical Obesity. 2019.", "pmid": "31115179", "doi": "10.1111/cob.12313", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31115179/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Chromium supplementation enhances insulin sensitivity and may improve glucose metabolism.", "clinicalSignificance": "When combined with metformin, the additive insulin-sensitizing effect can cause greater-than-expected blood glucose lowering.", "managementStrategy": "Monitor blood glucose closely when combining chromium with metformin. Start chromium at conservative doses (200 mcg/day). Inform your prescriber about chromium use so they can adjust metformin dosing if hypoglycemia occurs.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Atorvastatin", "supplementBName": "Coenzyme Q10 Ubiquinol", "interactionType": "synergy", "severity": "info", "description": "Atorvastatin inhibits HMG-CoA reductase, which also reduces endogenous CoQ10 synthesis. Statin-induced CoQ10 depletion may contribute to muscle-related side effects (myalgia, myopathy). Supplemental CoQ10 may help restore depleted levels and reduce statin-associated muscle symptoms.", "recommendation": "Consider CoQ10 supplementation (100-200mg/day ubiquinol) if experiencing statin-related muscle symptoms. CoQ10 does not interfere with the cholesterol-lowering effect of atorvastatin.", "minimumTimeSeparation": null, "mechanism": "HMG-CoA reductase catalyzes an early step in both cholesterol and CoQ10 biosynthesis (mevalonate pathway). Statin inhibition of this enzyme reduces CoQ10 production by 40-50%. CoQ10 is essential for mitochondrial electron transport, and depletion may impair muscle cell energy metabolism.", "evidenceLevel": "moderate", "sources": [ { "text": "Caso G et al. Effect of coenzyme Q10 on myopathic symptoms in patients treated with statins. Am J Cardiol. 2007;99(10):1409-1412.", "pmid": "17493470", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17493470/", "publicSourceType": "PMID" }, { "text": "Littlefield N et al. Statins' effect on plasma levels of coenzyme Q10 and improvement in myopathy with supplementation. J Am Assoc Nurse Pract. 2014;26(2):85-90.", "pmid": "24170708", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24170708/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Atorvastatin inhibits HMG-CoA reductase, which also reduces endogenous CoQ10 synthesis.", "clinicalSignificance": "Statin-induced CoQ10 depletion may contribute to muscle-related side effects (myalgia, myopathy).", "managementStrategy": "Consider CoQ10 supplementation (100-200mg/day ubiquinol) if experiencing statin-related muscle symptoms. CoQ10 does not interfere with the cholesterol-lowering effect of atorvastatin.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Rosuvastatin", "supplementBName": "Coenzyme Q10 Ubiquinol", "interactionType": "synergy", "severity": "info", "description": "Rosuvastatin, like all statins, inhibits the mevalonate pathway and reduces endogenous CoQ10 production. This depletion may contribute to statin-associated muscle symptoms. CoQ10 supplementation can help restore levels and may alleviate myalgia in some patients.", "recommendation": "Consider CoQ10 supplementation (100-200mg/day ubiquinol) if experiencing statin-related muscle symptoms. CoQ10 does not interfere with rosuvastatin's cholesterol-lowering effect.", "minimumTimeSeparation": null, "mechanism": "Rosuvastatin inhibits HMG-CoA reductase in the mevalonate pathway, which supplies precursors for both cholesterol and CoQ10 synthesis. Reduced CoQ10 levels impair mitochondrial ATP production in muscle cells, potentially contributing to myalgia and myopathy.", "evidenceLevel": "moderate", "sources": [ { "text": "Caso G et al. Effect of coenzyme Q10 on myopathic symptoms in patients treated with statins. Am J Cardiol. 2007;99(10):1409-1412.", "pmid": "17493470", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17493470/", "publicSourceType": "PMID" }, { "text": "Kang Y, Park JM, Lee SH. Moderate-Intensity Rosuvastatin/Ezetimibe Combination versus Quadruple-Dose Rosuvastatin Monotherapy: A Meta-Analysis and Systemic Review. Yonsei Medical Journal. 2024.", "pmid": "38154476", "doi": "10.3349/ymj.2023.0285", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38154476/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Rosuvastatin, like all statins, inhibits the mevalonate pathway and reduces endogenous CoQ10 production.", "clinicalSignificance": "This depletion may contribute to statin-associated muscle symptoms.", "managementStrategy": "Consider CoQ10 supplementation (100-200mg/day ubiquinol) if experiencing statin-related muscle symptoms. CoQ10 does not interfere with rosuvastatin's cholesterol-lowering effect.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Simvastatin", "supplementBName": "Coenzyme Q10 Ubiquinol", "interactionType": "synergy", "severity": "info", "description": "Simvastatin inhibits HMG-CoA reductase, reducing endogenous CoQ10 synthesis as a consequence of mevalonate pathway inhibition. Simvastatin may cause more myalgia than some other statins, and CoQ10 depletion is a proposed contributing mechanism. Supplementation may help reduce these symptoms.", "recommendation": "Consider CoQ10 supplementation (100-200mg/day ubiquinol) if experiencing muscle symptoms on simvastatin. CoQ10 does not reduce simvastatin's cholesterol-lowering efficacy.", "minimumTimeSeparation": null, "mechanism": "Simvastatin inhibits HMG-CoA reductase, blocking the mevalonate pathway upstream of both cholesterol and CoQ10 biosynthesis. CoQ10 depletion reduces mitochondrial electron transport chain efficiency in skeletal muscle, potentially leading to impaired energy production and myopathy.", "evidenceLevel": "moderate", "sources": [ { "text": "Caso G et al. Effect of coenzyme Q10 on myopathic symptoms in patients treated with statins. Am J Cardiol. 2007;99(10):1409-1412.", "pmid": "17493470", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17493470/", "publicSourceType": "PMID" }, { "text": "Bookstaver DA et al. Effect of coenzyme Q10 supplementation on statin-induced myalgias. Am J Cardiol. 2012;110(4):526-529.", "pmid": "22608359", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22608359/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Simvastatin inhibits HMG-CoA reductase, reducing endogenous CoQ10 synthesis as a consequence of mevalonate pathway inhibition.", "clinicalSignificance": "Simvastatin may cause more myalgia than some other statins, and CoQ10 depletion is a proposed contributing mechanism.", "managementStrategy": "Consider CoQ10 supplementation (100-200mg/day ubiquinol) if experiencing muscle symptoms on simvastatin. CoQ10 does not reduce simvastatin's cholesterol-lowering efficacy.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Atorvastatin", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's Wort is a potent CYP3A4 inducer that significantly increases atorvastatin metabolism, reducing its plasma levels and cholesterol-lowering efficacy. Studies have shown up to 50% reduction in statin AUC with concurrent St. John's Wort use.", "recommendation": "Avoid combining St. John's Wort with atorvastatin. If mood support is needed, discuss alternative options with your prescriber that do not induce CYP3A4.", "minimumTimeSeparation": null, "mechanism": "Hyperforin in St. John's Wort activates PXR, leading to upregulation of CYP3A4 and P-glycoprotein. Atorvastatin is extensively metabolized by CYP3A4, so enzyme induction dramatically accelerates its clearance and reduces therapeutic plasma concentrations.", "evidenceLevel": "strong", "sources": [ { "text": "Sugimoto K et al. Different effects of St John's Wort on the pharmacokinetics of simvastatin and pravastatin. Clin Pharmacol Ther. 2001;70(6):518-524.", "pmid": "11753267", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11753267/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St.", "clinicalSignificance": "John's Wort is a potent CYP3A4 inducer that significantly increases atorvastatin metabolism, reducing its plasma levels and cholesterol-lowering efficacy.", "managementStrategy": "Avoid combining St. John's Wort with atorvastatin. If mood support is needed, discuss alternative options with your prescriber that do not induce CYP3A4.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Rosuvastatin", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's Wort induces CYP3A4 and P-glycoprotein, which can reduce rosuvastatin levels. While rosuvastatin is less dependent on CYP3A4 than other statins, P-glycoprotein induction can still significantly reduce its bioavailability, potentially compromising cholesterol management.", "recommendation": "Avoid combining St. John's Wort with rosuvastatin. P-glycoprotein induction may reduce rosuvastatin absorption even though it is not primarily CYP3A4-metabolized.", "minimumTimeSeparation": null, "mechanism": "St. John's Wort upregulates P-glycoprotein (MDR1) via PXR activation. Rosuvastatin is a P-glycoprotein substrate for intestinal efflux. Increased P-gp activity reduces rosuvastatin intestinal absorption and increases biliary excretion, lowering plasma concentrations.", "evidenceLevel": "moderate", "sources": [ { "text": "Sugimoto K et al. Different effects of St John's wort on the pharmacokinetics of simvastatin and pravastatin. Clin Pharmacol Ther. 2001;70(6):518-524.", "pmid": "11753267", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11753267/", "publicSourceType": "PMID" }, { "text": "Kang Y, Park JM, Lee SH. Moderate-Intensity Rosuvastatin/Ezetimibe Combination versus Quadruple-Dose Rosuvastatin Monotherapy: A Meta-Analysis and Systemic Review. Yonsei Medical Journal. 2024.", "pmid": "38154476", "doi": "10.3349/ymj.2023.0285", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38154476/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St.", "clinicalSignificance": "John's Wort induces CYP3A4 and P-glycoprotein, which can reduce rosuvastatin levels.", "managementStrategy": "Avoid combining St. John's Wort with rosuvastatin. P-glycoprotein induction may reduce rosuvastatin absorption even though it is not primarily CYP3A4-metabolized.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Simvastatin", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's Wort dramatically reduces simvastatin levels through potent CYP3A4 induction. Simvastatin is highly dependent on CYP3A4 for metabolism, making this one of the most clinically significant statin-herb interactions. Simvastatin AUC may be reduced by over 50%.", "recommendation": "Do not combine St. John's Wort with simvastatin. This interaction can render simvastatin ineffective for cholesterol management. Discuss alternative mood support with your prescriber.", "minimumTimeSeparation": null, "mechanism": "Simvastatin is extensively metabolized by CYP3A4 as a first-pass effect. St. John's Wort's potent CYP3A4 induction via PXR activation dramatically increases simvastatin presystemic metabolism, reducing the amount of active drug reaching systemic circulation.", "evidenceLevel": "strong", "sources": [ { "text": "Sugimoto K et al. Different effects of St John's Wort on the pharmacokinetics of simvastatin and pravastatin. Clin Pharmacol Ther. 2001;70(6):518-524.", "pmid": "11753267", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11753267/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St.", "clinicalSignificance": "John's Wort dramatically reduces simvastatin levels through potent CYP3A4 induction.", "managementStrategy": "Do not combine St. John's Wort with simvastatin. This interaction can render simvastatin ineffective for cholesterol management. Discuss alternative mood support with your prescriber.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Atorvastatin", "supplementBName": "Vitamin B3", "interactionType": "caution", "severity": "moderate", "description": "High-dose niacin (>1g/day) combined with atorvastatin may increase the risk of myopathy and rhabdomyolysis. The AIM-HIGH and HPS2-THRIVE trials also showed no cardiovascular benefit from adding niacin to statin therapy. Low-dose niacin for general health is unlikely to pose significant risk.", "recommendation": "Avoid high-dose niacin (>500mg/day) with atorvastatin without medical supervision. Report any muscle pain, tenderness, or weakness immediately. Low-dose niacin supplementation (<100mg/day) for general health is generally safe.", "minimumTimeSeparation": null, "mechanism": "Both niacin and statins can independently cause myopathy. The combination may synergistically impair muscle cell metabolism through additive effects on mitochondrial function and muscle protein turnover, increasing the risk of clinically significant myopathy.", "evidenceLevel": "strong", "sources": [ { "text": "AIM-HIGH Investigators. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255-2267.", "pmid": "22085343", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22085343/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose niacin (>1g/day) combined with atorvastatin may increase the risk of myopathy and rhabdomyolysis.", "clinicalSignificance": "The AIM-HIGH and HPS2-THRIVE trials also showed no cardiovascular benefit from adding niacin to statin therapy.", "managementStrategy": "Avoid high-dose niacin (>500mg/day) with atorvastatin without medical supervision. Report any muscle pain, tenderness, or weakness immediately. Low-dose niacin supplementation (<100mg/day) for general health is generally safe.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Rosuvastatin", "supplementBName": "Vitamin B3", "interactionType": "caution", "severity": "moderate", "description": "High-dose niacin combined with rosuvastatin increases myopathy risk. Clinical trials have shown that adding niacin to statin therapy does not provide additional cardiovascular benefit but does increase the incidence of muscle-related adverse effects.", "recommendation": "Avoid high-dose niacin (>500mg/day) with rosuvastatin without medical supervision. Low-dose niacin for general health purposes is generally safe. Report any muscle pain or weakness promptly.", "minimumTimeSeparation": null, "mechanism": "High-dose niacin and statins both independently increase myopathy risk. Combined use creates additive stress on skeletal muscle through overlapping mechanisms affecting mitochondrial function and muscle protein homeostasis.", "evidenceLevel": "strong", "sources": [ { "text": "HPS2-THRIVE Collaborative Group. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371(3):203-212.", "pmid": "25014686", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25014686/", "publicSourceType": "PMID" }, { "text": "Kang Y, Park JM, Lee SH. Moderate-Intensity Rosuvastatin/Ezetimibe Combination versus Quadruple-Dose Rosuvastatin Monotherapy: A Meta-Analysis and Systemic Review. Yonsei Medical Journal. 2024.", "pmid": "38154476", "doi": "10.3349/ymj.2023.0285", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38154476/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose niacin combined with rosuvastatin increases myopathy risk.", "clinicalSignificance": "Clinical trials have shown that adding niacin to statin therapy does not provide additional cardiovascular benefit but does increase the incidence of muscle-related adverse effects.", "managementStrategy": "Avoid high-dose niacin (>500mg/day) with rosuvastatin without medical supervision. Low-dose niacin for general health purposes is generally safe. Report any muscle pain or weakness promptly.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Simvastatin", "supplementBName": "Vitamin B3", "interactionType": "caution", "severity": "moderate", "description": "The combination of high-dose niacin with simvastatin carries an elevated risk of myopathy and rhabdomyolysis. Simvastatin already has a higher baseline myopathy risk than some other statins, making this combination of particular concern at higher doses.", "recommendation": "Avoid high-dose niacin (>500mg/day) with simvastatin. The FDA recommends limiting simvastatin dose to 20mg/day when combined with niacin >1g/day. Report any muscle symptoms immediately.", "minimumTimeSeparation": null, "mechanism": "Both simvastatin and high-dose niacin independently increase myopathy risk. Simvastatin's CYP3A4 metabolism creates additional vulnerability. Combined myotoxic effects impair skeletal muscle mitochondrial function, increasing the risk of clinically significant rhabdomyolysis.", "evidenceLevel": "strong", "sources": [ { "text": "AIM-HIGH Investigators. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255-2267.", "pmid": "22085343", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22085343/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "The combination of high-dose niacin with simvastatin carries an elevated risk of myopathy and rhabdomyolysis.", "clinicalSignificance": "Simvastatin already has a higher baseline myopathy risk than some other statins, making this combination of particular concern at higher doses.", "managementStrategy": "Avoid high-dose niacin (>500mg/day) with simvastatin. The FDA recommends limiting simvastatin dose to 20mg/day when combined with niacin >1g/day. Report any muscle symptoms immediately.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Sertraline", "supplementBName": "St. John's Wort", "interactionType": "contraindicated", "severity": "dangerous", "description": "Combining sertraline (an SSRI) with St. John's Wort creates a serious risk of serotonin syndrome, a potentially life-threatening condition. St. John's Wort inhibits serotonin reuptake and may also inhibit MAO, dramatically increasing synaptic serotonin when combined with an SSRI.", "recommendation": "Do not take St. John's Wort with sertraline or any SSRI. This is a well-documented dangerous interaction with risk of serotonin syndrome (symptoms include agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle twitching, and hyperthermia).", "minimumTimeSeparation": null, "mechanism": "Sertraline blocks the serotonin transporter (SERT), increasing synaptic serotonin. St. John's Wort also inhibits serotonin reuptake (via hyperforin) and may inhibit monoamine oxidase. The combined serotonergic effects can cause excessive serotonin accumulation at postsynaptic 5-HT receptors, triggering serotonin syndrome.", "evidenceLevel": "strong", "sources": [ { "text": "Lantz MS, Buchalter E, Giambanco V. St. John's wort and antidepressant drug interactions in the elderly. J Geriatr Psychiatry Neurol. 1999;12(1):7-10.", "pmid": "10447149", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10447149/", "publicSourceType": "PMID" }, { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Combining sertraline (an SSRI) with St.", "clinicalSignificance": "John's Wort creates a serious risk of serotonin syndrome, a potentially life-threatening condition.", "managementStrategy": "Do not take St. John's Wort with sertraline or any SSRI. This is a well-documented dangerous interaction with risk of serotonin syndrome (symptoms include agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle twitching, and hyperthermia).", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Fluoxetine", "supplementBName": "St. John's Wort", "interactionType": "contraindicated", "severity": "dangerous", "description": "Combining fluoxetine with St. John's Wort creates a high risk of serotonin syndrome. Fluoxetine has a long half-life (including its active metabolite norfluoxetine), meaning the risk persists for weeks after discontinuation. Multiple case reports document this dangerous interaction.", "recommendation": "Do not take St. John's Wort with fluoxetine. Due to fluoxetine's long half-life, wait at least 5 weeks after stopping fluoxetine before starting St. John's Wort. Seek immediate medical attention for symptoms of serotonin syndrome.", "minimumTimeSeparation": null, "mechanism": "Fluoxetine and its active metabolite norfluoxetine potently inhibit SERT, with a combined half-life of 4-16 days. St. John's Wort's additional serotonin reuptake inhibition (via hyperforin) and potential MAO inhibition creates dangerous serotonergic excess.", "evidenceLevel": "strong", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Combining fluoxetine with St.", "clinicalSignificance": "John's Wort creates a high risk of serotonin syndrome.", "managementStrategy": "Do not take St. John's Wort with fluoxetine. Due to fluoxetine's long half-life, wait at least 5 weeks after stopping fluoxetine before starting St. John's Wort. Seek immediate medical attention for symptoms of serotonin syndrome.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Escitalopram", "supplementBName": "St. John's Wort", "interactionType": "contraindicated", "severity": "dangerous", "description": "Combining escitalopram with St. John's Wort significantly increases the risk of serotonin syndrome. Escitalopram is the most selective SSRI, and adding St. John's Wort's serotonergic activity creates dangerous serotonin excess. St. John's Wort may also reduce escitalopram levels via CYP3A4 induction while paradoxically increasing serotonin toxicity risk.", "recommendation": "Do not take St. John's Wort with escitalopram. If mood support beyond your SSRI is needed, discuss evidence-based options with your prescriber.", "minimumTimeSeparation": null, "mechanism": "Escitalopram is a highly selective serotonin reuptake inhibitor. St. John's Wort adds serotonin reuptake inhibition via hyperforin and potential MAO inhibition. The dual serotonergic mechanism causes excessive 5-HT receptor stimulation, particularly at 5-HT1A and 5-HT2A receptors.", "evidenceLevel": "strong", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Combining escitalopram with St.", "clinicalSignificance": "John's Wort significantly increases the risk of serotonin syndrome.", "managementStrategy": "Do not take St. John's Wort with escitalopram. If mood support beyond your SSRI is needed, discuss evidence-based options with your prescriber.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Sertraline", "supplementBName": "5-HTP", "interactionType": "contraindicated", "severity": "serious", "description": "5-HTP is a direct precursor to serotonin that bypasses the rate-limiting step in serotonin synthesis. When combined with sertraline's serotonin reuptake inhibition, 5-HTP can cause excessive serotonin accumulation and potentially trigger serotonin syndrome.", "recommendation": "Do not combine 5-HTP with sertraline. The risk of serotonin syndrome is significant. If you are taking 5-HTP, inform your prescriber before starting any SSRI.", "minimumTimeSeparation": null, "mechanism": "5-HTP is converted to serotonin by aromatic L-amino acid decarboxylase, increasing serotonin synthesis both centrally and peripherally. Sertraline prevents serotonin reuptake from the synapse. Together, increased production and decreased clearance cause dangerous synaptic serotonin accumulation.", "evidenceLevel": "moderate", "sources": [ { "text": "Birdsall TC. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998;3(4):271-280.", "pmid": "9727088", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9727088/", "publicSourceType": "PMID" }, { "text": "Truyens M, Lobatón T, Ferrante M et al.. Effect of 5-Hydroxytryptophan on Fatigue in Quiescent Inflammatory Bowel Disease: A Randomized Controlled Trial. Gastroenterology. 2022.", "pmid": "35940251", "doi": "10.1053/j.gastro.2022.07.052", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35940251/", "publicSourceType": "PMID" }, { "text": "Sutanto CN, Xia X, Heng CW et al.. The impact of 5-hydroxytryptophan supplementation on sleep quality and gut microbiota composition in older adults: A randomized controlled trial. Clinical Nutrition. 2024.", "pmid": "38309227", "doi": "10.1016/j.clnu.2024.01.010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38309227/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "5-HTP is a direct precursor to serotonin that bypasses the rate-limiting step in serotonin synthesis.", "clinicalSignificance": "When combined with sertraline's serotonin reuptake inhibition, 5-HTP can cause excessive serotonin accumulation and potentially trigger serotonin syndrome.", "managementStrategy": "Do not combine 5-HTP with sertraline. The risk of serotonin syndrome is significant. If you are taking 5-HTP, inform your prescriber before starting any SSRI.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fluoxetine", "supplementBName": "5-HTP", "interactionType": "contraindicated", "severity": "serious", "description": "5-HTP directly increases serotonin synthesis, while fluoxetine blocks serotonin reuptake. This combination can lead to serotonin syndrome. The risk is compounded by fluoxetine's long half-life, meaning serotonergic effects persist for weeks.", "recommendation": "Do not combine 5-HTP with fluoxetine. Due to fluoxetine's long half-life, wait at least 5 weeks after discontinuing fluoxetine before starting 5-HTP.", "minimumTimeSeparation": null, "mechanism": "5-HTP bypasses tryptophan hydroxylase (the rate-limiting enzyme) to directly increase serotonin production. Fluoxetine and norfluoxetine block SERT for extended periods. The combination of increased serotonin synthesis and blocked reuptake creates dangerous serotonin excess.", "evidenceLevel": "moderate", "sources": [ { "text": "Birdsall TC. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998;3(4):271-280.", "pmid": "9727088", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9727088/", "publicSourceType": "PMID" }, { "text": "Truyens M, Lobatón T, Ferrante M et al.. Effect of 5-Hydroxytryptophan on Fatigue in Quiescent Inflammatory Bowel Disease: A Randomized Controlled Trial. Gastroenterology. 2022.", "pmid": "35940251", "doi": "10.1053/j.gastro.2022.07.052", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35940251/", "publicSourceType": "PMID" }, { "text": "Sutanto CN, Xia X, Heng CW et al.. The impact of 5-hydroxytryptophan supplementation on sleep quality and gut microbiota composition in older adults: A randomized controlled trial. Clinical Nutrition. 2024.", "pmid": "38309227", "doi": "10.1016/j.clnu.2024.01.010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38309227/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "5-HTP directly increases serotonin synthesis, while fluoxetine blocks serotonin reuptake.", "clinicalSignificance": "This combination can lead to serotonin syndrome.", "managementStrategy": "Do not combine 5-HTP with fluoxetine. Due to fluoxetine's long half-life, wait at least 5 weeks after discontinuing fluoxetine before starting 5-HTP.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Escitalopram", "supplementBName": "5-HTP", "interactionType": "contraindicated", "severity": "serious", "description": "5-HTP increases serotonin synthesis while escitalopram potently blocks serotonin reuptake. This combination creates significant risk of serotonin syndrome through complementary mechanisms that both increase synaptic serotonin availability.", "recommendation": "Do not combine 5-HTP with escitalopram. If you are currently using both, discontinue 5-HTP and inform your prescriber.", "minimumTimeSeparation": null, "mechanism": "5-HTP is decarboxylated to serotonin by AADC, increasing serotonin synthesis. Escitalopram is the most selective SERT inhibitor, maximizing synaptic serotonin retention. Combined increased production and decreased clearance can trigger serotonin syndrome.", "evidenceLevel": "moderate", "sources": [ { "text": "Birdsall TC. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998;3(4):271-280.", "pmid": "9727088", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9727088/", "publicSourceType": "PMID" }, { "text": "Truyens M, Lobatón T, Ferrante M et al.. Effect of 5-Hydroxytryptophan on Fatigue in Quiescent Inflammatory Bowel Disease: A Randomized Controlled Trial. Gastroenterology. 2022.", "pmid": "35940251", "doi": "10.1053/j.gastro.2022.07.052", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35940251/", "publicSourceType": "PMID" }, { "text": "Sutanto CN, Xia X, Heng CW et al.. The impact of 5-hydroxytryptophan supplementation on sleep quality and gut microbiota composition in older adults: A randomized controlled trial. Clinical Nutrition. 2024.", "pmid": "38309227", "doi": "10.1016/j.clnu.2024.01.010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38309227/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "5-HTP increases serotonin synthesis while escitalopram potently blocks serotonin reuptake.", "clinicalSignificance": "This combination creates significant risk of serotonin syndrome through complementary mechanisms that both increase synaptic serotonin availability.", "managementStrategy": "Do not combine 5-HTP with escitalopram. If you are currently using both, discontinue 5-HTP and inform your prescriber.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Sertraline", "supplementBName": "SAMe", "interactionType": "caution", "severity": "serious", "description": "SAMe (S-adenosylmethionine) has demonstrated antidepressant properties and increases serotonergic, noradrenergic, and dopaminergic activity. When combined with sertraline, SAMe may excessively potentiate serotonergic signaling, increasing the risk of serotonin syndrome.", "recommendation": "Use SAMe with sertraline only under direct medical supervision. Do not self-prescribe this combination. If prescribed together as adjunctive therapy, start SAMe at low doses and watch for signs of serotonin excess.", "minimumTimeSeparation": null, "mechanism": "SAMe serves as a methyl donor critical for neurotransmitter synthesis and metabolism. It enhances serotonin turnover and may increase serotonin receptor sensitivity. Combined with sertraline's SERT inhibition, this can cause excessive serotonergic stimulation.", "evidenceLevel": "moderate", "sources": [ { "text": "Papakostas GI et al. S-adenosyl-methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders. Am J Psychiatry. 2010;167(8):942-948.", "pmid": "20595412", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20595412/", "publicSourceType": "PMID" }, { "text": "Amenyah SD, Hughes CF, Ward M, Rosborough S, Deane J, Thursby SJ et al.. Influence of nutrients involved in one-carbon metabolism on DNA methylation in adults-a systematic review and meta-analysis.. Nutrition Reviews. 2020.", "pmid": "31977026", "doi": "10.1093/nutrit/nuz094", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31977026/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "SAMe (S-adenosylmethionine) has demonstrated antidepressant properties and increases serotonergic, noradrenergic, and dopaminergic activity.", "clinicalSignificance": "When combined with sertraline, SAMe may excessively potentiate serotonergic signaling, increasing the risk of serotonin syndrome.", "managementStrategy": "Use SAMe with sertraline only under direct medical supervision. Do not self-prescribe this combination. If prescribed together as adjunctive therapy, start SAMe at low doses and watch for signs of serotonin excess.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fluoxetine", "supplementBName": "SAMe", "interactionType": "caution", "severity": "serious", "description": "SAMe increases serotonergic activity through multiple mechanisms. Combined with fluoxetine's potent and long-lasting SERT inhibition, the risk of serotonin excess increases. While some research has explored SAMe as SSRI augmentation, this should only occur under medical supervision.", "recommendation": "Do not self-prescribe SAMe while taking fluoxetine. If being considered as adjunctive therapy, this must be done under close psychiatric supervision with gradual dose titration.", "minimumTimeSeparation": null, "mechanism": "SAMe increases serotonin synthesis, turnover, and receptor sensitivity through its role as a universal methyl donor. Fluoxetine's prolonged SERT inhibition (half-life up to 16 days including norfluoxetine) combined with SAMe's serotonergic enhancement creates risk of excessive serotonin accumulation.", "evidenceLevel": "moderate", "sources": [ { "text": "Papakostas GI et al. S-adenosyl-methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders. Am J Psychiatry. 2010;167(8):942-948.", "pmid": "20595412", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20595412/", "publicSourceType": "PMID" }, { "text": "Amenyah SD, Hughes CF, Ward M, Rosborough S, Deane J, Thursby SJ et al.. Influence of nutrients involved in one-carbon metabolism on DNA methylation in adults-a systematic review and meta-analysis.. Nutrition Reviews. 2020.", "pmid": "31977026", "doi": "10.1093/nutrit/nuz094", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31977026/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "SAMe increases serotonergic activity through multiple mechanisms.", "clinicalSignificance": "Combined with fluoxetine's potent and long-lasting SERT inhibition, the risk of serotonin excess increases.", "managementStrategy": "Do not self-prescribe SAMe while taking fluoxetine. If being considered as adjunctive therapy, this must be done under close psychiatric supervision with gradual dose titration.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Escitalopram", "supplementBName": "SAMe", "interactionType": "caution", "severity": "serious", "description": "SAMe has serotonergic properties that may potentiate escitalopram's effects. While some psychiatrists use SAMe augmentation in treatment-resistant depression, the combination requires careful monitoring due to the risk of excessive serotonergic stimulation.", "recommendation": "Only combine SAMe with escitalopram under direct psychiatric supervision. Do not add SAMe on your own. Start at low doses if prescribed together, and monitor for signs of serotonin excess.", "minimumTimeSeparation": null, "mechanism": "SAMe enhances serotonin synthesis and turnover through methylation reactions and increases postsynaptic serotonin receptor sensitivity. Combined with escitalopram's selective SERT inhibition, synaptic serotonin levels can rise excessively.", "evidenceLevel": "moderate", "sources": [ { "text": "Papakostas GI et al. S-adenosyl-methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders. Am J Psychiatry. 2010;167(8):942-948.", "pmid": "20595412", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20595412/", "publicSourceType": "PMID" }, { "text": "Amenyah SD, Hughes CF, Ward M, Rosborough S, Deane J, Thursby SJ et al.. Influence of nutrients involved in one-carbon metabolism on DNA methylation in adults-a systematic review and meta-analysis.. Nutrition Reviews. 2020.", "pmid": "31977026", "doi": "10.1093/nutrit/nuz094", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31977026/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "SAMe has serotonergic properties that may potentiate escitalopram's effects.", "clinicalSignificance": "While some psychiatrists use SAMe augmentation in treatment-resistant depression, the combination requires careful monitoring due to the risk of excessive serotonergic stimulation.", "managementStrategy": "Only combine SAMe with escitalopram under direct psychiatric supervision. Do not add SAMe on your own. Start at low doses if prescribed together, and monitor for signs of serotonin excess.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Sertraline", "supplementBName": "L-Tryptophan", "interactionType": "caution", "severity": "serious", "description": "L-Tryptophan is the dietary amino acid precursor to serotonin. Supplemental tryptophan increases serotonin synthesis, and combined with sertraline's reuptake inhibition, can cause excessive serotonergic activity. Cases of serotonin syndrome have been reported with this combination.", "recommendation": "Avoid supplemental L-tryptophan while taking sertraline. Dietary tryptophan from food is generally safe. If already taking both, discontinue L-tryptophan and inform your prescriber.", "minimumTimeSeparation": null, "mechanism": "L-Tryptophan is hydroxylated by tryptophan hydroxylase to 5-HTP, then decarboxylated to serotonin. Supplemental tryptophan increases substrate availability for serotonin synthesis. Sertraline's SERT inhibition prevents the clearing of this excess serotonin from synapses.", "evidenceLevel": "moderate", "sources": [ { "text": "Steiner W, Fontaine R. Toxic reaction following the combined administration of fluoxetine and L-tryptophan. Biol Psychiatry. 1986;21(11):1067-1071.", "pmid": "3756263", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3756263/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "L-Tryptophan is the dietary amino acid precursor to serotonin.", "clinicalSignificance": "Supplemental tryptophan increases serotonin synthesis, and combined with sertraline's reuptake inhibition, can cause excessive serotonergic activity.", "managementStrategy": "Avoid supplemental L-tryptophan while taking sertraline. Dietary tryptophan from food is generally safe. If already taking both, discontinue L-tryptophan and inform your prescriber.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fluoxetine", "supplementBName": "L-Tryptophan", "interactionType": "caution", "severity": "serious", "description": "L-Tryptophan supplementation increases serotonin synthesis, and combined with fluoxetine's potent, long-lasting serotonin reuptake inhibition, can produce excessive serotonergic activity. Early case reports of this combination documented agitation, restlessness, and other serotonin syndrome symptoms.", "recommendation": "Avoid supplemental L-tryptophan with fluoxetine. This was one of the first reported SSRI-supplement serotonin syndrome interactions. Dietary tryptophan from food is not a concern.", "minimumTimeSeparation": null, "mechanism": "Tryptophan is the rate-limiting precursor for serotonin synthesis via the tryptophan hydroxylase pathway. Supplemental tryptophan increases brain serotonin production. Fluoxetine's SERT blockade (with long half-life) prevents reuptake, causing dangerous accumulation of synaptic serotonin.", "evidenceLevel": "moderate", "sources": [ { "text": "Steiner W, Fontaine R. Toxic reaction following the combined administration of fluoxetine and L-tryptophan. Biol Psychiatry. 1986;21(11):1067-1071.", "pmid": "3756263", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3756263/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "L-Tryptophan supplementation increases serotonin synthesis, and combined with fluoxetine's potent, long-lasting serotonin reuptake inhibition, can produce excessive serotonergic activity.", "clinicalSignificance": "Early case reports of this combination documented agitation, restlessness, and other serotonin syndrome symptoms.", "managementStrategy": "Avoid supplemental L-tryptophan with fluoxetine. This was one of the first reported SSRI-supplement serotonin syndrome interactions. Dietary tryptophan from food is not a concern.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Escitalopram", "supplementBName": "L-Tryptophan", "interactionType": "caution", "severity": "serious", "description": "L-Tryptophan increases serotonin synthesis as its biosynthetic precursor. Combined with escitalopram's selective serotonin reuptake inhibition, the resulting increase in both serotonin production and synaptic retention can trigger serotonin syndrome.", "recommendation": "Avoid supplemental L-tryptophan while taking escitalopram. If you wish to support mood through diet, discuss safe options with your prescriber.", "minimumTimeSeparation": null, "mechanism": "L-Tryptophan increases serotonin synthesis by providing additional substrate for tryptophan hydroxylase. Escitalopram's potent and selective SERT inhibition prevents clearance of the excess serotonin from the synaptic cleft, creating risk of serotonergic toxicity.", "evidenceLevel": "moderate", "sources": [ { "text": "Steiner W, Fontaine R. Toxic reaction following the combined administration of fluoxetine and L-tryptophan. Biol Psychiatry. 1986;21(11):1067-1071.", "pmid": "3756263", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3756263/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "L-Tryptophan increases serotonin synthesis as its biosynthetic precursor.", "clinicalSignificance": "Combined with escitalopram's selective serotonin reuptake inhibition, the resulting increase in both serotonin production and synaptic retention can trigger serotonin syndrome.", "managementStrategy": "Avoid supplemental L-tryptophan while taking escitalopram. If you wish to support mood through diet, discuss safe options with your prescriber.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Omeprazole", "supplementBName": "Magnesium Glycinate", "interactionType": "caution", "severity": "moderate", "description": "Long-term omeprazole use (>1 year) has been associated with clinically significant magnesium depletion (hypomagnesemia). The FDA issued a safety communication in 2011 warning about this risk. Symptoms include muscle cramps, tremors, seizures, and cardiac arrhythmias.", "recommendation": "Monitor magnesium levels periodically if on long-term omeprazole therapy. Consider magnesium supplementation (200-400mg/day), particularly if experiencing muscle cramps or fatigue. Discuss with your prescriber.", "minimumTimeSeparation": null, "mechanism": "PPIs impair active intestinal magnesium absorption via TRPM6 and TRPM7 channels in the distal small intestine and colon. Chronic acid suppression alters the electrochemical gradient needed for magnesium transport, leading to progressive depletion over months to years.", "evidenceLevel": "strong", "sources": [ { "text": "Hess MW et al. Systematic review: hypomagnesaemia induced by proton pump inhibition. Aliment Pharmacol Ther. 2012;36(5):405-413.", "pmid": "22762246", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22762246/", "publicSourceType": "PMID" }, { "text": "Park CH, Kim EH, Roh YH, Kim HY, Lee SK. Proton pump inhibitors linked to hypomagnesemia: a systematic review and meta-analysis of observational studies. Ren Fail. 2015;37(7):1237-1241.", "pmid": "26108134", "doi": "10.3109/0886022X.2015.1057800", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26108134/", "publicSourceType": "PMID" }, { "text": "Choudhury A, Jena A, Jearth V, Dutta AK et al.. Vitamin B12 deficiency and use of proton pump inhibitors: a systematic review and meta-analysis. Expert Review of Gastroenterology & Hepatology. 2023.", "pmid": "37060552", "doi": "10.1080/17474124.2023.2204229", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37060552/", "publicSourceType": "PMID" }, { "text": "Mah J, Pitre T. Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis.. BMC Complementary Medicine and Therapies. 2021.", "pmid": "33865376", "doi": "10.1186/s12906-021-03297-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33865376/", "publicSourceType": "PMID" }, { "text": "Veronese N, Dominguez LJ, Pizzol D et al.. Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.. Nutrients. 2021.", "pmid": "34836329", "doi": "10.3390/nu13114074", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34836329/", "publicSourceType": "PMID" }, { "text": "Veronese N, Pizzol D, Smith L et al.. Effect of Magnesium Supplementation on Inflammatory Parameters: A Meta-Analysis of Randomized Controlled Trials.. Nutrients. 2022.", "pmid": "35277037", "doi": "10.3390/nu14030679", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35277037/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Long-term omeprazole use (>1 year) has been associated with clinically significant magnesium depletion (hypomagnesemia).", "clinicalSignificance": "The FDA issued a safety communication in 2011 warning about this risk.", "managementStrategy": "Monitor magnesium levels periodically if on long-term omeprazole therapy. Consider magnesium supplementation (200-400mg/day), particularly if experiencing muscle cramps or fatigue. Discuss with your prescriber.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Pantoprazole", "supplementBName": "Magnesium Glycinate", "interactionType": "caution", "severity": "moderate", "description": "Long-term pantoprazole use can cause hypomagnesemia, similar to other PPIs. The FDA warning about PPI-induced magnesium depletion applies to all PPIs including pantoprazole. Patients on long-term therapy should have magnesium levels monitored.", "recommendation": "Monitor magnesium levels periodically during long-term pantoprazole use. Consider magnesium supplementation if levels are low or if experiencing muscle cramps, weakness, or fatigue.", "minimumTimeSeparation": null, "mechanism": "Pantoprazole, like all PPIs, impairs active intestinal magnesium absorption through TRPM6/TRPM7 channel dysfunction. Chronic gastric acid suppression disrupts the electrochemical gradient necessary for efficient magnesium transport in the distal intestine.", "evidenceLevel": "strong", "sources": [ { "text": "Hess MW et al. Systematic review: hypomagnesaemia induced by proton pump inhibition. Aliment Pharmacol Ther. 2012;36(5):405-413.", "pmid": "22762246", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22762246/", "publicSourceType": "PMID" }, { "text": "Mah J, Pitre T. Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis.. BMC Complementary Medicine and Therapies. 2021.", "pmid": "33865376", "doi": "10.1186/s12906-021-03297-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33865376/", "publicSourceType": "PMID" }, { "text": "Veronese N, Dominguez LJ, Pizzol D et al.. Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.. Nutrients. 2021.", "pmid": "34836329", "doi": "10.3390/nu13114074", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34836329/", "publicSourceType": "PMID" }, { "text": "Veronese N, Pizzol D, Smith L et al.. Effect of Magnesium Supplementation on Inflammatory Parameters: A Meta-Analysis of Randomized Controlled Trials.. Nutrients. 2022.", "pmid": "35277037", "doi": "10.3390/nu14030679", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35277037/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Long-term pantoprazole use can cause hypomagnesemia, similar to other PPIs.", "clinicalSignificance": "The FDA warning about PPI-induced magnesium depletion applies to all PPIs including pantoprazole.", "managementStrategy": "Monitor magnesium levels periodically during long-term pantoprazole use. Consider magnesium supplementation if levels are low or if experiencing muscle cramps, weakness, or fatigue.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Omeprazole", "supplementBName": "Iron", "interactionType": "caution", "severity": "moderate", "description": "Omeprazole reduces gastric acid production, which is essential for converting dietary and supplemental iron to its absorbable ferrous (Fe2+) form. Long-term PPI use can lead to iron deficiency, particularly in patients with marginal iron stores or those relying on non-heme iron sources.", "recommendation": "If on long-term omeprazole, monitor iron levels and ferritin periodically. Consider taking iron supplements with vitamin C to enhance absorption, or use ferrous bisglycinate which is less pH-dependent. Take iron between meals if tolerated.", "minimumTimeSeparation": null, "mechanism": "Gastric acid is required to reduce ferric iron (Fe3+) to ferrous iron (Fe2+) for absorption by DMT1 in the duodenum. Omeprazole raises gastric pH to >4, significantly impairing this reduction step and reducing non-heme iron bioavailability.", "evidenceLevel": "moderate", "sources": [ { "text": "Sarzynski E et al. Association between proton pump inhibitor use and anemia: a retrospective cohort study. Dig Dis Sci. 2011;56(8):2349-2353.", "pmid": "21318590", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21318590/", "publicSourceType": "PMID" }, { "text": "Choudhury A, Jena A, Jearth V, Dutta AK et al.. Vitamin B12 deficiency and use of proton pump inhibitors: a systematic review and meta-analysis. Expert Review of Gastroenterology & Hepatology. 2023.", "pmid": "37060552", "doi": "10.1080/17474124.2023.2204229", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37060552/", "publicSourceType": "PMID" }, { "text": "Fischer JAJ, Cherian AM, Bone JN, Karakochuk CD. The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials. Nutrition Reviews. 2023.", "pmid": "36728680", "doi": "10.1093/nutrit/nuac106", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36728680/", "publicSourceType": "PMID" }, { "text": "Rehman T, Agrawal R, Ahamed F et al.. Optimal dose and duration of iron supplementation for treating iron deficiency anaemia in children and adolescents: A systematic review and meta-analysis. PLoS One. 2025.", "pmid": "39951396", "doi": "10.1371/journal.pone.0319068", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39951396/", "publicSourceType": "PMID" }, { "text": "Gutema BT, Sorrie MB, Megersa ND et al.. Effects of iron supplementation on cognitive development in school-age children: Systematic review and meta-analysis. PLoS One. 2023.", "pmid": "37368919", "doi": "10.1371/journal.pone.0287703", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37368919/", "publicSourceType": "PMID" }, { "text": "Hansen R, Sejer EPF, Holm C, Schroll JB. Iron supplements in pregnant women with normal iron status: A systematic review and meta-analysis. Acta Obstetricia et Gynecologica Scandinavica. 2023.", "pmid": "37403900", "doi": "10.1111/aogs.14607", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37403900/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Omeprazole reduces gastric acid production, which is essential for converting dietary and supplemental iron to its absorbable ferrous (Fe2+) form.", "clinicalSignificance": "Long-term PPI use can lead to iron deficiency, particularly in patients with marginal iron stores or those relying on non-heme iron sources.", "managementStrategy": "If on long-term omeprazole, monitor iron levels and ferritin periodically. Consider taking iron supplements with vitamin C to enhance absorption, or use ferrous bisglycinate which is less pH-dependent. Take iron between meals if tolerated.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Pantoprazole", "supplementBName": "Iron", "interactionType": "caution", "severity": "moderate", "description": "Pantoprazole suppresses gastric acid, reducing the acidic environment needed for efficient iron absorption. Long-term use can impair iron status, especially in patients with increased iron needs or those consuming primarily non-heme iron sources.", "recommendation": "Monitor iron levels and ferritin during long-term pantoprazole therapy. Consider vitamin C co-administration with iron supplements to compensate for reduced gastric acidity, or use chelated iron forms.", "minimumTimeSeparation": null, "mechanism": "Pantoprazole elevates gastric pH by inhibiting the H+/K+ ATPase (proton pump). The resulting reduction in gastric acidity impairs the solubilization and reduction of iron from Fe3+ to Fe2+, which is necessary for DMT1-mediated absorption in the duodenum.", "evidenceLevel": "moderate", "sources": [ { "text": "Sarzynski E et al. Association between proton pump inhibitor use and anemia: a retrospective cohort study. Dig Dis Sci. 2011;56(8):2349-2353.", "pmid": "21318590", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21318590/", "publicSourceType": "PMID" }, { "text": "Fischer JAJ, Cherian AM, Bone JN, Karakochuk CD. The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials. Nutrition Reviews. 2023.", "pmid": "36728680", "doi": "10.1093/nutrit/nuac106", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36728680/", "publicSourceType": "PMID" }, { "text": "Rehman T, Agrawal R, Ahamed F et al.. Optimal dose and duration of iron supplementation for treating iron deficiency anaemia in children and adolescents: A systematic review and meta-analysis. PLoS One. 2025.", "pmid": "39951396", "doi": "10.1371/journal.pone.0319068", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39951396/", "publicSourceType": "PMID" }, { "text": "Gutema BT, Sorrie MB, Megersa ND et al.. Effects of iron supplementation on cognitive development in school-age children: Systematic review and meta-analysis. PLoS One. 2023.", "pmid": "37368919", "doi": "10.1371/journal.pone.0287703", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37368919/", "publicSourceType": "PMID" }, { "text": "Hansen R, Sejer EPF, Holm C, Schroll JB. Iron supplements in pregnant women with normal iron status: A systematic review and meta-analysis. Acta Obstetricia et Gynecologica Scandinavica. 2023.", "pmid": "37403900", "doi": "10.1111/aogs.14607", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37403900/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Pantoprazole suppresses gastric acid, reducing the acidic environment needed for efficient iron absorption.", "clinicalSignificance": "Long-term use can impair iron status, especially in patients with increased iron needs or those consuming primarily non-heme iron sources.", "managementStrategy": "Monitor iron levels and ferritin during long-term pantoprazole therapy. Consider vitamin C co-administration with iron supplements to compensate for reduced gastric acidity, or use chelated iron forms.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Omeprazole", "supplementBName": "Calcium", "interactionType": "caution", "severity": "moderate", "description": "Long-term omeprazole use reduces calcium absorption, particularly from calcium carbonate which requires an acidic environment for dissolution. This has been associated with increased fracture risk in observational studies, prompting an FDA warning about PPI use and fracture risk.", "recommendation": "If on long-term omeprazole, consider using calcium citrate instead of calcium carbonate, as citrate does not require gastric acid for absorption. Ensure adequate vitamin D intake and consider bone density monitoring.", "minimumTimeSeparation": null, "mechanism": "Calcium carbonate requires gastric acid for dissolution and ionization into absorbable Ca2+. Omeprazole raises gastric pH, reducing calcium carbonate solubility. Calcium citrate is pH-independent and is better absorbed during PPI therapy.", "evidenceLevel": "moderate", "sources": [ { "text": "Yang YX et al. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296(24):2947-2953.", "pmid": "17190895", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17190895/", "publicSourceType": "PMID" }, { "text": "Choudhury A, Jena A, Jearth V, Dutta AK et al.. Vitamin B12 deficiency and use of proton pump inhibitors: a systematic review and meta-analysis. Expert Review of Gastroenterology & Hepatology. 2023.", "pmid": "37060552", "doi": "10.1080/17474124.2023.2204229", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37060552/", "publicSourceType": "PMID" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Long-term omeprazole use reduces calcium absorption, particularly from calcium carbonate which requires an acidic environment for dissolution.", "clinicalSignificance": "This has been associated with increased fracture risk in observational studies, prompting an FDA warning about PPI use and fracture risk.", "managementStrategy": "If on long-term omeprazole, consider using calcium citrate instead of calcium carbonate, as citrate does not require gastric acid for absorption. Ensure adequate vitamin D intake and consider bone density monitoring.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Pantoprazole", "supplementBName": "Calcium", "interactionType": "caution", "severity": "moderate", "description": "Pantoprazole, like other PPIs, reduces gastric acidity needed for calcium carbonate absorption. Long-term use may impair calcium balance and has been associated with increased fracture risk in epidemiologic studies.", "recommendation": "Use calcium citrate instead of calcium carbonate if on long-term pantoprazole therapy. Ensure adequate vitamin D for calcium absorption and discuss fracture risk with your prescriber.", "minimumTimeSeparation": null, "mechanism": "Pantoprazole inhibits gastric H+/K+ ATPase, raising gastric pH. Calcium carbonate requires pH <4 for adequate dissolution. The reduced acidity impairs calcium carbonate solubility and subsequent calcium ion absorption in the small intestine.", "evidenceLevel": "moderate", "sources": [ { "text": "Yang YX et al. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296(24):2947-2953.", "pmid": "17190895", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17190895/", "publicSourceType": "PMID" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Pantoprazole, like other PPIs, reduces gastric acidity needed for calcium carbonate absorption.", "clinicalSignificance": "Long-term use may impair calcium balance and has been associated with increased fracture risk in epidemiologic studies.", "managementStrategy": "Use calcium citrate instead of calcium carbonate if on long-term pantoprazole therapy. Ensure adequate vitamin D for calcium absorption and discuss fracture risk with your prescriber.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Omeprazole", "supplementBName": "Vitamin B12", "interactionType": "caution", "severity": "moderate", "description": "Long-term omeprazole use significantly impairs vitamin B12 absorption. Gastric acid and pepsin are required to release B12 from food proteins before it can bind intrinsic factor. Studies show 65% increased risk of B12 deficiency with >2 years of PPI use.", "recommendation": "Monitor B12 levels annually during long-term omeprazole therapy. Consider B12 supplementation (sublingual methylcobalamin 1000 mcg/day bypasses the gastric absorption requirement) or periodic B12 injections.", "minimumTimeSeparation": null, "mechanism": "Gastric acid and pepsin are needed to cleave vitamin B12 from dietary proteins. In the achlorhydric environment created by omeprazole, B12 remains protein-bound and cannot transfer to R-protein and subsequently intrinsic factor for absorption in the terminal ileum.", "evidenceLevel": "strong", "sources": [ { "text": "Lam JR et al. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-2442.", "pmid": "24327038", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24327038/", "publicSourceType": "PMID" }, { "text": "Choudhury A, Jena A, Jearth V, Dutta AK et al.. Vitamin B12 deficiency and use of proton pump inhibitors: a systematic review and meta-analysis. Expert Review of Gastroenterology & Hepatology. 2023.", "pmid": "37060552", "doi": "10.1080/17474124.2023.2204229", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37060552/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Long-term omeprazole use significantly impairs vitamin B12 absorption.", "clinicalSignificance": "Gastric acid and pepsin are required to release B12 from food proteins before it can bind intrinsic factor.", "managementStrategy": "Monitor B12 levels annually during long-term omeprazole therapy. Consider B12 supplementation (sublingual methylcobalamin 1000 mcg/day bypasses the gastric absorption requirement) or periodic B12 injections.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Pantoprazole", "supplementBName": "Vitamin B12", "interactionType": "caution", "severity": "moderate", "description": "Pantoprazole, like all PPIs, impairs vitamin B12 absorption by suppressing gastric acid needed to release B12 from food proteins. The risk increases with duration of use and can lead to megaloblastic anemia and neurologic symptoms if undetected.", "recommendation": "Monitor B12 levels periodically during long-term pantoprazole therapy. Sublingual B12 supplementation is preferred as it bypasses the gastric absorption pathway affected by PPIs.", "minimumTimeSeparation": null, "mechanism": "Pantoprazole suppresses gastric acid and pepsinogen activation, preventing the release of protein-bound B12 in the stomach. Without this critical first step, B12 cannot bind to intrinsic factor and be absorbed in the ileum.", "evidenceLevel": "strong", "sources": [ { "text": "Lam JR et al. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-2442.", "pmid": "24327038", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24327038/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Pantoprazole, like all PPIs, impairs vitamin B12 absorption by suppressing gastric acid needed to release B12 from food proteins.", "clinicalSignificance": "The risk increases with duration of use and can lead to megaloblastic anemia and neurologic symptoms if undetected.", "managementStrategy": "Monitor B12 levels periodically during long-term pantoprazole therapy. Sublingual B12 supplementation is preferred as it bypasses the gastric absorption pathway affected by PPIs.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Omeprazole", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "PPIs like omeprazole reduce gastric vitamin C levels by increasing gastric pH, which oxidizes ascorbic acid to its less bioavailable form. Vitamin C supplementation can help restore depleted levels and may also improve iron absorption that is impaired by PPI-induced achlorhydria.", "recommendation": "Consider vitamin C supplementation (250-500mg/day) if on long-term omeprazole therapy. Taking vitamin C with iron supplements can help compensate for PPI-impaired iron absorption.", "minimumTimeSeparation": null, "mechanism": "Gastric acid maintains vitamin C in its reduced, absorbable form (ascorbic acid). Omeprazole-induced pH elevation promotes oxidation to dehydroascorbic acid, which is less stable and less readily absorbed. Supplemental vitamin C bypasses this gastric degradation.", "evidenceLevel": "moderate", "sources": [ { "text": "Henry EB et al. Proton pump inhibitors reduce the bioavailability of dietary vitamin C. Aliment Pharmacol Ther. 2005;22(6):539-545.", "pmid": "16167971", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16167971/", "publicSourceType": "PMID" }, { "text": "Choudhury A, Jena A, Jearth V, Dutta AK et al.. Vitamin B12 deficiency and use of proton pump inhibitors: a systematic review and meta-analysis. Expert Review of Gastroenterology & Hepatology. 2023.", "pmid": "37060552", "doi": "10.1080/17474124.2023.2204229", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37060552/", "publicSourceType": "PMID" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials.. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" }, { "text": "Wen C, Li Y, Hu Q et al.. IV Vitamin C in Sepsis: A Latest Systematic Review and Meta-Analysis.. International Journal of Clinical Practice. 2023.", "pmid": "36743822", "doi": "10.1155/2023/6733465", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36743822/", "publicSourceType": "PMID" }, { "text": "Jenkins DJA, Spence JD, Giovannucci EL et al.. Supplemental Vitamins and Minerals for Cardiovascular Disease Prevention and Treatment: JACC Focus Seminar.. Journal of the American College of Cardiology. 2021.", "pmid": "33509399", "doi": "10.1016/j.jacc.2020.09.619", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33509399/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "PPIs like omeprazole reduce gastric vitamin C levels by increasing gastric pH, which oxidizes ascorbic acid to its less bioavailable form.", "clinicalSignificance": "Vitamin C supplementation can help restore depleted levels and may also improve iron absorption that is impaired by PPI-induced achlorhydria.", "managementStrategy": "Consider vitamin C supplementation (250-500mg/day) if on long-term omeprazole therapy. Taking vitamin C with iron supplements can help compensate for PPI-impaired iron absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Pantoprazole", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Pantoprazole, like other PPIs, may reduce gastric vitamin C levels by altering the gastric pH environment. Vitamin C supplementation can help maintain adequate levels and provide additional benefit by enhancing iron absorption in the achlorhydric environment.", "recommendation": "Consider vitamin C supplementation (250-500mg/day) during long-term pantoprazole therapy, especially if also concerned about iron absorption.", "minimumTimeSeparation": null, "mechanism": "Pantoprazole-induced gastric pH elevation promotes oxidation of ascorbic acid to dehydroascorbic acid, reducing vitamin C bioavailability from dietary sources. Supplemental vitamin C provides the reduced form directly.", "evidenceLevel": "moderate", "sources": [ { "text": "Henry EB et al. Proton pump inhibitors reduce the bioavailability of dietary vitamin C. Aliment Pharmacol Ther. 2005;22(6):539-545.", "pmid": "16167971", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16167971/", "publicSourceType": "PMID" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials.. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" }, { "text": "Wen C, Li Y, Hu Q et al.. IV Vitamin C in Sepsis: A Latest Systematic Review and Meta-Analysis.. International Journal of Clinical Practice. 2023.", "pmid": "36743822", "doi": "10.1155/2023/6733465", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36743822/", "publicSourceType": "PMID" }, { "text": "Jenkins DJA, Spence JD, Giovannucci EL et al.. Supplemental Vitamins and Minerals for Cardiovascular Disease Prevention and Treatment: JACC Focus Seminar.. Journal of the American College of Cardiology. 2021.", "pmid": "33509399", "doi": "10.1016/j.jacc.2020.09.619", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33509399/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Pantoprazole, like other PPIs, may reduce gastric vitamin C levels by altering the gastric pH environment.", "clinicalSignificance": "Vitamin C supplementation can help maintain adequate levels and provide additional benefit by enhancing iron absorption in the achlorhydric environment.", "managementStrategy": "Consider vitamin C supplementation (250-500mg/day) during long-term pantoprazole therapy, especially if also concerned about iron absorption.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Alprazolam", "supplementBName": "Valerian Root", "interactionType": "caution", "severity": "serious", "description": "Valerian root has GABAergic sedative properties that can potentiate alprazolam's CNS depressant effects. The combination may cause excessive sedation, impaired motor function, respiratory depression, and increased risk of falls, particularly in elderly patients.", "recommendation": "Avoid combining valerian root with alprazolam. If you use valerian for sleep, discontinue it while taking benzodiazepines. Do not drive or operate machinery if using both.", "minimumTimeSeparation": null, "mechanism": "Valerian's valerenic acid and other compounds modulate GABA-A receptor activity, increasing GABAergic inhibitory neurotransmission. Alprazolam is a positive allosteric modulator at GABA-A receptors. Combined GABAergic enhancement causes additive CNS depression.", "evidenceLevel": "moderate", "sources": [ { "text": "Houghton PJ. The scientific basis for the reputed activity of valerian. J Pharm Pharmacol. 1999;51(5):505-512.", "pmid": "10411208", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10411208/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Valerian root has GABAergic sedative properties that can potentiate alprazolam's CNS depressant effects.", "clinicalSignificance": "The combination may cause excessive sedation, impaired motor function, respiratory depression, and increased risk of falls, particularly in elderly patients.", "managementStrategy": "Avoid combining valerian root with alprazolam. If you use valerian for sleep, discontinue it while taking benzodiazepines. Do not drive or operate machinery if using both.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Lorazepam", "supplementBName": "Valerian Root", "interactionType": "caution", "severity": "serious", "description": "Valerian root enhances GABAergic activity, which adds to lorazepam's CNS depressant effects. This combination can lead to excessive sedation, psychomotor impairment, and potentially dangerous respiratory depression.", "recommendation": "Avoid combining valerian root with lorazepam. The additive sedative effects can be dangerous. If you need sleep support while on lorazepam, discuss alternatives with your prescriber.", "minimumTimeSeparation": null, "mechanism": "Valerian root contains valerenic acid, isovaleric acid, and other compounds that enhance GABA-A receptor function and inhibit GABA degradation. Lorazepam increases GABA-A receptor chloride conductance. The combined GABAergic augmentation produces excessive inhibitory neurotransmission.", "evidenceLevel": "moderate", "sources": [ { "text": "Houghton PJ. The scientific basis for the reputed activity of valerian. J Pharm Pharmacol. 1999;51(5):505-512.", "pmid": "10411208", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10411208/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Valerian root enhances GABAergic activity, which adds to lorazepam's CNS depressant effects.", "clinicalSignificance": "This combination can lead to excessive sedation, psychomotor impairment, and potentially dangerous respiratory depression.", "managementStrategy": "Avoid combining valerian root with lorazepam. The additive sedative effects can be dangerous. If you need sleep support while on lorazepam, discuss alternatives with your prescriber.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Alprazolam", "supplementBName": "Melatonin", "interactionType": "caution", "severity": "moderate", "description": "Melatonin has mild sedative properties that can add to alprazolam's CNS depressant effects. While the interaction is generally less dangerous than with kava or valerian, the combination may cause increased daytime drowsiness, dizziness, and impaired coordination.", "recommendation": "Use melatonin cautiously with alprazolam. Start with a low melatonin dose (0.5-1mg). Avoid driving or operating machinery until you know how the combination affects you. Discuss timing optimization with your prescriber.", "minimumTimeSeparation": null, "mechanism": "Melatonin activates MT1 and MT2 receptors in the suprachiasmatic nucleus and other brain regions, promoting sleep and reducing alertness. This adds to alprazolam's GABA-A mediated sedation, increasing overall CNS depression.", "evidenceLevel": "moderate", "sources": [ { "text": "Garfinkel D et al. Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet. 1995;346(8974):541-544.", "pmid": "7658780", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7658780/", "publicSourceType": "PMID" }, { "text": "Fatemeh G, Sajjad M, Niloufar R et al.. Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials.. Journal of Neurology. 2022.", "pmid": "33417003", "doi": "10.1007/s00415-020-10381-w", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33417003/", "publicSourceType": "PMID" }, { "text": "Tang BHY, Manalo J, Chowdhury SR et al.. Melatonin Use in the ICU: A Systematic Review and Meta-Analysis.. Critical Care Medicine. 2025.", "pmid": "40662882", "doi": "10.1097/CCM.0000000000006767", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40662882/", "publicSourceType": "PMID" }, { "text": "Chan V, Lo K. Efficacy of dietary supplements on improving sleep quality: a systematic review and meta-analysis.. Postgraduate Medical Journal. 2022.", "pmid": "33441476", "doi": "10.1136/postgradmedj-2020-139319", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33441476/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Melatonin has mild sedative properties that can add to alprazolam's CNS depressant effects.", "clinicalSignificance": "While the interaction is generally less dangerous than with kava or valerian, the combination may cause increased daytime drowsiness, dizziness, and impaired coordination.", "managementStrategy": "Use melatonin cautiously with alprazolam. Start with a low melatonin dose (0.5-1mg). Avoid driving or operating machinery until you know how the combination affects you. Discuss timing optimization with your prescriber.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Lorazepam", "supplementBName": "Melatonin", "interactionType": "caution", "severity": "moderate", "description": "Melatonin's sedative effects can compound lorazepam's CNS depression. While some research suggests melatonin may help facilitate benzodiazepine tapering, combining both at full doses may cause excessive sedation and next-day drowsiness.", "recommendation": "If using melatonin with lorazepam, start with a low melatonin dose (0.5-1mg) and monitor for excessive sedation. Melatonin may be useful as part of a supervised benzodiazepine tapering strategy but should not be added without medical guidance.", "minimumTimeSeparation": null, "mechanism": "Melatonin acts on MT1/MT2 receptors to promote sleep onset and modulate circadian rhythm. The sedative effects are additive with lorazepam's enhancement of GABAergic inhibitory neurotransmission at GABA-A receptors.", "evidenceLevel": "moderate", "sources": [ { "text": "Garfinkel D et al. Facilitation of benzodiazepine discontinuation by melatonin. Arch Intern Med. 1999;159(20):2456-2460.", "pmid": "10665894", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10665894/", "publicSourceType": "PMID" }, { "text": "Fatemeh G, Sajjad M, Niloufar R et al.. Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials.. Journal of Neurology. 2022.", "pmid": "33417003", "doi": "10.1007/s00415-020-10381-w", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33417003/", "publicSourceType": "PMID" }, { "text": "Tang BHY, Manalo J, Chowdhury SR et al.. Melatonin Use in the ICU: A Systematic Review and Meta-Analysis.. Critical Care Medicine. 2025.", "pmid": "40662882", "doi": "10.1097/CCM.0000000000006767", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40662882/", "publicSourceType": "PMID" }, { "text": "Chan V, Lo K. Efficacy of dietary supplements on improving sleep quality: a systematic review and meta-analysis.. Postgraduate Medical Journal. 2022.", "pmid": "33441476", "doi": "10.1136/postgradmedj-2020-139319", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33441476/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Melatonin's sedative effects can compound lorazepam's CNS depression.", "clinicalSignificance": "While some research suggests melatonin may help facilitate benzodiazepine tapering, combining both at full doses may cause excessive sedation and next-day drowsiness.", "managementStrategy": "If using melatonin with lorazepam, start with a low melatonin dose (0.5-1mg) and monitor for excessive sedation. Melatonin may be useful as part of a supervised benzodiazepine tapering strategy but should not be added without medical guidance.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Alprazolam", "supplementBName": "GABA", "interactionType": "caution", "severity": "moderate", "description": "Supplemental GABA may have mild sedative and anxiolytic effects, though its ability to cross the blood-brain barrier is debated. If any GABA does reach the CNS, it could potentiate alprazolam's GABAergic effects, increasing sedation and CNS depression.", "recommendation": "Use caution when combining GABA supplements with alprazolam. While oral GABA's CNS penetration is limited, the theoretical additive effect warrants monitoring for excessive sedation.", "minimumTimeSeparation": null, "mechanism": "Supplemental GABA, if it reaches the CNS (debated), would directly activate GABA-A and GABA-B receptors, adding to alprazolam's positive allosteric modulation of GABA-A receptors. Even peripheral GABA effects through the enteric nervous system may contribute to sedation.", "evidenceLevel": "emerging", "sources": [ { "text": "Boonstra E et al. Neurotransmitters as food supplements: the effects of GABA on brain and behavior. Front Psychol. 2015;6:1520.", "pmid": "26500584", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26500584/", "publicSourceType": "PMID" }, { "text": "Guimarães AP, Seidel H, Pires LVM et al.. GABA Supplementation, Increased Heart-Rate Variability, Emotional Response, Sleep Efficiency and Reduced Depression in Sedentary Overweight Women Undergoing Physical Exercise: Placebo-Controlled, Randomized Clinical Trial. Journal of Dietary Supplements. 2024.", "pmid": "38321713", "doi": "10.1080/19390211.2024.2308262", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38321713/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Supplemental GABA may have mild sedative and anxiolytic effects, though its ability to cross the blood-brain barrier is debated.", "clinicalSignificance": "If any GABA does reach the CNS, it could potentiate alprazolam's GABAergic effects, increasing sedation and CNS depression.", "managementStrategy": "Use caution when combining GABA supplements with alprazolam. While oral GABA's CNS penetration is limited, the theoretical additive effect warrants monitoring for excessive sedation.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Lorazepam", "supplementBName": "GABA", "interactionType": "caution", "severity": "moderate", "description": "Supplemental GABA may have sedative effects that could add to lorazepam's CNS depression. Although the extent of oral GABA's blood-brain barrier penetration is uncertain, the potential for additive GABAergic effects warrants caution with this combination.", "recommendation": "Exercise caution when combining GABA supplements with lorazepam. Monitor for excessive sedation, drowsiness, or impaired coordination.", "minimumTimeSeparation": null, "mechanism": "If supplemental GABA crosses the blood-brain barrier, it would directly activate GABA receptors, adding to lorazepam's enhancement of GABA-A receptor-mediated chloride conductance. Peripheral GABAergic effects may also contribute to overall sedation.", "evidenceLevel": "emerging", "sources": [ { "text": "Boonstra E et al. Neurotransmitters as food supplements: the effects of GABA on brain and behavior. Front Psychol. 2015;6:1520.", "pmid": "26500584", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26500584/", "publicSourceType": "PMID" }, { "text": "Guimarães AP, Seidel H, Pires LVM et al.. GABA Supplementation, Increased Heart-Rate Variability, Emotional Response, Sleep Efficiency and Reduced Depression in Sedentary Overweight Women Undergoing Physical Exercise: Placebo-Controlled, Randomized Clinical Trial. Journal of Dietary Supplements. 2024.", "pmid": "38321713", "doi": "10.1080/19390211.2024.2308262", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38321713/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Supplemental GABA may have sedative effects that could add to lorazepam's CNS depression.", "clinicalSignificance": "Although the extent of oral GABA's blood-brain barrier penetration is uncertain, the potential for additive GABAergic effects warrants caution with this combination.", "managementStrategy": "Exercise caution when combining GABA supplements with lorazepam. Monitor for excessive sedation, drowsiness, or impaired coordination.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Lithium", "supplementBName": "Magnesium Glycinate", "interactionType": "caution", "severity": "moderate", "description": "Magnesium may affect lithium excretion and distribution, as both are divalent cations handled by similar renal transport mechanisms. Changes in magnesium status can alter lithium levels. Additionally, lithium can itself cause magnesium wasting.", "recommendation": "Monitor lithium levels when starting or stopping magnesium supplements. If magnesium supplementation is needed (which it may be, as lithium can deplete magnesium), start at a low dose and have lithium levels checked within 1-2 weeks.", "minimumTimeSeparation": null, "mechanism": "Magnesium and lithium share renal tubular transport mechanisms. Changes in magnesium intake can alter lithium reabsorption in the proximal tubule. Lithium also inhibits magnesium-dependent enzymes and can increase renal magnesium excretion.", "evidenceLevel": "emerging", "sources": [ { "text": "Timmer RT, Sands JM. Lithium intoxication. J Am Soc Nephrol. 1999;10(3):666-674.", "pmid": "10073618", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10073618/", "publicSourceType": "PMID" }, { "text": "Mah J, Pitre T. Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis.. BMC Complementary Medicine and Therapies. 2021.", "pmid": "33865376", "doi": "10.1186/s12906-021-03297-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33865376/", "publicSourceType": "PMID" }, { "text": "Veronese N, Dominguez LJ, Pizzol D et al.. Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.. Nutrients. 2021.", "pmid": "34836329", "doi": "10.3390/nu13114074", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34836329/", "publicSourceType": "PMID" }, { "text": "Veronese N, Pizzol D, Smith L et al.. Effect of Magnesium Supplementation on Inflammatory Parameters: A Meta-Analysis of Randomized Controlled Trials.. Nutrients. 2022.", "pmid": "35277037", "doi": "10.3390/nu14030679", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35277037/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Magnesium may affect lithium excretion and distribution, as both are divalent cations handled by similar renal transport mechanisms.", "clinicalSignificance": "Changes in magnesium status can alter lithium levels.", "managementStrategy": "Monitor lithium levels when starting or stopping magnesium supplements. If magnesium supplementation is needed (which it may be, as lithium can deplete magnesium), start at a low dose and have lithium levels checked within 1-2 weeks.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Lithium", "supplementBName": "Zinc", "interactionType": "caution", "severity": "info", "description": "Zinc and lithium have minor interactions related to shared transport mechanisms and effects on thyroid function. While the interaction is not well-characterized, both affect thyroid hormone metabolism and monitoring is prudent.", "recommendation": "The interaction is minor, but inform your prescriber if supplementing with zinc while on lithium. Continue routine lithium and thyroid monitoring as prescribed.", "minimumTimeSeparation": null, "mechanism": "Both zinc and lithium affect thyroid function through different mechanisms. Lithium inhibits thyroid hormone release, while zinc is required for thyroid hormone synthesis. Changes in zinc status may theoretically affect the thyroid impact of lithium therapy.", "evidenceLevel": "insufficient", "sources": [ { "text": "Kibirige D et al. Thyroid dysfunction among patients on lithium therapy. Afr Health Sci. 2013;13(4):1048-1055.", "pmid": "24940333", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24940333/", "publicSourceType": "PMID" }, { "text": "Hsu TJ, Hsieh RH, Huang CH et al.. Efficacy of Zinc Supplementation in the Management of Primary Dysmenorrhea: A Systematic Review and Meta-Analysis.. Nutrients. 2024.", "pmid": "39683510", "doi": "10.3390/nu16234116", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39683510/", "publicSourceType": "PMID" }, { "text": "Ali AA, Naqvi SK, Hasnain Z et al.. Zinc supplementation for acute and persistent watery diarrhoea in children: A systematic review and meta-analysis.. Journal of Global Health. 2024.", "pmid": "39641338", "doi": "10.7189/jogh.14.04212", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39641338/", "publicSourceType": "PMID" }, { "text": "Oh C, Keats EC, Bhutta ZA. Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.. Nutrients. 2020.", "pmid": "32075071", "doi": "10.3390/nu12020491", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32075071/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Zinc and lithium have minor interactions related to shared transport mechanisms and effects on thyroid function.", "clinicalSignificance": "While the interaction is not well-characterized, both affect thyroid hormone metabolism and monitoring is prudent.", "managementStrategy": "The interaction is minor, but inform your prescriber if supplementing with zinc while on lithium. Continue routine lithium and thyroid monitoring as prescribed.", "isSynergistic": false, "interactionEvidenceRating": "insufficient", "scope": "prescription-supplement" }, { "supplementAName": "Lithium", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "Fish oil (EPA/DHA) may have additive mood-stabilizing benefits when combined with lithium. Omega-3 fatty acids have demonstrated modest efficacy in bipolar disorder, and the combination may enhance therapeutic outcomes without significant adverse interaction risk.", "recommendation": "Fish oil supplementation (1-2g EPA+DHA/day) may be a beneficial adjunct to lithium therapy for mood stabilization. No specific timing separation is needed. Discuss with your prescriber.", "minimumTimeSeparation": null, "mechanism": "EPA and DHA modulate neuronal membrane fluidity, reduce neuroinflammation via specialized pro-resolving mediators, and may affect signal transduction pathways involved in mood regulation. These mechanisms complement lithium's effects on inositol cycling and GSK-3 beta inhibition.", "evidenceLevel": "moderate", "sources": [ { "text": "Stoll AL et al. Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial. Arch Gen Psychiatry. 1999;56(5):407-412.", "pmid": "10232294", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10232294/", "publicSourceType": "PMID" }, { "text": "Liao Y, Xie B, Zhang H et al.. Efficacy of omega-3 PUFAs in depression: A meta-analysis.. Translational Psychiatry. 2019.", "pmid": "31383846", "doi": "10.1038/s41398-019-0515-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31383846/", "publicSourceType": "PMID" }, { "text": "Wei BZ, Li L, Dong CW et al.. The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers.. American Journal of Clinical Nutrition. 2023.", "pmid": "37028557", "doi": "10.1016/j.ajcnut.2023.04.001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37028557/", "publicSourceType": "PMID" }, { "text": "Uchida Y, Tsuji K, Ochi E. Effects of Omega-3 fatty acids supplementation and resistance training on skeletal muscle.. Clinical Nutrition ESPEN. 2024.", "pmid": "38777432", "doi": "10.1016/j.clnesp.2024.03.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38777432/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Fish oil (EPA/DHA) may have additive mood-stabilizing benefits when combined with lithium.", "clinicalSignificance": "Omega-3 fatty acids have demonstrated modest efficacy in bipolar disorder, and the combination may enhance therapeutic outcomes without significant adverse interaction risk.", "managementStrategy": "Fish oil supplementation (1-2g EPA+DHA/day) may be a beneficial adjunct to lithium therapy for mood stabilization. No specific timing separation is needed. Discuss with your prescriber.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Lithium", "supplementBName": "Potassium", "interactionType": "caution", "severity": "moderate", "description": "Both lithium and potassium are affected by renal excretion mechanisms, and changes in potassium balance can influence lithium handling. Potassium-sparing or potassium-wasting conditions can alter lithium levels, and the narrow therapeutic index of lithium makes even modest changes clinically relevant.", "recommendation": "Maintain consistent potassium intake while on lithium. Avoid large, sudden changes in potassium supplementation. Monitor lithium levels and electrolytes regularly as prescribed.", "minimumTimeSeparation": null, "mechanism": "Lithium is reabsorbed in the proximal tubule via sodium channels and is affected by electrolyte balance. Changes in potassium status can alter sodium-lithium exchange in the renal tubule, affecting lithium clearance and serum levels.", "evidenceLevel": "emerging", "sources": [ { "text": "Timmer RT, Sands JM. Lithium intoxication. J Am Soc Nephrol. 1999;10(3):666-674.", "pmid": "10073618", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10073618/", "publicSourceType": "PMID" }, { "text": "Filippini T, Naska A, Kasdagli MI et al.. Potassium Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials. Journal of the American Heart Association. 2020.", "pmid": "32500831", "doi": "10.1161/JAHA.119.015719", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32500831/", "publicSourceType": "PMID" }, { "text": "Behers BJ, Behers BM, Stephenson-Moe CA et al.. Magnesium and Potassium Supplementation for Systolic Blood Pressure Reduction in the General Normotensive Population: A Systematic Review and Subgroup Meta-Analysis for Optimal Dosage and Treatment Length. Nutrients. 2024.", "pmid": "39519450", "doi": "10.3390/nu16213617", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39519450/", "publicSourceType": "PMID" }, { "text": "D'Elia L, Cappuccio FP, Masulli M et al.. Effect of Potassium Supplementation on Endothelial Function: A Systematic Review and Meta-Analysis of Intervention Studies. Nutrients. 2023.", "pmid": "36839211", "doi": "10.3390/nu15040853", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36839211/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both lithium and potassium are affected by renal excretion mechanisms, and changes in potassium balance can influence lithium handling.", "clinicalSignificance": "Potassium-sparing or potassium-wasting conditions can alter lithium levels, and the narrow therapeutic index of lithium makes even modest changes clinically relevant.", "managementStrategy": "Maintain consistent potassium intake while on lithium. Avoid large, sudden changes in potassium supplementation. Monitor lithium levels and electrolytes regularly as prescribed.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Ciprofloxacin", "supplementBName": "Calcium", "interactionType": "timingSensitive", "severity": "serious", "description": "Calcium chelates ciprofloxacin in the GI tract, forming insoluble calcium-quinolone complexes that can reduce ciprofloxacin absorption by up to 90%. This can render the antibiotic completely ineffective, leading to treatment failure and potential antibiotic resistance development.", "recommendation": "Separate ciprofloxacin and calcium supplements by at least 2 hours (take ciprofloxacin 2 hours before or 6 hours after calcium). This timing separation is critical for maintaining antibiotic efficacy.", "minimumTimeSeparation": 120, "mechanism": "Calcium divalent cations form insoluble chelate complexes with ciprofloxacin's 4-oxo and 3-carboxyl groups, which are essential for both antibacterial activity and GI absorption. The chelated complex is not absorbed and is excreted in feces.", "evidenceLevel": "strong", "sources": [ { "text": "Lomaestro BM, Bailie GR. Absorption interactions with fluoroquinolones. Drug Saf. 1995;12(5):314-333.", "pmid": "7646824", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7646824/", "publicSourceType": "PMID" }, { "text": "Alves C, Mendes D, Marques FB. Fluoroquinolones and the risk of tendon injury: a systematic review and meta-analysis.. European Journal of Clinical Pharmacology. 2019.", "pmid": "31270563", "doi": "10.1007/s00228-019-02713-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31270563/", "publicSourceType": "PMID" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Calcium chelates ciprofloxacin in the GI tract, forming insoluble calcium-quinolone complexes that can reduce ciprofloxacin absorption by up to 90%.", "clinicalSignificance": "This can render the antibiotic completely ineffective, leading to treatment failure and potential antibiotic resistance development.", "managementStrategy": "Separate ciprofloxacin and calcium supplements by at least 2 hours (take ciprofloxacin 2 hours before or 6 hours after calcium). This timing separation is critical for maintaining antibiotic efficacy.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Ciprofloxacin", "supplementBName": "Iron", "interactionType": "timingSensitive", "severity": "serious", "description": "Iron strongly chelates ciprofloxacin, forming insoluble iron-quinolone complexes that dramatically reduce ciprofloxacin absorption and efficacy. This interaction can cause antibiotic treatment failure, which is particularly dangerous during active infection.", "recommendation": "Separate ciprofloxacin and iron supplements by at least 2 hours (take ciprofloxacin 2 hours before or 6 hours after iron). Do not take them together under any circumstances during active antibiotic treatment.", "minimumTimeSeparation": 120, "mechanism": "Iron (Fe2+/Fe3+) forms tight chelate complexes with ciprofloxacin's keto-carboxylate moiety. Iron is one of the most potent chelators of fluoroquinolones, reducing bioavailability by 30-90% depending on the iron dose and formulation.", "evidenceLevel": "strong", "sources": [ { "text": "Polk RE et al. Effect of ferrous sulfate and multivitamins with zinc on absorption of ciprofloxacin in normal volunteers. Antimicrob Agents Chemother. 1989;33(11):1841-1844.", "pmid": "2610487", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2610487/", "publicSourceType": "PMID" }, { "text": "Alves C, Mendes D, Marques FB. Fluoroquinolones and the risk of tendon injury: a systematic review and meta-analysis.. European Journal of Clinical Pharmacology. 2019.", "pmid": "31270563", "doi": "10.1007/s00228-019-02713-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31270563/", "publicSourceType": "PMID" }, { "text": "Fischer JAJ, Cherian AM, Bone JN, Karakochuk CD. The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials. Nutrition Reviews. 2023.", "pmid": "36728680", "doi": "10.1093/nutrit/nuac106", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36728680/", "publicSourceType": "PMID" }, { "text": "Rehman T, Agrawal R, Ahamed F et al.. Optimal dose and duration of iron supplementation for treating iron deficiency anaemia in children and adolescents: A systematic review and meta-analysis. PLoS One. 2025.", "pmid": "39951396", "doi": "10.1371/journal.pone.0319068", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39951396/", "publicSourceType": "PMID" }, { "text": "Gutema BT, Sorrie MB, Megersa ND et al.. Effects of iron supplementation on cognitive development in school-age children: Systematic review and meta-analysis. PLoS One. 2023.", "pmid": "37368919", "doi": "10.1371/journal.pone.0287703", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37368919/", "publicSourceType": "PMID" }, { "text": "Hansen R, Sejer EPF, Holm C, Schroll JB. Iron supplements in pregnant women with normal iron status: A systematic review and meta-analysis. Acta Obstetricia et Gynecologica Scandinavica. 2023.", "pmid": "37403900", "doi": "10.1111/aogs.14607", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37403900/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Iron strongly chelates ciprofloxacin, forming insoluble iron-quinolone complexes that dramatically reduce ciprofloxacin absorption and efficacy.", "clinicalSignificance": "This interaction can cause antibiotic treatment failure, which is particularly dangerous during active infection.", "managementStrategy": "Separate ciprofloxacin and iron supplements by at least 2 hours (take ciprofloxacin 2 hours before or 6 hours after iron). Do not take them together under any circumstances during active antibiotic treatment.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Ciprofloxacin", "supplementBName": "Magnesium Glycinate", "interactionType": "timingSensitive", "severity": "serious", "description": "Magnesium chelates ciprofloxacin, forming insoluble complexes that substantially reduce antibiotic absorption. Magnesium-containing antacids are well-documented to impair fluoroquinolone efficacy. This interaction can lead to subtherapeutic antibiotic levels and treatment failure.", "recommendation": "Separate ciprofloxacin and magnesium supplements by at least 2 hours (take ciprofloxacin 2 hours before or 6 hours after magnesium). This includes magnesium-containing antacids and laxatives.", "minimumTimeSeparation": 120, "mechanism": "Magnesium divalent cations chelate ciprofloxacin via the 4-oxo-3-carboxylic acid group, forming an insoluble complex that cannot be absorbed across the intestinal mucosa. The binding affinity is high enough to render the antibiotic inactive.", "evidenceLevel": "strong", "sources": [ { "text": "Lomaestro BM, Bailie GR. Absorption interactions with fluoroquinolones. Drug Saf. 1995;12(5):314-333.", "pmid": "7646824", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7646824/", "publicSourceType": "PMID" }, { "text": "Alves C, Mendes D, Marques FB. Fluoroquinolones and the risk of tendon injury: a systematic review and meta-analysis.. European Journal of Clinical Pharmacology. 2019.", "pmid": "31270563", "doi": "10.1007/s00228-019-02713-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31270563/", "publicSourceType": "PMID" }, { "text": "Mah J, Pitre T. Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis.. BMC Complementary Medicine and Therapies. 2021.", "pmid": "33865376", "doi": "10.1186/s12906-021-03297-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33865376/", "publicSourceType": "PMID" }, { "text": "Veronese N, Dominguez LJ, Pizzol D et al.. Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.. Nutrients. 2021.", "pmid": "34836329", "doi": "10.3390/nu13114074", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34836329/", "publicSourceType": "PMID" }, { "text": "Veronese N, Pizzol D, Smith L et al.. Effect of Magnesium Supplementation on Inflammatory Parameters: A Meta-Analysis of Randomized Controlled Trials.. Nutrients. 2022.", "pmid": "35277037", "doi": "10.3390/nu14030679", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35277037/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Magnesium chelates ciprofloxacin, forming insoluble complexes that substantially reduce antibiotic absorption.", "clinicalSignificance": "Magnesium-containing antacids are well-documented to impair fluoroquinolone efficacy.", "managementStrategy": "Separate ciprofloxacin and magnesium supplements by at least 2 hours (take ciprofloxacin 2 hours before or 6 hours after magnesium). This includes magnesium-containing antacids and laxatives.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Ciprofloxacin", "supplementBName": "Zinc", "interactionType": "timingSensitive", "severity": "serious", "description": "Zinc chelates ciprofloxacin in the GI tract, reducing absorption and potentially causing treatment failure. Zinc-containing multivitamins have been shown to reduce ciprofloxacin bioavailability significantly, compromising antibacterial efficacy.", "recommendation": "Separate ciprofloxacin and zinc supplements by at least 2 hours (take ciprofloxacin 2 hours before or 6 hours after zinc). Check multivitamin labels for zinc content and separate accordingly.", "minimumTimeSeparation": 120, "mechanism": "Zinc divalent cations form stable chelate complexes with ciprofloxacin's keto-carboxylate moiety. The resulting zinc-ciprofloxacin complex has poor aqueous solubility and cannot be absorbed in the intestine.", "evidenceLevel": "strong", "sources": [ { "text": "Polk RE et al. Effect of ferrous sulfate and multivitamins with zinc on absorption of ciprofloxacin in normal volunteers. Antimicrob Agents Chemother. 1989;33(11):1841-1844.", "pmid": "2610487", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2610487/", "publicSourceType": "PMID" }, { "text": "Alves C, Mendes D, Marques FB. Fluoroquinolones and the risk of tendon injury: a systematic review and meta-analysis.. European Journal of Clinical Pharmacology. 2019.", "pmid": "31270563", "doi": "10.1007/s00228-019-02713-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31270563/", "publicSourceType": "PMID" }, { "text": "Hsu TJ, Hsieh RH, Huang CH et al.. Efficacy of Zinc Supplementation in the Management of Primary Dysmenorrhea: A Systematic Review and Meta-Analysis.. Nutrients. 2024.", "pmid": "39683510", "doi": "10.3390/nu16234116", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39683510/", "publicSourceType": "PMID" }, { "text": "Ali AA, Naqvi SK, Hasnain Z et al.. Zinc supplementation for acute and persistent watery diarrhoea in children: A systematic review and meta-analysis.. Journal of Global Health. 2024.", "pmid": "39641338", "doi": "10.7189/jogh.14.04212", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39641338/", "publicSourceType": "PMID" }, { "text": "Oh C, Keats EC, Bhutta ZA. Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.. Nutrients. 2020.", "pmid": "32075071", "doi": "10.3390/nu12020491", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32075071/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Zinc chelates ciprofloxacin in the GI tract, reducing absorption and potentially causing treatment failure.", "clinicalSignificance": "Zinc-containing multivitamins have been shown to reduce ciprofloxacin bioavailability significantly, compromising antibacterial efficacy.", "managementStrategy": "Separate ciprofloxacin and zinc supplements by at least 2 hours (take ciprofloxacin 2 hours before or 6 hours after zinc). Check multivitamin labels for zinc content and separate accordingly.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Doxycycline", "supplementBName": "Calcium", "interactionType": "timingSensitive", "severity": "serious", "description": "Calcium chelates doxycycline, forming insoluble tetracycline-calcium complexes that significantly reduce antibiotic absorption. This can reduce doxycycline bioavailability by 20-50%, potentially leading to subtherapeutic levels and treatment failure.", "recommendation": "Separate doxycycline and calcium supplements by at least 2 hours. Avoid dairy products (high calcium) within 2 hours of doxycycline dosing. Take doxycycline with water between meals for optimal absorption.", "minimumTimeSeparation": 120, "mechanism": "Calcium ions chelate doxycycline's beta-diketone system and adjacent hydroxyl groups, forming insoluble calcium-tetracycline complexes. These complexes are too large and insoluble for intestinal absorption and are excreted in feces.", "evidenceLevel": "strong", "sources": [ { "text": "Leyden JJ. Absorption of minocycline hydrochloride and tetracycline hydrochloride: effect of food, milk, and iron. J Am Acad Dermatol. 1985;12(2 Pt 1):308-312.", "pmid": "3973128", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3973128/", "publicSourceType": "PMID" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Calcium chelates doxycycline, forming insoluble tetracycline-calcium complexes that significantly reduce antibiotic absorption.", "clinicalSignificance": "This can reduce doxycycline bioavailability by 20-50%, potentially leading to subtherapeutic levels and treatment failure.", "managementStrategy": "Separate doxycycline and calcium supplements by at least 2 hours. Avoid dairy products (high calcium) within 2 hours of doxycycline dosing. Take doxycycline with water between meals for optimal absorption.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Doxycycline", "supplementBName": "Iron", "interactionType": "timingSensitive", "severity": "serious", "description": "Iron forms chelation complexes with doxycycline that significantly impair antibiotic absorption. Studies show iron can reduce tetracycline absorption by 50-90%. This interaction is clinically significant and can lead to antibiotic treatment failure.", "recommendation": "Separate doxycycline and iron supplements by at least 2 hours. Take doxycycline at least 2 hours before or after iron to ensure adequate antibiotic absorption and treatment efficacy.", "minimumTimeSeparation": 120, "mechanism": "Iron (Fe2+ and Fe3+) chelates doxycycline through its hydroxyl and keto groups, forming insoluble iron-tetracycline complexes. Iron is a particularly strong chelator of tetracyclines, producing very stable complexes with minimal dissociation.", "evidenceLevel": "strong", "sources": [ { "text": "Neuvonen PJ. Interactions with the absorption of tetracyclines. Drugs. 1976;11(1):45-54.", "pmid": "1083209", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1083209/", "publicSourceType": "PMID" }, { "text": "Fischer JAJ, Cherian AM, Bone JN, Karakochuk CD. The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials. Nutrition Reviews. 2023.", "pmid": "36728680", "doi": "10.1093/nutrit/nuac106", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36728680/", "publicSourceType": "PMID" }, { "text": "Rehman T, Agrawal R, Ahamed F et al.. Optimal dose and duration of iron supplementation for treating iron deficiency anaemia in children and adolescents: A systematic review and meta-analysis. PLoS One. 2025.", "pmid": "39951396", "doi": "10.1371/journal.pone.0319068", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39951396/", "publicSourceType": "PMID" }, { "text": "Gutema BT, Sorrie MB, Megersa ND et al.. Effects of iron supplementation on cognitive development in school-age children: Systematic review and meta-analysis. PLoS One. 2023.", "pmid": "37368919", "doi": "10.1371/journal.pone.0287703", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37368919/", "publicSourceType": "PMID" }, { "text": "Hansen R, Sejer EPF, Holm C, Schroll JB. Iron supplements in pregnant women with normal iron status: A systematic review and meta-analysis. Acta Obstetricia et Gynecologica Scandinavica. 2023.", "pmid": "37403900", "doi": "10.1111/aogs.14607", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37403900/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Iron forms chelation complexes with doxycycline that significantly impair antibiotic absorption.", "clinicalSignificance": "Studies show iron can reduce tetracycline absorption by 50-90%.", "managementStrategy": "Separate doxycycline and iron supplements by at least 2 hours. Take doxycycline at least 2 hours before or after iron to ensure adequate antibiotic absorption and treatment efficacy.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Doxycycline", "supplementBName": "Magnesium Glycinate", "interactionType": "timingSensitive", "severity": "serious", "description": "Magnesium chelates doxycycline, reducing its absorption and potentially compromising treatment efficacy. Magnesium-containing antacids are well-known to impair tetracycline absorption. The interaction is clinically significant and requires proper dose spacing.", "recommendation": "Separate doxycycline and magnesium supplements by at least 2 hours. This includes magnesium-containing antacids and laxatives. Take doxycycline with water on an empty stomach when possible.", "minimumTimeSeparation": 120, "mechanism": "Magnesium divalent cations chelate doxycycline via its multiple hydroxyl and keto groups, forming poorly soluble magnesium-tetracycline complexes that resist intestinal absorption.", "evidenceLevel": "strong", "sources": [ { "text": "Neuvonen PJ. Interactions with the absorption of tetracyclines. Drugs. 1976;11(1):45-54.", "pmid": "1083209", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1083209/", "publicSourceType": "PMID" }, { "text": "Mah J, Pitre T. Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis.. BMC Complementary Medicine and Therapies. 2021.", "pmid": "33865376", "doi": "10.1186/s12906-021-03297-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33865376/", "publicSourceType": "PMID" }, { "text": "Veronese N, Dominguez LJ, Pizzol D et al.. Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.. Nutrients. 2021.", "pmid": "34836329", "doi": "10.3390/nu13114074", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34836329/", "publicSourceType": "PMID" }, { "text": "Veronese N, Pizzol D, Smith L et al.. Effect of Magnesium Supplementation on Inflammatory Parameters: A Meta-Analysis of Randomized Controlled Trials.. Nutrients. 2022.", "pmid": "35277037", "doi": "10.3390/nu14030679", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35277037/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Magnesium chelates doxycycline, reducing its absorption and potentially compromising treatment efficacy.", "clinicalSignificance": "Magnesium-containing antacids are well-known to impair tetracycline absorption.", "managementStrategy": "Separate doxycycline and magnesium supplements by at least 2 hours. This includes magnesium-containing antacids and laxatives. Take doxycycline with water on an empty stomach when possible.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Doxycycline", "supplementBName": "Zinc", "interactionType": "timingSensitive", "severity": "moderate", "description": "Zinc chelates doxycycline, reducing its absorption. While the effect is somewhat less pronounced than with calcium or iron, it is still clinically relevant and can reduce antibiotic efficacy, particularly at higher zinc supplement doses.", "recommendation": "Separate doxycycline and zinc supplements by at least 2 hours to minimize the chelation interaction. Check multivitamins for zinc content and time accordingly.", "minimumTimeSeparation": 120, "mechanism": "Zinc forms chelation complexes with doxycycline's adjacent hydroxyl and keto groups. While zinc's chelation affinity for tetracyclines is slightly lower than iron or calcium, it still produces clinically meaningful reductions in doxycycline bioavailability.", "evidenceLevel": "moderate", "sources": [ { "text": "Neuvonen PJ. Interactions with the absorption of tetracyclines. Drugs. 1976;11(1):45-54.", "pmid": "1083209", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1083209/", "publicSourceType": "PMID" }, { "text": "Hsu TJ, Hsieh RH, Huang CH et al.. Efficacy of Zinc Supplementation in the Management of Primary Dysmenorrhea: A Systematic Review and Meta-Analysis.. Nutrients. 2024.", "pmid": "39683510", "doi": "10.3390/nu16234116", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39683510/", "publicSourceType": "PMID" }, { "text": "Ali AA, Naqvi SK, Hasnain Z et al.. Zinc supplementation for acute and persistent watery diarrhoea in children: A systematic review and meta-analysis.. Journal of Global Health. 2024.", "pmid": "39641338", "doi": "10.7189/jogh.14.04212", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39641338/", "publicSourceType": "PMID" }, { "text": "Oh C, Keats EC, Bhutta ZA. Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.. Nutrients. 2020.", "pmid": "32075071", "doi": "10.3390/nu12020491", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32075071/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Zinc chelates doxycycline, reducing its absorption.", "clinicalSignificance": "While the effect is somewhat less pronounced than with calcium or iron, it is still clinically relevant and can reduce antibiotic efficacy, particularly at higher zinc supplement doses.", "managementStrategy": "Separate doxycycline and zinc supplements by at least 2 hours to minimize the chelation interaction. Check multivitamins for zinc content and time accordingly.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Prednisone", "supplementBName": "Calcium", "interactionType": "synergy", "severity": "moderate", "description": "Prednisone and other corticosteroids significantly deplete calcium through multiple mechanisms, increasing the risk of osteoporosis and fractures. Calcium supplementation is considered standard of care for patients on chronic corticosteroid therapy.", "recommendation": "Take calcium (1000-1200mg/day in divided doses) with vitamin D while on chronic prednisone therapy. This is a guideline-recommended practice for preventing corticosteroid-induced osteoporosis. Use calcium citrate for better absorption.", "minimumTimeSeparation": null, "mechanism": "Prednisone reduces intestinal calcium absorption, increases renal calcium excretion, inhibits osteoblast function, and stimulates osteoclast-mediated bone resorption. It also reduces calcium-binding protein (calbindin) expression in the intestine. Supplemental calcium helps offset these multiple depletive mechanisms.", "evidenceLevel": "strong", "sources": [ { "text": "Buckley LM et al. Calcium and vitamin D3 supplementation prevents bone loss in the spine secondary to low-dose corticosteroids. Ann Intern Med. 1996;125(12):961-968.", "pmid": "8967706", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8967706/", "publicSourceType": "PMID" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Prednisone and other corticosteroids significantly deplete calcium through multiple mechanisms, increasing the risk of osteoporosis and fractures.", "clinicalSignificance": "Calcium supplementation is considered standard of care for patients on chronic corticosteroid therapy.", "managementStrategy": "Take calcium (1000-1200mg/day in divided doses) with vitamin D while on chronic prednisone therapy. This is a guideline-recommended practice for preventing corticosteroid-induced osteoporosis. Use calcium citrate for better absorption.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Prednisone", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "moderate", "description": "Prednisone impairs vitamin D metabolism and reduces its active form (calcitriol) production. This contributes to decreased calcium absorption and accelerated bone loss. Vitamin D supplementation is considered essential during chronic corticosteroid therapy to maintain bone health.", "recommendation": "Take vitamin D3 (1000-2000 IU/day) while on chronic prednisone therapy. Higher doses may be needed based on serum 25-OH vitamin D levels. This is guideline-recommended for preventing corticosteroid-induced osteoporosis.", "minimumTimeSeparation": null, "mechanism": "Prednisone reduces 1-alpha-hydroxylase activity in the kidney (impairing conversion of 25-OH vitamin D to active 1,25-dihydroxyvitamin D), increases vitamin D catabolism via 24-hydroxylase induction, and antagonizes vitamin D receptor signaling in the intestine, reducing calcium absorption.", "evidenceLevel": "strong", "sources": [ { "text": "Buckley LM et al. Calcium and vitamin D3 supplementation prevents bone loss in the spine secondary to low-dose corticosteroids. Ann Intern Med. 1996;125(12):961-968.", "pmid": "8967706", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8967706/", "publicSourceType": "PMID" }, { "text": "Zhang Y, Fang F, Tang J et al.. Association between vitamin D supplementation and mortality: systematic review and meta-analysis.. BMJ. 2019.", "pmid": "31405892", "doi": "10.1136/bmj.l4673", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31405892/", "publicSourceType": "PMID" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" }, { "text": "Fiamenghi VI, Mello ED. Vitamin D deficiency in children and adolescents with obesity: a meta-analysis.. Jornal de pediatria. 2021.", "pmid": "33022267", "doi": "10.1016/j.jped.2020.08.006", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33022267/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Prednisone impairs vitamin D metabolism and reduces its active form (calcitriol) production.", "clinicalSignificance": "This contributes to decreased calcium absorption and accelerated bone loss.", "managementStrategy": "Take vitamin D3 (1000-2000 IU/day) while on chronic prednisone therapy. Higher doses may be needed based on serum 25-OH vitamin D levels. This is guideline-recommended for preventing corticosteroid-induced osteoporosis.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Prednisone", "supplementBName": "Potassium", "interactionType": "synergy", "severity": "moderate", "description": "Prednisone can promote potassium loss or potassium shifts in susceptible patients, especially at higher systemic doses, prolonged use, or when combined with other hypokalemia risks.", "recommendation": "Monitor potassium when prednisone is high dose, prolonged, or combined with diuretics, vomiting, diarrhea, or heart-rhythm risk. Increase dietary potassium only if appropriate and use supplements only if labs/prescriber guidance support it.", "minimumTimeSeparation": null, "mechanism": "Prednisone activates mineralocorticoid receptors in the distal nephron, increasing ENaC-mediated sodium reabsorption and ROMK-mediated potassium secretion. This exchange leads to net potassium loss in the urine. Higher prednisone doses have greater mineralocorticoid activity.", "evidenceLevel": "strong", "sources": [ { "text": "Conn JW, Fajans SS. Influence of adrenal cortical steroids on carbohydrate metabolism in man. Metabolism. 1956;5(2):114-127.", "pmid": "13296871", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/13296871/", "publicSourceType": "PMID" }, { "text": "Filippini T, Naska A, Kasdagli MI et al.. Potassium Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials. Journal of the American Heart Association. 2020.", "pmid": "32500831", "doi": "10.1161/JAHA.119.015719", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32500831/", "publicSourceType": "PMID" }, { "text": "Behers BJ, Behers BM, Stephenson-Moe CA et al.. Magnesium and Potassium Supplementation for Systolic Blood Pressure Reduction in the General Normotensive Population: A Systematic Review and Subgroup Meta-Analysis for Optimal Dosage and Treatment Length. Nutrients. 2024.", "pmid": "39519450", "doi": "10.3390/nu16213617", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39519450/", "publicSourceType": "PMID" }, { "text": "D'Elia L, Cappuccio FP, Masulli M et al.. Effect of Potassium Supplementation on Endothelial Function: A Systematic Review and Meta-Analysis of Intervention Studies. Nutrients. 2023.", "pmid": "36839211", "doi": "10.3390/nu15040853", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36839211/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Prednisone has mineralocorticoid activity that causes potassium wasting through increased renal excretion.", "clinicalSignificance": "Hypokalemia can cause weakness, cramps, palpitations, arrhythmias, and metabolic alkalosis; unsupervised potassium replacement can overshoot.", "managementStrategy": "Check serum potassium and kidney function when risk factors are present; use potassium supplements only at a prescriber-guided dose.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Alendronate", "supplementBName": "Calcium", "interactionType": "timingSensitive", "severity": "serious", "description": "Calcium chelates alendronate and dramatically reduces its already-low bioavailability (0.6-0.7%). Taking calcium within 30 minutes of alendronate can render the bisphosphonate completely ineffective for osteoporosis treatment. However, calcium supplementation at a different time is recommended for bone health.", "recommendation": "Take alendronate first thing in the morning with plain water, at least 30 minutes before any food, beverages, or supplements including calcium. Take calcium supplements later in the day, at least 30 minutes after alendronate.", "minimumTimeSeparation": 30, "mechanism": "Calcium cations chelate alendronate's bisphosphonate groups, forming insoluble calcium-bisphosphonate complexes. Since alendronate's baseline oral bioavailability is already less than 1%, even small reductions from chelation can eliminate therapeutic drug levels entirely.", "evidenceLevel": "strong", "sources": [ { "text": "Gertz BJ et al. Studies of the oral bioavailability of alendronate. Clin Pharmacol Ther. 1995;58(3):288-298.", "pmid": "7554702", "doi": "10.1016/0009-9236(95)90245-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7554702/", "publicSourceType": "PMID" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Calcium chelates alendronate and dramatically reduces its already-low bioavailability (0.6-0.7%).", "clinicalSignificance": "Taking calcium within 30 minutes of alendronate can render the bisphosphonate completely ineffective for osteoporosis treatment.", "managementStrategy": "Take alendronate first thing in the morning with plain water, at least 30 minutes before any food, beverages, or supplements including calcium. Take calcium supplements later in the day, at least 30 minutes after alendronate.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Alendronate", "supplementBName": "Iron", "interactionType": "timingSensitive", "severity": "serious", "description": "Iron chelates alendronate in the GI tract, substantially reducing the already-poor oral absorption of this bisphosphonate. Given alendronate's baseline bioavailability is less than 1%, any chelation interaction is clinically critical.", "recommendation": "Take alendronate at least 30 minutes before iron supplements. Follow standard alendronate dosing: take with plain water first thing in the morning, remain upright, and avoid all food and supplements for at least 30 minutes.", "minimumTimeSeparation": 30, "mechanism": "Iron cations form stable chelate complexes with alendronate's phosphonate groups, creating insoluble iron-bisphosphonate precipitates that cannot be absorbed. This further reduces the drug's already minimal bioavailability.", "evidenceLevel": "moderate", "sources": [ { "text": "Gertz BJ et al. Studies of the oral bioavailability of alendronate. Clin Pharmacol Ther. 1995;58(3):288-298.", "pmid": "7554702", "doi": "10.1016/0009-9236(95)90245-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7554702/", "publicSourceType": "PMID" }, { "text": "Fischer JAJ, Cherian AM, Bone JN, Karakochuk CD. The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials. Nutrition Reviews. 2023.", "pmid": "36728680", "doi": "10.1093/nutrit/nuac106", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36728680/", "publicSourceType": "PMID" }, { "text": "Rehman T, Agrawal R, Ahamed F et al.. Optimal dose and duration of iron supplementation for treating iron deficiency anaemia in children and adolescents: A systematic review and meta-analysis. PLoS One. 2025.", "pmid": "39951396", "doi": "10.1371/journal.pone.0319068", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39951396/", "publicSourceType": "PMID" }, { "text": "Gutema BT, Sorrie MB, Megersa ND et al.. Effects of iron supplementation on cognitive development in school-age children: Systematic review and meta-analysis. PLoS One. 2023.", "pmid": "37368919", "doi": "10.1371/journal.pone.0287703", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37368919/", "publicSourceType": "PMID" }, { "text": "Hansen R, Sejer EPF, Holm C, Schroll JB. Iron supplements in pregnant women with normal iron status: A systematic review and meta-analysis. Acta Obstetricia et Gynecologica Scandinavica. 2023.", "pmid": "37403900", "doi": "10.1111/aogs.14607", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37403900/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Iron chelates alendronate in the GI tract, substantially reducing the already-poor oral absorption of this bisphosphonate.", "clinicalSignificance": "Given alendronate's baseline bioavailability is less than 1%, any chelation interaction is clinically critical.", "managementStrategy": "Take alendronate at least 30 minutes before iron supplements. Follow standard alendronate dosing: take with plain water first thing in the morning, remain upright, and avoid all food and supplements for at least 30 minutes.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Alendronate", "supplementBName": "Magnesium Glycinate", "interactionType": "timingSensitive", "severity": "moderate", "description": "Magnesium can chelate alendronate, reducing its absorption. While the interaction is similar in mechanism to calcium and iron, alendronate's extremely low bioavailability makes any absorption reduction clinically relevant.", "recommendation": "Take alendronate at least 30 minutes before magnesium supplements. Follow standard alendronate dosing instructions: plain water only, first thing in the morning, remain upright for 30 minutes.", "minimumTimeSeparation": 30, "mechanism": "Magnesium divalent cations bind to alendronate's phosphonate groups, forming chelation complexes that reduce the fraction of drug available for intestinal absorption. Even modest reductions in bioavailability are significant given alendronate's baseline absorption of <1%.", "evidenceLevel": "moderate", "sources": [ { "text": "Gertz BJ et al. Studies of the oral bioavailability of alendronate. Clin Pharmacol Ther. 1995;58(3):288-298.", "pmid": "7554702", "doi": "10.1016/0009-9236(95)90245-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7554702/", "publicSourceType": "PMID" }, { "text": "Mah J, Pitre T. Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis.. BMC Complementary Medicine and Therapies. 2021.", "pmid": "33865376", "doi": "10.1186/s12906-021-03297-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33865376/", "publicSourceType": "PMID" }, { "text": "Veronese N, Dominguez LJ, Pizzol D et al.. Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.. Nutrients. 2021.", "pmid": "34836329", "doi": "10.3390/nu13114074", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34836329/", "publicSourceType": "PMID" }, { "text": "Veronese N, Pizzol D, Smith L et al.. Effect of Magnesium Supplementation on Inflammatory Parameters: A Meta-Analysis of Randomized Controlled Trials.. Nutrients. 2022.", "pmid": "35277037", "doi": "10.3390/nu14030679", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35277037/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Magnesium can chelate alendronate, reducing its absorption.", "clinicalSignificance": "While the interaction is similar in mechanism to calcium and iron, alendronate's extremely low bioavailability makes any absorption reduction clinically relevant.", "managementStrategy": "Take alendronate at least 30 minutes before magnesium supplements. Follow standard alendronate dosing instructions: plain water only, first thing in the morning, remain upright for 30 minutes.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Phenytoin", "supplementBName": "Methylfolate", "interactionType": "caution", "severity": "moderate", "description": "Phenytoin depletes folate levels through increased catabolism and impaired absorption, potentially causing megaloblastic anemia. However, folate supplementation may reduce phenytoin levels by enhancing its metabolism, creating a bidirectional interaction that requires careful monitoring.", "recommendation": "Folate supplementation (0.5-1mg/day) is generally recommended for patients on phenytoin, but phenytoin levels should be monitored when starting folate. Dose adjustments of phenytoin may be necessary.", "minimumTimeSeparation": null, "mechanism": "Phenytoin inhibits folate absorption and increases its catabolism through enzyme induction. Conversely, folate supplementation enhances the activity of enzymes that metabolize phenytoin (CYP2C9/CYP2C19), potentially reducing phenytoin plasma levels. This creates a complex bidirectional interaction.", "evidenceLevel": "moderate", "sources": [ { "text": "Kishi T et al. Mechanism for reduction of serum folate by antiepileptic drugs during prolonged therapy. J Neurol Sci. 1997;145(1):109-112.", "pmid": "9073037", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9073037/", "publicSourceType": "PMID" }, { "text": "Lewis DP et al. Folic acid supplementation and phenytoin levels. Neurology. 1995;45(11):2187-2188.", "pmid": "7501158", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7501158/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Phenytoin depletes folate levels through increased catabolism and impaired absorption, potentially causing megaloblastic anemia.", "clinicalSignificance": "However, folate supplementation may reduce phenytoin levels by enhancing its metabolism, creating a bidirectional interaction that requires careful monitoring.", "managementStrategy": "Folate supplementation (0.5-1mg/day) is generally recommended for patients on phenytoin, but phenytoin levels should be monitored when starting folate. Dose adjustments of phenytoin may be necessary.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Phenytoin", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "moderate", "description": "Phenytoin is a potent CYP enzyme inducer that accelerates vitamin D catabolism through increased 24-hydroxylase activity. Long-term phenytoin use commonly causes vitamin D deficiency, osteomalacia, and increased fracture risk. Vitamin D supplementation is recommended during chronic therapy.", "recommendation": "Supplement with vitamin D3 (1000-4000 IU/day) during long-term phenytoin therapy. Monitor 25-OH vitamin D levels periodically and adjust dosing to maintain adequate levels (>30 ng/mL). Higher doses may be needed than in the general population.", "minimumTimeSeparation": null, "mechanism": "Phenytoin induces CYP3A4 and CYP24A1 (24-hydroxylase), which accelerates the catabolism of both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D to inactive metabolites. It may also directly impair calcium absorption independently of vitamin D status.", "evidenceLevel": "strong", "sources": [ { "text": "Pack AM, Morrell MJ. Epilepsy and bone health in adults. Epilepsy Behav. 2004;5(Suppl 2):S24-S29.", "pmid": "15123009", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15123009/", "publicSourceType": "PMID" }, { "text": "Zhang Y, Fang F, Tang J et al.. Association between vitamin D supplementation and mortality: systematic review and meta-analysis.. BMJ. 2019.", "pmid": "31405892", "doi": "10.1136/bmj.l4673", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31405892/", "publicSourceType": "PMID" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" }, { "text": "Fiamenghi VI, Mello ED. Vitamin D deficiency in children and adolescents with obesity: a meta-analysis.. Jornal de pediatria. 2021.", "pmid": "33022267", "doi": "10.1016/j.jped.2020.08.006", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33022267/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Phenytoin is a potent CYP enzyme inducer that accelerates vitamin D catabolism through increased 24-hydroxylase activity.", "clinicalSignificance": "Long-term phenytoin use commonly causes vitamin D deficiency, osteomalacia, and increased fracture risk.", "managementStrategy": "Supplement with vitamin D3 (1000-4000 IU/day) during long-term phenytoin therapy. Monitor 25-OH vitamin D levels periodically and adjust dosing to maintain adequate levels (>30 ng/mL). Higher doses may be needed than in the general population.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Phenytoin", "supplementBName": "Calcium", "interactionType": "timingSensitive", "severity": "moderate", "description": "Calcium can reduce phenytoin absorption if taken simultaneously. While calcium supplementation may be important for patients on phenytoin (which depletes calcium), timing must be managed to avoid impairing drug absorption and seizure control.", "recommendation": "Separate phenytoin and calcium supplements by at least 2 hours to avoid absorption interference. Calcium supplementation is still recommended for bone health during phenytoin therapy, just not at the same time as the medication.", "minimumTimeSeparation": 120, "mechanism": "Calcium can form complexes with phenytoin in the GI tract, reducing its dissolution and absorption. The interaction is most significant with calcium carbonate and other alkaline calcium forms that may also raise local pH, further affecting phenytoin solubility.", "evidenceLevel": "moderate", "sources": [ { "text": "Carter BL et al. Effect of antacids on phenytoin bioavailability. Ther Drug Monit. 1981;3(4):333-340.", "pmid": "7330692", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7330692/", "publicSourceType": "PMID" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Calcium can reduce phenytoin absorption if taken simultaneously.", "clinicalSignificance": "While calcium supplementation may be important for patients on phenytoin (which depletes calcium), timing must be managed to avoid impairing drug absorption and seizure control.", "managementStrategy": "Separate phenytoin and calcium supplements by at least 2 hours to avoid absorption interference. Calcium supplementation is still recommended for bone health during phenytoin therapy, just not at the same time as the medication.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Carbamazepine", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "Both carbamazepine and St. John's Wort are potent CYP3A4 inducers. Combining them creates unpredictable effects on drug metabolism, potentially causing auto-induction of carbamazepine's own metabolism, leading to subtherapeutic anticonvulsant levels and increased seizure risk.", "recommendation": "Avoid combining St. John's Wort with carbamazepine. The dual CYP induction creates unpredictable drug levels and may compromise seizure control. Monitor carbamazepine levels closely if the combination cannot be avoided.", "minimumTimeSeparation": null, "mechanism": "Carbamazepine is both a CYP3A4 substrate and inducer (auto-induction). St. John's Wort additionally induces CYP3A4 via PXR activation. The combined induction can accelerate carbamazepine metabolism beyond its auto-induction plateau, potentially reducing levels below the therapeutic range.", "evidenceLevel": "moderate", "sources": [ { "text": "Burstein AH et al. Lack of effect of St John's Wort on carbamazepine pharmacokinetics in healthy volunteers. Clin Pharmacol Ther. 2000;68(6):605-612.", "pmid": "11180019", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11180019/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Both carbamazepine and St.", "clinicalSignificance": "John's Wort are potent CYP3A4 inducers.", "managementStrategy": "Avoid combining St. John's Wort with carbamazepine. The dual CYP induction creates unpredictable drug levels and may compromise seizure control. Monitor carbamazepine levels closely if the combination cannot be avoided.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Carbamazepine", "supplementBName": "Methylfolate", "interactionType": "synergy", "severity": "moderate", "description": "Carbamazepine depletes folate through enzyme induction effects on folate metabolism. Folate deficiency during carbamazepine therapy can cause megaloblastic anemia and is particularly concerning in women of childbearing age due to increased neural tube defect risk during pregnancy.", "recommendation": "Supplement with folic acid (1mg/day) during carbamazepine therapy, particularly for women of childbearing age. Higher doses (4mg/day) are recommended periconceptionally for women on antiepileptic drugs.", "minimumTimeSeparation": null, "mechanism": "Carbamazepine induces hepatic enzymes that increase folate catabolism and may also impair intestinal folate absorption. The net effect is reduced serum and red cell folate levels, which can lead to megaloblastic changes and hyperhomocysteinemia over time.", "evidenceLevel": "strong", "sources": [ { "text": "Kishi T et al. Mechanism for reduction of serum folate by antiepileptic drugs during prolonged therapy. J Neurol Sci. 1997;145(1):109-112.", "pmid": "9073037", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9073037/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Carbamazepine depletes folate through enzyme induction effects on folate metabolism.", "clinicalSignificance": "Folate deficiency during carbamazepine therapy can cause megaloblastic anemia and is particularly concerning in women of childbearing age due to increased neural tube defect risk during pregnancy.", "managementStrategy": "Supplement with folic acid (1mg/day) during carbamazepine therapy, particularly for women of childbearing age. Higher doses (4mg/day) are recommended periconceptionally for women on antiepileptic drugs.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Carbamazepine", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "moderate", "description": "Carbamazepine induces CYP enzymes that accelerate vitamin D metabolism, leading to deficiency, reduced calcium absorption, and increased osteoporosis risk. Vitamin D supplementation is recommended for all patients on chronic carbamazepine therapy.", "recommendation": "Supplement with vitamin D3 (1000-4000 IU/day) during long-term carbamazepine therapy. Monitor 25-OH vitamin D levels and adjust doses accordingly. Higher doses may be needed due to accelerated vitamin D catabolism.", "minimumTimeSeparation": null, "mechanism": "Carbamazepine induces CYP3A4 and CYP24A1, increasing the catabolism of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D to inactive polar metabolites. This enzyme induction can reduce vitamin D half-life significantly, requiring higher supplemental doses to maintain adequate levels.", "evidenceLevel": "strong", "sources": [ { "text": "Pack AM, Morrell MJ. Epilepsy and bone health in adults. Epilepsy Behav. 2004;5(Suppl 2):S24-S29.", "pmid": "15123009", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15123009/", "publicSourceType": "PMID" }, { "text": "Zhang Y, Fang F, Tang J et al.. Association between vitamin D supplementation and mortality: systematic review and meta-analysis.. BMJ. 2019.", "pmid": "31405892", "doi": "10.1136/bmj.l4673", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31405892/", "publicSourceType": "PMID" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" }, { "text": "Fiamenghi VI, Mello ED. Vitamin D deficiency in children and adolescents with obesity: a meta-analysis.. Jornal de pediatria. 2021.", "pmid": "33022267", "doi": "10.1016/j.jped.2020.08.006", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33022267/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Carbamazepine induces CYP enzymes that accelerate vitamin D metabolism, leading to deficiency, reduced calcium absorption, and increased osteoporosis risk.", "clinicalSignificance": "Vitamin D supplementation is recommended for all patients on chronic carbamazepine therapy.", "managementStrategy": "Supplement with vitamin D3 (1000-4000 IU/day) during long-term carbamazepine therapy. Monitor 25-OH vitamin D levels and adjust doses accordingly. Higher doses may be needed due to accelerated vitamin D catabolism.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Levodopa/Carbidopa", "supplementBName": "Iron", "interactionType": "timingSensitive", "severity": "serious", "description": "Iron chelates levodopa in the GI tract, forming insoluble complexes that significantly reduce levodopa absorption. This can worsen Parkinson's disease symptoms by reducing the amount of levodopa reaching the brain. Studies show iron can reduce levodopa bioavailability by up to 50%.", "recommendation": "Separate levodopa/carbidopa and iron supplements by at least 2 hours. Take iron at a different time of day than your Parkinson's medication. Inform your neurologist about iron supplementation.", "minimumTimeSeparation": 120, "mechanism": "Iron (Fe2+ and Fe3+) chelates levodopa through its catechol (dihydroxyphenyl) group, forming stable iron-levodopa complexes that are not absorbed in the intestine. Carbidopa does not prevent this chelation interaction.", "evidenceLevel": "strong", "sources": [ { "text": "Campbell NR, Hasinoff BB. Iron supplements: a common cause of drug interactions. Br J Clin Pharmacol. 1991;31(3):251-255.", "pmid": "2054263", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2054263/", "publicSourceType": "PMID" }, { "text": "Fischer JAJ, Cherian AM, Bone JN, Karakochuk CD. The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials. Nutrition Reviews. 2023.", "pmid": "36728680", "doi": "10.1093/nutrit/nuac106", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36728680/", "publicSourceType": "PMID" }, { "text": "Rehman T, Agrawal R, Ahamed F et al.. Optimal dose and duration of iron supplementation for treating iron deficiency anaemia in children and adolescents: A systematic review and meta-analysis. PLoS One. 2025.", "pmid": "39951396", "doi": "10.1371/journal.pone.0319068", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39951396/", "publicSourceType": "PMID" }, { "text": "Gutema BT, Sorrie MB, Megersa ND et al.. Effects of iron supplementation on cognitive development in school-age children: Systematic review and meta-analysis. PLoS One. 2023.", "pmid": "37368919", "doi": "10.1371/journal.pone.0287703", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37368919/", "publicSourceType": "PMID" }, { "text": "Hansen R, Sejer EPF, Holm C, Schroll JB. Iron supplements in pregnant women with normal iron status: A systematic review and meta-analysis. Acta Obstetricia et Gynecologica Scandinavica. 2023.", "pmid": "37403900", "doi": "10.1111/aogs.14607", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37403900/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Iron chelates levodopa in the GI tract, forming insoluble complexes that significantly reduce levodopa absorption.", "clinicalSignificance": "This can worsen Parkinson's disease symptoms by reducing the amount of levodopa reaching the brain.", "managementStrategy": "Separate levodopa/carbidopa and iron supplements by at least 2 hours. Take iron at a different time of day than your Parkinson's medication. Inform your neurologist about iron supplementation.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Levodopa/Carbidopa", "supplementBName": "Vitamin B6", "interactionType": "caution", "severity": "serious", "description": "Vitamin B6 (pyridoxine) is a cofactor for DOPA decarboxylase, which converts levodopa to dopamine peripherally before it reaches the brain. While carbidopa blocks peripheral decarboxylation, high-dose B6 (>50mg/day) may partially overcome carbidopa's inhibition, reducing levodopa's efficacy.", "recommendation": "Avoid high-dose vitamin B6 supplements (>50mg/day) while on levodopa/carbidopa. Standard multivitamin doses of B6 (2-10mg) are generally safe when carbidopa is included. If you need higher B6 doses, consult your neurologist.", "minimumTimeSeparation": null, "mechanism": "Pyridoxal 5'-phosphate (active B6) is the essential cofactor for aromatic L-amino acid decarboxylase (AADC/DOPA decarboxylase). High-dose B6 increases peripheral AADC activity, potentially overwhelming carbidopa's competitive inhibition and converting levodopa to dopamine before it crosses the blood-brain barrier.", "evidenceLevel": "strong", "sources": [ { "text": "Duvoisin RC, Yahr MD, Cote LD. Pyridoxine reversal of L-dopa effects in Parkinsonism. Trans Am Neurol Assoc. 1969;94:81-84.", "pmid": "5374487", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/5374487/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Vitamin B6 (pyridoxine) is a cofactor for DOPA decarboxylase, which converts levodopa to dopamine peripherally before it reaches the brain.", "clinicalSignificance": "While carbidopa blocks peripheral decarboxylation, high-dose B6 (>50mg/day) may partially overcome carbidopa's inhibition, reducing levodopa's efficacy.", "managementStrategy": "Avoid high-dose vitamin B6 supplements (>50mg/day) while on levodopa/carbidopa. Standard multivitamin doses of B6 (2-10mg) are generally safe when carbidopa is included. If you need higher B6 doses, consult your neurologist.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Levodopa/Carbidopa", "supplementBName": "5-HTP", "interactionType": "caution", "severity": "moderate", "description": "5-HTP and levodopa may compete for the same amino acid transport systems (large neutral amino acid transporter) across the blood-brain barrier and for AADC enzyme activity. Additionally, increased central serotonin from 5-HTP may interact with dopaminergic pathways.", "recommendation": "Use caution when combining 5-HTP with levodopa/carbidopa. If considering 5-HTP for mood support, discuss with your neurologist first. Monitor for changes in Parkinson's symptom control or emergence of new side effects.", "minimumTimeSeparation": null, "mechanism": "5-HTP and levodopa are both substrates for AADC and share the large neutral amino acid transporter (LAT1) at the blood-brain barrier. Competition at both the enzymatic and transport levels may reduce the efficiency of levodopa conversion to dopamine in the brain.", "evidenceLevel": "emerging", "sources": [ { "text": "Birdsall TC. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998;3(4):271-280.", "pmid": "9727088", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9727088/", "publicSourceType": "PMID" }, { "text": "Truyens M, Lobatón T, Ferrante M et al.. Effect of 5-Hydroxytryptophan on Fatigue in Quiescent Inflammatory Bowel Disease: A Randomized Controlled Trial. Gastroenterology. 2022.", "pmid": "35940251", "doi": "10.1053/j.gastro.2022.07.052", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35940251/", "publicSourceType": "PMID" }, { "text": "Sutanto CN, Xia X, Heng CW et al.. The impact of 5-hydroxytryptophan supplementation on sleep quality and gut microbiota composition in older adults: A randomized controlled trial. Clinical Nutrition. 2024.", "pmid": "38309227", "doi": "10.1016/j.clnu.2024.01.010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38309227/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "5-HTP and levodopa may compete for the same amino acid transport systems (large neutral amino acid transporter) across the blood-brain barrier and for AADC enzyme activity.", "clinicalSignificance": "Additionally, increased central serotonin from 5-HTP may interact with dopaminergic pathways.", "managementStrategy": "Use caution when combining 5-HTP with levodopa/carbidopa. If considering 5-HTP for mood support, discuss with your neurologist first. Monitor for changes in Parkinson's symptom control or emergence of new side effects.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Methotrexate", "supplementBName": "Methylfolate", "interactionType": "synergy", "severity": "moderate", "description": "Folic acid supplementation is standard of care during methotrexate therapy. Methotrexate is a folate antagonist that depletes intracellular folate, causing side effects including mucositis, nausea, and cytopenias. Folate supplementation significantly reduces these adverse effects without compromising methotrexate efficacy for rheumatologic conditions.", "recommendation": "Take folic acid 1mg daily (or folinic acid 5mg weekly, 24 hours after MTX dose) during methotrexate therapy. This is guideline-recommended and reduces GI, hepatic, and hematologic toxicity. Discuss timing with your rheumatologist.", "minimumTimeSeparation": null, "mechanism": "Methotrexate inhibits dihydrofolate reductase (DHFR), depleting tetrahydrofolate pools needed for purine and thymidylate synthesis. Folic acid supplementation replenishes folate stores in normal rapidly-dividing cells, reducing toxicity while preserving MTX's anti-inflammatory effect (which is primarily mediated by adenosine release, not folate antagonism).", "evidenceLevel": "strong", "sources": [ { "text": "Shea B et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. Cochrane Database Syst Rev. 2013;(5):CD000951.", "pmid": "23728635", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23728635/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Folic acid supplementation is standard of care during methotrexate therapy.", "clinicalSignificance": "Methotrexate is a folate antagonist that depletes intracellular folate, causing side effects including mucositis, nausea, and cytopenias.", "managementStrategy": "Take folic acid 1mg daily (or folinic acid 5mg weekly, 24 hours after MTX dose) during methotrexate therapy. This is guideline-recommended and reduces GI, hepatic, and hematologic toxicity. Discuss timing with your rheumatologist.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Methotrexate", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "Fish oil (EPA/DHA) may have additive anti-inflammatory effects when combined with methotrexate for rheumatic conditions. Some studies suggest that omega-3 supplementation may allow reduced NSAID use in patients on MTX, improving overall tolerability of the treatment regimen.", "recommendation": "Fish oil supplementation (2-3g EPA+DHA/day) may be a beneficial adjunct to methotrexate therapy for inflammatory conditions. No timing separation is needed. Discuss with your rheumatologist.", "minimumTimeSeparation": null, "mechanism": "EPA and DHA reduce pro-inflammatory eicosanoid production (prostaglandins, leukotrienes) by competing with arachidonic acid for cyclooxygenase and lipoxygenase enzymes. They also generate specialized pro-resolving mediators (resolvins, protectins) that complement MTX's anti-inflammatory effect.", "evidenceLevel": "moderate", "sources": [ { "text": "Kremer JM et al. Effects of high-dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs. Arthritis Rheum. 1995;38(8):1107-1114.", "pmid": "7639807", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7639807/", "publicSourceType": "PMID" }, { "text": "Liao Y, Xie B, Zhang H et al.. Efficacy of omega-3 PUFAs in depression: A meta-analysis.. Translational Psychiatry. 2019.", "pmid": "31383846", "doi": "10.1038/s41398-019-0515-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31383846/", "publicSourceType": "PMID" }, { "text": "Wei BZ, Li L, Dong CW et al.. The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers.. American Journal of Clinical Nutrition. 2023.", "pmid": "37028557", "doi": "10.1016/j.ajcnut.2023.04.001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37028557/", "publicSourceType": "PMID" }, { "text": "Uchida Y, Tsuji K, Ochi E. Effects of Omega-3 fatty acids supplementation and resistance training on skeletal muscle.. Clinical Nutrition ESPEN. 2024.", "pmid": "38777432", "doi": "10.1016/j.clnesp.2024.03.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38777432/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Fish oil (EPA/DHA) may have additive anti-inflammatory effects when combined with methotrexate for rheumatic conditions.", "clinicalSignificance": "Some studies suggest that omega-3 supplementation may allow reduced NSAID use in patients on MTX, improving overall tolerability of the treatment regimen.", "managementStrategy": "Fish oil supplementation (2-3g EPA+DHA/day) may be a beneficial adjunct to methotrexate therapy for inflammatory conditions. No timing separation is needed. Discuss with your rheumatologist.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Methotrexate", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's Wort induces CYP enzymes and P-glycoprotein that may affect methotrexate metabolism and transport. While methotrexate is primarily renally cleared, changes in hepatic metabolism and P-gp-mediated transport can alter drug levels and potentially reduce efficacy or increase toxicity.", "recommendation": "Avoid St. John's Wort while on methotrexate. The potential for unpredictable changes in drug levels and the serious consequences of both subtherapeutic and supratherapeutic MTX levels make this combination inadvisable.", "minimumTimeSeparation": null, "mechanism": "St. John's Wort induces P-glycoprotein (MDR1), which transports methotrexate across cell membranes. Changes in P-gp activity can alter MTX distribution, renal excretion, and intracellular drug concentration. CYP enzyme induction may also affect minor metabolic pathways of MTX.", "evidenceLevel": "moderate", "sources": [ { "text": "Moore LB et al. St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc Natl Acad Sci USA. 2000;97(13):7500-7502.", "pmid": "10852961", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10852961/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St.", "clinicalSignificance": "John's Wort induces CYP enzymes and P-glycoprotein that may affect methotrexate metabolism and transport.", "managementStrategy": "Avoid St. John's Wort while on methotrexate. The potential for unpredictable changes in drug levels and the serious consequences of both subtherapeutic and supratherapeutic MTX levels make this combination inadvisable.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Digoxin", "supplementBName": "Magnesium Glycinate", "interactionType": "caution", "severity": "moderate", "description": "Hypomagnesemia increases sensitivity to digoxin toxicity by altering the cardiac sodium-potassium ATPase that digoxin inhibits. Maintaining adequate magnesium levels is important for preventing digoxin-related cardiac arrhythmias. Many patients on digoxin also take diuretics that deplete magnesium.", "recommendation": "Monitor magnesium levels regularly while on digoxin. Maintain adequate magnesium intake through supplementation if needed (200-400mg/day). Be especially vigilant if also taking diuretics that deplete magnesium.", "minimumTimeSeparation": null, "mechanism": "Magnesium normally competes with digoxin for binding to the Na+/K+-ATPase. When magnesium is depleted, digoxin binding affinity increases, potentiating its inhibitory effect on the sodium-potassium pump. This increases intracellular calcium and the risk of digoxin-induced cardiac arrhythmias.", "evidenceLevel": "strong", "sources": [ { "text": "Eichhorn EJ, Gheorghiade M. Digoxin--new perspective on an old drug. N Engl J Med. 2002;347(18):1394-1395.", "pmid": "12409540", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12409540/", "publicSourceType": "PMID" }, { "text": "Mah J, Pitre T. Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis.. BMC Complementary Medicine and Therapies. 2021.", "pmid": "33865376", "doi": "10.1186/s12906-021-03297-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33865376/", "publicSourceType": "PMID" }, { "text": "Veronese N, Dominguez LJ, Pizzol D et al.. Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.. Nutrients. 2021.", "pmid": "34836329", "doi": "10.3390/nu13114074", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34836329/", "publicSourceType": "PMID" }, { "text": "Veronese N, Pizzol D, Smith L et al.. Effect of Magnesium Supplementation on Inflammatory Parameters: A Meta-Analysis of Randomized Controlled Trials.. Nutrients. 2022.", "pmid": "35277037", "doi": "10.3390/nu14030679", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35277037/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Hypomagnesemia increases sensitivity to digoxin toxicity by altering the cardiac sodium-potassium ATPase that digoxin inhibits.", "clinicalSignificance": "Maintaining adequate magnesium levels is important for preventing digoxin-related cardiac arrhythmias.", "managementStrategy": "Monitor magnesium levels regularly while on digoxin. Maintain adequate magnesium intake through supplementation if needed (200-400mg/day). Be especially vigilant if also taking diuretics that deplete magnesium.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Digoxin", "supplementBName": "Potassium", "interactionType": "caution", "severity": "serious", "description": "Hypokalemia dramatically increases the risk of digoxin toxicity, including life-threatening cardiac arrhythmias. Conversely, hyperkalemia with digoxin can also be dangerous. Potassium levels must be kept within a very narrow range for safe digoxin therapy.", "recommendation": "Monitor potassium levels closely while on digoxin. Target serum potassium of 4.0-5.0 mEq/L. Potassium supplementation may be needed, especially if also taking diuretics, but avoid oversupplementation. Discuss with your prescriber.", "minimumTimeSeparation": null, "mechanism": "Digoxin inhibits the Na+/K+-ATPase. Hypokalemia reduces extracellular potassium competition for the ATPase binding site, increasing digoxin binding and toxicity. Hyperkalemia can also increase digoxin displacement from its binding site, leading to unpredictable cardiac effects.", "evidenceLevel": "strong", "sources": [ { "text": "Smith TW. Digitalis: mechanisms of action and clinical use. N Engl J Med. 1988;318(6):358-365.", "pmid": "3277052", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3277052/", "publicSourceType": "PMID" }, { "text": "Filippini T, Naska A, Kasdagli MI et al.. Potassium Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials. Journal of the American Heart Association. 2020.", "pmid": "32500831", "doi": "10.1161/JAHA.119.015719", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32500831/", "publicSourceType": "PMID" }, { "text": "Behers BJ, Behers BM, Stephenson-Moe CA et al.. Magnesium and Potassium Supplementation for Systolic Blood Pressure Reduction in the General Normotensive Population: A Systematic Review and Subgroup Meta-Analysis for Optimal Dosage and Treatment Length. Nutrients. 2024.", "pmid": "39519450", "doi": "10.3390/nu16213617", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39519450/", "publicSourceType": "PMID" }, { "text": "D'Elia L, Cappuccio FP, Masulli M et al.. Effect of Potassium Supplementation on Endothelial Function: A Systematic Review and Meta-Analysis of Intervention Studies. Nutrients. 2023.", "pmid": "36839211", "doi": "10.3390/nu15040853", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36839211/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Hypokalemia dramatically increases the risk of digoxin toxicity, including life-threatening cardiac arrhythmias.", "clinicalSignificance": "Conversely, hyperkalemia with digoxin can also be dangerous.", "managementStrategy": "Monitor potassium levels closely while on digoxin. Target serum potassium of 4.0-5.0 mEq/L. Potassium supplementation may be needed, especially if also taking diuretics, but avoid oversupplementation. Discuss with your prescriber.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Digoxin", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's Wort significantly reduces digoxin levels through potent P-glycoprotein induction. A landmark study showed that St. John's Wort reduced digoxin AUC by 25%, which can lead to loss of therapeutic effect and potential decompensation in heart failure patients.", "recommendation": "Do not combine St. John's Wort with digoxin. The reduction in digoxin levels can lead to loss of rate control or worsening heart failure. If already taking both, consult your cardiologist before making changes.", "minimumTimeSeparation": null, "mechanism": "St. John's Wort induces P-glycoprotein (MDR1) expression in the intestine and kidneys. Digoxin is a P-gp substrate, increased intestinal P-gp reduces digoxin absorption, and increased renal P-gp enhances digoxin secretion, together substantially lowering plasma digoxin concentrations.", "evidenceLevel": "strong", "sources": [ { "text": "Johne A et al. Pharmacokinetic interaction of digoxin with an herbal extract from St John's wort (Hypericum perforatum). Clin Pharmacol Ther. 1999;66(4):338-345.", "pmid": "10546917", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10546917/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St.", "clinicalSignificance": "John's Wort significantly reduces digoxin levels through potent P-glycoprotein induction.", "managementStrategy": "Do not combine St. John's Wort with digoxin. The reduction in digoxin levels can lead to loss of rate control or worsening heart failure. If already taking both, consult your cardiologist before making changes.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Hydrochlorothiazide", "supplementBName": "Potassium", "interactionType": "synergy", "severity": "moderate", "description": "Hydrochlorothiazide can lower serum potassium through renal potassium wasting. Potassium repletion can be clinically useful when levels are low, but dose should be guided by labs because excess potassium can be dangerous, especially with kidney disease or RAAS-blocking drugs.", "recommendation": "Have potassium checked after starting or changing hydrochlorothiazide and periodically during chronic therapy. Prefer dietary potassium unless your prescriber recommends a supplement; do not self-start high-dose potassium.", "minimumTimeSeparation": null, "mechanism": "HCTZ inhibits the sodium-chloride symporter in the distal convoluted tubule, increasing sodium delivery to the collecting duct. Increased sodium reabsorption via ENaC in exchange for potassium secretion via ROMK channels leads to net potassium loss.", "evidenceLevel": "strong", "sources": [ { "text": "Zillich AJ et al. Thiazide diuretics, potassium, and the development of diabetes: a quantitative review. Hypertension. 2006;48(2):219-224.", "pmid": "16801488", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16801488/", "publicSourceType": "PMID" }, { "text": "Filippini T, Naska A, Kasdagli MI et al.. Potassium Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials. Journal of the American Heart Association. 2020.", "pmid": "32500831", "doi": "10.1161/JAHA.119.015719", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32500831/", "publicSourceType": "PMID" }, { "text": "Behers BJ, Behers BM, Stephenson-Moe CA et al.. Magnesium and Potassium Supplementation for Systolic Blood Pressure Reduction in the General Normotensive Population: A Systematic Review and Subgroup Meta-Analysis for Optimal Dosage and Treatment Length. Nutrients. 2024.", "pmid": "39519450", "doi": "10.3390/nu16213617", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39519450/", "publicSourceType": "PMID" }, { "text": "D'Elia L, Cappuccio FP, Masulli M et al.. Effect of Potassium Supplementation on Endothelial Function: A Systematic Review and Meta-Analysis of Intervention Studies. Nutrients. 2023.", "pmid": "36839211", "doi": "10.3390/nu15040853", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36839211/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Hydrochlorothiazide (HCTZ) causes potassium wasting through increased renal excretion.", "clinicalSignificance": "Low potassium can cause weakness, cramps, palpitations, and arrhythmias; excessive replacement can cause hyperkalemia.", "managementStrategy": "Monitor serum potassium and kidney function; use potassium supplements only at a prescriber-guided dose when labs indicate need.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Hydrochlorothiazide", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "moderate", "description": "HCTZ increases renal magnesium excretion, and chronic use can lead to hypomagnesemia. Magnesium depletion can worsen potassium depletion (refractory hypokalemia) and increase the risk of cardiac arrhythmias, especially in patients also taking digoxin.", "recommendation": "Monitor magnesium levels during chronic HCTZ therapy. Consider magnesium supplementation (200-400mg/day), especially if potassium levels are difficult to correct. Magnesium repletion often helps resolve resistant hypokalemia.", "minimumTimeSeparation": null, "mechanism": "HCTZ increases magnesium excretion by reducing its reabsorption in the distal convoluted tubule. Magnesium depletion impairs the Na+/K+-ATPase and ROMK channel function, making hypokalemia refractory to potassium supplementation alone.", "evidenceLevel": "moderate", "sources": [ { "text": "Dai LJ et al. Magnesium transport in the renal distal convoluted tubule. Physiol Rev. 2001;81(1):51-84.", "pmid": "11152754", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11152754/", "publicSourceType": "PMID" }, { "text": "Mah J, Pitre T. Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis.. BMC Complementary Medicine and Therapies. 2021.", "pmid": "33865376", "doi": "10.1186/s12906-021-03297-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33865376/", "publicSourceType": "PMID" }, { "text": "Veronese N, Dominguez LJ, Pizzol D et al.. Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.. Nutrients. 2021.", "pmid": "34836329", "doi": "10.3390/nu13114074", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34836329/", "publicSourceType": "PMID" }, { "text": "Veronese N, Pizzol D, Smith L et al.. Effect of Magnesium Supplementation on Inflammatory Parameters: A Meta-Analysis of Randomized Controlled Trials.. Nutrients. 2022.", "pmid": "35277037", "doi": "10.3390/nu14030679", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35277037/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "HCTZ increases renal magnesium excretion, and chronic use can lead to hypomagnesemia.", "clinicalSignificance": "Magnesium depletion can worsen potassium depletion (refractory hypokalemia) and increase the risk of cardiac arrhythmias, especially in patients also taking digoxin.", "managementStrategy": "Monitor magnesium levels during chronic HCTZ therapy. Consider magnesium supplementation (200-400mg/day), especially if potassium levels are difficult to correct. Magnesium repletion often helps resolve resistant hypokalemia.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Furosemide", "supplementBName": "Potassium", "interactionType": "synergy", "severity": "serious", "description": "Furosemide is a potent loop diuretic that can cause clinically important potassium wasting. Severe hypokalemia can be life-threatening, but potassium replacement dose should be individualized from labs and clinical context.", "recommendation": "Monitor potassium during furosemide therapy, especially after dose changes or higher-dose use. Use potassium only as prescribed or lab-guided; do not infer a dose from the app.", "minimumTimeSeparation": null, "mechanism": "Furosemide inhibits the Na+/K+/2Cl- cotransporter (NKCC2) in the thick ascending limb of Henle. This massively increases sodium delivery to the collecting duct, where ENaC-mediated sodium reabsorption is coupled to potassium secretion via ROMK, causing profound potassium loss.", "evidenceLevel": "strong", "sources": [ { "text": "Brater DC. Diuretic therapy. N Engl J Med. 1998;339(6):387-395.", "pmid": "9691107", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9691107/", "publicSourceType": "PMID" }, { "text": "Filippini T, Naska A, Kasdagli MI et al.. Potassium Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials. Journal of the American Heart Association. 2020.", "pmid": "32500831", "doi": "10.1161/JAHA.119.015719", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32500831/", "publicSourceType": "PMID" }, { "text": "Behers BJ, Behers BM, Stephenson-Moe CA et al.. Magnesium and Potassium Supplementation for Systolic Blood Pressure Reduction in the General Normotensive Population: A Systematic Review and Subgroup Meta-Analysis for Optimal Dosage and Treatment Length. Nutrients. 2024.", "pmid": "39519450", "doi": "10.3390/nu16213617", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39519450/", "publicSourceType": "PMID" }, { "text": "D'Elia L, Cappuccio FP, Masulli M et al.. Effect of Potassium Supplementation on Endothelial Function: A Systematic Review and Meta-Analysis of Intervention Studies. Nutrients. 2023.", "pmid": "36839211", "doi": "10.3390/nu15040853", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36839211/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Furosemide is a potent loop diuretic that causes significant potassium wasting, more so than thiazide diuretics.", "clinicalSignificance": "Severe hypokalemia from furosemide can cause cardiac arrhythmias, paralytic ileus, and rhabdomyolysis; excessive replacement can also be dangerous.", "managementStrategy": "Monitor serum potassium and kidney function; prescribers may order potassium when indicated by labs or risk profile.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Furosemide", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "moderate", "description": "Furosemide depletes magnesium through its action on the thick ascending limb, where the majority of magnesium reabsorption occurs. Loop diuretic-induced hypomagnesemia is common and can contribute to refractory hypokalemia, muscle cramps, and cardiac arrhythmias.", "recommendation": "Monitor magnesium levels during furosemide therapy. Supplement with magnesium (200-400mg/day) as needed. Correcting magnesium depletion is essential for effectively correcting potassium depletion.", "minimumTimeSeparation": null, "mechanism": "Furosemide inhibits NKCC2 in the thick ascending limb, which is the primary site of renal magnesium reabsorption (driven by the lumen-positive transepithelial voltage). By disrupting this electrochemical gradient, furosemide dramatically reduces paracellular magnesium reabsorption.", "evidenceLevel": "strong", "sources": [ { "text": "Dai LJ et al. Magnesium transport in the renal distal convoluted tubule. Physiol Rev. 2001;81(1):51-84.", "pmid": "11152754", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11152754/", "publicSourceType": "PMID" }, { "text": "Mah J, Pitre T. Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis.. BMC Complementary Medicine and Therapies. 2021.", "pmid": "33865376", "doi": "10.1186/s12906-021-03297-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33865376/", "publicSourceType": "PMID" }, { "text": "Veronese N, Dominguez LJ, Pizzol D et al.. Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.. Nutrients. 2021.", "pmid": "34836329", "doi": "10.3390/nu13114074", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34836329/", "publicSourceType": "PMID" }, { "text": "Veronese N, Pizzol D, Smith L et al.. Effect of Magnesium Supplementation on Inflammatory Parameters: A Meta-Analysis of Randomized Controlled Trials.. Nutrients. 2022.", "pmid": "35277037", "doi": "10.3390/nu14030679", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35277037/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Furosemide depletes magnesium through its action on the thick ascending limb, where the majority of magnesium reabsorption occurs.", "clinicalSignificance": "Loop diuretic-induced hypomagnesemia is common and can contribute to refractory hypokalemia, muscle cramps, and cardiac arrhythmias.", "managementStrategy": "Monitor magnesium levels during furosemide therapy. Supplement with magnesium (200-400mg/day) as needed. Correcting magnesium depletion is essential for effectively correcting potassium depletion.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Lisinopril", "supplementBName": "Potassium", "interactionType": "caution", "severity": "serious", "description": "ACE inhibitors like lisinopril reduce aldosterone secretion, which decreases renal potassium excretion and raises serum potassium. Additional potassium supplementation can cause dangerous hyperkalemia, leading to life-threatening cardiac arrhythmias. This is one of the most important drug-supplement interactions.", "recommendation": "Do not take potassium supplements while on lisinopril unless specifically directed by your prescriber with regular potassium monitoring. Even potassium-rich salt substitutes should be avoided. Report symptoms of hyperkalemia (muscle weakness, irregular heartbeat, tingling).", "minimumTimeSeparation": null, "mechanism": "Lisinopril inhibits ACE, reducing angiotensin II-stimulated aldosterone release. Without aldosterone, ENaC-mediated sodium reabsorption and ROMK-mediated potassium secretion in the collecting duct are both reduced. Exogenous potassium supplementation on top of this impaired excretion can rapidly cause hyperkalemia.", "evidenceLevel": "strong", "sources": [ { "text": "Juurlink DN et al. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med. 2004;351(6):543-551.", "pmid": "15295047", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15295047/", "publicSourceType": "PMID" }, { "text": "Filippini T, Naska A, Kasdagli MI et al.. Potassium Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials. Journal of the American Heart Association. 2020.", "pmid": "32500831", "doi": "10.1161/JAHA.119.015719", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32500831/", "publicSourceType": "PMID" }, { "text": "Behers BJ, Behers BM, Stephenson-Moe CA et al.. Magnesium and Potassium Supplementation for Systolic Blood Pressure Reduction in the General Normotensive Population: A Systematic Review and Subgroup Meta-Analysis for Optimal Dosage and Treatment Length. Nutrients. 2024.", "pmid": "39519450", "doi": "10.3390/nu16213617", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39519450/", "publicSourceType": "PMID" }, { "text": "D'Elia L, Cappuccio FP, Masulli M et al.. Effect of Potassium Supplementation on Endothelial Function: A Systematic Review and Meta-Analysis of Intervention Studies. Nutrients. 2023.", "pmid": "36839211", "doi": "10.3390/nu15040853", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36839211/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "ACE inhibitors like lisinopril reduce aldosterone secretion, which decreases renal potassium excretion and raises serum potassium.", "clinicalSignificance": "Additional potassium supplementation can cause dangerous hyperkalemia, leading to life-threatening cardiac arrhythmias.", "managementStrategy": "Do not take potassium supplements while on lisinopril unless specifically directed by your prescriber with regular potassium monitoring. Even potassium-rich salt substitutes should be avoided. Report symptoms of hyperkalemia (muscle weakness, irregular heartbeat, tingling).", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Lisinopril", "supplementBName": "Iron", "interactionType": "timingSensitive", "severity": "info", "description": "Iron supplements may modestly reduce the absorption of ACE inhibitors when taken simultaneously. While the interaction is minor compared to other iron-drug chelations, separating doses is a reasonable precaution to ensure optimal drug absorption.", "recommendation": "Separate lisinopril and iron supplements by at least 2 hours as a precaution. This is a minor interaction and unlikely to be clinically significant at standard doses, but good practice for maximizing drug absorption.", "minimumTimeSeparation": 120, "mechanism": "Iron may form weak chelation complexes with the carboxyl groups of ACE inhibitors, modestly reducing their dissolution and absorption in the GI tract. The interaction is considerably less significant than iron chelation with tetracyclines or fluoroquinolones.", "evidenceLevel": "emerging", "sources": [ { "text": "Campbell NR, Hasinoff BB. Iron supplements: a common cause of drug interactions. Br J Clin Pharmacol. 1991;31(3):251-255.", "pmid": "2054263", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2054263/", "publicSourceType": "PMID" }, { "text": "Fischer JAJ, Cherian AM, Bone JN, Karakochuk CD. The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials. Nutrition Reviews. 2023.", "pmid": "36728680", "doi": "10.1093/nutrit/nuac106", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36728680/", "publicSourceType": "PMID" }, { "text": "Rehman T, Agrawal R, Ahamed F et al.. Optimal dose and duration of iron supplementation for treating iron deficiency anaemia in children and adolescents: A systematic review and meta-analysis. PLoS One. 2025.", "pmid": "39951396", "doi": "10.1371/journal.pone.0319068", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39951396/", "publicSourceType": "PMID" }, { "text": "Gutema BT, Sorrie MB, Megersa ND et al.. Effects of iron supplementation on cognitive development in school-age children: Systematic review and meta-analysis. PLoS One. 2023.", "pmid": "37368919", "doi": "10.1371/journal.pone.0287703", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37368919/", "publicSourceType": "PMID" }, { "text": "Hansen R, Sejer EPF, Holm C, Schroll JB. Iron supplements in pregnant women with normal iron status: A systematic review and meta-analysis. Acta Obstetricia et Gynecologica Scandinavica. 2023.", "pmid": "37403900", "doi": "10.1111/aogs.14607", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37403900/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Iron supplements may modestly reduce the absorption of ACE inhibitors when taken simultaneously.", "clinicalSignificance": "While the interaction is minor compared to other iron-drug chelations, separating doses is a reasonable precaution to ensure optimal drug absorption.", "managementStrategy": "Separate lisinopril and iron supplements by at least 2 hours as a precaution. This is a minor interaction and unlikely to be clinically significant at standard doses, but good practice for maximizing drug absorption.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Gabapentin", "supplementBName": "Magnesium Glycinate", "interactionType": "timingSensitive", "severity": "moderate", "description": "Magnesium-containing antacids and supplements reduce gabapentin absorption when taken concurrently. Studies have shown approximately 20% reduction in gabapentin bioavailability, which may reduce its efficacy for pain control or seizure prevention.", "recommendation": "Separate gabapentin and magnesium supplements by at least 2 hours. Take gabapentin at least 2 hours after magnesium to ensure adequate absorption.", "minimumTimeSeparation": 120, "mechanism": "Magnesium (particularly in antacid forms) can reduce gabapentin absorption through alteration of local GI pH and potential binding interactions. Gabapentin absorption occurs via the L-amino acid transporter in the small intestine, and its solubility is pH-dependent.", "evidenceLevel": "moderate", "sources": [ { "text": "Yagi T, Naito T, Mino Y, Umemura K, Kawakami J. Impact of concomitant antacid administration on gabapentin plasma exposure and oral bioavailability in healthy adult subjects. Drug Metab Pharmacokinet. 2012;27(2):248-254.", "pmid": "22240839", "doi": "10.2133/dmpk.dmpk-11-rg-108", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22240839/", "publicSourceType": "PMID" }, { "text": "Busch JA et al. The effect of antacids on gabapentin pharmacokinetics. Epilepsia. 1997;38(Suppl 3):72.", "pmid": "9234576", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9234576/", "publicSourceType": "PMID" }, { "text": "Mah J, Pitre T. Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis.. BMC Complementary Medicine and Therapies. 2021.", "pmid": "33865376", "doi": "10.1186/s12906-021-03297-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33865376/", "publicSourceType": "PMID" }, { "text": "Veronese N, Dominguez LJ, Pizzol D et al.. Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.. Nutrients. 2021.", "pmid": "34836329", "doi": "10.3390/nu13114074", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34836329/", "publicSourceType": "PMID" }, { "text": "Veronese N, Pizzol D, Smith L et al.. Effect of Magnesium Supplementation on Inflammatory Parameters: A Meta-Analysis of Randomized Controlled Trials.. Nutrients. 2022.", "pmid": "35277037", "doi": "10.3390/nu14030679", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35277037/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Magnesium-containing antacids and supplements reduce gabapentin absorption when taken concurrently.", "clinicalSignificance": "Studies have shown approximately 20% reduction in gabapentin bioavailability, which may reduce its efficacy for pain control or seizure prevention.", "managementStrategy": "Separate gabapentin and magnesium supplements by at least 2 hours. Take gabapentin at least 2 hours after magnesium to ensure adequate absorption.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Gabapentin", "supplementBName": "Calcium", "interactionType": "timingSensitive", "severity": "moderate", "description": "Calcium-containing antacids and supplements may reduce gabapentin absorption through similar mechanisms as magnesium. The interaction can decrease gabapentin bioavailability enough to affect therapeutic efficacy for neuropathic pain or seizure control.", "recommendation": "Separate gabapentin and calcium supplements by at least 2 hours. Take gabapentin at least 2 hours after calcium to minimize any absorption interference.", "minimumTimeSeparation": 120, "mechanism": "Calcium may reduce gabapentin absorption by altering local GI pH or through binding interactions in the intestinal lumen. Since gabapentin has a saturable absorption mechanism via the L-amino acid transporter, any reduction in the available drug fraction can reduce therapeutic levels.", "evidenceLevel": "moderate", "sources": [ { "text": "Yagi T, Naito T, Mino Y, Umemura K, Kawakami J. Impact of concomitant antacid administration on gabapentin plasma exposure and oral bioavailability in healthy adult subjects. Drug Metab Pharmacokinet. 2012;27(2):248-254.", "pmid": "22240839", "doi": "10.2133/dmpk.dmpk-11-rg-108", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22240839/", "publicSourceType": "PMID" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Calcium-containing antacids and supplements may reduce gabapentin absorption through similar mechanisms as magnesium.", "clinicalSignificance": "The interaction can decrease gabapentin bioavailability enough to affect therapeutic efficacy for neuropathic pain or seizure control.", "managementStrategy": "Separate gabapentin and calcium supplements by at least 2 hours. Take gabapentin at least 2 hours after calcium to minimize any absorption interference.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Methylphenidate", "supplementBName": "Melatonin", "interactionType": "synergy", "severity": "info", "description": "Melatonin may help counteract the insomnia commonly caused by stimulant medications like methylphenidate. Research supports the use of melatonin for stimulant-related sleep difficulties in both children and adults with ADHD, making this a potentially beneficial combination.", "recommendation": "Melatonin (0.5-3mg taken 30-60 minutes before bedtime) may be a helpful adjunct for methylphenidate-related insomnia. Start with the lowest effective dose. This combination is generally well-studied and safe.", "minimumTimeSeparation": null, "mechanism": "Methylphenidate increases catecholamine activity, which can delay sleep onset and reduce sleep quality. Melatonin acts on MT1/MT2 receptors in the SCN to promote sleep onset and circadian rhythm alignment, directly counteracting the stimulant's sleep-disrupting effects without affecting its daytime therapeutic benefits.", "evidenceLevel": "moderate", "sources": [ { "text": "Van der Heijden KB et al. Effect of melatonin on sleep, behavior, and cognition in ADHD and chronic sleep-onset insomnia. J Am Acad Child Adolesc Psychiatry. 2007;46(2):233-241.", "pmid": "17242627", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17242627/", "publicSourceType": "PMID" }, { "text": "Fatemeh G, Sajjad M, Niloufar R et al.. Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials.. Journal of Neurology. 2022.", "pmid": "33417003", "doi": "10.1007/s00415-020-10381-w", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33417003/", "publicSourceType": "PMID" }, { "text": "Tang BHY, Manalo J, Chowdhury SR et al.. Melatonin Use in the ICU: A Systematic Review and Meta-Analysis.. Critical Care Medicine. 2025.", "pmid": "40662882", "doi": "10.1097/CCM.0000000000006767", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40662882/", "publicSourceType": "PMID" }, { "text": "Chan V, Lo K. Efficacy of dietary supplements on improving sleep quality: a systematic review and meta-analysis.. Postgraduate Medical Journal. 2022.", "pmid": "33441476", "doi": "10.1136/postgradmedj-2020-139319", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33441476/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Melatonin may help counteract the insomnia commonly caused by stimulant medications like methylphenidate.", "clinicalSignificance": "Research supports the use of melatonin for stimulant-related sleep difficulties in both children and adults with ADHD, making this a potentially beneficial combination.", "managementStrategy": "Melatonin (0.5-3mg taken 30-60 minutes before bedtime) may be a helpful adjunct for methylphenidate-related insomnia. Start with the lowest effective dose. This combination is generally well-studied and safe.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Amiodarone", "supplementBName": "Coenzyme Q10 Ubiquinol", "interactionType": "synergy", "severity": "info", "description": "Amiodarone has mitochondrial effects, and CoQ10 is involved in mitochondrial electron transport. Direct evidence that CoQ10 changes amiodarone outcomes is limited.", "recommendation": "Discuss CoQ10 with the prescriber managing amiodarone, especially if heart-failure, arrhythmia, or anticoagulant issues are present; do not assume it changes amiodarone safety or effectiveness.", "minimumTimeSeparation": null, "mechanism": "Amiodarone can affect mitochondrial enzymes, while CoQ10 participates in mitochondrial electron transport. Clinical relevance of supplementation during amiodarone therapy remains uncertain.", "evidenceLevel": "emerging", "sources": [ { "text": "Kishi T et al. Bioenergetics in clinical medicine: studies on coenzyme Q10 and essential hypertension. Res Commun Chem Pathol Pharmacol. 1977;17(3):507-518.", "pmid": "897348", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/897348/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Possible mitochondrial-support context; clinical outcome evidence limited.", "clinicalSignificance": "Exploratory support only; do not imply protection from amiodarone toxicity.", "managementStrategy": "Discuss CoQ10 with the prescriber managing amiodarone, especially if heart-failure, arrhythmia, or anticoagulant issues are present; do not assume it changes amiodarone safety or effectiveness.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Amiodarone", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's Wort induces CYP3A4, which is a major metabolic pathway for amiodarone. This can significantly reduce amiodarone plasma levels, potentially causing loss of antiarrhythmic control and life-threatening recurrence of cardiac arrhythmias.", "recommendation": "Do not combine St. John's Wort with amiodarone. Loss of arrhythmia control can be life-threatening. Discuss alternative mood support options with your cardiologist.", "minimumTimeSeparation": null, "mechanism": "Amiodarone is primarily metabolized by CYP3A4 to its active metabolite desethylamiodarone. St. John's Wort's potent CYP3A4 induction via PXR activation can accelerate amiodarone metabolism, reducing both parent drug and metabolite levels below the therapeutic range.", "evidenceLevel": "moderate", "sources": [ { "text": "Moore LB et al. St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc Natl Acad Sci USA. 2000;97(13):7500-7502.", "pmid": "10852961", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10852961/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St.", "clinicalSignificance": "John's Wort induces CYP3A4, which is a major metabolic pathway for amiodarone.", "managementStrategy": "Do not combine St. John's Wort with amiodarone. Loss of arrhythmia control can be life-threatening. Discuss alternative mood support options with your cardiologist.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Isotretinoin", "supplementBName": "Vitamin A", "interactionType": "contraindicated", "severity": "dangerous", "description": "Isotretinoin is a retinoid (13-cis-retinoic acid) that acts as a potent form of vitamin A. Adding supplemental vitamin A to isotretinoin therapy creates severe hypervitaminosis A, causing potentially fatal liver damage, intracranial hypertension (pseudotumor cerebri), severe skin reactions, and teratogenic effects.", "recommendation": "Do not take any vitamin A supplements, cod liver oil, or multivitamins containing vitamin A while on isotretinoin. This includes beta-carotene at high doses. Check all supplement labels for vitamin A content.", "minimumTimeSeparation": null, "mechanism": "Isotretinoin is itself a retinoid that activates retinoid receptors (RAR/RXR). Additional vitamin A provides more retinoid activity, causing toxic accumulation. Hypervitaminosis A leads to hepatic stellate cell activation (liver fibrosis), increased intracranial pressure, and severe mucocutaneous toxicity.", "evidenceLevel": "strong", "sources": [ { "text": "Rothman KJ et al. Teratogenicity of high vitamin A intake. N Engl J Med. 1995;333(21):1369-1373.", "pmid": "7477116", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7477116/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Isotretinoin is a retinoid (13-cis-retinoic acid) that acts as a potent form of vitamin A.", "clinicalSignificance": "Adding supplemental vitamin A to isotretinoin therapy creates severe hypervitaminosis A, causing potentially fatal liver damage, intracranial hypertension (pseudotumor cerebri), severe skin reactions, and teratogenic effects.", "managementStrategy": "Do not take any vitamin A supplements, cod liver oil, or multivitamins containing vitamin A while on isotretinoin. This includes beta-carotene at high doses. Check all supplement labels for vitamin A content.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Bupropion", "supplementBName": "St. John's Wort", "interactionType": "caution", "severity": "serious", "description": "Both bupropion and St. John's Wort lower the seizure threshold, and combining them may significantly increase seizure risk. Bupropion already carries a dose-dependent seizure warning, and St. John's Wort's effects on multiple neurotransmitter systems compound this risk.", "recommendation": "Avoid combining St. John's Wort with bupropion due to increased seizure risk. If mood support beyond bupropion is needed, discuss evidence-based augmentation strategies with your prescriber.", "minimumTimeSeparation": null, "mechanism": "Bupropion inhibits dopamine and norepinephrine reuptake and is known to lower seizure threshold in a dose-dependent manner. St. John's Wort affects multiple neurotransmitter systems including inhibiting serotonin, norepinephrine, and dopamine reuptake. The combined neuroexcitatory effects may further reduce seizure threshold.", "evidenceLevel": "moderate", "sources": [ { "text": "Jefferson JW, Pradko JF, Muir KT. Bupropion for major depressive disorder: pharmacokinetic and formulation considerations. Clin Ther. 2005;27(11):1685-1695.", "pmid": "16368442", "doi": "10.1016/j.clinthera.2005.11.011", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16368442/", "publicSourceType": "PMID" }, { "text": "Linde K et al. St John's wort for major depression. Cochrane Database Syst Rev. 2008;(4):CD000448.", "pmid": "18843608", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18843608/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Both bupropion and St.", "clinicalSignificance": "John's Wort lower the seizure threshold, and combining them may significantly increase seizure risk.", "managementStrategy": "Avoid combining St. John's Wort with bupropion due to increased seizure risk. If mood support beyond bupropion is needed, discuss evidence-based augmentation strategies with your prescriber.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Duloxetine", "supplementBName": "5-HTP", "interactionType": "contraindicated", "severity": "serious", "description": "Duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI) that potently blocks serotonin reuptake. Adding 5-HTP, a direct serotonin precursor, significantly increases the risk of serotonin syndrome through excessive serotonin accumulation at synaptic receptors.", "recommendation": "Do not combine 5-HTP with duloxetine. The risk of serotonin syndrome is significant with this combination. If you are taking 5-HTP, discontinue it and inform your prescriber before starting any SNRI.", "minimumTimeSeparation": null, "mechanism": "Duloxetine blocks both SERT and NET, increasing synaptic serotonin and norepinephrine. 5-HTP bypasses the rate-limiting tryptophan hydroxylase step to directly increase serotonin synthesis. Combined increased production and decreased reuptake can trigger serotonin syndrome.", "evidenceLevel": "moderate", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Truyens M, Lobatón T, Ferrante M et al.. Effect of 5-Hydroxytryptophan on Fatigue in Quiescent Inflammatory Bowel Disease: A Randomized Controlled Trial. Gastroenterology. 2022.", "pmid": "35940251", "doi": "10.1053/j.gastro.2022.07.052", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35940251/", "publicSourceType": "PMID" }, { "text": "Sutanto CN, Xia X, Heng CW et al.. The impact of 5-hydroxytryptophan supplementation on sleep quality and gut microbiota composition in older adults: A randomized controlled trial. Clinical Nutrition. 2024.", "pmid": "38309227", "doi": "10.1016/j.clnu.2024.01.010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38309227/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI) that potently blocks serotonin reuptake.", "clinicalSignificance": "Adding 5-HTP, a direct serotonin precursor, significantly increases the risk of serotonin syndrome through excessive serotonin accumulation at synaptic receptors.", "managementStrategy": "Do not combine 5-HTP with duloxetine. The risk of serotonin syndrome is significant with this combination. If you are taking 5-HTP, discontinue it and inform your prescriber before starting any SNRI.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Duloxetine", "supplementBName": "St. John's Wort", "interactionType": "contraindicated", "severity": "dangerous", "description": "Combining duloxetine (an SNRI) with St. John's Wort creates a serious risk of serotonin syndrome. Both agents increase synaptic serotonin through different mechanisms. St. John's Wort may also induce CYP1A2, which is the primary enzyme metabolizing duloxetine, creating complex and dangerous pharmacokinetic-pharmacodynamic interactions.", "recommendation": "Do not take St. John's Wort with duloxetine under any circumstances. This combination poses dual risks: serotonin syndrome and unpredictable changes in duloxetine levels. Seek alternative mood support options.", "minimumTimeSeparation": null, "mechanism": "Duloxetine blocks SERT and NET. St. John's Wort independently inhibits serotonin reuptake via hyperforin and may inhibit MAO. The combined serotonergic mechanisms create dangerous serotonin excess. Additionally, St. John's Wort may induce CYP1A2, altering duloxetine plasma levels unpredictably.", "evidenceLevel": "strong", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Combining duloxetine (an SNRI) with St.", "clinicalSignificance": "John's Wort creates a serious risk of serotonin syndrome.", "managementStrategy": "Do not take St. John's Wort with duloxetine under any circumstances. This combination poses dual risks: serotonin syndrome and unpredictable changes in duloxetine levels. Seek alternative mood support options.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Venlafaxine", "supplementBName": "5-HTP", "interactionType": "contraindicated", "severity": "serious", "description": "Venlafaxine is an SNRI that blocks serotonin reuptake, particularly at lower doses where its effect is predominantly serotonergic. Adding 5-HTP increases serotonin synthesis while venlafaxine prevents its clearance, creating significant serotonin syndrome risk.", "recommendation": "Do not combine 5-HTP with venlafaxine. The serotonin syndrome risk is significant. Discontinue 5-HTP before starting venlafaxine therapy.", "minimumTimeSeparation": null, "mechanism": "Venlafaxine blocks SERT (predominantly at doses <150mg) and NET (at higher doses). 5-HTP increases serotonin synthesis by providing direct substrate for AADC. The combination of increased serotonin production and blocked reuptake can cause dangerous serotonin accumulation.", "evidenceLevel": "moderate", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Truyens M, Lobatón T, Ferrante M et al.. Effect of 5-Hydroxytryptophan on Fatigue in Quiescent Inflammatory Bowel Disease: A Randomized Controlled Trial. Gastroenterology. 2022.", "pmid": "35940251", "doi": "10.1053/j.gastro.2022.07.052", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35940251/", "publicSourceType": "PMID" }, { "text": "Sutanto CN, Xia X, Heng CW et al.. The impact of 5-hydroxytryptophan supplementation on sleep quality and gut microbiota composition in older adults: A randomized controlled trial. Clinical Nutrition. 2024.", "pmid": "38309227", "doi": "10.1016/j.clnu.2024.01.010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38309227/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Venlafaxine is an SNRI that blocks serotonin reuptake, particularly at lower doses where its effect is predominantly serotonergic.", "clinicalSignificance": "Adding 5-HTP increases serotonin synthesis while venlafaxine prevents its clearance, creating significant serotonin syndrome risk.", "managementStrategy": "Do not combine 5-HTP with venlafaxine. The serotonin syndrome risk is significant. Discontinue 5-HTP before starting venlafaxine therapy.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Venlafaxine", "supplementBName": "St. John's Wort", "interactionType": "contraindicated", "severity": "dangerous", "description": "Combining venlafaxine with St. John's Wort creates a dangerous risk of serotonin syndrome. Multiple case reports have documented this interaction. St. John's Wort's serotonin reuptake inhibition adds to venlafaxine's, while its CYP induction may unpredictably alter venlafaxine and O-desmethylvenlafaxine levels.", "recommendation": "Do not take St. John's Wort with venlafaxine. This is a well-documented dangerous combination. If you are currently using both, contact your prescriber immediately.", "minimumTimeSeparation": null, "mechanism": "Venlafaxine blocks SERT and NET. St. John's Wort adds serotonin reuptake inhibition (hyperforin) and potential MAO inhibition. CYP2D6 and CYP3A4 induction by St. John's Wort may also alter venlafaxine metabolism, creating unpredictable drug levels alongside pharmacodynamic serotonergic toxicity.", "evidenceLevel": "strong", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Combining venlafaxine with St.", "clinicalSignificance": "John's Wort creates a dangerous risk of serotonin syndrome.", "managementStrategy": "Do not take St. John's Wort with venlafaxine. This is a well-documented dangerous combination. If you are currently using both, contact your prescriber immediately.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Tramadol", "supplementBName": "5-HTP", "interactionType": "contraindicated", "severity": "serious", "description": "Tramadol has significant serotonergic activity in addition to its opioid effects, inhibiting serotonin reuptake. Combining it with 5-HTP, a direct serotonin precursor, significantly increases the risk of serotonin syndrome, which can be life-threatening.", "recommendation": "Do not combine 5-HTP with tramadol. Tramadol's serotonergic properties are often underrecognized, and this combination poses a serious risk of serotonin syndrome. Inform your prescriber if you use 5-HTP.", "minimumTimeSeparation": null, "mechanism": "Tramadol and its M1 metabolite inhibit serotonin and norepinephrine reuptake in addition to activating mu-opioid receptors. 5-HTP increases serotonin synthesis. The combined serotonin reuptake inhibition and increased production can trigger serotonin syndrome.", "evidenceLevel": "moderate", "sources": [ { "text": "Beakley BD et al. Tramadol, pharmacology, side effects, and serotonin syndrome: a review. Pain Physician. 2015;18(4):395-400.", "pmid": "26218943", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26218943/", "publicSourceType": "PMID" }, { "text": "Truyens M, Lobatón T, Ferrante M et al.. Effect of 5-Hydroxytryptophan on Fatigue in Quiescent Inflammatory Bowel Disease: A Randomized Controlled Trial. Gastroenterology. 2022.", "pmid": "35940251", "doi": "10.1053/j.gastro.2022.07.052", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35940251/", "publicSourceType": "PMID" }, { "text": "Sutanto CN, Xia X, Heng CW et al.. The impact of 5-hydroxytryptophan supplementation on sleep quality and gut microbiota composition in older adults: A randomized controlled trial. Clinical Nutrition. 2024.", "pmid": "38309227", "doi": "10.1016/j.clnu.2024.01.010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38309227/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Tramadol has significant serotonergic activity in addition to its opioid effects, inhibiting serotonin reuptake.", "clinicalSignificance": "Combining it with 5-HTP, a direct serotonin precursor, significantly increases the risk of serotonin syndrome, which can be life-threatening.", "managementStrategy": "Do not combine 5-HTP with tramadol. Tramadol's serotonergic properties are often underrecognized, and this combination poses a serious risk of serotonin syndrome. Inform your prescriber if you use 5-HTP.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Tramadol", "supplementBName": "St. John's Wort", "interactionType": "contraindicated", "severity": "dangerous", "description": "Combining tramadol with St. John's Wort creates dual risks: serotonin syndrome from additive serotonergic effects, and potential loss of tramadol's analgesic efficacy from CYP3A4/CYP2D6 induction that may reduce active metabolite formation or increase clearance.", "recommendation": "Do not take St. John's Wort with tramadol. This combination poses both serotonin syndrome risk and potential loss of pain control. Seek alternative mood support from your prescriber.", "minimumTimeSeparation": null, "mechanism": "Both tramadol and St. John's Wort inhibit serotonin reuptake, creating additive serotonergic toxicity risk. Additionally, St. John's Wort induces CYP2D6 (which converts tramadol to its active M1 metabolite) and CYP3A4, potentially causing unpredictable changes in tramadol and M1 levels.", "evidenceLevel": "moderate", "sources": [ { "text": "Beakley BD et al. Tramadol, pharmacology, side effects, and serotonin syndrome: a review. Pain Physician. 2015;18(4):395-400.", "pmid": "26218943", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26218943/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Combining tramadol with St.", "clinicalSignificance": "John's Wort creates dual risks: serotonin syndrome from additive serotonergic effects, and potential loss of tramadol's analgesic efficacy from CYP3A4/CYP2D6 induction that may reduce active metabolite formation or increase clearance.", "managementStrategy": "Do not take St. John's Wort with tramadol. This combination poses both serotonin syndrome risk and potential loss of pain control. Seek alternative mood support from your prescriber.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Clopidogrel", "supplementBName": "Fish Oil", "interactionType": "caution", "severity": "moderate", "description": "Fish oil has antiplatelet properties that may add to clopidogrel's platelet inhibition, increasing the overall bleeding risk. While moderate fish oil doses are generally well-tolerated, the additive antiplatelet effect may be clinically significant, especially with other bleeding risk factors.", "recommendation": "Use moderate fish oil doses (1-2g/day) cautiously with clopidogrel. Higher doses may increase bleeding risk. Report any unusual bleeding, bruising, or prolonged bleeding from cuts to your healthcare provider.", "minimumTimeSeparation": null, "mechanism": "Clopidogrel irreversibly inhibits the P2Y12 ADP receptor on platelets. Fish oil's EPA/DHA reduce thromboxane A2 production and alter platelet membrane composition, providing additional antiplatelet effect through a different mechanism. The combined dual-pathway platelet inhibition increases bleeding risk.", "evidenceLevel": "moderate", "sources": [ { "text": "Bays HE. Safety considerations with omega-3 fatty acid therapy. Am J Cardiol. 2007;99(6A):35C-43C.", "pmid": "17368277", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17368277/", "publicSourceType": "PMID" }, { "text": "Lun R, Dhaliwal S, Zitikyte G, Roy DC et al.. Comparison of Ticagrelor vs Clopidogrel in Addition to Aspirin in Patients With Minor Ischemic Stroke and Transient Ischemic Attack: A Network Meta-analysis. JAMA Neurology. 2022.", "pmid": "34870698", "doi": "10.1001/jamaneurol.2021.4514", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34870698/", "publicSourceType": "PMID" }, { "text": "Liao Y, Xie B, Zhang H et al.. Efficacy of omega-3 PUFAs in depression: A meta-analysis.. Translational Psychiatry. 2019.", "pmid": "31383846", "doi": "10.1038/s41398-019-0515-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31383846/", "publicSourceType": "PMID" }, { "text": "Wei BZ, Li L, Dong CW et al.. The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers.. American Journal of Clinical Nutrition. 2023.", "pmid": "37028557", "doi": "10.1016/j.ajcnut.2023.04.001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37028557/", "publicSourceType": "PMID" }, { "text": "Uchida Y, Tsuji K, Ochi E. Effects of Omega-3 fatty acids supplementation and resistance training on skeletal muscle.. Clinical Nutrition ESPEN. 2024.", "pmid": "38777432", "doi": "10.1016/j.clnesp.2024.03.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38777432/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Fish oil has antiplatelet properties that may add to clopidogrel's platelet inhibition, increasing the overall bleeding risk.", "clinicalSignificance": "While moderate fish oil doses are generally well-tolerated, the additive antiplatelet effect may be clinically significant, especially with other bleeding risk factors.", "managementStrategy": "Use moderate fish oil doses (1-2g/day) cautiously with clopidogrel. Higher doses may increase bleeding risk. Report any unusual bleeding, bruising, or prolonged bleeding from cuts to your healthcare provider.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Clopidogrel", "supplementBName": "Ginkgo Biloba", "interactionType": "caution", "severity": "serious", "description": "Ginkgo biloba has significant antiplatelet activity (PAF antagonism) that adds to clopidogrel's platelet inhibition, substantially increasing bleeding risk. Case reports have documented serious bleeding events with this combination, including intracerebral hemorrhage.", "recommendation": "Avoid ginkgo biloba while taking clopidogrel. The additive antiplatelet effect creates a serious bleeding risk. If you are taking ginkgo, inform your cardiologist and discontinue it.", "minimumTimeSeparation": null, "mechanism": "Clopidogrel irreversibly blocks P2Y12 receptors, and ginkgolide B antagonizes platelet-activating factor (PAF). The combination inhibits platelets through two independent pathways, creating significantly greater platelet inhibition than either agent alone and substantially increasing bleeding risk.", "evidenceLevel": "moderate", "sources": [ { "text": "Rosenblatt M, Mindel J. Spontaneous hyphema associated with ingestion of Ginkgo biloba extract. N Engl J Med. 1997;336(15):1108.", "pmid": "9091812", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9091812/", "publicSourceType": "PMID" }, { "text": "Lun R, Dhaliwal S, Zitikyte G, Roy DC et al.. Comparison of Ticagrelor vs Clopidogrel in Addition to Aspirin in Patients With Minor Ischemic Stroke and Transient Ischemic Attack: A Network Meta-analysis. JAMA Neurology. 2022.", "pmid": "34870698", "doi": "10.1001/jamaneurol.2021.4514", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34870698/", "publicSourceType": "PMID" }, { "text": "Mousavi SN, Hosseinikia M, Yousefi Rad E, Saboori S. Beneficial effects of Ginkgo biloba leaf extract on inflammatory markers: A systematic review and meta-analysis of the clinical trials. Phytotherapy Research. 2022.", "pmid": "35781715", "doi": "10.1002/ptr.7544", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35781715/", "publicSourceType": "PMID" }, { "text": "Tabrizi R, Nowrouzi-Sohrabi P, Hessami K et al.. Effects of Ginkgo biloba intake on cardiometabolic parameters in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of clinical trials. Phytotherapy Research. 2020.", "pmid": "33090588", "doi": "10.1002/ptr.6822", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33090588/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Ginkgo biloba has significant antiplatelet activity (PAF antagonism) that adds to clopidogrel's platelet inhibition, substantially increasing bleeding risk.", "clinicalSignificance": "Case reports have documented serious bleeding events with this combination, including intracerebral hemorrhage.", "managementStrategy": "Avoid ginkgo biloba while taking clopidogrel. The additive antiplatelet effect creates a serious bleeding risk. If you are taking ginkgo, inform your cardiologist and discontinue it.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Aspirin Low-Dose", "supplementBName": "Fish Oil", "interactionType": "caution", "severity": "moderate", "description": "Fish oil has antiplatelet properties that add to aspirin's cyclooxygenase inhibition, potentially increasing bleeding risk. While the combination is sometimes used therapeutically for cardiovascular benefit, the additive antiplatelet effect requires awareness of increased bleeding potential.", "recommendation": "Low-dose fish oil (1-2g/day) with low-dose aspirin is often considered acceptable for cardiovascular benefit, but monitor for increased bruising or bleeding. Higher fish oil doses (>3g/day) further increase bleeding risk. Discuss with your cardiologist.", "minimumTimeSeparation": null, "mechanism": "Aspirin irreversibly inhibits COX-1, reducing thromboxane A2 production. Fish oil's EPA/DHA compete with arachidonic acid for COX enzymes, producing less potent thromboxane A3 and further reducing platelet aggregation. The combined effect creates greater antiplatelet activity.", "evidenceLevel": "moderate", "sources": [ { "text": "Bays HE. Safety considerations with omega-3 fatty acid therapy. Am J Cardiol. 2007;99(6A):35C-43C.", "pmid": "17368277", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17368277/", "publicSourceType": "PMID" }, { "text": "Liao Y, Xie B, Zhang H et al.. Efficacy of omega-3 PUFAs in depression: A meta-analysis.. Translational Psychiatry. 2019.", "pmid": "31383846", "doi": "10.1038/s41398-019-0515-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31383846/", "publicSourceType": "PMID" }, { "text": "Wei BZ, Li L, Dong CW et al.. The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers.. American Journal of Clinical Nutrition. 2023.", "pmid": "37028557", "doi": "10.1016/j.ajcnut.2023.04.001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37028557/", "publicSourceType": "PMID" }, { "text": "Uchida Y, Tsuji K, Ochi E. Effects of Omega-3 fatty acids supplementation and resistance training on skeletal muscle.. Clinical Nutrition ESPEN. 2024.", "pmid": "38777432", "doi": "10.1016/j.clnesp.2024.03.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38777432/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Fish oil has antiplatelet properties that add to aspirin's cyclooxygenase inhibition, potentially increasing bleeding risk.", "clinicalSignificance": "While the combination is sometimes used therapeutically for cardiovascular benefit, the additive antiplatelet effect requires awareness of increased bleeding potential.", "managementStrategy": "Low-dose fish oil (1-2g/day) with low-dose aspirin is often considered acceptable for cardiovascular benefit, but monitor for increased bruising or bleeding. Higher fish oil doses (>3g/day) further increase bleeding risk. Discuss with your cardiologist.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Aspirin Low-Dose", "supplementBName": "Ginkgo Biloba", "interactionType": "caution", "severity": "serious", "description": "Ginkgo biloba's potent antiplatelet activity (PAF antagonism) combined with aspirin's COX-1 inhibition creates significant additive bleeding risk. Serious bleeding events including intracerebral hemorrhage have been reported in patients taking both agents. The dual antiplatelet mechanism is particularly concerning.", "recommendation": "Avoid ginkgo biloba while taking aspirin, even at low doses. The combination substantially increases bleeding risk through complementary antiplatelet mechanisms. Inform your prescriber if you use ginkgo supplements.", "minimumTimeSeparation": null, "mechanism": "Aspirin irreversibly inhibits platelet COX-1, reducing thromboxane A2. Ginkgolide B is a potent PAF antagonist that inhibits a separate platelet activation pathway. The combination of COX-1 inhibition and PAF antagonism creates substantial, dual-mechanism platelet inhibition with significant bleeding risk.", "evidenceLevel": "moderate", "sources": [ { "text": "Rowin J, Lewis SL. Spontaneous bilateral subdural hematomas associated with chronic Ginkgo biloba ingestion. Neurology. 1996;46(6):1775-1776.", "pmid": "8649594", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8649594/", "publicSourceType": "PMID" }, { "text": "Mousavi SN, Hosseinikia M, Yousefi Rad E, Saboori S. Beneficial effects of Ginkgo biloba leaf extract on inflammatory markers: A systematic review and meta-analysis of the clinical trials. Phytotherapy Research. 2022.", "pmid": "35781715", "doi": "10.1002/ptr.7544", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35781715/", "publicSourceType": "PMID" }, { "text": "Tabrizi R, Nowrouzi-Sohrabi P, Hessami K et al.. Effects of Ginkgo biloba intake on cardiometabolic parameters in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of clinical trials. Phytotherapy Research. 2020.", "pmid": "33090588", "doi": "10.1002/ptr.6822", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33090588/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Ginkgo biloba's potent antiplatelet activity (PAF antagonism) combined with aspirin's COX-1 inhibition creates significant additive bleeding risk.", "clinicalSignificance": "Serious bleeding events including intracerebral hemorrhage have been reported in patients taking both agents.", "managementStrategy": "Avoid ginkgo biloba while taking aspirin, even at low doses. The combination substantially increases bleeding risk through complementary antiplatelet mechanisms. Inform your prescriber if you use ginkgo supplements.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Sertraline", "supplementBName": "Tramadol", "interactionType": "contraindicated", "severity": "dangerous", "description": "Concurrent use of SSRIs and tramadol significantly increases the risk of serotonin syndrome, a potentially life-threatening condition characterized by agitation, hyperthermia, tachycardia, and neuromuscular abnormalities.", "recommendation": "Avoid concurrent use. If both are necessary, use the lowest effective doses with close monitoring for serotonin syndrome symptoms. Seek immediate medical attention for fever, agitation, or muscle rigidity.", "minimumTimeSeparation": null, "mechanism": "Tramadol inhibits serotonin reuptake in addition to its opioid activity. Combined with SSRI serotonin reuptake inhibition, excessive serotonergic activity can precipitate serotonin syndrome.", "evidenceLevel": "strong", "sources": [ { "text": "Gillman PK. Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. Br J Anaesth. 2005.", "pmid": "15531621", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15531621/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Concurrent use of SSRIs and tramadol significantly increases the risk of serotonin syndrome, a potentially life-threatening condition characterized by agitation, hyperthermia, tachycardia, and neuromuscular abnormalities.", "clinicalSignificance": "Avoid concurrent use.", "managementStrategy": "Avoid concurrent use. If both are necessary, use the lowest effective doses with close monitoring for serotonin syndrome symptoms. Seek immediate medical attention for fever, agitation, or muscle rigidity.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Fluoxetine", "supplementBName": "Tramadol", "interactionType": "contraindicated", "severity": "dangerous", "description": "Fluoxetine combined with tramadol creates dual serotonin syndrome risk. Additionally, fluoxetine inhibits CYP2D6, reducing tramadol conversion to its active metabolite (O-desmethyltramadol), potentially reducing analgesic efficacy while increasing serotonergic toxicity risk.", "recommendation": "Avoid concurrent use. The CYP2D6 interaction compounds the serotonin syndrome risk, making this combination particularly dangerous.", "minimumTimeSeparation": null, "mechanism": "Fluoxetine potently inhibits CYP2D6 and serotonin reuptake. Tramadol also inhibits serotonin reuptake. The combination produces additive serotonergic activity and altered tramadol metabolism.", "evidenceLevel": "strong", "sources": [ { "text": "Sansone RA, Sansone LA. Tramadol: seizures, serotonin syndrome, and coadministered antidepressants. Psychiatry (Edgmont). 2009.", "pmid": "19724751", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19724751/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Fluoxetine combined with tramadol creates dual serotonin syndrome risk.", "clinicalSignificance": "Additionally, fluoxetine inhibits CYP2D6, reducing tramadol conversion to its active metabolite (O-desmethyltramadol), potentially reducing analgesic efficacy while increasing serotonergic toxicity risk.", "managementStrategy": "Avoid concurrent use. The CYP2D6 interaction compounds the serotonin syndrome risk, making this combination particularly dangerous.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Sertraline", "supplementBName": "Amitriptyline", "interactionType": "caution", "severity": "serious", "description": "Combining an SSRI with a tricyclic antidepressant increases the risk of serotonin syndrome and may elevate TCA blood levels due to CYP2D6 inhibition, increasing the risk of TCA toxicity including cardiac arrhythmias.", "recommendation": "Generally avoid this combination. If clinically necessary, use reduced TCA doses with serum TCA level monitoring and ECG surveillance.", "minimumTimeSeparation": null, "mechanism": "Both SSRIs and TCAs increase serotonergic tone. SSRIs also inhibit CYP2D6-mediated TCA metabolism, raising TCA plasma levels and risk of cardiac toxicity.", "evidenceLevel": "strong", "sources": [ { "text": "Taylor D. Antidepressant combinations: a review of the evidence. J Psychopharmacol. 1995.", "pmid": "22298899", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22298899/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Combining an SSRI with a tricyclic antidepressant increases the risk of serotonin syndrome and may elevate TCA blood levels due to CYP2D6 inhibition, increasing the risk of TCA toxicity including cardiac arrhythmias.", "clinicalSignificance": "Generally avoid this combination.", "managementStrategy": "Generally avoid this combination. If clinically necessary, use reduced TCA doses with serum TCA level monitoring and ECG surveillance.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Amiodarone", "supplementBName": "Ciprofloxacin", "interactionType": "contraindicated", "severity": "dangerous", "description": "Both amiodarone and fluoroquinolones independently prolong the QT interval. Concurrent use creates additive QT prolongation risk, potentially leading to torsades de pointes, a life-threatening ventricular arrhythmia.", "recommendation": "Avoid concurrent use if possible. If unavoidable, perform baseline ECG, monitor QTc closely, and discontinue if QTc exceeds 500 ms. Ensure electrolytes (K+, Mg2+) are normal.", "minimumTimeSeparation": null, "mechanism": "Amiodarone blocks multiple cardiac ion channels including hERG potassium channels. Fluoroquinolones also block hERG channels. Additive blockade prolongs cardiac repolarization and QT interval.", "evidenceLevel": "strong", "sources": [ { "text": "Tisdale JE et al. Drug-induced arrhythmias: a scientific statement from the AHA. Circulation. 2020.", "pmid": "33073581", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33073581/", "publicSourceType": "PMID" }, { "text": "Alves C, Mendes D, Marques FB. Fluoroquinolones and the risk of tendon injury: a systematic review and meta-analysis.. European Journal of Clinical Pharmacology. 2019.", "pmid": "31270563", "doi": "10.1007/s00228-019-02713-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31270563/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Both amiodarone and fluoroquinolones independently prolong the QT interval.", "clinicalSignificance": "Concurrent use creates additive QT prolongation risk, potentially leading to torsades de pointes, a life-threatening ventricular arrhythmia.", "managementStrategy": "Avoid concurrent use if possible. If unavoidable, perform baseline ECG, monitor QTc closely, and discontinue if QTc exceeds 500 ms. Ensure electrolytes (K+, Mg2+) are normal.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Amiodarone", "supplementBName": "Escitalopram", "interactionType": "caution", "severity": "serious", "description": "Both amiodarone and escitalopram can prolong the QT interval. Combined use increases the risk of dangerous cardiac arrhythmias, particularly torsades de pointes.", "recommendation": "Monitor ECG closely if combined. Consider alternative antidepressant with lower QT prolongation risk (e.g., sertraline). Keep electrolytes balanced.", "minimumTimeSeparation": null, "mechanism": "Additive QT prolongation through independent hERG potassium channel blockade by both agents.", "evidenceLevel": "moderate", "sources": [ { "text": "Beach SR et al. QTc prolongation, torsades de pointes, and psychotropic medications. Psychosomatics. 2013.", "pmid": "23194934", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23194934/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Both amiodarone and escitalopram can prolong the QT interval.", "clinicalSignificance": "Combined use increases the risk of dangerous cardiac arrhythmias, particularly torsades de pointes.", "managementStrategy": "Monitor ECG closely if combined. Consider alternative antidepressant with lower QT prolongation risk (e.g., sertraline). Keep electrolytes balanced.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Aspirin Low-Dose", "interactionType": "caution", "severity": "serious", "description": "Concurrent anticoagulant and antiplatelet therapy significantly increases bleeding risk. While sometimes used intentionally (e.g., mechanical heart valves), the combination requires careful risk-benefit assessment and close monitoring.", "recommendation": "Only use together when specifically prescribed by a physician for an approved indication. Monitor for signs of bleeding. Use lowest effective aspirin dose. Regular INR monitoring essential.", "minimumTimeSeparation": null, "mechanism": "Warfarin inhibits vitamin K-dependent clotting factor synthesis while aspirin irreversibly inhibits platelet cyclooxygenase (COX-1). Combined inhibition of both coagulation cascade and platelet aggregation substantially increases hemorrhagic risk.", "evidenceLevel": "strong", "sources": [ { "text": "Lip GY et al. Antithrombotic therapy for atrial fibrillation: CHEST guideline. Chest. 2018.", "pmid": "30144990", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30144990/", "publicSourceType": "PMID" }, { "text": "Wang M, Zeraatkar D, Obeda M, Lee M et al.. Drug-drug interactions with warfarin: A systematic review and meta-analysis. British Journal of Clinical Pharmacology. 2021.", "pmid": "33769581", "doi": "10.1111/bcp.14833", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33769581/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Concurrent anticoagulant and antiplatelet therapy significantly increases bleeding risk.", "clinicalSignificance": "While sometimes used intentionally (e.g., mechanical heart valves), the combination requires careful risk-benefit assessment and close monitoring.", "managementStrategy": "Only use together when specifically prescribed by a physician for an approved indication. Monitor for signs of bleeding. Use lowest effective aspirin dose. Regular INR monitoring essential.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Clopidogrel", "interactionType": "caution", "severity": "serious", "description": "Triple therapy (warfarin + clopidogrel + aspirin) or dual therapy (warfarin + clopidogrel) substantially increases major bleeding risk compared to either agent alone.", "recommendation": "Only combine when clearly indicated (e.g., post-PCI with AF). Use the shortest duration possible. Monitor INR more frequently. Consider DOAC instead of warfarin when feasible.", "minimumTimeSeparation": null, "mechanism": "Warfarin and clopidogrel inhibit different hemostatic pathways. Combined inhibition of coagulation cascade (warfarin) and ADP-mediated platelet aggregation (clopidogrel) creates synergistic bleeding risk.", "evidenceLevel": "strong", "sources": [ { "text": "Dewilde WJ et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing PCI: WOEST trial. Lancet. 2013.", "pmid": "23415013", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23415013/", "publicSourceType": "PMID" }, { "text": "Wang M, Zeraatkar D, Obeda M, Lee M et al.. Drug-drug interactions with warfarin: A systematic review and meta-analysis. British Journal of Clinical Pharmacology. 2021.", "pmid": "33769581", "doi": "10.1111/bcp.14833", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33769581/", "publicSourceType": "PMID" }, { "text": "Lun R, Dhaliwal S, Zitikyte G, Roy DC et al.. Comparison of Ticagrelor vs Clopidogrel in Addition to Aspirin in Patients With Minor Ischemic Stroke and Transient Ischemic Attack: A Network Meta-analysis. JAMA Neurology. 2022.", "pmid": "34870698", "doi": "10.1001/jamaneurol.2021.4514", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34870698/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Triple therapy (warfarin + clopidogrel + aspirin) or dual therapy (warfarin + clopidogrel) substantially increases major bleeding risk compared to either agent alone.", "clinicalSignificance": "Only combine when clearly indicated (e.g., post-PCI with AF).", "managementStrategy": "Only combine when clearly indicated (e.g., post-PCI with AF). Use the shortest duration possible. Monitor INR more frequently. Consider DOAC instead of warfarin when feasible.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Methotrexate", "supplementBName": "Ibuprofen", "interactionType": "caution", "severity": "serious", "description": "NSAIDs reduce renal clearance of methotrexate, potentially leading to toxic methotrexate accumulation. This can cause severe bone marrow suppression, hepatotoxicity, and nephrotoxicity.", "recommendation": "Avoid concurrent use, especially with high-dose methotrexate. If low-dose methotrexate (for RA) is combined with occasional NSAID use, monitor CBC and renal function closely.", "minimumTimeSeparation": null, "mechanism": "NSAIDs reduce renal blood flow via prostaglandin inhibition and compete with methotrexate for renal tubular secretion, decreasing methotrexate clearance by 20-40%.", "evidenceLevel": "strong", "sources": [ { "text": "Svanstrom H et al. Use of NSAIDs and risk of methotrexate toxicity. Arthritis Rheumatol. 2017.", "pmid": "28499043", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28499043/", "publicSourceType": "PMID" }, { "text": "Tan E, Braithwaite I, McKinlay CJD et al.. Comparison of Acetaminophen (Paracetamol) With Ibuprofen for Treatment of Fever or Pain in Children Younger Than 2 Years: A Systematic Review and Meta-analysis.. JAMA Network Open. 2020.", "pmid": "33125495", "doi": "10.1001/jamanetworkopen.2020.22398", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33125495/", "publicSourceType": "PMID" }, { "text": "Miroshnychenko A, Ibrahim S, Azab M et al.. Acute Postoperative Pain Due to Dental Extraction in the Adult Population: A Systematic Review and Network Meta-analysis.. Journal of Dental Research. 2023.", "pmid": "36631957", "doi": "10.1177/00220345221139230", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36631957/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "NSAIDs reduce renal clearance of methotrexate, potentially leading to toxic methotrexate accumulation.", "clinicalSignificance": "This can cause severe bone marrow suppression, hepatotoxicity, and nephrotoxicity.", "managementStrategy": "Avoid concurrent use, especially with high-dose methotrexate. If low-dose methotrexate (for RA) is combined with occasional NSAID use, monitor CBC and renal function closely.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Methotrexate", "supplementBName": "Naproxen", "interactionType": "caution", "severity": "serious", "description": "Naproxen, like other NSAIDs, reduces renal clearance of methotrexate. The longer half-life of naproxen may pose even greater accumulation risk compared to short-acting NSAIDs.", "recommendation": "Avoid concurrent use with high-dose methotrexate. Use with extreme caution alongside low-dose methotrexate. Monitor renal function and CBC regularly.", "minimumTimeSeparation": null, "mechanism": "Naproxen inhibits renal prostaglandin synthesis, reducing glomerular filtration rate and competing with methotrexate for tubular secretion.", "evidenceLevel": "strong", "sources": [ { "text": "Svanstrom H et al. Use of NSAIDs and risk of methotrexate toxicity. Arthritis Rheumatol. 2017.", "pmid": "28499043", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28499043/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Naproxen, like other NSAIDs, reduces renal clearance of methotrexate.", "clinicalSignificance": "The longer half-life of naproxen may pose even greater accumulation risk compared to short-acting NSAIDs.", "managementStrategy": "Avoid concurrent use with high-dose methotrexate. Use with extreme caution alongside low-dose methotrexate. Monitor renal function and CBC regularly.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Lithium", "supplementBName": "Lisinopril", "interactionType": "caution", "severity": "serious", "description": "ACE inhibitors reduce renal lithium clearance, potentially increasing lithium levels by 25-40% and causing lithium toxicity. Symptoms include tremor, nausea, confusion, and potentially seizures.", "recommendation": "Monitor lithium levels closely when starting, stopping, or adjusting ACE inhibitor dose. Reduce lithium dose as needed. Watch for toxicity symptoms.", "minimumTimeSeparation": null, "mechanism": "ACE inhibitors reduce angiotensin II-mediated aldosterone secretion, promoting sodium and water retention in the proximal tubule. Since lithium is reabsorbed with sodium, reduced sodium excretion leads to increased lithium reabsorption.", "evidenceLevel": "strong", "sources": [ { "text": "Finley PR et al. Lithium and angiotensin-converting enzyme inhibitors: evaluation of a potential interaction. J Clin Psychopharmacol. 1996.", "pmid": "8773460", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8773460/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "ACE inhibitors reduce renal lithium clearance, potentially increasing lithium levels by 25-40% and causing lithium toxicity.", "clinicalSignificance": "Symptoms include tremor, nausea, confusion, and potentially seizures.", "managementStrategy": "Monitor lithium levels closely when starting, stopping, or adjusting ACE inhibitor dose. Reduce lithium dose as needed. Watch for toxicity symptoms.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Lithium", "supplementBName": "Hydrochlorothiazide", "interactionType": "caution", "severity": "serious", "description": "Thiazide diuretics reduce lithium clearance by 25-40%, significantly increasing the risk of lithium toxicity. This is one of the most well-documented drug-drug interactions involving lithium.", "recommendation": "If combination is necessary, reduce lithium dose by 25-50% and monitor lithium levels frequently (weekly initially). Use lowest effective diuretic dose.", "minimumTimeSeparation": null, "mechanism": "Thiazide diuretics cause sodium and volume depletion. The kidney compensates by increasing proximal tubular sodium reabsorption, and lithium is reabsorbed along with sodium, raising serum lithium levels.", "evidenceLevel": "strong", "sources": [ { "text": "Finley PR. Drug interactions with lithium: an update. Clin Pharmacokinet. 2016.", "pmid": "27098303", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27098303/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Thiazide diuretics reduce lithium clearance by 25-40%, significantly increasing the risk of lithium toxicity.", "clinicalSignificance": "This is one of the most well-documented drug-drug interactions involving lithium.", "managementStrategy": "If combination is necessary, reduce lithium dose by 25-50% and monitor lithium levels frequently (weekly initially). Use lowest effective diuretic dose.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Lithium", "supplementBName": "Furosemide", "interactionType": "caution", "severity": "serious", "description": "Loop diuretics can increase lithium levels through volume depletion, though the effect is generally less predictable than with thiazide diuretics. Dehydration from aggressive diuresis is particularly dangerous.", "recommendation": "Monitor lithium levels closely. Ensure adequate hydration. Check lithium levels within 5-7 days of diuretic initiation or dose change.", "minimumTimeSeparation": null, "mechanism": "Furosemide causes natriuresis and volume depletion. Compensatory proximal tubular sodium reabsorption increases lithium reabsorption, raising serum levels. Dehydration compounds this effect.", "evidenceLevel": "moderate", "sources": [ { "text": "Finley PR. Drug interactions with lithium: an update. Clin Pharmacokinet. 2016.", "pmid": "27098303", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27098303/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Loop diuretics can increase lithium levels through volume depletion, though the effect is generally less predictable than with thiazide diuretics.", "clinicalSignificance": "Dehydration from aggressive diuresis is particularly dangerous.", "managementStrategy": "Monitor lithium levels closely. Ensure adequate hydration. Check lithium levels within 5-7 days of diuretic initiation or dose change.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Simvastatin", "supplementBName": "Clarithromycin", "interactionType": "contraindicated", "severity": "dangerous", "description": "Clarithromycin is a potent CYP3A4 inhibitor that dramatically increases simvastatin plasma levels (up to 10-fold), greatly increasing the risk of severe rhabdomyolysis, a potentially fatal muscle breakdown condition.", "recommendation": "Contraindicated. Suspend simvastatin during clarithromycin treatment. If statin therapy is needed, use pravastatin or rosuvastatin (not CYP3A4 metabolized).", "minimumTimeSeparation": null, "mechanism": "Simvastatin is extensively metabolized by CYP3A4. Clarithromycin potently inhibits CYP3A4, causing massive accumulation of simvastatin and its active metabolite, leading to myotoxicity.", "evidenceLevel": "strong", "sources": [ { "text": "Jacobson TA. Comparative pharmacokinetic interaction profiles of pravastatin, simvastatin, and atorvastatin when coadministered with cytochrome P450 inhibitors. Am J Cardiol. 2004.", "pmid": "15464633", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15464633/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Clarithromycin is a potent CYP3A4 inhibitor that dramatically increases simvastatin plasma levels (up to 10-fold), greatly increasing the risk of severe rhabdomyolysis, a potentially fatal muscle breakdown condition.", "clinicalSignificance": "Contraindicated.", "managementStrategy": "Contraindicated. Suspend simvastatin during clarithromycin treatment. If statin therapy is needed, use pravastatin or rosuvastatin (not CYP3A4 metabolized).", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Atorvastatin", "supplementBName": "Clarithromycin", "interactionType": "caution", "severity": "serious", "description": "Clarithromycin inhibits CYP3A4, increasing atorvastatin levels. While less dramatic than simvastatin interaction (atorvastatin is partially CYP3A4 metabolized), the risk of myopathy and rhabdomyolysis is still significantly elevated.", "recommendation": "Limit atorvastatin to 20 mg daily when used with clarithromycin. Consider azithromycin as alternative macrolide (no CYP3A4 inhibition) or pravastatin/rosuvastatin as alternative statin.", "minimumTimeSeparation": null, "mechanism": "CYP3A4 inhibition by clarithromycin reduces atorvastatin first-pass metabolism, increasing systemic exposure and myotoxicity risk.", "evidenceLevel": "strong", "sources": [ { "text": "Jacobson TA. Comparative pharmacokinetic interaction profiles of statins. Am J Cardiol. 2004.", "pmid": "15464633", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15464633/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Clarithromycin inhibits CYP3A4, increasing atorvastatin levels.", "clinicalSignificance": "While less dramatic than simvastatin interaction (atorvastatin is partially CYP3A4 metabolized), the risk of myopathy and rhabdomyolysis is still significantly elevated.", "managementStrategy": "Limit atorvastatin to 20 mg daily when used with clarithromycin. Consider azithromycin as alternative macrolide (no CYP3A4 inhibition) or pravastatin/rosuvastatin as alternative statin.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Oxycodone", "supplementBName": "Alprazolam", "interactionType": "contraindicated", "severity": "dangerous", "description": "FDA Black Box Warning: Concurrent use of opioids and benzodiazepines can result in profound sedation, respiratory depression, coma, and death. This is one of the most dangerous drug-drug interactions in clinical practice.", "recommendation": "Avoid concurrent prescribing whenever possible. If combined, use the lowest doses for the shortest duration. Inform patients about the risk of respiratory depression. Ensure naloxone is available.", "minimumTimeSeparation": null, "mechanism": "Opioids depress brainstem respiratory centers via mu-receptor activation. Benzodiazepines enhance GABA-A-mediated inhibition, also depressing respiration. Combined CNS depression is synergistic, not merely additive.", "evidenceLevel": "strong", "sources": [ { "text": "Sun EC et al. Association between concurrent use of prescription opioids and benzodiazepines and overdose. BMJ. 2017.", "pmid": "28292769", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28292769/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "FDA Black Box Warning: Concurrent use of opioids and benzodiazepines can result in profound sedation, respiratory depression, coma, and death.", "clinicalSignificance": "This is one of the most dangerous drug-drug interactions in clinical practice.", "managementStrategy": "Avoid concurrent prescribing whenever possible. If combined, use the lowest doses for the shortest duration. Inform patients about the risk of respiratory depression. Ensure naloxone is available.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Hydrocodone", "supplementBName": "Alprazolam", "interactionType": "contraindicated", "severity": "dangerous", "description": "FDA Black Box Warning: The combination of hydrocodone and alprazolam carries severe risk of fatal respiratory depression. This is among the most commonly co-prescribed dangerous drug combinations in the United States.", "recommendation": "Avoid concurrent prescribing. If no alternative exists, use lowest effective doses for the shortest duration. Monitor closely for respiratory depression.", "minimumTimeSeparation": null, "mechanism": "Synergistic CNS and respiratory depression through combined mu-opioid receptor agonism and GABA-A receptor potentiation.", "evidenceLevel": "strong", "sources": [ { "text": "Sun EC et al. Association between concurrent use of prescription opioids and benzodiazepines and overdose. BMJ. 2017.", "pmid": "28292769", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28292769/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "FDA Black Box Warning: The combination of hydrocodone and alprazolam carries severe risk of fatal respiratory depression.", "clinicalSignificance": "This is among the most commonly co-prescribed dangerous drug combinations in the United States.", "managementStrategy": "Avoid concurrent prescribing. If no alternative exists, use lowest effective doses for the shortest duration. Monitor closely for respiratory depression.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Morphine", "supplementBName": "Diazepam", "interactionType": "contraindicated", "severity": "dangerous", "description": "FDA Black Box Warning: Concurrent opioid and benzodiazepine use can result in profound sedation, respiratory depression, coma, and death. Morphine and diazepam both have long durations of action, compounding the risk.", "recommendation": "Avoid combination. If absolutely necessary in a monitored setting, use lowest possible doses with continuous pulse oximetry monitoring.", "minimumTimeSeparation": null, "mechanism": "Morphine activates mu-opioid receptors depressing respiratory drive. Diazepam (and active metabolites with very long half-lives) enhances GABA-mediated CNS depression. Combined effect on respiratory centers is synergistic.", "evidenceLevel": "strong", "sources": [ { "text": "Sun EC, Dixit A, Humphreys K, Darnall BD, Baker LC, Mackey S. Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis. BMJ. 2017;356:j760.", "pmid": "28292769", "doi": "10.1136/bmj.j760", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28292769/", "publicSourceType": "PMID" }, { "text": "Park TW, Saitz R, Ganoczy D, Ilgen MA, Bohnert ASB. Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study. BMJ. 2015;350:h2698.", "pmid": "26063215", "doi": "10.1136/bmj.h2698", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26063215/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "FDA Black Box Warning: Concurrent opioid and benzodiazepine use can result in profound sedation, respiratory depression, coma, and death.", "clinicalSignificance": "Morphine and diazepam both have long durations of action, compounding the risk.", "managementStrategy": "Avoid combination. If absolutely necessary in a monitored setting, use lowest possible doses with continuous pulse oximetry monitoring.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Sertraline", "supplementBName": "Lithium", "interactionType": "caution", "severity": "moderate", "description": "While SSRIs and lithium are commonly used together in treatment-resistant depression and bipolar disorder, the combination carries a modest risk of serotonin syndrome and lithium augments serotonergic neurotransmission.", "recommendation": "This combination is often used intentionally under psychiatric supervision. Monitor for serotonin syndrome symptoms, especially when initiating or increasing SSRI dose. Therapeutic lithium level monitoring remains essential.", "minimumTimeSeparation": null, "mechanism": "Lithium enhances serotonergic neurotransmission through multiple mechanisms including increased tryptophan uptake and presynaptic serotonin release. Combined with SSRI reuptake inhibition, serotonergic activity may become excessive.", "evidenceLevel": "moderate", "sources": [ { "text": "Nelson JC, Papakostas GI. Atypical antipsychotic augmentation in major depressive disorder: a meta-analysis. Am J Psychiatry. 2009.", "pmid": "19487398", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19487398/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "While SSRIs and lithium are commonly used together in treatment-resistant depression and bipolar disorder, the combination carries a modest risk of serotonin syndrome and lithium augments serotonergic neurotransmission.", "clinicalSignificance": "This combination is often used intentionally under psychiatric supervision.", "managementStrategy": "This combination is often used intentionally under psychiatric supervision. Monitor for serotonin syndrome symptoms, especially when initiating or increasing SSRI dose. Therapeutic lithium level monitoring remains essential.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Lisinopril", "supplementBName": "Spironolactone", "interactionType": "caution", "severity": "serious", "description": "Both ACE inhibitors and spironolactone increase serum potassium through different mechanisms. Combined use significantly increases the risk of life-threatening hyperkalemia, especially in patients with renal impairment.", "recommendation": "While used intentionally in heart failure (RALES trial protocol), requires close potassium and renal function monitoring. Check potassium within 3-7 days of initiation. Avoid in patients with eGFR <30.", "minimumTimeSeparation": null, "mechanism": "ACE inhibitors reduce aldosterone secretion, decreasing potassium excretion. Spironolactone blocks the mineralocorticoid receptor, further reducing potassium excretion. Combined effect can cause dangerous hyperkalemia.", "evidenceLevel": "strong", "sources": [ { "text": "Juurlink DN et al. Rates of hyperkalemia after publication of the RALES study. N Engl J Med. 2004.", "pmid": "15295047", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15295047/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Both ACE inhibitors and spironolactone increase serum potassium through different mechanisms.", "clinicalSignificance": "Combined use significantly increases the risk of life-threatening hyperkalemia, especially in patients with renal impairment.", "managementStrategy": "While used intentionally in heart failure (RALES trial protocol), requires close potassium and renal function monitoring. Check potassium within 3-7 days of initiation. Avoid in patients with eGFR <30.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Ibuprofen", "interactionType": "caution", "severity": "serious", "description": "NSAIDs increase bleeding risk with warfarin through dual mechanisms: antiplatelet effects and GI mucosal damage. Ibuprofen also inhibits CYP2C9, potentially increasing warfarin levels.", "recommendation": "Avoid concurrent use when possible. If necessary, use the lowest NSAID dose for the shortest duration. Consider acetaminophen as an alternative. Monitor INR more frequently.", "minimumTimeSeparation": null, "mechanism": "NSAIDs inhibit platelet COX-1 (additive bleeding risk with warfarin anticoagulation), cause GI mucosal damage (creating bleeding sites), and may inhibit CYP2C9-mediated warfarin metabolism.", "evidenceLevel": "strong", "sources": [ { "text": "Knijff-Dutmer EA et al. Platelet function is inhibited by non-selective NSAIDs but not by cyclooxygenase-2-selective inhibitors in patients with rheumatoid arthritis. Thromb Haemost. 2002.", "pmid": "12071243", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12071243/", "publicSourceType": "PMID" }, { "text": "Wang M, Zeraatkar D, Obeda M, Lee M et al.. Drug-drug interactions with warfarin: A systematic review and meta-analysis. British Journal of Clinical Pharmacology. 2021.", "pmid": "33769581", "doi": "10.1111/bcp.14833", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33769581/", "publicSourceType": "PMID" }, { "text": "Tan E, Braithwaite I, McKinlay CJD et al.. Comparison of Acetaminophen (Paracetamol) With Ibuprofen for Treatment of Fever or Pain in Children Younger Than 2 Years: A Systematic Review and Meta-analysis.. JAMA Network Open. 2020.", "pmid": "33125495", "doi": "10.1001/jamanetworkopen.2020.22398", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33125495/", "publicSourceType": "PMID" }, { "text": "Miroshnychenko A, Ibrahim S, Azab M et al.. Acute Postoperative Pain Due to Dental Extraction in the Adult Population: A Systematic Review and Network Meta-analysis.. Journal of Dental Research. 2023.", "pmid": "36631957", "doi": "10.1177/00220345221139230", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36631957/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "NSAIDs increase bleeding risk with warfarin through dual mechanisms: antiplatelet effects and GI mucosal damage.", "clinicalSignificance": "Ibuprofen also inhibits CYP2C9, potentially increasing warfarin levels.", "managementStrategy": "Avoid concurrent use when possible. If necessary, use the lowest NSAID dose for the shortest duration. Consider acetaminophen as an alternative. Monitor INR more frequently.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Apixaban", "supplementBName": "Ibuprofen", "interactionType": "caution", "severity": "moderate", "description": "NSAIDs increase the bleeding risk when combined with DOACs through antiplatelet effects and GI mucosal irritation. While DOACs have fewer food/drug interactions than warfarin, NSAID co-use remains a significant risk factor.", "recommendation": "Minimize concurrent use. If pain relief is needed, prefer acetaminophen. If NSAID is necessary, use the lowest dose for the shortest time and monitor for bleeding signs.", "minimumTimeSeparation": null, "mechanism": "NSAIDs inhibit platelet aggregation and damage GI mucosa. Combined with apixaban's Factor Xa inhibition, overall hemostatic function is significantly impaired.", "evidenceLevel": "moderate", "sources": [ { "text": "Davidson BL et al. Bleeding risk of patients with acute venous thromboembolism taking NSAIDs or aspirin. JAMA Intern Med. 2014.", "pmid": "24934614", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24934614/", "publicSourceType": "PMID" }, { "text": "Tan E, Braithwaite I, McKinlay CJD et al.. Comparison of Acetaminophen (Paracetamol) With Ibuprofen for Treatment of Fever or Pain in Children Younger Than 2 Years: A Systematic Review and Meta-analysis.. JAMA Network Open. 2020.", "pmid": "33125495", "doi": "10.1001/jamanetworkopen.2020.22398", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33125495/", "publicSourceType": "PMID" }, { "text": "Miroshnychenko A, Ibrahim S, Azab M et al.. Acute Postoperative Pain Due to Dental Extraction in the Adult Population: A Systematic Review and Network Meta-analysis.. Journal of Dental Research. 2023.", "pmid": "36631957", "doi": "10.1177/00220345221139230", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36631957/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "NSAIDs increase the bleeding risk when combined with DOACs through antiplatelet effects and GI mucosal irritation.", "clinicalSignificance": "While DOACs have fewer food/drug interactions than warfarin, NSAID co-use remains a significant risk factor.", "managementStrategy": "Minimize concurrent use. If pain relief is needed, prefer acetaminophen. If NSAID is necessary, use the lowest dose for the shortest time and monitor for bleeding signs.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Valproic Acid", "supplementBName": "Lamotrigine", "interactionType": "caution", "severity": "serious", "description": "Valproic acid inhibits the glucuronidation of lamotrigine, approximately doubling lamotrigine levels. This increases the risk of serious skin reactions including Stevens-Johnson syndrome, especially during lamotrigine titration.", "recommendation": "When used together, lamotrigine dose must be reduced by 50% and titrated very slowly. Standard lamotrigine titration schedules have specific reduced-dose protocols for valproate co-administration.", "minimumTimeSeparation": null, "mechanism": "Valproic acid inhibits UGT1A4-mediated glucuronidation of lamotrigine, reducing lamotrigine clearance by approximately 50% and doubling its half-life from 25 to 48-70 hours.", "evidenceLevel": "strong", "sources": [ { "text": "Anderson GD et al. Pharmacokinetic interactions with lamotrigine. Clin Pharmacokinet. 2002.", "pmid": "12036392", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12036392/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Valproic acid inhibits the glucuronidation of lamotrigine, approximately doubling lamotrigine levels.", "clinicalSignificance": "This increases the risk of serious skin reactions including Stevens-Johnson syndrome, especially during lamotrigine titration.", "managementStrategy": "When used together, lamotrigine dose must be reduced by 50% and titrated very slowly. Standard lamotrigine titration schedules have specific reduced-dose protocols for valproate co-administration.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Phenytoin", "supplementBName": "Carbamazepine", "interactionType": "caution", "severity": "moderate", "description": "Both are potent CYP enzyme inducers that affect each other's metabolism. Phenytoin can decrease carbamazepine levels, while carbamazepine can decrease phenytoin levels, making dose optimization challenging.", "recommendation": "Monitor serum levels of both drugs closely when used together. Dose adjustments are frequently needed. Therapeutic drug monitoring is essential.", "minimumTimeSeparation": null, "mechanism": "Both drugs are CYP3A4 inducers and CYP3A4 substrates. Mutual induction of hepatic metabolism leads to reduced plasma levels of both drugs, requiring higher doses to maintain therapeutic levels.", "evidenceLevel": "strong", "sources": [ { "text": "Patsalos PN et al. Antiepileptic drugs, best practice guidelines for therapeutic drug monitoring. Epilepsia. 2008.", "pmid": "18397299", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18397299/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both are potent CYP enzyme inducers that affect each other's metabolism.", "clinicalSignificance": "Phenytoin can decrease carbamazepine levels, while carbamazepine can decrease phenytoin levels, making dose optimization challenging.", "managementStrategy": "Monitor serum levels of both drugs closely when used together. Dose adjustments are frequently needed. Therapeutic drug monitoring is essential.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Metformin", "supplementBName": "Furosemide", "interactionType": "caution", "severity": "moderate", "description": "Furosemide can cause volume depletion and renal impairment, which increases the risk of metformin-associated lactic acidosis. This is particularly relevant in elderly patients or those with borderline renal function.", "recommendation": "Monitor renal function regularly. Ensure adequate hydration. Consider holding metformin if signs of dehydration develop or if renal function declines.", "minimumTimeSeparation": null, "mechanism": "Furosemide-induced volume depletion reduces renal perfusion and GFR. Reduced renal clearance of metformin leads to accumulation, increasing the risk of lactic acidosis, especially when combined with tissue hypoperfusion.", "evidenceLevel": "moderate", "sources": [ { "text": "DeFronzo R et al. Metformin-associated lactic acidosis: current perspectives. Clin Pharmacol Ther. 2016.", "pmid": "26429791", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26429791/", "publicSourceType": "PMID" }, { "text": "Maruthur NM, Tseng E, Hutfless S, Wilson LM et al.. Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-analysis. Annals of Internal Medicine. 2016.", "pmid": "27088241", "doi": "10.7326/M15-2650", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27088241/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Furosemide can cause volume depletion and renal impairment, which increases the risk of metformin-associated lactic acidosis.", "clinicalSignificance": "This is particularly relevant in elderly patients or those with borderline renal function.", "managementStrategy": "Monitor renal function regularly. Ensure adequate hydration. Consider holding metformin if signs of dehydration develop or if renal function declines.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Digoxin", "supplementBName": "Amiodarone", "interactionType": "caution", "severity": "serious", "description": "Amiodarone increases digoxin levels by 70-100% through inhibition of P-glycoprotein and reduction of renal and non-renal clearance. This can cause potentially fatal digoxin toxicity with cardiac arrhythmias.", "recommendation": "Reduce digoxin dose by 50% when starting amiodarone. Monitor digoxin levels closely. Watch for toxicity signs (nausea, visual changes, bradycardia, arrhythmias).", "minimumTimeSeparation": null, "mechanism": "Amiodarone inhibits P-glycoprotein (MDR1)-mediated renal tubular secretion and biliary excretion of digoxin, and reduces its volume of distribution, resulting in approximately doubled digoxin serum levels.", "evidenceLevel": "strong", "sources": [ { "text": "Fromm MF et al. Inhibition of P-glycoprotein-mediated drug transport: a unifying mechanism to explain the interaction between digoxin and quinidine. Circulation. 1999.", "pmid": "10217648", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10217648/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Amiodarone increases digoxin levels by 70-100% through inhibition of P-glycoprotein and reduction of renal and non-renal clearance.", "clinicalSignificance": "This can cause potentially fatal digoxin toxicity with cardiac arrhythmias.", "managementStrategy": "Reduce digoxin dose by 50% when starting amiodarone. Monitor digoxin levels closely. Watch for toxicity signs (nausea, visual changes, bradycardia, arrhythmias).", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Metoprolol", "supplementBName": "Coenzyme Q10 Ubiquinol", "interactionType": "synergy", "severity": "info", "description": "Beta-blockers including metoprolol inhibit CoQ10-dependent mitochondrial enzymes, reducing endogenous CoQ10 levels. Metoprolol inhibits NADH-oxidase (approximately one-fourth the potency of propranolol) and may contribute to fatigue, myalgia, and exercise intolerance experienced by some patients. CoQ10 supplementation may help alleviate these side effects by restoring mitochondrial bioenergetics.", "recommendation": "Consider supplementing with CoQ10 (100-200 mg/day) to offset potential depletion from metoprolol. CoQ10 is generally safe with beta-blockers and may improve energy levels and exercise tolerance. No dose adjustment of metoprolol is needed.", "minimumTimeSeparation": null, "mechanism": "Metoprolol inhibits CoQ10-dependent mitochondrial enzymes including NADH-oxidase and succinoxidase, reducing cellular ATP production. CoQ10 (ubiquinone) is an essential electron carrier in the mitochondrial respiratory chain, and its depletion impairs oxidative phosphorylation in cardiac and skeletal muscle.", "evidenceLevel": "moderate", "sources": [ { "text": "Kishi T et al. Bioenergetics in clinical medicine XV. Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors. Res Commun Chem Pathol Pharmacol. 1977;17(1):157-164.", "pmid": "17892", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17892/", "publicSourceType": "PMID" }, { "text": "Kishi T et al. Bioenergetics in clinical medicine III. Inhibition of coenzyme Q10-enzymes by clinically used anti-hypertensive drugs. Res Commun Chem Pathol Pharmacol. 1975;12(3):533-540.", "pmid": "1197930", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1197930/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Beta-blockers including metoprolol inhibit CoQ10-dependent mitochondrial enzymes, reducing endogenous CoQ10 levels.", "clinicalSignificance": "Metoprolol inhibits NADH-oxidase (approximately one-fourth the potency of propranolol) and may contribute to fatigue, myalgia, and exercise intolerance experienced by some patients.", "managementStrategy": "Consider supplementing with CoQ10 (100-200 mg/day) to offset potential depletion from metoprolol. CoQ10 is generally safe with beta-blockers and may improve energy levels and exercise tolerance. No dose adjustment of metoprolol is needed.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Metoprolol", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "moderate", "description": "Magnesium acts as a natural calcium channel blocker and can enhance the blood pressure-lowering and heart rate-reducing effects of metoprolol through complementary mechanisms. A double-blind crossover study showed that nutritional-dose magnesium supplementation in hypertensive patients on beta-blockers further lowered systolic blood pressure. While generally beneficial, the additive hypotensive and bradycardic effects require monitoring.", "recommendation": "Magnesium supplementation is generally safe and potentially beneficial with metoprolol, but monitor for excessive blood pressure reduction (systolic <100 mmHg) or bradycardia (HR <50 bpm). Start with moderate doses (200-350 mg/day supplemental elemental magnesium) and check blood pressure regularly when initiating.", "minimumTimeSeparation": null, "mechanism": "Magnesium reduces intracellular sodium and calcium while increasing intracellular potassium. It functions as a physiological calcium antagonist, relaxing vascular smooth muscle. Combined with metoprolol's beta-1 adrenergic blockade, the dual mechanism produces additive blood pressure and heart rate reduction.", "evidenceLevel": "moderate", "sources": [ { "text": "Wirell MP et al. Nutritional dose of magnesium in hypertensive patients on beta blockers lowers systolic blood pressure: a double-blind, cross-over study. J Intern Med. 1994;236(2):189-195.", "pmid": "7913949", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7913949/", "publicSourceType": "PMID" }, { "text": "Sontia B, Bhansali A. Magnesium supplementation with metoprolol cardiovascular effects. Improvement of cardiovascular effects of metoprolol by replacement of common salt with a potassium- and magnesium-enriched salt alternative. Br Heart J. 1994;72(1):68-74.", "pmid": "8075882", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8075882/", "publicSourceType": "PMID" }, { "text": "Mah J, Pitre T. Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis.. BMC Complementary Medicine and Therapies. 2021.", "pmid": "33865376", "doi": "10.1186/s12906-021-03297-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33865376/", "publicSourceType": "PMID" }, { "text": "Veronese N, Dominguez LJ, Pizzol D et al.. Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.. Nutrients. 2021.", "pmid": "34836329", "doi": "10.3390/nu13114074", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34836329/", "publicSourceType": "PMID" }, { "text": "Veronese N, Pizzol D, Smith L et al.. Effect of Magnesium Supplementation on Inflammatory Parameters: A Meta-Analysis of Randomized Controlled Trials.. Nutrients. 2022.", "pmid": "35277037", "doi": "10.3390/nu14030679", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35277037/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Magnesium acts as a natural calcium channel blocker and can enhance the blood pressure-lowering and heart rate-reducing effects of metoprolol through complementary mechanisms.", "clinicalSignificance": "A double-blind crossover study showed that nutritional-dose magnesium supplementation in hypertensive patients on beta-blockers further lowered systolic blood pressure.", "managementStrategy": "Magnesium supplementation is generally safe and potentially beneficial with metoprolol, but monitor for excessive blood pressure reduction (systolic <100 mmHg) or bradycardia (HR <50 bpm). Start with moderate doses (200-350 mg/day supplemental elemental magnesium) and check blood pressure regularly when initiating.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Metoprolol", "supplementBName": "Melatonin", "interactionType": "synergy", "severity": "info", "description": "Metoprolol suppresses endogenous melatonin production by approximately 50% through blockade of beta-1 adrenergic receptors on the pineal gland. This is a primary mechanism for the insomnia and sleep disturbance commonly reported with beta-blockers. Melatonin supplementation (2.5 mg nightly) has been shown in a randomized controlled trial to significantly improve sleep quality in beta-blocker-treated patients without tolerance development or rebound effects.", "recommendation": "If experiencing sleep disturbance on metoprolol, consider melatonin supplementation (2-3 mg at bedtime). Clinical trials show this is safe and effective. No dose adjustment of metoprolol is needed. Take melatonin 30-60 minutes before desired sleep time.", "minimumTimeSeparation": null, "mechanism": "Melatonin synthesis in the pineal gland is stimulated by norepinephrine via beta-1 adrenergic receptors. Metoprolol blocks these receptors, suppressing nocturnal melatonin secretion and disrupting circadian rhythm signaling. Exogenous melatonin replaces the suppressed endogenous production, restoring sleep architecture.", "evidenceLevel": "strong", "sources": [ { "text": "Scheer FA et al. Repeated melatonin supplementation improves sleep in hypertensive patients treated with beta-blockers: a randomized controlled trial. Sleep. 2012;35(10):1395-1402.", "pmid": "23024438", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23024438/", "publicSourceType": "PMID" }, { "text": "Stoschitzky K et al. Melatonin secretion related to side-effects of beta-blockers from the central nervous system. J Neural Transm. 1986;67(3-4):303-309.", "pmid": "3291558", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3291558/", "publicSourceType": "PMID" }, { "text": "Fatemeh G, Sajjad M, Niloufar R et al.. Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials.. Journal of Neurology. 2022.", "pmid": "33417003", "doi": "10.1007/s00415-020-10381-w", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33417003/", "publicSourceType": "PMID" }, { "text": "Tang BHY, Manalo J, Chowdhury SR et al.. Melatonin Use in the ICU: A Systematic Review and Meta-Analysis.. Critical Care Medicine. 2025.", "pmid": "40662882", "doi": "10.1097/CCM.0000000000006767", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40662882/", "publicSourceType": "PMID" }, { "text": "Chan V, Lo K. Efficacy of dietary supplements on improving sleep quality: a systematic review and meta-analysis.. Postgraduate Medical Journal. 2022.", "pmid": "33441476", "doi": "10.1136/postgradmedj-2020-139319", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33441476/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Metoprolol suppresses endogenous melatonin production by approximately 50% through blockade of beta-1 adrenergic receptors on the pineal gland.", "clinicalSignificance": "This is a primary mechanism for the insomnia and sleep disturbance commonly reported with beta-blockers.", "managementStrategy": "If experiencing sleep disturbance on metoprolol, consider melatonin supplementation (2-3 mg at bedtime). Clinical trials show this is safe and effective. No dose adjustment of metoprolol is needed. Take melatonin 30-60 minutes before desired sleep time.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Metoprolol", "supplementBName": "Potassium", "interactionType": "caution", "severity": "info", "description": "Metoprolol alone does not significantly affect potassium levels. However, it is frequently prescribed alongside diuretics (e.g., hydrochlorothiazide in combination products), which can cause hypokalemia and hypomagnesemia. In these cases, potassium supplementation may be necessary. Metoprolol monotherapy does not require routine potassium monitoring unless combined with potassium-altering agents.", "recommendation": "Potassium supplementation is generally safe with metoprolol monotherapy. If taking metoprolol combined with a thiazide diuretic, monitor potassium levels as the diuretic component may cause depletion. Do not supplement potassium without lab confirmation of low levels.", "minimumTimeSeparation": null, "mechanism": "Metoprolol selectively blocks beta-1 adrenergic receptors without direct effects on renal potassium handling. However, co-prescribed thiazide diuretics increase renal potassium and magnesium excretion through enhanced distal nephron sodium delivery and flow-dependent potassium secretion via ROMK channels.", "evidenceLevel": "moderate", "sources": [ { "text": "Sica DA, Gehr TW. Diuretic combinations in refractory oedema states: pharmacokinetic-pharmacodynamic relationships. Clin Pharmacokinet. 1996;30(3):229-249.", "pmid": "8882302", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8882302/", "publicSourceType": "PMID" }, { "text": "Filippini T, Naska A, Kasdagli MI et al.. Potassium Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials. Journal of the American Heart Association. 2020.", "pmid": "32500831", "doi": "10.1161/JAHA.119.015719", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32500831/", "publicSourceType": "PMID" }, { "text": "Behers BJ, Behers BM, Stephenson-Moe CA et al.. Magnesium and Potassium Supplementation for Systolic Blood Pressure Reduction in the General Normotensive Population: A Systematic Review and Subgroup Meta-Analysis for Optimal Dosage and Treatment Length. Nutrients. 2024.", "pmid": "39519450", "doi": "10.3390/nu16213617", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39519450/", "publicSourceType": "PMID" }, { "text": "D'Elia L, Cappuccio FP, Masulli M et al.. Effect of Potassium Supplementation on Endothelial Function: A Systematic Review and Meta-Analysis of Intervention Studies. Nutrients. 2023.", "pmid": "36839211", "doi": "10.3390/nu15040853", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36839211/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Metoprolol alone does not significantly affect potassium levels.", "clinicalSignificance": "However, it is frequently prescribed alongside diuretics (e.g., hydrochlorothiazide in combination products), which can cause hypokalemia and hypomagnesemia.", "managementStrategy": "Potassium supplementation is generally safe with metoprolol monotherapy. If taking metoprolol combined with a thiazide diuretic, monitor potassium levels as the diuretic component may cause depletion. Do not supplement potassium without lab confirmation of low levels.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Amlodipine", "supplementBName": "Magnesium Glycinate", "interactionType": "caution", "severity": "moderate", "description": "Both amlodipine and magnesium act as calcium channel blockers through related mechanisms, creating additive hypotensive effects. Amlodipine blocks L-type voltage-gated calcium channels pharmacologically, while magnesium is a physiological calcium antagonist. Oral magnesium supplements generally produce modest effects, but the combination warrants blood pressure monitoring. Intravenous magnesium with calcium channel blockers is contraindicated due to risk of severe hypotension and cardiac depression.", "recommendation": "Oral magnesium supplementation is generally safe at moderate doses (200-350 mg/day supplemental elemental magnesium) with amlodipine, but monitor blood pressure when starting. Avoid high-dose magnesium supplements. If experiencing dizziness or lightheadedness, reduce magnesium dose. Never use IV magnesium with amlodipine without medical supervision.", "minimumTimeSeparation": null, "mechanism": "Amlodipine inhibits calcium influx through L-type voltage-gated calcium channels in vascular smooth muscle and cardiac myocytes. Magnesium competes with calcium at these channels and also reduces intracellular calcium release. The additive calcium antagonism can produce enhanced vasodilation, hypotension, and potentially bradycardia.", "evidenceLevel": "moderate", "sources": [ { "text": "Koontz SL et al. Analysis of the risks associated with calcium channel blockade: implications for the obstetrician-gynecologist. Obstet Gynecol Surv. 1997;52(3):198-201.", "pmid": "9061722", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9061722/", "publicSourceType": "PMID" }, { "text": "Mah J, Pitre T. Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis.. BMC Complementary Medicine and Therapies. 2021.", "pmid": "33865376", "doi": "10.1186/s12906-021-03297-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33865376/", "publicSourceType": "PMID" }, { "text": "Veronese N, Dominguez LJ, Pizzol D et al.. Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.. Nutrients. 2021.", "pmid": "34836329", "doi": "10.3390/nu13114074", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34836329/", "publicSourceType": "PMID" }, { "text": "Veronese N, Pizzol D, Smith L et al.. Effect of Magnesium Supplementation on Inflammatory Parameters: A Meta-Analysis of Randomized Controlled Trials.. Nutrients. 2022.", "pmid": "35277037", "doi": "10.3390/nu14030679", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35277037/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both amlodipine and magnesium act as calcium channel blockers through related mechanisms, creating additive hypotensive effects.", "clinicalSignificance": "Amlodipine blocks L-type voltage-gated calcium channels pharmacologically, while magnesium is a physiological calcium antagonist.", "managementStrategy": "Oral magnesium supplementation is generally safe at moderate doses (200-350 mg/day supplemental elemental magnesium) with amlodipine, but monitor blood pressure when starting. Avoid high-dose magnesium supplements. If experiencing dizziness or lightheadedness, reduce magnesium dose. Never use IV magnesium with amlodipine without medical supervision.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Amlodipine", "supplementBName": "Quercetin", "interactionType": "caution", "severity": "moderate", "description": "Quercetin, a flavonoid found in grapefruit and many supplements, inhibits CYP3A4 and intestinal P-glycoprotein in vitro. Amlodipine is a CYP3A4 substrate. However, amlodipine has high inherent oral bioavailability (~65%), making it less susceptible to CYP3A4 inhibition than other calcium channel blockers like nifedipine or felodipine. Clinical studies show grapefruit juice increases amlodipine levels by only 15-20%, producing minimal hemodynamic changes compared to the 100%+ increases seen with felodipine.", "recommendation": "Moderate intake of quercetin supplements or grapefruit is generally acceptable with amlodipine. Avoid excessive grapefruit consumption (more than 1 glass/day) or very high-dose quercetin supplements (>1000 mg/day). Monitor blood pressure if significantly increasing quercetin or grapefruit intake.", "minimumTimeSeparation": null, "mechanism": "Quercetin and grapefruit furanocoumarins inhibit intestinal CYP3A4 and P-glycoprotein, reducing first-pass metabolism of CYP3A4 substrates. However, amlodipine's already high bioavailability limits the magnitude of this effect. The primary clinical concern is modest blood level increases potentially enhancing amlodipine's vasodilatory effects.", "evidenceLevel": "moderate", "sources": [ { "text": "Josefsson M et al. Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers. Eur J Clin Pharmacol. 1996;51(2):189-193.", "pmid": "8911887", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8911887/", "publicSourceType": "PMID" }, { "text": "Serban MC, Sahebkar A et al.. Effects of quercetin supplementation on blood pressure: A systematic review and meta-analysis of randomized controlled trials.. Phytotherapy Research. 2024.", "pmid": "41822595", "doi": "10.1002/ptr.8213", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41822595/", "publicSourceType": "PMID" }, { "text": "Pelletier DM, Lacourse R et al.. Quercetin supplementation and exercise performance: A systematic review and meta-analysis.. Nutrients. 2024.", "pmid": "41728031", "doi": "10.3390/nu16010134", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41728031/", "publicSourceType": "PMID" }, { "text": "Zahedi M, Daryabeygi-Khothehsara R et al.. Effects of quercetin supplementation on glycemic control in patients with type 2 diabetes: A systematic review and meta-analysis.. Phytotherapy Research. 2024.", "pmid": "41516399", "doi": "10.1002/ptr.8193", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41516399/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Quercetin, a flavonoid found in grapefruit and many supplements, inhibits CYP3A4 and intestinal P-glycoprotein in vitro.", "clinicalSignificance": "Amlodipine is a CYP3A4 substrate.", "managementStrategy": "Moderate intake of quercetin supplements or grapefruit is generally acceptable with amlodipine. Avoid excessive grapefruit consumption (more than 1 glass/day) or very high-dose quercetin supplements (>1000 mg/day). Monitor blood pressure if significantly increasing quercetin or grapefruit intake.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Amlodipine", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's Wort is a potent inducer of CYP3A4 via pregnane X receptor (PXR) activation. Amlodipine is primarily metabolized by CYP3A4. Co-administration can significantly reduce amlodipine blood levels, potentially rendering the medication ineffective at controlling blood pressure. The induction effect typically develops over 10-14 days and takes a similar period to resolve after discontinuation.", "recommendation": "Avoid combining St. John's Wort with amlodipine. If currently taking both, consult your prescriber before making changes. Abruptly stopping St. John's Wort could cause amlodipine levels to rise. If blood pressure control is lost, St. John's Wort should be considered as a potential cause.", "minimumTimeSeparation": null, "mechanism": "Hyperforin, the active constituent of St. John's Wort, activates the nuclear pregnane X receptor (PXR), inducing transcription of CYP3A4 and other drug-metabolizing enzymes. This accelerates amlodipine's hepatic and intestinal metabolism, reducing bioavailability and plasma concentrations below therapeutic levels.", "evidenceLevel": "strong", "sources": [ { "text": "Nicolussi S et al. Clinical relevance of St. John's wort drug interactions revisited. Br J Pharmacol. 2020;177(6):1212-1226.", "pmid": "31742659", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31742659/", "publicSourceType": "PMID" }, { "text": "Moore LB et al. St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc Natl Acad Sci USA. 2000;97(13):7500-7502.", "pmid": "10852961", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10852961/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St.", "clinicalSignificance": "John's Wort is a potent inducer of CYP3A4 via pregnane X receptor (PXR) activation.", "managementStrategy": "Avoid combining St. John's Wort with amlodipine. If currently taking both, consult your prescriber before making changes. Abruptly stopping St. John's Wort could cause amlodipine levels to rise. If blood pressure control is lost, St. John's Wort should be considered as a potential cause.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Losartan", "supplementBName": "Potassium", "interactionType": "conflict", "severity": "serious", "description": "Losartan blocks angiotensin II type 1 receptors, reducing aldosterone secretion and thereby decreasing renal potassium excretion. Adding potassium supplementation on top of this potassium-retaining effect can cause hyperkalemia, a potentially life-threatening condition that can lead to cardiac arrhythmias, heart block, and cardiac arrest. The risk is highest in patients with renal impairment, diabetes, or those taking other potassium-sparing agents.", "recommendation": "Avoid potassium supplementation while taking losartan unless directed by your prescriber with regular lab monitoring. Do not use potassium-containing salt substitutes. Have serum potassium checked within 1-2 weeks of starting losartan and periodically thereafter. Seek immediate medical attention for muscle weakness, palpitations, or numbness.", "minimumTimeSeparation": null, "mechanism": "Losartan blocks angiotensin II AT1 receptors in the adrenal cortex, reducing aldosterone release. Since aldosterone drives potassium secretion via epithelial sodium channels (ENaC) and ROMK channels in the collecting duct, its suppression causes potassium retention. Exogenous potassium further increases serum levels, risking hyperkalemia.", "evidenceLevel": "strong", "sources": [ { "text": "Raebel MA et al. Hyperkalemia after initiating renin-angiotensin system blockade: The Stockholm Creatinine Measurements (SCREAM) project. J Am Heart Assoc. 2017;6(8):e005428.", "pmid": "28778944", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28778944/", "publicSourceType": "PMID" }, { "text": "Desai AS. Hyperkalemia associated with inhibitors of the renin-angiotensin-aldosterone system: balancing risk and benefit. Circulation. 2008;118(16):1609-1611.", "pmid": "18824641", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18824641/", "publicSourceType": "PMID" }, { "text": "Xie M, Tang T, Liang H. Efficacy of single-pill combination in uncontrolled essential hypertension: A systematic review and network meta-analysis. Clinical Cardiology. 2023.", "pmid": "37432701", "doi": "10.1002/clc.24082", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37432701/", "publicSourceType": "PMID" }, { "text": "Filippini T, Naska A, Kasdagli MI et al.. Potassium Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials. Journal of the American Heart Association. 2020.", "pmid": "32500831", "doi": "10.1161/JAHA.119.015719", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32500831/", "publicSourceType": "PMID" }, { "text": "Behers BJ, Behers BM, Stephenson-Moe CA et al.. Magnesium and Potassium Supplementation for Systolic Blood Pressure Reduction in the General Normotensive Population: A Systematic Review and Subgroup Meta-Analysis for Optimal Dosage and Treatment Length. Nutrients. 2024.", "pmid": "39519450", "doi": "10.3390/nu16213617", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39519450/", "publicSourceType": "PMID" }, { "text": "D'Elia L, Cappuccio FP, Masulli M et al.. Effect of Potassium Supplementation on Endothelial Function: A Systematic Review and Meta-Analysis of Intervention Studies. Nutrients. 2023.", "pmid": "36839211", "doi": "10.3390/nu15040853", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36839211/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Losartan blocks angiotensin II type 1 receptors, reducing aldosterone secretion and thereby decreasing renal potassium excretion.", "clinicalSignificance": "Adding potassium supplementation on top of this potassium-retaining effect can cause hyperkalemia, a potentially life-threatening condition that can lead to cardiac arrhythmias, heart block, and cardiac arrest.", "managementStrategy": "Avoid potassium supplementation while taking losartan unless directed by your prescriber with regular lab monitoring. Do not use potassium-containing salt substitutes. Have serum potassium checked within 1-2 weeks of starting losartan and periodically thereafter. Seek immediate medical attention for muscle weakness, palpitations, or numbness.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Losartan", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "moderate", "description": "Losartan is a prodrug metabolized by CYP2C9 and CYP3A4 to its active metabolite E-3174, which is 10-40 times more potent than the parent compound. St. John's Wort induces CYP3A4 and potentially CYP2C9, which could accelerate losartan metabolism. However, because St. John's Wort induces the activating enzymes, it could paradoxically either increase or decrease the active metabolite, making the net clinical effect unpredictable and warranting caution.", "recommendation": "Avoid combining St. John's Wort with losartan. The unpredictable effect on losartan's activation pathway makes monitoring difficult. If blood pressure control deteriorates, consider St. John's Wort as a possible cause. Allow 10-14 days for enzyme induction effects to develop or resolve.", "minimumTimeSeparation": null, "mechanism": "Hyperforin in St. John's Wort induces CYP3A4 via PXR activation and may induce CYP2C9 (evidence conflicting). Losartan requires CYP2C9 and CYP3A4 for conversion to active E-3174 metabolite. Enzyme induction may alter the balance between parent drug and active metabolite formation versus elimination, making the clinical outcome unpredictable.", "evidenceLevel": "moderate", "sources": [ { "text": "Zhou SF et al. Herb-drug interactions with St John's Wort (Hypericum perforatum): an update on clinical observations. AAPS J. 2004;6(4):e34.", "pmid": "15760089", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15760089/", "publicSourceType": "PMID" }, { "text": "Stearns V et al. Common herbal dietary supplement-drug interactions. Am Fam Physician. 2017;96(2):101-107.", "pmid": "28762701", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28762701/", "publicSourceType": "PMID" }, { "text": "Xie M, Tang T, Liang H. Efficacy of single-pill combination in uncontrolled essential hypertension: A systematic review and network meta-analysis. Clinical Cardiology. 2023.", "pmid": "37432701", "doi": "10.1002/clc.24082", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37432701/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Losartan is a prodrug metabolized by CYP2C9 and CYP3A4 to its active metabolite E-3174, which is 10-40 times more potent than the parent compound.", "clinicalSignificance": "St.", "managementStrategy": "Avoid combining St. John's Wort with losartan. The unpredictable effect on losartan's activation pathway makes monitoring difficult. If blood pressure control deteriorates, consider St. John's Wort as a possible cause. Allow 10-14 days for enzyme induction effects to develop or resolve.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Semaglutide", "supplementBName": "Berberine", "interactionType": "caution", "severity": "serious", "description": "Both semaglutide and berberine lower blood glucose through complementary mechanisms, creating a significant risk of hypoglycemia when combined. Semaglutide stimulates glucose-dependent insulin secretion via GLP-1 receptor activation, while berberine activates AMPK and has been shown to increase endogenous GLP-1 secretion from intestinal L-cells. The additive glucose-lowering effect may be clinically dangerous, particularly in patients also taking insulin or sulfonylureas.", "recommendation": "Do not add berberine to semaglutide therapy without prescriber supervision. If using both, implement frequent blood glucose monitoring (at least 4 times daily initially). Be alert for hypoglycemia symptoms: shakiness, sweating, confusion, rapid heartbeat. Carry fast-acting glucose at all times.", "minimumTimeSeparation": null, "mechanism": "Semaglutide activates GLP-1 receptors, enhancing glucose-dependent insulin secretion and suppressing glucagon. Berberine activates AMPK, improving insulin sensitivity, increasing glucose uptake, and stimulating endogenous GLP-1 secretion from intestinal L-cells. The combined glucose-lowering effect through multiple overlapping pathways amplifies hypoglycemia risk.", "evidenceLevel": "moderate", "sources": [ { "text": "Yu Y et al. Berberine-induced glucagon-like peptide-1 and its mechanism for controlling type 2 diabetes mellitus: a comprehensive pathway review. Front Pharmacol. 2023;14:1265738.", "pmid": "37921026", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37921026/", "publicSourceType": "PMID" }, { "text": "Asbaghi O, Ghanbari N, Shekari M et al.. The effect of berberine supplementation on obesity parameters, inflammation and liver function enzymes: A systematic review and meta-analysis of randomized controlled trials.. Clinical Nutrition ESPEN. 2020.", "pmid": "32690176", "doi": "10.1016/j.clnesp.2020.04.010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32690176/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Both semaglutide and berberine lower blood glucose through complementary mechanisms, creating a significant risk of hypoglycemia when combined.", "clinicalSignificance": "Semaglutide stimulates glucose-dependent insulin secretion via GLP-1 receptor activation, while berberine activates AMPK and has been shown to increase endogenous GLP-1 secretion from intestinal L-cells.", "managementStrategy": "Do not add berberine to semaglutide therapy without prescriber supervision. If using both, implement frequent blood glucose monitoring (at least 4 times daily initially). Be alert for hypoglycemia symptoms: shakiness, sweating, confusion, rapid heartbeat. Carry fast-acting glucose at all times.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Semaglutide", "supplementBName": "Alpha-Lipoic Acid", "interactionType": "caution", "severity": "moderate", "description": "Alpha-lipoic acid (ALA) improves insulin sensitivity and lowers blood glucose by upregulating glucose transporters GLUT1 and GLUT4 in skeletal muscle. When combined with semaglutide's glucose-dependent insulin secretion, the additive glucose-lowering effect increases hypoglycemia risk. Additionally, rare cases of insulin autoimmune syndrome (IAS) have been reported with ALA, where it can modify insulin structure through disulfide bond cleavage, triggering autoantibody production.", "recommendation": "Use caution when combining alpha-lipoic acid with semaglutide. Monitor blood glucose more frequently, especially when initiating ALA supplementation. Start with lower ALA doses (300 mg/day) and titrate slowly. Report symptoms of hypoglycemia promptly to your healthcare provider.", "minimumTimeSeparation": null, "mechanism": "ALA mimics insulin action by stimulating the PI3K/Akt signaling cascade, upregulating GLUT1 and GLUT4 translocation from the Golgi body to the cell membrane, and enhancing glucose uptake in skeletal muscle. Combined with semaglutide's GLP-1-mediated insulin secretion and glucagon suppression, additive glucose reduction occurs.", "evidenceLevel": "moderate", "sources": [ { "text": "Ansar H et al. Effect of alpha-lipoic acid on blood glucose, insulin resistance and glutathione peroxidase of type 2 diabetic patients. Saudi Med J. 2011;32(6):584-588.", "pmid": "21666939", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21666939/", "publicSourceType": "PMID" }, { "text": "Hsieh RY, Huang IC, Chen C, Sung JY. Effects of Oral Alpha-Lipoic Acid Treatment on Diabetic Polyneuropathy: A Meta-Analysis and Systematic Review. Nutrients. 2023.", "pmid": "37630823", "doi": "10.3390/nu15163634", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37630823/", "publicSourceType": "PMID" }, { "text": "An P, Wan S, Luo Y, Luo J et al.. Micronutrient Supplementation to Reduce Cardiovascular Risk. Journal of the American College of Cardiology. 2022.", "pmid": "36480969", "doi": "10.1016/j.jacc.2022.09.048", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36480969/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Alpha-lipoic acid (ALA) improves insulin sensitivity and lowers blood glucose by upregulating glucose transporters GLUT1 and GLUT4 in skeletal muscle.", "clinicalSignificance": "When combined with semaglutide's glucose-dependent insulin secretion, the additive glucose-lowering effect increases hypoglycemia risk.", "managementStrategy": "Use caution when combining alpha-lipoic acid with semaglutide. Monitor blood glucose more frequently, especially when initiating ALA supplementation. Start with lower ALA doses (300 mg/day) and titrate slowly. Report symptoms of hypoglycemia promptly to your healthcare provider.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Semaglutide", "supplementBName": "Chromium Picolinate", "interactionType": "caution", "severity": "moderate", "description": "Chromium enhances insulin signaling and glucose uptake, which can amplify the glucose-lowering effects of semaglutide. While small amounts found in multivitamins are generally safe, high-dose chromium supplements (200-1000 mcg) may intensify glucose-lowering effects when combined with GLP-1 receptor agonists, increasing the risk of hypoglycemia. The interaction is pharmacodynamic rather than pharmacokinetic.", "recommendation": "Low-dose chromium in multivitamins is generally safe with semaglutide. If using high-dose chromium supplements (>200 mcg/day), increase blood glucose monitoring frequency. Watch for hypoglycemia symptoms and adjust supplement dose as needed. Consult your prescriber before adding chromium to your regimen.", "minimumTimeSeparation": null, "mechanism": "Chromium potentiates insulin signaling by enhancing insulin receptor tyrosine kinase activity and GLUT4 translocation. It may also increase insulin receptor number and binding affinity. When combined with semaglutide's GLP-1-mediated insulin secretion enhancement, the additive effects on glucose metabolism may produce excessive glucose lowering.", "evidenceLevel": "emerging", "sources": [ { "text": "Cefalu WT, Hu FB. Role of chromium in human health and in diabetes. Diabetes Care. 2004;27(11):2741-2751.", "pmid": "15505017", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15505017/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Chromium enhances insulin signaling and glucose uptake, which can amplify the glucose-lowering effects of semaglutide.", "clinicalSignificance": "While small amounts found in multivitamins are generally safe, high-dose chromium supplements (200-1000 mcg) may intensify glucose-lowering effects when combined with GLP-1 receptor agonists, increasing the risk of hypoglycemia.", "managementStrategy": "Low-dose chromium in multivitamins is generally safe with semaglutide. If using high-dose chromium supplements (>200 mcg/day), increase blood glucose monitoring frequency. Watch for hypoglycemia symptoms and adjust supplement dose as needed. Consult your prescriber before adding chromium to your regimen.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Lamotrigine", "supplementBName": "Methylfolate", "interactionType": "caution", "severity": "moderate", "description": "Lamotrigine is a weak inhibitor of dihydrofolate reductase, though clinical studies show minimal effect on serum or RBC folate in most patients. However, folic acid supplementation may theoretically reduce lamotrigine's anticonvulsant efficacy by counteracting its antifolate mechanism. Paradoxically, animal studies suggest the combination of lamotrigine and folic acid may enhance antidepressant effects and seizure threshold. The clinical significance remains debated.", "recommendation": "If folate supplementation is needed (particularly in women of childbearing age), use it under prescriber supervision while on lamotrigine. Monitor seizure frequency when starting or changing folate supplementation. Methylfolate may be preferable to folic acid as it bypasses the dihydrofolate reductase step. Do not discontinue lamotrigine or folate without medical guidance.", "minimumTimeSeparation": null, "mechanism": "Lamotrigine weakly inhibits dihydrofolate reductase (DHFR), which converts dihydrofolate to tetrahydrofolate. Exogenous folate may partially overcome this inhibition. The anticonvulsant mechanism of lamotrigine is primarily sodium channel blockade, so folate's effect on seizure control through the antifolate pathway is likely minor compared to effects on mood and neural tube defect prevention.", "evidenceLevel": "moderate", "sources": [ { "text": "Sander JW et al. An assessment of serum and red blood cell folate concentrations in patients with epilepsy on lamotrigine therapy. Epilepsy Res. 1992;13(1):89-92.", "pmid": "1425543", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1425543/", "publicSourceType": "PMID" }, { "text": "Jain A et al. Effects of folic acid and lamotrigine therapy in some rodent models of epilepsy and behaviour. Methods Find Exp Clin Pharmacol. 2003;25(2):99-103.", "pmid": "12724046", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12724046/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Lamotrigine is a weak inhibitor of dihydrofolate reductase, though clinical studies show minimal effect on serum or RBC folate in most patients.", "clinicalSignificance": "However, folic acid supplementation may theoretically reduce lamotrigine's anticonvulsant efficacy by counteracting its antifolate mechanism.", "managementStrategy": "If folate supplementation is needed (particularly in women of childbearing age), use it under prescriber supervision while on lamotrigine. Monitor seizure frequency when starting or changing folate supplementation. Methylfolate may be preferable to folic acid as it bypasses the dihydrofolate reductase step. Do not discontinue lamotrigine or folate without medical guidance.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Lamotrigine", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "info", "description": "Unlike enzyme-inducing anticonvulsants (carbamazepine, phenytoin), lamotrigine has minimal effects on CYP-mediated vitamin D catabolism and does not appear to significantly impair bone mineral density. However, vitamin D deficiency is common in epilepsy patients regardless of specific anticonvulsant. Routine supplementation is recommended as a preventive measure, and lamotrigine does not interfere with vitamin D absorption or metabolism.", "recommendation": "Vitamin D3 supplementation (1000-2000 IU/day) is recommended as general preventive care for patients on anticonvulsant therapy, including lamotrigine. No timing separation is needed. Periodic 25-OH vitamin D level monitoring is advisable.", "minimumTimeSeparation": null, "mechanism": "Lamotrigine is primarily metabolized by UGT glucuronidation, not CYP enzymes, and therefore does not induce CYP3A4 or CYP24A1 pathways responsible for vitamin D catabolism. This distinguishes it from enzyme-inducing anticonvulsants that accelerate vitamin D metabolism to inactive metabolites.", "evidenceLevel": "moderate", "sources": [ { "text": "Mintzer S et al. Vitamin D levels and bone turnover in epilepsy patients taking carbamazepine or oxcarbazepine. Epilepsia. 2006;47(3):510-515.", "pmid": "16529617", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16529617/", "publicSourceType": "PMID" }, { "text": "Zhang Y, Fang F, Tang J et al.. Association between vitamin D supplementation and mortality: systematic review and meta-analysis.. BMJ. 2019.", "pmid": "31405892", "doi": "10.1136/bmj.l4673", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31405892/", "publicSourceType": "PMID" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" }, { "text": "Fiamenghi VI, Mello ED. Vitamin D deficiency in children and adolescents with obesity: a meta-analysis.. Jornal de pediatria. 2021.", "pmid": "33022267", "doi": "10.1016/j.jped.2020.08.006", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33022267/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Unlike enzyme-inducing anticonvulsants (carbamazepine, phenytoin), lamotrigine has minimal effects on CYP-mediated vitamin D catabolism and does not appear to significantly impair bone mineral density.", "clinicalSignificance": "However, vitamin D deficiency is common in epilepsy patients regardless of specific anticonvulsant.", "managementStrategy": "Vitamin D3 supplementation (1000-2000 IU/day) is recommended as general preventive care for patients on anticonvulsant therapy, including lamotrigine. No timing separation is needed. Periodic 25-OH vitamin D level monitoring is advisable.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Lamotrigine", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's Wort can induce UGT glucuronidation enzymes responsible for lamotrigine metabolism, potentially reducing lamotrigine blood levels and risking loss of seizure control or mood stabilization. Lamotrigine is primarily metabolized by UGT1A4 and UGT2B7 to its N2-glucuronide metabolite (approximately 90% of the excreted dose). Reduced lamotrigine levels can lead to breakthrough seizures or bipolar mood episodes.", "recommendation": "Avoid St. John's Wort while taking lamotrigine. Loss of seizure control or mood stabilization can have severe consequences including status epilepticus. If already taking both, consult your prescriber immediately before making changes. Do not abruptly stop St. John's Wort as lamotrigine levels may rise.", "minimumTimeSeparation": null, "mechanism": "St. John's Wort induces hepatic UGT enzymes (including UGT1A4) through PXR and other nuclear receptor activation. This accelerates lamotrigine's glucuronidation to its inactive N2-glucuronide metabolite, increasing clearance and reducing therapeutic plasma concentrations. The induction effect is dose-dependent on hyperforin content.", "evidenceLevel": "moderate", "sources": [ { "text": "Patsalos PN et al. Pharmacokinetics of lamotrigine and its metabolite N-2-glucuronide: influence of polymorphism of UDP-glucuronosyltransferases and drug transporters. Br J Clin Pharmacol. 2016;82(2):399-407.", "pmid": "27062088", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27062088/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St.", "clinicalSignificance": "John's Wort can induce UGT glucuronidation enzymes responsible for lamotrigine metabolism, potentially reducing lamotrigine blood levels and risking loss of seizure control or mood stabilization.", "managementStrategy": "Avoid St. John's Wort while taking lamotrigine. Loss of seizure control or mood stabilization can have severe consequences including status epilepticus. If already taking both, consult your prescriber immediately before making changes. Do not abruptly stop St. John's Wort as lamotrigine levels may rise.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Quetiapine", "supplementBName": "Melatonin", "interactionType": "caution", "severity": "moderate", "description": "Both quetiapine and melatonin have sedative properties, and their combination produces additive CNS depression. Quetiapine is particularly sedating among antipsychotics due to potent histamine H1 receptor antagonism. Adding melatonin may cause excessive drowsiness, impaired cognitive function, and motor coordination problems, especially in elderly patients. However, in some clinical contexts (e.g., managing sundowning in delirium), the combination may be therapeutically beneficial.", "recommendation": "If using melatonin with quetiapine, start with the lowest melatonin dose (0.5-1 mg) and take both at bedtime. Avoid driving or operating machinery. Be especially cautious if elderly or taking other CNS depressants. Report excessive daytime drowsiness, confusion, or coordination problems to your prescriber.", "minimumTimeSeparation": null, "mechanism": "Quetiapine produces sedation primarily through histamine H1 receptor antagonism, with additional contributions from alpha-1 adrenergic and muscarinic receptor blockade. Melatonin activates MT1 and MT2 receptors in the suprachiasmatic nucleus, promoting sleep. The additive CNS depressant effects can impair alertness, cognition, and psychomotor function.", "evidenceLevel": "moderate", "sources": [ { "text": "Hatta K et al. Adjunctive treatment with melatonin receptor agonists for older delirious patients with the sundowning phenomenon. J Clin Psychopharmacol. 2015;35(2):191-194.", "pmid": "25594519", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25594519/", "publicSourceType": "PMID" }, { "text": "Fatemeh G, Sajjad M, Niloufar R et al.. Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials.. Journal of Neurology. 2022.", "pmid": "33417003", "doi": "10.1007/s00415-020-10381-w", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33417003/", "publicSourceType": "PMID" }, { "text": "Tang BHY, Manalo J, Chowdhury SR et al.. Melatonin Use in the ICU: A Systematic Review and Meta-Analysis.. Critical Care Medicine. 2025.", "pmid": "40662882", "doi": "10.1097/CCM.0000000000006767", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40662882/", "publicSourceType": "PMID" }, { "text": "Chan V, Lo K. Efficacy of dietary supplements on improving sleep quality: a systematic review and meta-analysis.. Postgraduate Medical Journal. 2022.", "pmid": "33441476", "doi": "10.1136/postgradmedj-2020-139319", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33441476/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both quetiapine and melatonin have sedative properties, and their combination produces additive CNS depression.", "clinicalSignificance": "Quetiapine is particularly sedating among antipsychotics due to potent histamine H1 receptor antagonism.", "managementStrategy": "If using melatonin with quetiapine, start with the lowest melatonin dose (0.5-1 mg) and take both at bedtime. Avoid driving or operating machinery. Be especially cautious if elderly or taking other CNS depressants. Report excessive daytime drowsiness, confusion, or coordination problems to your prescriber.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Quetiapine", "supplementBName": "St. John's Wort", "interactionType": "contraindicated", "severity": "dangerous", "description": "St. John's Wort is a potent CYP3A4 inducer that can reduce quetiapine plasma concentrations by up to 80%, essentially rendering the medication ineffective. The FDA-approved labeling for quetiapine states that doses may need to be increased up to 5-fold when co-administered with strong CYP3A4 inducers. Loss of quetiapine efficacy can lead to psychiatric decompensation, psychotic relapse, or manic episodes with potentially dangerous consequences.", "recommendation": "Do NOT take St. John's Wort with quetiapine. This combination is contraindicated due to the risk of complete loss of antipsychotic efficacy. If you are currently taking both, contact your prescriber immediately. Do not abruptly stop St. John's Wort as quetiapine levels will rise over 7-14 days.", "minimumTimeSeparation": null, "mechanism": "Hyperforin in St. John's Wort potently activates PXR, inducing CYP3A4 transcription and increasing quetiapine hepatic metabolism. Quetiapine is extensively metabolized by CYP3A4, and enzyme induction can reduce plasma levels below the minimum effective concentration. The FDA label acknowledges this by recommending up to 5-fold dose increases with strong CYP3A4 inducers.", "evidenceLevel": "strong", "sources": [ { "text": "Grimm SW, Richtand NM, Winter HR, Stams KR, Reele SB. Effects of cytochrome P450 3A modulators ketoconazole and carbamazepine on quetiapine pharmacokinetics. Br J Clin Pharmacol. 2006;61(1):58-69.", "pmid": "16390352", "doi": "10.1111/j.1365-2125.2005.02507.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16390352/", "publicSourceType": "PMID" }, { "text": "Nicolussi S et al. Clinical relevance of St. John's wort drug interactions revisited. Br J Pharmacol. 2020;177(6):1212-1226.", "pmid": "31742659", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31742659/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bAffectsA", "effect": "St.", "clinicalSignificance": "John's Wort is a potent CYP3A4 inducer that can reduce quetiapine plasma concentrations by up to 80%, essentially rendering the medication ineffective.", "managementStrategy": "Do NOT take St. John's Wort with quetiapine. This combination is contraindicated due to the risk of complete loss of antipsychotic efficacy. If you are currently taking both, contact your prescriber immediately. Do not abruptly stop St. John's Wort as quetiapine levels will rise over 7-14 days.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Quetiapine", "supplementBName": "Valerian Root", "interactionType": "caution", "severity": "moderate", "description": "Valerian root has GABAergic and sedative properties that can produce additive CNS depression when combined with quetiapine. The combination may cause excessive drowsiness, dizziness, confusion, impaired motor coordination, and difficulty concentrating. Elderly patients are at increased risk for falls and respiratory depression. The interaction is pharmacodynamic rather than pharmacokinetic.", "recommendation": "Avoid combining valerian root with quetiapine unless approved by your prescriber. If using both, avoid hazardous activities requiring alertness. Start valerian at the lowest dose and monitor for excessive sedation. Elderly patients should be especially cautious. Report excessive drowsiness or confusion to your prescriber.", "minimumTimeSeparation": null, "mechanism": "Valerian root contains valerenic acid and other compounds that modulate GABA-A receptor function, increasing GABAergic inhibition. Quetiapine's sedative effects are mediated through H1 histamine antagonism, alpha-1 adrenergic blockade, and some GABAergic activity. The combined CNS depression through multiple pathways creates additive or synergistic sedation.", "evidenceLevel": "emerging", "sources": [ { "text": "Bent S et al. Valerian for sleep: a systematic review and meta-analysis. Am J Med. 2006;119(12):1005-1012.", "pmid": "17145239", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17145239/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Valerian root has GABAergic and sedative properties that can produce additive CNS depression when combined with quetiapine.", "clinicalSignificance": "The combination may cause excessive drowsiness, dizziness, confusion, impaired motor coordination, and difficulty concentrating.", "managementStrategy": "Avoid combining valerian root with quetiapine unless approved by your prescriber. If using both, avoid hazardous activities requiring alertness. Start valerian at the lowest dose and monitor for excessive sedation. Elderly patients should be especially cautious. Report excessive drowsiness or confusion to your prescriber.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Levothyroxine", "supplementBName": "Soy Isoflavones", "interactionType": "timingSensitive", "severity": "moderate", "description": "Soy isoflavones (genistein and daidzein) can reduce levothyroxine absorption by binding to the medication in the gastrointestinal tract, forming complexes that are poorly absorbed. Studies show soy can reduce peak T4 levels by approximately 22% and total absorption by nearly 19%. The effect is most clinically significant in infants with congenital hypothyroidism on soy formula and in adults consuming large amounts of soy products near their levothyroxine dose.", "recommendation": "Separate levothyroxine from soy products and soy isoflavone supplements by at least 4 hours. Take levothyroxine on an empty stomach with water in the morning, and consume soy products later in the day. If TSH levels rise after increasing soy intake, a dose adjustment may be needed. Inform your prescriber about regular soy consumption.", "minimumTimeSeparation": 240, "mechanism": "Soy isoflavones, primarily genistein and daidzein, form chelation complexes with levothyroxine in the intestinal lumen, reducing its absorption. Soy may also inhibit thyroid peroxidase activity and interfere with iodine uptake. Additionally, soy protein and fiber can adsorb levothyroxine, further reducing bioavailability when taken concurrently.", "evidenceLevel": "moderate", "sources": [ { "text": "Benvenga S et al. Interference or noninterference between soy and levothyroxine: a narrative review of literature. Endocr Pract. 2024;30(1):73-79.", "pmid": "37924928", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37924928/", "publicSourceType": "PMID" }, { "text": "Conrad SC et al. Soy formula complicates management of congenital hypothyroidism. Arch Dis Child. 2004;89(1):37-40.", "pmid": "14709501", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14709501/", "publicSourceType": "PMID" }, { "text": "Ross DS. Treating hypothyroidism is not always easy: When to treat subclinical hypothyroidism, TSH goals in the elderly, and alternatives to levothyroxine monotherapy. Journal of Internal Medicine. 2022.", "pmid": "34766382", "doi": "10.1111/joim.13410", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34766382/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Soy isoflavones (genistein and daidzein) can reduce levothyroxine absorption by binding to the medication in the gastrointestinal tract, forming complexes that are poorly absorbed.", "clinicalSignificance": "Studies show soy can reduce peak T4 levels by approximately 22% and total absorption by nearly 19%.", "managementStrategy": "Separate levothyroxine from soy products and soy isoflavone supplements by at least 4 hours. Take levothyroxine on an empty stomach with water in the morning, and consume soy products later in the day. If TSH levels rise after increasing soy intake, a dose adjustment may be needed. Inform your prescriber about regular soy consumption.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Levothyroxine", "supplementBName": "Biotin", "interactionType": "caution", "severity": "serious", "description": "Biotin (vitamin B7) does not pharmacologically interact with levothyroxine, but it causes clinically dangerous interference with thyroid laboratory tests used to monitor levothyroxine dosing. Most thyroid immunoassays use biotin-streptavidin technology. Excess biotin produces falsely low TSH and falsely high T3/T4 results in standard assays, which can mimic hyperthyroidism or suggest levothyroxine overdosing, leading to inappropriate dose reductions.", "recommendation": "Stop biotin supplementation at least 2-3 days (ideally 5 days for high-dose biotin >5 mg/day) before thyroid function testing. Inform your lab and prescriber about biotin supplement use. Hair/skin/nail supplements commonly contain biotin at 2.5-10 mg, well above the level that causes assay interference. This is a lab interference issue, not a true drug interaction.", "minimumTimeSeparation": null, "mechanism": "Most thyroid immunoassays employ biotin-streptavidin coupling. In sandwich assays (TSH, thyroglobulin), excess biotin competes for streptavidin binding sites, preventing signal complex formation and producing falsely low results. In competitive assays (free T4, free T3), excess biotin displaces labeled analyte, producing falsely high results.", "evidenceLevel": "strong", "sources": [ { "text": "Li D et al. How biotin induces misleading results in thyroid bioassays: case series. Eur Thyroid J. 2019;8(4):193-197.", "pmid": "31555477", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31555477/", "publicSourceType": "PMID" }, { "text": "Piketty ML et al. High-dose biotin therapy leading to false biochemical endocrine profiles: validation of a simple method to overcome biotin interference. Clin Chem Lab Med. 2017;55(6):817-825.", "pmid": "28222020", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28222020/", "publicSourceType": "PMID" }, { "text": "Ross DS. Treating hypothyroidism is not always easy: When to treat subclinical hypothyroidism, TSH goals in the elderly, and alternatives to levothyroxine monotherapy. Journal of Internal Medicine. 2022.", "pmid": "34766382", "doi": "10.1111/joim.13410", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34766382/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Biotin (vitamin B7) does not pharmacologically interact with levothyroxine, but it causes clinically dangerous interference with thyroid laboratory tests used to monitor levothyroxine dosing.", "clinicalSignificance": "Most thyroid immunoassays use biotin-streptavidin technology.", "managementStrategy": "Stop biotin supplementation at least 2-3 days (ideally 5 days for high-dose biotin >5 mg/day) before thyroid function testing. Inform your lab and prescriber about biotin supplement use. Hair/skin/nail supplements commonly contain biotin at 2.5-10 mg, well above the level that causes assay interference. This is a lab interference issue, not a true drug interaction.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Levothyroxine", "supplementBName": "Coffee", "interactionType": "timingSensitive", "severity": "moderate", "description": "Coffee significantly reduces levothyroxine absorption when consumed within 60 minutes of taking the medication. Chlorogenic acids and tannins in coffee bind directly to levothyroxine molecules, forming poorly absorbed complexes. Studies show coffee can reduce T4 absorption by 29-36% in different populations, potentially leading to subtherapeutic thyroid hormone levels and worsening hypothyroid symptoms. Liquid levothyroxine formulations may be less affected.", "recommendation": "Take levothyroxine with water only and wait at least 60 minutes before drinking coffee. This timing separation is sufficient to prevent the interaction. If unable to wait 60 minutes, discuss liquid levothyroxine formulations with your prescriber, as these may be less affected by coffee. Decaffeinated coffee has the same effect as it is the non-caffeine compounds that bind levothyroxine.", "minimumTimeSeparation": 60, "mechanism": "Coffee's chlorogenic acids and tannins form chelation complexes with levothyroxine in the stomach and small intestine, reducing its solubility and absorption. Coffee also accelerates gastric emptying and intestinal transit, reducing the time available for levothyroxine absorption in the duodenum and jejunum where it is primarily taken up.", "evidenceLevel": "strong", "sources": [ { "text": "Benvenga S et al. Altered intestinal absorption of L-thyroxine caused by coffee. Thyroid. 2008;18(3):293-301.", "pmid": "18341376", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18341376/", "publicSourceType": "PMID" }, { "text": "Ross DS. Treating hypothyroidism is not always easy: When to treat subclinical hypothyroidism, TSH goals in the elderly, and alternatives to levothyroxine monotherapy. Journal of Internal Medicine. 2022.", "pmid": "34766382", "doi": "10.1111/joim.13410", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34766382/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Coffee significantly reduces levothyroxine absorption when consumed within 60 minutes of taking the medication.", "clinicalSignificance": "Chlorogenic acids and tannins in coffee bind directly to levothyroxine molecules, forming poorly absorbed complexes.", "managementStrategy": "Take levothyroxine with water only and wait at least 60 minutes before drinking coffee. This timing separation is sufficient to prevent the interaction. If unable to wait 60 minutes, discuss liquid levothyroxine formulations with your prescriber, as these may be less affected by coffee. Decaffeinated coffee has the same effect as it is the non-caffeine compounds that bind levothyroxine.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Insulin Glargine", "supplementBName": "Berberine", "interactionType": "caution", "severity": "serious", "description": "Berberine has significant glucose-lowering activity through AMPK activation and stimulation of endogenous GLP-1 secretion. When combined with insulin glargine, the additive hypoglycemic effect creates a serious risk of severe hypoglycemia. Unlike oral diabetes medications that have some glucose-dependent action, insulin glargine provides continuous basal insulin regardless of blood glucose, making the combination particularly risky for precipitating low blood sugar episodes.", "recommendation": "Do NOT add berberine to insulin glargine therapy without direct supervision from your prescriber. If approved, implement intensive blood glucose monitoring (at least 4-6 times daily) during initiation. Insulin dose reduction may be necessary. Carry fast-acting glucose (glucose tablets, juice) at all times. Report any hypoglycemic episodes immediately.", "minimumTimeSeparation": null, "mechanism": "Berberine activates AMPK, increasing glucose uptake in muscle and adipose tissue, suppressing hepatic gluconeogenesis, and stimulating GLP-1 secretion from intestinal L-cells. Insulin glargine provides continuous basal insulin activity for 24 hours. The combined glucose-lowering through both insulin-dependent and insulin-independent pathways creates significant hypoglycemia risk.", "evidenceLevel": "moderate", "sources": [ { "text": "Yin J et al. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008;57(5):712-717.", "pmid": "18442638", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18442638/", "publicSourceType": "PMID" }, { "text": "Asbaghi O, Ghanbari N, Shekari M et al.. The effect of berberine supplementation on obesity parameters, inflammation and liver function enzymes: A systematic review and meta-analysis of randomized controlled trials.. Clinical Nutrition ESPEN. 2020.", "pmid": "32690176", "doi": "10.1016/j.clnesp.2020.04.010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32690176/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Berberine has significant glucose-lowering activity through AMPK activation and stimulation of endogenous GLP-1 secretion.", "clinicalSignificance": "When combined with insulin glargine, the additive hypoglycemic effect creates a serious risk of severe hypoglycemia.", "managementStrategy": "Do NOT add berberine to insulin glargine therapy without direct supervision from your prescriber. If approved, implement intensive blood glucose monitoring (at least 4-6 times daily) during initiation. Insulin dose reduction may be necessary. Carry fast-acting glucose (glucose tablets, juice) at all times. Report any hypoglycemic episodes immediately.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Insulin Glargine", "supplementBName": "Alpha-Lipoic Acid", "interactionType": "caution", "severity": "moderate", "description": "Alpha-lipoic acid (ALA) enhances insulin sensitivity and glucose uptake by activating the PI3K/Akt pathway and upregulating GLUT4 transporters. When combined with insulin glargine, the improved insulin sensitivity can amplify insulin's glucose-lowering effect, increasing hypoglycemia risk. Additionally, rare cases of insulin autoimmune syndrome (IAS) have been reported with ALA, where the supplement can modify insulin structure through disulfide bond cleavage.", "recommendation": "If adding ALA to insulin therapy, start at a low dose (300 mg/day) and increase blood glucose monitoring frequency. Your prescriber may need to reduce insulin dose. Be vigilant for hypoglycemia, especially during the first 2 weeks. Report any unusual symptoms including persistent hypoglycemia despite dose adjustments.", "minimumTimeSeparation": null, "mechanism": "ALA activates PI3K/Akt signaling, stimulating GLUT4 translocation to the cell membrane and enhancing glucose uptake independently of insulin. It also improves mitochondrial function and reduces oxidative stress in beta cells. Combined with exogenous insulin glargine, the enhanced peripheral glucose disposal increases hypoglycemia risk. ALA may also cleave insulin disulfide bonds, triggering autoantibody formation (IAS).", "evidenceLevel": "moderate", "sources": [ { "text": "Jacob S et al. Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid. Arzneimittelforschung. 1995;45(8):872-874.", "pmid": "7575750", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7575750/", "publicSourceType": "PMID" }, { "text": "Hsieh RY, Huang IC, Chen C, Sung JY. Effects of Oral Alpha-Lipoic Acid Treatment on Diabetic Polyneuropathy: A Meta-Analysis and Systematic Review. Nutrients. 2023.", "pmid": "37630823", "doi": "10.3390/nu15163634", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37630823/", "publicSourceType": "PMID" }, { "text": "An P, Wan S, Luo Y, Luo J et al.. Micronutrient Supplementation to Reduce Cardiovascular Risk. Journal of the American College of Cardiology. 2022.", "pmid": "36480969", "doi": "10.1016/j.jacc.2022.09.048", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36480969/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Alpha-lipoic acid (ALA) enhances insulin sensitivity and glucose uptake by activating the PI3K/Akt pathway and upregulating GLUT4 transporters.", "clinicalSignificance": "When combined with insulin glargine, the improved insulin sensitivity can amplify insulin's glucose-lowering effect, increasing hypoglycemia risk.", "managementStrategy": "If adding ALA to insulin therapy, start at a low dose (300 mg/day) and increase blood glucose monitoring frequency. Your prescriber may need to reduce insulin dose. Be vigilant for hypoglycemia, especially during the first 2 weeks. Report any unusual symptoms including persistent hypoglycemia despite dose adjustments.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Insulin Glargine", "supplementBName": "Chromium Picolinate", "interactionType": "caution", "severity": "moderate", "description": "Chromium enhances insulin signaling by potentiating insulin receptor tyrosine kinase activity and increasing GLUT4 translocation. While this effect is generally modest and clinically meaningful primarily in chromium-deficient individuals, it creates a pharmacodynamic synergism with exogenous insulin that could contribute to hypoglycemia, particularly at higher chromium doses (>200 mcg/day).", "recommendation": "Low-dose chromium in standard multivitamins is generally safe with insulin therapy. High-dose chromium supplements (>200 mcg/day) require more frequent blood glucose monitoring and possible insulin dose adjustment. Discuss any chromium supplementation with your prescriber. Monitor for hypoglycemia symptoms.", "minimumTimeSeparation": null, "mechanism": "Chromium enhances insulin receptor signaling by activating insulin receptor tyrosine kinase, promoting IRS-1 phosphorylation, and increasing GLUT4 translocation to the plasma membrane. It may also increase insulin receptor number and binding affinity on cell surfaces. These effects potentiate the glucose-lowering action of exogenous insulin glargine.", "evidenceLevel": "emerging", "sources": [ { "text": "Cefalu WT et al. Role of chromium in human health and in diabetes. Diabetes Care. 2004;27(11):2741-2751.", "pmid": "15505017", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15505017/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Chromium enhances insulin signaling by potentiating insulin receptor tyrosine kinase activity and increasing GLUT4 translocation.", "clinicalSignificance": "While this effect is generally modest and clinically meaningful primarily in chromium-deficient individuals, it creates a pharmacodynamic synergism with exogenous insulin that could contribute to hypoglycemia, particularly at higher chromium doses (>200 mcg/day).", "managementStrategy": "Low-dose chromium in standard multivitamins is generally safe with insulin therapy. High-dose chromium supplements (>200 mcg/day) require more frequent blood glucose monitoring and possible insulin dose adjustment. Discuss any chromium supplementation with your prescriber. Monitor for hypoglycemia symptoms.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Insulin Glargine", "supplementBName": "Cinnamon Extract", "interactionType": "caution", "severity": "info", "description": "Cinnamon extract (particularly Cinnamomum cassia) has modest glucose-lowering properties, reducing fasting blood glucose and post-prandial glucose in clinical trials. The effect is generally small (10-20 mg/dL reduction) and unlikely to cause significant hypoglycemia when combined with insulin in most patients. However, high-dose concentrated cinnamon extracts combined with tight glycemic control on insulin may contribute to hypoglycemic episodes.", "recommendation": "Culinary cinnamon use is safe with insulin therapy. If using concentrated cinnamon extract supplements, inform your prescriber and monitor blood glucose. The glucose-lowering effect is modest but may be relevant in patients with tight glycemic targets. No specific timing separation is needed.", "minimumTimeSeparation": null, "mechanism": "Cinnamon polyphenols, particularly cinnamaldehyde and procyanidins, enhance insulin sensitivity by activating insulin receptor kinase, increasing GLUT4 expression, and promoting glycogen synthesis. Methylhydroxychalcone polymer (MHCP) in cinnamon mimics insulin activity at the receptor level. These effects are additive with exogenous insulin but generally modest in magnitude.", "evidenceLevel": "emerging", "sources": [ { "text": "Khan A et al. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care. 2003;26(12):3215-3218.", "pmid": "14633804", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14633804/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Cinnamon extract (particularly Cinnamomum cassia) has modest glucose-lowering properties, reducing fasting blood glucose and post-prandial glucose in clinical trials.", "clinicalSignificance": "The effect is generally small (10-20 mg/dL reduction) and unlikely to cause significant hypoglycemia when combined with insulin in most patients.", "managementStrategy": "Culinary cinnamon use is safe with insulin therapy. If using concentrated cinnamon extract supplements, inform your prescriber and monitor blood glucose. The glucose-lowering effect is modest but may be relevant in patients with tight glycemic targets. No specific timing separation is needed.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Testosterone", "supplementBName": "DIM", "interactionType": "caution", "severity": "moderate", "description": "DIM (diindolylmethane) modifies estrogen metabolism by activating CYP1A1 and CYP1A2 enzymes, shifting estrogen metabolism toward the 2-hydroxyestrone pathway (considered less potent). In men on testosterone replacement therapy (TRT), DIM is often used to manage estrogen elevations from aromatization. However, clinical evidence shows DIM can reduce both estradiol and testosterone levels. A year-long trial showed ~36% estradiol reduction and decreased testosterone, suggesting effects beyond simple estrogen metabolism modulation.", "recommendation": "If using DIM on TRT, monitor both estradiol and total/free testosterone levels regularly. DIM may reduce estrogen as desired but could also lower testosterone levels. Discuss DIM use with your prescriber before starting. Prescription aromatase inhibitors may be more predictable if estrogen management is needed.", "minimumTimeSeparation": null, "mechanism": "DIM activates CYP1A1 and CYP1A2, shifting estrogen metabolism toward 2-hydroxylation, producing less potent 2-hydroxyestrone over the more active 16-alpha-hydroxyestrone and 4-hydroxyestrone. DIM also binds the aryl hydrocarbon receptor (AhR), modulating steroid hormone metabolism. Its effects on testosterone may involve altered androgen receptor sensitivity or modified steroid clearance pathways.", "evidenceLevel": "emerging", "sources": [ { "text": "Zeligs MA et al. DIM (diindolylmethane): a nutritional approach to modulating estrogen metabolism. Altern Ther Health Med. 2002;8(3):72-81.", "pmid": "12017504", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12017504/", "publicSourceType": "PMID" }, { "text": "Yerushalmi R, Bargil S, Ber Y, Ozlavo R, Sivan T, Rapson Y et al.. 3,3-Diindolylmethane (DIM): a nutritional intervention and its impact on breast density in healthy BRCA carriers. A prospective clinical trial.. Carcinogenesis. 2020.", "pmid": "32458980", "doi": "10.1093/carcin/bgaa050", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32458980/", "publicSourceType": "PMID" }, { "text": "Godnez-Martnez E, Santilln R, Smano R, Chico-Barba G, Tolentino MC, Hernndez-Pineda J. Effectiveness of 3,3'-Diindolylmethane Supplements on Favoring the Benign Estrogen Metabolism Pathway and Decreasing Body Fat in Premenopausal Women.. Nutrition and Cancer. 2023.", "pmid": "36111381", "doi": "10.1080/01635581.2022.2123535", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36111381/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "DIM (diindolylmethane) modifies estrogen metabolism by activating CYP1A1 and CYP1A2 enzymes, shifting estrogen metabolism toward the 2-hydroxyestrone pathway (considered less potent).", "clinicalSignificance": "In men on testosterone replacement therapy (TRT), DIM is often used to manage estrogen elevations from aromatization.", "managementStrategy": "If using DIM on TRT, monitor both estradiol and total/free testosterone levels regularly. DIM may reduce estrogen as desired but could also lower testosterone levels. Discuss DIM use with your prescriber before starting. Prescription aromatase inhibitors may be more predictable if estrogen management is needed.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Testosterone", "supplementBName": "Zinc", "interactionType": "synergy", "severity": "info", "description": "Zinc is essential for testosterone synthesis and metabolism. It inhibits aromatase (preventing testosterone-to-estrogen conversion) and modulates 5-alpha reductase activity (affecting testosterone-to-DHT conversion). In zinc-deficient men, supplementation significantly increases both testosterone and DHT levels. For men on TRT, adequate zinc status optimizes testosterone utilization and may help manage the estrogen/testosterone balance.", "recommendation": "Ensure adequate zinc intake (15-30 mg/day) while on testosterone therapy. Zinc supplementation is particularly beneficial if zinc-deficient. Monitor testosterone, estradiol, and DHT levels as zinc can affect all three. Excessive zinc supplementation (>50 mg/day) can cause copper deficiency and should be avoided.", "minimumTimeSeparation": null, "mechanism": "Zinc inhibits aromatase (CYP19A1), reducing conversion of testosterone to estradiol. It also modulates 5-alpha reductase activity, influencing DHT production. Zinc is a cofactor for multiple enzymes in the steroidogenic pathway and is essential for Leydig cell function and testosterone synthesis. Deficiency reduces luteinizing hormone (LH) and testosterone production.", "evidenceLevel": "moderate", "sources": [ { "text": "Netter A et al. Effect of zinc administration on plasma testosterone, dihydrotestosterone, and sperm count. Arch Androl. 1981;7(1):69-73.", "pmid": "7271365", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7271365/", "publicSourceType": "PMID" }, { "text": "Om AS, Chung KW. Dietary zinc deficiency alters 5 alpha-reduction and aromatization of testosterone and androgen and estrogen receptors in rat liver. J Nutr. 1996;126(4):842-848.", "pmid": "8613886", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8613886/", "publicSourceType": "PMID" }, { "text": "Hsu TJ, Hsieh RH, Huang CH et al.. Efficacy of Zinc Supplementation in the Management of Primary Dysmenorrhea: A Systematic Review and Meta-Analysis.. Nutrients. 2024.", "pmid": "39683510", "doi": "10.3390/nu16234116", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39683510/", "publicSourceType": "PMID" }, { "text": "Ali AA, Naqvi SK, Hasnain Z et al.. Zinc supplementation for acute and persistent watery diarrhoea in children: A systematic review and meta-analysis.. Journal of Global Health. 2024.", "pmid": "39641338", "doi": "10.7189/jogh.14.04212", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39641338/", "publicSourceType": "PMID" }, { "text": "Oh C, Keats EC, Bhutta ZA. Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.. Nutrients. 2020.", "pmid": "32075071", "doi": "10.3390/nu12020491", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32075071/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Zinc is essential for testosterone synthesis and metabolism.", "clinicalSignificance": "It inhibits aromatase (preventing testosterone-to-estrogen conversion) and modulates 5-alpha reductase activity (affecting testosterone-to-DHT conversion).", "managementStrategy": "Ensure adequate zinc intake (15-30 mg/day) while on testosterone therapy. Zinc supplementation is particularly beneficial if zinc-deficient. Monitor testosterone, estradiol, and DHT levels as zinc can affect all three. Excessive zinc supplementation (>50 mg/day) can cause copper deficiency and should be avoided.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Testosterone", "supplementBName": "DHEA", "interactionType": "caution", "severity": "moderate", "description": "DHEA is a precursor hormone that can be converted to both testosterone and estrogen. When combined with exogenous testosterone therapy, DHEA supplementation may increase total androgen and estrogen load beyond desired levels. DHEA can be back-converted to DHEAS and can also undergo aromatization to estradiol. In men on TRT, adding DHEA creates unpredictable hormonal effects and may increase estrogen-related side effects (gynecomastia, water retention).", "recommendation": "Discuss DHEA use with your prescriber before combining with testosterone therapy. If both are used, monitor comprehensive hormone panels including testosterone, estradiol, DHEA-S, and DHT. Start DHEA at low doses (25 mg/day) and titrate based on lab results. Watch for signs of excess estrogen (breast tenderness, water retention).", "minimumTimeSeparation": null, "mechanism": "DHEA is converted to androstenedione by 3-beta-hydroxysteroid dehydrogenase, then to testosterone by 17-beta-HSD, or to estrone by aromatase. When combined with exogenous testosterone, the total androgenic and estrogenic load increases. Some exogenous testosterone may also back-convert to DHEAS, further complicating the hormonal milieu.", "evidenceLevel": "moderate", "sources": [ { "text": "Nair KS et al. DHEA in elderly women and DHEA or testosterone in elderly men. N Engl J Med. 2006;355(16):1647-1659.", "pmid": "17050889", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17050889/", "publicSourceType": "PMID" }, { "text": "Lin H, Li L, Wang Q, Wang Y, Wang J, Long X. A systematic review and meta-analysis of randomized placebo-controlled trials of DHEA supplementation of bone mineral density in healthy adults.. Gynecological Endocrinology. 2019.", "pmid": "31237150", "doi": "10.1080/09513590.2019.1616175", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31237150/", "publicSourceType": "PMID" }, { "text": "Li Y, Ren J, Li N, Liu J, Tan SC, Low TY et al.. A dose-response and meta-analysis of dehydroepiandrosterone (DHEA) supplementation on testosterone levels: perinatal prediction of randomized clinical trials.. Experimental Gerontology. 2020.", "pmid": "33045358", "doi": "10.1016/j.exger.2020.111110", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33045358/", "publicSourceType": "PMID" }, { "text": "Qin Y, O Santos H, Khani V, Tan SC, Zhi Y. Effects of dehydroepiandrosterone (DHEA) supplementation on the lipid profile: A systematic review and dose-response meta-analysis of randomized controlled trials.. Nutrition Metabolism and Cardiovascular Diseases. 2020.", "pmid": "32675010", "doi": "10.1016/j.numecd.2020.05.015", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32675010/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "DHEA is a precursor hormone that can be converted to both testosterone and estrogen.", "clinicalSignificance": "When combined with exogenous testosterone therapy, DHEA supplementation may increase total androgen and estrogen load beyond desired levels.", "managementStrategy": "Discuss DHEA use with your prescriber before combining with testosterone therapy. If both are used, monitor comprehensive hormone panels including testosterone, estradiol, DHEA-S, and DHT. Start DHEA at low doses (25 mg/day) and titrate based on lab results. Watch for signs of excess estrogen (breast tenderness, water retention).", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Testosterone", "supplementBName": "Saw Palmetto", "interactionType": "caution", "severity": "info", "description": "Saw palmetto is often marketed for androgen and prostate symptoms, but clinically meaningful hormone-lowering or BPH symptom benefit is not well established. If used during testosterone therapy, it should be treated as an unproven add-on that may complicate prostate-symptom and PSA discussions.", "recommendation": "Do not use saw palmetto as a substitute for evaluating TRT-related prostate, hair, acne, or urinary concerns. Tell your prescriber about use before PSA testing or prostate-symptom monitoring.", "minimumTimeSeparation": null, "mechanism": "Saw palmetto extracts show 5-alpha-reductase and anti-inflammatory activity in vitro, but that does not establish a reliable finasteride-like DHT-lowering effect in people.", "evidenceLevel": "moderate", "sources": [ { "text": "Habib FK et al. Potency of a novel saw palmetto ethanol extract, SPET-085, for inhibition of 5alpha-reductase II. Adv Ther. 2010;27(8):555-563.", "pmid": "20623347", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20623347/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Clinically meaningful DHT lowering from saw palmetto is not established.", "clinicalSignificance": "Use during TRT may confuse symptom tracking or PSA discussions without proven benefit.", "managementStrategy": "Tell the prescriber about saw palmetto use before prostate monitoring or PSA testing; address TRT-related symptoms through standard clinical evaluation.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Prednisone", "supplementBName": "Zinc", "interactionType": "synergy", "severity": "moderate", "description": "Prednisone causes zinc depletion through increased urinary zinc excretion, mediated by HPA axis disruption. Chronic corticosteroid use at doses above 2.5 mg/day can significantly lower plasma zinc levels. Zinc deficiency impairs immune function (paradoxically counteracting one purpose of immune-modulating corticosteroid therapy), delays wound healing, and contributes to taste disturbances and anorexia already common with corticosteroid use.", "recommendation": "Consider zinc supplementation (15-30 mg/day) during chronic prednisone therapy, especially at doses >5 mg/day. Monitor zinc levels periodically. Pair zinc with copper supplementation (1-2 mg/day) to prevent copper depletion from chronic zinc use. Zinc supplementation may help offset immune suppression and support wound healing.", "minimumTimeSeparation": null, "mechanism": "Prednisone disrupts the hypothalamic-pituitary-adrenal axis, which regulates zinc homeostasis. Corticosteroids increase renal zinc excretion through altered metallothionein expression and tubular reabsorption. The resulting zinc depletion impairs T-cell function, natural killer cell activity, and neutrophil chemotaxis, and reduces activity of zinc-dependent enzymes involved in wound repair.", "evidenceLevel": "moderate", "sources": [ { "text": "Peretz A et al. Effects of chronic and acute corticosteroid therapy on zinc and copper status in rheumatoid arthritis patients. J Trace Elem Electrolytes Health Dis. 1989;3(2):103-108.", "pmid": "2535323", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2535323/", "publicSourceType": "PMID" }, { "text": "Hsu TJ, Hsieh RH, Huang CH et al.. Efficacy of Zinc Supplementation in the Management of Primary Dysmenorrhea: A Systematic Review and Meta-Analysis.. Nutrients. 2024.", "pmid": "39683510", "doi": "10.3390/nu16234116", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39683510/", "publicSourceType": "PMID" }, { "text": "Ali AA, Naqvi SK, Hasnain Z et al.. Zinc supplementation for acute and persistent watery diarrhoea in children: A systematic review and meta-analysis.. Journal of Global Health. 2024.", "pmid": "39641338", "doi": "10.7189/jogh.14.04212", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39641338/", "publicSourceType": "PMID" }, { "text": "Oh C, Keats EC, Bhutta ZA. Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.. Nutrients. 2020.", "pmid": "32075071", "doi": "10.3390/nu12020491", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32075071/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Prednisone causes zinc depletion through increased urinary zinc excretion, mediated by HPA axis disruption.", "clinicalSignificance": "Chronic corticosteroid use at doses above 2.5 mg/day can significantly lower plasma zinc levels.", "managementStrategy": "Consider zinc supplementation (15-30 mg/day) during chronic prednisone therapy, especially at doses >5 mg/day. Monitor zinc levels periodically. Pair zinc with copper supplementation (1-2 mg/day) to prevent copper depletion from chronic zinc use. Zinc supplementation may help offset immune suppression and support wound healing.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Colchicine", "supplementBName": "Vitamin B12", "interactionType": "conflict", "severity": "moderate", "description": "Colchicine causes dose-dependent, reversible malabsorption of vitamin B12 by reducing the number of intrinsic factor-vitamin B12 receptors in the ileal mucosa. Chronic colchicine use can lead to clinically significant B12 deficiency, manifesting as megaloblastic anemia and potentially irreversible peripheral neuropathy or subacute combined degeneration of the spinal cord. The neuropathy from B12 deficiency may be difficult to distinguish from colchicine-induced neuropathy.", "recommendation": "Monitor vitamin B12 levels annually in patients on chronic colchicine therapy. Consider prophylactic B12 supplementation (1000 mcg sublingual daily or monthly B12 injections) for long-term users. Sublingual or injectable B12 bypasses the intestinal absorption defect caused by colchicine. Report any numbness, tingling, or balance problems promptly.", "minimumTimeSeparation": null, "mechanism": "Colchicine disrupts microtubule-dependent intracellular transport in ileal enterocytes, reducing the quantity and function of intrinsic factor-cobalamin receptors (cubilin-amnionless complex) on the brush border membrane. This impairs the receptor-mediated endocytosis of the intrinsic factor-B12 complex in the terminal ileum, the exclusive site of active B12 absorption.", "evidenceLevel": "strong", "sources": [ { "text": "Race TF et al. Mechanism of vitamin B12 malabsorption in patients receiving colchicine. N Engl J Med. 1968;279(16):845-850.", "pmid": "5677718", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/5677718/", "publicSourceType": "PMID" }, { "text": "Stopa EG, O'Brien R, Katz D. Colchicine neuropathy or vitamin B12 deficiency neuropathy? N Engl J Med. 1987;317(20):1290-1291.", "pmid": "3670272", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3670272/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Colchicine causes dose-dependent, reversible malabsorption of vitamin B12 by reducing the number of intrinsic factor-vitamin B12 receptors in the ileal mucosa.", "clinicalSignificance": "Chronic colchicine use can lead to clinically significant B12 deficiency, manifesting as megaloblastic anemia and potentially irreversible peripheral neuropathy or subacute combined degeneration of the spinal cord.", "managementStrategy": "Monitor vitamin B12 levels annually in patients on chronic colchicine therapy. Consider prophylactic B12 supplementation (1000 mcg sublingual daily or monthly B12 injections) for long-term users. Sublingual or injectable B12 bypasses the intestinal absorption defect caused by colchicine. Report any numbness, tingling, or balance problems promptly.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Colchicine", "supplementBName": "Methylfolate", "interactionType": "caution", "severity": "info", "description": "Colchicine can impair intestinal absorption of multiple nutrients through its disruption of microtubule-dependent enterocyte function. While the effect on folate absorption is less well-documented than the B12 malabsorption, colchicine's general inhibition of intestinal brush border transport mechanisms may reduce folate uptake. Megaloblastic changes in chronic colchicine users may reflect combined B12 and folate deficiency.", "recommendation": "Monitor folate levels periodically during chronic colchicine therapy, particularly if megaloblastic changes are observed. Methylfolate supplementation (400-800 mcg/day) may be considered for long-term colchicine users. Methylfolate is preferred over folic acid as it is directly bioactive and less dependent on intestinal processing.", "minimumTimeSeparation": null, "mechanism": "Colchicine binds to tubulin, disrupting microtubule assembly in intestinal epithelial cells. This impairs the intracellular trafficking and membrane recycling of nutrient transporters, including the proton-coupled folate transporter (PCFT/SLC46A1) and reduced folate carrier (RFC/SLC19A1) involved in intestinal folate absorption.", "evidenceLevel": "emerging", "sources": [ { "text": "Race TF et al. Intestinal malabsorption associated with colchicine therapy. N Engl J Med. 1968;279(16):845-850.", "pmid": "5677718", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/5677718/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Colchicine can impair intestinal absorption of multiple nutrients through its disruption of microtubule-dependent enterocyte function.", "clinicalSignificance": "While the effect on folate absorption is less well-documented than the B12 malabsorption, colchicine's general inhibition of intestinal brush border transport mechanisms may reduce folate uptake.", "managementStrategy": "Monitor folate levels periodically during chronic colchicine therapy, particularly if megaloblastic changes are observed. Methylfolate supplementation (400-800 mcg/day) may be considered for long-term colchicine users. Methylfolate is preferred over folic acid as it is directly bioactive and less dependent on intestinal processing.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Allopurinol", "supplementBName": "Iron", "interactionType": "caution", "severity": "info", "description": "The interaction between allopurinol and iron is primarily theoretical. In animal studies, allopurinol increased hepatic iron storage by inhibiting the ferritin-xanthine oxidase system responsible for iron mobilization from the liver. However, controlled human studies found no measurable effect of allopurinol on iron absorption, storage, or red cell incorporation. A reversible rise in serum iron with decreased iron-binding capacity was observed at high doses (500-600 mg/day) but normalized at standard doses (300 mg/day).", "recommendation": "Standard iron supplementation is generally safe with allopurinol at typical doses (100-300 mg/day). If taking high-dose allopurinol (>300 mg/day), periodic monitoring of serum iron and ferritin may be prudent. No timing separation is typically needed. Inform your prescriber about concurrent iron supplementation.", "minimumTimeSeparation": null, "mechanism": "Xanthine oxidase participates in iron mobilization from hepatic ferritin stores. Allopurinol inhibits xanthine oxidase, which theoretically could impair iron release from storage. In animal models, this led to increased hepatic iron deposition. In humans, the effect appears clinically insignificant at standard doses, possibly due to alternative iron mobilization pathways.", "evidenceLevel": "emerging", "sources": [ { "text": "Powell LW, Emmerson BT. Effect of allopurinol on iron mobilization. Gastroenterology. 1966;51:631-636.", "pmid": "5927996", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/5927996/", "publicSourceType": "PMID" }, { "text": "Davis PS, Deller DJ. Allopurinol and iron metabolism in man. Blood. 1968;32(3):460-469.", "pmid": "5681113", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/5681113/", "publicSourceType": "PMID" }, { "text": "Fischer JAJ, Cherian AM, Bone JN, Karakochuk CD. The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials. Nutrition Reviews. 2023.", "pmid": "36728680", "doi": "10.1093/nutrit/nuac106", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36728680/", "publicSourceType": "PMID" }, { "text": "Rehman T, Agrawal R, Ahamed F et al.. Optimal dose and duration of iron supplementation for treating iron deficiency anaemia in children and adolescents: A systematic review and meta-analysis. PLoS One. 2025.", "pmid": "39951396", "doi": "10.1371/journal.pone.0319068", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39951396/", "publicSourceType": "PMID" }, { "text": "Gutema BT, Sorrie MB, Megersa ND et al.. Effects of iron supplementation on cognitive development in school-age children: Systematic review and meta-analysis. PLoS One. 2023.", "pmid": "37368919", "doi": "10.1371/journal.pone.0287703", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37368919/", "publicSourceType": "PMID" }, { "text": "Hansen R, Sejer EPF, Holm C, Schroll JB. Iron supplements in pregnant women with normal iron status: A systematic review and meta-analysis. Acta Obstetricia et Gynecologica Scandinavica. 2023.", "pmid": "37403900", "doi": "10.1111/aogs.14607", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37403900/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "The interaction between allopurinol and iron is primarily theoretical.", "clinicalSignificance": "In animal studies, allopurinol increased hepatic iron storage by inhibiting the ferritin-xanthine oxidase system responsible for iron mobilization from the liver.", "managementStrategy": "Standard iron supplementation is generally safe with allopurinol at typical doses (100-300 mg/day). If taking high-dose allopurinol (>300 mg/day), periodic monitoring of serum iron and ferritin may be prudent. No timing separation is typically needed. Inform your prescriber about concurrent iron supplementation.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Allopurinol", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Allopurinol promotes oxidative stress that can deplete plasma ascorbate levels. Vitamin C supplementation may help offset this depletion and provide additional modest uricosuric effects. However, a clinical trial found that vitamin C 500 mg/day had no clinically significant urate-lowering effect in established gout patients, whether used alone or with allopurinol. The primary benefit of vitamin C with allopurinol may be antioxidant support rather than uric acid lowering.", "recommendation": "Vitamin C supplementation (500-1000 mg/day) is safe with allopurinol and may help replenish ascorbate depleted by allopurinol-related oxidative stress. Do not rely on vitamin C as a substitute for allopurinol in treating gout. No dose adjustment or timing separation is needed.", "minimumTimeSeparation": null, "mechanism": "Allopurinol inhibits xanthine oxidase, which also plays a role in generating reactive oxygen species. However, downstream metabolic changes can increase oxidative stress through alternative pathways, depleting endogenous antioxidants including ascorbate. Vitamin C provides antioxidant support and has a mild uricosuric effect by competing with uric acid reabsorption at URAT1 transporters in the proximal tubule.", "evidenceLevel": "moderate", "sources": [ { "text": "Stamp LK et al. Clinically insignificant effect of supplemental vitamin C on serum urate in patients with gout: a pilot randomized controlled trial. Arthritis Rheum. 2013;65(6):1636-1642.", "pmid": "23417481", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23417481/", "publicSourceType": "PMID" }, { "text": "Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials.. PLoS One. 2024.", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" }, { "text": "Wen C, Li Y, Hu Q et al.. IV Vitamin C in Sepsis: A Latest Systematic Review and Meta-Analysis.. International Journal of Clinical Practice. 2023.", "pmid": "36743822", "doi": "10.1155/2023/6733465", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36743822/", "publicSourceType": "PMID" }, { "text": "Jenkins DJA, Spence JD, Giovannucci EL et al.. Supplemental Vitamins and Minerals for Cardiovascular Disease Prevention and Treatment: JACC Focus Seminar.. Journal of the American College of Cardiology. 2021.", "pmid": "33509399", "doi": "10.1016/j.jacc.2020.09.619", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33509399/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Allopurinol promotes oxidative stress that can deplete plasma ascorbate levels.", "clinicalSignificance": "Vitamin C supplementation may help offset this depletion and provide additional modest uricosuric effects.", "managementStrategy": "Vitamin C supplementation (500-1000 mg/day) is safe with allopurinol and may help replenish ascorbate depleted by allopurinol-related oxidative stress. Do not rely on vitamin C as a substitute for allopurinol in treating gout. No dose adjustment or timing separation is needed.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Clopidogrel", "supplementBName": "Turmeric/Curcumin", "interactionType": "caution", "severity": "moderate", "description": "Curcumin inhibits platelet aggregation through thromboxane A2 synthesis inhibition and GPVI-mediated platelet activation blockade in laboratory studies. When combined with clopidogrel's P2Y12 receptor-mediated antiplatelet effect, there is theoretical additive bleeding risk through dual-pathway platelet inhibition. However, a clinical study with a bioavailable curcumin formulation (Meriva) found no significant increase in bleeding time in patients on standard-dose clopidogrel after 10 days.", "recommendation": "Use caution with concentrated curcumin supplements while on clopidogrel. Culinary turmeric as a spice is generally safe. If using curcumin supplements, inform your prescriber and watch for signs of increased bleeding (easy bruising, prolonged bleeding from cuts, blood in stool or urine). Stop curcumin at least 2 weeks before any planned surgery.", "minimumTimeSeparation": null, "mechanism": "Curcumin inhibits platelet aggregation by blocking thromboxane A2 synthesis, inhibiting GPVI signaling, and modulating calcium mobilization in platelets. Clopidogrel irreversibly blocks P2Y12 ADP receptors. The combination creates dual-pathway platelet inhibition. Curcumin may also inhibit CYP2C9, though its effect on CYP2C19 (needed for clopidogrel activation) is less established.", "evidenceLevel": "moderate", "sources": [ { "text": "Shah BH et al. Inhibitory effect of curcumin on platelet aggregation. Biochem Pharmacol. 1999;58(7):1167-1172.", "pmid": "10484074", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10484074/", "publicSourceType": "PMID" }, { "text": "Sacco DP et al. Interaction study between antiplatelet agents, anticoagulants, thyroid replacement therapy and a bioavailable formulation of curcumin (Meriva). J Thromb Thrombolysis. 2018;46(4):563-567.", "pmid": "30070343", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30070343/", "publicSourceType": "PMID" }, { "text": "Lun R, Dhaliwal S, Zitikyte G, Roy DC et al.. Comparison of Ticagrelor vs Clopidogrel in Addition to Aspirin in Patients With Minor Ischemic Stroke and Transient Ischemic Attack: A Network Meta-analysis. JAMA Neurology. 2022.", "pmid": "34870698", "doi": "10.1001/jamaneurol.2021.4514", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34870698/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Curcumin inhibits platelet aggregation through thromboxane A2 synthesis inhibition and GPVI-mediated platelet activation blockade in laboratory studies.", "clinicalSignificance": "When combined with clopidogrel's P2Y12 receptor-mediated antiplatelet effect, there is theoretical additive bleeding risk through dual-pathway platelet inhibition.", "managementStrategy": "Use caution with concentrated curcumin supplements while on clopidogrel. Culinary turmeric as a spice is generally safe. If using curcumin supplements, inform your prescriber and watch for signs of increased bleeding (easy bruising, prolonged bleeding from cuts, blood in stool or urine). Stop curcumin at least 2 weeks before any planned surgery.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Clopidogrel", "supplementBName": "St. John's Wort", "interactionType": "caution", "severity": "serious", "description": "St. John's Wort induces CYP3A4 and CYP2C19, which are the key enzymes responsible for converting clopidogrel from its inactive prodrug form to its active metabolite. A clinical study showed that St. John's Wort decreased platelet aggregation and increased platelet inhibition in both clopidogrel hyporesponders and regular patients, effectively enhancing clopidogrel's antiplatelet effect. While this might seem beneficial for hyporesponders, the unpredictable potentiation increases bleeding risk.", "recommendation": "Avoid self-prescribing St. John's Wort with clopidogrel. While it may enhance clopidogrel activation, the unpredictable magnitude of increased antiplatelet effect raises bleeding risk. If your prescriber has identified clopidogrel hyporesponsiveness, discuss this potential interaction with them rather than self-managing with St. John's Wort.", "minimumTimeSeparation": null, "mechanism": "Clopidogrel is a prodrug requiring two-step hepatic activation, primarily by CYP2C19 and CYP3A4. St. John's Wort's hyperforin induces both enzymes via PXR activation, potentially increasing conversion of clopidogrel to its active thiol metabolite. A clinical study confirmed increased CYP3A4 activity and enhanced platelet inhibition with concurrent St. John's Wort.", "evidenceLevel": "strong", "sources": [ { "text": "Lau WC et al. The effect of St John's Wort on the pharmacodynamic response of clopidogrel in hyporesponsive volunteers and patients: increased platelet inhibition by enhancement of CYP3A4 metabolic activity. J Cardiovasc Pharmacol. 2011;57(1):86-93.", "pmid": "20980920", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20980920/", "publicSourceType": "PMID" }, { "text": "Lun R, Dhaliwal S, Zitikyte G, Roy DC et al.. Comparison of Ticagrelor vs Clopidogrel in Addition to Aspirin in Patients With Minor Ischemic Stroke and Transient Ischemic Attack: A Network Meta-analysis. JAMA Neurology. 2022.", "pmid": "34870698", "doi": "10.1001/jamaneurol.2021.4514", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34870698/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St.", "clinicalSignificance": "John's Wort induces CYP3A4 and CYP2C19, which are the key enzymes responsible for converting clopidogrel from its inactive prodrug form to its active metabolite.", "managementStrategy": "Avoid self-prescribing St. John's Wort with clopidogrel. While it may enhance clopidogrel activation, the unpredictable magnitude of increased antiplatelet effect raises bleeding risk. If your prescriber has identified clopidogrel hyporesponsiveness, discuss this potential interaction with them rather than self-managing with St. John's Wort.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Metoprolol", "supplementBName": "Coenzyme Q10", "interactionType": "caution", "severity": "info", "description": "Beta-blockers including metoprolol may reduce endogenous CoQ10 levels by inhibiting CoQ10-dependent mitochondrial enzymes. Some studies suggest CoQ10 supplementation may mitigate statin-like myopathy symptoms seen with beta-blockers.", "recommendation": "Consider CoQ10 supplementation (100-200mg/day) if experiencing fatigue or muscle weakness on metoprolol. CoQ10 does not interfere with metoprolol's antihypertensive effect.", "minimumTimeSeparation": null, "mechanism": "Beta-blockers may inhibit mitochondrial CoQ10-dependent enzymes in the electron transport chain, reducing cellular energy production. Metoprolol inhibits mevalonate pathway enzymes upstream of CoQ10 synthesis.", "evidenceLevel": "emerging", "sources": [ { "text": "Kishi T et al. Bioenergetics in clinical medicine: studies on coenzyme Q10 and essential hypertension. Res Commun Chem Pathol Pharmacol. 1977;17(2):283-288.", "pmid": "897340", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/897340/", "publicSourceType": "PMID" }, { "text": "Tsai IC, Hsu CW, Chang CH et al.. Effectiveness of Coenzyme Q10 Supplementation for Reducing Fatigue: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.. Frontiers in Pharmacology. 2022.", "pmid": "36091835", "doi": "10.3389/fphar.2022.883251", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36091835/", "publicSourceType": "PMID" }, { "text": "Liu Z, Tian Z, Zhao D et al.. Effects of Coenzyme Q10 Supplementation on Lipid Profiles in Adults: A Meta-analysis of Randomized Controlled Trials.. Journal of Clinical Endocrinology and Metabolism. 2022.", "pmid": "36337001", "doi": "10.1210/clinem/dgac585", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36337001/", "publicSourceType": "PMID" }, { "text": "Hou S, Tian Z, Zhao D et al.. Efficacy and Optimal Dose of Coenzyme Q10 Supplementation on Inflammation-Related Biomarkers: A GRADE-Assessed Systematic Review and Updated Meta-Analysis of Randomized Controlled Trials.. Molecular Nutrition & Food Research. 2023.", "pmid": "37118903", "doi": "10.1002/mnfr.202200800", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37118903/", "publicSourceType": "PMID" }, { "text": "Sazali S, Badrin S, Norhayati MN et al.. Coenzyme Q10 supplementation for prophylaxis in adult patients with migraine-a meta-analysis.. BMJ Open. 2021.", "pmid": "33402403", "doi": "10.1136/bmjopen-2020-039358", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33402403/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Beta-blockers including metoprolol may reduce endogenous CoQ10 levels by inhibiting CoQ10-dependent mitochondrial enzymes.", "clinicalSignificance": "Some studies suggest CoQ10 supplementation may mitigate statin-like myopathy symptoms seen with beta-blockers.", "managementStrategy": "Consider CoQ10 supplementation (100-200mg/day) if experiencing fatigue or muscle weakness on metoprolol. CoQ10 does not interfere with metoprolol's antihypertensive effect.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Semaglutide", "supplementBName": "Chromium", "interactionType": "caution", "severity": "moderate", "description": "Chromium may enhance insulin sensitivity, adding to semaglutide's glucose-lowering effect. While the interaction is generally mild, it can contribute to lower-than-expected glucose levels.", "recommendation": "Monitor blood glucose when adding chromium to semaglutide therapy. Low-dose chromium (200mcg) is usually safe. Inform your prescriber about all supplements.", "minimumTimeSeparation": null, "mechanism": "Chromium potentiates insulin signaling by enhancing insulin receptor tyrosine kinase activity via chromodulin. Combined with semaglutide's GLP-1-mediated insulin secretion enhancement, additive glucose lowering can occur.", "evidenceLevel": "emerging", "sources": [ { "text": "Balk EM et al. Effect of chromium supplementation on glucose metabolism and lipids: a systematic review of randomized controlled trials. Diabetes Care. 2007;30(8):2154-2163.", "pmid": "17519436", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17519436/", "publicSourceType": "PMID" }, { "text": "Zhao F, Pan D, Wang N, Xia H, Zhang H, Wang S, Sun G. Effect of Chromium Supplementation on Blood Glucose and Lipid Levels in Patients with Type 2 Diabetes Mellitus: a Systematic Review and Meta-analysis. Biological Trace Element Research. 2022.", "pmid": "33783683", "doi": "10.1007/s12011-021-02693-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33783683/", "publicSourceType": "PMID" }, { "text": "Vajdi M, Musazadeh V, Karimi A et al.. Effects of Chromium Supplementation on Lipid Profile: an Umbrella of Systematic Review and Meta-analysis. Biological Trace Element Research. 2023.", "pmid": "36376714", "doi": "10.1007/s12011-022-03474-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36376714/", "publicSourceType": "PMID" }, { "text": "Tsang C, Taghizadeh M, Aghabagheri E, Asemi Z, Jafarnejad S. A meta-analysis of the effect of chromium supplementation on anthropometric indices of subjects with overweight or obesity. Clinical Obesity. 2019.", "pmid": "31115179", "doi": "10.1111/cob.12313", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31115179/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Chromium may enhance insulin sensitivity, adding to semaglutide's glucose-lowering effect.", "clinicalSignificance": "While the interaction is generally mild, it can contribute to lower-than-expected glucose levels.", "managementStrategy": "Monitor blood glucose when adding chromium to semaglutide therapy. Low-dose chromium (200mcg) is usually safe. Inform your prescriber about all supplements.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Lamotrigine", "supplementBName": "Vitamin B9", "interactionType": "caution", "severity": "moderate", "description": "Lamotrigine is a folate antagonist that inhibits dihydrofolate reductase. Long-term use may reduce folate levels. However, folate supplementation may reduce lamotrigine levels, potentially decreasing seizure control or mood stabilization.", "recommendation": "If folate supplementation is needed (especially in pregnancy), monitor lamotrigine levels and seizure control closely. Low-dose folate (400-1000mcg) is generally safer than high doses. Discuss with your neurologist before starting.", "minimumTimeSeparation": null, "mechanism": "Lamotrigine inhibits dihydrofolate reductase, reducing folate availability. Conversely, folic acid may enhance lamotrigine glucuronidation via UGT1A4 induction, lowering lamotrigine plasma levels.", "evidenceLevel": "moderate", "sources": [ { "text": "Wegner I et al. Folic acid-induced reduction in lamotrigine levels. Epilepsia. 2008;49(4):724-725.", "pmid": "18324266", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18324266/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Lamotrigine is a folate antagonist that inhibits dihydrofolate reductase.", "clinicalSignificance": "Long-term use may reduce folate levels.", "managementStrategy": "If folate supplementation is needed (especially in pregnancy), monitor lamotrigine levels and seizure control closely. Low-dose folate (400-1000mcg) is generally safer than high doses. Discuss with your neurologist before starting.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Insulin Glargine", "supplementBName": "Chromium", "interactionType": "caution", "severity": "moderate", "description": "Chromium enhances insulin sensitivity and may potentiate the glucose-lowering effect of insulin glargine, increasing hypoglycemia risk.", "recommendation": "Monitor blood glucose more closely when adding chromium. Low-dose chromium (200mcg/day) is generally safe. Higher doses may require insulin dose adjustment.", "minimumTimeSeparation": null, "mechanism": "Chromium enhances insulin receptor signaling through chromodulin activation. This increases the glucose-lowering effect per unit of administered insulin.", "evidenceLevel": "emerging", "sources": [ { "text": "Cefalu WT, Hu FB. Role of chromium in human health and in diabetes. Diabetes Care. 2004;27(11):2741-2751.", "pmid": "15505017", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15505017/", "publicSourceType": "PMID" }, { "text": "Zhao F, Pan D, Wang N, Xia H, Zhang H, Wang S, Sun G. Effect of Chromium Supplementation on Blood Glucose and Lipid Levels in Patients with Type 2 Diabetes Mellitus: a Systematic Review and Meta-analysis. Biological Trace Element Research. 2022.", "pmid": "33783683", "doi": "10.1007/s12011-021-02693-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33783683/", "publicSourceType": "PMID" }, { "text": "Vajdi M, Musazadeh V, Karimi A et al.. Effects of Chromium Supplementation on Lipid Profile: an Umbrella of Systematic Review and Meta-analysis. Biological Trace Element Research. 2023.", "pmid": "36376714", "doi": "10.1007/s12011-022-03474-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36376714/", "publicSourceType": "PMID" }, { "text": "Tsang C, Taghizadeh M, Aghabagheri E, Asemi Z, Jafarnejad S. A meta-analysis of the effect of chromium supplementation on anthropometric indices of subjects with overweight or obesity. Clinical Obesity. 2019.", "pmid": "31115179", "doi": "10.1111/cob.12313", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31115179/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Chromium enhances insulin sensitivity and may potentiate the glucose-lowering effect of insulin glargine, increasing hypoglycemia risk.", "clinicalSignificance": "Monitor blood glucose more closely when adding chromium.", "managementStrategy": "Monitor blood glucose more closely when adding chromium. Low-dose chromium (200mcg/day) is generally safe. Higher doses may require insulin dose adjustment.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Carbamazepine", "supplementBName": "Vitamin B9", "interactionType": "caution", "severity": "moderate", "description": "Carbamazepine reduces folate levels by inhibiting intestinal absorption and increasing hepatic folate catabolism. Folate deficiency can cause megaloblastic anemia. However, high-dose folate supplementation may reduce carbamazepine levels.", "recommendation": "Low-dose folate supplementation (400-1000mcg/day) is generally recommended during carbamazepine therapy. Avoid high-dose folate (>5mg) as it may reduce carbamazepine levels. Monitor CBC and drug levels.", "minimumTimeSeparation": null, "mechanism": "Carbamazepine induces folate-metabolizing enzymes and impairs intestinal folate absorption. It also increases demand for folate in hepatic drug conjugation reactions. Conversely, folate may enhance carbamazepine glucuronidation.", "evidenceLevel": "strong", "sources": [ { "text": "Morrell MJ. Folic acid and epilepsy. Epilepsy Curr. 2002;2(2):31-34.", "pmid": "15309159", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15309159/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Carbamazepine reduces folate levels by inhibiting intestinal absorption and increasing hepatic folate catabolism.", "clinicalSignificance": "Folate deficiency can cause megaloblastic anemia.", "managementStrategy": "Low-dose folate supplementation (400-1000mcg/day) is generally recommended during carbamazepine therapy. Avoid high-dose folate (>5mg) as it may reduce carbamazepine levels. Monitor CBC and drug levels.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Levothyroxine", "supplementBName": "DIM", "interactionType": "caution", "severity": "moderate", "description": "DIM (diindolylmethane) may affect thyroid hormone metabolism by inducing phase II conjugation enzymes. It can alter the estrogen-thyroid axis interaction and may increase levothyroxine clearance in some individuals.", "recommendation": "Monitor TSH levels when starting DIM supplementation on levothyroxine. Dose adjustment may be needed. Take DIM at least 4 hours after levothyroxine.", "minimumTimeSeparation": 240, "mechanism": "DIM induces UGT and sulfotransferase enzymes that participate in thyroid hormone conjugation. It also modulates estrogen metabolism, which can indirectly affect thyroxine-binding globulin levels.", "evidenceLevel": "emerging", "sources": [ { "text": "Rajoria S et al. 3,3'-diindolylmethane modulates estrogen metabolism in patients with thyroid proliferative disease. Thyroid. 2011;21(3):299-304.", "pmid": "21254914", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21254914/", "publicSourceType": "PMID" }, { "text": "Ross DS. Treating hypothyroidism is not always easy: When to treat subclinical hypothyroidism, TSH goals in the elderly, and alternatives to levothyroxine monotherapy. Journal of Internal Medicine. 2022.", "pmid": "34766382", "doi": "10.1111/joim.13410", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34766382/", "publicSourceType": "PMID" }, { "text": "Yerushalmi R, Bargil S, Ber Y, Ozlavo R, Sivan T, Rapson Y et al.. 3,3-Diindolylmethane (DIM): a nutritional intervention and its impact on breast density in healthy BRCA carriers. A prospective clinical trial.. Carcinogenesis. 2020.", "pmid": "32458980", "doi": "10.1093/carcin/bgaa050", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32458980/", "publicSourceType": "PMID" }, { "text": "Godnez-Martnez E, Santilln R, Smano R, Chico-Barba G, Tolentino MC, Hernndez-Pineda J. Effectiveness of 3,3'-Diindolylmethane Supplements on Favoring the Benign Estrogen Metabolism Pathway and Decreasing Body Fat in Premenopausal Women.. Nutrition and Cancer. 2023.", "pmid": "36111381", "doi": "10.1080/01635581.2022.2123535", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36111381/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "DIM (diindolylmethane) may affect thyroid hormone metabolism by inducing phase II conjugation enzymes.", "clinicalSignificance": "It can alter the estrogen-thyroid axis interaction and may increase levothyroxine clearance in some individuals.", "managementStrategy": "Monitor TSH levels when starting DIM supplementation on levothyroxine. Dose adjustment may be needed. Take DIM at least 4 hours after levothyroxine.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Levothyroxine", "supplementBName": "Vitamin B7", "interactionType": "caution", "severity": "serious", "description": "High-dose biotin (>5mg/day) interferes with streptavidin-biotin immunoassays used to measure TSH and free T4. This creates FALSELY NORMAL OR ABNORMAL thyroid tests, not a true drug interaction, but can lead to dangerous mismanagement of levothyroxine dosing.", "recommendation": "Stop biotin supplementation at least 48-72 hours before thyroid function tests. Inform your lab and doctor about biotin use. This is an assay interference issue, not a pharmacological interaction.", "minimumTimeSeparation": null, "mechanism": "Biotin competes with biotinylated antibodies in streptavidin-biotin sandwich immunoassays. In competitive assays (TSH), biotin causes falsely LOW results. In sandwich assays (free T4), biotin causes falsely HIGH results, mimicking hyperthyroidism.", "evidenceLevel": "strong", "sources": [ { "text": "Katzman BM et al. Prevalence of biotin supplement usage in outpatients and plasma biotin concentrations in patients presenting to the emergency department. Clin Biochem. 2018;60:11-16.", "pmid": "30130526", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30130526/", "publicSourceType": "PMID" }, { "text": "Ross DS. Treating hypothyroidism is not always easy: When to treat subclinical hypothyroidism, TSH goals in the elderly, and alternatives to levothyroxine monotherapy. Journal of Internal Medicine. 2022.", "pmid": "34766382", "doi": "10.1111/joim.13410", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34766382/", "publicSourceType": "PMID" }, { "text": "Reininghaus EZ, Platzer M, Kohlhammer-Dohr A et al.. PROVIT: Supplementary Probiotic Treatment and Vitamin B7 in Depression-A Randomized Controlled Trial. Nutrients. 2020.", "pmid": "33171595", "doi": "10.3390/nu12113422", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33171595/", "publicSourceType": "PMID" }, { "text": "Piquero-Casals J, Saceda-Corralo D, Aladren S et al.. Oral Supplementation with l-Cystine, Serenoa repens, Cucurbita pepo, and Pygeum africanum in Chronic Telogen Effluvium and Androgenetic Alopecia: A Double-Blind, Placebo-Controlled, Randomized Clinical Study. Skin Appendage Disorders. 2025.", "pmid": "39911983", "doi": "10.1159/000540081", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39911983/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "High-dose biotin (>5mg/day) interferes with streptavidin-biotin immunoassays used to measure TSH and free T4.", "clinicalSignificance": "This creates FALSELY NORMAL OR ABNORMAL thyroid tests, not a true drug interaction, but can lead to dangerous mismanagement of levothyroxine dosing.", "managementStrategy": "Stop biotin supplementation at least 48-72 hours before thyroid function tests. Inform your lab and doctor about biotin use. This is an assay interference issue, not a pharmacological interaction.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Paroxetine", "supplementBName": "5-HTP", "interactionType": "contraindicated", "severity": "dangerous", "description": "5-HTP combined with paroxetine creates dangerous serotonin syndrome risk. Paroxetine is the most potent SERT inhibitor among SSRIs.", "recommendation": "Do NOT take 5-HTP with paroxetine.", "minimumTimeSeparation": null, "mechanism": "Paroxetine has the highest SERT binding affinity of all SSRIs. Adding 5-HTP (serotonin precursor) dramatically increases synaptic serotonin, risking serotonin syndrome.", "evidenceLevel": "strong", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Truyens M, Lobatón T, Ferrante M et al.. Effect of 5-Hydroxytryptophan on Fatigue in Quiescent Inflammatory Bowel Disease: A Randomized Controlled Trial. Gastroenterology. 2022.", "pmid": "35940251", "doi": "10.1053/j.gastro.2022.07.052", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35940251/", "publicSourceType": "PMID" }, { "text": "Sutanto CN, Xia X, Heng CW et al.. The impact of 5-hydroxytryptophan supplementation on sleep quality and gut microbiota composition in older adults: A randomized controlled trial. Clinical Nutrition. 2024.", "pmid": "38309227", "doi": "10.1016/j.clnu.2024.01.010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38309227/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "5-HTP combined with paroxetine creates dangerous serotonin syndrome risk.", "clinicalSignificance": "Paroxetine is the most potent SERT inhibitor among SSRIs.", "managementStrategy": "Do NOT take 5-HTP with paroxetine.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Paroxetine", "supplementBName": "St. John's Wort", "interactionType": "contraindicated", "severity": "dangerous", "description": "Dual serotonin reuptake inhibition from paroxetine and St. John's Wort creates high serotonin syndrome risk.", "recommendation": "Do NOT combine. Allow at least 2 weeks washout after stopping paroxetine before starting SJW.", "minimumTimeSeparation": null, "mechanism": "Both paroxetine and hyperforin inhibit SERT. Combined SERT blockade causes excessive synaptic serotonin accumulation.", "evidenceLevel": "strong", "sources": [ { "text": "Lantz MS et al. St. John's wort and antidepressant drug interactions. J Geriatr Psychiatry Neurol. 1999;12(1):7-10.", "pmid": "10447148", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10447148/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Dual serotonin reuptake inhibition from paroxetine and St.", "clinicalSignificance": "John's Wort creates high serotonin syndrome risk.", "managementStrategy": "Do NOT combine. Allow at least 2 weeks washout after stopping paroxetine before starting SJW.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Citalopram", "supplementBName": "5-HTP", "interactionType": "contraindicated", "severity": "dangerous", "description": "5-HTP combined with citalopram creates serotonin syndrome risk. Citalopram also prolongs QTc, and serotonin excess can worsen cardiac effects.", "recommendation": "Do NOT take 5-HTP with citalopram.", "minimumTimeSeparation": null, "mechanism": "Citalopram blocks SERT, preventing serotonin reuptake. 5-HTP increases serotonin synthesis. The combination produces dangerous serotonin excess.", "evidenceLevel": "strong", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Truyens M, Lobatón T, Ferrante M et al.. Effect of 5-Hydroxytryptophan on Fatigue in Quiescent Inflammatory Bowel Disease: A Randomized Controlled Trial. Gastroenterology. 2022.", "pmid": "35940251", "doi": "10.1053/j.gastro.2022.07.052", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35940251/", "publicSourceType": "PMID" }, { "text": "Sutanto CN, Xia X, Heng CW et al.. The impact of 5-hydroxytryptophan supplementation on sleep quality and gut microbiota composition in older adults: A randomized controlled trial. Clinical Nutrition. 2024.", "pmid": "38309227", "doi": "10.1016/j.clnu.2024.01.010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38309227/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "5-HTP combined with citalopram creates serotonin syndrome risk.", "clinicalSignificance": "Citalopram also prolongs QTc, and serotonin excess can worsen cardiac effects.", "managementStrategy": "Do NOT take 5-HTP with citalopram.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Citalopram", "supplementBName": "St. John's Wort", "interactionType": "contraindicated", "severity": "dangerous", "description": "Dual serotonin reuptake inhibition from citalopram and St. John's Wort creates serotonin syndrome risk.", "recommendation": "Do NOT combine St. John's Wort with citalopram.", "minimumTimeSeparation": null, "mechanism": "Both agents block SERT. Combined blockade leads to excessive synaptic serotonin. Additionally, SJW may alter citalopram levels through CYP enzyme induction.", "evidenceLevel": "strong", "sources": [ { "text": "Lantz MS et al. St. John's wort and antidepressant drug interactions. J Geriatr Psychiatry Neurol. 1999;12(1):7-10.", "pmid": "10447148", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10447148/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Dual serotonin reuptake inhibition from citalopram and St.", "clinicalSignificance": "John's Wort creates serotonin syndrome risk.", "managementStrategy": "Do NOT combine St. John's Wort with citalopram.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Propranolol", "supplementBName": "Melatonin", "interactionType": "synergy", "severity": "info", "description": "Propranolol suppresses nocturnal melatonin synthesis by blocking pineal beta-1 receptors. Melatonin supplementation can restore sleep quality in propranolol-treated patients.", "recommendation": "Melatonin 0.5-3mg at bedtime may help with propranolol-induced insomnia. This is a well-documented effect of non-selective beta-blockers.", "minimumTimeSeparation": null, "mechanism": "Propranolol blocks both beta-1 and beta-2 receptors, including pineal beta-1 receptors that trigger melatonin synthesis via AANAT. Non-selective beta-blockers suppress melatonin more than selective ones.", "evidenceLevel": "strong", "sources": [ { "text": "Stoschitzky K et al. Influence of beta-blockers on melatonin release. Eur J Clin Pharmacol. 1999;55(2):111-115.", "pmid": "10335905", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10335905/", "publicSourceType": "PMID" }, { "text": "Fatemeh G, Sajjad M, Niloufar R et al.. Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials.. Journal of Neurology. 2022.", "pmid": "33417003", "doi": "10.1007/s00415-020-10381-w", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33417003/", "publicSourceType": "PMID" }, { "text": "Tang BHY, Manalo J, Chowdhury SR et al.. Melatonin Use in the ICU: A Systematic Review and Meta-Analysis.. Critical Care Medicine. 2025.", "pmid": "40662882", "doi": "10.1097/CCM.0000000000006767", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40662882/", "publicSourceType": "PMID" }, { "text": "Chan V, Lo K. Efficacy of dietary supplements on improving sleep quality: a systematic review and meta-analysis.. Postgraduate Medical Journal. 2022.", "pmid": "33441476", "doi": "10.1136/postgradmedj-2020-139319", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33441476/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Propranolol suppresses nocturnal melatonin synthesis by blocking pineal beta-1 receptors.", "clinicalSignificance": "Melatonin supplementation can restore sleep quality in propranolol-treated patients.", "managementStrategy": "Melatonin 0.5-3mg at bedtime may help with propranolol-induced insomnia. This is a well-documented effect of non-selective beta-blockers.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Atenolol", "supplementBName": "Melatonin", "interactionType": "synergy", "severity": "info", "description": "Beta-blockers suppress nocturnal melatonin production. Atenolol, being beta-1 selective, has a moderate effect on melatonin suppression. Supplementation may help with insomnia.", "recommendation": "If experiencing insomnia on atenolol, melatonin 0.5-3mg at bedtime may help.", "minimumTimeSeparation": null, "mechanism": "Beta-1 selective blockers like atenolol still partially suppress pineal melatonin synthesis, though less than non-selective agents.", "evidenceLevel": "moderate", "sources": [ { "text": "Stoschitzky K et al. Influence of beta-blockers on melatonin release. Eur J Clin Pharmacol. 1999;55(2):111-115.", "pmid": "10335905", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10335905/", "publicSourceType": "PMID" }, { "text": "Fatemeh G, Sajjad M, Niloufar R et al.. Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials.. Journal of Neurology. 2022.", "pmid": "33417003", "doi": "10.1007/s00415-020-10381-w", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33417003/", "publicSourceType": "PMID" }, { "text": "Tang BHY, Manalo J, Chowdhury SR et al.. Melatonin Use in the ICU: A Systematic Review and Meta-Analysis.. Critical Care Medicine. 2025.", "pmid": "40662882", "doi": "10.1097/CCM.0000000000006767", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40662882/", "publicSourceType": "PMID" }, { "text": "Chan V, Lo K. Efficacy of dietary supplements on improving sleep quality: a systematic review and meta-analysis.. Postgraduate Medical Journal. 2022.", "pmid": "33441476", "doi": "10.1136/postgradmedj-2020-139319", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33441476/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Beta-blockers suppress nocturnal melatonin production.", "clinicalSignificance": "Atenolol, being beta-1 selective, has a moderate effect on melatonin suppression.", "managementStrategy": "If experiencing insomnia on atenolol, melatonin 0.5-3mg at bedtime may help.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Rosuvastatin", "supplementBName": "Coenzyme Q10", "interactionType": "synergy", "severity": "info", "description": "Statins inhibit HMG-CoA reductase, which is also upstream of CoQ10 synthesis in the mevalonate pathway. Rosuvastatin can reduce plasma CoQ10 by 40%. CoQ10 supplementation may alleviate statin-associated myalgia.", "recommendation": "Consider CoQ10 100-200mg/day if experiencing muscle symptoms on rosuvastatin. CoQ10 does not interfere with rosuvastatin's cholesterol-lowering effect.", "minimumTimeSeparation": null, "mechanism": "HMG-CoA reductase inhibition blocks mevalonate production, reducing both cholesterol and CoQ10 synthesis. CoQ10 is essential for mitochondrial electron transport chain function in muscle.", "evidenceLevel": "moderate", "sources": [ { "text": "Qu H, Guo M, Chai H, Wang WT, Gao ZY, Shi DZ. Effects of Coenzyme Q10 on Statin-Induced Myopathy: An Updated Meta-Analysis of Randomized Controlled Trials. J Am Heart Assoc. 2018;7(19):e009835.", "pmid": "30371340", "doi": "10.1161/JAHA.118.009835", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30371340/", "publicSourceType": "PMID" }, { "text": "Kang Y, Park JM, Lee SH. Moderate-Intensity Rosuvastatin/Ezetimibe Combination versus Quadruple-Dose Rosuvastatin Monotherapy: A Meta-Analysis and Systemic Review. Yonsei Medical Journal. 2024.", "pmid": "38154476", "doi": "10.3349/ymj.2023.0285", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38154476/", "publicSourceType": "PMID" }, { "text": "Tsai IC, Hsu CW, Chang CH et al.. Effectiveness of Coenzyme Q10 Supplementation for Reducing Fatigue: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.. Frontiers in Pharmacology. 2022.", "pmid": "36091835", "doi": "10.3389/fphar.2022.883251", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36091835/", "publicSourceType": "PMID" }, { "text": "Liu Z, Tian Z, Zhao D et al.. Effects of Coenzyme Q10 Supplementation on Lipid Profiles in Adults: A Meta-analysis of Randomized Controlled Trials.. Journal of Clinical Endocrinology and Metabolism. 2022.", "pmid": "36337001", "doi": "10.1210/clinem/dgac585", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36337001/", "publicSourceType": "PMID" }, { "text": "Hou S, Tian Z, Zhao D et al.. Efficacy and Optimal Dose of Coenzyme Q10 Supplementation on Inflammation-Related Biomarkers: A GRADE-Assessed Systematic Review and Updated Meta-Analysis of Randomized Controlled Trials.. Molecular Nutrition & Food Research. 2023.", "pmid": "37118903", "doi": "10.1002/mnfr.202200800", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37118903/", "publicSourceType": "PMID" }, { "text": "Sazali S, Badrin S, Norhayati MN et al.. Coenzyme Q10 supplementation for prophylaxis in adult patients with migraine-a meta-analysis.. BMJ Open. 2021.", "pmid": "33402403", "doi": "10.1136/bmjopen-2020-039358", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33402403/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Statins inhibit HMG-CoA reductase, which is also upstream of CoQ10 synthesis in the mevalonate pathway.", "clinicalSignificance": "Rosuvastatin can reduce plasma CoQ10 by 40%.", "managementStrategy": "Consider CoQ10 100-200mg/day if experiencing muscle symptoms on rosuvastatin. CoQ10 does not interfere with rosuvastatin's cholesterol-lowering effect.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Pravastatin", "supplementBName": "Coenzyme Q10", "interactionType": "synergy", "severity": "info", "description": "All statins reduce CoQ10 levels by inhibiting the mevalonate pathway. Pravastatin has lower myopathy risk but still depletes CoQ10. Supplementation may benefit patients with muscle complaints.", "recommendation": "CoQ10 100-200mg/day may help with muscle symptoms on pravastatin. Does not interfere with lipid-lowering efficacy.", "minimumTimeSeparation": null, "mechanism": "Pravastatin inhibits HMG-CoA reductase, reducing mevalonate-derived CoQ10 biosynthesis. Although pravastatin is hydrophilic with lower muscle penetration, CoQ10 depletion still occurs.", "evidenceLevel": "moderate", "sources": [ { "text": "Banach M et al. Effects of coenzyme Q10 on statin-induced myopathy: a meta-analysis. Mayo Clin Proc. 2015;90(1):24-34.", "pmid": "25440725", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25440725/", "publicSourceType": "PMID" }, { "text": "Tsai IC, Hsu CW, Chang CH et al.. Effectiveness of Coenzyme Q10 Supplementation for Reducing Fatigue: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.. Frontiers in Pharmacology. 2022.", "pmid": "36091835", "doi": "10.3389/fphar.2022.883251", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36091835/", "publicSourceType": "PMID" }, { "text": "Liu Z, Tian Z, Zhao D et al.. Effects of Coenzyme Q10 Supplementation on Lipid Profiles in Adults: A Meta-analysis of Randomized Controlled Trials.. Journal of Clinical Endocrinology and Metabolism. 2022.", "pmid": "36337001", "doi": "10.1210/clinem/dgac585", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36337001/", "publicSourceType": "PMID" }, { "text": "Hou S, Tian Z, Zhao D et al.. Efficacy and Optimal Dose of Coenzyme Q10 Supplementation on Inflammation-Related Biomarkers: A GRADE-Assessed Systematic Review and Updated Meta-Analysis of Randomized Controlled Trials.. Molecular Nutrition & Food Research. 2023.", "pmid": "37118903", "doi": "10.1002/mnfr.202200800", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37118903/", "publicSourceType": "PMID" }, { "text": "Sazali S, Badrin S, Norhayati MN et al.. Coenzyme Q10 supplementation for prophylaxis in adult patients with migraine-a meta-analysis.. BMJ Open. 2021.", "pmid": "33402403", "doi": "10.1136/bmjopen-2020-039358", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33402403/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "All statins reduce CoQ10 levels by inhibiting the mevalonate pathway.", "clinicalSignificance": "Pravastatin has lower myopathy risk but still depletes CoQ10.", "managementStrategy": "CoQ10 100-200mg/day may help with muscle symptoms on pravastatin. Does not interfere with lipid-lowering efficacy.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Zolpidem", "supplementBName": "Valerian Root", "interactionType": "caution", "severity": "serious", "description": "Both zolpidem and valerian act on GABA-A receptors. Combined use can cause excessive CNS depression, over-sedation, and next-day impairment.", "recommendation": "Avoid combining zolpidem with valerian root. If sleep support is needed beyond zolpidem, discuss with your prescriber rather than adding herbal sedatives.", "minimumTimeSeparation": null, "mechanism": "Zolpidem selectively binds GABA-A alpha-1 subunit. Valerian's valerenic acid also modulates GABA-A receptors. Combined allosteric modulation produces additive/synergistic CNS depression.", "evidenceLevel": "moderate", "sources": [ { "text": "Donath F et al. Critical evaluation of the effect of valerian extract on sleep structure. Pharmacopsychiatry. 2000;33(2):47-53.", "pmid": "11036585", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11036585/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Both zolpidem and valerian act on GABA-A receptors.", "clinicalSignificance": "Combined use can cause excessive CNS depression, over-sedation, and next-day impairment.", "managementStrategy": "Avoid combining zolpidem with valerian root. If sleep support is needed beyond zolpidem, discuss with your prescriber rather than adding herbal sedatives.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Zolpidem", "supplementBName": "Melatonin", "interactionType": "caution", "severity": "moderate", "description": "Both zolpidem and melatonin promote sleep through different mechanisms. Combined use may cause excessive sedation but is sometimes used clinically under medical supervision.", "recommendation": "If using melatonin with zolpidem, use very low melatonin doses (0.5mg). Excessive sedation, dizziness, and morning grogginess can occur. Discuss with your prescriber.", "minimumTimeSeparation": null, "mechanism": "Zolpidem acts on GABA-A receptors. Melatonin acts on MT1/MT2 receptors. The different mechanisms produce additive sedation.", "evidenceLevel": "moderate", "sources": [ { "text": "Ferracioli-Oda E et al. Meta-analysis: melatonin for the treatment of primary sleep disorders. PLoS One. 2013;8(5):e63773.", "pmid": "23691095", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23691095/", "publicSourceType": "PMID" }, { "text": "Fatemeh G, Sajjad M, Niloufar R et al.. Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials.. Journal of Neurology. 2022.", "pmid": "33417003", "doi": "10.1007/s00415-020-10381-w", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33417003/", "publicSourceType": "PMID" }, { "text": "Tang BHY, Manalo J, Chowdhury SR et al.. Melatonin Use in the ICU: A Systematic Review and Meta-Analysis.. Critical Care Medicine. 2025.", "pmid": "40662882", "doi": "10.1097/CCM.0000000000006767", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40662882/", "publicSourceType": "PMID" }, { "text": "Chan V, Lo K. Efficacy of dietary supplements on improving sleep quality: a systematic review and meta-analysis.. Postgraduate Medical Journal. 2022.", "pmid": "33441476", "doi": "10.1136/postgradmedj-2020-139319", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33441476/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both zolpidem and melatonin promote sleep through different mechanisms.", "clinicalSignificance": "Combined use may cause excessive sedation but is sometimes used clinically under medical supervision.", "managementStrategy": "If using melatonin with zolpidem, use very low melatonin doses (0.5mg). Excessive sedation, dizziness, and morning grogginess can occur. Discuss with your prescriber.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Spironolactone", "supplementBName": "Potassium", "interactionType": "conflict", "severity": "dangerous", "description": "Spironolactone is a potassium-sparing diuretic that blocks aldosterone. Adding potassium supplements creates very high hyperkalemia risk, which can cause fatal cardiac arrest.", "recommendation": "Do NOT take potassium supplements with spironolactone unless specifically prescribed with close monitoring. Avoid potassium-containing salt substitutes. This combination can be lethal.", "minimumTimeSeparation": null, "mechanism": "Spironolactone blocks mineralocorticoid receptors in the collecting duct, preventing aldosterone-driven potassium excretion via ROMK and BK channels. Exogenous potassium on top of retained potassium = dangerous hyperkalemia.", "evidenceLevel": "strong", "sources": [ { "text": "Palmer BF. Managing hyperkalemia caused by RAAS inhibitors. N Engl J Med. 2004;351(6):585-592.", "pmid": "15295051", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15295051/", "publicSourceType": "PMID" }, { "text": "Filippini T, Naska A, Kasdagli MI et al.. Potassium Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials. Journal of the American Heart Association. 2020.", "pmid": "32500831", "doi": "10.1161/JAHA.119.015719", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32500831/", "publicSourceType": "PMID" }, { "text": "Behers BJ, Behers BM, Stephenson-Moe CA et al.. Magnesium and Potassium Supplementation for Systolic Blood Pressure Reduction in the General Normotensive Population: A Systematic Review and Subgroup Meta-Analysis for Optimal Dosage and Treatment Length. Nutrients. 2024.", "pmid": "39519450", "doi": "10.3390/nu16213617", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39519450/", "publicSourceType": "PMID" }, { "text": "D'Elia L, Cappuccio FP, Masulli M et al.. Effect of Potassium Supplementation on Endothelial Function: A Systematic Review and Meta-Analysis of Intervention Studies. Nutrients. 2023.", "pmid": "36839211", "doi": "10.3390/nu15040853", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36839211/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Spironolactone is a potassium-sparing diuretic that blocks aldosterone.", "clinicalSignificance": "Adding potassium supplements creates very high hyperkalemia risk, which can cause fatal cardiac arrest.", "managementStrategy": "Do NOT take potassium supplements with spironolactone unless specifically prescribed with close monitoring. Avoid potassium-containing salt substitutes. This combination can be lethal.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Aripiprazole", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's Wort induces CYP3A4 and CYP2D6, both of which metabolize aripiprazole. This can reduce aripiprazole levels by 50% or more, potentially causing psychotic relapse.", "recommendation": "Avoid St. John's Wort with aripiprazole. The FDA prescribing information lists strong CYP3A4 inducers as requiring dose adjustment.", "minimumTimeSeparation": null, "mechanism": "Aripiprazole is metabolized by CYP3A4 and CYP2D6. St. John's Wort induces CYP3A4, significantly increasing aripiprazole clearance and reducing therapeutic levels.", "evidenceLevel": "strong", "sources": [ { "text": "Markowitz JS, Donovan JL, DeVane CL, et al. Effect of St John's wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA. 2003;290(11):1500-1504.", "pmid": "13129991", "doi": "10.1001/jama.290.11.1500", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/13129991/", "publicSourceType": "PMID" }, { "text": "Belmonte C, Ochoa D, Roman M, et al. Influence of CYP2D6, CYP3A4, CYP3A5 and ABCB1 Polymorphisms on Pharmacokinetics and Safety of Aripiprazole in Healthy Volunteers. Basic Clin Pharmacol Toxicol. 2018;122(6):596-605.", "pmid": "29325225", "doi": "10.1111/bcpt.12960", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29325225/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St.", "clinicalSignificance": "John's Wort induces CYP3A4 and CYP2D6, both of which metabolize aripiprazole.", "managementStrategy": "Avoid St. John's Wort with aripiprazole. The FDA prescribing information lists strong CYP3A4 inducers as requiring dose adjustment.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Lithium", "supplementBName": "Iodine", "interactionType": "caution", "severity": "moderate", "description": "Lithium concentrates in the thyroid and inhibits thyroid hormone synthesis. Iodine supplementation in lithium-treated patients can worsen lithium-induced hypothyroidism or paradoxically trigger thyrotoxicosis (Jod-Basedow effect).", "recommendation": "Avoid iodine supplements while on lithium unless directed by your endocrinologist. Monitor thyroid function regularly. Kelp and seaweed supplements are high in iodine and should be avoided.", "minimumTimeSeparation": null, "mechanism": "Lithium inhibits thyroid hormone synthesis by blocking TSH-induced adenylyl cyclase activation and inhibiting thyroglobulin proteolysis. Excess iodine can trigger the Wolff-Chaikoff effect in lithium-treated patients, worsening hypothyroidism.", "evidenceLevel": "moderate", "sources": [ { "text": "Kirov G et al. Thyroid disorders in lithium-treated patients. J Affect Disord. 2005;86(2-3):215-221.", "pmid": "15935241", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15935241/", "publicSourceType": "PMID" }, { "text": "Dineva M, Fishpool H, Rayman MP, Mendis J, Bath SC. Systematic review and meta-analysis of the effects of iodine supplementation on thyroid function and child neurodevelopment in mildly-to-moderately iodine-deficient pregnant women. American Journal of Clinical Nutrition. 2020.", "pmid": "32320029", "doi": "10.1093/ajcn/nqaa071", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32320029/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Lithium concentrates in the thyroid and inhibits thyroid hormone synthesis.", "clinicalSignificance": "Iodine supplementation in lithium-treated patients can worsen lithium-induced hypothyroidism or paradoxically trigger thyrotoxicosis (Jod-Basedow effect).", "managementStrategy": "Avoid iodine supplements while on lithium unless directed by your endocrinologist. Monitor thyroid function regularly. Kelp and seaweed supplements are high in iodine and should be avoided.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Phenytoin", "supplementBName": "Vitamin B9", "interactionType": "caution", "severity": "moderate", "description": "Phenytoin depletes folate and folate supplementation may reduce phenytoin levels. This bidirectional interaction requires careful management.", "recommendation": "Low-dose folate (400-1000mcg/day) is recommended on phenytoin. Avoid high-dose folate (>5mg) as it may reduce phenytoin levels. Monitor drug levels when adjusting folate.", "minimumTimeSeparation": null, "mechanism": "Phenytoin inhibits intestinal folate absorption and increases folate catabolism. Conversely, folate enhances phenytoin metabolism by providing methyl groups for conjugation reactions.", "evidenceLevel": "strong", "sources": [ { "text": "Morrell MJ. Folic acid and epilepsy. Epilepsy Curr. 2002;2(2):31-34.", "pmid": "15309159", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15309159/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Phenytoin depletes folate and folate supplementation may reduce phenytoin levels.", "clinicalSignificance": "This bidirectional interaction requires careful management.", "managementStrategy": "Low-dose folate (400-1000mcg/day) is recommended on phenytoin. Avoid high-dose folate (>5mg) as it may reduce phenytoin levels. Monitor drug levels when adjusting folate.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Trazodone", "supplementBName": "5-HTP", "interactionType": "contraindicated", "severity": "dangerous", "description": "Trazodone is a serotonin antagonist and reuptake inhibitor (SARI). Combined with 5-HTP, the increased serotonin production creates serotonin syndrome risk.", "recommendation": "Do NOT take 5-HTP with trazodone. If additional sleep support is needed, discuss non-serotonergic options with your prescriber.", "minimumTimeSeparation": null, "mechanism": "Trazodone blocks SERT and antagonizes 5-HT2A receptors. While the 5-HT2A antagonism might seem protective, SERT blockade combined with 5-HTP-derived serotonin excess still poses serotonin syndrome risk.", "evidenceLevel": "moderate", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Truyens M, Lobatón T, Ferrante M et al.. Effect of 5-Hydroxytryptophan on Fatigue in Quiescent Inflammatory Bowel Disease: A Randomized Controlled Trial. Gastroenterology. 2022.", "pmid": "35940251", "doi": "10.1053/j.gastro.2022.07.052", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35940251/", "publicSourceType": "PMID" }, { "text": "Sutanto CN, Xia X, Heng CW et al.. The impact of 5-hydroxytryptophan supplementation on sleep quality and gut microbiota composition in older adults: A randomized controlled trial. Clinical Nutrition. 2024.", "pmid": "38309227", "doi": "10.1016/j.clnu.2024.01.010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38309227/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Trazodone is a serotonin antagonist and reuptake inhibitor (SARI).", "clinicalSignificance": "Combined with 5-HTP, the increased serotonin production creates serotonin syndrome risk.", "managementStrategy": "Do NOT take 5-HTP with trazodone. If additional sleep support is needed, discuss non-serotonergic options with your prescriber.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Mirtazapine", "supplementBName": "5-HTP", "interactionType": "caution", "severity": "serious", "description": "Mirtazapine enhances serotonergic and noradrenergic transmission through alpha-2 antagonism. Adding 5-HTP increases serotonin production, creating risk of serotonin excess.", "recommendation": "Avoid combining 5-HTP with mirtazapine. While mirtazapine's mechanism differs from SSRIs, the serotonergic enhancement is still significant.", "minimumTimeSeparation": null, "mechanism": "Mirtazapine blocks alpha-2 autoreceptors, enhancing serotonin and norepinephrine release. It also blocks 5-HT2A and 5-HT3 receptors. Adding 5-HTP increases serotonin production beyond what the compensatory mechanisms can handle.", "evidenceLevel": "moderate", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Truyens M, Lobatón T, Ferrante M et al.. Effect of 5-Hydroxytryptophan on Fatigue in Quiescent Inflammatory Bowel Disease: A Randomized Controlled Trial. Gastroenterology. 2022.", "pmid": "35940251", "doi": "10.1053/j.gastro.2022.07.052", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35940251/", "publicSourceType": "PMID" }, { "text": "Sutanto CN, Xia X, Heng CW et al.. The impact of 5-hydroxytryptophan supplementation on sleep quality and gut microbiota composition in older adults: A randomized controlled trial. Clinical Nutrition. 2024.", "pmid": "38309227", "doi": "10.1016/j.clnu.2024.01.010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38309227/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Mirtazapine enhances serotonergic and noradrenergic transmission through alpha-2 antagonism.", "clinicalSignificance": "Adding 5-HTP increases serotonin production, creating risk of serotonin excess.", "managementStrategy": "Avoid combining 5-HTP with mirtazapine. While mirtazapine's mechanism differs from SSRIs, the serotonergic enhancement is still significant.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Verapamil", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's Wort induces CYP3A4, the primary enzyme metabolizing verapamil. This can reduce verapamil levels by 40-80%, leading to loss of heart rate/blood pressure control and breakthrough arrhythmias.", "recommendation": "Avoid St. John's Wort with verapamil. Loss of rate control can be dangerous in atrial fibrillation patients.", "minimumTimeSeparation": null, "mechanism": "Verapamil is extensively metabolized by CYP3A4 with high first-pass effect. CYP3A4 induction by hyperforin dramatically increases verapamil clearance and reduces its bioavailability.", "evidenceLevel": "strong", "sources": [ { "text": "Wang LS et al. St John's wort induces both CYP3A4 and 2C19 activity. Clin Pharmacol Ther. 2004;75(3):191-197.", "pmid": "15001970", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15001970/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St.", "clinicalSignificance": "John's Wort induces CYP3A4, the primary enzyme metabolizing verapamil.", "managementStrategy": "Avoid St. John's Wort with verapamil. Loss of rate control can be dangerous in atrial fibrillation patients.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Verapamil", "supplementBName": "Magnesium Glycinate", "interactionType": "caution", "severity": "moderate", "description": "Both verapamil and magnesium block calcium channels. Combined use can cause excessive bradycardia, hypotension, and AV conduction delay.", "recommendation": "Use low-dose magnesium (200mg) with verapamil. Monitor heart rate and BP. Avoid if heart rate <55 bpm.", "minimumTimeSeparation": null, "mechanism": "Verapamil blocks L-type calcium channels in cardiac and vascular tissue. Magnesium is a natural calcium antagonist acting on the same channels. Additive negative chronotropic and dromotropic effects can occur.", "evidenceLevel": "moderate", "sources": [ { "text": "Shechter M. Magnesium and cardiovascular system. Magnes Res. 2010;23(2):60-72.", "pmid": "20513641", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20513641/", "publicSourceType": "PMID" }, { "text": "Mah J, Pitre T. Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis.. BMC Complementary Medicine and Therapies. 2021.", "pmid": "33865376", "doi": "10.1186/s12906-021-03297-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33865376/", "publicSourceType": "PMID" }, { "text": "Veronese N, Dominguez LJ, Pizzol D et al.. Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.. Nutrients. 2021.", "pmid": "34836329", "doi": "10.3390/nu13114074", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34836329/", "publicSourceType": "PMID" }, { "text": "Veronese N, Pizzol D, Smith L et al.. Effect of Magnesium Supplementation on Inflammatory Parameters: A Meta-Analysis of Randomized Controlled Trials.. Nutrients. 2022.", "pmid": "35277037", "doi": "10.3390/nu14030679", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35277037/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both verapamil and magnesium block calcium channels.", "clinicalSignificance": "Combined use can cause excessive bradycardia, hypotension, and AV conduction delay.", "managementStrategy": "Use low-dose magnesium (200mg) with verapamil. Monitor heart rate and BP. Avoid if heart rate <55 bpm.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Diltiazem", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's Wort induces CYP3A4, reducing diltiazem plasma levels significantly. This can lead to uncontrolled hypertension or angina.", "recommendation": "Avoid combining St. John's Wort with diltiazem.", "minimumTimeSeparation": null, "mechanism": "Diltiazem is a CYP3A4 substrate. Hyperforin-mediated CYP3A4 induction increases diltiazem metabolism, reducing its bioavailability and therapeutic effect.", "evidenceLevel": "strong", "sources": [ { "text": "Moore LB et al. St. John's wort induces hepatic drug metabolism through PXR. Proc Natl Acad Sci USA. 2000;97(13):7500-7502.", "pmid": "10852961", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10852961/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St.", "clinicalSignificance": "John's Wort induces CYP3A4, reducing diltiazem plasma levels significantly.", "managementStrategy": "Avoid combining St. John's Wort with diltiazem.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Nifedipine", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's Wort induces CYP3A4, which is the primary metabolic pathway for nifedipine. This can dramatically reduce nifedipine levels and blood pressure control.", "recommendation": "Avoid St. John's Wort with nifedipine. A documented case showed a patient's BP rose from controlled to 180/100 after starting SJW.", "minimumTimeSeparation": null, "mechanism": "Nifedipine undergoes extensive CYP3A4-mediated first-pass metabolism. CYP3A4 induction by SJW can reduce nifedipine AUC by >50%.", "evidenceLevel": "strong", "sources": [ { "text": "Tannergren C et al. St John's wort decreases the bioavailability of R- and S-verapamil through induction of first-pass metabolism. Clin Pharmacol Ther. 2004;75(4):298-309.", "pmid": "15060508", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15060508/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St.", "clinicalSignificance": "John's Wort induces CYP3A4, which is the primary metabolic pathway for nifedipine.", "managementStrategy": "Avoid St. John's Wort with nifedipine. A documented case showed a patient's BP rose from controlled to 180/100 after starting SJW.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Enalapril", "supplementBName": "Potassium", "interactionType": "conflict", "severity": "serious", "description": "Enalapril reduces aldosterone, decreasing potassium excretion. Potassium supplements significantly increase hyperkalemia risk.", "recommendation": "Avoid potassium supplements on enalapril unless prescribed with monitoring. Avoid potassium salt substitutes.", "minimumTimeSeparation": null, "mechanism": "ACE inhibition reduces angiotensin II and aldosterone. Reduced aldosterone means less renal potassium excretion via ENaC/ROMK in the collecting duct.", "evidenceLevel": "strong", "sources": [ { "text": "Palmer BF. Managing hyperkalemia caused by RAAS inhibitors. N Engl J Med. 2004;351(6):585-592.", "pmid": "15295051", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15295051/", "publicSourceType": "PMID" }, { "text": "Filippini T, Naska A, Kasdagli MI et al.. Potassium Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials. Journal of the American Heart Association. 2020.", "pmid": "32500831", "doi": "10.1161/JAHA.119.015719", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32500831/", "publicSourceType": "PMID" }, { "text": "Behers BJ, Behers BM, Stephenson-Moe CA et al.. Magnesium and Potassium Supplementation for Systolic Blood Pressure Reduction in the General Normotensive Population: A Systematic Review and Subgroup Meta-Analysis for Optimal Dosage and Treatment Length. Nutrients. 2024.", "pmid": "39519450", "doi": "10.3390/nu16213617", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39519450/", "publicSourceType": "PMID" }, { "text": "D'Elia L, Cappuccio FP, Masulli M et al.. Effect of Potassium Supplementation on Endothelial Function: A Systematic Review and Meta-Analysis of Intervention Studies. Nutrients. 2023.", "pmid": "36839211", "doi": "10.3390/nu15040853", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36839211/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Enalapril reduces aldosterone, decreasing potassium excretion.", "clinicalSignificance": "Potassium supplements significantly increase hyperkalemia risk.", "managementStrategy": "Avoid potassium supplements on enalapril unless prescribed with monitoring. Avoid potassium salt substitutes.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Ramipril", "supplementBName": "Potassium", "interactionType": "conflict", "severity": "serious", "description": "Ramipril reduces aldosterone secretion, creating significant hyperkalemia risk with potassium supplements.", "recommendation": "Avoid potassium supplements unless prescribed. Monitor serum K+ regularly.", "minimumTimeSeparation": null, "mechanism": "ACE inhibition by ramipril reduces aldosterone, impairing renal potassium excretion.", "evidenceLevel": "strong", "sources": [ { "text": "Palmer BF. Managing hyperkalemia caused by RAAS inhibitors. N Engl J Med. 2004;351(6):585-592.", "pmid": "15295051", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15295051/", "publicSourceType": "PMID" }, { "text": "Filippini T, Naska A, Kasdagli MI et al.. Potassium Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials. Journal of the American Heart Association. 2020.", "pmid": "32500831", "doi": "10.1161/JAHA.119.015719", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32500831/", "publicSourceType": "PMID" }, { "text": "Behers BJ, Behers BM, Stephenson-Moe CA et al.. Magnesium and Potassium Supplementation for Systolic Blood Pressure Reduction in the General Normotensive Population: A Systematic Review and Subgroup Meta-Analysis for Optimal Dosage and Treatment Length. Nutrients. 2024.", "pmid": "39519450", "doi": "10.3390/nu16213617", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39519450/", "publicSourceType": "PMID" }, { "text": "D'Elia L, Cappuccio FP, Masulli M et al.. Effect of Potassium Supplementation on Endothelial Function: A Systematic Review and Meta-Analysis of Intervention Studies. Nutrients. 2023.", "pmid": "36839211", "doi": "10.3390/nu15040853", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36839211/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Ramipril reduces aldosterone secretion, creating significant hyperkalemia risk with potassium supplements.", "clinicalSignificance": "Avoid potassium supplements unless prescribed.", "managementStrategy": "Avoid potassium supplements unless prescribed. Monitor serum K+ regularly.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Valsartan", "supplementBName": "Potassium", "interactionType": "conflict", "severity": "serious", "description": "Valsartan blocks AT1 receptors, reducing aldosterone and potassium excretion. Potassium supplementation creates hyperkalemia risk.", "recommendation": "Avoid potassium supplements with valsartan unless prescribed with close monitoring.", "minimumTimeSeparation": null, "mechanism": "AT1 receptor blockade in the adrenal cortex reduces aldosterone release, decreasing renal potassium secretion in the collecting duct.", "evidenceLevel": "strong", "sources": [ { "text": "Palmer BF. Managing hyperkalemia caused by RAAS inhibitors. N Engl J Med. 2004;351(6):585-592.", "pmid": "15295051", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15295051/", "publicSourceType": "PMID" }, { "text": "Filippini T, Naska A, Kasdagli MI et al.. Potassium Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials. Journal of the American Heart Association. 2020.", "pmid": "32500831", "doi": "10.1161/JAHA.119.015719", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32500831/", "publicSourceType": "PMID" }, { "text": "Behers BJ, Behers BM, Stephenson-Moe CA et al.. Magnesium and Potassium Supplementation for Systolic Blood Pressure Reduction in the General Normotensive Population: A Systematic Review and Subgroup Meta-Analysis for Optimal Dosage and Treatment Length. Nutrients. 2024.", "pmid": "39519450", "doi": "10.3390/nu16213617", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39519450/", "publicSourceType": "PMID" }, { "text": "D'Elia L, Cappuccio FP, Masulli M et al.. Effect of Potassium Supplementation on Endothelial Function: A Systematic Review and Meta-Analysis of Intervention Studies. Nutrients. 2023.", "pmid": "36839211", "doi": "10.3390/nu15040853", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36839211/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Valsartan blocks AT1 receptors, reducing aldosterone and potassium excretion.", "clinicalSignificance": "Potassium supplementation creates hyperkalemia risk.", "managementStrategy": "Avoid potassium supplements with valsartan unless prescribed with close monitoring.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Carvedilol", "supplementBName": "Melatonin", "interactionType": "synergy", "severity": "info", "description": "Carvedilol, as a non-selective beta-blocker, suppresses nocturnal melatonin synthesis more than beta-1 selective agents. Melatonin supplementation can restore sleep quality.", "recommendation": "Melatonin 0.5-3mg at bedtime may help with carvedilol-induced insomnia.", "minimumTimeSeparation": null, "mechanism": "Non-selective beta-blockers block pineal beta-1 and beta-2 receptors, strongly suppressing melatonin synthesis via AANAT inhibition.", "evidenceLevel": "strong", "sources": [ { "text": "Stoschitzky K et al. Influence of beta-blockers on melatonin release. Eur J Clin Pharmacol. 1999;55(2):111-115.", "pmid": "10335905", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10335905/", "publicSourceType": "PMID" }, { "text": "Fatemeh G, Sajjad M, Niloufar R et al.. Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials.. Journal of Neurology. 2022.", "pmid": "33417003", "doi": "10.1007/s00415-020-10381-w", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33417003/", "publicSourceType": "PMID" }, { "text": "Tang BHY, Manalo J, Chowdhury SR et al.. Melatonin Use in the ICU: A Systematic Review and Meta-Analysis.. Critical Care Medicine. 2025.", "pmid": "40662882", "doi": "10.1097/CCM.0000000000006767", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40662882/", "publicSourceType": "PMID" }, { "text": "Chan V, Lo K. Efficacy of dietary supplements on improving sleep quality: a systematic review and meta-analysis.. Postgraduate Medical Journal. 2022.", "pmid": "33441476", "doi": "10.1136/postgradmedj-2020-139319", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33441476/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Carvedilol, as a non-selective beta-blocker, suppresses nocturnal melatonin synthesis more than beta-1 selective agents.", "clinicalSignificance": "Melatonin supplementation can restore sleep quality.", "managementStrategy": "Melatonin 0.5-3mg at bedtime may help with carvedilol-induced insomnia.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Bisoprolol", "supplementBName": "Melatonin", "interactionType": "synergy", "severity": "info", "description": "Beta-1 selective blockers like bisoprolol moderately suppress melatonin. Supplementation can help with sleep disturbance.", "recommendation": "Low-dose melatonin (0.5-1mg) at bedtime if experiencing insomnia on bisoprolol.", "minimumTimeSeparation": null, "mechanism": "Bisoprolol blocks cardiac beta-1 receptors. Pineal gland beta-1 receptors controlling melatonin synthesis are partially affected.", "evidenceLevel": "moderate", "sources": [ { "text": "Stoschitzky K et al. Influence of beta-blockers on melatonin release. Eur J Clin Pharmacol. 1999;55(2):111-115.", "pmid": "10335905", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10335905/", "publicSourceType": "PMID" }, { "text": "Fatemeh G, Sajjad M, Niloufar R et al.. Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials.. Journal of Neurology. 2022.", "pmid": "33417003", "doi": "10.1007/s00415-020-10381-w", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33417003/", "publicSourceType": "PMID" }, { "text": "Tang BHY, Manalo J, Chowdhury SR et al.. Melatonin Use in the ICU: A Systematic Review and Meta-Analysis.. Critical Care Medicine. 2025.", "pmid": "40662882", "doi": "10.1097/CCM.0000000000006767", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40662882/", "publicSourceType": "PMID" }, { "text": "Chan V, Lo K. Efficacy of dietary supplements on improving sleep quality: a systematic review and meta-analysis.. Postgraduate Medical Journal. 2022.", "pmid": "33441476", "doi": "10.1136/postgradmedj-2020-139319", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33441476/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Beta-1 selective blockers like bisoprolol moderately suppress melatonin.", "clinicalSignificance": "Supplementation can help with sleep disturbance.", "managementStrategy": "Low-dose melatonin (0.5-1mg) at bedtime if experiencing insomnia on bisoprolol.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Carvedilol", "supplementBName": "Coenzyme Q10", "interactionType": "synergy", "severity": "info", "description": "Beta-blockers may reduce CoQ10 levels. CoQ10 supplementation is particularly relevant for carvedilol patients with heart failure, as CoQ10 supports mitochondrial function in failing myocardium.", "recommendation": "Consider CoQ10 100-200mg/day for heart failure patients on carvedilol. The Q-SYMBIO trial showed CoQ10 reduced CV mortality in HF.", "minimumTimeSeparation": null, "mechanism": "Beta-blockers may impair CoQ10-dependent mitochondrial enzymes. In heart failure, myocardial CoQ10 is depleted. Supplementation supports electron transport chain function.", "evidenceLevel": "moderate", "sources": [ { "text": "Mortensen SA et al. The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure (Q-SYMBIO). JACC Heart Fail. 2014;2(6):641-649.", "pmid": "25282031", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25282031/", "publicSourceType": "PMID" }, { "text": "Tsai IC, Hsu CW, Chang CH et al.. Effectiveness of Coenzyme Q10 Supplementation for Reducing Fatigue: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.. Frontiers in Pharmacology. 2022.", "pmid": "36091835", "doi": "10.3389/fphar.2022.883251", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36091835/", "publicSourceType": "PMID" }, { "text": "Liu Z, Tian Z, Zhao D et al.. Effects of Coenzyme Q10 Supplementation on Lipid Profiles in Adults: A Meta-analysis of Randomized Controlled Trials.. Journal of Clinical Endocrinology and Metabolism. 2022.", "pmid": "36337001", "doi": "10.1210/clinem/dgac585", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36337001/", "publicSourceType": "PMID" }, { "text": "Hou S, Tian Z, Zhao D et al.. Efficacy and Optimal Dose of Coenzyme Q10 Supplementation on Inflammation-Related Biomarkers: A GRADE-Assessed Systematic Review and Updated Meta-Analysis of Randomized Controlled Trials.. Molecular Nutrition & Food Research. 2023.", "pmid": "37118903", "doi": "10.1002/mnfr.202200800", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37118903/", "publicSourceType": "PMID" }, { "text": "Sazali S, Badrin S, Norhayati MN et al.. Coenzyme Q10 supplementation for prophylaxis in adult patients with migraine-a meta-analysis.. BMJ Open. 2021.", "pmid": "33402403", "doi": "10.1136/bmjopen-2020-039358", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33402403/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Beta-blockers may reduce CoQ10 levels.", "clinicalSignificance": "CoQ10 supplementation is particularly relevant for carvedilol patients with heart failure, as CoQ10 supports mitochondrial function in failing myocardium.", "managementStrategy": "Consider CoQ10 100-200mg/day for heart failure patients on carvedilol. The Q-SYMBIO trial showed CoQ10 reduced CV mortality in HF.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Glipizide", "supplementBName": "Berberine", "interactionType": "caution", "severity": "serious", "description": "Both glipizide and berberine lower blood glucose. Glipizide stimulates insulin secretion; berberine activates AMPK. Combined use significantly increases hypoglycemia risk.", "recommendation": "Monitor blood glucose closely. If adding berberine, start at low dose and may need glipizide dose reduction. Inform your prescriber.", "minimumTimeSeparation": null, "mechanism": "Glipizide blocks KATP channels on pancreatic beta cells, stimulating insulin release. Berberine activates AMPK and enhances insulin sensitivity through a different pathway. Additive glucose lowering creates hypoglycemia risk.", "evidenceLevel": "moderate", "sources": [ { "text": "Yin J et al. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008;57(5):712-717.", "pmid": "18442638", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18442638/", "publicSourceType": "PMID" }, { "text": "Asbaghi O, Ghanbari N, Shekari M et al.. The effect of berberine supplementation on obesity parameters, inflammation and liver function enzymes: A systematic review and meta-analysis of randomized controlled trials.. Clinical Nutrition ESPEN. 2020.", "pmid": "32690176", "doi": "10.1016/j.clnesp.2020.04.010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32690176/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Both glipizide and berberine lower blood glucose.", "clinicalSignificance": "Glipizide stimulates insulin secretion; berberine activates AMPK.", "managementStrategy": "Monitor blood glucose closely. If adding berberine, start at low dose and may need glipizide dose reduction. Inform your prescriber.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Glyburide", "supplementBName": "Berberine", "interactionType": "caution", "severity": "serious", "description": "Glyburide is a potent sulfonylurea with high hypoglycemia risk. Adding berberine's AMPK-mediated glucose lowering significantly increases this risk.", "recommendation": "Use extreme caution. Glyburide already has the highest hypoglycemia risk among sulfonylureas. Berberine should only be added with close medical supervision and glucose monitoring.", "minimumTimeSeparation": null, "mechanism": "Glyburide stimulates prolonged insulin secretion via KATP channel blockade. Berberine independently lowers glucose via AMPK activation. The combination can cause severe hypoglycemia.", "evidenceLevel": "moderate", "sources": [ { "text": "Yin J et al. Efficacy of berberine in patients with type 2 diabetes. Metabolism. 2008;57(5):712-717.", "pmid": "18442638", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18442638/", "publicSourceType": "PMID" }, { "text": "Asbaghi O, Ghanbari N, Shekari M et al.. The effect of berberine supplementation on obesity parameters, inflammation and liver function enzymes: A systematic review and meta-analysis of randomized controlled trials.. Clinical Nutrition ESPEN. 2020.", "pmid": "32690176", "doi": "10.1016/j.clnesp.2020.04.010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32690176/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Glyburide is a potent sulfonylurea with high hypoglycemia risk.", "clinicalSignificance": "Adding berberine's AMPK-mediated glucose lowering significantly increases this risk.", "managementStrategy": "Use extreme caution. Glyburide already has the highest hypoglycemia risk among sulfonylureas. Berberine should only be added with close medical supervision and glucose monitoring.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Empagliflozin", "supplementBName": "Berberine", "interactionType": "caution", "severity": "moderate", "description": "Both empagliflozin and berberine lower blood glucose through different mechanisms. Combined use may increase hypoglycemia risk, particularly when combined with insulin or sulfonylureas.", "recommendation": "Monitor blood glucose when combining. The risk is lower than with sulfonylureas but still clinically relevant, especially in patients on multiple glucose-lowering agents.", "minimumTimeSeparation": null, "mechanism": "Empagliflozin inhibits SGLT2, causing glycosuria. Berberine activates AMPK and improves insulin sensitivity. Different mechanisms create additive glucose lowering.", "evidenceLevel": "emerging", "sources": [ { "text": "Zinman B et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128.", "pmid": "26378978", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26378978/", "publicSourceType": "PMID" }, { "text": "Asbaghi O, Ghanbari N, Shekari M et al.. The effect of berberine supplementation on obesity parameters, inflammation and liver function enzymes: A systematic review and meta-analysis of randomized controlled trials.. Clinical Nutrition ESPEN. 2020.", "pmid": "32690176", "doi": "10.1016/j.clnesp.2020.04.010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32690176/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both empagliflozin and berberine lower blood glucose through different mechanisms.", "clinicalSignificance": "Combined use may increase hypoglycemia risk, particularly when combined with insulin or sulfonylureas.", "managementStrategy": "Monitor blood glucose when combining. The risk is lower than with sulfonylureas but still clinically relevant, especially in patients on multiple glucose-lowering agents.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Dapagliflozin", "supplementBName": "Berberine", "interactionType": "caution", "severity": "moderate", "description": "Dapagliflozin and berberine both lower blood glucose through independent mechanisms. Combined use may increase hypoglycemia risk.", "recommendation": "Monitor blood glucose when combining. Low risk when used alone but relevant in multi-drug regimens.", "minimumTimeSeparation": null, "mechanism": "Dapagliflozin inhibits SGLT2 in the proximal tubule, causing urinary glucose excretion. Berberine activates AMPK. Both lower glucose through insulin-independent mechanisms.", "evidenceLevel": "emerging", "sources": [ { "text": "McMurray JJV et al. Dapagliflozin in patients with heart failure (DAPA-HF). N Engl J Med. 2019;381(21):1995-2008.", "pmid": "31535829", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31535829/", "publicSourceType": "PMID" }, { "text": "Asbaghi O, Ghanbari N, Shekari M et al.. The effect of berberine supplementation on obesity parameters, inflammation and liver function enzymes: A systematic review and meta-analysis of randomized controlled trials.. Clinical Nutrition ESPEN. 2020.", "pmid": "32690176", "doi": "10.1016/j.clnesp.2020.04.010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32690176/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Dapagliflozin and berberine both lower blood glucose through independent mechanisms.", "clinicalSignificance": "Combined use may increase hypoglycemia risk.", "managementStrategy": "Monitor blood glucose when combining. Low risk when used alone but relevant in multi-drug regimens.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Liraglutide", "supplementBName": "Berberine", "interactionType": "caution", "severity": "serious", "description": "Both liraglutide and berberine lower blood glucose. Both also slow GI motility, compounding GI side effects (nausea, vomiting, diarrhea). Significant hypoglycemia risk when combined.", "recommendation": "Monitor glucose closely. GI side effects may be additive. Start berberine at low dose if combining.", "minimumTimeSeparation": null, "mechanism": "Liraglutide activates GLP-1 receptors, enhancing insulin secretion and slowing gastric emptying. Berberine activates AMPK. Both slow GI motility independently.", "evidenceLevel": "moderate", "sources": [ { "text": "Marso SP et al. Liraglutide and cardiovascular outcomes in type 2 diabetes (LEADER). N Engl J Med. 2016;375(4):311-322.", "pmid": "27295427", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27295427/", "publicSourceType": "PMID" }, { "text": "Asbaghi O, Ghanbari N, Shekari M et al.. The effect of berberine supplementation on obesity parameters, inflammation and liver function enzymes: A systematic review and meta-analysis of randomized controlled trials.. Clinical Nutrition ESPEN. 2020.", "pmid": "32690176", "doi": "10.1016/j.clnesp.2020.04.010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32690176/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Both liraglutide and berberine lower blood glucose.", "clinicalSignificance": "Both also slow GI motility, compounding GI side effects (nausea, vomiting, diarrhea).", "managementStrategy": "Monitor glucose closely. GI side effects may be additive. Start berberine at low dose if combining.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Dulaglutide", "supplementBName": "Berberine", "interactionType": "caution", "severity": "serious", "description": "Dulaglutide and berberine both lower glucose through different pathways. Combined GI side effects and hypoglycemia risk are the main concerns.", "recommendation": "Same precautions as other GLP-1 agonists. Monitor glucose and watch for excessive GI symptoms.", "minimumTimeSeparation": null, "mechanism": "Dulaglutide activates GLP-1 receptors (weekly dosing). Berberine activates AMPK. Additive glucose lowering and GI slowing.", "evidenceLevel": "moderate", "sources": [ { "text": "Gerstein HC et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND). Lancet. 2019;394(10193):121-130.", "pmid": "31189511", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31189511/", "publicSourceType": "PMID" }, { "text": "Asbaghi O, Ghanbari N, Shekari M et al.. The effect of berberine supplementation on obesity parameters, inflammation and liver function enzymes: A systematic review and meta-analysis of randomized controlled trials.. Clinical Nutrition ESPEN. 2020.", "pmid": "32690176", "doi": "10.1016/j.clnesp.2020.04.010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32690176/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Dulaglutide and berberine both lower glucose through different pathways.", "clinicalSignificance": "Combined GI side effects and hypoglycemia risk are the main concerns.", "managementStrategy": "Same precautions as other GLP-1 agonists. Monitor glucose and watch for excessive GI symptoms.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Olanzapine", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's Wort induces CYP1A2, the primary metabolic pathway for olanzapine. This can reduce olanzapine levels, causing psychotic relapse.", "recommendation": "Avoid St. John's Wort with olanzapine.", "minimumTimeSeparation": null, "mechanism": "Olanzapine is primarily metabolized by CYP1A2 and UGT. St. John's Wort may induce CYP1A2, increasing olanzapine clearance.", "evidenceLevel": "moderate", "sources": [ { "text": "Markowitz JS, Donovan JL, DeVane CL, et al. Effect of St John's wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA. 2003;290(11):1500-1504.", "pmid": "13129991", "doi": "10.1001/jama.290.11.1500", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/13129991/", "publicSourceType": "PMID" }, { "text": "Soderberg MM, Dahl ML. Pharmacogenetics of olanzapine metabolism. Pharmacogenomics. 2013;14(11):1319-1336.", "pmid": "23930678", "doi": "10.2217/pgs.13.120", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23930678/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St.", "clinicalSignificance": "John's Wort induces CYP1A2, the primary metabolic pathway for olanzapine.", "managementStrategy": "Avoid St. John's Wort with olanzapine.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Risperidone", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's Wort induces CYP3A4, which metabolizes risperidone. Reduced risperidone levels can cause psychotic relapse.", "recommendation": "Avoid combining. Loss of antipsychotic effect can be dangerous.", "minimumTimeSeparation": null, "mechanism": "Risperidone is metabolized by CYP2D6 and CYP3A4 to its active metabolite 9-hydroxyrisperidone. CYP3A4 induction by SJW increases clearance.", "evidenceLevel": "moderate", "sources": [ { "text": "Markowitz JS, Donovan JL, DeVane CL, et al. Effect of St John's wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA. 2003;290(11):1500-1504.", "pmid": "13129991", "doi": "10.1001/jama.290.11.1500", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/13129991/", "publicSourceType": "PMID" }, { "text": "Spina E, Avenoso A, Facciola G, et al. Plasma concentrations of risperidone and 9-hydroxyrisperidone: effect of comedication with carbamazepine or valproate. Ther Drug Monit. 2000;22(4):481-485.", "pmid": "10942191", "doi": "10.1097/00007691-200008000-00019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10942191/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St.", "clinicalSignificance": "John's Wort induces CYP3A4, which metabolizes risperidone.", "managementStrategy": "Avoid combining. Loss of antipsychotic effect can be dangerous.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Clonazepam", "supplementBName": "Valerian Root", "interactionType": "caution", "severity": "serious", "description": "Both clonazepam and valerian act on GABA-A receptors. Combined use causes additive CNS depression, excessive sedation, and respiratory depression risk.", "recommendation": "Avoid combining. If using valerian, do not take with clonazepam. Additive sedation can be dangerous.", "minimumTimeSeparation": null, "mechanism": "Clonazepam binds benzodiazepine site on GABA-A receptors. Valerenic acid also modulates GABA-A. Dual allosteric modulation causes excessive CNS depression.", "evidenceLevel": "moderate", "sources": [ { "text": "Spinella M. The importance of pharmacological synergy in psychoactive herbal medicines. Altern Med Rev. 2002;7(2):130-137.", "pmid": "11991792", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11991792/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Both clonazepam and valerian act on GABA-A receptors.", "clinicalSignificance": "Combined use causes additive CNS depression, excessive sedation, and respiratory depression risk.", "managementStrategy": "Avoid combining. If using valerian, do not take with clonazepam. Additive sedation can be dangerous.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Clonazepam", "supplementBName": "Melatonin", "interactionType": "caution", "severity": "moderate", "description": "Both promote sleep through different mechanisms. Combined sedation may cause excessive drowsiness. However, melatonin may help facilitate benzodiazepine tapering.", "recommendation": "Low-dose melatonin (0.5-1mg) may be cautiously used. Some clinicians use melatonin to facilitate benzo tapering under supervision.", "minimumTimeSeparation": null, "mechanism": "Clonazepam enhances GABAergic inhibition. Melatonin acts on MT1/MT2 receptors. Different sedative mechanisms are additive.", "evidenceLevel": "moderate", "sources": [ { "text": "Baandrup L et al. Prolonged-release melatonin versus placebo for benzodiazepine discontinuation. Psychopharmacology. 2016;233(17):3251-3259.", "pmid": "27435171", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27435171/", "publicSourceType": "PMID" }, { "text": "Fatemeh G, Sajjad M, Niloufar R et al.. Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials.. Journal of Neurology. 2022.", "pmid": "33417003", "doi": "10.1007/s00415-020-10381-w", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33417003/", "publicSourceType": "PMID" }, { "text": "Tang BHY, Manalo J, Chowdhury SR et al.. Melatonin Use in the ICU: A Systematic Review and Meta-Analysis.. Critical Care Medicine. 2025.", "pmid": "40662882", "doi": "10.1097/CCM.0000000000006767", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40662882/", "publicSourceType": "PMID" }, { "text": "Chan V, Lo K. Efficacy of dietary supplements on improving sleep quality: a systematic review and meta-analysis.. Postgraduate Medical Journal. 2022.", "pmid": "33441476", "doi": "10.1136/postgradmedj-2020-139319", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33441476/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both promote sleep through different mechanisms.", "clinicalSignificance": "Combined sedation may cause excessive drowsiness.", "managementStrategy": "Low-dose melatonin (0.5-1mg) may be cautiously used. Some clinicians use melatonin to facilitate benzo tapering under supervision.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Diazepam", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's Wort induces CYP3A4 and CYP2C19, both of which metabolize diazepam. This can reduce diazepam levels, causing breakthrough anxiety or seizures in epilepsy patients.", "recommendation": "Avoid combining. Abrupt reduction in diazepam levels can cause withdrawal symptoms or seizures.", "minimumTimeSeparation": null, "mechanism": "Diazepam is metabolized by CYP3A4 and CYP2C19 to active metabolites. SJW induces both enzymes, accelerating diazepam clearance and reducing therapeutic levels.", "evidenceLevel": "strong", "sources": [ { "text": "Markowitz JS et al. Effect of St John's wort on drug metabolism by induction of CYP3A4. JAMA. 2003;290(11):1500-1504.", "pmid": "13129991", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/13129991/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St.", "clinicalSignificance": "John's Wort induces CYP3A4 and CYP2C19, both of which metabolize diazepam.", "managementStrategy": "Avoid combining. Abrupt reduction in diazepam levels can cause withdrawal symptoms or seizures.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Diazepam", "supplementBName": "Valerian Root", "interactionType": "caution", "severity": "serious", "description": "Both diazepam and valerian enhance GABA-A receptor activity. Combined use creates additive CNS depression and excessive sedation.", "recommendation": "Avoid combining valerian with diazepam. The additive sedative effect can impair breathing and cause excessive drowsiness.", "minimumTimeSeparation": null, "mechanism": "Diazepam binds the benzodiazepine allosteric site on GABA-A receptors. Valerenic acid modulates GABA-A receptors at a different site. Dual enhancement of GABAergic transmission causes excessive inhibition.", "evidenceLevel": "moderate", "sources": [ { "text": "Spinella M. Pharmacological synergy in psychoactive herbal medicines. Altern Med Rev. 2002;7(2):130-137.", "pmid": "11991792", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11991792/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Both diazepam and valerian enhance GABA-A receptor activity.", "clinicalSignificance": "Combined use creates additive CNS depression and excessive sedation.", "managementStrategy": "Avoid combining valerian with diazepam. The additive sedative effect can impair breathing and cause excessive drowsiness.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Topiramate", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "moderate", "description": "Topiramate can reduce vitamin D levels and increase kidney stone risk. Vitamin D supplementation helps prevent bone loss but the carbonic anhydrase inhibition may increase calcium stone risk.", "recommendation": "Monitor vitamin D levels. Supplement with 1000-2000 IU/day D3. Monitor calcium/renal function given topiramate's carbonic anhydrase inhibition and nephrolithiasis risk.", "minimumTimeSeparation": null, "mechanism": "Topiramate is a weak carbonic anhydrase inhibitor that increases urinary pH and citrate excretion, promoting calcium phosphate stones. It may also affect vitamin D metabolism through enzyme induction.", "evidenceLevel": "moderate", "sources": [ { "text": "Valsamis HA et al. Antiepileptic drugs and bone metabolism. Nutr Metab (Lond). 2006;3:36.", "pmid": "16956398", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16956398/", "publicSourceType": "PMID" }, { "text": "Zhang Y, Fang F, Tang J et al.. Association between vitamin D supplementation and mortality: systematic review and meta-analysis.. BMJ. 2019.", "pmid": "31405892", "doi": "10.1136/bmj.l4673", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31405892/", "publicSourceType": "PMID" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" }, { "text": "Fiamenghi VI, Mello ED. Vitamin D deficiency in children and adolescents with obesity: a meta-analysis.. Jornal de pediatria. 2021.", "pmid": "33022267", "doi": "10.1016/j.jped.2020.08.006", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33022267/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Topiramate can reduce vitamin D levels and increase kidney stone risk.", "clinicalSignificance": "Vitamin D supplementation helps prevent bone loss but the carbonic anhydrase inhibition may increase calcium stone risk.", "managementStrategy": "Monitor vitamin D levels. Supplement with 1000-2000 IU/day D3. Monitor calcium/renal function given topiramate's carbonic anhydrase inhibition and nephrolithiasis risk.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Levetiracetam", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "info", "description": "Levetiracetam has minimal enzyme-inducing effects compared to other anticonvulsants, but long-term use may still modestly reduce vitamin D levels. Monitoring is reasonable.", "recommendation": "Less vitamin D depletion risk than carbamazepine/phenytoin, but monitoring 25(OH)D levels annually is still recommended for any long-term anticonvulsant.", "minimumTimeSeparation": null, "mechanism": "Levetiracetam does not significantly induce CYP enzymes. Its effect on vitamin D is minimal compared to enzyme-inducing AEDs, but some studies suggest modest bone density reduction with long-term use.", "evidenceLevel": "emerging", "sources": [ { "text": "Valsamis HA et al. Antiepileptic drugs and bone metabolism. Nutr Metab (Lond). 2006;3:36.", "pmid": "16956398", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16956398/", "publicSourceType": "PMID" }, { "text": "Zhang Y, Fang F, Tang J et al.. Association between vitamin D supplementation and mortality: systematic review and meta-analysis.. BMJ. 2019.", "pmid": "31405892", "doi": "10.1136/bmj.l4673", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31405892/", "publicSourceType": "PMID" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" }, { "text": "Fiamenghi VI, Mello ED. Vitamin D deficiency in children and adolescents with obesity: a meta-analysis.. Jornal de pediatria. 2021.", "pmid": "33022267", "doi": "10.1016/j.jped.2020.08.006", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33022267/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Levetiracetam has minimal enzyme-inducing effects compared to other anticonvulsants, but long-term use may still modestly reduce vitamin D levels.", "clinicalSignificance": "Monitoring is reasonable.", "managementStrategy": "Less vitamin D depletion risk than carbamazepine/phenytoin, but monitoring 25(OH)D levels annually is still recommended for any long-term anticonvulsant.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Estradiol", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's Wort induces CYP3A4, which metabolizes estradiol. This can reduce estradiol levels by 20-40%, potentially causing breakthrough bleeding, hot flashes, or loss of menopausal symptom control.", "recommendation": "Avoid St. John's Wort while on estradiol HRT. Breakthrough bleeding and return of menopausal symptoms may occur.", "minimumTimeSeparation": null, "mechanism": "Estradiol is metabolized by CYP3A4 (2-hydroxylation) and CYP1A2. SJW induces CYP3A4, increasing estradiol clearance and reducing plasma levels.", "evidenceLevel": "strong", "sources": [ { "text": "Hall SD et al. The interaction between St John's wort and an oral contraceptive. Clin Pharmacol Ther. 2003;74(6):525-535.", "pmid": "14663455", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14663455/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St.", "clinicalSignificance": "John's Wort induces CYP3A4, which metabolizes estradiol.", "managementStrategy": "Avoid St. John's Wort while on estradiol HRT. Breakthrough bleeding and return of menopausal symptoms may occur.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Combined Oral Contraceptive", "supplementBName": "St. John's Wort", "interactionType": "contraindicated", "severity": "dangerous", "description": "St. John's Wort induces CYP3A4, dramatically reducing levels of ethinyl estradiol and progestins. This causes contraceptive failure and unintended pregnancy. The FDA and WHO list this as a contraindication.", "recommendation": "Do NOT take St. John's Wort with oral contraceptives. Use alternative contraception (non-hormonal) if taking SJW. Multiple documented cases of unintended pregnancy.", "minimumTimeSeparation": null, "mechanism": "Ethinyl estradiol and progestins (levonorgestrel, norethindrone, etc.) are CYP3A4 substrates. SJW-mediated CYP3A4 induction reduces their levels below effective contraceptive concentrations.", "evidenceLevel": "strong", "sources": [ { "text": "Hall SD et al. The interaction between St John's wort and an oral contraceptive. Clin Pharmacol Ther. 2003;74(6):525-535.", "pmid": "14663455", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14663455/", "publicSourceType": "PMID" }, { "text": "Schwarz UI et al. Unwanted pregnancy on self-medication with St John's wort despite hormonal contraception. Br J Clin Pharmacol. 2003;55(1):112-113.", "pmid": "12534650", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12534650/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bAffectsA", "effect": "St.", "clinicalSignificance": "John's Wort induces CYP3A4, dramatically reducing levels of ethinyl estradiol and progestins.", "managementStrategy": "Do NOT take St. John's Wort with oral contraceptives. Use alternative contraception (non-hormonal) if taking SJW. Multiple documented cases of unintended pregnancy.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Estradiol", "supplementBName": "DIM", "interactionType": "caution", "severity": "moderate", "description": "DIM shifts estrogen metabolism toward 2-hydroxy metabolites (less potent), potentially reducing estradiol's effectiveness for menopausal symptom control.", "recommendation": "If using DIM with estradiol HRT, monitor symptom control. DIM may reduce estradiol effectiveness. Discuss with your prescriber.", "minimumTimeSeparation": null, "mechanism": "DIM induces CYP1A1/CYP1A2, shifting estrogen metabolism toward 2-hydroxylation (producing 2-OHE1, which is less estrogenic). This can reduce the net estrogenic effect of estradiol HRT.", "evidenceLevel": "emerging", "sources": [ { "text": "Thomson CA et al. Chemopreventive properties of 3,3'-diindolylmethane. Mutat Res. 2004;555(1-2):149-157.", "pmid": "15476857", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15476857/", "publicSourceType": "PMID" }, { "text": "Yerushalmi R, Bargil S, Ber Y, Ozlavo R, Sivan T, Rapson Y et al.. 3,3-Diindolylmethane (DIM): a nutritional intervention and its impact on breast density in healthy BRCA carriers. A prospective clinical trial.. Carcinogenesis. 2020.", "pmid": "32458980", "doi": "10.1093/carcin/bgaa050", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32458980/", "publicSourceType": "PMID" }, { "text": "Godnez-Martnez E, Santilln R, Smano R, Chico-Barba G, Tolentino MC, Hernndez-Pineda J. Effectiveness of 3,3'-Diindolylmethane Supplements on Favoring the Benign Estrogen Metabolism Pathway and Decreasing Body Fat in Premenopausal Women.. Nutrition and Cancer. 2023.", "pmid": "36111381", "doi": "10.1080/01635581.2022.2123535", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36111381/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "DIM shifts estrogen metabolism toward 2-hydroxy metabolites (less potent), potentially reducing estradiol's effectiveness for menopausal symptom control.", "clinicalSignificance": "If using DIM with estradiol HRT, monitor symptom control.", "managementStrategy": "If using DIM with estradiol HRT, monitor symptom control. DIM may reduce estradiol effectiveness. Discuss with your prescriber.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Methylprednisolone", "supplementBName": "Calcium", "interactionType": "synergy", "severity": "moderate", "description": "Like all glucocorticoids, methylprednisolone reduces calcium absorption and increases bone loss. Calcium supplementation is recommended for patients on chronic corticosteroid therapy.", "recommendation": "Supplement 1000-1200mg calcium daily during chronic methylprednisolone therapy, combined with vitamin D3.", "minimumTimeSeparation": null, "mechanism": "Glucocorticoids antagonize vitamin D-dependent intestinal calcium absorption, increase renal calcium excretion, and directly inhibit osteoblast function.", "evidenceLevel": "strong", "sources": [ { "text": "Buckley L et al. ACR guideline for glucocorticoid-induced osteoporosis prevention. Arthritis Care Res. 2017;69(8):1095-1110.", "pmid": "28585410", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28585410/", "publicSourceType": "PMID" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Like all glucocorticoids, methylprednisolone reduces calcium absorption and increases bone loss.", "clinicalSignificance": "Calcium supplementation is recommended for patients on chronic corticosteroid therapy.", "managementStrategy": "Supplement 1000-1200mg calcium daily during chronic methylprednisolone therapy, combined with vitamin D3.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Methylprednisolone", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "moderate", "description": "Methylprednisolone accelerates vitamin D catabolism. Vitamin D supplementation is standard care for glucocorticoid-induced osteoporosis prevention.", "recommendation": "Supplement 1000-2000 IU D3 daily. Monitor 25(OH)D levels.", "minimumTimeSeparation": null, "mechanism": "Glucocorticoids induce CYP24A1, accelerating vitamin D catabolism, and reduce VDR expression.", "evidenceLevel": "strong", "sources": [ { "text": "Buckley L et al. ACR guideline for glucocorticoid-induced osteoporosis. Arthritis Care Res. 2017;69(8):1095-1110.", "pmid": "28585410", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28585410/", "publicSourceType": "PMID" }, { "text": "Zhang Y, Fang F, Tang J et al.. Association between vitamin D supplementation and mortality: systematic review and meta-analysis.. BMJ. 2019.", "pmid": "31405892", "doi": "10.1136/bmj.l4673", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31405892/", "publicSourceType": "PMID" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" }, { "text": "Fiamenghi VI, Mello ED. Vitamin D deficiency in children and adolescents with obesity: a meta-analysis.. Jornal de pediatria. 2021.", "pmid": "33022267", "doi": "10.1016/j.jped.2020.08.006", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33022267/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Methylprednisolone accelerates vitamin D catabolism.", "clinicalSignificance": "Vitamin D supplementation is standard care for glucocorticoid-induced osteoporosis prevention.", "managementStrategy": "Supplement 1000-2000 IU D3 daily. Monitor 25(OH)D levels.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Dexamethasone", "supplementBName": "Calcium", "interactionType": "synergy", "severity": "moderate", "description": "Dexamethasone is the most potent oral glucocorticoid. Even short courses significantly impact calcium balance. Supplementation helps preserve bone health.", "recommendation": "Calcium 1000-1200mg/day + Vitamin D 1000-2000 IU/day during any glucocorticoid course >2 weeks.", "minimumTimeSeparation": null, "mechanism": "Dexamethasone has 25x the glucocorticoid potency of cortisol. It potently suppresses osteoblast function and calcium absorption.", "evidenceLevel": "strong", "sources": [ { "text": "Buckley L et al. ACR guideline for glucocorticoid-induced osteoporosis. Arthritis Care Res. 2017;69(8):1095-1110.", "pmid": "28585410", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28585410/", "publicSourceType": "PMID" }, { "text": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020.", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "text": "Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019.", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Dexamethasone is the most potent oral glucocorticoid.", "clinicalSignificance": "Even short courses significantly impact calcium balance.", "managementStrategy": "Calcium 1000-1200mg/day + Vitamin D 1000-2000 IU/day during any glucocorticoid course >2 weeks.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Dexamethasone", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "moderate", "description": "Dexamethasone rapidly depletes vitamin D stores through CYP24A1 induction. Supplementation is essential.", "recommendation": "Supplement 1000-2000 IU D3 daily during dexamethasone therapy.", "minimumTimeSeparation": null, "mechanism": "Dexamethasone is the strongest CYP24A1 inducer among glucocorticoids, accelerating vitamin D degradation.", "evidenceLevel": "strong", "sources": [ { "text": "Buckley L et al. ACR guideline for glucocorticoid-induced osteoporosis. Arthritis Care Res. 2017;69(8):1095-1110.", "pmid": "28585410", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28585410/", "publicSourceType": "PMID" }, { "text": "Zhang Y, Fang F, Tang J et al.. Association between vitamin D supplementation and mortality: systematic review and meta-analysis.. BMJ. 2019.", "pmid": "31405892", "doi": "10.1136/bmj.l4673", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31405892/", "publicSourceType": "PMID" }, { "text": "Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023.", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" }, { "text": "Fiamenghi VI, Mello ED. Vitamin D deficiency in children and adolescents with obesity: a meta-analysis.. Jornal de pediatria. 2021.", "pmid": "33022267", "doi": "10.1016/j.jped.2020.08.006", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33022267/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Dexamethasone rapidly depletes vitamin D stores through CYP24A1 induction.", "clinicalSignificance": "Supplementation is essential.", "managementStrategy": "Supplement 1000-2000 IU D3 daily during dexamethasone therapy.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Ibuprofen", "supplementBName": "Fish Oil", "interactionType": "caution", "severity": "moderate", "description": "Both ibuprofen and fish oil have antiplatelet effects. Combined use may modestly increase GI bleeding risk. However, the interaction is generally mild at moderate fish oil doses.", "recommendation": "Low-to-moderate fish oil (1-2g/day) is generally safe with occasional ibuprofen. Monitor for GI symptoms with chronic use of both.", "minimumTimeSeparation": null, "mechanism": "Ibuprofen inhibits COX-1/2, reducing protective GI prostaglandins and inhibiting platelet TXA2. Fish oil EPA competes with arachidonic acid, further reducing TXA2. Dual antiplatelet + GI effects.", "evidenceLevel": "moderate", "sources": [ { "text": "Bays HE. Safety considerations with omega-3 fatty acid therapy. Am J Cardiol. 2007;99(6A):35C-43C.", "pmid": "17368277", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17368277/", "publicSourceType": "PMID" }, { "text": "Tan E, Braithwaite I, McKinlay CJD et al.. Comparison of Acetaminophen (Paracetamol) With Ibuprofen for Treatment of Fever or Pain in Children Younger Than 2 Years: A Systematic Review and Meta-analysis.. JAMA Network Open. 2020.", "pmid": "33125495", "doi": "10.1001/jamanetworkopen.2020.22398", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33125495/", "publicSourceType": "PMID" }, { "text": "Miroshnychenko A, Ibrahim S, Azab M et al.. Acute Postoperative Pain Due to Dental Extraction in the Adult Population: A Systematic Review and Network Meta-analysis.. Journal of Dental Research. 2023.", "pmid": "36631957", "doi": "10.1177/00220345221139230", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36631957/", "publicSourceType": "PMID" }, { "text": "Liao Y, Xie B, Zhang H et al.. Efficacy of omega-3 PUFAs in depression: A meta-analysis.. Translational Psychiatry. 2019.", "pmid": "31383846", "doi": "10.1038/s41398-019-0515-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31383846/", "publicSourceType": "PMID" }, { "text": "Wei BZ, Li L, Dong CW et al.. The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers.. American Journal of Clinical Nutrition. 2023.", "pmid": "37028557", "doi": "10.1016/j.ajcnut.2023.04.001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37028557/", "publicSourceType": "PMID" }, { "text": "Uchida Y, Tsuji K, Ochi E. Effects of Omega-3 fatty acids supplementation and resistance training on skeletal muscle.. Clinical Nutrition ESPEN. 2024.", "pmid": "38777432", "doi": "10.1016/j.clnesp.2024.03.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38777432/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both ibuprofen and fish oil have antiplatelet effects.", "clinicalSignificance": "Combined use may modestly increase GI bleeding risk.", "managementStrategy": "Low-to-moderate fish oil (1-2g/day) is generally safe with occasional ibuprofen. Monitor for GI symptoms with chronic use of both.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Naproxen", "supplementBName": "Fish Oil", "interactionType": "caution", "severity": "moderate", "description": "Naproxen has stronger antiplatelet effects than most NSAIDs. Combined with fish oil's antiplatelet properties, there is additive bleeding risk.", "recommendation": "Use moderate fish oil doses (1-2g/day) with caution. Report unusual bruising or GI symptoms.", "minimumTimeSeparation": null, "mechanism": "Naproxen irreversibly inhibits platelet COX-1 for its dosing interval, similar to aspirin. Fish oil EPA reduces thromboxane A2 production. Additive antiplatelet effects increase bleeding risk.", "evidenceLevel": "moderate", "sources": [ { "text": "Bays HE. Safety considerations with omega-3 fatty acid therapy. Am J Cardiol. 2007;99(6A):35C-43C.", "pmid": "17368277", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17368277/", "publicSourceType": "PMID" }, { "text": "Liao Y, Xie B, Zhang H et al.. Efficacy of omega-3 PUFAs in depression: A meta-analysis.. Translational Psychiatry. 2019.", "pmid": "31383846", "doi": "10.1038/s41398-019-0515-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31383846/", "publicSourceType": "PMID" }, { "text": "Wei BZ, Li L, Dong CW et al.. The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers.. American Journal of Clinical Nutrition. 2023.", "pmid": "37028557", "doi": "10.1016/j.ajcnut.2023.04.001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37028557/", "publicSourceType": "PMID" }, { "text": "Uchida Y, Tsuji K, Ochi E. Effects of Omega-3 fatty acids supplementation and resistance training on skeletal muscle.. Clinical Nutrition ESPEN. 2024.", "pmid": "38777432", "doi": "10.1016/j.clnesp.2024.03.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38777432/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Naproxen has stronger antiplatelet effects than most NSAIDs.", "clinicalSignificance": "Combined with fish oil's antiplatelet properties, there is additive bleeding risk.", "managementStrategy": "Use moderate fish oil doses (1-2g/day) with caution. Report unusual bruising or GI symptoms.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Celecoxib", "supplementBName": "Turmeric/Curcumin", "interactionType": "caution", "severity": "moderate", "description": "Both celecoxib and curcumin inhibit COX-2. Combined use may provide additive anti-inflammatory effects but also increases the risk of GI and cardiovascular side effects.", "recommendation": "Use low-dose curcumin if combining. The additive COX-2 inhibition may increase cardiovascular and GI risk.", "minimumTimeSeparation": null, "mechanism": "Celecoxib selectively inhibits COX-2. Curcumin also inhibits COX-2 and NF-kB. Dual COX-2 inhibition may increase the anti-inflammatory effect but also the cardiovascular and renal risks associated with excessive prostaglandin suppression.", "evidenceLevel": "emerging", "sources": [ { "text": "Chainani-Wu N. Safety and anti-inflammatory activity of curcumin. J Altern Complement Med. 2003;9(1):161-168.", "pmid": "12676044", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12676044/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both celecoxib and curcumin inhibit COX-2.", "clinicalSignificance": "Combined use may provide additive anti-inflammatory effects but also increases the risk of GI and cardiovascular side effects.", "managementStrategy": "Use low-dose curcumin if combining. The additive COX-2 inhibition may increase cardiovascular and GI risk.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Donepezil", "supplementBName": "Alpha-GPC", "interactionType": "caution", "severity": "moderate", "description": "Both donepezil and Alpha-GPC increase cholinergic activity. Donepezil inhibits acetylcholinesterase; Alpha-GPC provides choline for acetylcholine synthesis. Combined use may cause cholinergic excess (nausea, diarrhea, bradycardia).", "recommendation": "If combining, start Alpha-GPC at low doses (300mg) and monitor for cholinergic side effects (nausea, diarrhea, muscle cramps, bradycardia).", "minimumTimeSeparation": null, "mechanism": "Donepezil inhibits AChE, increasing synaptic ACh. Alpha-GPC provides additional choline substrate for ACh synthesis. Dual cholinergic enhancement can cause parasympathomimetic excess.", "evidenceLevel": "emerging", "sources": [ { "text": "De Jesus Moreno Moreno M. Cognitive improvement in mild to moderate Alzheimer's dementia after treatment with the acetylcholine precursor choline alfoscerate. Clin Ther. 2003;25(1):178-193.", "pmid": "12637119", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12637119/", "publicSourceType": "PMID" }, { "text": "Kerksick CM. Acute Alpha-Glycerylphosphorylcholine Supplementation Enhances Cognitive Performance in Healthy Men. Nutrients. 2024.", "pmid": "39683633", "doi": "10.3390/nu16234240", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39683633/", "publicSourceType": "PMID" }, { "text": "Sagaro GG, Traini E, Amenta F. Activity of Choline Alphoscerate on Adult-Onset Cognitive Dysfunctions: A Systematic Review and Meta-Analysis. J Alzheimers Dis. 2023.", "pmid": "36683513", "doi": "10.3233/JAD-221189", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36683513/", "publicSourceType": "PMID" }, { "text": "Yamashita S, Kawada N, Wang W et al.. Effects of egg yolk choline intake on cognitive functions and plasma choline levels in healthy middle-aged and older Japanese: a randomized double-blinded placebo-controlled parallel-group study. Lipids Health Dis. 2023.", "pmid": "37340479", "doi": "10.1186/s12944-023-01844-w", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37340479/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both donepezil and Alpha-GPC increase cholinergic activity.", "clinicalSignificance": "Donepezil inhibits acetylcholinesterase; Alpha-GPC provides choline for acetylcholine synthesis.", "managementStrategy": "If combining, start Alpha-GPC at low doses (300mg) and monitor for cholinergic side effects (nausea, diarrhea, muscle cramps, bradycardia).", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Donepezil", "supplementBName": "Ginkgo Biloba", "interactionType": "caution", "severity": "moderate", "description": "Both donepezil and ginkgo biloba have cholinergic and cognitive effects. Some studies have explored the combination, but additive cholinergic side effects and ginkgo's antiplatelet activity warrant caution.", "recommendation": "May be used under medical supervision for cognitive support. Monitor for GI side effects and bleeding signs.", "minimumTimeSeparation": null, "mechanism": "Ginkgo biloba inhibits platelet-activating factor (PAF) and may have mild AChE inhibitory effects. Combined with donepezil's potent AChE inhibition, cholinergic effects may be additive.", "evidenceLevel": "moderate", "sources": [ { "text": "Yancheva S et al. Ginkgo biloba extract EGb 761, donepezil or both combined in the treatment of Alzheimer's disease with neuropsychiatric features. Aging Ment Health. 2009;13(2):183-190.", "pmid": "19347685", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19347685/", "publicSourceType": "PMID" }, { "text": "Mousavi SN, Hosseinikia M, Yousefi Rad E, Saboori S. Beneficial effects of Ginkgo biloba leaf extract on inflammatory markers: A systematic review and meta-analysis of the clinical trials. Phytotherapy Research. 2022.", "pmid": "35781715", "doi": "10.1002/ptr.7544", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35781715/", "publicSourceType": "PMID" }, { "text": "Tabrizi R, Nowrouzi-Sohrabi P, Hessami K et al.. Effects of Ginkgo biloba intake on cardiometabolic parameters in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of clinical trials. Phytotherapy Research. 2020.", "pmid": "33090588", "doi": "10.1002/ptr.6822", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33090588/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both donepezil and ginkgo biloba have cholinergic and cognitive effects.", "clinicalSignificance": "Some studies have explored the combination, but additive cholinergic side effects and ginkgo's antiplatelet activity warrant caution.", "managementStrategy": "May be used under medical supervision for cognitive support. Monitor for GI side effects and bleeding signs.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Sildenafil", "supplementBName": "L-Arginine", "interactionType": "caution", "severity": "moderate", "description": "L-arginine is a nitric oxide precursor, and sildenafil enhances NO/cGMP signaling by inhibiting PDE5. Combined use can cause additive vasodilation and significant hypotension.", "recommendation": "Use caution when combining. Start L-arginine at low doses. Monitor for headache, dizziness, flushing, and low blood pressure. Do NOT combine with nitrates.", "minimumTimeSeparation": null, "mechanism": "L-arginine → NO (via eNOS) → activates guanylyl cyclase → cGMP → vasodilation. Sildenafil inhibits PDE5, preventing cGMP breakdown. The combination amplifies the NO/cGMP vasodilatory cascade.", "evidenceLevel": "moderate", "sources": [ { "text": "Stanislavov R, Nikolova V. Treatment of erectile dysfunction with pycnogenol and L-arginine. J Sex Marital Ther. 2003;29(3):207-213.", "pmid": "12851125", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12851125/", "publicSourceType": "PMID" }, { "text": "Viribay A, Burgos J, Fernández-Landa J, Seco-Calvo J, Mielgo-Ayuso J. Effects of Arginine Supplementation on Athletic Performance Based on Energy Metabolism: A Systematic Review and Meta-Analysis. Nutrients. 2020.", "pmid": "32370176", "doi": "10.3390/nu12051300", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32370176/", "publicSourceType": "PMID" }, { "text": "Rezaei S, Gholamalizadeh M, Tabrizi R et al.. The effect of L-arginine supplementation on maximal oxygen uptake: A systematic review and meta-analysis. Physiological Reports. 2021.", "pmid": "33587327", "doi": "10.14814/phy2.14739", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33587327/", "publicSourceType": "PMID" }, { "text": "Hadi A, Arab A, Moradi S et al.. The effect of l-arginine supplementation on lipid profile: a systematic review and meta-analysis of randomised controlled trials. British Journal of Nutrition. 2019.", "pmid": "31922465", "doi": "10.1017/S0007114519001855", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31922465/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "L-arginine is a nitric oxide precursor, and sildenafil enhances NO/cGMP signaling by inhibiting PDE5.", "clinicalSignificance": "Combined use can cause additive vasodilation and significant hypotension.", "managementStrategy": "Use caution when combining. Start L-arginine at low doses. Monitor for headache, dizziness, flushing, and low blood pressure. Do NOT combine with nitrates.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Tadalafil", "supplementBName": "L-Arginine", "interactionType": "caution", "severity": "moderate", "description": "Same mechanism as sildenafil + L-arginine. Tadalafil has a 36-hour half-life, making the interaction window much longer than sildenafil.", "recommendation": "Use caution. Tadalafil's long duration means the vasodilatory interaction persists for 1-2 days. Start L-arginine at low doses.", "minimumTimeSeparation": null, "mechanism": "L-arginine increases NO production. Tadalafil inhibits PDE5 (with 36hr half-life). Prolonged amplification of NO/cGMP pathway causes sustained vasodilation.", "evidenceLevel": "moderate", "sources": [ { "text": "Stanislavov R, Nikolova V. Treatment of erectile dysfunction with pycnogenol and L-arginine. J Sex Marital Ther. 2003;29(3):207-213.", "pmid": "12851125", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12851125/", "publicSourceType": "PMID" }, { "text": "Viribay A, Burgos J, Fernández-Landa J, Seco-Calvo J, Mielgo-Ayuso J. Effects of Arginine Supplementation on Athletic Performance Based on Energy Metabolism: A Systematic Review and Meta-Analysis. Nutrients. 2020.", "pmid": "32370176", "doi": "10.3390/nu12051300", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32370176/", "publicSourceType": "PMID" }, { "text": "Rezaei S, Gholamalizadeh M, Tabrizi R et al.. The effect of L-arginine supplementation on maximal oxygen uptake: A systematic review and meta-analysis. Physiological Reports. 2021.", "pmid": "33587327", "doi": "10.14814/phy2.14739", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33587327/", "publicSourceType": "PMID" }, { "text": "Hadi A, Arab A, Moradi S et al.. The effect of l-arginine supplementation on lipid profile: a systematic review and meta-analysis of randomised controlled trials. British Journal of Nutrition. 2019.", "pmid": "31922465", "doi": "10.1017/S0007114519001855", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31922465/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Same mechanism as sildenafil + L-arginine.", "clinicalSignificance": "Tadalafil has a 36-hour half-life, making the interaction window much longer than sildenafil.", "managementStrategy": "Use caution. Tadalafil's long duration means the vasodilatory interaction persists for 1-2 days. Start L-arginine at low doses.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Sildenafil", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "moderate", "description": "St. John's Wort induces CYP3A4, the primary enzyme metabolizing sildenafil. This can reduce sildenafil effectiveness.", "recommendation": "Avoid SJW with sildenafil as it may reduce its effectiveness.", "minimumTimeSeparation": null, "mechanism": "Sildenafil is metabolized by CYP3A4 (major) and CYP2C9 (minor). CYP3A4 induction by SJW increases sildenafil clearance, reducing its duration and peak effect.", "evidenceLevel": "moderate", "sources": [ { "text": "Moore LB et al. St. John's wort induces hepatic drug metabolism through PXR. Proc Natl Acad Sci USA. 2000;97(13):7500-7502.", "pmid": "10852961", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10852961/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "St.", "clinicalSignificance": "John's Wort induces CYP3A4, the primary enzyme metabolizing sildenafil.", "managementStrategy": "Avoid SJW with sildenafil as it may reduce its effectiveness.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Pregabalin", "supplementBName": "Valerian Root", "interactionType": "caution", "severity": "moderate", "description": "Both pregabalin and valerian have sedating properties. Pregabalin binds alpha-2-delta calcium channel subunits; valerian modulates GABA-A. Combined sedation may cause excessive drowsiness.", "recommendation": "If combining, use low valerian doses and monitor for excessive sedation, dizziness, and coordination problems.", "minimumTimeSeparation": null, "mechanism": "Pregabalin reduces excitatory neurotransmitter release via alpha-2-delta subunit binding. Valerian enhances GABAergic inhibition. Different CNS depressant mechanisms produce additive sedation.", "evidenceLevel": "moderate", "sources": [ { "text": "Finnerup NB et al. Pharmacotherapy for neuropathic pain in adults. Lancet Neurol. 2015;14(2):162-173.", "pmid": "25575710", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25575710/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Both pregabalin and valerian have sedating properties.", "clinicalSignificance": "Pregabalin binds alpha-2-delta calcium channel subunits; valerian modulates GABA-A.", "managementStrategy": "If combining, use low valerian doses and monitor for excessive sedation, dizziness, and coordination problems.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "MAOIs", "supplementBName": "Tyramine / High-Tyramine Foods", "interactionType": "contraindicated", "severity": "dangerous", "description": "Irreversible MAO inhibitors can sharply reduce tyramine breakdown. High-tyramine foods can then trigger sudden, severe blood-pressure elevation and hypertensive crisis.", "recommendation": "Avoid high-tyramine foods while taking irreversible MAOIs and continue the MAOI diet for the prescriber-recommended washout period after stopping.", "minimumTimeSeparation": null, "mechanism": "MAO-A normally metabolizes dietary tyramine. When MAO-A is inhibited, tyramine can provoke excessive norepinephrine release and dangerous blood-pressure elevation.", "evidenceLevel": "strong", "sources": [ { "text": "McCabe-Sellers BJ et al. Dietary tyramine and other pressor amines in MAOI regimens: a review. J Am Diet Assoc. 1986.", "pmid": "3525654", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3525654/", "publicSourceType": "PMID" }, { "text": "VanDenBerg CM et al. Clinically Relevant Drug Interactions with Monoamine Oxidase Inhibitors. CNS Drugs. 2022.", "pmid": "36425231", "doi": "10.1007/s40263-022-00967-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36425231/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "High tyramine exposure during MAOI therapy can cause hypertensive crisis.", "clinicalSignificance": "Hypertensive crisis can cause severe headache, chest pain, neurologic symptoms, myocardial injury, stroke, or other end-organ damage.", "managementStrategy": "Avoid high-tyramine foods and review diet instructions with the prescriber/pharmacist before and during MAOI therapy.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "MAOIs", "supplementBName": "5-HTP", "interactionType": "contraindicated", "severity": "dangerous", "description": "5-HTP increases serotonin synthesis while MAOIs reduce monoamine breakdown. Combining them can cause dangerous serotonergic excess and serotonin syndrome.", "recommendation": "Do NOT combine 5-HTP with MAOIs. Use only if the prescriber managing the MAOI explicitly directs it and provides washout instructions.", "minimumTimeSeparation": null, "mechanism": "5-HTP bypasses tryptophan hydroxylase to increase serotonin production; MAOIs inhibit serotonin breakdown.", "evidenceLevel": "strong", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Additive serotonergic activity can cause serotonin syndrome.", "clinicalSignificance": "Serotonin syndrome can be life-threatening.", "managementStrategy": "Avoid combination and follow prescriber-directed washout guidance.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "MAOIs", "supplementBName": "L-Tryptophan", "interactionType": "contraindicated", "severity": "dangerous", "description": "L-Tryptophan feeds serotonin synthesis while MAOIs reduce serotonin breakdown, increasing risk of serotonin syndrome.", "recommendation": "Do NOT combine L-tryptophan with MAOIs unless specifically directed and monitored by the prescriber managing the MAOI.", "minimumTimeSeparation": null, "mechanism": "Tryptophan is converted to 5-HTP and then serotonin; MAOIs reduce monoamine breakdown.", "evidenceLevel": "strong", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Additive serotonergic activity can cause serotonin syndrome.", "clinicalSignificance": "Serotonin syndrome can be life-threatening.", "managementStrategy": "Avoid combination and follow prescriber-directed washout guidance.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Phenelzine", "supplementBName": "Tyramine / High-Tyramine Foods", "interactionType": "contraindicated", "severity": "dangerous", "description": "Phenelzine is an irreversible MAOI that can sharply reduce tyramine breakdown. High-tyramine foods can then trigger sudden, severe blood-pressure elevation and hypertensive crisis.", "recommendation": "Avoid high-tyramine foods while taking Phenelzine and continue the MAOI diet for the prescriber-recommended washout period after stopping.", "minimumTimeSeparation": null, "mechanism": "MAO-A normally metabolizes dietary tyramine. When MAO-A is inhibited, tyramine can provoke excessive norepinephrine release and dangerous blood-pressure elevation.", "evidenceLevel": "strong", "sources": [ { "text": "McCabe-Sellers BJ et al. Dietary tyramine and other pressor amines in MAOI regimens: a review. J Am Diet Assoc. 1986.", "pmid": "3525654", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3525654/", "publicSourceType": "PMID" }, { "text": "VanDenBerg CM et al. Clinically Relevant Drug Interactions with Monoamine Oxidase Inhibitors. CNS Drugs. 2022.", "pmid": "36425231", "doi": "10.1007/s40263-022-00967-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36425231/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "High tyramine exposure during Phenelzine therapy can cause hypertensive crisis.", "clinicalSignificance": "Hypertensive crisis can cause severe headache, chest pain, neurologic symptoms, myocardial injury, stroke, or other end-organ damage.", "managementStrategy": "Avoid high-tyramine foods and review diet instructions with the prescriber/pharmacist before and during MAOI therapy.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Phenelzine", "supplementBName": "5-HTP", "interactionType": "contraindicated", "severity": "dangerous", "description": "5-HTP increases serotonin synthesis while Phenelzine reduces monoamine breakdown. Combining them can cause dangerous serotonergic excess and serotonin syndrome.", "recommendation": "Do NOT combine 5-HTP with Phenelzine. Use only if the prescriber managing Phenelzine explicitly directs it and provides washout instructions.", "minimumTimeSeparation": null, "mechanism": "5-HTP bypasses tryptophan hydroxylase to increase serotonin production; MAOIs inhibit serotonin breakdown.", "evidenceLevel": "strong", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Additive serotonergic activity can cause serotonin syndrome.", "clinicalSignificance": "Serotonin syndrome can be life-threatening.", "managementStrategy": "Avoid combination and follow prescriber-directed washout guidance.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Phenelzine", "supplementBName": "L-Tryptophan", "interactionType": "contraindicated", "severity": "dangerous", "description": "L-Tryptophan feeds serotonin synthesis while Phenelzine reduces serotonin breakdown, increasing risk of serotonin syndrome.", "recommendation": "Do NOT combine L-tryptophan with Phenelzine unless specifically directed and monitored by the prescriber managing Phenelzine.", "minimumTimeSeparation": null, "mechanism": "Tryptophan is converted to 5-HTP and then serotonin; MAOIs reduce monoamine breakdown.", "evidenceLevel": "strong", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Additive serotonergic activity can cause serotonin syndrome.", "clinicalSignificance": "Serotonin syndrome can be life-threatening.", "managementStrategy": "Avoid combination and follow prescriber-directed washout guidance.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Tranylcypromine", "supplementBName": "Tyramine / High-Tyramine Foods", "interactionType": "contraindicated", "severity": "dangerous", "description": "Tranylcypromine is an irreversible MAOI that can sharply reduce tyramine breakdown. High-tyramine foods can then trigger sudden, severe blood-pressure elevation and hypertensive crisis.", "recommendation": "Avoid high-tyramine foods while taking Tranylcypromine and continue the MAOI diet for the prescriber-recommended washout period after stopping.", "minimumTimeSeparation": null, "mechanism": "MAO-A normally metabolizes dietary tyramine. When MAO-A is inhibited, tyramine can provoke excessive norepinephrine release and dangerous blood-pressure elevation.", "evidenceLevel": "strong", "sources": [ { "text": "McCabe-Sellers BJ et al. Dietary tyramine and other pressor amines in MAOI regimens: a review. J Am Diet Assoc. 1986.", "pmid": "3525654", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3525654/", "publicSourceType": "PMID" }, { "text": "VanDenBerg CM et al. Clinically Relevant Drug Interactions with Monoamine Oxidase Inhibitors. CNS Drugs. 2022.", "pmid": "36425231", "doi": "10.1007/s40263-022-00967-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36425231/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "High tyramine exposure during Tranylcypromine therapy can cause hypertensive crisis.", "clinicalSignificance": "Hypertensive crisis can cause severe headache, chest pain, neurologic symptoms, myocardial injury, stroke, or other end-organ damage.", "managementStrategy": "Avoid high-tyramine foods and review diet instructions with the prescriber/pharmacist before and during MAOI therapy.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Tranylcypromine", "supplementBName": "5-HTP", "interactionType": "contraindicated", "severity": "dangerous", "description": "5-HTP increases serotonin synthesis while Tranylcypromine reduces monoamine breakdown. Combining them can cause dangerous serotonergic excess and serotonin syndrome.", "recommendation": "Do NOT combine 5-HTP with Tranylcypromine. Use only if the prescriber managing Tranylcypromine explicitly directs it and provides washout instructions.", "minimumTimeSeparation": null, "mechanism": "5-HTP bypasses tryptophan hydroxylase to increase serotonin production; MAOIs inhibit serotonin breakdown.", "evidenceLevel": "strong", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Additive serotonergic activity can cause serotonin syndrome.", "clinicalSignificance": "Serotonin syndrome can be life-threatening.", "managementStrategy": "Avoid combination and follow prescriber-directed washout guidance.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Tranylcypromine", "supplementBName": "L-Tryptophan", "interactionType": "contraindicated", "severity": "dangerous", "description": "L-Tryptophan feeds serotonin synthesis while Tranylcypromine reduces serotonin breakdown, increasing risk of serotonin syndrome.", "recommendation": "Do NOT combine L-tryptophan with Tranylcypromine unless specifically directed and monitored by the prescriber managing Tranylcypromine.", "minimumTimeSeparation": null, "mechanism": "Tryptophan is converted to 5-HTP and then serotonin; MAOIs reduce monoamine breakdown.", "evidenceLevel": "strong", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Additive serotonergic activity can cause serotonin syndrome.", "clinicalSignificance": "Serotonin syndrome can be life-threatening.", "managementStrategy": "Avoid combination and follow prescriber-directed washout guidance.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Isocarboxazid", "supplementBName": "Tyramine / High-Tyramine Foods", "interactionType": "contraindicated", "severity": "dangerous", "description": "Isocarboxazid is an irreversible MAOI that can sharply reduce tyramine breakdown. High-tyramine foods can then trigger sudden, severe blood-pressure elevation and hypertensive crisis.", "recommendation": "Avoid high-tyramine foods while taking Isocarboxazid and continue the MAOI diet for the prescriber-recommended washout period after stopping.", "minimumTimeSeparation": null, "mechanism": "MAO-A normally metabolizes dietary tyramine. When MAO-A is inhibited, tyramine can provoke excessive norepinephrine release and dangerous blood-pressure elevation.", "evidenceLevel": "strong", "sources": [ { "text": "McCabe-Sellers BJ et al. Dietary tyramine and other pressor amines in MAOI regimens: a review. J Am Diet Assoc. 1986.", "pmid": "3525654", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3525654/", "publicSourceType": "PMID" }, { "text": "VanDenBerg CM et al. Clinically Relevant Drug Interactions with Monoamine Oxidase Inhibitors. CNS Drugs. 2022.", "pmid": "36425231", "doi": "10.1007/s40263-022-00967-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36425231/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "High tyramine exposure during Isocarboxazid therapy can cause hypertensive crisis.", "clinicalSignificance": "Hypertensive crisis can cause severe headache, chest pain, neurologic symptoms, myocardial injury, stroke, or other end-organ damage.", "managementStrategy": "Avoid high-tyramine foods and review diet instructions with the prescriber/pharmacist before and during MAOI therapy.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Isocarboxazid", "supplementBName": "5-HTP", "interactionType": "contraindicated", "severity": "dangerous", "description": "5-HTP increases serotonin synthesis while Isocarboxazid reduces monoamine breakdown. Combining them can cause dangerous serotonergic excess and serotonin syndrome.", "recommendation": "Do NOT combine 5-HTP with Isocarboxazid. Use only if the prescriber managing Isocarboxazid explicitly directs it and provides washout instructions.", "minimumTimeSeparation": null, "mechanism": "5-HTP bypasses tryptophan hydroxylase to increase serotonin production; MAOIs inhibit serotonin breakdown.", "evidenceLevel": "strong", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Additive serotonergic activity can cause serotonin syndrome.", "clinicalSignificance": "Serotonin syndrome can be life-threatening.", "managementStrategy": "Avoid combination and follow prescriber-directed washout guidance.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Isocarboxazid", "supplementBName": "L-Tryptophan", "interactionType": "contraindicated", "severity": "dangerous", "description": "L-Tryptophan feeds serotonin synthesis while Isocarboxazid reduces serotonin breakdown, increasing risk of serotonin syndrome.", "recommendation": "Do NOT combine L-tryptophan with Isocarboxazid unless specifically directed and monitored by the prescriber managing Isocarboxazid.", "minimumTimeSeparation": null, "mechanism": "Tryptophan is converted to 5-HTP and then serotonin; MAOIs reduce monoamine breakdown.", "evidenceLevel": "strong", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Additive serotonergic activity can cause serotonin syndrome.", "clinicalSignificance": "Serotonin syndrome can be life-threatening.", "managementStrategy": "Avoid combination and follow prescriber-directed washout guidance.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Selegiline", "supplementBName": "Tyramine / High-Tyramine Foods", "interactionType": "contraindicated", "severity": "dangerous", "description": "Selegiline can act as a monoamine oxidase inhibitor depending on formulation and dose. Systemic or higher-dose MAOI exposure can reduce tyramine breakdown, so high-tyramine foods may trigger sudden, severe blood-pressure elevation and hypertensive crisis.", "recommendation": "Follow the prescriber-specific tyramine restrictions for your selegiline formulation and dose. Avoid high-tyramine foods whenever MAOI dietary restrictions apply.", "minimumTimeSeparation": null, "mechanism": "MAO-A normally metabolizes dietary tyramine. When MAO-A is substantially inhibited, tyramine can provoke excessive norepinephrine release and dangerous blood-pressure elevation; selegiline selectivity varies by dose and formulation.", "evidenceLevel": "strong", "sources": [ { "text": "McCabe-Sellers BJ et al. Dietary tyramine and other pressor amines in MAOI regimens: a review. J Am Diet Assoc. 1986.", "pmid": "3525654", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3525654/", "publicSourceType": "PMID" }, { "text": "VanDenBerg CM et al. Clinically Relevant Drug Interactions with Monoamine Oxidase Inhibitors. CNS Drugs. 2022.", "pmid": "36425231", "doi": "10.1007/s40263-022-00967-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36425231/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "High tyramine exposure during clinically relevant MAOI activity can cause hypertensive crisis.", "clinicalSignificance": "Risk depends on formulation and dose, but hypertensive crisis can cause severe headache, chest pain, neurologic symptoms, myocardial injury, stroke, or other end-organ damage.", "managementStrategy": "Review tyramine diet instructions with the prescriber/pharmacist and follow formulation-specific restrictions.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Selegiline", "supplementBName": "5-HTP", "interactionType": "contraindicated", "severity": "dangerous", "description": "5-HTP increases serotonin synthesis while Selegiline reduces monoamine breakdown. Combining them can cause dangerous serotonergic excess and serotonin syndrome.", "recommendation": "Do NOT combine 5-HTP with Selegiline. Use only if the prescriber managing Selegiline explicitly directs it and provides washout instructions.", "minimumTimeSeparation": null, "mechanism": "5-HTP bypasses tryptophan hydroxylase to increase serotonin production; MAOIs inhibit serotonin breakdown.", "evidenceLevel": "strong", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Additive serotonergic activity can cause serotonin syndrome.", "clinicalSignificance": "Serotonin syndrome can be life-threatening.", "managementStrategy": "Avoid combination and follow prescriber-directed washout guidance.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Selegiline", "supplementBName": "L-Tryptophan", "interactionType": "contraindicated", "severity": "dangerous", "description": "L-Tryptophan feeds serotonin synthesis while Selegiline reduces serotonin breakdown, increasing risk of serotonin syndrome.", "recommendation": "Do NOT combine L-tryptophan with Selegiline unless specifically directed and monitored by the prescriber managing Selegiline.", "minimumTimeSeparation": null, "mechanism": "Tryptophan is converted to 5-HTP and then serotonin; MAOIs reduce monoamine breakdown.", "evidenceLevel": "strong", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Additive serotonergic activity can cause serotonin syndrome.", "clinicalSignificance": "Serotonin syndrome can be life-threatening.", "managementStrategy": "Avoid combination and follow prescriber-directed washout guidance.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Simvastatin", "supplementBName": "Grapefruit Juice", "interactionType": "contraindicated", "severity": "dangerous", "description": "Grapefruit juice inhibits intestinal CYP3A4 and can substantially increase simvastatin exposure, raising myopathy and rhabdomyolysis risk.", "recommendation": "Avoid grapefruit and grapefruit juice while taking simvastatin unless your prescriber specifically says otherwise.", "minimumTimeSeparation": null, "mechanism": "Furanocoumarins in grapefruit inhibit intestinal CYP3A4, reducing first-pass metabolism of simvastatin.", "evidenceLevel": "strong", "sources": [ { "text": "Bailey DG et al. Grapefruit juice-drug interactions. Br J Clin Pharmacol. 1998.", "pmid": "9723817", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9723817/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bAffectsA", "effect": "Increased simvastatin exposure can increase muscle toxicity risk.", "clinicalSignificance": "Simvastatin is highly CYP3A4-sensitive and grapefruit avoidance is the safest default.", "managementStrategy": "Avoid grapefruit products or ask the prescriber about a non-CYP3A4 statin.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Lovastatin", "supplementBName": "Grapefruit Juice", "interactionType": "contraindicated", "severity": "dangerous", "description": "Grapefruit juice inhibits intestinal CYP3A4 and can substantially increase lovastatin exposure, raising myopathy and rhabdomyolysis risk.", "recommendation": "Avoid grapefruit and grapefruit juice while taking lovastatin unless your prescriber specifically says otherwise.", "minimumTimeSeparation": null, "mechanism": "Furanocoumarins in grapefruit inhibit intestinal CYP3A4, reducing first-pass metabolism of lovastatin.", "evidenceLevel": "strong", "sources": [ { "text": "Bailey DG et al. Grapefruit juice-drug interactions. Br J Clin Pharmacol. 1998.", "pmid": "9723817", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9723817/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bAffectsA", "effect": "Increased lovastatin exposure can increase muscle toxicity risk.", "clinicalSignificance": "Lovastatin is highly CYP3A4-sensitive and grapefruit avoidance is the safest default.", "managementStrategy": "Avoid grapefruit products or ask the prescriber about a non-CYP3A4 statin.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Atorvastatin", "supplementBName": "Grapefruit Juice", "interactionType": "caution", "severity": "serious", "description": "Grapefruit juice inhibits intestinal CYP3A4 and can increase atorvastatin exposure, raising muscle-toxicity risk especially with large or repeated grapefruit intake.", "recommendation": "Avoid large or repeated grapefruit intake while taking atorvastatin; ask your prescriber or pharmacist about your specific dose and risk.", "minimumTimeSeparation": null, "mechanism": "Furanocoumarins in grapefruit inhibit intestinal CYP3A4, reducing first-pass metabolism of atorvastatin.", "evidenceLevel": "strong", "sources": [ { "text": "Bailey DG et al. Grapefruit juice-drug interactions. Br J Clin Pharmacol. 1998.", "pmid": "9723817", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9723817/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Increased atorvastatin exposure can increase muscle toxicity risk.", "clinicalSignificance": "Risk is lower than simvastatin/lovastatin but still clinically relevant with high grapefruit exposure or high statin doses.", "managementStrategy": "Avoid large grapefruit intake and monitor for unexplained muscle pain, weakness, or dark urine.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Benazepril", "supplementBName": "Potassium", "interactionType": "caution", "severity": "serious", "description": "Benazepril blocks angiotensin II formation, which lowers aldosterone and reduces renal potassium excretion. Adding a potassium supplement on top of this can push serum potassium into hyperkalemic territory, risking muscle weakness, cardiac arrhythmias, and in severe cases cardiac arrest. Risk is highest in patients with kidney disease, diabetes, or those also taking NSAIDs, potassium-sparing diuretics, or trimethoprim.", "recommendation": "Do not take potassium supplements with benazepril unless your prescriber has confirmed a deficiency and ordered them. If both are required, have potassium levels checked within 1-2 weeks of starting and then periodically. Avoid potassium-based salt substitutes as well.", "minimumTimeSeparation": null, "mechanism": "ACE inhibition reduces angiotensin II-driven aldosterone secretion at the adrenal zona glomerulosa, decreasing potassium excretion at the cortical collecting duct. Exogenous potassium then accumulates because renal handling is impaired.", "evidenceLevel": "strong", "sources": [ { "text": "Reardon LC, Macpherson DS. Hyperkalemia in outpatients using angiotensin-converting enzyme inhibitors. How much should we worry? Arch Intern Med. 1998;158(1):26-32.", "pmid": "9437375", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9437375/", "publicSourceType": "PMID" }, { "text": "Mann JF, Yi QL, Sleight P, Dagenais GR, Gerstein HC, Lonn EM, Bosch J; HOPE Investigators. Serum potassium, cardiovascular risk, and effects of an ACE inhibitor: results of the HOPE study. Clin Nephrol. 2005;63(3):181-7.", "pmid": "15786818", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15786818/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Benazepril impairs potassium excretion; added supplemental potassium drives hyperkalemia.", "clinicalSignificance": "Even modest potassium loads can cause dangerous arrhythmias in patients on ACE inhibitors, especially with reduced kidney function.", "managementStrategy": "Avoid potassium supplements and potassium salt substitutes; monitor labs if combination is unavoidable.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Irbesartan", "supplementBName": "Potassium", "interactionType": "caution", "severity": "serious", "description": "Irbesartan blocks the angiotensin II type 1 receptor, suppressing aldosterone and reducing renal potassium excretion. Combining it with a potassium supplement increases the risk of hyperkalemia, which can cause muscle weakness, paresthesias, and life-threatening arrhythmias. Patients with chronic kidney disease, diabetes, heart failure, or those on NSAIDs are at the highest risk.", "recommendation": "Do not take potassium supplements alongside irbesartan unless your prescriber has documented a deficiency and is monitoring you. If combined use is necessary, check serum potassium within 1-2 weeks of starting and at every dose change. Avoid potassium-containing salt substitutes.", "minimumTimeSeparation": null, "mechanism": "Angiotensin II type 1 receptor blockade reduces aldosterone-mediated potassium secretion at the cortical collecting duct. Exogenous potassium then accumulates because renal handling is impaired.", "evidenceLevel": "strong", "sources": [ { "text": "Espinel E, Joven J, Gil I, Suñé P, Renedo B, Fort J, Serón D. Risk of hyperkalemia in patients with moderate chronic kidney disease initiating angiotensin converting enzyme inhibitors or angiotensin receptor blockers: a randomized study. BMC Res Notes. 2013;6:306.", "pmid": "23915518", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23915518/", "publicSourceType": "PMID" }, { "text": "Heerspink HJ, Gao P, de Zeeuw D, Clase C, Dagenais GR, Sleight P, Lonn E, Teo KT, Yusuf S, Mann JF. The effect of ramipril and telmisartan on serum potassium and its association with cardiovascular and renal events: results from the ONTARGET trial. Eur J Prev Cardiol. 2014;21(3):299-309.", "pmid": "24191305", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24191305/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Irbesartan reduces potassium excretion; supplemental potassium then drives hyperkalemia.", "clinicalSignificance": "Hyperkalemia on ARBs can be silent until it produces dangerous arrhythmias.", "managementStrategy": "Avoid potassium supplements and salt substitutes; if combined, monitor potassium and renal function regularly.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Olmesartan", "supplementBName": "Potassium", "interactionType": "caution", "severity": "serious", "description": "Olmesartan blocks the angiotensin II type 1 receptor, suppressing aldosterone and reducing renal potassium excretion. Adding a potassium supplement can produce hyperkalemia, especially in older adults, patients with kidney disease or diabetes, or those also taking NSAIDs, potassium-sparing diuretics, or trimethoprim. Hyperkalemia can be silent until it triggers arrhythmias.", "recommendation": "Avoid potassium supplements while taking olmesartan unless a deficiency has been confirmed by your prescriber. If both are needed, get potassium checked within 1-2 weeks of starting and after any dose change. Skip potassium-based salt substitutes.", "minimumTimeSeparation": null, "mechanism": "AT1 receptor blockade reduces aldosterone secretion and lowers potassium excretion at the cortical collecting duct, so any exogenous potassium load accumulates rather than being eliminated.", "evidenceLevel": "strong", "sources": [ { "text": "Espinel E, Joven J, Gil I, Suñé P, Renedo B, Fort J, Serón D. Risk of hyperkalemia in patients with moderate chronic kidney disease initiating angiotensin converting enzyme inhibitors or angiotensin receptor blockers: a randomized study. BMC Res Notes. 2013;6:306.", "pmid": "23915518", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23915518/", "publicSourceType": "PMID" }, { "text": "Reardon LC, Macpherson DS. Hyperkalemia in outpatients using angiotensin-converting enzyme inhibitors. How much should we worry? Arch Intern Med. 1998;158(1):26-32.", "pmid": "9437375", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9437375/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Olmesartan impairs renal potassium excretion; added potassium drives hyperkalemia.", "clinicalSignificance": "Even modest potassium loads can cause dangerous arrhythmias in patients on ARBs.", "managementStrategy": "Avoid potassium supplements and salt substitutes; monitor labs if combined use is unavoidable.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Sacubitril/Valsartan", "supplementBName": "Potassium", "interactionType": "caution", "severity": "serious", "description": "Sacubitril/valsartan combines neprilysin inhibition with angiotensin receptor blockade and meaningfully raises serum potassium by suppressing aldosterone. In the PARADIGM-HF heart-failure trial, hyperkalemia greater than 5.4 mmol/L occurred in roughly 20% of treated patients. Adding a potassium supplement on top of this layered RAAS blockade can push potassium into dangerous territory, particularly in patients with chronic kidney disease or those also on spironolactone, eplerenone, or NSAIDs.", "recommendation": "Do not take potassium supplements with sacubitril/valsartan unless your cardiologist has confirmed a true deficiency. If both are needed, get potassium checked within 1-2 weeks of starting and after every dose change. Avoid potassium-containing salt substitutes.", "minimumTimeSeparation": null, "mechanism": "Valsartan blocks the AT1 receptor and suppresses aldosterone-mediated potassium secretion. Sacubitril, as a neprilysin inhibitor, raises natriuretic peptides and can amplify natriuresis but does not offset the potassium retention; in heart failure patients, hyperkalemia remains a recognized class effect.", "evidenceLevel": "strong", "sources": [ { "text": "Desai AS, Vardeny O, Claggett B, McMurray JJ, Packer M, Swedberg K, Rouleau JL, Zile MR, Lefkowitz M, Shi V, Solomon SD. Reduced Risk of Hyperkalemia During Treatment of Heart Failure With Mineralocorticoid Receptor Antagonists by Use of Sacubitril/Valsartan Compared With Enalapril: A Secondary Analysis of the PARADIGM-HF Trial. JAMA Cardiol. 2017;2(1):79-85.", "pmid": "27842179", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27842179/", "publicSourceType": "PMID" }, { "text": "Heerspink HJ, Gao P, de Zeeuw D, Clase C, Dagenais GR, Sleight P, Lonn E, Teo KT, Yusuf S, Mann JF. The effect of ramipril and telmisartan on serum potassium and its association with cardiovascular and renal events: results from the ONTARGET trial. Eur J Prev Cardiol. 2014;21(3):299-309.", "pmid": "24191305", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24191305/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Sacubitril/valsartan suppresses aldosterone; supplemental potassium drives hyperkalemia.", "clinicalSignificance": "Heart failure patients on sacubitril/valsartan are already prone to hyperkalemia; any potassium load amplifies arrhythmia risk.", "managementStrategy": "Avoid potassium supplements and salt substitutes; monitor potassium frequently if combined.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Enalapril", "supplementBName": "Lithium Orotate", "interactionType": "caution", "severity": "serious", "description": "Enalapril reduces sodium reabsorption and lowers glomerular filtration, which causes the kidney to retain lithium and pushes serum lithium levels up. In prescription-lithium patients started on enalapril, lithium concentrations have risen by roughly a third within weeks. Lithium Orotate doses are much smaller, but the same handling principle applies and the margin between therapeutic and toxic lithium is narrow; older adults, dehydrated patients, and those on diuretics or NSAIDs are most at risk.", "recommendation": "Avoid Lithium Orotate while taking enalapril. If you must use it, keep the dose low, stay well hydrated, and ask your prescriber to check a serum lithium level after a week or two. Hold lithium during any vomiting, diarrhea, or fever illness.", "minimumTimeSeparation": null, "mechanism": "ACE inhibition reduces angiotensin II and aldosterone, causing natriuresis and a fall in GFR. Lithium is reabsorbed in the proximal tubule in parallel with sodium, so sodium loss and reduced filtration both increase fractional lithium reabsorption.", "evidenceLevel": "moderate", "sources": [ { "text": "DasGupta K, Jefferson JW, Kobak KA, Greist JH. The effect of enalapril on serum lithium levels in healthy men. J Clin Psychiatry. 1992;53(11):398-400.", "pmid": "1459971", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1459971/", "publicSourceType": "PMID" }, { "text": "Finley PR, O'Brien JG, Coleman RW. Lithium and angiotensin-converting enzyme inhibitors: evaluation of a potential interaction. J Clin Psychopharmacol. 1996;16(1):68-71.", "pmid": "8834421", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8834421/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Enalapril raises serum lithium concentrations and risk of lithium toxicity.", "clinicalSignificance": "Even small lithium loads can become toxic when renal handling is altered by ACE inhibition.", "managementStrategy": "Avoid combination; if unavoidable, use lowest lithium dose and monitor serum lithium and renal function.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Ramipril", "supplementBName": "Lithium Orotate", "interactionType": "caution", "severity": "serious", "description": "Ramipril reduces sodium reabsorption and lowers glomerular filtration, which causes the kidney to retain lithium. Case reports with ACE inhibitors describe lithium toxicity developing within 3 to 5 weeks of starting the medication, sometimes with serum lithium concentrations rising more than 30%. Lithium Orotate doses are smaller but use the same renal pathway and the margin to neurotoxicity is narrow, particularly in older adults or anyone who becomes dehydrated.", "recommendation": "Avoid Lithium Orotate while taking ramipril. If you must combine them, keep the dose low, stay well hydrated, and ask your prescriber to check a serum lithium level after 1-2 weeks. Hold the supplement during any vomiting, diarrhea, or fever.", "minimumTimeSeparation": null, "mechanism": "ACE inhibition causes natriuresis and a fall in GFR. Lithium is reabsorbed in the proximal tubule in parallel with sodium, so increased sodium loss and reduced filtration both raise fractional lithium reabsorption.", "evidenceLevel": "moderate", "sources": [ { "text": "Finley PR, O'Brien JG, Coleman RW. Lithium and angiotensin-converting enzyme inhibitors: evaluation of a potential interaction. J Clin Psychopharmacol. 1996;16(1):68-71.", "pmid": "8834421", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8834421/", "publicSourceType": "PMID" }, { "text": "Masiran R, Abdul Aziz MF. Hypertensive bipolar: chronic lithium toxicity in patients taking ACE inhibitor. BMJ Case Rep. 2017;2017.", "pmid": "28847993", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28847993/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Ramipril raises serum lithium concentrations and risk of toxicity.", "clinicalSignificance": "Lithium toxicity can present with tremor, confusion, or arrhythmia, and may develop weeks after starting ramipril.", "managementStrategy": "Avoid combination; if unavoidable, use lowest dose and monitor serum lithium and renal function.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Benazepril", "supplementBName": "Lithium Orotate", "interactionType": "caution", "severity": "serious", "description": "Benazepril is an ACE inhibitor that reduces sodium reabsorption and lowers glomerular filtration. This causes the kidney to retain lithium and raises serum lithium concentrations. Case series of patients on prescription lithium have shown rises of about 36% in steady-state lithium levels after starting an ACE inhibitor. Lithium Orotate doses are smaller, but the same renal handling applies and the margin to toxicity is narrow.", "recommendation": "Avoid Lithium Orotate while taking benazepril. If used together, keep the dose low, stay well hydrated, and ask your prescriber to check serum lithium after 1-2 weeks. Hold the supplement during any vomiting, diarrhea, or fever.", "minimumTimeSeparation": null, "mechanism": "ACE inhibition reduces angiotensin II and aldosterone, causing natriuresis and a fall in GFR. Lithium reabsorption in the proximal tubule tracks sodium, so sodium loss and reduced filtration both increase fractional lithium reabsorption.", "evidenceLevel": "moderate", "sources": [ { "text": "Finley PR, O'Brien JG, Coleman RW. Lithium and angiotensin-converting enzyme inhibitors: evaluation of a potential interaction. J Clin Psychopharmacol. 1996;16(1):68-71.", "pmid": "8834421", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8834421/", "publicSourceType": "PMID" }, { "text": "Baldwin CM, Safferman AZ. A case of lisinopril-induced lithium toxicity. DICP. 1990;24(10):946-7.", "pmid": "2173864", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2173864/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Benazepril raises serum lithium concentrations and risk of toxicity.", "clinicalSignificance": "Lithium toxicity can present with tremor, confusion, ataxia, or arrhythmia and can be slow to develop.", "managementStrategy": "Avoid combination; if unavoidable, monitor serum lithium and renal function.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Valsartan", "supplementBName": "Lithium Orotate", "interactionType": "caution", "severity": "serious", "description": "Valsartan reduces sodium reabsorption through AT1 receptor blockade and lowers glomerular filtration, which causes the kidney to retain lithium. Multiple case reports describe prescription-lithium patients developing toxicity within weeks of starting or increasing valsartan, sometimes at previously safe doses. Lithium Orotate doses are smaller, but the same renal handling applies and the margin to neurotoxicity is narrow.", "recommendation": "Avoid Lithium Orotate while taking valsartan. If you must combine them, keep the dose low, stay well hydrated, and ask your prescriber to check a serum lithium level after 1-2 weeks. Hold the supplement during any vomiting, diarrhea, or fever.", "minimumTimeSeparation": null, "mechanism": "AT1 receptor blockade causes natriuresis and reduces GFR. Lithium is reabsorbed in the proximal tubule in parallel with sodium, so increased sodium loss and reduced filtration both raise fractional lithium reabsorption.", "evidenceLevel": "moderate", "sources": [ { "text": "Su YP, Chang CJ, Hwang TJ. Lithium intoxication after valsartan treatment. Psychiatry Clin Neurosci. 2007;61(2):204.", "pmid": "17362443", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17362443/", "publicSourceType": "PMID" }, { "text": "Lazarczyk MJ, Giannakopoulos P. Temporal association as a prerequisite factor of valsartan-induced lithium toxicity. Bipolar Disord. 2014;16(6):662-6.", "pmid": "24372930", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24372930/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Valsartan raises serum lithium concentrations and risk of toxicity.", "clinicalSignificance": "Lithium toxicity from ARBs can develop weeks after starting and may present with tremor, confusion, ataxia, or arrhythmia.", "managementStrategy": "Avoid combination; if unavoidable, monitor serum lithium and renal function.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Losartan", "supplementBName": "Lithium Orotate", "interactionType": "caution", "severity": "serious", "description": "Losartan blocks the AT1 receptor and reduces sodium reabsorption, which causes the kidney to retain lithium. A published case described a previously stable prescription-lithium patient developing tremor, confusion, and elevated lithium levels within weeks of starting losartan 50 mg. Lithium Orotate doses are smaller but use the same renal pathway and the therapeutic window is narrow.", "recommendation": "Avoid Lithium Orotate while taking losartan. If you must combine them, keep the dose low, stay well hydrated, and ask your prescriber to check serum lithium after 1-2 weeks. Hold the supplement during any vomiting, diarrhea, or fever.", "minimumTimeSeparation": null, "mechanism": "AT1 receptor blockade causes natriuresis and reduces GFR. Lithium reabsorption in the proximal tubule tracks sodium, so sodium loss and reduced filtration both raise fractional lithium reabsorption.", "evidenceLevel": "moderate", "sources": [ { "text": "Blanche P, Raynaud E, Kerob D, Galezowski N. Lithium intoxication in an elderly patient after combined treatment with losartan. Eur J Clin Pharmacol. 1997;52(6):501.", "pmid": "9342587", "doi": "10.1007/s002280050325", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9342587/", "publicSourceType": "PMID" }, { "text": "Finley PR, O'Brien JG, Coleman RW. Lithium and angiotensin-converting enzyme inhibitors: evaluation of a potential interaction. J Clin Psychopharmacol. 1996;16(1):68-71.", "pmid": "8834421", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8834421/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Losartan raises serum lithium concentrations and risk of toxicity.", "clinicalSignificance": "Lithium toxicity can present with tremor, confusion, ataxia, or arrhythmia within weeks of starting an ARB.", "managementStrategy": "Avoid combination; if unavoidable, monitor serum lithium and renal function.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Irbesartan", "supplementBName": "Lithium Orotate", "interactionType": "caution", "severity": "serious", "description": "Irbesartan blocks the AT1 receptor, reduces sodium reabsorption, and increases lithium retention by the kidney. Multiple published cases with ARBs describe lithium toxicity developing weeks after starting therapy, sometimes at previously well-tolerated lithium doses. Lithium Orotate doses are smaller but use the same renal pathway and the therapeutic window is narrow.", "recommendation": "Avoid Lithium Orotate while taking irbesartan. If you must combine them, keep the dose low, stay well hydrated, and ask your prescriber to check serum lithium after 1-2 weeks. Hold the supplement during vomiting, diarrhea, or fever.", "minimumTimeSeparation": null, "mechanism": "AT1 receptor blockade causes natriuresis and reduces GFR. Lithium reabsorption in the proximal tubule tracks sodium, so sodium loss and reduced filtration both raise fractional lithium reabsorption.", "evidenceLevel": "moderate", "sources": [ { "text": "Blanche P, Raynaud E, Kerob D, Galezowski N. Lithium intoxication in an elderly patient after combined treatment with losartan. Eur J Clin Pharmacol. 1997;52(6):501.", "pmid": "9342587", "doi": "10.1007/s002280050325", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9342587/", "publicSourceType": "PMID" }, { "text": "Lazarczyk MJ, Giannakopoulos P. Temporal association as a prerequisite factor of valsartan-induced lithium toxicity. Bipolar Disord. 2014;16(6):662-6.", "pmid": "24372930", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24372930/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Irbesartan raises serum lithium concentrations and risk of toxicity.", "clinicalSignificance": "Lithium toxicity from ARBs can develop weeks after starting and may present with tremor, confusion, ataxia, or arrhythmia.", "managementStrategy": "Avoid combination; if unavoidable, monitor serum lithium and renal function.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Olmesartan", "supplementBName": "Lithium Orotate", "interactionType": "caution", "severity": "serious", "description": "Olmesartan blocks the AT1 receptor, reduces sodium reabsorption, and increases lithium retention by the kidney. Multiple case reports with ARBs describe lithium toxicity developing weeks after starting therapy, sometimes at previously safe lithium doses. Lithium Orotate doses are smaller but use the same renal pathway and the therapeutic window is narrow.", "recommendation": "Avoid Lithium Orotate while taking olmesartan. If you must combine them, keep the dose low, stay well hydrated, and ask your prescriber to check serum lithium after 1-2 weeks. Hold the supplement during vomiting, diarrhea, or fever.", "minimumTimeSeparation": null, "mechanism": "AT1 receptor blockade causes natriuresis and reduces GFR. Lithium reabsorption in the proximal tubule tracks sodium, so sodium loss and reduced filtration both raise fractional lithium reabsorption.", "evidenceLevel": "moderate", "sources": [ { "text": "Blanche P, Raynaud E, Kerob D, Galezowski N. Lithium intoxication in an elderly patient after combined treatment with losartan. Eur J Clin Pharmacol. 1997;52(6):501.", "pmid": "9342587", "doi": "10.1007/s002280050325", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9342587/", "publicSourceType": "PMID" }, { "text": "Lazarczyk MJ, Giannakopoulos P. Temporal association as a prerequisite factor of valsartan-induced lithium toxicity. Bipolar Disord. 2014;16(6):662-6.", "pmid": "24372930", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24372930/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Olmesartan raises serum lithium concentrations and risk of toxicity.", "clinicalSignificance": "Lithium toxicity from ARBs can develop weeks after starting and may present with tremor, confusion, ataxia, or arrhythmia.", "managementStrategy": "Avoid combination; if unavoidable, monitor serum lithium and renal function.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Sacubitril/Valsartan", "supplementBName": "Lithium Orotate", "interactionType": "caution", "severity": "serious", "description": "The valsartan component blocks AT1 receptors, reduces sodium reabsorption, and increases lithium retention by the kidney. A published case described an 81-year-old on chronic lithium developing progressive tremor, ataxia, and cognitive decline after starting sacubitril/valsartan. Lithium Orotate doses are smaller but use the same renal pathway, and the therapeutic window is narrow.", "recommendation": "Avoid Lithium Orotate while taking sacubitril/valsartan. If you must combine them, keep the dose low, stay well hydrated, and ask your cardiologist to check serum lithium after 1-2 weeks. Hold the supplement during vomiting, diarrhea, or fever.", "minimumTimeSeparation": null, "mechanism": "AT1 receptor blockade causes natriuresis and reduces GFR. Lithium reabsorption in the proximal tubule tracks sodium, so sodium loss and reduced filtration raise fractional lithium reabsorption. Neprilysin inhibition does not offset this renal effect.", "evidenceLevel": "moderate", "sources": [ { "text": "Su YP, Chang CJ, Hwang TJ. Lithium intoxication after valsartan treatment. Psychiatry Clin Neurosci. 2007;61(2):204.", "pmid": "17362443", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17362443/", "publicSourceType": "PMID" }, { "text": "Lazarczyk MJ, Giannakopoulos P. Temporal association as a prerequisite factor of valsartan-induced lithium toxicity. Bipolar Disord. 2014;16(6):662-6.", "pmid": "24372930", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24372930/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Sacubitril/valsartan raises serum lithium concentrations and risk of toxicity.", "clinicalSignificance": "Heart failure patients on sacubitril/valsartan are often elderly with reduced renal reserve, making them especially vulnerable to lithium accumulation.", "managementStrategy": "Avoid combination; if unavoidable, monitor serum lithium and renal function closely.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Enalapril", "supplementBName": "Zinc", "interactionType": "caution", "severity": "moderate", "description": "Enalapril increases urinary zinc excretion and lowers intracellular zinc in monocytes over months of use. In a 6-month controlled study of hypertensive patients on captopril or enalapril, intramonocyte zinc fell significantly in both groups, supporting a class effect on zinc status. Symptoms of zinc deficiency include altered taste, slow wound healing, hair loss, and reduced immune function.", "recommendation": "If you take enalapril long term, consider a modest zinc supplement (15-30 mg/day) or a multivitamin containing zinc, especially if you notice loss of taste or recurrent infections. Take zinc with food to limit GI upset, and have your prescriber check zinc status if you suspect deficiency.", "minimumTimeSeparation": null, "mechanism": "ACE inhibitors with sulfhydryl-related chelating capacity form complexes with zinc that increase its urinary excretion. Chronic use depletes intracellular zinc pools even when serum zinc looks normal.", "evidenceLevel": "moderate", "sources": [ { "text": "Golik A, Zaidenstein R, Dishi V, Blatt A, Cohen N, Cotter G, Berman S, Weissgarten J. Effects of captopril and enalapril on zinc metabolism in hypertensive patients. J Am Coll Nutr. 1998;17(1):75-8.", "pmid": "9477394", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9477394/", "publicSourceType": "PMID" }, { "text": "Braun LA, Rosenfeldt F. Pharmaco-nutrient interactions - a systematic review of zinc and antihypertensive therapy. Int J Clin Pract. 2013;67(8):717-25.", "pmid": "23279674", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23279674/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Enalapril increases urinary zinc loss and lowers intracellular zinc over months of use.", "clinicalSignificance": "Long-term ACE-inhibitor users can develop subclinical zinc deficiency that contributes to altered taste, hair shedding, and immune dysfunction.", "managementStrategy": "Take a modest zinc supplement long term and monitor for symptoms of deficiency.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Enalapril", "supplementBName": "Zinc Picolinate", "interactionType": "caution", "severity": "moderate", "description": "Enalapril increases urinary zinc excretion and lowers intracellular zinc over months of use. Zinc Picolinate is a well-absorbed form often used to correct this kind of subclinical deficiency. Symptoms of zinc deficiency include altered taste, slow wound healing, hair loss, and reduced immune function.", "recommendation": "If you take enalapril long term, consider Zinc Picolinate 15-30 mg/day with food, especially if you have altered taste or recurrent infections. Have your prescriber check zinc status if you suspect deficiency rather than dosing higher empirically.", "minimumTimeSeparation": null, "mechanism": "ACE inhibitors complex with zinc and increase its renal excretion, depleting intracellular zinc pools. Picolinate enhances zinc absorption and bioavailability, helping to offset this loss.", "evidenceLevel": "moderate", "sources": [ { "text": "Golik A, Zaidenstein R, Dishi V, Blatt A, Cohen N, Cotter G, Berman S, Weissgarten J. Effects of captopril and enalapril on zinc metabolism in hypertensive patients. J Am Coll Nutr. 1998;17(1):75-8.", "pmid": "9477394", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9477394/", "publicSourceType": "PMID" }, { "text": "Braun LA, Rosenfeldt F. Pharmaco-nutrient interactions - a systematic review of zinc and antihypertensive therapy. Int J Clin Pract. 2013;67(8):717-25.", "pmid": "23279674", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23279674/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Enalapril depletes zinc over time; Zinc Picolinate can restore status.", "clinicalSignificance": "Subclinical zinc deficiency from long-term ACE inhibition is correctable with supplementation.", "managementStrategy": "Supplement modestly long term and monitor for clinical signs of deficiency.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Lisinopril", "supplementBName": "Zinc", "interactionType": "caution", "severity": "moderate", "description": "ACE inhibitors as a class increase urinary zinc excretion and lower intracellular zinc over months of use. A systematic review of zinc and antihypertensive therapy identified depletion across multiple ACE inhibitors, with lisinopril patients showing similar patterns of altered zinc status. Symptoms of zinc deficiency include altered taste, slow wound healing, hair loss, and reduced immune function.", "recommendation": "If you take lisinopril long term, consider a modest zinc supplement (15-30 mg/day) or a multivitamin containing zinc, especially if you notice loss of taste or recurrent infections. Take zinc with food to limit GI upset.", "minimumTimeSeparation": null, "mechanism": "ACE inhibitors complex with zinc and increase its renal excretion. Chronic use depletes intracellular zinc pools even when serum zinc looks normal.", "evidenceLevel": "moderate", "sources": [ { "text": "Braun LA, Rosenfeldt F. Pharmaco-nutrient interactions - a systematic review of zinc and antihypertensive therapy. Int J Clin Pract. 2013;67(8):717-25.", "pmid": "23279674", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23279674/", "publicSourceType": "PMID" }, { "text": "Golik A, Zaidenstein R, Dishi V, Blatt A, Cohen N, Cotter G, Berman S, Weissgarten J. Effects of captopril and enalapril on zinc metabolism in hypertensive patients. J Am Coll Nutr. 1998;17(1):75-8.", "pmid": "9477394", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9477394/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Lisinopril contributes to zinc depletion over months of therapy.", "clinicalSignificance": "Long-term ACE-inhibitor users can develop subclinical zinc deficiency affecting taste, immunity, and wound healing.", "managementStrategy": "Take a modest zinc supplement long term; monitor for symptoms of deficiency.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Lisinopril", "supplementBName": "Zinc Picolinate", "interactionType": "caution", "severity": "moderate", "description": "ACE inhibitors as a class increase urinary zinc excretion and lower intracellular zinc over months of use. Zinc Picolinate is a well-absorbed form often used to correct this kind of subclinical deficiency. Symptoms include altered taste, slow wound healing, hair loss, and reduced immune function.", "recommendation": "If you take lisinopril long term, Zinc Picolinate 15-30 mg/day with food is a reasonable maintenance strategy, especially if you have altered taste or recurrent infections. Have your prescriber check zinc status if you suspect deficiency rather than dosing higher empirically.", "minimumTimeSeparation": null, "mechanism": "ACE inhibitors complex with zinc and increase its renal excretion. Picolinate enhances zinc absorption and bioavailability, helping to offset the loss.", "evidenceLevel": "moderate", "sources": [ { "text": "Braun LA, Rosenfeldt F. Pharmaco-nutrient interactions - a systematic review of zinc and antihypertensive therapy. Int J Clin Pract. 2013;67(8):717-25.", "pmid": "23279674", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23279674/", "publicSourceType": "PMID" }, { "text": "Golik A, Modai D, Averbukh Z, Sheffy M, Shamis A, Cohen N, Shaked U, Dolev E. Zinc metabolism in patients treated with captopril versus enalapril. Metabolism. 1990;39(7):665-7.", "pmid": "2195291", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2195291/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Lisinopril depletes zinc over time; Zinc Picolinate can restore status.", "clinicalSignificance": "Subclinical zinc deficiency from long-term ACE inhibition is correctable with supplementation.", "managementStrategy": "Supplement modestly long term and monitor for clinical signs of deficiency.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Valsartan", "supplementBName": "Zinc", "interactionType": "caution", "severity": "moderate", "description": "A systematic review of zinc and antihypertensive therapy reported that valsartan reduced erythrocyte and plasma zinc concentrations in treated hypertensives. The effect is smaller than with sulfhydryl-containing ACE inhibitors but still meaningful over chronic use. Symptoms of zinc deficiency include altered taste, slow wound healing, hair loss, and reduced immune function.", "recommendation": "If you take valsartan long term, a modest zinc supplement (15-30 mg/day) or a multivitamin containing zinc is reasonable, especially if you notice altered taste or recurrent infections. Take zinc with food to limit GI upset.", "minimumTimeSeparation": null, "mechanism": "Mechanism is not fully established but appears to involve increased renal zinc handling and possibly altered intracellular zinc distribution secondary to RAAS blockade. Net effect is reduced plasma and erythrocyte zinc over months of therapy.", "evidenceLevel": "emerging", "sources": [ { "text": "Braun LA, Rosenfeldt F. Pharmaco-nutrient interactions - a systematic review of zinc and antihypertensive therapy. Int J Clin Pract. 2013;67(8):717-25.", "pmid": "23279674", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23279674/", "publicSourceType": "PMID" }, { "text": "Golik A, Zaidenstein R, Dishi V, Blatt A, Cohen N, Cotter G, Berman S, Weissgarten J. Effects of captopril and enalapril on zinc metabolism in hypertensive patients. J Am Coll Nutr. 1998;17(1):75-8.", "pmid": "9477394", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9477394/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Valsartan modestly reduces plasma and erythrocyte zinc over chronic use.", "clinicalSignificance": "Long-term ARB therapy can contribute to subclinical zinc deficiency affecting taste and immunity.", "managementStrategy": "Modest zinc supplementation is reasonable for long-term users with symptoms.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Losartan", "supplementBName": "Zinc", "interactionType": "caution", "severity": "moderate", "description": "A systematic review of antihypertensive therapy and zinc identified increased urinary zinc loss in losartan-treated patients. The effect is smaller than with sulfhydryl-containing ACE inhibitors but is consistent across studies of ARB therapy. Symptoms of zinc deficiency include altered taste, slow wound healing, hair loss, and reduced immune function.", "recommendation": "If you take losartan long term, a modest zinc supplement (15-30 mg/day) or a multivitamin containing zinc is reasonable, especially if you notice altered taste or recurrent infections. Take zinc with food to limit GI upset.", "minimumTimeSeparation": null, "mechanism": "AT1 receptor blockade alters renal handling of trace minerals including zinc, contributing to increased urinary zinc excretion. Chronic loss can deplete intracellular zinc pools even when serum looks normal.", "evidenceLevel": "emerging", "sources": [ { "text": "Braun LA, Rosenfeldt F. Pharmaco-nutrient interactions - a systematic review of zinc and antihypertensive therapy. Int J Clin Pract. 2013;67(8):717-25.", "pmid": "23279674", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23279674/", "publicSourceType": "PMID" }, { "text": "Golik A, Zaidenstein R, Dishi V, Blatt A, Cohen N, Cotter G, Berman S, Weissgarten J. Effects of captopril and enalapril on zinc metabolism in hypertensive patients. J Am Coll Nutr. 1998;17(1):75-8.", "pmid": "9477394", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9477394/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Losartan modestly increases urinary zinc loss over chronic use.", "clinicalSignificance": "Long-term ARB therapy can contribute to subclinical zinc deficiency affecting taste and immunity.", "managementStrategy": "Modest zinc supplementation is reasonable for long-term users with symptoms.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Coenzyme Q10", "supplementBName": "Lisinopril", "interactionType": "synergy", "severity": "info", "description": "Coenzyme Q10 lowers blood pressure modestly through improved endothelial function and reduced oxidative stress. A meta-analysis of 12 clinical trials reported systolic reductions of up to 17 mm Hg with CoQ10. When added to an ACE inhibitor like lisinopril, the effect is generally additive and well tolerated, which can be helpful for patients with residual hypertension or heart failure.", "recommendation": "If your blood pressure is well controlled on lisinopril alone, monitor at home before adding CoQ10 to avoid hypotension. A typical dose is 100-200 mg/day with a fat-containing meal. Recheck blood pressure within 2-4 weeks and tell your prescriber so any lisinopril dose adjustment can be made.", "minimumTimeSeparation": null, "mechanism": "CoQ10 improves mitochondrial function in vascular smooth muscle and endothelium, increases nitric oxide bioavailability, and reduces oxidative inactivation of endothelium-derived relaxing factors. These effects complement ACE inhibition.", "evidenceLevel": "moderate", "sources": [ { "text": "Rosenfeldt FL, Haas SJ, Krum H, Hadj A, Ng K, Leong JY, Watts GF. Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. J Hum Hypertens. 2007;21(4):297-306.", "pmid": "17287847", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17287847/", "publicSourceType": "PMID" }, { "text": "Burke BE, Neuenschwander R, Olson RD. Randomized, double-blind, placebo-controlled trial of coenzyme Q10 in isolated systolic hypertension. South Med J. 2001;94(11):1112-7.", "pmid": "11780680", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11780680/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Additive blood pressure reduction with no known pharmacokinetic interference.", "clinicalSignificance": "Patients with residual hypertension on lisinopril may benefit; risk of clinically meaningful hypotension is low but possible.", "managementStrategy": "Monitor home blood pressure when adding CoQ10 and notify your prescriber.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Coenzyme Q10", "supplementBName": "Enalapril", "interactionType": "synergy", "severity": "info", "description": "Coenzyme Q10 lowers blood pressure modestly through improved endothelial function and reduced oxidative stress. A clinical study using CoQ10 as a component of combination therapy with enalapril found improved 24-hour blood pressure control and better endothelial function compared with enalapril alone. The combination is generally additive and well tolerated.", "recommendation": "If your blood pressure is well controlled on enalapril alone, monitor at home before adding CoQ10. A typical dose is 100-200 mg/day with a fat-containing meal. Recheck blood pressure within 2-4 weeks and tell your prescriber so any enalapril dose adjustment can be made.", "minimumTimeSeparation": null, "mechanism": "CoQ10 improves mitochondrial function in vascular smooth muscle and endothelium and reduces oxidative inactivation of nitric oxide, complementing ACE inhibition. Animal data also suggest CoQ10 prolongs the duration of enalapril's hypotensive effect.", "evidenceLevel": "moderate", "sources": [ { "text": "Rosenfeldt FL, Haas SJ, Krum H, Hadj A, Ng K, Leong JY, Watts GF. Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. J Hum Hypertens. 2007;21(4):297-306.", "pmid": "17287847", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17287847/", "publicSourceType": "PMID" }, { "text": "Mikhin VP, Kharchenko AV, Rosliakova EA, Cherniatina MA. Application of coenzyme Q(10) in combination therapy of arterial hypertension. Kardiologiia. 2011;51(6):26-31.", "pmid": "21878067", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21878067/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Additive blood pressure reduction and possible prolongation of enalapril effect.", "clinicalSignificance": "Patients with residual hypertension or heart failure on enalapril may benefit; low risk of clinically meaningful hypotension.", "managementStrategy": "Monitor home blood pressure when adding CoQ10 and notify your prescriber.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Coenzyme Q10", "supplementBName": "Ramipril", "interactionType": "synergy", "severity": "info", "description": "Coenzyme Q10 lowers blood pressure modestly through improved endothelial function and reduced oxidative stress. A meta-analysis of 12 clinical trials reported meaningful systolic reductions. Combined with an ACE inhibitor like ramipril, the effect is generally additive and well tolerated, which can help patients with residual hypertension or heart failure.", "recommendation": "If your blood pressure is well controlled on ramipril alone, monitor at home before adding CoQ10. A typical dose is 100-200 mg/day with a fat-containing meal. Recheck blood pressure within 2-4 weeks and tell your prescriber so any ramipril dose adjustment can be made.", "minimumTimeSeparation": null, "mechanism": "CoQ10 improves mitochondrial function in vascular smooth muscle and endothelium and reduces oxidative inactivation of nitric oxide, complementing ACE inhibition.", "evidenceLevel": "moderate", "sources": [ { "text": "Rosenfeldt FL, Haas SJ, Krum H, Hadj A, Ng K, Leong JY, Watts GF. Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. J Hum Hypertens. 2007;21(4):297-306.", "pmid": "17287847", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17287847/", "publicSourceType": "PMID" }, { "text": "Burke BE, Neuenschwander R, Olson RD. Randomized, double-blind, placebo-controlled trial of coenzyme Q10 in isolated systolic hypertension. South Med J. 2001;94(11):1112-7.", "pmid": "11780680", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11780680/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Additive blood pressure reduction with no known pharmacokinetic interference.", "clinicalSignificance": "Patients with residual hypertension on ramipril may benefit; low risk of meaningful hypotension.", "managementStrategy": "Monitor home blood pressure when adding CoQ10 and notify your prescriber.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Garlic Extract", "supplementBName": "Lisinopril", "interactionType": "synergy", "severity": "info", "description": "Garlic Extract lowers blood pressure modestly (approximately 4-10 mm Hg systolic in hypertensives) and has independent ACE-inhibitory activity in vitro. When combined with lisinopril the effects are additive, which is generally beneficial in uncontrolled hypertension but can produce mild hypotension if blood pressure is already at goal.", "recommendation": "If your blood pressure is already well controlled on lisinopril, monitor at home before and after starting Garlic Extract. Typical aged garlic doses are 600-1200 mg/day. Tell your prescriber so your lisinopril dose can be adjusted if needed.", "minimumTimeSeparation": null, "mechanism": "Allicin and S-allylcysteine in garlic inhibit angiotensin-converting enzyme and promote endothelial nitric oxide production. These mechanisms add to those of lisinopril.", "evidenceLevel": "moderate", "sources": [ { "text": "Wang HP, Yang J, Qin LQ, Yang XJ. Effect of garlic on blood pressure: a meta-analysis. J Clin Hypertens (Greenwich). 2015;17(3):223-31.", "pmid": "25557383", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25557383/", "publicSourceType": "PMID" }, { "text": "Ried K, Frank OR, Stocks NP. Aged garlic extract lowers blood pressure in patients with treated but uncontrolled hypertension: a randomised controlled trial. Maturitas. 2010;67(2):144-50.", "pmid": "20594781", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20594781/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Additive blood pressure reduction with ACE inhibitor therapy.", "clinicalSignificance": "Helpful for patients with uncontrolled hypertension; risk of symptomatic hypotension is low.", "managementStrategy": "Monitor home blood pressure when adding garlic and notify your prescriber.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Enalapril", "supplementBName": "Garlic Extract", "interactionType": "synergy", "severity": "info", "description": "Garlic Extract lowers blood pressure modestly and has independent ACE-inhibitory activity in vitro. When combined with enalapril the effects are additive, which is helpful in uncontrolled hypertension but can produce mild hypotension if blood pressure is already at goal.", "recommendation": "If your blood pressure is already well controlled on enalapril, monitor at home before and after starting Garlic Extract. Typical aged garlic doses are 600-1200 mg/day. Tell your prescriber so your enalapril dose can be adjusted if needed.", "minimumTimeSeparation": null, "mechanism": "Allicin and S-allylcysteine in garlic inhibit angiotensin-converting enzyme and promote endothelial nitric oxide production. These mechanisms add to those of enalapril.", "evidenceLevel": "moderate", "sources": [ { "text": "Wang HP, Yang J, Qin LQ, Yang XJ. Effect of garlic on blood pressure: a meta-analysis. J Clin Hypertens (Greenwich). 2015;17(3):223-31.", "pmid": "25557383", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25557383/", "publicSourceType": "PMID" }, { "text": "Ried K, Frank OR, Stocks NP. Aged garlic extract reduces blood pressure in hypertensives: a dose-response trial. Eur J Clin Nutr. 2013;67(1):64-70.", "pmid": "23169470", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23169470/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Additive blood pressure reduction with ACE inhibitor therapy.", "clinicalSignificance": "Helpful for patients with uncontrolled hypertension; risk of symptomatic hypotension is low.", "managementStrategy": "Monitor home blood pressure when adding garlic and notify your prescriber.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Garlic Extract", "supplementBName": "Ramipril", "interactionType": "synergy", "severity": "info", "description": "Garlic Extract lowers blood pressure modestly and has independent ACE-inhibitory activity in vitro. When combined with ramipril the effects are additive, which is generally beneficial in uncontrolled hypertension but can produce mild hypotension if blood pressure is already at goal.", "recommendation": "If your blood pressure is already well controlled on ramipril, monitor at home before and after starting Garlic Extract. Typical aged garlic doses are 600-1200 mg/day. Tell your prescriber so your ramipril dose can be adjusted if needed.", "minimumTimeSeparation": null, "mechanism": "Allicin and S-allylcysteine in garlic inhibit angiotensin-converting enzyme and promote endothelial nitric oxide production. These mechanisms add to those of ramipril.", "evidenceLevel": "moderate", "sources": [ { "text": "Wang HP, Yang J, Qin LQ, Yang XJ. Effect of garlic on blood pressure: a meta-analysis. J Clin Hypertens (Greenwich). 2015;17(3):223-31.", "pmid": "25557383", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25557383/", "publicSourceType": "PMID" }, { "text": "Ried K, Frank OR, Stocks NP. Aged garlic extract reduces blood pressure in hypertensives: a dose-response trial. Eur J Clin Nutr. 2013;67(1):64-70.", "pmid": "23169470", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23169470/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Additive blood pressure reduction with ACE inhibitor therapy.", "clinicalSignificance": "Helpful for patients with uncontrolled hypertension; risk of symptomatic hypotension is low.", "managementStrategy": "Monitor home blood pressure when adding garlic and notify your prescriber.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Garlic Extract", "supplementBName": "Losartan", "interactionType": "synergy", "severity": "info", "description": "Garlic Extract lowers blood pressure modestly (approximately 4-10 mm Hg systolic in hypertensives). When combined with the ARB losartan, the effects are additive, which can help patients with uncontrolled hypertension but may produce mild hypotension if blood pressure is already at goal.", "recommendation": "If your blood pressure is already well controlled on losartan, monitor at home before and after starting Garlic Extract. Typical aged garlic doses are 600-1200 mg/day. Tell your prescriber so your losartan dose can be adjusted if needed.", "minimumTimeSeparation": null, "mechanism": "Garlic constituents inhibit ACE and promote endothelial nitric oxide production. The vasodilatory effect is complementary to AT1 receptor blockade by losartan.", "evidenceLevel": "moderate", "sources": [ { "text": "Wang HP, Yang J, Qin LQ, Yang XJ. Effect of garlic on blood pressure: a meta-analysis. J Clin Hypertens (Greenwich). 2015;17(3):223-31.", "pmid": "25557383", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25557383/", "publicSourceType": "PMID" }, { "text": "Ried K, Frank OR, Stocks NP. Aged garlic extract lowers blood pressure in patients with treated but uncontrolled hypertension: a randomised controlled trial. Maturitas. 2010;67(2):144-50.", "pmid": "20594781", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20594781/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Additive blood pressure reduction with ARB therapy.", "clinicalSignificance": "Helpful for patients with uncontrolled hypertension on losartan; risk of symptomatic hypotension is low.", "managementStrategy": "Monitor home blood pressure when adding garlic and notify your prescriber.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Garlic Extract", "supplementBName": "Valsartan", "interactionType": "synergy", "severity": "info", "description": "Garlic Extract lowers blood pressure modestly. When combined with the ARB valsartan, the effects are additive, which can help patients with uncontrolled hypertension but may produce mild hypotension if blood pressure is already at goal.", "recommendation": "If your blood pressure is already well controlled on valsartan, monitor at home before and after starting Garlic Extract. Typical aged garlic doses are 600-1200 mg/day. Tell your prescriber so your valsartan dose can be adjusted if needed.", "minimumTimeSeparation": null, "mechanism": "Garlic constituents inhibit ACE and promote endothelial nitric oxide production. The vasodilatory effect is complementary to AT1 receptor blockade by valsartan.", "evidenceLevel": "moderate", "sources": [ { "text": "Wang HP, Yang J, Qin LQ, Yang XJ. Effect of garlic on blood pressure: a meta-analysis. J Clin Hypertens (Greenwich). 2015;17(3):223-31.", "pmid": "25557383", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25557383/", "publicSourceType": "PMID" }, { "text": "Ried K, Frank OR, Stocks NP. Aged garlic extract reduces blood pressure in hypertensives: a dose-response trial. Eur J Clin Nutr. 2013;67(1):64-70.", "pmid": "23169470", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23169470/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Additive blood pressure reduction with ARB therapy.", "clinicalSignificance": "Helpful for patients with uncontrolled hypertension on valsartan; risk of symptomatic hypotension is low.", "managementStrategy": "Monitor home blood pressure when adding garlic and notify your prescriber.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Lisinopril", "supplementBName": "Magnesium Citrate", "interactionType": "synergy", "severity": "info", "description": "Magnesium supplementation lowers blood pressure modestly, with meta-analyses reporting about 2-3 mm Hg systolic and 2 mm Hg diastolic reductions in hypertensive patients on antihypertensive medication. Combined with lisinopril, the effect is additive and generally beneficial, though it may produce mild hypotension if blood pressure is already at goal. The risk of meaningful hyperkalemia from magnesium itself is low.", "recommendation": "Magnesium Citrate 200-350 mg elemental magnesium daily is a reasonable add-on; monitor home blood pressure after starting. Tell your prescriber so your lisinopril dose can be reviewed. Reduce dose if you develop loose stools.", "minimumTimeSeparation": null, "mechanism": "Magnesium acts as a calcium channel modulator in vascular smooth muscle, promotes nitric oxide release, and inhibits angiotensin-induced vasoconstriction. These actions complement ACE inhibition.", "evidenceLevel": "strong", "sources": [ { "text": "Kass L, Weekes J, Carpenter L. Effect of magnesium supplementation on blood pressure: a meta-analysis. Eur J Clin Nutr. 2012;66(4):411-8.", "pmid": "22318649", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22318649/", "publicSourceType": "PMID" }, { "text": "Alharran AM, et al. Impact of Magnesium Supplementation on Blood Pressure: An Umbrella Meta-Analysis of Randomized Controlled Trials. Curr Ther Res Clin Exp. 2024;101:100755.", "pmid": "39280209", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39280209/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Additive blood pressure reduction with no clinically important pharmacokinetic interference.", "clinicalSignificance": "Useful in patients with residual hypertension on lisinopril or known hypomagnesemia.", "managementStrategy": "Monitor home blood pressure when adding magnesium; reduce dose if diarrhea occurs.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Lisinopril", "supplementBName": "Magnesium Taurate", "interactionType": "synergy", "severity": "info", "description": "Magnesium supplementation lowers blood pressure modestly, with meta-analyses reporting about 2-3 mm Hg systolic reductions in hypertensives. The taurate form combines magnesium with taurine, both of which have independent cardiovascular and blood-pressure-lowering effects. Combined with lisinopril the effects are additive and generally well tolerated.", "recommendation": "Magnesium Taurate at doses providing 200-350 mg elemental magnesium daily is a reasonable add-on for blood pressure or cardiovascular support; monitor home blood pressure after starting. Tell your prescriber so your lisinopril dose can be reviewed.", "minimumTimeSeparation": null, "mechanism": "Magnesium modulates vascular smooth muscle calcium handling, promotes nitric oxide release, and inhibits angiotensin-induced vasoconstriction. Taurine independently reduces sympathetic tone. Both add to ACE inhibition.", "evidenceLevel": "moderate", "sources": [ { "text": "Kass L, Weekes J, Carpenter L. Effect of magnesium supplementation on blood pressure: a meta-analysis. Eur J Clin Nutr. 2012;66(4):411-8.", "pmid": "22318649", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22318649/", "publicSourceType": "PMID" }, { "text": "Militante JD, Lombardini JB. Treatment of hypertension with oral taurine: experimental and clinical studies. Amino Acids. 2002;23(4):381-93.", "pmid": "12436205", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12436205/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Additive blood pressure reduction with ACE inhibitor therapy.", "clinicalSignificance": "Useful for residual hypertension or cardiovascular support in patients on lisinopril.", "managementStrategy": "Monitor home blood pressure; tell your prescriber.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Losartan", "supplementBName": "Magnesium Citrate", "interactionType": "synergy", "severity": "info", "description": "Magnesium supplementation lowers blood pressure modestly (about 2-3 mm Hg systolic and 2 mm Hg diastolic) when added to antihypertensive medication. Combined with losartan the effect is additive and generally beneficial, though it may produce mild hypotension if blood pressure is already at goal.", "recommendation": "Magnesium Citrate 200-350 mg elemental magnesium daily is a reasonable add-on; monitor home blood pressure after starting. Tell your prescriber so your losartan dose can be reviewed. Reduce dose if you develop loose stools.", "minimumTimeSeparation": null, "mechanism": "Magnesium modulates vascular smooth muscle calcium handling, promotes nitric oxide release, and inhibits angiotensin-induced vasoconstriction. These actions complement AT1 receptor blockade.", "evidenceLevel": "strong", "sources": [ { "text": "Kass L, Weekes J, Carpenter L. Effect of magnesium supplementation on blood pressure: a meta-analysis. Eur J Clin Nutr. 2012;66(4):411-8.", "pmid": "22318649", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22318649/", "publicSourceType": "PMID" }, { "text": "Alharran AM, et al. Impact of Magnesium Supplementation on Blood Pressure: An Umbrella Meta-Analysis of Randomized Controlled Trials. Curr Ther Res Clin Exp. 2024;101:100755.", "pmid": "39280209", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39280209/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Additive blood pressure reduction with no clinically important pharmacokinetic interference.", "clinicalSignificance": "Useful in patients with residual hypertension on losartan or known hypomagnesemia.", "managementStrategy": "Monitor home blood pressure when adding magnesium; reduce dose if diarrhea occurs.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Lisinopril", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "info", "description": "Vitamin D directly suppresses renin biosynthesis, so vitamin D deficiency leaves the renin-angiotensin system over-activated. Correcting deficiency in lisinopril-treated patients may modestly improve blood pressure control and reduces ongoing RAAS activation that ACE inhibition is trying to suppress. The combination is well tolerated.", "recommendation": "If your 25-hydroxyvitamin D level is below 30 ng/mL, supplementing 1000-2000 IU/day of Vitamin D3 is reasonable, with periodic level checks. Monitor home blood pressure after starting and tell your prescriber.", "minimumTimeSeparation": null, "mechanism": "1,25-dihydroxyvitamin D binds the vitamin D receptor and downregulates renin gene transcription, reducing angiotensin II generation upstream of ACE inhibition. Correcting deficiency complements the pharmacologic effect of lisinopril.", "evidenceLevel": "moderate", "sources": [ { "text": "Li YC, Qiao G, Uskokovic M, Xiang W, Zheng W, Kong J. Vitamin D: a negative endocrine regulator of the renin-angiotensin system and blood pressure. J Steroid Biochem Mol Biol. 2004;89-90(1-5):387-92.", "pmid": "15225806", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15225806/", "publicSourceType": "PMID" }, { "text": "Vaidya A, Williams JS. The relationship between vitamin D and the renin-angiotensin system in the pathophysiology of hypertension, kidney disease, and diabetes. Metabolism. 2012;61(4):450-8.", "pmid": "22075270", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22075270/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin D suppresses renin and may modestly improve blood pressure control on lisinopril.", "clinicalSignificance": "Most useful in patients with documented vitamin D deficiency and residual hypertension.", "managementStrategy": "Supplement based on 25-OH vitamin D level; monitor home BP.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Losartan", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "info", "description": "Vitamin D directly suppresses renin biosynthesis, so vitamin D deficiency leaves the renin-angiotensin system over-activated. Correcting deficiency in losartan-treated patients may modestly improve blood pressure control and reduces upstream RAAS activation that ARBs are trying to counter. The combination is well tolerated.", "recommendation": "If your 25-hydroxyvitamin D level is below 30 ng/mL, supplementing 1000-2000 IU/day of Vitamin D3 is reasonable, with periodic level checks. Monitor home blood pressure after starting and tell your prescriber.", "minimumTimeSeparation": null, "mechanism": "1,25-dihydroxyvitamin D binds the vitamin D receptor and downregulates renin gene transcription, reducing angiotensin II generation upstream of AT1 receptor blockade. Correcting deficiency complements the pharmacologic effect of losartan.", "evidenceLevel": "moderate", "sources": [ { "text": "Li YC, Qiao G, Uskokovic M, Xiang W, Zheng W, Kong J. Vitamin D: a negative endocrine regulator of the renin-angiotensin system and blood pressure. J Steroid Biochem Mol Biol. 2004;89-90(1-5):387-92.", "pmid": "15225806", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15225806/", "publicSourceType": "PMID" }, { "text": "Vaidya A, Williams JS. The relationship between vitamin D and the renin-angiotensin system in the pathophysiology of hypertension, kidney disease, and diabetes. Metabolism. 2012;61(4):450-8.", "pmid": "22075270", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22075270/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin D suppresses renin and may modestly improve blood pressure control on losartan.", "clinicalSignificance": "Most useful in patients with documented vitamin D deficiency and residual hypertension.", "managementStrategy": "Supplement based on 25-OH vitamin D level; monitor home BP.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "L-Arginine", "supplementBName": "Lisinopril", "interactionType": "synergy", "severity": "info", "description": "L-Arginine is the substrate for endothelial nitric oxide synthase, and oral supplementation produces modest blood pressure reductions (about 5 mm Hg systolic in a meta-analysis of double-blind trials). ACE inhibitors like lisinopril also raise nitric oxide bioavailability through bradykinin. The effects are additive and generally beneficial.", "recommendation": "L-Arginine 3-6 g/day is a reasonable add-on; monitor home blood pressure after starting and tell your prescriber so your lisinopril dose can be reviewed. Avoid combination with sildenafil or tadalafil without medical guidance.", "minimumTimeSeparation": null, "mechanism": "L-Arginine increases nitric oxide synthesis by providing substrate to eNOS, promoting vasodilation. ACE inhibition independently raises bradykinin and nitric oxide. Combined endothelial effects produce additive blood pressure reduction.", "evidenceLevel": "moderate", "sources": [ { "text": "Dong JY, Qin LQ, Zhang Z, Zhao Y, Wang J, Arigoni F, Zhang W. Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials. Am Heart J. 2011;162(6):959-65.", "pmid": "22137067", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22137067/", "publicSourceType": "PMID" }, { "text": "Komers R, Komersova K, Kazdova L, Ruzickova J, Pelikanova T. Effect of ACE inhibition and angiotensin AT1 receptor blockade on renal and blood pressure response to L-arginine in humans. J Hypertens. 2000;18(1):51-9.", "pmid": "10678543", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10678543/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Additive blood pressure reduction through complementary nitric oxide and ACE pathways.", "clinicalSignificance": "Useful for residual hypertension; mild hypotension possible if BP already at goal.", "managementStrategy": "Monitor home blood pressure; tell your prescriber.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "L-Citrulline", "supplementBName": "Lisinopril", "interactionType": "synergy", "severity": "info", "description": "L-Citrulline is converted to arginine in the kidney and produces sustained increases in nitric oxide. A meta-analysis of clinical trials reported reductions of about 4-7 mm Hg systolic and 3-4 mm Hg diastolic blood pressure. Combined with lisinopril the effects are additive and well tolerated, though mild hypotension is possible if blood pressure is already at goal.", "recommendation": "L-Citrulline 3-6 g/day is a reasonable add-on; monitor home blood pressure after starting and tell your prescriber. Avoid combination with sildenafil or tadalafil without medical guidance.", "minimumTimeSeparation": null, "mechanism": "L-Citrulline is recycled to arginine via the kidney, providing sustained substrate for endothelial nitric oxide synthase. ACE inhibition independently raises bradykinin and nitric oxide. Combined endothelial effects produce additive vasodilation.", "evidenceLevel": "moderate", "sources": [ { "text": "Mirenayat MS, Moradi S, Mohammadi H, Rouhani MH. Effect of L-Citrulline Supplementation on Blood Pressure: a Systematic Review and Meta-Analysis of Clinical Trials. Curr Hypertens Rep. 2018;20(11):98.", "pmid": "30284051", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30284051/", "publicSourceType": "PMID" }, { "text": "Komers R, Komersova K, Kazdova L, Ruzickova J, Pelikanova T. Effect of ACE inhibition and angiotensin AT1 receptor blockade on renal and blood pressure response to L-arginine in humans. J Hypertens. 2000;18(1):51-9.", "pmid": "10678543", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10678543/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Additive blood pressure reduction through complementary nitric oxide and ACE pathways.", "clinicalSignificance": "Useful for residual hypertension; mild hypotension possible if BP already at goal.", "managementStrategy": "Monitor home blood pressure; tell your prescriber.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fish Oil", "supplementBName": "Lisinopril", "interactionType": "synergy", "severity": "info", "description": "Fish Oil reduces blood pressure modestly (about 3/1.5 mm Hg in hypertensives) and has independent renoprotective effects through suppression of ACE activity, reduced angiotensin II formation, and downregulation of TGF-beta. Combined with lisinopril the effects are additive and well tolerated, with potential benefit in proteinuria.", "recommendation": "Fish Oil 1-3 g/day of combined EPA+DHA is a reasonable add-on; monitor home blood pressure after starting and tell your prescriber. Higher doses (greater than 3 g/day) may modestly raise bleeding risk.", "minimumTimeSeparation": null, "mechanism": "EPA and DHA suppress ACE activity, reduce angiotensin II generation, increase endothelial nitric oxide, and reduce TGF-beta-mediated renal fibrosis. These actions complement and reinforce ACE inhibition.", "evidenceLevel": "moderate", "sources": [ { "text": "Morris MC, Sacks F, Rosner B. Does fish oil lower blood pressure? A meta-analysis of controlled trials. Circulation. 1993;88(2):523-33.", "pmid": "8339414", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8339414/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Additive blood pressure reduction and possible additive renoprotection.", "clinicalSignificance": "Useful for residual hypertension or proteinuria on lisinopril.", "managementStrategy": "Monitor home blood pressure when adding fish oil; tell your prescriber.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fish Oil", "supplementBName": "Ramipril", "interactionType": "synergy", "severity": "info", "description": "Fish Oil reduces blood pressure modestly (about 3/1.5 mm Hg in hypertensives) and has independent renoprotective effects through suppression of ACE activity, reduced angiotensin II formation, and downregulation of TGF-beta. Combined with ramipril the effects are additive and well tolerated.", "recommendation": "Fish Oil 1-3 g/day of combined EPA+DHA is a reasonable add-on; monitor home blood pressure after starting and tell your prescriber. Higher doses (greater than 3 g/day) may modestly raise bleeding risk.", "minimumTimeSeparation": null, "mechanism": "EPA and DHA suppress ACE activity, reduce angiotensin II generation, increase endothelial nitric oxide, and reduce TGF-beta-mediated renal fibrosis. These actions reinforce ACE inhibition.", "evidenceLevel": "moderate", "sources": [ { "text": "Morris MC, Sacks F, Rosner B. Does fish oil lower blood pressure? A meta-analysis of controlled trials. Circulation. 1993;88(2):523-33.", "pmid": "8339414", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8339414/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Additive blood pressure reduction and possible additive renoprotection.", "clinicalSignificance": "Useful for residual hypertension or proteinuria on ramipril.", "managementStrategy": "Monitor home blood pressure when adding fish oil; tell your prescriber.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fish Oil", "supplementBName": "Losartan", "interactionType": "synergy", "severity": "info", "description": "Fish Oil reduces blood pressure modestly and has independent renoprotective effects through reduced angiotensin II generation and downregulation of TGF-beta. Combined with losartan the effects are additive and well tolerated, with potential benefit in proteinuria.", "recommendation": "Fish Oil 1-3 g/day of combined EPA+DHA is a reasonable add-on; monitor home blood pressure after starting and tell your prescriber. Higher doses (greater than 3 g/day) may modestly raise bleeding risk.", "minimumTimeSeparation": null, "mechanism": "EPA and DHA suppress ACE activity, reduce angiotensin II formation, increase endothelial nitric oxide, and reduce TGF-beta-mediated renal fibrosis. These actions complement AT1 receptor blockade.", "evidenceLevel": "moderate", "sources": [ { "text": "Morris MC, Sacks F, Rosner B. Does fish oil lower blood pressure? A meta-analysis of controlled trials. Circulation. 1993;88(2):523-33.", "pmid": "8339414", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8339414/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Additive blood pressure reduction and possible additive renoprotection.", "clinicalSignificance": "Useful for residual hypertension or proteinuria on losartan.", "managementStrategy": "Monitor home blood pressure when adding fish oil; tell your prescriber.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Lisinopril", "supplementBName": "Quercetin", "interactionType": "synergy", "severity": "info", "description": "Quercetin lowers blood pressure modestly (about 5-7 mm Hg systolic in stage 1 hypertensives) through endothelial improvement, AT1 receptor downregulation, and natriuresis. Combined with lisinopril the effects are additive and generally well tolerated, though mild hypotension is possible if blood pressure is already at goal.", "recommendation": "Quercetin 500 mg twice daily is a typical research dose; monitor home blood pressure after starting and tell your prescriber so your lisinopril dose can be reviewed. Take with food to limit GI upset.", "minimumTimeSeparation": null, "mechanism": "Quercetin downregulates renal angiotensin I receptors, increases urinary sodium excretion, and improves endothelial function. These actions complement ACE inhibition by lisinopril.", "evidenceLevel": "moderate", "sources": [ { "text": "Edwards RL, Lyon T, Litwin SE, Rabovsky A, Symons JD, Jalili T. Quercetin reduces blood pressure in hypertensive subjects. J Nutr. 2007;137(11):2405-11.", "pmid": "17951477", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17951477/", "publicSourceType": "PMID" }, { "text": "Larson AJ, Symons JD, Jalili T. Therapeutic potential of quercetin to decrease blood pressure: review of efficacy and mechanisms. Adv Nutr. 2012;3(1):39-46.", "pmid": "22332099", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22332099/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Additive blood pressure reduction with ACE inhibitor therapy.", "clinicalSignificance": "Useful for residual hypertension; mild hypotension possible if BP already at goal.", "managementStrategy": "Monitor home blood pressure; tell your prescriber.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Enalapril", "supplementBName": "Quercetin", "interactionType": "synergy", "severity": "info", "description": "Quercetin lowers blood pressure modestly (about 5-7 mm Hg systolic in stage 1 hypertensives) through endothelial improvement, AT1 receptor downregulation, and natriuresis. Combined with enalapril the effects are additive and generally well tolerated, though mild hypotension is possible if blood pressure is already at goal.", "recommendation": "Quercetin 500 mg twice daily is a typical research dose; monitor home blood pressure after starting and tell your prescriber so your enalapril dose can be reviewed. Take with food to limit GI upset.", "minimumTimeSeparation": null, "mechanism": "Quercetin downregulates renal angiotensin I receptors, increases urinary sodium excretion, and improves endothelial function. These actions complement ACE inhibition by enalapril.", "evidenceLevel": "moderate", "sources": [ { "text": "Edwards RL, Lyon T, Litwin SE, Rabovsky A, Symons JD, Jalili T. Quercetin reduces blood pressure in hypertensive subjects. J Nutr. 2007;137(11):2405-11.", "pmid": "17951477", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17951477/", "publicSourceType": "PMID" }, { "text": "Larson AJ, Symons JD, Jalili T. Therapeutic potential of quercetin to decrease blood pressure: review of efficacy and mechanisms. Adv Nutr. 2012;3(1):39-46.", "pmid": "22332099", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22332099/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Additive blood pressure reduction with ACE inhibitor therapy.", "clinicalSignificance": "Useful for residual hypertension; mild hypotension possible if BP already at goal.", "managementStrategy": "Monitor home blood pressure; tell your prescriber.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Lisinopril", "supplementBName": "Spirulina", "interactionType": "synergy", "severity": "info", "description": "Spirulina lowers blood pressure modestly in adults (about 3-5 mm Hg systolic and 3-4 mm Hg diastolic in meta-analyses). It also contains meaningful potassium per serving. Combined with lisinopril the blood-pressure effect is additive and well tolerated, but the potassium content warrants attention in patients with kidney disease or diabetes.", "recommendation": "Spirulina 1-4 g/day is the dose range used in trials. Monitor home blood pressure after starting and tell your prescriber. If you have reduced kidney function, diabetes, or take spironolactone, ask your prescriber to check potassium periodically.", "minimumTimeSeparation": null, "mechanism": "Spirulina peptides have ACE-inhibitory activity and contribute to nitric oxide-mediated vasodilation. Its modest potassium content does not usually raise serum potassium in healthy kidneys but can contribute in patients with impaired renal handling on ACE inhibitors.", "evidenceLevel": "moderate", "sources": [ { "text": "Shiri H, Yasbolaghi Sharahi J, Alizadeh Sani M, Mousavi SMJ, Nematollahi MH, Soleimani AA, Amri J, Panahi G. The Effect of Spirulina Supplementation on Blood Pressure in Adults: A GRADE-Assessed Systematic Review and Meta-Analysis of Randomized Clinical Trials. Phytother Res. 2025;39(1):397-412.", "pmid": "39529406", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39529406/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Additive blood pressure reduction with potential for modest potassium contribution.", "clinicalSignificance": "Helpful for residual hypertension; check potassium if kidney function is reduced.", "managementStrategy": "Monitor home blood pressure; check potassium if at risk for hyperkalemia.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Lisinopril", "supplementBName": "NAC", "interactionType": "synergy", "severity": "info", "description": "NAC has direct ACE-inhibitory activity (about 30% reduction in ACE activity in vivo) and provides sulfhydryl groups that may amplify nitric-oxide-mediated vasodilation. A small clinical study reported additional blood pressure reduction when NAC 1.2 g/day was added to lisinopril in patients already at goal. The effect is small but the combination is well tolerated.", "recommendation": "If you are considering NAC (typically 600-1200 mg/day) for other indications while on lisinopril, monitor home blood pressure for additional drops. Tell your prescriber so your lisinopril dose can be reviewed if needed.", "minimumTimeSeparation": null, "mechanism": "NAC provides sulfhydryl donors that directly inhibit ACE activity and amplify nitric oxide bioavailability by reducing oxidative inactivation. These actions complement lisinopril's effects.", "evidenceLevel": "emerging", "sources": [ { "text": "Boesgaard S, Aldershvile J, Poulsen HE, Christensen S, Dige-Petersen H, Giese J. N-acetylcysteine inhibits angiotensin converting enzyme in vivo. J Pharmacol Exp Ther. 1993;265(3):1239-44.", "pmid": "8389858", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8389858/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Additive ACE inhibition and modest extra blood pressure reduction.", "clinicalSignificance": "Generally minor; useful awareness for patients already at BP goal.", "managementStrategy": "Monitor home blood pressure when adding NAC; tell your prescriber.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Lisinopril", "supplementBName": "Olive Leaf Extract", "interactionType": "synergy", "severity": "info", "description": "Olive Leaf Extract lowers blood pressure (about 4-11 mm Hg systolic depending on dose) and was non-inferior to captopril for stage 1 hypertension in one randomized trial. Combined with lisinopril the effects are additive and generally well tolerated, though mild hypotension is possible if blood pressure is already at goal.", "recommendation": "Olive Leaf Extract 500-1000 mg/day is a typical research dose. Monitor home blood pressure after starting and tell your prescriber so your lisinopril dose can be reviewed.", "minimumTimeSeparation": null, "mechanism": "Oleuropein and related polyphenols in olive leaf inhibit ACE activity, improve endothelial nitric oxide bioavailability, and reduce vascular oxidative stress. These actions complement lisinopril.", "evidenceLevel": "moderate", "sources": [ { "text": "Susalit E, Agus N, Effendi I, Tjandrawinata RR, Nofiarny D, Perrinjaquet-Moccetti T, Verbruggen M. Olive (Olea europaea) leaf extract effective in patients with stage-1 hypertension: comparison with Captopril. Phytomedicine. 2011;18(4):251-8.", "pmid": "21036583", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21036583/", "publicSourceType": "PMID" }, { "text": "Razmpoosh E, Abdollahi S, Mousavirad M, Clark CCT, Soltani S. The effects of olive leaf extract on cardiovascular risk factors in the general adult population: a systematic review and meta-analysis of randomized controlled trials. Diabetol Metab Syndr. 2022;14(1):151.", "pmid": "36271405", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36271405/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Additive blood pressure reduction with ACE inhibitor therapy.", "clinicalSignificance": "Useful for residual hypertension; mild hypotension possible if BP already at goal.", "managementStrategy": "Monitor home blood pressure; tell your prescriber.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Grape Seed Extract", "supplementBName": "Lisinopril", "interactionType": "synergy", "severity": "info", "description": "Grape Seed Extract lowers blood pressure modestly (about 6 mm Hg systolic and 3 mm Hg diastolic in meta-analyses) through improved endothelial function and antioxidant effects. Combined with lisinopril the effects are additive and generally well tolerated, though mild hypotension is possible if blood pressure is already at goal.", "recommendation": "Grape Seed Extract 100-300 mg/day is a typical research dose; monitor home blood pressure after starting and tell your prescriber so your lisinopril dose can be reviewed.", "minimumTimeSeparation": null, "mechanism": "Grape seed proanthocyanidins increase endothelial nitric oxide production, scavenge superoxide, and improve flow-mediated dilation. These actions complement ACE inhibition by lisinopril.", "evidenceLevel": "moderate", "sources": [ { "text": "Zhang H, Liu S, Li L, Liu S, Liu S, Mi J, Tian G. The impact of grape seed extract treatment on blood pressure changes: A meta-analysis of 16 randomized controlled trials. Medicine (Baltimore). 2016;95(33):e4247.", "pmid": "27537554", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27537554/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Additive blood pressure reduction with ACE inhibitor therapy.", "clinicalSignificance": "Useful for residual hypertension; mild hypotension possible if BP already at goal.", "managementStrategy": "Monitor home blood pressure; tell your prescriber.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Pine Bark Extract", "supplementBName": "Ramipril", "interactionType": "synergy", "severity": "info", "description": "Pine Bark Extract (Pycnogenol) lowers blood pressure (about 3 mm Hg systolic and 3 mm Hg diastolic in a meta-analysis) and has independent ACE-inhibitory activity. Two trials specifically tested it as an adjunct to ramipril in hypertensive patients and reported significantly greater blood pressure reduction than ramipril alone. The combination is well tolerated.", "recommendation": "Pine Bark Extract 100-200 mg/day is a typical research dose; monitor home blood pressure after starting and tell your prescriber so your ramipril dose can be reviewed. Mild hypotension is possible if BP is already at goal.", "minimumTimeSeparation": null, "mechanism": "Pine bark procyanidins inhibit ACE in vitro and increase endothelial nitric oxide production. Direct adjunct trials with ramipril show clinically meaningful additive blood pressure reduction.", "evidenceLevel": "moderate", "sources": [ { "text": "Liu X, Wei J, Tan F, Zhou S, Würthwein G, Rohdewald P. Pycnogenol, French maritime pine bark extract, improves endothelial function of hypertensive patients. Life Sci. 2004;74(7):855-62.", "pmid": "14659974", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14659974/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Additive blood pressure reduction with ACE inhibitor therapy.", "clinicalSignificance": "Useful for residual hypertension on ramipril.", "managementStrategy": "Monitor home blood pressure; tell your prescriber.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Lisinopril", "supplementBName": "Taurine", "interactionType": "synergy", "severity": "info", "description": "Taurine lowers blood pressure in prehypertensive and hypertensive adults (about 7 mm Hg systolic in randomized trials) and reduces sympathetic nervous system overactivity. Combined with lisinopril the effects are additive and generally well tolerated, though mild hypotension is possible if blood pressure is already at goal.", "recommendation": "Taurine 1.5-3 g/day is the dose range used in clinical trials; monitor home blood pressure after starting and tell your prescriber so your lisinopril dose can be reviewed.", "minimumTimeSeparation": null, "mechanism": "Taurine modulates overactive sympathetic outflow, promotes endothelial nitric oxide via hydrogen sulfide-mediated pathways, and inhibits transient receptor potential channel-induced calcium influx in vascular smooth muscle. These actions complement ACE inhibition.", "evidenceLevel": "moderate", "sources": [ { "text": "Militante JD, Lombardini JB. Treatment of hypertension with oral taurine: experimental and clinical studies. Amino Acids. 2002;23(4):381-93.", "pmid": "12436205", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12436205/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Additive blood pressure reduction and sympathetic modulation.", "clinicalSignificance": "Useful for residual hypertension on lisinopril.", "managementStrategy": "Monitor home blood pressure; tell your prescriber.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Alpha-Lipoic Acid", "supplementBName": "Lisinopril", "interactionType": "synergy", "severity": "info", "description": "Alpha-Lipoic Acid lowers blood pressure modestly and improves endothelial function. The QUALITY study found that the blood pressure and endothelial benefits of alpha-lipoic acid were strongly potentiated when combined with the ACE inhibitor quinapril in diabetic patients with stage 1 hypertension. The combination is well tolerated; mild hypotension is possible.", "recommendation": "Alpha-Lipoic Acid 300-600 mg/day is a typical research dose; monitor home blood pressure after starting and tell your prescriber so your lisinopril dose can be reviewed. Best taken on an empty stomach.", "minimumTimeSeparation": null, "mechanism": "Alpha-lipoic acid scavenges reactive oxygen species, regenerates other antioxidants, and increases nitric oxide bioavailability in endothelial cells. ACE inhibition independently raises bradykinin and nitric oxide. The combined endothelial effects are amplified.", "evidenceLevel": "emerging", "sources": [ { "text": "Rahman ST, Merchant N, Haque T, Wahi J, Bhaheetharan S, Ferdinand KC, Khan BV. The impact of lipoic acid on endothelial function and proteinuria in quinapril-treated diabetic patients with stage I hypertension: results from the QUALITY study. J Cardiovasc Pharmacol Ther. 2012;17(2):139-45.", "pmid": "21750253", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21750253/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Additive endothelial and blood pressure improvement.", "clinicalSignificance": "Particularly relevant in diabetic hypertensives on ACE inhibitors.", "managementStrategy": "Monitor home blood pressure; tell your prescriber.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Amphetamine/Dextroamphetamine", "supplementBName": "Cocaine", "interactionType": "contraindicated", "severity": "dangerous", "description": "Cocaine and amphetamine/dextroamphetamine are both sympathomimetic stimulants. Using them together can intensify tachycardia, hypertension, coronary vasospasm, overheating, anxiety, and arrhythmia risk. The danger is higher with high stimulant doses, dehydration, strenuous activity, or any history of heart disease, high blood pressure, panic attacks, or stimulant use disorder.", "recommendation": "Do not use cocaine while taking amphetamine/dextroamphetamine. If cocaine exposure occurs, do not take extra stimulant doses and avoid exercise or overheating. Seek emergency care for chest pain, fainting, severe headache, severe agitation, shortness of breath, or a racing or irregular heartbeat.", "minimumTimeSeparation": null, "mechanism": "Cocaine blocks dopamine, norepinephrine, and serotonin reuptake and also has sodium-channel blocking effects. Amphetamine/dextroamphetamine increases catecholamine release through DAT and NET, so the combination can produce additive adrenergic stimulation and myocardial oxygen demand.", "evidenceLevel": "moderate", "sources": [ { "text": "Rush CR, Stoops WW, Hays LR. Cocaine effects during D-amphetamine maintenance: a human laboratory analysis of safety, tolerability and efficacy. Drug Alcohol Depend. 2009;99(1-3):261-271.", "pmid": "18926645", "doi": "10.1016/j.drugalcdep.2008.08.009", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18926645/", "publicSourceType": "PMID" }, { "text": "Kim ST, Park T. Acute and Chronic Effects of Cocaine on Cardiovascular Health. Int J Mol Sci. 2019;20(3):584.", "pmid": "30700023", "doi": "10.3390/ijms20030584", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30700023/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Cocaine and amphetamine/dextroamphetamine can additively increase sympathetic cardiovascular stress.", "clinicalSignificance": "This pairing can turn expected stimulant side effects into chest pain, severe hypertension, arrhythmia, or overheating.", "managementStrategy": "Avoid cocaine completely during amphetamine/dextroamphetamine therapy and seek urgent care for cardiovascular or severe neurologic symptoms.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Lisdexamfetamine", "supplementBName": "Cocaine", "interactionType": "contraindicated", "severity": "dangerous", "description": "Lisdexamfetamine is converted to dextroamphetamine and produces stimulant cardiovascular effects that can overlap with cocaine. Combining them can increase heart rate, blood pressure, myocardial oxygen demand, anxiety, insomnia, overheating, and arrhythmia risk. Controlled cocaine-use studies used careful screening and monitoring, so they should not be treated as proof that real-world co-use is safe.", "recommendation": "Do not use cocaine while taking lisdexamfetamine. Do not raise or repeat either substance to overcome a blunted effect. Seek emergency care for chest pain, severe headache, fainting, shortness of breath, confusion, severe agitation, or an irregular heartbeat.", "minimumTimeSeparation": null, "mechanism": "Lisdexamfetamine is a prodrug that produces systemic dextroamphetamine exposure. Cocaine blocks monoamine reuptake and has direct cardiac ion-channel effects, while dextroamphetamine increases catecholamine release; together they can amplify adrenergic load.", "evidenceLevel": "moderate", "sources": [ { "text": "Mooney ME, Herin DV, Specker S, Babb D, Levin FR, Grabowski J. Pilot study of the effects of lisdexamfetamine on cocaine use: A randomized, double-blind, placebo-controlled trial. Drug Alcohol Depend. 2015;153:94-103.", "pmid": "26116930", "doi": "10.1016/j.drugalcdep.2015.05.042", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26116930/", "publicSourceType": "PMID" }, { "text": "Dolder PC, Strajhar P, Vizeli P, Hammann F, Odermatt A, Liechti ME. Pharmacokinetics and Pharmacodynamics of Lisdexamfetamine Compared with D-Amphetamine in Healthy Subjects. Front Pharmacol. 2017;8:617.", "pmid": "28936175", "doi": "10.3389/fphar.2017.00617", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28936175/", "publicSourceType": "PMID" }, { "text": "Kim ST, Park T. Acute and Chronic Effects of Cocaine on Cardiovascular Health. Int J Mol Sci. 2019;20(3):584.", "pmid": "30700023", "doi": "10.3390/ijms20030584", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30700023/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Lisdexamfetamine and cocaine can combine dextroamphetamine exposure with cocaine-driven sympathetic and cardiac toxicity.", "clinicalSignificance": "The combination can raise the chance of severe cardiovascular or overheating events, especially outside monitored research settings.", "managementStrategy": "Avoid cocaine completely during lisdexamfetamine therapy and get urgent care for chest pain, syncope, severe agitation, or irregular heartbeat.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Methylphenidate", "supplementBName": "Cocaine", "interactionType": "contraindicated", "severity": "dangerous", "description": "Methylphenidate and cocaine both act as stimulant monoamine transporter blockers. A small controlled study did not find clinically significant physiologic toxicity at the tested doses, but cocaine still has well-established risks of acute hypertension, coronary spasm, arrhythmias, and myocardial infarction. Real-world cocaine dose, purity, route, and redosing make this combination unsafe.", "recommendation": "Do not use cocaine while taking methylphenidate. Do not take extra methylphenidate to counter cocaine withdrawal or fatigue. Seek emergency care for chest pain, severe headache, fainting, severe anxiety or agitation, shortness of breath, or a racing or irregular heartbeat.", "minimumTimeSeparation": null, "mechanism": "Methylphenidate blocks DAT and NET, increasing dopamine and norepinephrine signaling. Cocaine also blocks DAT, NET, and SERT and can impair cardiac conduction through sodium-channel blockade, creating additive stimulant and cardiovascular toxicity potential.", "evidenceLevel": "moderate", "sources": [ { "text": "Winhusen T, Somoza E, Singal BM, et al. Methylphenidate and cocaine: a placebo-controlled drug interaction study. Pharmacol Biochem Behav. 2006;85(1):29-38.", "pmid": "16916538", "doi": "10.1016/j.pbb.2006.06.023", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16916538/", "publicSourceType": "PMID" }, { "text": "Volkow ND, Wang GJ, Fowler JS, et al. Cardiovascular effects of methylphenidate in humans are associated with increases of dopamine in brain and of epinephrine in plasma. Psychopharmacology (Berl). 2003;166(3):264-270.", "pmid": "12589522", "doi": "10.1007/s00213-002-1340-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12589522/", "publicSourceType": "PMID" }, { "text": "Kim ST, Park T. Acute and Chronic Effects of Cocaine on Cardiovascular Health. Int J Mol Sci. 2019;20(3):584.", "pmid": "30700023", "doi": "10.3390/ijms20030584", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30700023/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Methylphenidate and cocaine can stack monoamine transporter blockade and cardiovascular stress.", "clinicalSignificance": "Cocaine's unpredictable dose and route make co-use risky even though low-dose monitored research did not show major toxicity.", "managementStrategy": "Avoid cocaine completely during methylphenidate therapy and seek urgent care for cardiovascular or severe neuropsychiatric symptoms.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Amphetamine/Dextroamphetamine", "supplementBName": "MDMA", "interactionType": "contraindicated", "severity": "dangerous", "description": "MDMA is a substituted amphetamine with strong serotonin, norepinephrine, and dopamine releasing effects. Combining it with amphetamine/dextroamphetamine can increase stimulant toxicity, including hypertension, tachycardia, hyperthermia, dehydration, agitation, panic, and arrhythmias. Risk rises sharply with dancing or strenuous activity, hot environments, redosing, or other serotonergic or stimulant substances.", "recommendation": "Do not use MDMA while taking amphetamine/dextroamphetamine. Do not redose either substance to chase effects or stay awake. Seek emergency care for high fever, confusion, severe agitation, chest pain, fainting, seizure, severe headache, or a racing or irregular heartbeat.", "minimumTimeSeparation": null, "mechanism": "Amphetamine/dextroamphetamine promotes dopamine and norepinephrine release through DAT and NET. MDMA releases serotonin through SERT and also releases norepinephrine and dopamine, producing overlapping adrenergic stimulation plus hyperthermia risk.", "evidenceLevel": "moderate", "sources": [ { "text": "Green AR, Mechan AO, Elliott JM, O'Shea E, Colado MI. The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, \"ecstasy\"). Pharmacol Rev. 2003;55(3):463-508.", "pmid": "12869661", "doi": "10.1124/pr.55.3.3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12869661/", "publicSourceType": "PMID" }, { "text": "Steinkellner T, Freissmuth M, Sitte HH, Montgomery T. The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy'), methamphetamine and D-amphetamine. Biol Chem. 2011;392(1-2):103-115.", "pmid": "21194370", "doi": "10.1515/BC.2011.016", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21194370/", "publicSourceType": "PMID" }, { "text": "O'Cain PA, Hletko SB, Ogden BA, Varner KJ. Cardiovascular and sympathetic responses and reflex changes elicited by MDMA. Physiol Behav. 2000;70(1-2):141-148.", "pmid": "10978489", "doi": "10.1016/s0031-9384(00)00235-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10978489/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "MDMA and amphetamine/dextroamphetamine can additively increase adrenergic stimulation and hyperthermia risk.", "clinicalSignificance": "This combination can escalate from expected stimulant effects to life-threatening overheating, arrhythmia, seizure, or severe agitation.", "managementStrategy": "Avoid MDMA completely during amphetamine/dextroamphetamine therapy and seek urgent care for hyperthermia or cardiovascular symptoms.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Lisdexamfetamine", "supplementBName": "MDMA", "interactionType": "contraindicated", "severity": "dangerous", "description": "Lisdexamfetamine produces dextroamphetamine exposure, and MDMA adds serotonergic and sympathomimetic stimulation. Co-use can increase risk of hypertension, tachycardia, hyperthermia, dehydration, agitation, panic, arrhythmias, and seizures. The longer duration of lisdexamfetamine can leave stimulant effects present well into the period when MDMA is being used or redosed.", "recommendation": "Do not use MDMA while taking lisdexamfetamine. Skipping or delaying a single dose does not reliably remove risk because stimulant effects may persist for much of the day. Seek emergency care for high fever, confusion, severe agitation, chest pain, fainting, seizure, or an irregular heartbeat.", "minimumTimeSeparation": null, "mechanism": "Lisdexamfetamine is converted in blood to dextroamphetamine, which increases catecholamine release. MDMA releases serotonin, norepinephrine, and dopamine through monoamine transporters, producing overlapping cardiovascular stimulation and thermoregulatory stress.", "evidenceLevel": "moderate", "sources": [ { "text": "Dolder PC, Strajhar P, Vizeli P, Hammann F, Odermatt A, Liechti ME. Pharmacokinetics and Pharmacodynamics of Lisdexamfetamine Compared with D-Amphetamine in Healthy Subjects. Front Pharmacol. 2017;8:617.", "pmid": "28936175", "doi": "10.3389/fphar.2017.00617", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28936175/", "publicSourceType": "PMID" }, { "text": "Green AR, Mechan AO, Elliott JM, O'Shea E, Colado MI. The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, \"ecstasy\"). Pharmacol Rev. 2003;55(3):463-508.", "pmid": "12869661", "doi": "10.1124/pr.55.3.3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12869661/", "publicSourceType": "PMID" }, { "text": "Steinkellner T, Freissmuth M, Sitte HH, Montgomery T. The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy'), methamphetamine and D-amphetamine. Biol Chem. 2011;392(1-2):103-115.", "pmid": "21194370", "doi": "10.1515/BC.2011.016", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21194370/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "MDMA can stack serotonergic and adrenergic toxicity on top of lisdexamfetamine-derived dextroamphetamine exposure.", "clinicalSignificance": "The combination can produce severe overheating, blood pressure elevation, arrhythmia, agitation, or seizure.", "managementStrategy": "Avoid MDMA completely during lisdexamfetamine therapy and seek urgent care for hyperthermia, seizure, chest pain, or fainting.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Methylphenidate", "supplementBName": "MDMA", "interactionType": "contraindicated", "severity": "dangerous", "description": "Methylphenidate and MDMA have a documented human pharmacodynamic interaction. In a controlled crossover study, the combination did not add desired psychoactive effects but did increase cardiovascular and adverse effects compared with either drug alone. This creates avoidable risk for hypertension, tachycardia, hyperthermia, anxiety, and arrhythmias, especially with redosing or hot environments.", "recommendation": "Do not use MDMA while taking methylphenidate. Do not take extra MDMA if the effect feels blunted or different. Seek emergency care for high fever, confusion, severe agitation, chest pain, fainting, seizure, or a racing or irregular heartbeat.", "minimumTimeSeparation": null, "mechanism": "Methylphenidate blocks dopamine and norepinephrine transporters, while MDMA enters monoamine neurons through transporters and promotes serotonin, norepinephrine, and dopamine release. The combination increases autonomic and endocrine stress without reliably increasing desired subjective effects.", "evidenceLevel": "moderate", "sources": [ { "text": "Hysek CM, Simmler LD, Schillinger N, et al. Pharmacokinetic and pharmacodynamic effects of methylphenidate and MDMA administered alone or in combination. Int J Neuropsychopharmacol. 2014;17(3):371-381.", "pmid": "24103254", "doi": "10.1017/S1461145713001132", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24103254/", "publicSourceType": "PMID" }, { "text": "Sarparast A, Thomas K, Malcolm B, Stauffer CS. Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review. Psychopharmacology (Berl). 2022;239(6):1945-1976.", "pmid": "35253070", "doi": "10.1007/s00213-022-06083-y", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35253070/", "publicSourceType": "PMID" }, { "text": "Green AR, Mechan AO, Elliott JM, O'Shea E, Colado MI. The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, \"ecstasy\"). Pharmacol Rev. 2003;55(3):463-508.", "pmid": "12869661", "doi": "10.1124/pr.55.3.3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12869661/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Methylphenidate plus MDMA increases cardiovascular and adverse stimulant effects without adding reliable benefit.", "clinicalSignificance": "The direct human interaction data support avoiding this pairing because toxicity can rise even when desired effects do not.", "managementStrategy": "Avoid MDMA completely during methylphenidate therapy and seek urgent care for hyperthermia or cardiovascular symptoms.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Amphetamine/Dextroamphetamine", "supplementBName": "Nicotine", "interactionType": "caution", "severity": "moderate", "description": "Nicotine can add sympathetic stimulation to amphetamine/dextroamphetamine and may also reinforce stimulant use patterns. The combination can worsen palpitations, jitteriness, anxiety, insomnia, appetite suppression, and blood pressure or heart rate elevation. Risk is higher with high-nicotine vaping, frequent nicotine pouches, multiple stimulant doses, or underlying cardiovascular disease.", "recommendation": "Limit nicotine while taking amphetamine/dextroamphetamine, especially around peak stimulant effect. Check blood pressure and pulse if you notice palpitations, chest tightness, anxiety, or headaches. Seek urgent care for chest pain, fainting, severe shortness of breath, or an irregular heartbeat.", "minimumTimeSeparation": null, "mechanism": "Nicotine activates nicotinic acetylcholine receptors on sympathetic nerve endings and the adrenal medulla, increasing catecholamine release. Amphetamine/dextroamphetamine increases dopamine and norepinephrine release, creating additive autonomic stimulation and possible reinforcement of co-use.", "evidenceLevel": "emerging", "sources": [ { "text": "McNealy KR, Weyrich L, Bevins RA. The co-use of nicotine and prescription psychostimulants: A review of their behavioral and neuropharmacological interactions. Drug Alcohol Depend. 2023;248:109906.", "pmid": "37216808", "doi": "10.1016/j.drugalcdep.2023.109906", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37216808/", "publicSourceType": "PMID" }, { "text": "Haass M, Kubler W. Nicotine and sympathetic neurotransmission. Cardiovasc Drugs Ther. 1997;10(6):657-665.", "pmid": "9110108", "doi": "10.1007/BF00053022", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9110108/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Nicotine can add sympathetic stimulation and reinforce co-use with amphetamine/dextroamphetamine.", "clinicalSignificance": "People who already get stimulant-related palpitations, anxiety, or insomnia may have noticeably worse symptoms with nicotine.", "managementStrategy": "Reduce nicotine exposure near stimulant peaks and monitor pulse, blood pressure, sleep, and anxiety symptoms.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Lisdexamfetamine", "supplementBName": "Nicotine", "interactionType": "caution", "severity": "moderate", "description": "Nicotine and prescription psychostimulants are commonly co-used and can interact behaviorally and physiologically. With lisdexamfetamine, nicotine may worsen palpitations, jitteriness, anxiety, insomnia, appetite suppression, and pulse elevation. High-dose nicotine products and frequent redosing are more likely to cause symptoms.", "recommendation": "Use the lowest practical nicotine exposure while taking lisdexamfetamine, especially during the first half of the day when stimulant effects are strongest. Monitor pulse, blood pressure, sleep, and anxiety if you vape or use nicotine pouches frequently. Seek urgent care for chest pain, fainting, severe shortness of breath, or an irregular heartbeat.", "minimumTimeSeparation": null, "mechanism": "Lisdexamfetamine is converted to dextroamphetamine, which increases catecholamine signaling. Nicotine stimulates sympathetic catecholamine release through nicotinic receptors, so the combination can add autonomic stimulation and may strengthen repeated co-use behavior.", "evidenceLevel": "emerging", "sources": [ { "text": "McNealy KR, Weyrich L, Bevins RA. The co-use of nicotine and prescription psychostimulants: A review of their behavioral and neuropharmacological interactions. Drug Alcohol Depend. 2023;248:109906.", "pmid": "37216808", "doi": "10.1016/j.drugalcdep.2023.109906", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37216808/", "publicSourceType": "PMID" }, { "text": "Dolder PC, Strajhar P, Vizeli P, Hammann F, Odermatt A, Liechti ME. Pharmacokinetics and Pharmacodynamics of Lisdexamfetamine Compared with D-Amphetamine in Healthy Subjects. Front Pharmacol. 2017;8:617.", "pmid": "28936175", "doi": "10.3389/fphar.2017.00617", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28936175/", "publicSourceType": "PMID" }, { "text": "Benowitz NL, Burbank AD. Cardiovascular toxicity of nicotine: Implications for electronic cigarette use. Trends Cardiovasc Med. 2016;26(6):515-523.", "pmid": "27079891", "doi": "10.1016/j.tcm.2016.03.001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27079891/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Nicotine can add cardiovascular stimulation and co-use reinforcement to lisdexamfetamine.", "clinicalSignificance": "Frequent nicotine use may make stimulant side effects harder to distinguish from overmedication or anxiety.", "managementStrategy": "Limit nicotine near lisdexamfetamine peak effect and monitor cardiovascular and sleep-related symptoms.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Methylphenidate", "supplementBName": "Nicotine", "interactionType": "caution", "severity": "moderate", "description": "Nicotine can add sympathetic stimulation to methylphenidate and may increase the likelihood of repeated co-use. The combination can worsen palpitations, jitteriness, anxiety, appetite suppression, insomnia, and blood pressure or heart rate elevation. People with hypertension, arrhythmias, panic symptoms, or heavy vaping or nicotine pouch use are more likely to notice problems.", "recommendation": "Limit nicotine while taking methylphenidate, especially around peak dose effect. Monitor pulse, blood pressure, anxiety, and sleep if you use nicotine daily. Seek urgent care for chest pain, fainting, severe shortness of breath, or a racing or irregular heartbeat.", "minimumTimeSeparation": null, "mechanism": "Methylphenidate increases catecholamine signaling by blocking DAT and NET. Nicotine activates sympathetic neurotransmission and catecholamine release, which can add to methylphenidate's cardiovascular and activating effects.", "evidenceLevel": "emerging", "sources": [ { "text": "McNealy KR, Weyrich L, Bevins RA. The co-use of nicotine and prescription psychostimulants: A review of their behavioral and neuropharmacological interactions. Drug Alcohol Depend. 2023;248:109906.", "pmid": "37216808", "doi": "10.1016/j.drugalcdep.2023.109906", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37216808/", "publicSourceType": "PMID" }, { "text": "Volkow ND, Wang GJ, Fowler JS, et al. Cardiovascular effects of methylphenidate in humans are associated with increases of dopamine in brain and of epinephrine in plasma. Psychopharmacology (Berl). 2003;166(3):264-270.", "pmid": "12589522", "doi": "10.1007/s00213-002-1340-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12589522/", "publicSourceType": "PMID" }, { "text": "Haass M, Kubler W. Nicotine and sympathetic neurotransmission. Cardiovasc Drugs Ther. 1997;10(6):657-665.", "pmid": "9110108", "doi": "10.1007/BF00053022", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9110108/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Nicotine can add sympathetic stimulation and co-use reinforcement to methylphenidate.", "clinicalSignificance": "The combination may worsen common stimulant adverse effects, especially palpitations, anxiety, and insomnia.", "managementStrategy": "Reduce nicotine exposure near methylphenidate peaks and monitor pulse, blood pressure, sleep, and anxiety.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Amphetamine/Dextroamphetamine", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Amphetamine/dextroamphetamine can partially counter alcohol-related psychomotor slowing without making the person sober. This can make intoxication feel less obvious and encourage more drinking, driving, risky activity, or additional stimulant use. Alcohol and stimulants can also add cardiovascular strain, especially with binge drinking or dehydration.", "recommendation": "Avoid alcohol on days you take amphetamine/dextroamphetamine when possible. If you drink, keep intake low, do not drive, and do not take extra stimulant doses to stay alert. Seek care for chest pain, fainting, severe agitation, confusion, or an irregular heartbeat.", "minimumTimeSeparation": null, "mechanism": "Dextroamphetamine increases catecholamine signaling and alertness, while ethanol impairs judgment, coordination, and reaction time through CNS depressant effects. The stimulant can mask perceived impairment without reversing alcohol's cognitive and motor risks, and both can increase cardiovascular workload.", "evidenceLevel": "moderate", "sources": [ { "text": "Perez-Reyes M, White WR, McDonald SA, Hicks RE. Interaction between ethanol and dextroamphetamine: effects on psychomotor performance. Alcohol Clin Exp Res. 1992;16(1):75-81.", "pmid": "1558306", "doi": "10.1111/j.1530-0277.1992.tb00640.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1558306/", "publicSourceType": "PMID" }, { "text": "Althobaiti YS, Sari Y. Alcohol Interactions with Psychostimulants: An Overview of Animal and Human Studies. J Addict Res Ther. 2016;7(3):281.", "pmid": "27478679", "doi": "10.4172/2155-6105.1000281", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27478679/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Amphetamine/dextroamphetamine can mask alcohol impairment while adding stimulant cardiovascular load.", "clinicalSignificance": "Feeling less drunk can increase the chance of overdrinking, unsafe driving, injury, or cardiovascular symptoms.", "managementStrategy": "Avoid or sharply limit alcohol during amphetamine/dextroamphetamine use and never use extra stimulant to offset drinking.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Methylphenidate", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Alcohol changes methylphenidate handling and can form ethylphenidate, an active transesterification metabolite. Ethanol can increase early methylphenidate exposure and may intensify euphoria, stimulation, impaired judgment, palpitations, and misuse risk. The combination is especially risky with immediate-release products, high methylphenidate doses, binge drinking, or a history of substance use disorder.", "recommendation": "Avoid alcohol while taking methylphenidate, especially around dose times and with immediate-release formulations. Do not drink to intensify methylphenidate or take extra methylphenidate while drinking. Seek care for chest pain, fainting, severe agitation, confusion, or a racing or irregular heartbeat.", "minimumTimeSeparation": null, "mechanism": "Ethanol competes with methylphenidate metabolism through carboxylesterase 1 and supports transesterification to ethylphenidate. This can increase parent-drug exposure and add a psychoactive stimulant metabolite while alcohol continues to impair judgment and coordination.", "evidenceLevel": "moderate", "sources": [ { "text": "Markowitz JS, DeVane CL, Boulton DW, et al. Ethylphenidate formation in human subjects after the administration of a single dose of methylphenidate and ethanol. Drug Metab Dispos. 2000;28(6):620-624.", "pmid": "10820132", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10820132/", "publicSourceType": "PMID" }, { "text": "Zhu HJ, Patrick KS, Markowitz JS. Enantiospecific determination of DL-methylphenidate and DL-ethylphenidate in plasma by liquid chromatography-tandem mass spectrometry: application to human ethanol interactions. J Chromatogr B Analyt Technol Biomed Life Sci. 2011;879(11-12):783-788.", "pmid": "21402502", "doi": "10.1016/j.jchromb.2011.02.033", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21402502/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Alcohol can increase methylphenidate exposure and produce ethylphenidate while both substances impair judgment.", "clinicalSignificance": "This can increase stimulant adverse effects and misuse risk rather than simply combining two independent substances.", "managementStrategy": "Avoid alcohol during methylphenidate therapy, particularly near dose times and with immediate-release products.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Guanfacine", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Guanfacine lowers sympathetic outflow and commonly causes sedation, fatigue, dizziness, bradycardia, and lower blood pressure. Alcohol can add CNS depression and worsen dizziness, slowed reaction time, orthostatic symptoms, and fainting risk. The combination is most concerning when starting guanfacine, increasing the dose, drinking heavily, or using other sedating substances.", "recommendation": "Avoid alcohol when starting guanfacine or after any dose increase. If you drink later in stable treatment, keep intake low and avoid driving, heat exposure, or standing quickly. Seek medical help for fainting, severe dizziness, very slow pulse, confusion, or repeated vomiting.", "minimumTimeSeparation": null, "mechanism": "Guanfacine is a central alpha-2A adrenergic agonist that reduces sympathetic tone, lowering blood pressure and heart rate while causing sedation in some users. Alcohol adds pharmacodynamic CNS depression and can worsen postural instability and impaired coordination.", "evidenceLevel": "moderate", "sources": [ { "text": "Sorkin EM, Heel RC. Guanfacine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of hypertension. Drugs. 1986;31(4):301-336.", "pmid": "3519177", "doi": "10.2165/00003495-198631040-00003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3519177/", "publicSourceType": "PMID" }, { "text": "Magometschnigg D, Bonelli J, Gassner A, et al. Duration of the hypotensive effect of guanfacine. Int J Clin Pharmacol Ther Toxicol. 1982;20(4):174-178.", "pmid": "7042594", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7042594/", "publicSourceType": "PMID" }, { "text": "Weathermon R, Crabb DW. Alcohol and medication interactions. Alcohol Res Health. 1999;23(1):40-54.", "pmid": "10890797", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10890797/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Alcohol can add sedation and orthostatic hypotension risk to guanfacine.", "clinicalSignificance": "The combination can cause falls, fainting, impaired driving, or excessive sedation, especially during titration.", "managementStrategy": "Avoid alcohol during guanfacine initiation or dose changes and keep intake low if use is resumed after stable treatment.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Ciprofloxacin", "supplementBName": "Aluminum/Magnesium Hydroxide", "interactionType": "timingSensitive", "severity": "serious", "description": "Aluminum and magnesium in antacids form insoluble chelate complexes with ciprofloxacin in the gut, dramatically reducing antibiotic absorption. Studies have shown bioavailability reductions of 50 to 90 percent when taken together, which can drop ciprofloxacin levels below the threshold needed to clear infection. This is one of the most clinically significant absorption interactions for fluoroquinolones.", "recommendation": "Take ciprofloxacin at least 2 hours before or 6 hours after any aluminum or magnesium hydroxide antacid. Do not co-administer in the same dose.", "minimumTimeSeparation": 360, "mechanism": "Polyvalent cations (Al3+, Mg2+) bind to the 4-oxo and 3-carboxyl groups on the fluoroquinolone ring, forming nonabsorbable chelate complexes in the small intestine and blocking enterocyte uptake.", "evidenceLevel": "strong", "sources": [ { "text": "Eljaaly K, Helal A, Almandeel T, Algarni R, Alshehri S. Multivalent cations interactions with fluoroquinolones or tetracyclines: A cross-sectional study. Saudi J Biol Sci. 2021;28(12):6929-6932.", "pmid": "34866992", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34866992/", "publicSourceType": "PMID" }, { "text": "Sultana N, Arayne MS, Hussain F. In vitro monitoring of ciprofloxacin antacids interactions by UV & HPLC. Pak J Pharm Sci. 2005;18(4):23-31.", "pmid": "16380354", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16380354/", "publicSourceType": "PMID" }, { "text": "Wiesner A, Zagrodzki P, Gawalska A, Paśko P. Together or Apart? Revealing the Impact of Dietary Interventions on Bioavailability of Quinolones: A Systematic Review with Meta-analyses. Clin Pharmacokinet. 2024;63(6):773-818.", "pmid": "38807006", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38807006/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Antacid cations chelate ciprofloxacin and block its absorption.", "clinicalSignificance": "Co-administration can reduce ciprofloxacin levels below therapeutic threshold and lead to treatment failure.", "managementStrategy": "Separate ciprofloxacin from antacid by at least 2 hours before or 6 hours after.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Ciprofloxacin", "supplementBName": "Calcium Carbonate", "interactionType": "timingSensitive", "severity": "serious", "description": "Calcium carbonate, whether taken as an antacid or calcium supplement, binds ciprofloxacin in the gut and reduces its absorption by 30 to 50 percent. Even calcium-fortified foods such as fortified orange juice or dairy can produce clinically meaningful reductions. Lower antibiotic exposure can lead to treatment failure and resistance.", "recommendation": "Take ciprofloxacin at least 2 hours before or 6 hours after calcium carbonate. Avoid taking with calcium-fortified drinks or dairy in the same window.", "minimumTimeSeparation": 360, "mechanism": "Ca2+ cations form insoluble chelates with the 3-carboxyl and 4-oxo groups of the fluoroquinolone core, preventing intestinal absorption.", "evidenceLevel": "strong", "sources": [ { "text": "Eljaaly K, Helal A, Almandeel T, Algarni R, Alshehri S. Multivalent cations interactions with fluoroquinolones or tetracyclines: A cross-sectional study. Saudi J Biol Sci. 2021;28(12):6929-6932.", "pmid": "34866992", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34866992/", "publicSourceType": "PMID" }, { "text": "Wiesner A, Zagrodzki P, Gawalska A, Paśko P. Together or Apart? Revealing the Impact of Dietary Interventions on Bioavailability of Quinolones: A Systematic Review with Meta-analyses. Clin Pharmacokinet. 2024;63(6):773-818.", "pmid": "38807006", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38807006/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Calcium carbonate chelates ciprofloxacin and lowers its bioavailability.", "clinicalSignificance": "Reduced absorption risks subtherapeutic dosing and treatment failure.", "managementStrategy": "Separate doses by at least 2 hours before or 6 hours after.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Ciprofloxacin", "supplementBName": "Iron Bisglycinate", "interactionType": "timingSensitive", "severity": "serious", "description": "Iron, including chelated forms like iron bisglycinate, binds ciprofloxacin in the gastrointestinal tract and forms insoluble complexes that prevent absorption. The reduction in ciprofloxacin bioavailability can exceed 50 percent. Although bisglycinate is marketed as gentler on the gut, it still contains free iron available for fluoroquinolone chelation in the intestinal lumen.", "recommendation": "Take ciprofloxacin at least 2 hours before or 6 hours after any iron supplement, including bisglycinate. Do not take together in the same dose.", "minimumTimeSeparation": 360, "mechanism": "Fe2+ and Fe3+ cations chelate the 3-carboxyl and 4-oxo groups of ciprofloxacin, forming insoluble complexes that are not absorbed across enterocytes.", "evidenceLevel": "strong", "sources": [ { "text": "Campbell NR, Hasinoff BB. Iron supplements: a common cause of drug interactions. Br J Clin Pharmacol. 1991;31(3):251-5.", "pmid": "2054263", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2054263/", "publicSourceType": "PMID" }, { "text": "Polk RE. Drug-drug interactions with ciprofloxacin and other fluoroquinolones. Am J Med. 1989;87(5A):76S-81S.", "pmid": "2686430", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2686430/", "publicSourceType": "PMID" }, { "text": "Wiesner A, Zagrodzki P, Gawalska A, Paśko P. Together or Apart? Revealing the Impact of Dietary Interventions on Bioavailability of Quinolones: A Systematic Review with Meta-analyses. Clin Pharmacokinet. 2024;63(6):773-818.", "pmid": "38807006", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38807006/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Iron bisglycinate chelates ciprofloxacin and blocks its absorption.", "clinicalSignificance": "Co-administration risks subtherapeutic antibiotic exposure and treatment failure.", "managementStrategy": "Separate ciprofloxacin from iron bisglycinate by 2 hours before or 6 hours after.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Ciprofloxacin", "supplementBName": "Magnesium Citrate", "interactionType": "timingSensitive", "severity": "serious", "description": "Magnesium citrate, like other magnesium salts, chelates ciprofloxacin in the gut and reduces its absorption. Single-dose studies have shown bioavailability reductions of more than 40 percent when magnesium and ciprofloxacin are taken together. Lower antibiotic concentrations risk treatment failure.", "recommendation": "Take ciprofloxacin at least 2 hours before or 6 hours after magnesium citrate. Do not co-administer in the same dose.", "minimumTimeSeparation": 360, "mechanism": "Mg2+ cations chelate the 3-carboxyl and 4-oxo groups on ciprofloxacin, forming insoluble complexes in the intestinal lumen that are not absorbed.", "evidenceLevel": "strong", "sources": [ { "text": "Eljaaly K, Helal A, Almandeel T, Algarni R, Alshehri S. Multivalent cations interactions with fluoroquinolones or tetracyclines: A cross-sectional study. Saudi J Biol Sci. 2021;28(12):6929-6932.", "pmid": "34866992", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34866992/", "publicSourceType": "PMID" }, { "text": "Wiesner A, Zagrodzki P, Gawalska A, Paśko P. Together or Apart? Revealing the Impact of Dietary Interventions on Bioavailability of Quinolones: A Systematic Review with Meta-analyses. Clin Pharmacokinet. 2024;63(6):773-818.", "pmid": "38807006", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38807006/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Magnesium citrate chelates ciprofloxacin and reduces its absorption.", "clinicalSignificance": "Co-administration risks subtherapeutic levels and treatment failure.", "managementStrategy": "Separate ciprofloxacin from magnesium citrate by 2 hours before or 6 hours after.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Ciprofloxacin", "supplementBName": "Magnesium L-Threonate", "interactionType": "timingSensitive", "severity": "serious", "description": "All forms of supplemental magnesium, including magnesium L-threonate used for cognitive support, chelate ciprofloxacin in the gut and reduce its absorption. The bioavailability reduction can exceed 40 percent. The chelation is driven by free Mg2+, which dissociates from any magnesium salt in the acidic environment of the stomach.", "recommendation": "Take ciprofloxacin at least 2 hours before or 6 hours after magnesium L-threonate. Do not combine in the same dose.", "minimumTimeSeparation": 360, "mechanism": "Mg2+ released from magnesium L-threonate chelates the 3-carboxyl and 4-oxo groups on the fluoroquinolone core, forming insoluble complexes that block enterocyte absorption.", "evidenceLevel": "strong", "sources": [ { "text": "Eljaaly K, Helal A, Almandeel T, Algarni R, Alshehri S. Multivalent cations interactions with fluoroquinolones or tetracyclines: A cross-sectional study. Saudi J Biol Sci. 2021;28(12):6929-6932.", "pmid": "34866992", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34866992/", "publicSourceType": "PMID" }, { "text": "Wiesner A, Zagrodzki P, Gawalska A, Paśko P. Together or Apart? Revealing the Impact of Dietary Interventions on Bioavailability of Quinolones: A Systematic Review with Meta-analyses. Clin Pharmacokinet. 2024;63(6):773-818.", "pmid": "38807006", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38807006/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Magnesium L-threonate chelates ciprofloxacin and reduces its absorption.", "clinicalSignificance": "Reduced absorption risks subtherapeutic dosing and treatment failure.", "managementStrategy": "Separate doses by 2 hours before or 6 hours after.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Ciprofloxacin", "supplementBName": "Magnesium Malate", "interactionType": "timingSensitive", "severity": "serious", "description": "Magnesium malate, like other magnesium salts, releases Mg2+ in the gut that chelates ciprofloxacin and reduces its absorption. The bioavailability reduction is clinically meaningful and can compromise antibiotic efficacy.", "recommendation": "Take ciprofloxacin at least 2 hours before or 6 hours after magnesium malate. Do not co-administer.", "minimumTimeSeparation": 360, "mechanism": "Mg2+ from magnesium malate chelates the 3-carboxyl and 4-oxo groups on the fluoroquinolone core, forming insoluble complexes that block enterocyte uptake.", "evidenceLevel": "strong", "sources": [ { "text": "Eljaaly K, Helal A, Almandeel T, Algarni R, Alshehri S. Multivalent cations interactions with fluoroquinolones or tetracyclines: A cross-sectional study. Saudi J Biol Sci. 2021;28(12):6929-6932.", "pmid": "34866992", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34866992/", "publicSourceType": "PMID" }, { "text": "Wiesner A, Zagrodzki P, Gawalska A, Paśko P. Together or Apart? Revealing the Impact of Dietary Interventions on Bioavailability of Quinolones: A Systematic Review with Meta-analyses. Clin Pharmacokinet. 2024;63(6):773-818.", "pmid": "38807006", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38807006/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Magnesium malate chelates ciprofloxacin and lowers its absorption.", "clinicalSignificance": "Risk of treatment failure if doses overlap.", "managementStrategy": "Separate doses by 2 hours before or 6 hours after.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Ciprofloxacin", "supplementBName": "Magnesium Taurate", "interactionType": "timingSensitive", "severity": "serious", "description": "Magnesium taurate dissociates in the gut to release free Mg2+, which chelates ciprofloxacin and dramatically reduces its absorption. Even modest doses of supplemental magnesium can lower fluoroquinolone bioavailability enough to cause treatment failure.", "recommendation": "Take ciprofloxacin at least 2 hours before or 6 hours after magnesium taurate. Do not co-administer.", "minimumTimeSeparation": 360, "mechanism": "Mg2+ from magnesium taurate chelates the 3-carboxyl and 4-oxo groups on the fluoroquinolone core, forming insoluble complexes that block intestinal absorption.", "evidenceLevel": "strong", "sources": [ { "text": "Eljaaly K, Helal A, Almandeel T, Algarni R, Alshehri S. Multivalent cations interactions with fluoroquinolones or tetracyclines: A cross-sectional study. Saudi J Biol Sci. 2021;28(12):6929-6932.", "pmid": "34866992", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34866992/", "publicSourceType": "PMID" }, { "text": "Wiesner A, Zagrodzki P, Gawalska A, Paśko P. Together or Apart? Revealing the Impact of Dietary Interventions on Bioavailability of Quinolones: A Systematic Review with Meta-analyses. Clin Pharmacokinet. 2024;63(6):773-818.", "pmid": "38807006", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38807006/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Magnesium taurate chelates ciprofloxacin and reduces its absorption.", "clinicalSignificance": "Reduced antibiotic levels risk treatment failure.", "managementStrategy": "Separate doses by 2 hours before or 6 hours after.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Ciprofloxacin", "supplementBName": "Zinc Picolinate", "interactionType": "timingSensitive", "severity": "serious", "description": "Zinc, including chelated forms like zinc picolinate, binds ciprofloxacin in the gut and reduces its absorption by approximately 24 to 56 percent depending on dose. Although the magnitude is smaller than with iron or calcium, the reduction is still enough to risk treatment failure in serious infections.", "recommendation": "Take ciprofloxacin at least 2 hours before or 6 hours after zinc picolinate. Do not take in the same dose.", "minimumTimeSeparation": 360, "mechanism": "Zn2+ chelates the 3-carboxyl and 4-oxo groups on the fluoroquinolone core, forming nonabsorbable complexes in the intestinal lumen.", "evidenceLevel": "strong", "sources": [ { "text": "Polk RE. Drug-drug interactions with ciprofloxacin and other fluoroquinolones. Am J Med. 1989;87(5A):76S-81S.", "pmid": "2686430", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2686430/", "publicSourceType": "PMID" }, { "text": "Wiesner A, Zagrodzki P, Gawalska A, Paśko P. Together or Apart? Revealing the Impact of Dietary Interventions on Bioavailability of Quinolones: A Systematic Review with Meta-analyses. Clin Pharmacokinet. 2024;63(6):773-818.", "pmid": "38807006", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38807006/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Zinc picolinate chelates ciprofloxacin and reduces its absorption.", "clinicalSignificance": "Reduced absorption risks subtherapeutic levels and treatment failure.", "managementStrategy": "Separate doses by 2 hours before or 6 hours after.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Ciprofloxacin", "supplementBName": "Zinc Carnosine", "interactionType": "timingSensitive", "severity": "serious", "description": "Zinc carnosine releases Zn2+ in the gut that chelates ciprofloxacin and reduces its absorption. The bioavailability reduction is sufficient to compromise antibiotic efficacy in serious infections.", "recommendation": "Take ciprofloxacin at least 2 hours before or 6 hours after zinc carnosine. Do not co-administer.", "minimumTimeSeparation": 360, "mechanism": "Zn2+ chelates the 3-carboxyl and 4-oxo groups on the fluoroquinolone core, forming nonabsorbable complexes in the intestinal lumen.", "evidenceLevel": "strong", "sources": [ { "text": "Polk RE. Drug-drug interactions with ciprofloxacin and other fluoroquinolones. Am J Med. 1989;87(5A):76S-81S.", "pmid": "2686430", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2686430/", "publicSourceType": "PMID" }, { "text": "Wiesner A, Zagrodzki P, Gawalska A, Paśko P. Together or Apart? Revealing the Impact of Dietary Interventions on Bioavailability of Quinolones: A Systematic Review with Meta-analyses. Clin Pharmacokinet. 2024;63(6):773-818.", "pmid": "38807006", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38807006/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Zinc carnosine chelates ciprofloxacin and lowers its absorption.", "clinicalSignificance": "Reduced absorption risks treatment failure.", "managementStrategy": "Separate doses by 2 hours before or 6 hours after.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Ciprofloxacin", "supplementBName": "Probiotics", "interactionType": "synergy", "severity": "info", "description": "Probiotic supplementation during ciprofloxacin therapy reduces the incidence of antibiotic-associated diarrhea by restoring colonization resistance in the gut microbiome. Meta-analyses of probiotics across antibiotic classes show roughly a 50 percent reduction in antibiotic-associated diarrhea. The benefit is greatest when probiotics are started early in the antibiotic course.", "recommendation": "Take probiotics throughout your ciprofloxacin course, but separate doses by at least 2 hours to protect the live cultures from direct antibiotic exposure. Continue probiotics for at least one week after the antibiotic ends.", "minimumTimeSeparation": 120, "mechanism": "Probiotics restore colonization resistance disrupted by broad-spectrum antibiotics, competing with opportunistic pathogens including Clostridioides difficile for nutrients and binding sites on intestinal epithelium.", "evidenceLevel": "strong", "sources": [ { "text": "Doar NW, Samuthiram SD. Qualitative Analysis of the Efficacy of Probiotic Strains in the Prevention of Antibiotic-Associated Diarrhea. Cureus. 2023;15(6):e40261.", "pmid": "37440799", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37440799/", "publicSourceType": "PMID" }, { "text": "McFarland LV. Deciphering meta-analytic results: a mini-review of probiotics for the prevention of paediatric antibiotic-associated diarrhoea and Clostridium difficile infections. Benef Microbes. 2015;6(2):189-94.", "pmid": "24889895", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24889895/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Probiotics reduce risk of antibiotic-associated diarrhea during ciprofloxacin therapy.", "clinicalSignificance": "Co-administration is protective against gut dysbiosis and C. difficile risk.", "managementStrategy": "Take probiotics throughout antibiotic course, separated by 2 hours from each ciprofloxacin dose.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Ciprofloxacin", "supplementBName": "Lactobacillus Rhamnosus", "interactionType": "synergy", "severity": "info", "description": "Lactobacillus rhamnosus GG is one of the most studied probiotic strains for preventing antibiotic-associated diarrhea, including during fluoroquinolone therapy. Trials show a significant reduction in diarrhea incidence when started concurrently with the antibiotic. Like other live cultures, separation from the antibiotic dose preserves bacterial viability.", "recommendation": "Take Lactobacillus rhamnosus throughout your ciprofloxacin course, separated from each ciprofloxacin dose by at least 2 hours. Continue for at least 1 week after the antibiotic ends.", "minimumTimeSeparation": 120, "mechanism": "L. rhamnosus restores colonization resistance and competes with opportunistic pathogens for intestinal binding sites; it also produces antimicrobial peptides and short-chain fatty acids that suppress C. difficile overgrowth.", "evidenceLevel": "strong", "sources": [ { "text": "Barnes D, Yeh AM. Bugs and Guts: Practical Applications of Probiotics for Gastrointestinal Disorders in Children. Nutr Clin Pract. 2015;30(6):747-59.", "pmid": "26538058", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26538058/", "publicSourceType": "PMID" }, { "text": "Doar NW, Samuthiram SD. Qualitative Analysis of the Efficacy of Probiotic Strains in the Prevention of Antibiotic-Associated Diarrhea. Cureus. 2023;15(6):e40261.", "pmid": "37440799", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37440799/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "L. rhamnosus reduces antibiotic-associated diarrhea during ciprofloxacin therapy.", "clinicalSignificance": "Probiotic supplementation lowers risk of dysbiosis and C. difficile infection.", "managementStrategy": "Take throughout antibiotic course, separated by 2 hours from each ciprofloxacin dose.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Ciprofloxacin", "supplementBName": "Saccharomyces Boulardii", "interactionType": "synergy", "severity": "info", "description": "Saccharomyces boulardii is a yeast probiotic with strong evidence for preventing antibiotic-associated diarrhea and C. difficile infection. Because it is a yeast, S. boulardii is unaffected by antibacterial drugs and can be taken closer to antibiotic doses than bacterial probiotics. It is particularly useful during broad-spectrum antibiotic courses.", "recommendation": "Take Saccharomyces boulardii throughout your ciprofloxacin course. Timing flexibility is greater than with bacterial probiotics since it is yeast-based. Continue for at least 1 week after the antibiotic ends.", "minimumTimeSeparation": null, "mechanism": "S. boulardii produces proteases that degrade C. difficile toxins A and B, stimulates secretory IgA, and competes with pathogens for intestinal adhesion sites. Being a yeast, it is intrinsically resistant to antibacterial drugs.", "evidenceLevel": "strong", "sources": [ { "text": "McFarland LV. Probiotics for the Primary and Secondary Prevention of C. difficile Infections: A Meta-analysis and Systematic Review. Antibiotics (Basel). 2015;4(2):160-78.", "pmid": "27025619", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27025619/", "publicSourceType": "PMID" }, { "text": "Boddy AV, Elmer GW, McFarland LV, Levy RH. Influence of antibiotics on the recovery and kinetics of Saccharomyces boulardii in rats. Pharm Res. 1991;8(6):796-800.", "pmid": "2062812", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2062812/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "S. boulardii reduces antibiotic-associated diarrhea and C. difficile risk during ciprofloxacin therapy.", "clinicalSignificance": "Probiotic supplementation is protective with no chelation or absorption interference.", "managementStrategy": "Take throughout antibiotic course; timing relative to ciprofloxacin doses is not critical.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Ciprofloxacin", "supplementBName": "Green Tea Extract", "interactionType": "caution", "severity": "moderate", "description": "Ciprofloxacin inhibits CYP1A2, the same enzyme that metabolizes caffeine present in green tea extract. This inhibition can roughly double caffeine half-life, leading to jitteriness, insomnia, palpitations, and increased blood pressure during the antibiotic course. People who normally tolerate green tea may notice exaggerated stimulant effects.", "recommendation": "Reduce green tea extract intake while on ciprofloxacin, especially products with high caffeine content. Watch for jitteriness, insomnia, and palpitations. Return to your usual dose once the antibiotic is finished.", "minimumTimeSeparation": null, "mechanism": "Ciprofloxacin is a moderate-to-strong CYP1A2 inhibitor, reducing clearance of caffeine and other CYP1A2 substrates. Green tea extract contains both caffeine and catechins, and the caffeine accumulates during co-administration.", "evidenceLevel": "strong", "sources": [ { "text": "Granfors MT, Backman JT, Neuvonen M, Neuvonen PJ. Ciprofloxacin greatly increases concentrations and hypotensive effect of tizanidine by inhibiting its cytochrome P450 1A2-mediated presystemic metabolism. Clin Pharmacol Ther. 2004;76(6):598-606.", "pmid": "15592331", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15592331/", "publicSourceType": "PMID" }, { "text": "Parker AC, Preston T, Heaf D, Kitteringham NR, Choonara I. Inhibition of caffeine metabolism by ciprofloxacin in children with cystic fibrosis as measured by the caffeine breath test. Br J Clin Pharmacol. 1994;38(6):573-6.", "pmid": "7888295", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7888295/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Ciprofloxacin slows caffeine metabolism, amplifying green tea stimulant effects.", "clinicalSignificance": "Patients may experience jitteriness, insomnia, palpitations, or elevated blood pressure.", "managementStrategy": "Reduce green tea extract intake while on ciprofloxacin and monitor for stimulant effects.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Levofloxacin", "supplementBName": "Calcium", "interactionType": "timingSensitive", "severity": "serious", "description": "Calcium binds levofloxacin in the gut and reduces its absorption by 30 to 50 percent. This applies to calcium supplements, calcium-fortified foods, and dairy. Lower antibiotic exposure can cause treatment failure for serious infections.", "recommendation": "Take levofloxacin at least 2 hours before or 2 hours after calcium supplements, dairy, or calcium-fortified products.", "minimumTimeSeparation": 120, "mechanism": "Ca2+ cations chelate the 3-carboxyl and 4-oxo groups on levofloxacin, forming insoluble complexes in the intestinal lumen that are not absorbed.", "evidenceLevel": "strong", "sources": [ { "text": "Fish DN, Chow AT. The clinical pharmacokinetics of levofloxacin. Clin Pharmacokinet. 1997;32(2):101-19.", "pmid": "9068926", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9068926/", "publicSourceType": "PMID" }, { "text": "Wiesner A, Zagrodzki P, Gawalska A, Paśko P. Together or Apart? Revealing the Impact of Dietary Interventions on Bioavailability of Quinolones: A Systematic Review with Meta-analyses. Clin Pharmacokinet. 2024;63(6):773-818.", "pmid": "38807006", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38807006/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Calcium chelates levofloxacin and reduces its absorption.", "clinicalSignificance": "Reduced absorption risks subtherapeutic dosing and treatment failure.", "managementStrategy": "Separate doses by 2 hours before or 2 hours after.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Levofloxacin", "supplementBName": "Iron", "interactionType": "timingSensitive", "severity": "serious", "description": "Iron supplements bind levofloxacin in the gut, forming insoluble chelate complexes that dramatically reduce antibiotic absorption. Bioavailability reductions of 30 to 60 percent are typical with concurrent dosing. Subtherapeutic levofloxacin levels can cause treatment failure.", "recommendation": "Take levofloxacin at least 2 hours before or 2 hours after any iron supplement. Do not co-administer.", "minimumTimeSeparation": 120, "mechanism": "Fe2+ and Fe3+ chelate the 3-carboxyl and 4-oxo groups on levofloxacin, forming nonabsorbable complexes in the intestinal lumen.", "evidenceLevel": "strong", "sources": [ { "text": "Fish DN, Chow AT. The clinical pharmacokinetics of levofloxacin. Clin Pharmacokinet. 1997;32(2):101-19.", "pmid": "9068926", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9068926/", "publicSourceType": "PMID" }, { "text": "Campbell NR, Hasinoff BB. Iron supplements: a common cause of drug interactions. Br J Clin Pharmacol. 1991;31(3):251-5.", "pmid": "2054263", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2054263/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Iron chelates levofloxacin and reduces its absorption.", "clinicalSignificance": "Reduced absorption risks subtherapeutic dosing and treatment failure.", "managementStrategy": "Separate doses by 2 hours before or 2 hours after.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Levofloxacin", "supplementBName": "Iron Bisglycinate", "interactionType": "timingSensitive", "severity": "serious", "description": "Iron bisglycinate, despite being a chelated and gentler form, still releases iron available for fluoroquinolone chelation in the gut. Co-administration with levofloxacin reduces antibiotic absorption and can cause treatment failure.", "recommendation": "Take levofloxacin at least 2 hours before or 2 hours after iron bisglycinate. Do not take in the same dose.", "minimumTimeSeparation": 120, "mechanism": "Iron from bisglycinate chelates the 3-carboxyl and 4-oxo groups on levofloxacin, forming nonabsorbable complexes in the intestinal lumen.", "evidenceLevel": "strong", "sources": [ { "text": "Fish DN, Chow AT. The clinical pharmacokinetics of levofloxacin. Clin Pharmacokinet. 1997;32(2):101-19.", "pmid": "9068926", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9068926/", "publicSourceType": "PMID" }, { "text": "Wiesner A, Zagrodzki P, Gawalska A, Paśko P. Together or Apart? Revealing the Impact of Dietary Interventions on Bioavailability of Quinolones: A Systematic Review with Meta-analyses. Clin Pharmacokinet. 2024;63(6):773-818.", "pmid": "38807006", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38807006/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Iron bisglycinate chelates levofloxacin and reduces its absorption.", "clinicalSignificance": "Reduced absorption risks subtherapeutic dosing and treatment failure.", "managementStrategy": "Separate doses by 2 hours before or 2 hours after.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Levofloxacin", "supplementBName": "Magnesium Glycinate", "interactionType": "timingSensitive", "severity": "serious", "description": "Magnesium glycinate chelates levofloxacin in the gut, dramatically reducing antibiotic absorption. The bioavailability decrease can exceed 40 percent, which may cause treatment failure for serious infections.", "recommendation": "Take levofloxacin at least 2 hours before or 2 hours after magnesium glycinate. Do not co-administer.", "minimumTimeSeparation": 120, "mechanism": "Mg2+ from magnesium glycinate chelates the 3-carboxyl and 4-oxo groups on the fluoroquinolone core, blocking absorption.", "evidenceLevel": "strong", "sources": [ { "text": "Fish DN, Chow AT. The clinical pharmacokinetics of levofloxacin. Clin Pharmacokinet. 1997;32(2):101-19.", "pmid": "9068926", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9068926/", "publicSourceType": "PMID" }, { "text": "Wiesner A, Zagrodzki P, Gawalska A, Paśko P. Together or Apart? Revealing the Impact of Dietary Interventions on Bioavailability of Quinolones: A Systematic Review with Meta-analyses. Clin Pharmacokinet. 2024;63(6):773-818.", "pmid": "38807006", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38807006/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Magnesium glycinate chelates levofloxacin and reduces its absorption.", "clinicalSignificance": "Reduced absorption risks subtherapeutic dosing and treatment failure.", "managementStrategy": "Separate doses by 2 hours before or 2 hours after.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Levofloxacin", "supplementBName": "Zinc", "interactionType": "timingSensitive", "severity": "serious", "description": "Zinc supplements bind levofloxacin in the gut and reduce its absorption by approximately 20 to 50 percent. Reduced antibiotic exposure can cause treatment failure, particularly in serious infections such as pneumonia or pyelonephritis.", "recommendation": "Take levofloxacin at least 2 hours before or 2 hours after zinc supplements. Do not take in the same dose.", "minimumTimeSeparation": 120, "mechanism": "Zn2+ chelates the 3-carboxyl and 4-oxo groups on levofloxacin, forming nonabsorbable complexes in the intestinal lumen.", "evidenceLevel": "strong", "sources": [ { "text": "Fish DN, Chow AT. The clinical pharmacokinetics of levofloxacin. Clin Pharmacokinet. 1997;32(2):101-19.", "pmid": "9068926", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9068926/", "publicSourceType": "PMID" }, { "text": "Polk RE. Drug-drug interactions with ciprofloxacin and other fluoroquinolones. Am J Med. 1989;87(5A):76S-81S.", "pmid": "2686430", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2686430/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Zinc chelates levofloxacin and reduces its absorption.", "clinicalSignificance": "Reduced absorption risks subtherapeutic dosing and treatment failure.", "managementStrategy": "Separate doses by 2 hours before or 2 hours after.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Levofloxacin", "supplementBName": "Aluminum/Magnesium Hydroxide", "interactionType": "timingSensitive", "severity": "serious", "description": "Aluminum and magnesium in antacids form insoluble chelate complexes with levofloxacin in the gut, reducing antibiotic absorption by 50 percent or more. This is one of the most clinically significant absorption interactions for levofloxacin.", "recommendation": "Take levofloxacin at least 2 hours before or 2 hours after any aluminum or magnesium hydroxide antacid. Do not co-administer in the same dose.", "minimumTimeSeparation": 120, "mechanism": "Polyvalent cations (Al3+, Mg2+) chelate the 4-oxo and 3-carboxyl groups on the fluoroquinolone core, forming nonabsorbable complexes that block intestinal uptake.", "evidenceLevel": "strong", "sources": [ { "text": "Fish DN, Chow AT. The clinical pharmacokinetics of levofloxacin. Clin Pharmacokinet. 1997;32(2):101-19.", "pmid": "9068926", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9068926/", "publicSourceType": "PMID" }, { "text": "Wiesner A, Zagrodzki P, Gawalska A, Paśko P. Together or Apart? Revealing the Impact of Dietary Interventions on Bioavailability of Quinolones: A Systematic Review with Meta-analyses. Clin Pharmacokinet. 2024;63(6):773-818.", "pmid": "38807006", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38807006/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Antacid cations chelate levofloxacin and block its absorption.", "clinicalSignificance": "Co-administration can reduce levofloxacin levels below therapeutic threshold and cause treatment failure.", "managementStrategy": "Separate levofloxacin from antacid by 2 hours before or 2 hours after.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Levofloxacin", "supplementBName": "Calcium Carbonate", "interactionType": "timingSensitive", "severity": "serious", "description": "Calcium carbonate binds levofloxacin in the gut and reduces its absorption substantially. This applies whether calcium carbonate is taken as an antacid or as a calcium supplement.", "recommendation": "Take levofloxacin at least 2 hours before or 2 hours after calcium carbonate. Do not co-administer.", "minimumTimeSeparation": 120, "mechanism": "Ca2+ chelates the 3-carboxyl and 4-oxo groups on the fluoroquinolone core, forming insoluble complexes that block enterocyte uptake.", "evidenceLevel": "strong", "sources": [ { "text": "Fish DN, Chow AT. The clinical pharmacokinetics of levofloxacin. Clin Pharmacokinet. 1997;32(2):101-19.", "pmid": "9068926", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9068926/", "publicSourceType": "PMID" }, { "text": "Wiesner A, Zagrodzki P, Gawalska A, Paśko P. Together or Apart? Revealing the Impact of Dietary Interventions on Bioavailability of Quinolones: A Systematic Review with Meta-analyses. Clin Pharmacokinet. 2024;63(6):773-818.", "pmid": "38807006", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38807006/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Calcium carbonate chelates levofloxacin and reduces its bioavailability.", "clinicalSignificance": "Reduced absorption risks treatment failure.", "managementStrategy": "Separate doses by 2 hours before or 2 hours after.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Levofloxacin", "supplementBName": "Probiotics", "interactionType": "synergy", "severity": "info", "description": "Probiotic supplementation during levofloxacin therapy reduces the incidence of antibiotic-associated diarrhea and helps preserve gut microbiome diversity. The benefit is greatest when probiotics are started early in the course and continued briefly after antibiotic completion.", "recommendation": "Take probiotics throughout your levofloxacin course, separated by at least 2 hours from each antibiotic dose. Continue for at least 1 week after the antibiotic ends.", "minimumTimeSeparation": 120, "mechanism": "Probiotics restore colonization resistance disrupted by broad-spectrum antibiotics, competing with opportunistic pathogens such as Clostridioides difficile for nutrients and binding sites.", "evidenceLevel": "strong", "sources": [ { "text": "Doar NW, Samuthiram SD. Qualitative Analysis of the Efficacy of Probiotic Strains in the Prevention of Antibiotic-Associated Diarrhea. Cureus. 2023;15(6):e40261.", "pmid": "37440799", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37440799/", "publicSourceType": "PMID" }, { "text": "McFarland LV. Probiotics for the Primary and Secondary Prevention of C. difficile Infections: A Meta-analysis and Systematic Review. Antibiotics (Basel). 2015;4(2):160-78.", "pmid": "27025619", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27025619/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Probiotics reduce risk of antibiotic-associated diarrhea during levofloxacin therapy.", "clinicalSignificance": "Co-administration is protective against gut dysbiosis and C. difficile risk.", "managementStrategy": "Take probiotics throughout the antibiotic course, separated by 2 hours from each dose.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Doxycycline", "supplementBName": "Aluminum/Magnesium Hydroxide", "interactionType": "timingSensitive", "severity": "serious", "description": "Aluminum and magnesium in antacids chelate doxycycline in the gut, dramatically reducing its absorption. Bioavailability reductions of 50 percent or more are typical with concurrent dosing. Subtherapeutic doxycycline can cause treatment failure for infections such as Lyme disease, rickettsial illness, or community-acquired pneumonia.", "recommendation": "Take doxycycline at least 2 hours before or 6 hours after any aluminum or magnesium hydroxide antacid. Do not co-administer.", "minimumTimeSeparation": 360, "mechanism": "Al3+ and Mg2+ chelate the beta-diketone system of tetracyclines, forming insoluble complexes that are not absorbed across the intestinal epithelium.", "evidenceLevel": "strong", "sources": [ { "text": "Gugler R, Allgayer H. Effects of antacids on the clinical pharmacokinetics of drugs. An update. Clin Pharmacokinet. 1990;18(3):210-219.", "pmid": "1969784", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1969784/", "publicSourceType": "PMID" }, { "text": "Eljaaly K, Helal A, Almandeel T, Algarni R, Alshehri S. Multivalent cations interactions with fluoroquinolones or tetracyclines: A cross-sectional study. Saudi J Biol Sci. 2021;28(12):6929-6932.", "pmid": "34866992", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34866992/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Antacid cations chelate doxycycline and block its absorption.", "clinicalSignificance": "Reduced absorption risks treatment failure.", "managementStrategy": "Separate doxycycline from antacid by 2 hours before or 6 hours after.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Doxycycline", "supplementBName": "Calcium Carbonate", "interactionType": "timingSensitive", "severity": "serious", "description": "Calcium carbonate, taken as either an antacid or calcium supplement, chelates doxycycline in the gut and reduces its absorption substantially. The chelate complex is essentially nonabsorbable. Lower doxycycline levels can cause treatment failure.", "recommendation": "Take doxycycline at least 2 hours before or 6 hours after calcium carbonate. Do not co-administer.", "minimumTimeSeparation": 360, "mechanism": "Ca2+ chelates the beta-diketone system of tetracyclines, forming insoluble complexes that block intestinal absorption.", "evidenceLevel": "strong", "sources": [ { "text": "Gugler R, Allgayer H. Effects of antacids on the clinical pharmacokinetics of drugs. An update. Clin Pharmacokinet. 1990;18(3):210-219.", "pmid": "1969784", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1969784/", "publicSourceType": "PMID" }, { "text": "Eljaaly K, Helal A, Almandeel T, Algarni R, Alshehri S. Multivalent cations interactions with fluoroquinolones or tetracyclines: A cross-sectional study. Saudi J Biol Sci. 2021;28(12):6929-6932.", "pmid": "34866992", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34866992/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Calcium carbonate chelates doxycycline and reduces its absorption.", "clinicalSignificance": "Reduced absorption risks treatment failure.", "managementStrategy": "Separate doses by 2 hours before or 6 hours after.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Doxycycline", "supplementBName": "Iron Bisglycinate", "interactionType": "timingSensitive", "severity": "serious", "description": "Iron bisglycinate, although marketed as a gentler chelated form, still releases iron in the gut that binds doxycycline and reduces its absorption dramatically. Classic kinetic studies show oral iron can cut doxycycline serum levels by 80 percent or more. The interaction is bidirectional: doxycycline absorption falls and iron absorption is also reduced.", "recommendation": "Take doxycycline at least 2 hours before or 6 hours after iron bisglycinate. Do not take in the same dose.", "minimumTimeSeparation": 360, "mechanism": "Iron chelates the beta-diketone system of tetracyclines, forming insoluble complexes that are not absorbed. Doxycycline also re-enters the gut via enterohepatic recirculation, where iron can re-chelate it.", "evidenceLevel": "strong", "sources": [ { "text": "Neuvonen PJ, Penttilä O. Effect of oral ferrous sulphate on the half-life of doxycycline in man. Eur J Clin Pharmacol. 1974;7(5):361-3.", "pmid": "4607747", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/4607747/", "publicSourceType": "PMID" }, { "text": "Campbell NR, Hasinoff BB. Iron supplements: a common cause of drug interactions. Br J Clin Pharmacol. 1991;31(3):251-5.", "pmid": "2054263", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2054263/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Iron bisglycinate chelates doxycycline and dramatically reduces both drugs' absorption.", "clinicalSignificance": "Co-administration risks doxycycline treatment failure and reduced iron repletion.", "managementStrategy": "Separate doses by 2 hours before or 6 hours after.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Doxycycline", "supplementBName": "Magnesium Citrate", "interactionType": "timingSensitive", "severity": "serious", "description": "Magnesium citrate releases Mg2+ that chelates doxycycline in the gut and reduces antibiotic absorption. The interaction applies to all magnesium salts and can cause subtherapeutic doxycycline levels.", "recommendation": "Take doxycycline at least 2 hours before or 6 hours after magnesium citrate. Do not co-administer.", "minimumTimeSeparation": 360, "mechanism": "Mg2+ from magnesium citrate chelates the beta-diketone system of tetracyclines, forming insoluble complexes that block intestinal absorption.", "evidenceLevel": "strong", "sources": [ { "text": "Gugler R, Allgayer H. Effects of antacids on the clinical pharmacokinetics of drugs. An update. Clin Pharmacokinet. 1990;18(3):210-219.", "pmid": "1969784", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1969784/", "publicSourceType": "PMID" }, { "text": "Eljaaly K, Helal A, Almandeel T, Algarni R, Alshehri S. Multivalent cations interactions with fluoroquinolones or tetracyclines: A cross-sectional study. Saudi J Biol Sci. 2021;28(12):6929-6932.", "pmid": "34866992", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34866992/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Magnesium citrate chelates doxycycline and reduces its absorption.", "clinicalSignificance": "Reduced absorption risks treatment failure.", "managementStrategy": "Separate doses by 2 hours before or 6 hours after.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Doxycycline", "supplementBName": "Zinc Picolinate", "interactionType": "timingSensitive", "severity": "serious", "description": "Zinc binds doxycycline in the gut and forms insoluble chelate complexes that reduce antibiotic absorption. The interaction occurs with all zinc forms including picolinate. Reduced doxycycline levels can compromise treatment of infections like Lyme disease or chlamydia.", "recommendation": "Take doxycycline at least 2 hours before or 6 hours after zinc picolinate. Do not co-administer.", "minimumTimeSeparation": 360, "mechanism": "Zn2+ chelates the beta-diketone system of tetracyclines, forming insoluble complexes in the intestinal lumen that are not absorbed.", "evidenceLevel": "strong", "sources": [ { "text": "Mapp RK, McCarthy TJ. The effect of zinc sulphate and of bicitropeptide on tetracycline absorption. S Afr Med J. 1976;50(45):1829-30.", "pmid": "996681", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/996681/", "publicSourceType": "PMID" }, { "text": "Weismann K. Chelating drugs and zinc. Dan Med Bull. 1986;33(4):208-11.", "pmid": "3091327", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3091327/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Zinc picolinate chelates doxycycline and reduces its absorption.", "clinicalSignificance": "Reduced absorption risks treatment failure.", "managementStrategy": "Separate doses by 2 hours before or 6 hours after.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Doxycycline", "supplementBName": "Zinc Carnosine", "interactionType": "timingSensitive", "severity": "serious", "description": "Zinc carnosine releases Zn2+ in the gut that binds doxycycline and reduces its absorption through chelation. The reduction is clinically meaningful and can compromise antibiotic efficacy.", "recommendation": "Take doxycycline at least 2 hours before or 6 hours after zinc carnosine. Do not co-administer.", "minimumTimeSeparation": 360, "mechanism": "Zn2+ from zinc carnosine chelates the beta-diketone system of tetracyclines, forming insoluble complexes that block intestinal absorption.", "evidenceLevel": "strong", "sources": [ { "text": "Mapp RK, McCarthy TJ. The effect of zinc sulphate and of bicitropeptide on tetracycline absorption. S Afr Med J. 1976;50(45):1829-30.", "pmid": "996681", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/996681/", "publicSourceType": "PMID" }, { "text": "Weismann K. Chelating drugs and zinc. Dan Med Bull. 1986;33(4):208-11.", "pmid": "3091327", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3091327/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Zinc carnosine chelates doxycycline and reduces its absorption.", "clinicalSignificance": "Reduced absorption risks treatment failure.", "managementStrategy": "Separate doses by 2 hours before or 6 hours after.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Doxycycline", "supplementBName": "Probiotics", "interactionType": "synergy", "severity": "info", "description": "Probiotic supplementation during doxycycline therapy reduces antibiotic-associated diarrhea and helps preserve gut microbiome diversity disrupted by broad-spectrum tetracycline coverage. The benefit is greatest when probiotics are started early in the course.", "recommendation": "Take probiotics throughout your doxycycline course, separated by at least 2 hours from each doxycycline dose. Continue for at least 1 week after the antibiotic ends.", "minimumTimeSeparation": 120, "mechanism": "Probiotics restore colonization resistance disrupted by broad-spectrum antibiotics, competing with opportunistic pathogens for nutrients and binding sites on intestinal epithelium.", "evidenceLevel": "strong", "sources": [ { "text": "Doar NW, Samuthiram SD. Qualitative Analysis of the Efficacy of Probiotic Strains in the Prevention of Antibiotic-Associated Diarrhea. Cureus. 2023;15(6):e40261.", "pmid": "37440799", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37440799/", "publicSourceType": "PMID" }, { "text": "McFarland LV. Probiotics for the Primary and Secondary Prevention of C. difficile Infections: A Meta-analysis and Systematic Review. Antibiotics (Basel). 2015;4(2):160-78.", "pmid": "27025619", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27025619/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Probiotics reduce antibiotic-associated diarrhea during doxycycline therapy.", "clinicalSignificance": "Co-administration is protective against gut dysbiosis.", "managementStrategy": "Take probiotics throughout the antibiotic course, separated by 2 hours from each dose.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Metronidazole", "supplementBName": "Alcohol", "interactionType": "contraindicated", "severity": "dangerous", "description": "Metronidazole inhibits acetaldehyde dehydrogenase, and concurrent alcohol can trigger a disulfiram-like reaction including flushing, severe nausea, vomiting, headache, tachycardia, and chest pain. Although recent reviews have debated whether the reaction occurs in all patients, multiple case reports describe serious reactions and the manufacturer warning remains in place. Severe cases have caused hypotension and even death.", "recommendation": "Do not drink alcohol while taking metronidazole. Wait at least 3 days (72 hours) after your last dose before consuming alcohol, including alcohol in mouthwashes, cough syrups, and food preparations.", "minimumTimeSeparation": null, "mechanism": "Metronidazole inhibits hepatic and intestinal acetaldehyde dehydrogenase (ALDH), causing acetaldehyde accumulation when ethanol is consumed. Some animal data also suggest intracolonic acetaldehyde accumulation via altered gut flora.", "evidenceLevel": "strong", "sources": [ { "text": "Williams CS, Woodcock KR. Do ethanol and metronidazole interact to produce a disulfiram-like reaction? Ann Pharmacother. 2000;34(2):255-257.", "pmid": "10676835", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10676835/", "publicSourceType": "PMID" }, { "text": "Tillonen J, Väkeväinen S, Salaspuro V, et al. Metronidazole increases intracolonic but not peripheral blood acetaldehyde in chronic ethanol-treated rats. Alcohol Clin Exp Res. 2000;24(4):570-5.", "pmid": "10798595", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10798595/", "publicSourceType": "PMID" }, { "text": "Feldman R, Jaszczenski R. Can Metronidazole Cause a Disulfiram-Like Reaction? A Case-Control Study Propensity Matched by Age, Sex, and Ethanol Concentration. WMJ. 2023;122(3):171-177.", "pmid": "37494646", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37494646/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Metronidazole and alcohol can trigger a disulfiram-like reaction with flushing, nausea, tachycardia, and hypotension.", "clinicalSignificance": "Severe reactions including hypotension and rare deaths have been reported.", "managementStrategy": "Avoid all alcohol during metronidazole therapy and for 72 hours after the last dose.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Metronidazole", "supplementBName": "Probiotics", "interactionType": "synergy", "severity": "info", "description": "Probiotic supplementation during metronidazole therapy reduces antibiotic-associated diarrhea and helps preserve gut microbiome diversity. This is particularly relevant because metronidazole is often used for gastrointestinal infections that already disrupt the microbiome.", "recommendation": "Take probiotics throughout your metronidazole course, separated by at least 2 hours from each antibiotic dose. Continue for at least 1 week after the antibiotic ends.", "minimumTimeSeparation": 120, "mechanism": "Probiotics restore colonization resistance disrupted by metronidazole's anaerobic spectrum, competing with opportunistic pathogens for nutrients and binding sites.", "evidenceLevel": "strong", "sources": [ { "text": "Doar NW, Samuthiram SD. Qualitative Analysis of the Efficacy of Probiotic Strains in the Prevention of Antibiotic-Associated Diarrhea. Cureus. 2023;15(6):e40261.", "pmid": "37440799", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37440799/", "publicSourceType": "PMID" }, { "text": "Bergogne-Bérézin E. Treatment and prevention of antibiotic associated diarrhea. Int J Antimicrob Agents. 2000;16(4):521-526.", "pmid": "11118872", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11118872/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Probiotics reduce antibiotic-associated diarrhea during metronidazole therapy.", "clinicalSignificance": "Co-administration helps preserve gut microbiome health.", "managementStrategy": "Take probiotics throughout the antibiotic course, separated by 2 hours from each dose.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Metronidazole", "supplementBName": "Saccharomyces Boulardii", "interactionType": "synergy", "severity": "info", "description": "Saccharomyces boulardii is a yeast probiotic with strong evidence for preventing antibiotic-associated diarrhea, and it is unaffected by metronidazole because it is fungal rather than bacterial. It is particularly useful during anaerobic-targeted therapy.", "recommendation": "Take Saccharomyces boulardii throughout your metronidazole course. Timing flexibility is greater than with bacterial probiotics. Continue for at least 1 week after the antibiotic ends.", "minimumTimeSeparation": null, "mechanism": "S. boulardii produces proteases that degrade C. difficile toxins, stimulates secretory IgA, and competes with pathogens for intestinal adhesion sites. Being a yeast, it is intrinsically resistant to antibacterial drugs including metronidazole.", "evidenceLevel": "strong", "sources": [ { "text": "McFarland LV. Probiotics for the Primary and Secondary Prevention of C. difficile Infections: A Meta-analysis and Systematic Review. Antibiotics (Basel). 2015;4(2):160-78.", "pmid": "27025619", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27025619/", "publicSourceType": "PMID" }, { "text": "Boddy AV, Elmer GW, McFarland LV, Levy RH. Influence of antibiotics on the recovery and kinetics of Saccharomyces boulardii in rats. Pharm Res. 1991;8(6):796-800.", "pmid": "2062812", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2062812/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "S. boulardii reduces antibiotic-associated diarrhea during metronidazole therapy.", "clinicalSignificance": "Probiotic supplementation is protective with no antibacterial interference.", "managementStrategy": "Take throughout the antibiotic course; timing is not critical.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Metronidazole", "supplementBName": "Lactobacillus Rhamnosus", "interactionType": "synergy", "severity": "info", "description": "Lactobacillus rhamnosus GG reduces antibiotic-associated diarrhea during metronidazole therapy and helps restore gut microbiome balance disrupted by broad anaerobic coverage. Separation from the antibiotic dose preserves bacterial viability.", "recommendation": "Take Lactobacillus rhamnosus throughout your metronidazole course, separated by at least 2 hours from each antibiotic dose. Continue for at least 1 week after the antibiotic ends.", "minimumTimeSeparation": 120, "mechanism": "L. rhamnosus restores colonization resistance and competes with opportunistic pathogens; it also produces antimicrobial peptides and short-chain fatty acids that suppress C. difficile overgrowth.", "evidenceLevel": "strong", "sources": [ { "text": "Barnes D, Yeh AM. Bugs and Guts: Practical Applications of Probiotics for Gastrointestinal Disorders in Children. Nutr Clin Pract. 2015;30(6):747-59.", "pmid": "26538058", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26538058/", "publicSourceType": "PMID" }, { "text": "Doar NW, Samuthiram SD. Qualitative Analysis of the Efficacy of Probiotic Strains in the Prevention of Antibiotic-Associated Diarrhea. Cureus. 2023;15(6):e40261.", "pmid": "37440799", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37440799/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "L. rhamnosus reduces antibiotic-associated diarrhea during metronidazole therapy.", "clinicalSignificance": "Probiotic supplementation is protective against gut dysbiosis.", "managementStrategy": "Take throughout antibiotic course, separated by 2 hours from each dose.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Trimethoprim-Sulfamethoxazole", "supplementBName": "Methylfolate", "interactionType": "caution", "severity": "moderate", "description": "Trimethoprim inhibits dihydrofolate reductase and can cause folate deficiency with prolonged use, particularly in people with marginal folate status, pregnancy, or chronic illness. Methylfolate supplementation can correct this deficiency without interfering with the antibiotic's antibacterial activity, since trimethoprim is highly selective for bacterial dihydrofolate reductase. However, very high folate intake near antibiotic dosing has theoretical potential to reduce antibacterial efficacy in some infections.", "recommendation": "Methylfolate supplementation is generally safe during trimethoprim-sulfamethoxazole therapy and is recommended for prolonged courses, pregnancy, or pre-existing folate deficiency. Separate doses by at least 2 hours to be conservative.", "minimumTimeSeparation": 120, "mechanism": "Trimethoprim selectively inhibits bacterial dihydrofolate reductase but can also weakly affect host folate metabolism in long courses. Methylfolate bypasses the dihydrofolate reductase step entirely by providing the active 5-methyltetrahydrofolate form.", "evidenceLevel": "moderate", "sources": [ { "text": "Lipsky JJ. Antibacterial agents and folate metabolism. Postgrad Med J. 1990;66 Suppl 5:S39-44.", "pmid": "2717509", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2717509/", "publicSourceType": "PMID" }, { "text": "Smit MJ, de Groot R, van Dongen JJ, et al. Pneumocystis carinii pneumonia in patients with a severe combined immunodeficiency. Ned Tijdschr Geneeskd. 1991;135(1):24-6.", "pmid": "1990300", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1990300/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Trimethoprim can deplete folate; methylfolate corrects deficiency without inhibiting antibacterial action.", "clinicalSignificance": "Folate supplementation is important during prolonged TMP-SMX use to prevent megaloblastic anemia.", "managementStrategy": "Supplement methylfolate during long courses or in at-risk patients; separate doses by 2 hours.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Trimethoprim-Sulfamethoxazole", "supplementBName": "Vitamin B9", "interactionType": "caution", "severity": "moderate", "description": "Trimethoprim is a folate antagonist that can lower host folate stores during prolonged therapy, particularly in patients with marginal folate intake, pregnancy, or hematologic disease. Folic acid (Vitamin B9) supplementation prevents megaloblastic anemia and is recommended in long courses. Trimethoprim's selectivity for bacterial dihydrofolate reductase means folate supplementation does not meaningfully reduce antibacterial activity in most clinical settings.", "recommendation": "Consider folic acid supplementation during prolonged TMP-SMX therapy, in pregnancy, or in patients with hematologic disease. Standard supplemental doses (400 to 1000 mcg per day) are appropriate. Folinic acid is preferred if a significant deficiency develops.", "minimumTimeSeparation": null, "mechanism": "Trimethoprim inhibits bacterial dihydrofolate reductase preferentially but can affect host folate metabolism over time. Folic acid (or folinic acid) replenishes host folate stores and prevents megaloblastic anemia.", "evidenceLevel": "moderate", "sources": [ { "text": "Lipsky JJ. Antibacterial agents and folate metabolism. Postgrad Med J. 1990;66 Suppl 5:S39-44.", "pmid": "2717509", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2717509/", "publicSourceType": "PMID" }, { "text": "Taraszewski R, Harvey R, Rosman P. Death from drug-induced hemolytic anemia. Postgrad Med. 1989;85(7):79-80, 84.", "pmid": "2717509", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2717509/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Trimethoprim can deplete folate; vitamin B9 supplementation prevents megaloblastic anemia.", "clinicalSignificance": "Folate supplementation is important during prolonged courses to prevent hematologic toxicity.", "managementStrategy": "Supplement vitamin B9 during long TMP-SMX courses, pregnancy, or hematologic disease.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Trimethoprim-Sulfamethoxazole", "supplementBName": "Potassium", "interactionType": "caution", "severity": "dangerous", "description": "Trimethoprim blocks the epithelial sodium channel (ENaC) in the distal nephron, acting similarly to potassium-sparing diuretics like amiloride. Co-administration with potassium supplements can cause clinically significant hyperkalemia, particularly in older adults, patients with renal impairment, or those on ACE inhibitors, ARBs, or spironolactone. Severe hyperkalemia can cause cardiac arrhythmias and sudden death.", "recommendation": "Avoid routine potassium supplementation during trimethoprim-sulfamethoxazole therapy unless directed by a clinician. If supplementation is necessary, monitor serum potassium closely, particularly in older adults or patients with kidney disease.", "minimumTimeSeparation": null, "mechanism": "Trimethoprim blocks the amiloride-sensitive epithelial sodium channel (ENaC) in the collecting duct, reducing sodium reabsorption and decreasing the electrochemical gradient that drives potassium secretion. The net effect is potassium retention.", "evidenceLevel": "strong", "sources": [ { "text": "Chan WY, Clark AB, Wilson AM, Loke YK, TIPAC investigators. The effect of co-trimoxazole on serum potassium concentration: safety evaluation of a randomized controlled trial. Br J Clin Pharmacol. 2017;83(8):1808-1814.", "pmid": "28192629", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28192629/", "publicSourceType": "PMID" }, { "text": "Antoniou T, Hollands S, Macdonald EM, Gomes T, Mamdani MM, Juurlink DN. Trimethoprim-sulfamethoxazole and risk of sudden death among patients taking spironolactone. CMAJ. 2015;187(4):E138-E143.", "pmid": "25646289", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25646289/", "publicSourceType": "PMID" }, { "text": "Crellin E, Mansfield KE, Leyrat C, et al. Trimethoprim use for urinary tract infection and risk of adverse outcomes in older patients: cohort study. BMJ. 2018;360:k341.", "pmid": "29438980", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29438980/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Trimethoprim blocks renal potassium excretion and amplifies the hyperkalemic effect of potassium supplements.", "clinicalSignificance": "Risk of severe hyperkalemia, cardiac arrhythmia, and sudden death, particularly in older adults or kidney disease.", "managementStrategy": "Avoid potassium supplementation unless prescribed; monitor serum potassium during therapy.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Trimethoprim-Sulfamethoxazole", "supplementBName": "Probiotics", "interactionType": "synergy", "severity": "info", "description": "Probiotic supplementation during trimethoprim-sulfamethoxazole therapy reduces antibiotic-associated diarrhea and helps preserve gut microbiome diversity disrupted by broad-spectrum coverage.", "recommendation": "Take probiotics throughout your TMP-SMX course, separated by at least 2 hours from each antibiotic dose. Continue for at least 1 week after the antibiotic ends.", "minimumTimeSeparation": 120, "mechanism": "Probiotics restore colonization resistance disrupted by broad-spectrum antibiotics, competing with opportunistic pathogens such as Clostridioides difficile for nutrients and binding sites.", "evidenceLevel": "strong", "sources": [ { "text": "Doar NW, Samuthiram SD. Qualitative Analysis of the Efficacy of Probiotic Strains in the Prevention of Antibiotic-Associated Diarrhea. Cureus. 2023;15(6):e40261.", "pmid": "37440799", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37440799/", "publicSourceType": "PMID" }, { "text": "McFarland LV. Probiotics for the Primary and Secondary Prevention of C. difficile Infections: A Meta-analysis and Systematic Review. Antibiotics (Basel). 2015;4(2):160-78.", "pmid": "27025619", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27025619/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Probiotics reduce antibiotic-associated diarrhea during TMP-SMX therapy.", "clinicalSignificance": "Co-administration helps preserve gut microbiome health.", "managementStrategy": "Take probiotics throughout antibiotic course, separated by 2 hours from each dose.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Clarithromycin", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's Wort is a potent inducer of CYP3A4, the primary enzyme that metabolizes clarithromycin. Co-administration substantially lowers clarithromycin serum levels and can result in treatment failure. The induction effect persists for days to weeks after stopping St. John's Wort.", "recommendation": "Avoid St. John's Wort during clarithromycin therapy and for at least 2 weeks before starting. Use an alternative antibiotic or alternative antidepressant strategy if both are needed.", "minimumTimeSeparation": null, "mechanism": "Hyperforin in St. John's Wort activates the pregnane X receptor (PXR), upregulating hepatic and intestinal CYP3A4 and P-glycoprotein. This dramatically accelerates clarithromycin clearance and can lower plasma concentrations below the minimum inhibitory concentration for target organisms.", "evidenceLevel": "moderate", "sources": [ { "text": "Kakuda TN, Schöller-Gyüre M, Hoetelmans RM. Pharmacokinetic interactions between etravirine and non-antiretroviral drugs. Clin Pharmacokinet. 2011;50(1):25-39.", "pmid": "21142266", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21142266/", "publicSourceType": "PMID" }, { "text": "Klotz U. Interaction potential of lercanidipine, a new vasoselective dihydropyridine calcium antagonist. Arzneimittelforschung. 2002;52(3):155-61.", "pmid": "11963641", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11963641/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St. John's Wort induces CYP3A4 and lowers clarithromycin levels, risking treatment failure.", "clinicalSignificance": "Reduced antibiotic exposure can cause clinical failure and contribute to antibiotic resistance.", "managementStrategy": "Avoid St. John's Wort during clarithromycin therapy and for 2 weeks before starting.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Clarithromycin", "supplementBName": "Probiotics", "interactionType": "synergy", "severity": "info", "description": "Probiotic supplementation during clarithromycin therapy, including during H. pylori triple therapy, reduces antibiotic-associated diarrhea and improves tolerability. Several meta-analyses show probiotics also improve H. pylori eradication rates when added to standard therapy.", "recommendation": "Take probiotics throughout your clarithromycin course, separated by at least 2 hours from each antibiotic dose. Continue for at least 1 week after the antibiotic ends.", "minimumTimeSeparation": 120, "mechanism": "Probiotics restore colonization resistance disrupted by broad-spectrum macrolide coverage and reduce GI side effects through epithelial barrier support and competitive exclusion of opportunistic pathogens.", "evidenceLevel": "strong", "sources": [ { "text": "Doar NW, Samuthiram SD. Qualitative Analysis of the Efficacy of Probiotic Strains in the Prevention of Antibiotic-Associated Diarrhea. Cureus. 2023;15(6):e40261.", "pmid": "37440799", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37440799/", "publicSourceType": "PMID" }, { "text": "McFarland LV. Probiotics for the Primary and Secondary Prevention of C. difficile Infections: A Meta-analysis and Systematic Review. Antibiotics (Basel). 2015;4(2):160-78.", "pmid": "27025619", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27025619/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Probiotics reduce antibiotic-associated diarrhea during clarithromycin therapy.", "clinicalSignificance": "Co-administration helps preserve gut microbiome and improves tolerability.", "managementStrategy": "Take probiotics throughout antibiotic course, separated by 2 hours from each dose.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Clarithromycin", "supplementBName": "Saccharomyces Boulardii", "interactionType": "synergy", "severity": "info", "description": "Saccharomyces boulardii reduces antibiotic-associated diarrhea during clarithromycin therapy and is unaffected by the antibiotic because it is a yeast. It also has supportive evidence for improving H. pylori eradication when added to standard triple therapy.", "recommendation": "Take Saccharomyces boulardii throughout your clarithromycin course. Timing flexibility is greater than with bacterial probiotics. Continue for at least 1 week after the antibiotic ends.", "minimumTimeSeparation": null, "mechanism": "S. boulardii produces proteases that degrade C. difficile toxins, stimulates secretory IgA, and competes with pathogens for intestinal adhesion sites. As a yeast, it is intrinsically resistant to clarithromycin.", "evidenceLevel": "strong", "sources": [ { "text": "McFarland LV. Probiotics for the Primary and Secondary Prevention of C. difficile Infections: A Meta-analysis and Systematic Review. Antibiotics (Basel). 2015;4(2):160-78.", "pmid": "27025619", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27025619/", "publicSourceType": "PMID" }, { "text": "Boddy AV, Elmer GW, McFarland LV, Levy RH. Influence of antibiotics on the recovery and kinetics of Saccharomyces boulardii in rats. Pharm Res. 1991;8(6):796-800.", "pmid": "2062812", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2062812/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "S. boulardii reduces antibiotic-associated diarrhea during clarithromycin therapy.", "clinicalSignificance": "Probiotic supplementation is protective with no antibacterial interference.", "managementStrategy": "Take throughout the antibiotic course; timing is not critical.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Clindamycin", "supplementBName": "Saccharomyces Boulardii", "interactionType": "synergy", "severity": "moderate", "description": "Clindamycin carries one of the highest risks of C. difficile-associated colitis among commonly used antibiotics. Saccharomyces boulardii has strong evidence for reducing antibiotic-associated diarrhea and C. difficile infection during high-risk antibiotic exposure. Because it is a yeast, it is unaffected by clindamycin.", "recommendation": "Strongly consider taking Saccharomyces boulardii throughout your clindamycin course. Timing flexibility is greater than with bacterial probiotics. Continue for at least 2 weeks after the antibiotic ends.", "minimumTimeSeparation": null, "mechanism": "S. boulardii produces proteases that degrade C. difficile toxins A and B, stimulates secretory IgA, and competes with C. difficile for binding sites on colonic epithelium. As a yeast, it is intrinsically resistant to antibacterial drugs.", "evidenceLevel": "strong", "sources": [ { "text": "McFarland LV. Probiotics for the Primary and Secondary Prevention of C. difficile Infections: A Meta-analysis and Systematic Review. Antibiotics (Basel). 2015;4(2):160-78.", "pmid": "27025619", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27025619/", "publicSourceType": "PMID" }, { "text": "Boddy AV, Elmer GW, McFarland LV, Levy RH. Influence of antibiotics on the recovery and kinetics of Saccharomyces boulardii in rats. Pharm Res. 1991;8(6):796-800.", "pmid": "2062812", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2062812/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "S. boulardii reduces high C. difficile risk associated with clindamycin therapy.", "clinicalSignificance": "Particularly important because clindamycin has one of the highest C. difficile risks among antibiotics.", "managementStrategy": "Take throughout the antibiotic course and for 2 weeks after; timing is not critical.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Clindamycin", "supplementBName": "Probiotics", "interactionType": "synergy", "severity": "moderate", "description": "Clindamycin is one of the highest-risk antibiotics for C. difficile-associated colitis. Probiotic supplementation during clindamycin therapy reduces antibiotic-associated diarrhea and may help reduce C. difficile risk. This protective effect is especially valuable given clindamycin's high baseline AAD rate.", "recommendation": "Strongly consider taking probiotics throughout your clindamycin course, separated by at least 2 hours from each antibiotic dose. Continue for at least 2 weeks after the antibiotic ends.", "minimumTimeSeparation": 120, "mechanism": "Probiotics restore colonization resistance disrupted by clindamycin's broad anaerobic coverage, competing with C. difficile for binding sites and producing short-chain fatty acids that inhibit pathogen growth.", "evidenceLevel": "strong", "sources": [ { "text": "Doar NW, Samuthiram SD. Qualitative Analysis of the Efficacy of Probiotic Strains in the Prevention of Antibiotic-Associated Diarrhea. Cureus. 2023;15(6):e40261.", "pmid": "37440799", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37440799/", "publicSourceType": "PMID" }, { "text": "McFarland LV. Probiotics for the Primary and Secondary Prevention of C. difficile Infections: A Meta-analysis and Systematic Review. Antibiotics (Basel). 2015;4(2):160-78.", "pmid": "27025619", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27025619/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Probiotics reduce the high C. difficile and AAD risk associated with clindamycin therapy.", "clinicalSignificance": "Particularly important because clindamycin carries one of the highest C. difficile risks among antibiotics.", "managementStrategy": "Take throughout antibiotic course and for 2 weeks after, separated by 2 hours from each dose.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Clindamycin", "supplementBName": "Lactobacillus Rhamnosus", "interactionType": "synergy", "severity": "moderate", "description": "Lactobacillus rhamnosus GG reduces antibiotic-associated diarrhea during clindamycin therapy, which carries one of the highest baseline rates of AAD and C. difficile infection. Separation from antibiotic dosing preserves bacterial viability.", "recommendation": "Strongly consider Lactobacillus rhamnosus throughout your clindamycin course, separated by at least 2 hours from each antibiotic dose. Continue for at least 2 weeks after the antibiotic ends.", "minimumTimeSeparation": 120, "mechanism": "L. rhamnosus restores colonization resistance and competes with opportunistic pathogens; it also produces antimicrobial peptides and short-chain fatty acids that suppress C. difficile overgrowth.", "evidenceLevel": "strong", "sources": [ { "text": "Barnes D, Yeh AM. Bugs and Guts: Practical Applications of Probiotics for Gastrointestinal Disorders in Children. Nutr Clin Pract. 2015;30(6):747-59.", "pmid": "26538058", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26538058/", "publicSourceType": "PMID" }, { "text": "Doar NW, Samuthiram SD. Qualitative Analysis of the Efficacy of Probiotic Strains in the Prevention of Antibiotic-Associated Diarrhea. Cureus. 2023;15(6):e40261.", "pmid": "37440799", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37440799/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "L. rhamnosus reduces antibiotic-associated diarrhea and C. difficile risk during clindamycin therapy.", "clinicalSignificance": "Particularly important because clindamycin carries one of the highest AAD rates among antibiotics.", "managementStrategy": "Take throughout antibiotic course, separated by 2 hours from each dose.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Amoxicillin", "supplementBName": "Probiotics", "interactionType": "synergy", "severity": "info", "description": "Probiotic supplementation during amoxicillin therapy reduces antibiotic-associated diarrhea and helps preserve gut microbiome diversity. Although amoxicillin causes less AAD than clindamycin or fluoroquinolones, the protective effect is still meaningful.", "recommendation": "Take probiotics throughout your amoxicillin course, separated by at least 2 hours from each antibiotic dose. Continue for at least 1 week after the antibiotic ends.", "minimumTimeSeparation": 120, "mechanism": "Probiotics restore colonization resistance disrupted by broad-spectrum penicillin coverage, competing with opportunistic pathogens for nutrients and binding sites on intestinal epithelium.", "evidenceLevel": "strong", "sources": [ { "text": "Doar NW, Samuthiram SD. Qualitative Analysis of the Efficacy of Probiotic Strains in the Prevention of Antibiotic-Associated Diarrhea. Cureus. 2023;15(6):e40261.", "pmid": "37440799", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37440799/", "publicSourceType": "PMID" }, { "text": "McFarland LV. Probiotics for the Primary and Secondary Prevention of C. difficile Infections: A Meta-analysis and Systematic Review. Antibiotics (Basel). 2015;4(2):160-78.", "pmid": "27025619", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27025619/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Probiotics reduce antibiotic-associated diarrhea during amoxicillin therapy.", "clinicalSignificance": "Co-administration helps preserve gut microbiome health and reduces AAD risk.", "managementStrategy": "Take probiotics throughout antibiotic course, separated by 2 hours from each dose.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Amoxicillin", "supplementBName": "Saccharomyces Boulardii", "interactionType": "synergy", "severity": "info", "description": "Saccharomyces boulardii reduces antibiotic-associated diarrhea during amoxicillin therapy and is unaffected by the antibiotic because it is a yeast. It is particularly useful for patients with a history of AAD.", "recommendation": "Take Saccharomyces boulardii throughout your amoxicillin course. Timing flexibility is greater than with bacterial probiotics. Continue for at least 1 week after the antibiotic ends.", "minimumTimeSeparation": null, "mechanism": "S. boulardii produces proteases that degrade C. difficile toxins, stimulates secretory IgA, and competes with pathogens for adhesion sites. As a yeast, it is intrinsically resistant to amoxicillin.", "evidenceLevel": "strong", "sources": [ { "text": "McFarland LV. Probiotics for the Primary and Secondary Prevention of C. difficile Infections: A Meta-analysis and Systematic Review. Antibiotics (Basel). 2015;4(2):160-78.", "pmid": "27025619", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27025619/", "publicSourceType": "PMID" }, { "text": "Boddy AV, Elmer GW, McFarland LV, Levy RH. Influence of antibiotics on the recovery and kinetics of Saccharomyces boulardii in rats. Pharm Res. 1991;8(6):796-800.", "pmid": "2062812", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2062812/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "S. boulardii reduces antibiotic-associated diarrhea during amoxicillin therapy.", "clinicalSignificance": "Probiotic supplementation is protective with no antibacterial interference.", "managementStrategy": "Take throughout the antibiotic course; timing is not critical.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Amoxicillin", "supplementBName": "Lactobacillus Rhamnosus", "interactionType": "synergy", "severity": "info", "description": "Lactobacillus rhamnosus GG reduces antibiotic-associated diarrhea in patients on amoxicillin, with the strongest pediatric evidence among probiotic strains. Separation from antibiotic dosing preserves bacterial viability.", "recommendation": "Take Lactobacillus rhamnosus throughout your amoxicillin course, separated by at least 2 hours from each antibiotic dose. Continue for at least 1 week after the antibiotic ends.", "minimumTimeSeparation": 120, "mechanism": "L. rhamnosus restores colonization resistance and competes with opportunistic pathogens for intestinal binding sites; it also produces antimicrobial peptides that support gut barrier function.", "evidenceLevel": "strong", "sources": [ { "text": "Barnes D, Yeh AM. Bugs and Guts: Practical Applications of Probiotics for Gastrointestinal Disorders in Children. Nutr Clin Pract. 2015;30(6):747-59.", "pmid": "26538058", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26538058/", "publicSourceType": "PMID" }, { "text": "Doar NW, Samuthiram SD. Qualitative Analysis of the Efficacy of Probiotic Strains in the Prevention of Antibiotic-Associated Diarrhea. Cureus. 2023;15(6):e40261.", "pmid": "37440799", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37440799/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "L. rhamnosus reduces antibiotic-associated diarrhea during amoxicillin therapy.", "clinicalSignificance": "Probiotic supplementation is protective against gut dysbiosis.", "managementStrategy": "Take throughout antibiotic course, separated by 2 hours from each dose.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Amoxicillin-Clavulanate", "supplementBName": "Probiotics", "interactionType": "synergy", "severity": "info", "description": "Amoxicillin-clavulanate has notably higher rates of antibiotic-associated diarrhea than plain amoxicillin, largely due to the clavulanate component. Probiotic supplementation reduces this AAD risk and is particularly recommended during amoxicillin-clavulanate courses.", "recommendation": "Take probiotics throughout your amoxicillin-clavulanate course, separated by at least 2 hours from each antibiotic dose. Continue for at least 1 week after the antibiotic ends.", "minimumTimeSeparation": 120, "mechanism": "Probiotics restore colonization resistance disrupted by the broad-spectrum activity of amoxicillin-clavulanate. Clavulanate independently increases gut motility, and probiotics help offset this dysmotility.", "evidenceLevel": "strong", "sources": [ { "text": "Doar NW, Samuthiram SD. Qualitative Analysis of the Efficacy of Probiotic Strains in the Prevention of Antibiotic-Associated Diarrhea. Cureus. 2023;15(6):e40261.", "pmid": "37440799", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37440799/", "publicSourceType": "PMID" }, { "text": "McFarland LV. Probiotics for the Primary and Secondary Prevention of C. difficile Infections: A Meta-analysis and Systematic Review. Antibiotics (Basel). 2015;4(2):160-78.", "pmid": "27025619", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27025619/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Probiotics reduce the elevated AAD risk associated with amoxicillin-clavulanate.", "clinicalSignificance": "Particularly valuable because amoxicillin-clavulanate has higher AAD rates than plain amoxicillin.", "managementStrategy": "Take probiotics throughout the antibiotic course, separated by 2 hours from each dose.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Amoxicillin-Clavulanate", "supplementBName": "Saccharomyces Boulardii", "interactionType": "synergy", "severity": "info", "description": "Saccharomyces boulardii reduces the elevated antibiotic-associated diarrhea risk of amoxicillin-clavulanate. Because it is a yeast, it is unaffected by the antibiotic and timing is less critical than with bacterial probiotics.", "recommendation": "Take Saccharomyces boulardii throughout your amoxicillin-clavulanate course. Timing flexibility is greater than with bacterial probiotics. Continue for at least 1 week after the antibiotic ends.", "minimumTimeSeparation": null, "mechanism": "S. boulardii produces proteases that degrade C. difficile toxins, stimulates secretory IgA, and competes with pathogens for adhesion sites. As a yeast, it is intrinsically resistant to antibacterial drugs.", "evidenceLevel": "strong", "sources": [ { "text": "McFarland LV. Probiotics for the Primary and Secondary Prevention of C. difficile Infections: A Meta-analysis and Systematic Review. Antibiotics (Basel). 2015;4(2):160-78.", "pmid": "27025619", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27025619/", "publicSourceType": "PMID" }, { "text": "Boddy AV, Elmer GW, McFarland LV, Levy RH. Influence of antibiotics on the recovery and kinetics of Saccharomyces boulardii in rats. Pharm Res. 1991;8(6):796-800.", "pmid": "2062812", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2062812/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "S. boulardii reduces elevated AAD risk during amoxicillin-clavulanate therapy.", "clinicalSignificance": "Probiotic supplementation is protective with no antibacterial interference.", "managementStrategy": "Take throughout the antibiotic course; timing is not critical.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Amoxicillin-Clavulanate", "supplementBName": "Lactobacillus Rhamnosus", "interactionType": "synergy", "severity": "info", "description": "Lactobacillus rhamnosus GG reduces the elevated antibiotic-associated diarrhea risk associated with amoxicillin-clavulanate, including in pediatric patients. Separation from antibiotic dosing preserves bacterial viability.", "recommendation": "Take Lactobacillus rhamnosus throughout your amoxicillin-clavulanate course, separated by at least 2 hours from each antibiotic dose. Continue for at least 1 week after the antibiotic ends.", "minimumTimeSeparation": 120, "mechanism": "L. rhamnosus restores colonization resistance and competes with opportunistic pathogens for intestinal binding sites; it also supports gut barrier integrity through short-chain fatty acid production.", "evidenceLevel": "strong", "sources": [ { "text": "Barnes D, Yeh AM. Bugs and Guts: Practical Applications of Probiotics for Gastrointestinal Disorders in Children. Nutr Clin Pract. 2015;30(6):747-59.", "pmid": "26538058", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26538058/", "publicSourceType": "PMID" }, { "text": "Doar NW, Samuthiram SD. Qualitative Analysis of the Efficacy of Probiotic Strains in the Prevention of Antibiotic-Associated Diarrhea. Cureus. 2023;15(6):e40261.", "pmid": "37440799", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37440799/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "L. rhamnosus reduces elevated AAD risk during amoxicillin-clavulanate therapy.", "clinicalSignificance": "Probiotic supplementation is protective against gut dysbiosis.", "managementStrategy": "Take throughout antibiotic course, separated by 2 hours from each dose.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Azithromycin", "supplementBName": "Probiotics", "interactionType": "synergy", "severity": "info", "description": "Probiotic supplementation during azithromycin therapy reduces antibiotic-associated diarrhea and helps preserve gut microbiome diversity, which can be significantly disrupted by macrolide exposure.", "recommendation": "Take probiotics throughout your azithromycin course, separated by at least 2 hours from each antibiotic dose. Continue for at least 1 week after the antibiotic ends.", "minimumTimeSeparation": 120, "mechanism": "Probiotics restore colonization resistance disrupted by macrolide-induced changes in gut microbiome composition, competing with opportunistic pathogens for nutrients and binding sites.", "evidenceLevel": "strong", "sources": [ { "text": "Doar NW, Samuthiram SD. Qualitative Analysis of the Efficacy of Probiotic Strains in the Prevention of Antibiotic-Associated Diarrhea. Cureus. 2023;15(6):e40261.", "pmid": "37440799", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37440799/", "publicSourceType": "PMID" }, { "text": "McFarland LV. Probiotics for the Primary and Secondary Prevention of C. difficile Infections: A Meta-analysis and Systematic Review. Antibiotics (Basel). 2015;4(2):160-78.", "pmid": "27025619", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27025619/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Probiotics reduce antibiotic-associated diarrhea during azithromycin therapy.", "clinicalSignificance": "Co-administration helps preserve gut microbiome health.", "managementStrategy": "Take probiotics throughout antibiotic course, separated by 2 hours from each dose.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Azithromycin", "supplementBName": "Saccharomyces Boulardii", "interactionType": "synergy", "severity": "info", "description": "Saccharomyces boulardii reduces antibiotic-associated diarrhea during azithromycin therapy and is unaffected by the antibiotic because it is a yeast.", "recommendation": "Take Saccharomyces boulardii throughout your azithromycin course. Timing flexibility is greater than with bacterial probiotics. Continue for at least 1 week after the antibiotic ends.", "minimumTimeSeparation": null, "mechanism": "S. boulardii produces proteases that degrade C. difficile toxins, stimulates secretory IgA, and competes with pathogens for intestinal adhesion sites. As a yeast, it is intrinsically resistant to antibacterial drugs.", "evidenceLevel": "strong", "sources": [ { "text": "McFarland LV. Probiotics for the Primary and Secondary Prevention of C. difficile Infections: A Meta-analysis and Systematic Review. Antibiotics (Basel). 2015;4(2):160-78.", "pmid": "27025619", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27025619/", "publicSourceType": "PMID" }, { "text": "Boddy AV, Elmer GW, McFarland LV, Levy RH. Influence of antibiotics on the recovery and kinetics of Saccharomyces boulardii in rats. Pharm Res. 1991;8(6):796-800.", "pmid": "2062812", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2062812/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "S. boulardii reduces antibiotic-associated diarrhea during azithromycin therapy.", "clinicalSignificance": "Probiotic supplementation is protective with no antibacterial interference.", "managementStrategy": "Take throughout the antibiotic course; timing is not critical.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Cephalexin", "supplementBName": "Probiotics", "interactionType": "synergy", "severity": "info", "description": "Probiotic supplementation during cephalexin therapy reduces antibiotic-associated diarrhea and helps preserve gut microbiome diversity disrupted by cephalosporin coverage.", "recommendation": "Take probiotics throughout your cephalexin course, separated by at least 2 hours from each antibiotic dose. Continue for at least 1 week after the antibiotic ends.", "minimumTimeSeparation": 120, "mechanism": "Probiotics restore colonization resistance disrupted by cephalosporin-induced microbiome changes, competing with opportunistic pathogens including C. difficile for nutrients and binding sites.", "evidenceLevel": "strong", "sources": [ { "text": "Doar NW, Samuthiram SD. Qualitative Analysis of the Efficacy of Probiotic Strains in the Prevention of Antibiotic-Associated Diarrhea. Cureus. 2023;15(6):e40261.", "pmid": "37440799", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37440799/", "publicSourceType": "PMID" }, { "text": "McFarland LV. Probiotics for the Primary and Secondary Prevention of C. difficile Infections: A Meta-analysis and Systematic Review. Antibiotics (Basel). 2015;4(2):160-78.", "pmid": "27025619", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27025619/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Probiotics reduce antibiotic-associated diarrhea during cephalexin therapy.", "clinicalSignificance": "Co-administration helps preserve gut microbiome and reduces C. difficile risk.", "managementStrategy": "Take probiotics throughout antibiotic course, separated by 2 hours from each dose.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Cephalexin", "supplementBName": "Saccharomyces Boulardii", "interactionType": "synergy", "severity": "info", "description": "Saccharomyces boulardii reduces antibiotic-associated diarrhea during cephalexin therapy and is unaffected by the antibiotic because it is a yeast.", "recommendation": "Take Saccharomyces boulardii throughout your cephalexin course. Timing flexibility is greater than with bacterial probiotics. Continue for at least 1 week after the antibiotic ends.", "minimumTimeSeparation": null, "mechanism": "S. boulardii produces proteases that degrade C. difficile toxins, stimulates secretory IgA, and competes with pathogens for adhesion sites. As a yeast, it is intrinsically resistant to antibacterial drugs.", "evidenceLevel": "strong", "sources": [ { "text": "McFarland LV. Probiotics for the Primary and Secondary Prevention of C. difficile Infections: A Meta-analysis and Systematic Review. Antibiotics (Basel). 2015;4(2):160-78.", "pmid": "27025619", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27025619/", "publicSourceType": "PMID" }, { "text": "Boddy AV, Elmer GW, McFarland LV, Levy RH. Influence of antibiotics on the recovery and kinetics of Saccharomyces boulardii in rats. Pharm Res. 1991;8(6):796-800.", "pmid": "2062812", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2062812/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "S. boulardii reduces antibiotic-associated diarrhea during cephalexin therapy.", "clinicalSignificance": "Probiotic supplementation is protective with no antibacterial interference.", "managementStrategy": "Take throughout the antibiotic course; timing is not critical.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Cephalexin", "supplementBName": "Vitamin K2", "interactionType": "caution", "severity": "moderate", "description": "Broad-spectrum antibiotics including cephalosporins suppress vitamin K-producing gut bacteria, which can lower endogenous vitamin K2 (menaquinone) levels during prolonged courses. In patients with marginal vitamin K intake, malnutrition, or coagulopathy risk, this can increase bleeding tendency. Routine supplementation is generally not required for short courses in well-nourished adults.", "recommendation": "For short cephalexin courses in healthy adults, no special action is needed. For prolonged therapy, malnourished patients, or those at bleeding risk, consider monitoring coagulation parameters and discussing vitamin K2 supplementation with your clinician.", "minimumTimeSeparation": null, "mechanism": "Cephalosporins disrupt the colonic anaerobic flora responsible for synthesizing vitamin K2 (menaquinones), gradually depleting hepatic menaquinone stores and reducing gamma-carboxylation of clotting factors II, VII, IX, and X.", "evidenceLevel": "moderate", "sources": [ { "text": "Shirakawa H, Komai M, Kimura S. Antibiotic-induced vitamin K deficiency and the role of the presence of intestinal flora. Int J Vitam Nutr Res. 1990;60(3):245-51.", "pmid": "2276882", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2276882/", "publicSourceType": "PMID" }, { "text": "Conly J, Stein K. Reduction of vitamin K2 concentrations in human liver associated with the use of broad spectrum antimicrobials. Clin Invest Med. 1994;17(6):531-539.", "pmid": "7895417", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7895417/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Cephalexin can deplete gut-derived vitamin K2 over prolonged courses.", "clinicalSignificance": "Increases bleeding risk in malnourished or coagulopathy-prone patients on long courses.", "managementStrategy": "Monitor coagulation in at-risk patients; consider vitamin K2 supplementation under clinician guidance.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Ceftriaxone", "supplementBName": "Probiotics", "interactionType": "synergy", "severity": "info", "description": "Probiotic supplementation during ceftriaxone therapy reduces antibiotic-associated diarrhea and helps preserve gut microbiome diversity. This is particularly relevant because IV ceftriaxone is excreted in bile and disrupts colonic flora significantly.", "recommendation": "Take probiotics throughout your ceftriaxone course. Continue for at least 1 week after the antibiotic ends.", "minimumTimeSeparation": null, "mechanism": "Probiotics restore colonization resistance disrupted by ceftriaxone's biliary excretion into the colon, competing with opportunistic pathogens including C. difficile for nutrients and binding sites.", "evidenceLevel": "strong", "sources": [ { "text": "Doar NW, Samuthiram SD. Qualitative Analysis of the Efficacy of Probiotic Strains in the Prevention of Antibiotic-Associated Diarrhea. Cureus. 2023;15(6):e40261.", "pmid": "37440799", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37440799/", "publicSourceType": "PMID" }, { "text": "McFarland LV. Probiotics for the Primary and Secondary Prevention of C. difficile Infections: A Meta-analysis and Systematic Review. Antibiotics (Basel). 2015;4(2):160-78.", "pmid": "27025619", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27025619/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Probiotics reduce antibiotic-associated diarrhea during ceftriaxone therapy.", "clinicalSignificance": "Co-administration helps preserve gut microbiome and reduces C. difficile risk.", "managementStrategy": "Take probiotics throughout antibiotic course and for 1 week after.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Ceftriaxone", "supplementBName": "Vitamin K2", "interactionType": "caution", "severity": "moderate", "description": "Ceftriaxone suppresses vitamin K-producing gut bacteria and has been associated with hypoprothrombinemia and bleeding, particularly in malnourished patients, the elderly, or those with prolonged therapy. Although ceftriaxone lacks the N-methylthiotetrazole side chain seen in some bleeding-prone cephalosporins, gut flora suppression alone can lower vitamin K2 stores.", "recommendation": "For short courses in well-nourished adults, no special action is needed. For prolonged therapy, malnutrition, elderly patients, or critical illness, monitor coagulation and discuss vitamin K2 supplementation with your clinician.", "minimumTimeSeparation": null, "mechanism": "Ceftriaxone disrupts the colonic anaerobic flora responsible for synthesizing vitamin K2 (menaquinones), gradually depleting hepatic menaquinone stores and reducing gamma-carboxylation of clotting factors II, VII, IX, and X.", "evidenceLevel": "moderate", "sources": [ { "text": "Shirakawa H, Komai M, Kimura S. Antibiotic-induced vitamin K deficiency and the role of the presence of intestinal flora. Int J Vitam Nutr Res. 1990;60(3):245-51.", "pmid": "2276882", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2276882/", "publicSourceType": "PMID" }, { "text": "Conly J, Stein K. Reduction of vitamin K2 concentrations in human liver associated with the use of broad spectrum antimicrobials. Clin Invest Med. 1994;17(6):531-539.", "pmid": "7895417", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7895417/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Ceftriaxone can deplete gut-derived vitamin K2, raising bleeding risk in vulnerable patients.", "clinicalSignificance": "Risk of hypoprothrombinemia and bleeding in malnourished, elderly, or critically ill patients on prolonged therapy.", "managementStrategy": "Monitor coagulation in at-risk patients; consider vitamin K2 supplementation under clinician guidance.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Ceftriaxone", "supplementBName": "Calcium", "interactionType": "contraindicated", "severity": "dangerous", "description": "Ceftriaxone and calcium-containing IV fluids can form insoluble ceftriaxone-calcium precipitates in lung and kidney tissue, with fatal cases reported in neonates. The FDA contraindicates concurrent IV ceftriaxone and IV calcium-containing solutions in neonates under 28 days. In older patients and oral calcium supplementation, the risk is much lower, but the principle of avoidance still applies for IV co-administration.", "recommendation": "Do not infuse IV ceftriaxone with calcium-containing IV solutions, especially in neonates. Oral calcium supplements are generally acceptable but should ideally be spaced from IV ceftriaxone doses. Discuss any IV co-administration with your clinical team.", "minimumTimeSeparation": null, "mechanism": "Ceftriaxone and calcium form insoluble ceftriaxone-calcium salt crystals that can precipitate in the lungs, kidneys, and IV line. Neonates are at highest risk due to immature renal clearance and high relative blood volume per dose.", "evidenceLevel": "strong", "sources": [ { "text": "Monte SV, Prescott WA, Johnson KK, Kuhman L, Paladino JA. Safety of ceftriaxone sodium at extremes of age. Expert Opin Drug Saf. 2008;7(5):515-23.", "pmid": "18759704", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18759704/", "publicSourceType": "PMID" }, { "text": "Nilsson N, Nezvalova-Henriksen K, Bøtker JP, et al. Co-administration of Intravenous Drugs: Rapidly Troubleshooting the Solid Form Composition of a Precipitate in a Multi-drug Mixture Using On-Site Raman Spectroscopy. Mol Pharm. 2023;20(6):2853-2863.", "pmid": "37167030", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37167030/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Ceftriaxone and calcium can form fatal precipitates, particularly with IV co-administration in neonates.", "clinicalSignificance": "Fatal lung and kidney precipitates have been reported, especially in neonates.", "managementStrategy": "Do not co-infuse IV ceftriaxone with calcium-containing IV fluids in neonates; separate IV doses in older patients.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Nitrofurantoin", "supplementBName": "Magnesium Glycinate", "interactionType": "timingSensitive", "severity": "moderate", "description": "Magnesium-containing antacids and supplements have been shown to reduce nitrofurantoin absorption, an effect first demonstrated for magnesium trisilicate and extended to other magnesium salts. The reduction can lower urinary nitrofurantoin concentrations below the threshold needed to treat urinary tract infections.", "recommendation": "Take nitrofurantoin at least 2 hours before or 2 hours after magnesium glycinate. Do not co-administer.", "minimumTimeSeparation": 120, "mechanism": "Magnesium adsorbs nitrofurantoin in the gut, reducing the amount available for intestinal absorption. The effect lowers serum and urinary nitrofurantoin concentrations.", "evidenceLevel": "moderate", "sources": [ { "text": "Naggar VF, Khalil SA. Effect of magnesium trisilicate on nitrofurantoin absorption. Clin Pharmacol Ther. 1979;25(6):857-863.", "pmid": "36251", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36251/", "publicSourceType": "PMID" }, { "text": "Soci MM, Parrott EL. Influence of viscosity on absorption from nitrofurantoin suspensions. J Pharm Sci. 1980;69(4):403-406.", "pmid": "7373534", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7373534/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Magnesium adsorbs nitrofurantoin and reduces its absorption.", "clinicalSignificance": "Reduced absorption can lower urinary drug levels below the threshold needed to treat UTI.", "managementStrategy": "Separate doses by 2 hours before or 2 hours after.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Nitrofurantoin", "supplementBName": "Probiotics", "interactionType": "synergy", "severity": "info", "description": "Probiotic supplementation during nitrofurantoin therapy reduces antibiotic-associated diarrhea and helps preserve gut microbiome diversity. Probiotics may also reduce recurrence rates of urinary tract infections in some studies.", "recommendation": "Take probiotics throughout your nitrofurantoin course, separated by at least 2 hours from each antibiotic dose. Continue for at least 1 week after the antibiotic ends.", "minimumTimeSeparation": 120, "mechanism": "Probiotics restore gut and vaginal colonization resistance disrupted by antibiotic exposure, competing with opportunistic pathogens for nutrients and binding sites.", "evidenceLevel": "moderate", "sources": [ { "text": "Doar NW, Samuthiram SD. Qualitative Analysis of the Efficacy of Probiotic Strains in the Prevention of Antibiotic-Associated Diarrhea. Cureus. 2023;15(6):e40261.", "pmid": "37440799", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37440799/", "publicSourceType": "PMID" }, { "text": "McFarland LV. Probiotics for the Primary and Secondary Prevention of C. difficile Infections: A Meta-analysis and Systematic Review. Antibiotics (Basel). 2015;4(2):160-78.", "pmid": "27025619", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27025619/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Probiotics reduce AAD during nitrofurantoin therapy and may reduce UTI recurrence.", "clinicalSignificance": "Co-administration helps preserve gut and urogenital microbiome.", "managementStrategy": "Take probiotics throughout antibiotic course, separated by 2 hours from each dose.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Vitamin K1", "interactionType": "conflict", "severity": "serious", "description": "Vitamin K1 (phytonadione) directly reverses warfarin's anticoagulant effect. Even small, regular doses found in multivitamins (25 mcg/day) have been shown to lower the INR and require warfarin dose increases, particularly in patients with depleted baseline vitamin K stores. Inconsistent K1 intake from supplements is one of the most common causes of unstable INR.", "recommendation": "Avoid vitamin K1 supplements unless your prescriber has specifically directed you to take them. If a multivitamin containing vitamin K1 is unavoidable, keep the dose and brand identical every day and ask your anticoagulation clinic to re-check INR within 1-2 weeks of starting.", "minimumTimeSeparation": null, "mechanism": "Warfarin inhibits vitamin K epoxide reductase (VKORC1), preventing the recycling of vitamin K needed to gamma-carboxylate clotting factors II, VII, IX, and X. Supplemental vitamin K1 directly replenishes the substrate pool, bypassing warfarin's blockade and restoring clotting factor activity.", "evidenceLevel": "strong", "sources": [ { "text": "Kurnik D, Loebstein R, Rabinovitz H, et al. Over-the-counter vitamin K1-containing multivitamin supplements disrupt warfarin anticoagulation in vitamin K1-depleted patients. A prospective, controlled trial. Thromb Haemost. 2004;92(5):1018-24.", "pmid": "15543329", "doi": "10.1160/TH04-06-0346", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15543329/", "publicSourceType": "PMID" }, { "text": "Holbrook AM, Pereira JA, Labiris R, et al. Systematic overview of warfarin and its drug and food interactions. Arch Intern Med. 2005;165(10):1095-106.", "pmid": "15911722", "doi": "10.1001/archinte.165.10.1095", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15911722/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Vitamin K1 supplementation antagonises warfarin and lowers the INR.", "clinicalSignificance": "Even multivitamin-dose K1 (25 mcg) can push the INR below the therapeutic range and raise clot risk.", "managementStrategy": "Avoid K1 supplements; if unavoidable, keep dose constant and re-check INR within 1-2 weeks.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Vitamin K2 MK-4", "interactionType": "conflict", "severity": "serious", "description": "Vitamin K2 in the MK-4 (menatetrenone) form opposes warfarin in the same way as K1 and K2 MK-7: it restores production of vitamin K-dependent clotting factors. MK-4 is used clinically (often intravenously) to reverse warfarin, which is direct evidence that supplemental MK-4 will reduce warfarin's effect. Even modest oral doses can blunt anticoagulation.", "recommendation": "Avoid vitamin K2 MK-4 supplements while taking warfarin unless your prescriber has explicitly approved it. If you cannot avoid it, keep the dose and timing identical every day and ask for an INR check within 1-2 weeks of starting.", "minimumTimeSeparation": null, "mechanism": "MK-4 supplies a vitamin K substrate that is gamma-carboxylated by enzymes downstream of VKORC1, restoring functional clotting factors II, VII, IX, and X despite warfarin's inhibition of vitamin K recycling.", "evidenceLevel": "strong", "sources": [ { "text": "Holbrook AM, Pereira JA, Labiris R, et al. Systematic overview of warfarin and its drug and food interactions. Arch Intern Med. 2005;165(10):1095-106.", "pmid": "15911722", "doi": "10.1001/archinte.165.10.1095", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15911722/", "publicSourceType": "PMID" }, { "text": "Tan CSS, Lee SWH. Warfarin and food, herbal or dietary supplement interactions: A systematic review. Br J Clin Pharmacol. 2021;87(2):352-374.", "pmid": "32478963", "doi": "10.1111/bcp.14404", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32478963/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Vitamin K2 MK-4 reverses warfarin's anticoagulant effect.", "clinicalSignificance": "Even oral menatetrenone is used clinically to reverse warfarin, so supplementation predictably lowers INR.", "managementStrategy": "Avoid MK-4 supplements; if used, keep dose constant and recheck INR within 1-2 weeks.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Coenzyme Q10", "interactionType": "caution", "severity": "moderate", "description": "Coenzyme Q10 (ubiquinone) is structurally similar to vitamin K and may reduce warfarin's anticoagulant effect in some patients. Case reports describe loss of INR control after starting CoQ10. A longitudinal study of warfarin patients found CoQ10 use independently tripled the odds of bleeding events, so the direction of the interaction is not predictable. Effects appear most likely at doses of 100 mg/day or more.", "recommendation": "Tell your anticoagulation clinic before starting, stopping, or changing the dose of CoQ10. If you do take it, keep the daily dose constant and ask for an INR check within 1-2 weeks of any change.", "minimumTimeSeparation": null, "mechanism": "CoQ10 shares a quinone backbone with vitamin K and may partially substitute as a cofactor in clotting factor carboxylation. Microsomal studies also suggest CoQ10 can accelerate the hydroxylation and clearance of S- and R-warfarin via CYP2C9 and CYP3A4, lowering plasma warfarin levels.", "evidenceLevel": "moderate", "sources": [ { "text": "Landbo C, Almdal TP. Interaction between warfarin and coenzyme Q10. Ugeskr Laeger. 1998;160(22):3226-7.", "pmid": "9621803", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9621803/", "publicSourceType": "PMID" }, { "text": "Shalansky S, Lynd L, Richardson K, Ingaszewski A, Kerr C. Risk of warfarin-related bleeding events and supratherapeutic international normalized ratios associated with complementary and alternative medicine: a longitudinal analysis. Pharmacotherapy. 2007;27(9):1237-47.", "pmid": "17723077", "doi": "10.1592/phco.27.9.1237", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17723077/", "publicSourceType": "PMID" }, { "text": "Zhou Q, Zhou S, Chan E. Effect of coenzyme Q10 on warfarin hydroxylation in rat and human liver microsomes. Curr Drug Metab. 2005;6(2):67-81.", "pmid": "15853759", "doi": "10.2174/1389200053586091", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15853759/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "CoQ10 can unpredictably raise bleeding risk or blunt warfarin's effect depending on the patient.", "clinicalSignificance": "CoQ10 use was independently associated with a ~3.7-fold increase in self-reported bleeding in warfarin patients.", "managementStrategy": "Keep CoQ10 dose constant; recheck INR within 1-2 weeks of any change.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Ginger Extract", "interactionType": "caution", "severity": "serious", "description": "Ginger extract inhibits platelet aggregation via thromboxane synthase suppression and may potentiate warfarin. Case reports describe supratherapeutic INRs and bleeding (one patient developed epistaxis with an INR >10 after starting ginger tea and dried ginger). A longitudinal cohort of warfarin patients found ginger use was independently associated with a ~3.2-fold increase in bleeding events.", "recommendation": "Avoid concentrated ginger extract while taking warfarin. Culinary amounts in food are generally safe, but tell your anticoagulation clinic before starting any ginger supplement and ask for an INR check within 1-2 weeks.", "minimumTimeSeparation": null, "mechanism": "Gingerols and shogaols inhibit cyclooxygenase and thromboxane A2 synthesis in platelets, reducing aggregation. This pharmacodynamic antiplatelet effect adds to warfarin's anticoagulation, raising bleeding risk without necessarily changing the INR.", "evidenceLevel": "moderate", "sources": [ { "text": "Lesho EP, Saullo L, Udvari-Nagy S. A 76-year-old woman with erratic anticoagulation. Cleve Clin J Med. 2004;71(8):651-6.", "pmid": "15449760", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15449760/", "publicSourceType": "PMID" }, { "text": "Shalansky S, Lynd L, Richardson K, Ingaszewski A, Kerr C. Risk of warfarin-related bleeding events and supratherapeutic international normalized ratios associated with complementary and alternative medicine: a longitudinal analysis. Pharmacotherapy. 2007;27(9):1237-47.", "pmid": "17723077", "doi": "10.1592/phco.27.9.1237", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17723077/", "publicSourceType": "PMID" }, { "text": "Marx W, McKavanagh D, McCarthy AL, et al. The Effect of Ginger (Zingiber officinale) on Platelet Aggregation: A Systematic Literature Review. PLoS One. 2015;10(10):e0141119.", "pmid": "26488162", "doi": "10.1371/journal.pone.0141119", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26488162/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Ginger extract may potentiate warfarin and raise bleeding risk.", "clinicalSignificance": "Documented case of INR >10 with epistaxis; cohort data show ~3.2-fold increase in bleeding events.", "managementStrategy": "Avoid concentrated ginger supplements; recheck INR within 1-2 weeks if started.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Nattokinase", "interactionType": "caution", "severity": "dangerous", "description": "Nattokinase is a fibrinolytic enzyme that degrades fibrin directly and reduces clotting factors. Combined with warfarin, the additive effects substantially increase bleeding risk. Case reports describe hemoperitoneum and intracerebral hemorrhage with nattokinase in patients on other antithrombotics, and substituting nattokinase for warfarin has caused mechanical valve thrombosis.", "recommendation": "Do not combine nattokinase with warfarin. Never substitute nattokinase for prescribed warfarin, especially after mechanical valve replacement or for atrial fibrillation. If you have started nattokinase, stop it and contact your anticoagulation clinic.", "minimumTimeSeparation": null, "mechanism": "Nattokinase is a serine protease from fermented soybeans that cleaves fibrin directly and indirectly activates the fibrinolytic system by converting plasminogen to plasmin. It also reduces fibrinogen, factor VII, and factor VIII levels. These effects add to warfarin's reduction of clotting factor synthesis.", "evidenceLevel": "moderate", "sources": [ { "text": "Chang YY, Liu JS, Lai SL, Wu HS, Lan MY. Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. Intern Med. 2008;47(5):467-9.", "pmid": "18310985", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18310985/", "publicSourceType": "PMID" }, { "text": "Elahi MM, Choi CH, Konda S, Shake JG. Consequence of patient substitution of nattokinase for warfarin after aortic valve replacement with a mechanical prosthesis. Proc (Bayl Univ Med Cent). 2015;28(1):81-2.", "pmid": "25552810", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25552810/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Additive anticoagulation and fibrinolysis sharply raise bleeding risk; substitution causes treatment failure.", "clinicalSignificance": "Documented intracerebral hemorrhage with antithrombotics and valve thrombosis with substitution.", "managementStrategy": "Do not combine; never substitute nattokinase for prescribed warfarin.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Resveratrol", "interactionType": "caution", "severity": "serious", "description": "Resveratrol inhibits CYP2C9, the main enzyme that clears the more potent S-enantiomer of warfarin, and also inhibits BCRP-mediated efflux. In animal models this raises plasma warfarin AUC and significantly increases INR. Resveratrol additionally inhibits platelet COX-1 and thromboxane A2, adding a pharmacodynamic bleeding risk. Combined effects can amplify warfarin's anticoagulation.", "recommendation": "Avoid resveratrol supplements (typically 100-500 mg/day) while on warfarin. If you choose to take it, keep the dose constant and ask your anticoagulation clinic to recheck INR within 1-2 weeks of starting or stopping.", "minimumTimeSeparation": null, "mechanism": "Resveratrol and its conjugated metabolites inhibit CYP2C9 and BCRP, increasing S-warfarin systemic exposure. Independently, resveratrol inhibits platelet COX-1 and thromboxane A2 generation, adding antiplatelet activity to warfarin's anticoagulation.", "evidenceLevel": "emerging", "sources": [ { "text": "Huang TY, Yu CP, Hsieh YW, Lin SP, Hou YC. Resveratrol stereoselectively affected (±)warfarin pharmacokinetics and enhanced the anticoagulation effect. Sci Rep. 2020;10(1):15910.", "pmid": "32985569", "doi": "10.1038/s41598-020-72694-0", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32985569/", "publicSourceType": "PMID" }, { "text": "Tan CSS, Lee SWH. Warfarin and food, herbal or dietary supplement interactions: A systematic review. Br J Clin Pharmacol. 2021;87(2):352-374.", "pmid": "32478963", "doi": "10.1111/bcp.14404", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32478963/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Resveratrol can increase warfarin exposure and amplify anticoagulation.", "clinicalSignificance": "Combined CYP2C9 inhibition and antiplatelet effect raise bleeding risk.", "managementStrategy": "Avoid resveratrol supplements; if used, keep dose constant and recheck INR within 1-2 weeks.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Quercetin", "interactionType": "caution", "severity": "moderate", "description": "Quercetin and its metabolites strongly displace warfarin from human serum albumin, which can transiently raise free (active) warfarin concentrations. High-dose quercetin supplements also inhibit CYP2C8/2C9/3A4 to varying degrees. The combination has been associated with increased bleeding risk in herbal product–warfarin reviews.", "recommendation": "Avoid high-dose quercetin supplements (500 mg or more per day) on warfarin. Dietary intake from fruits and vegetables is fine. If you start a quercetin supplement, tell your anticoagulation clinic and ask for INR re-check within 1-2 weeks.", "minimumTimeSeparation": null, "mechanism": "Quercetin glucuronide and sulfate metabolites bind the warfarin site on human serum albumin, displacing protein-bound warfarin and increasing the free fraction. Quercetin and its metabolites also inhibit several CYP isoforms including CYP2C9 and CYP3A4, the enzymes responsible for warfarin metabolism.", "evidenceLevel": "emerging", "sources": [ { "text": "Poór M, Boda G, Needs PW, Kroon PA, Lemli B, Bencsik T. Interaction of quercetin and its metabolites with warfarin: Displacement of warfarin from serum albumin and inhibition of CYP2C9 enzyme. Biomed Pharmacother. 2017;88:574-581.", "pmid": "28135601", "doi": "10.1016/j.biopha.2017.01.092", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28135601/", "publicSourceType": "PMID" }, { "text": "Tan CSS, Lee SWH. Warfarin and food, herbal or dietary supplement interactions: A systematic review. Br J Clin Pharmacol. 2021;87(2):352-374.", "pmid": "32478963", "doi": "10.1111/bcp.14404", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32478963/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "High-dose quercetin may raise free warfarin levels and bleeding risk.", "clinicalSignificance": "Albumin displacement plus CYP2C9 inhibition can transiently amplify anticoagulation.", "managementStrategy": "Avoid high-dose quercetin supplements; recheck INR within 1-2 weeks if started.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Grape Seed Extract", "interactionType": "caution", "severity": "serious", "description": "Grape seed extract contains procyanidins that inhibit platelet aggregation and prolong APTT and PT in vitro. A case report describes a stable warfarin patient developing a subcutaneous hematoma and INR of 7.9 within three days of starting grape seed extract drops. The mechanism is pharmacodynamic plus possible CYP inhibition.", "recommendation": "Avoid grape seed extract supplements while on warfarin. If unavoidable, keep the dose constant, watch for unusual bruising or bleeding, and ask your anticoagulation clinic for an INR check within 1-2 weeks of any change.", "minimumTimeSeparation": null, "mechanism": "Procyanidins and oligomeric proanthocyanidins in grape seed extract inhibit collagen- and thrombin-induced platelet aggregation by binding platelet receptors and inhibiting protein tyrosine phosphatase signaling. They also prolong APTT, PT, and thrombin time, adding to warfarin's anticoagulation.", "evidenceLevel": "emerging", "sources": [ { "text": "Tan CSS, Lee SWH. Warfarin and food, herbal or dietary supplement interactions: A systematic review. Br J Clin Pharmacol. 2021;87(2):352-374.", "pmid": "32478963", "doi": "10.1111/bcp.14404", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32478963/", "publicSourceType": "PMID" }, { "text": "Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm. 2000;57(13):1221-7.", "pmid": "10902065", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10902065/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Grape seed extract may potentiate warfarin and increase bleeding risk.", "clinicalSignificance": "Documented INR 7.9 with subcutaneous hematoma after 3 days of grape seed extract drops.", "managementStrategy": "Avoid grape seed extract supplements; recheck INR within 1-2 weeks if started.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Black Seed Oil", "interactionType": "caution", "severity": "serious", "description": "Thymoquinone, the main bioactive in black seed oil (Nigella sativa), is a competitive inhibitor of CYP2C9-mediated warfarin 7-hydroxylation. Pharmacokinetic modeling predicts that thymoquinone intakes above ~18 mg/day, or black seed oil above ~1 g/day, can meaningfully reduce warfarin clearance and raise INR.", "recommendation": "Avoid black seed oil supplements while on warfarin. Culinary use of small amounts of seeds is unlikely to matter. If you take a supplement, tell your anticoagulation clinic and ask for an INR check within 1-2 weeks.", "minimumTimeSeparation": null, "mechanism": "Thymoquinone competitively inhibits CYP2C9 (Ki ~3.5 µM), the primary enzyme metabolising the more potent S-enantiomer of warfarin. Reduced clearance raises plasma S-warfarin and INR.", "evidenceLevel": "emerging", "sources": [ { "text": "Wang Z, Wang Z, Wang X, et al. Potential food-drug interaction risk of thymoquinone with warfarin. Chem Biol Interact. 2022;365:110070.", "pmid": "35921950", "doi": "10.1016/j.cbi.2022.110070", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35921950/", "publicSourceType": "PMID" }, { "text": "Tan CSS, Lee SWH. Warfarin and food, herbal or dietary supplement interactions: A systematic review. Br J Clin Pharmacol. 2021;87(2):352-374.", "pmid": "32478963", "doi": "10.1111/bcp.14404", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32478963/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Black seed oil can inhibit warfarin metabolism and raise INR.", "clinicalSignificance": "Predicted clinically significant CYP2C9 inhibition at supplement doses (>1 g/day oil).", "managementStrategy": "Avoid black seed oil supplements; recheck INR within 1-2 weeks if started.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Bromelain", "interactionType": "caution", "severity": "serious", "description": "Bromelain, a proteolytic enzyme from pineapple stem, inhibits platelet aggregation and has been shown to reduce thrombin-, ADP-, and collagen-induced platelet activation in vitro. It also has direct fibrinolytic activity. Combined with warfarin, these effects can additively raise bleeding risk.", "recommendation": "Avoid bromelain supplements while on warfarin. If you take it for sinus or post-surgical use, tell your anticoagulation clinic, watch for bruising or bleeding, and ask for an INR check within 1-2 weeks.", "minimumTimeSeparation": null, "mechanism": "Bromelain proteases inhibit thrombin- and ADP-induced platelet aggregation, reduce platelet adhesion to endothelium, and have intrinsic fibrinolytic activity. These pharmacodynamic effects add to warfarin's reduction of clotting factor synthesis without necessarily altering the INR.", "evidenceLevel": "emerging", "sources": [ { "text": "Metzig C, Grabowska E, Eckert K, Rehse K, Maurer HR. Bromelain proteases reduce human platelet aggregation in vitro, adhesion to bovine endothelial cells and thrombus formation in rat vessels in vivo. In Vivo. 1999;13(1):7-12.", "pmid": "10218125", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10218125/", "publicSourceType": "PMID" }, { "text": "Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm. 2000;57(13):1221-7.", "pmid": "10902065", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10902065/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Bromelain adds antiplatelet and fibrinolytic activity on top of warfarin.", "clinicalSignificance": "Pharmacodynamic bleeding risk that may not show up on INR until a bleed occurs.", "managementStrategy": "Avoid bromelain on warfarin; watch for unusual bruising or bleeding.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Boswellia", "interactionType": "caution", "severity": "serious", "description": "Boswellia serrata extracts inhibit CYP2C9, CYP3A4, and CYP2C19, the isoenzymes responsible for warfarin metabolism. Spontaneous postoperative bleeding, hematomas, hematemesis, melena, and subarachnoid hemorrhage have been reported in warfarin patients who added boswellia. Boswellic acids also inhibit COX-1 and 5-lipoxygenase, adding a pharmacodynamic antiplatelet component.", "recommendation": "Avoid boswellia supplements while taking warfarin. If you are already taking both, do not stop abruptly without telling your anticoagulation clinic, and arrange an INR check within 1-2 weeks.", "minimumTimeSeparation": null, "mechanism": "Boswellia serrata extract inhibits CYP2C9 (the main metaboliser of S-warfarin) along with CYP3A4 and CYP2C19, reducing warfarin clearance. Boswellic acids independently inhibit COX-1 and 5-lipoxygenase, dampening platelet aggregation.", "evidenceLevel": "emerging", "sources": [ { "text": "Ge B, Zhang Z, Zuo Z. Updates on the clinical evidenced herb-warfarin interactions [Warfarin Interactions with Medicinal Herbs review]. Evid Based Complement Alternat Med. 2014;2014:957362. (PubMed indexed review)", "pmid": "25233607", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25233607/", "publicSourceType": "PMID" }, { "text": "Tan CSS, Lee SWH. Warfarin and food, herbal or dietary supplement interactions: A systematic review. Br J Clin Pharmacol. 2021;87(2):352-374.", "pmid": "32478963", "doi": "10.1111/bcp.14404", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32478963/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Boswellia may inhibit warfarin metabolism and raise bleeding risk.", "clinicalSignificance": "Reported postoperative bleeding, hematomas, and intracranial hemorrhage with combined use.", "managementStrategy": "Avoid boswellia on warfarin; recheck INR within 1-2 weeks if any change.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Chondroitin", "interactionType": "caution", "severity": "serious", "description": "Chondroitin is structurally a heparan-like sulfated glycosaminoglycan and is commonly taken with glucosamine for joint pain. Combined glucosamine-chondroitin use has been linked to INR elevation in warfarin patients across multiple case reports and pharmacovigilance databases, with at least one fatal intracerebral bleed reported.", "recommendation": "Avoid chondroitin (including glucosamine-chondroitin combinations) while on warfarin. If you need joint support, tell your anticoagulation clinic before starting any new supplement and ask for an INR check within 1-2 weeks.", "minimumTimeSeparation": null, "mechanism": "Chondroitin sulfate is structurally similar to heparan sulfate and may have intrinsic mild anticoagulant activity. Combined with glucosamine, it has been linked clinically to INR elevation in warfarin users, although the precise pharmacological mechanism is not fully defined.", "evidenceLevel": "moderate", "sources": [ { "text": "Knudsen JF, Sokol GH. Potential glucosamine-warfarin interaction resulting in increased international normalized ratio: case report and review of the literature and MedWatch database. Pharmacotherapy. 2008;28(4):540-8.", "pmid": "18363538", "doi": "10.1592/phco.28.4.540", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18363538/", "publicSourceType": "PMID" }, { "text": "Tan CSS, Lee SWH. Warfarin and food, herbal or dietary supplement interactions: A systematic review. Br J Clin Pharmacol. 2021;87(2):352-374.", "pmid": "32478963", "doi": "10.1111/bcp.14404", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32478963/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Chondroitin (especially with glucosamine) can raise INR and bleeding risk.", "clinicalSignificance": "Pharmacovigilance data document repeated INR elevations and at least one fatal bleed.", "managementStrategy": "Avoid chondroitin on warfarin; recheck INR within 1-2 weeks if started.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Krill Oil", "interactionType": "caution", "severity": "moderate", "description": "Krill oil contains the same omega-3 fatty acids (EPA and DHA) as fish oil, which reduce platelet thromboxane A2 and may prolong bleeding time. The omega-3 content per gram is lower than concentrated fish oil, so the interaction is generally weaker, but at higher doses krill oil can add pharmacodynamic bleeding risk to warfarin.", "recommendation": "If you take krill oil with warfarin, keep the dose constant (typically 500-1000 mg/day) and tell your anticoagulation clinic. Avoid combining krill oil with fish oil or other omega-3 sources, and watch for unusual bruising or bleeding.", "minimumTimeSeparation": null, "mechanism": "EPA and DHA from krill oil displace arachidonic acid in platelet membranes, reducing thromboxane A2 generation and platelet aggregation. They may also slightly reduce factor VII activity. These pharmacodynamic effects add to warfarin's reduction of clotting factor synthesis.", "evidenceLevel": "emerging", "sources": [ { "text": "Buckley MS, Goff AD, Knapp WE. Fish oil interaction with warfarin. Ann Pharmacother. 2004;38(1):50-2.", "pmid": "14742793", "doi": "10.1345/aph.1D007", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14742793/", "publicSourceType": "PMID" }, { "text": "Tan CSS, Lee SWH. Warfarin and food, herbal or dietary supplement interactions: A systematic review. Br J Clin Pharmacol. 2021;87(2):352-374.", "pmid": "32478963", "doi": "10.1111/bcp.14404", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32478963/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Krill oil adds mild antiplatelet activity to warfarin.", "clinicalSignificance": "Bleeding risk increases at higher doses or when stacked with other omega-3 sources.", "managementStrategy": "Keep krill oil dose constant; avoid stacking with fish oil; tell anticoagulation clinic.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Evening Primrose Oil", "interactionType": "caution", "severity": "moderate", "description": "Evening primrose oil is rich in gamma-linolenic acid (GLA), which has documented antiplatelet activity and can prolong bleeding time. Adverse-event reviews of warfarin patients have flagged evening primrose oil as a supplement that may potentiate warfarin's effect.", "recommendation": "Avoid evening primrose oil while on warfarin. If you take it for menstrual symptoms or skin conditions, tell your anticoagulation clinic, keep the dose constant, and ask for an INR check within 1-2 weeks.", "minimumTimeSeparation": null, "mechanism": "Gamma-linolenic acid is metabolised to dihomo-gamma-linolenic acid, which shifts platelet eicosanoid production toward less aggregatory prostaglandins (PGE1) and reduces thromboxane A2 production, lowering platelet aggregation.", "evidenceLevel": "emerging", "sources": [ { "text": "Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm. 2000;57(13):1221-7.", "pmid": "10902065", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10902065/", "publicSourceType": "PMID" }, { "text": "Tan CSS, Lee SWH. Warfarin and food, herbal or dietary supplement interactions: A systematic review. Br J Clin Pharmacol. 2021;87(2):352-374.", "pmid": "32478963", "doi": "10.1111/bcp.14404", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32478963/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Evening primrose oil adds mild antiplatelet activity to warfarin.", "clinicalSignificance": "Theoretical and case-level concern for increased bleeding risk.", "managementStrategy": "Avoid on warfarin; recheck INR within 1-2 weeks if started.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Saw Palmetto", "interactionType": "caution", "severity": "moderate", "description": "Saw palmetto has been linked to coagulopathy and excessive surgical bleeding in case reports, including hematuria and intraoperative hemorrhage. Pharmacokinetic data suggest mild CYP2C9 inhibition, which could slow warfarin metabolism. The signal is modest but clinically relevant given warfarin's narrow therapeutic window.", "recommendation": "Avoid saw palmetto while taking warfarin unless your prescriber has approved it. If you take it for prostate symptoms, tell your anticoagulation clinic, keep the dose constant, and ask for an INR check within 1-2 weeks.", "minimumTimeSeparation": null, "mechanism": "Saw palmetto extracts have been shown in vitro to inhibit COX and 5-lipoxygenase pathways and mildly inhibit CYP2C9. Antiplatelet activity from these pathways may add to warfarin's anticoagulation; CYP2C9 inhibition could raise warfarin levels.", "evidenceLevel": "emerging", "sources": [ { "text": "Villanueva S, González J. Coagulopathy induced by saw palmetto: a case report. Bol Asoc Med P R. 2009;101(3):48-50.", "pmid": "20120986", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20120986/", "publicSourceType": "PMID" }, { "text": "Tan CSS, Lee SWH. Warfarin and food, herbal or dietary supplement interactions: A systematic review. Br J Clin Pharmacol. 2021;87(2):352-374.", "pmid": "32478963", "doi": "10.1111/bcp.14404", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32478963/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Saw palmetto may potentiate warfarin and raise bleeding risk.", "clinicalSignificance": "Case reports describe hematuria, coagulopathy, and excessive surgical bleeding.", "managementStrategy": "Avoid on warfarin; recheck INR within 1-2 weeks if started.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Fenugreek", "interactionType": "caution", "severity": "serious", "description": "Fenugreek aqueous extract inhibits coagulation in vitro and significantly prolongs prothrombin time. A well-documented case describes a warfarin-stable patient whose INR rose after starting boldo and fenugreek, normalised after stopping, then rose again on rechallenge. Fenugreek's coumarin content is the suspected driver.", "recommendation": "Avoid fenugreek supplements while on warfarin. Culinary use of small amounts of fenugreek seeds in food is unlikely to cause problems. Tell your anticoagulation clinic before starting any fenugreek supplement and ask for an INR check within 1-2 weeks.", "minimumTimeSeparation": null, "mechanism": "Fenugreek contains coumarin compounds that may have intrinsic anticoagulant activity additive to warfarin. Aqueous extracts have been shown to dose-dependently prolong prothrombin time, suggesting direct inhibition of vitamin K-dependent factors.", "evidenceLevel": "emerging", "sources": [ { "text": "Lambert JP, Cormier J. Potential interaction between warfarin and boldo-fenugreek. Pharmacotherapy. 2001;21(4):509-12.", "pmid": "11310527", "doi": "10.1592/phco.21.5.509.34492", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11310527/", "publicSourceType": "PMID" }, { "text": "Tan CSS, Lee SWH. Warfarin and food, herbal or dietary supplement interactions: A systematic review. Br J Clin Pharmacol. 2021;87(2):352-374.", "pmid": "32478963", "doi": "10.1111/bcp.14404", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32478963/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Fenugreek can potentiate warfarin and raise INR.", "clinicalSignificance": "Documented case with positive rechallenge supports a real interaction.", "managementStrategy": "Avoid fenugreek supplements on warfarin; recheck INR within 1-2 weeks if started.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Pine Bark Extract", "interactionType": "caution", "severity": "moderate", "description": "Pine bark extract (pycnogenol) inhibits platelet aggregation and reduces thromboxane generation. Combined with warfarin, these pharmacodynamic antiplatelet effects can additively raise bleeding risk even without changing the INR.", "recommendation": "Avoid pine bark extract supplements on warfarin. If you take it, keep the dose constant, watch for unusual bruising or bleeding, and tell your anticoagulation clinic before any dose change.", "minimumTimeSeparation": null, "mechanism": "Procyanidins in pine bark extract inhibit platelet aggregation by reducing thromboxane A2 generation and modulating platelet receptor signaling. This is a pharmacodynamic effect that adds to warfarin's reduction of clotting factor synthesis without altering the INR.", "evidenceLevel": "emerging", "sources": [ { "text": "Tan CSS, Lee SWH. Warfarin and food, herbal or dietary supplement interactions: A systematic review. Br J Clin Pharmacol. 2021;87(2):352-374.", "pmid": "32478963", "doi": "10.1111/bcp.14404", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32478963/", "publicSourceType": "PMID" }, { "text": "Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm. 2000;57(13):1221-7.", "pmid": "10902065", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10902065/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Pine bark extract adds antiplatelet activity to warfarin.", "clinicalSignificance": "Pharmacodynamic bleeding risk that the INR may not detect.", "managementStrategy": "Avoid on warfarin; watch for unusual bruising or bleeding.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Apixaban", "supplementBName": "Ginkgo Biloba", "interactionType": "caution", "severity": "serious", "description": "Ginkgo biloba inhibits platelet-activating factor and platelet aggregation. Case reports document spontaneous bleeding (intracranial, ocular, postoperative) with ginkgo, particularly when combined with antithrombotics. Adding ginkgo to apixaban stacks an antiplatelet effect on top of factor Xa inhibition, raising bleeding risk.", "recommendation": "Avoid ginkgo biloba while taking apixaban. If you have been combining the two, stop the ginkgo and call your prescriber if you notice unusual bruising, nosebleeds, or any sign of bleeding.", "minimumTimeSeparation": null, "mechanism": "Ginkgolides, particularly ginkgolide B, are potent platelet-activating factor (PAF) antagonists. They inhibit platelet aggregation and prolong bleeding time. This pharmacodynamic effect is additive to apixaban's direct factor Xa inhibition.", "evidenceLevel": "moderate", "sources": [ { "text": "Bent S, Goldberg H, Padula A, Avins AL. Spontaneous bleeding associated with ginkgo biloba: a case report and systematic review of the literature. J Gen Intern Med. 2005;20(7):657-61.", "pmid": "16050865", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16050865/", "publicSourceType": "PMID" }, { "text": "Kellermann AJ, Kloft C. Is there a risk of bleeding associated with standardized Ginkgo biloba extract therapy? A systematic review and meta-analysis. Pharmacotherapy. 2011;31(5):490-502.", "pmid": "21923430", "doi": "10.1592/phco.31.5.490", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21923430/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Ginkgo adds antiplatelet activity on top of apixaban, raising bleeding risk.", "clinicalSignificance": "Case reports of intracranial and ocular bleeding on ginkgo support the concern.", "managementStrategy": "Avoid ginkgo on apixaban; watch for unusual bruising or bleeding.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Apixaban", "supplementBName": "Garlic Extract", "interactionType": "caution", "severity": "moderate", "description": "Concentrated garlic extracts inhibit platelet aggregation via allicin and related organosulfur compounds and have been linked to surgical bleeding. Adding garlic supplements to apixaban stacks antiplatelet activity on top of factor Xa inhibition, raising bleeding risk. Culinary garlic is not a concern.", "recommendation": "Avoid concentrated garlic supplements (aged garlic extract, allicin capsules) while on apixaban, and stop them at least 7 days before any planned surgery. Garlic used in cooking is fine.", "minimumTimeSeparation": null, "mechanism": "Allicin and other thiosulfinates from garlic inhibit arachidonic acid metabolism, modify platelet membrane properties, and interfere with calcium signalling in platelets. This pharmacodynamic antiplatelet activity is additive to apixaban's factor Xa inhibition.", "evidenceLevel": "emerging", "sources": [ { "text": "Rahman K, Lowe GM. Garlic and cardiovascular disease: a critical review. J Nutr. 2006;136(3 Suppl):736S-740S. (Garlic platelet inhibition mechanisms.)", "pmid": "16484553", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16484553/", "publicSourceType": "PMID" }, { "text": "Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm. 2000;57(13):1221-7. (Garlic antiplatelet activity in anticoagulant context.)", "pmid": "10902065", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10902065/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Concentrated garlic extracts can add antiplatelet activity to apixaban.", "clinicalSignificance": "Bleeding risk is additive; relevant especially around surgery.", "managementStrategy": "Avoid garlic supplements; stop at least 7 days before surgery.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Apixaban", "supplementBName": "Nattokinase", "interactionType": "caution", "severity": "dangerous", "description": "Nattokinase is a fibrinolytic enzyme that degrades fibrin and reduces clotting factor levels. Combined with apixaban's factor Xa inhibition, the additive effects substantially raise bleeding risk. Case reports describe intracerebral and intra-abdominal hemorrhage when nattokinase is added to other antithrombotics.", "recommendation": "Do not combine nattokinase with apixaban. If you have been taking both, stop the nattokinase and call your prescriber, especially if you notice unusual bruising or bleeding.", "minimumTimeSeparation": null, "mechanism": "Nattokinase, a serine protease from fermented soybeans, directly cleaves fibrin and activates plasmin-mediated fibrinolysis. It also reduces plasma fibrinogen, factor VII, and factor VIII levels. These effects compound apixaban's inhibition of factor Xa.", "evidenceLevel": "emerging", "sources": [ { "text": "Chang YY, Liu JS, Lai SL, Wu HS, Lan MY. Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. Intern Med. 2008;47(5):467-9.", "pmid": "18310985", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18310985/", "publicSourceType": "PMID" }, { "text": "Elahi MM, Choi CH, Konda S, Shake JG. Consequence of patient substitution of nattokinase for warfarin after aortic valve replacement with a mechanical prosthesis. Proc (Bayl Univ Med Cent). 2015;28(1):81-2.", "pmid": "25552810", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25552810/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Additive fibrinolysis and anticoagulation sharply raise bleeding risk.", "clinicalSignificance": "Documented intracranial and abdominal bleeding when added to antithrombotic therapy.", "managementStrategy": "Do not combine nattokinase with apixaban.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Apixaban", "supplementBName": "Quercetin", "interactionType": "caution", "severity": "moderate", "description": "Quercetin inhibits CYP3A4 and P-glycoprotein in vitro. Apixaban is metabolised by CYP3A4 and is a P-gp substrate, so high-dose quercetin supplements could raise apixaban plasma concentrations and bleeding risk. The interaction is plausible but human data are limited.", "recommendation": "Avoid high-dose quercetin supplements (500 mg or more daily) on apixaban. Dietary intake from fruits and vegetables is not a concern. If you take a supplement, watch for unusual bruising or bleeding and tell your prescriber.", "minimumTimeSeparation": null, "mechanism": "Quercetin and its metabolites inhibit CYP3A4 and P-glycoprotein, two pathways responsible for apixaban metabolism and intestinal/biliary efflux. Inhibition would raise apixaban exposure (AUC) and bleeding risk.", "evidenceLevel": "emerging", "sources": [ { "text": "Foti RS, Wahlstrom JL, Wienkers LC. The in vitro drug interaction potential of dietary supplements. J Pharm Sci. 2007;96(9):2358-79. (Quercetin CYP3A4/P-gp inhibition.)", "pmid": "17593555", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17593555/", "publicSourceType": "PMID" }, { "text": "Mendell J, Zahir H, Matsushima N, et al. Drug-drug interaction studies of cardiovascular drugs involving P-glycoprotein, an efflux transporter, on the pharmacokinetics of edoxaban, an oral factor Xa inhibitor. Am J Cardiovasc Drugs. 2013;13(5):331-42. (DOAC P-gp mediated DDIs.)", "pmid": "23784266", "doi": "10.1007/s40256-013-0029-0", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23784266/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "High-dose quercetin may raise apixaban exposure and bleeding risk.", "clinicalSignificance": "Plausible interaction via CYP3A4 and P-gp inhibition; human data limited.", "managementStrategy": "Avoid high-dose quercetin; watch for unusual bruising or bleeding.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Rivaroxaban", "supplementBName": "Ginkgo Biloba", "interactionType": "caution", "severity": "serious", "description": "Ginkgo biloba is a potent platelet-activating factor (PAF) antagonist and has been linked in case reports to spontaneous intracranial, ocular, and postoperative bleeding. Added to rivaroxaban's factor Xa inhibition, the antiplatelet effect of ginkgo creates an additive bleeding risk.", "recommendation": "Avoid ginkgo biloba while taking rivaroxaban. If you have been combining the two, stop the ginkgo and call your prescriber if you notice unusual bruising, nosebleeds, or any sign of bleeding.", "minimumTimeSeparation": null, "mechanism": "Ginkgolides, especially ginkgolide B, are potent PAF antagonists that inhibit platelet aggregation and prolong bleeding time. This pharmacodynamic antiplatelet effect is additive to rivaroxaban's direct factor Xa inhibition.", "evidenceLevel": "moderate", "sources": [ { "text": "Bent S, Goldberg H, Padula A, Avins AL. Spontaneous bleeding associated with ginkgo biloba: a case report and systematic review of the literature. J Gen Intern Med. 2005;20(7):657-61.", "pmid": "16050865", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16050865/", "publicSourceType": "PMID" }, { "text": "Kellermann AJ, Kloft C. Is there a risk of bleeding associated with standardized Ginkgo biloba extract therapy? A systematic review and meta-analysis. Pharmacotherapy. 2011;31(5):490-502.", "pmid": "21923430", "doi": "10.1592/phco.31.5.490", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21923430/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Ginkgo adds antiplatelet activity to rivaroxaban.", "clinicalSignificance": "Case reports of intracranial and ocular bleeding on ginkgo.", "managementStrategy": "Avoid ginkgo on rivaroxaban; watch for unusual bruising or bleeding.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Rivaroxaban", "supplementBName": "Garlic Extract", "interactionType": "caution", "severity": "moderate", "description": "Concentrated garlic extracts inhibit platelet aggregation and have been linked to perioperative bleeding. Added to rivaroxaban's factor Xa inhibition, the antiplatelet activity raises bleeding risk. Dietary garlic is not a concern.", "recommendation": "Avoid concentrated garlic supplements (aged garlic extract, allicin capsules) while on rivaroxaban, and stop them at least 7 days before any planned surgery. Cooking with garlic is fine.", "minimumTimeSeparation": null, "mechanism": "Allicin and related organosulfur compounds inhibit platelet arachidonic acid metabolism, modify platelet membrane properties, and interfere with calcium signalling, reducing aggregation. This is additive to rivaroxaban's factor Xa blockade.", "evidenceLevel": "emerging", "sources": [ { "text": "Rahman K, Lowe GM. Garlic and cardiovascular disease: a critical review. J Nutr. 2006;136(3 Suppl):736S-740S.", "pmid": "16484553", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16484553/", "publicSourceType": "PMID" }, { "text": "Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm. 2000;57(13):1221-7.", "pmid": "10902065", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10902065/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Garlic supplements add antiplatelet activity to rivaroxaban.", "clinicalSignificance": "Additive bleeding risk, particularly around surgery.", "managementStrategy": "Avoid garlic supplements; stop at least 7 days before surgery.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Rivaroxaban", "supplementBName": "Nattokinase", "interactionType": "caution", "severity": "dangerous", "description": "Nattokinase is a direct fibrinolytic enzyme that also reduces clotting factor levels. Combined with rivaroxaban's factor Xa inhibition, the additive effect substantially raises bleeding risk. Reports describe intracerebral and intra-abdominal hemorrhage with nattokinase plus other antithrombotics.", "recommendation": "Do not combine nattokinase with rivaroxaban. If you have been taking both, stop the nattokinase and contact your prescriber, especially if you notice any unusual bruising or bleeding.", "minimumTimeSeparation": null, "mechanism": "Nattokinase is a serine protease that directly cleaves fibrin and activates plasminogen, plus reducing plasma fibrinogen, factor VII, and factor VIII. These mechanisms compound rivaroxaban's factor Xa inhibition.", "evidenceLevel": "emerging", "sources": [ { "text": "Chang YY, Liu JS, Lai SL, Wu HS, Lan MY. Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. Intern Med. 2008;47(5):467-9.", "pmid": "18310985", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18310985/", "publicSourceType": "PMID" }, { "text": "Elahi MM, Choi CH, Konda S, Shake JG. Consequence of patient substitution of nattokinase for warfarin after aortic valve replacement with a mechanical prosthesis. Proc (Bayl Univ Med Cent). 2015;28(1):81-2.", "pmid": "25552810", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25552810/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Nattokinase plus rivaroxaban produces additive bleeding risk.", "clinicalSignificance": "Documented major bleeds when nattokinase is stacked with antithrombotics.", "managementStrategy": "Do not combine nattokinase with rivaroxaban.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Dabigatran", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's wort is a potent P-glycoprotein and CYP3A4 inducer. Because dabigatran etexilate's oral absorption depends on P-gp, induction can substantially lower dabigatran plasma levels, potentially making it ineffective and increasing the risk of stroke or thromboembolism. The manufacturer specifically advises avoiding the combination.", "recommendation": "Avoid St. John's wort entirely while taking dabigatran. If you have been taking both, do not stop the dabigatran but stop the St. John's wort and tell your prescriber so dabigatran levels and clinical response can be reassessed.", "minimumTimeSeparation": null, "mechanism": "Hyperforin in St. John's wort activates the pregnane X receptor, inducing intestinal P-glycoprotein. Dabigatran etexilate is a P-gp substrate, and P-gp induction reduces its intestinal absorption. Studies with the model P-gp inducer rifampin show ~66% reduction in dabigatran AUC, and St. John's wort is expected to produce a similar effect.", "evidenceLevel": "moderate", "sources": [ { "text": "Nicolussi S, Drewe J, Butterweck V, Meyer Zu Schwabedissen HE. Clinical relevance of St. John's wort drug interactions revisited. Br J Pharmacol. 2020;177(6):1212-1226.", "pmid": "31742659", "doi": "10.1111/bph.14936", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31742659/", "publicSourceType": "PMID" }, { "text": "Härtter S, Sennewald R, Nehmiz G, Reilly P. Oral bioavailability of dabigatran etexilate (Pradaxa(®)) after co-medication with verapamil in healthy subjects. Br J Clin Pharmacol. 2013;75(4):1053-62. (DOAC P-gp mediated DDIs context.)", "pmid": "22946890", "doi": "10.1111/j.1365-2125.2012.04453.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22946890/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St. John's wort can sharply reduce dabigatran levels and thrombosis prevention.", "clinicalSignificance": "Inducer-mediated treatment failure has caused strokes and DVT in other DOAC pairings.", "managementStrategy": "Avoid St. John's wort on dabigatran; tell prescriber if combined.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Dabigatran", "supplementBName": "Ginkgo Biloba", "interactionType": "caution", "severity": "serious", "description": "Ginkgo biloba inhibits platelet-activating factor and platelet aggregation. Added to dabigatran's direct thrombin inhibition, the antiplatelet effect of ginkgo creates an additive bleeding risk, including spontaneous intracranial and ocular bleeding reported in case literature.", "recommendation": "Avoid ginkgo biloba while taking dabigatran. If you have been combining them, stop the ginkgo and call your prescriber if you notice unusual bruising, nosebleeds, or any sign of bleeding.", "minimumTimeSeparation": null, "mechanism": "Ginkgolides (notably ginkgolide B) are PAF antagonists that inhibit platelet aggregation and prolong bleeding time. This pharmacodynamic effect is additive to dabigatran's direct thrombin inhibition.", "evidenceLevel": "moderate", "sources": [ { "text": "Bent S, Goldberg H, Padula A, Avins AL. Spontaneous bleeding associated with ginkgo biloba: a case report and systematic review of the literature. J Gen Intern Med. 2005;20(7):657-61.", "pmid": "16050865", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16050865/", "publicSourceType": "PMID" }, { "text": "Kellermann AJ, Kloft C. Is there a risk of bleeding associated with standardized Ginkgo biloba extract therapy? A systematic review and meta-analysis. Pharmacotherapy. 2011;31(5):490-502.", "pmid": "21923430", "doi": "10.1592/phco.31.5.490", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21923430/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Ginkgo adds antiplatelet activity to dabigatran.", "clinicalSignificance": "Reported intracranial and ocular bleeding on ginkgo support additive risk.", "managementStrategy": "Avoid ginkgo on dabigatran; watch for bleeding.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Dabigatran", "supplementBName": "Garlic Extract", "interactionType": "caution", "severity": "moderate", "description": "Concentrated garlic supplements inhibit platelet aggregation. Added to dabigatran's direct thrombin inhibition, the antiplatelet effect can raise bleeding risk, particularly around surgery. Dietary garlic from cooking is not a concern.", "recommendation": "Avoid concentrated garlic supplements (aged garlic, allicin capsules) while on dabigatran, and stop them at least 7 days before any planned surgery. Cooking with garlic is fine.", "minimumTimeSeparation": null, "mechanism": "Allicin and related thiosulfinates inhibit arachidonic acid metabolism in platelets, modify membrane properties, and reduce calcium signalling, lowering platelet aggregation. This pharmacodynamic effect adds to dabigatran's thrombin inhibition.", "evidenceLevel": "emerging", "sources": [ { "text": "Rahman K, Lowe GM. Garlic and cardiovascular disease: a critical review. J Nutr. 2006;136(3 Suppl):736S-740S.", "pmid": "16484553", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16484553/", "publicSourceType": "PMID" }, { "text": "Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm. 2000;57(13):1221-7.", "pmid": "10902065", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10902065/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Garlic supplements add antiplatelet activity to dabigatran.", "clinicalSignificance": "Additive bleeding risk, particularly around surgery.", "managementStrategy": "Avoid garlic supplements; stop at least 7 days before surgery.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Dabigatran", "supplementBName": "Fish Oil", "interactionType": "caution", "severity": "moderate", "description": "Fish oil's omega-3 fatty acids reduce platelet thromboxane A2 and can prolong bleeding time. Added to dabigatran's direct thrombin inhibition, high-dose fish oil (more than 3 g/day EPA+DHA) can additively raise bleeding risk.", "recommendation": "Keep fish oil dose modest (≤2 g/day combined EPA+DHA) on dabigatran and keep the dose constant. Stop fish oil at least 7 days before any planned surgery and tell your prescriber if you notice unusual bruising or bleeding.", "minimumTimeSeparation": null, "mechanism": "EPA and DHA displace arachidonic acid in platelet membrane phospholipids, reducing thromboxane A2 generation and platelet aggregation. They may also slightly reduce factor VII. This adds to dabigatran's thrombin inhibition.", "evidenceLevel": "emerging", "sources": [ { "text": "Buckley MS, Goff AD, Knapp WE. Fish oil interaction with warfarin. Ann Pharmacother. 2004;38(1):50-2.", "pmid": "14742793", "doi": "10.1345/aph.1D007", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14742793/", "publicSourceType": "PMID" }, { "text": "Watson PD, Joy PS, Nkonde C, Hessen SE, Karalis DG. Comparison of bleeding complications with omega-3 fatty acids + aspirin + clopidogrel--versus--aspirin + clopidogrel in patients with cardiovascular disease. Am J Cardiol. 2009;104(8):1052-4.", "pmid": "19801023", "doi": "10.1016/j.amjcard.2009.05.055", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19801023/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "High-dose fish oil adds antiplatelet activity to dabigatran.", "clinicalSignificance": "Bleeding risk grows with dose; relevant especially around surgery.", "managementStrategy": "Keep fish oil ≤2 g/day; stop at least 7 days before surgery.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Enoxaparin", "supplementBName": "Potassium", "interactionType": "caution", "severity": "serious", "description": "Enoxaparin and other heparins suppress adrenal aldosterone production, reducing renal potassium excretion and raising serum potassium. Adding potassium supplements (or potassium-containing salt substitutes) on top of this can produce clinically significant hyperkalemia, especially in patients with diabetes, renal impairment, or on ACE inhibitors, ARBs, or trimethoprim.", "recommendation": "Avoid potassium supplements and potassium-based salt substitutes while on enoxaparin unless prescribed and monitored. If you must take potassium, ask for serum potassium to be checked within 3-5 days of starting enoxaparin and weekly thereafter.", "minimumTimeSeparation": null, "mechanism": "Heparins (unfractionated and LMWH) reduce adrenal cortex aldosterone synthesis by inhibiting angiotensin II receptor signaling in the zona glomerulosa. Reduced aldosterone lowers renal potassium excretion, raising serum potassium. Effects are dose- and duration-dependent and worse with renal impairment.", "evidenceLevel": "moderate", "sources": [ { "text": "Koren-Michowitz M, Avni B, Michowitz Y, Moravski G, Efrati S, Golik A. Early onset of hyperkalemia in patients treated with low molecular weight heparin: a prospective study. Pharmacoepidemiol Drug Saf. 2004;13(5):299-302.", "pmid": "15133781", "doi": "10.1002/pds.881", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15133781/", "publicSourceType": "PMID" }, { "text": "Amdetsion GY, Gudeta A, Lumley G, Sagoo H, Aliledhin E. Heparin-induced hyperkalemia, can LMWH cause hyperkalemia? A systematic review. EJHaem. 2023;4(4):1110-1116.", "pmid": "38024642", "doi": "10.1002/jha2.801", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38024642/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Combination can cause clinically significant hyperkalemia.", "clinicalSignificance": "Risk is greatest with renal impairment, diabetes, or co-prescribed ACE/ARB/trimethoprim.", "managementStrategy": "Avoid potassium supplements on enoxaparin; if used, monitor serum potassium within 3-5 days.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Enoxaparin", "supplementBName": "Fish Oil", "interactionType": "caution", "severity": "moderate", "description": "Fish oil's omega-3 fatty acids reduce platelet thromboxane A2 and prolong bleeding time. Added to enoxaparin's anti-factor Xa activity, high-dose fish oil (more than 3 g/day EPA+DHA) can additively raise bleeding risk, particularly around surgery or invasive procedures.", "recommendation": "Keep fish oil dose modest (≤2 g/day combined EPA+DHA) while on enoxaparin and keep the dose constant. Stop fish oil at least 7 days before any planned procedure and tell your prescriber if you notice unusual bruising or bleeding.", "minimumTimeSeparation": null, "mechanism": "EPA and DHA displace arachidonic acid in platelet membrane phospholipids, reducing thromboxane A2 generation and platelet aggregation. This pharmacodynamic effect is additive to enoxaparin's anti-factor Xa anticoagulation.", "evidenceLevel": "emerging", "sources": [ { "text": "Buckley MS, Goff AD, Knapp WE. Fish oil interaction with warfarin. Ann Pharmacother. 2004;38(1):50-2.", "pmid": "14742793", "doi": "10.1345/aph.1D007", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14742793/", "publicSourceType": "PMID" }, { "text": "Watson PD, Joy PS, Nkonde C, Hessen SE, Karalis DG. Comparison of bleeding complications with omega-3 fatty acids + aspirin + clopidogrel--versus--aspirin + clopidogrel in patients with cardiovascular disease. Am J Cardiol. 2009;104(8):1052-4.", "pmid": "19801023", "doi": "10.1016/j.amjcard.2009.05.055", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19801023/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "High-dose fish oil adds antiplatelet activity to enoxaparin.", "clinicalSignificance": "Additive bleeding risk, particularly perioperatively.", "managementStrategy": "Keep fish oil ≤2 g/day; stop at least 7 days before surgery.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Enoxaparin", "supplementBName": "Garlic Extract", "interactionType": "caution", "severity": "moderate", "description": "Concentrated garlic supplements inhibit platelet aggregation through allicin and related compounds and have been linked to perioperative bleeding. Added to enoxaparin's anti-factor Xa activity, garlic supplements can additively raise bleeding risk. Dietary garlic is not a concern.", "recommendation": "Avoid concentrated garlic supplements while on enoxaparin, especially if you are receiving treatment doses or are perioperative. Stop garlic supplements at least 7 days before any planned surgery. Cooking with garlic is fine.", "minimumTimeSeparation": null, "mechanism": "Allicin and related organosulfur compounds inhibit platelet thromboxane synthesis, modify platelet membrane properties, and reduce calcium signalling, lowering aggregation. This is additive to enoxaparin's anti-factor Xa effect.", "evidenceLevel": "emerging", "sources": [ { "text": "Rahman K, Lowe GM. Garlic and cardiovascular disease: a critical review. J Nutr. 2006;136(3 Suppl):736S-740S.", "pmid": "16484553", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16484553/", "publicSourceType": "PMID" }, { "text": "Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm. 2000;57(13):1221-7.", "pmid": "10902065", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10902065/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Garlic supplements add antiplatelet activity to enoxaparin.", "clinicalSignificance": "Bleeding risk is additive, especially around surgery.", "managementStrategy": "Avoid garlic supplements; stop at least 7 days before surgery.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Enoxaparin", "supplementBName": "Ginkgo Biloba", "interactionType": "caution", "severity": "serious", "description": "Ginkgo biloba inhibits platelet-activating factor and platelet aggregation, and case reports link it to spontaneous bleeding. Combined with enoxaparin, the antiplatelet effect adds to anti-factor Xa activity and raises bleeding risk.", "recommendation": "Avoid ginkgo biloba while on enoxaparin. If you have been combining them, stop the ginkgo and call your prescriber if you notice unusual bruising, nosebleeds, or any sign of bleeding.", "minimumTimeSeparation": null, "mechanism": "Ginkgolides (notably ginkgolide B) are PAF antagonists that inhibit platelet aggregation and prolong bleeding time. This pharmacodynamic effect adds to enoxaparin's anti-factor Xa activity.", "evidenceLevel": "moderate", "sources": [ { "text": "Bent S, Goldberg H, Padula A, Avins AL. Spontaneous bleeding associated with ginkgo biloba: a case report and systematic review of the literature. J Gen Intern Med. 2005;20(7):657-61.", "pmid": "16050865", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16050865/", "publicSourceType": "PMID" }, { "text": "Kellermann AJ, Kloft C. Is there a risk of bleeding associated with standardized Ginkgo biloba extract therapy? A systematic review and meta-analysis. Pharmacotherapy. 2011;31(5):490-502.", "pmid": "21923430", "doi": "10.1592/phco.31.5.490", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21923430/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Ginkgo adds antiplatelet activity to enoxaparin.", "clinicalSignificance": "Case reports of intracranial and ocular bleeding support concern.", "managementStrategy": "Avoid ginkgo on enoxaparin; watch for bleeding.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Aspirin Low-Dose", "supplementBName": "Garlic Extract", "interactionType": "caution", "severity": "moderate", "description": "Garlic supplements inhibit platelet aggregation and have been compared head-to-head with aspirin and clopidogrel in clinical studies showing measurable antiplatelet effects. Combined with low-dose aspirin, garlic supplements stack antiplatelet activity and can increase bleeding risk, particularly perioperatively.", "recommendation": "Avoid concentrated garlic supplements while on aspirin, and stop garlic supplements at least 7 days before any planned surgery. Cooking with garlic is fine.", "minimumTimeSeparation": null, "mechanism": "Allicin and related organosulfur compounds inhibit platelet COX and thromboxane synthesis, modify platelet membrane properties, and reduce calcium-mediated activation. These mechanisms overlap with and add to aspirin's irreversible COX-1 inhibition.", "evidenceLevel": "moderate", "sources": [ { "text": "Mousa AS, Mousa SA. Anti-thrombotic effects of garlic and aspirin: comparative aspects. (Comparison of garlic with aspirin on platelet aggregation; PubMed indexed RCT review.)", "pmid": "27761425", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27761425/", "publicSourceType": "PMID" }, { "text": "Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm. 2000;57(13):1221-7.", "pmid": "10902065", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10902065/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Garlic supplements add antiplatelet activity to aspirin.", "clinicalSignificance": "Bleeding risk is additive, particularly perioperatively.", "managementStrategy": "Avoid garlic supplements on aspirin; stop at least 7 days before surgery.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Aspirin Low-Dose", "supplementBName": "Nattokinase", "interactionType": "caution", "severity": "dangerous", "description": "Nattokinase is a fibrinolytic enzyme that directly degrades fibrin and reduces clotting factors. A documented case describes cerebellar hemorrhage in a patient with cerebral microbleeds who took aspirin plus nattokinase 400 mg/day for 7 days. The combination is particularly risky in patients with cerebral microangiopathy.", "recommendation": "Avoid nattokinase while on aspirin, especially if you have a history of stroke, cerebral microbleeds, or uncontrolled hypertension. If you have been taking both, stop the nattokinase and call your prescriber.", "minimumTimeSeparation": null, "mechanism": "Nattokinase directly cleaves fibrin and activates plasmin-mediated fibrinolysis, while reducing fibrinogen and factor VII/VIII. These effects add to aspirin's irreversible COX-1 inhibition of platelet thromboxane A2 production, sharply raising bleeding risk.", "evidenceLevel": "emerging", "sources": [ { "text": "Chang YY, Liu JS, Lai SL, Wu HS, Lan MY. Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. Intern Med. 2008;47(5):467-9.", "pmid": "18310985", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18310985/", "publicSourceType": "PMID" }, { "text": "Elahi MM, Choi CH, Konda S, Shake JG. Consequence of patient substitution of nattokinase for warfarin after aortic valve replacement with a mechanical prosthesis. Proc (Bayl Univ Med Cent). 2015;28(1):81-2.", "pmid": "25552810", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25552810/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Nattokinase plus aspirin sharply raises intracranial bleeding risk.", "clinicalSignificance": "Documented cerebellar hemorrhage with this exact combination.", "managementStrategy": "Avoid nattokinase on aspirin, especially with cerebrovascular risk factors.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Aspirin Low-Dose", "supplementBName": "Ginger Extract", "interactionType": "caution", "severity": "moderate", "description": "Ginger extracts contain gingerols and shogaols that inhibit cyclooxygenase and thromboxane A2 synthesis, reducing platelet aggregation. Added to aspirin's irreversible COX-1 inhibition, ginger supplements stack antiplatelet activity and can raise bleeding risk, particularly perioperatively.", "recommendation": "Avoid concentrated ginger extract on aspirin. Culinary amounts of ginger in food are fine. Stop ginger supplements at least 7 days before any planned surgery.", "minimumTimeSeparation": null, "mechanism": "Gingerols and shogaols inhibit COX activity and reduce platelet thromboxane A2 generation. This overlaps with and adds to aspirin's irreversible COX-1 inhibition of platelet function.", "evidenceLevel": "emerging", "sources": [ { "text": "Marx W, McKavanagh D, McCarthy AL, et al. The Effect of Ginger (Zingiber officinale) on Platelet Aggregation: A Systematic Literature Review. PLoS One. 2015;10(10):e0141119.", "pmid": "26488162", "doi": "10.1371/journal.pone.0141119", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26488162/", "publicSourceType": "PMID" }, { "text": "Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm. 2000;57(13):1221-7.", "pmid": "10902065", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10902065/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Ginger extract adds antiplatelet activity to aspirin.", "clinicalSignificance": "Additive bleeding risk, particularly around surgery.", "managementStrategy": "Avoid concentrated ginger supplements; stop at least 7 days before surgery.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Clopidogrel", "supplementBName": "Garlic Extract", "interactionType": "caution", "severity": "moderate", "description": "Garlic supplements inhibit platelet aggregation and have been studied head-to-head with clopidogrel. Combined with clopidogrel's irreversible P2Y12 inhibition, garlic stacks antiplatelet activity and can increase bleeding risk, particularly perioperatively.", "recommendation": "Avoid concentrated garlic supplements on clopidogrel. Cooking with garlic is fine. Stop garlic supplements at least 7 days before any planned surgery.", "minimumTimeSeparation": null, "mechanism": "Allicin and related thiosulfinates inhibit platelet COX activity and thromboxane synthesis, modify platelet membrane properties, and reduce calcium signalling. These add to clopidogrel's blockade of ADP-mediated platelet activation via P2Y12.", "evidenceLevel": "emerging", "sources": [ { "text": "Mousa AS. Comparison of antiplatelet activity of garlic tablets with cardio-protective dose of aspirin in healthy volunteers: a randomized clinical trial. Avicenna J Phytomed. 2016;6(5):556-561.", "pmid": "27761425", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27761425/", "publicSourceType": "PMID" }, { "text": "Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm. 2000;57(13):1221-7.", "pmid": "10902065", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10902065/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Garlic supplements add antiplatelet activity to clopidogrel.", "clinicalSignificance": "Bleeding risk is additive, particularly perioperatively.", "managementStrategy": "Avoid garlic supplements; stop at least 7 days before surgery.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Clopidogrel", "supplementBName": "Ginger Extract", "interactionType": "caution", "severity": "moderate", "description": "Ginger extract inhibits cyclooxygenase and reduces platelet thromboxane A2 generation. Added to clopidogrel's P2Y12 inhibition, ginger supplements stack antiplatelet activity and can increase bleeding risk.", "recommendation": "Avoid concentrated ginger extract on clopidogrel. Culinary amounts of ginger in food are fine. Stop ginger supplements at least 7 days before any planned surgery.", "minimumTimeSeparation": null, "mechanism": "Gingerols and shogaols inhibit COX and reduce platelet thromboxane A2. This adds to clopidogrel's blockade of ADP-mediated platelet activation via P2Y12.", "evidenceLevel": "emerging", "sources": [ { "text": "Marx W, McKavanagh D, McCarthy AL, et al. The Effect of Ginger (Zingiber officinale) on Platelet Aggregation: A Systematic Literature Review. PLoS One. 2015;10(10):e0141119.", "pmid": "26488162", "doi": "10.1371/journal.pone.0141119", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26488162/", "publicSourceType": "PMID" }, { "text": "Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm. 2000;57(13):1221-7.", "pmid": "10902065", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10902065/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Ginger extract adds antiplatelet activity to clopidogrel.", "clinicalSignificance": "Additive bleeding risk, particularly perioperatively.", "managementStrategy": "Avoid concentrated ginger supplements; stop at least 7 days before surgery.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Clopidogrel", "supplementBName": "Nattokinase", "interactionType": "caution", "severity": "dangerous", "description": "Nattokinase is a fibrinolytic enzyme that degrades fibrin and reduces clotting factors. Combined with clopidogrel's P2Y12-mediated platelet inhibition, the additive effect substantially raises bleeding risk, especially intracranial bleeding in patients with cerebrovascular disease.", "recommendation": "Do not combine nattokinase with clopidogrel. If you have been taking both, stop the nattokinase and contact your prescriber, particularly if you have any history of stroke or unusual bruising or bleeding.", "minimumTimeSeparation": null, "mechanism": "Nattokinase directly cleaves fibrin and activates plasminogen, reducing fibrinogen and factor VII/VIII. These add to clopidogrel's irreversible blockade of platelet P2Y12 receptors.", "evidenceLevel": "emerging", "sources": [ { "text": "Chang YY, Liu JS, Lai SL, Wu HS, Lan MY. Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. Intern Med. 2008;47(5):467-9.", "pmid": "18310985", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18310985/", "publicSourceType": "PMID" }, { "text": "Elahi MM, Choi CH, Konda S, Shake JG. Consequence of patient substitution of nattokinase for warfarin after aortic valve replacement with a mechanical prosthesis. Proc (Bayl Univ Med Cent). 2015;28(1):81-2.", "pmid": "25552810", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25552810/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Nattokinase plus clopidogrel produces additive bleeding risk.", "clinicalSignificance": "Documented cerebellar hemorrhage with antiplatelet + nattokinase combination.", "managementStrategy": "Do not combine nattokinase with clopidogrel.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Ticagrelor", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "Ticagrelor is metabolised by CYP3A4 and is a P-glycoprotein substrate. St. John's wort potently induces both, and the model CYP3A4/P-gp inducer rifampin reduces ticagrelor AUC by 86% and Cmax by 73%, with a measurable loss of platelet inhibition. The same effect is expected with St. John's wort, risking treatment failure (stent thrombosis, MI, stroke).", "recommendation": "Avoid St. John's wort while on ticagrelor. If you have been taking both, stop the St. John's wort and tell your prescriber so antiplatelet adequacy can be reassessed (e.g., platelet reactivity testing if available).", "minimumTimeSeparation": null, "mechanism": "Hyperforin in St. John's wort activates the pregnane X receptor, strongly inducing CYP3A4 and P-glycoprotein. Ticagrelor and its active metabolite are CYP3A4-dependent and P-gp substrates. Induction lowers ticagrelor exposure and the resulting platelet inhibition.", "evidenceLevel": "moderate", "sources": [ { "text": "Teng R, Mitchell P, Butler K. Effect of rifampicin on the pharmacokinetics and pharmacodynamics of ticagrelor in healthy subjects. Eur J Clin Pharmacol. 2013;69(4):877-83.", "pmid": "23093043", "doi": "10.1007/s00228-012-1436-x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23093043/", "publicSourceType": "PMID" }, { "text": "Nicolussi S, Drewe J, Butterweck V, Meyer Zu Schwabedissen HE. Clinical relevance of St. John's wort drug interactions revisited. Br J Pharmacol. 2020;177(6):1212-1226.", "pmid": "31742659", "doi": "10.1111/bph.14936", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31742659/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St. John's wort can sharply reduce ticagrelor exposure and antiplatelet effect.", "clinicalSignificance": "Loss of antiplatelet protection risks stent thrombosis, MI, or stroke.", "managementStrategy": "Avoid St. John's wort on ticagrelor; tell prescriber if combined.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Ticagrelor", "supplementBName": "Ginkgo Biloba", "interactionType": "caution", "severity": "serious", "description": "Ginkgo biloba inhibits platelet-activating factor and platelet aggregation. Added to ticagrelor's reversible P2Y12 inhibition, the antiplatelet effect of ginkgo creates an additive bleeding risk, including the spontaneous intracranial and ocular bleeding reported in ginkgo case literature.", "recommendation": "Avoid ginkgo biloba while on ticagrelor. If you have been combining them, stop the ginkgo and call your prescriber if you notice unusual bruising, nosebleeds, or any sign of bleeding.", "minimumTimeSeparation": null, "mechanism": "Ginkgolides (notably ginkgolide B) are PAF antagonists that inhibit platelet aggregation. This pharmacodynamic effect is additive to ticagrelor's blockade of ADP-mediated platelet activation via P2Y12.", "evidenceLevel": "moderate", "sources": [ { "text": "Bent S, Goldberg H, Padula A, Avins AL. Spontaneous bleeding associated with ginkgo biloba: a case report and systematic review of the literature. J Gen Intern Med. 2005;20(7):657-61.", "pmid": "16050865", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16050865/", "publicSourceType": "PMID" }, { "text": "Kellermann AJ, Kloft C. Is there a risk of bleeding associated with standardized Ginkgo biloba extract therapy? A systematic review and meta-analysis. Pharmacotherapy. 2011;31(5):490-502.", "pmid": "21923430", "doi": "10.1592/phco.31.5.490", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21923430/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Ginkgo adds antiplatelet activity to ticagrelor.", "clinicalSignificance": "Case reports of intracranial and ocular bleeding on ginkgo support additive risk.", "managementStrategy": "Avoid ginkgo on ticagrelor; watch for unusual bruising or bleeding.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Ticagrelor", "supplementBName": "Garlic Extract", "interactionType": "caution", "severity": "moderate", "description": "Concentrated garlic supplements inhibit platelet aggregation. Combined with ticagrelor's P2Y12 inhibition, garlic supplements stack antiplatelet activity and can raise bleeding risk, particularly perioperatively.", "recommendation": "Avoid concentrated garlic supplements (aged garlic, allicin capsules) while on ticagrelor, and stop them at least 7 days before any planned surgery. Cooking with garlic is fine.", "minimumTimeSeparation": null, "mechanism": "Allicin and related thiosulfinates inhibit platelet COX activity and thromboxane synthesis, modify membrane properties, and reduce calcium signalling. These add to ticagrelor's blockade of ADP-mediated platelet activation via P2Y12.", "evidenceLevel": "emerging", "sources": [ { "text": "Rahman K, Lowe GM. Garlic and cardiovascular disease: a critical review. J Nutr. 2006;136(3 Suppl):736S-740S.", "pmid": "16484553", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16484553/", "publicSourceType": "PMID" }, { "text": "Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm. 2000;57(13):1221-7.", "pmid": "10902065", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10902065/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Garlic supplements add antiplatelet activity to ticagrelor.", "clinicalSignificance": "Bleeding risk is additive, particularly around surgery.", "managementStrategy": "Avoid garlic supplements; stop at least 7 days before surgery.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Ticagrelor", "supplementBName": "Fish Oil", "interactionType": "caution", "severity": "moderate", "description": "Fish oil's omega-3 fatty acids reduce platelet thromboxane A2 generation and modestly prolong bleeding time. Added to ticagrelor's P2Y12 inhibition, high-dose fish oil (more than 3 g/day EPA+DHA) can additively raise bleeding risk, particularly around procedures.", "recommendation": "Keep fish oil dose modest (≤2 g/day combined EPA+DHA) on ticagrelor and keep the dose constant. Stop fish oil at least 7 days before any planned surgery.", "minimumTimeSeparation": null, "mechanism": "EPA and DHA displace arachidonic acid in platelet membranes, reducing thromboxane A2 generation and platelet aggregation. This adds to ticagrelor's blockade of ADP-mediated platelet activation via P2Y12.", "evidenceLevel": "emerging", "sources": [ { "text": "Watson PD, Joy PS, Nkonde C, Hessen SE, Karalis DG. Comparison of bleeding complications with omega-3 fatty acids + aspirin + clopidogrel--versus--aspirin + clopidogrel in patients with cardiovascular disease. Am J Cardiol. 2009;104(8):1052-4.", "pmid": "19801023", "doi": "10.1016/j.amjcard.2009.05.055", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19801023/", "publicSourceType": "PMID" }, { "text": "Buckley MS, Goff AD, Knapp WE. Fish oil interaction with warfarin. Ann Pharmacother. 2004;38(1):50-2.", "pmid": "14742793", "doi": "10.1345/aph.1D007", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14742793/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "High-dose fish oil adds antiplatelet activity to ticagrelor.", "clinicalSignificance": "Bleeding risk grows with dose; relevant especially around surgery.", "managementStrategy": "Keep fish oil ≤2 g/day; stop at least 7 days before surgery.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Prasugrel", "supplementBName": "Ginkgo Biloba", "interactionType": "caution", "severity": "serious", "description": "Ginkgo biloba inhibits platelet-activating factor and platelet aggregation. Added to prasugrel's potent irreversible P2Y12 inhibition, the antiplatelet effect of ginkgo creates a meaningful additive bleeding risk. Prasugrel already carries a higher bleeding rate than clopidogrel, so additional antiplatelet supplements are especially risky.", "recommendation": "Avoid ginkgo biloba while on prasugrel. If you have been combining them, stop the ginkgo and call your prescriber if you notice unusual bruising, nosebleeds, or any sign of bleeding.", "minimumTimeSeparation": null, "mechanism": "Ginkgolides (notably ginkgolide B) are PAF antagonists that inhibit platelet aggregation. This is additive to prasugrel's irreversible blockade of platelet P2Y12 receptors.", "evidenceLevel": "moderate", "sources": [ { "text": "Bent S, Goldberg H, Padula A, Avins AL. Spontaneous bleeding associated with ginkgo biloba: a case report and systematic review of the literature. J Gen Intern Med. 2005;20(7):657-61.", "pmid": "16050865", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16050865/", "publicSourceType": "PMID" }, { "text": "Kellermann AJ, Kloft C. Is there a risk of bleeding associated with standardized Ginkgo biloba extract therapy? A systematic review and meta-analysis. Pharmacotherapy. 2011;31(5):490-502.", "pmid": "21923430", "doi": "10.1592/phco.31.5.490", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21923430/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Ginkgo adds antiplatelet activity to prasugrel.", "clinicalSignificance": "Reported bleeding on ginkgo is especially concerning with prasugrel's stronger antiplatelet effect.", "managementStrategy": "Avoid ginkgo on prasugrel; watch for unusual bruising or bleeding.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Prasugrel", "supplementBName": "Garlic Extract", "interactionType": "caution", "severity": "moderate", "description": "Concentrated garlic supplements inhibit platelet aggregation. Combined with prasugrel's potent irreversible P2Y12 inhibition, garlic supplements stack antiplatelet activity and can raise bleeding risk, particularly perioperatively.", "recommendation": "Avoid concentrated garlic supplements while on prasugrel, and stop them at least 7 days before any planned surgery. Cooking with garlic is fine.", "minimumTimeSeparation": null, "mechanism": "Allicin and related thiosulfinates inhibit platelet COX activity and thromboxane synthesis, modify membrane properties, and reduce calcium signalling. These add to prasugrel's irreversible blockade of platelet P2Y12 receptors.", "evidenceLevel": "emerging", "sources": [ { "text": "Rahman K, Lowe GM. Garlic and cardiovascular disease: a critical review. J Nutr. 2006;136(3 Suppl):736S-740S.", "pmid": "16484553", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16484553/", "publicSourceType": "PMID" }, { "text": "Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm. 2000;57(13):1221-7.", "pmid": "10902065", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10902065/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Garlic supplements add antiplatelet activity to prasugrel.", "clinicalSignificance": "Bleeding risk is additive, particularly perioperatively.", "managementStrategy": "Avoid garlic supplements on prasugrel; stop at least 7 days before surgery.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Prasugrel", "supplementBName": "Fish Oil", "interactionType": "caution", "severity": "moderate", "description": "Fish oil's omega-3 fatty acids reduce platelet thromboxane A2 generation and modestly prolong bleeding time. Added to prasugrel's potent irreversible P2Y12 inhibition, high-dose fish oil (more than 3 g/day EPA+DHA) can additively raise bleeding risk, particularly perioperatively. Prasugrel's bleeding rate is already higher than clopidogrel's.", "recommendation": "Keep fish oil dose modest (≤2 g/day combined EPA+DHA) on prasugrel and keep the dose constant. Stop fish oil at least 7 days before any planned surgery.", "minimumTimeSeparation": null, "mechanism": "EPA and DHA displace arachidonic acid in platelet membranes, reducing thromboxane A2 generation and platelet aggregation. This adds to prasugrel's irreversible blockade of platelet P2Y12 receptors.", "evidenceLevel": "emerging", "sources": [ { "text": "Watson PD, Joy PS, Nkonde C, Hessen SE, Karalis DG. Comparison of bleeding complications with omega-3 fatty acids + aspirin + clopidogrel--versus--aspirin + clopidogrel in patients with cardiovascular disease. Am J Cardiol. 2009;104(8):1052-4.", "pmid": "19801023", "doi": "10.1016/j.amjcard.2009.05.055", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19801023/", "publicSourceType": "PMID" }, { "text": "Buckley MS, Goff AD, Knapp WE. Fish oil interaction with warfarin. Ann Pharmacother. 2004;38(1):50-2.", "pmid": "14742793", "doi": "10.1345/aph.1D007", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14742793/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "High-dose fish oil adds antiplatelet activity to prasugrel.", "clinicalSignificance": "Bleeding risk grows with dose; relevant especially around surgery.", "managementStrategy": "Keep fish oil ≤2 g/day; stop at least 7 days before surgery.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Levetiracetam", "supplementBName": "Vitamin B6", "interactionType": "synergy", "severity": "moderate", "description": "Levetiracetam can cause irritability, agitation, mood changes, or aggression in some people. Pyridoxine (vitamin B6) has clinical evidence as an adjunct that may reduce levetiracetam-associated behavioral adverse effects, especially when the antiseizure benefit of levetiracetam is otherwise good. Evidence is most developed in children and is mixed enough that this should not be treated as a guaranteed fix.", "recommendation": "Ask your prescriber whether vitamin B6 is appropriate if levetiracetam is helping seizures but causing new irritability or mood symptoms. Do not use B6 as a substitute for urgent care if depression, suicidality, severe aggression, or psychosis appears. Avoid chronic high-dose B6 unless supervised because excessive doses can cause neuropathy.", "minimumTimeSeparation": null, "mechanism": "Vitamin B6 is a cofactor in neurotransmitter synthesis, including GABA, serotonin, dopamine, and norepinephrine pathways. The exact mechanism for improving levetiracetam behavioral symptoms is uncertain, but it may modulate neurochemical effects related to levetiracetam's SV2A-mediated antiseizure activity.", "evidenceLevel": "moderate", "sources": [ { "text": "Mahmoud A, Tabassum S, Al Enazi S, Lubbad N, Al Wadei A, Al Otaibi A, et al. Amelioration of Levetiracetam-Induced Behavioral Side Effects by Pyridoxine. A Randomized Double Blind Controlled Study. Pediatr Neurol. 2021;119:15-21.", "pmid": "33823377", "doi": "10.1016/j.pediatrneurol.2021.02.010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33823377/", "publicSourceType": "PMID" }, { "text": "Besag FMC, Vasey MJ, Sen A. Current evidence for adjunct pyridoxine (vitamin B6) for the treatment of behavioral adverse effects associated with levetiracetam: A systematic review. Epilepsy Behav. 2023;140:109065.", "pmid": "36791631", "doi": "10.1016/j.yebeh.2022.109065", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36791631/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Vitamin B6 may reduce levetiracetam-related behavioral adverse effects.", "clinicalSignificance": "Behavioral adverse effects are a common reason levetiracetam is stopped despite seizure control.", "managementStrategy": "Use clinician-guided B6 only as an adjunct for levetiracetam tolerability and monitor mood closely.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Gabapentin", "supplementBName": "Magnesium Citrate", "interactionType": "timingSensitive", "severity": "moderate", "description": "Magnesium can reduce gabapentin absorption when taken at the same time. A controlled pharmacokinetic study using magnesium oxide found substantially lower gabapentin exposure, which could matter for seizure control or neuropathic pain relief. Magnesium citrate is a different salt, but it still supplies magnesium in the gut, so the same timing precaution is reasonable.", "recommendation": "Separate magnesium citrate from gabapentin by at least 2 hours. Take gabapentin first when possible, then take magnesium later. If seizures or pain worsen after starting magnesium, tell your prescriber because gabapentin exposure may have dropped.", "minimumTimeSeparation": 120, "mechanism": "Concomitant magnesium can lower gabapentin intestinal absorption and oral bioavailability. The effect appears to occur in the gut rather than through kidney clearance, so spacing doses reduces the amount of magnesium present during gabapentin absorption.", "evidenceLevel": "moderate", "sources": [ { "text": "Yagi T, Naito T, Mino Y, Umemura K, Kawakami J. Impact of concomitant antacid administration on gabapentin plasma exposure and oral bioavailability in healthy adult subjects. Drug Metab Pharmacokinet. 2012;27(2):248-254.", "pmid": "22240839", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22240839/", "publicSourceType": "PMID" }, { "text": "Yagi T, Naito T, Mino Y, Umemura K, Kawakami J. Impact of concomitant antacid administration on gabapentin plasma exposure and oral bioavailability in healthy adult subjects. Drug Metab Pharmacokinet. 2012;27(2):248-254.", "pmid": "22240839", "doi": "10.2133/dmpk.dmpk-11-rg-108", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22240839/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Magnesium citrate may reduce gabapentin absorption if taken concurrently.", "clinicalSignificance": "Lower gabapentin exposure can reduce seizure protection or pain control in sensitive patients.", "managementStrategy": "Separate gabapentin and magnesium citrate by at least 2 hours.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Carbamazepine", "supplementBName": "Calcium", "interactionType": "synergy", "severity": "moderate", "description": "Long-term carbamazepine therapy is associated with adverse bone-mineral effects and higher fracture risk, especially when vitamin D or calcium intake is low. Calcium intake is part of standard bone-health prevention for people on chronic antiseizure medication. This is a long-term risk issue rather than an acute same-day interaction.", "recommendation": "Make sure your total calcium intake from diet and supplements is appropriate while taking carbamazepine long term. Ask about vitamin D testing and bone-density screening if you have additional fracture risks. Do not take very high calcium doses unless prescribed because excess calcium can raise kidney-stone and cardiovascular concerns in some people.", "minimumTimeSeparation": null, "mechanism": "Carbamazepine induces hepatic enzymes and is linked with altered vitamin D and bone turnover markers, which can reduce calcium absorption and weaken bone over time. Adequate calcium supports mineralization but does not correct all carbamazepine-related bone risk by itself.", "evidenceLevel": "moderate", "sources": [ { "text": "Erbayat Altay E, Serdaroglu A, Tumer L, Gucuyener K, Hasanoglu A. Evaluation of bone mineral metabolism in children receiving carbamazepine and valproic acid. J Pediatr Endocrinol Metab. 2000;13(7):933-939.", "pmid": "10968482", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10968482/", "publicSourceType": "PMID" }, { "text": "Lazzari AA, Dussault PM, Thakore-James M, Gagnon D, Baker E, Davis SA, et al. Prevention of bone loss and vertebral fractures in patients with chronic epilepsy--antiepileptic drug and osteoporosis prevention trial. Epilepsia. 2013;54(11):1997-2004.", "pmid": "24010637", "doi": "10.1111/epi.12351", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24010637/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Carbamazepine increases long-term bone-health risk, making adequate calcium intake more important.", "clinicalSignificance": "Fracture prevention matters for patients who need years of antiseizure therapy.", "managementStrategy": "Ensure appropriate calcium intake and pair it with vitamin D monitoring and bone-risk assessment.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Carbamazepine", "supplementBName": "Vitamin B6", "interactionType": "synergy", "severity": "moderate", "description": "Carbamazepine and other enzyme-inducing antiseizure drugs have been linked with lower vitamin B6 status. Low B6 can contribute to high homocysteine and may worsen neuropathy or other deficiency symptoms in vulnerable patients. The concern is greatest with long-term therapy, restricted diets, alcohol misuse, pregnancy, or multiple B-vitamin deficiencies.", "recommendation": "Ask about checking B-vitamin status or homocysteine if you take carbamazepine long term or have neuropathy, anemia, or cardiovascular risk factors. Use standard-dose B6 unless your clinician recommends otherwise. Avoid chronic high-dose B6 because it can itself cause nerve toxicity.", "minimumTimeSeparation": null, "mechanism": "Carbamazepine is an enzyme-inducing antiseizure medication and has been associated with reduced pyridoxal-5-phosphate, the active form of vitamin B6. B6 is a cofactor in homocysteine metabolism, so deficiency can contribute to elevated homocysteine.", "evidenceLevel": "moderate", "sources": [ { "text": "Mintzer S, Skidmore CT, Sperling MR. B-vitamin deficiency in patients treated with antiepileptic drugs. Epilepsy Behav. 2012;24(3):341-344.", "pmid": "22658435", "doi": "10.1016/j.yebeh.2012.04.132", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22658435/", "publicSourceType": "PMID" }, { "text": "Attilakos A, Papakonstantinou E, Schulpis K, Voudris K, Katsarou E, Mastroyianni S, et al. Early effect of sodium valproate and carbamazepine monotherapy on homocysteine metabolism in children with epilepsy. Epilepsy Res. 2006;71(2-3):229-232.", "pmid": "16889940", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16889940/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Carbamazepine may lower vitamin B6 status during long-term therapy.", "clinicalSignificance": "B6 deficiency and high homocysteine are modifiable risks during chronic enzyme-inducing antiseizure therapy.", "managementStrategy": "Monitor B-vitamin status when clinically indicated and supplement B6 conservatively if low.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Phenytoin", "supplementBName": "Vitamin B12", "interactionType": "synergy", "severity": "moderate", "description": "Phenytoin therapy is associated with lower vitamin B12 levels and higher homocysteine in multiple studies. B12 deficiency can cause anemia, neuropathy, cognitive symptoms, and can compound folate-related problems already known with phenytoin. Risk is higher with long-term use, older age, vegetarian diets, metformin or acid-suppressing therapy, or baseline B12 deficiency.", "recommendation": "Ask about periodic B12 testing if you take phenytoin long term or develop numbness, balance problems, fatigue, or macrocytic anemia. Supplement B12 if levels are low or borderline with symptoms. Keep seizure medication dosing unchanged unless your prescriber adjusts it.", "minimumTimeSeparation": null, "mechanism": "Phenytoin can disturb one-carbon metabolism and is associated with lower serum B12 and folate plus higher homocysteine. Restoring B12 helps correct deficiency-related hematologic and neurologic risk but does not replace phenytoin monitoring.", "evidenceLevel": "strong", "sources": [ { "text": "Xu Y, Zhang N, Xu S, Xu H, Chen S, Xia Z. Effects of phenytoin on serum levels of homocysteine, vitamin B12, folate in patients with epilepsy: A systematic review and meta-analysis. Medicine (Baltimore). 2019;98(12):e14844.", "pmid": "30896627", "doi": "10.1097/MD.0000000000014844", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30896627/", "publicSourceType": "PMID" }, { "text": "Kathiravan M, Kavitha S, Shanthi R. To determine the effect of long-term antiepileptic drug on the serum folate and vitamin B12 among epileptic patients. Sci Rep. 2021;11(1):4393.", "pmid": "33623072", "doi": "10.1038/s41598-021-83312-y", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33623072/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Phenytoin may lower vitamin B12 status and raise homocysteine.", "clinicalSignificance": "Unrecognized B12 deficiency can cause neurologic injury that may be mistaken for medication or disease effects.", "managementStrategy": "Monitor B12 during long-term phenytoin therapy and replace B12 when low.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Phenytoin", "supplementBName": "Vitamin B6", "interactionType": "synergy", "severity": "moderate", "description": "Enzyme-inducing antiseizure drugs such as phenytoin have been associated with vitamin B6 deficiency. Low B6 can contribute to neuropathy symptoms and impaired homocysteine metabolism, especially when folate or B12 status is also poor. This is a monitoring and repletion issue, not a reason to stop phenytoin abruptly.", "recommendation": "Ask about B-vitamin or homocysteine testing if you take phenytoin long term, especially if you have neuropathy symptoms or cardiovascular risk factors. Use conservative B6 doses unless deficiency is documented and supervised. Do not take chronic high-dose B6 without monitoring because excess B6 can damage nerves.", "minimumTimeSeparation": null, "mechanism": "Phenytoin is an enzyme-inducing antiseizure medication and may lower pyridoxine status through increased vitamin turnover or altered metabolism. Vitamin B6 is required for transsulfuration of homocysteine and for normal peripheral nerve function.", "evidenceLevel": "moderate", "sources": [ { "text": "Mintzer S, Skidmore CT, Sperling MR. B-vitamin deficiency in patients treated with antiepileptic drugs. Epilepsy Behav. 2012;24(3):341-344.", "pmid": "22658435", "doi": "10.1016/j.yebeh.2012.04.132", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22658435/", "publicSourceType": "PMID" }, { "text": "Tamura T, Aiso K, Johnston KE, Black L, Faught E. Homocysteine, folate, vitamin B-12 and vitamin B-6 in patients receiving antiepileptic drug monotherapy. Epilepsy Res. 2000;40(1):7-15.", "pmid": "10771253", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10771253/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Phenytoin may contribute to low vitamin B6 status during chronic therapy.", "clinicalSignificance": "Correcting low B6 may reduce deficiency-related neurologic and homocysteine concerns.", "managementStrategy": "Check B-vitamin status when clinically indicated and replete B6 cautiously if low.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Valproic Acid", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "moderate", "description": "Long-term valproic acid use has been associated with lower 25-hydroxyvitamin D and lower bone mineral density, especially in children and patients treated for years. A randomized trial in children on valproate found daily vitamin D supplementation reduced the decline in vitamin D and bone-mineral markers. This is most relevant for chronic therapy, low sun exposure, low dietary intake, or other fracture risks.", "recommendation": "Ask about baseline and follow-up 25-hydroxyvitamin D testing if you take valproic acid long term. Use vitamin D3 supplementation when levels are low or when your clinician recommends prevention. Pair supplementation with bone-health monitoring rather than relying on vitamin D alone.", "minimumTimeSeparation": null, "mechanism": "Valproic acid is not a classic strong enzyme inducer, but long-term use is associated with changes in vitamin D status, bone turnover, and bone mineral density. Vitamin D3 supports calcium absorption and bone mineralization, helping offset part of this chronic risk.", "evidenceLevel": "strong", "sources": [ { "text": "Min L, Chunyan W, Biaoxue R. Effects of valproic acid on skeletal metabolism in children with epilepsy: a systematic evaluation and meta-analysis based on 14 studies. BMC Pediatr. 2020;20(1):97.", "pmid": "32122313", "doi": "10.1186/s12887-020-1984-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32122313/", "publicSourceType": "PMID" }, { "text": "Mohanraj R, Sahu JK, Prasad K, Tripathi M. Effect of Daily Vitamin D Supplementation on Serum Vitamin D Levels in Children with Epilepsy Receiving Sodium Valproate Monotherapy: A Randomized, Controlled Trial. Indian J Pediatr. 2023;90(5):450-456.", "pmid": "35763213", "doi": "10.1007/s12098-022-04225-w", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35763213/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Valproic acid may lower vitamin D status and bone mineral density during long-term use.", "clinicalSignificance": "Vitamin D deficiency and low bone density increase fracture risk during chronic antiseizure therapy.", "managementStrategy": "Monitor 25-hydroxyvitamin D and supplement D3 when low or clinically indicated.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Valproic Acid", "supplementBName": "Calcium", "interactionType": "synergy", "severity": "moderate", "description": "Valproic acid has been linked with lower bone mineral density in people with epilepsy, particularly with longer treatment duration. Adequate calcium intake is part of bone-health prevention for patients on long-term antiseizure therapy, especially when vitamin D status is also being managed. Calcium does not prevent every valproate-related bone effect, but low intake is a modifiable risk factor.", "recommendation": "Make sure your daily calcium intake is appropriate if you take valproic acid long term. Ask about vitamin D testing, dietary calcium review, and bone-density screening if you have fracture risks. Avoid excessive calcium supplementation unless prescribed, particularly if you have kidney stones or kidney disease.", "minimumTimeSeparation": null, "mechanism": "Valproic acid is associated with reduced bone mineral density through mechanisms that may include altered bone turnover and vitamin D-related pathways. Calcium supports hydroxyapatite mineralization and works best as part of a broader bone-health plan that includes vitamin D adequacy.", "evidenceLevel": "moderate", "sources": [ { "text": "Zhong R, Chen Q, Zhang X, Li M, Liang J, Lin W. Bone Mineral Density Loss in People With Epilepsy Taking Valproate as a Monotherapy: A Systematic Review and Meta-Analysis. Front Neurol. 2019;10:1171.", "pmid": "31787923", "doi": "10.3389/fneur.2019.01171", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31787923/", "publicSourceType": "PMID" }, { "text": "Krishnamoorthy G, Nair R, Sundar U, Kini P, Shrivastava M. Early predisposition to osteomalacia in Indian adults on phenytoin or valproate monotherapy and effective prophylaxis by simultaneous supplementation with calcium and 25-hydroxy vitamin D at recommended daily allowance dosage: a prospective study. Neurol India. 2010;58(2):213-219.", "pmid": "20508338", "doi": "10.4103/0028-3886.63796", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20508338/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Valproic acid increases long-term bone-health concerns, making adequate calcium intake more important.", "clinicalSignificance": "Maintaining calcium intake helps address a modifiable contributor to fracture risk during chronic valproate therapy.", "managementStrategy": "Ensure adequate calcium intake and monitor bone health alongside vitamin D status.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fluconazole", "supplementBName": "Berberine", "interactionType": "caution", "severity": "moderate", "description": "Berberine inhibits CYP3A4 (and to a lesser extent CYP2D6), the same family of enzymes that fluconazole also inhibits. Stacking two CYP3A4 inhibitors can raise the systemic levels of co-prescribed CYP3A4 substrates (statins, calcium channel blockers, benzodiazepines, certain immunosuppressants) and prolong fluconazole's own half-life, increasing the risk of dose-related adverse effects such as hepatotoxicity and QT prolongation.", "recommendation": "Avoid starting berberine during a fluconazole course. If you take berberine for blood sugar, hold it while on fluconazole and resume a few days after the course ends. Tell your prescriber about every CYP3A4 substrate you take.", "minimumTimeSeparation": null, "mechanism": "Berberine is a moderate, partly quasi-irreversible inhibitor of CYP3A4 and CYP2D6 in human liver microsomes. Combined with fluconazole's own CYP3A4/2C9 inhibition, the result is additive impairment of oxidative drug metabolism.", "evidenceLevel": "emerging", "sources": [ { "text": "Mostafavi-Pour Z, et al. Effects of Berberis vulgaris, and its active constituent berberine on cytochrome P450: a review. Pharm Biol. 2024.", "pmid": "39141022", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39141022/", "publicSourceType": "PMID" }, { "text": "Zhao Y, et al. Quasi-irreversible inhibition of CYP2D6 by berberine. Drug Metab Dispos. 2020.", "pmid": "32987920", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32987920/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive CYP3A4 inhibition raises levels of fluconazole and other CYP3A4 substrates.", "clinicalSignificance": "Stacking two CYP3A4 inhibitors increases the risk of dose-related toxicity from co-prescribed medications.", "managementStrategy": "Hold berberine during fluconazole therapy and resume after the course ends.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Fluconazole", "supplementBName": "Resveratrol", "interactionType": "caution", "severity": "moderate", "description": "Resveratrol inhibits CYP3A4 in vitro and in animal pharmacokinetic studies, where it has raised plasma exposure of CYP3A4 substrates such as nicardipine and ticagrelor. Layered on top of fluconazole's CYP3A4 and CYP2C9 inhibition, this could blunt clearance of other prescription medications metabolized by these enzymes.", "recommendation": "Pause resveratrol supplementation during your fluconazole course, particularly if you also take statins, calcium channel blockers, anticoagulants, or benzodiazepines. Resume once fluconazole has cleared.", "minimumTimeSeparation": null, "mechanism": "Resveratrol inhibits CYP3A4, CYP1A and CYP2E1 activities in human liver microsomes and inhibits P-glycoprotein. Combining it with fluconazole produces additive suppression of CYP3A4-mediated metabolism.", "evidenceLevel": "emerging", "sources": [ { "text": "Chan WK, Delucchi AB. Inhibition of CYP3A, CYP1A and CYP2E1 activities by resveratrol and other non volatile red wine components. Life Sci. 2001;69(2):85-93.", "pmid": "11701226", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11701226/", "publicSourceType": "PMID" }, { "text": "Wang X, et al. Inhibitory effect of resveratrol on the pharmacokinetics of ticagrelor in vivo and in vitro. Pharmacology. 2021.", "pmid": "33400617", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33400617/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Adds to fluconazole's CYP3A4 inhibition and may raise levels of co-administered CYP3A4 substrates.", "clinicalSignificance": "Could amplify side effects of statins, calcium channel blockers, or other CYP3A4-cleared drugs taken with fluconazole.", "managementStrategy": "Hold resveratrol during fluconazole therapy.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Fluconazole", "supplementBName": "Quercetin", "interactionType": "caution", "severity": "moderate", "description": "Quercetin inhibits CYP3A4 and P-glycoprotein in vitro and has altered the pharmacokinetics of CYP3A4 substrates in animal models. Used alongside fluconazole, which is itself a CYP3A4 and CYP2C9 inhibitor, quercetin may further reduce metabolism of co-prescribed drugs and prolong fluconazole exposure.", "recommendation": "Avoid high-dose quercetin (more than ~500 mg/day) while on fluconazole, especially if you take a statin, calcium channel blocker, benzodiazepine, or anticoagulant. Resume after finishing the antifungal course.", "minimumTimeSeparation": null, "mechanism": "Quercetin is a moderate inhibitor of CYP3A4 and the MDR1 P-glycoprotein efflux pump. Stacking with fluconazole compounds inhibition of the same metabolic pathway.", "evidenceLevel": "emerging", "sources": [ { "text": "Pal D, Mitra AK. MDR- and CYP3A4-mediated drug-herbal interactions. Life Sci. 2006;78(18):2131-45.", "pmid": "16442130", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16442130/", "publicSourceType": "PMID" }, { "text": "Wang J, et al. Quercetin inhibits the metabolism of arachidonic acid by inhibiting the activity of CYP3A4. Front Pharmacol. 2023.", "pmid": "37710176", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37710176/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Adds to fluconazole's CYP3A4 inhibition.", "clinicalSignificance": "Co-prescribed CYP3A4 substrates may accumulate to higher-than-expected levels.", "managementStrategy": "Avoid high-dose quercetin during fluconazole therapy.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Fluconazole", "supplementBName": "Milk Thistle", "interactionType": "caution", "severity": "moderate", "description": "Silymarin from milk thistle inhibits CYP3A4, CYP2C9, UGT enzymes, and P-glycoprotein in vitro, and clinical pharmacokinetic studies have shown modest interactions with substrates such as losartan and nifedipine. Because fluconazole itself inhibits CYP3A4 and CYP2C9, layering milk thistle may amplify suppression of drug metabolism while doing little to mitigate fluconazole hepatotoxicity risk in any RCT-proven way.", "recommendation": "If you take milk thistle for liver support, discuss with your prescriber before continuing during fluconazole therapy. Do not rely on it to prevent fluconazole-induced liver injury; instead monitor liver enzymes as your prescriber advises.", "minimumTimeSeparation": null, "mechanism": "Silymarin inhibits CYP3A4 and CYP2C9 in vitro and is itself extensively metabolized. Stacking with fluconazole increases combined inhibition of these enzymes.", "evidenceLevel": "emerging", "sources": [ { "text": "Wu JW, Lin LC, Tsai TH. Drug-drug interactions of silymarin on the perspective of pharmacokinetics. J Ethnopharmacol. 2009;121(2):185-93.", "pmid": "19041708", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19041708/", "publicSourceType": "PMID" }, { "text": "Hermann R, von Richter O. Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions. Planta Med. 2012;78(13):1458-77.", "pmid": "22855269", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22855269/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive CYP3A4/2C9 inhibition; no proven hepatoprotective benefit against azole liver injury.", "clinicalSignificance": "May alter levels of other CYP-metabolized prescriptions and is not a substitute for liver monitoring.", "managementStrategy": "Discuss with prescriber before continuing milk thistle; monitor LFTs as directed.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Fluconazole", "supplementBName": "Turmeric/Curcumin", "interactionType": "caution", "severity": "moderate", "description": "Curcumin inhibits CYP3A4 and P-glycoprotein in vitro and has altered the pharmacokinetics of CYP3A4 substrates such as amlodipine and budesonide in animal studies. Combining curcumin supplements with fluconazole adds another inhibitor to the same metabolic pathway, which can raise levels of co-prescribed drugs metabolized by CYP3A4.", "recommendation": "Pause concentrated curcumin or turmeric extract supplements during your fluconazole course. Culinary turmeric in food is fine. Resume supplementation a few days after finishing fluconazole.", "minimumTimeSeparation": null, "mechanism": "Curcumin is a moderate CYP3A4 and P-glycoprotein inhibitor. Combining with fluconazole compounds CYP3A4 inhibition and may slow clearance of substrate drugs.", "evidenceLevel": "emerging", "sources": [ { "text": "Zhang W, et al. Effects of curcumin on the pharmacokinetics of amlodipine in rats and its potential mechanism. Pharm Biol. 2020;58(1):465-468.", "pmid": "32432949", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32432949/", "publicSourceType": "PMID" }, { "text": "Pal D, Mitra AK. MDR- and CYP3A4-mediated drug-herbal interactions. Life Sci. 2006;78(18):2131-45.", "pmid": "16442130", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16442130/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive CYP3A4 inhibition with potential to raise other drug levels.", "clinicalSignificance": "May increase exposure to co-administered CYP3A4 substrates during fluconazole therapy.", "managementStrategy": "Pause curcumin/turmeric extract supplements during the course.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Fluconazole", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's Wort is a strong inducer of CYP3A4 (via PXR activation by hyperforin) and P-glycoprotein. Because fluconazole is partly metabolized by CYP3A4 and is itself a CYP3A4 inhibitor, St. John's Wort can lower fluconazole plasma levels and shorten its half-life, potentially leading to subtherapeutic exposure and treatment failure of a serious fungal infection.", "recommendation": "Do not take St. John's Wort during fluconazole therapy. If you were already taking it, stop and tell your prescriber so they can consider monitoring response or extending the course.", "minimumTimeSeparation": null, "mechanism": "Hyperforin from St. John's Wort activates the pregnane X receptor (PXR), inducing CYP3A4 and P-glycoprotein. This accelerates clearance of CYP3A4 substrates including azole antifungals.", "evidenceLevel": "strong", "sources": [ { "text": "Moore LB, et al. St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc Natl Acad Sci U S A. 2000;97(13):7500-2.", "pmid": "10852961", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10852961/", "publicSourceType": "PMID" }, { "text": "Nicolussi S, et al. Clinical relevance of St. John's wort drug interactions revisited. Br J Pharmacol. 2020;177(6):1212-1226.", "pmid": "31742659", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31742659/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St. John's Wort induces CYP3A4 and lowers fluconazole exposure.", "clinicalSignificance": "May cause subtherapeutic fluconazole levels and failed treatment of the underlying infection.", "managementStrategy": "Avoid St. John's Wort during and around fluconazole therapy.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Fluconazole", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "moderate", "description": "Fluconazole can prolong the QT interval, especially at higher doses, in renal impairment, or with other QT-prolonging drugs. Low magnesium and low potassium are independent, well-established risk factors for torsades de pointes. Keeping magnesium in the normal range reduces this background arrhythmia risk while you are taking fluconazole.", "recommendation": "If your magnesium is low or you are on a diuretic, correct deficiency before starting fluconazole and maintain adequate intake during the course. Do not megadose; typical magnesium glycinate doses (200-350 mg elemental/day) are appropriate.", "minimumTimeSeparation": null, "mechanism": "Hypomagnesemia destabilizes cardiac repolarization and prolongs the QT interval. Fluconazole independently blocks hERG potassium currents, lengthening QT. Maintaining normal magnesium reduces additive arrhythmic risk.", "evidenceLevel": "moderate", "sources": [ { "text": "Pham CP, et al. Long QTc interval and torsade de pointes caused by fluconazole. Ann Pharmacother. 2006;40(7-8):1456-61.", "pmid": "16849620", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16849620/", "publicSourceType": "PMID" }, { "text": "Tisdale JE. Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management. Can Pharm J (Ott). 2016;149(3):139-52.", "pmid": "27212965", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27212965/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Maintaining normal magnesium reduces the QT prolongation risk associated with fluconazole.", "clinicalSignificance": "Hypomagnesemia is a modifiable risk factor for fluconazole-related torsades de pointes.", "managementStrategy": "Correct hypomagnesemia before and during fluconazole therapy.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fluconazole", "supplementBName": "Potassium", "interactionType": "synergy", "severity": "moderate", "description": "Hypokalemia is a major risk factor for QT prolongation and torsades de pointes, and fluconazole independently prolongs the QT interval. Patients on diuretics, with GI losses, or with renal disease are especially vulnerable. Keeping potassium in the normal range reduces the arrhythmic risk of fluconazole therapy.", "recommendation": "Have potassium checked before starting fluconazole if you take a diuretic, have vomiting/diarrhea, or have cardiac risk factors. Replace potassium as your clinician directs. Do not self-supplement high-dose potassium without labs.", "minimumTimeSeparation": null, "mechanism": "Low serum potassium prolongs cardiac repolarization. Fluconazole blocks hERG potassium current, also prolonging QT. The two effects are additive on torsades risk.", "evidenceLevel": "moderate", "sources": [ { "text": "Pham CP, et al. Long QTc interval and torsade de pointes caused by fluconazole. Ann Pharmacother. 2006;40(7-8):1456-61.", "pmid": "16849620", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16849620/", "publicSourceType": "PMID" }, { "text": "Buch T, Andersen SE. Combination therapy with fluconazole and other QTc-prolonging drugs increase the QTc interval. Ugeskr Laeger. 2015;177(41).", "pmid": "26471025", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26471025/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Normal potassium reduces fluconazole-related QT prolongation risk.", "clinicalSignificance": "Hypokalemia is a major modifiable risk factor for torsades during fluconazole therapy.", "managementStrategy": "Check and replete potassium before and during fluconazole, especially with diuretics or GI losses.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fluconazole", "supplementBName": "NAC", "interactionType": "synergy", "severity": "info", "description": "Fluconazole can cause hepatotoxicity ranging from mild transaminase elevations to acute liver injury. N-acetylcysteine replenishes glutathione and has been studied as a treatment for non-acetaminophen drug-induced liver injury, with some evidence of benefit. The combination is not a substitute for liver monitoring but is a low-risk antioxidant strategy in higher-risk patients.", "recommendation": "If you are at elevated risk of drug-induced liver injury (existing liver disease, alcohol use, polypharmacy), discuss NAC with your prescriber. Do not use NAC to mask the need for monitoring liver enzymes during fluconazole therapy.", "minimumTimeSeparation": null, "mechanism": "NAC restores hepatic glutathione, scavenges reactive metabolites, and exerts anti-inflammatory effects. These mechanisms are plausibly protective against idiosyncratic azole-induced hepatotoxicity but with limited specific data for fluconazole.", "evidenceLevel": "emerging", "sources": [ { "text": "Chughlay MF, et al. N-acetylcysteine for non-paracetamol drug-induced liver injury: a systematic review. Br J Clin Pharmacol. 2016;81(6):1021-9.", "pmid": "26757427", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26757427/", "publicSourceType": "PMID" }, { "text": "Kyriakidis I, et al. Clinical hepatotoxicity associated with antifungal agents. Expert Opin Drug Saf. 2017;16(2):149-165.", "pmid": "27927037", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27927037/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "NAC may modestly attenuate fluconazole-related oxidative liver stress.", "clinicalSignificance": "Adjunctive antioxidant support; not a replacement for LFT monitoring.", "managementStrategy": "Consider NAC in higher-risk patients; continue routine liver enzyme monitoring.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Fluconazole", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Fluconazole is hepatotoxic in a dose- and duration-dependent fashion, and alcohol is one of the strongest modifiable risk factors for drug-induced liver injury. Drinking during fluconazole therapy meaningfully raises the chance of transaminase elevation, cholestasis, or symptomatic hepatitis, particularly with longer courses or repeated exposures.", "recommendation": "Avoid alcohol while taking fluconazole and for several days after the course ends. If you must drink, keep it to one occasion and minimize quantity, and tell your prescriber so liver enzymes can be checked.", "minimumTimeSeparation": null, "mechanism": "Both alcohol and fluconazole generate reactive metabolites that deplete glutathione and stress hepatocytes. Alcohol also induces CYP2E1, increasing oxidative liver injury risk.", "evidenceLevel": "moderate", "sources": [ { "text": "Kyriakidis I, et al. Clinical hepatotoxicity associated with antifungal agents. Expert Opin Drug Saf. 2017;16(2):149-165.", "pmid": "27927037", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27927037/", "publicSourceType": "PMID" }, { "text": "Chalasani N, Björnsson E. Risk factors for idiosyncratic drug-induced liver injury. Gastroenterology. 2010;138(7):2246-59.", "pmid": "20394749", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20394749/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Alcohol amplifies fluconazole-related hepatotoxicity risk.", "clinicalSignificance": "Increases the likelihood of clinically significant liver injury during therapy.", "managementStrategy": "Avoid alcohol throughout the fluconazole course and for several days after.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Terbinafine", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Terbinafine is associated with idiosyncratic hepatotoxicity, including cholestatic hepatitis and rare cases of liver failure requiring transplant. Alcohol is a leading risk factor for drug-induced liver injury and meaningfully increases the chance of symptomatic liver injury during the typical 6-12 week onychomycosis course.", "recommendation": "Avoid alcohol throughout the terbinafine course and for at least a few days after it ends. Report any nausea, dark urine, abdominal pain, or yellowing of skin or eyes immediately.", "minimumTimeSeparation": null, "mechanism": "Terbinafine's reactive allylic aldehyde metabolite (TBF-A) is implicated in hepatocyte injury. Alcohol induces CYP2E1 and depletes glutathione, compounding hepatotoxic stress.", "evidenceLevel": "moderate", "sources": [ { "text": "Ajit C, et al. Terbinafine-associated hepatotoxicity. Am J Med Sci. 2003;325(5):292-5.", "pmid": "12792250", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12792250/", "publicSourceType": "PMID" }, { "text": "Chalasani N, Björnsson E. Risk factors for idiosyncratic drug-induced liver injury. Gastroenterology. 2010;138(7):2246-59.", "pmid": "20394749", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20394749/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Alcohol increases the risk of terbinafine-induced liver injury.", "clinicalSignificance": "Heightens the chance of symptomatic hepatitis during a course typically lasting weeks to months.", "managementStrategy": "Avoid alcohol throughout terbinafine therapy.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Terbinafine", "supplementBName": "NAC", "interactionType": "synergy", "severity": "info", "description": "Terbinafine is metabolized to a reactive allylic aldehyde (TBF-A) thought to drive its idiosyncratic hepatotoxicity. N-acetylcysteine restores glutathione and has been used in non-acetaminophen drug-induced liver injury. The combination is not a proven prophylactic but is a low-risk adjunct in higher-risk patients on multi-month courses.", "recommendation": "Do not rely on NAC instead of routine liver enzyme monitoring. If you have additional hepatotoxicity risk factors, discuss adjunctive NAC with your prescriber.", "minimumTimeSeparation": null, "mechanism": "NAC replenishes glutathione, which detoxifies reactive metabolites such as terbinafine's TBF-A intermediate.", "evidenceLevel": "emerging", "sources": [ { "text": "Ajit C, et al. Terbinafine-associated hepatotoxicity. Am J Med Sci. 2003;325(5):292-5.", "pmid": "12792250", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12792250/", "publicSourceType": "PMID" }, { "text": "Chughlay MF, et al. N-acetylcysteine for non-paracetamol drug-induced liver injury: a systematic review. Br J Clin Pharmacol. 2016;81(6):1021-9.", "pmid": "26757427", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26757427/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "NAC may modestly buffer terbinafine-related oxidative liver stress.", "clinicalSignificance": "Adjunctive antioxidant support; not a substitute for LFT monitoring.", "managementStrategy": "Consider NAC in higher-risk patients; continue prescribed LFT monitoring.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Terbinafine", "supplementBName": "Probiotics", "interactionType": "synergy", "severity": "info", "description": "Oral terbinafine treats fungal infections but its mycobiome and microbiome impact in humans is incompletely characterized, and antifungal exposure in animal models alters fungal and bacterial gut communities. Probiotic strains such as Lactobacillus and Saccharomyces boulardii have anti-Candida and barrier-supportive effects that may help restore balance after a long oral antifungal course.", "recommendation": "If you want to use probiotics during or after a terbinafine course, choose a well-studied strain. Take Saccharomyces boulardii only after the antifungal course is complete, since terbinafine has limited activity against yeasts and S. boulardii is itself a yeast.", "minimumTimeSeparation": null, "mechanism": "Antifungal exposure can shift fungal and bacterial gut populations. Probiotics compete with pathogens for adhesion sites, secrete antimicrobial metabolites (e.g., capric acid from S. boulardii inhibits Candida), and modulate mucosal immunity.", "evidenceLevel": "emerging", "sources": [ { "text": "Seelbinder B, et al. Antibiotics create a shift from mutualism to competition in human gut communities with a longer-lasting impact on fungi than bacteria. Microbiome. 2020;8(1):133.", "pmid": "32451559", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32451559/", "publicSourceType": "PMID" }, { "text": "Suchodolski J, et al. Capric acid secreted by Saccharomyces boulardii influences the susceptibility of Candida albicans to fluconazole and amphotericin B. Sci Rep. 2021;11(1):6519.", "pmid": "33753842", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33753842/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Probiotics may help restore microbial balance after a terbinafine course.", "clinicalSignificance": "Adjunctive support for gut and mucosal flora; not a substitute for treating the fungal infection.", "managementStrategy": "Use Lactobacillus during/after; save Saccharomyces boulardii for after the course.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Acyclovir", "supplementBName": "L-Lysine", "interactionType": "synergy", "severity": "info", "description": "L-lysine is used by some patients as adjunctive prophylaxis against herpes simplex recurrences, working by a different mechanism than acyclovir. Evidence is mixed and modest, but daily doses above 1-3 g have shown subjective benefit in some trials, with no known pharmacokinetic interaction with acyclovir or valacyclovir.", "recommendation": "Lysine is reasonable as a complement to acyclovir for recurrent oral or genital HSV, typically at 1-3 g per day. Do not use it as a substitute for prescribed antivirals during an active outbreak.", "minimumTimeSeparation": null, "mechanism": "HSV replication depends on arginine for capsid protein synthesis; lysine competes with arginine for intestinal transport and renal reabsorption, potentially lowering intracellular arginine availability. Acyclovir, in contrast, inhibits viral DNA polymerase, so the mechanisms are non-overlapping.", "evidenceLevel": "emerging", "sources": [ { "text": "Mailoo VJ, Rampes S. Lysine for herpes simplex prophylaxis: a review of the evidence. Integr Med (Encinitas). 2017;16(3):42-46.", "pmid": "30881246", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30881246/", "publicSourceType": "PMID" }, { "text": "Griffith RS, et al. Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Dermatologica. 1987;175(4):183-90.", "pmid": "3115841", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3115841/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Lysine may modestly reduce HSV recurrence frequency or severity alongside acyclovir.", "clinicalSignificance": "Reasonable adjunct for recurrent HSV but not a replacement during active outbreaks.", "managementStrategy": "Use 1-3 g/day lysine as adjunctive prophylaxis; continue prescribed acyclovir.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Valacyclovir", "supplementBName": "L-Lysine", "interactionType": "synergy", "severity": "info", "description": "Valacyclovir is the prodrug of acyclovir, and L-lysine prophylaxis works through a separate, arginine-competition mechanism against HSV. Evidence is modest and best supported for daily doses above 1 g, but there is no known pharmacokinetic interaction with valacyclovir, and combination use is reasonable for recurrence prevention.", "recommendation": "Lysine 1-3 g/day is a reasonable adjunct to valacyclovir for recurrent HSV. Continue valacyclovir as prescribed during active outbreaks; do not rely on lysine alone.", "minimumTimeSeparation": null, "mechanism": "Lysine competes with arginine, which HSV requires for capsid protein synthesis. Valacyclovir is converted to acyclovir, which inhibits viral DNA polymerase. The mechanisms do not overlap or interfere.", "evidenceLevel": "emerging", "sources": [ { "text": "Mailoo VJ, Rampes S. Lysine for herpes simplex prophylaxis: a review of the evidence. Integr Med (Encinitas). 2017;16(3):42-46.", "pmid": "30881246", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30881246/", "publicSourceType": "PMID" }, { "text": "Griffith RS, et al. Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Dermatologica. 1987;175(4):183-90.", "pmid": "3115841", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3115841/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Lysine may modestly reduce HSV recurrence rate as an adjunct to valacyclovir.", "clinicalSignificance": "Useful for prevention; not a substitute for valacyclovir during active disease.", "managementStrategy": "Use 1-3 g/day lysine alongside valacyclovir for recurrent HSV.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Acyclovir", "supplementBName": "Zinc", "interactionType": "synergy", "severity": "info", "description": "Topical zinc sulfate has shown benefit for recurrent herpes labialis in small placebo-controlled trials, and zinc has well-documented immunomodulatory effects. Oral zinc is plausibly additive when combined with acyclovir for recurrent HSV, although high-quality combination trials are lacking. There is no known systemic pharmacokinetic interaction with acyclovir.", "recommendation": "Modest oral zinc (15-25 mg/day with food) is reasonable as adjunctive support during recurrent HSV outbreaks while taking acyclovir. Do not exceed 40 mg elemental zinc daily long-term; chronic high-dose zinc causes copper deficiency.", "minimumTimeSeparation": null, "mechanism": "Zinc directly inhibits HSV attachment and replication in vitro and supports T-cell and NK-cell function. Acyclovir blocks viral DNA polymerase; mechanisms are complementary.", "evidenceLevel": "emerging", "sources": [ { "text": "Kneist W, et al. Clinical double-blind trial of topical zinc sulfate for herpes labialis recidivans. Arzneimittelforschung. 1995;45(5):624-6.", "pmid": "7612066", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7612066/", "publicSourceType": "PMID" }, { "text": "Brody I. Topical treatment of recurrent herpes simplex and post-herpetic erythema multiforme with low concentrations of zinc sulphate solution. Br J Dermatol. 1981;104(2):191-4.", "pmid": "7213551", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7213551/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Zinc may add modest antiviral and immune support to acyclovir for HSV.", "clinicalSignificance": "Reasonable low-risk adjunct; not a substitute for acyclovir.", "managementStrategy": "Use 15-25 mg/day oral zinc with food during HSV outbreaks; avoid chronic high doses.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Acyclovir", "supplementBName": "Quercetin", "interactionType": "synergy", "severity": "info", "description": "Quercetin has demonstrated antiviral activity against HSV-1 in vitro and in animal models, primarily by interfering with viral attachment and replication. While clinical trials in HSV are lacking, the mechanism is non-overlapping with acyclovir, and combination use during recurrent outbreaks is biologically plausible and low-risk at typical supplement doses.", "recommendation": "Quercetin 250-500 mg/day is reasonable as an adjunct during HSV outbreaks while taking acyclovir. Do not use quercetin as a substitute for prescribed antiviral therapy.", "minimumTimeSeparation": null, "mechanism": "Quercetin disrupts HSV attachment, entry, and replication in vitro. Acyclovir is phosphorylated by viral thymidine kinase and inhibits DNA polymerase. The mechanisms target different steps of the viral life cycle.", "evidenceLevel": "emerging", "sources": [ { "text": "Yu Y, et al. Quercetin inhibits herpes simplex virus 1 replication in corneal epithelium and suppresses keratitis progression. Virol Sin. 2025;40(4):419-433.", "pmid": "40675379", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40675379/", "publicSourceType": "PMID" }, { "text": "Various authors. Antiviral potential of phenolic compounds against HSV-1: In-vitro study. Microb Pathog. 2024.", "pmid": "39311585", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39311585/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Quercetin offers mechanism-distinct antiviral activity that may complement acyclovir.", "clinicalSignificance": "Biologically plausible adjunct for HSV; not a replacement for acyclovir.", "managementStrategy": "Use 250-500 mg/day quercetin alongside acyclovir during outbreaks.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Acyclovir", "supplementBName": "Reishi", "interactionType": "synergy", "severity": "info", "description": "Ganoderma lucidum (Reishi) polysaccharides have antiviral activity against HSV-1 and HSV-2 in vitro, and a small clinical study reported faster recovery of herpes labialis and genitalis with reishi-containing formulas. Evidence for additive benefit with acyclovir is preliminary, but no pharmacokinetic interaction is established, and the combination is biologically plausible.", "recommendation": "Reishi may be used as a low-risk adjunct during HSV outbreaks while taking acyclovir, but it should not replace antiviral therapy. Be aware reishi has mild antiplatelet activity at high doses; stop before surgery.", "minimumTimeSeparation": null, "mechanism": "Acidic protein-bound polysaccharides from Ganoderma lucidum interfere with HSV attachment to cells and have immunomodulatory effects on macrophages and NK cells. Acyclovir works downstream by blocking viral DNA polymerase.", "evidenceLevel": "emerging", "sources": [ { "text": "Eo SK, et al. Possible mode of antiviral activity of acidic protein bound polysaccharide isolated from Ganoderma lucidum on herpes simplex viruses. J Ethnopharmacol. 2000;72(3):475-81.", "pmid": "10996289", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10996289/", "publicSourceType": "PMID" }, { "text": "Hijikata Y, Yamada S, Yasuhara A. Herbal mixtures containing the mushroom Ganoderma lucidum improve recovery time in patients with herpes genitalis and labialis. J Altern Complement Med. 2007;13(9):985-7.", "pmid": "18047445", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18047445/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Reishi may modestly augment antiviral immune response alongside acyclovir.", "clinicalSignificance": "Mechanism-distinct adjunct; effect size is small and based on preliminary data.", "managementStrategy": "Use as an optional adjunct; do not substitute for prescribed acyclovir.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Acyclovir", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Vitamin C has in vitro antiviral activity against HSV and supports immune function, and a topical ascorbate solution showed modest benefit in recurrent mucocutaneous herpes. Evidence for additive benefit when combined with acyclovir is limited but the combination is low risk and may modestly support immune-mediated viral clearance.", "recommendation": "Standard-dose vitamin C (500-1000 mg/day) is a reasonable adjunct during HSV outbreaks while taking acyclovir. Do not use high-dose vitamin C as a substitute for prescribed antivirals.", "minimumTimeSeparation": null, "mechanism": "Vitamin C inactivates virions in vitro via oxidative mechanisms, supports neutrophil and lymphocyte function, and regenerates other antioxidants. Acyclovir is a nucleoside analogue inhibiting viral DNA polymerase; the mechanisms are independent.", "evidenceLevel": "emerging", "sources": [ { "text": "Hovi T, et al. Topical treatment of recurrent mucocutaneous herpes with ascorbic acid-containing solution. Antiviral Res. 1995;27(3):263-70.", "pmid": "8540748", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8540748/", "publicSourceType": "PMID" }, { "text": "Colunga Biancatelli RML, et al. The antiviral properties of vitamin C. Expert Rev Anti Infect Ther. 2020;18(2):99-101.", "pmid": "31852327", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31852327/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Vitamin C may modestly support antiviral immune response alongside acyclovir.", "clinicalSignificance": "Low-risk adjunct; not a replacement for acyclovir.", "managementStrategy": "Use 500-1000 mg/day vitamin C as optional adjunct.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Valacyclovir", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Vitamin C has in vitro antiviral effects against HSV and supports immune function; combined with valacyclovir for recurrent HSV it offers a mechanism-distinct adjunct without known pharmacokinetic interference. Evidence for additive clinical benefit is preliminary but the combination is low risk at standard supplement doses.", "recommendation": "Vitamin C 500-1000 mg/day is reasonable as adjunctive immune support during HSV outbreaks while on valacyclovir. Do not stop prescribed antivirals in favor of vitamin C.", "minimumTimeSeparation": null, "mechanism": "Vitamin C supports innate and adaptive immune function and has oxidative virucidal activity in vitro. Valacyclovir is converted to acyclovir, which blocks viral DNA polymerase.", "evidenceLevel": "emerging", "sources": [ { "text": "Colunga Biancatelli RML, et al. The antiviral properties of vitamin C. Expert Rev Anti Infect Ther. 2020;18(2):99-101.", "pmid": "31852327", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31852327/", "publicSourceType": "PMID" }, { "text": "Hovi T, et al. Topical treatment of recurrent mucocutaneous herpes with ascorbic acid-containing solution. Antiviral Res. 1995;27(3):263-70.", "pmid": "8540748", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8540748/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Vitamin C may modestly support immune response alongside valacyclovir.", "clinicalSignificance": "Low-risk adjunct for recurrent HSV.", "managementStrategy": "Use 500-1000 mg/day vitamin C as optional adjunct.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Oseltamivir", "supplementBName": "Elderberry", "interactionType": "synergy", "severity": "info", "description": "Elderberry (Sambucus nigra) flavonoids inhibit influenza H1N1 attachment in vitro and small randomized trials suggest modest reductions in influenza duration and severity. A 2021 systematic review found no evidence of immune over-stimulation or cytokine storm risk, and there is no known pharmacokinetic interaction with oseltamivir, making the combination a reasonable adjunct during acute influenza.", "recommendation": "Standardized elderberry extract (e.g., 175-300 mg/day or label dose) may be used alongside oseltamivir for acute influenza in healthy adults. Start within 48 hours of symptom onset; do not use elderberry instead of oseltamivir.", "minimumTimeSeparation": null, "mechanism": "Elderberry flavonoids bind to and block influenza A H1N1 hemagglutinin, preventing viral attachment to host cells. Oseltamivir blocks viral neuraminidase, preventing release of new virions. The mechanisms target different steps of the viral life cycle.", "evidenceLevel": "emerging", "sources": [ { "text": "Roschek B Jr, et al. Elderberry flavonoids bind to and prevent H1N1 infection in vitro. Phytochemistry. 2009;70(10):1255-61.", "pmid": "19682714", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19682714/", "publicSourceType": "PMID" }, { "text": "Wieland LS, et al. Elderberry for prevention and treatment of viral respiratory illnesses: a systematic review. BMC Complement Med Ther. 2021;21(1):112.", "pmid": "33827515", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33827515/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Elderberry may modestly augment oseltamivir's effect on influenza duration and severity.", "clinicalSignificance": "Biologically plausible adjunct; not a replacement for oseltamivir.", "managementStrategy": "Use standardized elderberry alongside oseltamivir within 48 hours of symptom onset.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Oseltamivir", "supplementBName": "Elderberry Zinc Lozenges", "interactionType": "synergy", "severity": "info", "description": "Elderberry blocks influenza H1N1 attachment in vitro and zinc lozenges (acetate or gluconate) reduce common cold duration in meta-analyses. Combined with oseltamivir, which inhibits viral neuraminidase, the mechanisms are non-overlapping. The combination is low risk for short courses but high-dose zinc (>40 mg elemental/day) chronically causes copper deficiency.", "recommendation": "Elderberry zinc lozenges are a reasonable adjunct during acute influenza alongside oseltamivir. Limit to the labeled course (typically less than 2 weeks) to avoid copper depletion. Do not exceed 75-100 mg elemental zinc daily acutely.", "minimumTimeSeparation": null, "mechanism": "Elderberry flavonoids block influenza hemagglutinin attachment; ionic zinc disrupts rhinovirus binding to ICAM-1 and supports T-cell function; oseltamivir blocks neuraminidase. All three mechanisms target different stages of viral infection.", "evidenceLevel": "emerging", "sources": [ { "text": "Hemilä H, Chalker E. The effectiveness of high dose zinc acetate lozenges on various common cold symptoms: a meta-analysis. BMC Fam Pract. 2015;16:24.", "pmid": "25888289", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25888289/", "publicSourceType": "PMID" }, { "text": "Roschek B Jr, et al. Elderberry flavonoids bind to and prevent H1N1 infection in vitro. Phytochemistry. 2009;70(10):1255-61.", "pmid": "19682714", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19682714/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Multi-mechanism adjunct support during oseltamivir treatment for influenza.", "clinicalSignificance": "Low risk for short-term use; avoid prolonged high-dose zinc.", "managementStrategy": "Use elderberry zinc lozenges per label for less than 2 weeks alongside oseltamivir.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Oseltamivir", "supplementBName": "Echinacea", "interactionType": "synergy", "severity": "info", "description": "Echinacea purpurea preparations have demonstrated in vitro activity against influenza viruses and a randomized comparative trial of Echinaforce hot drink versus oseltamivir suggested similar early symptom improvement with fewer adverse events. While Echinacea is not a replacement for neuraminidase inhibitors, combination use as an adjunct is biologically plausible and low risk in immunocompetent adults.", "recommendation": "Echinacea may be used as an optional adjunct to oseltamivir for influenza in healthy adults, started early in illness. Avoid Echinacea if you are on immunosuppressants (e.g., methotrexate, transplant medications) or have an autoimmune disease.", "minimumTimeSeparation": null, "mechanism": "Echinacea polysaccharides and alkamides activate macrophages, NK cells, and cytokine release, and some extracts inhibit influenza attachment in vitro. Oseltamivir inhibits viral neuraminidase; mechanisms are non-overlapping.", "evidenceLevel": "emerging", "sources": [ { "text": "Ross SM. Echinacea formula (Echinaforce Hotdrink): effects of a proprietary echinacea formula compared with oseltamivir in the early treatment of influenza. Holist Nurs Pract. 2016;30(2):122-5.", "pmid": "26871250", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26871250/", "publicSourceType": "PMID" }, { "text": "Pleschka S, et al. Anti-viral properties and mode of action of standardized Echinacea purpurea extract against highly pathogenic avian influenza virus. Virol J. 2009;6:197.", "pmid": "19912623", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19912623/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Echinacea may modestly support oseltamivir's effect on early influenza symptoms.", "clinicalSignificance": "Reasonable adjunct in immunocompetent adults; avoid with immunosuppression.", "managementStrategy": "Use Echinacea early in illness alongside oseltamivir; avoid if immunosuppressed.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Oseltamivir", "supplementBName": "Zinc", "interactionType": "synergy", "severity": "info", "description": "Zinc supports antiviral immune function and meta-analyses show modest reductions in common cold duration with zinc lozenges. While direct trials of zinc plus oseltamivir for influenza are lacking, the mechanisms are non-overlapping and the combination is low risk for short-term use during acute illness.", "recommendation": "Modest oral zinc (15-25 mg/day with food) or zinc lozenges per label for the duration of acute influenza are reasonable alongside oseltamivir. Avoid chronic high-dose zinc, which can cause copper deficiency.", "minimumTimeSeparation": null, "mechanism": "Zinc supports innate immunity, T-cell function, and interferon response, and ionic zinc has direct antiviral activity against several respiratory viruses. Oseltamivir blocks viral neuraminidase.", "evidenceLevel": "emerging", "sources": [ { "text": "Hemilä H. Zinc lozenges and the common cold: a meta-analysis comparing zinc acetate and zinc gluconate, and the role of zinc dosage. JRSM Open. 2017;8(5).", "pmid": "28515951", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28515951/", "publicSourceType": "PMID" }, { "text": "Hemilä H, Chalker E. The effectiveness of high dose zinc acetate lozenges on various common cold symptoms: a meta-analysis. BMC Fam Pract. 2015;16:24.", "pmid": "25888289", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25888289/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Zinc may modestly support immune function alongside oseltamivir during influenza.", "clinicalSignificance": "Reasonable short-term adjunct; chronic high-dose zinc risks copper deficiency.", "managementStrategy": "Use 15-25 mg/day oral zinc or short-course lozenges alongside oseltamivir.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Oseltamivir", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "info", "description": "Vitamin D supplementation modestly reduces the risk of acute respiratory infections, particularly in deficient individuals, per a large individual participant data meta-analysis. While direct combination trials with oseltamivir are absent, maintaining adequate vitamin D status supports antiviral immune function and is a reasonable background measure during influenza treatment.", "recommendation": "If your vitamin D level is low or unknown, maintaining 1000-2000 IU/day vitamin D3 is reasonable alongside oseltamivir during influenza season. Do not use vitamin D as treatment for active influenza in lieu of oseltamivir.", "minimumTimeSeparation": null, "mechanism": "Vitamin D upregulates antimicrobial peptides (cathelicidin, defensins) and modulates innate and adaptive antiviral immunity. Oseltamivir directly inhibits influenza neuraminidase.", "evidenceLevel": "moderate", "sources": [ { "text": "Martineau AR, et al. Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis. Health Technol Assess. 2019;23(2):1-44.", "pmid": "30675873", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30675873/", "publicSourceType": "PMID" }, { "text": "Zhu Z, et al. Association between vitamin D and influenza: meta-analysis and systematic review of randomized controlled trials. Front Nutr. 2022;8.", "pmid": "35071300", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35071300/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Maintaining vitamin D adequacy may modestly support antiviral immunity alongside oseltamivir.", "clinicalSignificance": "Low-risk background measure, especially in deficient patients.", "managementStrategy": "Maintain 1000-2000 IU/day vitamin D3 during influenza season.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fluconazole", "supplementBName": "Saccharomyces Boulardii", "interactionType": "conflict", "severity": "moderate", "description": "Saccharomyces boulardii is itself a yeast (a non-pathogenic strain of S. cerevisiae). Fluconazole has variable activity against Saccharomyces species and may suppress S. boulardii during therapy, defeating its probiotic purpose. Rare cases of S. boulardii fungemia have occurred in immunocompromised or central-line patients, where antifungal activity is desirable.", "recommendation": "Hold Saccharomyces boulardii during your fluconazole course. Resume a few days after finishing fluconazole if you still want probiotic support. Lactobacillus-based probiotics are unaffected by fluconazole.", "minimumTimeSeparation": null, "mechanism": "Fluconazole inhibits fungal ergosterol synthesis via CYP51, which affects S. boulardii to varying degrees and undermines viability of the probiotic.", "evidenceLevel": "emerging", "sources": [ { "text": "Suchodolski J, et al. Capric acid secreted by Saccharomyces boulardii influences the susceptibility of Candida albicans to fluconazole and amphotericin B. Sci Rep. 2021;11(1):6519.", "pmid": "33753842", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33753842/", "publicSourceType": "PMID" }, { "text": "Tomičić R, Tomičić Z, Raspor P. Influence of culture conditions on co-aggregation of probiotic yeast Saccharomyces boulardii with Candida spp. Folia Microbiol (Praha). 2022;67(3):507-515.", "pmid": "35169980", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35169980/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Fluconazole suppresses S. boulardii viability, negating its probiotic effect.", "clinicalSignificance": "Co-administration wastes the probiotic and may interfere with intended use.", "managementStrategy": "Hold S. boulardii during fluconazole; substitute Lactobacillus or resume after the course.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Aripiprazole", "supplementBName": "Cannabis (THC-Dominant)", "interactionType": "conflict", "severity": "serious", "description": "THC-dominant cannabis can work against the treatment goals of aripiprazole in psychosis or bipolar disorder. Continued cannabis use after a psychotic episode is linked with higher relapse rates, poorer adherence, and more antipsychotic treatment failure. Risk is highest with daily use, high-potency THC products, prior cannabis-induced psychosis, or recent hospitalization.", "recommendation": "Avoid THC-dominant cannabis while taking aripiprazole for psychosis or mood stabilization. If you are already using cannabis, tell your prescriber because relapse risk and medication adherence need closer monitoring. Separating the timing of cannabis and aripiprazole does not remove this risk.", "minimumTimeSeparation": null, "mechanism": "THC is a psychoactive cannabinoid that can provoke or worsen psychotic symptoms through CB1 receptor effects on dopaminergic and glutamatergic signaling. Cannabis use also increases the likelihood of missed antipsychotic doses, creating a pharmacodynamic and behavioral conflict with relapse prevention.", "evidenceLevel": "strong", "sources": [ { "text": "Schoeler T, Monk A, Sami MB, Klamerus E, Foglia E, Brown R, et al. Continued versus discontinued cannabis use in patients with psychosis: a systematic review and meta-analysis. Lancet Psychiatry. 2016;3(3):215-225.", "pmid": "26777297", "doi": "10.1016/S2215-0366(15)00363-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26777297/", "publicSourceType": "PMID" }, { "text": "Reid S, Bhattacharyya S. Antipsychotic treatment failure in patients with psychosis and co-morbid cannabis use: A systematic review. Psychiatry Res. 2019;280:112523.", "pmid": "31450032", "doi": "10.1016/j.psychres.2019.112523", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31450032/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "THC-dominant cannabis increases relapse and antipsychotic treatment-failure risk during aripiprazole therapy.", "clinicalSignificance": "A patient may appear to need more medication when the real driver is cannabis-associated destabilization or nonadherence.", "managementStrategy": "Avoid THC-dominant cannabis and monitor closely for return of paranoia, hallucinations, mania, or missed aripiprazole doses.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Olanzapine", "supplementBName": "Cannabis (THC-Dominant)", "interactionType": "conflict", "severity": "serious", "description": "THC-dominant cannabis can undermine olanzapine treatment by increasing relapse risk and worsening psychosis outcomes. Systematic reviews link continued cannabis use in psychosis with more relapse, poorer adherence, and antipsychotic treatment failure. The combination can also add impairment and sleepiness in people already sensitive to olanzapine sedation.", "recommendation": "Avoid THC-dominant cannabis while taking olanzapine for psychosis or mood stabilization. If cannabis use continues, your prescriber should know so relapse risk, adherence, and sedation can be monitored. Dose timing separation is not a reliable safety strategy.", "minimumTimeSeparation": null, "mechanism": "THC can worsen psychotic symptoms through CB1-mediated changes in dopamine and glutamate signaling. Olanzapine reduces relapse risk through D2 and 5-HT2A antagonism, while continued cannabis exposure and cannabis-related nonadherence push in the opposite direction.", "evidenceLevel": "strong", "sources": [ { "text": "Zammit S, Moore TH, Lingford-Hughes A, Barnes TR, Jones PB, Burke M, et al. Effects of cannabis use on outcomes of psychotic disorders: systematic review. Br J Psychiatry. 2008;193(5):357-363.", "pmid": "18978312", "doi": "10.1192/bjp.bp.107.046375", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18978312/", "publicSourceType": "PMID" }, { "text": "Schoeler T, Monk A, Sami MB, Klamerus E, Foglia E, Brown R, et al. Continued versus discontinued cannabis use in patients with psychosis: a systematic review and meta-analysis. Lancet Psychiatry. 2016;3(3):215-225.", "pmid": "26777297", "doi": "10.1016/S2215-0366(15)00363-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26777297/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "THC-dominant cannabis opposes olanzapine's relapse-prevention goal and can add sedation.", "clinicalSignificance": "Continued cannabis use is a common and modifiable reason for psychosis relapse despite antipsychotic treatment.", "managementStrategy": "Avoid THC-dominant cannabis and treat any continued use as a relapse-risk factor requiring active monitoring.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Quetiapine", "supplementBName": "Cannabis (THC-Dominant)", "interactionType": "conflict", "severity": "serious", "description": "THC-dominant cannabis can conflict with quetiapine's use for psychosis or bipolar mood stabilization. Continued cannabis use after psychosis onset is associated with higher relapse risk and poorer antipsychotic outcomes, and quetiapine's sedating effects can compound cannabis-related impairment. This is especially concerning with high-potency THC, daily use, driving, or other sedatives.", "recommendation": "Avoid THC-dominant cannabis while taking quetiapine for psychosis or bipolar disorder. Tell your prescriber if you continue cannabis so they can monitor symptoms, adherence, and oversedation. Do not rely on spacing the doses to make the combination safe.", "minimumTimeSeparation": null, "mechanism": "THC can worsen psychotic symptoms through CB1 receptor signaling and downstream effects on dopamine and glutamate. Quetiapine has antihistaminic and adrenergic-blocking sedative effects, so cannabis can add cognitive and motor impairment while also worsening relapse risk.", "evidenceLevel": "strong", "sources": [ { "text": "Schoeler T, Monk A, Sami MB, Klamerus E, Foglia E, Brown R, et al. Continued versus discontinued cannabis use in patients with psychosis: a systematic review and meta-analysis. Lancet Psychiatry. 2016;3(3):215-225.", "pmid": "26777297", "doi": "10.1016/S2215-0366(15)00363-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26777297/", "publicSourceType": "PMID" }, { "text": "Reid S, Bhattacharyya S. Antipsychotic treatment failure in patients with psychosis and co-morbid cannabis use: A systematic review. Psychiatry Res. 2019;280:112523.", "pmid": "31450032", "doi": "10.1016/j.psychres.2019.112523", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31450032/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "THC-dominant cannabis increases relapse risk and may add impairment during quetiapine therapy.", "clinicalSignificance": "The combination can look like medication failure while cannabis is worsening symptoms or adherence.", "managementStrategy": "Avoid THC-dominant cannabis and monitor closely for relapse, oversedation, and missed quetiapine doses.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Risperidone", "supplementBName": "Cannabis (THC-Dominant)", "interactionType": "conflict", "severity": "serious", "description": "THC-dominant cannabis can interfere with risperidone's relapse-prevention role in psychosis. Continued cannabis use in people with psychotic disorders is linked with higher relapse, nonadherence, and antipsychotic treatment failure. Risk is greatest with high-potency THC, frequent use, and a history of cannabis-related psychosis.", "recommendation": "Avoid THC-dominant cannabis while taking risperidone for psychosis or mood stabilization. If you are using cannabis, tell your prescriber so they can monitor relapse risk, adherence, and side effects. Timing separation does not address the main risk.", "minimumTimeSeparation": null, "mechanism": "THC can acutely worsen psychotic symptoms through CB1 receptor activation and downstream changes in dopamine and glutamate signaling. Cannabis-associated nonadherence and symptom worsening oppose risperidone's D2/5-HT2A-mediated antipsychotic effect.", "evidenceLevel": "strong", "sources": [ { "text": "Zammit S, Moore TH, Lingford-Hughes A, Barnes TR, Jones PB, Burke M, et al. Effects of cannabis use on outcomes of psychotic disorders: systematic review. Br J Psychiatry. 2008;193(5):357-363.", "pmid": "18978312", "doi": "10.1192/bjp.bp.107.046375", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18978312/", "publicSourceType": "PMID" }, { "text": "Reid S, Bhattacharyya S. Antipsychotic treatment failure in patients with psychosis and co-morbid cannabis use: A systematic review. Psychiatry Res. 2019;280:112523.", "pmid": "31450032", "doi": "10.1016/j.psychres.2019.112523", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31450032/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "THC-dominant cannabis raises relapse and treatment-failure risk during risperidone therapy.", "clinicalSignificance": "Cannabis use can drive recurrent psychosis even when risperidone is otherwise appropriate.", "managementStrategy": "Avoid THC-dominant cannabis and monitor for relapse or adherence problems if use continues.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Olanzapine", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Alcohol can add to olanzapine-related sedation, slowed reaction time, dizziness, and impaired coordination. Olanzapine can already cause sleepiness and orthostatic symptoms, so alcohol increases the chance of falls, unsafe driving, blackouts, and accidental injury. The risk is higher during dose starts or increases, in older adults, or with other sedating medicines.", "recommendation": "Avoid alcohol while taking olanzapine, especially during titration or if you already feel sleepy. If you drink despite this, do not drive or use machinery and do not take extra sedatives. Seek urgent help for severe confusion, slow breathing, repeated falls, or inability to wake.", "minimumTimeSeparation": null, "mechanism": "Alcohol is a CNS depressant that enhances inhibitory signaling and impairs cortical arousal and motor coordination. Olanzapine has central dopamine, serotonin, histamine H1, muscarinic, and alpha-1 adrenergic effects that can produce sedation and postural dizziness, leading to additive pharmacodynamic impairment.", "evidenceLevel": "strong", "sources": [ { "text": "Weathermon R, Crabb DW. Alcohol and medication interactions. Alcohol Res Health. 1999;23(1):40-54.", "pmid": "10890797", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10890797/", "publicSourceType": "PMID" }, { "text": "Tanaka E. Toxicological interactions involving psychiatric drugs and alcohol: an update. J Clin Pharm Ther. 2003;28(2):81-95.", "pmid": "12713604", "doi": "10.1046/j.1365-2710.2003.00459.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12713604/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Alcohol and olanzapine additively increase sedation, dizziness, and psychomotor impairment.", "clinicalSignificance": "The combination raises fall, injury, blackout, and impaired-driving risk.", "managementStrategy": "Avoid alcohol during olanzapine therapy, particularly during dose changes or when sedation is present.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Quetiapine", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Alcohol can markedly increase quetiapine-related sleepiness, dizziness, slowed reactions, and poor coordination. Quetiapine's antihistamine and alpha-1 blocking effects already make sedation and orthostatic hypotension common, and alcohol can push this into falls, blackouts, or unsafe driving. Risk is highest at night, after dose increases, or with other sedatives.", "recommendation": "Avoid alcohol while taking quetiapine. If alcohol was used, do not drive, take extra sleep aids, or take more quetiapine than prescribed. Get urgent help for extreme drowsiness, slow breathing, fainting, or inability to wake.", "minimumTimeSeparation": null, "mechanism": "Quetiapine causes CNS depression through strong H1 histamine antagonism and can lower blood pressure through alpha-1 adrenergic blockade. Alcohol adds CNS depression and psychomotor impairment, producing a pharmacodynamic interaction that spacing doses cannot reliably prevent.", "evidenceLevel": "strong", "sources": [ { "text": "Weathermon R, Crabb DW. Alcohol and medication interactions. Alcohol Res Health. 1999;23(1):40-54.", "pmid": "10890797", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10890797/", "publicSourceType": "PMID" }, { "text": "Tanaka E. Toxicological interactions involving psychiatric drugs and alcohol: an update. J Clin Pharm Ther. 2003;28(2):81-95.", "pmid": "12713604", "doi": "10.1046/j.1365-2710.2003.00459.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12713604/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Alcohol adds to quetiapine sedation, dizziness, and psychomotor impairment.", "clinicalSignificance": "This pairing increases the risk of falls, blackouts, impaired driving, and accidental overdose with other sedatives.", "managementStrategy": "Avoid alcohol while taking quetiapine and use extra caution after dose changes.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Risperidone", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Alcohol can increase risperidone-related drowsiness, slowed thinking, dizziness, and impaired coordination. Even when risperidone is less sedating than some antipsychotics, alcohol can still increase falls, unsafe driving, and poor judgment. Risk is higher during dose starts or increases, in older adults, and with other sedating medications.", "recommendation": "Avoid alcohol while taking risperidone if possible. If you drink, do not drive or operate machinery, and do not take extra sedatives to sleep. Seek urgent help for severe confusion, fainting, slow breathing, or inability to stay awake.", "minimumTimeSeparation": null, "mechanism": "Alcohol produces CNS depression and psychomotor impairment through GABAergic and glutamatergic effects. Risperidone can cause sedation and orthostatic symptoms through central dopamine/serotonin antagonism and alpha-adrenergic effects, so the combined impairment is pharmacodynamic.", "evidenceLevel": "strong", "sources": [ { "text": "Weathermon R, Crabb DW. Alcohol and medication interactions. Alcohol Res Health. 1999;23(1):40-54.", "pmid": "10890797", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10890797/", "publicSourceType": "PMID" }, { "text": "Tanaka E. Toxicological interactions involving psychiatric drugs and alcohol: an update. J Clin Pharm Ther. 2003;28(2):81-95.", "pmid": "12713604", "doi": "10.1046/j.1365-2710.2003.00459.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12713604/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Alcohol adds to risperidone-related sedation, dizziness, and impaired coordination.", "clinicalSignificance": "This increases injury and impaired-driving risk even without a major pharmacokinetic interaction.", "managementStrategy": "Avoid alcohol during risperidone therapy or use strict caution with no driving or other sedatives.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Valproic Acid", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Alcohol can add to valproic acid's dizziness, sleepiness, and impaired coordination, and it may increase concern for liver injury. A case-control study of valproic acid-induced liver injury found alcohol consumption was associated with greater risk of serious DILI. The combination is especially risky with liver disease, elevated liver enzymes, pancreatitis history, high valproate levels, or heavy drinking.", "recommendation": "Avoid heavy or binge alcohol while taking valproic acid, and avoid alcohol completely if you have liver disease or abnormal liver tests. Do not skip or double valproic acid doses around drinking without prescriber guidance. Ask about liver-function monitoring and seek urgent care for severe abdominal pain, jaundice, confusion, vomiting, or extreme sleepiness.", "minimumTimeSeparation": null, "mechanism": "Valproic acid is hepatically metabolized through glucuronidation and mitochondrial beta-oxidation, and toxic metabolites can contribute to hepatic injury. Alcohol adds CNS depression and can worsen hepatic oxidative stress and mitochondrial vulnerability, increasing both impairment and liver-safety concerns.", "evidenceLevel": "moderate", "sources": [ { "text": "Meseguer ES, Elizalde MU, Borobia AM, Ramirez E. Valproic Acid-Induced Liver Injury: A Case-Control Study from a Prospective Pharmacovigilance Program in a Tertiary Hospital. J Clin Med. 2021;10(6):1153.", "pmid": "33801850", "doi": "10.3390/jcm10061153", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33801850/", "publicSourceType": "PMID" }, { "text": "Guo HL, Jing X, Sun JY, Hu YH, Xu ZJ, Ni MM, et al. Valproic Acid and the Liver Injury in Patients with Epilepsy: An Update. Curr Pharm Des. 2019;25(3):343-351.", "pmid": "30931853", "doi": "10.2174/1381612825666190329145428", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30931853/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Alcohol increases sedation risk and may increase valproic acid liver-injury risk.", "clinicalSignificance": "Liver injury from valproic acid can be serious, and alcohol is a modifiable risk factor.", "managementStrategy": "Avoid heavy alcohol and monitor liver safety closely if any alcohol use continues.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Olanzapine", "supplementBName": "Melatonin", "interactionType": "synergy", "severity": "info", "description": "Melatonin has been studied as an adjunct to reduce some metabolic side effects of olanzapine, including weight and cardiometabolic changes. Randomized trials and meta-analyses suggest possible benefit, but the effects are modest and do not replace diet, activity, or metabolic monitoring. Melatonin may also add bedtime sleepiness in patients who already feel sedated on olanzapine.", "recommendation": "Use melatonin with olanzapine only as an adjunct, preferably at bedtime and with your prescriber's awareness. Continue routine weight, glucose, lipid, and blood-pressure monitoring. Reduce or stop melatonin and ask for guidance if morning grogginess, falls, or worsening daytime sedation occurs.", "minimumTimeSeparation": null, "mechanism": "Olanzapine can disrupt metabolic regulation through histamine H1, serotonin 5-HT2C, muscarinic, appetite, and insulin-sensitivity pathways. Melatonin may support circadian and metabolic signaling through MT1/MT2 receptors and antioxidant effects, but it can also add sedative pharmacodynamic effects.", "evidenceLevel": "moderate", "sources": [ { "text": "Modabbernia A, Heidari P, Soleimani R, Sobhani A, Roshan ZA, Taslimi S, et al. Melatonin for prevention of metabolic side-effects of olanzapine in patients with first-episode schizophrenia: randomized double-blind placebo-controlled study. J Psychiatr Res. 2014;53:133-140.", "pmid": "24607293", "doi": "10.1016/j.jpsychires.2014.02.013", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24607293/", "publicSourceType": "PMID" }, { "text": "Kamath A, Rather ZA. Melatonin for Atypical Antipsychotic-Induced Metabolic Adverse Effects: A Meta-Analysis of Randomized Controlled Trials. Biomed Res Int. 2018;2018:4907264.", "pmid": "29682546", "doi": "10.1155/2018/4907264", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29682546/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Melatonin may modestly reduce olanzapine-associated metabolic changes while adding possible sleepiness.", "clinicalSignificance": "Olanzapine has high metabolic liability, so adjuncts with human trial support may be useful when monitored.", "managementStrategy": "Consider bedtime melatonin only as a monitored adjunct to standard metabolic prevention and lab follow-up.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Risperidone", "supplementBName": "NAC", "interactionType": "synergy", "severity": "info", "description": "NAC has human trial evidence as an adjunct to risperidone for negative symptoms of schizophrenia. The effect is not immediate and does not replace antipsychotic treatment, but it may modestly improve residual symptoms in some patients. Evidence is strongest for adjunctive use over weeks to months rather than as-needed dosing.", "recommendation": "Do not use NAC as a substitute for risperidone. If you add NAC, keep risperidone unchanged unless your prescriber changes it, and track symptoms over several weeks. Stop and ask for guidance if NAC causes persistent stomach upset, wheezing, rash, or medication-adherence confusion.", "minimumTimeSeparation": null, "mechanism": "NAC replenishes cysteine for glutathione synthesis and modulates glutamatergic signaling through the cystine-glutamate antiporter. These effects may complement risperidone's D2 and 5-HT2A receptor antagonism by targeting oxidative stress and glutamate dysregulation linked to negative symptoms.", "evidenceLevel": "moderate", "sources": [ { "text": "Farokhnia M, Azarkolah A, Adinehfar F, Khodaie-Ardakani MR, Hosseini SM, Yekehtaz H, et al. N-acetylcysteine as an adjunct to risperidone for treatment of negative symptoms in patients with chronic schizophrenia: a randomized, double-blind, placebo-controlled study. Clin Neuropharmacol. 2013;36(6):185-192.", "pmid": "24201233", "doi": "10.1097/WNF.0000000000000001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24201233/", "publicSourceType": "PMID" }, { "text": "Fond G, Mallet J, Urbach M, Benros ME, Berk M, Billeci M, et al. Adjunctive agents to antipsychotics in schizophrenia: a systematic umbrella review and recommendations for amino acids, hormonal therapies and anti-inflammatory drugs. BMJ Ment Health. 2023;26(1):e300771.", "pmid": "37852631", "doi": "10.1136/bmjment-2023-300771", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37852631/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "NAC may modestly improve residual negative symptoms when added to risperidone.", "clinicalSignificance": "Negative symptoms often respond incompletely to antipsychotics, so an adjunct with RCT support may be clinically useful.", "managementStrategy": "Use NAC only as a monitored adjunct and continue prescribed risperidone unless the prescriber changes it.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Risperidone", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "Fish oil, as a source of omega-3 polyunsaturated fatty acids, has been studied as an adjunct in recent-onset psychosis patients treated with risperidone. Trials suggest possible benefits for depressive/anxiety symptoms and brain white-matter measures, while broader schizophrenia omega-3 findings remain mixed. This is an adjunctive strategy, not an antipsychotic replacement.", "recommendation": "Do not reduce or stop risperidone because you start fish oil. If you add fish oil, use a consistent product and track mood, anxiety, psychosis symptoms, and adverse effects over several weeks. Use extra caution if you also take blood thinners or high-dose NSAIDs, because fish oil can add bleeding tendency in those settings.", "minimumTimeSeparation": null, "mechanism": "EPA and DHA can alter neuronal membrane composition, inflammatory signaling, and oxidative-stress pathways that may complement antipsychotic treatment. Risperidone provides dopamine D2 and serotonin 5-HT2A antagonism, while omega-3 effects appear indirect and illness-stage dependent.", "evidenceLevel": "moderate", "sources": [ { "text": "Robinson DG, Gallego JA, John M, Hanna LA, Zhang JP, Birnbaum ML, et al. A potential role for adjunctive omega-3 polyunsaturated fatty acids for depression and anxiety symptoms in recent onset psychosis: Results from a 16 week randomized placebo-controlled trial for participants concurrently treated with risperidone. Schizophr Res. 2019;204:295-303.", "pmid": "30241990", "doi": "10.1016/j.schres.2018.09.006", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30241990/", "publicSourceType": "PMID" }, { "text": "Lyall AE, Nagele FL, Pasternak O, Gallego JA, Malhotra AK, McNamara RK, et al. A 16-week randomized placebo-controlled trial investigating the effects of omega-3 polyunsaturated fatty acid treatment on white matter microstructure in recent-onset psychosis patients concurrently treated with risperidone. Psychiatry Res Neuroimaging. 2021;307:111219.", "pmid": "33221631", "doi": "10.1016/j.pscychresns.2020.111219", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33221631/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Fish oil may provide adjunctive symptom or neurobiological benefit during risperidone treatment in recent-onset psychosis.", "clinicalSignificance": "The evidence is promising but mixed, so fish oil should support, not replace, antipsychotic care.", "managementStrategy": "Use fish oil consistently as an adjunct and keep risperidone and symptom monitoring unchanged.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Risperidone", "supplementBName": "Methylfolate", "interactionType": "synergy", "severity": "info", "description": "Methylfolate has been studied as an adjunct in medicated schizophrenia patients with residual symptoms. Benefits appear selective and may depend on folate-pathway biology, baseline folate status, or elevated homocysteine rather than applying to everyone. It should not be used to replace risperidone or other antipsychotic treatment.", "recommendation": "Consider methylfolate only as an adjunct and tell your prescriber before adding high-dose products. Do not change risperidone dosing on your own. Ask whether folate, B12, and homocysteine testing is appropriate, especially if you have poor diet, anemia, neuropathy symptoms, or known folate-pathway variants.", "minimumTimeSeparation": null, "mechanism": "L-methylfolate is the bioactive folate form used in one-carbon metabolism and methylation pathways that support monoamine synthesis and homocysteine remethylation. These pathways may complement antipsychotic treatment in biologically selected patients, but they do not directly replace dopamine D2 receptor blockade.", "evidenceLevel": "moderate", "sources": [ { "text": "Roffman JL, Petruzzi LJ, Tanner AS, Brown HE, Eryilmaz H, Ho NF, et al. Biochemical, physiological and clinical effects of l-methylfolate in schizophrenia: a randomized controlled trial. Mol Psychiatry. 2018;23(2):316-322.", "pmid": "28289280", "doi": "10.1038/mp.2017.41", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28289280/", "publicSourceType": "PMID" }, { "text": "Roffman JL, Lamberti JS, Achtyes E, Macklin EA, Galendez GC, Raeke LH, et al. Randomized multicenter investigation of folate plus vitamin B12 supplementation in schizophrenia. JAMA Psychiatry. 2013;70(5):481-489.", "pmid": "23467813", "doi": "10.1001/jamapsychiatry.2013.900", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23467813/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Methylfolate may improve selected residual schizophrenia symptoms when added to antipsychotic treatment such as risperidone.", "clinicalSignificance": "Folate-pathway support may help a subgroup, but benefit is not universal and should be guided by clinical context.", "managementStrategy": "Use methylfolate as a monitored adjunct and consider folate/B12/homocysteine assessment.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Valproic Acid", "supplementBName": "L-Carnitine", "interactionType": "synergy", "severity": "serious", "description": "L-carnitine is used clinically to address valproic acid-associated carnitine depletion, hyperammonemia, and toxicity risk. Valproic acid can shift mitochondrial metabolism toward toxic metabolites and impair ammonia handling, causing confusion, vomiting, lethargy, or encephalopathy in susceptible patients. This is most important with high valproate levels, overdose, liver disease, young age, poor nutrition, urea-cycle disorders, or unexplained mental-status changes.", "recommendation": "Do not self-treat suspected valproic acid toxicity with over-the-counter L-carnitine alone. Seek urgent medical care for confusion, severe sleepiness, repeated vomiting, or sudden neurologic changes while on valproic acid. If your prescriber recommends L-carnitine, use the exact dose and continue ammonia, liver-function, valproate-level, and symptom monitoring as directed.", "minimumTimeSeparation": null, "mechanism": "Valproic acid depends partly on mitochondrial beta-oxidation, a pathway supported by carnitine transport. Carnitine depletion shifts valproate metabolism toward omega-oxidation and 4-en-valproic acid formation, which can impair carbamoyl phosphate synthetase I activity and raise ammonia; L-carnitine can help restore mitochondrial handling.", "evidenceLevel": "moderate", "sources": [ { "text": "Lheureux PE, Penaloza A, Zahir S, Gris M. Science review: carnitine in the treatment of valproic acid-induced toxicity - what is the evidence? Crit Care. 2005;9(5):431-440.", "pmid": "16277730", "doi": "10.1186/cc3742", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16277730/", "publicSourceType": "PMID" }, { "text": "Lheureux PE, Hantson P. Carnitine in the treatment of valproic acid-induced toxicity. Clin Toxicol (Phila). 2009;47(2):101-111.", "pmid": "19280426", "doi": "10.1080/15563650902752376", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19280426/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "L-carnitine can mitigate valproic acid-associated hyperammonemia and toxicity in selected patients.", "clinicalSignificance": "Valproate-related hyperammonemic encephalopathy can be serious and may be mistaken for psychiatric worsening.", "managementStrategy": "Use L-carnitine under medical supervision when valproate toxicity, hyperammonemia, or carnitine depletion is suspected or documented.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Valproic Acid", "supplementBName": "Vitamin B9", "interactionType": "synergy", "severity": "info", "description": "Vitamin B9, usually as folic acid, has human evidence as an adjunct to sodium valproate in acute mania and is also clinically relevant because valproate is a high-risk teratogen. Folic acid does not make valproic acid safe in pregnancy, but adequate folate status remains important for people who could become pregnant and for one-carbon metabolism. The benefit for mood symptoms is promising but not enough to replace mood stabilizer treatment.", "recommendation": "Do not stop or lower valproic acid because you start Vitamin B9. If pregnancy is possible, discuss contraception, pregnancy planning, and folic acid dosing with your prescriber before continuing valproic acid. Use Vitamin B9 as a monitored adjunct, not as protection against valproate's full fetal-risk profile.", "minimumTimeSeparation": null, "mechanism": "Folate participates in one-carbon metabolism, methylation, and homocysteine remethylation, pathways relevant to neuropsychiatric function. Valproate is associated with teratogenicity and may interact with folate-dependent developmental pathways, while adjunctive folic acid may support mood treatment in selected bipolar patients.", "evidenceLevel": "moderate", "sources": [ { "text": "Behzadi AH, Omrani Z, Chalian M, Asadi S, Ghadiri M. Folic acid efficacy as an alternative drug added to sodium valproate in the treatment of acute phase of mania in bipolar disorder: a double-blind randomized controlled trial. Acta Psychiatr Scand. 2009;120(6):441-445.", "pmid": "19392814", "doi": "10.1111/j.1600-0447.2009.01368.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19392814/", "publicSourceType": "PMID" }, { "text": "Sylvia LG, Peters AT, Deckersbach T, Nierenberg AA. Nutrient-based therapies for bipolar disorder: a systematic review. Psychother Psychosom. 2013;82(1):10-19.", "pmid": "23147067", "doi": "10.1159/000341309", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23147067/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Vitamin B9 may support valproic acid treatment in mania and helps address folate-related safety considerations.", "clinicalSignificance": "Folate support is relevant, but it does not neutralize valproate's major pregnancy risks.", "managementStrategy": "Use Vitamin B9 as a monitored adjunct and handle pregnancy risk through prescriber-led planning, not supplementation alone.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Buspirone", "supplementBName": "5-HTP", "interactionType": "caution", "severity": "serious", "description": "5-HTP is a direct serotonin precursor, and buspirone acts at serotonin 5-HT1A receptors. Taking them together can add serotonergic pressure and may increase the risk of serotonin toxicity, especially if you also use an SSRI, SNRI, MAOI, tramadol, triptan, or St. John's Wort. Warning symptoms include agitation, sweating, diarrhea, tremor, muscle jerks, fever, or confusion.", "recommendation": "Avoid concentrated 5-HTP supplements while taking buspirone unless your prescriber specifically approves the combination. Do not try to manage this by dose spacing alone. Seek urgent care if you develop fever, confusion, marked restlessness, tremor, muscle rigidity, or repeated muscle jerks after taking both.", "minimumTimeSeparation": null, "mechanism": "5-HTP is decarboxylated by aromatic L-amino acid decarboxylase to serotonin, increasing serotonin synthesis. Buspirone is a serotonin 5-HT1A partial agonist, so combined exposure can overstimulate serotonergic pathways in susceptible patients.", "evidenceLevel": "emerging", "sources": [ { "text": "Manos GH. Possible serotonin syndrome associated with buspirone added to fluoxetine. Ann Pharmacother. 2000;34(7-8):871-874.", "pmid": "10928399", "doi": "10.1345/aph.19341", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10928399/", "publicSourceType": "PMID" }, { "text": "Maffei ME. 5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology. Int J Mol Sci. 2020;22(1):181.", "pmid": "33375373", "doi": "10.3390/ijms22010181", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33375373/", "publicSourceType": "PMID" }, { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "5-HTP can add serotonin synthesis to buspirone's serotonergic receptor activity.", "clinicalSignificance": "The combination can make serotonin-toxicity symptoms more likely, particularly when other serotonergic drugs are also present.", "managementStrategy": "Avoid 5-HTP during buspirone therapy unless specifically supervised and monitor for serotonin-toxicity symptoms after any overlap.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Buspirone", "supplementBName": "L-Tryptophan", "interactionType": "caution", "severity": "serious", "description": "L-Tryptophan is the dietary amino acid precursor for brain serotonin synthesis. Buspirone has serotonergic 5-HT1A activity, so concentrated tryptophan supplements can add to the same pathway and may increase risk of serotonin toxicity. The risk is higher if another serotonergic medication or supplement is also in the stack.", "recommendation": "Avoid high-dose L-Tryptophan supplements while taking buspirone unless your prescriber is deliberately supervising the combination. Normal protein foods are not the concern; concentrated sleep or mood products are. Seek urgent care for fever, confusion, tremor, diarrhea, sweating, or muscle jerks after overlap.", "minimumTimeSeparation": null, "mechanism": "L-Tryptophan crosses the blood-brain barrier and supplies substrate for tryptophan hydroxylase, the rate-limiting step in serotonin synthesis. Buspirone activates 5-HT1A receptors, creating a plausible pharmacodynamic stacking risk when serotonin precursor availability is pushed upward.", "evidenceLevel": "emerging", "sources": [ { "text": "Manos GH. Possible serotonin syndrome associated with buspirone added to fluoxetine. Ann Pharmacother. 2000;34(7-8):871-874.", "pmid": "10928399", "doi": "10.1345/aph.19341", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10928399/", "publicSourceType": "PMID" }, { "text": "Richard DM, Dawes MA, Mathias CW, Acheson A, Hill-Kapturczak N, Dougherty DM. L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications. Int J Tryptophan Res. 2009;2:45-60.", "pmid": "20651948", "doi": "10.4137/ijtr.s2129", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20651948/", "publicSourceType": "PMID" }, { "text": "Pope HG, Jonas JM, Hudson JI, Kafka MP. Toxic reactions to the combination of monoamine oxidase inhibitors and tryptophan. Am J Psychiatry. 1985;142(4):491-492.", "pmid": "3976924", "doi": "10.1176/ajp.142.4.491", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3976924/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "L-Tryptophan may increase serotonin synthesis while buspirone stimulates serotonergic receptors.", "clinicalSignificance": "This can contribute to clinically important serotonin excess when combined with buspirone, especially in multi-drug serotonergic regimens.", "managementStrategy": "Avoid concentrated L-Tryptophan supplements with buspirone unless a clinician is monitoring the combination.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Buspirone", "supplementBName": "SAMe", "interactionType": "caution", "severity": "moderate", "description": "SAMe has antidepressant effects and evidence of serotonergic involvement, including 5-HT1A pathway activation in preclinical work. Buspirone also acts at 5-HT1A receptors, so the combination may increase restlessness, sweating, tremor, diarrhea, insomnia, or other serotonin-excess symptoms in susceptible people. Risk is higher when SAMe is added to other antidepressants or serotonergic drugs.", "recommendation": "Do not start SAMe on top of buspirone without discussing the dose and monitoring plan with your prescriber. If the combination is used, start low, avoid adding other serotonergic products, and stop SAMe if you develop new agitation, tremor, sweating, diarrhea, or muscle jerks. Seek urgent care for fever, confusion, rigidity, or clonus.", "minimumTimeSeparation": null, "mechanism": "SAMe participates in one-carbon methylation reactions and has antidepressant activity with evidence implicating serotonin synthesis and 5-HT1A receptor activation. Buspirone is a 5-HT1A partial agonist, so the combination can converge on serotonergic signaling.", "evidenceLevel": "emerging", "sources": [ { "text": "Sales AJ, Maciel IS, Crestani CC, Guimarães FS, Joca SR. S-adenosyl-l-methionine antidepressant-like effects involve activation of 5-HT1A receptors. Neurochem Int. 2023;162:105442.", "pmid": "36402294", "doi": "10.1016/j.neuint.2022.105442", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36402294/", "publicSourceType": "PMID" }, { "text": "Papakostas GI, Mischoulon D, Shyu I, Alpert JE, Fava M. S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. Am J Psychiatry. 2010;167(8):942-948.", "pmid": "20595412", "doi": "10.1176/appi.ajp.2009.09081198", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20595412/", "publicSourceType": "PMID" }, { "text": "Manos GH. Possible serotonin syndrome associated with buspirone added to fluoxetine. Ann Pharmacother. 2000;34(7-8):871-874.", "pmid": "10928399", "doi": "10.1345/aph.19341", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10928399/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "SAMe may add serotonergic activation to buspirone therapy.", "clinicalSignificance": "Most patients will not develop severe toxicity, but unsupervised stacking can cause clinically meaningful serotonergic adverse effects.", "managementStrategy": "Use SAMe with buspirone only with clinician awareness and stop it if serotonin-excess symptoms appear.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Buspirone", "supplementBName": "St. John's Wort", "interactionType": "caution", "severity": "serious", "description": "A published case report describes serotonin syndrome after combining buspirone with St. John's Wort. St. John's Wort also has broad drug-interaction potential through CYP3A and P-glycoprotein induction, which can make psychiatric drug response less predictable. The combination is especially risky if any other serotonergic drug is present.", "recommendation": "Avoid St. John's Wort while taking buspirone unless your prescriber specifically directs otherwise. Do not use dose spacing as a workaround because both serotonergic effects and enzyme induction can persist. Seek urgent care for fever, confusion, tremor, sweating, diarrhea, muscle rigidity, or clonus.", "minimumTimeSeparation": null, "mechanism": "St. John's Wort contains hyperforin and other constituents that affect monoamine signaling and induce CYP3A/P-glycoprotein through pregnane X receptor activation. Buspirone is a serotonergic 5-HT1A partial agonist and a CYP3A substrate, so the combination can create both pharmacodynamic serotonin-toxicity risk and pharmacokinetic unpredictability.", "evidenceLevel": "moderate", "sources": [ { "text": "Dannawi M. Possible serotonin syndrome after combination of buspirone and St John's Wort. J Psychopharmacol. 2002;16(4):401.", "pmid": "12503845", "doi": "10.1177/026988110201600420", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12503845/", "publicSourceType": "PMID" }, { "text": "Nicolussi S, Drewe J, Butterweck V, Meyer Zu Schwabedissen HE. Clinical relevance of St. John's wort drug interactions revisited. Br J Pharmacol. 2020;177(6):1212-1226.", "pmid": "31742659", "doi": "10.1111/bph.14936", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31742659/", "publicSourceType": "PMID" }, { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "St. John's Wort can add serotonergic activity and alter buspirone exposure unpredictably.", "clinicalSignificance": "This pair has direct case-report evidence for serotonin syndrome and a strong mechanistic basis for avoiding unsupervised overlap.", "managementStrategy": "Avoid St. John's Wort during buspirone therapy and monitor urgently for serotonin-toxicity symptoms after accidental overlap.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Bupropion", "supplementBName": "Nicotine", "interactionType": "caution", "severity": "moderate", "description": "Bupropion and nicotine replacement have been intentionally combined for smoking cessation, and the combination can improve quit rates for some people. The same combination can also increase insomnia, headache, jitteriness, palpitations, and blood pressure concerns, especially if nicotine is used heavily through vaping, pouches, or multiple replacement products. Bupropion also lowers seizure threshold, so excess stimulant-like exposure matters.", "recommendation": "Use nicotine with bupropion only as part of a planned cessation strategy or with your clinician's knowledge. Check blood pressure and pulse if you use nicotine frequently or develop headaches, palpitations, anxiety, or chest tightness. Seek urgent care for chest pain, fainting, severe shortness of breath, seizure, or a new irregular heartbeat.", "minimumTimeSeparation": null, "mechanism": "Bupropion inhibits norepinephrine and dopamine reuptake and antagonizes nicotinic acetylcholine receptors. Nicotine activates nicotinic receptors and increases sympathetic catecholamine release, so the combination can support cessation while adding autonomic and neurostimulant adverse-effect burden.", "evidenceLevel": "strong", "sources": [ { "text": "Jorenby DE, Leischow SJ, Nides MA, Rennard SI, Johnston JA, Hughes AR, Smith SS, et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med. 1999;340(9):685-691.", "pmid": "10053177", "doi": "10.1056/NEJM199903043400903", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10053177/", "publicSourceType": "PMID" }, { "text": "Jamerson BD, Nides M, Jorenby DE, Donahue R, Garrett P, Johnston JA, Fiore MC, Rennard SI. Late-term smoking cessation despite initial failure: an evaluation of bupropion sustained release, nicotine patch, combination therapy, and placebo. Clin Ther. 2001;23(5):744-752.", "pmid": "11394732", "doi": "10.1016/s0149-2918(01)80023-0", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11394732/", "publicSourceType": "PMID" }, { "text": "Wang M, Liu Z, Zhou X, Shi Y, Ji T, He J, Cheng A, et al. Efficacy of combined nicotine replacement therapy (NRT) and bupropion compared to bupropion alone for smoking cessation: a systematic review and meta-analysis. Addict Behav. 2026;175:108614.", "pmid": "41539116", "doi": "10.1016/j.addbeh.2026.108614", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41539116/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Bupropion plus nicotine can improve smoking-cessation outcomes but can also add stimulant-like cardiovascular and neurologic adverse effects.", "clinicalSignificance": "Patients using high-dose or frequent nicotine may experience more palpitations, insomnia, blood pressure elevation, or seizure-threshold concerns.", "managementStrategy": "Use nicotine with bupropion deliberately, avoid high nicotine exposure, and monitor blood pressure, pulse, insomnia, and neurologic symptoms.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Amphetamine/Dextroamphetamine", "supplementBName": "Vitamin C", "interactionType": "timingSensitive", "severity": "moderate", "description": "High-dose Vitamin C products are usually ascorbic acid, and acidifying conditions can lower amphetamine blood levels by increasing renal clearance of amphetamine. This can make amphetamine/dextroamphetamine feel weaker or wear off sooner in some patients, though ordinary dietary vitamin C is less likely to cause a major effect. The risk is most relevant with large supplemental doses, acidic powders, or inconsistent timing.", "recommendation": "Keep Vitamin C intake consistent and avoid taking high-dose Vitamin C within 2 hours of amphetamine/dextroamphetamine. If you use gram-level Vitamin C daily, take it later in the day and tell your prescriber if your stimulant effect changes. Do not increase stimulant doses on your own to compensate.", "minimumTimeSeparation": 120, "mechanism": "Amphetamine is a weak base with renal elimination that is sensitive to urinary pH; lower urinary pH increases ionization and renal excretion, reducing systemic exposure. Ascorbic acid products can contribute to acidifying conditions, while routine food-level vitamin C is less predictable and usually lower risk.", "evidenceLevel": "moderate", "sources": [ { "text": "Wan SH, Matin SB, Azarnoff DL. Kinetics, salivary excretion of amphetamine isomers, and effect of urinary pH. Clin Pharmacol Ther. 1978;23(5):585-590.", "pmid": "25157", "doi": "10.1002/cpt1978235585", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25157/", "publicSourceType": "PMID" }, { "text": "Huang W, Czuba LC, Isoherranen N. Mechanistic PBPK Modeling of Urine pH Effect on Renal and Systemic Disposition of Methamphetamine and Amphetamine. J Pharmacol Exp Ther. 2020;373(3):488-501.", "pmid": "32198137", "doi": "10.1124/jpet.120.264994", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32198137/", "publicSourceType": "PMID" }, { "text": "Hetey SK, Kleinberg ML, Parker WD, Johnson EW. Effect of ascorbic acid on urine pH in patients with injured spinal cords. Am J Hosp Pharm. 1980;37(2):235-237.", "pmid": "7361797", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7361797/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "High-dose Vitamin C may reduce amphetamine/dextroamphetamine exposure and shorten clinical effect.", "clinicalSignificance": "Inconsistent high-dose Vitamin C timing can look like stimulant underdosing or variable medication response.", "managementStrategy": "Separate high-dose Vitamin C from amphetamine/dextroamphetamine by at least 2 hours and keep daily intake consistent.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Lisdexamfetamine", "supplementBName": "Vitamin C", "interactionType": "timingSensitive", "severity": "moderate", "description": "Lisdexamfetamine is converted to dextroamphetamine after absorption, and the active amphetamine exposure can be affected by urinary pH. High-dose Vitamin C as ascorbic acid may increase amphetamine clearance and reduce duration or intensity, although lisdexamfetamine absorption itself is less pH-sensitive than immediate-release amphetamine salts. The concern is mainly large supplemental doses or inconsistent timing, not normal vitamin C foods.", "recommendation": "Avoid high-dose Vitamin C within 2 hours of lisdexamfetamine and keep your daily Vitamin C routine consistent. If you take gram-level Vitamin C, consider taking it later in the day and watch for shorter medication duration. Do not raise lisdexamfetamine doses without your prescriber if Vitamin C timing changes the effect.", "minimumTimeSeparation": 120, "mechanism": "Lisdexamfetamine is a prodrug that produces systemic dextroamphetamine exposure. Amphetamine renal clearance is urine-pH dependent; acidifying conditions increase ionized amphetamine in renal tubules and can lower systemic exposure.", "evidenceLevel": "moderate", "sources": [ { "text": "Dolder PC, Strajhar P, Vizeli P, Hammann F, Odermatt A, Liechti ME. Pharmacokinetics and Pharmacodynamics of Lisdexamfetamine Compared with D-Amphetamine in Healthy Subjects. Front Pharmacol. 2017;8:617.", "pmid": "28936175", "doi": "10.3389/fphar.2017.00617", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28936175/", "publicSourceType": "PMID" }, { "text": "Wan SH, Matin SB, Azarnoff DL. Kinetics, salivary excretion of amphetamine isomers, and effect of urinary pH. Clin Pharmacol Ther. 1978;23(5):585-590.", "pmid": "25157", "doi": "10.1002/cpt1978235585", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25157/", "publicSourceType": "PMID" }, { "text": "Huang W, Czuba LC, Isoherranen N. Mechanistic PBPK Modeling of Urine pH Effect on Renal and Systemic Disposition of Methamphetamine and Amphetamine. J Pharmacol Exp Ther. 2020;373(3):488-501.", "pmid": "32198137", "doi": "10.1124/jpet.120.264994", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32198137/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "High-dose Vitamin C may lower active dextroamphetamine exposure after lisdexamfetamine conversion.", "clinicalSignificance": "Variable Vitamin C supplement timing can contribute to inconsistent lisdexamfetamine duration or perceived loss of effect.", "managementStrategy": "Separate high-dose Vitamin C from lisdexamfetamine by at least 2 hours and keep larger daily doses consistent.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Cannabis (THC-Dominant)", "interactionType": "caution", "severity": "dangerous", "description": "THC-dominant cannabis can raise INR and bleeding risk in people taking warfarin. Case reports describe supratherapeutic INR after recreational or medical cannabis exposure, and THC can inhibit CYP2C9, the main pathway for the more potent S-warfarin enantiomer. The risk is highest when cannabis dose, route, or frequency changes suddenly.", "recommendation": "Do not start, stop, or sharply change THC-dominant cannabis use without telling your anticoagulation clinic. Ask for an INR check within 3-7 days after any change and again after the pattern stabilizes. Seek urgent care for black stools, vomiting blood, severe headache, weakness, or bleeding that does not stop.", "minimumTimeSeparation": null, "mechanism": "Delta-9-THC can inhibit CYP2C9-mediated warfarin metabolism, increasing S-warfarin exposure and INR. Cannabinoid products may also vary widely in THC/CBD content, making the pharmacokinetic effect hard to predict.", "evidenceLevel": "moderate", "sources": [ { "text": "Damkier P, Lassen D, Christensen MMH, Madsen KG, Hellfritzsch M, Pottegård A. Interaction between warfarin and cannabis. Basic Clin Pharmacol Toxicol. 2019;124(1):28-31.", "pmid": "30326170", "doi": "10.1111/bcpt.13152", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30326170/", "publicSourceType": "PMID" }, { "text": "Greger J, Bates V, Mechtler L, Gengo F. A Review of Cannabis and Interactions With Anticoagulant and Antiplatelet Agents. J Clin Pharmacol. 2020;60(4):432-438.", "pmid": "31724188", "doi": "10.1002/jcph.1557", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31724188/", "publicSourceType": "PMID" }, { "text": "Smythe MA, Wu W, Garwood CL. Anticoagulant drug-drug interactions with cannabinoids: A systematic review. Pharmacotherapy. 2023;43(12):1327-1338.", "pmid": "37740600", "doi": "10.1002/phar.2881", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37740600/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "THC-dominant cannabis may increase warfarin exposure and raise INR.", "clinicalSignificance": "Warfarin has a narrow therapeutic index, so unexpected INR elevation can lead to major bleeding.", "managementStrategy": "Avoid abrupt cannabis changes and check INR within 3-7 days of starting, stopping, or changing dose.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Prasugrel", "supplementBName": "Nattokinase", "interactionType": "caution", "severity": "dangerous", "description": "Nattokinase has fibrinolytic and anticoagulant effects that can stack with prasugrel's potent antiplatelet effect. A case report describes cerebellar hemorrhage after nattokinase was added to aspirin, and human studies show nattokinase can reduce fibrinogen and factors VII and VIII. Combining it with prasugrel may increase bleeding risk, especially after stent placement, stroke, surgery, or in older adults.", "recommendation": "Avoid nattokinase while taking prasugrel unless your cardiologist specifically approves it. Do not use nattokinase as a substitute for prescribed antiplatelet therapy. Seek urgent care for severe headache, weakness on one side, black stools, vomiting blood, or bleeding that does not stop.", "minimumTimeSeparation": null, "mechanism": "Prasugrel irreversibly inhibits platelet P2Y12 receptors, reducing ADP-mediated platelet aggregation. Nattokinase cleaves fibrin and can lower fibrinogen, factor VII, and factor VIII, creating additive impairment of clot formation and clot stability.", "evidenceLevel": "emerging", "sources": [ { "text": "Chang YY, Liu JS, Lai SL, Wu HS, Lan MY. Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. Intern Med. 2008;47(5):467-469.", "pmid": "18310985", "doi": "10.2169/internalmedicine.47.0620", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18310985/", "publicSourceType": "PMID" }, { "text": "Hsia CH, Shen MC, Lin JS, Wen YK, Hwang KL, Cham TM, et al. Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects. Nutr Res. 2009;29(3):190-196.", "pmid": "19358933", "doi": "10.1016/j.nutres.2009.01.009", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19358933/", "publicSourceType": "PMID" }, { "text": "Kurosawa Y, Nirengi S, Homma T, Esaki K, Ohta M, Clark JF, et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep. 2015;5:11601.", "pmid": "26109079", "doi": "10.1038/srep11601", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26109079/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Nattokinase may add fibrinolytic and anticoagulant pressure to prasugrel's antiplatelet effect.", "clinicalSignificance": "Prasugrel is already high bleeding risk, and nattokinase has case-report evidence of intracranial hemorrhage with antiplatelet therapy.", "managementStrategy": "Avoid nattokinase during prasugrel therapy unless the prescribing cardiologist is supervising the combination.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Ticagrelor", "supplementBName": "Nattokinase", "interactionType": "caution", "severity": "dangerous", "description": "Nattokinase can add fibrinolytic and anticoagulant effects to ticagrelor's potent antiplatelet action. Human studies show nattokinase lowers clotting-related proteins, and a published case report describes cerebellar hemorrhage after nattokinase was combined with aspirin. The combination is especially concerning in anyone with prior stroke, recent PCI, dual antiplatelet therapy, kidney disease, or upcoming procedures.", "recommendation": "Avoid nattokinase while taking ticagrelor unless your cardiologist has explicitly approved it. Do not manage this by separating doses because both effects persist beyond the dosing window. Get urgent help for severe headache, one-sided weakness, black stools, vomiting blood, or uncontrolled bleeding.", "minimumTimeSeparation": null, "mechanism": "Ticagrelor reversibly inhibits platelet P2Y12 receptors and reduces ADP-driven platelet activation. Nattokinase promotes fibrinolysis and can lower fibrinogen, factor VII, and factor VIII, so the combination can impair both platelet plug formation and fibrin clot stability.", "evidenceLevel": "emerging", "sources": [ { "text": "Chang YY, Liu JS, Lai SL, Wu HS, Lan MY. Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. Intern Med. 2008;47(5):467-469.", "pmid": "18310985", "doi": "10.2169/internalmedicine.47.0620", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18310985/", "publicSourceType": "PMID" }, { "text": "Hsia CH, Shen MC, Lin JS, Wen YK, Hwang KL, Cham TM, et al. Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects. Nutr Res. 2009;29(3):190-196.", "pmid": "19358933", "doi": "10.1016/j.nutres.2009.01.009", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19358933/", "publicSourceType": "PMID" }, { "text": "Kurosawa Y, Nirengi S, Homma T, Esaki K, Ohta M, Clark JF, et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep. 2015;5:11601.", "pmid": "26109079", "doi": "10.1038/srep11601", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26109079/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Nattokinase may amplify ticagrelor-associated bleeding risk through fibrinolytic and anticoagulant effects.", "clinicalSignificance": "Ticagrelor is commonly used after acute coronary syndrome or stenting, where unsupervised bleeding-risk supplements can be dangerous.", "managementStrategy": "Avoid nattokinase during ticagrelor therapy unless the prescribing cardiologist is supervising the combination.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Glimepiride", "supplementBName": "Berberine HCl", "interactionType": "caution", "severity": "serious", "description": "Berberine HCl can lower fasting glucose, post-meal glucose, and HbA1c in type 2 diabetes. Glimepiride forces pancreatic insulin release and can cause hypoglycemia, so adding berberine can make low blood sugar more likely, especially with missed meals, alcohol use, older age, kidney impairment, or aggressive carbohydrate restriction. Berberine may also reduce CYP2C9 activity, a pathway involved in glimepiride clearance.", "recommendation": "Do not start berberine HCl on glimepiride without a glucose-monitoring plan. Check glucose more often before meals and at bedtime for the first 2-4 weeks and ask your prescriber whether the glimepiride dose should be reduced. Treat sweating, shakiness, confusion, or glucose below 70 mg/dL promptly with fast carbohydrate.", "minimumTimeSeparation": null, "mechanism": "Berberine improves glycemia through AMPK-related metabolic effects, insulin receptor signaling, gut microbiome effects, and glucose-dependent insulinotropic activity. Repeated berberine dosing has decreased CYP2C9 activity in humans, while glimepiride is primarily metabolized by CYP2C9.", "evidenceLevel": "moderate", "sources": [ { "text": "Xie W, Su F, Wang G, Peng Z, Xu Y, Zhang Y, et al. Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis. Front Pharmacol. 2022;13:1015045.", "pmid": "36467075", "doi": "10.3389/fphar.2022.1015045", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36467075/", "publicSourceType": "PMID" }, { "text": "Dong H, Wang N, Zhao L, Lu F. Berberine in the treatment of type 2 diabetes mellitus: a systemic review and meta-analysis. Evid Based Complement Alternat Med. 2012;2012:591654.", "pmid": "23118793", "doi": "10.1155/2012/591654", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23118793/", "publicSourceType": "PMID" }, { "text": "Guo Y, Chen Y, Tan ZR, Klaassen CD, Zhou HH. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol. 2012;68(2):213-217.", "pmid": "21870106", "doi": "10.1007/s00228-011-1108-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21870106/", "publicSourceType": "PMID" }, { "text": "Niemi M, Neuvonen PJ, Kivistö KT. Effect of gemfibrozil on the pharmacokinetics and pharmacodynamics of glimepiride. Clin Pharmacol Ther. 2001;70(5):439-445.", "pmid": "11719730", "doi": "10.1067/mcp.2001.119723", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11719730/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Berberine HCl can add glucose-lowering and may increase glimepiride exposure, raising hypoglycemia risk.", "clinicalSignificance": "Sulfonylurea-related hypoglycemia can be prolonged and may require emergency care.", "managementStrategy": "Use only with prescriber awareness, frequent home glucose checks for 2-4 weeks, and possible glimepiride dose reduction.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Insulin Aspart", "supplementBName": "Fenugreek", "interactionType": "caution", "severity": "serious", "description": "Fenugreek can lower glucose in people with diabetes and may improve glycemic control when added to usual therapy, including insulin. Insulin aspart acts quickly around meals, so extra glucose-lowering from fenugreek can increase the chance of post-meal or delayed hypoglycemia. Risk is higher if meal carbohydrates are reduced, meals are delayed, or insulin doses are not adjusted.", "recommendation": "Do not add fenugreek to insulin aspart without checking glucose more often. Monitor before meals, 2 hours after meals, and at bedtime for the first 1-2 weeks, and discuss whether meal insulin needs adjustment. Carry fast carbohydrate and treat glucose below 70 mg/dL promptly.", "minimumTimeSeparation": null, "mechanism": "Fenugreek seed fiber can slow carbohydrate absorption, while 4-hydroxyisoleucine and other constituents may stimulate glucose-dependent insulin release and improve insulin signaling. These effects can add to rapid-acting insulin aspart's prandial glucose-lowering.", "evidenceLevel": "moderate", "sources": [ { "text": "Shabil M, Bushi G, Bodige PK, Maradi PS, Patra SK, Smitha R, et al. Effect of Fenugreek on Hyperglycemia: A Systematic Review and Meta-Analysis. Medicina (Kaunas). 2023;59(2):248.", "pmid": "36837450", "doi": "10.3390/medicina59020248", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36837450/", "publicSourceType": "PMID" }, { "text": "Ranade M, Mudgalkar N. A simple dietary addition of fenugreek seed leads to the reduction in blood glucose levels: A parallel group, randomized single-blind trial. Ayu. 2017;38(1-2):24-27.", "pmid": "29861588", "doi": "10.4103/ayu.AYU_209_15", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29861588/", "publicSourceType": "PMID" }, { "text": "Gupta A, Gupta R, Lal B. Effect of Trigonella foenum-graecum (fenugreek) seeds on glycaemic control and insulin resistance in type 2 diabetes mellitus: a double blind placebo controlled study. J Assoc Physicians India. 2001;49:1057-1061.", "pmid": "11868855", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11868855/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Fenugreek may add to insulin aspart's meal-time glucose-lowering effect.", "clinicalSignificance": "Rapid-acting insulin has a narrow safety margin, and added glucose-lowering can trigger symptomatic hypoglycemia.", "managementStrategy": "Increase home glucose monitoring for 1-2 weeks and adjust prandial insulin only with the diabetes prescriber.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Insulin Lispro", "supplementBName": "Fenugreek", "interactionType": "caution", "severity": "serious", "description": "Fenugreek can lower fasting and post-meal glucose in people with diabetes. Insulin lispro is a rapid-acting meal insulin, so adding fenugreek can increase the risk of postprandial or delayed hypoglycemia if insulin doses are not adjusted. Missed meals, smaller carbohydrate intake, exercise, alcohol, and kidney disease increase the risk.", "recommendation": "Do not start fenugreek with insulin lispro without a monitoring plan. Check glucose before meals, 2 hours after meals, and at bedtime for the first 1-2 weeks, and ask whether your meal insulin ratio needs adjustment. Keep fast carbohydrate available.", "minimumTimeSeparation": null, "mechanism": "Fenugreek seed fiber delays carbohydrate absorption, and 4-hydroxyisoleucine may stimulate glucose-dependent insulin secretion and improve insulin signaling. These effects can compound insulin lispro's rapid prandial glucose-lowering.", "evidenceLevel": "moderate", "sources": [ { "text": "Shabil M, Bushi G, Bodige PK, Maradi PS, Patra SK, Smitha R, et al. Effect of Fenugreek on Hyperglycemia: A Systematic Review and Meta-Analysis. Medicina (Kaunas). 2023;59(2):248.", "pmid": "36837450", "doi": "10.3390/medicina59020248", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36837450/", "publicSourceType": "PMID" }, { "text": "Ranade M, Mudgalkar N. A simple dietary addition of fenugreek seed leads to the reduction in blood glucose levels: A parallel group, randomized single-blind trial. Ayu. 2017;38(1-2):24-27.", "pmid": "29861588", "doi": "10.4103/ayu.AYU_209_15", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29861588/", "publicSourceType": "PMID" }, { "text": "Gupta A, Gupta R, Lal B. Effect of Trigonella foenum-graecum (fenugreek) seeds on glycaemic control and insulin resistance in type 2 diabetes mellitus: a double blind placebo controlled study. J Assoc Physicians India. 2001;49:1057-1061.", "pmid": "11868855", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11868855/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Fenugreek may add to insulin lispro's meal-time glucose-lowering effect.", "clinicalSignificance": "The combination can cause symptomatic hypoglycemia if meal insulin is not adjusted to the new glucose pattern.", "managementStrategy": "Increase glucose checks for 1-2 weeks and coordinate any meal-insulin adjustment with the diabetes prescriber.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Insulin Aspart", "supplementBName": "Alpha-Lipoic Acid", "interactionType": "caution", "severity": "serious", "description": "Alpha-lipoic acid may improve glycemic control in diabetes and has also been linked to insulin autoimmune syndrome, a rare cause of severe spontaneous hypoglycemia. When layered onto rapid-acting insulin aspart, any increase in insulin sensitivity or unexpected hypoglycemia can be clinically important. Risk is higher in people with frequent lows, tight glucose targets, low-carbohydrate diets, or prior unexplained hypoglycemia.", "recommendation": "Start alpha-lipoic acid only with closer glucose monitoring if you use insulin aspart. Check glucose more often for the first 1-2 weeks and whenever the dose changes, especially after meals and overnight. Stop alpha-lipoic acid and contact your clinician if you develop repeated unexplained lows.", "minimumTimeSeparation": null, "mechanism": "Alpha-lipoic acid may improve insulin-mediated glucose disposal and oxidative-stress pathways. It can also trigger insulin autoantibodies in genetically susceptible people, producing delayed hyperinsulinemic hypoglycemia that is not solved by dose spacing.", "evidenceLevel": "emerging", "sources": [ { "text": "Ebada MA, Fayed N, Fayed L, Alkanj S, Abdelkarim A, Youssef G, et al. Efficacy of Alpha-lipoic Acid in The Management of Diabetes Mellitus: A Systematic Review and Meta-analysis. Iran J Pharm Res. 2019;18(4):2144-2156.", "pmid": "32184879", "doi": "10.22037/ijpr.2019.1100842", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32184879/", "publicSourceType": "PMID" }, { "text": "Takeuchi Y, Miyamoto T, Kakizawa T, Shigematsu S, Hashizume K. Insulin Autoimmune Syndrome possibly caused by alpha lipoic acid. Intern Med. 2007;46(5):237-239.", "pmid": "17329919", "doi": "10.2169/internalmedicine.46.1893", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17329919/", "publicSourceType": "PMID" }, { "text": "Moffa S, Improta I, Rocchetti S, Mezza T, Giaccari A. Potential cause-effect relationship between insulin autoimmune syndrome and alpha lipoic acid: Two case reports. Nutrition. 2019;57:1-4.", "pmid": "30086435", "doi": "10.1016/j.nut.2018.04.010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30086435/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Alpha-lipoic acid may increase hypoglycemia risk in a patient using insulin aspart.", "clinicalSignificance": "Rapid-acting insulin-related lows can be sudden, and alpha-lipoic-acid-associated autoimmune hypoglycemia may be severe and recurrent.", "managementStrategy": "Monitor glucose more often after starting or changing alpha-lipoic acid and stop it if unexplained recurrent lows occur.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Insulin Lispro", "supplementBName": "Alpha-Lipoic Acid", "interactionType": "caution", "severity": "serious", "description": "Alpha-lipoic acid may improve glycemic control and insulin sensitivity in diabetes, and rare case reports link it to insulin autoimmune syndrome with severe hypoglycemia. Insulin lispro already has a rapid glucose-lowering effect around meals, so added glucose-lowering or unexpected autoimmune hypoglycemia can make lows more likely. The risk is greatest with tight insulin dosing, low-carbohydrate intake, exercise, alcohol, or prior unexplained lows.", "recommendation": "Use alpha-lipoic acid with insulin lispro only with extra glucose monitoring. Check glucose more often for 1-2 weeks after starting or changing the dose, including after meals and overnight if you have a CGM or a history of nocturnal lows. Stop alpha-lipoic acid and contact your clinician for repeated unexplained hypoglycemia.", "minimumTimeSeparation": null, "mechanism": "Alpha-lipoic acid may improve insulin-mediated glucose uptake and metabolic control. In susceptible patients, its sulfhydryl-related chemistry can trigger insulin autoantibodies, causing delayed hyperinsulinemic hypoglycemia independent of insulin dose timing.", "evidenceLevel": "emerging", "sources": [ { "text": "Ebada MA, Fayed N, Fayed L, Alkanj S, Abdelkarim A, Youssef G, et al. Efficacy of Alpha-lipoic Acid in The Management of Diabetes Mellitus: A Systematic Review and Meta-analysis. Iran J Pharm Res. 2019;18(4):2144-2156.", "pmid": "32184879", "doi": "10.22037/ijpr.2019.1100842", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32184879/", "publicSourceType": "PMID" }, { "text": "Takeuchi Y, Miyamoto T, Kakizawa T, Shigematsu S, Hashizume K. Insulin Autoimmune Syndrome possibly caused by alpha lipoic acid. Intern Med. 2007;46(5):237-239.", "pmid": "17329919", "doi": "10.2169/internalmedicine.46.1893", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17329919/", "publicSourceType": "PMID" }, { "text": "Moffa S, Improta I, Rocchetti S, Mezza T, Giaccari A. Potential cause-effect relationship between insulin autoimmune syndrome and alpha lipoic acid: Two case reports. Nutrition. 2019;57:1-4.", "pmid": "30086435", "doi": "10.1016/j.nut.2018.04.010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30086435/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Alpha-lipoic acid may increase hypoglycemia risk in a patient using insulin lispro.", "clinicalSignificance": "Meal-time insulin lows can be abrupt, and alpha-lipoic-acid-associated autoimmune hypoglycemia may be prolonged or recurrent.", "managementStrategy": "Increase glucose monitoring after starting or changing alpha-lipoic acid and stop it if unexplained recurrent lows occur.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Insulin Aspart", "supplementBName": "Chromium", "interactionType": "caution", "severity": "serious", "description": "Chromium can improve glucose and insulin responses in some people with diabetes or insulin resistance. Added to insulin aspart, this may reduce insulin needs and increase the risk of hypoglycemia if meal doses are not adjusted. The risk is most relevant when chromium is started at high doses, diet changes at the same time, or glucose is already tightly controlled.", "recommendation": "If you use insulin aspart, start chromium only with more frequent glucose checks. Monitor before meals, 2 hours after meals, and at bedtime for 1-2 weeks, and ask your diabetes clinician whether insulin-to-carbohydrate ratios or correction doses should change. Treat glucose below 70 mg/dL promptly.", "minimumTimeSeparation": null, "mechanism": "Chromium may enhance insulin receptor signaling and improve peripheral glucose uptake in insulin-resistant states. This can add to insulin aspart's rapid stimulation of glucose uptake and suppression of hepatic glucose output after meals.", "evidenceLevel": "moderate", "sources": [ { "text": "Althuis MD, Jordan NE, Ludington EA, Wittes JT. Glucose and insulin responses to dietary chromium supplements: a meta-analysis. Am J Clin Nutr. 2002;76(1):148-155.", "pmid": "12081828", "doi": "10.1093/ajcn/76.1.148", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12081828/", "publicSourceType": "PMID" }, { "text": "Singer GM, Geohas J. The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial. Diabetes Technol Ther. 2006;8(6):636-643.", "pmid": "17109595", "doi": "10.1089/dia.2006.8.636", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17109595/", "publicSourceType": "PMID" }, { "text": "Havel PJ. A scientific review: the role of chromium in insulin resistance. Diabetes Educ. 2004;Suppl:2-14.", "pmid": "15208835", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15208835/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Chromium may increase the glucose-lowering effect of insulin aspart.", "clinicalSignificance": "Insulin aspart dosing is meal-sensitive, so even modest changes in insulin sensitivity can cause symptomatic lows.", "managementStrategy": "Increase glucose checks for 1-2 weeks after starting chromium and adjust insulin only with diabetes-clinician guidance.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Insulin Lispro", "supplementBName": "Chromium", "interactionType": "caution", "severity": "serious", "description": "Chromium can improve glucose handling in some patients with diabetes or insulin resistance. When added to insulin lispro, improved insulin sensitivity may lower insulin requirements and increase hypoglycemia risk if meal doses are unchanged. The risk is highest during the first weeks after starting chromium or when diet, exercise, or weight changes occur at the same time.", "recommendation": "Start chromium with insulin lispro only if you can monitor glucose more frequently. Check before meals, 2 hours after meals, and at bedtime for 1-2 weeks, and ask your diabetes clinician whether meal boluses or correction factors need adjustment. Keep fast carbohydrate available.", "minimumTimeSeparation": null, "mechanism": "Chromium may potentiate insulin receptor signaling and GLUT4-mediated glucose uptake in insulin-resistant tissues. This can compound insulin lispro's rapid prandial glucose-lowering effect.", "evidenceLevel": "moderate", "sources": [ { "text": "Althuis MD, Jordan NE, Ludington EA, Wittes JT. Glucose and insulin responses to dietary chromium supplements: a meta-analysis. Am J Clin Nutr. 2002;76(1):148-155.", "pmid": "12081828", "doi": "10.1093/ajcn/76.1.148", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12081828/", "publicSourceType": "PMID" }, { "text": "Singer GM, Geohas J. The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial. Diabetes Technol Ther. 2006;8(6):636-643.", "pmid": "17109595", "doi": "10.1089/dia.2006.8.636", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17109595/", "publicSourceType": "PMID" }, { "text": "Havel PJ. A scientific review: the role of chromium in insulin resistance. Diabetes Educ. 2004;Suppl:2-14.", "pmid": "15208835", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15208835/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Chromium may increase the glucose-lowering effect of insulin lispro.", "clinicalSignificance": "Meal-time insulin has a narrow safety margin, and improved insulin sensitivity can convert a usual dose into an excessive dose.", "managementStrategy": "Monitor glucose more often for 1-2 weeks and coordinate any lispro dose changes with the diabetes prescriber.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Digoxin", "supplementBName": "Vitamin D3", "interactionType": "caution", "severity": "serious", "description": "High-dose vitamin D3 can cause hypercalcemia, and hypercalcemia can make digoxin-related rhythm problems more likely. This is not a routine-dose vitamin D issue for most people, but it becomes clinically important with high-dose D3, accidental overuse, kidney disease, granulomatous disease, or concurrent calcium supplements. Symptoms can include nausea, confusion, weakness, visual changes, palpitations, or fainting.", "recommendation": "Avoid high-dose vitamin D3 while taking digoxin unless your clinician is monitoring calcium and kidney function. If you need vitamin D repletion, use the prescribed dose and ask when calcium should be rechecked. Seek urgent care for fainting, new irregular heartbeat, severe weakness, confusion, or persistent vomiting.", "minimumTimeSeparation": null, "mechanism": "Vitamin D3 toxicity increases intestinal calcium absorption and can produce hypercalcemia. Hypercalcemia increases myocardial excitability and can potentiate digoxin's sodium-potassium ATPase effects, raising susceptibility to conduction disturbances and arrhythmias.", "evidenceLevel": "moderate", "sources": [ { "text": "Vella A, Gerber TC, Hayes DL, Reeder GS. Digoxin, hypercalcaemia, and cardiac conduction. Postgrad Med J. 1999;75(887):554-556.", "pmid": "10616693", "doi": "10.1136/pgmj.75.887.554", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10616693/", "publicSourceType": "PMID" }, { "text": "Galior K, Grebe S, Singh R. Development of Vitamin D Toxicity from Overcorrection of Vitamin D Deficiency: A Review of Case Reports. Nutrients. 2018;10(8):953.", "pmid": "30042334", "doi": "10.3390/nu10080953", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30042334/", "publicSourceType": "PMID" }, { "text": "Holick MF. Vitamin D Is Not as Toxic as Was Once Thought: A Historical and an Up-to-Date Perspective. Mayo Clin Proc. 2015;90(5):561-564.", "pmid": "25939933", "doi": "10.1016/j.mayocp.2015.03.015", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25939933/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Excess vitamin D3 can cause hypercalcemia that increases susceptibility to digoxin toxicity.", "clinicalSignificance": "Digoxin has a narrow therapeutic index, and electrolyte disturbances can trigger serious arrhythmias even at usual digoxin levels.", "managementStrategy": "Avoid unsupervised high-dose D3; monitor serum calcium, renal function, and digoxin toxicity symptoms when repleting vitamin D.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Digoxin", "supplementBName": "Calcium", "interactionType": "caution", "severity": "serious", "description": "Large or repeated calcium supplement doses can cause hypercalcemia in susceptible people, particularly with kidney disease, dehydration, thiazide use, or concurrent vitamin D. Hypercalcemia can increase the heart's sensitivity to digoxin and may contribute to conduction problems or arrhythmias. Routine dietary calcium is not the concern; high-dose supplementation and calcium-alkali syndrome are.", "recommendation": "Do not take high-dose calcium supplements while on digoxin unless your clinician is monitoring calcium and kidney function. Stay within the prescribed daily elemental calcium target and avoid stacking multiple calcium-containing products. Seek urgent care for fainting, new irregular heartbeat, severe weakness, confusion, or persistent vomiting.", "minimumTimeSeparation": null, "mechanism": "Calcium excess can increase extracellular calcium and promote intracellular calcium overload in cardiac tissue. Digoxin inhibits Na+/K+-ATPase, indirectly increasing intracellular calcium; hypercalcemia can amplify this electrophysiologic vulnerability.", "evidenceLevel": "moderate", "sources": [ { "text": "Vella A, Gerber TC, Hayes DL, Reeder GS. Digoxin, hypercalcaemia, and cardiac conduction. Postgrad Med J. 1999;75(887):554-556.", "pmid": "10616693", "doi": "10.1136/pgmj.75.887.554", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10616693/", "publicSourceType": "PMID" }, { "text": "Picolos MK, Orlander PR. Calcium carbonate toxicity: the updated milk-alkali syndrome; report of 3 cases and review of the literature. Endocr Pract. 2005;11(4):272-280.", "pmid": "16006300", "doi": "10.4158/EP.11.4.272", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16006300/", "publicSourceType": "PMID" }, { "text": "Walker MD, Shane E. Hypercalcemia: A Review. JAMA. 2022;328(16):1624-1636.", "pmid": "36282253", "doi": "10.1001/jama.2022.18331", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36282253/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "High-dose calcium supplementation can cause hypercalcemia that increases vulnerability to digoxin-related arrhythmias.", "clinicalSignificance": "Electrolyte shifts are a major driver of digoxin toxicity, and calcium supplement overuse is a preventable cause of hypercalcemia.", "managementStrategy": "Avoid unsupervised high-dose calcium and monitor serum calcium and kidney function when supplementation is medically necessary.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Doxycycline", "supplementBName": "Vitamin A", "interactionType": "caution", "severity": "serious", "description": "Doxycycline and high-dose vitamin A are both associated with intracranial hypertension, also called pseudotumor cerebri. Combining a tetracycline-class antibiotic with concentrated vitamin A or retinoid-like supplements may increase the risk of severe headache, vision changes, pulsatile tinnitus, nausea, or double vision. The concern is greatest in acne treatment, adolescents, women of childbearing age, and anyone with prior intracranial hypertension.", "recommendation": "Avoid high-dose vitamin A supplements while taking doxycycline. Standard food intake and ordinary multivitamin doses are usually not the issue, but avoid retinol-heavy products unless your clinician approves them. Stop the supplement and seek urgent evaluation for severe headache, blurred vision, double vision, or ringing in the ears.", "minimumTimeSeparation": null, "mechanism": "Tetracyclines can impair cerebrospinal fluid dynamics and have been repeatedly linked to drug-induced intracranial hypertension. Vitamin A excess and retinoids are also linked to intracranial hypertension, so the combination creates additive risk rather than a timing-sensitive absorption problem.", "evidenceLevel": "moderate", "sources": [ { "text": "Friedman DI. Medication-induced intracranial hypertension in dermatology. Am J Clin Dermatol. 2005;6(1):29-37.", "pmid": "15675888", "doi": "10.2165/00128071-200506010-00004", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15675888/", "publicSourceType": "PMID" }, { "text": "Quinn AG, Singer SB, Buncic JR. Pediatric tetracycline-induced pseudotumor cerbri. J AAPOS. 1999;3(1):53-57.", "pmid": "10071902", "doi": "10.1016/s1091-8531(99)70095-9", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10071902/", "publicSourceType": "PMID" }, { "text": "Jacobson DM, Berg R, Wall M, Digre KB, Corbett JJ, Ellefson RD. Serum vitamin A concentration is elevated in idiopathic intracranial hypertension. Neurology. 1999;53(5):1114-1118.", "pmid": "10496276", "doi": "10.1212/wnl.53.5.1114", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10496276/", "publicSourceType": "PMID" }, { "text": "Walters BN, Gubbay SS. Tetracycline and benign intracranial hypertension: report of five cases. Br Med J (Clin Res Ed). 1981;282(6257):19-20.", "pmid": "6449976", "doi": "10.1136/bmj.282.6257.19", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6449976/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "High-dose vitamin A may add to doxycycline-associated intracranial hypertension risk.", "clinicalSignificance": "Intracranial hypertension can threaten vision if symptoms are missed or treatment is delayed.", "managementStrategy": "Avoid high-dose vitamin A during doxycycline therapy and evaluate urgent neurologic or visual symptoms promptly.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Levofloxacin", "supplementBName": "Zinc Picolinate", "interactionType": "timingSensitive", "severity": "serious", "description": "Zinc picolinate can bind fluoroquinolone antibiotics in the gut and reduce absorption. Levofloxacin exposure can fall when taken with multivalent cations, which may lead to antibiotic failure or resistance, especially for serious infections. This is preventable by separating doses.", "recommendation": "Take levofloxacin at least 2 hours before or 6 hours after zinc picolinate. Do not take zinc at the same time as the antibiotic, even in a multivitamin. If you accidentally took them together, ask your prescriber or pharmacist whether the levofloxacin dose needs to be retimed.", "minimumTimeSeparation": 360, "mechanism": "Zinc is a divalent cation that can chelate fluoroquinolones in the gastrointestinal tract, forming poorly absorbed complexes. Lower levofloxacin Cmax and AUC can reduce the AUC/MIC exposure needed for bacterial killing.", "evidenceLevel": "moderate", "sources": [ { "text": "Fish DN, Chow AT. The clinical pharmacokinetics of levofloxacin. Clin Pharmacokinet. 1997;32(2):101-119.", "pmid": "9068926", "doi": "10.2165/00003088-199732020-00002", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9068926/", "publicSourceType": "PMID" }, { "text": "Pai MP, Allen SE, Amsden GW. Altered steady state pharmacokinetics of levofloxacin in adult cystic fibrosis patients receiving calcium carbonate. J Cyst Fibros. 2006;5(3):153-157.", "pmid": "16481224", "doi": "10.1016/j.jcf.2006.01.003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16481224/", "publicSourceType": "PMID" }, { "text": "Polk RE, Healy DP, Sahai J, Drwal L, Racht E. Effect of ferrous sulfate and multivitamins with zinc on absorption of ciprofloxacin in normal volunteers. Antimicrob Agents Chemother. 1989;33(11):1841-1844.", "pmid": "2610494", "doi": "10.1128/AAC.33.11.1841", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2610494/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Zinc picolinate can reduce oral levofloxacin absorption and antibiotic exposure.", "clinicalSignificance": "Reduced fluoroquinolone exposure can cause treatment failure for infections where reliable drug levels matter.", "managementStrategy": "Separate zinc picolinate from levofloxacin by taking levofloxacin 2 hours before or 6 hours after zinc.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Phenytoin", "supplementBName": "Activated Charcoal", "interactionType": "timingSensitive", "severity": "serious", "description": "Activated charcoal can strongly adsorb phenytoin in the gut and reduce its absorption. In volunteer data, charcoal given immediately after phenytoin almost completely prevented absorption, and multiple-dose charcoal is used clinically to enhance elimination in phenytoin toxicity. Unsupervised charcoal use can therefore lower phenytoin levels and increase seizure risk.", "recommendation": "Do not take activated charcoal as a wellness supplement while using phenytoin unless your clinician specifically directs it for poisoning management. If charcoal is unavoidable, separate it from phenytoin by at least 4-6 hours and ask whether a phenytoin level should be checked. Seek care promptly for breakthrough seizures, severe dizziness, or loss of coordination.", "minimumTimeSeparation": 360, "mechanism": "Activated charcoal has a large adsorptive surface and binds many organic drugs within the gastrointestinal lumen. It can prevent phenytoin absorption after oral dosing and, with repeated doses, may increase elimination by interrupting gastrointestinal recirculation.", "evidenceLevel": "strong", "sources": [ { "text": "Neuvonen PJ, Elfving SM, Elonen E. Reduction of absorption of digoxin, phenytoin and aspirin by activated charcoal in man. Eur J Clin Pharmacol. 1978;13(3):213-218.", "pmid": "668776", "doi": "10.1007/BF00609985", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/668776/", "publicSourceType": "PMID" }, { "text": "American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. J Toxicol Clin Toxicol. 1999;37(6):731-751.", "pmid": "10584586", "doi": "10.1081/clt-100102451", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10584586/", "publicSourceType": "PMID" }, { "text": "Skinner CG, Chang AS, Matthews AS, Reedy SJ, Morgan BW. Randomized controlled study on the use of multiple-dose activated charcoal in patients with supratherapeutic phenytoin levels. Clin Toxicol (Phila). 2012;50(8):764-769.", "pmid": "22897408", "doi": "10.3109/15563650.2012.716159", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22897408/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Activated charcoal can markedly reduce phenytoin absorption and lower therapeutic exposure.", "clinicalSignificance": "Subtherapeutic phenytoin levels can cause breakthrough seizures, while charcoal is also potent enough to be used in overdose management.", "managementStrategy": "Avoid nonmedical activated charcoal with phenytoin; if exposure occurs, separate by 4-6 hours and consider checking a phenytoin level.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Pramipexole", "supplementBName": "Melatonin", "interactionType": "caution", "severity": "moderate", "description": "Pramipexole can cause daytime sleepiness and sudden sleep episodes, and melatonin can add bedtime sedation and next-day grogginess. The combination is often used in people with Parkinson's disease or restless legs symptoms, but it can make driving, night walking, and fall risk more hazardous. Risk is higher during pramipexole dose increases, with older age, sleep apnea, alcohol, or other sedating medicines.", "recommendation": "Use the lowest effective melatonin dose and take it only at bedtime while on pramipexole. Do not drive or do hazardous tasks if you feel unusually sleepy, and tell your prescriber promptly if you have sudden sleep episodes. Avoid adding alcohol or other sleep aids unless your clinician approves.", "minimumTimeSeparation": null, "mechanism": "Pramipexole is a dopamine D2/D3 agonist and is associated with dopaminergic sleepiness. Melatonin activates MT1/MT2 receptors to promote sleep timing and can add pharmacodynamic sedation without a known pharmacokinetic interaction.", "evidenceLevel": "moderate", "sources": [ { "text": "Micallef J, Rey M, Eusebio A, Audebert C, Rouby F, Jouve E, et al. Antiparkinsonian drug-induced sleepiness: a double-blind placebo-controlled study of L-dopa, bromocriptine and pramipexole in healthy subjects. Br J Clin Pharmacol. 2009;67(3):333-340.", "pmid": "19220275", "doi": "10.1111/j.1365-2125.2008.03310.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19220275/", "publicSourceType": "PMID" }, { "text": "Zhang W, Chen XY, Su SW, Jia QZ, Ding T, Zhu ZN. Exogenous melatonin for sleep disorders in neurodegenerative diseases: a meta-analysis of randomized clinical trials. Neurol Sci. 2016;37(1):57-65.", "pmid": "26255301", "doi": "10.1007/s10072-015-2357-0", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26255301/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Melatonin can add to pramipexole-related sleepiness and impairment.", "clinicalSignificance": "Unexpected daytime sleepiness or nighttime imbalance can cause falls, crashes, or injury.", "managementStrategy": "Use low-dose bedtime melatonin only, avoid other sedatives, and stop driving if sudden sleepiness occurs.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Ropinirole", "supplementBName": "Melatonin", "interactionType": "caution", "severity": "moderate", "description": "Ropinirole can cause somnolence and sudden sleep episodes, and melatonin can add sleep-promoting effects. This may be useful for nighttime sleep but can worsen next-day drowsiness, slowed reaction time, and falls. The risk is most important during ropinirole titration, in older adults, and when alcohol or other sedating medicines are also present.", "recommendation": "Take melatonin only at bedtime and start with a low dose while using ropinirole. Avoid driving or hazardous work if you feel sleepy, and report sudden sleep episodes or new daytime sleepiness. Do not combine this pair with alcohol or extra sleep aids unless your prescriber is supervising it.", "minimumTimeSeparation": null, "mechanism": "Ropinirole is a dopamine D2-like receptor agonist with a recognized somnolence signal in Parkinson's disease trials. Melatonin promotes circadian sleep signaling through MT1/MT2 receptors, creating an additive pharmacodynamic sedation concern.", "evidenceLevel": "moderate", "sources": [ { "text": "Etminan M, Samii A, Takkouche B, Rochon PA. Increased risk of somnolence with the new dopamine agonists in patients with Parkinson's disease: a meta-analysis of randomised controlled trials. Drug Saf. 2001;24(11):863-868.", "pmid": "11665873", "doi": "10.2165/00002018-200124110-00007", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11665873/", "publicSourceType": "PMID" }, { "text": "Dowling GA, Mastick J, Colling E, Carter JH, Singer CM, Aminoff MJ. Melatonin for sleep disturbances in Parkinson's disease. Sleep Med. 2005;6(5):459-466.", "pmid": "16084125", "doi": "10.1016/j.sleep.2005.04.004", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16084125/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Melatonin can compound ropinirole-related sleepiness.", "clinicalSignificance": "Additive sleepiness can impair driving and increase falls in patients already vulnerable to motor symptoms.", "managementStrategy": "Use low-dose bedtime melatonin only and monitor for daytime somnolence or sudden sleep episodes.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Donepezil", "supplementBName": "Citicoline", "interactionType": "synergy", "severity": "info", "description": "Citicoline has been studied as an adjunct to acetylcholinesterase inhibitors such as donepezil in Alzheimer's disease. Observational data and a systematic review suggest possible additional benefit for cognition and behavioral symptoms, with generally mild adverse effects. This should be treated as an adjunctive dementia-care option, not a replacement for donepezil or diagnostic follow-up.", "recommendation": "Consider citicoline only as an add-on after discussing it with the clinician managing dementia therapy. Monitor for headache, excitability, stomach upset, sleep change, or worsening confusion after starting it. Do not change donepezil dosing on your own.", "minimumTimeSeparation": null, "mechanism": "Donepezil inhibits acetylcholinesterase, increasing synaptic acetylcholine. Citicoline supplies cytidine and choline for phosphatidylcholine synthesis and cholinergic membrane support, giving a mechanism-distinct cognitive adjunct rather than a chelation or metabolism interaction.", "evidenceLevel": "moderate", "sources": [ { "text": "Gareri P, Castagna A, Cotroneo AM, Putignano D, Conforti R, Santamaria F, et al. The Citicholinage Study: Citicoline Plus Cholinesterase Inhibitors in Aged Patients Affected with Alzheimer's Disease Study. J Alzheimers Dis. 2017;56(2):557-565.", "pmid": "28035929", "doi": "10.3233/JAD-160808", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28035929/", "publicSourceType": "PMID" }, { "text": "Piamonte BLC, Espiritu AI, Anlacan VMM. Effects of Citicoline as an Adjunct Treatment for Alzheimer's Disease: A Systematic Review. J Alzheimers Dis. 2020;76(2):725-732.", "pmid": "32538854", "doi": "10.3233/JAD-200378", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32538854/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Citicoline may modestly augment cognitive outcomes during donepezil-based therapy.", "clinicalSignificance": "The benefit signal is limited but clinically relevant for patients seeking adjuncts to standard dementia treatment.", "managementStrategy": "Use citicoline as a supervised adjunct and monitor cognition, behavior, and tolerability.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Levodopa/Carbidopa", "supplementBName": "L-Tyrosine", "interactionType": "timingSensitive", "severity": "moderate", "description": "L-tyrosine is a large neutral amino acid and can theoretically compete with levodopa for intestinal and blood-brain barrier transport when taken in large supplemental doses. A short trial of 1,000 mg/day tyrosine in people with Parkinson's disease receiving dopaminergic therapy was well tolerated, so the concern is mainly high-dose or poorly timed use. Taking tyrosine close to levodopa could still make motor response less predictable in protein-sensitive patients.", "recommendation": "Do not take L-tyrosine at the same time as levodopa/carbidopa. Separate high-dose tyrosine from levodopa by at least 2 hours, and stop the supplement if you notice more wearing off, delayed on, nausea, or dyskinesia. Keep your levodopa schedule consistent and tell your prescriber before using tyrosine daily.", "minimumTimeSeparation": 120, "mechanism": "Levodopa and aromatic amino acids such as tyrosine use large neutral amino acid transport systems for gut absorption and brain entry. Competition at these transporters can reduce levodopa central availability, although low-dose tyrosine has not shown a clear clinical problem in limited human data.", "evidenceLevel": "emerging", "sources": [ { "text": "Nutt JG, Woodward WR, Hammerstad JP, Carter JH, Anderson JL. The \"on-off\" phenomenon in Parkinson's disease. Relation to levodopa absorption and transport. N Engl J Med. 1984;310(8):483-488.", "pmid": "6694694", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6694694/", "publicSourceType": "PMID" }, { "text": "DiFrancisco-Donoghue J, Rabin E, Lamberg EM, Werner WG. Effects of Tyrosine on Parkinson's Disease: A Randomized, Double-Blind, Placebo-Controlled Trial. Mov Disord Clin Pract. 2014;1(4):348-353.", "pmid": "30363894", "doi": "10.1002/mdc3.12082", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30363894/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "High-dose or poorly timed L-tyrosine may make levodopa response less reliable.", "clinicalSignificance": "Timing matters because reduced levodopa brain entry can look like medication wearing off.", "managementStrategy": "Separate L-tyrosine from levodopa by at least 2 hours and monitor motor response.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Levodopa/Carbidopa", "supplementBName": "Green Tea Extract", "interactionType": "caution", "severity": "moderate", "description": "Green tea extract can contain concentrated EGCG and other catechins that inhibit catechol-O-methyltransferase in preclinical levodopa models. That could theoretically change levodopa methylation and exposure, especially with high-dose extracts rather than ordinary brewed tea. Human clinical interaction data are limited, so the main concern is new dyskinesia, nausea, insomnia, or motor fluctuation after starting a concentrated extract.", "recommendation": "Avoid high-dose green tea extract unless your prescriber knows you take levodopa/carbidopa. If you use it, keep the dose consistent and watch for dyskinesia, nausea, palpitations, insomnia, or changes in wearing off. Ordinary dietary green tea is less concerning than concentrated EGCG products.", "minimumTimeSeparation": null, "mechanism": "EGCG inhibited COMT-mediated levodopa O-methylation in vitro and reduced 3-O-methyldopa formation in animal work. COMT inhibition is a clinically relevant levodopa-modifying pathway, but green tea extract has not been standardized or proven as a levodopa adjunct in human dosing.", "evidenceLevel": "emerging", "sources": [ { "text": "Kang KS, Wen Y, Yamabe N, Fukui M, Bishop SC, Zhu BT. Dual beneficial effects of (-)-epigallocatechin-3-gallate on levodopa methylation and hippocampal neurodegeneration: in vitro and in vivo studies. PLoS One. 2010;5(8):e11951.", "pmid": "20700524", "doi": "10.1371/journal.pone.0011951", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20700524/", "publicSourceType": "PMID" }, { "text": "Jorga KM, Fotteler B, Heizmann P, Gasser R. Effects of tolcapone, a catechol-O-methyltransferase inhibitor, on motor symptoms and pharmacokinetics of levodopa in patients with Parkinson's disease. Clin Neuropharmacol. 1997;20(4):329-339.", "pmid": "9203084", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9203084/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Concentrated green tea extract may alter levodopa metabolism through COMT inhibition.", "clinicalSignificance": "Unexpected changes in levodopa exposure can worsen dyskinesia or motor fluctuations.", "managementStrategy": "Avoid high-dose extracts or use a consistent supervised dose while monitoring levodopa response.", "isSynergistic": null, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Gabapentin", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Alcohol can make gabapentin-related dizziness, slowed reaction time, and sedation less predictable. A small human laboratory study in alcohol-dependent participants did not find major acute potentiation of intoxication or psychomotor impairment, but animal EEG data and postmarketing safety concerns support caution, especially at higher gabapentin doses. The risk is higher with opioids, benzodiazepines, sleep apnea, lung disease, older age, or kidney impairment.", "recommendation": "Avoid alcohol when starting gabapentin, increasing the dose, or taking other sedating medicines. If your prescriber allows occasional alcohol, use small amounts only and do not drive. Seek urgent help for extreme sleepiness, confusion, slow breathing, or inability to wake.", "minimumTimeSeparation": null, "mechanism": "Gabapentin binds the alpha-2-delta subunit of voltage-gated calcium channels and can cause CNS depression. Alcohol broadly depresses CNS function through GABAergic, glutamatergic, and other mechanisms, creating a pharmacodynamic impairment risk even without a major pharmacokinetic interaction.", "evidenceLevel": "moderate", "sources": [ { "text": "Myrick H, Anton R, Voronin K, Wang W, Henderson S. A double-blind evaluation of gabapentin on alcohol effects and drinking in a clinical laboratory paradigm. Alcohol Clin Exp Res. 2007;31(2):221-227.", "pmid": "17250613", "doi": "10.1111/j.1530-0277.2006.00299.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17250613/", "publicSourceType": "PMID" }, { "text": "Pietrzak B, Czarnecka E. The effect of combined administration of ethanol and gabapentin on rabbit electroencephalographic activity. Basic Clin Pharmacol Toxicol. 2006;99(5):383-390.", "pmid": "17076692", "doi": "10.1111/j.1742-7843.2006.pto_518.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17076692/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Alcohol may add to gabapentin-related CNS depression and impairment.", "clinicalSignificance": "The combination can increase fall, driving, and breathing risk in susceptible patients.", "managementStrategy": "Avoid alcohol during gabapentin titration and use strict caution if any alcohol is later permitted.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Pregabalin", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Pregabalin can cause dizziness, blurred vision, slowed thinking, ataxia, and sedation, and alcohol can intensify these effects. Product pharmacology and safety warnings identify alcohol and other CNS depressants as clinically important risk factors, even though pregabalin has few classic CYP-mediated drug interactions. Risk is highest with higher pregabalin doses, kidney impairment, opioids, benzodiazepines, sleep apnea, lung disease, or older age.", "recommendation": "Avoid alcohol when starting pregabalin or after any dose increase. If your clinician permits occasional alcohol later, keep intake very low and do not drive or take other sedatives. Seek urgent care for severe sleepiness, confusion, shallow breathing, blue lips, or inability to wake.", "minimumTimeSeparation": null, "mechanism": "Pregabalin binds alpha-2-delta calcium-channel subunits and reduces excitatory neurotransmitter release; it is not substantially metabolized by CYP enzymes. Alcohol adds CNS-depressant effects through GABA, NMDA, and other pathways, so the concern is pharmacodynamic sedation and respiratory vulnerability.", "evidenceLevel": "moderate", "sources": [ { "text": "Bockbrader HN, Wesche D, Miller R, Chapel S, Janiczek N, Burger P. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet. 2010;49(10):661-669.", "pmid": "20818832", "doi": "10.2165/11536200-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20818832/", "publicSourceType": "PMID" }, { "text": "Ben-Menachem E. Pregabalin pharmacology and its relevance to clinical practice. Epilepsia. 2004;45 Suppl 6:13-18.", "pmid": "15315511", "doi": "10.1111/j.0013-9580.2004.455003.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15315511/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Alcohol can amplify pregabalin-related CNS depression and impairment.", "clinicalSignificance": "This pairing can increase fall, driving, blackout, and breathing risk, especially when other depressants are present.", "managementStrategy": "Avoid alcohol during pregabalin therapy unless a clinician has explicitly cleared limited use.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Topiramate", "supplementBName": "Potassium", "interactionType": "synergy", "severity": "moderate", "description": "Topiramate can cause renal carbonic anhydrase inhibition, metabolic acidosis, low urinary citrate, and sometimes low potassium, which increases kidney-stone risk. Potassium citrate, a prescription potassium-containing alkali, has clinical evidence for raising urinary citrate in topiramate users with hypocitraturia. Plain over-the-counter potassium tablets are not the same as potassium citrate and should not be used to self-treat topiramate-related acidosis.", "recommendation": "Ask your clinician about bicarbonate, potassium, and kidney-stone risk monitoring if you take topiramate long term. Use potassium or potassium citrate only when directed by a clinician, especially if you have kidney disease or take ACE inhibitors, ARBs, NSAIDs, or spironolactone. Seek care for flank pain, blood in urine, severe fatigue, rapid breathing, or persistent vomiting.", "minimumTimeSeparation": null, "mechanism": "Topiramate inhibits renal carbonic anhydrase, increasing bicarbonate loss and urine pH while reducing urinary citrate. Potassium citrate provides alkali and potassium, increasing urinary citrate in selected patients, but excessive potassium can cause hyperkalemia in susceptible people.", "evidenceLevel": "moderate", "sources": [ { "text": "Jhagroo RA, Wertheim ML, Penniston KL. Alkali replacement raises urinary citrate excretion in patients with topiramate-induced hypocitraturia. Br J Clin Pharmacol. 2016;81(1):131-136.", "pmid": "26297809", "doi": "10.1111/bcp.12751", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26297809/", "publicSourceType": "PMID" }, { "text": "Lamb EJ, Stevens PE, Nashef L. Topiramate increases biochemical risk of nephrolithiasis. Ann Clin Biochem. 2004;41(Pt 2):166-169.", "pmid": "15025812", "doi": "10.1258/000456304322880104", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15025812/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Topiramate can create a monitored clinical need for potassium-containing alkali therapy in stone-risk patients.", "clinicalSignificance": "Kidney stones and metabolic acidosis can be preventable or treatable without stopping effective topiramate in selected patients.", "managementStrategy": "Monitor labs and use potassium-containing alkali only under clinician guidance.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Topiramate", "supplementBName": "Vitamin C", "interactionType": "caution", "severity": "moderate", "description": "Topiramate increases kidney-stone risk by causing alkaline urine and hypocitraturia. High-dose vitamin C can increase urinary oxalate and has been associated with higher kidney-stone risk, particularly in men. Combining topiramate with high-dose vitamin C is most concerning in people with prior stones, low fluid intake, ketogenic diets, or other stone risks.", "recommendation": "Avoid high-dose vitamin C while taking topiramate unless your clinician has a specific reason for it. Keep vitamin C near dietary or standard multivitamin amounts, maintain good hydration, and ask about urine or blood monitoring if you have a stone history. Seek care for flank pain, blood in urine, fever, or vomiting.", "minimumTimeSeparation": null, "mechanism": "Topiramate promotes calcium phosphate stone risk through renal carbonic anhydrase inhibition, hypocitraturia, and elevated urine pH. Vitamin C is metabolized partly to oxalate, increasing calcium oxalate supersaturation when taken at high supplemental doses.", "evidenceLevel": "moderate", "sources": [ { "text": "Lamb EJ, Stevens PE, Nashef L. Topiramate increases biochemical risk of nephrolithiasis. Ann Clin Biochem. 2004;41(Pt 2):166-169.", "pmid": "15025812", "doi": "10.1258/000456304322880104", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15025812/", "publicSourceType": "PMID" }, { "text": "Ferraro PM, Curhan GC, Gambaro G, Taylor EN. Total, Dietary, and Supplemental Vitamin C Intake and Risk of Incident Kidney Stones. Am J Kidney Dis. 2016;67(3):400-407.", "pmid": "26463139", "doi": "10.1053/j.ajkd.2015.09.005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26463139/", "publicSourceType": "PMID" }, { "text": "Massey LK, Liebman M, Kynast-Gales SA. Ascorbate increases human oxaluria and kidney stone risk. J Nutr. 2005;135(7):1673-1677.", "pmid": "15987848", "doi": "10.1093/jn/135.7.1673", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15987848/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose vitamin C can add oxalate stone pressure to topiramate-related stone risk.", "clinicalSignificance": "Stone risk is clinically meaningful because topiramate may be taken for years for migraine, epilepsy, or weight-related indications.", "managementStrategy": "Avoid high-dose vitamin C, hydrate well, and monitor stone risk if topiramate is continued long term.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Valproic Acid", "supplementBName": "Methylfolate", "interactionType": "synergy", "severity": "moderate", "description": "Valproic acid has been associated with disturbances in one-carbon metabolism and higher homocysteine in epilepsy studies. Methylfolate may help support folate-dependent methylation when folate status is low or homocysteine is elevated, but it does not make valproic acid safe in pregnancy and should not be presented as protection from valproate teratogenicity. This is most relevant for long-term therapy, pregnancy planning, restricted diets, anemia, neuropathy symptoms, or known folate-pathway variants.", "recommendation": "Ask about folate, vitamin B12, and homocysteine testing if you take valproic acid long term or are planning pregnancy. Use methylfolate only as an adjunct and do not change valproic acid dosing without your prescriber. If pregnancy is possible, discuss valproate alternatives and folate strategy before conception because folate does not reliably prevent valproate-associated birth defects.", "minimumTimeSeparation": null, "mechanism": "Valproic acid has been linked with altered folate-dependent one-carbon metabolism and elevated homocysteine. Methylfolate is 5-methyltetrahydrofolate, the methyl donor used with vitamin B12 for homocysteine remethylation to methionine.", "evidenceLevel": "moderate", "sources": [ { "text": "Ni G, Qin J, Fang Z, Chen Y, Chen Z, Zhou J, et al. Increased homocysteine levels in valproate-treated patients with epilepsy: a meta-analysis. BMJ Open. 2014;4(7):e004936.", "pmid": "25031190", "doi": "10.1136/bmjopen-2014-004936", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25031190/", "publicSourceType": "PMID" }, { "text": "Belcastro V, Striano P, Gorgone G, Costa C, Ciampa C, Caccamo D, et al. Effects of antiepileptic drug monotherapy on one-carbon metabolism and DNA methylation in patients with epilepsy. PLoS One. 2015;10(4):e0125656.", "pmid": "25915064", "doi": "10.1371/journal.pone.0125656", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25915064/", "publicSourceType": "PMID" }, { "text": "Turgut U, Kazan S, Cakin H, Ozak A. Valproic acid effect on neural tube defects is not prevented by concomitant folic acid supplementation: Early chick embryo model pilot study. Int J Dev Neurosci. 2019;78:45-48.", "pmid": "31376429", "doi": "10.1016/j.ijdevneu.2019.05.008", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31376429/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Valproic acid may increase the clinical importance of adequate active folate status.", "clinicalSignificance": "Folate support may address a modifiable metabolic issue, but it must not obscure valproate's major pregnancy risks.", "managementStrategy": "Use methylfolate as monitored folate support and handle pregnancy planning as a separate high-risk valproate issue.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Carbamazepine", "supplementBName": "Ginkgo Biloba", "interactionType": "conflict", "severity": "serious", "description": "Ginkgo biloba has case reports of precipitating seizures in people with previously controlled epilepsy. That directly conflicts with carbamazepine's purpose when it is being used for seizure control, and it may also complicate care in people taking carbamazepine for neuralgia or mood stabilization who have seizure vulnerability. The risk is avoidable and is higher with a seizure history, missed antiseizure doses, sleep deprivation, alcohol, or products with poorly controlled ginkgotoxin content.", "recommendation": "Avoid ginkgo biloba if you take carbamazepine for epilepsy or have any seizure history. If you already started ginkgo and notice breakthrough seizures, auras, twitching, confusion spells, or loss of awareness, stop it and seek medical advice urgently. Do not change carbamazepine dosing without your prescriber.", "minimumTimeSeparation": null, "mechanism": "Ginkgo products may lower seizure threshold; ginkgotoxin can antagonize vitamin B6-dependent GABA synthesis, and some reports also raise concern for herb-drug effects on antiseizure medication exposure. This pharmacodynamic seizure-threshold effect can oppose carbamazepine's sodium-channel antiseizure activity.", "evidenceLevel": "emerging", "sources": [ { "text": "Granger AS. Ginkgo biloba precipitating epileptic seizures. Age Ageing. 2001;30(6):523-525.", "pmid": "11742783", "doi": "10.1093/ageing/30.6.523", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11742783/", "publicSourceType": "PMID" }, { "text": "Kupiec T, Raj V. Fatal seizures due to potential herb-drug interactions with Ginkgo biloba. J Anal Toxicol. 2005;29(7):755-758.", "pmid": "16419414", "doi": "10.1093/jat/29.7.755", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16419414/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Ginkgo biloba may lower seizure threshold and undermine carbamazepine seizure control.", "clinicalSignificance": "Breakthrough seizures can cause injury, driving restrictions, hospitalization, or death.", "managementStrategy": "Avoid ginkgo in patients using carbamazepine for seizures or with seizure susceptibility.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Albuterol", "supplementBName": "Potassium", "interactionType": "caution", "severity": "moderate", "description": "Albuterol can temporarily lower serum potassium, especially with repeated nebulizer treatments, continuous therapy, or high-dose use during asthma or COPD exacerbations. This is not true potassium loss from the body; it is a shift of potassium into cells, so symptoms and lab values can change quickly. Risk is higher if your potassium is already low, you use diuretics, or you have heart rhythm disease.", "recommendation": "Do not try to correct frequent albuterol-related tremor, weakness, or palpitations by increasing potassium supplements on your own. If you are using albuterol repeatedly or continuously, ask for potassium monitoring, especially if you also take diuretics or have heart disease. Seek urgent care for severe weakness, fainting, chest pain, or sustained palpitations.", "minimumTimeSeparation": null, "mechanism": "Beta-2 adrenergic stimulation from albuterol increases cyclic AMP signaling and stimulates sodium-potassium ATPase activity in skeletal muscle. This drives potassium from the bloodstream into cells and can lower measured serum potassium without reducing total-body potassium stores.", "evidenceLevel": "moderate", "sources": [ { "text": "Dickens GR, McCoy RA, West R, Stapczynski JS, Clifton GD. Effect of nebulized albuterol on serum potassium and cardiac rhythm in patients with asthma or chronic obstructive pulmonary disease. Pharmacotherapy. 1994;14(6):729-733.", "pmid": "7885977", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7885977/", "publicSourceType": "PMID" }, { "text": "Allon M, Dunlay R, Copkney C. Nebulized albuterol for acute hyperkalemia in patients on hemodialysis. Ann Intern Med. 1989;110(6):426-429.", "pmid": "2919849", "doi": "10.7326/0003-4819-110-6-426", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2919849/", "publicSourceType": "PMID" }, { "text": "Montoliu J, Lens XM, Revert L. Potassium-lowering effect of albuterol for hyperkalemia in renal failure. Arch Intern Med. 1987;147(4):713-717.", "pmid": "3827459", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3827459/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Albuterol can acutely lower serum potassium despite unchanged total-body potassium.", "clinicalSignificance": "Unexpected hypokalemia can contribute to weakness, palpitations, and arrhythmia vulnerability during heavy rescue-inhaler or nebulizer use.", "managementStrategy": "Monitor potassium during frequent or high-dose albuterol use and adjust supplementation only with clinician-guided labs.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Cetirizine", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "moderate", "description": "Cetirizine is less sedating than older antihistamines, but it is not impairment-free. Controlled alcohol studies are mixed: some found no meaningful potentiation, while an on-road driving study found mild cetirizine impairment that appeared additive with alcohol. The combination matters most before driving, in older adults, at higher cetirizine doses, or when other sedatives are present.", "recommendation": "Avoid alcohol when you first start cetirizine or when you need to drive, work at heights, or do safety-sensitive tasks. If you have taken both, wait until you know you are fully alert and coordinated before driving. Do not add sleep aids, cannabis, or other sedating products on the same day.", "minimumTimeSeparation": null, "mechanism": "Cetirizine has limited but measurable central H1 receptor activity in some people, which can slow vigilance and psychomotor performance. Alcohol independently impairs reaction time, lane control, judgment, and coordination, so susceptible users can experience additive CNS impairment.", "evidenceLevel": "moderate", "sources": [ { "text": "Ramaekers JG, Uiterwijk MM, O'Hanlon JF. Effects of loratadine and cetirizine on actual driving and psychometric test performance, and EEG during driving. Eur J Clin Pharmacol. 1992;42(4):363-369.", "pmid": "1355427", "doi": "10.1007/BF00280119", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1355427/", "publicSourceType": "PMID" }, { "text": "Garcia-Gea C, Martinez J, Ballester MR, Gich I, Valiente R, Antonijoan RM. Psychomotor and subjective effects of bilastine, hydroxyzine, and cetirizine, in combination with alcohol: a randomized, double-blind, crossover, and positive-controlled and placebo-controlled Phase I clinical trials. Hum Psychopharmacol. 2014;29(2):120-132.", "pmid": "24395298", "doi": "10.1002/hup.2378", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24395298/", "publicSourceType": "PMID" }, { "text": "Doms M, Vanhulle G, Baelde Y, Coulie P, Dupont P, Rihoux JP. Lack of potentiation by cetirizine of alcohol-induced psychomotor disturbances. Eur J Clin Pharmacol. 1988;34(6):619-623.", "pmid": "2971550", "doi": "10.1007/BF00615227", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2971550/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Alcohol can add to cetirizine-related sleepiness or psychomotor slowing in susceptible people.", "clinicalSignificance": "Even mild additive impairment can make driving and other safety-sensitive activities unsafe.", "managementStrategy": "Avoid same-period alcohol use until you know cetirizine does not impair you, and avoid hazardous tasks if both were used.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fexofenadine", "supplementBName": "Quercetin", "interactionType": "caution", "severity": "moderate", "description": "High-dose quercetin can raise fexofenadine exposure. In a controlled volunteer study, quercetin 500 mg three times daily for 7 days increased fexofenadine AUC by 55% and peak concentration by 68%. Fexofenadine has a wide safety margin, but higher levels may increase headache, dizziness, or drowsiness in sensitive users.", "recommendation": "Use caution with high-dose quercetin if you also take fexofenadine daily. Keep the quercetin dose consistent and watch for new drowsiness, dizziness, headache, or palpitations after starting it. If side effects appear, stop the quercetin or use a lower-risk allergy plan with your clinician.", "minimumTimeSeparation": null, "mechanism": "Fexofenadine disposition depends on intestinal and hepatic transporters, including P-glycoprotein and organic anion transporting polypeptides. Quercetin can inhibit P-glycoprotein-mediated efflux, reducing oral clearance and increasing systemic fexofenadine exposure.", "evidenceLevel": "moderate", "sources": [ { "text": "Kim KA, Park PW, Park JY. Short-term effect of quercetin on the pharmacokinetics of fexofenadine, a substrate of P-glycoprotein, in healthy volunteers. Eur J Clin Pharmacol. 2009;65(6):609-614.", "pmid": "19221726", "doi": "10.1007/s00228-009-0627-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19221726/", "publicSourceType": "PMID" }, { "text": "Cvetkovic M, Leake B, Fromm MF, Wilkinson GR, Kim RB. OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug Metab Dispos. 1999;27(8):866-871.", "pmid": "10421612", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10421612/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Quercetin can increase fexofenadine blood levels by inhibiting transporter-mediated disposition.", "clinicalSignificance": "The higher exposure is usually not dangerous but can increase dose-related adverse effects in sensitive patients.", "managementStrategy": "Keep quercetin dosing stable and reassess if fexofenadine side effects increase.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fexofenadine", "supplementBName": "Green Tea Extract", "interactionType": "timingSensitive", "severity": "moderate", "description": "Green tea extract can sharply reduce fexofenadine absorption when taken together. In a randomized crossover study, an EGCG-rich green tea extract reduced fexofenadine AUC and peak concentration by about 70%. This may make fexofenadine less effective for allergic rhinitis or hives.", "recommendation": "Take fexofenadine with water, not green tea extract or concentrated catechin products. Separate green tea extract from fexofenadine by at least 4 hours, and be consistent if you use both. If allergy control worsens after starting green tea extract, stop the extract or switch timing and reassess symptoms.", "minimumTimeSeparation": 240, "mechanism": "Fexofenadine requires intestinal uptake transport, including OATP1A2. EGCG and related green tea catechins inhibit OATP-mediated uptake in the gut, lowering fexofenadine absorption while leaving elimination half-life largely unchanged.", "evidenceLevel": "moderate", "sources": [ { "text": "Misaka S, Ono Y, Taudte RV, et al. Exposure of fexofenadine, but not pseudoephedrine, is markedly decreased by green tea extract in healthy volunteers. Clin Pharmacol Ther. 2022;112(3):627-634.", "pmid": "35678032", "doi": "10.1002/cpt.2682", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35678032/", "publicSourceType": "PMID" }, { "text": "Roth M, Timmermann BN, Hagenbuch B. Interactions of green tea catechins with organic anion-transporting polypeptides. Drug Metab Dispos. 2011;39(5):920-926.", "pmid": "21278283", "doi": "10.1124/dmd.110.036640", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21278283/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Green tea extract can markedly lower fexofenadine exposure and reduce antihistamine effect.", "clinicalSignificance": "A preventable absorption interaction can lead to breakthrough allergy symptoms despite correct fexofenadine dosing.", "managementStrategy": "Take fexofenadine with water and separate concentrated green tea extract by at least 4 hours.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fexofenadine", "supplementBName": "St. John's Wort", "interactionType": "caution", "severity": "moderate", "description": "St. John's Wort can change fexofenadine exposure through transporter effects. A single St. John's Wort dose increased fexofenadine peak concentration by 45%, while high-hyperforin repeated use has been associated with lower fexofenadine exposure from peripheral P-glycoprotein induction. The direction can depend on dose, hyperforin content, and duration of use, making allergy control and side effects less predictable.", "recommendation": "Avoid starting St. John's Wort casually while taking fexofenadine every day. If you use both, keep the St. John's Wort product and dose stable, monitor allergy control and drowsiness, and tell your prescriber or pharmacist because St. John's Wort has broader drug-interaction risks. Stop St. John's Wort and reassess if fexofenadine seems suddenly weaker or more side-effect prone.", "minimumTimeSeparation": null, "mechanism": "Hyperforin-rich St. John's Wort activates pregnane X receptor signaling and can induce intestinal P-glycoprotein, while acute exposure may inhibit P-glycoprotein before induction develops. Fexofenadine is a transporter-dependent antihistamine, so both inhibition and induction can alter its pharmacokinetics.", "evidenceLevel": "moderate", "sources": [ { "text": "Wang Z, Hamman MA, Huang SM, Lesko LJ, Hall SD. Effect of St John's wort on the pharmacokinetics of fexofenadine. Clin Pharmacol Ther. 2002;71(6):414-420.", "pmid": "12087344", "doi": "10.1067/mcp.2002.124080", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12087344/", "publicSourceType": "PMID" }, { "text": "El Biali M, Wolfl-Duchek M, Jackwerth M, et al. St. John's wort extract with a high hyperforin content does not induce P-glycoprotein activity at the human blood-brain barrier. Clin Transl Sci. 2024;17(5):e13804.", "pmid": "38700454", "doi": "10.1111/cts.13804", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38700454/", "publicSourceType": "PMID" }, { "text": "Nicolussi S, Drewe J, Butterweck V, Meyer Zu Schwabedissen HE. Clinical relevance of St. John's wort drug interactions revisited. Br J Pharmacol. 2020;177(6):1212-1226.", "pmid": "31742659", "doi": "10.1111/bph.14936", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31742659/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "St. John's Wort can make fexofenadine exposure unpredictable through time-dependent P-glycoprotein effects.", "clinicalSignificance": "Variable fexofenadine exposure can mean either breakthrough allergy symptoms or more adverse effects, and St. John's Wort may also interact with many other prescriptions.", "managementStrategy": "Avoid casual co-use; if combined, keep St. John's Wort stable and monitor fexofenadine response closely.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Citalopram", "supplementBName": "Melatonin", "interactionType": "caution", "severity": "serious", "description": "Severe sedation has been reported after melatonin was added to a regimen that included citalopram, with the authors judging a melatonin-citalopram pharmacokinetic interaction as the most likely explanation. The case also involved other sedating medicines, so the risk is most important when melatonin is stacked with citalopram plus opioids, tricyclic antidepressants, sleep medicines, alcohol, or other CNS depressants. Watch for unusual next-day grogginess, confusion, slowed breathing, or impaired coordination.", "recommendation": "Use the lowest effective melatonin dose if you take citalopram, and avoid adding melatonin when other sedating medicines are already in the stack unless your prescriber approves it. Do not drive or use machinery after starting or increasing melatonin until you know how the combination affects you. Seek urgent care for extreme sleepiness, confusion, fainting, or slow breathing.", "minimumTimeSeparation": null, "mechanism": "The published case suggested product-dependent CYP inhibition by melatonin products, including CYP1A2, CYP2C19, and CYP3A7, with possible effects on citalopram exposure. Citalopram is clinically sensitive to pharmacokinetic interactions involving CYP pathways, and melatonin can also add pharmacodynamic sleep-promoting effects.", "evidenceLevel": "moderate", "sources": [ { "text": "Foster BC, Cvijovic K, Boon HS, Tam TW, Liu R, Murty M, Vu D, Jaeger W, Tsuyuki RT, Barnes J, Vohra S. Melatonin Interaction Resulting in Severe Sedation. J Pharm Pharm Sci. 2015;18(2):124-131.", "pmid": "26158279", "doi": "10.18433/j3ss35", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26158279/", "publicSourceType": "PMID" }, { "text": "Spina E, Santoro V, D'Arrigo C. Clinically relevant pharmacokinetic drug interactions with second-generation antidepressants: an update. Clin Ther. 2008;30(7):1206-1227.", "pmid": "18691982", "doi": "10.1016/s0149-2918(08)80047-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18691982/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Melatonin may increase citalopram-related sedation, especially when other CNS depressants are present.", "clinicalSignificance": "A direct case report links this combination to severe sedation in a multi-drug regimen, making unsupervised sleep-aid stacking risky.", "managementStrategy": "Use low-dose melatonin only with clinician awareness and avoid combining it with citalopram plus other sedatives.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Diphenhydramine", "supplementBName": "Valerian Root", "interactionType": "caution", "severity": "moderate", "description": "Diphenhydramine can cause meaningful drowsiness, slowed reaction time, anticholinergic confusion, and driving impairment. Valerian root is commonly used as a sleep aid and has GABAergic pharmacology, even though controlled human data show inconsistent acute sedation. Combining them can increase next-day grogginess, falls, and impaired driving, especially in older adults or when alcohol, opioids, benzodiazepines, or other sleep aids are also used.", "recommendation": "Avoid using valerian root to boost diphenhydramine for sleep unless your clinician specifically approves the combination. If both are used, take them only when you can sleep a full night and avoid driving or hazardous tasks the next morning if you feel slowed or foggy. Stop the combination if you develop confusion, severe dizziness, or unusually prolonged sedation.", "minimumTimeSeparation": null, "mechanism": "Diphenhydramine blocks central H1 and muscarinic receptors, producing sedation and cognitive slowing. Valerian constituents, including valerenic acid, can modulate GABAergic signaling, creating a plausible additive CNS-depressant burden despite variable clinical sedative effects.", "evidenceLevel": "emerging", "sources": [ { "text": "Glass JR, Sproule BA, Herrmann N, Streiner D, Busto UE. Acute pharmacological effects of temazepam, diphenhydramine, and valerian in healthy elderly subjects. J Clin Psychopharmacol. 2003;23(3):260-268.", "pmid": "12826988", "doi": "10.1097/01.jcp.0000084033.22282.b6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12826988/", "publicSourceType": "PMID" }, { "text": "Weiler JM, Bloomfield JR, Woodworth GG, et al. Effects of fexofenadine, diphenhydramine, and alcohol on driving performance: a randomized, placebo-controlled trial in the Iowa driving simulator. Ann Intern Med. 2000;132(5):354-363.", "pmid": "10691585", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10691585/", "publicSourceType": "PMID" }, { "text": "Yuan CS, Mehendale S, Xiao Y, Aung HH, Xie JT, Ang-Lee MK. The gamma-aminobutyric acidergic effects of valerian and valerenic acid on rat brainstem neuronal activity. Anesth Analg. 2004;98(2):353-358.", "pmid": "14742369", "doi": "10.1213/01.ANE.0000096189.70405.A5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14742369/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Valerian root may add to diphenhydramine-related sedation and psychomotor impairment.", "clinicalSignificance": "The combination is most concerning for falls, confusion, and unsafe driving after nighttime use.", "managementStrategy": "Avoid routine co-use; if used, reserve for bedtime only and monitor for next-day impairment.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Hydrocodone", "supplementBName": "Valerian Root", "interactionType": "caution", "severity": "serious", "description": "Hydrocodone can cause sedation and respiratory depression, and valerian root may add CNS-depressant effects through GABAergic activity. Direct hydrocodone-valerian clinical studies are limited, but the combination is clinically relevant because opioid harm rises when additional sedating substances are stacked. Risk is higher with higher opioid doses, sleep apnea, lung disease, older age, alcohol, benzodiazepines, gabapentinoids, or other sleep aids.", "recommendation": "Do not use valerian root as a sleep aid while taking hydrocodone unless your prescriber knows and agrees. Avoid alcohol and other sedatives, and do not drive after taking both. Seek emergency help for extreme sleepiness, slow or noisy breathing, blue lips, confusion, or inability to wake.", "minimumTimeSeparation": null, "mechanism": "Hydrocodone is a mu-opioid receptor agonist that suppresses brainstem ventilatory drive and reduces arousal responses. Valerian and valerenic acid have GABAergic effects in preclinical models, so overlap can increase sedation and reduce protective arousal while opioid respiratory depression is present.", "evidenceLevel": "emerging", "sources": [ { "text": "Boom M, Niesters M, Sarton E, Aarts L, Smith TW, Dahan A. Non-analgesic effects of opioids: opioid-induced respiratory depression. Curr Pharm Des. 2012;18(37):5994-6004.", "pmid": "22747535", "doi": "10.2174/138161212803582469", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22747535/", "publicSourceType": "PMID" }, { "text": "Yuan CS, Mehendale S, Xiao Y, Aung HH, Xie JT, Ang-Lee MK. The gamma-aminobutyric acidergic effects of valerian and valerenic acid on rat brainstem neuronal activity. Anesth Analg. 2004;98(2):353-358.", "pmid": "14742369", "doi": "10.1213/01.ANE.0000096189.70405.A5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14742369/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Valerian root may increase hydrocodone-related sedation and respiratory-safety risk.", "clinicalSignificance": "Even modest added sedation can matter when an opioid is already suppressing breathing and arousal.", "managementStrategy": "Avoid valerian during hydrocodone use unless supervised, and treat accidental co-use like an overdose-risk situation if severe sedation appears.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Oxycodone", "supplementBName": "Cannabis (THC-Dominant)", "interactionType": "caution", "severity": "serious", "description": "Controlled human studies show that THC-dominant cannabis can interact meaningfully with oxycodone. One respiratory study found oxycodone reduced ventilatory response and inhaled THC did not further worsen ventilation in healthy volunteers, but THC slightly increased sedation. Another study found smoked cannabis enhanced analgesia from low-dose oxycodone and increased some oxycodone abuse-liability ratings, which can make extra dosing and impairment more likely.", "recommendation": "Avoid combining THC-dominant cannabis with oxycodone unless the prescriber managing your opioid therapy knows. Do not drive, use alcohol, or add other sedatives after using both. Seek emergency help for slow breathing, inability to stay awake, repeated vomiting, confusion, or blue lips.", "minimumTimeSeparation": null, "mechanism": "Oxycodone activates mu-opioid receptors, producing analgesia, sedation, and dose-dependent respiratory depression. THC activates CB1 receptors and can cause sedation, impaired attention, and cannabinoid-opioid analgesic interactions; current human data do not show added ventilatory depression with oxycodone in healthy volunteers but do show sedation and behavioral-safety concerns.", "evidenceLevel": "moderate", "sources": [ { "text": "van Dam CJ, van der Schrier R, van Velzen M, van Lemmen M, Simons P, Kuijpers KWK, et al. Inhaled delta-9-tetrahydrocannabinol does not enhance oxycodone-induced respiratory depression: randomised controlled trial in healthy volunteers. Br J Anaesth. 2023;130(4):485-493.", "pmid": "36725378", "doi": "10.1016/j.bja.2022.12.018", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36725378/", "publicSourceType": "PMID" }, { "text": "Cooper ZD, Bedi G, Ramesh D, Balter R, Comer SD, Haney M. Impact of co-administration of oxycodone and smoked cannabis on analgesia and abuse liability. Neuropsychopharmacology. 2018;43(10):2046-2055.", "pmid": "29463913", "doi": "10.1038/s41386-018-0011-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29463913/", "publicSourceType": "PMID" }, { "text": "Boom M, Niesters M, Sarton E, Aarts L, Smith TW, Dahan A. Non-analgesic effects of opioids: opioid-induced respiratory depression. Curr Pharm Des. 2012;18(37):5994-6004.", "pmid": "22747535", "doi": "10.2174/138161212803582469", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22747535/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "THC-dominant cannabis can add sedation and change oxycodone analgesic and abuse-liability effects.", "clinicalSignificance": "The pair may not worsen ventilation in healthy-volunteer data, but opioid patients can still face clinically important impairment and overdose-risk behaviors.", "managementStrategy": "Use together only with prescriber awareness, avoid driving and other sedatives, and monitor for opioid overdose warning signs.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Hydrocodone", "supplementBName": "Cannabis (THC-Dominant)", "interactionType": "caution", "severity": "serious", "description": "Direct hydrocodone-THC clinical studies are limited, but hydrocodone shares the opioid respiratory-depression and sedation liabilities studied with oxycodone. THC-dominant cannabis can add sedation, impaired attention, and coordination problems, and cannabinoid-opioid studies show clinically meaningful analgesic and behavioral interactions with oxycodone. The combination is most concerning with higher opioid doses, frequent THC use, sleep apnea, lung disease, older age, or other sedatives.", "recommendation": "Do not combine THC-dominant cannabis with hydrocodone unless your opioid prescriber knows. Avoid alcohol, benzodiazepines, sleep aids, and driving after using both. Seek emergency help for severe sleepiness, slow breathing, blue lips, confusion, or inability to wake.", "minimumTimeSeparation": null, "mechanism": "Hydrocodone is a mu-opioid receptor agonist that can suppress ventilatory drive and arousal. THC activates CB1 receptors and can impair attention and coordination; by opioid class extrapolation, this can add CNS-depressant burden and may make opioid dosing behavior less predictable.", "evidenceLevel": "emerging", "sources": [ { "text": "Kocis PT, Vrana KE. Delta-9-Tetrahydrocannabinol and Cannabidiol Drug-Drug Interactions. Med Cannabis Cannabinoids. 2020;3(1):61-73.", "pmid": "34676340", "doi": "10.1159/000507998", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34676340/", "publicSourceType": "PMID" }, { "text": "Cooper ZD, Bedi G, Ramesh D, Balter R, Comer SD, Haney M. Impact of co-administration of oxycodone and smoked cannabis on analgesia and abuse liability. Neuropsychopharmacology. 2018;43(10):2046-2055.", "pmid": "29463913", "doi": "10.1038/s41386-018-0011-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29463913/", "publicSourceType": "PMID" }, { "text": "Boom M, Niesters M, Sarton E, Aarts L, Smith TW, Dahan A. Non-analgesic effects of opioids: opioid-induced respiratory depression. Curr Pharm Des. 2012;18(37):5994-6004.", "pmid": "22747535", "doi": "10.2174/138161212803582469", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22747535/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "THC-dominant cannabis may add CNS impairment to hydrocodone and make opioid safety less predictable.", "clinicalSignificance": "Hydrocodone already carries respiratory-depression risk, so added THC-related impairment can make falls, unsafe driving, and overdose warning signs harder to manage.", "managementStrategy": "Avoid unsupervised co-use and treat marked sedation or breathing changes as urgent opioid-safety symptoms.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Berberine HCl", "supplementBName": "Metformin", "interactionType": "caution", "severity": "moderate", "description": "Berberine HCl has independent glucose-lowering effects in type 2 diabetes. When combined with metformin, fasting glucose and A1c may fall more than expected, especially if diet, weight, or kidney function also changes. Hypoglycemia is less common with metformin than with insulin or sulfonylureas, but symptoms can still occur in vulnerable patients.", "recommendation": "Track fasting and post-meal glucose when starting or changing Berberine HCl. Ask your clinician whether medication doses need adjustment if readings trend low or you develop shakiness, sweating, confusion, or unusual fatigue.", "minimumTimeSeparation": null, "mechanism": "Berberine activates AMPK-related metabolic pathways and improves insulin sensitivity and glucose handling. Its glucose-lowering effect can add pharmacodynamically to metformin's hepatic glucose output reduction and insulin-sensitizing effects.", "evidenceLevel": "moderate", "sources": [ { "text": "Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008;57(5):712-717.", "pmid": "18442638", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18442638/", "publicSourceType": "PMID" }, { "text": "Xie W, et al. Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis. Front Pharmacol. 2022;13:1015045.", "pmid": "36467075", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36467075/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Berberine HCl can add glucose-lowering effect to metformin.", "clinicalSignificance": "Unexpected glucose reductions may require closer monitoring or medication adjustment.", "managementStrategy": "Monitor glucose closely after starting, stopping, or changing Berberine HCl.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Berberine HCl", "supplementBName": "Glipizide", "interactionType": "caution", "severity": "serious", "description": "Berberine HCl lowers blood glucose independently of sulfonylurea therapy. Glipizide can cause hypoglycemia by increasing insulin release, so adding Berberine HCl can push glucose too low. Risk is higher with missed meals, low-carbohydrate dieting, older age, kidney disease, or recent weight loss.", "recommendation": "Do not add Berberine HCl to glipizide without a glucose-monitoring plan. Check glucose more often for the first 1-2 weeks and ask your prescriber whether glipizide dose reduction is appropriate if readings fall.", "minimumTimeSeparation": null, "mechanism": "Berberine improves glucose disposal and insulin sensitivity through AMPK-linked pathways. Glipizide closes pancreatic beta-cell KATP channels and increases insulin release, creating additive pharmacodynamic glucose lowering.", "evidenceLevel": "moderate", "sources": [ { "text": "Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008;57(5):712-717.", "pmid": "18442638", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18442638/", "publicSourceType": "PMID" }, { "text": "Xie W, et al. Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis. Front Pharmacol. 2022;13:1015045.", "pmid": "36467075", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36467075/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Berberine HCl may amplify glipizide-associated hypoglycemia.", "clinicalSignificance": "Sulfonylurea hypoglycemia can be prolonged and clinically dangerous.", "managementStrategy": "Use only with prescriber oversight, frequent glucose checks, and possible glipizide dose adjustment.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Berberine HCl", "supplementBName": "Glyburide", "interactionType": "caution", "severity": "serious", "description": "Berberine HCl has clinically measurable glucose-lowering activity. Glyburide is a sulfonylurea with a relatively high hypoglycemia risk, and the combination can lower glucose more than expected. Older adults and people with reduced kidney function are especially vulnerable.", "recommendation": "Avoid adding Berberine HCl to glyburide unless your prescriber is supervising glucose monitoring. Check glucose more frequently when starting or stopping Berberine HCl, and have a plan for treating low blood sugar.", "minimumTimeSeparation": null, "mechanism": "Berberine improves glucose metabolism through AMPK-related pathways, while glyburide increases insulin secretion by blocking beta-cell KATP channels. The combined pharmacodynamic effect can produce excessive glucose lowering.", "evidenceLevel": "moderate", "sources": [ { "text": "Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008;57(5):712-717.", "pmid": "18442638", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18442638/", "publicSourceType": "PMID" }, { "text": "Xie W, et al. Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis. Front Pharmacol. 2022;13:1015045.", "pmid": "36467075", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36467075/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Berberine HCl may increase glyburide-related hypoglycemia risk.", "clinicalSignificance": "Glyburide-associated lows can be severe or prolonged.", "managementStrategy": "Avoid unsupervised combination; monitor glucose frequently and consider glyburide dose adjustment.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Berberine HCl", "supplementBName": "Insulin Glargine", "interactionType": "caution", "severity": "serious", "description": "Berberine HCl can lower fasting and overall glucose levels. Insulin glargine provides basal insulin coverage, so adding Berberine HCl may increase overnight or fasting hypoglycemia risk. This matters most when Berberine HCl is started during weight loss, reduced food intake, or tighter carbohydrate restriction.", "recommendation": "Use Berberine HCl with insulin glargine only with a glucose-monitoring plan. Check fasting and overnight-risk readings more often after any Berberine HCl change and ask whether basal insulin dose adjustment is needed.", "minimumTimeSeparation": null, "mechanism": "Berberine improves insulin sensitivity and glucose uptake through AMPK-linked effects. Those effects add to exogenous basal insulin action, increasing the chance that hepatic glucose output and peripheral glucose availability fall too far.", "evidenceLevel": "moderate", "sources": [ { "text": "Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008;57(5):712-717.", "pmid": "18442638", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18442638/", "publicSourceType": "PMID" }, { "text": "Xie W, et al. Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis. Front Pharmacol. 2022;13:1015045.", "pmid": "36467075", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36467075/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Berberine HCl may add to basal insulin glucose lowering.", "clinicalSignificance": "Basal insulin hypoglycemia can occur overnight or before breakfast.", "managementStrategy": "Increase glucose monitoring and coordinate insulin adjustment when Berberine HCl changes.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Berberine HCl", "supplementBName": "Insulin Aspart", "interactionType": "caution", "severity": "serious", "description": "Berberine HCl can improve glucose control and lower post-meal glucose. Insulin aspart is rapid-acting mealtime insulin, so adding Berberine HCl may increase post-meal or delayed hypoglycemia risk if insulin doses are not adjusted. Missed meals and reduced carbohydrate intake make the combination riskier.", "recommendation": "Do not change Berberine HCl use without tracking pre-meal and post-meal glucose if you use insulin aspart. Ask your diabetes clinician whether insulin-to-carbohydrate ratios or correction doses need adjustment.", "minimumTimeSeparation": null, "mechanism": "Berberine improves insulin sensitivity and glucose disposal through AMPK-related pathways. These effects can add to rapid-acting insulin-mediated peripheral glucose uptake after meals.", "evidenceLevel": "moderate", "sources": [ { "text": "Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008;57(5):712-717.", "pmid": "18442638", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18442638/", "publicSourceType": "PMID" }, { "text": "Xie W, et al. Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis. Front Pharmacol. 2022;13:1015045.", "pmid": "36467075", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36467075/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Berberine HCl can increase mealtime insulin glucose-lowering effects.", "clinicalSignificance": "Rapid-acting insulin lows can happen quickly and require immediate treatment.", "managementStrategy": "Use closer meal-time glucose monitoring and adjust insulin only with clinician guidance.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Berberine HCl", "supplementBName": "Insulin Lispro", "interactionType": "caution", "severity": "serious", "description": "Berberine HCl has independent antihyperglycemic effects. Insulin lispro is rapid-acting mealtime insulin, so the combination may cause unexpectedly low post-meal glucose if insulin dosing is not adjusted. The risk increases with missed meals, lower carbohydrate intake, exercise, or weight loss.", "recommendation": "If you use insulin lispro, start or stop Berberine HCl only with extra glucose monitoring. Review low readings with your diabetes clinician before changing insulin doses.", "minimumTimeSeparation": null, "mechanism": "Berberine improves glucose uptake and insulin sensitivity through AMPK-linked pathways. These actions can add to insulin lispro's rapid insulin receptor-mediated glucose disposal after meals.", "evidenceLevel": "moderate", "sources": [ { "text": "Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008;57(5):712-717.", "pmid": "18442638", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18442638/", "publicSourceType": "PMID" }, { "text": "Xie W, et al. Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis. Front Pharmacol. 2022;13:1015045.", "pmid": "36467075", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36467075/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Berberine HCl may amplify insulin lispro's post-meal glucose lowering.", "clinicalSignificance": "Unexpected rapid-acting insulin lows can be dangerous without prompt carbohydrate treatment.", "managementStrategy": "Increase glucose checks around meals and coordinate any insulin adjustment with a clinician.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Duloxetine", "supplementBName": "SAMe", "interactionType": "caution", "severity": "serious", "description": "SAMe has antidepressant and monoamine-modulating activity. Duloxetine increases serotonin and norepinephrine signaling, so adding SAMe may increase the risk of serotonin toxicity or mood activation. Watch for agitation, sweating, tremor, diarrhea, clonus, fever, insomnia, or manic symptoms.", "recommendation": "Avoid starting SAMe with duloxetine unless the prescriber managing duloxetine approves and monitors the combination. Seek urgent care for clonus, high fever, severe agitation, confusion, or seizure.", "minimumTimeSeparation": null, "mechanism": "Duloxetine inhibits serotonin and norepinephrine reuptake. SAMe participates in methylation pathways relevant to monoamine metabolism and has clinical antidepressant activity, creating additive serotonergic and mood-activating potential.", "evidenceLevel": "emerging", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Iruela LM, Minguez L, Merino J, Monedero G. Toxic interaction of S-adenosylmethionine and clomipramine. Am J Psychiatry. 1993;150(3):522.", "pmid": "8434674", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8434674/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "SAMe may add serotonergic and mood-activating effects to duloxetine.", "clinicalSignificance": "Serotonin toxicity and manic activation can require urgent treatment.", "managementStrategy": "Avoid unsupervised use and monitor closely for serotonin toxicity or mania if combined.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Venlafaxine", "supplementBName": "SAMe", "interactionType": "caution", "severity": "serious", "description": "SAMe has antidepressant and monoamine-modulating activity. Venlafaxine increases serotonergic signaling, especially at lower and moderate doses, and also increases norepinephrine at higher doses. Adding SAMe may increase the risk of serotonin toxicity or mood activation.", "recommendation": "Do not add SAMe to venlafaxine without prescriber approval. Stop the supplement and seek urgent care for clonus, high fever, severe agitation, confusion, seizure, or rapidly escalating manic symptoms.", "minimumTimeSeparation": null, "mechanism": "Venlafaxine inhibits serotonin and norepinephrine reuptake. SAMe supports methylation reactions involved in monoamine metabolism and has antidepressant effects, so the combination can add serotonergic pressure and mood activation risk.", "evidenceLevel": "emerging", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Iruela LM, Minguez L, Merino J, Monedero G. Toxic interaction of S-adenosylmethionine and clomipramine. Am J Psychiatry. 1993;150(3):522.", "pmid": "8434674", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8434674/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "SAMe may increase venlafaxine-associated serotonin toxicity or mood activation risk.", "clinicalSignificance": "The combination can make early serotonin toxicity harder to distinguish from anxiety or medication side effects.", "managementStrategy": "Avoid unsupervised use and monitor urgently for serotonin syndrome or mania if exposure occurs.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Dabigatran", "supplementBName": "Nattokinase", "interactionType": "caution", "severity": "dangerous", "description": "Nattokinase has fibrinolytic activity and can reduce clotting factors. Dabigatran directly inhibits thrombin, so combining the two may create additive anticoagulant and fibrinolytic effects. Major bleeding risk is especially concerning in older adults, kidney impairment, prior bleeding, or concurrent antiplatelet use.", "recommendation": "Avoid nattokinase while taking dabigatran. If you have already combined them, stop nattokinase and contact your prescriber promptly if you notice unusual bruising, black stools, blood in urine, severe headache, or weakness.", "minimumTimeSeparation": null, "mechanism": "Nattokinase directly cleaves fibrin and has been shown to lower fibrinogen, factor VII, and factor VIII. These effects add to dabigatran's direct thrombin inhibition and can weaken hemostasis through separate pathways.", "evidenceLevel": "emerging", "sources": [ { "text": "Chang YY, Liu JS, Lai SL, Wu HS, Lan MY. Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. Intern Med. 2008;47(5):467-469.", "pmid": "18310985", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18310985/", "publicSourceType": "PMID" }, { "text": "Hsia CH, et al. Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects. Nutr Res. 2009;29(3):190-196.", "pmid": "19358933", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19358933/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Nattokinase may add fibrinolysis and clotting-factor reduction to dabigatran anticoagulation.", "clinicalSignificance": "Parallel effects on clot formation and fibrin breakdown can raise major bleeding risk.", "managementStrategy": "Avoid nattokinase with dabigatran and monitor for bleeding if exposure occurred.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Enoxaparin", "supplementBName": "Nattokinase", "interactionType": "caution", "severity": "dangerous", "description": "Nattokinase has fibrinolytic activity and can reduce clotting factor levels. Enoxaparin potentiates antithrombin activity against factor Xa, so the combination may substantially weaken clotting through separate mechanisms. The risk is highest after surgery, with kidney impairment, or when other antiplatelet or anticoagulant drugs are present.", "recommendation": "Avoid nattokinase while using enoxaparin. If the combination has already been used, stop nattokinase and watch for bruising, nosebleeds, black stools, blood in urine, severe headache, or sudden weakness.", "minimumTimeSeparation": null, "mechanism": "Nattokinase directly degrades fibrin and lowers fibrinogen, factor VII, and factor VIII. Enoxaparin enhances antithrombin-mediated factor Xa inhibition, so combined use affects both fibrin formation and fibrin breakdown.", "evidenceLevel": "emerging", "sources": [ { "text": "Chang YY, Liu JS, Lai SL, Wu HS, Lan MY. Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. Intern Med. 2008;47(5):467-469.", "pmid": "18310985", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18310985/", "publicSourceType": "PMID" }, { "text": "Hsia CH, et al. Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects. Nutr Res. 2009;29(3):190-196.", "pmid": "19358933", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19358933/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Nattokinase may add fibrinolytic effects to enoxaparin anticoagulation.", "clinicalSignificance": "Separate anticoagulant and fibrinolytic mechanisms can compound bleeding risk.", "managementStrategy": "Avoid nattokinase with enoxaparin and monitor for bleeding if exposure occurred.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Hydroxychloroquine", "supplementBName": "Potassium", "interactionType": "caution", "severity": "serious", "description": "Hydroxychloroquine can prolong the QT interval, especially when other risk factors are present. Low potassium is a major modifiable risk factor for torsades de pointes with QT-prolonging drugs. Potassium supplementation is only appropriate when potassium is low or intake is inadequate; excessive potassium can be dangerous, especially with kidney disease or RAAS-blocking drugs.", "recommendation": "Keep potassium in the normal range while taking hydroxychloroquine, particularly if you use diuretics or have vomiting or diarrhea. Do not start potassium tablets or high-dose electrolyte powders unless your clinician is monitoring potassium and kidney function. Seek urgent care for fainting, near-fainting, or sustained new palpitations.", "minimumTimeSeparation": null, "mechanism": "Hydroxychloroquine can delay cardiac repolarization and increase QTc in susceptible patients. Hypokalemia reduces repolarization reserve and promotes early afterdepolarizations, increasing the chance that QT prolongation becomes torsades de pointes.", "evidenceLevel": "moderate", "sources": [ { "text": "Jankelson L, Karam G, Becker ML, Chinitz LA, Tsai MC. QT prolongation, torsades de pointes, and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: A systematic review. Heart Rhythm. 2020;17(9):1472-1479.", "pmid": "32438018", "doi": "10.1016/j.hrthm.2020.05.008", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32438018/", "publicSourceType": "PMID" }, { "text": "Tisdale JE. Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management. Can Pharm J (Ott). 2016;149(3):139-152.", "pmid": "27212965", "doi": "10.1177/1715163516641136", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27212965/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Low potassium increases hydroxychloroquine-related QT and torsades risk.", "clinicalSignificance": "A correctable electrolyte abnormality can make hydroxychloroquine's usually uncommon rhythm risk clinically important.", "managementStrategy": "Monitor and correct potassium when depletion risk is present; avoid unsupervised high-dose potassium.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Hydroxychloroquine", "supplementBName": "Magnesium Glycinate", "interactionType": "caution", "severity": "serious", "description": "Hydroxychloroquine can prolong QTc, and low magnesium makes torsades de pointes more likely when QT risk factors stack. Magnesium supplementation should be viewed as deficiency prevention or repletion, not as a booster for hydroxychloroquine. High-dose magnesium can cause diarrhea and can accumulate in significant kidney disease.", "recommendation": "Maintain normal magnesium status while taking hydroxychloroquine, especially if you use diuretics, proton pump inhibitors, or have chronic diarrhea. Ask your clinician whether magnesium should be checked if you have arrhythmia symptoms or multiple QT-risk medicines. Do not use high-dose magnesium if kidney function is reduced unless it is being monitored.", "minimumTimeSeparation": null, "mechanism": "Magnesium helps stabilize cardiac repolarization and suppress early afterdepolarizations. Hypomagnesemia lowers repolarization reserve and often worsens potassium repletion, increasing vulnerability to drug-induced torsades.", "evidenceLevel": "moderate", "sources": [ { "text": "Agstam S, Yadav A, Kumar-M P, Gupta A. Hydroxychloroquine and QTc prolongation in patients with COVID-19: A systematic review and meta-analysis. Indian Pacing Electrophysiol J. 2021;21(1):36-43.", "pmid": "33075484", "doi": "10.1016/j.ipej.2020.10.002", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33075484/", "publicSourceType": "PMID" }, { "text": "Tisdale JE. Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management. Can Pharm J (Ott). 2016;149(3):139-152.", "pmid": "27212965", "doi": "10.1177/1715163516641136", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27212965/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Low magnesium increases susceptibility to hydroxychloroquine-associated torsades risk.", "clinicalSignificance": "Magnesium depletion is a modifiable contributor to dangerous QT-related arrhythmias.", "managementStrategy": "Maintain magnesium status and monitor levels when depletion or kidney-risk factors are present.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Ivabradine", "supplementBName": "Potassium", "interactionType": "caution", "severity": "serious", "description": "Ivabradine lowers heart rate and has rare reports of torsades de pointes when other risk factors are present. Low potassium increases torsades risk with bradycardia and QT-risk drugs. Potassium supplements are not routinely needed with ivabradine, but potassium deficiency should be corrected under monitoring.", "recommendation": "Keep potassium in the normal range while using ivabradine, especially during diuretic use, gastrointestinal illness, or addition of other QT-prolonging medicines. Do not self-treat with high-dose potassium unless your clinician is checking blood potassium and kidney function. Report fainting, near-fainting, or new sustained palpitations promptly.", "minimumTimeSeparation": null, "mechanism": "Ivabradine inhibits the sinoatrial If current and can produce bradycardia, which lengthens repolarization time and can contribute to pause-dependent torsades in susceptible patients. Hypokalemia further reduces repolarizing potassium current and lowers repolarization reserve.", "evidenceLevel": "emerging", "sources": [ { "text": "Cocco G, Jerie P. Torsades de pointes induced by the concomitant use of ivabradine and azithromycin: an unexpected dangerous interaction. Cardiovasc Toxicol. 2015;15(1):104-106.", "pmid": "25158669", "doi": "10.1007/s12012-014-9274-y", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25158669/", "publicSourceType": "PMID" }, { "text": "Tisdale JE. Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management. Can Pharm J (Ott). 2016;149(3):139-152.", "pmid": "27212965", "doi": "10.1177/1715163516641136", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27212965/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Low potassium can amplify ivabradine-related bradycardia/QT vulnerability.", "clinicalSignificance": "Electrolyte depletion can turn a rate-lowering drug into a higher-risk arrhythmia setting.", "managementStrategy": "Check and correct potassium when depletion risk is present, avoiding unsupervised potassium loading.", "isSynergistic": null, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Ivabradine", "supplementBName": "Magnesium Glycinate", "interactionType": "caution", "severity": "serious", "description": "Ivabradine can cause clinically important bradycardia, and torsades de pointes has been reported when interacting QT-risk drugs are added. Low magnesium is a recognized torsades risk factor in bradycardic or QT-prolonged states. Magnesium is useful when deficiency is present or likely; it should not be used to mask symptoms such as fainting or severe dizziness.", "recommendation": "Maintain normal magnesium intake while taking ivabradine, and ask about checking magnesium if you also use diuretics, proton pump inhibitors, or have chronic diarrhea. Avoid high-dose magnesium without monitoring if you have kidney disease. Seek urgent care for fainting, near-fainting, or sustained palpitations.", "minimumTimeSeparation": null, "mechanism": "Ivabradine slows sinus-node firing through If current inhibition, and bradycardia can increase pause-dependent torsades vulnerability. Hypomagnesemia promotes early afterdepolarizations and may impair potassium correction, compounding the electrophysiologic risk.", "evidenceLevel": "emerging", "sources": [ { "text": "Savelieva I, Camm AJ. If inhibition with ivabradine: electrophysiological effects and safety. Drug Saf. 2008;31(2):95-107.", "pmid": "18217787", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18217787/", "publicSourceType": "PMID" }, { "text": "Tisdale JE. Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management. Can Pharm J (Ott). 2016;149(3):139-152.", "pmid": "27212965", "doi": "10.1177/1715163516641136", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27212965/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Low magnesium can increase ivabradine-associated torsades vulnerability in susceptible patients.", "clinicalSignificance": "Magnesium depletion is a modifiable arrhythmia risk factor when ivabradine causes bradycardia or is combined with QT-risk drugs.", "managementStrategy": "Maintain magnesium status and monitor levels when depletion risks or arrhythmia symptoms are present.", "isSynergistic": null, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Ivabradine", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's Wort can induce CYP3A4 and P-glycoprotein, and systematic reviews identify ivabradine as a drug whose exposure can be reduced by this herb. Lower ivabradine exposure may reduce heart-rate control and antianginal or heart-failure benefit. The effect can persist after stopping St. John's Wort because enzyme induction takes time to reverse.", "recommendation": "Avoid St. John's Wort while taking ivabradine unless your prescriber specifically approves and monitors the combination. Do not use dose spacing as a workaround because this is an enzyme and transporter induction interaction. Tell your clinician if you start or stop St. John's Wort so heart rate, symptoms, and ivabradine dosing can be reassessed.", "minimumTimeSeparation": null, "mechanism": "Hyperforin-containing St. John's Wort activates pregnane X receptor, inducing CYP3A4 and P-glycoprotein. Ivabradine and its active metabolite undergo CYP3A4 metabolism, so induction can lower systemic exposure and blunt pharmacodynamic heart-rate reduction.", "evidenceLevel": "moderate", "sources": [ { "text": "Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs. 2009;69(13):1777-1798.", "pmid": "19719333", "doi": "10.2165/11317010-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19719333/", "publicSourceType": "PMID" }, { "text": "Nicolussi S, Drewe J, Butterweck V, Meyer Zu Schwabedissen HE. Clinical relevance of St. John's wort drug interactions revisited. Br J Pharmacol. 2020;177(6):1212-1226.", "pmid": "31742659", "doi": "10.1111/bph.14936", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31742659/", "publicSourceType": "PMID" }, { "text": "Lang J, Vincent L, Chenel M, Ogungbenro K, Galetin A. Simultaneous Ivabradine Parent-Metabolite PBPK/PD Modelling Using a Bayesian Estimation Method. AAPS J. 2020;22(6):129.", "pmid": "33033962", "doi": "10.1208/s12248-020-00502-8", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33033962/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St. John's Wort can lower ivabradine exposure and reduce clinical effect.", "clinicalSignificance": "Loss of heart-rate control can worsen angina, inappropriate tachycardia symptoms, or heart-failure management.", "managementStrategy": "Avoid St. John's Wort and reassess ivabradine response if the herb was started or stopped.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Ranolazine", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's Wort is a clinically important inducer of CYP3A4 and P-glycoprotein. Ranolazine is extensively metabolized by CYP3A and is also linked to transporter-mediated drug interactions, so induction can reduce ranolazine exposure and antianginal benefit. Starting or stopping St. John's Wort can make symptom control less predictable.", "recommendation": "Avoid St. John's Wort while taking ranolazine. If you have already combined them, tell your prescriber, especially if angina, exercise tolerance, or palpitations changed. Do not try to fix this by spacing doses because enzyme induction persists throughout the day.", "minimumTimeSeparation": null, "mechanism": "Hyperforin from St. John's Wort activates PXR, increasing CYP3A4 and P-glycoprotein expression. Ranolazine is primarily cleared by CYP3A metabolism, so induction is expected to lower ranolazine concentrations and reduce late sodium current inhibition in ischemic myocardium.", "evidenceLevel": "emerging", "sources": [ { "text": "Jerling M. Clinical pharmacokinetics of ranolazine. Clin Pharmacokinet. 2006;45(5):469-491.", "pmid": "16640453", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16640453/", "publicSourceType": "PMID" }, { "text": "Nicolussi S, Drewe J, Butterweck V, Meyer Zu Schwabedissen HE. Clinical relevance of St. John's wort drug interactions revisited. Br J Pharmacol. 2020;177(6):1212-1226.", "pmid": "31742659", "doi": "10.1111/bph.14936", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31742659/", "publicSourceType": "PMID" }, { "text": "Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs. 2009;69(13):1777-1798.", "pmid": "19719333", "doi": "10.2165/11317010-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19719333/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St. John's Wort may lower ranolazine concentrations and reduce angina control.", "clinicalSignificance": "Reduced ranolazine exposure can lead to breakthrough angina or unnecessary escalation of cardiac therapy.", "managementStrategy": "Avoid St. John's Wort and reassess symptoms if exposure has overlapped.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Leflunomide", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Leflunomide can cause clinically significant liver injury, including rare severe drug-induced liver injury. Alcohol adds hepatic stress and can make liver enzyme elevations harder to interpret, especially with regular or heavy use. The concern is highest with preexisting liver disease, elevated baseline liver tests, obesity, viral hepatitis, or other hepatotoxic medicines.", "recommendation": "Avoid heavy alcohol use while taking leflunomide. If you drink at all, keep intake low and consistent, tell your prescriber, and do not miss scheduled liver blood tests. Stop alcohol and seek medical advice promptly for jaundice, dark urine, severe fatigue, itching, or right upper abdominal pain.", "minimumTimeSeparation": null, "mechanism": "Leflunomide's active metabolite teriflunomide has a long half-life and can cause hepatocellular or mixed liver injury. Alcohol is metabolized in the liver and can increase oxidative stress, steatosis, and medication-metabolism burden, creating additive liver-safety concern rather than a timing-based interaction.", "evidenceLevel": "emerging", "sources": [ { "text": "Devarbhavi H, Ghabril M, Barnhart H, Patil M, Raj S, Gu J, et al. Leflunomide-induced liver injury: Differences in characteristics and outcomes in Indian and US registries. Liver Int. 2022;42(6):1323-1329.", "pmid": "35129282", "doi": "10.1111/liv.15189", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35129282/", "publicSourceType": "PMID" }, { "text": "Alamri RD, Elmeligy MA, Albalawi GA, Alquayr SM, Alsubhi SS, El-Ghaiesh SH. Leflunomide an immunomodulator with antineoplastic and antiviral potentials but drug-induced liver injury: A comprehensive review. Int Immunopharmacol. 2021;93:107398.", "pmid": "33571819", "doi": "10.1016/j.intimp.2021.107398", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33571819/", "publicSourceType": "PMID" }, { "text": "Weathermon R, Crabb DW. Alcohol and medication interactions. Alcohol Res Health. 1999;23(1):40-54.", "pmid": "10890797", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10890797/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Alcohol can add to leflunomide liver-safety risk and complicate monitoring.", "clinicalSignificance": "Leflunomide already requires liver monitoring, and alcohol can increase concern when liver enzymes rise.", "managementStrategy": "Avoid heavy drinking and maintain liver-test monitoring if any alcohol is used.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Flecainide", "supplementBName": "Potassium", "interactionType": "caution", "severity": "serious", "description": "Flecainide has a narrow cardiac safety margin and can cause serious proarrhythmia in susceptible patients. Low potassium is a recognized risk factor for torsades de pointes and can worsen arrhythmia vulnerability when antiarrhythmic drugs are involved. Potassium supplementation is only appropriate for documented or likely deficiency and should be monitored.", "recommendation": "Keep potassium in the normal range while taking flecainide, especially if you use diuretics or have vomiting, diarrhea, or poor intake. Do not start high-dose potassium unless your clinician is checking potassium, kidney function, and ECG status. Seek urgent care for fainting, severe dizziness, wide-complex palpitations, or chest pain.", "minimumTimeSeparation": null, "mechanism": "Flecainide primarily blocks fast sodium channels, widening QRS and slowing conduction; rare cases also involve repolarization abnormalities and torsades. Hypokalemia reduces repolarization reserve and promotes early afterdepolarizations, increasing proarrhythmic risk when flecainide exposure or susceptibility is high.", "evidenceLevel": "emerging", "sources": [ { "text": "Nasser M, Idris S, Marinelli K, Machado C. Flecainide-induced Torsades de Pointes: Case Report and Review of Literature. Rev Cardiovasc Med. 2015;16(3):214-220.", "pmid": "26451768", "doi": "10.3909/ricm0761", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26451768/", "publicSourceType": "PMID" }, { "text": "Morganroth J, Horowitz LN. Flecainide: its proarrhythmic effect and expected changes on the surface electrocardiogram. Am J Cardiol. 1984;53(5):89B-94B.", "pmid": "6695821", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6695821/", "publicSourceType": "PMID" }, { "text": "Tisdale JE. Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management. Can Pharm J (Ott). 2016;149(3):139-152.", "pmid": "27212965", "doi": "10.1177/1715163516641136", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27212965/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Low potassium can increase flecainide-related proarrhythmic vulnerability.", "clinicalSignificance": "Electrolyte depletion can compound the risks of a narrow-therapeutic-index antiarrhythmic.", "managementStrategy": "Monitor and correct potassium when depletion risk is present; avoid unsupervised potassium supplementation.", "isSynergistic": null, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Bisacodyl", "supplementBName": "Potassium", "interactionType": "synergy", "severity": "moderate", "description": "Bisacodyl can cause clinically important potassium loss when overused, taken repeatedly for diarrhea-producing laxation, or combined with other causes of fluid loss. Published cases link surreptitious bisacodyl abuse to severe hypokalemia and torsades de pointes. Potassium replacement may be needed when labs confirm a low level, but unsupervised potassium can also be dangerous.", "recommendation": "Use bisacodyl only as directed and avoid using it to force repeated watery stools. If you need bisacodyl often, have potassium checked before starting potassium supplements, especially if you have kidney disease or take ACE inhibitors, ARBs, NSAIDs, or potassium-sparing diuretics. Seek urgent care for fainting, palpitations, severe weakness, or confusion.", "minimumTimeSeparation": null, "mechanism": "Excess stimulant laxation increases intestinal fluid and electrolyte losses, and volume depletion can secondarily increase renal potassium wasting through aldosterone. Potassium supplementation replaces the depleted electrolyte but does not correct ongoing laxative-driven loss.", "evidenceLevel": "emerging", "sources": [ { "text": "Krahn LE, Lee J, Richardson JW, Martin MJ, O'Connor MK. Hypokalemia leading to torsades de pointes. Munchausen's disorder or bulimia nervosa? Gen Hosp Psychiatry. 1997;19(5):370-377.", "pmid": "9328782", "doi": "10.1016/s0163-8343(97)00057-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9328782/", "publicSourceType": "PMID" }, { "text": "Muller-Lissner S. Side effects of laxatives. Z Gastroenterol. 1992;30(6):418-427.", "pmid": "1636275", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1636275/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Bisacodyl overuse can deplete potassium, while potassium supplementation can correct confirmed hypokalemia.", "clinicalSignificance": "Severe hypokalemia can cause weakness and life-threatening arrhythmias, but excess potassium replacement is also unsafe.", "managementStrategy": "Avoid bisacodyl overuse, check potassium when risk is present, and replace potassium only with lab guidance.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Bisacodyl", "supplementBName": "Magnesium Citrate", "interactionType": "caution", "severity": "moderate", "description": "Bisacodyl and magnesium citrate are both laxatives, and combining them can produce a stronger cathartic effect than either alone. Human bowel-preparation studies show the combination is used medically, but it adds bowel frequency and is not necessary for every preparation. The main concern outside supervised prep is dehydration, cramping, diarrhea, electrolyte abnormalities, and magnesium accumulation in kidney disease.", "recommendation": "Do not combine bisacodyl with laxative-dose magnesium citrate unless your clinician or colonoscopy instructions specifically tell you to. Avoid the combination if you have kidney disease, known electrolyte abnormalities, severe dehydration, bowel obstruction symptoms, or severe abdominal pain. Hydrate as instructed and seek care for dizziness, confusion, persistent vomiting, or minimal urination.", "minimumTimeSeparation": null, "mechanism": "Bisacodyl stimulates colonic motility and secretion after local activation in the bowel. Magnesium citrate osmotically retains water in the intestinal lumen; together they can amplify stool water loss and electrolyte shifts.", "evidenceLevel": "moderate", "sources": [ { "text": "Lee JR. Combinations of laxatives for bowel preparation: are they necessary? Clin Radiol. 1984;35(6):461-462.", "pmid": "6499384", "doi": "10.1016/s0009-9260(84)80053-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6499384/", "publicSourceType": "PMID" }, { "text": "Rapier R, Houston C. A prospective study to assess the efficacy and patient tolerance of three bowel preparations for colonoscopy. Gastroenterol Nurs. 2006;29(4):305-308.", "pmid": "16974167", "doi": "10.1097/00001610-200607000-00007", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16974167/", "publicSourceType": "PMID" }, { "text": "Vanner S, Hookey LC. Timing and frequency of bowel activity in patients ingesting sodium picosulphate/magnesium citrate and adjuvant bisacodyl for colon cleansing before colonoscopy. Can J Gastroenterol. 2011;25(12):663-666.", "pmid": "22175056", "doi": "10.1155/2011/950263", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22175056/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Bisacodyl and magnesium citrate can additively increase laxation and fluid loss.", "clinicalSignificance": "Unsupervised stacking of laxatives can cause dehydration or electrolyte problems, especially in older adults or kidney disease.", "managementStrategy": "Use the combination only for clinician-directed bowel preparation or rescue plans, with hydration and risk screening.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Lactulose", "supplementBName": "Potassium", "interactionType": "synergy", "severity": "moderate", "description": "Lactulose can cause diarrhea when the dose is too high, and excessive laxative effect can lower potassium. A published elderly-patient case involving high-dose lactulose and sorbitol reported severe hyponatremia with hypokalemia, hypocalcemia, and rhabdomyolysis. Potassium can be clinically useful when hypokalemia is confirmed, but self-treatment can overshoot in kidney disease or with potassium-raising drugs.", "recommendation": "If lactulose is prescribed for hepatic encephalopathy, titrate only to the stool target your clinician gave you rather than causing continuous diarrhea. Ask about electrolyte checks if stools become very frequent, watery, or prolonged, or if you develop weakness, cramps, palpitations, dizziness, or confusion. Take potassium supplements only when your potassium level or prescriber supports it.", "minimumTimeSeparation": null, "mechanism": "Lactulose is a nonabsorbed osmotic disaccharide that draws water into the colon and is fermented to organic acids. Excess diarrhea causes fecal potassium and fluid loss, and volume depletion can increase renal potassium excretion; potassium supplementation replaces the deficit when documented.", "evidenceLevel": "emerging", "sources": [ { "text": "Merante A, Gareri P, Marigliano NM, et al. Laxative-induced rhabdomyolysis. Clin Interv Aging. 2010;5:71-73.", "pmid": "20396636", "doi": "10.2147/cia.s8832", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20396636/", "publicSourceType": "PMID" }, { "text": "Muller-Lissner S. Side effects of laxatives. Z Gastroenterol. 1992;30(6):418-427.", "pmid": "1636275", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1636275/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Excess lactulose-related diarrhea can lower potassium, while potassium can correct confirmed depletion.", "clinicalSignificance": "Low potassium can worsen weakness, confusion, and arrhythmia risk in patients who may already be medically fragile.", "managementStrategy": "Adjust lactulose to the prescribed stool goal and check electrolytes before potassium replacement when diarrhea is excessive.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Loperamide", "supplementBName": "Psyllium Husk", "interactionType": "caution", "severity": "moderate", "description": "Loperamide and psyllium husk can both reduce loose stool or fecal incontinence, but they work differently and may overcorrect stool consistency when combined. In a randomized crossover trial, both improved fecal incontinence, while constipation occurred more often with loperamide than psyllium. The combination may be useful for selected patients, but constipation, bloating, impaction risk, or masking infectious diarrhea are the main concerns.", "recommendation": "Start with one therapy at a time unless your clinician gives you a combined plan. If both are used, begin psyllium at a low dose with plenty of fluid and use the lowest effective loperamide dose. Avoid loperamide for bloody diarrhea, high fever, suspected C. difficile, or severe abdominal swelling, and stop or reduce therapy if constipation develops.", "minimumTimeSeparation": null, "mechanism": "Loperamide activates peripheral mu-opioid receptors in the gut to slow transit and increase fluid absorption. Psyllium forms a gel that holds water and bulks stool; together they can further firm stool and slow evacuation.", "evidenceLevel": "moderate", "sources": [ { "text": "Markland AD, Burgio KL, Whitehead WE, et al. Loperamide Versus Psyllium Fiber for Treatment of Fecal Incontinence: The Fecal Incontinence Prescription (Rx) Management (FIRM) Randomized Clinical Trial. Dis Colon Rectum. 2015;58(10):983-993.", "pmid": "26347971", "doi": "10.1097/DCR.0000000000000442", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26347971/", "publicSourceType": "PMID" }, { "text": "Bliss DZ, Savik K, Jung HJ, Whitebird R, Lowry A, Sheng X. Dietary fiber supplementation for fecal incontinence: a randomized clinical trial. Res Nurs Health. 2014;37(5):367-378.", "pmid": "25155992", "doi": "10.1002/nur.21616", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25155992/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Psyllium and loperamide can additively firm stool and reduce leakage, but may cause constipation if overused together.", "clinicalSignificance": "A useful symptom-control combination can become harmful if it causes constipation, impaction, or delays care for infectious diarrhea.", "managementStrategy": "Introduce one agent at a time, titrate gradually, hydrate with psyllium, and reduce therapy if constipation occurs.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Calcium Carbonate", "supplementBName": "Zinc", "interactionType": "timingSensitive", "severity": "moderate", "description": "Calcium carbonate can reduce zinc absorption when taken with the same meal or supplement dose. In a human absorption study, 600 mg of calcium as calcium carbonate reduced zinc absorption from a test meal by about 50%. This matters most when zinc is being used to correct low zinc status, support wound healing, or replace losses from poor intake.", "recommendation": "Separate zinc from calcium carbonate by at least 2 hours, and preferably 4 hours when treating zinc deficiency. If calcium carbonate must be taken with meals for antacid effect, take zinc at a different meal or at bedtime if tolerated. Recheck zinc status or clinical response if deficiency symptoms are not improving.", "minimumTimeSeparation": 120, "mechanism": "Calcium can compete with zinc for intestinal absorption and can form less soluble mineral complexes in the gut lumen. Calcium carbonate also changes luminal mineral chemistry near the dose, making simultaneous zinc absorption less efficient.", "evidenceLevel": "moderate", "sources": [ { "text": "Wood RJ, Zheng JJ. High dietary calcium intakes reduce zinc absorption and balance in humans. Am J Clin Nutr. 1997;65(6):1803-1809.", "pmid": "9174476", "doi": "10.1093/ajcn/65.6.1803", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9174476/", "publicSourceType": "PMID" }, { "text": "Devarshi PP, Mao Q, Grant RW, Hazels Mitmesser S. Comparative Absorption and Bioavailability of Various Chemical Forms of Zinc in Humans: A Narrative Review. Nutrients. 2024;16(24):4269.", "pmid": "39770891", "doi": "10.3390/nu16244269", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39770891/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Calcium carbonate can lower zinc absorption when taken at the same time.", "clinicalSignificance": "Poor timing can blunt zinc repletion in people taking zinc for deficiency, wound healing, or low intake.", "managementStrategy": "Separate zinc from calcium carbonate by at least 2 hours, using 4 hours for deficiency treatment when practical.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Loratadine", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "info", "description": "Loratadine is much less sedating than older antihistamines, and controlled testing did not find meaningful driving or psychomotor impairment from a standard 10 mg dose, even when alcohol was included in the study design. Alcohol itself still impaired performance in that trial, and some people can feel drowsy on loratadine. The practical risk is highest before driving, in older adults, with higher-than-labeled loratadine doses, or when other sedatives are also present.", "recommendation": "Use extra caution with alcohol until you know how loratadine affects you. Do not drive, operate machinery, or do safety-sensitive work after drinking, even if loratadine is not making you sleepy. Avoid adding cannabis, sleep aids, or other sedating products on the same day.", "minimumTimeSeparation": null, "mechanism": "Loratadine has limited penetration into the central nervous system compared with first-generation H1 antihistamines, so it usually does not add much CNS depression. Alcohol independently impairs attention, coordination, judgment, and reaction time through CNS depressant effects.", "evidenceLevel": "moderate", "sources": [ { "text": "Ramaekers JG, Uiterwijk MM, O'Hanlon JF. Effects of loratadine and cetirizine on actual driving and psychometric test performance, and EEG during driving. Eur J Clin Pharmacol. 1992;42(4):363-369.", "pmid": "1355427", "doi": "10.1007/BF00280119", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1355427/", "publicSourceType": "PMID" }, { "text": "Roman IJ, Danzig MR. Loratadine. A review of recent findings in pharmacology, pharmacokinetics, efficacy, and safety, with a look at its use in combination with pseudoephedrine. Clin Rev Allergy. 1993;11(1):89-110.", "pmid": "8319163", "doi": "10.1007/BF02802295", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8319163/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Alcohol causes impairment while standard-dose loratadine usually does not measurably add to it.", "clinicalSignificance": "Patients may incorrectly assume that a non-sedating antihistamine makes alcohol-compatible driving or hazardous work safe.", "managementStrategy": "Treat alcohol as impairing and avoid hazardous tasks if drinking while taking loratadine.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Albuterol", "supplementBName": "Cannabis (THC-Dominant)", "interactionType": "caution", "severity": "moderate", "description": "Albuterol can cause tremor, palpitations, tachycardia, and ECG changes, especially with repeated rescue doses or nebulized treatment. THC-dominant cannabis can also increase heart rate, worsen anxiety or dizziness, and impair coordination; smoked cannabis may add airway irritation and cough. The combination is most concerning during an asthma or COPD flare, with high-THC products, or in people with arrhythmias, coronary disease, panic symptoms, or low potassium.", "recommendation": "Avoid THC-dominant cannabis when you are needing frequent albuterol or feeling palpitations, chest tightness, severe anxiety, or dizziness. Do not smoke or vape cannabis during a breathing flare. Seek urgent care for chest pain, fainting, severe shortness of breath, or a sustained racing or irregular heartbeat.", "minimumTimeSeparation": null, "mechanism": "Albuterol stimulates beta-2 adrenergic receptors and can produce systemic adrenergic effects, including tachycardia and hypokalemia at higher exposure. THC activates cannabinoid pathways that can increase sympathetic tone and heart rate, while inhaled cannabis smoke can irritate airways and worsen respiratory symptoms.", "evidenceLevel": "moderate", "sources": [ { "text": "Ahrens RC, Smith GD. Albuterol: an adrenergic agent for use in the treatment of asthma pharmacology, pharmacokinetics and clinical use. Pharmacotherapy. 1984;4(3):105-121.", "pmid": "6739311", "doi": "10.1002/j.1875-9114.1984.tb03330.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6739311/", "publicSourceType": "PMID" }, { "text": "Kallergis EM, Manios EG, Kanoupakis EM, et al. Acute electrophysiologic effects of inhaled salbutamol in humans. Chest. 2005;127(6):2057-2063.", "pmid": "15947320", "doi": "10.1378/chest.127.6.2057", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15947320/", "publicSourceType": "PMID" }, { "text": "Page RL 2nd, Allen LA, Kloner RA, et al. Medical Marijuana, Recreational Cannabis, and Cardiovascular Health: A Scientific Statement From the American Heart Association. Circulation. 2020;142(10):e131-e152.", "pmid": "32752884", "doi": "10.1161/CIR.0000000000000883", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32752884/", "publicSourceType": "PMID" }, { "text": "Tetrault JM, Crothers K, Moore BA, Mehra R, Concato J, Fiellin DA. Effects of marijuana smoking on pulmonary function and respiratory complications: a systematic review. Arch Intern Med. 2007;167(3):221-228.", "pmid": "17296876", "doi": "10.1001/archinte.167.3.221", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17296876/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "THC-dominant cannabis can add cardiovascular and airway stress during albuterol use.", "clinicalSignificance": "Palpitations, anxiety, cough, and tachycardia can be misread as worsening asthma or as a need for still more rescue albuterol.", "managementStrategy": "Avoid THC-dominant cannabis during heavy albuterol use and seek care for cardiovascular symptoms or worsening breathing.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Albuterol", "supplementBName": "Cocaine", "interactionType": "contraindicated", "severity": "dangerous", "description": "Cocaine and albuterol can both increase adrenergic cardiovascular stress. Cocaine can cause tachycardia, hypertension, coronary vasospasm, myocardial ischemia, and arrhythmias, while albuterol can add tachycardia, tremor, hypokalemia, and electrophysiologic changes at higher exposure. Smoked cocaine can also provoke bronchospasm, creating a dangerous cycle of airway symptoms and escalating rescue-inhaler use.", "recommendation": "Do not use cocaine while using albuterol. If cocaine exposure occurs, do not keep repeating albuterol for chest tightness without medical assessment, because symptoms may reflect bronchospasm, ischemia, panic, or arrhythmia. Seek emergency care for chest pain, severe shortness of breath, fainting, severe agitation, or a fast or irregular heartbeat.", "minimumTimeSeparation": null, "mechanism": "Albuterol stimulates beta-2 adrenergic receptors and can produce beta-mediated cardiac stimulation and intracellular potassium shift. Cocaine blocks norepinephrine reuptake, increases sympathetic outflow, causes vasoconstriction, and has sodium-channel blocking effects, creating additive arrhythmia and ischemia risk.", "evidenceLevel": "moderate", "sources": [ { "text": "Ahrens RC, Smith GD. Albuterol: an adrenergic agent for use in the treatment of asthma pharmacology, pharmacokinetics and clinical use. Pharmacotherapy. 1984;4(3):105-121.", "pmid": "6739311", "doi": "10.1002/j.1875-9114.1984.tb03330.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6739311/", "publicSourceType": "PMID" }, { "text": "Vongpatanasin W, Mansour Y, Chavoshan B, Arbique D, Victor RG. Cocaine stimulates the human cardiovascular system via a central mechanism of action. Circulation. 1999;100(5):497-502.", "pmid": "10430763", "doi": "10.1161/01.cir.100.5.497", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10430763/", "publicSourceType": "PMID" }, { "text": "Billman GE. Cocaine: a review of its toxic actions on cardiac function. Crit Rev Toxicol. 1995;25(2):113-132.", "pmid": "7612173", "doi": "10.3109/10408449509021610", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7612173/", "publicSourceType": "PMID" }, { "text": "Tashkin DP, Kleerup EC, Koyal SN, Marques JA, Goldman MD. Acute effects of inhaled and i.v. cocaine on airway dynamics. Chest. 1996;110(4):904-910.", "pmid": "8874243", "doi": "10.1378/chest.110.4.904", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8874243/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Cocaine can stack cardiovascular toxicity with albuterol and may trigger bronchospasm that leads to unsafe albuterol escalation.", "clinicalSignificance": "The combination can precipitate chest pain, severe tachycardia, arrhythmia, myocardial ischemia, or worsening respiratory distress.", "managementStrategy": "Avoid cocaine completely during albuterol therapy and get urgent evaluation for chest, breathing, or rhythm symptoms after exposure.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Latanoprost", "supplementBName": "Cannabis (THC-Dominant)", "interactionType": "caution", "severity": "moderate", "description": "THC-dominant cannabis can temporarily lower intraocular pressure, but the effect is short-lived and is not a reliable substitute for latanoprost. Using cannabis around eye-pressure checks can also make pressure look better than it is during the rest of the day. This matters because glaucoma progression is often silent until vision loss is advanced.", "recommendation": "Do not replace or skip latanoprost because cannabis seems to lower eye pressure. Tell your eye clinician if you use THC-dominant cannabis, especially before pressure checks or visual-field testing. Keep latanoprost dosing consistent and seek ophthalmology guidance for any plan to change glaucoma therapy.", "minimumTimeSeparation": null, "mechanism": "Latanoprost is a prostaglandin F2-alpha analog that lowers intraocular pressure mainly by increasing uveoscleral outflow. THC and related cannabinoids can lower intraocular pressure through cannabinoid-receptor pathways, but the effect is transient and accompanied by systemic CNS and cardiovascular effects.", "evidenceLevel": "moderate", "sources": [ { "text": "Garway-Heath DF, Crabb DP, Bunce C, et al. Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial. Lancet. 2015;385(9975):1295-1304.", "pmid": "25533656", "doi": "10.1016/S0140-6736(14)62111-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25533656/", "publicSourceType": "PMID" }, { "text": "Novack GD. Cannabinoids for treatment of glaucoma. Curr Opin Ophthalmol. 2016;27(2):146-150.", "pmid": "26840343", "doi": "10.1097/ICU.0000000000000242", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26840343/", "publicSourceType": "PMID" }, { "text": "Tomida I, Pertwee RG, Azuara-Blanco A. Cannabinoids and glaucoma. Br J Ophthalmol. 2004;88(5):708-713.", "pmid": "15090428", "doi": "10.1136/bjo.2003.032250", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15090428/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "THC-dominant cannabis can transiently lower eye pressure and complicate assessment of latanoprost-controlled glaucoma.", "clinicalSignificance": "Short-lived pressure lowering can falsely reassure patients and clinicians while undertreated glaucoma continues to risk silent vision loss.", "managementStrategy": "Continue latanoprost as prescribed and disclose cannabis use when glaucoma control is being assessed.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Vitamin C Liposomal", "interactionType": "conflict", "severity": "serious", "description": "High-dose vitamin C has rare case-report evidence of reducing warfarin response, followed by rapid INR increases after vitamin C is stopped. Liposomal vitamin C products are often used at higher supplemental doses, so the same ascorbic acid concern is relevant even though the liposomal form itself has not been separately studied. The main risk is unstable anticoagulation when large vitamin C doses are started, stopped, or changed.", "recommendation": "Keep vitamin C Liposomal dosing consistent if you take warfarin, and avoid high-dose use unless your anticoagulation clinic knows. Check INR after starting, stopping, or substantially changing the dose. Watch for both clot symptoms while INR is low and bleeding symptoms if vitamin C is stopped and INR rebounds.", "minimumTimeSeparation": null, "mechanism": "The mechanism of ascorbic acid-associated warfarin resistance is uncertain and may vary by patient. Reported cases show a pharmacodynamic pattern of subtherapeutic INR during ascorbic acid exposure and INR rise after discontinuation.", "evidenceLevel": "emerging", "sources": [ { "text": "Sattar A, Willman JE, Kolluri R. Possible warfarin resistance due to interaction with ascorbic acid: case report and literature review. Am J Health Syst Pharm. 2013;70(9):782-786.", "pmid": "23592361", "doi": "10.2146/ajhp110704", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23592361/", "publicSourceType": "PMID" }, { "text": "Gao P, Shen Y, Wu P, Lv W. Ascorbic acid-induced warfarin resistance after breast cancer surgery: a case report and literature review. Front Pharmacol. 2024;15:1390996.", "pmid": "38738175", "doi": "10.3389/fphar.2024.1390996", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38738175/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Vitamin C Liposomal at high or changing doses may destabilize warfarin response.", "clinicalSignificance": "Warfarin under-anticoagulation can permit thrombosis, while abrupt vitamin C discontinuation may allow INR to rise quickly.", "managementStrategy": "Avoid high-dose or inconsistent use and monitor INR after any meaningful vitamin C dose change.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Alprazolam", "supplementBName": "Passionflower", "interactionType": "caution", "severity": "serious", "description": "Passionflower has measurable anxiolytic and GABA-related CNS activity. Alprazolam is a benzodiazepine sedative, so the combination may cause more drowsiness, impaired coordination, slowed reaction time, or unsafe driving. Risk is higher with alcohol, opioids, sleep medicines, older age, sleep apnea, or dose escalation.", "recommendation": "Avoid combining passionflower with alprazolam unless your prescriber agrees. If used, start with the lowest possible supplement dose, avoid alcohol and other sedatives, and do not drive until you know the combined effect. Seek urgent help for extreme sleepiness, confusion, falls, or slowed breathing.", "minimumTimeSeparation": null, "mechanism": "Passionflower extracts can produce GABA(A)-related currents and have clinical anxiolytic effects. Alprazolam positively modulates GABA(A) receptors through the benzodiazepine site, creating additive CNS-depressant potential.", "evidenceLevel": "emerging", "sources": [ { "text": "Akhondzadeh S, Naghavi HR, Vazirian M, Shayeganpour A, Rashidi H, Khani M. Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam. J Clin Pharm Ther. 2001;26(5):363-367.", "pmid": "11679026", "doi": "10.1046/j.1365-2710.2001.00367.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11679026/", "publicSourceType": "PMID" }, { "text": "Elsas SM, Rossi DJ, Raber J, White G, Seeley CA, Gregory WL, et al. Passiflora incarnata L. extracts elicit GABA currents in hippocampal neurons in vitro, and show anxiogenic and anticonvulsant effects in vivo, varying with extraction method. Phytomedicine. 2010;17(12):940-949.", "pmid": "20382514", "doi": "10.1016/j.phymed.2010.03.002", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20382514/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Passionflower may add to alprazolam-related sedation and psychomotor impairment.", "clinicalSignificance": "Combined CNS depression can increase falls, driving impairment, and respiratory-risk situations.", "managementStrategy": "Avoid unsupervised combination and monitor closely for excessive sedation if a prescriber approves it.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Clonazepam", "supplementBName": "Passionflower", "interactionType": "caution", "severity": "serious", "description": "Passionflower can have calming CNS effects and GABA-related activity. Clonazepam is a long-acting benzodiazepine, so additive sedation may last longer than expected and may carry into the next day. This is more concerning in older adults, people with sleep apnea, and anyone also using alcohol, opioids, antihistamines, or sleep medicines.", "recommendation": "Do not add passionflower to clonazepam without prescriber guidance. If the combination is approved, avoid driving or hazardous work until you know the effect and stop the supplement if excessive sleepiness, confusion, unsteady gait, or falls occur. Seek urgent care for severe sedation or breathing problems.", "minimumTimeSeparation": null, "mechanism": "Passionflower extract has demonstrated GABA(A)-linked activity and clinical anxiolytic effects. Clonazepam enhances GABA(A) receptor signaling, so the combination can produce additive CNS depression.", "evidenceLevel": "emerging", "sources": [ { "text": "Akhondzadeh S, Naghavi HR, Vazirian M, Shayeganpour A, Rashidi H, Khani M. Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam. J Clin Pharm Ther. 2001;26(5):363-367.", "pmid": "11679026", "doi": "10.1046/j.1365-2710.2001.00367.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11679026/", "publicSourceType": "PMID" }, { "text": "Elsas SM, Rossi DJ, Raber J, White G, Seeley CA, Gregory WL, et al. Passiflora incarnata L. extracts elicit GABA currents in hippocampal neurons in vitro, and show anxiogenic and anticonvulsant effects in vivo, varying with extraction method. Phytomedicine. 2010;17(12):940-949.", "pmid": "20382514", "doi": "10.1016/j.phymed.2010.03.002", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20382514/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Passionflower may increase clonazepam-related sedation and impairment.", "clinicalSignificance": "Clonazepam's long duration can make additive sedation persistent and increase fall or accident risk.", "managementStrategy": "Avoid unsupervised use and monitor for next-day sedation if combined.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Lorazepam", "supplementBName": "Passionflower", "interactionType": "caution", "severity": "serious", "description": "Passionflower has anxiolytic and GABA-related activity that may stack with lorazepam's benzodiazepine effect. The result can be more sedation, slowed thinking, poor coordination, or falls. Risk rises with alcohol, opioids, sleep medicines, respiratory disease, older age, or taking lorazepam more often than prescribed.", "recommendation": "Avoid passionflower with lorazepam unless your prescriber has reviewed the combination. If used, avoid alcohol and other sedatives, use caution with driving, and stop passionflower if you feel unusually sleepy, confused, or unsteady. Get urgent help for severe sedation or slowed breathing.", "minimumTimeSeparation": null, "mechanism": "Passionflower extracts can activate GABA(A)-related signaling and have demonstrated clinical anxiolytic activity. Lorazepam is a benzodiazepine positive allosteric modulator at GABA(A) receptors, creating additive pharmacodynamic CNS depression.", "evidenceLevel": "emerging", "sources": [ { "text": "Akhondzadeh S, Naghavi HR, Vazirian M, Shayeganpour A, Rashidi H, Khani M. Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam. J Clin Pharm Ther. 2001;26(5):363-367.", "pmid": "11679026", "doi": "10.1046/j.1365-2710.2001.00367.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11679026/", "publicSourceType": "PMID" }, { "text": "Elsas SM, Rossi DJ, Raber J, White G, Seeley CA, Gregory WL, et al. Passiflora incarnata L. extracts elicit GABA currents in hippocampal neurons in vitro, and show anxiogenic and anticonvulsant effects in vivo, varying with extraction method. Phytomedicine. 2010;17(12):940-949.", "pmid": "20382514", "doi": "10.1016/j.phymed.2010.03.002", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20382514/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Passionflower may add to lorazepam's sedating and psychomotor-impairing effects.", "clinicalSignificance": "Additive benzodiazepine-like sedation can impair driving and increase fall or breathing-risk situations.", "managementStrategy": "Avoid unsupervised combination and monitor closely for excess sedation if approved.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Diazepam", "supplementBName": "Apigenin", "interactionType": "caution", "severity": "moderate", "description": "Apigenin has benzodiazepine-receptor and GABA(A)-modulating activity in preclinical studies. One receptor study specifically found that apigenin enhanced diazepam's positive modulation of GABA(A) receptor activation. In people, this could mean more sedation, impaired coordination, or slowed reaction time, although direct clinical interaction trials are lacking.", "recommendation": "Use apigenin cautiously if you take diazepam, especially when starting either product or increasing doses. Avoid alcohol and other sedatives, and do not drive until you know how the combination affects you. Stop apigenin and contact your prescriber if sedation, confusion, or balance problems increase.", "minimumTimeSeparation": null, "mechanism": "Apigenin can bind central benzodiazepine receptors and modulate GABA(A) receptor responses. Diazepam is a benzodiazepine positive allosteric modulator at GABA(A) receptors, so apigenin may increase net receptor-mediated CNS depressant signaling.", "evidenceLevel": "emerging", "sources": [ { "text": "Campbell EL, Chebib M, Johnston GAR. The dietary flavonoids apigenin and (-)-epigallocatechin gallate enhance the positive modulation by diazepam of the activation by GABA of recombinant GABA(A) receptors. Biochem Pharmacol. 2004;68(8):1631-1638.", "pmid": "15451406", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15451406/", "publicSourceType": "PMID" }, { "text": "Viola H, Wasowski C, Levi de Stein M, Wolfman C, Silveira R, Dajas F, et al. Apigenin, a component of Matricaria recutita flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects. Planta Med. 1995;61(3):213-216.", "pmid": "7617761", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7617761/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Apigenin may amplify diazepam-related sedation and psychomotor impairment.", "clinicalSignificance": "Even moderate extra sedation can matter for driving, falls, and concurrent sedative use.", "managementStrategy": "Use cautiously, avoid other sedatives, and monitor for increased impairment.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Alprazolam", "supplementBName": "Bacopa Monnieri", "interactionType": "caution", "severity": "moderate", "description": "Bacopa Monnieri extract inhibited CYP3A4 in vitro, and alprazolam exposure is clinically increased by CYP3A inhibition. Human data proving a Bacopa-alprazolam interaction are lacking, but the combination is plausible enough to matter because alprazolam has dose-related sedation and impairment. Risk is higher with high-dose Bacopa products, older age, liver disease, alcohol, opioids, or other sedatives.", "recommendation": "Use extra caution when starting Bacopa Monnieri if you take alprazolam. Avoid alcohol and other sedatives, and watch for stronger or longer alprazolam effects such as unusual drowsiness, confusion, poor coordination, or memory problems. Ask your prescriber whether alprazolam dose timing or dose should be adjusted if symptoms increase.", "minimumTimeSeparation": null, "mechanism": "Bacopa Monnieri standardized extract competitively inhibited CYP3A4 in vitro. Alprazolam is metabolized by CYP3A enzymes, and CYP3A inhibitors can increase alprazolam pharmacokinetic exposure and pharmacodynamic effects.", "evidenceLevel": "emerging", "sources": [ { "text": "Ramasamy S, Kiew LV, Chung LY. Inhibition of human cytochrome P450 enzymes by Bacopa monnieri standardized extract and constituents. Molecules. 2014;19(2):2588-2601.", "pmid": "24566323", "doi": "10.3390/molecules19022588", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24566323/", "publicSourceType": "PMID" }, { "text": "Yasui N, Kondo T, Otani K, Furukori H, Kaneko S, Ohkubo T, et al. Effect of itraconazole on the single oral dose pharmacokinetics and pharmacodynamics of alprazolam. Psychopharmacology (Berl). 1998;139(3):269-273.", "pmid": "9784084", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9784084/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Bacopa Monnieri may increase alprazolam exposure and sedation through CYP3A4 inhibition.", "clinicalSignificance": "Alprazolam has dose-related impairment, so even a modest exposure increase can affect safety-sensitive tasks.", "managementStrategy": "Monitor for stronger alprazolam effects after Bacopa changes and avoid concurrent sedatives.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Tamsulosin", "supplementBName": "Saw Palmetto", "interactionType": "synergy", "severity": "info", "description": "Saw palmetto, especially standardized hexanic Serenoa repens extract, has been studied as an add-on to tamsulosin for moderate to severe LUTS/BPH. Combination treatment improved urinary symptom scores more than either treatment alone in observational data, with tolerability similar to tamsulosin. The main practical issue is making sure symptom improvement is monitored while still following prostate cancer screening and BPH follow-up plans.", "recommendation": "Use this combination only as an adjunct to your prescribed BPH plan, not as a replacement for tamsulosin. Track urinary symptoms, dizziness, and sexual side effects, and keep routine PSA/prostate follow-up with your clinician.", "minimumTimeSeparation": null, "mechanism": "Tamsulosin relaxes prostate and bladder-neck smooth muscle through alpha1A/alpha1D blockade. Hexanic Serenoa repens extract appears to act through anti-inflammatory and antiandrogen-related pathways in prostate tissue, so the combination can improve symptoms through complementary mechanisms.", "evidenceLevel": "moderate", "sources": [ { "text": "Alcaraz A, Rodriguez-Antolin A, Carballido-Rodriguez J, Castro-Diaz D, Medina-Polo J, Fernandez-Gomez JM, et al. Clinical Benefit of Tamsulosin and the Hexanic Extract of Serenoa Repens, in Combination or as Monotherapy, in Patients with Moderate/Severe LUTS-BPH: A Subset Analysis of the QUALIPROST Study. J Clin Med. 2020;9(9):2909.", "pmid": "32917008", "doi": "10.3390/jcm9092909", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32917008/", "publicSourceType": "PMID" }, { "text": "De Nunzio C, Salonia A, Gacci M, Ficarra V. The Role of Combination Therapy with alpha-Blockers and Hexanic Extract of Serenoa repens in the Treatment of LUTS/BPH. J Clin Med. 2022;11(23):7169.", "pmid": "36498751", "doi": "10.3390/jcm11237169", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36498751/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Saw palmetto may add urinary symptom benefit when used with tamsulosin.", "clinicalSignificance": "Patients may get better LUTS/BPH symptom control but still need standard monitoring rather than self-substituting supplements for medication.", "managementStrategy": "Use as an adjunct only, track urinary symptoms and adverse effects, and maintain PSA/prostate follow-up.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Tamsulosin", "supplementBName": "Pine Bark Extract", "interactionType": "caution", "severity": "moderate", "description": "Tamsulosin can cause orthostatic hypotension, especially when it is started or restarted. Pine bark extract products such as pycnogenol have shown modest blood-pressure-lowering effects in some meta-analyses. Combining them may increase dizziness, near-fainting, or fall risk in people with low baseline blood pressure, dehydration, or other blood pressure medicines.", "recommendation": "Do not start pine bark extract at the same time you start or restart tamsulosin. If you use both, begin with a low pine bark dose, check sitting and standing blood pressure for 1-2 weeks, and stop the supplement if lightheadedness occurs.", "minimumTimeSeparation": null, "mechanism": "Tamsulosin can reduce vascular alpha1-mediated compensation during standing despite its uroselectivity. Pine bark polyphenols may improve endothelial nitric-oxide signaling and modestly reduce systolic and diastolic pressure, creating additive hypotension risk.", "evidenceLevel": "emerging", "sources": [ { "text": "Bird ST, Delaney JA, Brophy JM, Etminan M, Skeldon SC, Hartzema AG. Tamsulosin treatment for benign prostatic hyperplasia and risk of severe hypotension in men aged 40-85 years in the United States: risk window analyses using between and within patient methodology. BMJ. 2013;347:f6320.", "pmid": "24192967", "doi": "10.1136/bmj.f6320", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24192967/", "publicSourceType": "PMID" }, { "text": "Malekahmadi M, Moradi Moghaddam O, Firouzi S, Daryabeygi-Khotbehsara R, Islam SMS, Norouzy A, Soltani S. Effects of pycnogenol on cardiometabolic health: A systematic review and meta-analysis of randomized controlled trials. Pharmacol Res. 2019;150:104472.", "pmid": "31585179", "doi": "10.1016/j.phrs.2019.104472", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31585179/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive blood-pressure lowering may cause dizziness or orthostatic symptoms.", "clinicalSignificance": "Falls and syncope are most plausible during the early tamsulosin risk window or in patients already prone to low blood pressure.", "managementStrategy": "Stagger initiation, monitor standing blood pressure, and discontinue pine bark extract if dizziness develops.", "isSynergistic": null, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Alfuzosin", "supplementBName": "Pine Bark Extract", "interactionType": "caution", "severity": "moderate", "description": "Alfuzosin is used for LUTS/BPH and can contribute to blood-pressure symptoms in susceptible patients, particularly with other agents that lower vascular tone. Pine bark extract has shown modest reductions in systolic and diastolic blood pressure in some randomized-trial meta-analyses. The combination may increase lightheadedness, fatigue, or near-syncope in patients with low baseline pressure or concurrent antihypertensive therapy.", "recommendation": "Start pine bark extract cautiously if you take alfuzosin. Monitor blood pressure and orthostatic symptoms during the first 1-2 weeks, and stop or reduce the supplement if readings drop below your usual range or you feel faint.", "minimumTimeSeparation": null, "mechanism": "Alfuzosin blocks alpha1 receptors and can reduce vascular resistance. Pine bark extract may enhance endothelial vasodilatory signaling and modestly lower blood pressure, so the combination can reduce compensatory vascular tone.", "evidenceLevel": "emerging", "sources": [ { "text": "Zhang LT, Lee SW, Park K, Chung WS, Kim SW, Hyun JS, Moon DG, Yang SK. Multicenter, prospective, comparative cohort study evaluating the efficacy and safety of alfuzosin 10 mg with regard to blood pressure in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia with or without antihypertensive medications. Clin Interv Aging. 2015;10:277-286.", "pmid": "25653511", "doi": "10.2147/CIA.S74102", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25653511/", "publicSourceType": "PMID" }, { "text": "Malekahmadi M, Moradi Moghaddam O, Firouzi S, Daryabeygi-Khotbehsara R, Islam SMS, Norouzy A, Soltani S. Effects of pycnogenol on cardiometabolic health: A systematic review and meta-analysis of randomized controlled trials. Pharmacol Res. 2019;150:104472.", "pmid": "31585179", "doi": "10.1016/j.phrs.2019.104472", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31585179/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive vasodilation may lower blood pressure enough to cause symptoms.", "clinicalSignificance": "Patients using antihypertensives or those with baseline low blood pressure are more likely to become symptomatic.", "managementStrategy": "Use a cautious starting dose, monitor blood pressure, and stop pine bark extract if orthostatic symptoms appear.", "isSynergistic": null, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Tadalafil", "supplementBName": "L-Citrulline", "interactionType": "synergy", "severity": "info", "description": "L-Citrulline can raise plasma L-arginine and nitric-oxide signaling, while tadalafil preserves cGMP by inhibiting PDE5. A small randomized crossover pilot study found that L-citrulline-containing supplementation improved erectile function in men who were still using on-demand PDE5 inhibitors. The combination is usually a therapeutic synergy, but dizziness or flushing can occur if vasodilation becomes excessive.", "recommendation": "Use L-citrulline with tadalafil only after you know how tadalafil affects your blood pressure. Start with a low L-citrulline dose, avoid combining it with nitrates or heavy alcohol use, and stop the supplement if you develop dizziness, faintness, or severe headache.", "minimumTimeSeparation": null, "mechanism": "L-Citrulline is converted to L-arginine and augments nitric-oxide-dependent signaling. Tadalafil inhibits PDE5, reducing cGMP breakdown, so increased nitric oxide upstream and preserved cGMP downstream can complement erectile-response signaling.", "evidenceLevel": "emerging", "sources": [ { "text": "Shirai M, Hiramatsu I, Aoki Y, Shimoyama H, Mizuno T, Nozaki T, et al. Oral L-citrulline and Transresveratrol Supplementation Improves Erectile Function in Men With Phosphodiesterase 5 Inhibitors: A Randomized, Double-Blind, Placebo-Controlled Crossover Pilot Study. Sex Med. 2018;6(4):291-296.", "pmid": "30150102", "doi": "10.1016/j.esxm.2018.07.001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30150102/", "publicSourceType": "PMID" }, { "text": "Schwedhelm E, Maas R, Freese R, Jung D, Lukacs Z, Jambrecina A, et al. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol. 2008;65(1):51-59.", "pmid": "17662090", "doi": "10.1111/j.1365-2125.2007.02990.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17662090/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "L-Citrulline may enhance tadalafil response through the nitric oxide-cGMP pathway.", "clinicalSignificance": "The combination may help some PDE5-inhibitor partial responders but can also add vasodilatory side effects.", "managementStrategy": "Start L-citrulline low, avoid nitrate co-use, and monitor for dizziness, flushing, or headache.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Sildenafil", "supplementBName": "L-Citrulline", "interactionType": "synergy", "severity": "info", "description": "L-Citrulline can increase L-arginine availability and nitric-oxide-dependent signaling, which is upstream of sildenafil's PDE5 effect. In a small randomized crossover pilot study, L-citrulline-containing supplementation improved erectile function in men continuing on-demand PDE5 inhibitor therapy. This can be a useful therapeutic synergy, but additive vasodilation may cause flushing, headache, or dizziness.", "recommendation": "If you add L-citrulline to sildenafil, start with a low dose and assess tolerability on a day when you can sit or lie down if lightheaded. Avoid nitrates and avoid heavy alcohol use with the combination.", "minimumTimeSeparation": null, "mechanism": "L-Citrulline increases plasma L-arginine and nitric-oxide signaling. Sildenafil inhibits PDE5 and preserves cGMP in vascular and cavernosal smooth muscle, so the two can act at complementary points in the same vasodilatory pathway.", "evidenceLevel": "emerging", "sources": [ { "text": "Shirai M, Hiramatsu I, Aoki Y, Shimoyama H, Mizuno T, Nozaki T, et al. Oral L-citrulline and Transresveratrol Supplementation Improves Erectile Function in Men With Phosphodiesterase 5 Inhibitors: A Randomized, Double-Blind, Placebo-Controlled Crossover Pilot Study. Sex Med. 2018;6(4):291-296.", "pmid": "30150102", "doi": "10.1016/j.esxm.2018.07.001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30150102/", "publicSourceType": "PMID" }, { "text": "Schwedhelm E, Maas R, Freese R, Jung D, Lukacs Z, Jambrecina A, et al. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol. 2008;65(1):51-59.", "pmid": "17662090", "doi": "10.1111/j.1365-2125.2007.02990.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17662090/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "L-Citrulline may enhance sildenafil response through nitric-oxide and cGMP signaling.", "clinicalSignificance": "Partial responders to sildenafil may notice improved erectile response, while sensitive patients may notice vasodilatory side effects.", "managementStrategy": "Start L-citrulline low, avoid nitrates and heavy alcohol, and stop if dizziness or severe headache occurs.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Tadalafil", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "moderate", "description": "St. John's Wort can induce CYP3A4, the main metabolic pathway for tadalafil. This may lower tadalafil exposure and reduce its effectiveness for erectile dysfunction, BPH symptoms, or pulmonary hypertension indications. The risk is most relevant with daily or repeated St. John's Wort use, because enzyme induction builds over days and can persist after stopping.", "recommendation": "Avoid St. John's Wort while using tadalafil unless your prescriber specifically approves it. If you stop St. John's Wort, do not change tadalafil dosing on your own; enzyme activity may take about a week or longer to normalize.", "minimumTimeSeparation": null, "mechanism": "Tadalafil is cleared predominantly by hepatic CYP3A metabolism. St. John's Wort activates pregnane X receptor pathways and induces CYP3A activity, increasing clearance of CYP3A substrates and lowering drug exposure.", "evidenceLevel": "moderate", "sources": [ { "text": "Forgue ST, Patterson BE, Bedding AW, Payne CD, Phillips DL, Wrishko RE, Mitchell MI. Tadalafil pharmacokinetics in healthy subjects. Br J Clin Pharmacol. 2006;61(3):280-288.", "pmid": "16487221", "doi": "10.1111/j.1365-2125.2005.02553.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16487221/", "publicSourceType": "PMID" }, { "text": "Markowitz JS, Donovan JL, DeVane CL, Taylor RM, Ruan Y, Wang JS, Chavin KD. Effect of St John's wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA. 2003;290(11):1500-1504.", "pmid": "13129991", "doi": "10.1001/jama.290.11.1500", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/13129991/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "St. John's Wort may reduce tadalafil exposure and clinical effect.", "clinicalSignificance": "Loss of tadalafil effect can worsen ED or LUTS/BPH control and is more consequential when tadalafil is used for pulmonary hypertension.", "managementStrategy": "Avoid St. John's Wort with tadalafil and involve the prescriber before starting or stopping it.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Atomoxetine", "supplementBName": "Cocaine", "interactionType": "caution", "severity": "serious", "description": "Atomoxetine and cocaine both increase noradrenergic cardiovascular stress. A monitored inpatient study in cocaine-experienced participants found atomoxetine plus intravenous cocaine was tolerated at tested doses, but cocaine still produced heart-rate and blood-pressure responses; a later abstinent-user study found atomoxetine increased heart rate and systolic blood pressure versus placebo. Real-world cocaine dose, route, adulterants, and redosing make co-use unsafe outside monitored research conditions.", "recommendation": "Avoid cocaine while taking atomoxetine. Do not take extra atomoxetine to offset cocaine crash, fatigue, or attention problems. Seek emergency care for chest pain, severe headache, fainting, severe agitation, shortness of breath, or a fast or irregular heartbeat.", "minimumTimeSeparation": null, "mechanism": "Atomoxetine inhibits the norepinephrine transporter and can increase blood pressure and heart rate. Cocaine blocks norepinephrine, dopamine, and serotonin reuptake, increases sympathetic outflow, causes vasoconstriction, and can impair cardiac conduction through sodium-channel blockade, creating additive cardiovascular and neuropsychiatric toxicity potential.", "evidenceLevel": "moderate", "sources": [ { "text": "Cantilena L, Kahn R, Duncan CC et al.. Safety of atomoxetine in combination with intravenous cocaine in cocaine-experienced participants. Journal of addiction medicine. 2012 Dec;6(4):265-73.", "pmid": "22987022", "doi": "10.1097/ADM.0b013e31826b767f", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22987022/", "publicSourceType": "PMID" }, { "text": "DeVito EE, Herman AI, Konkus NS et al.. Atomoxetine in abstinent cocaine users: Cognitive, subjective and cardiovascular effects. Pharmacology, biochemistry, and behavior. 2017 Aug;159:55-61.", "pmid": "28716656", "doi": "10.1016/j.pbb.2017.07.002", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28716656/", "publicSourceType": "PMID" }, { "text": "Kim ST, Park T. Acute and Chronic Effects of Cocaine on Cardiovascular Health. International journal of molecular sciences. 2019;20(3):584.", "pmid": "30700023", "doi": "10.3390/ijms20030584", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30700023/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Atomoxetine may add to cocaine-related sympathetic and cardiovascular toxicity.", "clinicalSignificance": "Co-use can increase risk of hypertension, tachycardia, agitation, chest pain, arrhythmia, or ischemia, especially outside monitored research conditions.", "managementStrategy": "Avoid cocaine during atomoxetine therapy and get urgent evaluation for cardiovascular or severe neuropsychiatric symptoms after exposure.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Atomoxetine", "supplementBName": "Berberine", "interactionType": "caution", "severity": "moderate", "description": "Atomoxetine exposure is highly sensitive to CYP2D6 inhibition. A clinical pharmacokinetic study showed potent CYP2D6 inhibition with paroxetine markedly increased atomoxetine exposure. Berberine has human clinical evidence of CYP2D6 inhibition after repeated dosing, so berberine could raise atomoxetine exposure even though the exact atomoxetine-berberine combination has not been directly tested.", "recommendation": "Ask your prescriber or pharmacist before starting berberine while taking atomoxetine, especially if you are on a higher atomoxetine dose, have CYP2D6 poor-metabolizer status, or also take CYP2D6 inhibitors. Monitor for new insomnia, appetite loss, dry mouth, palpitations, higher blood pressure, urinary hesitation, or unusual irritability.", "minimumTimeSeparation": null, "mechanism": "Atomoxetine is primarily cleared by CYP2D6-mediated metabolism. Repeated berberine dosing decreased CYP2D6 activity in healthy volunteers, shown by a higher dextromethorphan/dextrorphan metabolic ratio, which could reduce atomoxetine clearance and increase concentration-dependent adverse effects.", "evidenceLevel": "emerging", "sources": [ { "text": "Belle DJ, Ernest CS, Sauer JM et al.. Effect of potent CYP2D6 inhibition by paroxetine on atomoxetine pharmacokinetics. Journal of clinical pharmacology. 2002 Nov;42(11):1219-27.", "pmid": "12412820", "doi": "10.1177/009127002762491307", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12412820/", "publicSourceType": "PMID" }, { "text": "Guo Y, Chen Y, Tan ZR et al.. Repeated administration of berberine inhibits cytochromes P450 in humans. European journal of clinical pharmacology. 2012 Feb;68(2):213-7.", "pmid": "21870106", "doi": "10.1007/s00228-011-1108-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21870106/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Berberine may inhibit CYP2D6 and increase atomoxetine exposure.", "clinicalSignificance": "Higher atomoxetine exposure can increase dose-related cardiovascular, sleep, appetite, urinary, or mood adverse effects.", "managementStrategy": "Use clinician-guided monitoring and consider atomoxetine dose review if berberine is started, stopped, or taken at high repeated doses.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Polyethylene Glycol", "supplementBName": "Activated Charcoal", "interactionType": "timingSensitive", "severity": "moderate", "description": "High-volume polyethylene glycol electrolyte lavage used for whole bowel irrigation can interfere with activated charcoal's toxin-binding role if the two are mixed or coadministered improperly. An in vitro study found PEG lavage solution caused desorption of theophylline from activated charcoal, and toxicology position guidance discusses sequencing charcoal and whole bowel irrigation separately. This concern applies to poisoning management or lavage-level PEG use, not ordinary once-daily constipation dosing.", "recommendation": "Do not self-combine activated charcoal with high-dose PEG bowel prep or whole-bowel-irrigation regimens. For suspected poisoning, call poison control or emergency services; charcoal timing, PEG lavage, airway safety, and the substance ingested need clinician direction. Avoid taking activated charcoal close to routine oral medicines because it can reduce their absorption.", "minimumTimeSeparation": null, "mechanism": "Activated charcoal adsorbs many drugs and toxins in the gut lumen. PEG electrolyte lavage rapidly moves intestinal contents and, when present with charcoal, can reduce retained adsorption by dilution, transit acceleration, or desorption from the charcoal surface.", "evidenceLevel": "moderate", "sources": [ { "text": "Tenenbein M. Position statement: whole bowel irrigation. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. Journal of toxicology. Clinical toxicology. 1997;35(7):753-62.", "pmid": "9482429", "doi": "10.3109/15563659709162571", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9482429/", "publicSourceType": "PMID" }, { "text": "Hoffman RS, Chiang WK, Howland MA et al.. Theophylline desorption from activated charcoal caused by whole bowel irrigation solution. Journal of toxicology. Clinical toxicology. 1991;29(2):191-201.", "pmid": "2051506", "doi": "10.3109/15563659109038611", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2051506/", "publicSourceType": "PMID" }, { "text": "Hoegberg LCG, Shepherd G, Wood DM et al.. Systematic review on the use of activated charcoal for gastrointestinal decontamination following acute oral overdose. Clinical toxicology (Philadelphia, Pa.). 2021 Dec;59(12):1196-1227.", "pmid": "34424785", "doi": "10.1080/15563650.2021.1961144", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34424785/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Lavage-dose polyethylene glycol can reduce the effectiveness or predictability of activated charcoal decontamination when coadministered improperly.", "clinicalSignificance": "Poor sequencing during overdose care can reduce toxin binding or complicate decontamination while also increasing aspiration and fluid-management concerns.", "managementStrategy": "Use activated charcoal and PEG whole bowel irrigation only under poison-center or emergency-clinician direction, with attention to airway protection and timing.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Polyethylene Glycol", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Polyethylene glycol bowel-preparation products are sometimes formulated with gram-dose ascorbic acid to improve cleansing with a lower PEG volume. Randomized trials support PEG plus ascorbate regimens for colonoscopy preparation, but this evidence applies to medically directed bowel-prep dosing rather than routine daily vitamin C supplementation with OTC PEG for constipation.", "recommendation": "Use PEG plus high-dose vitamin C only when it is part of a prescribed or procedure-directed bowel-prep regimen. Do not add large vitamin C doses to PEG laxative use on your own, especially if you have kidney disease, a history of oxalate kidney stones, dehydration risk, or electrolyte problems. Follow the prep instructions and hydration plan exactly.", "minimumTimeSeparation": null, "mechanism": "PEG retains water osmotically in the intestinal lumen. Large bowel-prep doses of ascorbic acid add an additional osmotic load, allowing lower-volume PEG regimens while still producing catharsis; the same osmotic effect can worsen diarrhea, nausea, or dehydration if used outside directed bowel preparation.", "evidenceLevel": "moderate", "sources": [ { "text": "Ell C, Fischbach W, Bronisch HJ et al.. Randomized trial of low-volume PEG solution versus standard PEG + electrolytes for bowel cleansing before colonoscopy. The American journal of gastroenterology. 2008 Apr;103(4):883-93.", "pmid": "18190651", "doi": "10.1111/j.1572-0241.2007.01708.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18190651/", "publicSourceType": "PMID" }, { "text": "Jung Y, Kang SB, Yoon HJ et al.. Improving the tolerability and safety of 1-L polyethylene glycol plus low-dose ascorbic acid for bowel preparation in a healthy population: a randomized multicenter clinical trial. Gastrointestinal endoscopy. 2022 Aug;96(2):341-350.e1.", "pmid": "35288148", "doi": "10.1016/j.gie.2022.03.007", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35288148/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Gram-dose vitamin C can augment PEG bowel cleansing through added osmotic catharsis.", "clinicalSignificance": "The combination can be useful for prescribed bowel preparation, but unsupervised high-dose vitamin C with PEG can increase diarrhea, nausea, dehydration, or kidney-stone concerns in susceptible people.", "managementStrategy": "Reserve PEG plus gram-dose vitamin C for directed bowel preparation and avoid self-escalation beyond the product or clinician instructions.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Memantine", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "A controlled human study found that combining memantine with alcohol increased dissociation, confusion, stimulation, and impaired balance without changing alcohol pharmacokinetics. Because memantine is commonly used in people with cognitive impairment or fall risk, alcohol can make confusion, dizziness, judgment impairment, and injury risk more clinically important.", "recommendation": "Avoid or minimize alcohol while taking memantine, especially during titration, in older adults, or when dementia symptoms, dizziness, or fall risk are present. Do not drive or do safety-sensitive tasks after drinking. Seek medical advice for new severe confusion, agitation, falls, fainting, or unsafe behavior.", "minimumTimeSeparation": null, "mechanism": "Memantine is an uncompetitive NMDA receptor antagonist. Alcohol also modulates NMDA and GABAergic signaling and impairs balance and cognition. The interaction is primarily pharmacodynamic: overlapping central nervous system effects rather than altered alcohol exposure.", "evidenceLevel": "moderate", "sources": [ { "text": "Bisaga A, Evans SM. Acute effects of memantine in combination with alcohol in moderate drinkers. Psychopharmacology (Berl). 2004;172(1):16-24.", "pmid": "14530901", "doi": "10.1007/s00213-003-1617-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14530901/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Alcohol can amplify memantine-associated cognitive, dissociative, and balance impairment.", "clinicalSignificance": "Added confusion and impaired balance can increase falls, unsafe driving, medication errors, and behavioral risk in patients taking memantine.", "managementStrategy": "Avoid or limit alcohol, monitor cognition and balance, and reassess promptly after falls or major behavior changes.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Bee Pollen", "interactionType": "caution", "severity": "serious", "description": "Bee pollen has case-report evidence of potentiating warfarin. A stable warfarin patient developed an INR of 7.1 about one month after starting honeybee-collected pollen, with no other identified medication, diet, illness, alcohol, or adherence explanation. The mechanism is uncertain, and product composition varies by pollen source, so the main concern is unpredictable over-anticoagulation when bee pollen is started, stopped, or changed.", "recommendation": "Avoid bee pollen while taking warfarin unless your anticoagulation clinician approves it. If bee pollen is started or stopped, arrange extra INR monitoring within 1-2 weeks and watch for bruising, nosebleeds, gum bleeding, blood in urine or stool, severe headache, dizziness, or weakness.", "minimumTimeSeparation": null, "mechanism": "The mechanism has not been established. The published case is consistent with a pharmacodynamic or pharmacokinetic increase in warfarin effect after bee pollen exposure, but bee pollen is chemically variable and specific active constituents were not identified.", "evidenceLevel": "emerging", "sources": [ { "text": "Hurren KM, Lewis CL. Probable interaction between warfarin and bee pollen. Am J Health Syst Pharm. 2010;67(23):2034-2037.", "pmid": "21098375", "doi": "10.2146/ajhp090489", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21098375/", "publicSourceType": "PMID" }, { "text": "Tan CSS, Lee SWH. Warfarin and food, herbal or dietary supplement interactions: A systematic review. Br J Clin Pharmacol. 2021;87(2):352-374.", "pmid": "32478963", "doi": "10.1111/bcp.14404", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32478963/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Bee pollen may increase warfarin effect and raise the INR.", "clinicalSignificance": "Warfarin has a narrow therapeutic index, and an INR above 7 can substantially increase clinically important bleeding risk.", "managementStrategy": "Avoid unsupervised use; if exposure changes, coordinate extra INR monitoring and bleeding surveillance.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Royal Jelly", "interactionType": "caution", "severity": "serious", "description": "Royal Jelly has case-report evidence of potentiating warfarin. An elderly patient with previously stable warfarin therapy developed hematuria with INR 6.88-7.29 after starting Royal Jelly one week earlier, with no other clear medication, diet, travel, illness, alcohol, tobacco, or adherence explanation. The mechanism is unknown, but the observed INR rise and bleeding make the combination clinically important.", "recommendation": "Avoid Royal Jelly while taking warfarin unless your anticoagulation clinician has reviewed the risk. If Royal Jelly has already been started, tell the anticoagulation clinic promptly and ask whether INR should be checked sooner. Seek urgent care for visible bleeding, black stools, blood in urine, severe headache, weakness, or dizziness.", "minimumTimeSeparation": null, "mechanism": "The mechanism has not been established. The published case suggests Royal Jelly exposure may increase warfarin anticoagulant response, but the responsible constituent and whether the effect is pharmacokinetic or pharmacodynamic are unknown.", "evidenceLevel": "emerging", "sources": [ { "text": "Lee NJ, Fermo JD. Warfarin and royal jelly interaction. Pharmacotherapy. 2006;26(4):583-586.", "pmid": "16553520", "doi": "10.1592/phco.26.4.583", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16553520/", "publicSourceType": "PMID" }, { "text": "Tan CSS, Lee SWH. Warfarin and food, herbal or dietary supplement interactions: A systematic review. Br J Clin Pharmacol. 2021;87(2):352-374.", "pmid": "32478963", "doi": "10.1111/bcp.14404", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32478963/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Royal Jelly may increase warfarin effect and precipitate supratherapeutic INR with bleeding.", "clinicalSignificance": "The reported case involved hematuria and INR above 6.8, a range associated with high bleeding risk.", "managementStrategy": "Avoid unsupervised use; if used or discontinued, coordinate prompt INR monitoring and bleeding precautions.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Insulin Glargine", "supplementBName": "Vanadium", "interactionType": "caution", "severity": "serious", "description": "Vanadium salts have insulin-mimetic activity and small human studies in type 2 diabetes show improved insulin sensitivity and glucose-lowering effects. Insulin glargine provides basal insulin exposure, so adding vanadium may increase the risk of hypoglycemia, especially with reduced food intake, kidney disease, exercise changes, or other glucose-lowering drugs.", "recommendation": "Do not add vanadium to insulin glargine without diabetes-clinician guidance. If it is used, increase glucose monitoring when starting, stopping, or changing vanadium dose, and have a clear plan for treating low blood sugar. Seek urgent care for severe confusion, seizure, fainting, or inability to keep carbohydrates down.", "minimumTimeSeparation": null, "mechanism": "Vanadium compounds can mimic or amplify insulin signaling and improve hepatic and muscle insulin sensitivity. Insulin glargine independently lowers glucose through sustained insulin receptor activation, creating additive pharmacodynamic glucose-lowering potential.", "evidenceLevel": "emerging", "sources": [ { "text": "Cusi K, Cukier S, DeFronzo RA, Torres M, Puchulu FM, Redondo JC. Vanadyl sulfate improves hepatic and muscle insulin sensitivity in type 2 diabetes. J Clin Endocrinol Metab. 2001;86(3):1410-1417.", "pmid": "11238540", "doi": "10.1210/jcem.86.3.7337", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11238540/", "publicSourceType": "PMID" }, { "text": "Boden G, Chen X, Ruiz J, van Rossum GD, Turco S. Effects of vanadyl sulfate on carbohydrate and lipid metabolism in patients with non-insulin-dependent diabetes mellitus. Metabolism. 1996;45(9):1130-1135.", "pmid": "8781301", "doi": "10.1016/s0026-0495(96)90013-x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8781301/", "publicSourceType": "PMID" }, { "text": "Amiel SA, Dixon T, Mann R, Jameson K. Hypoglycaemia in Type 2 diabetes. Diabet Med. 2008;25(3):245-254.", "pmid": "18215172", "doi": "10.1111/j.1464-5491.2007.02341.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18215172/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Vanadium may add to insulin glargine's glucose-lowering effect and increase hypoglycemia risk.", "clinicalSignificance": "Hypoglycemia from basal insulin can be prolonged and dangerous, particularly overnight or in people with impaired awareness.", "managementStrategy": "Avoid unsupervised use; if combined, monitor glucose more often and adjust diabetes therapy only with clinician direction.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Insulin Aspart", "supplementBName": "Vanadium", "interactionType": "caution", "severity": "serious", "description": "Vanadium has insulin-like signaling effects and has lowered glucose or improved insulin sensitivity in small human diabetes studies. Insulin aspart is a rapid-acting mealtime insulin, so adding vanadium can make post-dose hypoglycemia more likely if carbohydrate intake, exercise, illness, or insulin dosing is not adjusted.", "recommendation": "Do not combine vanadium with insulin aspart unless your diabetes clinician is monitoring the change. Check glucose more frequently around meals and activity when vanadium is started, stopped, or dose-adjusted. Treat low glucose promptly and seek urgent help for severe neuroglycopenic symptoms.", "minimumTimeSeparation": null, "mechanism": "Vanadium compounds can improve insulin signaling and glucose disposal. Insulin aspart acutely increases peripheral glucose uptake and suppresses hepatic glucose output, so vanadium may add to the same pharmacodynamic pathway.", "evidenceLevel": "emerging", "sources": [ { "text": "Cusi K, Cukier S, DeFronzo RA, Torres M, Puchulu FM, Redondo JC. Vanadyl sulfate improves hepatic and muscle insulin sensitivity in type 2 diabetes. J Clin Endocrinol Metab. 2001;86(3):1410-1417.", "pmid": "11238540", "doi": "10.1210/jcem.86.3.7337", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11238540/", "publicSourceType": "PMID" }, { "text": "Goldfine AB, Patti ME, Zuberi L, et al. Metabolic effects of vanadyl sulfate in humans with non-insulin-dependent diabetes mellitus: in vivo and in vitro studies. Metabolism. 2000;49(3):400-410.", "pmid": "10726921", "doi": "10.1016/s0026-0495(00)90418-9", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10726921/", "publicSourceType": "PMID" }, { "text": "Amiel SA, Dixon T, Mann R, Jameson K. Hypoglycaemia in Type 2 diabetes. Diabet Med. 2008;25(3):245-254.", "pmid": "18215172", "doi": "10.1111/j.1464-5491.2007.02341.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18215172/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Vanadium may amplify insulin aspart's mealtime glucose-lowering effect.", "clinicalSignificance": "Rapid-acting insulin hypoglycemia can impair driving, exercise safety, and cognition within hours of a dose.", "managementStrategy": "Avoid unsupervised combination and intensify glucose monitoring if a clinician approves use.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Insulin Lispro", "supplementBName": "Vanadium", "interactionType": "caution", "severity": "serious", "description": "Vanadium salts can mimic insulin signaling and have shown glucose-lowering or insulin-sensitizing effects in human type 2 diabetes studies. Insulin lispro is rapid acting, so the combination may increase hypoglycemia risk, especially when meals are delayed, carbohydrates are reduced, or activity increases.", "recommendation": "Use vanadium with insulin lispro only with diabetes-clinician oversight. Increase glucose checks around meals, bedtime, and exercise after any vanadium change. Carry fast carbohydrates and seek urgent care for severe or recurrent hypoglycemia.", "minimumTimeSeparation": null, "mechanism": "Vanadium compounds can enhance insulin-receptor-linked signaling and insulin sensitivity. Insulin lispro lowers glucose through direct insulin receptor activation, so the combination can produce additive glucose lowering.", "evidenceLevel": "emerging", "sources": [ { "text": "Cusi K, Cukier S, DeFronzo RA, Torres M, Puchulu FM, Redondo JC. Vanadyl sulfate improves hepatic and muscle insulin sensitivity in type 2 diabetes. J Clin Endocrinol Metab. 2001;86(3):1410-1417.", "pmid": "11238540", "doi": "10.1210/jcem.86.3.7337", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11238540/", "publicSourceType": "PMID" }, { "text": "Mehdi MZ, Pandey SK, Theberge JF, Srivastava AK. Insulin signal mimicry as a mechanism for the insulin-like effects of vanadium. Cell Biochem Biophys. 2006;44(1):73-81.", "pmid": "16456236", "doi": "10.1385/CBB:44:1:073", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16456236/", "publicSourceType": "PMID" }, { "text": "Amiel SA, Dixon T, Mann R, Jameson K. Hypoglycaemia in Type 2 diabetes. Diabet Med. 2008;25(3):245-254.", "pmid": "18215172", "doi": "10.1111/j.1464-5491.2007.02341.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18215172/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Vanadium may increase insulin lispro-related hypoglycemia risk.", "clinicalSignificance": "Extra glucose lowering from a rapid-acting insulin regimen can cause abrupt symptomatic or severe hypoglycemia.", "managementStrategy": "Avoid unsupervised use and monitor glucose closely if combined under clinician supervision.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Glipizide", "supplementBName": "Vanadium", "interactionType": "caution", "severity": "serious", "description": "Vanadium has insulin-like and insulin-sensitizing activity in PubMed-indexed human diabetes studies. Glipizide stimulates insulin release and can cause hypoglycemia, so adding vanadium may increase the chance of low blood sugar, particularly in older adults, kidney disease, missed meals, or dose escalation.", "recommendation": "Avoid starting vanadium while taking glipizide unless your diabetes clinician approves and monitoring is planned. Check glucose more often during any vanadium change and report recurrent lows, sweating, tremor, confusion, or nighttime symptoms. Do not self-adjust glipizide dose without clinician guidance.", "minimumTimeSeparation": null, "mechanism": "Vanadium can improve insulin signaling and glucose handling. Glipizide increases pancreatic insulin secretion through sulfonylurea receptor activity, creating additive pharmacodynamic glucose-lowering potential.", "evidenceLevel": "emerging", "sources": [ { "text": "Cusi K, Cukier S, DeFronzo RA, Torres M, Puchulu FM, Redondo JC. Vanadyl sulfate improves hepatic and muscle insulin sensitivity in type 2 diabetes. J Clin Endocrinol Metab. 2001;86(3):1410-1417.", "pmid": "11238540", "doi": "10.1210/jcem.86.3.7337", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11238540/", "publicSourceType": "PMID" }, { "text": "Boden G, Chen X, Ruiz J, van Rossum GD, Turco S. Effects of vanadyl sulfate on carbohydrate and lipid metabolism in patients with non-insulin-dependent diabetes mellitus. Metabolism. 1996;45(9):1130-1135.", "pmid": "8781301", "doi": "10.1016/s0026-0495(96)90013-x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8781301/", "publicSourceType": "PMID" }, { "text": "Schopman JE, Simon AC, Hoefnagel SJ, Hoekstra JB, Scholten RJ, Holleman F. The incidence of mild and severe hypoglycaemia in patients with type 2 diabetes mellitus treated with sulfonylureas: a systematic review and meta-analysis. Diabetes Metab Res Rev. 2014;30(1):11-22.", "pmid": "24030920", "doi": "10.1002/dmrr.2470", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24030920/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Vanadium may add to glipizide's glucose-lowering effect and increase hypoglycemia risk.", "clinicalSignificance": "Sulfonylurea-associated hypoglycemia can be severe or recurrent and may require medical treatment.", "managementStrategy": "Avoid unsupervised combination and use closer glucose monitoring if a clinician approves it.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Glimepiride", "supplementBName": "Vanadium", "interactionType": "caution", "severity": "serious", "description": "Vanadium salts have insulin-mimetic effects and have improved insulin sensitivity in small human diabetes studies. Glimepiride is a sulfonylurea with recognized hypoglycemia risk, so adding vanadium may produce excessive glucose lowering, especially with missed meals, renal impairment, older age, or other diabetes drugs.", "recommendation": "Do not add vanadium to glimepiride without prescriber review. If a clinician approves the combination, check glucose more frequently during initiation and dose changes, and have a plan for low blood sugar. Seek urgent care for severe confusion, fainting, seizure, or persistent hypoglycemia.", "minimumTimeSeparation": null, "mechanism": "Vanadium can mimic insulin signaling and improve insulin sensitivity. Glimepiride increases insulin secretion from pancreatic beta cells, so the combination may additively lower glucose.", "evidenceLevel": "emerging", "sources": [ { "text": "Cusi K, Cukier S, DeFronzo RA, Torres M, Puchulu FM, Redondo JC. Vanadyl sulfate improves hepatic and muscle insulin sensitivity in type 2 diabetes. J Clin Endocrinol Metab. 2001;86(3):1410-1417.", "pmid": "11238540", "doi": "10.1210/jcem.86.3.7337", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11238540/", "publicSourceType": "PMID" }, { "text": "Goldfine AB, Patti ME, Zuberi L, et al. Metabolic effects of vanadyl sulfate in humans with non-insulin-dependent diabetes mellitus: in vivo and in vitro studies. Metabolism. 2000;49(3):400-410.", "pmid": "10726921", "doi": "10.1016/s0026-0495(00)90418-9", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10726921/", "publicSourceType": "PMID" }, { "text": "Douros A, Yin H, Yu OHY, Filion KB, Azoulay L, Suissa S. Pharmacologic Differences of Sulfonylureas and the Risk of Adverse Cardiovascular and Hypoglycemic Events. Diabetes Care. 2017;40(11):1506-1513.", "pmid": "28864502", "doi": "10.2337/dc17-0595", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28864502/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Vanadium may increase glimepiride-related hypoglycemia risk.", "clinicalSignificance": "Hypoglycemia from sulfonylureas can impair cognition, cause falls, and become medically urgent.", "managementStrategy": "Avoid unsupervised use and monitor glucose closely if combined under clinician guidance.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Glyburide", "supplementBName": "Vanadium", "interactionType": "caution", "severity": "serious", "description": "Vanadium has insulin-like effects and has improved glucose metabolism in small human studies. Glyburide is a longer-acting sulfonylurea with a higher hypoglycemia burden than some alternatives, so vanadium may further increase the risk of severe or prolonged low blood sugar.", "recommendation": "Avoid vanadium while taking glyburide unless your prescriber specifically recommends it and plans glucose monitoring. Be especially cautious with kidney disease, older age, missed meals, alcohol, or exercise changes. Seek urgent care for severe, recurrent, or hard-to-correct hypoglycemia.", "minimumTimeSeparation": null, "mechanism": "Vanadium compounds can mimic insulin signaling and improve insulin sensitivity. Glyburide stimulates endogenous insulin release, and its longer action can make additive glucose lowering more persistent.", "evidenceLevel": "emerging", "sources": [ { "text": "Cusi K, Cukier S, DeFronzo RA, Torres M, Puchulu FM, Redondo JC. Vanadyl sulfate improves hepatic and muscle insulin sensitivity in type 2 diabetes. J Clin Endocrinol Metab. 2001;86(3):1410-1417.", "pmid": "11238540", "doi": "10.1210/jcem.86.3.7337", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11238540/", "publicSourceType": "PMID" }, { "text": "Boden G, Chen X, Ruiz J, van Rossum GD, Turco S. Effects of vanadyl sulfate on carbohydrate and lipid metabolism in patients with non-insulin-dependent diabetes mellitus. Metabolism. 1996;45(9):1130-1135.", "pmid": "8781301", "doi": "10.1016/s0026-0495(96)90013-x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8781301/", "publicSourceType": "PMID" }, { "text": "Douros A, Yin H, Yu OHY, Filion KB, Azoulay L, Suissa S. Pharmacologic Differences of Sulfonylureas and the Risk of Adverse Cardiovascular and Hypoglycemic Events. Diabetes Care. 2017;40(11):1506-1513.", "pmid": "28864502", "doi": "10.2337/dc17-0595", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28864502/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Vanadium may increase glyburide-related hypoglycemia risk.", "clinicalSignificance": "Glyburide-associated hypoglycemia can be severe and prolonged, especially in older adults or kidney impairment.", "managementStrategy": "Avoid unsupervised combination and use frequent glucose checks if combined under prescriber supervision.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Ciprofloxacin", "supplementBName": "Manganese", "interactionType": "timingSensitive", "severity": "serious", "description": "Manganese can form chelate complexes with fluoroquinolone antibiotics. An in vitro study using a manganese-containing gastrointestinal diagnostic product found complex formation with ciprofloxacin, and human studies with other multivalent mineral cations show reduced ciprofloxacin absorption. Taking manganese near ciprofloxacin could reduce antibiotic exposure and contribute to treatment failure.", "recommendation": "Separate manganese supplements from ciprofloxacin by at least 2 hours, and follow any stricter antibiotic instructions from your prescriber or pharmacist. Avoid taking ciprofloxacin with mineral stacks, multivitamins, or antacids. Contact your clinician if infection symptoms worsen or fail to improve.", "minimumTimeSeparation": 120, "mechanism": "Ciprofloxacin chelates multivalent metal cations through quinolone functional groups, forming less absorbable complexes in the gut. Manganese is a multivalent cation and has demonstrated complex formation with ciprofloxacin under clinically relevant test conditions.", "evidenceLevel": "moderate", "sources": [ { "text": "Hosono M, Yokoyama H, Takayanagi R, Yamada Y. Interactions between new quinolone antibacterials and diagnostic drug containing manganese. Eur J Drug Metab Pharmacokinet. 2013;38(4):255-259.", "pmid": "23444035", "doi": "10.1007/s13318-013-0120-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23444035/", "publicSourceType": "PMID" }, { "text": "Polk RE, Healy DP, Sahai J, Drwal L, Racht E. Effect of ferrous sulfate and multivitamins with zinc on absorption of ciprofloxacin in normal volunteers. Antimicrob Agents Chemother. 1989;33(11):1841-1844.", "pmid": "2610494", "doi": "10.1128/AAC.33.11.1841", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2610494/", "publicSourceType": "PMID" }, { "text": "Deppermann KM, Lode H. Fluoroquinolones: interaction profile during enteral absorption. Drugs. 1993;45 Suppl 3:65-72.", "pmid": "7689454", "doi": "10.2165/00003495-199300453-00013", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7689454/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Manganese may lower ciprofloxacin absorption if taken at the same time.", "clinicalSignificance": "Reduced fluoroquinolone exposure can matter when treating susceptible bacterial infections where adequate drug levels are needed.", "managementStrategy": "Separate doses and avoid coadministration with mineral-containing products.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Levofloxacin", "supplementBName": "Manganese", "interactionType": "timingSensitive", "severity": "serious", "description": "Levofloxacin can chelate with multivalent cations. PubMed-indexed in vitro work found complex formation between levofloxacin and a manganese-containing gastrointestinal diagnostic drug, while fluoroquinolone reviews and human cation studies support reduced absorption as the clinically important concern. Taking manganese at the same time may reduce levofloxacin exposure.", "recommendation": "Separate manganese supplements from levofloxacin by at least 2 hours, and follow any stricter directions on your prescription label. Do not take levofloxacin with mineral blends, multivitamins, or antacids unless your pharmacist confirms the timing. Seek care if infection symptoms persist or worsen.", "minimumTimeSeparation": 120, "mechanism": "Levofloxacin has quinolone metal-binding sites that can form poorly absorbed chelate complexes with multivalent cations. Manganese-containing products have demonstrated complex formation with levofloxacin in vitro.", "evidenceLevel": "moderate", "sources": [ { "text": "Hosono M, Yokoyama H, Takayanagi R, Yamada Y. Interactions between new quinolone antibacterials and diagnostic drug containing manganese. Eur J Drug Metab Pharmacokinet. 2013;38(4):255-259.", "pmid": "23444035", "doi": "10.1007/s13318-013-0120-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23444035/", "publicSourceType": "PMID" }, { "text": "Deppermann KM, Lode H. Fluoroquinolones: interaction profile during enteral absorption. Drugs. 1993;45 Suppl 3:65-72.", "pmid": "7689454", "doi": "10.2165/00003495-199300453-00013", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7689454/", "publicSourceType": "PMID" }, { "text": "Polk RE, Healy DP, Sahai J, Drwal L, Racht E. Effect of ferrous sulfate and multivitamins with zinc on absorption of ciprofloxacin in normal volunteers. Antimicrob Agents Chemother. 1989;33(11):1841-1844.", "pmid": "2610494", "doi": "10.1128/AAC.33.11.1841", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2610494/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Manganese may reduce levofloxacin absorption when taken together.", "clinicalSignificance": "Lower antibiotic exposure may increase the chance of inadequate infection response.", "managementStrategy": "Separate manganese from levofloxacin and avoid same-time mineral coadministration.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Aspirin Low-Dose", "supplementBName": "Lycopene", "interactionType": "caution", "severity": "moderate", "description": "Lycopene has antiplatelet activity in platelet studies, and an in vitro human platelet study directly evaluated lycopene with aspirin and found additive inhibition of platelet aggregation under test conditions. Direct clinical bleeding outcome data are lacking, but the combination is plausible enough to matter in people already at bleeding risk.", "recommendation": "Use lycopene supplements cautiously with low-dose aspirin, especially if you also take anticoagulants, clopidogrel, NSAIDs, SSRIs/SNRIs, or have a history of ulcers or bleeding. Keep doses stable and report easy bruising, nosebleeds, black stools, or prolonged bleeding. Do not stop prescribed aspirin without clinician guidance.", "minimumTimeSeparation": null, "mechanism": "Aspirin irreversibly inhibits platelet cyclooxygenase and thromboxane-mediated aggregation. Lycopene has shown inhibition of platelet activation and aggregation pathways in vitro; together they may increase net antiplatelet effect.", "evidenceLevel": "emerging", "sources": [ { "text": "Sawardekar SB, Patel TC, Uchil D. Comparative evaluation of antiplatelet effect of lycopene with aspirin and the effect of their combination on platelet aggregation: An in vitro study. Indian J Pharmacol. 2016;48(1):26-31.", "pmid": "26997718", "doi": "10.4103/0253-7613.174428", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26997718/", "publicSourceType": "PMID" }, { "text": "Hsiao G, Wang Y, Tzu NH, Fong TH, Shen MY, Lin KH, Chou DS, Sheu JR. Inhibitory effects of lycopene on in vitro platelet activation and in vivo prevention of thrombus formation. J Lab Clin Med. 2005;146(4):216-226.", "pmid": "16194683", "doi": "10.1016/j.lab.2005.03.018", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16194683/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Lycopene may add to aspirin's antiplatelet effect.", "clinicalSignificance": "The main concern is incremental bruising or bleeding risk in patients already using antiplatelet therapy or other bleeding-risk drugs.", "managementStrategy": "Use cautiously, avoid stacking multiple bleeding-risk agents without clinician review, and monitor for bleeding symptoms.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Finasteride", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "moderate", "description": "St. John's Wort can lower finasteride exposure. In healthy men, 14 days of St. John's Wort pretreatment significantly reduced finasteride Cmax, AUC, and half-life, and a PubMed-indexed clinical correspondence describes a BPH patient with a PSA rise after starting 900 mg/day St. John's Wort while controlled on finasteride. The concern is reduced finasteride effect, with possible worsening BPH control or less reliable PSA suppression.", "recommendation": "Avoid St. John's Wort while taking finasteride unless the prescriber specifically approves it. If St. John's Wort has already been started or stopped, tell the clinician interpreting PSA or urinary symptom changes because finasteride exposure and PSA suppression may change over several weeks.", "minimumTimeSeparation": null, "mechanism": "Hyperforin-containing St. John's Wort induces CYP3A4 and P-glycoprotein through pregnane X receptor activation. Finasteride is metabolized by CYP3A pathways, and human pharmacokinetic data show reduced finasteride exposure after St. John's Wort induction.", "evidenceLevel": "moderate", "sources": [ { "text": "Lundahl A, Hedeland M, Bondesson U, Knutson L, Lennernas H. The effect of St. John's wort on the pharmacokinetics, metabolism and biliary excretion of finasteride and its metabolites in healthy men. Eur J Pharm Sci. 2009;36(4-5):433-443.", "pmid": "19073252", "doi": "10.1016/j.ejps.2008.11.009", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19073252/", "publicSourceType": "PMID" }, { "text": "Lochner S, Kirch W. [Does St. John's wort interact with finasteride?]. Dtsch Med Wochenschr. 2011;136(34-35):1746.", "pmid": "21877309", "doi": "10.1055/s-0031-1286070", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21877309/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "St. John's Wort can reduce finasteride exposure and may weaken DHT and PSA suppression.", "clinicalSignificance": "Loss of finasteride effect can matter in BPH follow-up because symptoms and PSA interpretation depend on stable 5-alpha-reductase inhibition.", "managementStrategy": "Avoid co-use; if combined or recently stopped, monitor urinary symptoms and interpret PSA changes with the prescriber.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Dutasteride", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "moderate", "description": "Dutasteride exposure is vulnerable to CYP3A-related changes, and St. John's Wort is a clinically important inducer of CYP3A4 and P-glycoprotein. Direct St. John's Wort-dutasteride coadministration data are limited, but dutasteride has documented CYP3A-mediated interaction potential and St. John's Wort has well-established induction effects. The practical concern is reduced dutasteride exposure and less complete DHT suppression during chronic BPH or alopecia treatment.", "recommendation": "Avoid St. John's Wort while taking dutasteride unless the prescriber specifically approves it. Do not adjust dutasteride dosing yourself; instead, report any worsening urinary symptoms or hair-loss control after starting or stopping St. John's Wort.", "minimumTimeSeparation": null, "mechanism": "Dutasteride undergoes CYP3A-mediated metabolism, and CYP3A inhibition has altered dutasteride pharmacokinetics in experimental interaction studies. St. John's Wort activates pregnane X receptor signaling, inducing CYP3A4 and P-glycoprotein, which can lower exposure to susceptible substrates.", "evidenceLevel": "emerging", "sources": [ { "text": "Seo SW, Park JW, Han DG, Kim JM, Kim S, Park T, et al. In Vitro and In Vivo Assessment of Metabolic Drug Interaction Potential of Dutasteride with Ketoconazole. Pharmaceutics. 2019;11(12):673.", "pmid": "31835695", "doi": "10.3390/pharmaceutics11120673", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31835695/", "publicSourceType": "PMID" }, { "text": "Villapalos-Garcia G, Zubiaur P, Navares-Gomez M, Saiz-Rodriguez M, Mejia-Abril G, Martin-Vilchez S, et al. Effects of Cytochrome P450 and Transporter Polymorphisms on the Bioavailability and Safety of Dutasteride and Tamsulosin. Front Pharmacol. 2021;12:718281.", "pmid": "34690761", "doi": "10.3389/fphar.2021.718281", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34690761/", "publicSourceType": "PMID" }, { "text": "Nicolussi S, Drewe J, Butterweck V, Meyer Zu Schwabedissen HE. Clinical relevance of St. John's wort drug interactions revisited. Br J Pharmacol. 2020;177(6):1212-1226.", "pmid": "31742659", "doi": "10.1111/bph.14936", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31742659/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "St. John's Wort may reduce dutasteride exposure through enzyme and transporter induction.", "clinicalSignificance": "Reduced dutasteride exposure could weaken long-term DHT suppression, especially if urinary symptoms or PSA interpretation are being followed over time.", "managementStrategy": "Avoid co-use when possible; monitor symptom control and inform the prescriber if St. John's Wort is started or stopped.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Oxybutynin", "supplementBName": "Potassium", "interactionType": "caution", "severity": "serious", "description": "Solid oral potassium chloride supplements can injure the upper gastrointestinal mucosa, and controlled endoscopy studies found more frequent or worse lesions when gastric motility was slowed with an anticholinergic. Oxybutynin is an antimuscarinic that can cause constipation and is contraindicated in gastric retention. The concern is greatest with wax-matrix or other solid potassium chloride products, high potassium doses, dehydration, or existing swallowing or GI motility problems.", "recommendation": "Do not start solid potassium tablets or capsules while taking oxybutynin unless a clinician has recommended them and checked that they are necessary. If potassium is needed, ask whether liquid, powder-in-water, dietary potassium, or a monitored alternative is safer. Seek care for severe abdominal pain, black stools, vomiting blood, or painful swallowing.", "minimumTimeSeparation": null, "mechanism": "Oxybutynin blocks muscarinic signaling and can slow gastrointestinal motility. Prolonged mucosal contact with concentrated potassium chloride from solid formulations can cause erosions or ulceration; anticholinergic-induced delayed emptying increases that contact time.", "evidenceLevel": "moderate", "sources": [ { "text": "Dwyer J, Tafuri SM, LaGrange CA. Oxybutynin. StatPearls. 2026.", "pmid": "29763161", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29763161/", "publicSourceType": "PMID" }, { "text": "McMahon FG, Ryan JR, Akdamar K, Ertan A. Upper gastrointestinal lesions after potassium chloride supplements: a controlled clinical trial. Lancet. 1982;2(8307):1059-1061.", "pmid": "6127542", "doi": "10.1016/s0140-6736(82)90002-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6127542/", "publicSourceType": "PMID" }, { "text": "McMahon FG, Ryan JR, Akdamar K, Ertan A. Effect of potassium chloride supplements on upper gastrointestinal mucosa. Clin Pharmacol Ther. 1984;35(6):852-855.", "pmid": "6734038", "doi": "10.1038/clpt.1984.124", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6734038/", "publicSourceType": "PMID" }, { "text": "Sinar DR, Bozymski EM, Blackshear JL. Effects of oral potassium supplements on upper gastrointestinal mucosa: multicenter clinical comparison of three formulations and placebo. Clin Ther. 1986;8(2):157-163.", "pmid": "3698061", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3698061/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Oxybutynin-related anticholinergic slowing can increase the GI injury risk from solid potassium chloride supplements.", "clinicalSignificance": "Potassium-induced erosions or ulcers may be silent until clinically important bleeding, pain, or esophageal injury occurs.", "managementStrategy": "Avoid unsupervised solid potassium; use monitored alternatives when replacement is necessary and evaluate GI warning symptoms promptly.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Finasteride", "supplementBName": "Saw Palmetto", "interactionType": "caution", "severity": "moderate", "description": "Saw palmetto (Serenoa repens) has antiandrogenic and 5-alpha-reductase-related activity, overlapping with finasteride therapy for BPH or androgenetic alopecia. A prostate tissue study compared saw palmetto and finasteride effects on prostatic androgens, and a PubMed-indexed case series described persistent sexual and psychiatric symptoms after Serenoa exposure, including combined Serenoa therapies such as finasteride. The concern is additive sexual, mood, or PSA/DHT interpretation effects rather than an acute toxicity syndrome.", "recommendation": "Avoid adding saw palmetto to finasteride unless the prescriber knows you are using both. Tell the clinician interpreting PSA, urinary symptoms, hair-loss response, libido, erectile function, mood, or persistent sexual adverse effects if saw palmetto is started or stopped.", "minimumTimeSeparation": null, "mechanism": "Finasteride inhibits type II 5-alpha reductase and lowers dihydrotestosterone. Saw palmetto extracts have been studied for BPH with proposed 5-alpha-reductase and antiandrogenic effects, creating overlapping endocrine and symptom-monitoring effects.", "evidenceLevel": "emerging", "sources": [ { "text": "Marks LS, Hess DL, Dorey FJ, Macairan ML, Cruz Santos PB, Tyler VE. Tissue effects of saw palmetto and finasteride: use of biopsy cores for in situ quantification of prostatic androgens. Urology. 2001;57(5):999-1005.", "pmid": "11337315", "doi": "10.1016/s0090-4295(00)01052-9", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11337315/", "publicSourceType": "PMID" }, { "text": "Can we identify a post-Serenoa syndrome (PSS)? A case series on sexual and psychiatric side effects of Serenoa repens. Br J Clin Pharmacol. 2026 Apr.", "pmid": "41507085", "doi": "10.1002/bcp.70442", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41507085/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Saw palmetto may overlap with finasteride antiandrogen effects and complicate monitoring for sexual, mood, urinary, hair, or PSA changes.", "clinicalSignificance": "Unreported co-use can obscure whether symptoms or PSA/DHT-related changes reflect finasteride, saw palmetto, or the underlying condition.", "managementStrategy": "Avoid unsupervised combination and keep the prescriber aware of saw palmetto exposure when monitoring finasteride response or adverse effects.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Dutasteride", "supplementBName": "Saw Palmetto", "interactionType": "caution", "severity": "moderate", "description": "Saw palmetto is used for LUTS/BPH and has proposed antiandrogenic activity that overlaps with dutasteride, a dual 5-alpha-reductase inhibitor. PubMed-indexed BPH literature directly compares Serenoa-containing therapy with dutasteride and reviews beta-sitosterol/saw-palmetto pathways, while a recent case series raises concern for persistent sexual and psychiatric symptoms after Serenoa exposure. Co-use may complicate assessment of BPH response, PSA interpretation, sexual adverse effects, and mood symptoms.", "recommendation": "Do not add saw palmetto to dutasteride without telling the prescriber. Report changes in libido, erectile function, mood, breast tenderness, urinary symptoms, or PSA monitoring context, especially after starting or stopping saw palmetto.", "minimumTimeSeparation": null, "mechanism": "Dutasteride inhibits type I and type II 5-alpha reductase and substantially lowers DHT. Saw palmetto preparations have proposed antiandrogenic and 5-alpha-reductase-related effects, so the overlap is pharmacodynamic and monitoring-related rather than a proven pharmacokinetic interaction.", "evidenceLevel": "emerging", "sources": [ { "text": "Comparison of Serenoa repens, lycopene, and selenium versus dutasteride for the treatment of LUTS/BPH: an Italian multicenter case-control prospective study (COMP study). Front Urol. 2025.", "pmid": "40777606", "doi": "10.3389/fruro.2025.1565240", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40777606/", "publicSourceType": "PMID" }, { "text": "The use of beta-sitosterol for the treatment of prostate cancer and benign prostatic hyperplasia. Am J Clin Exp Urol. 2023.", "pmid": "38148931", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38148931/", "publicSourceType": "PMID" }, { "text": "Can we identify a post-Serenoa syndrome (PSS)? A case series on sexual and psychiatric side effects of Serenoa repens. Br J Clin Pharmacol. 2026 Apr.", "pmid": "41507085", "doi": "10.1002/bcp.70442", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41507085/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Saw palmetto may overlap with dutasteride antiandrogen effects and complicate BPH, PSA, sexual, or mood monitoring.", "clinicalSignificance": "Patients may not report saw palmetto as a supplement, making it harder to interpret dutasteride effectiveness or adverse effects.", "managementStrategy": "Avoid unsupervised combination and document saw palmetto use during dutasteride follow-up.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Alprazolam", "supplementBName": "Alcohol", "interactionType": "contraindicated", "severity": "dangerous", "description": "Alcohol can sharply amplify alprazolam's sedating and coordination-impairing effects. The combination increases risk of blackouts, falls, motor vehicle crashes, respiratory depression, and accidental overdose. Risk is highest with higher alprazolam doses, older age, sleep apnea, lung disease, or any additional sedating medication.", "recommendation": "Do not drink alcohol while taking alprazolam. If you drank recently, avoid non-urgent alprazolam dosing and ask your prescriber or pharmacist for individualized guidance. Seek urgent help for extreme sleepiness, slow breathing, confusion, or inability to wake.", "minimumTimeSeparation": null, "mechanism": "Alprazolam is a positive allosteric modulator of GABA-A receptors. Alcohol also enhances inhibitory GABAergic tone and impairs cortical and brainstem arousal, producing additive CNS depression and psychomotor impairment.", "evidenceLevel": "strong", "sources": [ { "text": "Weathermon R, Crabb DW. Alcohol and medication interactions. Alcohol Res Health. 1999;23(1):40-54.", "pmid": "10890797", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10890797/", "publicSourceType": "PMID" }, { "text": "Drummer OH. Benzodiazepines - Effects on Human Performance and Behavior. Forensic Sci Rev. 2002;14(1-2):1-14.", "pmid": "26256485", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26256485/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Alcohol and alprazolam combine to produce excessive sedation, impaired coordination, and overdose risk.", "clinicalSignificance": "This is a high-risk pairing for blackouts, injury, and respiratory depression.", "managementStrategy": "Avoid alcohol completely while using alprazolam.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Clonazepam", "supplementBName": "Alcohol", "interactionType": "contraindicated", "severity": "dangerous", "description": "Alcohol adds to clonazepam's CNS-depressant effects and can produce marked drowsiness, slowed reaction time, ataxia, memory gaps, and respiratory depression. Because clonazepam has a long half-life, alcohol can still interact even when doses are separated by many hours. Older adults and people with sleep apnea or lung disease are at higher risk.", "recommendation": "Avoid alcohol while taking clonazepam. Do not drive or operate machinery if any alcohol was used near a clonazepam dose. Seek emergency care for severe confusion, slow breathing, blue lips, or inability to wake.", "minimumTimeSeparation": null, "mechanism": "Clonazepam enhances GABA-A receptor signaling; alcohol also potentiates GABA-A activity and suppresses excitatory NMDA signaling. The overlap increases neuronal inhibition and reduces arousal and ventilatory safety margins.", "evidenceLevel": "strong", "sources": [ { "text": "Weathermon R, Crabb DW. Alcohol and medication interactions. Alcohol Res Health. 1999;23(1):40-54.", "pmid": "10890797", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10890797/", "publicSourceType": "PMID" }, { "text": "Ingum J, Bjørnstad S, Mørland J. Relationship between drug plasma concentrations and psychomotor performance after single doses of ethanol and benzodiazepines. Psychopharmacology (Berl). 1992;107(1):11-17.", "pmid": "1589558", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1589558/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Alcohol adds to clonazepam-related sedation and impairment.", "clinicalSignificance": "Long clonazepam exposure means alcohol can compound impairment well beyond the dosing time.", "managementStrategy": "Avoid alcohol during clonazepam therapy.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Diazepam", "supplementBName": "Alcohol", "interactionType": "contraindicated", "severity": "dangerous", "description": "Alcohol and diazepam together produce additive psychomotor impairment, slowed reactions, memory problems, and excessive sedation. Diazepam and its active metabolites last a long time, so alcohol can interact the same day and sometimes the next day. The combination is especially unsafe before driving or in people at fall or respiratory risk.", "recommendation": "Do not drink alcohol while taking diazepam. Avoid driving if you have taken diazepam and consumed alcohol within the same day. Get urgent help if you develop severe drowsiness, confusion, or slow breathing.", "minimumTimeSeparation": null, "mechanism": "Diazepam enhances GABA-A receptor opening frequency, while alcohol enhances inhibitory GABAergic tone and impairs excitatory neurotransmission. Their overlapping pharmacodynamic effects deepen sedation and coordination impairment.", "evidenceLevel": "strong", "sources": [ { "text": "Palva ES, Linnoila M, Saario I, Mattila MJ. Acute and subacute effects of diazepam on psychomotor skills: interaction with alcohol. Acta Pharmacol Toxicol (Copenh). 1979;45(4):257-264.", "pmid": "393076", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/393076/", "publicSourceType": "PMID" }, { "text": "Ingum J, Bjørnstad S, Mørland J. Relationship between drug plasma concentrations and psychomotor performance after single doses of ethanol and benzodiazepines. Psychopharmacology (Berl). 1992;107(1):11-17.", "pmid": "1589558", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1589558/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Alcohol and diazepam additively impair psychomotor performance and arousal.", "clinicalSignificance": "The combination increases crash, fall, blackout, and overdose risk.", "managementStrategy": "Avoid alcohol while diazepam remains active.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Lorazepam", "supplementBName": "Alcohol", "interactionType": "contraindicated", "severity": "dangerous", "description": "Alcohol compounds lorazepam's sedating, amnestic, and coordination-impairing effects. Even if lorazepam is not strongly CYP-metabolized, the interaction is pharmacodynamic and can still cause dangerous impairment. Combining them raises the risk of falls, blackouts, aspiration, and respiratory depression.", "recommendation": "Avoid alcohol while taking lorazepam. If alcohol was used, do not take extra lorazepam for anxiety or sleep without medical guidance. Seek urgent care for severe sedation, slow breathing, or inability to stay awake.", "minimumTimeSeparation": null, "mechanism": "Lorazepam potentiates GABA-A receptor signaling. Alcohol adds GABAergic inhibition and reduces excitatory glutamatergic tone, causing additive CNS depression independent of hepatic metabolism.", "evidenceLevel": "strong", "sources": [ { "text": "Weathermon R, Crabb DW. Alcohol and medication interactions. Alcohol Res Health. 1999;23(1):40-54.", "pmid": "10890797", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10890797/", "publicSourceType": "PMID" }, { "text": "Drummer OH. Benzodiazepines - Effects on Human Performance and Behavior. Forensic Sci Rev. 2002;14(1-2):1-14.", "pmid": "26256485", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26256485/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Alcohol and lorazepam additively increase sedation, amnesia, and respiratory risk.", "clinicalSignificance": "The interaction is pharmacodynamic, so spacing doses does not reliably make it safe.", "managementStrategy": "Avoid alcohol during lorazepam use.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Zolpidem", "supplementBName": "Alcohol", "interactionType": "contraindicated", "severity": "dangerous", "description": "Alcohol adds to zolpidem's hypnotic and psychomotor-impairing effects. Controlled testing showed both zolpidem and alcohol impaired cognitive and motor performance, and real-world reports link zolpidem to confusion, amnesia, sleep-driving, and complex behaviors. Alcohol increases the danger of these behaviors and next-day impairment.", "recommendation": "Do not drink alcohol on nights you take zolpidem. Do not take zolpidem after drinking, even if you feel awake. Seek help if sleepwalking, sleep-driving, severe confusion, or unusual behavior occurs.", "minimumTimeSeparation": null, "mechanism": "Zolpidem is a GABA-A receptor positive modulator with relative alpha-1 selectivity. Alcohol adds broad CNS depression through GABA-A potentiation and NMDA inhibition, worsening vigilance, memory, balance, and reaction time.", "evidenceLevel": "strong", "sources": [ { "text": "Wilkinson CJ. The acute effects of zolpidem, administered alone and with alcohol, on cognitive and psychomotor function. J Clin Psychiatry. 1995;56(7):309-318.", "pmid": "7615484", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7615484/", "publicSourceType": "PMID" }, { "text": "Poceta JS. Zolpidem ingestion, automatisms, and sleep driving: a clinical and legal case series. J Clin Sleep Med. 2011;7(6):632-638.", "pmid": "22171202", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22171202/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Alcohol worsens zolpidem-related impairment and complex sleep behaviors.", "clinicalSignificance": "This pairing increases risk of amnesia, injury, sleep-driving, and unsafe next-day performance.", "managementStrategy": "Avoid alcohol completely on zolpidem nights.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Eszopiclone", "supplementBName": "Alcohol", "interactionType": "contraindicated", "severity": "dangerous", "description": "Alcohol can add to eszopiclone's hypnotic and psychomotor-impairing effects. The combination can cause excessive sedation, impaired coordination, confusion, falls, and complex sleep behaviors. Older adults and people taking other sedatives are at higher risk.", "recommendation": "Do not drink alcohol when taking eszopiclone. Skip eszopiclone rather than combining it with alcohol unless your prescriber gives different individualized instructions. Do not drive or perform hazardous tasks if both were used.", "minimumTimeSeparation": null, "mechanism": "Eszopiclone acts at the benzodiazepine site of GABA-A receptors as a nonbenzodiazepine hypnotic. Alcohol adds GABAergic CNS depression and impairs attention, balance, and memory.", "evidenceLevel": "moderate", "sources": [ { "text": "McCrae CS, Lichstein KL. Eszopiclone for late-life insomnia. Clin Interv Aging. 2007;2(3):313-326.", "pmid": "18044182", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18044182/", "publicSourceType": "PMID" }, { "text": "Richter G, Liao VWY, Ahring PK, Chebib M. The Z-Drugs Zolpidem, Zaleplon, and Eszopiclone Have Varying Actions on Human GABA(A) Receptors Containing gamma1, gamma2, and gamma3 Subunits. Front Neurosci. 2020;14:599812.", "pmid": "33328871", "doi": "10.3389/fnins.2020.599812", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33328871/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Alcohol adds to eszopiclone-related sedation and psychomotor impairment.", "clinicalSignificance": "The combination can lead to falls, impaired driving, amnesia, and complex sleep behaviors.", "managementStrategy": "Avoid alcohol on any night eszopiclone is used.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Suvorexant", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Alcohol can add to suvorexant-related sleepiness and impaired alertness. A clinical alcohol coadministration study found additive negative effects on psychomotor performance, balance, memory, and alertness. The risk is most relevant at bedtime, with higher suvorexant doses, or when next-day driving is required.", "recommendation": "Avoid alcohol when taking suvorexant. Do not take suvorexant after evening drinking, and do not drive the next morning if you feel sleepy or slowed. Use extra caution if you are older or also take other sedating medicines.", "minimumTimeSeparation": null, "mechanism": "Suvorexant blocks orexin OX1R and OX2R signaling, reducing wake drive. Alcohol depresses CNS arousal and coordination through GABAergic and glutamatergic effects, creating additive impairment without a major pharmacokinetic interaction.", "evidenceLevel": "moderate", "sources": [ { "text": "Sun H, Yee KL, Gill S, Liu W, Li X, Panebianco D, et al. Psychomotor effects, pharmacokinetics and safety of the orexin receptor antagonist suvorexant administered in combination with alcohol in healthy subjects. J Psychopharmacol. 2015;29(11):1159-1169.", "pmid": "26464455", "doi": "10.1177/0269881115609015", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26464455/", "publicSourceType": "PMID" }, { "text": "Rhyne DN, Anderson SL. Suvorexant in insomnia: efficacy, safety and place in therapy. Ther Adv Drug Saf. 2015;6(5):189-195.", "pmid": "26478806", "doi": "10.1177/2042098615595359", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26478806/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Alcohol and suvorexant additively impair alertness, balance, memory, and psychomotor performance.", "clinicalSignificance": "This can increase falls, impaired driving, and unsafe next-day performance.", "managementStrategy": "Avoid alcohol on suvorexant nights and avoid driving if residual sedation occurs.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Alprazolam", "supplementBName": "St. John's Wort", "interactionType": "caution", "severity": "moderate", "description": "St. John's Wort can induce CYP3A4, the main enzyme clearing alprazolam. High-hyperforin St. John's Wort products may lower alprazolam exposure and reduce anxiety control; stopping the herb can then allow alprazolam levels to rise again. Low-hyperforin products may have little effect, so product variability is a major issue.", "recommendation": "Avoid starting or stopping St. John's Wort while taking alprazolam unless your prescriber is managing the change. Do not increase alprazolam on your own if anxiety worsens after starting the herb. Watch for oversedation if St. John's Wort is stopped after an alprazolam dose increase.", "minimumTimeSeparation": null, "mechanism": "Hyperforin in St. John's Wort activates pregnane X receptor signaling and induces CYP3A4. Alprazolam is a CYP3A substrate, so induction can increase clearance and lower active exposure.", "evidenceLevel": "moderate", "sources": [ { "text": "Markowitz JS, Donovan JL, DeVane CL, Taylor RM, Ruan Y, Wang JS, et al. Effect of St John's wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA. 2003;290(11):1500-1504.", "pmid": "13129991", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/13129991/", "publicSourceType": "PMID" }, { "text": "Arold G, Donath F, Maurer A, Diefenbach K, Bauer S, Henneicke-von Zepelin HH, et al. No relevant interaction with alprazolam, caffeine, tolbutamide, and digoxin by treatment with a low-hyperforin St John's wort extract. Planta Med. 2005;71(4):331-337.", "pmid": "15856409", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15856409/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "St. John's Wort may lower alprazolam exposure depending on hyperforin content.", "clinicalSignificance": "Variable alprazolam levels can cause loss of symptom control or oversedation after herb discontinuation.", "managementStrategy": "Avoid unsupervised St. John's Wort changes while on alprazolam.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Zolpidem", "supplementBName": "St. John's Wort", "interactionType": "caution", "severity": "moderate", "description": "St. John's Wort can induce CYP3A4 and P-glycoprotein, while zolpidem is partly cleared through CYP3A-mediated metabolism. The combination may reduce zolpidem exposure and make sleep benefit less reliable; stopping St. John's Wort may reverse induction and increase zolpidem effect. Product hyperforin content makes the size of the interaction unpredictable.", "recommendation": "Avoid changing St. John's Wort use while taking zolpidem unless your prescriber agrees. Do not raise zolpidem on your own if it seems weaker after starting the herb. Watch for stronger sedation if the herb is stopped.", "minimumTimeSeparation": null, "mechanism": "Hyperforin-containing St. John's Wort induces CYP3A4 through pregnane X receptor activation. Zolpidem undergoes hepatic oxidation that includes CYP3A pathways, so induction can lower hypnotic exposure.", "evidenceLevel": "emerging", "sources": [ { "text": "Hesse LM, von Moltke LL, Greenblatt DJ. Clinically important drug interactions with zopiclone, zolpidem and zaleplon. CNS Drugs. 2003;17(7):513-532.", "pmid": "12751920", "doi": "10.2165/00023210-200317070-00004", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12751920/", "publicSourceType": "PMID" }, { "text": "Nicolussi S, Drewe J, Butterweck V, Meyer zu Schwabedissen HE. Clinical relevance of St. John's wort drug interactions revisited. Br J Pharmacol. 2020;177(6):1212-1226.", "pmid": "31742659", "doi": "10.1111/bph.14936", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31742659/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "St. John's Wort may reduce zolpidem exposure and destabilize hypnotic response.", "clinicalSignificance": "Patients may respond by taking extra zolpidem, creating oversedation risk if the herb is later stopped.", "managementStrategy": "Avoid unsupervised St. John's Wort changes while using zolpidem.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Suvorexant", "supplementBName": "St. John's Wort", "interactionType": "caution", "severity": "moderate", "description": "Suvorexant exposure is sensitive to CYP3A modulation, and St. John's Wort can induce CYP3A4. Combining them may lower suvorexant levels and reduce sleep benefit; stopping St. John's Wort can then restore exposure and increase next-day sleepiness. The effect depends on the hyperforin content of the St. John's Wort product.", "recommendation": "Avoid St. John's Wort while using suvorexant unless your prescriber approves. Do not raise suvorexant to overcome reduced effect from the herb. If St. John's Wort is stopped, monitor for stronger sedation and next-day impairment.", "minimumTimeSeparation": null, "mechanism": "St. John's Wort induces CYP3A4 via hyperforin-mediated pregnane X receptor activation. Suvorexant is primarily metabolized by CYP3A, so induction can reduce systemic exposure and hypnotic effect.", "evidenceLevel": "emerging", "sources": [ { "text": "Rhyne DN, Anderson SL. Suvorexant in insomnia: efficacy, safety and place in therapy. Ther Adv Drug Saf. 2015;6(5):189-195.", "pmid": "26478806", "doi": "10.1177/2042098615595359", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26478806/", "publicSourceType": "PMID" }, { "text": "Nicolussi S, Drewe J, Butterweck V, Meyer zu Schwabedissen HE. Clinical relevance of St. John's wort drug interactions revisited. Br J Pharmacol. 2020;177(6):1212-1226.", "pmid": "31742659", "doi": "10.1111/bph.14936", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31742659/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "St. John's Wort may lower suvorexant exposure through CYP3A induction.", "clinicalSignificance": "Changing the herb can cause loss of sleep effect or later oversedation if suvorexant dosing was adjusted.", "managementStrategy": "Avoid unsupervised St. John's Wort use with suvorexant.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Metoprolol", "supplementBName": "L-Arginine", "interactionType": "caution", "severity": "moderate", "description": "L-Arginine is a nitric oxide precursor that lowers blood pressure on its own. Stacked with metoprolol's beta1 blockade, the combined fall in blood pressure can produce symptomatic hypotension, dizziness, or lightheadedness, especially when standing. Patients who are already well-controlled on metoprolol are the most likely to overshoot.", "recommendation": "If you take metoprolol for blood pressure, check your readings before and after starting L-arginine, and start with lower doses (e.g., 1-3 g/day). Stop or reduce the dose if you develop dizziness, fatigue, or readings below your usual range, and tell your prescriber.", "minimumTimeSeparation": null, "mechanism": "L-Arginine is the substrate for endothelial nitric oxide synthase (eNOS); supplementation raises NO availability, causing vasodilation and a modest reduction in systolic and diastolic pressure. This adds to metoprolol's reduction in cardiac output via beta1 blockade.", "evidenceLevel": "moderate", "sources": [ { "text": "Dong JY, Qin LQ, Zhang Z, et al. Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials. Am Heart J. 2011;162(6):959-65.", "pmid": "22137067", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22137067/", "publicSourceType": "PMID" }, { "text": "Khalaf D, Krüger M, Wehland M, Infanger M, Grimm D. The Effects of Oral l-Arginine and l-Citrulline Supplementation on Blood Pressure. Nutrients. 2019;11(7):1679.", "pmid": "31336573", "doi": "10.3390/nu11071679", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31336573/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive blood-pressure lowering that can cause symptomatic hypotension.", "clinicalSignificance": "Patients already controlled on metoprolol may develop dizziness, fatigue, or falls if BP drops further.", "managementStrategy": "Monitor blood pressure when starting L-arginine and reduce or stop if symptomatic hypotension occurs.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Metoprolol", "supplementBName": "L-Citrulline", "interactionType": "caution", "severity": "moderate", "description": "L-Citrulline is converted to L-arginine and raises plasma arginine more efficiently than arginine itself, producing nitric-oxide-mediated vasodilation and modest blood-pressure reductions. Added on top of metoprolol's heart-rate and contractility suppression, this can drop blood pressure further than intended.", "recommendation": "If you take metoprolol, start L-citrulline at lower doses (3 g/day or less) and track your blood pressure for 1-2 weeks. Reduce the dose or stop if you become lightheaded, fatigued, or your readings fall below your usual range.", "minimumTimeSeparation": null, "mechanism": "L-Citrulline bypasses hepatic first-pass metabolism, raises systemic arginine, and increases endothelial NO synthase substrate availability. This causes vasodilation that adds to metoprolol's reduction in cardiac output.", "evidenceLevel": "moderate", "sources": [ { "text": "Khalaf D, Krüger M, Wehland M, Infanger M, Grimm D. The Effects of Oral l-Arginine and l-Citrulline Supplementation on Blood Pressure. Nutrients. 2019;11(7):1679.", "pmid": "31336573", "doi": "10.3390/nu11071679", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31336573/", "publicSourceType": "PMID" }, { "text": "Mirenayat MS, Moradi S, Mohammadi H, Rouhani MH. Effect of L-Citrulline Supplementation on Blood Pressure: a Systematic Review and Meta-Analysis of Clinical Trials. Curr Hypertens Rep. 2018;20(11):98.", "pmid": "30284051", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30284051/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive vasodilation and blood-pressure lowering.", "clinicalSignificance": "Combined effect can produce symptomatic hypotension in patients already controlled on metoprolol.", "managementStrategy": "Start low, monitor BP, and adjust if readings drop or you become symptomatic.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Metoprolol", "supplementBName": "Taurine", "interactionType": "caution", "severity": "moderate", "description": "Taurine modestly lowers both systolic and diastolic blood pressure (~3 mmHg each in meta-analysis) and has direct heart-rate-lowering effects. Layered on metoprolol, the combination can produce additive bradycardia or hypotension in sensitive patients, though the overall effect is usually mild.", "recommendation": "If you take metoprolol, taurine doses up to 1.5-3 g/day are usually well-tolerated, but check your blood pressure and resting heart rate when you start. Hold or reduce the dose if your HR drops below 50 bpm or you develop dizziness.", "minimumTimeSeparation": null, "mechanism": "Taurine modulates vascular tone via calcium handling and nitric oxide, blunts sympathetic outflow, and stabilizes cardiomyocyte membranes. These effects overlap with metoprolol's beta1 blockade, producing additive reductions in heart rate and blood pressure.", "evidenceLevel": "moderate", "sources": [ { "text": "Waldron M, Patterson SD, Tallent J, Jeffries O. The Effects of Oral Taurine on Resting Blood Pressure in Humans: a Meta-Analysis. Curr Hypertens Rep. 2018;20(9):81.", "pmid": "30006901", "doi": "10.1007/s11906-018-0881-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30006901/", "publicSourceType": "PMID" }, { "text": "Tzang CC, Lin WC, Lin LH, et al. Insights into the cardiovascular benefits of taurine: a systematic review and meta-analysis. Nutr J. 2024;23(1):93.", "pmid": "39148075", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39148075/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive blood-pressure and heart-rate lowering.", "clinicalSignificance": "Mostly mild, but can amplify bradycardia or hypotension in well-controlled patients.", "managementStrategy": "Monitor BP and HR when initiating taurine; reduce if symptomatic.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fish Oil", "supplementBName": "Metoprolol", "interactionType": "synergy", "severity": "info", "description": "Omega-3 fatty acids in fish oil produce small but consistent reductions in blood pressure (~2-3 mmHg systolic at doses of 2-3 g/day) and lower triglycerides, complementing metoprolol's hemodynamic effects. The combination is generally beneficial in patients with hypertension or cardiovascular disease, with minimal risk at typical doses.", "recommendation": "Fish oil at 1-3 g/day combined with metoprolol is appropriate for most patients with cardiovascular risk. Monitor blood pressure when starting, and inform your prescriber if you take high doses (>3 g/day) since hemodynamic effects can become additive.", "minimumTimeSeparation": null, "mechanism": "EPA and DHA enhance endothelial nitric oxide production, reduce vascular inflammation, and modulate ion channels in cardiomyocytes. These effects complement metoprolol's reduction in heart rate and cardiac workload via beta1 blockade.", "evidenceLevel": "strong", "sources": [ { "text": "Zhang X, Ritonja JA, Zhou N, Chen BE, Li X. Omega-3 Polyunsaturated Fatty Acids Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials. J Am Heart Assoc. 2022;11(11):e025071.", "pmid": "35647665", "doi": "10.1161/JAHA.121.025071", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35647665/", "publicSourceType": "PMID" }, { "text": "Morris MC, Sacks F, Rosner B. Does fish oil lower blood pressure? A meta-analysis of controlled trials. Circulation. 1993;88(2):523-33.", "pmid": "8339414", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8339414/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Modest additive blood-pressure and cardiovascular benefit.", "clinicalSignificance": "Generally favorable combination for cardiovascular patients.", "managementStrategy": "Standard doses are well-tolerated; monitor BP if exceeding 3 g/day.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Garlic Extract", "supplementBName": "Metoprolol", "interactionType": "caution", "severity": "moderate", "description": "Aged garlic extract lowers systolic blood pressure by roughly 8 mmHg in hypertensive patients, comparable to first-line antihypertensives. Added to metoprolol, the combined effect can drive blood pressure below target, especially in patients already at goal.", "recommendation": "If you take metoprolol for hypertension, monitor your blood pressure for 2-4 weeks after starting garlic extract. Tell your prescriber so they can adjust your metoprolol dose if your readings consistently fall below your target.", "minimumTimeSeparation": null, "mechanism": "Garlic's organosulfur compounds (allicin, S-allyl cysteine) increase nitric oxide and hydrogen sulfide signaling, causing vasodilation. Animal data show garlic potentiates the blood-pressure-lowering effect of beta-blockers.", "evidenceLevel": "moderate", "sources": [ { "text": "Ried K. Garlic Lowers Blood Pressure in Hypertensive Individuals, Regulates Serum Cholesterol, and Stimulates Immunity: An Updated Meta-analysis and Review. J Nutr. 2016;146(2):389S-396S.", "pmid": "26764326", "doi": "10.3945/jn.114.202192", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26764326/", "publicSourceType": "PMID" }, { "text": "Asdaq SM, Inamdar MN. Pharmacodynamic and Pharmacokinetic Interactions of Propranolol with Garlic (Allium sativum) in Rats. Evid Based Complement Alternat Med. 2011;2011:824042.", "pmid": "21792365", "doi": "10.1093/ecam/neq076", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21792365/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive blood-pressure reduction.", "clinicalSignificance": "Combined effect can over-shoot blood-pressure targets in treated hypertensives.", "managementStrategy": "Monitor BP and have your prescriber adjust metoprolol if readings fall too low.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "L-Theanine", "supplementBName": "Metoprolol", "interactionType": "caution", "severity": "info", "description": "L-Theanine blunts stress-induced rises in blood pressure and heart rate in high-stress-responder subjects. Combined with metoprolol, the effect is usually mild but can deepen the drug's anxiolytic and cardiovascular effects, particularly when taken at the same time as a dose.", "recommendation": "L-Theanine at typical doses (100-400 mg) is generally compatible with metoprolol. Monitor for additive sedation or lower-than-expected heart-rate readings, and reduce the dose if symptomatic.", "minimumTimeSeparation": null, "mechanism": "L-Theanine modulates GABA, glutamate, and catecholamine signaling, reducing sympathetic drive. This adds to metoprolol's beta1 antagonism, attenuating both basal and stress-evoked blood pressure and heart rate.", "evidenceLevel": "emerging", "sources": [ { "text": "Yoto A, Motoki M, Murao S, Yokogoshi H. Effects of L-theanine or caffeine intake on changes in blood pressure under physical and psychological stresses. J Physiol Anthropol. 2012;31(1):28.", "pmid": "23107346", "doi": "10.1186/1880-6805-31-28", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23107346/", "publicSourceType": "PMID" }, { "text": "Rogers PJ, Smith JE, Heatherley SV, Pleydell-Pearce CW. Time for tea: mood, blood pressure and cognitive performance effects of caffeine and theanine administered alone and together. Psychopharmacology (Berl). 2008;195(4):569-77.", "pmid": "17891480", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17891480/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Mild additive blunting of stress-related blood-pressure and heart-rate responses.", "clinicalSignificance": "Usually well-tolerated; rarely problematic at standard supplement doses.", "managementStrategy": "Monitor BP and HR when combining; reduce if additive effects occur.", "isSynergistic": null, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Metoprolol", "supplementBName": "Resveratrol", "interactionType": "synergy", "severity": "info", "description": "High-dose resveratrol (≥150 mg/day) modestly reduces systolic blood pressure and improves endothelial function. Combined with metoprolol, the net effect is generally beneficial for vascular health, though additive blood-pressure lowering is possible at higher doses.", "recommendation": "Resveratrol at typical supplement doses (100-500 mg/day) is generally compatible with metoprolol. Monitor blood pressure when adding higher doses (≥150 mg/day) and tell your prescriber if readings drop below target.", "minimumTimeSeparation": null, "mechanism": "Resveratrol activates SIRT1 and enhances endothelial nitric oxide synthase activity, improving vasodilation and reducing oxidative stress. These effects complement metoprolol's reduction in cardiac workload.", "evidenceLevel": "moderate", "sources": [ { "text": "Liu Y, Ma W, Zhang P, He S, Huang D. Effect of resveratrol on blood pressure: a meta-analysis of randomized controlled trials. Clin Nutr. 2015;34(1):27-34.", "pmid": "24731650", "doi": "10.1016/j.clnu.2014.03.009", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24731650/", "publicSourceType": "PMID" }, { "text": "Fogacci F, Tocci G, Presta V, Fratter A, Borghi C, Cicero AFG. Effect of resveratrol on blood pressure: A systematic review and meta-analysis of randomized, controlled, clinical trials. Crit Rev Food Sci Nutr. 2019;59(10):1605-1618.", "pmid": "29359958", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29359958/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Mild additive cardiovascular and blood-pressure benefit.", "clinicalSignificance": "Generally favorable; rarely causes over-shoot at supplement doses.", "managementStrategy": "Monitor BP at higher resveratrol doses; otherwise no action needed.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Atenolol", "supplementBName": "Coenzyme Q10", "interactionType": "synergy", "severity": "info", "description": "Like other beta-blockers, atenolol inhibits mitochondrial CoQ10-dependent enzymes, contributing to fatigue and reduced exercise tolerance. CoQ10 supplementation (100-200 mg/day) can replenish levels and may improve symptoms, with the added benefit of modest blood-pressure reduction in some patients.", "recommendation": "Consider CoQ10 100-200 mg/day with food if you experience fatigue, exercise intolerance, or muscle aches on atenolol. Monitor blood pressure since CoQ10 can produce a small additional drop.", "minimumTimeSeparation": null, "mechanism": "Beta-blockers inhibit CoQ10-dependent NADH-oxidase and succinate-oxidase in mitochondria, reducing ATP production in cardiac and skeletal muscle. Supplemental CoQ10 restores enzyme activity and improves mitochondrial bioenergetics.", "evidenceLevel": "moderate", "sources": [ { "text": "Kishi T, Watanabe T, Folkers K. Bioenergetics in clinical medicine XV. Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors. Res Commun Chem Pathol Pharmacol. 1977;17(1):157-64.", "pmid": "17892", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17892/", "publicSourceType": "PMID" }, { "text": "Rosenfeldt FL, Haas SJ, Krum H, et al. Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. J Hum Hypertens. 2007;21(4):297-306.", "pmid": "17287847", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17287847/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "CoQ10 replenishes drug-induced depletion and may produce small additive BP-lowering.", "clinicalSignificance": "May reduce beta-blocker-related fatigue; monitor BP for additive effects.", "managementStrategy": "Take 100-200 mg CoQ10 with food; monitor blood pressure.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Atenolol", "supplementBName": "L-Arginine", "interactionType": "caution", "severity": "moderate", "description": "L-Arginine modestly lowers blood pressure through nitric oxide-mediated vasodilation. Stacked with atenolol's beta1 blockade, the combined drop can produce symptomatic hypotension, especially in older adults or those already well-controlled.", "recommendation": "If you take atenolol, start L-arginine at lower doses (1-3 g/day) and monitor your blood pressure for 1-2 weeks. Reduce or stop if you develop dizziness, fatigue, or readings below your usual range.", "minimumTimeSeparation": null, "mechanism": "L-Arginine is the substrate for eNOS; supplementation raises NO production and vasodilation. This adds to atenolol's reduction in cardiac output via beta1 blockade.", "evidenceLevel": "moderate", "sources": [ { "text": "Dong JY, Qin LQ, Zhang Z, et al. Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials. Am Heart J. 2011;162(6):959-65.", "pmid": "22137067", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22137067/", "publicSourceType": "PMID" }, { "text": "Khalaf D, Krüger M, Wehland M, Infanger M, Grimm D. The Effects of Oral l-Arginine and l-Citrulline Supplementation on Blood Pressure. Nutrients. 2019;11(7):1679.", "pmid": "31336573", "doi": "10.3390/nu11071679", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31336573/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive blood-pressure lowering that can cause symptomatic hypotension.", "clinicalSignificance": "Patients well-controlled on atenolol may overshoot target BP.", "managementStrategy": "Start low; monitor BP for 1-2 weeks after initiation.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Atenolol", "supplementBName": "Taurine", "interactionType": "caution", "severity": "moderate", "description": "Taurine lowers blood pressure modestly and has direct heart-rate-lowering effects. Combined with atenolol, the effects can be additive, producing further reductions in heart rate and blood pressure.", "recommendation": "Taurine at 1-3 g/day is typically safe with atenolol but check resting heart rate and blood pressure when you start. Reduce the dose if HR drops below 50 bpm or you develop dizziness.", "minimumTimeSeparation": null, "mechanism": "Taurine modulates cardiomyocyte calcium handling, blunts sympathetic outflow, and supports endothelial NO production. These effects add to atenolol's beta1 blockade.", "evidenceLevel": "moderate", "sources": [ { "text": "Waldron M, Patterson SD, Tallent J, Jeffries O. The Effects of Oral Taurine on Resting Blood Pressure in Humans: a Meta-Analysis. Curr Hypertens Rep. 2018;20(9):81.", "pmid": "30006901", "doi": "10.1007/s11906-018-0881-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30006901/", "publicSourceType": "PMID" }, { "text": "Tzang CC, Lin WC, Lin LH, et al. Insights into the cardiovascular benefits of taurine: a systematic review and meta-analysis. Nutr J. 2024;23(1):93.", "pmid": "39148075", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39148075/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive heart-rate and blood-pressure lowering.", "clinicalSignificance": "Can amplify bradycardia or hypotension in well-controlled patients.", "managementStrategy": "Monitor HR and BP when starting; adjust dose if symptomatic.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Atenolol", "supplementBName": "Garlic Extract", "interactionType": "caution", "severity": "moderate", "description": "Aged garlic extract reduces systolic blood pressure by approximately 8 mmHg in hypertensives. Layered on atenolol, the combined effect can drive blood pressure below target, particularly in older patients prone to orthostatic symptoms.", "recommendation": "If you take atenolol, monitor your blood pressure for 2-4 weeks after starting garlic extract. Have your prescriber re-evaluate your atenolol dose if your readings consistently fall below your target range.", "minimumTimeSeparation": null, "mechanism": "Organosulfur compounds in garlic enhance NO and H2S signaling, producing vasodilation. The hemodynamic effect adds to atenolol's beta1 blockade.", "evidenceLevel": "moderate", "sources": [ { "text": "Ried K. Garlic Lowers Blood Pressure in Hypertensive Individuals, Regulates Serum Cholesterol, and Stimulates Immunity: An Updated Meta-analysis and Review. J Nutr. 2016;146(2):389S-396S.", "pmid": "26764326", "doi": "10.3945/jn.114.202192", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26764326/", "publicSourceType": "PMID" }, { "text": "Ried K, Frank OR, Stocks NP, Fakler P, Sullivan T. Effect of garlic on blood pressure: a systematic review and meta-analysis. BMC Cardiovasc Disord. 2008;8:13.", "pmid": "18554422", "doi": "10.1186/1471-2261-8-13", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18554422/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive blood-pressure reduction.", "clinicalSignificance": "Can cause over-shoot of BP target in atenolol-treated hypertensives.", "managementStrategy": "Monitor BP and have prescriber adjust atenolol if readings drop too low.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Atenolol", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "Fish oil (EPA/DHA) at 2-3 g/day produces small reductions in blood pressure and lowers triglycerides, complementing atenolol's hemodynamic effects in patients with hypertension or cardiovascular disease.", "recommendation": "Fish oil at 1-3 g/day is generally compatible with atenolol and may add cardiovascular benefit. Monitor blood pressure when starting, and let your prescriber know if you take high doses (>3 g/day).", "minimumTimeSeparation": null, "mechanism": "EPA and DHA enhance NO production, reduce vascular inflammation, and improve membrane fluidity. These effects complement atenolol's reduction in heart rate and oxygen demand.", "evidenceLevel": "strong", "sources": [ { "text": "Zhang X, Ritonja JA, Zhou N, Chen BE, Li X. Omega-3 Polyunsaturated Fatty Acids Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials. J Am Heart Assoc. 2022;11(11):e025071.", "pmid": "35647665", "doi": "10.1161/JAHA.121.025071", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35647665/", "publicSourceType": "PMID" }, { "text": "Morris MC, Sacks F, Rosner B. Does fish oil lower blood pressure? A meta-analysis of controlled trials. Circulation. 1993;88(2):523-33.", "pmid": "8339414", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8339414/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Modest additive blood-pressure and cardiovascular benefit.", "clinicalSignificance": "Generally favorable; check BP if exceeding 3 g/day.", "managementStrategy": "Standard doses are well-tolerated; monitor BP at high doses.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Coenzyme Q10", "supplementBName": "Propranolol", "interactionType": "synergy", "severity": "info", "description": "Propranolol is the strongest CoQ10-enzyme inhibitor among beta-blockers, which contributes to fatigue and exercise intolerance. CoQ10 supplementation restores mitochondrial enzyme activity and may help offset these side effects, with the bonus of modest blood-pressure lowering.", "recommendation": "Consider CoQ10 100-200 mg/day with food if you experience fatigue, exercise intolerance, or muscle aches on propranolol. Monitor blood pressure since CoQ10 may produce a small additional drop.", "minimumTimeSeparation": null, "mechanism": "Propranolol potently inhibits NADH-oxidase and succinate-oxidase activity in mitochondria, depleting functional CoQ10. Supplementation restores enzyme activity and ATP synthesis in cardiac and skeletal muscle.", "evidenceLevel": "moderate", "sources": [ { "text": "Kishi T, Watanabe T, Folkers K. Bioenergetics in clinical medicine XV. Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors. Res Commun Chem Pathol Pharmacol. 1977;17(1):157-64.", "pmid": "17892", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17892/", "publicSourceType": "PMID" }, { "text": "Rosenfeldt FL, Haas SJ, Krum H, et al. Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. J Hum Hypertens. 2007;21(4):297-306.", "pmid": "17287847", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17287847/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Replenishes drug-induced CoQ10 enzyme inhibition.", "clinicalSignificance": "May reduce fatigue and exercise intolerance on propranolol.", "managementStrategy": "Take 100-200 mg CoQ10 with food; monitor BP.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Green Tea Extract", "supplementBName": "Propranolol", "interactionType": "caution", "severity": "moderate", "description": "Green tea extract contains caffeine, which propranolol blunts the cardiovascular response to, and vice versa. High-dose green tea extract can also modestly raise blood pressure acutely from caffeine while EGCG produces opposite chronic vasodilatory effects, giving an unpredictable net effect when stacked with propranolol.", "recommendation": "Limit high-dose green tea extract supplements while on propranolol; modest dietary green tea is usually fine. If you take a concentrated extract, monitor blood pressure and heart rate when starting.", "minimumTimeSeparation": null, "mechanism": "Caffeine in green tea is a non-selective adenosine receptor antagonist that produces transient blood pressure rises blunted by beta blockade. EGCG and other catechins have separate effects on endothelial function and lipid absorption that complicate the net hemodynamic response.", "evidenceLevel": "emerging", "sources": [ { "text": "Smits P, Hoffmann H, Thien T, Houben H, van't Laar A. Hemodynamic and humoral effects of coffee after beta 1-selective and nonselective beta-blockade. Clin Pharmacol Ther. 1983;34(2):153-8.", "pmid": "6347498", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6347498/", "publicSourceType": "PMID" }, { "text": "Belza A, Toubro S, Stender S, Astrup A. Effect of diet-induced energy deficit and body fat reduction on high-sensitive CRP and other inflammatory markers in obese subjects. Int J Obes (Lond). 2009;33(4):456-64. (caffeine/thermogenesis interaction)", "pmid": "19497591", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19497591/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Unpredictable acute hemodynamic effects when high-dose green tea extract is combined with propranolol.", "clinicalSignificance": "Patients with hypertension or arrhythmia may notice variable BP or HR changes.", "managementStrategy": "Limit concentrated extracts; monitor BP and HR if combining.", "isSynergistic": null, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "L-Theanine", "supplementBName": "Propranolol", "interactionType": "synergy", "severity": "info", "description": "Both L-theanine and propranolol blunt the cardiovascular response to acute stress. The combination can produce slightly greater anxiolytic effects, which is desirable for patients using propranolol for performance anxiety or essential tremor, but may add to heart-rate suppression.", "recommendation": "L-Theanine 100-400 mg combined with propranolol is generally well-tolerated and may augment anxiolytic benefit. Monitor heart rate and watch for excessive sedation when starting.", "minimumTimeSeparation": null, "mechanism": "L-Theanine modulates GABA and glutamate signaling and dampens sympathetic stress responses. This complements propranolol's blockade of beta1 (and beta2) receptors, attenuating stress-induced cardiovascular reactivity.", "evidenceLevel": "emerging", "sources": [ { "text": "Yoto A, Motoki M, Murao S, Yokogoshi H. Effects of L-theanine or caffeine intake on changes in blood pressure under physical and psychological stresses. J Physiol Anthropol. 2012;31(1):28.", "pmid": "23107346", "doi": "10.1186/1880-6805-31-28", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23107346/", "publicSourceType": "PMID" }, { "text": "Rogers PJ, Smith JE, Heatherley SV, Pleydell-Pearce CW. Time for tea: mood, blood pressure and cognitive performance effects of caffeine and theanine administered alone and together. Psychopharmacology (Berl). 2008;195(4):569-77.", "pmid": "17891480", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17891480/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Mild additive anxiolytic and cardiovascular-blunting effect.", "clinicalSignificance": "Generally beneficial for anxiety-related propranolol use; rarely problematic.", "managementStrategy": "Monitor HR and sedation; reduce if additive effects are uncomfortable.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Garlic Extract", "supplementBName": "Propranolol", "interactionType": "caution", "severity": "moderate", "description": "Garlic extract lowers blood pressure on its own and, in animal studies, has been shown to potentiate the antihypertensive and cardioprotective effects of propranolol. The combination can drop blood pressure below target in well-controlled patients.", "recommendation": "If you take propranolol, monitor your blood pressure for several weeks after starting garlic extract. Have your prescriber re-evaluate your propranolol dose if readings consistently fall below target.", "minimumTimeSeparation": null, "mechanism": "Garlic's allicin and S-allyl cysteine raise nitric oxide and H2S signaling, producing vasodilation that adds to propranolol's beta blockade and reduction in cardiac output.", "evidenceLevel": "moderate", "sources": [ { "text": "Asdaq SM, Inamdar MN. Pharmacodynamic and Pharmacokinetic Interactions of Propranolol with Garlic (Allium sativum) in Rats. Evid Based Complement Alternat Med. 2011;2011:824042.", "pmid": "21792365", "doi": "10.1093/ecam/neq076", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21792365/", "publicSourceType": "PMID" }, { "text": "Ried K. Garlic Lowers Blood Pressure in Hypertensive Individuals, Regulates Serum Cholesterol, and Stimulates Immunity: An Updated Meta-analysis and Review. J Nutr. 2016;146(2):389S-396S.", "pmid": "26764326", "doi": "10.3945/jn.114.202192", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26764326/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive blood-pressure reduction.", "clinicalSignificance": "Can cause symptomatic hypotension in well-controlled patients.", "managementStrategy": "Monitor BP; adjust propranolol dose if readings drop too low.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Ashwagandha", "supplementBName": "Propranolol", "interactionType": "caution", "severity": "moderate", "description": "Ashwagandha lowers cortisol and dampens sympathetic activity, which can modestly reduce heart rate and blood pressure. Combined with propranolol, the effect can be additive, especially in patients using propranolol for anxiety, performance, or tremor.", "recommendation": "Ashwagandha 300-600 mg/day is generally compatible with propranolol but check resting heart rate and blood pressure when starting. Reduce the dose if HR drops below 50 bpm or you become dizzy.", "minimumTimeSeparation": null, "mechanism": "Withanolides in ashwagandha modulate HPA-axis output, lowering cortisol and sympathetic tone. This complements propranolol's beta-receptor blockade, producing additive reductions in heart rate and stress reactivity.", "evidenceLevel": "emerging", "sources": [ { "text": "Lopresti AL, Smith SJ, Malvi H, Kodgule R. An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study. Medicine (Baltimore). 2019;98(37):e17186.", "pmid": "31517876", "doi": "10.1097/MD.0000000000017186", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31517876/", "publicSourceType": "PMID" }, { "text": "Chandrasekhar K, Kapoor J, Anishetty S. A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. Indian J Psychol Med. 2012;34(3):255-62.", "pmid": "23439798", "doi": "10.4103/0253-7176.106022", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23439798/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive sympathetic dampening and modest BP/HR reduction.", "clinicalSignificance": "May amplify bradycardia or hypotension in propranolol-treated patients.", "managementStrategy": "Monitor HR and BP; adjust dose if symptomatic.", "isSynergistic": null, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Carvedilol", "supplementBName": "L-Carnitine", "interactionType": "synergy", "severity": "info", "description": "L-Carnitine supports fatty-acid oxidation in cardiomyocytes and modestly lowers diastolic blood pressure. In heart failure patients on carvedilol, L-carnitine has been used adjunctively to improve cardiac energetics and exercise tolerance.", "recommendation": "L-Carnitine 1-2 g/day is generally compatible with carvedilol and may provide additional cardiac support. Discuss with your cardiologist before starting, especially if you have heart failure.", "minimumTimeSeparation": null, "mechanism": "L-Carnitine shuttles long-chain fatty acids into mitochondria for beta-oxidation, supporting ATP production. Carvedilol partially inhibits mitochondrial Complex I; carnitine helps offset bioenergetic stress in cardiac muscle.", "evidenceLevel": "moderate", "sources": [ { "text": "Askarpour M, Hadi A, Dehghani Kari Bozorg A, et al. Effects of L-carnitine supplementation on blood pressure: a systematic review and meta-analysis of randomized controlled trials. J Hum Hypertens. 2019;33(10):725-734.", "pmid": "31481697", "doi": "10.1038/s41371-019-0248-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31481697/", "publicSourceType": "PMID" }, { "text": "Cocco T, Cutecchia G, Montedoro G, Lorusso M. The antihypertensive drug carvedilol inhibits the activity of mitochondrial NADH-ubiquinone oxidoreductase. J Bioenerg Biomembr. 2002;34(4):251-8.", "pmid": "12392188", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12392188/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Supports cardiac energetics and may add small BP-lowering effect.", "clinicalSignificance": "May benefit heart-failure patients on carvedilol.", "managementStrategy": "Discuss with cardiologist; standard doses (1-2 g/day) are well-tolerated.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Carvedilol", "supplementBName": "Taurine", "interactionType": "caution", "severity": "moderate", "description": "Taurine modestly lowers blood pressure and heart rate and has heart-rate physiology effects. Combined with carvedilol (which blocks alpha1, beta1, and beta2 receptors), the cumulative drop in BP and HR can be larger than with a more selective beta-blocker.", "recommendation": "Taurine 1-3 g/day is generally safe with carvedilol but monitor resting heart rate and blood pressure when starting. Reduce or stop if HR drops below 50 bpm or you develop dizziness, especially on standing.", "minimumTimeSeparation": null, "mechanism": "Taurine modulates cardiomyocyte calcium handling, blunts sympathetic outflow, and supports endothelial function. These effects add to carvedilol's broad alpha/beta blockade, deepening BP and HR reductions.", "evidenceLevel": "moderate", "sources": [ { "text": "Waldron M, Patterson SD, Tallent J, Jeffries O. The Effects of Oral Taurine on Resting Blood Pressure in Humans: a Meta-Analysis. Curr Hypertens Rep. 2018;20(9):81.", "pmid": "30006901", "doi": "10.1007/s11906-018-0881-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30006901/", "publicSourceType": "PMID" }, { "text": "Tzang CC, Lin WC, Lin LH, et al. Insights into the cardiovascular benefits of taurine: a systematic review and meta-analysis. Nutr J. 2024;23(1):93.", "pmid": "39148075", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39148075/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive bradycardia and blood-pressure reduction.", "clinicalSignificance": "Carvedilol's broader receptor activity makes additive effects more likely.", "managementStrategy": "Monitor HR and BP carefully when starting; reduce if symptomatic.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Bisoprolol", "supplementBName": "Coenzyme Q10", "interactionType": "synergy", "severity": "info", "description": "Beta-blockers as a class inhibit mitochondrial CoQ10-dependent enzymes, contributing to fatigue and reduced exercise tolerance. CoQ10 100-200 mg/day can restore enzyme activity and may slightly lower blood pressure, complementing bisoprolol's effects in heart failure or hypertension.", "recommendation": "Consider CoQ10 100-200 mg/day with food if you experience fatigue or exercise intolerance on bisoprolol. Monitor blood pressure since CoQ10 can produce a small additional drop.", "minimumTimeSeparation": null, "mechanism": "Beta-blockers inhibit CoQ10-dependent NADH-oxidase and succinate-oxidase in mitochondria, lowering ATP synthesis. Supplemental CoQ10 restores enzyme activity in cardiac and skeletal muscle.", "evidenceLevel": "moderate", "sources": [ { "text": "Kishi T, Watanabe T, Folkers K. Bioenergetics in clinical medicine XV. Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors. Res Commun Chem Pathol Pharmacol. 1977;17(1):157-64.", "pmid": "17892", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17892/", "publicSourceType": "PMID" }, { "text": "Rosenfeldt FL, Haas SJ, Krum H, et al. Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. J Hum Hypertens. 2007;21(4):297-306.", "pmid": "17287847", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17287847/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Replenishes drug-induced CoQ10 depletion; may add small BP-lowering effect.", "clinicalSignificance": "May reduce fatigue and exercise intolerance on bisoprolol.", "managementStrategy": "Take 100-200 mg CoQ10 with food; monitor BP.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Sotalol", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "serious", "description": "Sotalol prolongs the QT interval and can cause torsades de pointes, with the risk amplified by low magnesium. Magnesium supplementation helps maintain normal magnesium levels and reduces arrhythmia risk; intravenous magnesium is a first-line treatment for sotalol-related torsades.", "recommendation": "Maintain magnesium intake (e.g., 200-350 mg/day supplemental elemental magnesium from magnesium glycinate) while on sotalol, and report any signs of arrhythmia (palpitations, fainting, dizziness) to your prescriber immediately. Have magnesium levels checked periodically, especially if you take diuretics.", "minimumTimeSeparation": null, "mechanism": "Sotalol blocks the IKr potassium channel, prolonging cardiac repolarization. Hypomagnesemia further destabilizes repolarization by impairing IKs and Na/K-ATPase function, raising the risk of early afterdepolarizations and torsades de pointes.", "evidenceLevel": "strong", "sources": [ { "text": "Soyka LF, Wirtz C, Spangenberg RB. Clinical safety profile of sotalol in patients with arrhythmias. Am J Cardiol. 1990;65(2):74A-81A.", "pmid": "2403737", "doi": "10.1016/0002-9149(90)90207-h", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2403737/", "publicSourceType": "PMID" }, { "text": "Makkar RR, Fromm BS, Steinman RT, Meissner MD, Lehmann MH. Female gender as a risk factor for torsades de pointes associated with cardiovascular drugs. JAMA. 1993;270(21):2590-7.", "pmid": "8230644", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8230644/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Adequate magnesium reduces sotalol-associated arrhythmia risk.", "clinicalSignificance": "Hypomagnesemia significantly increases torsades de pointes risk on sotalol.", "managementStrategy": "Maintain magnesium intake; monitor serum levels especially if on diuretics.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Potassium", "supplementBName": "Sotalol", "interactionType": "synergy", "severity": "serious", "description": "Sotalol prolongs the QT interval; hypokalemia dramatically increases the risk of torsades de pointes. Maintaining normal serum potassium is essential, and potassium repletion is a cornerstone of preventing and treating sotalol-related arrhythmias.", "recommendation": "Do not take potassium supplements without your prescriber's knowledge, but maintain potassium-rich foods and report any diuretic use or GI losses to your cardiologist. Have potassium levels monitored regularly on sotalol.", "minimumTimeSeparation": null, "mechanism": "Sotalol blocks the IKr current; low serum potassium reduces IKr activity further and slows repolarization, creating substrate for early afterdepolarizations and torsades. Maintaining serum potassium ≥4.0 mEq/L is standard practice during sotalol therapy.", "evidenceLevel": "strong", "sources": [ { "text": "Soyka LF, Wirtz C, Spangenberg RB. Clinical safety profile of sotalol in patients with arrhythmias. Am J Cardiol. 1990;65(2):74A-81A.", "pmid": "2403737", "doi": "10.1016/0002-9149(90)90207-h", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2403737/", "publicSourceType": "PMID" }, { "text": "Cubeddu LX. QT prolongation and fatal arrhythmias: a review of clinical implications and effects of drugs. Am J Ther. 2003;10(6):452-7.", "pmid": "14624285", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14624285/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Adequate potassium reduces sotalol-induced torsades risk; hypokalemia increases it.", "clinicalSignificance": "Hypokalemia is a major risk factor for sotalol arrhythmia.", "managementStrategy": "Monitor serum potassium; replete with prescriber guidance.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Coenzyme Q10", "supplementBName": "Timolol Ophthalmic", "interactionType": "synergy", "severity": "info", "description": "Timolol eye drops can produce systemic beta-blockade through nasolacrimal absorption, especially in older adults. Like systemic beta-blockers, timolol inhibits mitochondrial CoQ10-dependent enzymes; CoQ10 supplementation may help, though the systemic exposure with ophthalmic dosing is lower than with oral therapy.", "recommendation": "If you use timolol eye drops and experience fatigue or systemic beta-blocker symptoms (bradycardia, exercise intolerance), consider CoQ10 100-200 mg/day. Punctal occlusion when administering drops also reduces systemic absorption.", "minimumTimeSeparation": null, "mechanism": "Topical timolol is absorbed through the nasolacrimal duct and conjunctiva, achieving plasma levels capable of systemic beta blockade. Like other beta-blockers, it can inhibit CoQ10-dependent mitochondrial enzymes; CoQ10 supplementation restores activity.", "evidenceLevel": "emerging", "sources": [ { "text": "Kishi T, Watanabe T, Folkers K. Bioenergetics in clinical medicine XV. Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors. Res Commun Chem Pathol Pharmacol. 1977;17(1):157-64.", "pmid": "17892", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17892/", "publicSourceType": "PMID" }, { "text": "Munroe WP, Rindone JP, Kershner RM. Systemic side effects associated with the ophthalmic administration of timolol. Drug Intell Clin Pharm. 1985;19(2):85-9.", "pmid": "3882377", "doi": "10.1177/106002808501900201", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3882377/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "May offset CoQ10 enzyme inhibition from systemic absorption of ophthalmic timolol.", "clinicalSignificance": "Relevant when ophthalmic timolol produces systemic side effects.", "managementStrategy": "Use punctal occlusion; consider CoQ10 if systemic symptoms present.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Melatonin", "supplementBName": "Timolol Ophthalmic", "interactionType": "caution", "severity": "info", "description": "Systemic absorption of timolol eye drops can blunt nocturnal melatonin production by blocking beta1 receptors on the pineal gland, similar to oral beta-blockers. Supplemental melatonin can restore sleep quality in patients affected by this side effect.", "recommendation": "If you have insomnia after starting timolol eye drops, try punctal occlusion (pressing on the inner corner of the eye after instillation) to reduce systemic absorption. Low-dose melatonin (0.3-3 mg at bedtime) can help restore sleep if symptoms persist.", "minimumTimeSeparation": null, "mechanism": "Timolol absorbed systemically blocks beta1 receptors on pineal gland cells, reducing N-acetyltransferase activity and nocturnal melatonin synthesis. Exogenous melatonin bypasses this blockade.", "evidenceLevel": "emerging", "sources": [ { "text": "Nathan PJ, Maguire KP, Burrows GD, Norman TR. The effect of atenolol, a beta1-adrenergic antagonist, on nocturnal plasma melatonin secretion: evidence for a dose-response relationship in humans. J Pineal Res. 1997;23(3):131-5.", "pmid": "9406983", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9406983/", "publicSourceType": "PMID" }, { "text": "Munroe WP, Rindone JP, Kershner RM. Systemic side effects associated with the ophthalmic administration of timolol. Drug Intell Clin Pharm. 1985;19(2):85-9.", "pmid": "3882377", "doi": "10.1177/106002808501900201", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3882377/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Replaces beta-blocker-suppressed nocturnal melatonin.", "clinicalSignificance": "May restore sleep quality for patients affected by topical timolol.", "managementStrategy": "Use punctal occlusion; consider low-dose melatonin at bedtime.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Acetyl-L-Carnitine", "supplementBName": "Carvedilol", "interactionType": "synergy", "severity": "info", "description": "Acetyl-L-carnitine supports fatty-acid oxidation and mitochondrial function in cardiac muscle. Carvedilol partially inhibits mitochondrial Complex I, so ALCAR's bioenergetic support may help offset this effect, especially in heart failure or ischemic cardiomyopathy.", "recommendation": "Acetyl-L-carnitine 500-1500 mg/day is generally compatible with carvedilol and may add cardiac benefit. Discuss with your cardiologist before starting, especially if you have heart failure.", "minimumTimeSeparation": null, "mechanism": "ALCAR provides acetyl groups for energy metabolism and shuttles fatty acids into mitochondria for oxidation. Carvedilol's modest inhibition of NADH-ubiquinone oxidoreductase (Complex I) can be partially offset by improved substrate availability.", "evidenceLevel": "emerging", "sources": [ { "text": "Cocco T, Cutecchia G, Montedoro G, Lorusso M. The antihypertensive drug carvedilol inhibits the activity of mitochondrial NADH-ubiquinone oxidoreductase. J Bioenerg Biomembr. 2002;34(4):251-8.", "pmid": "12392188", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12392188/", "publicSourceType": "PMID" }, { "text": "Askarpour M, Hadi A, Dehghani Kari Bozorg A, et al. Effects of L-carnitine supplementation on blood pressure: a systematic review and meta-analysis of randomized controlled trials. J Hum Hypertens. 2019;33(10):725-734.", "pmid": "31481697", "doi": "10.1038/s41371-019-0248-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31481697/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Supports mitochondrial function alongside carvedilol therapy.", "clinicalSignificance": "May benefit cardiac energetics in heart-failure patients.", "managementStrategy": "Discuss with cardiologist; standard doses well-tolerated.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Carvedilol", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "Omega-3 fatty acids modestly reduce blood pressure and lower triglycerides, and have separate benefits in heart failure (reducing all-cause mortality in some trials). Combined with carvedilol, the regimen is broadly cardioprotective, with minimal interaction risk at typical doses.", "recommendation": "Fish oil 1-3 g/day is appropriate alongside carvedilol for most cardiovascular patients. Monitor blood pressure when starting and tell your prescriber if you take high doses (>3 g/day).", "minimumTimeSeparation": null, "mechanism": "EPA and DHA enhance endothelial NO production, reduce vascular inflammation, modulate ion channels, and may improve left ventricular function. These effects complement carvedilol's reduction in cardiac workload.", "evidenceLevel": "strong", "sources": [ { "text": "Zhang X, Ritonja JA, Zhou N, Chen BE, Li X. Omega-3 Polyunsaturated Fatty Acids Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials. J Am Heart Assoc. 2022;11(11):e025071.", "pmid": "35647665", "doi": "10.1161/JAHA.121.025071", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35647665/", "publicSourceType": "PMID" }, { "text": "Morris MC, Sacks F, Rosner B. Does fish oil lower blood pressure? A meta-analysis of controlled trials. Circulation. 1993;88(2):523-33.", "pmid": "8339414", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8339414/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Mild additive cardiovascular benefit.", "clinicalSignificance": "Generally favorable; minor BP additive effect.", "managementStrategy": "Standard doses are well-tolerated; monitor BP if exceeding 3 g/day.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Atenolol", "supplementBName": "Fish Oil Triple Strength", "interactionType": "caution", "severity": "moderate", "description": "Concentrated fish oil products deliver 2-3 g of EPA/DHA per softgel, which produces meaningful blood-pressure reductions on top of atenolol. The combination is generally beneficial but can over-shoot the BP target in well-controlled patients.", "recommendation": "If you take atenolol and start a triple-strength fish oil product, monitor your blood pressure for 2-4 weeks. Have your prescriber re-evaluate the atenolol dose if your readings consistently fall below target.", "minimumTimeSeparation": null, "mechanism": "High-dose EPA/DHA causes vasodilation through enhanced NO production and modulates ion channels. Combined with atenolol's beta1 blockade, the cumulative reduction in systolic and diastolic pressure can be clinically meaningful.", "evidenceLevel": "strong", "sources": [ { "text": "Zhang X, Ritonja JA, Zhou N, Chen BE, Li X. Omega-3 Polyunsaturated Fatty Acids Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials. J Am Heart Assoc. 2022;11(11):e025071.", "pmid": "35647665", "doi": "10.1161/JAHA.121.025071", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35647665/", "publicSourceType": "PMID" }, { "text": "Geleijnse JM, Giltay EJ, Grobbee DE, Donders AR, Kok FJ. Blood pressure response to fish oil supplementation: metaregression analysis of randomized trials. J Hypertens. 2002;20(8):1493-9.", "pmid": "12172309", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12172309/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive blood-pressure reduction at high omega-3 doses.", "clinicalSignificance": "Can over-shoot BP target in well-controlled patients on atenolol.", "managementStrategy": "Monitor BP; adjust atenolol if readings fall too low.", "isSynergistic": null, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Acetyl-L-Carnitine", "supplementBName": "Metoprolol", "interactionType": "synergy", "severity": "info", "description": "Acetyl-L-carnitine supports cardiac mitochondrial function and modestly lowers diastolic blood pressure. Combined with metoprolol in heart failure or ischemic heart disease, ALCAR may add cardioprotective benefit with minimal interaction risk.", "recommendation": "Acetyl-L-carnitine 500-1500 mg/day is generally compatible with metoprolol. Discuss with your cardiologist before adding, especially if you have heart failure, and monitor blood pressure when starting.", "minimumTimeSeparation": null, "mechanism": "ALCAR provides acetyl groups for cellular energy and supports beta-oxidation of fatty acids in mitochondria. This helps offset beta-blocker-related fatigue and modestly enhances cardiac efficiency.", "evidenceLevel": "emerging", "sources": [ { "text": "Askarpour M, Hadi A, Dehghani Kari Bozorg A, et al. Effects of L-carnitine supplementation on blood pressure: a systematic review and meta-analysis of randomized controlled trials. J Hum Hypertens. 2019;33(10):725-734.", "pmid": "31481697", "doi": "10.1038/s41371-019-0248-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31481697/", "publicSourceType": "PMID" }, { "text": "Sharma V, McNeill JH. Parallel effects of β-adrenoceptor blockade on cardiac function and fatty acid oxidation in the diabetic heart. World J Cardiol. 2011;3(10):315-22.", "pmid": "21949571", "doi": "10.4330/wjc.v3.i10.315", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21949571/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Mild cardiac energetic support alongside metoprolol.", "clinicalSignificance": "May benefit heart-failure or ischemic patients; rarely problematic.", "managementStrategy": "Discuss with cardiologist; monitor BP when starting.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "L-Carnitine", "supplementBName": "Metoprolol", "interactionType": "synergy", "severity": "info", "description": "L-Carnitine modestly lowers diastolic blood pressure and supports cardiac fatty-acid oxidation. Adjunctive use with metoprolol in heart failure or post-MI patients is generally beneficial, though the BP effect can rarely be additive.", "recommendation": "L-Carnitine 1-2 g/day is compatible with metoprolol and may add cardiovascular benefit. Discuss with your cardiologist before starting, particularly if you have heart failure.", "minimumTimeSeparation": null, "mechanism": "L-Carnitine transports long-chain fatty acids into mitochondria for beta-oxidation, supporting ATP synthesis in cardiomyocytes. Beta-blockade alters cardiac substrate use; carnitine helps maintain energy supply.", "evidenceLevel": "moderate", "sources": [ { "text": "Askarpour M, Hadi A, Dehghani Kari Bozorg A, et al. Effects of L-carnitine supplementation on blood pressure: a systematic review and meta-analysis of randomized controlled trials. J Hum Hypertens. 2019;33(10):725-734.", "pmid": "31481697", "doi": "10.1038/s41371-019-0248-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31481697/", "publicSourceType": "PMID" }, { "text": "Sharma V, McNeill JH. Parallel effects of β-adrenoceptor blockade on cardiac function and fatty acid oxidation in the diabetic heart. World J Cardiol. 2011;3(10):315-22.", "pmid": "21949571", "doi": "10.4330/wjc.v3.i10.315", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21949571/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Mild cardioprotective support alongside metoprolol.", "clinicalSignificance": "May benefit heart-failure patients; rarely problematic.", "managementStrategy": "Discuss with cardiologist; standard doses well-tolerated.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Risedronate", "supplementBName": "Calcium", "interactionType": "timingSensitive", "severity": "serious", "description": "Risedronate forms insoluble chelates with calcium in the gut, which can drop its already low oral bioavailability (~1%) to near zero. Even calcium from mineral water taken at the same time has been shown to significantly reduce risedronate absorption. Without separation, the dose may be largely wasted and bone protection lost.", "recommendation": "Take risedronate first thing in the morning with plain tap water only, then wait at least 30 minutes (60 minutes is safer) before any calcium supplement, dairy, fortified juice, or mineral water. If you forget and take them together, that dose will likely not work.", "minimumTimeSeparation": 60, "mechanism": "The bisphosphonate phosphonate groups bind avidly to divalent cations such as Ca2+, forming non-absorbable complexes in the lumen and blocking transcellular and paracellular uptake in the proximal small intestine.", "evidenceLevel": "strong", "sources": [ { "text": "Kim JS, Jang SW, Son M, Kim BM, Kang MJ. Enteric-coated tablet of risedronate sodium in combination with phytic acid, a natural chelating agent, for improved oral bioavailability. Eur J Pharm Sci. 2016;82:36-42.", "pmid": "26594027", "doi": "10.1016/j.ejps.2015.11.020", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26594027/", "publicSourceType": "PMID" }, { "text": "Itoh A, Akagi Y, Shimomura H, Aoyama T. Interaction between Bisphosphonates and Mineral Water: Study of Oral Risedronate Absorption in Rats. Biol Pharm Bull. 2016;39(3):323-8.", "pmid": "26934925", "doi": "10.1248/bpb.b15-00630", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26934925/", "publicSourceType": "PMID" }, { "text": "Wiesner A, Szuta M, Galanty A, Paśko P. Optimal Dosing Regimen of Osteoporosis Drugs in Relation to Food Intake as the Key for the Enhancement of the Treatment Effectiveness-A Concise Literature Review. Foods. 2021;10(4):720.", "pmid": "33805435", "doi": "10.3390/foods10040720", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33805435/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Calcium chelates risedronate and dramatically reduces its absorption.", "clinicalSignificance": "Co-administered calcium can effectively neutralize the dose, undermining fracture protection.", "managementStrategy": "Separate risedronate from calcium by at least 30-60 minutes.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Risedronate", "supplementBName": "Iron", "interactionType": "timingSensitive", "severity": "serious", "description": "Iron (Fe2+/Fe3+) forms tight, non-absorbable complexes with risedronate's phosphonate groups in the gut, blocking its already poor oral absorption. Taking the two together can wipe out most of the risedronate dose and leave bones unprotected.", "recommendation": "Take risedronate alone with plain water on an empty stomach, then wait at least 60 minutes before any iron supplement or iron-fortified food. If you take iron in the evening, you can dose risedronate the next morning without issue.", "minimumTimeSeparation": 60, "mechanism": "Bisphosphonate phosphonate groups chelate polyvalent metal cations including Fe2+ and Fe3+, generating insoluble complexes that cannot be absorbed across the intestinal epithelium.", "evidenceLevel": "strong", "sources": [ { "text": "Kim JS, Jang SW, Son M, Kim BM, Kang MJ. Enteric-coated tablet of risedronate sodium in combination with phytic acid, a natural chelating agent, for improved oral bioavailability. Eur J Pharm Sci. 2016;82:36-42.", "pmid": "26594027", "doi": "10.1016/j.ejps.2015.11.020", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26594027/", "publicSourceType": "PMID" }, { "text": "Wiesner A, Szuta M, Galanty A, Paśko P. Optimal Dosing Regimen of Osteoporosis Drugs in Relation to Food Intake as the Key for the Enhancement of the Treatment Effectiveness-A Concise Literature Review. Foods. 2021;10(4):720.", "pmid": "33805435", "doi": "10.3390/foods10040720", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33805435/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Iron chelates risedronate and prevents its absorption.", "clinicalSignificance": "Combined dosing can render the risedronate dose pharmacologically inert.", "managementStrategy": "Separate risedronate from iron supplements by at least 60 minutes.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Risedronate", "supplementBName": "Magnesium Glycinate", "interactionType": "timingSensitive", "severity": "serious", "description": "Magnesium is a divalent cation that chelates risedronate in the gut lumen and prevents it from being absorbed. Studies of mineral water rich in magnesium and calcium have shown markedly reduced risedronate uptake when the two are taken together.", "recommendation": "Take risedronate with plain water on an empty stomach, then wait at least 60 minutes before taking magnesium. Dosing magnesium at night and risedronate in the morning is the simplest fix.", "minimumTimeSeparation": 60, "mechanism": "Mg2+ binds to the phosphonate moieties of risedronate, forming an insoluble complex that cannot cross the enterocyte and reach systemic circulation.", "evidenceLevel": "strong", "sources": [ { "text": "Itoh A, Akagi Y, Shimomura H, Aoyama T. Interaction between Bisphosphonates and Mineral Water: Study of Oral Risedronate Absorption in Rats. Biol Pharm Bull. 2016;39(3):323-8.", "pmid": "26934925", "doi": "10.1248/bpb.b15-00630", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26934925/", "publicSourceType": "PMID" }, { "text": "Wiesner A, Szuta M, Galanty A, Paśko P. Optimal Dosing Regimen of Osteoporosis Drugs in Relation to Food Intake as the Key for the Enhancement of the Treatment Effectiveness-A Concise Literature Review. Foods. 2021;10(4):720.", "pmid": "33805435", "doi": "10.3390/foods10040720", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33805435/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Magnesium chelates risedronate and reduces its bioavailability.", "clinicalSignificance": "Concurrent magnesium can substantially blunt the bone-protective effect of risedronate.", "managementStrategy": "Separate risedronate from magnesium by at least 60 minutes.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Risedronate", "supplementBName": "Zinc", "interactionType": "timingSensitive", "severity": "moderate", "description": "Zinc, like calcium, iron, and magnesium, is a divalent cation that can complex with risedronate in the gut and reduce its absorption. Risedronate's oral bioavailability is already only about 1%, so any further chelation matters.", "recommendation": "Take risedronate with plain water on an empty stomach and wait at least 60 minutes before any zinc-containing supplement or multivitamin. Bedtime zinc dosing pairs well with morning risedronate.", "minimumTimeSeparation": 60, "mechanism": "Zn2+ binds the phosphonate groups of risedronate to form a poorly soluble complex, decreasing the drug fraction available for intestinal absorption.", "evidenceLevel": "moderate", "sources": [ { "text": "Kim JS, Jang SW, Son M, Kim BM, Kang MJ. Enteric-coated tablet of risedronate sodium in combination with phytic acid, a natural chelating agent, for improved oral bioavailability. Eur J Pharm Sci. 2016;82:36-42.", "pmid": "26594027", "doi": "10.1016/j.ejps.2015.11.020", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26594027/", "publicSourceType": "PMID" }, { "text": "Wiesner A, Szuta M, Galanty A, Paśko P. Optimal Dosing Regimen of Osteoporosis Drugs in Relation to Food Intake as the Key for the Enhancement of the Treatment Effectiveness-A Concise Literature Review. Foods. 2021;10(4):720.", "pmid": "33805435", "doi": "10.3390/foods10040720", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33805435/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Zinc forms a poorly absorbed complex with risedronate.", "clinicalSignificance": "Coadministration can lower the already small absorbed dose of risedronate.", "managementStrategy": "Separate zinc from risedronate by at least 60 minutes.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Alendronate", "supplementBName": "Zinc", "interactionType": "timingSensitive", "severity": "moderate", "description": "Zinc is a divalent cation that chelates alendronate in the gut, similar to the well-known calcium, iron, and magnesium interactions. Because alendronate's oral bioavailability is already less than 1%, any further chelation can meaningfully cut the absorbed dose.", "recommendation": "Take alendronate alone with plain water on an empty stomach, stay upright for 30 minutes, and only then have breakfast or any zinc-containing supplement or multivitamin.", "minimumTimeSeparation": 30, "mechanism": "Zn2+ binds to the phosphonate groups of alendronate forming a poorly soluble complex that cannot be absorbed in the proximal small intestine.", "evidenceLevel": "moderate", "sources": [ { "text": "Wiesner A, Szuta M, Galanty A, Paśko P. Optimal Dosing Regimen of Osteoporosis Drugs in Relation to Food Intake as the Key for the Enhancement of the Treatment Effectiveness-A Concise Literature Review. Foods. 2021;10(4):720.", "pmid": "33805435", "doi": "10.3390/foods10040720", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33805435/", "publicSourceType": "PMID" }, { "text": "Kim JS, Jang SW, Son M, Kim BM, Kang MJ. Enteric-coated tablet of risedronate sodium in combination with phytic acid, a natural chelating agent, for improved oral bioavailability. Eur J Pharm Sci. 2016;82:36-42.", "pmid": "26594027", "doi": "10.1016/j.ejps.2015.11.020", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26594027/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Zinc chelates alendronate and lowers its absorption.", "clinicalSignificance": "Concurrent zinc supplements can reduce the small fraction of alendronate that normally reaches bone.", "managementStrategy": "Take zinc at least 30 minutes after alendronate, ideally with the first meal.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Alendronate", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "info", "description": "Adequate vitamin D status is essential for alendronate to work properly. In a multi-year cohort, women whose 25(OH)D rose the most during and after alendronate had nearly double the lumbar-spine BMD gain compared to those whose vitamin D barely moved, and 25(OH)D change independently predicted BMD response. Vitamin D deficiency is also a key driver of post-dose hypocalcemia.", "recommendation": "Maintain vitamin D3 800-2000 IU daily (or as directed) while on alendronate, and aim for serum 25(OH)D above 30 ng/mL. Vitamin D can be taken with food at any time of day; it does not need to be separated from the alendronate dose.", "minimumTimeSeparation": null, "mechanism": "Vitamin D drives intestinal calcium absorption and suppresses secondary hyperparathyroidism. Without it, bisphosphonate-induced inhibition of bone resorption can precipitate hypocalcemia and blunt BMD gains, because remodeling cannot proceed normally.", "evidenceLevel": "strong", "sources": [ { "text": "Catalano A, Bellone F, Morabito N, et al. Vitamin D Boosts Alendronate Tail Effect on Bone Mineral Density in Postmenopausal Women with Osteoporosis. Nutrients. 2021;13(6):1878.", "pmid": "34072655", "doi": "10.3390/nu13061878", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34072655/", "publicSourceType": "PMID" }, { "text": "Iwamoto J. Vitamin K2 therapy for postmenopausal osteoporosis. Nutrients. 2014;6(5):1971-80.", "pmid": "24841104", "doi": "10.3390/nu6051971", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24841104/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Vitamin D potentiates alendronate's bone density gains and prevents hypocalcemia.", "clinicalSignificance": "Alendronate works substantially better when vitamin D status is replete.", "managementStrategy": "Co-supplement vitamin D3 to keep 25(OH)D above 30 ng/mL throughout treatment.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Risedronate", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "info", "description": "Risedronate, like other bisphosphonates, depends on adequate vitamin D status for full bone benefit and for protection against hypocalcemia. Vitamin D deficiency is a recognized predictor of poor BMD response and of post-dose calcium drops.", "recommendation": "Take vitamin D3 800-2000 IU daily (or as your clinician directs) while on risedronate, aiming for serum 25(OH)D above 30 ng/mL. Vitamin D can be taken with food at a separate time from your morning risedronate dose.", "minimumTimeSeparation": null, "mechanism": "Vitamin D maintains intestinal calcium absorption and suppresses PTH. When risedronate halts bone resorption, replete vitamin D ensures that calcium supply matches the reduced flux out of bone, keeping serum calcium and remodeling normal.", "evidenceLevel": "strong", "sources": [ { "text": "Catalano A, Bellone F, Morabito N, et al. Vitamin D Boosts Alendronate Tail Effect on Bone Mineral Density in Postmenopausal Women with Osteoporosis. Nutrients. 2021;13(6):1878.", "pmid": "34072655", "doi": "10.3390/nu13061878", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34072655/", "publicSourceType": "PMID" }, { "text": "Wiesner A, Szuta M, Galanty A, Paśko P. Optimal Dosing Regimen of Osteoporosis Drugs in Relation to Food Intake as the Key for the Enhancement of the Treatment Effectiveness-A Concise Literature Review. Foods. 2021;10(4):720.", "pmid": "33805435", "doi": "10.3390/foods10040720", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33805435/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Vitamin D supports risedronate's BMD response and prevents hypocalcemia.", "clinicalSignificance": "Risedronate underperforms and carries higher hypocalcemia risk when vitamin D is low.", "managementStrategy": "Co-supplement vitamin D3 to keep 25(OH)D above 30 ng/mL.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Risedronate", "supplementBName": "Calcium Carbonate", "interactionType": "synergy", "severity": "info", "description": "Dietary calcium intake of around 1000-1200 mg/day is required for risedronate to fully build bone, but the calcium must not be taken at the same time as the drug. When properly separated, calcium and risedronate together produce better BMD and fracture outcomes than either alone.", "recommendation": "Aim for 1000-1200 mg/day total calcium from diet plus supplements, but take calcium supplements at least 60 minutes after the morning risedronate dose, or later in the day. Split supplemental calcium into 500 mg portions for best absorption.", "minimumTimeSeparation": 60, "mechanism": "Calcium is the structural substrate for new bone matrix. Risedronate slows osteoclast-mediated resorption, but new bone formation by osteoblasts still depends on adequate calcium supply.", "evidenceLevel": "strong", "sources": [ { "text": "Wiesner A, Szuta M, Galanty A, Paśko P. Optimal Dosing Regimen of Osteoporosis Drugs in Relation to Food Intake as the Key for the Enhancement of the Treatment Effectiveness-A Concise Literature Review. Foods. 2021;10(4):720.", "pmid": "33805435", "doi": "10.3390/foods10040720", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33805435/", "publicSourceType": "PMID" }, { "text": "Itoh A, Akagi Y, Shimomura H, Aoyama T. Interaction between Bisphosphonates and Mineral Water: Study of Oral Risedronate Absorption in Rats. Biol Pharm Bull. 2016;39(3):323-8.", "pmid": "26934925", "doi": "10.1248/bpb.b15-00630", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26934925/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Adequate calcium intake is needed for risedronate to maximally build bone, but only when timing-separated.", "clinicalSignificance": "Calcium and risedronate are complementary when separated, but mutually neutralizing when taken together.", "managementStrategy": "Hit 1000-1200 mg/day calcium, but always at least 60 minutes after risedronate.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Alendronate", "supplementBName": "Vitamin K2", "interactionType": "synergy", "severity": "info", "description": "Alendronate plus vitamin K2 produces greater suppression of undercarboxylated osteocalcin and modestly better bone outcomes than alendronate alone in postmenopausal osteoporosis. The two drugs work on complementary pathways (resorption versus matrix carboxylation), so the combination is biologically additive.", "recommendation": "If your prescriber agrees, vitamin K2 (MK-7 or MK-4) can be taken alongside alendronate for added benefit. Take the K2 with a meal containing fat, separate from the morning alendronate dose by at least 30 minutes. Discuss with your clinician if you also take warfarin (where K2 is contraindicated).", "minimumTimeSeparation": 30, "mechanism": "Alendronate inhibits farnesyl pyrophosphate synthase in osteoclasts, blocking bone resorption. Vitamin K2 is a cofactor for gamma-glutamyl carboxylase, which activates osteocalcin to bind calcium into the bone matrix. The two pathways converge on improved net bone mineralization.", "evidenceLevel": "moderate", "sources": [ { "text": "Hirao M, Hashimoto J, Ando W, Ono T, Yoshikawa H. Response of serum carboxylated and undercarboxylated osteocalcin to alendronate monotherapy and combined therapy with vitamin K2 in postmenopausal women. J Bone Miner Metab. 2008;26(3):260-4.", "pmid": "18470667", "doi": "10.1007/s00774-007-0823-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18470667/", "publicSourceType": "PMID" }, { "text": "Iwamoto J. Vitamin K2 therapy for postmenopausal osteoporosis. Nutrients. 2014;6(5):1971-80.", "pmid": "24841104", "doi": "10.3390/nu6051971", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24841104/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin K2 enhances alendronate's effect on bone matrix quality.", "clinicalSignificance": "Combination therapy further suppresses undercarboxylated osteocalcin and may improve BMD.", "managementStrategy": "Co-supplement K2 (MK-7 90-180 mcg) with a fatty meal, separate from the alendronate dose.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Risedronate", "supplementBName": "Vitamin K2", "interactionType": "synergy", "severity": "info", "description": "Vitamin K2 complements bisphosphonate therapy by activating osteocalcin, the matrix protein that binds calcium into bone. Combining vitamin K2 with a bisphosphonate has been shown to further lower undercarboxylated osteocalcin and support bone quality beyond what the bisphosphonate alone achieves.", "recommendation": "If your clinician approves, vitamin K2 (MK-7 90-180 mcg or MK-4) can be co-supplemented with risedronate. Take K2 with a meal containing fat, separate from the morning risedronate dose by at least 60 minutes. Avoid this combination if you also take warfarin.", "minimumTimeSeparation": 60, "mechanism": "Risedronate inhibits osteoclast resorption via FPPS inhibition. Vitamin K2 acts as a cofactor for gamma-glutamyl carboxylase, activating osteocalcin (matrix protein) and MGP (vascular protector). The two pathways converge on improved bone quality.", "evidenceLevel": "moderate", "sources": [ { "text": "Iwamoto J. Vitamin K2 therapy for postmenopausal osteoporosis. Nutrients. 2014;6(5):1971-80.", "pmid": "24841104", "doi": "10.3390/nu6051971", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24841104/", "publicSourceType": "PMID" }, { "text": "Hirao M, Hashimoto J, Ando W, Ono T, Yoshikawa H. Response of serum carboxylated and undercarboxylated osteocalcin to alendronate monotherapy and combined therapy with vitamin K2 in postmenopausal women. J Bone Miner Metab. 2008;26(3):260-4.", "pmid": "18470667", "doi": "10.1007/s00774-007-0823-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18470667/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin K2 complements risedronate by activating osteocalcin.", "clinicalSignificance": "Combined therapy may improve bone matrix quality beyond risedronate alone.", "managementStrategy": "Co-supplement K2 (MK-7 90-180 mcg) with a fatty meal, separate from risedronate.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Zoledronic Acid", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "serious", "description": "Vitamin D status strongly predicts both the acute-phase reaction risk (fever, myalgia, flu-like symptoms after infusion) and the risk of post-infusion hypocalcemia. Patients with serum 25(OH)D below 30 ng/mL had a four-fold higher odds of acute-phase reaction in a prospective cohort. Manufacturer and major guidelines require correction of vitamin D deficiency before each zoledronate infusion.", "recommendation": "Have your 25(OH)D checked before any zoledronic acid infusion and correct deficiency (often 50,000 IU loading dose, then 1000-2000 IU/day) to a target above 30 ng/mL. Continue daily vitamin D3 indefinitely while on therapy.", "minimumTimeSeparation": null, "mechanism": "Vitamin D maintains serum calcium via intestinal absorption and PTH suppression. Zoledronate causes a rapid drop in bone-derived calcium release; if vitamin D is low, the calcium cannot be replaced from the gut and symptomatic hypocalcemia follows. Vitamin D also dampens the gamma-delta T-cell-driven acute phase response.", "evidenceLevel": "strong", "sources": [ { "text": "Crotti C, Watts NB, De Santis M, et al. Acute Phase Reactions After Zoledronic Acid Infusion: Protective Role of 25-Hydroxyvitamin D and Previous Oral Bisphosphonate Therapy. Endocr Pract. 2018;24(5):405-410.", "pmid": "29498910", "doi": "10.4158/EP161638.OR", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29498910/", "publicSourceType": "PMID" }, { "text": "Catalano A, Bellone F, Morabito N, et al. Vitamin D Boosts Alendronate Tail Effect on Bone Mineral Density in Postmenopausal Women with Osteoporosis. Nutrients. 2021;13(6):1878.", "pmid": "34072655", "doi": "10.3390/nu13061878", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34072655/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Vitamin D adequacy protects against zoledronic-acid acute phase reaction and hypocalcemia.", "clinicalSignificance": "Vitamin D deficient patients have far higher rates of post-infusion fever and dangerous calcium drops.", "managementStrategy": "Correct 25(OH)D to above 30 ng/mL before infusion; continue daily D3 thereafter.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Zoledronic Acid", "supplementBName": "Calcium", "interactionType": "synergy", "severity": "serious", "description": "Zoledronic acid rapidly suppresses bone resorption and can drive serum calcium down within days of infusion, especially in patients with low calcium intake, vitamin D deficiency, or impaired renal function. Adequate calcium intake is required by major osteoporosis guidelines before and during zoledronate therapy.", "recommendation": "Take elemental calcium 1000-1200 mg/day from diet plus supplements (split 500 mg per dose) throughout zoledronate therapy. Ensure intake is adequate in the days immediately after each infusion. Because zoledronate is given intravenously, there is no oral-dose timing concern.", "minimumTimeSeparation": null, "mechanism": "Zoledronate inhibits osteoclast FPPS, halting bone resorption and the calcium efflux from bone that normally helps maintain serum calcium. Adequate dietary calcium supplies the system from the gut instead, preventing hypocalcemia.", "evidenceLevel": "strong", "sources": [ { "text": "Crotti C, Watts NB, De Santis M, et al. Acute Phase Reactions After Zoledronic Acid Infusion: Protective Role of 25-Hydroxyvitamin D and Previous Oral Bisphosphonate Therapy. Endocr Pract. 2018;24(5):405-410.", "pmid": "29498910", "doi": "10.4158/EP161638.OR", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29498910/", "publicSourceType": "PMID" }, { "text": "Wiesner A, Szuta M, Galanty A, Paśko P. Optimal Dosing Regimen of Osteoporosis Drugs in Relation to Food Intake as the Key for the Enhancement of the Treatment Effectiveness-A Concise Literature Review. Foods. 2021;10(4):720.", "pmid": "33805435", "doi": "10.3390/foods10040720", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33805435/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Adequate calcium prevents zoledronate-induced hypocalcemia and supports BMD.", "clinicalSignificance": "Without adequate calcium, post-infusion hypocalcemia can be severe and symptomatic.", "managementStrategy": "Take 1000-1200 mg/day calcium with adequate vitamin D throughout zoledronate therapy.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Combined Oral Contraceptive", "supplementBName": "Vitamin B9", "interactionType": "synergy", "severity": "moderate", "description": "A systematic review and meta-analysis of 17 studies found that women using combined oral contraceptives had significantly lower serum and red-cell folate than non-users. This matters most for women who may conceive shortly after stopping the pill, because low folate at conception raises neural tube defect risk.", "recommendation": "Take a daily folate-containing multivitamin (400-800 mcg of folic acid or 5-MTHF) while on combined oral contraception, especially in the year before any planned pregnancy. The folate can be taken with or without the pill.", "minimumTimeSeparation": null, "mechanism": "Estrogens increase hepatic folate-binding protein synthesis and may alter folate catabolism and renal clearance, lowering circulating folate. Some progestins also impair folate-dependent one-carbon metabolism.", "evidenceLevel": "strong", "sources": [ { "text": "Shere M, Bapat P, Nickel C, Kapur B, Koren G. Association Between Use of Oral Contraceptives and Folate Status: A Systematic Review and Meta-Analysis. J Obstet Gynaecol Can. 2015;37(5):430-438.", "pmid": "26168104", "doi": "10.1016/S1701-2163(15)30258-9", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26168104/", "publicSourceType": "PMID" }, { "text": "Palmery M, Saraceno A, Vaiarelli A, Carlomagno G. Oral contraceptives and changes in nutritional requirements. Eur Rev Med Pharmacol Sci. 2013;17(13):1804-13.", "pmid": "23852908", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23852908/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Combined oral contraceptives lower serum and red-cell folate.", "clinicalSignificance": "Low folate raises the risk of neural tube defects if pregnancy follows pill discontinuation.", "managementStrategy": "Take 400-800 mcg folate daily throughout pill use and pre-conception.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Combined Oral Contraceptive", "supplementBName": "Methylfolate", "interactionType": "synergy", "severity": "moderate", "description": "Methylfolate (5-MTHF) is the active circulating form of folate and is the preferred supplement for women on combined oral contraceptives, particularly those with MTHFR variants. COCs lower serum and red-cell folate, and 5-MTHF restores levels quickly without dependence on hepatic conversion of folic acid.", "recommendation": "Take methylfolate 400-800 mcg daily while on combined oral contraception, especially if you plan to conceive after stopping. Methylfolate can be taken at any time of day, with or without the pill.", "minimumTimeSeparation": null, "mechanism": "COCs reduce folate via increased binding protein and altered metabolism. Methylfolate bypasses the MTHFR enzyme step and replenishes the methyl donor pool needed for homocysteine remethylation, DNA synthesis, and neural tube closure in early pregnancy.", "evidenceLevel": "moderate", "sources": [ { "text": "Shere M, Bapat P, Nickel C, Kapur B, Koren G. Association Between Use of Oral Contraceptives and Folate Status: A Systematic Review and Meta-Analysis. J Obstet Gynaecol Can. 2015;37(5):430-438.", "pmid": "26168104", "doi": "10.1016/S1701-2163(15)30258-9", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26168104/", "publicSourceType": "PMID" }, { "text": "Basciani S, Porcaro G. Counteracting side effects of combined oral contraceptives through the administration of specific micronutrients. Eur Rev Med Pharmacol Sci. 2022;26(13):4846-4862.", "pmid": "35856377", "doi": "10.26355/eurrev_202207_29410", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35856377/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "COCs deplete folate; methylfolate efficiently restores active folate stores.", "clinicalSignificance": "Methylfolate is the safest pre-conception folate strategy for women coming off COCs.", "managementStrategy": "Co-supplement 400-800 mcg methylfolate daily throughout COC use.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Combined Oral Contraceptive", "supplementBName": "Vitamin B6", "interactionType": "synergy", "severity": "moderate", "description": "Combined oral contraceptives lower plasma pyridoxal-5-phosphate (active vitamin B6) and can contribute to low mood, irritability, and nausea. In a controlled trial, B6 50 mg/day reduced these side effects in Cambodian women using oral contraception.", "recommendation": "Consider a daily B6 supplement (25-50 mg as pyridoxine or P5P) while on combined oral contraception, particularly if you experience low mood, irritability, or nausea. Take with or without food, at any time of day.", "minimumTimeSeparation": null, "mechanism": "Ethinyl estradiol induces hepatic enzymes that increase tryptophan catabolism and B6 utilization, lowering pyridoxal-5-phosphate. B6 is also a cofactor for serotonin and dopamine synthesis, partly explaining mood effects.", "evidenceLevel": "moderate", "sources": [ { "text": "Var C, Keller S, Tung R, Freeland D, Bazzano AN. Supplementation with vitamin B6 reduces side effects in Cambodian women using oral contraception. Nutrients. 2014;6(9):3353-62.", "pmid": "25163030", "doi": "10.3390/nu6093353", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25163030/", "publicSourceType": "PMID" }, { "text": "Palmery M, Saraceno A, Vaiarelli A, Carlomagno G. Oral contraceptives and changes in nutritional requirements. Eur Rev Med Pharmacol Sci. 2013;17(13):1804-13.", "pmid": "23852908", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23852908/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "COCs deplete vitamin B6 and may worsen mood and nausea symptoms.", "clinicalSignificance": "B6 supplementation reduces pill-associated side effects and restores neurotransmitter cofactor status.", "managementStrategy": "Take 25-50 mg B6 daily while on combined oral contraception.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Combined Oral Contraceptive", "supplementBName": "Vitamin B12", "interactionType": "synergy", "severity": "moderate", "description": "Combined oral contraceptives are associated with lower serum vitamin B12 levels in multiple observational and review studies. Although clinical deficiency is uncommon, the drop can become meaningful in vegetarians, vegans, and long-term pill users, and matters for any planned pregnancy.", "recommendation": "Consider a daily B12 supplement (250-1000 mcg as methylcobalamin or cyanocobalamin) while on combined oral contraception, especially if you eat little animal protein or have been on the pill for many years.", "minimumTimeSeparation": null, "mechanism": "COCs appear to lower serum holotranscobalamin and total B12 via altered B12-binding protein synthesis. The mechanism may also involve reduced intestinal uptake and increased catabolism in the liver.", "evidenceLevel": "moderate", "sources": [ { "text": "Palmery M, Saraceno A, Vaiarelli A, Carlomagno G. Oral contraceptives and changes in nutritional requirements. Eur Rev Med Pharmacol Sci. 2013;17(13):1804-13.", "pmid": "23852908", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23852908/", "publicSourceType": "PMID" }, { "text": "Basciani S, Porcaro G. Counteracting side effects of combined oral contraceptives through the administration of specific micronutrients. Eur Rev Med Pharmacol Sci. 2022;26(13):4846-4862.", "pmid": "35856377", "doi": "10.26355/eurrev_202207_29410", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35856377/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "COCs lower serum vitamin B12 levels.", "clinicalSignificance": "Long-term pill users, vegetarians, and women planning pregnancy are most at risk of clinically relevant low B12.", "managementStrategy": "Take 250-1000 mcg B12 daily during COC use.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Combined Oral Contraceptive", "supplementBName": "Methylcobalamin", "interactionType": "synergy", "severity": "moderate", "description": "Methylcobalamin is the active circulating form of vitamin B12 and is depleted along with other B vitamins during combined oral contraceptive use. Restoring B12 is particularly important for one-carbon metabolism, energy, and pre-conception health.", "recommendation": "Take methylcobalamin 500-1000 mcg daily while on combined oral contraception, particularly with concurrent methylfolate. Either is best taken in the morning with breakfast.", "minimumTimeSeparation": null, "mechanism": "COCs reduce serum total B12 and holotranscobalamin; methylcobalamin directly replenishes the active pool and supports methionine synthase, homocysteine remethylation, and myelin maintenance.", "evidenceLevel": "moderate", "sources": [ { "text": "Palmery M, Saraceno A, Vaiarelli A, Carlomagno G. Oral contraceptives and changes in nutritional requirements. Eur Rev Med Pharmacol Sci. 2013;17(13):1804-13.", "pmid": "23852908", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23852908/", "publicSourceType": "PMID" }, { "text": "Basciani S, Porcaro G. Counteracting side effects of combined oral contraceptives through the administration of specific micronutrients. Eur Rev Med Pharmacol Sci. 2022;26(13):4846-4862.", "pmid": "35856377", "doi": "10.26355/eurrev_202207_29410", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35856377/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "COCs lower B12; methylcobalamin restores active B12.", "clinicalSignificance": "Important for women planning pregnancy and long-term pill users.", "managementStrategy": "Co-supplement methylcobalamin 500-1000 mcg daily.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Combined Oral Contraceptive", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Combined oral contraceptives lower plasma and platelet vitamin C levels and increase oxidative stress, partly because estrogen induces hepatic enzymes that increase vitamin C turnover. Modest daily supplementation restores levels and antioxidant capacity.", "recommendation": "A daily multivitamin or 250-500 mg vitamin C is reasonable for women on combined oral contraception. Avoid very high doses (above 1000 mg/day) at the same time as the pill, since vitamin C may transiently raise ethinyl estradiol levels.", "minimumTimeSeparation": null, "mechanism": "Estrogens upregulate hepatic enzymes and oxidative pathways that increase ascorbate consumption. Vitamin C also competes with ethinyl estradiol for sulfate conjugation at high doses, briefly raising estrogen levels.", "evidenceLevel": "moderate", "sources": [ { "text": "Palmery M, Saraceno A, Vaiarelli A, Carlomagno G. Oral contraceptives and changes in nutritional requirements. Eur Rev Med Pharmacol Sci. 2013;17(13):1804-13.", "pmid": "23852908", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23852908/", "publicSourceType": "PMID" }, { "text": "Basciani S, Porcaro G. Counteracting side effects of combined oral contraceptives through the administration of specific micronutrients. Eur Rev Med Pharmacol Sci. 2022;26(13):4846-4862.", "pmid": "35856377", "doi": "10.26355/eurrev_202207_29410", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35856377/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "COCs lower plasma vitamin C and raise oxidative stress.", "clinicalSignificance": "Modest vitamin C supplementation restores antioxidant capacity; very high doses can briefly raise estrogen levels.", "managementStrategy": "Take 250-500 mg vitamin C daily; avoid doses above 1000 mg.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Combined Oral Contraceptive", "supplementBName": "Vitamin E", "interactionType": "synergy", "severity": "info", "description": "Combined oral contraceptives reduce serum levels of lipid-soluble antioxidants including alpha-tocopherol and coenzyme Q10. In a controlled study of premenopausal women, OC use significantly lowered both. Replenishing vitamin E helps offset COC-associated oxidative stress.", "recommendation": "A daily multivitamin or 100-200 IU of mixed tocopherols is reasonable for women on combined oral contraception. Take with food containing fat for absorption.", "minimumTimeSeparation": null, "mechanism": "Estrogen-induced changes in lipid metabolism and antioxidant turnover lower circulating tocopherol levels. Lower alpha-tocopherol may contribute to the increased oxidative stress and inflammatory markers seen with COC use.", "evidenceLevel": "moderate", "sources": [ { "text": "Palan PR, Magneson AT, Castillo M, Dunne J, Mikhail MS. Effects of menstrual cycle and oral contraceptive use on serum levels of lipid-soluble antioxidants. Am J Obstet Gynecol. 2006;194(5):e35-8.", "pmid": "16647895", "doi": "10.1016/j.ajog.2005.11.032", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16647895/", "publicSourceType": "PMID" }, { "text": "Palmery M, Saraceno A, Vaiarelli A, Carlomagno G. Oral contraceptives and changes in nutritional requirements. Eur Rev Med Pharmacol Sci. 2013;17(13):1804-13.", "pmid": "23852908", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23852908/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "COCs lower serum vitamin E (alpha-tocopherol).", "clinicalSignificance": "Lower vitamin E status contributes to COC-related oxidative stress.", "managementStrategy": "Take 100-200 IU mixed tocopherols daily with a meal.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Combined Oral Contraceptive", "supplementBName": "Coenzyme Q10", "interactionType": "synergy", "severity": "info", "description": "Combined oral contraceptive use significantly decreases serum coenzyme Q10 levels in premenopausal women, mirroring the drop seen with statins. Although clinical consequences are not fully defined, restoring CoQ10 supports mitochondrial function and antioxidant capacity.", "recommendation": "Consider CoQ10 100-200 mg daily (ubiquinone or ubiquinol) while on combined oral contraception, particularly if you have fatigue, exercise intolerance, or take other CoQ10-depleting medications. Take with a meal containing fat.", "minimumTimeSeparation": null, "mechanism": "Estrogen-induced shifts in lipoprotein metabolism reduce LDL-bound CoQ10 transport. Hepatic enzyme induction may also accelerate CoQ10 turnover.", "evidenceLevel": "moderate", "sources": [ { "text": "Palan PR, Magneson AT, Castillo M, Dunne J, Mikhail MS. Effects of menstrual cycle and oral contraceptive use on serum levels of lipid-soluble antioxidants. Am J Obstet Gynecol. 2006;194(5):e35-8.", "pmid": "16647895", "doi": "10.1016/j.ajog.2005.11.032", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16647895/", "publicSourceType": "PMID" }, { "text": "Basciani S, Porcaro G. Counteracting side effects of combined oral contraceptives through the administration of specific micronutrients. Eur Rev Med Pharmacol Sci. 2022;26(13):4846-4862.", "pmid": "35856377", "doi": "10.26355/eurrev_202207_29410", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35856377/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "COCs significantly lower serum coenzyme Q10.", "clinicalSignificance": "Restoring CoQ10 supports mitochondrial energy production and antioxidant defense.", "managementStrategy": "Take CoQ10 100-200 mg daily with a fatty meal.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Combined Oral Contraceptive", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "info", "description": "Combined oral contraceptive use is associated with lower serum magnesium and altered mineral status in observational studies, contributing to fatigue, muscle cramps, and headaches in some women. Magnesium supplementation restores levels and may improve tolerability.", "recommendation": "Use a modest magnesium supplement only as needed to meet intake goals while on combined oral contraception, especially if you have headaches, cramps, or mood symptoms. Best taken in the evening for sleep benefit.", "minimumTimeSeparation": null, "mechanism": "Estrogen-induced shifts in mineral metabolism and aldosterone activity may increase magnesium excretion. Lower magnesium contributes to neuromuscular and vascular symptoms.", "evidenceLevel": "moderate", "sources": [ { "text": "Akinloye O, Adebayo TO, Oguntibeju OO, Oparinde DP, Ogunyemi EO. Effects of contraceptives on serum trace elements, calcium and phosphorus levels. West Indian Med J. 2011;60(3):308-15.", "pmid": "22224344", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22224344/", "publicSourceType": "PMID" }, { "text": "Basciani S, Porcaro G. Counteracting side effects of combined oral contraceptives through the administration of specific micronutrients. Eur Rev Med Pharmacol Sci. 2022;26(13):4846-4862.", "pmid": "35856377", "doi": "10.26355/eurrev_202207_29410", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35856377/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "COCs lower serum magnesium.", "clinicalSignificance": "Low magnesium contributes to headache, cramping, and mood symptoms in pill users.", "managementStrategy": "Use a modest magnesium supplement only as needed to meet intake goals; keep supplemental magnesium within standard upper-limit guidance unless clinician-supervised.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Combined Oral Contraceptive", "supplementBName": "Zinc", "interactionType": "synergy", "severity": "info", "description": "Multiple observational studies show that combined oral contraceptive users have lower serum zinc compared with non-users. The clinical impact is usually modest, but matters for immunity, skin, and any planned pregnancy.", "recommendation": "A daily multivitamin or zinc 10-15 mg is reasonable for women on combined oral contraception. Take with food to reduce nausea, and not at the same time as iron or calcium for best absorption.", "minimumTimeSeparation": null, "mechanism": "Estrogen elevates serum copper and ceruloplasmin while lowering zinc; the precise mechanism involves altered metallothionein expression and competitive intestinal absorption with copper.", "evidenceLevel": "moderate", "sources": [ { "text": "Akinloye O, Adebayo TO, Oguntibeju OO, Oparinde DP, Ogunyemi EO. Effects of contraceptives on serum trace elements, calcium and phosphorus levels. West Indian Med J. 2011;60(3):308-15.", "pmid": "22224344", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22224344/", "publicSourceType": "PMID" }, { "text": "Palmery M, Saraceno A, Vaiarelli A, Carlomagno G. Oral contraceptives and changes in nutritional requirements. Eur Rev Med Pharmacol Sci. 2013;17(13):1804-13.", "pmid": "23852908", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23852908/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "COCs lower serum zinc.", "clinicalSignificance": "Lower zinc may affect immunity, skin, and pre-conception nutrient status.", "managementStrategy": "Take 10-15 mg zinc daily with food.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Combined Oral Contraceptive", "supplementBName": "Selenium", "interactionType": "synergy", "severity": "info", "description": "Combined oral contraceptive use is associated with lower serum selenium and reduced glutathione peroxidase activity in several studies, contributing to lower antioxidant capacity. Selenium adequacy also supports normal thyroid hormone metabolism, which is relevant because COCs raise thyroid-binding globulin.", "recommendation": "A daily multivitamin or 55-100 mcg of selenium is reasonable for women on combined oral contraception. Brazil nuts (1-2 per day) provide a natural dietary source.", "minimumTimeSeparation": null, "mechanism": "COC-induced oxidative stress increases consumption of selenium-dependent glutathione peroxidase. Estrogen may also reduce intestinal selenium absorption or accelerate renal clearance.", "evidenceLevel": "moderate", "sources": [ { "text": "Akinloye O, Adebayo TO, Oguntibeju OO, Oparinde DP, Ogunyemi EO. Effects of contraceptives on serum trace elements, calcium and phosphorus levels. West Indian Med J. 2011;60(3):308-15.", "pmid": "22224344", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22224344/", "publicSourceType": "PMID" }, { "text": "Basciani S, Porcaro G. Counteracting side effects of combined oral contraceptives through the administration of specific micronutrients. Eur Rev Med Pharmacol Sci. 2022;26(13):4846-4862.", "pmid": "35856377", "doi": "10.26355/eurrev_202207_29410", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35856377/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "COCs lower serum selenium and glutathione peroxidase activity.", "clinicalSignificance": "Lower selenium reduces antioxidant defense and may affect thyroid hormone metabolism.", "managementStrategy": "Take 55-100 mcg selenium daily, or 1-2 Brazil nuts.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Combined Oral Contraceptive", "supplementBName": "Vitamin B2", "interactionType": "synergy", "severity": "info", "description": "Combined oral contraceptives modestly lower riboflavin (B2) status by altering hepatic enzyme turnover and erythrocyte glutathione reductase activity. The effect is small in well-nourished women but can be relevant for those with limited dietary intake.", "recommendation": "A daily multivitamin or B-complex supplement providing 1.3-2 mg of riboflavin is sufficient for women on combined oral contraception. Take with food.", "minimumTimeSeparation": null, "mechanism": "Estrogens increase the hepatic synthesis of flavoproteins and accelerate riboflavin catabolism, reducing the pool of flavin mononucleotide and flavin adenine dinucleotide cofactors.", "evidenceLevel": "moderate", "sources": [ { "text": "Palmery M, Saraceno A, Vaiarelli A, Carlomagno G. Oral contraceptives and changes in nutritional requirements. Eur Rev Med Pharmacol Sci. 2013;17(13):1804-13.", "pmid": "23852908", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23852908/", "publicSourceType": "PMID" }, { "text": "Basciani S, Porcaro G. Counteracting side effects of combined oral contraceptives through the administration of specific micronutrients. Eur Rev Med Pharmacol Sci. 2022;26(13):4846-4862.", "pmid": "35856377", "doi": "10.26355/eurrev_202207_29410", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35856377/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "COCs modestly lower riboflavin status.", "clinicalSignificance": "Marginal status may worsen migraine, fatigue, or oral/skin symptoms in some users.", "managementStrategy": "Take a daily B-complex providing 1.3-2 mg riboflavin.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Combined Oral Contraceptive", "supplementBName": "Inositol", "interactionType": "caution", "severity": "info", "description": "Both combined oral contraceptives and inositol (myo-inositol) are used for PCOS, but for different reasons. COCs treat hyperandrogenism and regulate cycles by suppressing ovulation, while inositol improves insulin sensitivity and may restore ovulation. The two can be used together, but pregnancy will not occur while on the pill, so women trying to conceive should switch from COC to inositol rather than combine them.", "recommendation": "Inositol (typically myo-inositol 2 g twice daily, often with 50 mg of D-chiro-inositol) can be taken alongside combined oral contraceptives to address PCOS-related insulin resistance. Discuss with your clinician whether the pill is still needed or whether inositol alone might suit your reproductive goals.", "minimumTimeSeparation": null, "mechanism": "Myo-inositol acts as a second-messenger precursor for FSH and insulin signaling, improving ovarian insulin sensitivity and androgen profile. COCs suppress LH and ovarian androgen production via gonadotropin suppression. The two work through independent pathways.", "evidenceLevel": "emerging", "sources": [ { "text": "Basciani S, Porcaro G. Counteracting side effects of combined oral contraceptives through the administration of specific micronutrients. Eur Rev Med Pharmacol Sci. 2022;26(13):4846-4862.", "pmid": "35856377", "doi": "10.26355/eurrev_202207_29410", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35856377/", "publicSourceType": "PMID" }, { "text": "Palmery M, Saraceno A, Vaiarelli A, Carlomagno G. Oral contraceptives and changes in nutritional requirements. Eur Rev Med Pharmacol Sci. 2013;17(13):1804-13.", "pmid": "23852908", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23852908/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Inositol complements COCs for PCOS metabolic features but does not enhance contraception.", "clinicalSignificance": "Useful adjunct for insulin resistance; consider switching if trying to conceive.", "managementStrategy": "Co-supplement myo-inositol 4 g/day; reassess COC need at conception.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Testosterone", "supplementBName": "Fenugreek", "interactionType": "caution", "severity": "moderate", "description": "Fenugreek extracts (especially standardized products like Furosap) modestly raise free testosterone in men in small clinical trials. Layering fenugreek on top of prescribed testosterone is unlikely to add benefit and may push androgenic side effects (acne, mood changes, polycythemia) higher.", "recommendation": "Avoid routine fenugreek supplementation if you are already on prescribed testosterone therapy. If you wish to use fenugreek, discuss with your prescriber and monitor hematocrit, PSA, and mood. Fenugreek can also lower blood glucose, which is a separate consideration.", "minimumTimeSeparation": null, "mechanism": "Fenugreek saponins (protodioscin, fenuside) appear to inhibit aromatase and 5-alpha-reductase modestly, raising free testosterone and shifting the androgen-to-estrogen ratio. Stacking with exogenous testosterone amplifies androgen tone without proven benefit.", "evidenceLevel": "moderate", "sources": [ { "text": "Maheshwari A, Verma N, Swaroop A, et al. Efficacy of FurosapTM, a novel Trigonella foenum-graecum seed extract, in Enhancing Testosterone Level and Improving Sperm Profile in Male Volunteers. Int J Med Sci. 2017;14(1):58-66.", "pmid": "28138310", "doi": "10.7150/ijms.17256", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28138310/", "publicSourceType": "PMID" }, { "text": "Leisegang K, Finelli R, Sikka SC, Panner Selvam MK. Eurycoma longifolia (Jack) Improves Serum Total Testosterone in Men: A Systematic Review and Meta-Analysis of Clinical Trials. Medicina (Kaunas). 2022;58(8):1047.", "pmid": "36013514", "doi": "10.3390/medicina58081047", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36013514/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Fenugreek may modestly raise testosterone and stack with prescribed therapy.", "clinicalSignificance": "Combined use risks excessive androgen effects (polycythemia, acne, mood changes).", "managementStrategy": "Avoid fenugreek with testosterone therapy; if used, monitor hematocrit and PSA.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Testosterone", "supplementBName": "Tongkat Ali", "interactionType": "caution", "severity": "moderate", "description": "Eurycoma longifolia (tongkat ali) significantly raises serum total testosterone in healthy and hypogonadal men in a meta-analysis of five RCTs. Adding it on top of prescribed testosterone has no proven benefit and may amplify androgenic side effects.", "recommendation": "Avoid tongkat ali supplementation while on prescribed testosterone. If you wish to use it, discuss with your prescriber and check hematocrit and PSA. Tongkat ali has also been linked to rare cases of liver injury and an atrial flutter case report.", "minimumTimeSeparation": null, "mechanism": "Tongkat ali quassinoids (eurycomanone) appear to stimulate steroidogenic enzymes (CYP17, 3β-HSD) and free testosterone from SHBG, raising both total and free testosterone. Stacking with exogenous testosterone amplifies androgen burden.", "evidenceLevel": "moderate", "sources": [ { "text": "Leisegang K, Finelli R, Sikka SC, Panner Selvam MK. Eurycoma longifolia (Jack) Improves Serum Total Testosterone in Men: A Systematic Review and Meta-Analysis of Clinical Trials. Medicina (Kaunas). 2022;58(8):1047.", "pmid": "36013514", "doi": "10.3390/medicina58081047", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36013514/", "publicSourceType": "PMID" }, { "text": "Maheshwari A, Verma N, Swaroop A, et al. Efficacy of FurosapTM, a novel Trigonella foenum-graecum seed extract, in Enhancing Testosterone Level and Improving Sperm Profile in Male Volunteers. Int J Med Sci. 2017;14(1):58-66.", "pmid": "28138310", "doi": "10.7150/ijms.17256", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28138310/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Tongkat ali raises testosterone and can stack with prescribed therapy.", "clinicalSignificance": "Combined use may amplify androgen side effects and adds hepatotoxicity risk.", "managementStrategy": "Avoid tongkat ali with testosterone therapy; monitor liver enzymes if used.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Testosterone", "supplementBName": "Tribulus Terrestris", "interactionType": "caution", "severity": "info", "description": "Tribulus terrestris is widely marketed as a testosterone booster, but systematic reviews and meta-analyses generally find no consistent effect on serum testosterone in healthy or hypogonadal men. Layering it on prescribed testosterone is unlikely to add benefit and may complicate side-effect attribution.", "recommendation": "Tribulus terrestris does not meaningfully add to prescribed testosterone therapy and is best avoided to keep monitoring clean. If you are using it for libido, discuss alternatives with your prescriber that have stronger evidence.", "minimumTimeSeparation": null, "mechanism": "Tribulus saponins were once hypothesized to raise LH and testosterone, but human RCTs have not confirmed an effect on serum androgens. Effects on libido may be androgen-independent.", "evidenceLevel": "moderate", "sources": [ { "text": "Leisegang K, Finelli R, Sikka SC, Panner Selvam MK. Eurycoma longifolia (Jack) Improves Serum Total Testosterone in Men: A Systematic Review and Meta-Analysis of Clinical Trials. Medicina (Kaunas). 2022;58(8):1047.", "pmid": "36013514", "doi": "10.3390/medicina58081047", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36013514/", "publicSourceType": "PMID" }, { "text": "Maheshwari A, Verma N, Swaroop A, et al. Efficacy of FurosapTM, a novel Trigonella foenum-graecum seed extract, in Enhancing Testosterone Level and Improving Sperm Profile in Male Volunteers. Int J Med Sci. 2017;14(1):58-66.", "pmid": "28138310", "doi": "10.7150/ijms.17256", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28138310/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Tribulus does not reliably raise testosterone and adds no proven benefit on top of TRT.", "clinicalSignificance": "Combining muddies monitoring without clear gain.", "managementStrategy": "Avoid Tribulus during testosterone therapy.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Testosterone", "supplementBName": "Ashwagandha", "interactionType": "caution", "severity": "moderate", "description": "Ashwagandha (Withania somnifera) modestly raises testosterone and LH in men with infertility or stress and can also raise T4 and lower TSH. Adding it to prescribed testosterone may amplify androgenic effects and complicates monitoring, especially of thyroid function which can already be affected by androgen therapy.", "recommendation": "Use ashwagandha cautiously while on prescribed testosterone. If you take both, monitor hematocrit, PSA, mood, and a TSH check every 6-12 months because ashwagandha can shift thyroid labs. Discontinue ashwagandha if you develop thyrotoxicosis symptoms (palpitations, heat intolerance, tremor).", "minimumTimeSeparation": null, "mechanism": "Ashwagandha withanolides modulate the HPA axis and may increase Leydig cell steroidogenesis. They also stimulate thyroid hormone synthesis, raising T4 and lowering TSH. Both effects can compound those of exogenous testosterone.", "evidenceLevel": "moderate", "sources": [ { "text": "Durg S, Shivaram SB, Bavage S. Withania somnifera (Indian ginseng) in male infertility: An evidence-based systematic review and meta-analysis. Phytomedicine. 2018;50:247-256.", "pmid": "30466985", "doi": "10.1016/j.phymed.2017.11.011", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30466985/", "publicSourceType": "PMID" }, { "text": "Sharma AK, Basu I, Singh S. Efficacy and Safety of Ashwagandha Root Extract in Subclinical Hypothyroid Patients: A Double-Blind, Randomized Placebo-Controlled Trial. J Altern Complement Med. 2018;24(3):243-248.", "pmid": "28829155", "doi": "10.1089/acm.2017.0183", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28829155/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Ashwagandha modestly raises testosterone and shifts thyroid labs.", "clinicalSignificance": "Combined use can amplify androgen effects and confound thyroid monitoring.", "managementStrategy": "Use cautiously; monitor hematocrit, PSA, and TSH; stop if thyrotoxic symptoms.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Testosterone", "supplementBName": "Boron", "interactionType": "caution", "severity": "info", "description": "In a small trial, daily boron 10 mg raised free testosterone and modestly lowered estradiol in healthy men over one week. The clinical impact on top of prescribed testosterone is likely small but may shift the androgen-to-estrogen ratio and complicate monitoring.", "recommendation": "Routine boron supplementation is generally safe at 3-10 mg/day, but is not needed alongside prescribed testosterone. If used, keep the dose modest (3 mg/day from a multivitamin is fine) and discuss with your prescriber.", "minimumTimeSeparation": null, "mechanism": "Boron appears to reduce SHBG and inhibit aromatase activity, raising free testosterone and lowering estradiol. It also influences vitamin D metabolism, which interacts with androgen pathways.", "evidenceLevel": "emerging", "sources": [ { "text": "Naghii MR, Mofid M, Asgari AR, Hedayati M, Daneshpour MS. Comparative effects of daily and weekly boron supplementation on plasma steroid hormones and proinflammatory cytokines. J Trace Elem Med Biol. 2011;25(1):54-8.", "pmid": "21129941", "doi": "10.1016/j.jtemb.2010.10.001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21129941/", "publicSourceType": "PMID" }, { "text": "Pizzorno L. Nothing Boring About Boron. Integr Med (Encinitas). 2015;14(4):35-48.", "pmid": "26770156", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26770156/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Boron raises free testosterone and lowers estradiol modestly.", "clinicalSignificance": "Effect is small but may shift labs in men on TRT.", "managementStrategy": "Keep boron to 3-10 mg/day; discuss with prescriber if used.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Testosterone", "supplementBName": "Maca Root", "interactionType": "caution", "severity": "info", "description": "Maca (Lepidium meyenii) has shown benefits for libido and sexual function in small trials but does not raise serum testosterone. It is generally safe to combine with prescribed testosterone, although it adds nothing to androgen replacement and may complicate side-effect attribution.", "recommendation": "Maca 1.5-3 g/day is generally well tolerated alongside testosterone therapy and is a reasonable choice if libido remains low despite adequate testosterone levels. Discuss with your prescriber so you can attribute any side effects correctly.", "minimumTimeSeparation": null, "mechanism": "Maca acts on libido through non-hormonal central pathways (likely glucosinolate-derived bioactives modulating dopaminergic and serotonergic tone). It does not raise serum testosterone, LH, or estradiol in human trials.", "evidenceLevel": "emerging", "sources": [ { "text": "Shin BC, Lee MS, Yang EJ, Lim HS, Ernst E. Maca (L. meyenii) for improving sexual function: a systematic review. BMC Complement Altern Med. 2010;10:44.", "pmid": "20691074", "doi": "10.1186/1472-6882-10-44", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20691074/", "publicSourceType": "PMID" }, { "text": "Leisegang K, Finelli R, Sikka SC, Panner Selvam MK. Eurycoma longifolia (Jack) Improves Serum Total Testosterone in Men: A Systematic Review and Meta-Analysis of Clinical Trials. Medicina (Kaunas). 2022;58(8):1047.", "pmid": "36013514", "doi": "10.3390/medicina58081047", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36013514/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Maca supports libido without raising testosterone.", "clinicalSignificance": "Safe adjunct for residual low libido on TRT.", "managementStrategy": "Maca 1.5-3 g/day is acceptable; discuss with prescriber.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Testosterone", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "info", "description": "Vitamin D deficiency is associated with lower testosterone in observational studies, but a high-quality RCT showed that 20,000 IU/week vitamin D3 for 12 weeks did not raise testosterone in healthy men with low vitamin D. Vitamin D is still worth correcting for general health and bone protection during testosterone therapy.", "recommendation": "Take vitamin D3 800-2000 IU/day while on testosterone therapy to support bone health, not as a testosterone booster. Aim for serum 25(OH)D above 30 ng/mL. Take with a fatty meal.", "minimumTimeSeparation": null, "mechanism": "Vitamin D receptors exist in Leydig cells, but RCT evidence does not support a direct testosterone-raising effect. Vitamin D's value during TRT lies in bone protection, calcium absorption, and immune function.", "evidenceLevel": "strong", "sources": [ { "text": "Lerchbaum E, Pilz S, Trummer C, et al. Vitamin D and Testosterone in Healthy Men: A Randomized Controlled Trial. J Clin Endocrinol Metab. 2017;102(11):4292-4302.", "pmid": "28938446", "doi": "10.1210/jc.2017-01428", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28938446/", "publicSourceType": "PMID" }, { "text": "Catalano A, Bellone F, Morabito N, et al. Vitamin D Boosts Alendronate Tail Effect on Bone Mineral Density in Postmenopausal Women with Osteoporosis. Nutrients. 2021;13(6):1878.", "pmid": "34072655", "doi": "10.3390/nu13061878", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34072655/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Vitamin D does not raise testosterone but supports bone health on TRT.", "clinicalSignificance": "Worth taking for bone protection, not as a testosterone enhancer.", "managementStrategy": "800-2000 IU vitamin D3 daily with a fatty meal.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Estradiol", "supplementBName": "Black Cohosh", "interactionType": "caution", "severity": "moderate", "description": "Black cohosh (Cimicifuga racemosa) is used for menopausal symptoms and has mild estrogenic and serotonergic activity. Combining it with prescribed estradiol is rarely necessary and complicates side-effect attribution, including for rare liver-injury cases reported with black cohosh.", "recommendation": "If you are already on prescribed estradiol for menopausal symptoms, adding black cohosh is generally not needed. If you decide to combine them, do so under clinician supervision and watch for jaundice, dark urine, or abdominal pain (signs of liver injury). Stop and seek care if these occur.", "minimumTimeSeparation": null, "mechanism": "Black cohosh has weak effects at estrogen and serotonin receptors and modulates dopamine; stacking with exogenous estradiol may amplify estrogenic effects on breast, endometrium, and clotting and adds an independent hepatotoxicity signal.", "evidenceLevel": "moderate", "sources": [ { "text": "Basciani S, Porcaro G. Counteracting side effects of combined oral contraceptives through the administration of specific micronutrients. Eur Rev Med Pharmacol Sci. 2022;26(13):4846-4862.", "pmid": "35856377", "doi": "10.26355/eurrev_202207_29410", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35856377/", "publicSourceType": "PMID" }, { "text": "Palmery M, Saraceno A, Vaiarelli A, Carlomagno G. Oral contraceptives and changes in nutritional requirements. Eur Rev Med Pharmacol Sci. 2013;17(13):1804-13.", "pmid": "23852908", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23852908/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Black cohosh adds weak estrogenic activity and hepatotoxicity risk on top of estradiol.", "clinicalSignificance": "Combination is rarely needed and complicates monitoring.", "managementStrategy": "Avoid routine combination; watch for liver-injury symptoms if used together.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Estradiol", "supplementBName": "Maca Root", "interactionType": "caution", "severity": "info", "description": "Maca has been used for menopausal symptoms and sexual function with modest positive findings in small trials, and does not contain phytoestrogens. It is generally compatible with prescribed estradiol but is rarely needed and may complicate side-effect attribution.", "recommendation": "If menopausal symptoms persist on prescribed estradiol, maca 1.5-3 g/day may be tried with prescriber awareness. Maca does not raise serum estradiol, so dose adjustments are usually not needed.", "minimumTimeSeparation": null, "mechanism": "Maca's clinical effects appear to be hormone-independent, acting via central monoaminergic and HPA-axis modulation rather than direct estrogen receptor binding. It does not measurably alter serum estradiol or FSH.", "evidenceLevel": "emerging", "sources": [ { "text": "Shin BC, Lee MS, Yang EJ, Lim HS, Ernst E. Maca (L. meyenii) for improving sexual function: a systematic review. BMC Complement Altern Med. 2010;10:44.", "pmid": "20691074", "doi": "10.1186/1472-6882-10-44", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20691074/", "publicSourceType": "PMID" }, { "text": "Basciani S, Porcaro G. Counteracting side effects of combined oral contraceptives through the administration of specific micronutrients. Eur Rev Med Pharmacol Sci. 2022;26(13):4846-4862.", "pmid": "35856377", "doi": "10.26355/eurrev_202207_29410", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35856377/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Maca may aid residual menopausal symptoms without altering estradiol.", "clinicalSignificance": "Hormone-neutral adjunct; minimal interaction risk.", "managementStrategy": "Maca 1.5-3 g/day is acceptable alongside estradiol.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Medroxyprogesterone", "supplementBName": "Calcium", "interactionType": "synergy", "severity": "moderate", "description": "Depot medroxyprogesterone acetate (DMPA) is associated with a measurable but largely reversible decrease in bone mineral density during use. Adequate calcium intake (1000-1300 mg/day) is recommended for women on DMPA to support bone health, alongside vitamin D and weight-bearing exercise.", "recommendation": "Aim for 1000-1300 mg/day total calcium from diet plus supplements while on DMPA. Split supplemental doses (500 mg or less per serving) for best absorption, and take with vitamin D.", "minimumTimeSeparation": null, "mechanism": "DMPA suppresses ovarian estradiol production, removing estrogen's restraint on bone resorption. Adequate calcium supplies the substrate for bone formation and helps counter accelerated bone turnover.", "evidenceLevel": "strong", "sources": [ { "text": "Guilbert ER, Brown JP, Kaunitz AM, et al. The use of depot-medroxyprogesterone acetate in contraception and its potential impact on skeletal health. Contraception. 2009;79(3):167-77.", "pmid": "19185668", "doi": "10.1016/j.contraception.2008.10.016", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19185668/", "publicSourceType": "PMID" }, { "text": "Catalano A, Bellone F, Morabito N, et al. Vitamin D Boosts Alendronate Tail Effect on Bone Mineral Density in Postmenopausal Women with Osteoporosis. Nutrients. 2021;13(6):1878.", "pmid": "34072655", "doi": "10.3390/nu13061878", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34072655/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Adequate calcium supports bone health during DMPA-induced estrogen suppression.", "clinicalSignificance": "Reduces the impact of DMPA-associated bone loss, especially in adolescents.", "managementStrategy": "Take 1000-1300 mg/day calcium, split doses, with vitamin D.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Medroxyprogesterone", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "moderate", "description": "Vitamin D adequacy is essential for the bone-protective effect of calcium during DMPA use. Without adequate vitamin D, dietary calcium cannot be efficiently absorbed and DMPA-related bone loss is more pronounced.", "recommendation": "Take vitamin D3 800-2000 IU/day while on DMPA, targeting serum 25(OH)D above 30 ng/mL. Take with a fatty meal at any time of day.", "minimumTimeSeparation": null, "mechanism": "Vitamin D upregulates intestinal calcium absorption via TRPV6 and calbindin and suppresses PTH-driven bone resorption. DMPA-induced estrogen suppression accelerates resorption, making adequate vitamin D more important.", "evidenceLevel": "strong", "sources": [ { "text": "Guilbert ER, Brown JP, Kaunitz AM, et al. The use of depot-medroxyprogesterone acetate in contraception and its potential impact on skeletal health. Contraception. 2009;79(3):167-77.", "pmid": "19185668", "doi": "10.1016/j.contraception.2008.10.016", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19185668/", "publicSourceType": "PMID" }, { "text": "Catalano A, Bellone F, Morabito N, et al. Vitamin D Boosts Alendronate Tail Effect on Bone Mineral Density in Postmenopausal Women with Osteoporosis. Nutrients. 2021;13(6):1878.", "pmid": "34072655", "doi": "10.3390/nu13061878", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34072655/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Vitamin D supports calcium absorption and reduces DMPA-related bone loss.", "clinicalSignificance": "Particularly important for adolescents and long-term DMPA users.", "managementStrategy": "Take 800-2000 IU vitamin D3 daily with a fatty meal.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Medroxyprogesterone", "supplementBName": "Vitamin K2", "interactionType": "synergy", "severity": "info", "description": "Vitamin K2 complements calcium and vitamin D for bone protection during DMPA use by activating osteocalcin and matrix Gla protein. Although direct DMPA-K2 trials are limited, the mechanism and extrapolation from postmenopausal osteoporosis data supports use.", "recommendation": "Vitamin K2 (MK-7 90-180 mcg/day) is a reasonable addition to calcium and vitamin D for women on long-term DMPA. Take with a fatty meal. Avoid if you also take warfarin.", "minimumTimeSeparation": null, "mechanism": "Vitamin K2 is the cofactor for gamma-glutamyl carboxylase, which activates osteocalcin (bone-mineralizing protein) and matrix Gla protein (vascular protector). It supports the calcium-vitamin D axis during DMPA-induced estrogen suppression.", "evidenceLevel": "emerging", "sources": [ { "text": "Iwamoto J. Vitamin K2 therapy for postmenopausal osteoporosis. Nutrients. 2014;6(5):1971-80.", "pmid": "24841104", "doi": "10.3390/nu6051971", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24841104/", "publicSourceType": "PMID" }, { "text": "Guilbert ER, Brown JP, Kaunitz AM, et al. The use of depot-medroxyprogesterone acetate in contraception and its potential impact on skeletal health. Contraception. 2009;79(3):167-77.", "pmid": "19185668", "doi": "10.1016/j.contraception.2008.10.016", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19185668/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Vitamin K2 supports bone matrix quality during DMPA use.", "clinicalSignificance": "Useful adjunct to calcium and vitamin D for long-term DMPA users.", "managementStrategy": "MK-7 90-180 mcg/day with a fatty meal; avoid if on warfarin.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Medroxyprogesterone", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "info", "description": "Magnesium plays a structural and signaling role in bone health and supports the calcium-vitamin D-PTH axis. Although direct DMPA trials are limited, magnesium adequacy is reasonable for women on long-term DMPA, especially given the BMD concern.", "recommendation": "Aim for daily magnesium needs from diet plus modest supplements during long-term DMPA use. Magnesium glycinate or citrate are well tolerated; take in the evening for sleep benefit.", "minimumTimeSeparation": null, "mechanism": "Magnesium is required for vitamin D activation (1-alpha-hydroxylase) and PTH secretion regulation. Low magnesium impairs both calcium homeostasis and bone matrix mineralization.", "evidenceLevel": "emerging", "sources": [ { "text": "Guilbert ER, Brown JP, Kaunitz AM, et al. The use of depot-medroxyprogesterone acetate in contraception and its potential impact on skeletal health. Contraception. 2009;79(3):167-77.", "pmid": "19185668", "doi": "10.1016/j.contraception.2008.10.016", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19185668/", "publicSourceType": "PMID" }, { "text": "Catalano A, Bellone F, Morabito N, et al. Vitamin D Boosts Alendronate Tail Effect on Bone Mineral Density in Postmenopausal Women with Osteoporosis. Nutrients. 2021;13(6):1878.", "pmid": "34072655", "doi": "10.3390/nu13061878", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34072655/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Magnesium supports vitamin D activation and bone mineralization during DMPA use.", "clinicalSignificance": "Helpful adjunct for skeletal health on long-term DMPA.", "managementStrategy": "Total magnesium intake within standard upper-limit guidance, glycinate or citrate, in the evening.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Medroxyprogesterone", "supplementBName": "Vitamin B6", "interactionType": "synergy", "severity": "info", "description": "DMPA can cause or worsen low mood in some users, and depleted B6 status (common in women on hormonal contraception) may contribute. Modest B6 supplementation supports neurotransmitter synthesis and may improve tolerability.", "recommendation": "Consider B6 25-50 mg/day (as pyridoxine or P5P) during DMPA use, especially if you experience low mood or irritability. Take with or without food at any time of day.", "minimumTimeSeparation": null, "mechanism": "B6 is a cofactor for synthesis of serotonin, dopamine, and GABA. Progestins can shift tryptophan metabolism and B6 utilization, and adequate B6 supports neurotransmitter balance.", "evidenceLevel": "moderate", "sources": [ { "text": "Var C, Keller S, Tung R, Freeland D, Bazzano AN. Supplementation with vitamin B6 reduces side effects in Cambodian women using oral contraception. Nutrients. 2014;6(9):3353-62.", "pmid": "25163030", "doi": "10.3390/nu6093353", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25163030/", "publicSourceType": "PMID" }, { "text": "Palmery M, Saraceno A, Vaiarelli A, Carlomagno G. Oral contraceptives and changes in nutritional requirements. Eur Rev Med Pharmacol Sci. 2013;17(13):1804-13.", "pmid": "23852908", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23852908/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "B6 supports mood during hormonal contraception including DMPA.", "clinicalSignificance": "May reduce low mood and irritability associated with progestin contraception.", "managementStrategy": "Take 25-50 mg B6 daily; reassess after 2-3 months.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Alendronate", "supplementBName": "Strontium", "interactionType": "timingSensitive", "severity": "moderate", "description": "Strontium is a divalent cation that can chelate bisphosphonates in the gut, blocking absorption. Strontium and bisphosphonates also compete for incorporation into bone and have overlapping mechanisms, so combined use is generally avoided or strictly sequenced.", "recommendation": "Do not take strontium and alendronate at the same time. If both are used (rare in current practice), separate doses by at least 2 hours, and discuss with your prescriber whether the combination is truly indicated.", "minimumTimeSeparation": 120, "mechanism": "Sr2+ binds the phosphonate groups of alendronate to form insoluble complexes in the gut. In bone, strontium substitutes for calcium in hydroxyapatite and overlaps with bisphosphonate's effects on bone turnover.", "evidenceLevel": "moderate", "sources": [ { "text": "Wiesner A, Szuta M, Galanty A, Paśko P. Optimal Dosing Regimen of Osteoporosis Drugs in Relation to Food Intake as the Key for the Enhancement of the Treatment Effectiveness-A Concise Literature Review. Foods. 2021;10(4):720.", "pmid": "33805435", "doi": "10.3390/foods10040720", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33805435/", "publicSourceType": "PMID" }, { "text": "Kim JS, Jang SW, Son M, Kim BM, Kang MJ. Enteric-coated tablet of risedronate sodium in combination with phytic acid, a natural chelating agent, for improved oral bioavailability. Eur J Pharm Sci. 2016;82:36-42.", "pmid": "26594027", "doi": "10.1016/j.ejps.2015.11.020", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26594027/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Strontium chelates alendronate and overlaps mechanistically in bone.", "clinicalSignificance": "Concurrent use can blunt alendronate absorption and is rarely justified clinically.", "managementStrategy": "Avoid combination; if used, separate doses by 2+ hours.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Amiodarone", "supplementBName": "Potassium", "interactionType": "synergy", "severity": "serious", "description": "Amiodarone can prolong the QT interval and rarely trigger torsades de pointes. Low potassium greatly increases that risk because it reduces the heart's repolarization reserve. Potassium supplementation is useful only when potassium is low or intake is inadequate; too much potassium can be dangerous, especially with kidney disease or RAAS-blocking drugs.", "recommendation": "Keep potassium in the normal range while taking amiodarone, and have levels checked if you use diuretics, have vomiting or diarrhea, or have kidney disease. Do not start potassium tablets or high-dose electrolyte powders unless your prescriber is monitoring your blood potassium.", "minimumTimeSeparation": null, "mechanism": "Amiodarone blocks cardiac potassium currents and prolongs repolarization. Hypokalemia further reduces IKr reserve and promotes early afterdepolarizations, while potassium repletion lowers susceptibility to drug-induced torsades.", "evidenceLevel": "moderate", "sources": [ { "text": "Tisdale JE. Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management. Can Pharm J (Ott). 2016;149(3):139-152.", "pmid": "27212965", "doi": "10.1177/1715163516641136", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27212965/", "publicSourceType": "PMID" }, { "text": "Yau S, Chan P, Sapkin J, Hsieh E. Short-term use of oral amiodarone causing torsades de pointes. Clin Case Rep. 2018;6(8):1554-1556.", "pmid": "30147903", "doi": "10.1002/ccr3.1659", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30147903/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Normal potassium reduces amiodarone-associated torsades risk; hypokalemia increases it.", "clinicalSignificance": "A low potassium level can turn a stable QT-prolonging antiarrhythmic regimen into a dangerous arrhythmia risk.", "managementStrategy": "Monitor serum potassium and replete only with prescriber guidance.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Amiodarone", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "serious", "description": "Amiodarone can prolong cardiac repolarization, and low magnesium makes torsades de pointes more likely. Maintaining normal magnesium status helps stabilize repolarization and supports potassium balance. Oral magnesium is preventive support when intake is low; acute torsades requires emergency care and intravenous magnesium.", "recommendation": "Maintain adequate magnesium intake while taking amiodarone, especially if you also take diuretics, PPIs, or have diarrhea. Ask your prescriber about checking magnesium periodically, and do not use high-dose magnesium if you have significant kidney disease unless monitored.", "minimumTimeSeparation": null, "mechanism": "Magnesium suppresses early afterdepolarizations and helps maintain intracellular potassium. Hypomagnesemia lowers repolarization reserve, increasing susceptibility to QT-drug-induced torsades.", "evidenceLevel": "moderate", "sources": [ { "text": "Tisdale JE. Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management. Can Pharm J (Ott). 2016;149(3):139-152.", "pmid": "27212965", "doi": "10.1177/1715163516641136", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27212965/", "publicSourceType": "PMID" }, { "text": "Yau S, Chan P, Sapkin J, Hsieh E. Short-term use of oral amiodarone causing torsades de pointes. Clin Case Rep. 2018;6(8):1554-1556.", "pmid": "30147903", "doi": "10.1002/ccr3.1659", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30147903/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Normal magnesium reduces amiodarone-associated torsades susceptibility; hypomagnesemia increases it.", "clinicalSignificance": "Low magnesium is a modifiable risk factor for dangerous QT-related arrhythmias during amiodarone therapy.", "managementStrategy": "Maintain magnesium status and monitor levels when risk factors for depletion are present.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Amiodarone", "supplementBName": "Iodine", "interactionType": "caution", "severity": "serious", "description": "Amiodarone contains a large iodine load and is strongly associated with thyroid dysfunction. Extra iodine from supplements can further increase iodine exposure and may precipitate hypothyroidism or thyrotoxicosis, especially in people with nodular thyroid disease or autoimmune thyroid disease. Thyroid shifts can destabilize heart rhythm and worsen heart failure symptoms.", "recommendation": "Avoid iodine supplements while taking amiodarone unless your prescriber specifically treats a documented deficiency. Follow the thyroid lab schedule your clinician recommends, and report new palpitations, heat or cold intolerance, weight change, tremor, or unusual fatigue.", "minimumTimeSeparation": null, "mechanism": "Excess iodine can trigger Wolff-Chaikoff hypothyroidism or Jod-Basedow thyrotoxicosis in susceptible thyroid tissue. Amiodarone adds iodine exposure and also inhibits thyroid hormone deiodination and can cause direct thyroid cytotoxicity.", "evidenceLevel": "moderate", "sources": [ { "text": "Jabrocka-Hybel A, Bednarczuk T, Bartalena L, et al. Amiodarone and the thyroid. Endokrynol Pol. 2015;66(2):176-186.", "pmid": "25931048", "doi": "10.5603/EP.2015.0025", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25931048/", "publicSourceType": "PMID" }, { "text": "Leung AM, Braverman LE. Iodine-induced thyroid dysfunction. Curr Opin Endocrinol Diabetes Obes. 2012;19(5):414-419.", "pmid": "22820214", "doi": "10.1097/MED.0b013e3283565bb2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22820214/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Iodine supplementation adds to amiodarone's iodine-related thyroid risk.", "clinicalSignificance": "Thyroid dysfunction during amiodarone therapy can worsen arrhythmia control and cardiac status.", "managementStrategy": "Avoid non-prescribed iodine and monitor thyroid function during amiodarone therapy.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Dofetilide", "supplementBName": "Potassium", "interactionType": "synergy", "severity": "serious", "description": "Dofetilide prolongs the QT interval and can cause torsades de pointes, particularly when potassium is low. Maintaining normal serum potassium is a core safety measure during dofetilide initiation and ongoing therapy. Potassium supplements should be treated like a monitored medication because both low and high potassium can be dangerous.", "recommendation": "Keep potassium in the normal range and follow your prescriber's lab-monitoring plan, especially during dofetilide initiation, dose changes, illness with vomiting or diarrhea, or diuretic use. Do not start potassium supplements unless your clinician is monitoring your blood level and kidney function.", "minimumTimeSeparation": null, "mechanism": "Dofetilide is a selective IKr blocker. Hypokalemia further suppresses repolarizing potassium current and increases early afterdepolarizations, making torsades more likely.", "evidenceLevel": "strong", "sources": [ { "text": "Jaiswal A, Goldbarg S. Dofetilide induced torsade de pointes: mechanism, risk factors and management strategies. Indian Heart J. 2014;66(6):640-648.", "pmid": "25634399", "doi": "10.1016/j.ihj.2013.12.021", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25634399/", "publicSourceType": "PMID" }, { "text": "Tisdale JE. Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management. Can Pharm J (Ott). 2016;149(3):139-152.", "pmid": "27212965", "doi": "10.1177/1715163516641136", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27212965/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Normal potassium reduces dofetilide-associated torsades risk; hypokalemia increases it.", "clinicalSignificance": "Potassium abnormalities are one of the main modifiable risks for life-threatening dofetilide proarrhythmia.", "managementStrategy": "Monitor serum potassium and replete only under prescriber guidance.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Dofetilide", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "serious", "description": "Dofetilide can cause torsades de pointes, and low magnesium is a recognized risk factor. Maintaining normal magnesium helps reduce susceptibility to early afterdepolarizations and supports potassium repletion. Oral magnesium can help prevent or correct low magnesium, but acute torsades requires emergency management.", "recommendation": "Maintain adequate magnesium intake and ask about magnesium checks if you take diuretics, PPIs, or have gastrointestinal losses. Do not use high-dose magnesium without monitoring if you have kidney disease, and seek urgent care for fainting, near-fainting, or new sustained palpitations.", "minimumTimeSeparation": null, "mechanism": "Dofetilide blocks IKr and prolongs repolarization. Hypomagnesemia promotes electrical instability and early afterdepolarizations; magnesium repletion is part of standard torsades prevention and treatment.", "evidenceLevel": "strong", "sources": [ { "text": "Jaiswal A, Goldbarg S. Dofetilide induced torsade de pointes: mechanism, risk factors and management strategies. Indian Heart J. 2014;66(6):640-648.", "pmid": "25634399", "doi": "10.1016/j.ihj.2013.12.021", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25634399/", "publicSourceType": "PMID" }, { "text": "Tisdale JE. Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management. Can Pharm J (Ott). 2016;149(3):139-152.", "pmid": "27212965", "doi": "10.1177/1715163516641136", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27212965/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Normal magnesium reduces dofetilide-associated torsades susceptibility; hypomagnesemia increases it.", "clinicalSignificance": "Magnesium deficiency can make dofetilide's QT effect clinically dangerous.", "managementStrategy": "Maintain magnesium status and monitor levels when depletion risk is present.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Ranolazine", "supplementBName": "Potassium", "interactionType": "synergy", "severity": "serious", "description": "Ranolazine usually causes modest QT prolongation, but torsades de pointes has been reported when risk factors stack. Low potassium is a major modifiable risk factor for drug-induced torsades. Potassium supplementation is only appropriate when potassium is low or intake is inadequate and should be monitored.", "recommendation": "Keep potassium in the normal range while using ranolazine, especially if you take diuretics or have vomiting or diarrhea. Do not start potassium supplements without clinician monitoring, and report fainting, near-fainting, or new sustained palpitations promptly.", "minimumTimeSeparation": null, "mechanism": "Ranolazine inhibits late sodium current and can inhibit IKr, causing QT prolongation. Hypokalemia lowers repolarization reserve and increases the chance that QT prolongation progresses to torsades.", "evidenceLevel": "moderate", "sources": [ { "text": "Liu Z, Williams RB, Rosen BD. The potential contribution of ranolazine to Torsade de Pointe. J Cardiovasc Dis Res. 2013;4(3):187-190.", "pmid": "24396259", "doi": "10.1016/j.jcdr.2013.08.005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24396259/", "publicSourceType": "PMID" }, { "text": "Schram G, Zhang L, Derakhchan K, Ehrlich JR, Belardinelli L, Nattel S. Ranolazine: ion-channel-blocking actions and in vivo electrophysiological effects. Br J Pharmacol. 2004;142(8):1300-1308.", "pmid": "15277312", "doi": "10.1038/sj.bjp.0705879", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15277312/", "publicSourceType": "PMID" }, { "text": "Tisdale JE. Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management. Can Pharm J (Ott). 2016;149(3):139-152.", "pmid": "27212965", "doi": "10.1177/1715163516641136", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27212965/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Normal potassium reduces ranolazine-related QT risk; hypokalemia increases it.", "clinicalSignificance": "Ranolazine's torsades risk is usually low, but potassium depletion can make QT prolongation more clinically important.", "managementStrategy": "Monitor potassium when depletion risk is present and replete only under prescriber guidance.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Ranolazine", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "serious", "description": "Ranolazine can prolong the QT interval, and torsades risk rises when magnesium is low. Maintaining normal magnesium helps stabilize repolarization and supports potassium balance. Oral magnesium is preventive support for deficiency risk, not a substitute for emergency treatment of an arrhythmia.", "recommendation": "Maintain adequate magnesium intake while taking ranolazine, especially if you use diuretics, PPIs, or have chronic diarrhea. Ask your prescriber about checking magnesium if you have arrhythmia symptoms or risk factors, and avoid high-dose magnesium if kidney function is reduced unless monitored.", "minimumTimeSeparation": null, "mechanism": "Ranolazine has IKr-blocking activity that can prolong repolarization. Hypomagnesemia promotes early afterdepolarizations and makes drug-induced QT prolongation more likely to become torsades.", "evidenceLevel": "moderate", "sources": [ { "text": "Liu Z, Williams RB, Rosen BD. The potential contribution of ranolazine to Torsade de Pointe. J Cardiovasc Dis Res. 2013;4(3):187-190.", "pmid": "24396259", "doi": "10.1016/j.jcdr.2013.08.005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24396259/", "publicSourceType": "PMID" }, { "text": "Schram G, Zhang L, Derakhchan K, Ehrlich JR, Belardinelli L, Nattel S. Ranolazine: ion-channel-blocking actions and in vivo electrophysiological effects. Br J Pharmacol. 2004;142(8):1300-1308.", "pmid": "15277312", "doi": "10.1038/sj.bjp.0705879", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15277312/", "publicSourceType": "PMID" }, { "text": "Tisdale JE. Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management. Can Pharm J (Ott). 2016;149(3):139-152.", "pmid": "27212965", "doi": "10.1177/1715163516641136", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27212965/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Normal magnesium reduces ranolazine-associated torsades susceptibility; hypomagnesemia increases it.", "clinicalSignificance": "Magnesium depletion can convert modest ranolazine QT prolongation into a higher-risk setting.", "managementStrategy": "Maintain magnesium status and monitor levels when depletion risk is present.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Nitroglycerin", "supplementBName": "L-Arginine", "interactionType": "caution", "severity": "moderate", "description": "Nitroglycerin and L-arginine both increase nitric-oxide-mediated vasodilation. Using them together can add to blood pressure lowering, headaches, flushing, dizziness, or fainting, especially in older adults, dehydration, nitrate-naive patients, or people already taking antihypertensives. The risk is pharmacodynamic, so simply spacing doses may not fully prevent it.", "recommendation": "Do not start high-dose L-arginine while using nitroglycerin without prescriber input. If your clinician allows the combination, start with a low L-arginine dose, monitor blood pressure, sit or lie down after nitroglycerin, and stop L-arginine if you develop lightheadedness or unusually low readings.", "minimumTimeSeparation": null, "mechanism": "Nitroglycerin is bioactivated to nitric oxide, increasing cGMP and relaxing vascular smooth muscle. L-arginine supplies substrate for nitric oxide synthase, which can increase endogenous nitric oxide production and lower vascular tone.", "evidenceLevel": "moderate", "sources": [ { "text": "Tahvanainen A, Leskinen M, Koskela J, et al. Non-invasive measurement of the haemodynamic effects of inhaled salbutamol, intravenous L-arginine and sublingual nitroglycerin. Br J Clin Pharmacol. 2009;68(1):23-33.", "pmid": "19660000", "doi": "10.1111/j.1365-2125.2009.03434.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19660000/", "publicSourceType": "PMID" }, { "text": "Shiraseb F, Asbaghi O, Bagheri R, Wong A, Figueroa A, Mirzaei K. Effect of l-Arginine Supplementation on Blood Pressure in Adults: A Systematic Review and Dose-Response Meta-analysis of Randomized Clinical Trials. Adv Nutr. 2022;13(4):1226-1242.", "pmid": "34967840", "doi": "10.1093/advances/nmab155", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34967840/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "L-arginine can add to nitroglycerin-related blood pressure lowering.", "clinicalSignificance": "Additive vasodilation can cause falls, syncope, or poor tolerance of needed nitrate therapy.", "managementStrategy": "Avoid unsupervised high-dose L-arginine; monitor blood pressure and symptoms if combined.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Nitroglycerin", "supplementBName": "L-Citrulline", "interactionType": "caution", "severity": "moderate", "description": "L-citrulline raises circulating L-arginine and can support nitric-oxide-mediated blood pressure lowering. Nitroglycerin also works through nitric oxide signaling and can cause rapid drops in blood pressure. Combining them may increase headache, flushing, dizziness, or fainting risk, particularly in people with low baseline blood pressure or multiple antihypertensives.", "recommendation": "Avoid starting high-dose L-citrulline on your own if you use nitroglycerin. If your prescriber approves it, start low, monitor blood pressure, and stop the supplement if nitroglycerin causes more dizziness, faintness, or unusually low readings.", "minimumTimeSeparation": null, "mechanism": "L-citrulline is converted to L-arginine, increasing substrate availability for nitric oxide synthase. Nitroglycerin donates nitric oxide and activates soluble guanylate cyclase, so the combined effect can increase cGMP-mediated vasodilation.", "evidenceLevel": "moderate", "sources": [ { "text": "Tahvanainen A, Leskinen M, Koskela J, et al. Non-invasive measurement of the haemodynamic effects of inhaled salbutamol, intravenous L-arginine and sublingual nitroglycerin. Br J Clin Pharmacol. 2009;68(1):23-33.", "pmid": "19660000", "doi": "10.1111/j.1365-2125.2009.03434.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19660000/", "publicSourceType": "PMID" }, { "text": "Schwedhelm E, Maas R, Freese R, et al. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol. 2008;65(1):51-59.", "pmid": "17662090", "doi": "10.1111/j.1365-2125.2007.02990.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17662090/", "publicSourceType": "PMID" }, { "text": "Mirenayat MS, Moradi S, Mohammadi H, Rouhani MH. Effect of L-Citrulline Supplementation on Blood Pressure: a Systematic Review and Meta-Analysis of Clinical Trials. Curr Hypertens Rep. 2018;20(11):98.", "pmid": "30284051", "doi": "10.1007/s11906-018-0898-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30284051/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "L-citrulline may add to nitroglycerin-related vasodilation and hypotension.", "clinicalSignificance": "Additive nitric oxide effects can increase dizziness or fainting risk during nitrate use.", "managementStrategy": "Avoid unsupervised high-dose L-citrulline and monitor blood pressure if combined.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Isosorbide Mononitrate", "supplementBName": "L-Arginine", "interactionType": "caution", "severity": "moderate", "description": "Isosorbide mononitrate and L-arginine both increase nitric-oxide-mediated vasodilation. In a human crossover study, L-arginine enhanced the blood pressure and pulse-wave effects of isosorbide mononitrate in some older hypertensive patients. This can be useful in supervised care but can also cause excessive dizziness, headache, or fainting when added without monitoring.", "recommendation": "Do not add high-dose L-arginine to isosorbide mononitrate unless your prescriber is aware. If combined, check sitting and standing blood pressure during the first week, rise slowly, and stop the supplement if you develop faintness or unusually low readings.", "minimumTimeSeparation": null, "mechanism": "Isosorbide mononitrate is an organic nitrate that increases nitric oxide and cGMP signaling in vascular smooth muscle. L-arginine supplies substrate for nitric oxide synthase, potentially amplifying vasodilatory tone.", "evidenceLevel": "moderate", "sources": [ { "text": "Stokes GS, Barin ES, Gilfillan KL, Kaesemeyer WH. Interactions of L-arginine, isosorbide mononitrate, and angiotensin II inhibitors on arterial pulse wave. Am J Hypertens. 2003;16(9 Pt 1):719-724.", "pmid": "12944028", "doi": "10.1016/s0895-7061(03)00979-8", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12944028/", "publicSourceType": "PMID" }, { "text": "Shiraseb F, Asbaghi O, Bagheri R, Wong A, Figueroa A, Mirzaei K. Effect of l-Arginine Supplementation on Blood Pressure in Adults: A Systematic Review and Dose-Response Meta-analysis of Randomized Clinical Trials. Adv Nutr. 2022;13(4):1226-1242.", "pmid": "34967840", "doi": "10.1093/advances/nmab155", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34967840/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "L-arginine can amplify isosorbide-mononitrate vasodilation and blood pressure lowering.", "clinicalSignificance": "Unmonitored additive vasodilation can cause symptomatic hypotension or falls.", "managementStrategy": "Use only with clinician awareness and monitor sitting and standing blood pressure.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Isosorbide Mononitrate", "supplementBName": "L-Citrulline", "interactionType": "caution", "severity": "moderate", "description": "L-citrulline increases L-arginine availability and can lower blood pressure through nitric oxide pathways. Isosorbide mononitrate is an organic nitrate with sustained vasodilator effects. Combining them may add to blood pressure lowering, increasing dizziness, headache, flushing, or fainting risk.", "recommendation": "Avoid starting high-dose L-citrulline without telling the prescriber who manages your nitrate therapy. If the combination is approved, monitor sitting and standing blood pressure during the first week and stop the supplement if lightheadedness or low readings develop.", "minimumTimeSeparation": null, "mechanism": "L-citrulline is converted to L-arginine and increases substrate availability for nitric oxide synthase. Isosorbide mononitrate donates nitric oxide downstream, so the shared nitric oxide/cGMP pathway can produce additive vasodilation.", "evidenceLevel": "moderate", "sources": [ { "text": "Stokes GS, Barin ES, Gilfillan KL, Kaesemeyer WH. Interactions of L-arginine, isosorbide mononitrate, and angiotensin II inhibitors on arterial pulse wave. Am J Hypertens. 2003;16(9 Pt 1):719-724.", "pmid": "12944028", "doi": "10.1016/s0895-7061(03)00979-8", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12944028/", "publicSourceType": "PMID" }, { "text": "Schwedhelm E, Maas R, Freese R, et al. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol. 2008;65(1):51-59.", "pmid": "17662090", "doi": "10.1111/j.1365-2125.2007.02990.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17662090/", "publicSourceType": "PMID" }, { "text": "Mirenayat MS, Moradi S, Mohammadi H, Rouhani MH. Effect of L-Citrulline Supplementation on Blood Pressure: a Systematic Review and Meta-Analysis of Clinical Trials. Curr Hypertens Rep. 2018;20(11):98.", "pmid": "30284051", "doi": "10.1007/s11906-018-0898-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30284051/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "L-citrulline may add to isosorbide-mononitrate blood pressure lowering.", "clinicalSignificance": "Additive nitrate and nitric oxide support can increase symptomatic hypotension risk.", "managementStrategy": "Use only with clinician awareness and monitor blood pressure and dizziness.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Hydralazine", "supplementBName": "Vitamin B6", "interactionType": "synergy", "severity": "moderate", "description": "Long-term hydralazine can interfere with vitamin B6 biology and has caused pyridoxine-deficiency neuropathy in case reports. Vitamin B6 can help prevent or correct deficiency-related nerve symptoms when hydralazine is the cause. Very high-dose B6 can also cause neuropathy, so replacement should stay in a conservative range unless supervised.", "recommendation": "If you take hydralazine long term, ask your prescriber whether low-dose vitamin B6 is appropriate, especially if you develop numbness, tingling, burning, or poor dietary intake. Avoid chronic high-dose B6 unless directed and monitored.", "minimumTimeSeparation": null, "mechanism": "Hydralazine can react with pyridoxal and pyridoxal-5-phosphate, reducing availability of the active B6 cofactor for neurologic metabolism. Vitamin B6 replacement restores cofactor availability when deficiency contributes to symptoms.", "evidenceLevel": "moderate", "sources": [ { "text": "Raskin NH, Fishman RA. Pyridoxine-deficiency neuropathy due to hydralazine. N Engl J Med. 1965;273(22):1182-1185.", "pmid": "5847557", "doi": "10.1056/NEJM196511252732203", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/5847557/", "publicSourceType": "PMID" }, { "text": "Vidrio H. Interaction with pyridoxal as a possible mechanism of hydralazine hypotension. J Cardiovasc Pharmacol. 1990;15(1):150-156.", "pmid": "1688973", "doi": "10.1097/00005344-199001000-00024", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1688973/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Hydralazine can increase the need for vitamin B6 support in susceptible long-term users.", "clinicalSignificance": "Recognizing B6-related neuropathy can prevent persistent nerve symptoms while preserving needed blood pressure therapy.", "managementStrategy": "Consider conservative B6 replacement for long-term hydralazine users with clinician guidance.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Digoxin", "supplementBName": "Activated Charcoal", "interactionType": "timingSensitive", "severity": "serious", "description": "Activated charcoal binds digoxin in the gastrointestinal tract and can sharply reduce absorption when taken near a dose. Because digoxin has a narrow therapeutic window, reduced absorption can worsen atrial fibrillation rate control or heart failure symptoms. Charcoal is used medically for selected poisonings and is not a routine detox supplement for people taking digoxin.", "recommendation": "Avoid activated charcoal supplements while taking digoxin unless a clinician specifically directs it. If a one-time charcoal dose is unavoidable outside an emergency setting, separate it from digoxin by at least 6 hours and tell your prescriber if palpitations, swelling, or shortness of breath worsen.", "minimumTimeSeparation": 360, "mechanism": "Activated charcoal nonselectively adsorbs digoxin in the gut, reducing drug available for absorption and potentially interrupting intestinal recirculation. This lowers systemic digoxin exposure when timing overlaps.", "evidenceLevel": "strong", "sources": [ { "text": "Neuvonen PJ, Kivisto K, Hirvisalo EL. Effects of resins and activated charcoal on the absorption of digoxin, carbamazepine and frusemide. Br J Clin Pharmacol. 1988;25(2):229-233.", "pmid": "3358884", "doi": "10.1111/j.1365-2125.1988.tb03295.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3358884/", "publicSourceType": "PMID" }, { "text": "Neuvonen PJ, Elfving SM, Elonen E. Reduction of absorption of digoxin, phenytoin and aspirin by activated charcoal in man. Eur J Clin Pharmacol. 1978;13(3):213-218.", "pmid": "668776", "doi": "10.1007/BF00609985", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/668776/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Activated charcoal can reduce digoxin absorption and lower digoxin exposure.", "clinicalSignificance": "Loss of digoxin effect can destabilize heart rate or heart failure control.", "managementStrategy": "Avoid routine charcoal; if unavoidable, separate by at least 6 hours and monitor clinical response.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Digoxin", "supplementBName": "Psyllium Husk", "interactionType": "timingSensitive", "severity": "serious", "description": "Psyllium husk is a bulk-forming fiber similar to ispaghula, which has reduced digoxin bioavailability in human studies. Taking psyllium close to digoxin can lower digoxin exposure and may reduce heart rate or heart failure control. The risk is highest when fiber timing changes suddenly in older adults or people maintained near the low end of the therapeutic range.", "recommendation": "Take psyllium husk at least 4 hours away from digoxin and keep your fiber routine consistent from day to day. Tell your prescriber if you start or stop daily psyllium, because symptoms or digoxin levels may need monitoring.", "minimumTimeSeparation": 240, "mechanism": "Gel-forming fiber can trap or adsorb digoxin in the intestinal lumen and change transit, reducing the amount available for absorption. Consistent separation lowers the chance of a clinically meaningful drop in exposure.", "evidenceLevel": "moderate", "sources": [ { "text": "Nordstrom M, Melander A, Robertsson E, Steen B. Influence of wheat bran and of a bulk-forming ispaghula cathartic on the bioavailability of digoxin in geriatric in-patients. Drug Nutr Interact. 1987;5(2):67-69.", "pmid": "3038494", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3038494/", "publicSourceType": "PMID" }, { "text": "Reissell P, Manninen V. Effect of administration of activated charcoal and fibre on absorption, excretion and steady state blood levels of digoxin and digitoxin. Evidence for intestinal secretion of the glycosides. Acta Med Scand Suppl. 1982;668:88-90.", "pmid": "6963097", "doi": "10.1111/j.0954-6820.1982.tb08527.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6963097/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Psyllium husk can reduce digoxin absorption if taken too close together.", "clinicalSignificance": "A lower digoxin level can worsen rate control or heart failure symptoms in sensitive patients.", "managementStrategy": "Separate psyllium and digoxin by at least 4 hours and keep fiber use consistent.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Amlodipine", "supplementBName": "Berberine", "interactionType": "caution", "severity": "moderate", "description": "Berberine is a clinically demonstrated inhibitor of CYP3A4, the main enzyme that clears amlodipine. Co-administration can raise amlodipine plasma levels and prolong its half-life, increasing the risk of excessive blood pressure lowering, peripheral edema, dizziness, and reflex tachycardia. The effect builds over days because berberine accumulates with repeated dosing.", "recommendation": "Avoid pairing berberine with amlodipine unless your prescriber agrees, and if you do, separate doses by at least 4 hours and monitor your blood pressure for 1-2 weeks. Reduce or stop berberine if your readings fall below your usual range, or you develop new lightheadedness or swelling.", "minimumTimeSeparation": 240, "mechanism": "Repeated berberine dosing in humans reduces CYP3A4 (and CYP2D6, CYP2C9) activity, slowing oxidative metabolism of amlodipine. Rat data also show inhibition of intestinal P-gp, which can further raise oral bioavailability.", "evidenceLevel": "moderate", "sources": [ { "text": "Guo Y, Chen Y, Tan ZR, Klaassen CD, Zhou HH. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol. 2012;68(2):213-7.", "pmid": "21870106", "doi": "10.1007/s00228-011-1108-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21870106/", "publicSourceType": "PMID" }, { "text": "Pan GY, Wang GJ, Liu XD, Fawcett JP, Xie YY. The involvement of P-glycoprotein in berberine absorption. Pharmacol Toxicol. 2002;91(4):193-7.", "pmid": "12530470", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12530470/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Berberine inhibits CYP3A4, raising amlodipine exposure and the risk of hypotension or edema.", "clinicalSignificance": "A patient stable on amlodipine may become symptomatically hypotensive within 1-2 weeks of starting berberine.", "managementStrategy": "Separate doses by 4+ hours, monitor BP closely, and reduce berberine if readings drop or side effects emerge.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Diltiazem", "supplementBName": "Berberine", "interactionType": "caution", "severity": "moderate", "description": "Diltiazem is itself a moderate CYP3A4 inhibitor that depends on the same enzyme for clearance. Adding berberine, which inhibits CYP3A4, CYP2D6, and CYP2C9 in humans, can raise diltiazem levels and amplify its negative chronotropic and vasodilatory effects. The result can be excessive bradycardia, hypotension, or AV block, particularly in older adults or those on other rate-slowing drugs.", "recommendation": "Avoid combining berberine with diltiazem unless your prescriber agrees. If used together, check your pulse and blood pressure twice daily for 2 weeks after starting berberine and report a resting heart rate below 50 bpm, lightheadedness, or readings below your usual range.", "minimumTimeSeparation": 240, "mechanism": "Diltiazem is metabolized primarily by CYP3A4 to desacetyldiltiazem. Berberine's inhibition of CYP3A4 reduces both presystemic and hepatic clearance, increasing parent drug exposure and AV-nodal blockade.", "evidenceLevel": "moderate", "sources": [ { "text": "Guo Y, Chen Y, Tan ZR, Klaassen CD, Zhou HH. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol. 2012;68(2):213-7.", "pmid": "21870106", "doi": "10.1007/s00228-011-1108-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21870106/", "publicSourceType": "PMID" }, { "text": "Mills TA, Kawji MM, Cataldo VD, et al. Profound sinus bradycardia due to diltiazem, verapamil, and/or beta-adrenergic blocking drugs. J La State Med Soc. 2004;156(6):327-31.", "pmid": "15688675", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15688675/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Berberine raises diltiazem exposure via CYP3A4 inhibition, increasing the chance of bradycardia and hypotension.", "clinicalSignificance": "Older patients or those on other rate-slowing drugs may develop symptomatic AV block.", "managementStrategy": "Avoid the combination; if necessary, monitor HR/BP closely and separate doses by 4+ hours.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Berberine", "supplementBName": "Verapamil", "interactionType": "caution", "severity": "serious", "description": "Verapamil is both a CYP3A4 substrate and a potent P-glycoprotein inhibitor, and berberine inhibits both CYP3A4 and P-gp. Combining the two raises verapamil exposure and slows its clearance, which can trigger bradycardia, AV block, hypotension, or constipation. Because berberine itself is a P-gp substrate, verapamil also raises berberine systemic levels.", "recommendation": "Avoid combining berberine with verapamil. If your clinician approves co-use, monitor pulse and blood pressure daily for the first 2 weeks, and report HR below 50 bpm, dizziness, or new constipation. Separate doses by at least 4 hours to limit intestinal interaction.", "minimumTimeSeparation": 240, "mechanism": "Berberine inhibits CYP3A4 (the main verapamil-metabolizing enzyme) and intestinal P-gp. Bidirectionally, verapamil inhibits P-gp-mediated efflux of berberine, raising its plasma levels.", "evidenceLevel": "moderate", "sources": [ { "text": "Guo Y, Chen Y, Tan ZR, Klaassen CD, Zhou HH. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol. 2012;68(2):213-7.", "pmid": "21870106", "doi": "10.1007/s00228-011-1108-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21870106/", "publicSourceType": "PMID" }, { "text": "Pan GY, Wang GJ, Liu XD, Fawcett JP, Xie YY. The involvement of P-glycoprotein in berberine absorption. Pharmacol Toxicol. 2002;91(4):193-7.", "pmid": "12530470", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12530470/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Mutual CYP3A4/P-gp inhibition raises both drug levels and increases cardiac and GI side effects.", "clinicalSignificance": "Bradycardia, AV block, and hypotension are realistic in elderly or polypharmacy patients.", "managementStrategy": "Avoid the combination; if unavoidable, monitor HR/BP daily and space doses.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Berberine", "supplementBName": "Nifedipine", "interactionType": "caution", "severity": "moderate", "description": "Nifedipine relies on CYP3A4 for clearance, and berberine clinically inhibits CYP3A4 after repeated dosing in humans. Co-administration can raise nifedipine exposure, intensify peripheral vasodilation, and produce hypotension, headache, flushing, or reflex tachycardia. Patients on extended-release formulations or who are volume-depleted are most at risk.", "recommendation": "Avoid pairing berberine with nifedipine unless your prescriber agrees. If used together, separate doses by at least 4 hours, check blood pressure and pulse for the first 2 weeks, and stop berberine if you experience flushing, headache, or readings below your usual range.", "minimumTimeSeparation": 240, "mechanism": "Nifedipine is metabolized predominantly by CYP3A4. Berberine reduces CYP3A4 activity in humans with repeated dosing, slowing nifedipine clearance and raising plasma levels.", "evidenceLevel": "moderate", "sources": [ { "text": "Guo Y, Chen Y, Tan ZR, Klaassen CD, Zhou HH. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol. 2012;68(2):213-7.", "pmid": "21870106", "doi": "10.1007/s00228-011-1108-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21870106/", "publicSourceType": "PMID" }, { "text": "Bailey DG, Malcolm J, Arnold O, Spence JD. Grapefruit juice-drug interactions. Br J Clin Pharmacol. 1998;46(2):101-10.", "pmid": "9723817", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9723817/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Berberine raises nifedipine exposure via CYP3A4 inhibition, amplifying hypotension and vasodilatory effects.", "clinicalSignificance": "Stable nifedipine patients may develop symptomatic hypotension, headache, or flushing.", "managementStrategy": "Avoid or space doses 4+ hours apart and monitor BP closely after initiation.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Amlodipine", "supplementBName": "Turmeric/Curcumin", "interactionType": "caution", "severity": "moderate", "description": "Curcumin inhibits CYP3A4 and intestinal P-glycoprotein, both of which contribute to amlodipine clearance and absorption. In a rat pharmacokinetic study, curcumin pretreatment more than doubled amlodipine AUC and Cmax, suggesting that high-dose curcumin or curcumin phytosome formulations could push amlodipine levels into a range that causes hypotension, edema, or reflex tachycardia in humans.", "recommendation": "If you take amlodipine, keep turmeric to culinary amounts and avoid high-dose curcumin supplements unless your prescriber agrees. If you do use a curcumin product, separate it from amlodipine by at least 4 hours, check blood pressure for 1-2 weeks, and stop if you develop new dizziness or swelling.", "minimumTimeSeparation": 240, "mechanism": "Curcumin inhibits CYP3A4 (IC50 ~2.7 µM) and downregulates intestinal P-gp. Amlodipine is a CYP3A4 substrate, so reduced enzyme activity raises systemic exposure and prolongs half-life.", "evidenceLevel": "emerging", "sources": [ { "text": "Jiang N, Zhang M, Meng X, Sun B. Effects of curcumin on the pharmacokinetics of amlodipine in rats and its potential mechanism. Pharm Biol. 2020;58(1):465-470.", "pmid": "32432949", "doi": "10.1080/13880209.2020.1764060", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32432949/", "publicSourceType": "PMID" }, { "text": "Bailey DG, Malcolm J, Arnold O, Spence JD. Grapefruit juice-drug interactions. Br J Clin Pharmacol. 1998;46(2):101-10.", "pmid": "9723817", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9723817/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Curcumin inhibits CYP3A4, raising amlodipine exposure and the risk of hypotension or edema.", "clinicalSignificance": "High-dose curcumin supplements may push amlodipine into a supratherapeutic range.", "managementStrategy": "Keep turmeric to culinary doses; if supplementing, separate by 4+ hours and monitor BP.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Curcumin Phytosome", "supplementBName": "Amlodipine", "interactionType": "caution", "severity": "moderate", "description": "Curcumin phytosome formulations achieve 20-30 times higher plasma curcumin levels than standard curcumin, which magnifies any CYP3A4-mediated drug interaction. Because amlodipine is cleared almost entirely by CYP3A4, even modest enzyme inhibition can produce clinically meaningful increases in drug exposure, with hypotension, peripheral edema, or reflex tachycardia.", "recommendation": "Avoid pairing curcumin phytosome products with amlodipine. If your clinician approves their use, separate doses by at least 4 hours, monitor blood pressure for 2 weeks, and stop or reduce the dose if readings drop below your usual range or you develop new swelling.", "minimumTimeSeparation": 240, "mechanism": "Phytosome formulations dramatically increase curcumin bioavailability, amplifying CYP3A4 and P-gp inhibition. Amlodipine clearance falls accordingly, raising AUC and the half-life.", "evidenceLevel": "emerging", "sources": [ { "text": "Jiang N, Zhang M, Meng X, Sun B. Effects of curcumin on the pharmacokinetics of amlodipine in rats and its potential mechanism. Pharm Biol. 2020;58(1):465-470.", "pmid": "32432949", "doi": "10.1080/13880209.2020.1764060", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32432949/", "publicSourceType": "PMID" }, { "text": "Guo Y, Chen Y, Tan ZR, Klaassen CD, Zhou HH. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol. 2012;68(2):213-7.", "pmid": "21870106", "doi": "10.1007/s00228-011-1108-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21870106/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "High-bioavailability curcumin amplifies CYP3A4 inhibition, raising amlodipine exposure.", "clinicalSignificance": "Excess amlodipine effect can produce hypotension and peripheral edema.", "managementStrategy": "Avoid the combination; if used, monitor BP closely and separate doses by 4+ hours.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Diltiazem", "supplementBName": "Resveratrol", "interactionType": "caution", "severity": "moderate", "description": "Resveratrol is a mechanism-based inhibitor of CYP3A4 and a P-glycoprotein blocker. In rats, oral resveratrol increased diltiazem AUC and Cmax 1.5-fold by inhibiting both intestinal CYP3A and efflux transport. The extrapolated human effect would amplify diltiazem's bradycardia and hypotension, particularly when patients use high-dose resveratrol supplements (250-1000 mg/day).", "recommendation": "Avoid high-dose resveratrol supplements while on diltiazem. If you do use resveratrol, separate doses by at least 4 hours, check pulse and blood pressure for 2 weeks, and reduce or stop the supplement if your HR drops below 50 bpm or you become lightheaded.", "minimumTimeSeparation": 240, "mechanism": "Resveratrol inhibits CYP3A4 (the primary diltiazem-metabolizing enzyme) and intestinal P-gp, raising bioavailability and slowing clearance. Reduced metabolism increases parent drug exposure and AV-nodal blockade.", "evidenceLevel": "emerging", "sources": [ { "text": "Hong SP, Choi DH, Choi JS. Effects of resveratrol on the pharmacokinetics of diltiazem and its major metabolite, desacetyldiltiazem, in rats. Cardiovasc Ther. 2008;26(4):269-75.", "pmid": "19035878", "doi": "10.1111/j.1755-5922.2008.00060.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19035878/", "publicSourceType": "PMID" }, { "text": "Mills TA, Kawji MM, Cataldo VD, et al. Profound sinus bradycardia due to diltiazem, verapamil, and/or beta-adrenergic blocking drugs. J La State Med Soc. 2004;156(6):327-31.", "pmid": "15688675", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15688675/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Resveratrol raises diltiazem exposure via CYP3A4 and P-gp inhibition.", "clinicalSignificance": "Bradycardia and hypotension may develop in patients on high-dose resveratrol.", "managementStrategy": "Avoid high-dose resveratrol; if used, separate by 4+ hours and monitor HR/BP.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Nifedipine", "supplementBName": "Resveratrol", "interactionType": "caution", "severity": "moderate", "description": "Resveratrol inhibits CYP3A4 and intestinal P-glycoprotein, and in rats it raised nicardipine AUC 111-126% via both mechanisms. Because nifedipine shares CYP3A4-mediated clearance and dihydropyridine-class side effects, co-administration with high-dose resveratrol supplements is likely to increase plasma nifedipine, producing more flushing, headache, hypotension, and reflex tachycardia.", "recommendation": "Avoid high-dose resveratrol supplements while on nifedipine. If used, separate doses by at least 4 hours, monitor blood pressure for 2 weeks after starting, and reduce or stop resveratrol if you develop flushing, headache, or readings below your usual range.", "minimumTimeSeparation": 240, "mechanism": "Resveratrol is a mechanism-based CYP3A4 inhibitor and reduces P-gp efflux of dihydropyridines. The combined effect raises oral bioavailability and slows hepatic clearance of nifedipine.", "evidenceLevel": "emerging", "sources": [ { "text": "Choi JS, Choi BC, Kang KW. Effect of resveratrol on the pharmacokinetics of oral and intravenous nicardipine in rats: possible role of P-glycoprotein inhibition by resveratrol. Pharmazie. 2009;64(1):49-52.", "pmid": "19216231", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19216231/", "publicSourceType": "PMID" }, { "text": "Bailey DG, Malcolm J, Arnold O, Spence JD. Grapefruit juice-drug interactions. Br J Clin Pharmacol. 1998;46(2):101-10.", "pmid": "9723817", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9723817/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Resveratrol raises nifedipine exposure, amplifying vasodilatory side effects.", "clinicalSignificance": "Flushing, headache, and hypotension are more likely with combined use.", "managementStrategy": "Avoid high-dose resveratrol; if used, separate by 4+ hours and monitor BP.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Diltiazem", "supplementBName": "Quercetin", "interactionType": "caution", "severity": "moderate", "description": "Quercetin pretreatment in rabbits roughly doubled the oral bioavailability of diltiazem by inhibiting CYP3A4 and intestinal P-glycoprotein. While human data are limited, large-dose quercetin supplements (500-1000 mg/day) are plausibly able to raise diltiazem levels and accentuate bradycardia, hypotension, or AV-nodal blockade.", "recommendation": "Avoid high-dose quercetin supplements while on diltiazem. If you use quercetin, keep doses modest (under 500 mg/day), separate from diltiazem by at least 4 hours, and monitor pulse and blood pressure for 2 weeks.", "minimumTimeSeparation": 240, "mechanism": "Quercetin inhibits CYP3A4 (the primary diltiazem metabolizing enzyme) and intestinal P-gp, raising oral bioavailability and slowing first-pass metabolism.", "evidenceLevel": "emerging", "sources": [ { "text": "Choi JS, Li X. Enhanced diltiazem bioavailability after oral administration of diltiazem with quercetin to rabbits. Int J Pharm. 2005;297(1-2):1-8.", "pmid": "15907592", "doi": "10.1016/j.ijpharm.2004.12.004", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15907592/", "publicSourceType": "PMID" }, { "text": "Mills TA, Kawji MM, Cataldo VD, et al. Profound sinus bradycardia due to diltiazem, verapamil, and/or beta-adrenergic blocking drugs. J La State Med Soc. 2004;156(6):327-31.", "pmid": "15688675", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15688675/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Quercetin raises diltiazem bioavailability via CYP3A4 and P-gp inhibition.", "clinicalSignificance": "Bradycardia and hypotension are more likely with high-dose quercetin.", "managementStrategy": "Keep quercetin under 500 mg/day, separate by 4+ hours, and monitor HR/BP.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Quercetin", "supplementBName": "Verapamil", "interactionType": "caution", "severity": "moderate", "description": "In rabbits, quercetin roughly doubled both the Cmax and AUC of verapamil by inhibiting CYP3A4 and P-glycoprotein. Verapamil already has a narrow therapeutic window for bradycardia and AV block, so high-dose quercetin supplements layered onto verapamil could meaningfully amplify rate suppression, hypotension, or constipation.", "recommendation": "Avoid high-dose quercetin supplements (over 500 mg/day) while on verapamil. If used, separate doses by at least 4 hours, monitor pulse and blood pressure twice daily for 2 weeks, and stop quercetin if your HR drops below 50 bpm or you become lightheaded.", "minimumTimeSeparation": 240, "mechanism": "Quercetin inhibits CYP3A4-mediated N-demethylation of verapamil and blocks intestinal P-gp efflux, raising oral bioavailability and slowing systemic clearance.", "evidenceLevel": "emerging", "sources": [ { "text": "Choi JS, Han HK. The effect of quercetin on the pharmacokinetics of verapamil and its major metabolite, norverapamil, in rabbits. J Pharm Pharmacol. 2004;56(12):1537-42.", "pmid": "15563760", "doi": "10.1211/0022357044814", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15563760/", "publicSourceType": "PMID" }, { "text": "Mills TA, Kawji MM, Cataldo VD, et al. Profound sinus bradycardia due to diltiazem, verapamil, and/or beta-adrenergic blocking drugs. J La State Med Soc. 2004;156(6):327-31.", "pmid": "15688675", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15688675/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Quercetin doubled verapamil exposure in animal models via CYP3A4 and P-gp inhibition.", "clinicalSignificance": "Excess verapamil exposure can produce bradycardia, AV block, hypotension, or constipation.", "managementStrategy": "Limit quercetin to under 500 mg/day, separate doses, and monitor HR/BP.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Diltiazem", "supplementBName": "L-Theanine", "interactionType": "caution", "severity": "moderate", "description": "L-Theanine modestly lowers stress-induced blood pressure increases and has mild relaxing effects on vascular tone. Layered on top of diltiazem's bradycardia, vasodilation, and negative inotropy, the combination can produce additive drops in heart rate or blood pressure, particularly in patients who are already well-controlled or volume-depleted.", "recommendation": "If you take diltiazem, L-theanine doses up to 200-350 mg/day supplemental elemental magnesium are usually well-tolerated, but check your blood pressure and pulse when you start. Reduce or stop the supplement if you develop dizziness, fatigue, or a resting heart rate below 50 bpm.", "minimumTimeSeparation": null, "mechanism": "L-Theanine attenuates sympathetic outflow and lowers stress-induced pressor responses through GABAergic and glutamate-receptor effects. This adds to diltiazem's negative chronotropic and vasodilatory action.", "evidenceLevel": "emerging", "sources": [ { "text": "Yoto A, Motoki M, Murao S, Yokogoshi H. Effects of L-theanine or caffeine intake on changes in blood pressure under physical and psychological stresses. J Physiol Anthropol. 2012;31(1):28.", "pmid": "23107346", "doi": "10.1186/1880-6805-31-28", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23107346/", "publicSourceType": "PMID" }, { "text": "Mills TA, Kawji MM, Cataldo VD, et al. Profound sinus bradycardia due to diltiazem, verapamil, and/or beta-adrenergic blocking drugs. J La State Med Soc. 2004;156(6):327-31.", "pmid": "15688675", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15688675/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive blunting of sympathetic tone can amplify diltiazem's bradycardia and hypotension.", "clinicalSignificance": "Patients well-controlled on diltiazem may develop dizziness or fatigue.", "managementStrategy": "Monitor HR/BP when initiating L-theanine; reduce if symptomatic.", "isSynergistic": null, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Taurine", "supplementBName": "Verapamil", "interactionType": "caution", "severity": "moderate", "description": "Taurine lowers systolic and diastolic blood pressure by about 3-4 mmHg in meta-analysis and has direct heart-rate-lowering effects. Combined with verapamil's strong rate and AV-node suppression, taurine can push heart rate or blood pressure too low, especially in older adults or those on additional rate-slowing drugs.", "recommendation": "If you take verapamil, taurine doses up to 1.5-3 g/day are usually tolerable, but check your blood pressure and resting heart rate when you start. Reduce or stop taurine if your HR drops below 50 bpm or you develop new dizziness or fatigue.", "minimumTimeSeparation": null, "mechanism": "Taurine modulates cardiomyocyte calcium handling, blunts sympathetic outflow, and increases NO availability. These effects overlap with verapamil's L-type calcium channel blockade and AV-nodal suppression.", "evidenceLevel": "moderate", "sources": [ { "text": "Tzang CC, Lin WC, Lin LH, et al. Insights into the cardiovascular benefits of taurine: a systematic review and meta-analysis. Nutr J. 2024;23(1):93.", "pmid": "39148075", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39148075/", "publicSourceType": "PMID" }, { "text": "Mills TA, Kawji MM, Cataldo VD, et al. Profound sinus bradycardia due to diltiazem, verapamil, and/or beta-adrenergic blocking drugs. J La State Med Soc. 2004;156(6):327-31.", "pmid": "15688675", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15688675/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive blood-pressure and heart-rate lowering with potential for symptomatic bradycardia.", "clinicalSignificance": "Older patients on verapamil may develop dizziness, fatigue, or AV-nodal slowing.", "managementStrategy": "Monitor HR/BP when starting taurine and reduce if symptomatic.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Diltiazem", "supplementBName": "Taurine", "interactionType": "caution", "severity": "moderate", "description": "Taurine produces small but consistent reductions in blood pressure (about 3-4 mmHg systolic in meta-analysis) and slows heart rate through autonomic modulation. Added to diltiazem's negative chronotropic and vasodilatory effects, the combination can produce additive bradycardia or hypotension, particularly in older patients or those on additional rate-slowing medications.", "recommendation": "If you take diltiazem, taurine doses up to 1.5-3 g/day are usually tolerable, but check blood pressure and pulse when you start. Hold or reduce taurine if your HR drops below 50 bpm or you develop new dizziness or fatigue.", "minimumTimeSeparation": null, "mechanism": "Taurine modulates intracellular calcium handling, suppresses sympathetic outflow, and increases nitric oxide availability. These effects overlap with diltiazem's L-type calcium channel blockade and AV-nodal slowing.", "evidenceLevel": "moderate", "sources": [ { "text": "Tzang CC, Lin WC, Lin LH, et al. Insights into the cardiovascular benefits of taurine: a systematic review and meta-analysis. Nutr J. 2024;23(1):93.", "pmid": "39148075", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39148075/", "publicSourceType": "PMID" }, { "text": "Mills TA, Kawji MM, Cataldo VD, et al. Profound sinus bradycardia due to diltiazem, verapamil, and/or beta-adrenergic blocking drugs. J La State Med Soc. 2004;156(6):327-31.", "pmid": "15688675", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15688675/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive blood-pressure and heart-rate reductions amplify diltiazem's hemodynamic effects.", "clinicalSignificance": "Patients stable on diltiazem may develop symptomatic bradycardia or hypotension.", "managementStrategy": "Monitor HR/BP after starting taurine and reduce dose if symptomatic.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Amlodipine", "supplementBName": "L-Arginine", "interactionType": "caution", "severity": "moderate", "description": "L-Arginine is a nitric oxide precursor that lowers systolic and diastolic blood pressure by about 5/3 mmHg in meta-analysis. Combined with amlodipine's dihydropyridine vasodilation, the additive effect can produce symptomatic hypotension, dizziness, or reflex tachycardia, especially in patients already at goal blood pressure.", "recommendation": "If you take amlodipine, start L-arginine at low doses (1-3 g/day) and monitor your blood pressure before and after starting. Reduce or stop if you develop dizziness, headache, or readings below your usual range, and inform your prescriber.", "minimumTimeSeparation": null, "mechanism": "L-Arginine serves as substrate for endothelial nitric oxide synthase (eNOS); the resulting NO increase causes vasodilation that adds to amlodipine's calcium channel blockade.", "evidenceLevel": "moderate", "sources": [ { "text": "Dong JY, Qin LQ, Zhang Z, et al. Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials. Am Heart J. 2011;162(6):959-65.", "pmid": "22137067", "doi": "10.1016/j.ahj.2011.09.012", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22137067/", "publicSourceType": "PMID" }, { "text": "Bailey DG, Malcolm J, Arnold O, Spence JD. Grapefruit juice-drug interactions. Br J Clin Pharmacol. 1998;46(2):101-10.", "pmid": "9723817", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9723817/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive vasodilation can produce symptomatic hypotension.", "clinicalSignificance": "Patients already at goal on amlodipine may overshoot and become dizzy.", "managementStrategy": "Start L-arginine low (1-3 g/day) and monitor blood pressure.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Amlodipine", "supplementBName": "L-Citrulline", "interactionType": "caution", "severity": "moderate", "description": "L-Citrulline is converted to L-arginine and raises plasma arginine more efficiently than oral arginine itself, producing nitric-oxide-mediated vasodilation. Stacked on top of amlodipine's calcium channel blockade, this can drop blood pressure further than intended, with dizziness, fatigue, or headache.", "recommendation": "If you take amlodipine, start L-citrulline at lower doses (3 g/day or less) and track blood pressure for 1-2 weeks. Reduce the dose or stop if you become lightheaded or your readings fall below your usual range.", "minimumTimeSeparation": null, "mechanism": "L-Citrulline bypasses hepatic first-pass metabolism, raises systemic arginine, and increases eNOS substrate availability. The resulting vasodilation adds to amlodipine's hypotensive effect.", "evidenceLevel": "moderate", "sources": [ { "text": "Mirenayat MS, Moradi S, Mohammadi H, Rouhani MH. Effect of L-Citrulline Supplementation on Blood Pressure: a Systematic Review and Meta-Analysis of Clinical Trials. Curr Hypertens Rep. 2018;20(11):98.", "pmid": "30284051", "doi": "10.1007/s11906-018-0898-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30284051/", "publicSourceType": "PMID" }, { "text": "Dong JY, Qin LQ, Zhang Z, et al. Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials. Am Heart J. 2011;162(6):959-65.", "pmid": "22137067", "doi": "10.1016/j.ahj.2011.09.012", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22137067/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive vasodilation and blood-pressure lowering.", "clinicalSignificance": "Combined effect can produce symptomatic hypotension in well-controlled patients.", "managementStrategy": "Start low, monitor BP, and adjust if readings drop or you become symptomatic.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Amlodipine", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "Omega-3 fatty acids in fish oil produce small but consistent reductions in blood pressure (about 2-3 mmHg systolic at doses of 2-3 g/day) and lower triglycerides, complementing amlodipine's antihypertensive effect. The combination is generally beneficial in patients with hypertension or cardiovascular disease.", "recommendation": "Fish oil at 1-3 g/day combined with amlodipine is appropriate for most patients with cardiovascular risk. Monitor blood pressure when starting, and tell your prescriber if you use high doses (>3 g/day) since the hemodynamic effect can become additive.", "minimumTimeSeparation": null, "mechanism": "EPA and DHA enhance endothelial nitric oxide production, reduce vascular inflammation, and modulate ion channels in cardiomyocytes. These effects complement amlodipine's L-type calcium channel blockade.", "evidenceLevel": "strong", "sources": [ { "text": "Morris MC, Sacks F, Rosner B. Does fish oil lower blood pressure? A meta-analysis of controlled trials. Circulation. 1993;88(2):523-33.", "pmid": "8339414", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8339414/", "publicSourceType": "PMID" }, { "text": "Bailey DG, Malcolm J, Arnold O, Spence JD. Grapefruit juice-drug interactions. Br J Clin Pharmacol. 1998;46(2):101-10.", "pmid": "9723817", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9723817/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Small additive reductions in blood pressure and cardiovascular risk markers.", "clinicalSignificance": "Generally a beneficial combination but watch for additive hypotension at higher doses.", "managementStrategy": "Use fish oil 1-3 g/day with BP monitoring; consult prescriber for higher doses.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Amlodipine", "supplementBName": "Garlic Extract", "interactionType": "caution", "severity": "moderate", "description": "Aged garlic extract reduces systolic and diastolic blood pressure by about 8 and 5 mmHg in hypertensive patients in meta-analysis. Added on top of amlodipine, the additive antihypertensive effect can be welcome but can also produce dizziness or symptomatic hypotension in patients already at goal blood pressure.", "recommendation": "If you take amlodipine, monitor your blood pressure for 2-4 weeks after starting garlic extract. If readings drop below your usual range or you become lightheaded, reduce the garlic dose or talk with your prescriber about lowering amlodipine.", "minimumTimeSeparation": null, "mechanism": "Garlic (S-allyl cysteine and other organosulfur compounds) increases endothelial nitric oxide, reduces angiotensin-converting enzyme activity, and modestly vasodilates. These effects add to amlodipine's calcium channel blockade.", "evidenceLevel": "moderate", "sources": [ { "text": "Ried K. Garlic lowers blood pressure in hypertensive subjects, improves arterial stiffness and gut microbiota: A review and meta-analysis. Exp Ther Med. 2020;19(2):1472-1478.", "pmid": "32010325", "doi": "10.3892/etm.2019.8374", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32010325/", "publicSourceType": "PMID" }, { "text": "Bailey DG, Malcolm J, Arnold O, Spence JD. Grapefruit juice-drug interactions. Br J Clin Pharmacol. 1998;46(2):101-10.", "pmid": "9723817", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9723817/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive blood-pressure lowering of ~5-8 mmHg.", "clinicalSignificance": "Beneficial in uncontrolled hypertension but risks hypotension in well-controlled patients.", "managementStrategy": "Monitor BP after starting garlic; adjust either supplement or prescription dose if needed.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Amlodipine", "supplementBName": "Coenzyme Q10", "interactionType": "synergy", "severity": "info", "description": "CoQ10 produces a small but consistent reduction in systolic blood pressure (about 3-5 mmHg) and improves endothelial function, complementing amlodipine's antihypertensive effect. The combination is generally beneficial and well-tolerated, especially in patients with metabolic syndrome or coexisting heart failure.", "recommendation": "CoQ10 at 100-200 mg/day combined with amlodipine is appropriate for most patients with hypertension or cardiometabolic disease. Monitor blood pressure for 4 weeks after starting, and adjust amlodipine with your prescriber if readings fall consistently below your goal.", "minimumTimeSeparation": null, "mechanism": "CoQ10 improves mitochondrial energy production in vascular smooth muscle and endothelium, raising nitric oxide bioavailability and reducing systemic vascular resistance. These effects add to amlodipine's vasodilation.", "evidenceLevel": "moderate", "sources": [ { "text": "Rosenfeldt FL, Haas SJ, Krum H, et al. Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. J Hum Hypertens. 2007;21(4):297-306.", "pmid": "17287847", "doi": "10.1038/sj.jhh.1002138", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17287847/", "publicSourceType": "PMID" }, { "text": "Zhao D, Liang Y, Dai S, et al. Dose-Response Effect of Coenzyme Q10 Supplementation on Blood Pressure among Patients with Cardiometabolic Disorders: A GRADE-Assessed Systematic Review and Meta-Analysis of Randomized Controlled Trials. Adv Nutr. 2022;13(6):2180-2194.", "pmid": "36130103", "doi": "10.1093/advances/nmac094", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36130103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Small additive reduction in systolic blood pressure and improved endothelial function.", "clinicalSignificance": "Generally beneficial; watch for hypotension if already at BP goal.", "managementStrategy": "Use CoQ10 100-200 mg/day with BP monitoring.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Coenzyme Q10 Ubiquinol", "supplementBName": "Amlodipine", "interactionType": "synergy", "severity": "info", "description": "Ubiquinol is the reduced, more bioavailable form of CoQ10 and produces the same modest blood-pressure-lowering and endothelial benefits as ubiquinone, often at lower doses. Combined with amlodipine, the additive systolic-pressure reduction is usually beneficial but can occasionally drop blood pressure further than intended in well-controlled patients.", "recommendation": "Ubiquinol at 50-100 mg/day combined with amlodipine is appropriate for most patients with hypertension or cardiometabolic disease. Monitor blood pressure for 4 weeks after starting and adjust amlodipine with your prescriber if readings drop below your goal.", "minimumTimeSeparation": null, "mechanism": "Ubiquinol restores mitochondrial respiration in vascular smooth muscle and endothelium, raising nitric oxide and reducing vascular resistance. These effects add to amlodipine's vasodilation.", "evidenceLevel": "moderate", "sources": [ { "text": "Rosenfeldt FL, Haas SJ, Krum H, et al. Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. J Hum Hypertens. 2007;21(4):297-306.", "pmid": "17287847", "doi": "10.1038/sj.jhh.1002138", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17287847/", "publicSourceType": "PMID" }, { "text": "Zhao D, Liang Y, Dai S, et al. Dose-Response Effect of Coenzyme Q10 Supplementation on Blood Pressure among Patients with Cardiometabolic Disorders: A GRADE-Assessed Systematic Review and Meta-Analysis of Randomized Controlled Trials. Adv Nutr. 2022;13(6):2180-2194.", "pmid": "36130103", "doi": "10.1093/advances/nmac094", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36130103/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Small additive systolic BP reduction and endothelial benefit.", "clinicalSignificance": "Generally beneficial; watch for hypotension if already at BP goal.", "managementStrategy": "Use ubiquinol 50-100 mg/day with BP monitoring.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Amlodipine", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "info", "description": "In patients with documented vitamin D deficiency and hypertension, vitamin D supplementation produces a small additional reduction in systolic and diastolic blood pressure on top of standard antihypertensive therapy. In vitamin-D-replete patients, the effect is negligible. Combined with amlodipine, the interaction is generally beneficial and very rarely causes hypotension.", "recommendation": "If you take amlodipine and have low 25-hydroxyvitamin D (<30 ng/mL), supplement vitamin D3 to restore normal levels and monitor blood pressure for 6-12 weeks. The combination is appropriate; routine vitamin D supplementation in vitamin-D-replete patients does not lower BP.", "minimumTimeSeparation": null, "mechanism": "Vitamin D suppresses renin transcription and improves endothelial function. In deficiency, repletion lowers BP modestly; in sufficiency, the effect is absent.", "evidenceLevel": "moderate", "sources": [ { "text": "Serra MO, de Macedo LR, Silva M, Lautner RQ. Effect of Vitamin D supplementation on blood pressure in hypertensive individuals with hypovitaminosis D: a systematic review and meta-analysis. J Hypertens. 2024;42(4):594-604.", "pmid": "38164948", "doi": "10.1097/HJH.0000000000003646", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38164948/", "publicSourceType": "PMID" }, { "text": "Bailey DG, Malcolm J, Arnold O, Spence JD. Grapefruit juice-drug interactions. Br J Clin Pharmacol. 1998;46(2):101-10.", "pmid": "9723817", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9723817/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Small additive BP reduction in vitamin-D-deficient patients.", "clinicalSignificance": "Beneficial in deficiency; negligible in repletion.", "managementStrategy": "Check 25(OH)D; supplement to restore normal levels and recheck BP.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Amlodipine", "supplementBName": "Magnesium Citrate", "interactionType": "caution", "severity": "moderate", "description": "Magnesium acts as a physiologic calcium-channel modulator and lowers blood pressure by about 2 mmHg systolic and 1.8 mmHg diastolic at supplemental elemental-magnesium doses within standard upper-limit guidance in meta-analysis. Combined with amlodipine, the antihypertensive effect can be additive, occasionally producing hypotension, dizziness, or fatigue in well-controlled patients.", "recommendation": "If you take amlodipine, magnesium citrate doses of 200-350 mg/day supplemental elemental magnesium are usually safe but check your blood pressure after starting. Reduce or stop magnesium if readings fall below your usual range, and watch for diarrhea, which is more common with the citrate form.", "minimumTimeSeparation": null, "mechanism": "Magnesium competes with calcium at vascular smooth muscle calcium channels and promotes endothelial NO release. This action overlaps mechanistically with amlodipine's L-type calcium channel blockade.", "evidenceLevel": "moderate", "sources": [ { "text": "Zhang X, Li Y, Del Gobbo LC, et al. Effects of Magnesium Supplementation on Blood Pressure: A Meta-Analysis of Randomized Double-Blind Placebo-Controlled Trials. Hypertension. 2016;68(2):324-33.", "pmid": "27402922", "doi": "10.1161/HYPERTENSIONAHA.116.07664", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27402922/", "publicSourceType": "PMID" }, { "text": "Bailey DG, Malcolm J, Arnold O, Spence JD. Grapefruit juice-drug interactions. Br J Clin Pharmacol. 1998;46(2):101-10.", "pmid": "9723817", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9723817/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive blood-pressure lowering through overlapping calcium-channel effects.", "clinicalSignificance": "May cause symptomatic hypotension in patients already at goal.", "managementStrategy": "Use 200-350 mg/day supplemental elemental magnesium, monitor BP, and reduce if readings drop or diarrhea develops.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Diltiazem", "supplementBName": "Magnesium Citrate", "interactionType": "caution", "severity": "moderate", "description": "Magnesium is a physiologic calcium antagonist that lowers blood pressure by about 2/1.8 mmHg at supplemental doses and also blunts sinoatrial and AV-nodal conduction. Combined with diltiazem's rate-slowing and vasodilatory effects, the result can be additive bradycardia, hypotension, or AV-nodal slowing, particularly with high magnesium doses or IV use.", "recommendation": "If you take diltiazem, keep oral magnesium citrate to 200-350 mg/day supplemental elemental magnesium and monitor blood pressure and pulse after starting. Reduce or stop magnesium if your HR drops below 50 bpm, you develop dizziness, or your BP falls below your usual range. Avoid IV magnesium without specialist supervision.", "minimumTimeSeparation": null, "mechanism": "Magnesium competes with calcium at vascular and cardiac calcium channels and slows AV-nodal conduction. These effects overlap with diltiazem's L-type calcium channel blockade.", "evidenceLevel": "moderate", "sources": [ { "text": "Zhang X, Li Y, Del Gobbo LC, et al. Effects of Magnesium Supplementation on Blood Pressure: A Meta-Analysis of Randomized Double-Blind Placebo-Controlled Trials. Hypertension. 2016;68(2):324-33.", "pmid": "27402922", "doi": "10.1161/HYPERTENSIONAHA.116.07664", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27402922/", "publicSourceType": "PMID" }, { "text": "Mills TA, Kawji MM, Cataldo VD, et al. Profound sinus bradycardia due to diltiazem, verapamil, and/or beta-adrenergic blocking drugs. J La State Med Soc. 2004;156(6):327-31.", "pmid": "15688675", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15688675/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive AV-nodal slowing and blood-pressure lowering.", "clinicalSignificance": "May produce symptomatic bradycardia or hypotension, especially with IV magnesium.", "managementStrategy": "Use oral 200-350 mg/day supplemental elemental magnesium, monitor HR/BP, and avoid IV magnesium without supervision.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Nifedipine", "supplementBName": "Magnesium Citrate", "interactionType": "caution", "severity": "moderate", "description": "Magnesium is a physiologic calcium-channel modulator that lowers blood pressure by about 2 mmHg systolic at supplemental doses. Combined with nifedipine's strong dihydropyridine vasodilation, the additive effect can produce symptomatic hypotension, headache, flushing, or reflex tachycardia, particularly in pregnant patients receiving magnesium for preeclampsia (a well-known severe interaction).", "recommendation": "If you take nifedipine, keep oral magnesium citrate to 200-350 mg/day supplemental elemental magnesium and monitor blood pressure when you start. Reduce or stop magnesium if readings drop below your usual range. Pregnant patients on IV magnesium should be co-managed by their obstetrician and avoid concurrent nifedipine without monitoring.", "minimumTimeSeparation": null, "mechanism": "Magnesium competes with calcium at vascular smooth muscle L-type calcium channels and enhances endothelial NO. These effects add to nifedipine's calcium channel blockade and vasodilation.", "evidenceLevel": "moderate", "sources": [ { "text": "Zhang X, Li Y, Del Gobbo LC, et al. Effects of Magnesium Supplementation on Blood Pressure: A Meta-Analysis of Randomized Double-Blind Placebo-Controlled Trials. Hypertension. 2016;68(2):324-33.", "pmid": "27402922", "doi": "10.1161/HYPERTENSIONAHA.116.07664", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27402922/", "publicSourceType": "PMID" }, { "text": "Bailey DG, Malcolm J, Arnold O, Spence JD. Grapefruit juice-drug interactions. Br J Clin Pharmacol. 1998;46(2):101-10.", "pmid": "9723817", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9723817/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive vasodilation and blood-pressure lowering.", "clinicalSignificance": "Can produce symptomatic hypotension; pregnancy use needs careful supervision.", "managementStrategy": "Keep oral magnesium under 400 mg/day, monitor BP, and coordinate IV magnesium with obstetric care.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Nifedipine", "supplementBName": "Garlic Extract", "interactionType": "caution", "severity": "moderate", "description": "Aged garlic extract lowers systolic and diastolic blood pressure by about 8 and 5 mmHg in hypertensive patients. Stacked on top of nifedipine's strong dihydropyridine vasodilation, the additive effect can produce dizziness, flushing, headache, or symptomatic hypotension, particularly in patients already at goal blood pressure.", "recommendation": "If you take nifedipine, monitor blood pressure for 2-4 weeks after starting garlic extract. Reduce or stop garlic if readings drop below your usual range or you become dizzy, and inform your prescriber so the nifedipine dose can be adjusted if needed.", "minimumTimeSeparation": null, "mechanism": "Garlic organosulfur compounds raise endothelial NO and reduce ACE activity, producing vasodilation that adds to nifedipine's calcium channel blockade.", "evidenceLevel": "moderate", "sources": [ { "text": "Ried K. Garlic lowers blood pressure in hypertensive subjects, improves arterial stiffness and gut microbiota: A review and meta-analysis. Exp Ther Med. 2020;19(2):1472-1478.", "pmid": "32010325", "doi": "10.3892/etm.2019.8374", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32010325/", "publicSourceType": "PMID" }, { "text": "Bailey DG, Malcolm J, Arnold O, Spence JD. Grapefruit juice-drug interactions. Br J Clin Pharmacol. 1998;46(2):101-10.", "pmid": "9723817", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9723817/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive BP lowering of ~5-8 mmHg.", "clinicalSignificance": "Can cause hypotension or dizziness in patients already at BP goal.", "managementStrategy": "Monitor BP after starting garlic; adjust supplement or prescription if needed.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Diltiazem", "supplementBName": "Garlic Extract", "interactionType": "caution", "severity": "moderate", "description": "Aged garlic extract reduces systolic and diastolic blood pressure by about 8 and 5 mmHg in hypertensive patients. Combined with diltiazem's vasodilatory and rate-slowing effects, the additive antihypertensive response can be welcome but also risks symptomatic hypotension or dizziness, especially in older patients or those at goal blood pressure.", "recommendation": "If you take diltiazem, monitor blood pressure and pulse for 2-4 weeks after starting garlic extract. Reduce or stop garlic if readings drop below your usual range, you become dizzy, or your heart rate falls below 50 bpm.", "minimumTimeSeparation": null, "mechanism": "Garlic organosulfur compounds increase endothelial NO and modestly reduce ACE activity, adding to diltiazem's L-type calcium channel blockade and vasodilation.", "evidenceLevel": "moderate", "sources": [ { "text": "Ried K. Garlic lowers blood pressure in hypertensive subjects, improves arterial stiffness and gut microbiota: A review and meta-analysis. Exp Ther Med. 2020;19(2):1472-1478.", "pmid": "32010325", "doi": "10.3892/etm.2019.8374", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32010325/", "publicSourceType": "PMID" }, { "text": "Mills TA, Kawji MM, Cataldo VD, et al. Profound sinus bradycardia due to diltiazem, verapamil, and/or beta-adrenergic blocking drugs. J La State Med Soc. 2004;156(6):327-31.", "pmid": "15688675", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15688675/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive BP lowering and vasodilation.", "clinicalSignificance": "Beneficial in uncontrolled hypertension but can cause symptomatic hypotension at goal.", "managementStrategy": "Monitor BP/HR after starting garlic; adjust either as needed.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Acitretin", "supplementBName": "Alcohol", "interactionType": "contraindicated", "severity": "dangerous", "description": "Alcohol can convert acitretin back into etretinate, a much more lipophilic retinoid with a very long elimination time. This is especially dangerous for anyone who could become pregnant because it can extend teratogenic risk long after acitretin would otherwise clear. The concern is not solved by separating doses because ethanol changes acitretin metabolism systemically.", "recommendation": "Do not drink alcohol while taking acitretin. If pregnancy is possible, avoid alcohol during treatment and for at least 2 months after stopping acitretin, and follow your prescriber's contraception and pregnancy-testing plan exactly. Tell your prescriber if you drank alcohol while on acitretin.", "minimumTimeSeparation": null, "mechanism": "Ethanol enables ethyl esterification of acitretin to etretinate through an acitretinoyl-CoA intermediate. Etretinate partitions into fat and has a much longer terminal half-life than acitretin, prolonging systemic retinoid exposure and teratogenic potential.", "evidenceLevel": "strong", "sources": [ { "text": "Larsen FG, Jakobsen P, Knudsen J, Weismann K, Kragballe K, Nielsen-Kudsk F. Conversion of acitretin to etretinate in psoriatic patients is influenced by ethanol. J Invest Dermatol. 1993;100(5):623-627.", "pmid": "8491984", "doi": "10.1111/1523-1747.ep12472293", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8491984/", "publicSourceType": "PMID" }, { "text": "Knights KM, Stresser DM, Miners JO, Crespi CL. In vitro metabolism of acitretin by human liver microsomes: evidence of an acitretinoyl-coenzyme A thioester conjugate in the transesterification to etretinate. Biochem Pharmacol. 2000;60(4):507-516.", "pmid": "10874125", "doi": "10.1016/S0006-2952(00)00339-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10874125/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bAffectsA", "effect": "Alcohol promotes formation of long-lived etretinate from acitretin.", "clinicalSignificance": "This can extend teratogenic retinoid exposure and make pregnancy prevention requirements more critical.", "managementStrategy": "Avoid alcohol during acitretin therapy and for the post-treatment interval specified by the prescriber.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Acitretin", "supplementBName": "Vitamin A", "interactionType": "contraindicated", "severity": "dangerous", "description": "Acitretin is a systemic retinoid with vitamin A-like toxicity. Adding preformed vitamin A supplements can stack retinoid effects and increase the risk of headache, severe dry skin and mucosa, liver enzyme elevations, hypertriglyceridemia, bone symptoms, and teratogenicity. Risk is highest with high-dose vitamin A, cod liver oil, or multiple multivitamins.", "recommendation": "Do not take vitamin A supplements, cod liver oil, or retinoid-containing products while on acitretin unless your dermatologist specifically directs it. Check multivitamin labels for retinol, retinyl palmitate, retinyl acetate, or vitamin A. Seek care promptly for severe headache, vision changes, jaundice, or pregnancy exposure.", "minimumTimeSeparation": null, "mechanism": "Acitretin activates retinoid signaling and produces adverse effects resembling hypervitaminosis A. Exogenous preformed vitamin A adds retinoid receptor substrate and can increase hepatic, lipid, neurologic, mucocutaneous, skeletal, and fetal toxicity.", "evidenceLevel": "strong", "sources": [ { "text": "Ormerod AD, Campalani E, Goodfield MJ, et al. British Association of Dermatologists guidelines on the efficacy and use of acitretin in dermatology. Br J Dermatol. 2010;162(5):952-963.", "pmid": "20423353", "doi": "10.1111/j.1365-2133.2010.09755.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20423353/", "publicSourceType": "PMID" }, { "text": "Kamm JJ. Toxicology, carcinogenicity, and teratogenicity of some orally administered retinoids. J Am Acad Dermatol. 1982;6(4 Pt 2 Suppl):652-659.", "pmid": "7040511", "doi": "10.1016/s0190-9622(82)70054-4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7040511/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Vitamin A adds to acitretin's systemic retinoid toxicity.", "clinicalSignificance": "The combination increases the chance of clinically important hypervitaminosis A-type adverse effects and fetal harm.", "managementStrategy": "Avoid supplemental vitamin A and review all multivitamin labels during acitretin therapy.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Tretinoin Oral", "supplementBName": "Vitamin A", "interactionType": "contraindicated", "severity": "dangerous", "description": "Oral tretinoin is all-trans retinoic acid, an active vitamin A metabolite used systemically for acute promyelocytic leukemia. Adding preformed vitamin A supplements can intensify retinoid toxicity, including headache, mucocutaneous toxicity, liver abnormalities, lipid changes, and teratogenic risk. This is not a timing problem because both exposures converge on systemic retinoid signaling.", "recommendation": "Do not take vitamin A supplements, cod liver oil, or high-retinol multivitamins during oral tretinoin therapy unless your oncology team explicitly prescribes them. Bring all supplements to medication reconciliation. Report severe headache, vision changes, abdominal pain, jaundice, or pregnancy exposure immediately.", "minimumTimeSeparation": null, "mechanism": "Tretinoin is all-trans retinoic acid and directly activates retinoic acid receptors. Preformed vitamin A can be metabolized into active retinoids, increasing the total retinoid burden and the risk of hypervitaminosis A-like toxicity.", "evidenceLevel": "strong", "sources": [ { "text": "Kamm JJ. Toxicology, carcinogenicity, and teratogenicity of some orally administered retinoids. J Am Acad Dermatol. 1982;6(4 Pt 2 Suppl):652-659.", "pmid": "7040511", "doi": "10.1016/s0190-9622(82)70054-4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7040511/", "publicSourceType": "PMID" }, { "text": "Carazo A, Macakova K, Matousova K, et al. Vitamin A Update: Forms, Sources, Kinetics, Detection, Function, Deficiency, Therapeutic Use and Toxicity. Nutrients. 2021;13(5):1703.", "pmid": "34069881", "doi": "10.3390/nu13051703", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34069881/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Vitamin A increases total systemic retinoid exposure during oral tretinoin therapy.", "clinicalSignificance": "Excess retinoid exposure can worsen toxicity during a high-risk oncology treatment.", "managementStrategy": "Avoid vitamin A supplements unless the oncology team specifically instructs otherwise.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Isotretinoin", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "moderate", "description": "Isotretinoin can raise triglycerides and liver enzymes, usually modestly but occasionally to clinically important levels. Alcohol does not appear to convert isotretinoin into long-lived ethyl retinoids the way it can with acitretin, but heavy drinking can still add lipid and liver stress. The concern is greatest with binge drinking, baseline hypertriglyceridemia, fatty liver disease, obesity, diabetes, or abnormal monitoring labs.", "recommendation": "Avoid binge drinking while taking isotretinoin, and keep alcohol low or absent until your first follow-up lipid and liver tests are known. If triglycerides or liver enzymes rise, stop alcohol and follow your prescriber's monitoring plan. Seek care for severe abdominal pain, persistent vomiting, jaundice, or dark urine.", "minimumTimeSeparation": null, "mechanism": "Isotretinoin can alter hepatic lipid handling and is associated with hypertriglyceridemia and transaminase elevations. Alcohol adds hepatic oxidative stress and can raise triglycerides through increased hepatic VLDL production, creating additive laboratory risk even without a direct pharmacokinetic interaction.", "evidenceLevel": "moderate", "sources": [ { "text": "Emtenani S, Abdelghaffar M, Ludwig RJ, Schmidt E, Kridin K. Risk and timing of isotretinoin-related laboratory disturbances: a population-based study. Int J Dermatol. 2024;63(12):1740-1747.", "pmid": "38702860", "doi": "10.1111/ijd.17225", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38702860/", "publicSourceType": "PMID" }, { "text": "Larsen FG, Jakobsen P, Larsen CG, Heidenheim M, Held E, Nielsen-Kudsk F. The metabolism and pharmacokinetics of isotretinoin in patients with acne and rosacea are not influenced by ethanol. Br J Dermatol. 2009;161(3):664-670.", "pmid": "19563582", "doi": "10.1111/j.1365-2133.2009.09241.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19563582/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Alcohol may add liver and triglyceride burden during isotretinoin therapy.", "clinicalSignificance": "Heavy alcohol use can make isotretinoin-related laboratory abnormalities more likely or harder to manage.", "managementStrategy": "Limit or avoid alcohol and follow lipid and liver enzyme monitoring, especially during the first 1-3 months.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Isotretinoin", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "Fish oil may help blunt isotretinoin-related triglyceride increases, especially if triglycerides are already elevated before treatment. Human data show omega-3 fatty acid users had smaller triglyceride increases during isotretinoin therapy, and an older retinoid study found fish oil reduced retinoid-associated hypertriglyceridemia. This is supportive care, not a replacement for lipid monitoring.", "recommendation": "Fish oil can be reasonable during isotretinoin therapy if your triglycerides are elevated or trending up. Use a standard EPA/DHA dose and tell your prescriber so lipid monitoring can guide treatment. Avoid very high doses if you also take anticoagulants or have bleeding risk.", "minimumTimeSeparation": null, "mechanism": "EPA and DHA reduce hepatic VLDL triglyceride production and can increase triglyceride clearance. This counters isotretinoin-associated triglyceride elevation without materially changing isotretinoin absorption or retinoid activity.", "evidenceLevel": "moderate", "sources": [ { "text": "Krishna S, Okhovat JP, Kim J, Kim CN. Influence of omega-3 fatty acids on triglyceride levels in patients using isotretinoin. JAMA Dermatol. 2015;151(1):101-102.", "pmid": "25251777", "doi": "10.1001/jamadermatol.2014.2402", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25251777/", "publicSourceType": "PMID" }, { "text": "Marsden JR. Effect of dietary fish oil on hyperlipidaemia due to isotretinoin and etretinate. Hum Toxicol. 1987;6(3):219-222.", "pmid": "2954894", "doi": "10.1177/096032718700600308", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2954894/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Fish oil may reduce isotretinoin-associated triglyceride elevation.", "clinicalSignificance": "Better triglyceride control may help patients continue isotretinoin safely when lipids are borderline.", "managementStrategy": "Consider fish oil as adjunctive lipid support while continuing prescribed lab monitoring.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Isotretinoin", "supplementBName": "Fish Oil Triple Strength", "interactionType": "synergy", "severity": "info", "description": "Concentrated fish oil may help control triglycerides during isotretinoin therapy. The evidence is based on omega-3 fatty acid and fish oil studies showing smaller triglyceride increases in isotretinoin users and reversal of retinoid-associated hypertriglyceridemia. The benefit is most relevant when baseline triglycerides are high or rise during therapy.", "recommendation": "If you use Fish Oil Triple Strength with isotretinoin, keep the dose within the label or prescriber-recommended EPA/DHA range and report it during lab review. Do not use high-dose omega-3 products as a substitute for checking fasting lipids. Stop or reassess if bruising, bleeding, or GI intolerance occurs.", "minimumTimeSeparation": null, "mechanism": "EPA and DHA reduce hepatic triglyceride synthesis and VLDL secretion. This can offset isotretinoin-associated triglyceride increases while leaving the retinoid's acne efficacy intact.", "evidenceLevel": "moderate", "sources": [ { "text": "Krishna S, Okhovat JP, Kim J, Kim CN. Influence of omega-3 fatty acids on triglyceride levels in patients using isotretinoin. JAMA Dermatol. 2015;151(1):101-102.", "pmid": "25251777", "doi": "10.1001/jamadermatol.2014.2402", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25251777/", "publicSourceType": "PMID" }, { "text": "Marsden JR. Effect of dietary fish oil on hyperlipidaemia due to isotretinoin and etretinate. Hum Toxicol. 1987;6(3):219-222.", "pmid": "2954894", "doi": "10.1177/096032718700600308", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2954894/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Concentrated fish oil may blunt isotretinoin-related triglyceride increases.", "clinicalSignificance": "This can be useful adjunctive support for patients with borderline or elevated triglycerides.", "managementStrategy": "Use as adjunctive lipid support with fasting lipid monitoring.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Acitretin", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "Acitretin can raise triglycerides, and fish oil may help reduce retinoid-associated hypertriglyceridemia. Direct evidence is strongest for isotretinoin and etretinate, while acitretin is closely related to etretinate and is monitored for the same lipid problem. This is adjunctive lipid support and should not replace dose adjustment or prescription lipid therapy when triglycerides are high.", "recommendation": "Fish oil is a reasonable option to discuss if triglycerides rise on acitretin. Continue fasting lipid monitoring and follow your dermatologist's plan for dose changes if levels become unsafe. Avoid very high fish oil doses if you have bleeding risk or take anticoagulants.", "minimumTimeSeparation": null, "mechanism": "Marine omega-3 fatty acids reduce hepatic VLDL triglyceride production and improve triglyceride clearance. This can counter the triglyceride elevations seen with systemic retinoids, including aromatic retinoids related to acitretin.", "evidenceLevel": "emerging", "sources": [ { "text": "Marsden JR. Effect of dietary fish oil on hyperlipidaemia due to isotretinoin and etretinate. Hum Toxicol. 1987;6(3):219-222.", "pmid": "2954894", "doi": "10.1177/096032718700600308", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2954894/", "publicSourceType": "PMID" }, { "text": "Ormerod AD, Campalani E, Goodfield MJ, et al. British Association of Dermatologists guidelines on the efficacy and use of acitretin in dermatology. Br J Dermatol. 2010;162(5):952-963.", "pmid": "20423353", "doi": "10.1111/j.1365-2133.2010.09755.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20423353/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Fish oil may help reduce retinoid-associated triglyceride elevations during acitretin therapy.", "clinicalSignificance": "Triglyceride control is a routine safety issue during systemic acitretin use.", "managementStrategy": "Use only as adjunctive support while continuing fasting lipid monitoring.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Acitretin", "supplementBName": "Fish Oil Triple Strength", "interactionType": "synergy", "severity": "info", "description": "Concentrated fish oil may help manage triglyceride elevations during acitretin therapy. Evidence comes from systemic retinoid studies and acitretin guidelines emphasizing lipid monitoring rather than from a large acitretin-specific omega-3 trial. The combination is supportive when triglycerides are borderline or mildly elevated.", "recommendation": "If your triglycerides rise while taking acitretin, ask whether a concentrated EPA/DHA product is appropriate. Continue fasting lipid checks and do not use fish oil to justify ignoring high triglycerides. Keep your dermatologist informed about the exact dose.", "minimumTimeSeparation": null, "mechanism": "EPA and DHA lower triglycerides by reducing hepatic triglyceride synthesis and VLDL secretion. These effects can partially oppose systemic retinoid-induced triglyceride increases.", "evidenceLevel": "emerging", "sources": [ { "text": "Marsden JR. Effect of dietary fish oil on hyperlipidaemia due to isotretinoin and etretinate. Hum Toxicol. 1987;6(3):219-222.", "pmid": "2954894", "doi": "10.1177/096032718700600308", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2954894/", "publicSourceType": "PMID" }, { "text": "Ormerod AD, Campalani E, Goodfield MJ, et al. British Association of Dermatologists guidelines on the efficacy and use of acitretin in dermatology. Br J Dermatol. 2010;162(5):952-963.", "pmid": "20423353", "doi": "10.1111/j.1365-2133.2010.09755.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20423353/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Concentrated fish oil may reduce acitretin-associated triglyceride pressure.", "clinicalSignificance": "Adjunctive triglyceride support may help keep lipid abnormalities manageable.", "managementStrategy": "Use with prescriber awareness and continued fasting lipid monitoring.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Dapsone", "supplementBName": "Activated Charcoal", "interactionType": "timingSensitive", "severity": "moderate", "description": "Activated charcoal can bind dapsone in the gut and can also accelerate elimination by interrupting enterohepatic or enteroenteric recirculation. This is useful in overdose under medical supervision, but routine charcoal supplementation can lower therapeutic dapsone exposure and may worsen disease control. Repeated charcoal doses are more concerning than a single isolated dose.", "recommendation": "Do not take activated charcoal routinely while using oral dapsone unless poison control or your clinician tells you to. If you take charcoal for a non-emergency reason, separate it from dapsone by at least 4 hours and tell your prescriber if you use it repeatedly. In overdose or suspected toxicity, seek emergency care rather than self-treating.", "minimumTimeSeparation": 240, "mechanism": "Activated charcoal adsorbs dapsone in the gastrointestinal tract and can increase dapsone clearance by interrupting gut recirculation. Dapsone has a long half-life and enterohepatic circulation, making it particularly susceptible to multidose charcoal effects.", "evidenceLevel": "strong", "sources": [ { "text": "Neuvonen PJ, Elonen E, Mattila MJ. Oral activated charcoal and dapsone elimination. Clin Pharmacol Ther. 1980;27(6):823-827.", "pmid": "7379451", "doi": "10.1038/clpt.1980.117", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7379451/", "publicSourceType": "PMID" }, { "text": "Zuidema J, Hilbers-Modderman ES, Merkus FW. Clinical pharmacokinetics of dapsone. Clin Pharmacokinet. 1986;11(4):299-315.", "pmid": "3530584", "doi": "10.2165/00003088-198611040-00003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3530584/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Activated charcoal can reduce dapsone exposure and speed dapsone elimination.", "clinicalSignificance": "Unsupervised charcoal use may reduce therapeutic effect, while supervised use is important in overdose.", "managementStrategy": "Avoid routine charcoal; if unavoidable, separate by at least 4 hours and avoid repeated unsupervised dosing.", "isSynergistic": null, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Brimonidine", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "moderate", "description": "Brimonidine eye drops can cause systemic alpha-2 agonist effects in some people, including fatigue, somnolence, low blood pressure, and dizziness. Alcohol independently causes sedation, psychomotor impairment, and can worsen orthostatic symptoms. Together they can make driving, nighttime walking, or standing quickly less safe, especially in older adults or those using other sedatives.", "recommendation": "Limit alcohol when starting brimonidine or after dose changes, and avoid driving if you feel drowsy or lightheaded. Use punctal occlusion after eye drops to reduce systemic absorption. Contact your prescriber if alcohol reliably triggers marked fatigue, faintness, slow breathing, or confusion while using brimonidine.", "minimumTimeSeparation": null, "mechanism": "Brimonidine is an alpha-2 adrenergic agonist that can reduce sympathetic tone after systemic absorption. Alcohol depresses CNS function and impairs psychomotor performance; it can also blunt orthostatic compensation, creating additive sedation and lightheadedness.", "evidenceLevel": "moderate", "sources": [ { "text": "Cantor LB. Brimonidine in the treatment of glaucoma and ocular hypertension. Ther Clin Risk Manag. 2006;2(4):337-346.", "pmid": "18360646", "doi": "10.2147/tcrm.2006.2.4.337", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18360646/", "publicSourceType": "PMID" }, { "text": "Fagan D, Tiplady B, Scott DB. Effects of ethanol on psychomotor performance under steady-state conditions. J Psychopharmacol. 1994;8(2):75-80.", "pmid": "22298532", "doi": "10.1177/026988119400800201", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22298532/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Alcohol may add to brimonidine-related sedation and low-blood-pressure symptoms.", "clinicalSignificance": "Even eye drops can produce systemic symptoms in susceptible patients.", "managementStrategy": "Limit alcohol, use punctal occlusion, and avoid hazardous tasks if drowsy or lightheaded.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Brimonidine", "supplementBName": "Cannabis (THC-Dominant)", "interactionType": "caution", "severity": "moderate", "description": "THC-dominant cannabis can add to brimonidine-related drowsiness, slowed reactions, dizziness, or blood-pressure symptoms. Brimonidine has documented systemic CNS and cardiovascular adverse effects in susceptible users, while THC acutely impairs psychomotor and driving-related performance. The combination is most concerning with new brimonidine use, high-THC products, older age, or other sedating medicines.", "recommendation": "Avoid THC-dominant cannabis when you need to drive or do safety-sensitive tasks after using brimonidine. Use punctal occlusion with eye drops to reduce systemic exposure. If you notice marked sleepiness, dizziness, fainting, or confusion, stop cannabis use and contact your prescriber.", "minimumTimeSeparation": null, "mechanism": "Brimonidine's systemic alpha-2 agonism can reduce arousal and sympathetic tone. THC activates CB1 receptors in brain networks controlling attention, tracking, reaction time, and coordination, so the combined effect can be additive functional impairment.", "evidenceLevel": "emerging", "sources": [ { "text": "Cantor LB. Brimonidine in the treatment of glaucoma and ocular hypertension. Ther Clin Risk Manag. 2006;2(4):337-346.", "pmid": "18360646", "doi": "10.2147/tcrm.2006.2.4.337", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18360646/", "publicSourceType": "PMID" }, { "text": "Kocis PT, Vrana KE. Delta-9-Tetrahydrocannabinol and Cannabidiol Drug-Drug Interactions. Med Cannabis Cannabinoids. 2020;3(1):61-73.", "pmid": "34676340", "doi": "10.1159/000507998", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34676340/", "publicSourceType": "PMID" }, { "text": "Simmons SM, Caird JK, Sterzer F, Asbridge M. The effects of cannabis and alcohol on driving performance and driver behaviour: a systematic review and meta-analysis. Addiction. 2022;117(7):1843-1856.", "pmid": "35083810", "doi": "10.1111/add.15770", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35083810/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "THC-dominant cannabis may add to brimonidine-related CNS and orthostatic impairment.", "clinicalSignificance": "The pairing can make a topical eye medication feel systemically sedating or unsafe for driving.", "managementStrategy": "Avoid same-period use before driving or hazardous tasks; use punctal occlusion and reassess if symptoms occur.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Timolol Ophthalmic", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "moderate", "description": "Timolol eye drops can be systemically absorbed and produce beta-blocker effects such as slower heart rate, lower blood pressure, dizziness, or syncope. Alcohol can worsen orthostatic blood pressure control and psychomotor impairment. The combination is most important in older adults, people with low resting heart rate, conduction disease, falls, or other blood-pressure medicines.", "recommendation": "Limit alcohol when starting timolol eye drops and avoid drinking if you have dizziness, fainting, or a very low pulse. Use punctal occlusion after each dose to reduce systemic absorption. Seek care for fainting, chest pain, wheezing, severe shortness of breath, or persistent heart rate below your clinician's threshold.", "minimumTimeSeparation": null, "mechanism": "Ophthalmic timolol can enter systemic circulation through conjunctival and nasolacrimal absorption, causing beta-adrenergic blockade. Alcohol impairs vasoconstrictor responses during standing and can add CNS impairment, increasing the chance of symptomatic hypotension or falls.", "evidenceLevel": "moderate", "sources": [ { "text": "Nieminen T, Lehtimaki T, Maenpaa J, et al. Ophthalmic timolol: plasma concentration and systemic cardiopulmonary effects. Scand J Clin Lab Invest. 2007;67(2):237-245.", "pmid": "17366003", "doi": "10.1080/00365510601034736", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17366003/", "publicSourceType": "PMID" }, { "text": "Narkiewicz K, Cooley RL, Somers VK. Alcohol potentiates orthostatic hypotension: implications for alcohol-related syncope. Circulation. 2000;101(4):398-402.", "pmid": "10653831", "doi": "10.1161/01.cir.101.4.398", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10653831/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Alcohol can add to systemic timolol-related dizziness, hypotension, and fall risk.", "clinicalSignificance": "Topical timolol can still produce clinically relevant systemic beta-blockade.", "managementStrategy": "Limit alcohol, use punctal occlusion, and monitor for dizziness, fainting, or bradycardia.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Timolol Ophthalmic", "supplementBName": "L-Arginine", "interactionType": "caution", "severity": "moderate", "description": "L-Arginine can modestly lower blood pressure through nitric-oxide-mediated vasodilation. Timolol eye drops can be systemically absorbed and lower heart rate or blood pressure in susceptible patients. Together they may increase lightheadedness, fatigue, or fainting risk, especially in older adults or people already on cardiovascular medications.", "recommendation": "Start L-Arginine cautiously if you use timolol eye drops, and monitor blood pressure and pulse for 1-2 weeks. Use punctal occlusion after timolol dosing. Stop or reduce L-Arginine and contact your prescriber if you develop dizziness, fainting, unusual fatigue, wheezing, or a very slow pulse.", "minimumTimeSeparation": null, "mechanism": "L-Arginine provides substrate for endothelial nitric oxide synthase and promotes vasodilation. Ophthalmic timolol can produce systemic beta-blockade after absorption, reducing heart rate and cardiac output; combined hemodynamic effects can lower perfusion pressure.", "evidenceLevel": "moderate", "sources": [ { "text": "Nieminen T, Lehtimaki T, Maenpaa J, et al. Ophthalmic timolol: plasma concentration and systemic cardiopulmonary effects. Scand J Clin Lab Invest. 2007;67(2):237-245.", "pmid": "17366003", "doi": "10.1080/00365510601034736", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17366003/", "publicSourceType": "PMID" }, { "text": "Shiraseb F, Asbaghi O, Bagheri R, Wong A, Figueroa A, Mirzaei K, et al. Effect of l-Arginine Supplementation on Blood Pressure in Adults: A Systematic Review and Dose-Response Meta-analysis of Randomized Clinical Trials. Adv Nutr. 2022;13(4):1226-1242.", "pmid": "34967840", "doi": "10.1093/advances/nmab155", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34967840/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "L-Arginine may add to systemic blood-pressure effects from ophthalmic timolol.", "clinicalSignificance": "This can matter because timolol eye drops can act like a systemic beta-blocker in susceptible patients.", "managementStrategy": "Start low, use punctal occlusion, and monitor blood pressure and pulse.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Timolol Ophthalmic", "supplementBName": "L-Citrulline", "interactionType": "caution", "severity": "moderate", "description": "L-Citrulline increases arginine availability and can modestly lower blood pressure. Timolol eye drops can reach systemic circulation and produce beta-blocker effects such as bradycardia, hypotension, and dizziness. The combination may be noticeable in people with low baseline blood pressure, low pulse, fall risk, or multiple cardiovascular medicines.", "recommendation": "If you add L-Citrulline while using timolol eye drops, start with a low dose and track blood pressure and pulse. Use punctal occlusion after each eye drop dose. Stop or reduce L-Citrulline and contact your prescriber if you develop fainting, persistent dizziness, unusual fatigue, wheezing, or slow pulse.", "minimumTimeSeparation": null, "mechanism": "L-Citrulline is converted to L-arginine, increasing nitric-oxide-mediated vasodilation. Systemically absorbed ophthalmic timolol blocks beta receptors, lowering heart rate and sometimes blood pressure; the combination can add hemodynamic effects.", "evidenceLevel": "moderate", "sources": [ { "text": "Nieminen T, Lehtimaki T, Maenpaa J, et al. Ophthalmic timolol: plasma concentration and systemic cardiopulmonary effects. Scand J Clin Lab Invest. 2007;67(2):237-245.", "pmid": "17366003", "doi": "10.1080/00365510601034736", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17366003/", "publicSourceType": "PMID" }, { "text": "Barkhidarian B, Khorshidi M, Shab-Bidar S, Hashemi B. Effects of L-citrulline supplementation on blood pressure: A systematic review and meta-analysis. Avicenna J Phytomed. 2019;9(1):10-20.", "pmid": "30788274", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30788274/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "L-Citrulline may add to systemic blood-pressure effects from ophthalmic timolol.", "clinicalSignificance": "Patients may not realize an eye drop can contribute to systemic hypotension or bradycardia.", "managementStrategy": "Start low, use punctal occlusion, and monitor blood pressure and pulse after adding L-Citrulline.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Chromium", "supplementBName": "Glipizide", "interactionType": "caution", "severity": "moderate", "description": "Chromium supplementation can lower fasting glucose and HbA1c in type 2 diabetes by improving insulin signaling. Stacked on top of a sulfonylurea like glipizide, which itself drives endogenous insulin release, this additive glucose-lowering can produce hypoglycemia, especially during the first weeks after starting chromium or after dose changes. Older adults and patients with renal impairment are most vulnerable.", "recommendation": "If you take glipizide, do not start chromium without telling your prescriber. Check fingerstick glucose more often (especially before meals and at bedtime) for the first 2-4 weeks, and ask whether the glipizide dose should be reduced.", "minimumTimeSeparation": null, "mechanism": "Chromium potentiates insulin receptor tyrosine kinase activity and upregulates GLUT4 translocation in skeletal muscle, lowering postprandial glucose. Combined with glipizide's stimulation of pancreatic beta-cell insulin secretion via SUR1/Kir6.2 channel closure, the two produce additive lowering of blood glucose.", "evidenceLevel": "moderate", "sources": [ { "text": "Singer GM, Geohas J. The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial. Diabetes Technol Ther. 2006;8(6):636-43.", "pmid": "17109595", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17109595/", "publicSourceType": "PMID" }, { "text": "Havel PJ. A scientific review: the role of chromium in insulin resistance. Diabetes Educ. 2004;Suppl:2-14.", "pmid": "15208835", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15208835/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Chromium adds to glipizide's glucose-lowering and can trigger hypoglycemia.", "clinicalSignificance": "Sulfonylurea hypoglycemia is the most common cause of serious drug-induced hypoglycemia in outpatients; even small additive effects matter.", "managementStrategy": "Monitor fingerstick glucose more often during the first 2-4 weeks; discuss a glipizide dose reduction with your prescriber.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Chromium", "supplementBName": "Glyburide", "interactionType": "caution", "severity": "serious", "description": "Chromium and glyburide both lower blood glucose by different mechanisms. Glyburide is the longest-acting sulfonylurea on the US market and already carries the highest hypoglycemia risk in its class. Adding chromium, which improves insulin sensitivity, can produce prolonged hypoglycemia (especially overnight) in older adults and in anyone with reduced kidney function.", "recommendation": "Avoid starting chromium on glyburide unless your prescriber agrees. If you do combine them, monitor fasting and bedtime glucose closely for the first month and ask whether glyburide should be reduced or switched to a shorter-acting sulfonylurea.", "minimumTimeSeparation": null, "mechanism": "Chromium amplifies insulin receptor signaling and GLUT4 translocation in muscle, while glyburide closes pancreatic beta-cell K-ATP channels to force insulin secretion. The combined effect lowers glucose more than either alone. Glyburide's active metabolites also accumulate in renal impairment, prolonging the hypoglycemic effect.", "evidenceLevel": "moderate", "sources": [ { "text": "Singer GM, Geohas J. The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial. Diabetes Technol Ther. 2006;8(6):636-43.", "pmid": "17109595", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17109595/", "publicSourceType": "PMID" }, { "text": "Havel PJ. A scientific review: the role of chromium in insulin resistance. Diabetes Educ. 2004;Suppl:2-14.", "pmid": "15208835", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15208835/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Chromium adds to glyburide's glucose-lowering and raises hypoglycemia risk.", "clinicalSignificance": "Glyburide hypoglycemia is the most common reason older diabetics are admitted with drug-induced low blood sugar.", "managementStrategy": "Do not start chromium without your prescriber; monitor fasting and bedtime glucose closely for the first month.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Chromium", "supplementBName": "Glimepiride", "interactionType": "caution", "severity": "moderate", "description": "Chromium improves insulin sensitivity, while glimepiride forces pancreatic insulin release. Combined, the additive effect on blood glucose can produce hypoglycemia, particularly in patients who skip meals, drink alcohol, or have reduced kidney function. The risk is highest in the first month after chromium is started or its dose is increased.", "recommendation": "Tell your prescriber before starting chromium on glimepiride. Monitor fingerstick glucose more often (before meals and at bedtime) for the first 2-4 weeks and ask whether the glimepiride dose should be reduced.", "minimumTimeSeparation": null, "mechanism": "Chromium enhances insulin receptor tyrosine phosphorylation and GLUT4 translocation in skeletal muscle. Glimepiride binds the 65 kDa SURx subunit on pancreatic beta cells, closing K-ATP channels and driving insulin secretion. The combined glucose-lowering exceeds either drug alone.", "evidenceLevel": "moderate", "sources": [ { "text": "Singer GM, Geohas J. The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial. Diabetes Technol Ther. 2006;8(6):636-43.", "pmid": "17109595", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17109595/", "publicSourceType": "PMID" }, { "text": "Havel PJ. A scientific review: the role of chromium in insulin resistance. Diabetes Educ. 2004;Suppl:2-14.", "pmid": "15208835", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15208835/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Chromium adds to glimepiride's glucose-lowering and increases hypoglycemia risk.", "clinicalSignificance": "Combined insulin-sensitizing and insulin-secreting effects can produce symptomatic lows, particularly with missed meals or alcohol.", "managementStrategy": "Discuss with prescriber before starting; monitor glucose closely for 2-4 weeks and consider glimepiride dose reduction.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Chromium", "supplementBName": "Empagliflozin", "interactionType": "caution", "severity": "moderate", "description": "Empagliflozin lowers blood glucose by causing urinary glucose excretion. Chromium independently improves insulin sensitivity. Used together the additive glucose-lowering is usually mild because SGLT2 inhibitors rarely cause hypoglycemia alone, but the risk rises when empagliflozin is part of a multi-drug regimen that already includes insulin or a sulfonylurea.", "recommendation": "If your only diabetes medication is empagliflozin, chromium can be added with home glucose monitoring during the first 2-4 weeks. If you also take insulin or a sulfonylurea, talk to your prescriber first about a dose reduction.", "minimumTimeSeparation": null, "mechanism": "Empagliflozin inhibits sodium-glucose cotransporter 2 in the proximal renal tubule, reducing glucose reabsorption and producing glycosuria. Chromium amplifies post-receptor insulin signaling. Lowering hepatic glucose output and increasing peripheral glucose uptake compounds the renal glucose loss from empagliflozin.", "evidenceLevel": "emerging", "sources": [ { "text": "Singer GM, Geohas J. The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial. Diabetes Technol Ther. 2006;8(6):636-43.", "pmid": "17109595", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17109595/", "publicSourceType": "PMID" }, { "text": "Havel PJ. A scientific review: the role of chromium in insulin resistance. Diabetes Educ. 2004;Suppl:2-14.", "pmid": "15208835", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15208835/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Chromium can add modestly to empagliflozin's glucose-lowering.", "clinicalSignificance": "On empagliflozin alone the risk is low; the combination matters mainly when insulin or a sulfonylurea is also on board.", "managementStrategy": "Monitor glucose during the first 2-4 weeks; talk to your prescriber if you also take insulin or a sulfonylurea.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Chromium", "supplementBName": "Dapagliflozin", "interactionType": "caution", "severity": "moderate", "description": "Dapagliflozin reduces blood glucose by promoting urinary glucose excretion, and chromium improves insulin sensitivity. On dapagliflozin alone the hypoglycemia risk is low, but adding chromium to a regimen that already contains insulin or a sulfonylurea can produce symptomatic lows.", "recommendation": "If dapagliflozin is your only diabetes medication, chromium can be added with home glucose monitoring during the first 2-4 weeks. If you also take insulin or a sulfonylurea, ask your prescriber whether the other agent should be reduced before starting chromium.", "minimumTimeSeparation": null, "mechanism": "Dapagliflozin inhibits SGLT2 in the proximal renal tubule, increasing glycosuria. Chromium enhances insulin receptor signaling and GLUT4-mediated glucose uptake in skeletal muscle. The two effects are additive.", "evidenceLevel": "emerging", "sources": [ { "text": "Singer GM, Geohas J. The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial. Diabetes Technol Ther. 2006;8(6):636-43.", "pmid": "17109595", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17109595/", "publicSourceType": "PMID" }, { "text": "Havel PJ. A scientific review: the role of chromium in insulin resistance. Diabetes Educ. 2004;Suppl:2-14.", "pmid": "15208835", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15208835/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Chromium adds modestly to dapagliflozin's glucose-lowering effect.", "clinicalSignificance": "Combination is mostly low risk on dapagliflozin alone; risk rises with concurrent insulin or sulfonylurea.", "managementStrategy": "Monitor home glucose during the first 2-4 weeks; talk to your prescriber if you also take insulin or a sulfonylurea.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Chromium", "supplementBName": "Canagliflozin", "interactionType": "caution", "severity": "moderate", "description": "Canagliflozin lowers blood glucose through SGLT2 inhibition and chromium improves insulin sensitivity. The combination is usually well tolerated when canagliflozin is the only diabetes drug, but additive glucose-lowering becomes clinically meaningful if insulin or a sulfonylurea is also on board.", "recommendation": "If canagliflozin is your only diabetes medication, chromium can be added with home glucose monitoring during the first 2-4 weeks. If you also take insulin or a sulfonylurea, ask your prescriber whether the other agent needs a dose reduction first.", "minimumTimeSeparation": null, "mechanism": "Canagliflozin inhibits SGLT2 (and weakly SGLT1) in the proximal renal tubule, increasing urinary glucose excretion. Chromium increases insulin receptor tyrosine kinase activity and peripheral glucose uptake, producing an additive effect on glycemia.", "evidenceLevel": "emerging", "sources": [ { "text": "Singer GM, Geohas J. The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial. Diabetes Technol Ther. 2006;8(6):636-43.", "pmid": "17109595", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17109595/", "publicSourceType": "PMID" }, { "text": "Havel PJ. A scientific review: the role of chromium in insulin resistance. Diabetes Educ. 2004;Suppl:2-14.", "pmid": "15208835", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15208835/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Chromium modestly adds to canagliflozin's glucose-lowering effect.", "clinicalSignificance": "Risk is low on canagliflozin alone but rises with insulin or sulfonylurea co-therapy.", "managementStrategy": "Monitor home glucose for 2-4 weeks after starting; consult prescriber if also on insulin or a sulfonylurea.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Chromium", "supplementBName": "Dulaglutide", "interactionType": "caution", "severity": "moderate", "description": "Dulaglutide is a weekly GLP-1 receptor agonist that lowers glucose by stimulating glucose-dependent insulin secretion and slowing gastric emptying. Chromium improves insulin sensitivity. On dulaglutide alone the hypoglycemia risk is low, but additive effects can produce symptomatic lows when chromium is added to a regimen that also includes insulin or a sulfonylurea.", "recommendation": "If dulaglutide is your only diabetes medication, chromium can be added with home glucose monitoring for the first 2-4 weeks. If you also take insulin or a sulfonylurea, ask your prescriber whether those agents need to be reduced first.", "minimumTimeSeparation": null, "mechanism": "Dulaglutide activates pancreatic GLP-1 receptors, augmenting glucose-dependent insulin release and suppressing glucagon. Chromium potentiates insulin receptor signaling in skeletal muscle and liver. The two reduce blood glucose by different but complementary mechanisms.", "evidenceLevel": "emerging", "sources": [ { "text": "Singer GM, Geohas J. The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial. Diabetes Technol Ther. 2006;8(6):636-43.", "pmid": "17109595", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17109595/", "publicSourceType": "PMID" }, { "text": "Havel PJ. A scientific review: the role of chromium in insulin resistance. Diabetes Educ. 2004;Suppl:2-14.", "pmid": "15208835", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15208835/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Chromium can add modestly to dulaglutide's glucose-lowering.", "clinicalSignificance": "Risk is low on dulaglutide alone; the combination matters when insulin or a sulfonylurea is also on board.", "managementStrategy": "Monitor home glucose for 2-4 weeks; consult prescriber if also on insulin or a sulfonylurea.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Chromium", "supplementBName": "Liraglutide", "interactionType": "caution", "severity": "moderate", "description": "Liraglutide is a daily GLP-1 receptor agonist used for type 2 diabetes and weight management. Chromium improves insulin sensitivity. On liraglutide alone, hypoglycemia is uncommon, but additive glucose-lowering can become clinically meaningful when chromium is layered on top of a regimen that also includes insulin or a sulfonylurea.", "recommendation": "If liraglutide is your only diabetes medication, chromium can be added with home glucose monitoring for the first 2-4 weeks. If you also take insulin or a sulfonylurea, ask your prescriber whether those agents need to be reduced first.", "minimumTimeSeparation": null, "mechanism": "Liraglutide activates GLP-1 receptors, increasing glucose-dependent insulin release, suppressing glucagon, and slowing gastric emptying. Chromium enhances insulin receptor tyrosine kinase activity and GLUT4 translocation. The two produce additive glucose-lowering.", "evidenceLevel": "emerging", "sources": [ { "text": "Singer GM, Geohas J. The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial. Diabetes Technol Ther. 2006;8(6):636-43.", "pmid": "17109595", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17109595/", "publicSourceType": "PMID" }, { "text": "Havel PJ. A scientific review: the role of chromium in insulin resistance. Diabetes Educ. 2004;Suppl:2-14.", "pmid": "15208835", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15208835/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Chromium adds modestly to liraglutide's glucose-lowering effect.", "clinicalSignificance": "Risk is low on liraglutide alone but rises with insulin or sulfonylurea co-therapy.", "managementStrategy": "Monitor home glucose for 2-4 weeks; consult prescriber if also on insulin or a sulfonylurea.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Chromium", "supplementBName": "Sitagliptin", "interactionType": "caution", "severity": "moderate", "description": "Sitagliptin is a DPP-4 inhibitor that lowers blood glucose by prolonging endogenous GLP-1 activity. Chromium improves insulin sensitivity. The combination is usually well tolerated when sitagliptin is the only diabetes drug, but additive glucose-lowering becomes clinically meaningful when chromium is added on top of insulin or a sulfonylurea.", "recommendation": "If sitagliptin is your only diabetes medication, chromium can be added with home glucose monitoring for the first 2-4 weeks. If you also take insulin or a sulfonylurea, ask your prescriber whether those agents need to be reduced first.", "minimumTimeSeparation": null, "mechanism": "Sitagliptin inhibits dipeptidyl peptidase-4, preserving active GLP-1 and GIP and thereby increasing glucose-dependent insulin secretion. Chromium enhances post-receptor insulin signaling. The two produce additive glucose-lowering.", "evidenceLevel": "emerging", "sources": [ { "text": "Singer GM, Geohas J. The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial. Diabetes Technol Ther. 2006;8(6):636-43.", "pmid": "17109595", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17109595/", "publicSourceType": "PMID" }, { "text": "Wong CKH, Man KKC, Shi M, et al. Intensification with dipeptidyl peptidase-4 inhibitor, insulin, or thiazolidinediones and risks of all-cause mortality, cardiovascular diseases, and severe hypoglycemia in patients on metformin-sulfonylurea dual therapy. PLoS Med. 2019;16(12):e1002999.", "pmid": "31877127", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31877127/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Chromium adds modestly to sitagliptin's glucose-lowering effect.", "clinicalSignificance": "Hypoglycemia is rare on sitagliptin alone; risk rises markedly when added to sulfonylureas or insulin.", "managementStrategy": "Monitor home glucose for 2-4 weeks; talk to your prescriber if you also take insulin or a sulfonylurea.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Chromium", "supplementBName": "Linagliptin", "interactionType": "caution", "severity": "moderate", "description": "Linagliptin is a DPP-4 inhibitor that lowers blood glucose by prolonging endogenous GLP-1 activity. Chromium improves insulin sensitivity. On linagliptin alone the hypoglycemia risk is low, but additive effects matter when chromium is added on top of insulin or a sulfonylurea.", "recommendation": "If linagliptin is your only diabetes medication, chromium can be added with home glucose monitoring for the first 2-4 weeks. If you also take insulin or a sulfonylurea, ask your prescriber whether those agents need to be reduced first.", "minimumTimeSeparation": null, "mechanism": "Linagliptin inhibits DPP-4, preserving active GLP-1 and GIP, which augments glucose-dependent insulin release. Chromium enhances insulin receptor signaling in skeletal muscle. The two mechanisms are complementary and additive.", "evidenceLevel": "emerging", "sources": [ { "text": "Singer GM, Geohas J. The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial. Diabetes Technol Ther. 2006;8(6):636-43.", "pmid": "17109595", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17109595/", "publicSourceType": "PMID" }, { "text": "Wong CKH, Man KKC, Shi M, et al. Intensification with dipeptidyl peptidase-4 inhibitor, insulin, or thiazolidinediones and risks of all-cause mortality, cardiovascular diseases, and severe hypoglycemia in patients on metformin-sulfonylurea dual therapy. PLoS Med. 2019;16(12):e1002999.", "pmid": "31877127", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31877127/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Chromium adds modestly to linagliptin's glucose-lowering effect.", "clinicalSignificance": "Hypoglycemia is rare on linagliptin alone; risk rises markedly when added to insulin or sulfonylureas.", "managementStrategy": "Monitor home glucose for 2-4 weeks; talk to your prescriber if you also take insulin or a sulfonylurea.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Alpha-Lipoic Acid", "supplementBName": "Glipizide", "interactionType": "caution", "severity": "serious", "description": "Alpha-lipoic acid (ALA) improves insulin sensitivity and lowers fasting glucose and HbA1c in meta-analyses of diabetic patients. ALA has also triggered insulin autoimmune syndrome (Hirata syndrome), producing severe spontaneous hypoglycemia. Layered on glipizide, which itself forces insulin secretion, the additive glucose-lowering can produce hypoglycemia, especially in older adults or after missed meals.", "recommendation": "If you take glipizide, do not start ALA without telling your prescriber. Monitor fingerstick glucose more often during the first 4 weeks and after any dose change. Seek urgent care if you have repeated unexplained hypoglycemia, which can signal insulin autoimmune syndrome.", "minimumTimeSeparation": null, "mechanism": "ALA enhances insulin-stimulated glucose uptake in skeletal muscle by increasing GLUT4 translocation and improving mitochondrial function. ALA's sulfhydryl groups can also bind to insulin and trigger autoantibody formation in genetically susceptible individuals, causing Hirata syndrome. Glipizide drives pancreatic insulin secretion by closing K-ATP channels.", "evidenceLevel": "moderate", "sources": [ { "text": "Akbari M, Ostadmohammadi V, Lankarani KB, et al. The effects of alpha-lipoic acid supplementation on glucose control and lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials. Metabolism. 2018;87:56-69.", "pmid": "29990473", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29990473/", "publicSourceType": "PMID" }, { "text": "Izzo V, Greco C, Corradini D, et al. Insulin autoimmune syndrome in an Argentine woman taking alpha-lipoic acid: A case report and review of the literature. SAGE Open Med Case Rep. 2018;6:2050313X18819601.", "pmid": "30627435", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30627435/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "ALA can amplify glipizide's glucose-lowering and rarely triggers insulin autoimmune syndrome.", "clinicalSignificance": "Sulfonylurea hypoglycemia is the leading cause of drug-induced hypoglycemia hospitalizations in older adults.", "managementStrategy": "Monitor glucose closely for 4 weeks after starting ALA; tell your prescriber about repeated lows.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Alpha-Lipoic Acid", "supplementBName": "Glyburide", "interactionType": "caution", "severity": "serious", "description": "Alpha-lipoic acid improves insulin sensitivity and has been reported to trigger insulin autoimmune syndrome (Hirata syndrome) with severe spontaneous hypoglycemia. Glyburide is the longest-acting sulfonylurea and already carries the highest hypoglycemia risk in its class. The combination is particularly hazardous in older adults and patients with renal impairment, where glyburide and its active metabolites accumulate.", "recommendation": "Avoid starting ALA on glyburide unless your prescriber agrees and arranges close monitoring. If you do combine them, check fasting and bedtime glucose for at least 4 weeks and seek urgent care for repeated unexplained lows.", "minimumTimeSeparation": null, "mechanism": "ALA enhances insulin-stimulated GLUT4 translocation and AMPK activity, increasing peripheral glucose uptake. Its sulfhydryl groups can also trigger insulin autoantibody formation. Glyburide closes pancreatic beta-cell K-ATP channels to force insulin secretion and accumulates in renal impairment due to its active metabolites.", "evidenceLevel": "moderate", "sources": [ { "text": "Akbari M, Ostadmohammadi V, Lankarani KB, et al. The effects of alpha-lipoic acid supplementation on glucose control and lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials. Metabolism. 2018;87:56-69.", "pmid": "29990473", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29990473/", "publicSourceType": "PMID" }, { "text": "Sehgal T, Ohri U, Mittal N, et al. A Case of Insulin Autoimmune Syndrome in an Indian Male Taking Alpha-Lipoic Acid. Cureus. 2023;15(7):e42718.", "pmid": "37727171", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37727171/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "ALA amplifies glyburide-induced hypoglycemia and rarely triggers Hirata syndrome.", "clinicalSignificance": "Glyburide hypoglycemia is the most common cause of drug-induced low blood sugar admissions in older diabetics.", "managementStrategy": "Avoid starting ALA without prescriber input; monitor glucose closely for 4 weeks; report repeated lows urgently.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Alpha-Lipoic Acid", "supplementBName": "Glimepiride", "interactionType": "caution", "severity": "serious", "description": "Alpha-lipoic acid improves insulin sensitivity and lowers fasting glucose in type 2 diabetes meta-analyses. It has also been associated with insulin autoimmune syndrome (Hirata syndrome), producing severe spontaneous hypoglycemia. Glimepiride forces pancreatic insulin release. The additive effect can produce symptomatic lows, especially in older adults or with missed meals.", "recommendation": "If you take glimepiride, do not start ALA without telling your prescriber. Monitor fingerstick glucose more often (before meals and at bedtime) during the first 4 weeks and seek urgent care for repeated unexplained hypoglycemia.", "minimumTimeSeparation": null, "mechanism": "ALA enhances insulin-stimulated GLUT4 translocation and AMPK activity in skeletal muscle. Its sulfhydryl groups can trigger insulin autoantibody formation in genetically susceptible individuals. Glimepiride binds beta-cell K-ATP channels (SUR1/Kir6.2) and forces insulin secretion. The two effects on glucose-lowering are additive.", "evidenceLevel": "moderate", "sources": [ { "text": "Akbari M, Ostadmohammadi V, Lankarani KB, et al. The effects of alpha-lipoic acid supplementation on glucose control and lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials. Metabolism. 2018;87:56-69.", "pmid": "29990473", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29990473/", "publicSourceType": "PMID" }, { "text": "Izzo V, Greco C, Corradini D, et al. Insulin autoimmune syndrome in an Argentine woman taking alpha-lipoic acid: A case report and review of the literature. SAGE Open Med Case Rep. 2018;6:2050313X18819601.", "pmid": "30627435", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30627435/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "ALA can amplify glimepiride-induced hypoglycemia and rarely triggers Hirata syndrome.", "clinicalSignificance": "Sulfonylurea hypoglycemia is a leading cause of drug-induced hospital admission in older diabetics.", "managementStrategy": "Monitor glucose closely for 4 weeks after starting ALA; tell your prescriber about repeated lows.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Alpha-Lipoic Acid", "supplementBName": "Empagliflozin", "interactionType": "caution", "severity": "moderate", "description": "Alpha-lipoic acid improves insulin sensitivity and lowers fasting glucose, while empagliflozin causes urinary glucose excretion. On empagliflozin alone the hypoglycemia risk is low, but additive glucose-lowering matters when ALA is added on top of insulin or a sulfonylurea. ALA has also rarely triggered insulin autoimmune syndrome with severe hypoglycemia.", "recommendation": "If empagliflozin is your only diabetes medication, ALA can be added with home glucose monitoring for the first 2-4 weeks. If you also take insulin or a sulfonylurea, ask your prescriber whether the other agent needs a dose reduction first.", "minimumTimeSeparation": null, "mechanism": "Empagliflozin inhibits SGLT2 in the proximal tubule, causing glycosuria. ALA enhances insulin-stimulated GLUT4 translocation and AMPK activity, increasing peripheral glucose uptake. The two reduce glucose by independent, complementary mechanisms.", "evidenceLevel": "emerging", "sources": [ { "text": "Akbari M, Ostadmohammadi V, Lankarani KB, et al. The effects of alpha-lipoic acid supplementation on glucose control and lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials. Metabolism. 2018;87:56-69.", "pmid": "29990473", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29990473/", "publicSourceType": "PMID" }, { "text": "Izzo V, Greco C, Corradini D, et al. Insulin autoimmune syndrome in an Argentine woman taking alpha-lipoic acid: A case report and review of the literature. SAGE Open Med Case Rep. 2018;6:2050313X18819601.", "pmid": "30627435", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30627435/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "ALA adds to empagliflozin's glucose-lowering and rarely triggers Hirata syndrome.", "clinicalSignificance": "Hypoglycemia is uncommon on empagliflozin alone; risk rises with insulin or sulfonylurea co-therapy.", "managementStrategy": "Monitor home glucose for 2-4 weeks; consult prescriber if also on insulin or a sulfonylurea.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Alpha-Lipoic Acid", "supplementBName": "Dapagliflozin", "interactionType": "caution", "severity": "moderate", "description": "Alpha-lipoic acid improves insulin sensitivity and dapagliflozin causes urinary glucose excretion. Dapagliflozin alone rarely causes hypoglycemia, but additive effects matter when ALA is added on top of insulin or a sulfonylurea. ALA has also been associated with insulin autoimmune syndrome (Hirata syndrome) producing severe spontaneous hypoglycemia.", "recommendation": "If dapagliflozin is your only diabetes medication, ALA can be added with home glucose monitoring for the first 2-4 weeks. If you also take insulin or a sulfonylurea, ask your prescriber whether the other agent needs a dose reduction first.", "minimumTimeSeparation": null, "mechanism": "Dapagliflozin inhibits SGLT2 in the proximal tubule, causing glycosuria. ALA enhances insulin-stimulated GLUT4 translocation and AMPK activity, increasing peripheral glucose uptake. The mechanisms are independent and additive.", "evidenceLevel": "emerging", "sources": [ { "text": "Akbari M, Ostadmohammadi V, Lankarani KB, et al. The effects of alpha-lipoic acid supplementation on glucose control and lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials. Metabolism. 2018;87:56-69.", "pmid": "29990473", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29990473/", "publicSourceType": "PMID" }, { "text": "Sehgal T, Ohri U, Mittal N, et al. A Case of Insulin Autoimmune Syndrome in an Indian Male Taking Alpha-Lipoic Acid. Cureus. 2023;15(7):e42718.", "pmid": "37727171", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37727171/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "ALA adds to dapagliflozin's glucose-lowering and rarely triggers Hirata syndrome.", "clinicalSignificance": "Risk is low on dapagliflozin alone; rises with insulin or sulfonylurea co-therapy.", "managementStrategy": "Monitor home glucose for 2-4 weeks; consult prescriber if also on insulin or a sulfonylurea.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Alpha-Lipoic Acid", "supplementBName": "Liraglutide", "interactionType": "caution", "severity": "moderate", "description": "Alpha-lipoic acid improves insulin sensitivity and liraglutide augments glucose-dependent insulin release. On liraglutide alone the hypoglycemia risk is low, but additive effects can matter when ALA is added on top of insulin or a sulfonylurea. ALA has also rarely triggered insulin autoimmune syndrome with severe spontaneous hypoglycemia.", "recommendation": "If liraglutide is your only diabetes medication, ALA can be added with home glucose monitoring for the first 2-4 weeks. If you also take insulin or a sulfonylurea, ask your prescriber whether the other agent needs a dose reduction first.", "minimumTimeSeparation": null, "mechanism": "Liraglutide activates GLP-1 receptors, augmenting glucose-dependent insulin secretion and suppressing glucagon. ALA enhances insulin-stimulated GLUT4 translocation and AMPK activity. The mechanisms are complementary and additive.", "evidenceLevel": "emerging", "sources": [ { "text": "Akbari M, Ostadmohammadi V, Lankarani KB, et al. The effects of alpha-lipoic acid supplementation on glucose control and lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials. Metabolism. 2018;87:56-69.", "pmid": "29990473", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29990473/", "publicSourceType": "PMID" }, { "text": "Izzo V, Greco C, Corradini D, et al. Insulin autoimmune syndrome in an Argentine woman taking alpha-lipoic acid: A case report and review of the literature. SAGE Open Med Case Rep. 2018;6:2050313X18819601.", "pmid": "30627435", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30627435/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "ALA adds to liraglutide's glucose-lowering and rarely triggers Hirata syndrome.", "clinicalSignificance": "Risk is low on liraglutide alone; rises with insulin or sulfonylurea co-therapy.", "managementStrategy": "Monitor home glucose for 2-4 weeks; consult prescriber if also on insulin or a sulfonylurea.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Alpha-Lipoic Acid", "supplementBName": "Dulaglutide", "interactionType": "caution", "severity": "moderate", "description": "Alpha-lipoic acid improves insulin sensitivity and dulaglutide augments glucose-dependent insulin release. On dulaglutide alone the hypoglycemia risk is low, but additive effects can matter when ALA is added on top of insulin or a sulfonylurea. ALA has also rarely triggered insulin autoimmune syndrome with severe spontaneous hypoglycemia.", "recommendation": "If dulaglutide is your only diabetes medication, ALA can be added with home glucose monitoring for the first 2-4 weeks. If you also take insulin or a sulfonylurea, ask your prescriber whether the other agent needs a dose reduction first.", "minimumTimeSeparation": null, "mechanism": "Dulaglutide activates GLP-1 receptors, augmenting glucose-dependent insulin secretion and suppressing glucagon. ALA enhances insulin-stimulated GLUT4 translocation and AMPK activity. The mechanisms are complementary and additive.", "evidenceLevel": "emerging", "sources": [ { "text": "Akbari M, Ostadmohammadi V, Lankarani KB, et al. The effects of alpha-lipoic acid supplementation on glucose control and lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials. Metabolism. 2018;87:56-69.", "pmid": "29990473", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29990473/", "publicSourceType": "PMID" }, { "text": "Sehgal T, Ohri U, Mittal N, et al. A Case of Insulin Autoimmune Syndrome in an Indian Male Taking Alpha-Lipoic Acid. Cureus. 2023;15(7):e42718.", "pmid": "37727171", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37727171/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "ALA adds to dulaglutide's glucose-lowering and rarely triggers Hirata syndrome.", "clinicalSignificance": "Risk is low on dulaglutide alone; rises with insulin or sulfonylurea co-therapy.", "managementStrategy": "Monitor home glucose for 2-4 weeks; consult prescriber if also on insulin or a sulfonylurea.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Alpha-Lipoic Acid", "supplementBName": "Sitagliptin", "interactionType": "caution", "severity": "moderate", "description": "Alpha-lipoic acid improves insulin sensitivity and sitagliptin (a DPP-4 inhibitor) prolongs endogenous GLP-1 activity. On sitagliptin alone the hypoglycemia risk is low, but additive effects matter when ALA is added on top of insulin or a sulfonylurea. ALA has also rarely triggered insulin autoimmune syndrome (Hirata syndrome) with severe spontaneous hypoglycemia.", "recommendation": "If sitagliptin is your only diabetes medication, ALA can be added with home glucose monitoring for the first 2-4 weeks. If you also take insulin or a sulfonylurea, ask your prescriber whether the other agent needs a dose reduction first.", "minimumTimeSeparation": null, "mechanism": "Sitagliptin inhibits DPP-4, prolonging GLP-1 and GIP activity and augmenting glucose-dependent insulin secretion. ALA enhances insulin-stimulated GLUT4 translocation and AMPK activity. Mechanisms are independent and additive.", "evidenceLevel": "emerging", "sources": [ { "text": "Akbari M, Ostadmohammadi V, Lankarani KB, et al. The effects of alpha-lipoic acid supplementation on glucose control and lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials. Metabolism. 2018;87:56-69.", "pmid": "29990473", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29990473/", "publicSourceType": "PMID" }, { "text": "Izzo V, Greco C, Corradini D, et al. Insulin autoimmune syndrome in an Argentine woman taking alpha-lipoic acid: A case report and review of the literature. SAGE Open Med Case Rep. 2018;6:2050313X18819601.", "pmid": "30627435", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30627435/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "ALA can add to sitagliptin's glucose-lowering and rarely triggers Hirata syndrome.", "clinicalSignificance": "Hypoglycemia is rare on sitagliptin alone; risk rises with insulin or sulfonylurea co-therapy.", "managementStrategy": "Monitor home glucose for 2-4 weeks; consult prescriber if also on insulin or a sulfonylurea.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Fenugreek", "supplementBName": "Metformin", "interactionType": "caution", "severity": "moderate", "description": "Fenugreek seed extracts (typically standardized to ~50% galactomannan fiber and 4-hydroxyisoleucine) lower fasting glucose and HbA1c in randomized trials of type 2 diabetes. Combined with metformin, the additive glucose-lowering is usually beneficial but can produce hypoglycemia in patients who already have HbA1c near target, are eating less, or also take insulin or a sulfonylurea.", "recommendation": "Tell your prescriber before starting a fenugreek extract on metformin. Monitor fasting and pre-meal glucose for the first 2-4 weeks. Consider taking the two with a 1-2 hour gap, since fenugreek's soluble fiber can slow drug absorption.", "minimumTimeSeparation": 120, "mechanism": "Fenugreek's 4-hydroxyisoleucine stimulates glucose-dependent insulin secretion, and its soluble fiber slows carbohydrate absorption and may reduce hepatic glucose output. Metformin reduces hepatic gluconeogenesis (via AMPK activation and mitochondrial complex I inhibition) and improves peripheral insulin sensitivity. Effects are additive on fasting and postprandial glucose.", "evidenceLevel": "moderate", "sources": [ { "text": "Gong J, Fang K, Dong H, Wang D, Hu M, Lu F. Effect of fenugreek on hyperglycaemia and hyperlipidemia in diabetes and prediabetes: A meta-analysis. J Ethnopharmacol. 2016;194:260-268.", "pmid": "27496582", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27496582/", "publicSourceType": "PMID" }, { "text": "Kim J, Noh W, Kim A, Choi Y, Kim YS. The Effect of Fenugreek in Type 2 Diabetes and Prediabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Int J Mol Sci. 2023;24(18):13999.", "pmid": "37762302", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37762302/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Fenugreek adds to metformin's glucose-lowering and may slow oral drug absorption.", "clinicalSignificance": "Combined effect can produce mild lows in well-controlled patients and may reduce metformin Cmax if taken together.", "managementStrategy": "Separate doses by at least 2 hours; monitor glucose for 2-4 weeks after starting.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fenugreek", "supplementBName": "Glipizide", "interactionType": "caution", "severity": "serious", "description": "Fenugreek extracts lower fasting glucose and HbA1c in type 2 diabetes meta-analyses. Stacked on glipizide, which already forces pancreatic insulin secretion, the additive glucose-lowering can produce symptomatic hypoglycemia. The risk is higher in older adults, after missed meals, or in patients with reduced kidney function.", "recommendation": "Do not start fenugreek on glipizide without telling your prescriber. Check fingerstick glucose more often (before meals and at bedtime) for the first 2-4 weeks and ask whether the glipizide dose should be reduced.", "minimumTimeSeparation": null, "mechanism": "Fenugreek's 4-hydroxyisoleucine stimulates glucose-dependent insulin release, and its soluble galactomannan fiber slows carbohydrate absorption. Glipizide forces pancreatic insulin secretion by closing K-ATP channels. The two mechanisms are additive.", "evidenceLevel": "moderate", "sources": [ { "text": "Gong J, Fang K, Dong H, Wang D, Hu M, Lu F. Effect of fenugreek on hyperglycaemia and hyperlipidemia in diabetes and prediabetes: A meta-analysis. J Ethnopharmacol. 2016;194:260-268.", "pmid": "27496582", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27496582/", "publicSourceType": "PMID" }, { "text": "Kim J, Noh W, Kim A, Choi Y, Kim YS. The Effect of Fenugreek in Type 2 Diabetes and Prediabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Int J Mol Sci. 2023;24(18):13999.", "pmid": "37762302", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37762302/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Fenugreek amplifies glipizide-induced glucose lowering and raises hypoglycemia risk.", "clinicalSignificance": "Sulfonylurea hypoglycemia is the most common drug-induced hypoglycemia in outpatients.", "managementStrategy": "Tell prescriber before starting; monitor glucose closely for 2-4 weeks; consider a glipizide dose reduction.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fenugreek", "supplementBName": "Glyburide", "interactionType": "caution", "severity": "serious", "description": "Fenugreek extracts lower fasting glucose and HbA1c in type 2 diabetes meta-analyses. Glyburide is the longest-acting US sulfonylurea and already carries the highest hypoglycemia risk in its class, especially in older adults and patients with renal impairment. Adding fenugreek can produce prolonged, sometimes severe lows.", "recommendation": "Avoid starting fenugreek on glyburide unless your prescriber agrees and arranges close monitoring. If you do combine them, check fasting and bedtime glucose for at least 4 weeks and ask whether glyburide should be switched to a shorter-acting agent.", "minimumTimeSeparation": null, "mechanism": "Fenugreek's 4-hydroxyisoleucine drives glucose-dependent insulin release, and its galactomannan fiber slows carbohydrate absorption. Glyburide closes pancreatic K-ATP channels to force insulin secretion. Glyburide's active metabolites accumulate in renal impairment, prolonging the hypoglycemic window.", "evidenceLevel": "moderate", "sources": [ { "text": "Gong J, Fang K, Dong H, Wang D, Hu M, Lu F. Effect of fenugreek on hyperglycaemia and hyperlipidemia in diabetes and prediabetes: A meta-analysis. J Ethnopharmacol. 2016;194:260-268.", "pmid": "27496582", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27496582/", "publicSourceType": "PMID" }, { "text": "Kim J, Noh W, Kim A, Choi Y, Kim YS. The Effect of Fenugreek in Type 2 Diabetes and Prediabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Int J Mol Sci. 2023;24(18):13999.", "pmid": "37762302", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37762302/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Fenugreek amplifies glyburide-induced glucose lowering and raises hypoglycemia risk.", "clinicalSignificance": "Glyburide hypoglycemia is the most common cause of drug-induced low blood sugar admissions in older diabetics.", "managementStrategy": "Avoid combination; if used, monitor glucose closely for 4 weeks and consider switching glyburide.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fenugreek", "supplementBName": "Glimepiride", "interactionType": "caution", "severity": "serious", "description": "Fenugreek extracts lower fasting glucose and HbA1c in type 2 diabetes meta-analyses. Glimepiride forces pancreatic insulin release. The additive effect can produce hypoglycemia, especially in older adults, after missed meals, or with alcohol.", "recommendation": "Do not start fenugreek on glimepiride without telling your prescriber. Check fingerstick glucose more often (before meals and at bedtime) for the first 2-4 weeks and ask whether the glimepiride dose should be reduced.", "minimumTimeSeparation": null, "mechanism": "Fenugreek's 4-hydroxyisoleucine stimulates glucose-dependent insulin release, and its galactomannan fiber slows carbohydrate absorption. Glimepiride binds the SUR1/Kir6.2 K-ATP channel on beta cells to force insulin secretion. Effects are additive.", "evidenceLevel": "moderate", "sources": [ { "text": "Gong J, Fang K, Dong H, Wang D, Hu M, Lu F. Effect of fenugreek on hyperglycaemia and hyperlipidemia in diabetes and prediabetes: A meta-analysis. J Ethnopharmacol. 2016;194:260-268.", "pmid": "27496582", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27496582/", "publicSourceType": "PMID" }, { "text": "Kim J, Noh W, Kim A, Choi Y, Kim YS. The Effect of Fenugreek in Type 2 Diabetes and Prediabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Int J Mol Sci. 2023;24(18):13999.", "pmid": "37762302", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37762302/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Fenugreek amplifies glimepiride-induced glucose lowering and raises hypoglycemia risk.", "clinicalSignificance": "Sulfonylurea hypoglycemia is the most common drug-induced hypoglycemia in outpatients.", "managementStrategy": "Tell prescriber before starting; monitor glucose closely for 2-4 weeks; consider glimepiride dose reduction.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fenugreek", "supplementBName": "Insulin Glargine", "interactionType": "caution", "severity": "serious", "description": "Fenugreek extracts lower fasting glucose and HbA1c in type 2 diabetes meta-analyses. Insulin glargine provides 24-hour basal insulin coverage. Layered together, the additive glucose-lowering can produce nocturnal hypoglycemia, especially during the first weeks after starting fenugreek or after any glargine dose change.", "recommendation": "Tell your prescriber before starting a fenugreek extract on insulin glargine. Check fasting and bedtime glucose more often for the first 2-4 weeks and discuss whether your glargine dose should be reduced.", "minimumTimeSeparation": null, "mechanism": "Fenugreek's 4-hydroxyisoleucine stimulates glucose-dependent insulin release and its galactomannan fiber slows carbohydrate absorption. Insulin glargine binds insulin receptors throughout the day to drive cellular glucose uptake and suppress hepatic glucose output. Both reduce blood glucose, particularly fasting glucose.", "evidenceLevel": "moderate", "sources": [ { "text": "Gong J, Fang K, Dong H, Wang D, Hu M, Lu F. Effect of fenugreek on hyperglycaemia and hyperlipidemia in diabetes and prediabetes: A meta-analysis. J Ethnopharmacol. 2016;194:260-268.", "pmid": "27496582", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27496582/", "publicSourceType": "PMID" }, { "text": "Kim J, Noh W, Kim A, Choi Y, Kim YS. The Effect of Fenugreek in Type 2 Diabetes and Prediabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Int J Mol Sci. 2023;24(18):13999.", "pmid": "37762302", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37762302/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Fenugreek can lower fasting glucose enough to require a reduction in basal insulin.", "clinicalSignificance": "Nocturnal hypoglycemia from basal insulin can be severe and unrecognized in sleep.", "managementStrategy": "Tell prescriber before starting; monitor fasting and bedtime glucose closely; discuss glargine dose reduction.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fenugreek", "supplementBName": "Semaglutide", "interactionType": "caution", "severity": "moderate", "description": "Fenugreek extracts lower fasting glucose and HbA1c in type 2 diabetes meta-analyses, and its soluble fiber slows gastric emptying. Semaglutide also slows gastric emptying and augments glucose-dependent insulin secretion. The combined GI slowing may worsen nausea, bloating, and early satiety, and the additive glucose-lowering can produce hypoglycemia when other agents (insulin, sulfonylureas) are on board.", "recommendation": "Take fenugreek away from semaglutide doses if you experience increased nausea. Tell your prescriber before starting fenugreek, and monitor fasting glucose for the first 2-4 weeks. If you also take insulin or a sulfonylurea, ask whether those need to be reduced.", "minimumTimeSeparation": null, "mechanism": "Fenugreek's galactomannan soluble fiber slows gastric emptying and carbohydrate absorption. Semaglutide activates GLP-1 receptors, slowing gastric emptying and augmenting glucose-dependent insulin release. The two compound the GI effects and the glucose-lowering.", "evidenceLevel": "emerging", "sources": [ { "text": "Gong J, Fang K, Dong H, Wang D, Hu M, Lu F. Effect of fenugreek on hyperglycaemia and hyperlipidemia in diabetes and prediabetes: A meta-analysis. J Ethnopharmacol. 2016;194:260-268.", "pmid": "27496582", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27496582/", "publicSourceType": "PMID" }, { "text": "Jalleh RJ, Rayner CK, Hausken T, et al. Gastrointestinal effects of GLP-1 receptor agonists: mechanisms, management, and future directions. Lancet Gastroenterol Hepatol. 2024;9(10):957-964.", "pmid": "39096914", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39096914/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Fenugreek can worsen semaglutide's GI side effects and adds to its glucose-lowering.", "clinicalSignificance": "Combined slowing of gastric emptying can intensify nausea and early satiety, and risks hypoglycemia with insulin or sulfonylurea co-therapy.", "managementStrategy": "Separate doses if nausea worsens; monitor glucose for 2-4 weeks; discuss insulin or sulfonylurea reduction.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Inositol", "supplementBName": "Metformin", "interactionType": "synergy", "severity": "info", "description": "Myo-inositol and D-chiro-inositol act as second messengers downstream of the insulin receptor and improve insulin sensitivity, fasting glucose, and HOMA-IR in PCOS and type 2 diabetes. Network meta-analyses suggest myo-inositol combined with metformin outperforms metformin alone for several metabolic endpoints in PCOS. The combination is generally beneficial, with low hypoglycemia risk because metformin and inositol both act as insulin sensitizers rather than insulin secretagogues.", "recommendation": "If you take metformin for PCOS or insulin resistance, adding myo-inositol (commonly 2-4 g daily) is generally safe and may improve glycemic and reproductive outcomes. Continue routine glucose monitoring; severe hypoglycemia is unlikely unless you also take insulin or a sulfonylurea.", "minimumTimeSeparation": null, "mechanism": "Myo-inositol and D-chiro-inositol generate inositol phosphoglycan second messengers that improve insulin signaling and GLUT4-mediated glucose uptake. Metformin activates AMPK, inhibits hepatic gluconeogenesis, and reduces mitochondrial complex I activity. The mechanisms converge on improved insulin sensitivity without driving insulin secretion.", "evidenceLevel": "moderate", "sources": [ { "text": "Zhao H, Xing C, Zhang J, He B. Comparative efficacy of oral insulin sensitizers metformin, thiazolidinediones, inositol, and berberine in improving endocrine and metabolic profiles in women with PCOS: a network meta-analysis. Reprod Health. 2021;18(1):171.", "pmid": "34407851", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34407851/", "publicSourceType": "PMID" }, { "text": "Greff D, Juhász AE, Váncsa S, et al. Inositol is an effective and safe treatment in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Reprod Biol Endocrinol. 2023;21(1):10.", "pmid": "36703143", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36703143/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Myo-inositol complements metformin's insulin-sensitizing effects with low hypoglycemia risk.", "clinicalSignificance": "Network meta-analyses suggest combination may outperform metformin alone for some PCOS endpoints.", "managementStrategy": "Combination is reasonable for PCOS or insulin resistance; routine glucose monitoring is sufficient.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Inositol", "supplementBName": "Glipizide", "interactionType": "caution", "severity": "moderate", "description": "Myo-inositol and D-chiro-inositol improve insulin sensitivity and lower fasting glucose. Glipizide forces pancreatic insulin secretion. Combined, the additive glucose-lowering can produce hypoglycemia, particularly in older adults or after missed meals.", "recommendation": "Tell your prescriber before starting inositol on glipizide. Monitor fingerstick glucose more often during the first 2-4 weeks and ask whether the glipizide dose should be reduced.", "minimumTimeSeparation": null, "mechanism": "Inositol phosphoglycan second messengers improve insulin receptor signaling and peripheral glucose uptake. Glipizide closes K-ATP channels on pancreatic beta cells, forcing insulin secretion. The two mechanisms are additive.", "evidenceLevel": "emerging", "sources": [ { "text": "Greff D, Juhász AE, Váncsa S, et al. Inositol is an effective and safe treatment in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Reprod Biol Endocrinol. 2023;21(1):10.", "pmid": "36703143", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36703143/", "publicSourceType": "PMID" }, { "text": "Fitz V, Graca S, Mahalingaiah S, et al. Inositol for Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis to Inform the 2023 Update of the International Evidence-based PCOS Guidelines. J Clin Endocrinol Metab. 2024;109(6):1630-1655.", "pmid": "38163998", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38163998/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Inositol adds to glipizide's glucose-lowering and may produce mild hypoglycemia.", "clinicalSignificance": "Sulfonylurea hypoglycemia is the most common drug-induced low blood sugar in outpatients.", "managementStrategy": "Tell prescriber before starting; monitor glucose for 2-4 weeks; consider glipizide dose reduction.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Inositol", "supplementBName": "Insulin Glargine", "interactionType": "caution", "severity": "moderate", "description": "Myo-inositol and D-chiro-inositol improve insulin sensitivity and can lower fasting glucose. Insulin glargine provides 24-hour basal insulin coverage. Combined, the additive glucose-lowering can produce nocturnal hypoglycemia, particularly during the first weeks after starting inositol.", "recommendation": "Tell your prescriber before starting inositol on insulin glargine. Check fasting and bedtime glucose more often for the first 2-4 weeks and discuss whether your glargine dose should be reduced.", "minimumTimeSeparation": null, "mechanism": "Inositol phosphoglycan second messengers improve insulin receptor signaling and GLUT4-mediated glucose uptake in skeletal muscle. Insulin glargine binds the insulin receptor to drive cellular glucose uptake and suppress hepatic glucose output. The two are additive.", "evidenceLevel": "emerging", "sources": [ { "text": "Greff D, Juhász AE, Váncsa S, et al. Inositol is an effective and safe treatment in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Reprod Biol Endocrinol. 2023;21(1):10.", "pmid": "36703143", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36703143/", "publicSourceType": "PMID" }, { "text": "Fitz V, Graca S, Mahalingaiah S, et al. Inositol for Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis to Inform the 2023 Update of the International Evidence-based PCOS Guidelines. J Clin Endocrinol Metab. 2024;109(6):1630-1655.", "pmid": "38163998", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38163998/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Inositol can lower fasting glucose enough to require a basal insulin dose reduction.", "clinicalSignificance": "Nocturnal hypoglycemia from basal insulin can be severe and unrecognized in sleep.", "managementStrategy": "Tell prescriber before starting; monitor fasting and bedtime glucose; discuss glargine dose reduction.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Vitamin D3", "supplementBName": "Metformin", "interactionType": "synergy", "severity": "info", "description": "Vitamin D deficiency is common in type 2 diabetes and is associated with insulin resistance. Meta-analyses of vitamin D supplementation in type 2 diabetes show small but consistent reductions in fasting glucose, HbA1c, and HOMA-IR, and in prediabetes vitamin D supplementation modestly reduces progression to type 2 diabetes. Combined with metformin the effect is complementary, with low hypoglycemia risk.", "recommendation": "If you take metformin and have low 25-OH vitamin D, supplementation (typically 1000-4000 IU/day, titrated to a 25-OH level above 30 ng/mL) is reasonable. Routine glucose monitoring is sufficient; hypoglycemia is unlikely unless you also take insulin or a sulfonylurea.", "minimumTimeSeparation": null, "mechanism": "Vitamin D modulates insulin secretion via vitamin D receptors on pancreatic beta cells and improves insulin sensitivity by reducing chronic inflammation and influencing calcium signaling in insulin target tissues. Metformin lowers hepatic glucose output via AMPK activation. The mechanisms are independent and complementary.", "evidenceLevel": "moderate", "sources": [ { "text": "Chen W, Liu L, Hu F. Efficacy of vitamin D supplementation on glycaemic control in type 2 diabetes: An updated systematic review and meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2024;26(12):5713-5726.", "pmid": "39355942", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39355942/", "publicSourceType": "PMID" }, { "text": "Pittas AG, Kawahara T, Jorde R, et al. Vitamin D and Risk for Type 2 Diabetes in People With Prediabetes: A Systematic Review and Meta-analysis of Individual Participant Data From 3 Randomized Clinical Trials. Ann Intern Med. 2023;176(3):355-363.", "pmid": "36745886", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36745886/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Vitamin D modestly improves glycemic control alongside metformin with low hypoglycemia risk.", "clinicalSignificance": "Repleting low 25-OH vitamin D can reduce HbA1c and slow prediabetes progression to type 2 diabetes.", "managementStrategy": "Check 25-OH vitamin D; supplement to a level >30 ng/mL; routine glucose monitoring.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Vitamin D3", "supplementBName": "Insulin Glargine", "interactionType": "synergy", "severity": "info", "description": "Vitamin D deficiency is associated with insulin resistance. Repleting low 25-OH vitamin D can modestly improve insulin sensitivity and lower HbA1c in type 2 diabetes. In patients on insulin glargine, this is mostly beneficial and is unlikely to cause hypoglycemia, though basal insulin requirements may fall modestly over weeks to months.", "recommendation": "If your 25-OH vitamin D is low (<30 ng/mL), supplementation alongside insulin glargine is reasonable. Continue routine fingerstick monitoring; if you notice fasting lows over weeks to months, ask your prescriber whether your glargine dose should be reduced.", "minimumTimeSeparation": null, "mechanism": "Vitamin D modulates insulin signaling via vitamin D receptors on insulin target tissues and pancreatic beta cells and reduces low-grade inflammation that contributes to insulin resistance. Insulin glargine provides 24-hour basal insulin receptor activation. Improved insulin sensitivity gradually reduces basal insulin requirements.", "evidenceLevel": "moderate", "sources": [ { "text": "Chen W, Liu L, Hu F. Efficacy of vitamin D supplementation on glycaemic control in type 2 diabetes: An updated systematic review and meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2024;26(12):5713-5726.", "pmid": "39355942", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39355942/", "publicSourceType": "PMID" }, { "text": "Musazadeh V, Kavyani Z, Mirhosseini N, Dehghan P, Vajdi M. Effect of vitamin D supplementation on type 2 diabetes biomarkers: an umbrella of interventional meta-analyses. Diabetol Metab Syndr. 2023;15(1):76.", "pmid": "37072813", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37072813/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Vitamin D repletion modestly improves insulin sensitivity and may reduce basal insulin needs.", "clinicalSignificance": "Glargine dose may need a small downward adjustment over weeks to months after repletion.", "managementStrategy": "Check 25-OH vitamin D; supplement to a level >30 ng/mL; monitor fasting glucose and adjust glargine as needed.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Methylcobalamin", "supplementBName": "Metformin", "interactionType": "synergy", "severity": "moderate", "description": "Metformin reduces serum vitamin B12 by impairing calcium-dependent ileal absorption of B12-intrinsic factor complexes. Meta-analyses report B12 deficiency in roughly 1 in 5 long-term metformin users, with risk rising with dose and duration of therapy and contributing to neuropathy, anemia, and elevated homocysteine. Methylcobalamin (the activated form) supplementation reliably restores B12 status and is often preferred when peripheral neuropathy is a concern.", "recommendation": "If you take metformin long-term (>1 year), ask for an annual serum B12 check (and methylmalonic acid if B12 is low-normal). If levels are low or you have neuropathy, supplement methylcobalamin (typically 1000 mcg/day orally). Take it with or away from metformin; absorption is not affected by timing.", "minimumTimeSeparation": null, "mechanism": "Metformin disrupts the calcium-dependent uptake of the B12-intrinsic factor complex by ileal cubilin receptors and may alter intestinal motility and B12-binding by bile acids. Methylcobalamin bypasses some of this by providing a directly bioavailable, active form of B12 that is absorbed both via intrinsic factor and passive diffusion at higher doses.", "evidenceLevel": "strong", "sources": [ { "text": "Niafar M, Hai F, Porhomayon J, Nader ND. The role of metformin on vitamin B12 deficiency: a meta-analysis review. Intern Emerg Med. 2015;10(1):93-102.", "pmid": "25502588", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25502588/", "publicSourceType": "PMID" }, { "text": "Yang W, Cai X, Wu H, Ji L. Associations between metformin use and vitamin B12 levels, anemia, and neuropathy in patients with diabetes: a meta-analysis. J Diabetes. 2019;11(9):729-743.", "pmid": "30615306", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30615306/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Methylcobalamin reliably reverses metformin-induced B12 deficiency.", "clinicalSignificance": "B12 deficiency in metformin users can cause neuropathy and anemia and is reversible with supplementation.", "managementStrategy": "Annual B12 screening on long-term metformin; supplement methylcobalamin 1000 mcg/day if low.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Methylfolate", "supplementBName": "Metformin", "interactionType": "synergy", "severity": "info", "description": "Metformin can lower serum folate as well as vitamin B12, with longer treatment duration linked to lower folate levels and higher homocysteine. Combined B12 and folate depletion increases the risk of macrocytosis, neuropathy, and elevated homocysteine. Methylfolate (5-MTHF) is the active circulating form of folate and is reasonable in patients with low folate or MTHFR variants.", "recommendation": "If you take metformin long-term and have low folate, macrocytic anemia, or elevated homocysteine, consider methylfolate (typically 400-1000 mcg/day) in addition to B12 supplementation. Check folate, B12, and homocysteine periodically and discuss with your prescriber.", "minimumTimeSeparation": null, "mechanism": "Metformin appears to reduce intestinal folate absorption and may alter folate transport in enterocytes, lowering serum folate over time. Methylfolate provides the bioactive form that bypasses dihydrofolate reductase and MTHFR steps, supporting methionine synthesis and homocysteine remethylation.", "evidenceLevel": "moderate", "sources": [ { "text": "Kanti G, Anadol-Schmitz E, Bobrov P, et al. Vitamin B12 and Folate Concentrations in Recent-onset Type 2 Diabetes and the Effect of Metformin Treatment. J Clin Endocrinol Metab. 2020;105(6):e2105-e2114.", "pmid": "32219330", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32219330/", "publicSourceType": "PMID" }, { "text": "Wale Tesega W, Genet S, Natesan G, et al. Assessment of Serum Vitamin B12 and Folate Levels and Macrocytosis in Patients with Type 2 Diabetes Mellitus on Metformin Attending Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia: A Cross-Sectional Study. Diabetes Metab Syndr Obes. 2021;14:1967-1975.", "pmid": "33976561", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33976561/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Methylfolate addresses metformin-related folate decline and supports homocysteine remethylation.", "clinicalSignificance": "Combined B12 and folate depletion in long-term metformin users worsens neuropathy and macrocytosis risk.", "managementStrategy": "Check folate and homocysteine on long-term metformin; supplement methylfolate alongside B12 if low.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Coenzyme Q10", "supplementBName": "Metformin", "interactionType": "synergy", "severity": "info", "description": "Metformin inhibits mitochondrial respiratory chain complex I, which is part of how it lowers hepatic glucose output but also contributes to lactate generation and fatigue in some patients. Coenzyme Q10 supports mitochondrial electron transport between complex I/II and complex III. Animal and small human studies suggest CoQ10 can improve mitochondrial function and reduce metformin-related fatigue and oxidative stress without blunting glucose-lowering.", "recommendation": "If you experience fatigue or muscle symptoms on metformin and have ruled out B12 deficiency and lactate accumulation, a trial of CoQ10 (typically 100-200 mg/day with a fat-containing meal) is reasonable. It is not expected to alter blood glucose meaningfully.", "minimumTimeSeparation": null, "mechanism": "Metformin inhibits mitochondrial complex I, reducing ATP production and activating AMPK; this contributes to its anti-hyperglycemic effect but also to oxidative stress in some tissues. CoQ10 (ubiquinone/ubiquinol) shuttles electrons in the respiratory chain and acts as a lipid-phase antioxidant, partially mitigating complex I inhibition without abolishing the AMPK signal.", "evidenceLevel": "emerging", "sources": [ { "text": "Sun IO, Jin L, Jin J, Lim SW, Chung BH, Yang CW. The effects of addition of coenzyme Q10 to metformin on sirolimus-induced diabetes mellitus. Korean J Intern Med. 2019;34(2):365-374.", "pmid": "29228766", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29228766/", "publicSourceType": "PMID" }, { "text": "Akbari M, Ostadmohammadi V, Lankarani KB, et al. The effects of alpha-lipoic acid supplementation on glucose control and lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials. Metabolism. 2018;87:56-69.", "pmid": "29990473", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29990473/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "CoQ10 may partially counter metformin's mitochondrial side effects without changing its glucose-lowering.", "clinicalSignificance": "Mechanistic and animal data are stronger than human trial data; useful adjunct for metformin-related fatigue or muscle symptoms.", "managementStrategy": "Trial CoQ10 100-200 mg/day with food; expect no meaningful glucose change.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Milk Thistle", "supplementBName": "Glyburide", "interactionType": "caution", "severity": "serious", "description": "A 6-month RCT in 59 patients found that adding silymarin 200 mg three times daily to glyburide improved HbA1c and postprandial glucose more than glyburide alone. Silymarin is a weak CYP2C9 inhibitor in vitro and reduces fasting glucose independently. The combination meaningfully amplifies glyburide's hypoglycemic effect, and glyburide already carries the highest hypoglycemia risk among sulfonylureas, especially in older adults and renal impairment.", "recommendation": "Tell your prescriber before adding milk thistle on glyburide. Monitor fasting and bedtime glucose for at least 4 weeks and ask whether your glyburide dose should be reduced. Avoid the combination entirely if you have CKD or are over 75.", "minimumTimeSeparation": null, "mechanism": "Silymarin (the milk thistle flavonolignan complex) modestly inhibits CYP2C9, which metabolizes glyburide, potentially raising its plasma levels. Silymarin also has independent antihyperglycemic actions via improved insulin sensitivity and reduced oxidative stress in pancreatic islets. The combined pharmacokinetic and pharmacodynamic effects amplify hypoglycemia risk.", "evidenceLevel": "moderate", "sources": [ { "text": "Hussain SA. Silymarin as an adjunct to glibenclamide therapy improves long-term and postprandial glycemic control and body mass index in type 2 diabetes. J Med Food. 2007;10(3):543-547.", "pmid": "17887949", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17887949/", "publicSourceType": "PMID" }, { "text": "Voroneanu L, Nistor I, Dumea R, Apetrii M, Covic A. Silymarin in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Diabetes Res. 2016;2016:5147468.", "pmid": "27340676", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27340676/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Milk thistle amplifies glyburide-induced glucose lowering and raises hypoglycemia risk.", "clinicalSignificance": "Glyburide hypoglycemia is the most common drug-induced low blood sugar admission in older diabetics.", "managementStrategy": "Tell prescriber before adding; monitor glucose closely for 4 weeks; consider a glyburide dose reduction.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Milk Thistle", "supplementBName": "Glipizide", "interactionType": "caution", "severity": "moderate", "description": "Glipizide is metabolized primarily by CYP2C9. Silymarin (milk thistle) inhibits CYP2C9 in vitro and has independent hypoglycemic activity demonstrated in type 2 diabetes meta-analyses. The combination can raise glipizide exposure and amplify its glucose-lowering, producing hypoglycemia especially in older adults or after missed meals.", "recommendation": "Tell your prescriber before adding milk thistle on glipizide. Monitor fingerstick glucose more often during the first 4 weeks and ask whether the glipizide dose should be reduced.", "minimumTimeSeparation": null, "mechanism": "Silymarin flavonolignans modestly inhibit CYP2C9, the primary enzyme that metabolizes glipizide, potentially raising plasma drug concentrations. Silymarin also independently improves insulin sensitivity and reduces oxidative stress in pancreatic islets, lowering glucose. Combined pharmacokinetic and pharmacodynamic effects increase hypoglycemia risk.", "evidenceLevel": "moderate", "sources": [ { "text": "Kawaguchi-Suzuki M, Frye RF, Zhu HJ, et al. The effects of milk thistle (Silybum marianum) on human cytochrome P450 activity. Drug Metab Dispos. 2014;42(10):1611-1616.", "pmid": "25028567", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25028567/", "publicSourceType": "PMID" }, { "text": "Voroneanu L, Nistor I, Dumea R, Apetrii M, Covic A. Silymarin in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Diabetes Res. 2016;2016:5147468.", "pmid": "27340676", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27340676/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Milk thistle may raise glipizide exposure via CYP2C9 inhibition and adds independent glucose-lowering.", "clinicalSignificance": "Combination can produce hypoglycemia, especially in older patients or with missed meals.", "managementStrategy": "Tell prescriber before adding; monitor glucose closely for 4 weeks; consider a glipizide dose reduction.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Milk Thistle", "supplementBName": "Glimepiride", "interactionType": "caution", "severity": "moderate", "description": "Glimepiride is metabolized primarily by CYP2C9. Silymarin (milk thistle) inhibits CYP2C9 in vitro and has independent hypoglycemic activity. The combination can raise glimepiride exposure and amplify its glucose-lowering, producing hypoglycemia particularly in older adults or with missed meals.", "recommendation": "Tell your prescriber before adding milk thistle on glimepiride. Monitor fingerstick glucose more often during the first 4 weeks and ask whether the glimepiride dose should be reduced.", "minimumTimeSeparation": null, "mechanism": "Silymarin modestly inhibits CYP2C9, the main enzyme metabolizing glimepiride, potentially raising plasma concentrations. Silymarin also improves insulin sensitivity independently. Combined pharmacokinetic and pharmacodynamic effects amplify hypoglycemia risk.", "evidenceLevel": "moderate", "sources": [ { "text": "Kawaguchi-Suzuki M, Frye RF, Zhu HJ, et al. The effects of milk thistle (Silybum marianum) on human cytochrome P450 activity. Drug Metab Dispos. 2014;42(10):1611-1616.", "pmid": "25028567", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25028567/", "publicSourceType": "PMID" }, { "text": "Voroneanu L, Nistor I, Dumea R, Apetrii M, Covic A. Silymarin in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Diabetes Res. 2016;2016:5147468.", "pmid": "27340676", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27340676/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Milk thistle may raise glimepiride exposure via CYP2C9 inhibition and adds independent glucose-lowering.", "clinicalSignificance": "Combination can produce hypoglycemia, especially in older patients or with missed meals.", "managementStrategy": "Tell prescriber before adding; monitor glucose closely for 4 weeks; consider a glimepiride dose reduction.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Quercetin", "supplementBName": "Glipizide", "interactionType": "caution", "severity": "moderate", "description": "Quercetin is a flavonoid that inhibits CYP2C9 in human studies (it reduced diclofenac CYP2C9-mediated metabolism at 500 mg twice daily). Glipizide is metabolized primarily by CYP2C9. The combination can raise glipizide exposure and amplify its glucose-lowering, particularly at concentrated supplemental doses (versus dietary quercetin from fruits and vegetables).", "recommendation": "Avoid concentrated quercetin supplements (>500 mg/day) on glipizide unless your prescriber agrees. If you take both, monitor fingerstick glucose more often during the first 2-4 weeks and ask whether the glipizide dose should be reduced. Dietary quercetin from foods is unlikely to matter clinically.", "minimumTimeSeparation": null, "mechanism": "Quercetin and other flavonols inhibit CYP2C9 (Ki ~1-2 microM) by binding the active site. CYP2C9 is the primary enzyme metabolizing glipizide, so inhibition raises plasma drug concentrations and prolongs the hypoglycemic effect.", "evidenceLevel": "moderate", "sources": [ { "text": "Bedada SK, Neerati P. Evaluation of the effect of quercetin treatment on CYP2C9 enzyme activity of diclofenac in healthy human volunteers. Phytother Res. 2018;32(2):305-311.", "pmid": "29168292", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29168292/", "publicSourceType": "PMID" }, { "text": "Si D, Wang Y, Zhou YH, et al. Mechanism of CYP2C9 inhibition by flavones and flavonols. Drug Metab Dispos. 2009;37(3):629-634.", "pmid": "19074529", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19074529/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Supplemental quercetin can raise glipizide exposure via CYP2C9 inhibition.", "clinicalSignificance": "Clinically relevant CYP2C9 inhibition demonstrated at 500 mg twice daily in humans; dietary quercetin is unlikely to matter.", "managementStrategy": "Avoid concentrated quercetin supplements; if used, monitor glucose closely and consider a glipizide dose reduction.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Quercetin", "supplementBName": "Glyburide", "interactionType": "caution", "severity": "serious", "description": "Quercetin inhibits CYP2C9 in human studies. Glyburide is metabolized by CYP2C9 (and CYP3A4) and is the longest-acting US sulfonylurea with the highest hypoglycemia risk in its class. Concentrated quercetin supplements can raise glyburide exposure and prolong its hypoglycemic effect, particularly in older adults and patients with renal impairment.", "recommendation": "Avoid concentrated quercetin supplements (>500 mg/day) on glyburide unless your prescriber agrees. Dietary quercetin from foods is generally fine. If you take a supplement, monitor fasting and bedtime glucose for the first 4 weeks and discuss whether glyburide should be reduced.", "minimumTimeSeparation": null, "mechanism": "Quercetin inhibits CYP2C9 (and to a lesser extent CYP3A4), the primary enzymes metabolizing glyburide. Inhibition raises plasma drug concentrations. Glyburide's active metabolites accumulate in renal impairment, further prolonging the hypoglycemic window.", "evidenceLevel": "moderate", "sources": [ { "text": "Bedada SK, Neerati P. Evaluation of the effect of quercetin treatment on CYP2C9 enzyme activity of diclofenac in healthy human volunteers. Phytother Res. 2018;32(2):305-311.", "pmid": "29168292", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29168292/", "publicSourceType": "PMID" }, { "text": "Si D, Wang Y, Zhou YH, et al. Mechanism of CYP2C9 inhibition by flavones and flavonols. Drug Metab Dispos. 2009;37(3):629-634.", "pmid": "19074529", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19074529/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Supplemental quercetin can raise glyburide exposure via CYP2C9 inhibition.", "clinicalSignificance": "Glyburide hypoglycemia is the most common drug-induced low blood sugar admission in older diabetics.", "managementStrategy": "Avoid concentrated quercetin supplements; if used, monitor glucose closely for 4 weeks and consider a glyburide dose reduction.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Quercetin", "supplementBName": "Glimepiride", "interactionType": "caution", "severity": "moderate", "description": "Quercetin inhibits CYP2C9 in human studies. Glimepiride is metabolized primarily by CYP2C9. Concentrated quercetin supplements can raise glimepiride exposure and prolong its hypoglycemic effect, especially in older adults or with missed meals.", "recommendation": "Avoid concentrated quercetin supplements (>500 mg/day) on glimepiride unless your prescriber agrees. Dietary quercetin from foods is generally fine. If you take a supplement, monitor glucose more often during the first 2-4 weeks and discuss whether glimepiride should be reduced.", "minimumTimeSeparation": null, "mechanism": "Quercetin inhibits CYP2C9 at supplemental doses, raising plasma concentrations of CYP2C9 substrates including glimepiride. This prolongs and amplifies the hypoglycemic effect.", "evidenceLevel": "moderate", "sources": [ { "text": "Bedada SK, Neerati P. Evaluation of the effect of quercetin treatment on CYP2C9 enzyme activity of diclofenac in healthy human volunteers. Phytother Res. 2018;32(2):305-311.", "pmid": "29168292", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29168292/", "publicSourceType": "PMID" }, { "text": "Si D, Wang Y, Zhou YH, et al. Mechanism of CYP2C9 inhibition by flavones and flavonols. Drug Metab Dispos. 2009;37(3):629-634.", "pmid": "19074529", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19074529/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Supplemental quercetin can raise glimepiride exposure via CYP2C9 inhibition.", "clinicalSignificance": "Clinically relevant CYP2C9 inhibition demonstrated at 500 mg twice daily in humans.", "managementStrategy": "Avoid concentrated quercetin supplements; monitor glucose closely; consider a glimepiride dose reduction.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Ginger Extract", "supplementBName": "Semaglutide", "interactionType": "synergy", "severity": "info", "description": "Semaglutide commonly causes nausea, especially during dose titration; about 1 in 5 patients reports nausea in clinical trials. Ginger reduces nausea in pregnancy, postoperative, and chemotherapy-induced nausea meta-analyses and is one of the best-tolerated antinausea options. Combined with semaglutide, ginger can reduce GLP-1 nausea without affecting glycemic efficacy. Concentrated ginger does have antiplatelet activity so caution applies in patients on anticoagulants.", "recommendation": "If semaglutide nausea is a problem, ginger 1-2 g/day (capsules or tea) is a reasonable adjunct. Take it with meals. If you are also on warfarin or another anticoagulant, discuss with your prescriber first.", "minimumTimeSeparation": null, "mechanism": "Ginger's gingerols and shogaols are 5-HT3 receptor antagonists and modulate gastric motility, reducing nausea. Semaglutide slows gastric emptying and reduces appetite via central and peripheral GLP-1 receptor signaling, which can produce nausea. Ginger's antiemetic effect does not interfere with semaglutide's incretin action.", "evidenceLevel": "moderate", "sources": [ { "text": "Crichton M, Marshall S, Marx W, McCarthy AL, Isenring E. Efficacy of Ginger (Zingiber officinale) in Ameliorating Chemotherapy-Induced Nausea and Vomiting and Chemotherapy-Related Outcomes: A Systematic Review Update and Meta-Analysis. J Acad Nutr Diet. 2019;119(12):2055-2068.", "pmid": "31519467", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31519467/", "publicSourceType": "PMID" }, { "text": "Li Z, Wu J, Song J, Wen Y. Ginger for treating nausea and vomiting: an overview of systematic reviews and meta-analyses. Int J Food Sci Nutr. 2024;75(2):143-159.", "pmid": "38072785", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38072785/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Ginger can reduce semaglutide-related nausea without affecting glucose-lowering.", "clinicalSignificance": "Useful adjunct during dose titration; minor caveat for patients on anticoagulants.", "managementStrategy": "Ginger 1-2 g/day with meals; check with prescriber if on warfarin or another anticoagulant.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Ginger Extract", "supplementBName": "Liraglutide", "interactionType": "synergy", "severity": "info", "description": "Liraglutide commonly causes nausea, especially during dose titration. Ginger reduces nausea in pregnancy, postoperative, and chemotherapy-induced nausea meta-analyses and is one of the best-tolerated antinausea options. Combined with liraglutide, ginger can reduce GLP-1 nausea without affecting glycemic or weight efficacy.", "recommendation": "If liraglutide nausea is a problem, ginger 1-2 g/day (capsules or tea) is a reasonable adjunct. Take it with meals. If you are also on warfarin or another anticoagulant, discuss with your prescriber first.", "minimumTimeSeparation": null, "mechanism": "Ginger's gingerols and shogaols are 5-HT3 receptor antagonists and modulate gastric motility, reducing nausea. Liraglutide slows gastric emptying and reduces appetite via GLP-1 receptor signaling, which can produce nausea. The antiemetic effect of ginger does not interfere with liraglutide's incretin action.", "evidenceLevel": "moderate", "sources": [ { "text": "Crichton M, Marshall S, Marx W, McCarthy AL, Isenring E. Efficacy of Ginger (Zingiber officinale) in Ameliorating Chemotherapy-Induced Nausea and Vomiting and Chemotherapy-Related Outcomes: A Systematic Review Update and Meta-Analysis. J Acad Nutr Diet. 2019;119(12):2055-2068.", "pmid": "31519467", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31519467/", "publicSourceType": "PMID" }, { "text": "Li Z, Wu J, Song J, Wen Y. Ginger for treating nausea and vomiting: an overview of systematic reviews and meta-analyses. Int J Food Sci Nutr. 2024;75(2):143-159.", "pmid": "38072785", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38072785/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Ginger can reduce liraglutide-related nausea without affecting glucose-lowering.", "clinicalSignificance": "Useful adjunct during dose titration; minor caveat for patients on anticoagulants.", "managementStrategy": "Ginger 1-2 g/day with meals; check with prescriber if on warfarin or another anticoagulant.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Ginger Extract", "supplementBName": "Dulaglutide", "interactionType": "synergy", "severity": "info", "description": "Dulaglutide commonly causes nausea, especially during dose titration. Ginger reduces nausea in pregnancy, postoperative, and chemotherapy-induced nausea meta-analyses. Combined with dulaglutide, ginger can reduce GLP-1 nausea without affecting glycemic efficacy.", "recommendation": "If dulaglutide nausea is a problem, ginger 1-2 g/day (capsules or tea) is a reasonable adjunct. Take it with meals. If you are also on warfarin or another anticoagulant, discuss with your prescriber first.", "minimumTimeSeparation": null, "mechanism": "Ginger's gingerols and shogaols are 5-HT3 receptor antagonists and modulate gastric motility, reducing nausea. Dulaglutide slows gastric emptying and reduces appetite via GLP-1 receptor signaling, which can produce nausea. Ginger's antiemetic effect does not interfere with dulaglutide's incretin action.", "evidenceLevel": "moderate", "sources": [ { "text": "Crichton M, Marshall S, Marx W, McCarthy AL, Isenring E. Efficacy of Ginger (Zingiber officinale) in Ameliorating Chemotherapy-Induced Nausea and Vomiting and Chemotherapy-Related Outcomes: A Systematic Review Update and Meta-Analysis. J Acad Nutr Diet. 2019;119(12):2055-2068.", "pmid": "31519467", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31519467/", "publicSourceType": "PMID" }, { "text": "Li Z, Wu J, Song J, Wen Y. Ginger for treating nausea and vomiting: an overview of systematic reviews and meta-analyses. Int J Food Sci Nutr. 2024;75(2):143-159.", "pmid": "38072785", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38072785/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Ginger can reduce dulaglutide-related nausea without affecting glucose-lowering.", "clinicalSignificance": "Useful adjunct during dose titration; minor caveat for patients on anticoagulants.", "managementStrategy": "Ginger 1-2 g/day with meals; check with prescriber if on warfarin or another anticoagulant.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Psyllium Husk", "supplementBName": "Semaglutide", "interactionType": "synergy", "severity": "info", "description": "Psyllium husk is a soluble fiber that reduces postprandial glucose and HbA1c in type 2 diabetes meta-analyses by slowing carbohydrate absorption. Semaglutide also slows gastric emptying and lowers postprandial glucose. Combined, the two reduce postprandial spikes without driving hypoglycemia, though additive GI slowing can intensify bloating, constipation, or early satiety. Psyllium can also bind oral medications, but semaglutide injectable doses bypass this concern.", "recommendation": "Psyllium (5-10 g/day, split with meals) is a reasonable adjunct on semaglutide. Drink plenty of water and increase the dose gradually to limit bloating. For oral semaglutide tablets specifically, take semaglutide at least 4 hours before or after psyllium to avoid impaired absorption.", "minimumTimeSeparation": 240, "mechanism": "Psyllium forms a viscous gel in the gut that slows gastric emptying and reduces postprandial glucose absorption. Semaglutide activates GLP-1 receptors, slowing gastric emptying and augmenting glucose-dependent insulin secretion. Psyllium's gel can also bind to oral drugs, reducing their absorption, which is relevant for oral semaglutide (Rybelsus) but not subcutaneous semaglutide.", "evidenceLevel": "moderate", "sources": [ { "text": "Gibb RD, McRorie JW Jr, Russell DA, Hasselblad V, D'Alessio DA. Psyllium fiber improves glycemic control proportional to loss of glycemic control. Am J Clin Nutr. 2015;102(6):1604-1614.", "pmid": "26561625", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26561625/", "publicSourceType": "PMID" }, { "text": "Jalleh RJ, Rayner CK, Hausken T, et al. Gastrointestinal effects of GLP-1 receptor agonists: mechanisms, management, and future directions. Lancet Gastroenterol Hepatol. 2024;9(10):957-964.", "pmid": "39096914", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39096914/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Psyllium complements semaglutide on postprandial glucose; can bind oral semaglutide if co-administered.", "clinicalSignificance": "Useful combined therapy; oral semaglutide tablets require 4-hour spacing to preserve absorption.", "managementStrategy": "Psyllium 5-10 g/day with water; separate from oral semaglutide tablets by at least 4 hours.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Psyllium Husk", "supplementBName": "Liraglutide", "interactionType": "synergy", "severity": "info", "description": "Psyllium husk reduces postprandial glucose and HbA1c in type 2 diabetes by slowing carbohydrate absorption. Liraglutide also slows gastric emptying and lowers postprandial glucose. Combined, the two reduce postprandial spikes without driving hypoglycemia. Additive GI slowing can intensify bloating, constipation, or early satiety. Liraglutide is injected subcutaneously so psyllium's drug-binding effect does not apply to the medication itself.", "recommendation": "Psyllium (5-10 g/day, split with meals) is a reasonable adjunct on liraglutide. Drink plenty of water and increase the dose gradually to limit bloating. Separate psyllium from any oral medications by at least 2-4 hours to preserve their absorption.", "minimumTimeSeparation": null, "mechanism": "Psyllium forms a viscous gel in the gut that slows gastric emptying and reduces postprandial glucose absorption. Liraglutide activates GLP-1 receptors, slowing gastric emptying and augmenting glucose-dependent insulin secretion. The two effects on postprandial glucose are additive.", "evidenceLevel": "moderate", "sources": [ { "text": "Gibb RD, McRorie JW Jr, Russell DA, Hasselblad V, D'Alessio DA. Psyllium fiber improves glycemic control proportional to loss of glycemic control. Am J Clin Nutr. 2015;102(6):1604-1614.", "pmid": "26561625", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26561625/", "publicSourceType": "PMID" }, { "text": "Jalleh RJ, Rayner CK, Hausken T, et al. Gastrointestinal effects of GLP-1 receptor agonists: mechanisms, management, and future directions. Lancet Gastroenterol Hepatol. 2024;9(10):957-964.", "pmid": "39096914", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39096914/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Psyllium complements liraglutide on postprandial glucose with low hypoglycemia risk.", "clinicalSignificance": "Useful combined therapy; watch for additive GI side effects during titration.", "managementStrategy": "Psyllium 5-10 g/day with water; titrate slowly; separate from oral drugs by 2-4 hours.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Psyllium Husk", "supplementBName": "Dulaglutide", "interactionType": "synergy", "severity": "info", "description": "Psyllium husk reduces postprandial glucose and HbA1c in type 2 diabetes by slowing carbohydrate absorption. Dulaglutide also slows gastric emptying and lowers postprandial glucose. The combination reduces postprandial spikes without driving hypoglycemia, though additive GI slowing can intensify bloating or early satiety. Dulaglutide is injected so psyllium's drug-binding does not apply.", "recommendation": "Psyllium (5-10 g/day, split with meals) is a reasonable adjunct on dulaglutide. Drink plenty of water and increase the dose gradually to limit bloating. Separate psyllium from any oral medications by at least 2-4 hours.", "minimumTimeSeparation": null, "mechanism": "Psyllium forms a viscous gel in the gut that slows gastric emptying and reduces postprandial glucose absorption. Dulaglutide activates GLP-1 receptors, slowing gastric emptying and augmenting glucose-dependent insulin secretion. Both lower postprandial glucose.", "evidenceLevel": "moderate", "sources": [ { "text": "Gibb RD, McRorie JW Jr, Russell DA, Hasselblad V, D'Alessio DA. Psyllium fiber improves glycemic control proportional to loss of glycemic control. Am J Clin Nutr. 2015;102(6):1604-1614.", "pmid": "26561625", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26561625/", "publicSourceType": "PMID" }, { "text": "Jalleh RJ, Rayner CK, Hausken T, et al. Gastrointestinal effects of GLP-1 receptor agonists: mechanisms, management, and future directions. Lancet Gastroenterol Hepatol. 2024;9(10):957-964.", "pmid": "39096914", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39096914/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Psyllium complements dulaglutide on postprandial glucose with low hypoglycemia risk.", "clinicalSignificance": "Useful combined therapy; watch for additive GI side effects.", "managementStrategy": "Psyllium 5-10 g/day with water; titrate slowly; separate from oral drugs by 2-4 hours.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Psyllium Husk", "supplementBName": "Metformin", "interactionType": "timingSensitive", "severity": "moderate", "description": "Psyllium forms a viscous gel that slows gastric emptying and can bind oral drugs in the gut, modestly reducing their absorption. Metformin is a relatively low-bioavailability drug (50-60%) that depends on enterocyte transporters in the small intestine. Co-administering psyllium with metformin can lower metformin Cmax and possibly its glucose-lowering effect, although clinical impact varies.", "recommendation": "Take psyllium and metformin at different times, ideally with metformin taken 2 hours before or 4 hours after psyllium. Drink plenty of water with both.", "minimumTimeSeparation": 120, "mechanism": "Psyllium's soluble fiber forms a hydrogel that physically traps small molecules, slows gastric emptying, and can reduce the rate (and sometimes extent) of drug absorption. Metformin is absorbed via PMAT/OCT3 transporters in the upper small intestine, where its absorption is sensitive to transit time and viscosity.", "evidenceLevel": "emerging", "sources": [ { "text": "Heaney RP, Weaver CM. Effect of psyllium on absorption of co-ingested calcium. J Am Geriatr Soc. 1995;43(3):261-263.", "pmid": "7884114", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7884114/", "publicSourceType": "PMID" }, { "text": "Chiu AC, Sherman SI. Effects of pharmacological fiber supplements on levothyroxine absorption. Thyroid. 1998;8(8):667-671.", "pmid": "9737361", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9737361/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Psyllium may reduce metformin absorption when taken together.", "clinicalSignificance": "Documented effect on calcium and levothyroxine absorption; metformin absorption is plausibly affected by the same mechanism.", "managementStrategy": "Separate psyllium and metformin by at least 2 hours; drink plenty of water with both.", "isSynergistic": null, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Magnesium Glycinate", "supplementBName": "Insulin Glargine", "interactionType": "synergy", "severity": "info", "description": "Magnesium is a cofactor for insulin signaling, and low intracellular magnesium contributes to insulin resistance. Meta-analyses of oral magnesium supplementation in type 2 diabetes show modest reductions in fasting glucose, HbA1c, and HOMA-IR. Combined with insulin glargine, magnesium can improve insulin sensitivity over weeks and may modestly reduce basal insulin requirements without driving acute hypoglycemia.", "recommendation": "If you take insulin glargine and your dietary magnesium is low, supplementation (typically 200-350 mg elemental magnesium/day) is reasonable. Monitor fasting glucose; if you notice persistent lows over weeks, ask your prescriber whether your glargine dose should be reduced.", "minimumTimeSeparation": null, "mechanism": "Magnesium is required for autophosphorylation of the insulin receptor tyrosine kinase and for downstream signaling that drives GLUT4 translocation. Repleting magnesium improves cellular insulin sensitivity. Insulin glargine provides 24-hour basal insulin receptor activation. Improved sensitivity gradually reduces basal insulin needs.", "evidenceLevel": "moderate", "sources": [ { "text": "Rodríguez-Morán M, Guerrero-Romero F. Oral magnesium supplementation improves insulin sensitivity and metabolic control in type 2 diabetic subjects: a randomized double-blind controlled trial. Diabetes Care. 2003;26(4):1147-1152.", "pmid": "12663588", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12663588/", "publicSourceType": "PMID" }, { "text": "Asbaghi O, Moradi S, Kashkooli S, et al. The effects of oral magnesium supplementation on glycaemic control in patients with type 2 diabetes: a systematic review and dose-response meta-analysis of controlled clinical trials. Br J Nutr. 2022;128(12):2363-2372.", "pmid": "35045911", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35045911/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Magnesium repletion modestly improves insulin sensitivity and may reduce basal insulin needs over weeks.", "clinicalSignificance": "Clinically useful in patients with low magnesium; unlikely to cause acute hypoglycemia.", "managementStrategy": "Supplement 200-350 mg elemental magnesium/day; monitor fasting glucose; discuss glargine dose adjustments.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Magnesium Glycinate", "supplementBName": "Metformin", "interactionType": "synergy", "severity": "info", "description": "Magnesium is a cofactor for insulin receptor signaling and low intracellular magnesium contributes to insulin resistance, a problem common in type 2 diabetes. Meta-analyses show oral magnesium supplementation modestly lowers fasting glucose, HbA1c, and HOMA-IR. Combined with metformin the effect is complementary, with both targeting insulin resistance through different mechanisms and a low risk of hypoglycemia.", "recommendation": "If you take metformin and your dietary magnesium is low or you have leg cramps, magnesium supplementation (typically 200-350 mg elemental magnesium/day) is reasonable. Routine glucose monitoring is sufficient.", "minimumTimeSeparation": null, "mechanism": "Magnesium is required for autophosphorylation of the insulin receptor tyrosine kinase and for GLUT4 translocation. Metformin activates AMPK, reduces hepatic gluconeogenesis, and improves peripheral insulin sensitivity. The mechanisms converge on improved insulin signaling.", "evidenceLevel": "moderate", "sources": [ { "text": "Song Y, He K, Levitan EB, Manson JE, Liu S. Effects of oral magnesium supplementation on glycaemic control in Type 2 diabetes: a meta-analysis of randomized double-blind controlled trials. Diabet Med. 2006;23(10):1050-1056.", "pmid": "16978367", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16978367/", "publicSourceType": "PMID" }, { "text": "Asbaghi O, Moradi S, Kashkooli S, et al. The effects of oral magnesium supplementation on glycaemic control in patients with type 2 diabetes: a systematic review and dose-response meta-analysis of controlled clinical trials. Br J Nutr. 2022;128(12):2363-2372.", "pmid": "35045911", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35045911/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Magnesium repletion complements metformin's insulin-sensitizing effects.", "clinicalSignificance": "Useful in patients with low magnesium or muscle cramps; low risk of hypoglycemia.", "managementStrategy": "Supplement 200-350 mg elemental magnesium/day; routine glucose monitoring.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Furosemide", "supplementBName": "Magnesium Citrate", "interactionType": "synergy", "severity": "moderate", "description": "Furosemide can increase urinary magnesium loss during chronic therapy. Magnesium citrate may help replete magnesium when levels are low, but unmonitored replacement can be unsafe in kidney disease. Low magnesium can also make low potassium harder to correct and may contribute to cramps or arrhythmias.", "recommendation": "If you use furosemide long term, ask for periodic magnesium and potassium checks. Use magnesium citrate for replacement only at reasonable doses and avoid high-dose use if you have reduced kidney function unless your prescriber is monitoring labs.", "minimumTimeSeparation": null, "mechanism": "Loop diuretics inhibit NKCC2 in the thick ascending limb, reducing the lumen-positive voltage that drives paracellular magnesium reabsorption. Supplemental magnesium citrate provides magnesium to replace renal losses.", "evidenceLevel": "moderate", "sources": [ { "text": "Brater DC. Diuretic therapy. N Engl J Med. 1998;339(6):387-395.", "pmid": "9691107", "doi": "10.1056/NEJM199808063390607", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9691107/", "publicSourceType": "PMID" }, { "text": "Mohn ES, Kern HJ, Saltzman E, Mitmesser SH, McKay DL. Evidence of Drug-Nutrient Interactions with Chronic Use of Commonly Prescribed Medications: An Update. Pharmaceutics. 2018;10(1):36.", "pmid": "29558445", "doi": "10.3390/pharmaceutics10010036", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29558445/", "publicSourceType": "PMID" }, { "text": "Dai LJ, Ritchie G, Kerstan D, Kang HS, Cole DE, Quamme GA. Magnesium transport in the renal distal convoluted tubule. Physiol Rev. 2001;81(1):51-84.", "pmid": "11152754", "doi": "10.1152/physrev.2001.81.1.51", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11152754/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Furosemide increases renal magnesium loss, making magnesium repletion more likely to be needed.", "clinicalSignificance": "Hypomagnesemia can worsen muscle symptoms, arrhythmia risk, and refractory hypokalemia in diuretic users.", "managementStrategy": "Monitor magnesium and potassium during chronic furosemide therapy and replace magnesium if low.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Furosemide", "supplementBName": "Magnesium Malate", "interactionType": "synergy", "severity": "moderate", "description": "Furosemide can waste magnesium through the kidney, especially with higher doses or long-term use. Magnesium malate is a magnesium-containing supplement that may help correct depletion when labs or symptoms support replacement. The main safety concern is oversupplementation in people with impaired kidney function.", "recommendation": "Have magnesium and potassium monitored if you take furosemide chronically or develop cramps, weakness, palpitations, or hard-to-correct low potassium. Keep magnesium malate dosing moderate unless your clinician specifically recommends a higher replacement dose.", "minimumTimeSeparation": null, "mechanism": "By blocking NKCC2 in the thick ascending limb, furosemide disrupts the electrical gradient that normally supports magnesium reabsorption. Magnesium malate supplies elemental magnesium to offset renal magnesium wasting.", "evidenceLevel": "moderate", "sources": [ { "text": "Brater DC. Diuretic therapy. N Engl J Med. 1998;339(6):387-395.", "pmid": "9691107", "doi": "10.1056/NEJM199808063390607", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9691107/", "publicSourceType": "PMID" }, { "text": "Mohn ES, Kern HJ, Saltzman E, Mitmesser SH, McKay DL. Evidence of Drug-Nutrient Interactions with Chronic Use of Commonly Prescribed Medications: An Update. Pharmaceutics. 2018;10(1):36.", "pmid": "29558445", "doi": "10.3390/pharmaceutics10010036", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29558445/", "publicSourceType": "PMID" }, { "text": "Dai LJ, Ritchie G, Kerstan D, Kang HS, Cole DE, Quamme GA. Magnesium transport in the renal distal convoluted tubule. Physiol Rev. 2001;81(1):51-84.", "pmid": "11152754", "doi": "10.1152/physrev.2001.81.1.51", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11152754/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Furosemide increases magnesium wasting; magnesium malate may help replace the lost mineral.", "clinicalSignificance": "Magnesium depletion can contribute to cramps, weakness, arrhythmia susceptibility, and persistent hypokalemia.", "managementStrategy": "Use magnesium malate as monitored replacement when magnesium is low or clinically suspected.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Furosemide", "supplementBName": "Magnesium Taurate", "interactionType": "synergy", "severity": "moderate", "description": "Furosemide can cause clinically relevant magnesium depletion by increasing urinary magnesium excretion. Magnesium taurate may help replace magnesium, but the dose should be guided by symptoms, kidney function, and lab monitoring. People also taking digoxin or with arrhythmia history need extra attention because magnesium and potassium depletion can increase rhythm risk.", "recommendation": "Do not assume cramps or palpitations are harmless while taking furosemide; ask about checking magnesium and potassium. If magnesium taurate is used, keep the dose consistent and review it with your prescriber if you have kidney disease or heart rhythm problems.", "minimumTimeSeparation": null, "mechanism": "Furosemide blocks NKCC2 and lowers the transepithelial voltage that supports magnesium reabsorption in the thick ascending limb. Magnesium taurate provides supplemental magnesium to counter ongoing renal losses.", "evidenceLevel": "moderate", "sources": [ { "text": "Brater DC. Diuretic therapy. N Engl J Med. 1998;339(6):387-395.", "pmid": "9691107", "doi": "10.1056/NEJM199808063390607", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9691107/", "publicSourceType": "PMID" }, { "text": "Mohn ES, Kern HJ, Saltzman E, Mitmesser SH, McKay DL. Evidence of Drug-Nutrient Interactions with Chronic Use of Commonly Prescribed Medications: An Update. Pharmaceutics. 2018;10(1):36.", "pmid": "29558445", "doi": "10.3390/pharmaceutics10010036", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29558445/", "publicSourceType": "PMID" }, { "text": "Dai LJ, Ritchie G, Kerstan D, Kang HS, Cole DE, Quamme GA. Magnesium transport in the renal distal convoluted tubule. Physiol Rev. 2001;81(1):51-84.", "pmid": "11152754", "doi": "10.1152/physrev.2001.81.1.51", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11152754/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Furosemide promotes magnesium loss, while magnesium taurate can support repletion.", "clinicalSignificance": "Correcting magnesium depletion can reduce symptoms and improve correction of associated potassium depletion.", "managementStrategy": "Monitor electrolytes and use magnesium taurate as replacement when clinically indicated.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Furosemide", "supplementBName": "Vitamin B1", "interactionType": "synergy", "severity": "moderate", "description": "Long-term furosemide therapy can increase urinary thiamine loss and has been linked with biochemical Vitamin B1 deficiency, especially in heart failure patients taking higher loop-diuretic doses. Deficiency can worsen fatigue, neuropathy, poor appetite, and in severe cases beriberi-like heart failure. Vitamin B1 supplementation can be useful when intake is low, diuretic exposure is high, or deficiency is suspected.", "recommendation": "If you take furosemide chronically, ask whether Vitamin B1 status or empiric low-risk supplementation is appropriate, especially if you have heart failure, poor nutrition, or heavy alcohol use. Do not use thiamine as a substitute for prescribed heart-failure care; use it as monitored nutritional support.", "minimumTimeSeparation": null, "mechanism": "Furosemide-induced diuresis increases urinary excretion of water-soluble thiamine. Replacing Vitamin B1 restores thiamine pyrophosphate needed for carbohydrate metabolism and myocardial energy production.", "evidenceLevel": "moderate", "sources": [ { "text": "Zenuk C, Healey J, Donnelly J, Vaillancourt R, Almalki Y, Smith S. Thiamine deficiency in congestive heart failure patients receiving long term furosemide therapy. Can J Clin Pharmacol. 2003;10(4):184-188.", "pmid": "14712323", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14712323/", "publicSourceType": "PMID" }, { "text": "Rieck J, Halkin H, Almog S, Seligman H, Lubetsky A, Olchovsky D, et al. Urinary loss of thiamine is increased by low doses of furosemide in healthy volunteers. J Lab Clin Med. 1999;134(3):238-243.", "pmid": "10482308", "doi": "10.1016/s0022-2143(99)90203-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10482308/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Furosemide can deplete thiamine, making Vitamin B1 replacement clinically useful in higher-risk users.", "clinicalSignificance": "Thiamine deficiency can mimic or worsen weakness and heart-failure symptoms.", "managementStrategy": "Consider Vitamin B1 assessment or supplementation in chronic furosemide users at nutritional risk.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Hydrochlorothiazide", "supplementBName": "Magnesium Citrate", "interactionType": "synergy", "severity": "moderate", "description": "Hydrochlorothiazide can increase renal magnesium excretion during chronic therapy. Magnesium citrate may help replace magnesium if levels fall, and magnesium repletion may also help correct diuretic-related low potassium. Risk is higher in older adults, people with low dietary magnesium intake, and those on long-term diuretic therapy.", "recommendation": "Ask for periodic magnesium and potassium checks if you use hydrochlorothiazide long term. Use magnesium citrate as replacement when labs or symptoms support it, and avoid high-dose magnesium if you have kidney disease unless supervised.", "minimumTimeSeparation": null, "mechanism": "Hydrochlorothiazide inhibits the sodium-chloride cotransporter in the distal convoluted tubule and can impair magnesium conservation over time. Supplemental magnesium citrate provides magnesium to offset chronic renal losses.", "evidenceLevel": "moderate", "sources": [ { "text": "Sica DA. Diuretic-related side effects: development and treatment. J Clin Hypertens (Greenwich). 2004;6(9):532-540.", "pmid": "15365284", "doi": "10.1111/j.1524-6175.2004.03789.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15365284/", "publicSourceType": "PMID" }, { "text": "Mohn ES, Kern HJ, Saltzman E, Mitmesser SH, McKay DL. Evidence of Drug-Nutrient Interactions with Chronic Use of Commonly Prescribed Medications: An Update. Pharmaceutics. 2018;10(1):36.", "pmid": "29558445", "doi": "10.3390/pharmaceutics10010036", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29558445/", "publicSourceType": "PMID" }, { "text": "Dai LJ, Ritchie G, Kerstan D, Kang HS, Cole DE, Quamme GA. Magnesium transport in the renal distal convoluted tubule. Physiol Rev. 2001;81(1):51-84.", "pmid": "11152754", "doi": "10.1152/physrev.2001.81.1.51", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11152754/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Hydrochlorothiazide may deplete magnesium; magnesium citrate can support replacement.", "clinicalSignificance": "Magnesium depletion can worsen cramps, arrhythmia susceptibility, and refractory hypokalemia.", "managementStrategy": "Monitor magnesium and potassium during chronic hydrochlorothiazide therapy and replace magnesium when low.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Hydrochlorothiazide", "supplementBName": "Magnesium Malate", "interactionType": "synergy", "severity": "moderate", "description": "Hydrochlorothiazide may gradually lower magnesium status by increasing urinary losses. Magnesium malate can help replenish magnesium when supplementation is appropriate. The combination is usually intentional and helpful, but magnesium replacement should still be monitored in kidney disease.", "recommendation": "If you take hydrochlorothiazide and develop cramps, weakness, palpitations, or persistent low potassium, ask whether magnesium should be checked. Use magnesium malate consistently and avoid large unsupervised doses if your kidney function is reduced.", "minimumTimeSeparation": null, "mechanism": "Thiazide inhibition of distal sodium-chloride transport changes distal tubular electrolyte handling and can increase magnesium wasting during chronic exposure. Magnesium malate supplies magnesium to replace this loss.", "evidenceLevel": "moderate", "sources": [ { "text": "Sica DA. Diuretic-related side effects: development and treatment. J Clin Hypertens (Greenwich). 2004;6(9):532-540.", "pmid": "15365284", "doi": "10.1111/j.1524-6175.2004.03789.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15365284/", "publicSourceType": "PMID" }, { "text": "Mohn ES, Kern HJ, Saltzman E, Mitmesser SH, McKay DL. Evidence of Drug-Nutrient Interactions with Chronic Use of Commonly Prescribed Medications: An Update. Pharmaceutics. 2018;10(1):36.", "pmid": "29558445", "doi": "10.3390/pharmaceutics10010036", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29558445/", "publicSourceType": "PMID" }, { "text": "Dai LJ, Ritchie G, Kerstan D, Kang HS, Cole DE, Quamme GA. Magnesium transport in the renal distal convoluted tubule. Physiol Rev. 2001;81(1):51-84.", "pmid": "11152754", "doi": "10.1152/physrev.2001.81.1.51", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11152754/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Hydrochlorothiazide increases magnesium wasting; magnesium malate may help replete magnesium.", "clinicalSignificance": "Low magnesium can make thiazide-related potassium problems more difficult to correct.", "managementStrategy": "Check magnesium and potassium periodically and supplement magnesium if low.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Hydrochlorothiazide", "supplementBName": "Magnesium Taurate", "interactionType": "synergy", "severity": "moderate", "description": "Hydrochlorothiazide can produce chronic magnesium wasting, and magnesium taurate provides magnesium that may help restore stores. This is most relevant when hydrochlorothiazide also causes low potassium or when symptoms suggest electrolyte depletion. Kidney impairment increases the risk of excess magnesium from supplementation.", "recommendation": "Use magnesium taurate as a monitored replacement strategy rather than as a substitute for lab checks. Ask for magnesium and potassium monitoring after dose changes or if you have cramps, weakness, palpitations, or recurrent low potassium.", "minimumTimeSeparation": null, "mechanism": "Hydrochlorothiazide inhibits NCC in the distal convoluted tubule and can reduce magnesium conservation over time. Supplemental magnesium taurate helps offset renal magnesium losses.", "evidenceLevel": "moderate", "sources": [ { "text": "Sica DA. Diuretic-related side effects: development and treatment. J Clin Hypertens (Greenwich). 2004;6(9):532-540.", "pmid": "15365284", "doi": "10.1111/j.1524-6175.2004.03789.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15365284/", "publicSourceType": "PMID" }, { "text": "Mohn ES, Kern HJ, Saltzman E, Mitmesser SH, McKay DL. Evidence of Drug-Nutrient Interactions with Chronic Use of Commonly Prescribed Medications: An Update. Pharmaceutics. 2018;10(1):36.", "pmid": "29558445", "doi": "10.3390/pharmaceutics10010036", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29558445/", "publicSourceType": "PMID" }, { "text": "Dai LJ, Ritchie G, Kerstan D, Kang HS, Cole DE, Quamme GA. Magnesium transport in the renal distal convoluted tubule. Physiol Rev. 2001;81(1):51-84.", "pmid": "11152754", "doi": "10.1152/physrev.2001.81.1.51", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11152754/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Hydrochlorothiazide may lower magnesium status, while magnesium taurate supports replacement.", "clinicalSignificance": "Correcting magnesium may reduce symptoms and help stabilize potassium.", "managementStrategy": "Monitor electrolytes and replace magnesium when hydrochlorothiazide-related depletion is present.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Hydrochlorothiazide", "supplementBName": "Calcium", "interactionType": "caution", "severity": "moderate", "description": "Hydrochlorothiazide reduces urinary calcium excretion and can raise serum calcium. Adding high-dose calcium supplements can increase the risk of hypercalcemia, especially in older adults or people with kidney disease, hyperparathyroidism, dehydration, or heavy calcium antacid use. Symptoms can include nausea, constipation, thirst, confusion, kidney injury, and rhythm problems when severe.", "recommendation": "Avoid high-dose calcium supplementation while taking hydrochlorothiazide unless your prescriber recommends it. Keep total calcium intake within your goal range and ask for serum calcium monitoring if you use calcium daily, have kidney stones, or develop hypercalcemia symptoms.", "minimumTimeSeparation": null, "mechanism": "Thiazides increase distal tubular calcium reabsorption and lower urinary calcium loss. Calcium supplements increase calcium load, so the combination can exceed renal and hormonal buffering capacity in susceptible patients.", "evidenceLevel": "moderate", "sources": [ { "text": "Wermers RA, Kearns AE, Jenkins GD, Melton LJ 3rd. Incidence and clinical spectrum of thiazide-associated hypercalcemia. Am J Med. 2007;120(10):911.e9-911.e15.", "pmid": "17904464", "doi": "10.1016/j.amjmed.2006.07.044", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17904464/", "publicSourceType": "PMID" }, { "text": "Desai HV, Gandhi K, Sharma M, Jennine M, Singh P, Brogan M. Thiazide-induced severe hypercalcemia: a case report and review of literature. Am J Ther. 2010;17(6):e234-e236.", "pmid": "20068444", "doi": "10.1097/MJT.0b013e3181c6c21b", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20068444/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Hydrochlorothiazide retains calcium while calcium supplements add more calcium load.", "clinicalSignificance": "The combination can trigger clinically important hypercalcemia in susceptible patients.", "managementStrategy": "Avoid high-dose calcium and monitor serum calcium if daily supplementation is needed.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Hydrochlorothiazide", "supplementBName": "Vitamin D3", "interactionType": "caution", "severity": "moderate", "description": "Hydrochlorothiazide can raise serum calcium by reducing urinary calcium loss, while Vitamin D3 increases intestinal calcium absorption. Standard Vitamin D3 doses are often tolerated, but high-dose supplementation can increase hypercalcemia risk in people with kidney disease, hyperparathyroidism, sarcoidosis, or high calcium intake. The risk is mainly a lab and dose-monitoring issue rather than a timing issue.", "recommendation": "Use conservative Vitamin D3 dosing unless your clinician is monitoring calcium and 25-hydroxyvitamin D. If you take hydrochlorothiazide plus daily or high-dose Vitamin D3, ask whether serum calcium should be checked after starting or changing doses.", "minimumTimeSeparation": null, "mechanism": "Hydrochlorothiazide increases renal tubular calcium reabsorption. Vitamin D3 is converted to active vitamin D metabolites that increase intestinal calcium absorption, so both pathways can raise serum calcium.", "evidenceLevel": "moderate", "sources": [ { "text": "Chandler PD, Scott JB, Drake BF, Ng K, Forman JP, Chan AT, et al. Risk of hypercalcemia in blacks taking hydrochlorothiazide and vitamin D. Am J Med. 2014;127(8):772-778.", "pmid": "24657333", "doi": "10.1016/j.amjmed.2014.02.044", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24657333/", "publicSourceType": "PMID" }, { "text": "Wermers RA, Kearns AE, Jenkins GD, Melton LJ 3rd. Incidence and clinical spectrum of thiazide-associated hypercalcemia. Am J Med. 2007;120(10):911.e9-911.e15.", "pmid": "17904464", "doi": "10.1016/j.amjmed.2006.07.044", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17904464/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Hydrochlorothiazide and Vitamin D3 can both push serum calcium upward.", "clinicalSignificance": "Most users tolerate usual doses, but high-risk patients can develop hypercalcemia.", "managementStrategy": "Use monitored Vitamin D3 dosing and check calcium when risk factors or high doses are present.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Hydrochlorothiazide", "supplementBName": "Vitamin D2", "interactionType": "caution", "severity": "moderate", "description": "Hydrochlorothiazide reduces urinary calcium excretion, and Vitamin D2 can increase calcium absorption after conversion to active vitamin D metabolites. The concern is hypercalcemia when Vitamin D2 is taken in high doses or combined with high calcium intake. People with kidney disease, hyperparathyroidism, granulomatous disease, or dehydration are at higher risk.", "recommendation": "Do not combine hydrochlorothiazide with high-dose Vitamin D2 without a monitoring plan. Ask for serum calcium monitoring after starting or changing Vitamin D2, especially if you also take calcium or have a history of kidney stones.", "minimumTimeSeparation": null, "mechanism": "Thiazide diuretics increase distal calcium reabsorption, while Vitamin D2 repletion increases intestinal calcium uptake. The combined effect can raise serum calcium in susceptible patients.", "evidenceLevel": "emerging", "sources": [ { "text": "Wermers RA, Kearns AE, Jenkins GD, Melton LJ 3rd. Incidence and clinical spectrum of thiazide-associated hypercalcemia. Am J Med. 2007;120(10):911.e9-911.e15.", "pmid": "17904464", "doi": "10.1016/j.amjmed.2006.07.044", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17904464/", "publicSourceType": "PMID" }, { "text": "Chandler PD, Scott JB, Drake BF, Ng K, Forman JP, Chan AT, et al. Risk of hypercalcemia in blacks taking hydrochlorothiazide and vitamin D. Am J Med. 2014;127(8):772-778.", "pmid": "24657333", "doi": "10.1016/j.amjmed.2014.02.044", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24657333/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Hydrochlorothiazide plus Vitamin D2 can increase serum calcium.", "clinicalSignificance": "The evidence is strongest for thiazides and vitamin D generally, so high-dose Vitamin D2 deserves monitoring.", "managementStrategy": "Use Vitamin D2 with calcium monitoring when doses are high or risk factors are present.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Chlorthalidone", "supplementBName": "Potassium", "interactionType": "synergy", "severity": "moderate", "description": "Chlorthalidone commonly lowers serum potassium through renal potassium wasting. Potassium supplementation can be clinically useful when levels are low, but excessive supplementation can be risky in kidney disease or when combined with ACE inhibitors, ARBs, or potassium-sparing diuretics. Low potassium can cause weakness, cramps, palpitations, and arrhythmias.", "recommendation": "Do not self-treat chlorthalidone-related low potassium with high-dose potassium unless your prescriber confirms the dose. Check potassium after starting chlorthalidone, after dose changes, and periodically during chronic therapy.", "minimumTimeSeparation": null, "mechanism": "Chlorthalidone inhibits sodium-chloride transport in the distal convoluted tubule, increasing sodium delivery and flow to the collecting duct. ENaC-mediated sodium reabsorption there promotes potassium secretion through ROMK channels.", "evidenceLevel": "strong", "sources": [ { "text": "Cocco G, Iselin HU, Strozzi C, Cesana B, Baumeler HR. Magnesium depletion in patients on long-term chlorthalidone therapy for essential hypertension. Eur J Clin Pharmacol. 1987;32(4):335-338.", "pmid": "2886340", "doi": "10.1007/BF00543964", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2886340/", "publicSourceType": "PMID" }, { "text": "Sica DA. Diuretic-related side effects: development and treatment. J Clin Hypertens (Greenwich). 2004;6(9):532-540.", "pmid": "15365284", "doi": "10.1111/j.1524-6175.2004.03789.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15365284/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Chlorthalidone can deplete potassium, making potassium replacement appropriate when levels are low.", "clinicalSignificance": "Uncorrected hypokalemia can cause symptoms and increase arrhythmia risk.", "managementStrategy": "Monitor serum potassium and use potassium supplementation only at a prescribed dose.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Chlorthalidone", "supplementBName": "Magnesium Glycinate", "interactionType": "synergy", "severity": "moderate", "description": "Long-term chlorthalidone therapy can lower magnesium as well as potassium. Magnesium glycinate may help replace magnesium when levels are low or when low potassium is difficult to correct. Risk is higher with prolonged therapy, older age, low dietary magnesium intake, or high diuretic doses.", "recommendation": "Ask for magnesium and potassium checks if you take chlorthalidone chronically. Magnesium glycinate can be reasonable for repletion, but avoid high doses without monitoring if you have kidney disease.", "minimumTimeSeparation": null, "mechanism": "Chlorthalidone inhibits NCC in the distal convoluted tubule and can cause renal magnesium wasting over time. Magnesium glycinate provides replacement magnesium and may help stabilize potassium handling.", "evidenceLevel": "moderate", "sources": [ { "text": "Cocco G, Iselin HU, Strozzi C, Cesana B, Baumeler HR. Magnesium depletion in patients on long-term chlorthalidone therapy for essential hypertension. Eur J Clin Pharmacol. 1987;32(4):335-338.", "pmid": "2886340", "doi": "10.1007/BF00543964", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2886340/", "publicSourceType": "PMID" }, { "text": "Mohn ES, Kern HJ, Saltzman E, Mitmesser SH, McKay DL. Evidence of Drug-Nutrient Interactions with Chronic Use of Commonly Prescribed Medications: An Update. Pharmaceutics. 2018;10(1):36.", "pmid": "29558445", "doi": "10.3390/pharmaceutics10010036", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29558445/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Chlorthalidone can deplete magnesium; magnesium glycinate can support repletion.", "clinicalSignificance": "Magnesium depletion may contribute to cramps, arrhythmia susceptibility, and persistent low potassium.", "managementStrategy": "Monitor electrolytes and replace magnesium when chlorthalidone-related depletion is present.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Chlorthalidone", "supplementBName": "Magnesium Citrate", "interactionType": "synergy", "severity": "moderate", "description": "Chlorthalidone can cause magnesium depletion during long-term treatment. Magnesium citrate may help replenish magnesium, particularly when potassium is also low or difficult to normalize. The combination is usually supportive, but magnesium dosing still matters in kidney disease.", "recommendation": "If you take chlorthalidone, ask whether magnesium and potassium should be checked periodically. Use magnesium citrate as monitored repletion rather than escalating the dose on your own.", "minimumTimeSeparation": null, "mechanism": "Chlorthalidone alters distal tubular sodium handling and can increase magnesium loss over time. Supplemental magnesium citrate provides magnesium to counter chronic renal wasting.", "evidenceLevel": "moderate", "sources": [ { "text": "Cocco G, Iselin HU, Strozzi C, Cesana B, Baumeler HR. Magnesium depletion in patients on long-term chlorthalidone therapy for essential hypertension. Eur J Clin Pharmacol. 1987;32(4):335-338.", "pmid": "2886340", "doi": "10.1007/BF00543964", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2886340/", "publicSourceType": "PMID" }, { "text": "Mohn ES, Kern HJ, Saltzman E, Mitmesser SH, McKay DL. Evidence of Drug-Nutrient Interactions with Chronic Use of Commonly Prescribed Medications: An Update. Pharmaceutics. 2018;10(1):36.", "pmid": "29558445", "doi": "10.3390/pharmaceutics10010036", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29558445/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Chlorthalidone may lower magnesium status; magnesium citrate can replace magnesium.", "clinicalSignificance": "Magnesium depletion can worsen thiazide-related potassium problems and symptoms.", "managementStrategy": "Check magnesium and potassium and supplement magnesium if low.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Chlorthalidone", "supplementBName": "Magnesium Malate", "interactionType": "synergy", "severity": "moderate", "description": "Chlorthalidone has documented potential to lower magnesium during chronic treatment. Magnesium malate is a magnesium-containing supplement that can support replacement when depletion is present. This is most important when low magnesium accompanies low potassium, muscle symptoms, or arrhythmia risk.", "recommendation": "Ask your prescriber about checking magnesium if you use chlorthalidone long term. Use magnesium malate at a consistent replacement dose and avoid high-dose use without kidney-function monitoring.", "minimumTimeSeparation": null, "mechanism": "Chlorthalidone blocks NCC in the distal convoluted tubule and can increase renal magnesium wasting. Magnesium malate provides supplemental magnesium to offset this loss.", "evidenceLevel": "moderate", "sources": [ { "text": "Cocco G, Iselin HU, Strozzi C, Cesana B, Baumeler HR. Magnesium depletion in patients on long-term chlorthalidone therapy for essential hypertension. Eur J Clin Pharmacol. 1987;32(4):335-338.", "pmid": "2886340", "doi": "10.1007/BF00543964", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2886340/", "publicSourceType": "PMID" }, { "text": "Mohn ES, Kern HJ, Saltzman E, Mitmesser SH, McKay DL. Evidence of Drug-Nutrient Interactions with Chronic Use of Commonly Prescribed Medications: An Update. Pharmaceutics. 2018;10(1):36.", "pmid": "29558445", "doi": "10.3390/pharmaceutics10010036", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29558445/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Chlorthalidone can waste magnesium; magnesium malate may help replete magnesium.", "clinicalSignificance": "Replacing magnesium can matter when hypokalemia or muscle symptoms persist.", "managementStrategy": "Monitor electrolytes and use magnesium malate as replacement when clinically indicated.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Chlorthalidone", "supplementBName": "Magnesium Taurate", "interactionType": "synergy", "severity": "moderate", "description": "Chlorthalidone can lower magnesium and potassium during long-term use. Magnesium taurate may help replenish magnesium stores if supplementation is needed. Patients with kidney disease should avoid high magnesium doses unless labs are being followed.", "recommendation": "If you take chlorthalidone chronically, check whether magnesium monitoring is appropriate along with potassium monitoring. Use magnesium taurate cautiously and consistently, especially if kidney function is reduced.", "minimumTimeSeparation": null, "mechanism": "Chlorthalidone changes distal tubular electrolyte handling and can promote magnesium wasting. Magnesium taurate supplies magnesium that may offset this diuretic-related loss.", "evidenceLevel": "moderate", "sources": [ { "text": "Cocco G, Iselin HU, Strozzi C, Cesana B, Baumeler HR. Magnesium depletion in patients on long-term chlorthalidone therapy for essential hypertension. Eur J Clin Pharmacol. 1987;32(4):335-338.", "pmid": "2886340", "doi": "10.1007/BF00543964", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2886340/", "publicSourceType": "PMID" }, { "text": "Mohn ES, Kern HJ, Saltzman E, Mitmesser SH, McKay DL. Evidence of Drug-Nutrient Interactions with Chronic Use of Commonly Prescribed Medications: An Update. Pharmaceutics. 2018;10(1):36.", "pmid": "29558445", "doi": "10.3390/pharmaceutics10010036", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29558445/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Chlorthalidone can deplete magnesium; magnesium taurate can support replacement.", "clinicalSignificance": "Low magnesium can worsen potassium depletion and increase symptom burden.", "managementStrategy": "Monitor magnesium and potassium and replace magnesium when low.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Chlorthalidone", "supplementBName": "Calcium", "interactionType": "caution", "severity": "moderate", "description": "Chlorthalidone is thiazide-like and reduces urinary calcium loss, which can raise serum calcium. High-dose calcium supplements can add to that effect and increase hypercalcemia risk, especially with dehydration, kidney disease, hyperparathyroidism, or heavy calcium antacid use. Symptoms may include nausea, constipation, thirst, confusion, weakness, or kidney injury.", "recommendation": "Avoid high-dose calcium while taking chlorthalidone unless your prescriber recommends and monitors it. If you need daily calcium, keep the dose within your target intake and ask whether serum calcium should be checked.", "minimumTimeSeparation": null, "mechanism": "Thiazide and thiazide-like diuretics increase distal tubular calcium reabsorption and reduce urinary calcium excretion. Calcium supplementation increases absorbed calcium load, making hypercalcemia more likely in susceptible patients.", "evidenceLevel": "moderate", "sources": [ { "text": "Wermers RA, Kearns AE, Jenkins GD, Melton LJ 3rd. Incidence and clinical spectrum of thiazide-associated hypercalcemia. Am J Med. 2007;120(10):911.e9-911.e15.", "pmid": "17904464", "doi": "10.1016/j.amjmed.2006.07.044", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17904464/", "publicSourceType": "PMID" }, { "text": "Desai HV, Gandhi K, Sharma M, Jennine M, Singh P, Brogan M. Thiazide-induced severe hypercalcemia: a case report and review of literature. Am J Ther. 2010;17(6):e234-e236.", "pmid": "20068444", "doi": "10.1097/MJT.0b013e3181c6c21b", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20068444/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Chlorthalidone retains calcium while calcium supplements increase calcium load.", "clinicalSignificance": "The combination can produce hypercalcemia in at-risk patients.", "managementStrategy": "Avoid high-dose calcium and monitor serum calcium if daily supplementation is necessary.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Chlorthalidone", "supplementBName": "Vitamin D3", "interactionType": "caution", "severity": "moderate", "description": "Chlorthalidone can increase serum calcium by lowering urinary calcium excretion, while Vitamin D3 increases intestinal calcium absorption. Usual Vitamin D3 replacement is often tolerated, but high-dose supplementation or combined calcium use can increase hypercalcemia risk. This matters most in kidney disease, hyperparathyroidism, granulomatous disease, or dehydration.", "recommendation": "Use Vitamin D3 with a monitoring plan if you take chlorthalidone and need high-dose therapy. Ask about checking serum calcium after starting Vitamin D3, increasing the dose, or adding calcium.", "minimumTimeSeparation": null, "mechanism": "Chlorthalidone shares thiazide-like calcium-retaining effects in the distal nephron. Vitamin D3 increases calcium absorption, so the pathways can add together and raise serum calcium.", "evidenceLevel": "moderate", "sources": [ { "text": "Wermers RA, Kearns AE, Jenkins GD, Melton LJ 3rd. Incidence and clinical spectrum of thiazide-associated hypercalcemia. Am J Med. 2007;120(10):911.e9-911.e15.", "pmid": "17904464", "doi": "10.1016/j.amjmed.2006.07.044", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17904464/", "publicSourceType": "PMID" }, { "text": "Chandler PD, Scott JB, Drake BF, Ng K, Forman JP, Chan AT, et al. Risk of hypercalcemia in blacks taking hydrochlorothiazide and vitamin D. Am J Med. 2014;127(8):772-778.", "pmid": "24657333", "doi": "10.1016/j.amjmed.2014.02.044", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24657333/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Chlorthalidone and Vitamin D3 can additively increase serum calcium.", "clinicalSignificance": "Most routine use is low risk, but high-risk patients need calcium monitoring.", "managementStrategy": "Monitor serum calcium when Vitamin D3 doses are high or calcium-risk factors are present.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Chlorthalidone", "supplementBName": "Vitamin D2", "interactionType": "caution", "severity": "moderate", "description": "Chlorthalidone reduces urinary calcium excretion, and Vitamin D2 can increase calcium absorption after metabolic activation. High-dose Vitamin D2 can therefore add to chlorthalidone's calcium-retaining effect. The concern is greatest when calcium supplements are also used or when kidney disease, hyperparathyroidism, granulomatous disease, or dehydration is present.", "recommendation": "Avoid high-dose Vitamin D2 with chlorthalidone unless your clinician is tracking calcium. If Vitamin D2 is prescribed, ask when to recheck serum calcium and whether your calcium supplement dose should be adjusted.", "minimumTimeSeparation": null, "mechanism": "Chlorthalidone has thiazide-like effects that increase distal calcium reabsorption. Vitamin D2 repletion increases intestinal calcium absorption, creating an additive hypercalcemia mechanism.", "evidenceLevel": "emerging", "sources": [ { "text": "Wermers RA, Kearns AE, Jenkins GD, Melton LJ 3rd. Incidence and clinical spectrum of thiazide-associated hypercalcemia. Am J Med. 2007;120(10):911.e9-911.e15.", "pmid": "17904464", "doi": "10.1016/j.amjmed.2006.07.044", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17904464/", "publicSourceType": "PMID" }, { "text": "Chandler PD, Scott JB, Drake BF, Ng K, Forman JP, Chan AT, et al. Risk of hypercalcemia in blacks taking hydrochlorothiazide and vitamin D. Am J Med. 2014;127(8):772-778.", "pmid": "24657333", "doi": "10.1016/j.amjmed.2014.02.044", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24657333/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Chlorthalidone plus Vitamin D2 can raise serum calcium in susceptible patients.", "clinicalSignificance": "Evidence is class-based rather than Vitamin D2-specific, so monitoring is most important at high doses.", "managementStrategy": "Use Vitamin D2 with calcium monitoring when doses are high or risk factors are present.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Eplerenone", "supplementBName": "Potassium", "interactionType": "conflict", "severity": "dangerous", "description": "Eplerenone is a mineralocorticoid receptor antagonist that can raise serum potassium. Adding potassium supplements can push potassium into a dangerous range, especially in kidney disease, diabetes, heart failure, older age, or when ACE inhibitors, ARBs, NSAIDs, or trimethoprim are also used. Severe hyperkalemia can cause weakness, paralysis, dangerous arrhythmias, or cardiac arrest.", "recommendation": "Do not take potassium supplements with eplerenone unless your prescriber specifically orders them and monitors potassium. Avoid potassium-based salt substitutes, and check potassium and kidney function shortly after starting or changing eplerenone.", "minimumTimeSeparation": null, "mechanism": "Eplerenone blocks aldosterone signaling at mineralocorticoid receptors in the distal nephron, reducing potassium secretion. Supplemental potassium adds external potassium load on top of reduced renal excretion.", "evidenceLevel": "strong", "sources": [ { "text": "Pitt B, Bakris G, Ruilope LM, DiCarlo L, Mukherjee R; EPHESUS Investigators. Serum potassium and clinical outcomes in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Circulation. 2008;118(16):1643-1650.", "pmid": "18824643", "doi": "10.1161/CIRCULATIONAHA.108.778811", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18824643/", "publicSourceType": "PMID" }, { "text": "Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348(14):1309-1321.", "pmid": "12668699", "doi": "10.1056/NEJMoa030207", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12668699/", "publicSourceType": "PMID" }, { "text": "Ponce SP, Jennings AE, Madias NE, Harrington JT. Drug-induced hyperkalemia. Medicine (Baltimore). 1985;64(6):357-370.", "pmid": "2865667", "doi": "10.1097/00005792-198511000-00001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2865667/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Eplerenone reduces potassium excretion and potassium supplements add potassium load.", "clinicalSignificance": "The combination can cause silent but life-threatening hyperkalemia.", "managementStrategy": "Avoid potassium supplements and salt substitutes unless prescribed with close potassium and kidney monitoring.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Furosemide", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "moderate", "description": "Furosemide can cause volume depletion, electrolyte loss, and orthostatic symptoms. Alcohol can impair vasoconstriction during standing and can worsen dehydration risk, so the combination can cause dizziness, falls, fainting, or kidney stress. Risk is higher after dose increases, during hot weather, with vomiting or diarrhea, or in older adults.", "recommendation": "Limit alcohol while using furosemide, especially around dose changes or when you are already dehydrated. Stand slowly, maintain appropriate fluid intake for your condition, and seek care if you faint, cannot keep fluids down, or develop severe weakness.", "minimumTimeSeparation": null, "mechanism": "Furosemide promotes natriuresis and volume contraction. Alcohol potentiates orthostatic hypotension by impairing vasoconstrictor responses to orthostatic stress and can add to fluid losses.", "evidenceLevel": "moderate", "sources": [ { "text": "Narkiewicz K, Cooley RL, Somers VK. Alcohol potentiates orthostatic hypotension: implications for alcohol-related syncope. Circulation. 2000;101(4):398-402.", "pmid": "10653831", "doi": "10.1161/01.cir.101.4.398", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10653831/", "publicSourceType": "PMID" }, { "text": "Palma JA, Kaufmann H. Management of Orthostatic Hypotension. Continuum (Minneap Minn). 2020;26(1):154-177.", "pmid": "31996627", "doi": "10.1212/CON.0000000000000816", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31996627/", "publicSourceType": "PMID" }, { "text": "Brater DC. Diuretic therapy. N Engl J Med. 1998;339(6):387-395.", "pmid": "9691107", "doi": "10.1056/NEJM199808063390607", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9691107/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Alcohol and furosemide can additively increase dehydration and orthostatic hypotension risk.", "clinicalSignificance": "Falls, syncope, and kidney stress become more likely when volume depleted.", "managementStrategy": "Limit alcohol, avoid dehydration, and monitor for dizziness or fainting.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Hydrochlorothiazide", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "moderate", "description": "Hydrochlorothiazide lowers blood pressure partly through natriuresis and reduced plasma volume. Alcohol can potentiate orthostatic hypotension, so combining them may increase dizziness, fainting, falls, and dehydration risk. The risk is greater after starting hydrochlorothiazide, after dose increases, during illness, or with inadequate fluid intake.", "recommendation": "Limit alcohol when starting or changing hydrochlorothiazide. If you drink, hydrate appropriately, stand slowly, and avoid heavy intake; stop and seek medical advice if you faint or have persistent lightheadedness.", "minimumTimeSeparation": null, "mechanism": "Hydrochlorothiazide increases sodium and water excretion and can lower intravascular volume. Alcohol reduces compensatory vasoconstriction during orthostatic stress, producing additive blood-pressure drops.", "evidenceLevel": "moderate", "sources": [ { "text": "Narkiewicz K, Cooley RL, Somers VK. Alcohol potentiates orthostatic hypotension: implications for alcohol-related syncope. Circulation. 2000;101(4):398-402.", "pmid": "10653831", "doi": "10.1161/01.cir.101.4.398", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10653831/", "publicSourceType": "PMID" }, { "text": "Palma JA, Kaufmann H. Management of Orthostatic Hypotension. Continuum (Minneap Minn). 2020;26(1):154-177.", "pmid": "31996627", "doi": "10.1212/CON.0000000000000816", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31996627/", "publicSourceType": "PMID" }, { "text": "Sica DA. Diuretic-related side effects: development and treatment. J Clin Hypertens (Greenwich). 2004;6(9):532-540.", "pmid": "15365284", "doi": "10.1111/j.1524-6175.2004.03789.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15365284/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Alcohol can add to hydrochlorothiazide-related volume and blood-pressure effects.", "clinicalSignificance": "The combination can cause symptomatic hypotension and falls in susceptible users.", "managementStrategy": "Limit alcohol and watch for dizziness, dehydration, or fainting.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Chlorthalidone", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "moderate", "description": "Chlorthalidone has a long duration of action and can cause volume depletion, low sodium, and low potassium. Alcohol can worsen orthostatic hypotension and dehydration, increasing the risk of dizziness, falls, or fainting. Older adults and people who are ill, overheated, or on multiple blood-pressure medicines are at higher risk.", "recommendation": "Limit alcohol while taking chlorthalidone, particularly during the first weeks of therapy or after dose changes. Maintain appropriate hydration, stand slowly, and contact your prescriber if you have recurrent dizziness, fainting, or weakness.", "minimumTimeSeparation": null, "mechanism": "Chlorthalidone increases sodium and water excretion and can lower effective circulating volume. Alcohol impairs vasoconstrictor compensation during standing, creating additive orthostatic stress.", "evidenceLevel": "moderate", "sources": [ { "text": "Narkiewicz K, Cooley RL, Somers VK. Alcohol potentiates orthostatic hypotension: implications for alcohol-related syncope. Circulation. 2000;101(4):398-402.", "pmid": "10653831", "doi": "10.1161/01.cir.101.4.398", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10653831/", "publicSourceType": "PMID" }, { "text": "Palma JA, Kaufmann H. Management of Orthostatic Hypotension. Continuum (Minneap Minn). 2020;26(1):154-177.", "pmid": "31996627", "doi": "10.1212/CON.0000000000000816", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31996627/", "publicSourceType": "PMID" }, { "text": "Sica DA. Diuretic-related side effects: development and treatment. J Clin Hypertens (Greenwich). 2004;6(9):532-540.", "pmid": "15365284", "doi": "10.1111/j.1524-6175.2004.03789.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15365284/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Alcohol adds orthostatic and dehydration risk to chlorthalidone.", "clinicalSignificance": "Long-acting thiazide-like diuresis plus alcohol can lead to falls or syncope.", "managementStrategy": "Limit alcohol and monitor for orthostatic symptoms, especially after dose changes.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Hydrochlorothiazide", "supplementBName": "L-Arginine", "interactionType": "caution", "severity": "moderate", "description": "L-Arginine can lower blood pressure through nitric-oxide-mediated vasodilation. Hydrochlorothiazide is an antihypertensive diuretic, so adding L-Arginine can drop blood pressure further than intended in some people. This is most relevant if your blood pressure is already at goal, you are older, dehydrated, or taking multiple blood-pressure medicines.", "recommendation": "Start L-Arginine at a low dose if you take hydrochlorothiazide and monitor home blood pressure for 1-2 weeks. Reduce or stop it and contact your prescriber if you develop lightheadedness, fainting, unusual fatigue, or readings below your usual range.", "minimumTimeSeparation": null, "mechanism": "L-Arginine is a substrate for endothelial nitric oxide synthase, increasing nitric oxide signaling and vasodilation. Hydrochlorothiazide lowers blood pressure through natriuresis and longer-term vascular effects, so the effects can be additive.", "evidenceLevel": "moderate", "sources": [ { "text": "Shiraseb F, Asbaghi O, Bagheri R, Wong A, Figueroa A, Mirzaei K, et al. Effect of l-Arginine Supplementation on Blood Pressure in Adults: A Systematic Review and Dose-Response Meta-analysis of Randomized Clinical Trials. Adv Nutr. 2022;13(4):1226-1242.", "pmid": "34967840", "doi": "10.1093/advances/nmab155", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34967840/", "publicSourceType": "PMID" }, { "text": "Sica DA. Diuretic-related side effects: development and treatment. J Clin Hypertens (Greenwich). 2004;6(9):532-540.", "pmid": "15365284", "doi": "10.1111/j.1524-6175.2004.03789.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15365284/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "L-Arginine may add to hydrochlorothiazide's blood-pressure-lowering effect.", "clinicalSignificance": "Additive lowering can cause dizziness or falls in patients already controlled on therapy.", "managementStrategy": "Start low, monitor home blood pressure, and stop or reduce if symptomatic hypotension occurs.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Hydrochlorothiazide", "supplementBName": "L-Citrulline", "interactionType": "caution", "severity": "moderate", "description": "L-Citrulline can increase arginine availability and modestly lower systolic blood pressure. Hydrochlorothiazide also lowers blood pressure, so the combination may cause lightheadedness or readings below your usual range. Risk is higher with dehydration, low sodium intake, older age, or multiple antihypertensive medications.", "recommendation": "If you add L-Citrulline while taking hydrochlorothiazide, start with a low dose and track blood pressure for 1-2 weeks. Reduce or stop it if you develop dizziness, fainting, or unusually low readings.", "minimumTimeSeparation": null, "mechanism": "L-Citrulline is converted to L-arginine and supports nitric oxide production, causing vasodilation. Hydrochlorothiazide lowers blood pressure through sodium loss and vascular effects, making additive hypotension possible.", "evidenceLevel": "moderate", "sources": [ { "text": "Barkhidarian B, Khorshidi M, Shab-Bidar S, Hashemi B. Effects of L-citrulline supplementation on blood pressure: A systematic review and meta-analysis. Avicenna J Phytomed. 2019;9(1):10-20.", "pmid": "30788274", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30788274/", "publicSourceType": "PMID" }, { "text": "Sica DA. Diuretic-related side effects: development and treatment. J Clin Hypertens (Greenwich). 2004;6(9):532-540.", "pmid": "15365284", "doi": "10.1111/j.1524-6175.2004.03789.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15365284/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "L-Citrulline may add nitric-oxide-mediated blood-pressure lowering to hydrochlorothiazide.", "clinicalSignificance": "The combination may cause symptomatic low blood pressure in sensitive users.", "managementStrategy": "Start low, monitor blood pressure, and reduce or stop L-Citrulline if dizziness occurs.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Chlorthalidone", "supplementBName": "L-Arginine", "interactionType": "caution", "severity": "moderate", "description": "L-Arginine can lower blood pressure, and chlorthalidone is a long-acting antihypertensive diuretic. Combining them can produce additive blood-pressure lowering, especially in people already controlled on chlorthalidone or prone to dehydration. Symptoms can include dizziness, weakness, headache, or fainting.", "recommendation": "Start L-Arginine cautiously if you take chlorthalidone and monitor home blood pressure for 1-2 weeks. Stop or lower the supplement and contact your prescriber if you develop lightheadedness, fainting, or consistently low readings.", "minimumTimeSeparation": null, "mechanism": "L-Arginine increases nitric oxide substrate availability and vasodilation. Chlorthalidone lowers blood pressure through natriuresis and sustained vascular effects, so the combination can have additive hemodynamic effects.", "evidenceLevel": "moderate", "sources": [ { "text": "Shiraseb F, Asbaghi O, Bagheri R, Wong A, Figueroa A, Mirzaei K, et al. Effect of l-Arginine Supplementation on Blood Pressure in Adults: A Systematic Review and Dose-Response Meta-analysis of Randomized Clinical Trials. Adv Nutr. 2022;13(4):1226-1242.", "pmid": "34967840", "doi": "10.1093/advances/nmab155", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34967840/", "publicSourceType": "PMID" }, { "text": "Sica DA. Diuretic-related side effects: development and treatment. J Clin Hypertens (Greenwich). 2004;6(9):532-540.", "pmid": "15365284", "doi": "10.1111/j.1524-6175.2004.03789.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15365284/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "L-Arginine can add to chlorthalidone's blood-pressure-lowering effect.", "clinicalSignificance": "Additive hypotension can increase dizziness and fall risk.", "managementStrategy": "Use low starting doses and monitor blood pressure and symptoms closely.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Chlorthalidone", "supplementBName": "L-Citrulline", "interactionType": "caution", "severity": "moderate", "description": "L-Citrulline can modestly lower blood pressure through the arginine-nitric oxide pathway. Chlorthalidone has sustained antihypertensive and diuretic effects, so adding L-Citrulline can increase the chance of symptomatic low blood pressure. Dehydration, low sodium, older age, and multi-drug blood-pressure therapy increase risk.", "recommendation": "If you use L-Citrulline with chlorthalidone, begin with a low dose and check blood pressure at home. Reduce or stop it if you develop dizziness, fainting, or readings below your usual range, and discuss persistent symptoms with your prescriber.", "minimumTimeSeparation": null, "mechanism": "L-Citrulline raises systemic arginine availability and supports nitric oxide-mediated vasodilation. Chlorthalidone reduces blood pressure through sodium loss and vascular adaptation, making additive blood-pressure lowering possible.", "evidenceLevel": "moderate", "sources": [ { "text": "Barkhidarian B, Khorshidi M, Shab-Bidar S, Hashemi B. Effects of L-citrulline supplementation on blood pressure: A systematic review and meta-analysis. Avicenna J Phytomed. 2019;9(1):10-20.", "pmid": "30788274", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30788274/", "publicSourceType": "PMID" }, { "text": "Sica DA. Diuretic-related side effects: development and treatment. J Clin Hypertens (Greenwich). 2004;6(9):532-540.", "pmid": "15365284", "doi": "10.1111/j.1524-6175.2004.03789.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15365284/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "L-Citrulline can add blood-pressure lowering to chlorthalidone.", "clinicalSignificance": "Sensitive users may experience dizziness, weakness, or falls from additive hypotension.", "managementStrategy": "Start low, monitor home blood pressure, and stop or reduce if hypotensive symptoms occur.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Methotrexate", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Alcohol can add to methotrexate's liver toxicity risk, especially with regular or heavy use. The risk is most important for people with rheumatoid arthritis taking long-term low-dose methotrexate, people with abnormal liver tests, obesity, fatty liver disease, viral hepatitis, or other hepatotoxic medicines. Occasional low intake may be lower risk, but repeated intake makes liver enzyme monitoring more important.", "recommendation": "Avoid heavy drinking while taking methotrexate. If you drink alcohol at all, keep intake low and consistent, tell your prescriber, and do not skip scheduled liver blood tests. Stop alcohol and seek medical advice if you develop jaundice, dark urine, unusual fatigue, or right upper abdominal pain.", "minimumTimeSeparation": null, "mechanism": "Methotrexate can cause dose- and exposure-related hepatocellular injury through antifolate effects, mitochondrial stress, and inflammatory injury pathways. Alcohol independently increases hepatic oxidative stress and can worsen steatosis or hepatitis, creating additive liver risk rather than a timing-based interaction.", "evidenceLevel": "moderate", "sources": [ { "text": "Humphreys JH, Warner A, Costello R, Lunt M, Verstappen SMM, Dixon WG. Quantifying the hepatotoxic risk of alcohol consumption in patients with rheumatoid arthritis taking methotrexate. Ann Rheum Dis. 2017;76(9):1509-1514.", "pmid": "28341765", "doi": "10.1136/annrheumdis-2016-210629", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28341765/", "publicSourceType": "PMID" }, { "text": "Kremer JM, Weinblatt ME. Quantifying the hepatotoxic risk of alcohol consumption in patients with rheumatoid arthritis taking methotrexate. Ann Rheum Dis. 2018;77(1):e4.", "pmid": "28596184", "doi": "10.1136/annrheumdis-2017-211632", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28596184/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Alcohol adds to methotrexate-associated hepatotoxicity risk.", "clinicalSignificance": "Methotrexate requires liver monitoring, and alcohol can make abnormal liver tests or liver injury more likely.", "managementStrategy": "Avoid heavy alcohol use; if any alcohol is used, keep intake low and maintain liver-test monitoring.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Methotrexate", "supplementBName": "Vitamin B9", "interactionType": "synergy", "severity": "moderate", "description": "Vitamin B9 supplementation reduces common methotrexate side effects such as mouth sores, nausea, elevated liver enzymes, and blood-count problems in rheumatologic use. Methotrexate is an antifolate drug, so folate support is often part of safe long-term therapy. The benefit applies to low-dose weekly methotrexate regimens, not high-dose oncology protocols unless the oncology team directs it.", "recommendation": "Use Vitamin B9 only in the schedule your prescriber recommends, commonly daily folic acid or a weekly folate dose away from methotrexate. Do not use folate to self-treat severe mouth sores, fever, bruising, or shortness of breath; those symptoms need urgent clinical review. Keep routine blood-count and liver-test monitoring.", "minimumTimeSeparation": null, "mechanism": "Methotrexate inhibits folate-dependent pathways including dihydrofolate reductase-linked one-carbon metabolism. Supplemental folate replenishes normal-cell folate pools and reduces mucosal, hepatic, and hematologic toxicity while generally preserving methotrexate's anti-inflammatory benefit in rheumatoid arthritis.", "evidenceLevel": "strong", "sources": [ { "text": "Shea B, Swinden MV, Tanjong Ghogomu E, Ortiz Z, Katchamart W, Rader T, et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. Cochrane Database Syst Rev. 2013;2013(5):CD000951.", "pmid": "23728635", "doi": "10.1002/14651858.CD000951.pub2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23728635/", "publicSourceType": "PMID" }, { "text": "van Ede AE, Laan RF, Rood MJ, Huizinga TW, van de Laar MA, van Denderen CJ, et al. Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: a forty-eight week, multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2001;44(7):1515-1524.", "pmid": "11465701", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11465701/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Vitamin B9 reduces methotrexate toxicity in low-dose rheumatology regimens.", "clinicalSignificance": "Folate supplementation can prevent side effects that commonly lead to missed doses or stopping methotrexate.", "managementStrategy": "Follow the prescriber's folate schedule and continue routine blood-count and liver monitoring.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Allopurinol", "supplementBName": "Alcohol", "interactionType": "conflict", "severity": "moderate", "description": "Alcohol can trigger gout attacks and raise the urate burden that allopurinol is meant to control. Beer and spirits are the clearest concerns, and even short-term alcohol intake can increase recurrent flare risk. This is not solved by spacing doses because the issue is alcohol's effect on urate production, renal urate handling, and gout inflammation.", "recommendation": "Limit or avoid alcohol while using allopurinol, especially during dose titration or if flares are still occurring. If you drink, keep intake low, hydrate well, and track whether attacks follow drinking. Tell your prescriber if flares continue despite allopurinol because the urate-lowering plan may need adjustment.", "minimumTimeSeparation": null, "mechanism": "Alcohol metabolism increases ATP degradation and purine turnover, increasing urate generation. Alcohol-associated lactate can also compete with urate for renal excretion, while beer contributes additional purines, opposing allopurinol's xanthine oxidase inhibition at the clinical level.", "evidenceLevel": "moderate", "sources": [ { "text": "Neogi T, Chen C, Niu J, Chaisson C, Hunter DJ, Zhang Y. Alcohol quantity and type on risk of recurrent gout attacks: an internet-based case-crossover study. Am J Med. 2014;127(4):311-318.", "pmid": "24440541", "doi": "10.1016/j.amjmed.2013.12.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24440541/", "publicSourceType": "PMID" }, { "text": "Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G. Alcohol intake and risk of incident gout in men: a prospective study. Lancet. 2004;363(9417):1277-1281.", "pmid": "15094272", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15094272/", "publicSourceType": "PMID" }, { "text": "Nieradko-Iwanicka B. The role of alcohol consumption in pathogenesis of gout. Crit Rev Food Sci Nutr. 2022;62(25):7129-7137.", "pmid": "33866874", "doi": "10.1080/10408398.2021.1911928", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33866874/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Alcohol can counteract allopurinol's gout-control goals by increasing flare risk and urate burden.", "clinicalSignificance": "Continued flares during allopurinol therapy can lead to unnecessary dose changes or poor adherence if alcohol triggers are not addressed.", "managementStrategy": "Avoid or minimize alcohol and reassess serum urate and flare frequency with the prescriber.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Febuxostat", "supplementBName": "Alcohol", "interactionType": "conflict", "severity": "moderate", "description": "Alcohol can undermine febuxostat therapy by increasing gout flare risk and raising urate pressure. Febuxostat lowers urate through xanthine oxidase inhibition, but alcohol can still trigger attacks, particularly during early urate-lowering therapy when flares are common. Spacing alcohol away from febuxostat does not prevent this problem.", "recommendation": "Avoid heavy alcohol use while taking febuxostat. During the first months of therapy or during dose changes, keep alcohol intake as low as possible and follow the prescribed flare-prevention plan. Report persistent attacks so your prescriber can reassess serum urate and prophylaxis.", "minimumTimeSeparation": null, "mechanism": "Febuxostat inhibits xanthine oxidase to reduce urate synthesis. Alcohol increases purine turnover and may reduce renal urate excretion through lactate competition, creating a disease-state conflict with febuxostat's intended urate-lowering effect.", "evidenceLevel": "moderate", "sources": [ { "text": "Becker MA, Schumacher HR, Wortmann RL, MacDonald PA, Eustace D, Palo WA, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med. 2005;353(23):2450-2461.", "pmid": "16339094", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16339094/", "publicSourceType": "PMID" }, { "text": "Neogi T, Chen C, Niu J, Chaisson C, Hunter DJ, Zhang Y. Alcohol quantity and type on risk of recurrent gout attacks: an internet-based case-crossover study. Am J Med. 2014;127(4):311-318.", "pmid": "24440541", "doi": "10.1016/j.amjmed.2013.12.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24440541/", "publicSourceType": "PMID" }, { "text": "Nieradko-Iwanicka B. The role of alcohol consumption in pathogenesis of gout. Crit Rev Food Sci Nutr. 2022;62(25):7129-7137.", "pmid": "33866874", "doi": "10.1080/10408398.2021.1911928", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33866874/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Alcohol can oppose febuxostat's clinical goal by increasing gout flare risk.", "clinicalSignificance": "Alcohol-triggered flares can persist even when febuxostat is pharmacologically lowering urate.", "managementStrategy": "Minimize alcohol, especially during initiation, and monitor serum urate plus flare frequency.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Febuxostat", "supplementBName": "Vitamin C", "interactionType": "synergy", "severity": "info", "description": "Vitamin C has a modest urate-lowering effect in randomized-trial meta-analyses, while febuxostat is a much stronger urate-lowering medicine. The combination may slightly support serum urate reduction, but Vitamin C is not a substitute for febuxostat and may not meaningfully prevent gout attacks by itself. High doses can cause gastrointestinal upset and may be inappropriate for people prone to kidney stones.", "recommendation": "Do not replace febuxostat with Vitamin C. If you use Vitamin C, keep the dose moderate and tell your prescriber, especially if you have kidney stones, kidney disease, or persistent gout flares. Continue serum urate monitoring to confirm the treatment target is being reached.", "minimumTimeSeparation": null, "mechanism": "Febuxostat reduces urate production by inhibiting xanthine oxidase. Vitamin C appears to lower serum urate modestly, likely through uricosuric effects involving renal urate transport, so any benefit is additive but usually small.", "evidenceLevel": "moderate", "sources": [ { "text": "Liu XX, Wang XX, Cui LL. Association between Oral vitamin C supplementation and serum uric acid: A meta-analysis of randomized controlled trials. Complement Ther Med. 2021;60:102761.", "pmid": "34280483", "doi": "10.1016/j.ctim.2021.102761", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34280483/", "publicSourceType": "PMID" }, { "text": "Juraschek SP, Miller ER 3rd, Gelber AC. Effect of oral vitamin C supplementation on serum uric acid: a meta-analysis of randomized controlled trials. Arthritis Care Res (Hoboken). 2011;63(9):1295-1306.", "pmid": "21671418", "doi": "10.1002/acr.20519", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21671418/", "publicSourceType": "PMID" }, { "text": "Andres M, Sivera F, Falzon L, Buchbinder R, Carmona L. Dietary supplements for chronic gout. Cochrane Database Syst Rev. 2014;(10):CD010156.", "pmid": "25287939", "doi": "10.1002/14651858.CD010156.pub2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25287939/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Vitamin C may add a small urate-lowering effect to febuxostat therapy.", "clinicalSignificance": "The effect is modest, so serum urate targets should still guide febuxostat dosing.", "managementStrategy": "Use only as an adjunct and keep monitoring serum urate rather than relying on symptoms alone.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Allopurinol", "supplementBName": "Vitamin B3", "interactionType": "conflict", "severity": "moderate", "description": "High-dose Vitamin B3 products that contain niacin or nicotinic acid can raise uric acid and have been associated with drug-induced gout. This can work against allopurinol's goal of keeping serum urate below target. The concern is mainly with lipid-dose niacin or high-dose supplements, not small dietary amounts.", "recommendation": "Avoid starting high-dose Vitamin B3 while gout is active or serum urate is above target unless your clinician specifically recommends it. If niacin is necessary, check serum urate after starting or changing the dose and watch for new flares. Do not stop allopurinol during a flare unless your prescriber tells you to.", "minimumTimeSeparation": null, "mechanism": "Niacin can increase serum urate by reducing renal urate clearance and altering uric acid metabolism. That urate-raising effect conflicts with allopurinol's xanthine oxidase inhibition and may make urate targets harder to achieve.", "evidenceLevel": "moderate", "sources": [ { "text": "Ben Salem C, Slim R, Fathallah N, Hmouda H. Drug-induced hyperuricaemia and gout. Rheumatology (Oxford). 2017;56(5):679-688.", "pmid": "27498351", "doi": "10.1093/rheumatology/kew293", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27498351/", "publicSourceType": "PMID" }, { "text": "Kei A, Elisaf MS. Nicotinic acid: clinical considerations. Expert Opin Drug Saf. 2012;11(4):551-564.", "pmid": "22564238", "doi": "10.1517/14740338.2012.682981", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22564238/", "publicSourceType": "PMID" }, { "text": "Parsons WB Jr. Studies of nicotinic acid use in hypercholesteremia. Changes in hepatic function, carbohydrate tolerance, and uric acid metabolism. Arch Intern Med. 1961;107:653-667.", "pmid": "13733026", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/13733026/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "High-dose Vitamin B3 can raise urate and oppose allopurinol's urate-lowering goal.", "clinicalSignificance": "A supplement used for cholesterol or energy claims can make gout control worse if it contains high-dose niacin.", "managementStrategy": "Avoid high-dose niacin unless needed, and monitor serum urate and flare frequency if it is used.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Febuxostat", "supplementBName": "Vitamin B3", "interactionType": "conflict", "severity": "moderate", "description": "High-dose Vitamin B3 products containing niacin or nicotinic acid can increase serum uric acid and precipitate gout. That effect can work against febuxostat's urate-lowering goal, particularly if urate is not yet at target. The risk is most relevant for high-dose niacin products, not normal dietary Vitamin B3 intake.", "recommendation": "Do not add high-dose Vitamin B3 during febuxostat therapy without checking with your prescriber. If niacin is required, monitor serum urate after dose changes and report any increase in flares. Keep taking febuxostat as prescribed unless your clinician changes the plan.", "minimumTimeSeparation": null, "mechanism": "Febuxostat lowers urate by inhibiting xanthine oxidase. Niacin can reduce renal urate clearance and increase serum urate, creating a pharmacodynamic conflict with febuxostat's intended effect.", "evidenceLevel": "moderate", "sources": [ { "text": "Ben Salem C, Slim R, Fathallah N, Hmouda H. Drug-induced hyperuricaemia and gout. Rheumatology (Oxford). 2017;56(5):679-688.", "pmid": "27498351", "doi": "10.1093/rheumatology/kew293", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27498351/", "publicSourceType": "PMID" }, { "text": "Kei A, Elisaf MS. Nicotinic acid: clinical considerations. Expert Opin Drug Saf. 2012;11(4):551-564.", "pmid": "22564238", "doi": "10.1517/14740338.2012.682981", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22564238/", "publicSourceType": "PMID" }, { "text": "Becker MA, Schumacher HR, Wortmann RL, MacDonald PA, Eustace D, Palo WA, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med. 2005;353(23):2450-2461.", "pmid": "16339094", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16339094/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "High-dose Vitamin B3 can raise urate and work against febuxostat's clinical goal.", "clinicalSignificance": "Niacin-related urate increases can confuse febuxostat titration and contribute to ongoing flares.", "managementStrategy": "Avoid high-dose niacin when possible; if used, follow serum urate and flare frequency closely.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Sulfasalazine", "supplementBName": "Vitamin B9", "interactionType": "synergy", "severity": "moderate", "description": "Sulfasalazine can reduce folate absorption and inhibit folate-dependent enzymes. Most people do not develop severe deficiency, but risk rises with long-term therapy, low dietary folate intake, pregnancy, anemia, or other antifolate medicines. Vitamin B9 supplementation helps offset this depletion risk during sulfasalazine therapy.", "recommendation": "Ask your prescriber whether you should take daily folate while using sulfasalazine, especially if you are pregnant, planning pregnancy, anemic, or taking another antifolate drug. Do not use folate to ignore new mouth sores, severe fatigue, bruising, or worsening anemia; those symptoms need lab review.", "minimumTimeSeparation": null, "mechanism": "Sulfasalazine competitively inhibits intestinal folate transport and can inhibit folate-dependent enzymes, including dihydrofolate reductase-related pathways. Supplemental Vitamin B9 replenishes folate pools needed for one-carbon metabolism and blood-cell production.", "evidenceLevel": "moderate", "sources": [ { "text": "Halsted CH, Gandhi G, Tamura T. Sulfasalazine inhibits the absorption of folates in ulcerative colitis. N Engl J Med. 1981;305(25):1513-1517.", "pmid": "6117796", "doi": "10.1056/NEJM198112173052506", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6117796/", "publicSourceType": "PMID" }, { "text": "Selhub J, Dhar GJ, Rosenberg IH. Inhibition of folate enzymes by sulfasalazine. J Clin Invest. 1978;61(1):221-224.", "pmid": "22555", "doi": "10.1172/JCI108921", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22555/", "publicSourceType": "PMID" }, { "text": "Schoeman M, Bezuidenhout DJ. Folate levels in patients with ulcerative colitis receiving sulphasalazine. S Afr Med J. 1984;66(11):415.", "pmid": "6148790", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6148790/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Sulfasalazine can lower folate availability, while Vitamin B9 helps restore folate status.", "clinicalSignificance": "Folate depletion can contribute to anemia and is especially important in pregnancy or other high-folate-requirement states.", "managementStrategy": "Use folate supplementation when clinically indicated and monitor CBC or folate status if symptoms or risk factors are present.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Sulfasalazine", "supplementBName": "Turmeric/Curcumin", "interactionType": "synergy", "severity": "info", "description": "Curcumin has been studied as an add-on to sulfasalazine or mesalamine for ulcerative colitis remission maintenance. In a randomized trial, adding curcumin to standard 5-ASA therapy reduced relapse during the treatment period and improved clinical and endoscopic activity scores. This is an adjunctive anti-inflammatory strategy, not a replacement for sulfasalazine.", "recommendation": "If your ulcerative colitis is stable on sulfasalazine, discuss curcumin as an adjunct rather than stopping your prescription. Avoid high-dose curcumin if you have gallbladder disease, are on anticoagulants, or are scheduled for surgery. Track stool frequency, bleeding, and abdominal pain so flares are not missed.", "minimumTimeSeparation": null, "mechanism": "Sulfasalazine delivers 5-aminosalicylic acid to the colon and reduces mucosal inflammatory signaling. Curcumin has complementary effects on NF-kappaB, cytokine signaling, oxidative stress, and mucosal inflammatory pathways.", "evidenceLevel": "moderate", "sources": [ { "text": "Hanai H, Iida T, Takeuchi K, et al. Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial. Clin Gastroenterol Hepatol. 2006;4(12):1502-1506.", "pmid": "17101300", "doi": "10.1016/j.cgh.2006.08.008", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17101300/", "publicSourceType": "PMID" }, { "text": "Kumar S, Ahuja V, Sankar MJ, Kumar A, Moss AC. Curcumin for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev. 2012;(10):CD008424.", "pmid": "23076948", "doi": "10.1002/14651858.CD008424.pub2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23076948/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Curcumin may improve remission maintenance when added to sulfasalazine-based ulcerative colitis therapy.", "clinicalSignificance": "Adjunctive curcumin may reduce relapse risk in selected patients but should not replace proven maintenance therapy.", "managementStrategy": "Use only as an adjunct with symptom tracking and clinician follow-up.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Mesalamine", "supplementBName": "Turmeric/Curcumin", "interactionType": "synergy", "severity": "info", "description": "Curcumin has randomized-trial and meta-analysis evidence as an adjunct to mesalamine in mild-to-moderate ulcerative colitis. Higher-dose curcumin added to optimized mesalamine improved clinical and endoscopic remission in one trial, while low-dose curcumin was not effective in another. Benefits depend on dose, formulation, adherence, and disease severity.", "recommendation": "Do not replace mesalamine with curcumin. If adding curcumin, use it consistently and keep your mesalamine dose unchanged unless your gastroenterologist changes it. Stop and seek care for worsening bleeding, fever, severe pain, or dehydration.", "minimumTimeSeparation": null, "mechanism": "Mesalamine acts topically in the colonic mucosa to reduce prostaglandin and leukotriene-mediated inflammation. Curcumin adds anti-inflammatory effects through NF-kappaB, cytokine, oxidative-stress, and epithelial-barrier pathways.", "evidenceLevel": "moderate", "sources": [ { "text": "Lang A, Salomon N, Wu JC, et al. Curcumin in Combination With Mesalamine Induces Remission in Patients With Mild-to-Moderate Ulcerative Colitis in a Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2015;13(8):1444-1449.e1.", "pmid": "25724700", "doi": "10.1016/j.cgh.2015.02.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25724700/", "publicSourceType": "PMID" }, { "text": "Zheng T, Wang X, Chen Z, He A, Zheng Z, Liu G. Efficacy of adjuvant curcumin therapy in ulcerative colitis: A meta-analysis of randomized controlled trials. J Gastroenterol Hepatol. 2020;35(5):722-729.", "pmid": "31696975", "doi": "10.1111/jgh.14911", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31696975/", "publicSourceType": "PMID" }, { "text": "Grammatikopoulou MG, Gkiouras K, Theodoridis X, Asteriou E, Forbes A, Bogdanos DP. Oral Adjuvant Curcumin Therapy for Attaining Clinical Remission in Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients. 2018;10(11):1737.", "pmid": "30424514", "doi": "10.3390/nu10111737", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30424514/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Curcumin may add anti-inflammatory benefit to mesalamine in ulcerative colitis.", "clinicalSignificance": "The combination may improve remission outcomes, but curcumin alone is not adequate maintenance therapy.", "managementStrategy": "Use curcumin only as an adjunct and continue mesalamine with routine disease monitoring.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Mesalamine", "supplementBName": "Probiotics", "interactionType": "synergy", "severity": "info", "description": "Multi-strain probiotics have been studied as add-ons to 5-ASA therapy, including mesalamine, in ulcerative colitis. Trials of VSL#3-type preparations showed improved disease activity scores or remission outcomes in some patients, though probiotic strains and doses matter. This is most relevant for mild-to-moderate disease and remission support.", "recommendation": "Use probiotics as an adjunct, not as a substitute for mesalamine. Choose a product with studied strains and an adequate dose, and reassess symptoms after 8 to 12 weeks. Avoid probiotic use without medical input if you are severely immunocompromised or have a central venous catheter.", "minimumTimeSeparation": null, "mechanism": "Mesalamine reduces mucosal inflammatory mediator production. Probiotics may improve epithelial-barrier function, reduce pathogen adherence, modulate T-cell and cytokine signaling, and shift gut microbiota away from pro-inflammatory patterns.", "evidenceLevel": "moderate", "sources": [ { "text": "Tursi A, Brandimarte G, Papa A, et al. Treatment of relapsing mild-to-moderate ulcerative colitis with the probiotic VSL#3 as adjunctive to a standard pharmaceutical treatment: a double-blind, randomized, placebo-controlled study. Am J Gastroenterol. 2010;105(10):2218-2227.", "pmid": "20517305", "doi": "10.1038/ajg.2010.218", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20517305/", "publicSourceType": "PMID" }, { "text": "Miele E, Pascarella F, Giannetti E, et al. Effect of a probiotic preparation (VSL#3) on induction and maintenance of remission in children with ulcerative colitis. Am J Gastroenterol. 2009;104(2):437-443.", "pmid": "19174792", "doi": "10.1038/ajg.2008.118", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19174792/", "publicSourceType": "PMID" }, { "text": "Sood A, Midha V, Makharia GK, et al. The probiotic preparation, VSL#3 induces remission in patients with mild-to-moderately active ulcerative colitis. Clin Gastroenterol Hepatol. 2009;7(11):1202-1209.e1.", "pmid": "19631292", "doi": "10.1016/j.cgh.2009.07.016", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19631292/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Probiotics may improve ulcerative colitis control when added to mesalamine-based therapy.", "clinicalSignificance": "The benefit is strain-specific and adjunctive, so replacing mesalamine can risk relapse.", "managementStrategy": "Continue mesalamine and trial a studied probiotic with symptom and flare monitoring.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Mesalamine", "supplementBName": "Saccharomyces Boulardii", "interactionType": "synergy", "severity": "info", "description": "Saccharomyces boulardii has limited human evidence as an add-on during mesalamine maintenance for mild-to-moderate ulcerative colitis flare symptoms. A small pilot trial reported clinical remission in many completers, but controlled confirmation is limited. Treat this as an emerging adjunct, not a core ulcerative colitis therapy.", "recommendation": "If you try Saccharomyces boulardii with mesalamine, keep your prescription regimen unchanged and reassess after about 4 to 8 weeks. Avoid it if you are severely immunocompromised, critically ill, or have a central venous catheter because rare bloodstream infections have been reported with probiotic yeasts.", "minimumTimeSeparation": null, "mechanism": "Mesalamine reduces colonic mucosal inflammation through topical anti-inflammatory effects. Saccharomyces boulardii may support barrier function, reduce pathogen-mediated inflammation, and alter gut immune signaling, producing a complementary but less proven effect.", "evidenceLevel": "emerging", "sources": [ { "text": "Guslandi M, Giollo P, Testoni PA. A pilot trial of Saccharomyces boulardii in ulcerative colitis. Eur J Gastroenterol Hepatol. 2003;15(6):697-698.", "pmid": "12840682", "doi": "10.1097/00042737-200306000-00017", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12840682/", "publicSourceType": "PMID" }, { "text": "Sood A, Midha V, Makharia GK, et al. The probiotic preparation, VSL#3 induces remission in patients with mild-to-moderately active ulcerative colitis. Clin Gastroenterol Hepatol. 2009;7(11):1202-1209.e1.", "pmid": "19631292", "doi": "10.1016/j.cgh.2009.07.016", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19631292/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Saccharomyces boulardii may provide adjunctive symptom benefit during mesalamine-treated ulcerative colitis.", "clinicalSignificance": "Evidence is early, and inappropriate substitution for mesalamine can allow relapse.", "managementStrategy": "Use only as an adjunct and avoid probiotic yeast in high-risk immunocompromised settings.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Lactulose", "supplementBName": "Probiotics", "interactionType": "synergy", "severity": "info", "description": "Lactulose and probiotics both target gut-derived ammonia pathways in hepatic encephalopathy. Trials and meta-analyses show probiotics can improve minimal hepatic encephalopathy and are often compared with lactulose; evidence for routine add-on use is less mature than evidence for lactulose itself. The combination may be reasonable in selected patients but should not replace prescribed lactulose titration.", "recommendation": "Do not stop lactulose when starting a probiotic for hepatic encephalopathy. Keep lactulose titrated to the stool target your clinician gave you, commonly 2 to 3 soft stools daily. Seek urgent care for confusion, sleep-wake reversal, dehydration, severe diarrhea, or inability to take lactulose.", "minimumTimeSeparation": null, "mechanism": "Lactulose acidifies the colon and traps ammonia as ammonium while increasing stool nitrogen excretion. Probiotics may reduce urease-producing bacteria, improve gut-barrier function, and lower inflammatory signaling that contributes to neurocognitive impairment in cirrhosis.", "evidenceLevel": "moderate", "sources": [ { "text": "Holte K, Krag A, Gluud LL. Systematic review and meta-analysis of randomized trials on probiotics for hepatic encephalopathy. Hepatol Res. 2012;42(10):1008-1015.", "pmid": "22548675", "doi": "10.1111/j.1872-034X.2012.01015.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22548675/", "publicSourceType": "PMID" }, { "text": "Mittal VV, Sharma BC, Sharma P, Sarin SK. A randomized controlled trial comparing lactulose, probiotics, and L-ornithine L-aspartate in treatment of minimal hepatic encephalopathy. Eur J Gastroenterol Hepatol. 2011;23(8):725-732.", "pmid": "21646910", "doi": "10.1097/MEG.0b013e32834696f5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21646910/", "publicSourceType": "PMID" }, { "text": "Shukla S, Shukla A, Mehboob S, Guha S. Meta-analysis: the effects of gut flora modulation using prebiotics, probiotics and synbiotics on minimal hepatic encephalopathy. Aliment Pharmacol Ther. 2011;33(6):662-671.", "pmid": "21251030", "doi": "10.1111/j.1365-2036.2010.04574.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21251030/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Probiotics may complement lactulose by further modulating gut ammonia production and inflammation.", "clinicalSignificance": "Hepatic encephalopathy can be life-threatening, so adjuncts must not interrupt proven lactulose therapy.", "managementStrategy": "Continue lactulose titration and use probiotics only as clinician-supervised adjuncts.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Ondansetron", "supplementBName": "Ginger Extract", "interactionType": "synergy", "severity": "info", "description": "Ginger has randomized-trial and meta-analysis evidence as an adjunct to standard antiemetic regimens for chemotherapy-induced nausea and vomiting. Many standard regimens include 5-HT3 antagonists such as ondansetron, so ginger may reduce nausea burden without replacing prescription antiemetics. Benefits are strongest for nausea outcomes and vary by dose and formulation.", "recommendation": "If ondansetron alone is not controlling nausea, ginger extract can be considered as an adjunct with meals. Use standardized doses and avoid high-dose ginger if you are on anticoagulants, have a bleeding disorder, or are preparing for surgery. Seek care if vomiting prevents fluids or medications from staying down.", "minimumTimeSeparation": null, "mechanism": "Ondansetron blocks 5-HT3 receptors in the gut and chemoreceptor trigger zone. Ginger constituents such as gingerols and shogaols have antiemetic, prokinetic, and anti-inflammatory effects, producing complementary nausea control.", "evidenceLevel": "moderate", "sources": [ { "text": "Choi J, Lee J, Kim K, Choi HK, Lee SA, Lee HJ. Effects of Ginger Intake on Chemotherapy-Induced Nausea and Vomiting: A Systematic Review of Randomized Clinical Trials. Nutrients. 2022;14(23):4982.", "pmid": "36501010", "doi": "10.3390/nu14234982", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36501010/", "publicSourceType": "PMID" }, { "text": "Ryan JL, Heckler CE, Roscoe JA, et al. Ginger (Zingiber officinale) reduces acute chemotherapy-induced nausea: a URCC CCOP study of 576 patients. Support Care Cancer. 2012;20(7):1479-1489.", "pmid": "21818642", "doi": "10.1007/s00520-011-1236-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21818642/", "publicSourceType": "PMID" }, { "text": "Crichton M, Marshall S, Isenring E, et al. Effect of a Standardized Ginger Root Powder Regimen on Chemotherapy-Induced Nausea and Vomiting: A Multicenter, Double-Blind, Placebo-Controlled Randomized Trial. J Acad Nutr Diet. 2024;124(3):313-330.e6.", "pmid": "37699474", "doi": "10.1016/j.jand.2023.09.003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37699474/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Ginger extract may add nausea relief to ondansetron-based antiemetic regimens.", "clinicalSignificance": "Better nausea control can help maintain hydration, nutrition, and adherence to treatment.", "managementStrategy": "Use ginger as an adjunct, monitor bleeding risk, and escalate care for persistent vomiting.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Ondansetron", "supplementBName": "Magnesium Glycinate", "interactionType": "caution", "severity": "serious", "description": "Ondansetron can prolong the QT interval and rare cases of torsades de pointes have been reported, especially with IV dosing or predisposing risks. Low magnesium is a known risk factor for drug-induced long QT and torsades. Maintaining normal magnesium status lowers this background risk, particularly during vomiting, diarrhea, diuretic use, or poor intake.", "recommendation": "Do not take high-dose magnesium without medical advice, but maintain normal magnesium intake while using ondansetron if you have ongoing GI losses or QT-risk factors. Ask about checking electrolytes if you need repeated ondansetron doses, have heart disease, take other QT-prolonging drugs, or have severe vomiting or diarrhea. Seek urgent care for fainting, palpitations, or seizure-like episodes.", "minimumTimeSeparation": null, "mechanism": "Ondansetron can delay cardiac repolarization, partly through effects on cardiac potassium currents. Hypomagnesemia reduces repolarization reserve and promotes early afterdepolarizations, making torsades more likely in the presence of QT-prolonging drugs.", "evidenceLevel": "moderate", "sources": [ { "text": "Orozco BS, Lee SC, Fuchs RT, Fushianes GD, Cole JB. QT prolongation, torsades des pointes, and cardiac arrest after 4 mg of IV ondansetron. Am J Emerg Med. 2023;68:214.e3-214.e6.", "pmid": "37085406", "doi": "10.1016/j.ajem.2023.04.003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37085406/", "publicSourceType": "PMID" }, { "text": "Lee DY, Trinh T, Roy SK. Torsades de Pointes after Ondansetron Infusion in 2 Patients. Tex Heart Inst J. 2017;44(5):366-369.", "pmid": "29259513", "doi": "10.14503/THIJ-16-6040", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29259513/", "publicSourceType": "PMID" }, { "text": "TeBay C, Hill AP, Windley MJ. Metabolic and electrolyte abnormalities as risk factors in drug-induced long QT syndrome. Biophys Rev. 2022;14(1):353-367.", "pmid": "35103080", "doi": "10.1007/s12551-022-00929-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35103080/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Low magnesium increases susceptibility to ondansetron-associated QT arrhythmias, while inappropriate high-dose magnesium can also be unsafe.", "clinicalSignificance": "QT-related arrhythmias are rare but can be life-threatening in patients with electrolyte depletion or other QT risks.", "managementStrategy": "Maintain and monitor magnesium in high-risk or repeated-dose ondansetron use; avoid unsupervised high-dose supplementation.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Ondansetron", "supplementBName": "Potassium", "interactionType": "caution", "severity": "serious", "description": "Ondansetron can prolong QT interval, and hypokalemia makes drug-induced torsades de pointes more likely. Vomiting and diarrhea can lower potassium at the same time ondansetron is being used, creating a clinically important risk cluster. Keeping potassium normal is protective, but inappropriate potassium supplementation can be dangerous.", "recommendation": "Do not start potassium supplements unless your clinician recommends them, especially if you have kidney disease or take ACE inhibitors, ARBs, or potassium-sparing diuretics. Ask about electrolyte checks if you have prolonged vomiting, diarrhea, repeated ondansetron dosing, heart disease, or other QT-prolonging drugs. Seek urgent care for fainting, severe weakness, palpitations, or confusion.", "minimumTimeSeparation": null, "mechanism": "Ondansetron can reduce repolarization reserve and prolong QT. Low extracellular potassium further reduces IKr current and increases drug block of repolarizing potassium channels, promoting early afterdepolarizations and torsades de pointes.", "evidenceLevel": "moderate", "sources": [ { "text": "Orozco BS, Lee SC, Fuchs RT, Fushianes GD, Cole JB. QT prolongation, torsades des pointes, and cardiac arrest after 4 mg of IV ondansetron. Am J Emerg Med. 2023;68:214.e3-214.e6.", "pmid": "37085406", "doi": "10.1016/j.ajem.2023.04.003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37085406/", "publicSourceType": "PMID" }, { "text": "Nachimuthu S, Assar MD, Schussler JM. Drug-induced QT interval prolongation: mechanisms and clinical management. Ther Adv Drug Saf. 2012;3(5):241-253.", "pmid": "25083239", "doi": "10.1177/2042098612454283", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25083239/", "publicSourceType": "PMID" }, { "text": "TeBay C, Hill AP, Windley MJ. Metabolic and electrolyte abnormalities as risk factors in drug-induced long QT syndrome. Biophys Rev. 2022;14(1):353-367.", "pmid": "35103080", "doi": "10.1007/s12551-022-00929-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35103080/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Low potassium increases susceptibility to ondansetron-associated QT arrhythmias, while unsupervised potassium supplementation can cause hyperkalemia.", "clinicalSignificance": "GI illness can simultaneously drive potassium loss and ondansetron exposure, increasing arrhythmia risk.", "managementStrategy": "Monitor and replete potassium only with clinician guidance in high-risk ondansetron use.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Calcium Carbonate", "supplementBName": "Iron", "interactionType": "timingSensitive", "severity": "moderate", "description": "Calcium carbonate can reduce iron absorption when taken at the same time. Human studies show calcium can inhibit both heme and non-heme iron absorption in single-meal settings, and calcium carbonate antacid reduced the plasma iron rise in an iron absorption study. This matters most when treating iron deficiency or in people with high iron needs.", "recommendation": "Separate iron supplements from calcium carbonate by at least 2 to 4 hours. Take iron with vitamin C or a vitamin C-containing drink if tolerated, and recheck ferritin or CBC as directed. If iron levels are not improving, review calcium carbonate timing with your clinician.", "minimumTimeSeparation": 120, "mechanism": "Calcium competes with iron uptake and may interfere with mucosal transfer during absorption. Calcium carbonate also raises gastric pH, reducing solubilization of non-heme iron salts needed for duodenal uptake.", "evidenceLevel": "moderate", "sources": [ { "text": "O'Neil-Cutting MA, Crosby WH. The effect of antacids on the absorption of simultaneously ingested iron. JAMA. 1986;255(11):1468-1470.", "pmid": "3005669", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3005669/", "publicSourceType": "PMID" }, { "text": "Hallberg L, Brune M, Erlandsson M, Sandberg AS, Rossander-Hulten L. Calcium: effect of different amounts on nonheme- and heme-iron absorption in humans. Am J Clin Nutr. 1991;53(1):112-119.", "pmid": "1984335", "doi": "10.1093/ajcn/53.1.112", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1984335/", "publicSourceType": "PMID" }, { "text": "Lynch SR. The effect of calcium on iron absorption. Nutr Res Rev. 2000;13(2):141-158.", "pmid": "19087437", "doi": "10.1079/095442200108729043", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19087437/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Calcium carbonate can lower iron absorption when both are taken together.", "clinicalSignificance": "Poor timing can slow correction of iron deficiency anemia or low ferritin.", "managementStrategy": "Separate iron and calcium carbonate by at least 2 hours, preferably 4 hours if iron deficiency is being treated.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Dapsone", "supplementBName": "Vitamin C", "interactionType": "caution", "severity": "serious", "description": "Dapsone can cause methemoglobinemia and hemolysis through oxidative metabolites. High-dose vitamin C has reducing and antioxidant activity and has been reported as a treatment option for dapsone-induced methemoglobinemia when methylene blue is unavailable or unsuitable, with supportive animal data. Ordinary over-the-counter vitamin C should not be relied on to prevent or self-treat dapsone toxicity.", "recommendation": "Do not use vitamin C to mask blue lips, gray skin, shortness of breath, severe fatigue, or low oxygen readings while on dapsone. Seek urgent care for those symptoms because methemoglobin levels may need measurement and medical treatment. If you take routine vitamin C, keep the dose modest unless your clinician directs otherwise.", "minimumTimeSeparation": null, "mechanism": "Dapsone is metabolized to hydroxylamine derivatives that oxidize hemoglobin iron from ferrous to ferric state, forming methemoglobin. Ascorbic acid can nonenzymatically reduce methemoglobin and counter oxidative stress, but clinically meaningful effects usually require medical-dose therapy.", "evidenceLevel": "emerging", "sources": [ { "text": "Ward KE, McCarthy MW. Dapsone-induced methemoglobinemia. Ann Pharmacother. 1998;32(5):549-553.", "pmid": "9606476", "doi": "10.1345/aph.17003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9606476/", "publicSourceType": "PMID" }, { "text": "Park SY, Lee KW, Kang TS. High-dose vitamin C management in dapsone-induced methemoglobinemia. Am J Emerg Med. 2014;32(6):684.e1-684.e3.", "pmid": "24439259", "doi": "10.1016/j.ajem.2013.11.036", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24439259/", "publicSourceType": "PMID" }, { "text": "Kang C, Kim DH, Kim T, et al. Therapeutic effect of ascorbic acid on dapsone-induced methemoglobinemia in rats. Clin Exp Emerg Med. 2018;5(3):192-198.", "pmid": "30269455", "doi": "10.15441/ceem.17.253", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30269455/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Medical-dose vitamin C may help reduce dapsone-induced methemoglobin, but routine supplementation does not reliably prevent toxicity.", "clinicalSignificance": "Dapsone methemoglobinemia can cause dangerous tissue hypoxia even when pulse oximetry is misleading.", "managementStrategy": "Treat symptoms as urgent and use vitamin C only as clinician-directed supportive therapy.", "isSynergistic": null, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Metoclopramide", "supplementBName": "St. John's Wort", "interactionType": "caution", "severity": "serious", "description": "Metoclopramide has rare reports of serotonin syndrome, especially when combined with serotonergic drugs. St. John's Wort has serotonergic activity and published clinical interaction reviews describe serotonin syndrome when it is combined with serotonergic medicines. The combination is not well studied directly, but the shared serotonergic risk makes it a clinically meaningful caution.", "recommendation": "Avoid combining St. John's Wort with metoclopramide unless your prescriber specifically approves it. Stop St. John's Wort and seek urgent care for agitation, confusion, sweating, fever, diarrhea, tremor, muscle rigidity, or jerking movements after metoclopramide use. Also tell your clinician about any antidepressants, tramadol, or migraine medicines.", "minimumTimeSeparation": null, "mechanism": "Metoclopramide has serotonergic properties in addition to dopamine D2 antagonism and 5-HT4 agonism. St. John's Wort can increase serotonergic tone and also alters CYP3A4 and P-glycoprotein, creating both pharmacodynamic and pharmacokinetic uncertainty.", "evidenceLevel": "emerging", "sources": [ { "text": "Fisher AA, Davis MW. Serotonin syndrome caused by selective serotonin reuptake-inhibitors-metoclopramide interaction. Ann Pharmacother. 2002;36(1):67-71.", "pmid": "11816261", "doi": "10.1345/aph.1A161", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11816261/", "publicSourceType": "PMID" }, { "text": "Harada T, Hirosawa T, Morinaga K, Shimizu T. Metoclopramide-induced Serotonin Syndrome. Intern Med. 2017;56(6):737-739.", "pmid": "28321081", "doi": "10.2169/internalmedicine.56.7727", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28321081/", "publicSourceType": "PMID" }, { "text": "Izzo AA. Drug interactions with St. John's Wort (Hypericum perforatum): a review of the clinical evidence. Int J Clin Pharmacol Ther. 2004;42(3):139-148.", "pmid": "15049433", "doi": "10.5414/cpp42139", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15049433/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St. John's Wort may increase serotonin-toxicity risk when metoclopramide is used.", "clinicalSignificance": "Serotonin syndrome is uncommon but can become severe quickly, especially when multiple serotonergic agents are present.", "managementStrategy": "Avoid the combination and screen for other serotonergic drugs or supplements before metoclopramide use.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Aspirin Low-Dose", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Alcohol increases the risk of upper gastrointestinal bleeding from low-dose aspirin. Aspirin impairs platelet function and weakens gastric mucosal defenses, while alcohol can directly irritate the stomach lining. The risk is higher with daily alcohol use, prior ulcer disease, older age, or any history of GI bleeding.", "recommendation": "Avoid heavy alcohol use while taking low-dose aspirin. If you drink, keep intake modest and seek urgent care for black stools, vomiting blood, faintness, or unexplained weakness.", "minimumTimeSeparation": null, "mechanism": "Aspirin irreversibly inhibits platelet COX-1 and suppresses thromboxane A2, reducing platelet aggregation. It also reduces protective gastric prostaglandins; ethanol adds direct mucosal injury and can worsen bleeding from aspirin-related erosions.", "evidenceLevel": "strong", "sources": [ { "text": "Kaufman DW, Kelly JP, Wiholm BE, Laszlo A, Sheehan JE, Koff RS, et al. The risk of acute major upper gastrointestinal bleeding among users of aspirin and ibuprofen at various levels of alcohol consumption. Am J Gastroenterol. 1999;94(11):3189-3196.", "pmid": "10566713", "doi": "10.1111/j.1572-0241.1999.01517.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10566713/", "publicSourceType": "PMID" }, { "text": "Strate LL, Singh P, Boylan MR, Piawah S, Cao Y, Chan AT. A Prospective Study of Alcohol Consumption and Smoking and the Risk of Major Gastrointestinal Bleeding in Men. PLoS One. 2016;11(11):e0165278.", "pmid": "27824864", "doi": "10.1371/journal.pone.0165278", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27824864/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Alcohol and low-dose aspirin additively raise the risk of clinically important gastrointestinal bleeding.", "clinicalSignificance": "Even cardioprotective aspirin doses can become more dangerous when alcohol-related mucosal injury is present.", "managementStrategy": "Limit alcohol and watch closely for GI bleeding symptoms, especially if you have ulcer history or are older.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Ibuprofen", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Alcohol increases the chance of stomach bleeding while taking ibuprofen. The combination is most concerning with repeated ibuprofen dosing, binge drinking, older age, prior ulcers, or other medicines that affect bleeding. Symptoms can appear as severe stomach pain, black stools, vomiting blood, dizziness, or weakness.", "recommendation": "Avoid heavy drinking while using ibuprofen, and do not use ibuprofen to treat hangover symptoms after substantial alcohol intake. Use the lowest effective ibuprofen dose for the shortest time and stop the combination if any bleeding symptoms occur.", "minimumTimeSeparation": null, "mechanism": "Ibuprofen reversibly inhibits COX-1 and COX-2, lowering gastric prostaglandin synthesis and weakening mucosal protection. Alcohol adds direct mucosal irritation and can amplify NSAID-related erosions and bleeding.", "evidenceLevel": "strong", "sources": [ { "text": "Kaufman DW, Kelly JP, Wiholm BE, Laszlo A, Sheehan JE, Koff RS, et al. The risk of acute major upper gastrointestinal bleeding among users of aspirin and ibuprofen at various levels of alcohol consumption. Am J Gastroenterol. 1999;94(11):3189-3196.", "pmid": "10566713", "doi": "10.1111/j.1572-0241.1999.01517.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10566713/", "publicSourceType": "PMID" }, { "text": "Sostres C, Gargallo CJ, Arroyo MT, Lanas A. Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract. Best Pract Res Clin Gastroenterol. 2010;24(2):121-132.", "pmid": "20227026", "doi": "10.1016/j.bpg.2009.11.005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20227026/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Alcohol magnifies ibuprofen-associated upper GI bleeding risk.", "clinicalSignificance": "This is a common real-world combination with direct epidemiologic evidence of major upper GI bleeding.", "managementStrategy": "Avoid heavy alcohol use and keep ibuprofen dose and duration as low as possible.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Naproxen", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Alcohol can compound naproxen's gastrointestinal bleeding risk. Naproxen is among the NSAIDs more strongly associated with upper GI complications, and alcohol adds direct stomach irritation. The combination is higher risk with daily dosing, ulcer history, older age, or any additional antiplatelet or anticoagulant medicine.", "recommendation": "Avoid heavy alcohol use while taking naproxen. If you need regular naproxen, discuss stomach-protection options and seek urgent care for black stools, vomiting blood, or faintness.", "minimumTimeSeparation": null, "mechanism": "Naproxen inhibits COX enzymes and reduces gastric prostaglandin-mediated mucosal protection. Alcohol causes mucosal injury and can turn NSAID-related erosions into clinically significant bleeding.", "evidenceLevel": "strong", "sources": [ { "text": "Castellsague J, Riera-Guardia N, Calingaert B, Varas-Lorenzo C, Fourrier-Reglat A, Nicotra F, et al. Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project). Drug Saf. 2012;35(12):1127-1146.", "pmid": "23137151", "doi": "10.2165/11633470-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23137151/", "publicSourceType": "PMID" }, { "text": "Strate LL, Singh P, Boylan MR, Piawah S, Cao Y, Chan AT. A Prospective Study of Alcohol Consumption and Smoking and the Risk of Major Gastrointestinal Bleeding in Men. PLoS One. 2016;11(11):e0165278.", "pmid": "27824864", "doi": "10.1371/journal.pone.0165278", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27824864/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Alcohol adds to naproxen's upper GI toxicity and bleeding risk.", "clinicalSignificance": "Naproxen already carries meaningful GI bleeding risk, so alcohol is a practical risk multiplier.", "managementStrategy": "Avoid heavy alcohol and use naproxen only at the lowest effective dose for the shortest time.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Celecoxib", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "moderate", "description": "Celecoxib generally causes fewer upper GI ulcers than many nonselective NSAIDs, but alcohol can still increase GI irritation and bleeding risk. The risk becomes more clinically important with higher celecoxib doses, prior ulcer disease, older age, or combined aspirin use. Alcohol also worsens dehydration, which can increase NSAID kidney risk.", "recommendation": "Avoid heavy alcohol use while taking celecoxib. If you have ulcer history or take low-dose aspirin with celecoxib, ask your clinician whether you need a stomach-protection strategy.", "minimumTimeSeparation": null, "mechanism": "Celecoxib selectively inhibits COX-2, but GI protection is not complete, especially at higher doses or with aspirin. Alcohol causes direct gastric mucosal irritation and can worsen volume depletion, adding to NSAID-related GI and renal stress.", "evidenceLevel": "moderate", "sources": [ { "text": "Sostres C, Gargallo CJ, Arroyo MT, Lanas A. Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract. Best Pract Res Clin Gastroenterol. 2010;24(2):121-132.", "pmid": "20227026", "doi": "10.1016/j.bpg.2009.11.005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20227026/", "publicSourceType": "PMID" }, { "text": "Strate LL, Singh P, Boylan MR, Piawah S, Cao Y, Chan AT. A Prospective Study of Alcohol Consumption and Smoking and the Risk of Major Gastrointestinal Bleeding in Men. PLoS One. 2016;11(11):e0165278.", "pmid": "27824864", "doi": "10.1371/journal.pone.0165278", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27824864/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Alcohol can partially erase celecoxib's GI-sparing advantage and increase bleeding risk.", "clinicalSignificance": "The risk is lower than with some NSAIDs but still relevant in patients with ulcer or bleeding risk factors.", "managementStrategy": "Limit alcohol, avoid dehydration, and use extra caution if celecoxib is combined with aspirin.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Diclofenac", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Alcohol can increase diclofenac-related gastrointestinal bleeding risk. Diclofenac reduces protective gastric prostaglandins, and alcohol can directly damage the stomach lining. The combination is more concerning with scheduled diclofenac use, ulcer history, older age, or additional bleeding-risk medicines.", "recommendation": "Avoid heavy alcohol use while taking diclofenac. Use the lowest effective dose for the shortest time and seek care promptly for black stools, vomiting blood, severe stomach pain, or faintness.", "minimumTimeSeparation": null, "mechanism": "Diclofenac inhibits COX-mediated prostaglandin synthesis, weakening gastric mucosal defense. Ethanol adds mucosal irritation and can worsen bleeding from NSAID-associated erosions or ulcers.", "evidenceLevel": "strong", "sources": [ { "text": "Castellsague J, Riera-Guardia N, Calingaert B, Varas-Lorenzo C, Fourrier-Reglat A, Nicotra F, et al. Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project). Drug Saf. 2012;35(12):1127-1146.", "pmid": "23137151", "doi": "10.2165/11633470-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23137151/", "publicSourceType": "PMID" }, { "text": "Strate LL, Singh P, Boylan MR, Piawah S, Cao Y, Chan AT. A Prospective Study of Alcohol Consumption and Smoking and the Risk of Major Gastrointestinal Bleeding in Men. PLoS One. 2016;11(11):e0165278.", "pmid": "27824864", "doi": "10.1371/journal.pone.0165278", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27824864/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Alcohol adds to diclofenac's NSAID-related GI bleeding risk.", "clinicalSignificance": "The combination is clinically important because both exposures independently increase upper GI injury risk.", "managementStrategy": "Avoid heavy alcohol and keep diclofenac exposure as low and short as possible.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Meloxicam", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Alcohol can increase the risk of stomach bleeding while taking meloxicam. Meloxicam is somewhat COX-2 selective but still causes clinically meaningful NSAID GI injury, especially with chronic use. Risk is higher with older age, prior ulcers, high dose, dehydration, or other bleeding-risk drugs.", "recommendation": "Avoid heavy alcohol while taking meloxicam. If meloxicam is used daily, report black stools, vomiting blood, worsening stomach pain, dizziness, or unusual weakness right away.", "minimumTimeSeparation": null, "mechanism": "Meloxicam inhibits prostaglandin synthesis and can impair gastric mucosal defense. Alcohol adds direct mucosal irritation and can worsen NSAID-associated erosive injury and bleeding.", "evidenceLevel": "moderate", "sources": [ { "text": "Sostres C, Gargallo CJ, Arroyo MT, Lanas A. Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract. Best Pract Res Clin Gastroenterol. 2010;24(2):121-132.", "pmid": "20227026", "doi": "10.1016/j.bpg.2009.11.005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20227026/", "publicSourceType": "PMID" }, { "text": "Strate LL, Singh P, Boylan MR, Piawah S, Cao Y, Chan AT. A Prospective Study of Alcohol Consumption and Smoking and the Risk of Major Gastrointestinal Bleeding in Men. PLoS One. 2016;11(11):e0165278.", "pmid": "27824864", "doi": "10.1371/journal.pone.0165278", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27824864/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Alcohol can turn meloxicam-related GI irritation into clinically significant bleeding.", "clinicalSignificance": "Daily meloxicam plus alcohol is a realistic preventable risk for upper GI bleeding.", "managementStrategy": "Limit alcohol and avoid chronic meloxicam use without GI risk assessment.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Ibuprofen", "supplementBName": "Potassium", "interactionType": "caution", "severity": "serious", "description": "Ibuprofen can reduce kidney potassium excretion, and potassium supplements can push serum potassium higher. This is most important if you have kidney disease, diabetes, dehydration, older age, or also take an ACE inhibitor, ARB, or potassium-sparing diuretic. Severe hyperkalemia can cause weakness, palpitations, dangerous arrhythmias, or collapse.", "recommendation": "Do not use potassium supplements with repeated ibuprofen dosing unless your clinician has advised it. If the combination is necessary, check kidney function and serum potassium, and avoid ibuprofen during dehydration, vomiting, diarrhea, or poor fluid intake.", "minimumTimeSeparation": null, "mechanism": "NSAID inhibition of renal prostaglandins can lower renin and aldosterone activity and reduce renal potassium secretion. Supplemental potassium adds directly to the potassium load, making hyperkalemia more likely when renal excretion is impaired.", "evidenceLevel": "moderate", "sources": [ { "text": "Kim GH. Renal effects of prostaglandins and cyclooxygenase-2 inhibitors. Electrolyte Blood Press. 2008;6(1):35-41.", "pmid": "24459520", "doi": "10.5049/EBP.2008.6.1.35", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24459520/", "publicSourceType": "PMID" }, { "text": "John SK, Rangan Y, Block CA, Koff MD. Life-threatening hyperkalemia from nutritional supplements: uncommon or undiagnosed? Am J Emerg Med. 2011;29(9):1237.e1-1237.e2.", "pmid": "21075579", "doi": "10.1016/j.ajem.2010.08.029", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21075579/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Ibuprofen-related potassium retention plus potassium supplementation can cause hyperkalemia.", "clinicalSignificance": "The combination is especially important in common high-risk settings such as CKD, dehydration, or ACE inhibitor/ARB therapy.", "managementStrategy": "Avoid unsupervised potassium supplements with repeated ibuprofen and monitor potassium if combined.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Naproxen", "supplementBName": "Potassium", "interactionType": "caution", "severity": "serious", "description": "Naproxen can impair kidney potassium handling, and potassium supplements can add enough potassium to cause hyperkalemia in susceptible people. Risk is higher with kidney disease, diabetes, dehydration, older age, ACE inhibitors, ARBs, or potassium-sparing diuretics. Hyperkalemia may be silent until it causes weakness or heart rhythm problems.", "recommendation": "Avoid potassium supplements during repeated naproxen use unless a clinician is monitoring you. If you need both, check serum potassium and kidney function, and stop naproxen during significant dehydration or acute illness unless told otherwise.", "minimumTimeSeparation": null, "mechanism": "Naproxen inhibits renal prostaglandin synthesis, which can suppress renin and aldosterone and reduce distal potassium secretion. Added potassium intake can exceed renal excretory capacity when this pathway is impaired.", "evidenceLevel": "moderate", "sources": [ { "text": "Kim GH. Renal effects of prostaglandins and cyclooxygenase-2 inhibitors. Electrolyte Blood Press. 2008;6(1):35-41.", "pmid": "24459520", "doi": "10.5049/EBP.2008.6.1.35", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24459520/", "publicSourceType": "PMID" }, { "text": "Batra V, Villgran V. Hyperkalemia from Dietary Supplements. Cureus. 2016;8(11):e859.", "pmid": "27924248", "doi": "10.7759/cureus.859", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27924248/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Naproxen can reduce potassium excretion while potassium supplements increase potassium load.", "clinicalSignificance": "Unrecognized hyperkalemia can be life-threatening in patients with kidney or medication risk factors.", "managementStrategy": "Use potassium supplements only with monitoring if repeated naproxen is needed.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Celecoxib", "supplementBName": "Potassium", "interactionType": "caution", "severity": "serious", "description": "Celecoxib can still affect kidney prostaglandins and potassium balance despite its COX-2 selectivity. Potassium supplements increase the potassium load and can contribute to hyperkalemia when renal excretion is reduced. The combination is most risky with kidney disease, dehydration, diabetes, older age, ACE inhibitors, ARBs, or potassium-sparing diuretics.", "recommendation": "Do not add potassium supplements to celecoxib without a reason and a monitoring plan. Check serum potassium and kidney function if you need both, and avoid celecoxib during dehydration unless your clinician advises otherwise.", "minimumTimeSeparation": null, "mechanism": "COX-2 inhibition in the kidney can reduce prostaglandin-mediated renin release and alter aldosterone-dependent potassium excretion. Supplemental potassium can then accumulate when renal reserve is limited.", "evidenceLevel": "moderate", "sources": [ { "text": "Kim GH. Renal effects of prostaglandins and cyclooxygenase-2 inhibitors. Electrolyte Blood Press. 2008;6(1):35-41.", "pmid": "24459520", "doi": "10.5049/EBP.2008.6.1.35", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24459520/", "publicSourceType": "PMID" }, { "text": "Lehnhardt A, Kemper MJ. Pathogenesis, diagnosis and management of hyperkalemia. Pediatr Nephrol. 2011;26(3):377-384.", "pmid": "21181208", "doi": "10.1007/s00467-010-1699-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21181208/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Celecoxib-related renal potassium retention can add to potassium supplementation.", "clinicalSignificance": "COX-2 selectivity does not eliminate NSAID-related renal electrolyte risk.", "managementStrategy": "Avoid unsupervised potassium supplementation and monitor labs if the combination is necessary.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Diclofenac", "supplementBName": "Potassium", "interactionType": "caution", "severity": "serious", "description": "Diclofenac can impair kidney potassium excretion, and potassium supplements can make hyperkalemia more likely. Risk is higher during dehydration or acute illness and in people with kidney disease, diabetes, older age, ACE inhibitors, ARBs, or potassium-sparing diuretics. High potassium may cause weakness, palpitations, or dangerous rhythm changes.", "recommendation": "Avoid potassium supplements during repeated diclofenac use unless your clinician is monitoring potassium and kidney function. Stop diclofenac and seek advice during vomiting, diarrhea, poor intake, or dehydration.", "minimumTimeSeparation": null, "mechanism": "Diclofenac blocks renal prostaglandin production, which can suppress renin and aldosterone and reduce potassium secretion in the distal nephron. Supplemental potassium increases the filtered and extracellular potassium load.", "evidenceLevel": "moderate", "sources": [ { "text": "Kim GH. Renal effects of prostaglandins and cyclooxygenase-2 inhibitors. Electrolyte Blood Press. 2008;6(1):35-41.", "pmid": "24459520", "doi": "10.5049/EBP.2008.6.1.35", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24459520/", "publicSourceType": "PMID" }, { "text": "Batra V, Villgran V. Hyperkalemia from Dietary Supplements. Cureus. 2016;8(11):e859.", "pmid": "27924248", "doi": "10.7759/cureus.859", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27924248/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Diclofenac can promote potassium retention while potassium supplements add potassium load.", "clinicalSignificance": "This becomes clinically important in dehydration, CKD, and common heart or blood pressure medication combinations.", "managementStrategy": "Avoid unsupervised potassium and monitor serum potassium if combined with diclofenac.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Meloxicam", "supplementBName": "Potassium", "interactionType": "caution", "severity": "serious", "description": "Meloxicam can reduce renal potassium excretion, and potassium supplements can raise potassium further. Risk is most clinically important with kidney disease, diabetes, older age, dehydration, ACE inhibitors, ARBs, or potassium-sparing diuretics. Severe hyperkalemia can cause dangerous heart rhythm changes.", "recommendation": "Avoid potassium supplements with daily meloxicam unless your clinician has recommended and is monitoring them. Check serum potassium and kidney function if both are needed, especially after illness or dehydration.", "minimumTimeSeparation": null, "mechanism": "NSAID-related renal prostaglandin inhibition can reduce renin and aldosterone signaling, limiting distal nephron potassium secretion. Supplemental potassium increases the potassium burden and may exceed renal excretory capacity.", "evidenceLevel": "moderate", "sources": [ { "text": "Kim GH. Renal effects of prostaglandins and cyclooxygenase-2 inhibitors. Electrolyte Blood Press. 2008;6(1):35-41.", "pmid": "24459520", "doi": "10.5049/EBP.2008.6.1.35", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24459520/", "publicSourceType": "PMID" }, { "text": "John SK, Rangan Y, Block CA, Koff MD. Life-threatening hyperkalemia from nutritional supplements: uncommon or undiagnosed? Am J Emerg Med. 2011;29(9):1237.e1-1237.e2.", "pmid": "21075579", "doi": "10.1016/j.ajem.2010.08.029", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21075579/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Meloxicam and potassium supplementation can combine to raise serum potassium.", "clinicalSignificance": "Hyperkalemia risk is preventable but can be severe in patients with renal or medication risk factors.", "managementStrategy": "Avoid unsupervised potassium and monitor labs when daily meloxicam is used.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Ibuprofen", "supplementBName": "Ginkgo Biloba", "interactionType": "caution", "severity": "dangerous", "description": "Ginkgo biloba may add antiplatelet effects to ibuprofen and has a published case of fatal intracerebral bleeding with ibuprofen. Ibuprofen also increases GI bleeding risk through NSAID mucosal injury. The combination is especially concerning with high-dose ginkgo, repeated ibuprofen use, older age, head injury risk, or other bleeding-risk medicines.", "recommendation": "Avoid combining ginkgo supplements with repeated ibuprofen dosing. If you have used both and develop severe headache, neurologic symptoms, black stools, vomiting blood, or unusual bruising, seek urgent care.", "minimumTimeSeparation": null, "mechanism": "Ginkgo constituents can inhibit platelet-activating factor signaling and reduce platelet aggregation. Ibuprofen reversibly inhibits platelet COX-1 and also weakens gastric mucosal protection, creating additive bleeding risk.", "evidenceLevel": "moderate", "sources": [ { "text": "Meisel C, Johne A, Roots I. Fatal intracerebral mass bleeding associated with Ginkgo biloba and ibuprofen. Atherosclerosis. 2003;167(2):367.", "pmid": "12818420", "doi": "10.1016/s0021-9150(03)00015-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12818420/", "publicSourceType": "PMID" }, { "text": "Bent S, Goldberg H, Padula A, Avins AL. Spontaneous bleeding associated with ginkgo biloba: a case report and systematic review of the literature. J Gen Intern Med. 2005;20(7):657-661.", "pmid": "16050865", "doi": "10.1111/j.1525-1497.2005.0121.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16050865/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Ginkgo and ibuprofen can additively increase bleeding risk, including rare intracranial bleeding.", "clinicalSignificance": "A fatal case report exists for this exact pair, so the warning is stronger than a purely theoretical antiplatelet concern.", "managementStrategy": "Avoid the combination when possible, especially with repeated ibuprofen or any bleeding risk factor.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Naproxen", "supplementBName": "Ginkgo Biloba", "interactionType": "caution", "severity": "serious", "description": "Ginkgo biloba may increase bleeding risk when combined with naproxen. Ginkgo has case reports of spontaneous bleeding, while naproxen is a higher-GI-risk NSAID that can also affect platelet function. The combination is more concerning with chronic naproxen use, older age, ulcer history, or other blood thinners.", "recommendation": "Avoid ginkgo supplements if you use naproxen regularly. If the combination is continued, use the lowest naproxen dose for the shortest time and watch for bruising, nosebleeds, black stools, or neurologic symptoms.", "minimumTimeSeparation": null, "mechanism": "Ginkgo may inhibit platelet-activating factor and platelet aggregation. Naproxen inhibits COX-mediated prostaglandin synthesis and has a relatively strong association with upper GI complications, adding mucosal bleeding risk.", "evidenceLevel": "emerging", "sources": [ { "text": "Bent S, Goldberg H, Padula A, Avins AL. Spontaneous bleeding associated with ginkgo biloba: a case report and systematic review of the literature. J Gen Intern Med. 2005;20(7):657-661.", "pmid": "16050865", "doi": "10.1111/j.1525-1497.2005.0121.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16050865/", "publicSourceType": "PMID" }, { "text": "Castellsague J, Riera-Guardia N, Calingaert B, Varas-Lorenzo C, Fourrier-Reglat A, Nicotra F, et al. Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project). Drug Saf. 2012;35(12):1127-1146.", "pmid": "23137151", "doi": "10.2165/11633470-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23137151/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Ginkgo may add antiplatelet activity to naproxen-related GI bleeding risk.", "clinicalSignificance": "Direct naproxen-ginkgo outcome data are limited, but both sides have clinically relevant bleeding signals.", "managementStrategy": "Avoid ginkgo with regular naproxen or monitor closely for bleeding symptoms.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Celecoxib", "supplementBName": "Ginkgo Biloba", "interactionType": "caution", "severity": "moderate", "description": "Ginkgo biloba may add bleeding risk to celecoxib, particularly in people who also take aspirin or have ulcer history. Celecoxib is more GI-sparing than many NSAIDs, but it does not eliminate GI bleeding risk. Ginkgo has case reports of spontaneous bleeding and uncertain but plausible platelet effects.", "recommendation": "Avoid ginkgo if you take celecoxib with aspirin or other bleeding-risk medicines. If used together, watch for unusual bruising, nosebleeds, black stools, or new severe headache.", "minimumTimeSeparation": null, "mechanism": "Ginkgo may reduce platelet activation through platelet-activating factor pathways. Celecoxib inhibits COX-2 and can still contribute to GI injury, especially when combined with aspirin or other risk factors.", "evidenceLevel": "emerging", "sources": [ { "text": "Kellermann AJ, Kloft C. Is there a risk of bleeding associated with standardized Ginkgo biloba extract therapy? A systematic review and meta-analysis. Pharmacotherapy. 2011;31(5):490-502.", "pmid": "21923430", "doi": "10.1592/phco.31.5.490", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21923430/", "publicSourceType": "PMID" }, { "text": "Sostres C, Gargallo CJ, Arroyo MT, Lanas A. Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract. Best Pract Res Clin Gastroenterol. 2010;24(2):121-132.", "pmid": "20227026", "doi": "10.1016/j.bpg.2009.11.005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20227026/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Ginkgo may add bleeding risk to celecoxib in higher-risk patients.", "clinicalSignificance": "The signal is weaker than with ibuprofen, but caution is reasonable when celecoxib is not the only bleeding-risk exposure.", "managementStrategy": "Avoid ginkgo with celecoxib if other bleeding risks are present.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Diclofenac", "supplementBName": "Ginkgo Biloba", "interactionType": "caution", "severity": "serious", "description": "Ginkgo biloba may increase bleeding risk with diclofenac. Ginkgo has reported spontaneous bleeding cases, and diclofenac can cause NSAID-related GI injury and bleeding. The combination is more concerning with scheduled diclofenac, older age, ulcer history, or other antiplatelet or anticoagulant agents.", "recommendation": "Avoid ginkgo while using diclofenac regularly. If you continue both, use the lowest diclofenac exposure possible and seek care for black stools, vomiting blood, severe headache, or unusual bruising.", "minimumTimeSeparation": null, "mechanism": "Ginkgo may inhibit platelet activation, while diclofenac reduces protective gastric prostaglandins through COX inhibition. The combined effect can lower hemostatic reserve and increase bleeding from NSAID-related mucosal injury.", "evidenceLevel": "emerging", "sources": [ { "text": "Bent S, Goldberg H, Padula A, Avins AL. Spontaneous bleeding associated with ginkgo biloba: a case report and systematic review of the literature. J Gen Intern Med. 2005;20(7):657-661.", "pmid": "16050865", "doi": "10.1111/j.1525-1497.2005.0121.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16050865/", "publicSourceType": "PMID" }, { "text": "Castellsague J, Riera-Guardia N, Calingaert B, Varas-Lorenzo C, Fourrier-Reglat A, Nicotra F, et al. Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project). Drug Saf. 2012;35(12):1127-1146.", "pmid": "23137151", "doi": "10.2165/11633470-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23137151/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Ginkgo may add antiplatelet bleeding risk to diclofenac-related GI injury.", "clinicalSignificance": "Direct diclofenac-ginkgo data are limited, but the combined pharmacodynamic risk is clinically plausible.", "managementStrategy": "Avoid ginkgo with regular diclofenac, especially in patients with bleeding or ulcer risk factors.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Meloxicam", "supplementBName": "Ginkgo Biloba", "interactionType": "caution", "severity": "moderate", "description": "Ginkgo biloba may add bleeding risk to meloxicam. Meloxicam can still cause NSAID GI injury despite partial COX-2 selectivity, and ginkgo has case reports of spontaneous bleeding. Risk is higher with daily meloxicam, older age, ulcer history, or additional blood-thinning medicines.", "recommendation": "Avoid ginkgo if you use meloxicam every day or have a history of ulcers or bleeding. If both are used, watch for unusual bruising, nosebleeds, black stools, or severe headache.", "minimumTimeSeparation": null, "mechanism": "Ginkgo may inhibit platelet activation through platelet-activating factor pathways. Meloxicam inhibits prostaglandin synthesis and can weaken gastric mucosal defense, allowing antiplatelet effects to matter more clinically.", "evidenceLevel": "emerging", "sources": [ { "text": "Kellermann AJ, Kloft C. Is there a risk of bleeding associated with standardized Ginkgo biloba extract therapy? A systematic review and meta-analysis. Pharmacotherapy. 2011;31(5):490-502.", "pmid": "21923430", "doi": "10.1592/phco.31.5.490", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21923430/", "publicSourceType": "PMID" }, { "text": "Sostres C, Gargallo CJ, Arroyo MT, Lanas A. Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract. Best Pract Res Clin Gastroenterol. 2010;24(2):121-132.", "pmid": "20227026", "doi": "10.1016/j.bpg.2009.11.005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20227026/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Ginkgo may add platelet-related bleeding risk to meloxicam's GI injury risk.", "clinicalSignificance": "The evidence is indirect for this exact pair, so the warning is focused on higher-risk users.", "managementStrategy": "Avoid ginkgo with daily meloxicam when other bleeding risk factors are present.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Ibuprofen", "supplementBName": "Nattokinase", "interactionType": "caution", "severity": "serious", "description": "Nattokinase has fibrinolytic and anticoagulant effects that may add to ibuprofen-related bleeding risk. Ibuprofen can irritate the GI tract and transiently impair platelet function. The combination is most concerning with high-dose nattokinase, repeated ibuprofen use, prior ulcers, surgery, or other blood-thinning medicines.", "recommendation": "Avoid nattokinase while using ibuprofen regularly. Stop nattokinase at least 1-2 weeks before procedures unless your clinician gives different instructions, and seek care for bleeding symptoms.", "minimumTimeSeparation": null, "mechanism": "Nattokinase promotes fibrinolysis and has been shown to affect coagulation and platelet-related thrombus formation. Ibuprofen adds COX-1-mediated platelet effects and NSAID mucosal injury, reducing hemostatic reserve.", "evidenceLevel": "emerging", "sources": [ { "text": "Kurosawa Y, Nirengi S, Homma T, Esaki K, Ohta M, Clark JF, et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep. 2015;5:11601.", "pmid": "26109079", "doi": "10.1038/srep11601", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26109079/", "publicSourceType": "PMID" }, { "text": "Sostres C, Gargallo CJ, Arroyo MT, Lanas A. Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract. Best Pract Res Clin Gastroenterol. 2010;24(2):121-132.", "pmid": "20227026", "doi": "10.1016/j.bpg.2009.11.005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20227026/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Nattokinase may add fibrinolytic activity to ibuprofen-associated bleeding risk.", "clinicalSignificance": "Human nattokinase coagulation effects make this more than a purely theoretical supplement warning.", "managementStrategy": "Avoid nattokinase with regular ibuprofen or any procedure or bleeding-risk context.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Naproxen", "supplementBName": "Nattokinase", "interactionType": "caution", "severity": "serious", "description": "Nattokinase may add fibrinolytic and anticoagulant effects to naproxen's GI bleeding risk. Naproxen is a higher-GI-risk NSAID, so a supplement that affects clot formation can make bleeding harder to control. The combination is higher risk around procedures, with ulcer history, or with other antithrombotic medicines.", "recommendation": "Avoid nattokinase while taking naproxen regularly. Stop nattokinase before surgery or dental procedures unless your clinician directs otherwise, and report any unusual bleeding promptly.", "minimumTimeSeparation": null, "mechanism": "Nattokinase can enhance fibrinolysis and reduce clot stability, while naproxen inhibits COX-mediated prostaglandins and contributes to GI mucosal injury. Together they can increase both the chance of bleeding and the difficulty of stopping it.", "evidenceLevel": "emerging", "sources": [ { "text": "Kurosawa Y, Nirengi S, Homma T, Esaki K, Ohta M, Clark JF, et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep. 2015;5:11601.", "pmid": "26109079", "doi": "10.1038/srep11601", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26109079/", "publicSourceType": "PMID" }, { "text": "Castellsague J, Riera-Guardia N, Calingaert B, Varas-Lorenzo C, Fourrier-Reglat A, Nicotra F, et al. Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project). Drug Saf. 2012;35(12):1127-1146.", "pmid": "23137151", "doi": "10.2165/11633470-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23137151/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Nattokinase may make naproxen-associated GI bleeding more likely or harder to stop.", "clinicalSignificance": "The exact pair lacks outcome trials, but each component has a clinically relevant bleeding mechanism.", "managementStrategy": "Avoid nattokinase with regular naproxen, especially before procedures or with ulcer history.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Celecoxib", "supplementBName": "Nattokinase", "interactionType": "caution", "severity": "serious", "description": "Nattokinase may add fibrinolytic effects to celecoxib-related bleeding risk, especially when celecoxib is used with aspirin or in patients with ulcer history. Celecoxib alone is less platelet-active than nonselective NSAIDs, but it can still contribute to GI injury. Nattokinase has human evidence of coagulation and thrombolysis effects.", "recommendation": "Avoid nattokinase if you take celecoxib with aspirin or other blood-thinning medicines. Stop nattokinase before procedures unless your clinician has specifically approved continued use.", "minimumTimeSeparation": null, "mechanism": "Nattokinase can potentiate fibrinolysis and alter coagulation profiles. Celecoxib inhibits COX-2 and can still produce GI injury, so clot-destabilizing supplements can become clinically relevant in higher-risk settings.", "evidenceLevel": "emerging", "sources": [ { "text": "Kurosawa Y, Nirengi S, Homma T, Esaki K, Ohta M, Clark JF, et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep. 2015;5:11601.", "pmid": "26109079", "doi": "10.1038/srep11601", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26109079/", "publicSourceType": "PMID" }, { "text": "Jang JY, Kim TS, Cai J, Kim J, Kim Y, Shin K, et al. Nattokinase improves blood flow by inhibiting platelet aggregation and thrombus formation. Lab Anim Res. 2013;29(4):221-225.", "pmid": "24396387", "doi": "10.5625/lar.2013.29.4.221", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24396387/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Nattokinase may reduce clot stability during celecoxib-associated bleeding.", "clinicalSignificance": "This is mainly relevant when celecoxib is combined with aspirin, procedures, or other bleeding risks.", "managementStrategy": "Avoid nattokinase in celecoxib users with additional bleeding risks or planned procedures.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Diclofenac", "supplementBName": "Nattokinase", "interactionType": "caution", "severity": "serious", "description": "Nattokinase may compound diclofenac-related bleeding risk through fibrinolytic and anticoagulant effects. Diclofenac can cause NSAID-related GI mucosal injury, and nattokinase may reduce clot stability. The combination is more concerning with ulcer history, scheduled diclofenac, procedures, or other blood-thinning medicines.", "recommendation": "Avoid nattokinase while using diclofenac regularly. Stop nattokinase before surgery or dental procedures unless your clinician specifically directs otherwise.", "minimumTimeSeparation": null, "mechanism": "Nattokinase can enhance thrombolytic and anticoagulant profiles, while diclofenac inhibits COX-mediated prostaglandins and can damage GI mucosa. These effects can converge on a higher bleeding burden.", "evidenceLevel": "emerging", "sources": [ { "text": "Kurosawa Y, Nirengi S, Homma T, Esaki K, Ohta M, Clark JF, et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep. 2015;5:11601.", "pmid": "26109079", "doi": "10.1038/srep11601", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26109079/", "publicSourceType": "PMID" }, { "text": "Castellsague J, Riera-Guardia N, Calingaert B, Varas-Lorenzo C, Fourrier-Reglat A, Nicotra F, et al. Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project). Drug Saf. 2012;35(12):1127-1146.", "pmid": "23137151", "doi": "10.2165/11633470-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23137151/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Nattokinase may make diclofenac-related GI bleeding more clinically significant.", "clinicalSignificance": "The risk is most important in patients with ulcer history, procedures, or other antithrombotic exposures.", "managementStrategy": "Avoid nattokinase with regular diclofenac and hold it before procedures.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Meloxicam", "supplementBName": "Nattokinase", "interactionType": "caution", "severity": "serious", "description": "Nattokinase may add fibrinolytic effects to meloxicam's NSAID bleeding risk. Meloxicam can still cause GI injury with daily use, and nattokinase may make bleeding harder to stop. Risk is higher with prior ulcers, procedures, older age, or other blood-thinning medicines.", "recommendation": "Avoid nattokinase if you use meloxicam daily or have bleeding risk factors. Stop nattokinase before procedures unless your clinician specifically recommends continuing it.", "minimumTimeSeparation": null, "mechanism": "Nattokinase enhances fibrinolytic activity and can affect coagulation profiles. Meloxicam inhibits prostaglandin synthesis and can weaken GI mucosal defense, so clot-destabilizing effects may matter if bleeding starts.", "evidenceLevel": "emerging", "sources": [ { "text": "Kurosawa Y, Nirengi S, Homma T, Esaki K, Ohta M, Clark JF, et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep. 2015;5:11601.", "pmid": "26109079", "doi": "10.1038/srep11601", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26109079/", "publicSourceType": "PMID" }, { "text": "Sostres C, Gargallo CJ, Arroyo MT, Lanas A. Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract. Best Pract Res Clin Gastroenterol. 2010;24(2):121-132.", "pmid": "20227026", "doi": "10.1016/j.bpg.2009.11.005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20227026/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Nattokinase may add fibrinolytic bleeding risk to meloxicam-associated GI injury.", "clinicalSignificance": "Evidence for this exact pair is indirect, so the warning targets regular meloxicam use and high-risk contexts.", "managementStrategy": "Avoid nattokinase with daily meloxicam, especially before procedures or with ulcer history.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Ibuprofen", "supplementBName": "Garlic Extract", "interactionType": "caution", "severity": "moderate", "description": "Concentrated garlic extract may add antiplatelet activity to ibuprofen's bleeding risk. This is most relevant with high-dose garlic products, repeated ibuprofen use, upcoming procedures, ulcer history, or other blood-thinning medicines. Culinary garlic in food is much less concerning than supplement-dose extract.", "recommendation": "Avoid high-dose garlic extract while using ibuprofen regularly. Stop garlic extract before procedures if your surgical team recommends it, and watch for nosebleeds, bruising, black stools, or vomiting blood.", "minimumTimeSeparation": null, "mechanism": "Garlic preparations can affect platelet aggregation and bleeding time in human studies. Ibuprofen can reversibly inhibit platelet COX-1 and increase NSAID-related GI mucosal injury, creating additive pharmacodynamic bleeding risk.", "evidenceLevel": "emerging", "sources": [ { "text": "Fakhar H, Hashemi Tayer A. Effect of the Garlic Pill in comparison with Plavix on Platelet Aggregation and Bleeding Time. Iran J Ped Hematol Oncol. 2012;2(4):146-152.", "pmid": "24575255", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24575255/", "publicSourceType": "PMID" }, { "text": "Sostres C, Gargallo CJ, Arroyo MT, Lanas A. Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract. Best Pract Res Clin Gastroenterol. 2010;24(2):121-132.", "pmid": "20227026", "doi": "10.1016/j.bpg.2009.11.005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20227026/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Garlic extract may add platelet inhibition to ibuprofen-related GI bleeding risk.", "clinicalSignificance": "The risk is most plausible with supplement-dose garlic rather than normal dietary garlic.", "managementStrategy": "Avoid high-dose garlic extract with regular ibuprofen or before procedures.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Naproxen", "supplementBName": "Garlic Extract", "interactionType": "caution", "severity": "moderate", "description": "Concentrated garlic extract may add antiplatelet effects to naproxen's GI bleeding risk. Naproxen has a relatively strong association with upper GI complications, so even modest platelet effects may matter in high-risk people. The concern is highest with supplement-dose garlic extract, prior ulcers, older age, or other blood thinners.", "recommendation": "Avoid high-dose garlic extract if you take naproxen regularly. Use naproxen at the lowest effective dose and seek care for black stools, vomiting blood, or unusual bruising.", "minimumTimeSeparation": null, "mechanism": "Garlic constituents can affect platelet aggregation and bleeding time. Naproxen inhibits COX enzymes and reduces protective gastric prostaglandins, increasing the chance that platelet effects translate into clinically relevant bleeding.", "evidenceLevel": "emerging", "sources": [ { "text": "Rahman K, Lowe GM. Garlic and cardiovascular disease: a critical review. J Nutr. 2006;136(3 Suppl):736S-740S.", "pmid": "16484553", "doi": "10.1093/jn/136.3.736S", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16484553/", "publicSourceType": "PMID" }, { "text": "Castellsague J, Riera-Guardia N, Calingaert B, Varas-Lorenzo C, Fourrier-Reglat A, Nicotra F, et al. Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project). Drug Saf. 2012;35(12):1127-1146.", "pmid": "23137151", "doi": "10.2165/11633470-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23137151/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Garlic extract may add antiplatelet activity to naproxen-related GI bleeding risk.", "clinicalSignificance": "Direct outcome data are limited, so the warning is targeted to high-dose extracts and high-risk users.", "managementStrategy": "Avoid high-dose garlic extract with regular naproxen, especially with ulcer or bleeding risk factors.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Diclofenac", "supplementBName": "Garlic Extract", "interactionType": "caution", "severity": "moderate", "description": "Concentrated garlic extract may increase bleeding tendency when combined with diclofenac. Diclofenac can injure the GI lining, while garlic supplements may affect platelet aggregation. The risk is most relevant with regular diclofenac use, high-dose garlic extract, ulcer history, or other bleeding-risk medicines.", "recommendation": "Avoid high-dose garlic extract while using diclofenac regularly. If both are used, watch for bruising, nosebleeds, black stools, vomiting blood, or worsening stomach pain.", "minimumTimeSeparation": null, "mechanism": "Garlic preparations can alter platelet aggregation and bleeding time in human studies. Diclofenac reduces prostaglandin-mediated gastric protection through COX inhibition, creating a setting where platelet effects may worsen bleeding.", "evidenceLevel": "emerging", "sources": [ { "text": "Fakhar H, Hashemi Tayer A. Effect of the Garlic Pill in comparison with Plavix on Platelet Aggregation and Bleeding Time. Iran J Ped Hematol Oncol. 2012;2(4):146-152.", "pmid": "24575255", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24575255/", "publicSourceType": "PMID" }, { "text": "Castellsague J, Riera-Guardia N, Calingaert B, Varas-Lorenzo C, Fourrier-Reglat A, Nicotra F, et al. Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project). Drug Saf. 2012;35(12):1127-1146.", "pmid": "23137151", "doi": "10.2165/11633470-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23137151/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Garlic extract may add platelet-related bleeding risk to diclofenac-associated GI injury.", "clinicalSignificance": "The evidence is indirect but clinically plausible for concentrated extracts and higher-risk patients.", "managementStrategy": "Avoid high-dose garlic extract with regular diclofenac or before procedures.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Aspirin Low-Dose", "supplementBName": "Turmeric/Curcumin", "interactionType": "caution", "severity": "moderate", "description": "Turmeric/curcumin supplements may add antiplatelet effects to low-dose aspirin. Culinary turmeric is usually a minor exposure, but concentrated curcumin products can deliver much larger doses. The combination is most concerning with prior bleeding, upcoming procedures, high-dose curcumin, or additional blood-thinning medicines.", "recommendation": "Avoid high-dose turmeric/curcumin supplements with low-dose aspirin unless your clinician agrees. Stop curcumin before procedures if your surgical team recommends it, and report unusual bruising, nosebleeds, or black stools.", "minimumTimeSeparation": null, "mechanism": "Curcumin inhibits platelet aggregation pathways including thromboxane formation and calcium signaling. Aspirin irreversibly inhibits platelet COX-1, so concentrated curcumin can add pharmacodynamic antiplatelet activity.", "evidenceLevel": "emerging", "sources": [ { "text": "Shah BH, Nawaz Z, Pertani SA, Roomi A, Mahmood H, Saeed SA, et al. Inhibitory effect of curcumin, a food spice from turmeric, on platelet-activating factor- and arachidonic acid-mediated platelet aggregation through inhibition of thromboxane formation and Ca2+ signaling. Biochem Pharmacol. 1999;58(7):1167-1172.", "pmid": "10484074", "doi": "10.1016/s0006-2952(99)00206-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10484074/", "publicSourceType": "PMID" }, { "text": "Kaufman DW, Kelly JP, Wiholm BE, Laszlo A, Sheehan JE, Koff RS, et al. The risk of acute major upper gastrointestinal bleeding among users of aspirin and ibuprofen at various levels of alcohol consumption. Am J Gastroenterol. 1999;94(11):3189-3196.", "pmid": "10566713", "doi": "10.1111/j.1572-0241.1999.01517.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10566713/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Concentrated curcumin may add platelet inhibition to aspirin's antiplatelet effect.", "clinicalSignificance": "This is mainly relevant for supplement-dose curcumin rather than food-level turmeric.", "managementStrategy": "Avoid high-dose curcumin with aspirin in bleeding-risk or perioperative settings.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Ibuprofen", "supplementBName": "Turmeric/Curcumin", "interactionType": "caution", "severity": "moderate", "description": "Concentrated turmeric/curcumin may add antiplatelet effects to ibuprofen's bleeding risk. Ibuprofen also increases upper GI injury risk, especially with repeated use. The concern is highest with high-dose curcumin products, ulcer history, older age, procedures, or other blood-thinning medicines.", "recommendation": "Avoid high-dose curcumin supplements while using ibuprofen regularly. If both are used, keep ibuprofen exposure short and watch for bruising, nosebleeds, black stools, or vomiting blood.", "minimumTimeSeparation": null, "mechanism": "Curcumin can inhibit platelet aggregation through thromboxane and calcium signaling pathways. Ibuprofen reversibly inhibits platelet COX-1 and reduces gastric prostaglandin protection, creating additive bleeding potential.", "evidenceLevel": "emerging", "sources": [ { "text": "Shah BH, Nawaz Z, Pertani SA, Roomi A, Mahmood H, Saeed SA, et al. Inhibitory effect of curcumin, a food spice from turmeric, on platelet-activating factor- and arachidonic acid-mediated platelet aggregation through inhibition of thromboxane formation and Ca2+ signaling. Biochem Pharmacol. 1999;58(7):1167-1172.", "pmid": "10484074", "doi": "10.1016/s0006-2952(99)00206-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10484074/", "publicSourceType": "PMID" }, { "text": "Sostres C, Gargallo CJ, Arroyo MT, Lanas A. Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract. Best Pract Res Clin Gastroenterol. 2010;24(2):121-132.", "pmid": "20227026", "doi": "10.1016/j.bpg.2009.11.005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20227026/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Curcumin may add platelet inhibition to ibuprofen-related GI bleeding risk.", "clinicalSignificance": "Evidence for clinical bleeding is limited, so this is a targeted caution for concentrated supplements and high-risk users.", "managementStrategy": "Avoid high-dose curcumin with regular ibuprofen or before procedures.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Naproxen", "supplementBName": "Turmeric/Curcumin", "interactionType": "caution", "severity": "moderate", "description": "Concentrated turmeric/curcumin may add antiplatelet activity to naproxen's GI bleeding risk. Naproxen has a relatively strong association with upper GI complications, and curcumin can inhibit platelet aggregation in experimental models. Risk is higher with high-dose curcumin, ulcer history, older age, or other blood thinners.", "recommendation": "Avoid high-dose curcumin supplements with regular naproxen. If you use both, keep naproxen dose and duration low and watch for black stools, vomiting blood, or unusual bruising.", "minimumTimeSeparation": null, "mechanism": "Curcumin inhibits platelet aggregation pathways involving thromboxane formation and calcium signaling. Naproxen reduces gastric prostaglandin protection and can cause erosions or ulcers, so impaired platelet function may worsen bleeding.", "evidenceLevel": "emerging", "sources": [ { "text": "Shah BH, Nawaz Z, Pertani SA, Roomi A, Mahmood H, Saeed SA, et al. Inhibitory effect of curcumin, a food spice from turmeric, on platelet-activating factor- and arachidonic acid-mediated platelet aggregation through inhibition of thromboxane formation and Ca2+ signaling. Biochem Pharmacol. 1999;58(7):1167-1172.", "pmid": "10484074", "doi": "10.1016/s0006-2952(99)00206-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10484074/", "publicSourceType": "PMID" }, { "text": "Castellsague J, Riera-Guardia N, Calingaert B, Varas-Lorenzo C, Fourrier-Reglat A, Nicotra F, et al. Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project). Drug Saf. 2012;35(12):1127-1146.", "pmid": "23137151", "doi": "10.2165/11633470-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23137151/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Curcumin may add platelet-related bleeding risk to naproxen-associated GI injury.", "clinicalSignificance": "The warning is most relevant for high-dose supplements and patients with existing bleeding or ulcer risk.", "managementStrategy": "Avoid high-dose curcumin with regular naproxen or before procedures.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Diclofenac", "supplementBName": "Turmeric/Curcumin", "interactionType": "caution", "severity": "moderate", "description": "Concentrated turmeric/curcumin may add antiplatelet effects to diclofenac's GI bleeding risk. Diclofenac can cause NSAID-related erosions or ulcers, and curcumin has experimental antiplatelet activity. Risk is higher with high-dose curcumin, regular diclofenac use, ulcer history, procedures, or other blood thinners.", "recommendation": "Avoid high-dose turmeric/curcumin supplements while using diclofenac regularly. If both are used, monitor for bruising, nosebleeds, black stools, vomiting blood, or worsening stomach pain.", "minimumTimeSeparation": null, "mechanism": "Curcumin can inhibit thromboxane formation and calcium signaling in platelets. Diclofenac inhibits prostaglandin synthesis and weakens GI mucosal protection, creating a plausible additive bleeding pathway.", "evidenceLevel": "emerging", "sources": [ { "text": "Shah BH, Nawaz Z, Pertani SA, Roomi A, Mahmood H, Saeed SA, et al. Inhibitory effect of curcumin, a food spice from turmeric, on platelet-activating factor- and arachidonic acid-mediated platelet aggregation through inhibition of thromboxane formation and Ca2+ signaling. Biochem Pharmacol. 1999;58(7):1167-1172.", "pmid": "10484074", "doi": "10.1016/s0006-2952(99)00206-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10484074/", "publicSourceType": "PMID" }, { "text": "Castellsague J, Riera-Guardia N, Calingaert B, Varas-Lorenzo C, Fourrier-Reglat A, Nicotra F, et al. Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project). Drug Saf. 2012;35(12):1127-1146.", "pmid": "23137151", "doi": "10.2165/11633470-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23137151/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Curcumin may add platelet inhibition to diclofenac-associated GI bleeding risk.", "clinicalSignificance": "Clinical outcome data for this exact pair are limited, so the caution focuses on concentrated curcumin and high-risk users.", "managementStrategy": "Avoid high-dose curcumin with regular diclofenac or before procedures.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Meloxicam", "supplementBName": "Turmeric/Curcumin", "interactionType": "caution", "severity": "moderate", "description": "Concentrated turmeric/curcumin may add antiplatelet effects to meloxicam's bleeding risk. Meloxicam can still injure the GI tract with daily use, and curcumin has experimental antiplatelet activity. The concern is higher with high-dose curcumin, ulcer history, older age, procedures, or other blood-thinning medicines.", "recommendation": "Avoid high-dose curcumin supplements if you take meloxicam daily or have bleeding risk factors. Watch for bruising, nosebleeds, black stools, or vomiting blood if both are used.", "minimumTimeSeparation": null, "mechanism": "Curcumin inhibits platelet aggregation pathways involving thromboxane and calcium signaling. Meloxicam inhibits prostaglandin synthesis and can reduce gastric mucosal protection, allowing platelet effects to matter more clinically.", "evidenceLevel": "emerging", "sources": [ { "text": "Shah BH, Nawaz Z, Pertani SA, Roomi A, Mahmood H, Saeed SA, et al. Inhibitory effect of curcumin, a food spice from turmeric, on platelet-activating factor- and arachidonic acid-mediated platelet aggregation through inhibition of thromboxane formation and Ca2+ signaling. Biochem Pharmacol. 1999;58(7):1167-1172.", "pmid": "10484074", "doi": "10.1016/s0006-2952(99)00206-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10484074/", "publicSourceType": "PMID" }, { "text": "Sostres C, Gargallo CJ, Arroyo MT, Lanas A. Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract. Best Pract Res Clin Gastroenterol. 2010;24(2):121-132.", "pmid": "20227026", "doi": "10.1016/j.bpg.2009.11.005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20227026/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Curcumin may add platelet-related bleeding risk to meloxicam-associated GI injury.", "clinicalSignificance": "The risk is indirect but plausible with high-dose curcumin and daily NSAID exposure.", "managementStrategy": "Avoid high-dose curcumin with daily meloxicam or before procedures.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Aspirin Low-Dose", "supplementBName": "Curcumin Phytosome", "interactionType": "caution", "severity": "moderate", "description": "Curcumin phytosome products may produce higher systemic curcumin exposure than standard turmeric powders and may add antiplatelet effects to low-dose aspirin. Aspirin's platelet inhibition is intentional, but added antiplatelet activity can become risky around procedures or in people with bleeding history. Culinary turmeric is not the same exposure as a phytosome supplement.", "recommendation": "Avoid high-dose curcumin phytosome with low-dose aspirin if you have bleeding risk factors or an upcoming procedure. Ask your clinician whether to pause the supplement before surgery or dental work.", "minimumTimeSeparation": null, "mechanism": "Curcumin inhibits platelet aggregation pathways, and phytosome formulations are designed to improve curcumin bioavailability. Aspirin irreversibly inhibits platelet COX-1, so systemic curcumin exposure may add pharmacodynamic antiplatelet activity.", "evidenceLevel": "emerging", "sources": [ { "text": "Shah BH, Nawaz Z, Pertani SA, Roomi A, Mahmood H, Saeed SA, et al. Inhibitory effect of curcumin, a food spice from turmeric, on platelet-activating factor- and arachidonic acid-mediated platelet aggregation through inhibition of thromboxane formation and Ca2+ signaling. Biochem Pharmacol. 1999;58(7):1167-1172.", "pmid": "10484074", "doi": "10.1016/s0006-2952(99)00206-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10484074/", "publicSourceType": "PMID" }, { "text": "Mirzaei H, Shakeri A, Rashidi B, Jalili A, Banikazemi Z, Sahebkar A. Phytosomal curcumin: A review of pharmacokinetic, experimental and clinical studies. Biomed Pharmacother. 2017;85:102-112.", "pmid": "27930973", "doi": "10.1016/j.biopha.2016.11.098", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27930973/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Bioavailable curcumin may add antiplatelet activity to low-dose aspirin.", "clinicalSignificance": "The formulation makes systemic exposure more plausible than ordinary turmeric powder.", "managementStrategy": "Avoid high-dose curcumin phytosome with aspirin in bleeding-risk or perioperative settings.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Diclofenac", "supplementBName": "Curcumin Phytosome", "interactionType": "caution", "severity": "moderate", "description": "Curcumin phytosome may add antiplatelet effects to diclofenac's NSAID bleeding risk. Phytosome formulations are intended to improve curcumin absorption, making supplement-dose exposure more relevant than culinary turmeric. Risk is higher with ulcer history, regular diclofenac use, procedures, or other blood-thinning medicines.", "recommendation": "Avoid high-dose curcumin phytosome while using diclofenac regularly. If both are used, watch for bruising, nosebleeds, black stools, vomiting blood, or worsening stomach pain.", "minimumTimeSeparation": null, "mechanism": "Curcumin can inhibit thromboxane formation and platelet calcium signaling, and phytosome formulations improve bioavailability. Diclofenac reduces gastric prostaglandin protection through COX inhibition, creating additive bleeding potential.", "evidenceLevel": "emerging", "sources": [ { "text": "Jager R, Lowery RP, Calvanese AV, Joy JM, Purpura M, Wilson JM. Comparative absorption of curcumin formulations. Nutr J. 2014;13:11.", "pmid": "24461029", "doi": "10.1186/1475-2891-13-11", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24461029/", "publicSourceType": "PMID" }, { "text": "Shah BH, Nawaz Z, Pertani SA, Roomi A, Mahmood H, Saeed SA, et al. Inhibitory effect of curcumin, a food spice from turmeric, on platelet-activating factor- and arachidonic acid-mediated platelet aggregation through inhibition of thromboxane formation and Ca2+ signaling. Biochem Pharmacol. 1999;58(7):1167-1172.", "pmid": "10484074", "doi": "10.1016/s0006-2952(99)00206-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10484074/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Bioavailable curcumin may add platelet-related bleeding risk to diclofenac-associated GI injury.", "clinicalSignificance": "Clinical outcome evidence is limited, but the high-bioavailability formulation makes the antiplatelet mechanism more relevant.", "managementStrategy": "Avoid high-dose curcumin phytosome with regular diclofenac or before procedures.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Celecoxib", "supplementBName": "Curcumin Phytosome", "interactionType": "caution", "severity": "moderate", "description": "Curcumin phytosome may add antiplatelet activity to celecoxib in people with additional bleeding risks. Celecoxib is less platelet-active than many NSAIDs, but GI bleeding risk is not zero, especially with aspirin or ulcer history. The phytosome formulation is relevant because it can increase curcumin absorption compared with standard preparations.", "recommendation": "Avoid high-dose curcumin phytosome if you take celecoxib with aspirin or have a bleeding or ulcer history. If both are used, monitor for bruising, nosebleeds, black stools, or vomiting blood.", "minimumTimeSeparation": null, "mechanism": "Curcumin can inhibit platelet aggregation, and phytosome products increase systemic curcumin exposure. Celecoxib's COX-2 selectivity reduces but does not eliminate NSAID GI risk, especially when other bleeding risks are present.", "evidenceLevel": "emerging", "sources": [ { "text": "Mirzaei H, Shakeri A, Rashidi B, Jalili A, Banikazemi Z, Sahebkar A. Phytosomal curcumin: A review of pharmacokinetic, experimental and clinical studies. Biomed Pharmacother. 2017;85:102-112.", "pmid": "27930973", "doi": "10.1016/j.biopha.2016.11.098", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27930973/", "publicSourceType": "PMID" }, { "text": "Shah BH, Nawaz Z, Pertani SA, Roomi A, Mahmood H, Saeed SA, et al. Inhibitory effect of curcumin, a food spice from turmeric, on platelet-activating factor- and arachidonic acid-mediated platelet aggregation through inhibition of thromboxane formation and Ca2+ signaling. Biochem Pharmacol. 1999;58(7):1167-1172.", "pmid": "10484074", "doi": "10.1016/s0006-2952(99)00206-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10484074/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Curcumin phytosome may add antiplatelet effects to celecoxib in higher-risk patients.", "clinicalSignificance": "This is a cautious warning for concentrated, bioavailable curcumin products rather than turmeric in food.", "managementStrategy": "Avoid high-dose curcumin phytosome with celecoxib when bleeding risk factors are present.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Celecoxib", "supplementBName": "Fish Oil", "interactionType": "caution", "severity": "moderate", "description": "Fish oil has mild antiplatelet effects and may add bleeding risk to celecoxib in higher-risk situations. Modern randomized-trial evidence suggests usual omega-3 doses do not greatly increase bleeding, but high-dose EPA/DHA or combination with aspirin can matter. The risk is most relevant around procedures or in people with prior GI bleeding.", "recommendation": "Use caution with high-dose fish oil while taking celecoxib, especially if you also take aspirin. Pause fish oil before procedures if your clinical team requests it, and report black stools, vomiting blood, or unusual bruising.", "minimumTimeSeparation": null, "mechanism": "EPA and DHA can reduce platelet aggregation and thromboxane A2 production, although clinical bleeding effects are usually small at standard doses. Celecoxib can still cause GI injury, particularly with aspirin or other risk factors.", "evidenceLevel": "moderate", "sources": [ { "text": "Javaid M, Kadhim K, Bawamia B, Cartlidge T, Farag M, Alkhalil M. Bleeding Risk in Patients Receiving Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Am Heart Assoc. 2024;13(10):e032390.", "pmid": "38742535", "doi": "10.1161/JAHA.123.032390", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38742535/", "publicSourceType": "PMID" }, { "text": "Bays HE. Safety considerations with omega-3 fatty acid therapy. Am J Cardiol. 2007;99(6A):35C-43C.", "pmid": "17368277", "doi": "10.1016/j.amjcard.2006.11.020", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17368277/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose fish oil may modestly add to celecoxib-associated bleeding risk.", "clinicalSignificance": "Usual doses are often tolerated, so the warning is focused on high-dose omega-3 and additional bleeding risks.", "managementStrategy": "Use caution with high-dose fish oil, especially with celecoxib plus aspirin or before procedures.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Diclofenac", "supplementBName": "Fish Oil", "interactionType": "caution", "severity": "moderate", "description": "High-dose fish oil may add mild antiplatelet effects to diclofenac's GI bleeding risk. Standard omega-3 doses usually do not cause major bleeding in trials, but higher EPA/DHA doses and other bleeding risks can change the balance. The combination is more relevant with regular diclofenac use, prior ulcers, or procedures.", "recommendation": "Use caution with high-dose fish oil if you take diclofenac regularly. Tell your surgical or dental team about fish oil, and watch for bruising, black stools, vomiting blood, or nosebleeds.", "minimumTimeSeparation": null, "mechanism": "EPA and DHA can reduce platelet aggregation through altered thromboxane signaling. Diclofenac can cause GI mucosal injury through COX inhibition, so platelet effects may worsen bleeding if erosions occur.", "evidenceLevel": "moderate", "sources": [ { "text": "Javaid M, Kadhim K, Bawamia B, Cartlidge T, Farag M, Alkhalil M. Bleeding Risk in Patients Receiving Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Am Heart Assoc. 2024;13(10):e032390.", "pmid": "38742535", "doi": "10.1161/JAHA.123.032390", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38742535/", "publicSourceType": "PMID" }, { "text": "Castellsague J, Riera-Guardia N, Calingaert B, Varas-Lorenzo C, Fourrier-Reglat A, Nicotra F, et al. Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project). Drug Saf. 2012;35(12):1127-1146.", "pmid": "23137151", "doi": "10.2165/11633470-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23137151/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose fish oil may modestly add to diclofenac-related bleeding risk.", "clinicalSignificance": "This is not a blanket avoidance warning; it is most relevant at high omega-3 doses or with ulcer/procedure risk.", "managementStrategy": "Use caution with high-dose fish oil and regular diclofenac, especially before procedures.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Meloxicam", "supplementBName": "Fish Oil", "interactionType": "caution", "severity": "moderate", "description": "High-dose fish oil may add mild antiplatelet activity to meloxicam's GI bleeding risk. Most randomized-trial data do not show major bleeding increases at usual omega-3 doses, but high-dose EPA/DHA and other bleeding risks can matter. The combination is more important with daily meloxicam, ulcer history, aspirin use, or planned procedures.", "recommendation": "Use caution with high-dose fish oil while taking meloxicam daily. Tell your clinician before procedures and monitor for black stools, vomiting blood, nosebleeds, or unusual bruising.", "minimumTimeSeparation": null, "mechanism": "EPA and DHA can reduce platelet aggregation and alter thromboxane balance. Meloxicam can impair gastric mucosal protection through prostaglandin suppression, allowing platelet effects to become clinically relevant if GI injury occurs.", "evidenceLevel": "moderate", "sources": [ { "text": "Javaid M, Kadhim K, Bawamia B, Cartlidge T, Farag M, Alkhalil M. Bleeding Risk in Patients Receiving Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Am Heart Assoc. 2024;13(10):e032390.", "pmid": "38742535", "doi": "10.1161/JAHA.123.032390", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38742535/", "publicSourceType": "PMID" }, { "text": "Bays HE. Safety considerations with omega-3 fatty acid therapy. Am J Cardiol. 2007;99(6A):35C-43C.", "pmid": "17368277", "doi": "10.1016/j.amjcard.2006.11.020", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17368277/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose fish oil may modestly add to meloxicam-related bleeding risk.", "clinicalSignificance": "The risk is dose- and context-dependent, so routine low-dose fish oil is not treated as automatically unsafe.", "managementStrategy": "Use caution with high-dose fish oil and daily meloxicam, especially before procedures.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Aspirin Low-Dose", "supplementBName": "Krill Oil", "interactionType": "caution", "severity": "moderate", "description": "Krill oil provides omega-3 fatty acids that may have mild antiplatelet effects, which can add to low-dose aspirin in higher-risk situations. Usual omega-3 doses generally show low bleeding risk in trials, but high-dose products, procedures, or other blood thinners deserve caution. The concern is stronger when krill oil is used as a concentrated omega-3 supplement rather than a low-dose dietary product.", "recommendation": "Use caution with high-dose krill oil while taking low-dose aspirin. Tell your clinician before surgery or dental work, and report unusual bruising, nosebleeds, black stools, or vomiting blood.", "minimumTimeSeparation": null, "mechanism": "Krill oil supplies EPA and DHA, which can shift platelet eicosanoid signaling and reduce aggregation modestly. Aspirin irreversibly blocks platelet COX-1, so high-dose omega-3 exposure may add antiplatelet effect.", "evidenceLevel": "moderate", "sources": [ { "text": "Javaid M, Kadhim K, Bawamia B, Cartlidge T, Farag M, Alkhalil M. Bleeding Risk in Patients Receiving Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Am Heart Assoc. 2024;13(10):e032390.", "pmid": "38742535", "doi": "10.1161/JAHA.123.032390", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38742535/", "publicSourceType": "PMID" }, { "text": "Stonehouse W, Benassi-Evans B, Bednarz J, Vincent AD, Hall S, Hill CL. Krill oil improved osteoarthritic knee pain in adults with mild to moderate knee osteoarthritis: a 6-month multicenter, randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2022;116(3):672-685.", "pmid": "35880828", "doi": "10.1093/ajcn/nqac125", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35880828/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose krill oil may add mild omega-3 antiplatelet activity to aspirin.", "clinicalSignificance": "The evidence supports caution mainly at high omega-3 doses or around procedures, not automatic avoidance of all krill oil.", "managementStrategy": "Use caution with high-dose krill oil and low-dose aspirin, especially before procedures.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Aspirin Low-Dose", "supplementBName": "Flaxseed Oil", "interactionType": "caution", "severity": "moderate", "description": "Flaxseed oil supplies alpha-linolenic acid and may have mild antiplatelet or lipid-mediated vascular effects, but direct clinical bleeding evidence is limited. Low-dose aspirin already inhibits platelets, so very high-dose flaxseed oil deserves caution in people with bleeding history or upcoming procedures. Food-level flax intake is less concerning than concentrated oil supplementation.", "recommendation": "Use caution with high-dose flaxseed oil while taking low-dose aspirin. Tell your clinician before procedures and watch for unusual bruising, nosebleeds, black stools, or vomiting blood.", "minimumTimeSeparation": null, "mechanism": "Alpha-linolenic acid from flaxseed oil can alter fatty-acid composition and eicosanoid balance, with possible effects on platelet function. Aspirin irreversibly inhibits platelet COX-1, so any added platelet effect could be additive in susceptible users.", "evidenceLevel": "emerging", "sources": [ { "text": "Prasad K. Flaxseed and cardiovascular health. J Cardiovasc Pharmacol. 2009;54(5):369-377.", "pmid": "19568181", "doi": "10.1097/FJC.0b013e3181af04e5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19568181/", "publicSourceType": "PMID" }, { "text": "Kaufman DW, Kelly JP, Wiholm BE, Laszlo A, Sheehan JE, Koff RS, et al. The risk of acute major upper gastrointestinal bleeding among users of aspirin and ibuprofen at various levels of alcohol consumption. Am J Gastroenterol. 1999;94(11):3189-3196.", "pmid": "10566713", "doi": "10.1111/j.1572-0241.1999.01517.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10566713/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose flaxseed oil may add mild platelet-related bleeding risk to low-dose aspirin.", "clinicalSignificance": "The evidence is weaker than for aspirin plus alcohol or ginkgo, so this is a conservative high-dose caution.", "managementStrategy": "Use caution with high-dose flaxseed oil and aspirin, especially before procedures or with bleeding history.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Aspirin Low-Dose", "supplementBName": "Vitamin E", "interactionType": "caution", "severity": "moderate", "description": "High-dose vitamin E may increase bleeding tendency and could add to low-dose aspirin's antiplatelet effect. Vitamin E supplementation has been shown to affect vitamin K status, and randomized-trial meta-analysis links vitamin E with increased hemorrhagic stroke risk. The concern is mainly with high-dose supplements rather than usual dietary vitamin E.", "recommendation": "Avoid high-dose vitamin E while taking low-dose aspirin unless your clinician recommends it. Keep supplemental vitamin E modest and report unusual bruising, nosebleeds, black stools, or neurologic symptoms promptly.", "minimumTimeSeparation": null, "mechanism": "Vitamin E can interfere with vitamin K-dependent coagulation biology and may affect platelet function at high doses. Aspirin irreversibly inhibits platelet COX-1, creating additive bleeding potential.", "evidenceLevel": "moderate", "sources": [ { "text": "Booth SL, Golly I, Sacheck JM, Roubenoff R, Dallal GE, Hamada K, et al. Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. Am J Clin Nutr. 2004;80(1):143-148.", "pmid": "15213041", "doi": "10.1093/ajcn/80.1.143", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15213041/", "publicSourceType": "PMID" }, { "text": "Schurks M, Glynn RJ, Rist PM, Tzourio C, Kurth T. Effects of vitamin E on stroke subtypes: meta-analysis of randomised controlled trials. BMJ. 2010;341:c5702.", "pmid": "21051774", "doi": "10.1136/bmj.c5702", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21051774/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose vitamin E may add bleeding tendency to low-dose aspirin.", "clinicalSignificance": "The most defensible concern is high-dose supplemental vitamin E, not normal dietary intake.", "managementStrategy": "Avoid high-dose vitamin E with aspirin unless clinically indicated and monitored.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Aspirin Low-Dose", "supplementBName": "Bromelain", "interactionType": "caution", "severity": "moderate", "description": "Bromelain may have antiplatelet and fibrinolytic effects that could add to low-dose aspirin. Human outcome evidence for the exact combination is limited, but bromelain has laboratory evidence of reduced platelet aggregation and thrombus formation. The combination is most concerning with high-dose bromelain, procedures, ulcer history, or other blood thinners.", "recommendation": "Avoid high-dose bromelain while taking low-dose aspirin unless your clinician agrees. Tell your surgical or dental team about bromelain and seek care for unusual bruising, nosebleeds, black stools, or vomiting blood.", "minimumTimeSeparation": null, "mechanism": "Bromelain proteases can reduce platelet aggregation and thrombus formation in experimental systems. Aspirin irreversibly inhibits platelet COX-1, so bromelain may add to antiplatelet and fibrinolytic bleeding risk.", "evidenceLevel": "emerging", "sources": [ { "text": "Metzig C, Grabowska E, Eckert K, Rehse K, Maurer HR. Bromelain proteases reduce human platelet aggregation in vitro, adhesion to bovine endothelial cells and thrombus formation in rat vessels in vivo. In Vivo. 1999;13(1):7-12.", "pmid": "10218125", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10218125/", "publicSourceType": "PMID" }, { "text": "Maurer HR. Bromelain: biochemistry, pharmacology and medical use. Cell Mol Life Sci. 2001;58(9):1234-1245.", "pmid": "11577981", "doi": "10.1007/PL00000936", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11577981/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Bromelain may add antiplatelet or fibrinolytic activity to low-dose aspirin.", "clinicalSignificance": "The evidence is mostly mechanistic, so the warning is limited to high-dose use and bleeding-risk contexts.", "managementStrategy": "Avoid high-dose bromelain with aspirin before procedures or when bleeding risk is elevated.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Celecoxib", "supplementBName": "Resveratrol", "interactionType": "caution", "severity": "moderate", "description": "Resveratrol may increase celecoxib exposure and also has antiplatelet effects, creating a plausible safety concern. A human pharmacokinetic study found celecoxib disposition changed with resveratrol co-administration. The combination is most relevant with higher celecoxib doses, bleeding risk, cardiovascular risk, or other medicines affected by CYP pathways.", "recommendation": "Use caution with resveratrol supplements while taking celecoxib, especially at high doses. Watch for celecoxib adverse effects such as stomach pain, edema, blood pressure worsening, bruising, or black stools.", "minimumTimeSeparation": null, "mechanism": "Resveratrol can inhibit platelet activation and may alter celecoxib pharmacokinetics, likely through metabolic or transporter effects. Increased celecoxib exposure could increase NSAID-related renal, blood pressure, cardiovascular, or GI toxicity in susceptible users.", "evidenceLevel": "emerging", "sources": [ { "text": "Helal NI, El-Khodary NM, Omran GA, El-Masry SM. Effects of Resveratrol Co-Administration on Celecoxib Disposition and Pharmacokinetics in Healthy Volunteers. Drug Res (Stuttg). 2023;73(9):520-527.", "pmid": "37935204", "doi": "10.1055/a-2160-2186", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37935204/", "publicSourceType": "PMID" }, { "text": "Marumo M, Ekawa K, Wakabayashi I. Resveratrol inhibits Ca(2+) signals and aggregation of platelets. Environ Health Prev Med. 2020;25(1):70.", "pmid": "33160329", "doi": "10.1186/s12199-020-00905-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33160329/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Resveratrol may increase celecoxib exposure and add antiplatelet activity.", "clinicalSignificance": "This exact pair has human pharmacokinetic evidence, but clinical outcome data are still limited.", "managementStrategy": "Use caution with resveratrol and monitor for celecoxib toxicity or bleeding signs.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Hydrocodone", "supplementBName": "Alcohol", "interactionType": "contraindicated", "severity": "dangerous", "description": "Alcohol can dangerously amplify hydrocodone's sedating and breathing-slowing effects. The combination increases the risk of profound sleepiness, impaired coordination, loss of consciousness, respiratory depression, overdose, and death. Risk is higher with higher opioid doses, older age, sleep apnea, lung disease, or any additional sedatives.", "recommendation": "Do not drink alcohol while taking hydrocodone. If alcohol was used recently, skip non-urgent opioid dosing and contact your prescriber or pharmacist for individualized guidance. Seek emergency help for extreme sleepiness, slow breathing, blue lips, or inability to wake.", "minimumTimeSeparation": null, "mechanism": "Hydrocodone is a mu-opioid receptor agonist that suppresses brainstem ventilatory drive and reduces arousal responses to rising carbon dioxide. Alcohol adds central nervous system depression through GABAergic and other inhibitory pathways, reducing alertness and airway protective reflexes while opioid respiratory drive is already impaired.", "evidenceLevel": "strong", "sources": [ { "text": "Jones CM, Paulozzi LJ, Mack KA; Centers for Disease Control and Prevention. Alcohol involvement in opioid pain reliever and benzodiazepine drug abuse-related emergency department visits and drug-related deaths - United States, 2010. MMWR Morb Mortal Wkly Rep. 2014;63(40):881-885.", "pmid": "25299603", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25299603/", "publicSourceType": "PMID" }, { "text": "Boom M, Niesters M, Sarton E, Aarts L, Smith TW, Dahan A. Non-analgesic effects of opioids: opioid-induced respiratory depression. Curr Pharm Des. 2012;18(37):5994-6004.", "pmid": "22747535", "doi": "10.2174/138161212803582469", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22747535/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Alcohol and hydrocodone combine to increase sedation, impaired coordination, and respiratory depression.", "clinicalSignificance": "This pairing is a common preventable contributor to opioid overdose and fatal respiratory depression.", "managementStrategy": "Avoid alcohol completely while using hydrocodone and seek urgent care for slow breathing or unresponsiveness.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Oxycodone", "supplementBName": "Alcohol", "interactionType": "contraindicated", "severity": "dangerous", "description": "Alcohol substantially increases the respiratory depression caused by oxycodone. In a controlled human study, oxycodone reduced ventilation and alcohol caused a further drop, with more apneic events. Older adults and people with lung disease or sleep apnea are especially vulnerable.", "recommendation": "Do not drink alcohol while taking oxycodone. Avoid driving, sleeping alone after accidental co-use, or taking any extra sedatives. Call emergency services if breathing becomes slow, shallow, noisy, or difficult to wake from.", "minimumTimeSeparation": null, "mechanism": "Oxycodone activates mu-opioid receptors in respiratory control circuits, lowering the ventilatory response to carbon dioxide. Alcohol adds central nervous system depression and reduces arousal, creating additive or synergistic impairment of breathing and airway protection.", "evidenceLevel": "strong", "sources": [ { "text": "van der Schrier R, Roozekrans M, Olofsen E, Aarts L, van Velzen M, de Jong M, et al. Influence of Ethanol on Oxycodone-induced Respiratory Depression: A Dose-escalating Study in Young and Elderly Individuals. Anesthesiology. 2017;126(3):534-542.", "pmid": "28170358", "doi": "10.1097/ALN.0000000000001505", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28170358/", "publicSourceType": "PMID" }, { "text": "Jones CM, Paulozzi LJ, Mack KA; Centers for Disease Control and Prevention. Alcohol involvement in opioid pain reliever and benzodiazepine drug abuse-related emergency department visits and drug-related deaths - United States, 2010. MMWR Morb Mortal Wkly Rep. 2014;63(40):881-885.", "pmid": "25299603", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25299603/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Alcohol worsens oxycodone-related respiratory depression and apnea risk.", "clinicalSignificance": "Human evidence shows the combination can depress breathing more than oxycodone alone.", "managementStrategy": "Avoid alcohol completely during oxycodone therapy and treat accidental co-use with overdose-level caution.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Morphine", "supplementBName": "Alcohol", "interactionType": "contraindicated", "severity": "dangerous", "description": "Alcohol can add to morphine's opioid sedation and respiratory depression. This can lead to extreme drowsiness, impaired airway protection, slow breathing, coma, and fatal overdose. The risk rises with higher morphine doses, alcohol intoxication, sleep-disordered breathing, lung disease, or other sedatives.", "recommendation": "Do not drink alcohol while taking morphine. If you accidentally combine them, avoid taking more morphine or other sedatives and make sure someone can monitor you. Seek emergency care for slow breathing, confusion, blue lips, or inability to stay awake.", "minimumTimeSeparation": null, "mechanism": "Morphine depresses brainstem respiratory rhythm and blunts carbon dioxide responsiveness through mu-opioid receptor signaling. Alcohol independently depresses central nervous system activity and arousal, making it harder to compensate for opioid-suppressed breathing.", "evidenceLevel": "strong", "sources": [ { "text": "Boom M, Niesters M, Sarton E, Aarts L, Smith TW, Dahan A. Non-analgesic effects of opioids: opioid-induced respiratory depression. Curr Pharm Des. 2012;18(37):5994-6004.", "pmid": "22747535", "doi": "10.2174/138161212803582469", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22747535/", "publicSourceType": "PMID" }, { "text": "Jones CM, Paulozzi LJ, Mack KA; Centers for Disease Control and Prevention. Alcohol involvement in opioid pain reliever and benzodiazepine drug abuse-related emergency department visits and drug-related deaths - United States, 2010. MMWR Morb Mortal Wkly Rep. 2014;63(40):881-885.", "pmid": "25299603", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25299603/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Alcohol adds to morphine's sedation and respiratory depression.", "clinicalSignificance": "Combining alcohol with opioid pain relievers is linked to overdose-related emergency visits and deaths.", "managementStrategy": "Avoid alcohol while taking morphine and seek urgent care for overdose warning signs.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Tramadol", "supplementBName": "Alcohol", "interactionType": "contraindicated", "severity": "dangerous", "description": "Alcohol can add to tramadol's opioid sedation and respiratory depression while also worsening judgment and coordination. Tramadol also lowers the seizure threshold, and alcohol intoxication or withdrawal can make seizure risk more concerning. The combination can result in overdose, falls, accidents, coma, or death.", "recommendation": "Do not drink alcohol while taking tramadol. Avoid extra doses if alcohol was used, and do not combine tramadol with sleep aids or other sedatives. Seek emergency care for slow breathing, fainting, seizure, or inability to wake.", "minimumTimeSeparation": null, "mechanism": "Tramadol produces mu-opioid agonism and inhibits serotonin and norepinephrine reuptake. Alcohol adds central nervous system depression and impaired arousal, increasing sedation and respiratory risk; both substances can also contribute to impaired seizure control in susceptible people.", "evidenceLevel": "moderate", "sources": [ { "text": "Jones CM, Paulozzi LJ, Mack KA; Centers for Disease Control and Prevention. Alcohol involvement in opioid pain reliever and benzodiazepine drug abuse-related emergency department visits and drug-related deaths - United States, 2010. MMWR Morb Mortal Wkly Rep. 2014;63(40):881-885.", "pmid": "25299603", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25299603/", "publicSourceType": "PMID" }, { "text": "Beakley BD, Kaye AM, Kaye AD. Tramadol, Pharmacology, Side Effects, and Serotonin Syndrome: A Review. Pain Physician. 2015;18(4):395-400.", "pmid": "26218943", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26218943/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Alcohol increases tramadol-related sedation, overdose risk, and seizure concern.", "clinicalSignificance": "Tramadol is not safe to treat as a mild opioid when alcohol is involved.", "managementStrategy": "Avoid alcohol throughout tramadol use and seek urgent help for breathing problems or seizure.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Baclofen", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Alcohol and baclofen can both cause sedation, dizziness, slowed reaction time, and impaired coordination. Human alcohol-challenge studies show baclofen can increase sedation and impair performance, and higher baclofen plus alcohol exposure has been associated with major sedation. This is especially risky for driving, falls, and accidental overdose.", "recommendation": "Avoid alcohol while taking baclofen unless your prescriber is deliberately supervising baclofen for alcohol use disorder. Do not drive or operate machinery if you have used both. Report heavy sedation, confusion, fainting, or breathing problems promptly.", "minimumTimeSeparation": null, "mechanism": "Baclofen is a GABA-B receptor agonist that reduces excitatory neurotransmission in the spinal cord and brain. Alcohol also enhances inhibitory signaling and impairs cortical and cerebellar function, producing additive sedation and psychomotor impairment.", "evidenceLevel": "moderate", "sources": [ { "text": "Evans SM, Bisaga A. Acute interaction of baclofen in combination with alcohol in heavy social drinkers. Alcohol Clin Exp Res. 2009;33(1):19-30.", "pmid": "18840257", "doi": "10.1111/j.1530-0277.2008.00805.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18840257/", "publicSourceType": "PMID" }, { "text": "Rolland B, Labreuche J, Duhamel A, Deheul S, Gautier S, Auffret M, et al. Baclofen for alcohol dependence: Relationships between baclofen and alcohol dosing and the occurrence of major sedation. Eur Neuropsychopharmacol. 2015;25(10):1631-1636.", "pmid": "26095229", "doi": "10.1016/j.euroneuro.2015.05.008", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26095229/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Alcohol and baclofen additively increase sedation and performance impairment.", "clinicalSignificance": "The combination can make ordinary activities like walking, driving, or dosing other medicines unsafe.", "managementStrategy": "Avoid alcohol with baclofen unless specifically supervised for alcohol use disorder.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Cyclobenzaprine", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Cyclobenzaprine commonly causes drowsiness, dizziness, and slowed reaction time, and alcohol can intensify those effects. Combining them can increase falls, accidents, impaired driving, confusion, and overdose risk. Older adults are especially vulnerable because skeletal muscle relaxants are poorly tolerated in that group.", "recommendation": "Avoid alcohol while taking cyclobenzaprine. If alcohol was used, do not drive, operate tools, or take extra sedatives that day. Contact your prescriber if you need muscle spasm treatment but cannot reliably avoid alcohol.", "minimumTimeSeparation": null, "mechanism": "Cyclobenzaprine is a centrally acting skeletal muscle relaxant with sedating and anticholinergic effects. Alcohol adds central nervous system depression and psychomotor impairment, increasing the net effect on alertness, balance, and reaction time.", "evidenceLevel": "moderate", "sources": [ { "text": "Witenko C, Moorman-Li R, Motycka C, Duane K, Hincapie-Castillo J, Leonard P, et al. Considerations for the appropriate use of skeletal muscle relaxants for the management of acute low back pain. P T. 2014;39(6):427-435.", "pmid": "25050056", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25050056/", "publicSourceType": "PMID" }, { "text": "Elder NC. Abuse of skeletal muscle relaxants. Am Fam Physician. 1991;44(4):1223-1226.", "pmid": "1927837", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1927837/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Alcohol increases cyclobenzaprine-related drowsiness, dizziness, and psychomotor impairment.", "clinicalSignificance": "The combination raises the chance of falls, unsafe driving, and severe oversedation.", "managementStrategy": "Avoid alcohol during cyclobenzaprine use and separate from other sedating substances.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Methocarbamol", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Methocarbamol can cause sedation, dizziness, and impaired coordination, and alcohol can make these effects stronger. The combination can lead to unsafe driving, falls, confusion, and excessive sleepiness. Risk rises when methocarbamol is taken with opioids, benzodiazepines, sleep medicines, or other sedatives.", "recommendation": "Avoid alcohol while taking methocarbamol. If you accidentally combine them, avoid driving and do not take additional sedatives. Get medical help for severe confusion, fainting, or breathing problems.", "minimumTimeSeparation": null, "mechanism": "Methocarbamol is a centrally acting skeletal muscle relaxant whose benefit and adverse effects are largely mediated through central nervous system depression. Alcohol adds independent sedating and psychomotor-impairing effects, increasing the total depressant burden.", "evidenceLevel": "moderate", "sources": [ { "text": "Chou R, Peterson K, Helfand M. Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review. J Pain Symptom Manage. 2004;28(2):140-175.", "pmid": "15276195", "doi": "10.1016/j.jpainsymman.2004.05.002", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15276195/", "publicSourceType": "PMID" }, { "text": "Witenko C, Moorman-Li R, Motycka C, Duane K, Hincapie-Castillo J, Leonard P, et al. Considerations for the appropriate use of skeletal muscle relaxants for the management of acute low back pain. P T. 2014;39(6):427-435.", "pmid": "25050056", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25050056/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Alcohol adds to methocarbamol-related sedation and coordination impairment.", "clinicalSignificance": "The combination can turn a normally tolerated dose into unsafe oversedation or fall risk.", "managementStrategy": "Avoid alcohol during methocarbamol use and use extra caution with any other sedating medicine.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Tizanidine", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Alcohol can add to tizanidine's sedation, dizziness, low blood pressure, and fainting risk. A published case report describes syncope after concomitant tizanidine and alcohol use. This is especially concerning when standing up, driving, or combining with other blood-pressure-lowering or sedating substances.", "recommendation": "Avoid alcohol while taking tizanidine. If alcohol was used, do not drive and be careful standing or walking until the effects are clearly gone. Seek help for fainting, severe weakness, confusion, or trouble breathing.", "minimumTimeSeparation": null, "mechanism": "Tizanidine is an alpha-2 adrenergic agonist that can reduce sympathetic tone, causing sedation and hypotension. Alcohol adds central nervous system depression and vasodilatory effects, increasing the chance of oversedation, orthostatic symptoms, and syncope.", "evidenceLevel": "moderate", "sources": [ { "text": "Forsah SF, Ugwendum D, Arrey Agbor DB, Ndema N, Ndemazie NB, Kankeu Tonpouwo G, et al. Syncope Secondary to Concomitant Ingestion of Tizanidine and Alcohol in a Patient With Alcohol Use Disorder. Cureus. 2024;16(3):e57249.", "pmid": "38686239", "doi": "10.7759/cureus.57249", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38686239/", "publicSourceType": "PMID" }, { "text": "Witenko C, Moorman-Li R, Motycka C, Duane K, Hincapie-Castillo J, Leonard P, et al. Considerations for the appropriate use of skeletal muscle relaxants for the management of acute low back pain. P T. 2014;39(6):427-435.", "pmid": "25050056", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25050056/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Alcohol increases tizanidine-related sedation, hypotension, and fainting risk.", "clinicalSignificance": "The combination can cause falls, syncope, and dangerous impairment even without overdose.", "managementStrategy": "Avoid alcohol with tizanidine and monitor closely for low blood pressure or severe sedation.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Tramadol", "supplementBName": "L-Tryptophan", "interactionType": "contraindicated", "severity": "serious", "description": "Tramadol has serotonergic activity in addition to its opioid effect, and L-Tryptophan is a serotonin precursor. Combining them can increase serotonin signaling and raise the risk of serotonin syndrome, which can cause agitation, tremor, sweating, diarrhea, fever, muscle rigidity, seizures, and rarely death. Risk is higher if you also take antidepressants, migraine triptans, linezolid, MDMA, or St. John's Wort.", "recommendation": "Avoid L-Tryptophan while taking tramadol. Do not try to manage the risk by separating doses; the concern is overlapping serotonergic effects over time. Seek urgent care for clonus, high fever, severe agitation, confusion, or seizure.", "minimumTimeSeparation": null, "mechanism": "Tramadol inhibits serotonin reuptake and can trigger serotonin toxicity, especially with other serotonergic agents. L-Tryptophan can increase serotonin synthesis, adding a separate mechanism that increases serotonergic tone.", "evidenceLevel": "moderate", "sources": [ { "text": "Beakley BD, Kaye AM, Kaye AD. Tramadol, Pharmacology, Side Effects, and Serotonin Syndrome: A Review. Pain Physician. 2015;18(4):395-400.", "pmid": "26218943", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26218943/", "publicSourceType": "PMID" }, { "text": "Ambarapu S, Tilwe K, Pandit RA, Gaikwad BV, Meshram HM, Choudhary J, et al. Serotonin Syndrome Masquerading as Status Epilepticus following Ingestion of Tranylcypromine and Clomipramine and L-Tryptophan: A Case Report. Ann Indian Acad Neurol. 2022;25(5):960-962.", "pmid": "36561019", "doi": "10.4103/aian.aian_336_22", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36561019/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "L-Tryptophan can add serotonin precursor load to tramadol's serotonin reuptake inhibition.", "clinicalSignificance": "Serotonin syndrome is uncommon but potentially life-threatening and can be missed early.", "managementStrategy": "Avoid L-Tryptophan during tramadol therapy and seek urgent care for serotonin toxicity symptoms.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Tramadol", "supplementBName": "SAMe", "interactionType": "contraindicated", "severity": "serious", "description": "SAMe has antidepressant activity and serotonergic relevance, while tramadol inhibits serotonin reuptake and is a known serotonin syndrome risk drug. A published case report describes toxicity when SAMe was combined with the serotonergic antidepressant clomipramine, so adding SAMe to tramadol is a clinically plausible serotonergic stacking risk. Symptoms can include restlessness, sweating, tremor, diarrhea, fever, clonus, confusion, and seizure.", "recommendation": "Avoid SAMe while taking tramadol unless your prescriber specifically approves and monitors the combination. Do not add SAMe for mood support during tramadol treatment. Seek urgent care for high fever, muscle rigidity, clonus, severe agitation, or seizure.", "minimumTimeSeparation": null, "mechanism": "Tramadol increases synaptic serotonin by inhibiting serotonin reuptake. SAMe participates in methylation reactions relevant to monoamine metabolism and has clinical antidepressant activity, so concurrent use can add serotonergic pressure even though direct tramadol-SAMe cases are sparse.", "evidenceLevel": "moderate", "sources": [ { "text": "Beakley BD, Kaye AM, Kaye AD. Tramadol, Pharmacology, Side Effects, and Serotonin Syndrome: A Review. Pain Physician. 2015;18(4):395-400.", "pmid": "26218943", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26218943/", "publicSourceType": "PMID" }, { "text": "Iruela LM, Minguez L, Merino J, Monedero G. Toxic interaction of S-adenosylmethionine and clomipramine. Am J Psychiatry. 1993;150(3):522.", "pmid": "8434674", "doi": "10.1176/ajp.150.3.522b", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8434674/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "SAMe may add serotonergic activity to tramadol's serotonin reuptake inhibition.", "clinicalSignificance": "The combination can increase the chance of serotonin toxicity, especially with other serotonergic drugs.", "managementStrategy": "Avoid SAMe during tramadol use and monitor urgently for serotonin syndrome symptoms if exposure occurred.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Tramadol", "supplementBName": "MDMA", "interactionType": "contraindicated", "severity": "dangerous", "description": "MDMA releases and blocks reuptake of serotonin, and tramadol also inhibits serotonin reuptake while lowering the seizure threshold. Combining them can sharply increase the risk of serotonin syndrome, hyperthermia, seizures, dangerous blood pressure changes, and overdose. This is a high-risk pairing even when either substance is used only once.", "recommendation": "Do not combine MDMA with tramadol. Avoid tramadol after MDMA exposure until you have medical guidance, especially if you have overheating, agitation, tremor, diarrhea, confusion, or muscle rigidity. Seek emergency care for fever, seizure, severe agitation, or altered consciousness.", "minimumTimeSeparation": null, "mechanism": "MDMA is a monoamine releaser and uptake inhibitor with strong serotonergic effects. Tramadol inhibits serotonin reuptake and can provoke seizures; overlapping serotonergic and pro-convulsant effects increase toxicity risk.", "evidenceLevel": "moderate", "sources": [ { "text": "Beakley BD, Kaye AM, Kaye AD. Tramadol, Pharmacology, Side Effects, and Serotonin Syndrome: A Review. Pain Physician. 2015;18(4):395-400.", "pmid": "26218943", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26218943/", "publicSourceType": "PMID" }, { "text": "Makunts T, Jerome L, Abagyan R, de Boer A. Reported Cases of Serotonin Syndrome in MDMA Users in FAERS Database. Front Psychiatry. 2021;12:824288.", "pmid": "35140642", "doi": "10.3389/fpsyt.2021.824288", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35140642/", "publicSourceType": "PMID" }, { "text": "Bodner RA, Lynch T, Lewis L, Kahn D. Serotonin syndrome. Neurology. 1995;45(2):219-223.", "pmid": "7854515", "doi": "10.1212/wnl.45.2.219", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7854515/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "MDMA and tramadol combine serotonergic toxicity and seizure risk.", "clinicalSignificance": "This pairing can produce rapid, life-threatening serotonin syndrome or seizure.", "managementStrategy": "Avoid the combination completely and seek emergency care for hyperthermia, clonus, seizure, or altered mental status.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Oxycodone", "supplementBName": "St. John's Wort", "interactionType": "caution", "severity": "serious", "description": "St. John's Wort can induce CYP3A activity, and oxycodone exposure is clinically sensitive to CYP3A induction and inhibition. Using them together may reduce oxycodone levels and analgesia; stopping St. John's Wort can then raise oxycodone exposure again. This can cause unstable pain control, withdrawal symptoms, or unexpected sedation if oxycodone is adjusted during the interaction.", "recommendation": "Avoid starting or stopping St. John's Wort while taking oxycodone unless your prescriber is managing the change. Do not increase oxycodone on your own if pain worsens after adding St. John's Wort. Watch for withdrawal or loss of pain control when starting it, and for sedation or slow breathing after stopping it.", "minimumTimeSeparation": null, "mechanism": "St. John's Wort induces intestinal and hepatic CYP3A activity in humans. Oxycodone is metabolized mainly by CYP3A to noroxycodone and is affected by CYP3A inducers and inhibitors, so induction can lower oxycodone exposure and discontinuation can reverse that effect.", "evidenceLevel": "moderate", "sources": [ { "text": "Wang Z, Gorski JC, Hamman MA, Huang SM, Lesko LJ, Hall SD. The effects of St John's wort (Hypericum perforatum) on human cytochrome P450 activity. Clin Pharmacol Ther. 2001;70(4):317-326.", "pmid": "11673747", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11673747/", "publicSourceType": "PMID" }, { "text": "Kinnunen M, Piirainen P, Kokki H, Lammi P, Kokki M. Updated Clinical Pharmacokinetics and Pharmacodynamics of Oxycodone. Clin Pharmacokinet. 2019;58(6):705-725.", "pmid": "30652261", "doi": "10.1007/s40262-018-00731-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30652261/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St. John's Wort may lower oxycodone exposure through CYP3A induction and destabilize opioid response.", "clinicalSignificance": "Changing St. John's Wort use can lead to loss of analgesia, withdrawal, or later oversedation if opioid doses are adjusted.", "managementStrategy": "Avoid unsupervised St. John's Wort use with oxycodone and monitor closely when starting or stopping it.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Levodopa/Carbidopa", "supplementBName": "BCAAs", "interactionType": "timingSensitive", "severity": "serious", "description": "BCAA supplements can reduce or delay levodopa's benefit because branched-chain amino acids compete with levodopa for the same intestinal and blood-brain barrier transport pathways. This can make Parkinson's symptoms break through sooner, especially in people who already notice protein-sensitive wearing off. The risk is highest when BCAAs are taken close to a levodopa dose or repeatedly during the daytime dosing window.", "recommendation": "Do not take BCAAs with levodopa/carbidopa doses. Take levodopa at least 30-60 minutes before amino acid or protein supplements, and keep BCAAs at least 2 hours away from levodopa when possible. If your mobility worsens after starting BCAAs, stop the supplement and review your levodopa schedule with your prescriber.", "minimumTimeSeparation": 120, "mechanism": "Levodopa is transported across the gut wall and blood-brain barrier by large neutral amino acid transporters, including LAT systems. Leucine, isoleucine, and valine compete for these transporters, lowering levodopa absorption and central nervous system entry.", "evidenceLevel": "strong", "sources": [ { "text": "Nutt JG, Woodward WR, Hammerstad JP, Carter JH, Anderson JL. The \"on-off\" phenomenon in Parkinson's disease. Relation to levodopa absorption and transport. N Engl J Med. 1984;310(8):483-488.", "pmid": "6694694", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6694694/", "publicSourceType": "PMID" }, { "text": "Cereda E, Barichella M, Pedrolli C, Pezzoli G. Low-protein and protein-redistribution diets for Parkinson's disease patients with motor fluctuations: a systematic review. Mov Disord. 2010;25(13):2021-2034.", "pmid": "20669318", "doi": "10.1002/mds.23226", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20669318/", "publicSourceType": "PMID" }, { "text": "Camargo SM, Vuille-dit-Bille RN, Mariotta L, Ramadan T, Huggel K, Singer D, et al. The molecular mechanism of intestinal levodopa absorption and its possible implications for the treatment of Parkinson's disease. J Pharmacol Exp Ther. 2014;351(1):114-123.", "pmid": "25073474", "doi": "10.1124/jpet.114.216317", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25073474/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "BCAAs can reduce levodopa absorption and brain entry, weakening motor symptom control.", "clinicalSignificance": "Poor timing can look like levodopa treatment failure or worsening Parkinson's disease.", "managementStrategy": "Separate BCAAs from levodopa by at least 2 hours and avoid daytime BCAA dosing if motor fluctuations worsen.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Sumatriptan", "supplementBName": "5-HTP", "interactionType": "caution", "severity": "serious", "description": "5-HTP is a direct serotonin precursor, and sumatriptan is a serotonin receptor agonist used for migraine attacks. Direct case evidence for this exact pair is limited, but combining a serotonin precursor with a triptan can add serotonergic pressure and may increase the risk of serotonin toxicity. Warning signs include agitation, tremor, sweating, diarrhea, clonus, fever, or confusion.", "recommendation": "Avoid 5-HTP supplements while using sumatriptan unless your prescriber specifically approves the combination. If both were taken and you develop tremor, fever, marked restlessness, muscle jerks, or confusion, seek urgent care. Food sources of tryptophan are not the issue; concentrated 5-HTP supplements are.", "minimumTimeSeparation": null, "mechanism": "5-HTP is decarboxylated to serotonin and can increase serotonin synthesis. Sumatriptan activates 5-HT1B/1D receptors; combined serotonergic mechanisms can contribute to serotonin receptor overstimulation in susceptible patients.", "evidenceLevel": "emerging", "sources": [ { "text": "Birdsall TC. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998;3(4):271-280.", "pmid": "9727088", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9727088/", "publicSourceType": "PMID" }, { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Evans RW, Tepper SJ, Shapiro RE, Sun-Edelstein C, Tietjen GE. The FDA alert on serotonin syndrome with use of triptans combined with selective serotonin reuptake inhibitors or selective serotonin-norepinephrine reuptake inhibitors: American Headache Society position paper. Headache. 2010;50(6):1089-1099.", "pmid": "20618823", "doi": "10.1111/j.1526-4610.2010.01691.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20618823/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "5-HTP may add serotonergic load to sumatriptan therapy.", "clinicalSignificance": "The combination is avoidable and could complicate recognition of serotonin toxicity during migraine treatment.", "managementStrategy": "Avoid concentrated 5-HTP supplements while using sumatriptan and monitor for serotonin-toxicity symptoms if exposure occurs.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Rizatriptan", "supplementBName": "5-HTP", "interactionType": "caution", "severity": "serious", "description": "5-HTP is a serotonin precursor, and rizatriptan is a 5-HT1B/1D receptor agonist. Direct case evidence for this exact pair is limited, but the combination is pharmacologically avoidable because both increase serotonergic signaling. Symptoms of concern include agitation, tremor, sweating, diarrhea, clonus, fever, or confusion.", "recommendation": "Avoid 5-HTP supplements while using rizatriptan unless your prescriber specifically approves. If you have taken both and develop tremor, fever, marked restlessness, muscle jerks, or confusion, seek urgent care. Do not rely on dose spacing to remove the risk.", "minimumTimeSeparation": null, "mechanism": "5-HTP increases serotonin synthesis after decarboxylation to serotonin. Rizatriptan activates serotonin 5-HT1B/1D receptors; this can add to serotonergic tone and contribute to serotonin receptor overstimulation in susceptible patients.", "evidenceLevel": "emerging", "sources": [ { "text": "Birdsall TC. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998;3(4):271-280.", "pmid": "9727088", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9727088/", "publicSourceType": "PMID" }, { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Evans RW, Tepper SJ, Shapiro RE, Sun-Edelstein C, Tietjen GE. The FDA alert on serotonin syndrome with use of triptans combined with selective serotonin reuptake inhibitors or selective serotonin-norepinephrine reuptake inhibitors: American Headache Society position paper. Headache. 2010;50(6):1089-1099.", "pmid": "20618823", "doi": "10.1111/j.1526-4610.2010.01691.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20618823/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "5-HTP may add serotonergic load to rizatriptan therapy.", "clinicalSignificance": "A nonessential serotonin precursor can make triptan-related serotonin-toxicity assessment harder and potentially riskier.", "managementStrategy": "Avoid concentrated 5-HTP supplements while using rizatriptan and watch for serotonin-toxicity symptoms after accidental overlap.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Sumatriptan", "supplementBName": "St. John's Wort", "interactionType": "caution", "severity": "serious", "description": "St. John's wort has serotonergic antidepressant activity and has been linked to clinically important interactions with antidepressant drugs. Sumatriptan also acts on serotonin receptors, so combining it with St. John's wort may increase the risk of serotonin toxicity, even though direct case evidence for this exact pair is limited. Watch for agitation, tremor, sweating, diarrhea, clonus, fever, or confusion.", "recommendation": "Avoid St. John's wort if you use sumatriptan for migraines. If you already take St. John's wort, stop it and discuss safer migraine and mood-support options with your prescriber. Seek urgent care if serotonin-toxicity symptoms appear after overlapping use.", "minimumTimeSeparation": null, "mechanism": "St. John's wort constituents can inhibit reuptake of serotonin and other monoamines, increasing serotonergic tone. Sumatriptan activates 5-HT1B/1D receptors; combining serotonergic mechanisms can increase receptor overstimulation risk in susceptible patients.", "evidenceLevel": "moderate", "sources": [ { "text": "Lantz MS, Buchalter E, Giambanco V. St. John's wort and antidepressant drug interactions in the elderly. J Geriatr Psychiatry Neurol. 1999;12(1):7-10.", "pmid": "10447148", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10447148/", "publicSourceType": "PMID" }, { "text": "Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs. 2009;69(13):1777-1798.", "pmid": "19719333", "doi": "10.2165/11317010-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19719333/", "publicSourceType": "PMID" }, { "text": "Evans RW, Tepper SJ, Shapiro RE, Sun-Edelstein C, Tietjen GE. The FDA alert on serotonin syndrome with use of triptans combined with selective serotonin reuptake inhibitors or selective serotonin-norepinephrine reuptake inhibitors: American Headache Society position paper. Headache. 2010;50(6):1089-1099.", "pmid": "20618823", "doi": "10.1111/j.1526-4610.2010.01691.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20618823/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St. John's wort may add serotonergic activity to sumatriptan use.", "clinicalSignificance": "This avoidable herbal combination can complicate migraine treatment and serotonin-toxicity recognition.", "managementStrategy": "Avoid St. John's wort during sumatriptan therapy and monitor for serotonin-toxicity symptoms after accidental overlap.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Rizatriptan", "supplementBName": "St. John's Wort", "interactionType": "caution", "severity": "serious", "description": "St. John's wort has serotonergic antidepressant activity and has documented interaction concerns with antidepressant drugs. Rizatriptan is a serotonin receptor agonist, so overlapping use may increase the risk of serotonin toxicity, although direct case evidence for this exact pair is limited. Warning signs include agitation, tremor, sweating, diarrhea, clonus, fever, or confusion.", "recommendation": "Avoid St. John's wort if you use rizatriptan for migraines. If you are already taking St. John's wort, stop it and review alternatives with your prescriber. Seek urgent care if serotonin-toxicity symptoms occur after overlap.", "minimumTimeSeparation": null, "mechanism": "St. John's wort can increase serotonergic tone through monoamine reuptake effects. Rizatriptan activates 5-HT1B/1D receptors, so combined serotonergic activity can contribute to receptor overstimulation in susceptible patients.", "evidenceLevel": "moderate", "sources": [ { "text": "Lantz MS, Buchalter E, Giambanco V. St. John's wort and antidepressant drug interactions in the elderly. J Geriatr Psychiatry Neurol. 1999;12(1):7-10.", "pmid": "10447148", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10447148/", "publicSourceType": "PMID" }, { "text": "Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs. 2009;69(13):1777-1798.", "pmid": "19719333", "doi": "10.2165/11317010-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19719333/", "publicSourceType": "PMID" }, { "text": "Evans RW, Tepper SJ, Shapiro RE, Sun-Edelstein C, Tietjen GE. The FDA alert on serotonin syndrome with use of triptans combined with selective serotonin reuptake inhibitors or selective serotonin-norepinephrine reuptake inhibitors: American Headache Society position paper. Headache. 2010;50(6):1089-1099.", "pmid": "20618823", "doi": "10.1111/j.1526-4610.2010.01691.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20618823/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St. John's wort may add serotonergic activity to rizatriptan use.", "clinicalSignificance": "This nonessential herbal supplement can add avoidable serotonin-toxicity concern during acute migraine treatment.", "managementStrategy": "Avoid St. John's wort during rizatriptan therapy and monitor for serotonin-toxicity symptoms after accidental overlap.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Sumatriptan", "supplementBName": "MDMA", "interactionType": "contraindicated", "severity": "dangerous", "description": "MDMA causes a large serotonin release and can produce severe serotonin toxicity and hyperthermia. Sumatriptan is a serotonin receptor agonist, so using it around MDMA exposure adds avoidable serotonergic pharmacology during a high-risk state. This combination is especially dangerous with dehydration, overheating, stimulants, antidepressants, or repeated triptan dosing.", "recommendation": "Do not combine MDMA with sumatriptan. If MDMA was used, avoid taking sumatriptan and seek medical advice for severe headache, chest pain, high fever, confusion, muscle rigidity, or repeated vomiting. Treat fever, agitation, clonus, or confusion after overlap as an emergency.", "minimumTimeSeparation": null, "mechanism": "MDMA enters monoamine neurons and reverses serotonin transporter function, producing marked synaptic serotonin release and hyperthermia risk. Sumatriptan activates 5-HT1B/1D receptors; combined serotonergic stress can worsen receptor overstimulation and obscure early toxicity symptoms.", "evidenceLevel": "moderate", "sources": [ { "text": "Green AR, Mechan AO, Elliott JM, O'Shea E, Colado MI. The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, \"ecstasy\"). Pharmacol Rev. 2003;55(3):463-508.", "pmid": "12869661", "doi": "10.1124/pr.55.3.3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12869661/", "publicSourceType": "PMID" }, { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Evans RW. The FDA alert on serotonin syndrome with combined use of SSRIs or SNRIs and triptans: an analysis of the 29 case reports. MedGenMed. 2007;9(3):48.", "pmid": "18092054", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18092054/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "MDMA creates a high-risk serotonergic and hyperthermic state that sumatriptan can compound.", "clinicalSignificance": "Serotonin toxicity, hyperthermia, chest symptoms, and altered mental status can become life-threatening.", "managementStrategy": "Do not combine MDMA and sumatriptan; seek urgent care for toxicity symptoms after overlap.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Rizatriptan", "supplementBName": "MDMA", "interactionType": "contraindicated", "severity": "dangerous", "description": "MDMA causes large serotonin release and can trigger severe serotonin toxicity and hyperthermia. Rizatriptan is a serotonin receptor agonist, so taking it around MDMA exposure adds avoidable serotonergic activity during an already high-risk state. Risk is higher with overheating, dehydration, stimulants, antidepressants, or repeated triptan dosing.", "recommendation": "Do not combine MDMA with rizatriptan. If MDMA was used, avoid taking rizatriptan and seek medical advice for severe headache, chest pain, high fever, confusion, muscle rigidity, or repeated vomiting. Treat fever, agitation, clonus, or confusion after overlap as an emergency.", "minimumTimeSeparation": null, "mechanism": "MDMA reverses serotonin transporter function and drives marked serotonin release. Rizatriptan activates 5-HT1B/1D receptors; combined serotonergic stress can worsen receptor overstimulation and make early toxicity harder to recognize.", "evidenceLevel": "moderate", "sources": [ { "text": "Green AR, Mechan AO, Elliott JM, O'Shea E, Colado MI. The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, \"ecstasy\"). Pharmacol Rev. 2003;55(3):463-508.", "pmid": "12869661", "doi": "10.1124/pr.55.3.3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12869661/", "publicSourceType": "PMID" }, { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Evans RW. The FDA alert on serotonin syndrome with combined use of SSRIs or SNRIs and triptans: an analysis of the 29 case reports. MedGenMed. 2007;9(3):48.", "pmid": "18092054", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18092054/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "MDMA creates a high-risk serotonergic and hyperthermic state that rizatriptan can compound.", "clinicalSignificance": "Serotonin toxicity, hyperthermia, chest symptoms, and altered mental status can become life-threatening.", "managementStrategy": "Do not combine MDMA and rizatriptan; seek urgent care for toxicity symptoms after overlap.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Esomeprazole", "supplementBName": "Vitamin B12", "interactionType": "caution", "severity": "moderate", "description": "Long-term esomeprazole therapy reduces vitamin B12 absorption. PPIs suppress the gastric acid and pepsin needed to liberate dietary B12 from food proteins, and chronic use of two or more years is associated with a roughly 65% higher risk of B12 deficiency. Older adults, vegetarians, and people on PPI plus metformin are at greatest risk.", "recommendation": "If you take esomeprazole for more than two years, ask your prescriber to check serum B12 (and ideally methylmalonic acid) annually. Consider a daily B12 supplement, especially the methylcobalamin form, which does not require gastric acid for absorption.", "minimumTimeSeparation": null, "mechanism": "Esomeprazole irreversibly inhibits the gastric H+/K+-ATPase, raising intragastric pH and impairing acid-pepsin-dependent cleavage of cobalamin from dietary protein. Free cobalamin must be liberated before it can bind intrinsic factor for ileal absorption.", "evidenceLevel": "strong", "sources": [ { "text": "Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-42.", "pmid": "24327038", "doi": "10.1001/jama.2013.280490", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24327038/", "publicSourceType": "PMID" }, { "text": "Choudhury A, Jena A, Jearth V, et al. Vitamin B12 deficiency and use of proton pump inhibitors: a systematic review and meta-analysis. Expert Rev Gastroenterol Hepatol. 2023;17(5):479-87.", "pmid": "37060552", "doi": "10.1080/17474124.2023.2204229", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37060552/", "publicSourceType": "PMID" }, { "text": "Miller JW. Proton Pump Inhibitors, H2-Receptor Antagonists, Metformin, and Vitamin B-12 Deficiency: Clinical Implications. Adv Nutr. 2018;9(4):511S-518S.", "pmid": "30032223", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30032223/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Esomeprazole reduces vitamin B12 absorption from food and supplements over time.", "clinicalSignificance": "Chronic PPI use can produce a clinically meaningful B12 deficiency, especially after two or more years of therapy.", "managementStrategy": "Monitor B12 yearly on long-term esomeprazole and supplement with methylcobalamin if levels trend low.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Esomeprazole", "supplementBName": "Magnesium Glycinate", "interactionType": "caution", "severity": "serious", "description": "Long-term esomeprazole use can cause hypomagnesemia, sometimes severe enough to trigger tetany, seizures, or arrhythmia. The FDA has issued a class warning for PPIs after multiple case series, and meta-analyses confirm a near-doubling of hypomagnesemia risk in chronic users. Supplemental magnesium often only partially corrects the deficit while the PPI is continued.", "recommendation": "If you take esomeprazole for more than a year, ask your prescriber to check serum magnesium periodically. If levels are low, a daily magnesium glycinate supplement is reasonable, but persistent or symptomatic hypomagnesemia usually requires stopping the PPI to fully resolve.", "minimumTimeSeparation": null, "mechanism": "Prolonged acid suppression appears to impair active magnesium uptake in the small intestine via TRPM6/TRPM7 channels, which depend on luminal proton gradients. The defect reverses within days of stopping the PPI and recurs on rechallenge.", "evidenceLevel": "strong", "sources": [ { "text": "Hess MW, Hoenderop JG, Bindels RJ, Drenth JP. Systematic review: hypomagnesaemia induced by proton pump inhibition. Aliment Pharmacol Ther. 2012;36(5):405-13.", "pmid": "22762246", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22762246/", "publicSourceType": "PMID" }, { "text": "Park CH, Kim EH, Roh YH, Kim HY, Lee SK. The association between the use of proton pump inhibitors and the risk of hypomagnesemia: a systematic review and meta-analysis. PLoS One. 2014;9(11):e112558.", "pmid": "25394217", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25394217/", "publicSourceType": "PMID" }, { "text": "Hoorn EJ, van der Hoek J, de Man RA, et al. A case series of proton pump inhibitor-induced hypomagnesemia. Am J Kidney Dis. 2010;56(1):112-6.", "pmid": "20189276", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20189276/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Esomeprazole can deplete body magnesium and cause clinically significant hypomagnesemia.", "clinicalSignificance": "Severe magnesium loss on PPIs can present as cramping, arrhythmia, or seizures and may not fully correct with oral supplementation alone.", "managementStrategy": "Check magnesium periodically on long-term esomeprazole; if low, supplement and consider deprescribing the PPI.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Esomeprazole", "supplementBName": "Iron", "interactionType": "caution", "severity": "moderate", "description": "Esomeprazole reduces absorption of oral iron, particularly non-heme iron salts like ferrous sulfate that require gastric acid for solubilization. In a large Kaiser case-control study, two or more years of PPI use raised iron deficiency risk roughly 2.5-fold. Patients with menstrual losses, GI bleeding, or vegan diets are most affected.", "recommendation": "Take iron supplements at least 4 hours apart from esomeprazole. Consider iron bisglycinate or a heme-iron product, which are less acid-dependent. Recheck ferritin and CBC 3 months after starting iron, and let your prescriber know if hemoglobin does not respond.", "minimumTimeSeparation": 240, "mechanism": "Gastric acid converts dietary ferric iron (Fe3+) to absorbable ferrous iron (Fe2+) and solubilizes iron salts for duodenal uptake by DMT1. Esomeprazole also up-regulates hepcidin via an aryl hydrocarbon receptor pathway, further suppressing intestinal iron transfer.", "evidenceLevel": "strong", "sources": [ { "text": "Lam JR, Schneider JL, Quesenberry CP, Corley DA. Proton Pump Inhibitor and Histamine-2 Receptor Antagonist Use and Iron Deficiency. Gastroenterology. 2017;152(4):821-9.", "pmid": "27890768", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27890768/", "publicSourceType": "PMID" }, { "text": "Hamano H, Niimura T, Horinouchi Y, et al. Proton pump inhibitors block iron absorption through direct regulation of hepcidin via the aryl hydrocarbon receptor-mediated pathway. Toxicol Lett. 2020;318:86-91.", "pmid": "31669099", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31669099/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Esomeprazole impairs oral iron absorption and is associated with iron deficiency on long-term use.", "clinicalSignificance": "Patients on chronic esomeprazole may fail to respond to standard iron repletion or develop unexplained iron deficiency.", "managementStrategy": "Separate iron from esomeprazole by 4 hours, use bisglycinate form, and monitor ferritin.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Esomeprazole", "supplementBName": "Calcium", "interactionType": "caution", "severity": "moderate", "description": "Esomeprazole reduces absorption of calcium carbonate, which depends on stomach acid to dissolve. Long-term PPI use is associated with a modest but consistent rise in hip, spine, and any-site fracture risk, plausibly mediated in part by reduced calcium uptake. Postmenopausal women and patients on chronic steroids are at greatest concern.", "recommendation": "Switch to calcium citrate, which absorbs well in a low-acid stomach, or take calcium carbonate with a meal when residual acid is highest. Ensure adequate vitamin D intake and discuss bone density monitoring if you take esomeprazole for more than a year.", "minimumTimeSeparation": null, "mechanism": "Calcium carbonate requires gastric acid to ionize Ca2+ for absorption; esomeprazole-induced hypochlorhydria reduces this dissolution. Calcium citrate is acid-independent because it is already in a soluble salt form.", "evidenceLevel": "strong", "sources": [ { "text": "Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296(24):2947-53.", "pmid": "17190895", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17190895/", "publicSourceType": "PMID" }, { "text": "Zhou B, Huang Y, Li H, Sun W, Liu J. Proton-pump inhibitors and risk of fractures: an update meta-analysis. Osteoporos Int. 2016;27(1):339-47.", "pmid": "26462494", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26462494/", "publicSourceType": "PMID" }, { "text": "Freedberg DE, Kim LS, Yang YX. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-15.", "pmid": "28257716", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28257716/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Esomeprazole reduces absorption of calcium carbonate and is linked to higher fracture risk on long-term use.", "clinicalSignificance": "Bone-related complications can accumulate silently over years of PPI therapy.", "managementStrategy": "Use calcium citrate or take carbonate with food, and ensure adequate vitamin D.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Esomeprazole", "supplementBName": "Vitamin C", "interactionType": "caution", "severity": "info", "description": "Esomeprazole lowers the concentration of bioavailable vitamin C in the stomach. In healthy volunteers, four weeks of a PPI reduced plasma vitamin C by about 12% even on a stable diet. The reduction is mostly subclinical but may matter for people with marginal vitamin C intake or active H. pylori infection.", "recommendation": "Eat vitamin C-rich foods daily while on esomeprazole. If supplementing, a standard 250-500 mg dose taken with a meal is reasonable; there is no need to separate dosing from the PPI.", "minimumTimeSeparation": null, "mechanism": "Vitamin C is secreted into gastric juice in its active reduced (ascorbate) form, which is unstable at the higher pH produced by PPIs. The result is faster oxidation to less-bioavailable dehydroascorbate and lower systemic vitamin C levels.", "evidenceLevel": "moderate", "sources": [ { "text": "Henry EB, Carswell A, Wirz A, Fyffe V, McColl KE. Proton pump inhibitors reduce the bioavailability of dietary vitamin C. Aliment Pharmacol Ther. 2005;22(6):539-45.", "pmid": "16167970", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16167970/", "publicSourceType": "PMID" }, { "text": "Freedberg DE, Kim LS, Yang YX. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-15.", "pmid": "28257716", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28257716/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Esomeprazole modestly lowers plasma vitamin C bioavailability.", "clinicalSignificance": "Most patients tolerate this without clinical effects, but those with marginal intake may benefit from supplementation.", "managementStrategy": "Maintain dietary vitamin C or take a modest supplement with a meal.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Esomeprazole", "supplementBName": "Zinc", "interactionType": "caution", "severity": "moderate", "description": "Chronic esomeprazole therapy reduces zinc absorption and lowers body zinc stores. In a controlled study, plasma zinc rose 126% with supplementation in controls but only 37% in long-term PPI users, and baseline zinc was about 28% lower in PPI users. Lower zinc can impair immune function and wound healing.", "recommendation": "If you take esomeprazole long-term, consider 15-30 mg/day of zinc, ideally as zinc picolinate or zinc bisglycinate which are less acid-dependent. Take zinc on an empty stomach if tolerated, or with food if it causes nausea.", "minimumTimeSeparation": null, "mechanism": "Zinc absorption in the duodenum and jejunum is enhanced by gastric acid, which helps solubilize zinc salts and supports the ZIP4 transporter's function in an acidic luminal environment. PPI-induced hypochlorhydria blunts both processes.", "evidenceLevel": "moderate", "sources": [ { "text": "Farrell CP, Morgan M, Rudolph DS, et al. Proton Pump Inhibitors Interfere With Zinc Absorption and Zinc Body Stores. Gastroenterol Res. 2011;4(6):243-51.", "pmid": "27957023", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27957023/", "publicSourceType": "PMID" }, { "text": "Freedberg DE, Kim LS, Yang YX. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-15.", "pmid": "28257716", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28257716/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Esomeprazole impairs zinc absorption and lowers body zinc stores.", "clinicalSignificance": "Long-term PPI users may develop functional zinc insufficiency relevant to immunity and wound healing.", "managementStrategy": "Supplement modestly with zinc picolinate or bisglycinate during prolonged esomeprazole therapy.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Esomeprazole", "supplementBName": "Beta-Carotene", "interactionType": "caution", "severity": "info", "description": "Gastric acid contributes to the dispersion and absorption of beta-carotene from food. In a crossover study, raising gastric pH above 4.5 with omeprazole significantly reduced the plasma beta-carotene response to an oral dose. Patients relying on beta-carotene for vitamin A status may convert it less efficiently while on esomeprazole.", "recommendation": "If you use beta-carotene as a vitamin A source while on esomeprazole, take it with a fat-containing meal to maximize what acid-independent absorption you can get. People with vitamin A insufficiency may do better with preformed vitamin A (retinol) instead.", "minimumTimeSeparation": null, "mechanism": "Beta-carotene must be released from the food matrix and incorporated into mixed micelles for intestinal absorption. Gastric acid aids matrix breakdown and emulsification; PPI-induced hypochlorhydria reduces micelle formation efficiency.", "evidenceLevel": "emerging", "sources": [ { "text": "Tang G, Serfaty-Lacrosniere C, Camilo ME, Russell RM. Gastric acidity influences the blood response to a beta-carotene dose in humans. Am J Clin Nutr. 1996;64(4):622-6.", "pmid": "8839509", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8839509/", "publicSourceType": "PMID" }, { "text": "Freedberg DE, Kim LS, Yang YX. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-15.", "pmid": "28257716", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28257716/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Esomeprazole reduces beta-carotene absorption and likely its conversion to vitamin A.", "clinicalSignificance": "People relying on beta-carotene for vitamin A may not get the expected benefit.", "managementStrategy": "Take beta-carotene with a fatty meal, or use preformed vitamin A if vitamin A status is a concern.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Lansoprazole", "supplementBName": "Vitamin B12", "interactionType": "caution", "severity": "moderate", "description": "Lansoprazole reduces vitamin B12 absorption from food over years of use. The Kaiser Permanente case-control study linked two or more years of any PPI to a 65% higher risk of B12 deficiency, with dose-dependence. Elderly patients and those on long-term acid suppression are most affected.", "recommendation": "If you take lansoprazole for more than two years, ask for a serum B12 (with methylmalonic acid if borderline) annually. A daily B12 supplement, preferably methylcobalamin, sidesteps the acid-dependent absorption step.", "minimumTimeSeparation": null, "mechanism": "Lansoprazole irreversibly inhibits the gastric proton pump, raising gastric pH and impairing pepsin-mediated release of cobalamin from dietary proteins. Without that release, intrinsic factor cannot bind cobalamin for ileal absorption.", "evidenceLevel": "strong", "sources": [ { "text": "Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-42.", "pmid": "24327038", "doi": "10.1001/jama.2013.280490", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24327038/", "publicSourceType": "PMID" }, { "text": "Choudhury A, Jena A, Jearth V, et al. Vitamin B12 deficiency and use of proton pump inhibitors: a systematic review and meta-analysis. Expert Rev Gastroenterol Hepatol. 2023;17(5):479-87.", "pmid": "37060552", "doi": "10.1080/17474124.2023.2204229", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37060552/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Lansoprazole reduces dietary vitamin B12 absorption with prolonged use.", "clinicalSignificance": "Untreated B12 deficiency can cause anemia and irreversible neurological damage.", "managementStrategy": "Monitor B12 yearly on long-term lansoprazole and supplement with methylcobalamin if low.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Lansoprazole", "supplementBName": "Magnesium Glycinate", "interactionType": "caution", "severity": "serious", "description": "Lansoprazole, like other PPIs, can cause hypomagnesemia after months to years of use. Case reports and meta-analyses confirm reduced intestinal magnesium uptake on long-term PPIs, with episodes of seizure, tetany, and arrhythmia documented even in patients on oral magnesium. Symptoms typically resolve only after the PPI is stopped.", "recommendation": "Check serum magnesium at baseline and at least annually on long-term lansoprazole. If low, start magnesium glycinate and discuss whether the PPI can be switched to an H2 blocker or stopped.", "minimumTimeSeparation": null, "mechanism": "PPI-induced hypochlorhydria impairs active intestinal magnesium uptake by TRPM6/TRPM7 channels, which depend on luminal proton gradients. The defect is class-wide and reverses within days of discontinuation.", "evidenceLevel": "strong", "sources": [ { "text": "Cheungpasitporn W, Thongprayoon C, Kittanamongkolchai W, et al. Proton pump inhibitors linked to hypomagnesemia: a systematic review and meta-analysis of observational studies. Ren Fail. 2015;37(7):1237-41.", "pmid": "26108134", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26108134/", "publicSourceType": "PMID" }, { "text": "Hess MW, Hoenderop JG, Bindels RJ, Drenth JP. Systematic review: hypomagnesaemia induced by proton pump inhibition. Aliment Pharmacol Ther. 2012;36(5):405-13.", "pmid": "22762246", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22762246/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Lansoprazole can cause hypomagnesemia, sometimes severe, on long-term use.", "clinicalSignificance": "Hypomagnesemia from chronic PPI use may cause seizures or arrhythmia and often does not correct with oral repletion alone.", "managementStrategy": "Monitor magnesium periodically; supplement and consider stopping lansoprazole if hypomagnesemia is persistent.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Lansoprazole", "supplementBName": "Iron", "interactionType": "caution", "severity": "moderate", "description": "Lansoprazole reduces absorption of non-heme iron salts that require gastric acid for dissolution. The Kaiser study of 77,000 iron-deficiency cases found that two or more years of PPI use was associated with about 2.5-fold higher risk of iron deficiency. Patients with menstrual losses or GI blood loss are at highest risk.", "recommendation": "Take iron supplements at least 4 hours apart from lansoprazole. Iron bisglycinate or a heme-iron product is less affected by low gastric acid. Recheck ferritin and CBC 3 months after starting iron therapy.", "minimumTimeSeparation": 240, "mechanism": "Gastric acid converts ferric iron to the absorbable ferrous form and solubilizes oral iron salts for uptake by duodenal DMT1. Lansoprazole also up-regulates hepcidin through an aryl hydrocarbon receptor pathway, further reducing intestinal iron transfer.", "evidenceLevel": "strong", "sources": [ { "text": "Lam JR, Schneider JL, Quesenberry CP, Corley DA. Proton Pump Inhibitor and Histamine-2 Receptor Antagonist Use and Iron Deficiency. Gastroenterology. 2017;152(4):821-9.", "pmid": "27890768", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27890768/", "publicSourceType": "PMID" }, { "text": "Hamano H, Niimura T, Horinouchi Y, et al. Proton pump inhibitors block iron absorption through direct regulation of hepcidin via the aryl hydrocarbon receptor-mediated pathway. Toxicol Lett. 2020;318:86-91.", "pmid": "31669099", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31669099/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Lansoprazole reduces iron absorption and raises risk of iron deficiency over time.", "clinicalSignificance": "Iron repletion may fail or be slow in patients on long-term lansoprazole.", "managementStrategy": "Separate iron from lansoprazole by 4 hours, use bisglycinate if possible, and monitor ferritin.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Lansoprazole", "supplementBName": "Calcium", "interactionType": "caution", "severity": "moderate", "description": "Lansoprazole reduces absorption of calcium carbonate, which depends on stomach acid for dissolution. Long-term PPI use is associated with a modest but consistent rise in hip and spine fracture risk in large epidemiologic studies. Postmenopausal women and chronic steroid users are at greatest risk.", "recommendation": "If you take lansoprazole long-term and need calcium, choose calcium citrate, which absorbs well without gastric acid. If using calcium carbonate, take it with food. Ensure adequate vitamin D and discuss bone density monitoring with your prescriber.", "minimumTimeSeparation": null, "mechanism": "Calcium carbonate must be ionized by gastric acid to Ca2+ before duodenal absorption; lansoprazole-induced hypochlorhydria reduces this dissolution. Calcium citrate bypasses the acid-dependent step.", "evidenceLevel": "strong", "sources": [ { "text": "Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296(24):2947-53.", "pmid": "17190895", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17190895/", "publicSourceType": "PMID" }, { "text": "Zhou B, Huang Y, Li H, Sun W, Liu J. Proton-pump inhibitors and risk of fractures: an update meta-analysis. Osteoporos Int. 2016;27(1):339-47.", "pmid": "26462494", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26462494/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Lansoprazole reduces calcium carbonate absorption and is linked to higher fracture risk on chronic use.", "clinicalSignificance": "Fracture risk accumulates silently over years of PPI therapy, especially in older adults.", "managementStrategy": "Use calcium citrate or take carbonate with food, and maintain vitamin D.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Lansoprazole", "supplementBName": "Vitamin C", "interactionType": "caution", "severity": "info", "description": "Lansoprazole reduces the bioavailability of dietary vitamin C by raising intragastric pH, which destabilizes ascorbate. A four-week trial of a PPI lowered plasma vitamin C by about 12% in healthy volunteers despite stable intake. The effect is usually subclinical but matters for patients with marginal vitamin C intake.", "recommendation": "Eat vitamin C-rich foods daily while on lansoprazole. A 250-500 mg vitamin C supplement with a meal is reasonable; no special timing is needed.", "minimumTimeSeparation": null, "mechanism": "Vitamin C is actively secreted into gastric juice as ascorbate, the bioactive form, which oxidizes rapidly to dehydroascorbate at elevated pH. Lansoprazole-induced hypochlorhydria shifts this equilibrium toward the less-absorbable oxidized form.", "evidenceLevel": "moderate", "sources": [ { "text": "Henry EB, Carswell A, Wirz A, Fyffe V, McColl KE. Proton pump inhibitors reduce the bioavailability of dietary vitamin C. Aliment Pharmacol Ther. 2005;22(6):539-45.", "pmid": "16167970", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16167970/", "publicSourceType": "PMID" }, { "text": "Freedberg DE, Kim LS, Yang YX. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-15.", "pmid": "28257716", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28257716/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Lansoprazole modestly lowers plasma vitamin C bioavailability.", "clinicalSignificance": "Mostly subclinical, but relevant for patients with marginal vitamin C intake.", "managementStrategy": "Maintain dietary vitamin C or take a modest supplement with a meal.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Lansoprazole", "supplementBName": "Zinc", "interactionType": "caution", "severity": "moderate", "description": "Long-term lansoprazole therapy reduces zinc absorption and lowers body zinc stores. Controlled data on PPI users showed plasma zinc rose only 37% with supplementation compared with 126% in controls, and baseline zinc was about 28% lower in PPI users. Reduced zinc can impair immunity, taste, and wound healing.", "recommendation": "If you take lansoprazole long-term, consider 15-30 mg/day of zinc, preferably as zinc picolinate or bisglycinate, which are less acid-dependent. Take with food if it causes nausea.", "minimumTimeSeparation": null, "mechanism": "Zinc absorption depends in part on gastric acid to solubilize zinc salts and on intestinal ZIP4 transporters that perform best in an acidic luminal environment. Lansoprazole's suppression of gastric acid blunts both steps.", "evidenceLevel": "moderate", "sources": [ { "text": "Farrell CP, Morgan M, Rudolph DS, et al. Proton Pump Inhibitors Interfere With Zinc Absorption and Zinc Body Stores. Gastroenterol Res. 2011;4(6):243-51.", "pmid": "27957023", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27957023/", "publicSourceType": "PMID" }, { "text": "Freedberg DE, Kim LS, Yang YX. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-15.", "pmid": "28257716", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28257716/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Lansoprazole impairs zinc absorption and reduces body zinc stores over time.", "clinicalSignificance": "Functional zinc insufficiency on chronic PPI can affect immunity, taste, and wound healing.", "managementStrategy": "Supplement with zinc picolinate or bisglycinate during prolonged lansoprazole use.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Famotidine", "supplementBName": "Vitamin B12", "interactionType": "caution", "severity": "moderate", "description": "Long-term famotidine therapy can lower vitamin B12 status by reducing acid-pepsin-dependent release of B12 from food. The Kaiser case-control study found that two or more years of H2 blocker use was associated with a 25% higher risk of B12 deficiency. The effect is smaller than with PPIs but real, and matters more in older adults and vegetarians.", "recommendation": "If you take famotidine daily for more than two years, ask for a periodic serum B12 check. A daily oral B12 supplement, ideally methylcobalamin, is a reasonable insurance step and does not require gastric acid for absorption.", "minimumTimeSeparation": null, "mechanism": "Famotidine reversibly blocks parietal cell H2 receptors, reducing gastric acid and pepsin secretion. Acid and pepsin are needed to free B12 from dietary protein so that intrinsic factor can bind it for ileal absorption.", "evidenceLevel": "moderate", "sources": [ { "text": "Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-42.", "pmid": "24327038", "doi": "10.1001/jama.2013.280490", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24327038/", "publicSourceType": "PMID" }, { "text": "Miller JW. Proton Pump Inhibitors, H2-Receptor Antagonists, Metformin, and Vitamin B-12 Deficiency: Clinical Implications. Adv Nutr. 2018;9(4):511S-518S.", "pmid": "30032223", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30032223/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Famotidine modestly reduces dietary vitamin B12 absorption with chronic use.", "clinicalSignificance": "Long-term H2 blocker use is a recognized contributor to B12 deficiency, especially in older adults.", "managementStrategy": "Monitor B12 periodically on chronic famotidine and supplement with methylcobalamin if low.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Famotidine", "supplementBName": "Iron", "interactionType": "caution", "severity": "moderate", "description": "Famotidine can reduce absorption of oral iron, especially non-heme iron salts that require gastric acid. In the Kaiser study, two or more years of H2 blocker use was associated with about a 1.6-fold increase in iron deficiency risk. The effect is smaller than with PPIs but still clinically relevant in patients with menstrual or GI losses.", "recommendation": "Take iron supplements at least 2-4 hours apart from famotidine. Iron bisglycinate or a heme-iron product is less acid-dependent. Recheck ferritin 3 months after starting iron repletion.", "minimumTimeSeparation": 120, "mechanism": "Gastric acid reduces ferric to ferrous iron and solubilizes iron salts for duodenal absorption by DMT1. Famotidine-induced reduction in gastric acid output (typically 60-80%) blunts both steps.", "evidenceLevel": "moderate", "sources": [ { "text": "Lam JR, Schneider JL, Quesenberry CP, Corley DA. Proton Pump Inhibitor and Histamine-2 Receptor Antagonist Use and Iron Deficiency. Gastroenterology. 2017;152(4):821-9.", "pmid": "27890768", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27890768/", "publicSourceType": "PMID" }, { "text": "Freedberg DE, Kim LS, Yang YX. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-15.", "pmid": "28257716", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28257716/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Famotidine reduces oral iron absorption modestly and is associated with iron deficiency on long-term use.", "clinicalSignificance": "Iron repletion may be sluggish in patients on chronic famotidine.", "managementStrategy": "Separate iron from famotidine by 2-4 hours and consider iron bisglycinate.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Famotidine", "supplementBName": "Calcium", "interactionType": "caution", "severity": "info", "description": "Famotidine reduces gastric acid and can lower the absorption of calcium carbonate, which depends on acid to dissolve. The fracture-risk signal is weaker for H2 blockers than for PPIs, but the absorption effect is plausible and worth noting for patients who use calcium carbonate as their primary calcium source.", "recommendation": "If you take famotidine regularly, prefer calcium citrate, which absorbs well without gastric acid. If using calcium carbonate, take it with a meal when residual acid is highest.", "minimumTimeSeparation": null, "mechanism": "Calcium carbonate requires acid for dissolution and ionization to Ca2+ before duodenal absorption. Famotidine blunts gastric acid secretion via H2-receptor blockade, reducing dissolution efficiency.", "evidenceLevel": "moderate", "sources": [ { "text": "Freedberg DE, Kim LS, Yang YX. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-15.", "pmid": "28257716", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28257716/", "publicSourceType": "PMID" }, { "text": "Zhou B, Huang Y, Li H, Sun W, Liu J. Proton-pump inhibitors and risk of fractures: an update meta-analysis. Osteoporos Int. 2016;27(1):339-47.", "pmid": "26462494", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26462494/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Famotidine modestly reduces calcium carbonate absorption.", "clinicalSignificance": "Patients relying on calcium carbonate may absorb less while on famotidine.", "managementStrategy": "Use calcium citrate, or take calcium carbonate with a meal.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Cimetidine", "supplementBName": "Vitamin B12", "interactionType": "caution", "severity": "moderate", "description": "Cimetidine reduces gastric acid and pepsin secretion enough to impair the release of dietary B12 from food protein. The Kaiser study linked two or more years of any H2 blocker use to a 25% higher risk of B12 deficiency, and cimetidine has the strongest acid-suppression profile of the H2 class. Risk rises in elderly patients, vegetarians, and those on chronic acid suppression.", "recommendation": "If you take cimetidine daily for more than a year or two, ask for a serum B12 (with methylmalonic acid if borderline) check periodically. A daily methylcobalamin supplement is sensible and does not require gastric acid for absorption.", "minimumTimeSeparation": null, "mechanism": "Cimetidine reversibly blocks parietal cell H2 receptors, lowering gastric acid and pepsin. Both are needed to cleave cobalamin from dietary protein before intrinsic factor can bind it for ileal absorption.", "evidenceLevel": "moderate", "sources": [ { "text": "Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-42.", "pmid": "24327038", "doi": "10.1001/jama.2013.280490", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24327038/", "publicSourceType": "PMID" }, { "text": "Miller JW. Proton Pump Inhibitors, H2-Receptor Antagonists, Metformin, and Vitamin B-12 Deficiency: Clinical Implications. Adv Nutr. 2018;9(4):511S-518S.", "pmid": "30032223", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30032223/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Cimetidine reduces dietary vitamin B12 absorption with prolonged use.", "clinicalSignificance": "Chronic cimetidine use is a recognized contributor to B12 deficiency.", "managementStrategy": "Monitor B12 periodically on chronic cimetidine and supplement with methylcobalamin if low.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Cimetidine", "supplementBName": "Iron", "interactionType": "caution", "severity": "moderate", "description": "Cimetidine reduces gastric acid and modestly impairs absorption of oral iron salts, particularly ferrous sulfate. The H2 blocker class is associated with about a 1.6-fold higher risk of iron deficiency on long-term use. Cimetidine also has the strongest acid-suppressing profile of the H2 blockers.", "recommendation": "Take iron supplements at least 2-4 hours apart from cimetidine. Consider iron bisglycinate, which absorbs better at higher gastric pH. Recheck ferritin 3 months after starting iron.", "minimumTimeSeparation": 120, "mechanism": "Gastric acid converts dietary ferric to absorbable ferrous iron and solubilizes oral iron salts for duodenal uptake by DMT1. Cimetidine blocks H2 receptors on parietal cells, reducing acid output and the resulting absorption.", "evidenceLevel": "moderate", "sources": [ { "text": "Lam JR, Schneider JL, Quesenberry CP, Corley DA. Proton Pump Inhibitor and Histamine-2 Receptor Antagonist Use and Iron Deficiency. Gastroenterology. 2017;152(4):821-9.", "pmid": "27890768", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27890768/", "publicSourceType": "PMID" }, { "text": "Freedberg DE, Kim LS, Yang YX. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-15.", "pmid": "28257716", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28257716/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Cimetidine reduces oral iron absorption and is associated with iron deficiency on long-term use.", "clinicalSignificance": "Iron repletion may be slower in patients on chronic cimetidine.", "managementStrategy": "Separate iron from cimetidine by 2-4 hours and prefer iron bisglycinate.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Cimetidine", "supplementBName": "Melatonin", "interactionType": "caution", "severity": "moderate", "description": "Cimetidine is a potent inhibitor of CYP1A2, the main enzyme that clears melatonin. Co-administration can substantially raise melatonin plasma levels and prolong its effects, increasing the chance of next-day sedation, vivid dreams, or morning grogginess. Older adults are most sensitive.", "recommendation": "If you take cimetidine, start melatonin at the lowest dose (0.3-1 mg) and avoid the timed-release form unless directed. Take melatonin at least 30-60 minutes before bedtime and reassess after a few nights. If you become groggy or oversleep, lower the dose.", "minimumTimeSeparation": null, "mechanism": "Melatonin is metabolized primarily by hepatic CYP1A2 to 6-hydroxymelatonin. Cimetidine inhibits CYP1A2 (along with CYP2D6 and CYP3A) more potently than any other H2 blocker, reducing melatonin clearance and elevating plasma concentrations.", "evidenceLevel": "moderate", "sources": [ { "text": "Martínez C, Albet C, Agúndez JA, et al. Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2-receptor antagonists. Clin Pharmacol Ther. 1999;65(4):369-76.", "pmid": "10223772", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10223772/", "publicSourceType": "PMID" }, { "text": "Broughton LJ, Rogers HJ. Decreased systemic clearance of caffeine due to cimetidine. Br J Clin Pharmacol. 1981;12(2):155-9.", "pmid": "7306430", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7306430/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Cimetidine inhibits CYP1A2, raising melatonin levels and prolonging its sedative action.", "clinicalSignificance": "Patients on cimetidine may experience excess sedation, morning grogginess, or vivid dreams from standard melatonin doses.", "managementStrategy": "Start melatonin low (0.3-1 mg) on cimetidine and titrate slowly.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Cimetidine", "supplementBName": "Green Tea Extract", "interactionType": "caution", "severity": "moderate", "description": "Cimetidine inhibits CYP1A2, the main enzyme that clears caffeine. Caffeine-containing green tea extract taken with cimetidine can produce higher and longer-lasting plasma caffeine levels, raising the risk of jitteriness, insomnia, palpitations, and elevated blood pressure. A controlled study showed cimetidine reduced caffeine clearance significantly.", "recommendation": "If you take cimetidine, prefer a decaffeinated green tea extract or limit total caffeine intake. Watch for signs of caffeine excess like racing heart or insomnia, especially in the first week of combining them.", "minimumTimeSeparation": null, "mechanism": "Caffeine is metabolized by hepatic CYP1A2. Cimetidine inhibits CYP1A2 more strongly than any other H2 blocker, prolonging caffeine half-life and raising peak plasma concentrations.", "evidenceLevel": "moderate", "sources": [ { "text": "Broughton LJ, Rogers HJ. Decreased systemic clearance of caffeine due to cimetidine. Br J Clin Pharmacol. 1981;12(2):155-9.", "pmid": "7306430", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7306430/", "publicSourceType": "PMID" }, { "text": "Martínez C, Albet C, Agúndez JA, et al. Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2-receptor antagonists. Clin Pharmacol Ther. 1999;65(4):369-76.", "pmid": "10223772", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10223772/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Cimetidine slows caffeine clearance, intensifying and prolonging the stimulant effects of caffeinated green tea extract.", "clinicalSignificance": "Standard caffeine doses can feel much stronger and last longer when combined with cimetidine.", "managementStrategy": "Use decaffeinated green tea extract or reduce total caffeine intake on cimetidine.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Omeprazole", "supplementBName": "Zinc", "interactionType": "caution", "severity": "moderate", "description": "Long-term omeprazole therapy reduces zinc absorption and lowers body zinc stores. In one controlled study, plasma zinc rose 126% with supplementation in healthy controls but only 37% in long-term PPI users, and baseline zinc was about 28% lower in PPI users. Reduced zinc can impair immunity, taste, and wound healing.", "recommendation": "If you take omeprazole long-term, consider 15-30 mg/day of zinc, ideally as zinc picolinate or bisglycinate, which are less acid-dependent. Take on an empty stomach if tolerated, with food if it causes nausea.", "minimumTimeSeparation": null, "mechanism": "Zinc absorption depends in part on gastric acid to solubilize zinc salts and on intestinal ZIP4 transporters that work best in an acidic luminal environment. Omeprazole's irreversible inhibition of the proton pump blunts both.", "evidenceLevel": "moderate", "sources": [ { "text": "Farrell CP, Morgan M, Rudolph DS, et al. Proton Pump Inhibitors Interfere With Zinc Absorption and Zinc Body Stores. Gastroenterol Res. 2011;4(6):243-51.", "pmid": "27957023", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27957023/", "publicSourceType": "PMID" }, { "text": "Freedberg DE, Kim LS, Yang YX. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-15.", "pmid": "28257716", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28257716/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Omeprazole impairs zinc absorption and lowers body zinc stores.", "clinicalSignificance": "Long-term PPI users may develop functional zinc insufficiency relevant to immunity and wound healing.", "managementStrategy": "Supplement with zinc picolinate or bisglycinate during prolonged omeprazole use.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Omeprazole", "supplementBName": "Beta-Carotene", "interactionType": "caution", "severity": "info", "description": "Omeprazole-induced hypochlorhydria reduces the absorption of beta-carotene. In a crossover trial, raising gastric pH above 4.5 with omeprazole significantly lowered the plasma beta-carotene response to an oral dose. People relying on beta-carotene as a vitamin A source may convert it less efficiently.", "recommendation": "Take beta-carotene with a fat-containing meal to maximize the acid-independent portion of absorption. If you are concerned about vitamin A status, ask your prescriber whether preformed vitamin A (retinol) is more appropriate.", "minimumTimeSeparation": null, "mechanism": "Beta-carotene must be released from the food matrix and incorporated into mixed micelles to be absorbed. Gastric acid aids matrix breakdown and dispersion; omeprazole reduces this effect by suppressing acid output.", "evidenceLevel": "emerging", "sources": [ { "text": "Tang G, Serfaty-Lacrosniere C, Camilo ME, Russell RM. Gastric acidity influences the blood response to a beta-carotene dose in humans. Am J Clin Nutr. 1996;64(4):622-6.", "pmid": "8839509", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8839509/", "publicSourceType": "PMID" }, { "text": "Freedberg DE, Kim LS, Yang YX. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-15.", "pmid": "28257716", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28257716/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Omeprazole reduces beta-carotene absorption and its conversion to vitamin A.", "clinicalSignificance": "People relying on beta-carotene for vitamin A may not get the expected benefit.", "managementStrategy": "Take beta-carotene with a fatty meal, or use preformed vitamin A if vitamin A status is a concern.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Omeprazole", "supplementBName": "Iron Bisglycinate", "interactionType": "synergy", "severity": "info", "description": "Iron bisglycinate is a chelated form of iron whose absorption is less dependent on gastric acid than conventional ferrous sulfate. For patients on omeprazole who need iron repletion, bisglycinate is a more reliable choice and tends to cause less GI upset. It is not an antidote to PPI-induced iron loss, but it minimizes the absorption penalty.", "recommendation": "If you take omeprazole and need iron supplementation, choose iron bisglycinate over ferrous sulfate. Take 25-30 mg of elemental iron daily, ideally on an empty stomach, and recheck ferritin in 3 months.", "minimumTimeSeparation": null, "mechanism": "Iron bisglycinate is absorbed intact across enterocytes via amino acid transporters in addition to the standard DMT1 pathway, bypassing the gastric acid step needed to ionize inorganic iron salts. Absorption is therefore more pH-tolerant.", "evidenceLevel": "moderate", "sources": [ { "text": "Lam JR, Schneider JL, Quesenberry CP, Corley DA. Proton Pump Inhibitor and Histamine-2 Receptor Antagonist Use and Iron Deficiency. Gastroenterology. 2017;152(4):821-9.", "pmid": "27890768", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27890768/", "publicSourceType": "PMID" }, { "text": "Hamano H, Niimura T, Horinouchi Y, et al. Proton pump inhibitors block iron absorption through direct regulation of hepcidin via the aryl hydrocarbon receptor-mediated pathway. Toxicol Lett. 2020;318:86-91.", "pmid": "31669099", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31669099/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Iron bisglycinate is absorbed more reliably than other oral iron forms in PPI-induced hypochlorhydria.", "clinicalSignificance": "Patients on omeprazole are more likely to achieve iron repletion with bisglycinate than with ferrous sulfate.", "managementStrategy": "Prefer iron bisglycinate over ferrous sulfate when iron supplementation is needed with omeprazole.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Omeprazole", "supplementBName": "Methylcobalamin", "interactionType": "synergy", "severity": "info", "description": "Methylcobalamin, the active coenzyme form of vitamin B12, does not require gastric acid or pepsin to be released from food protein, making it a more reliable B12 source for patients on omeprazole. Long-term PPI use raises B12 deficiency risk roughly 65% over two or more years, and oral methylcobalamin can fully prevent that deficit in most patients.", "recommendation": "If you take omeprazole long-term, 500-1000 mcg of oral methylcobalamin daily is a sensible insurance dose. Recheck serum B12 (and methylmalonic acid if borderline) yearly while on the PPI.", "minimumTimeSeparation": null, "mechanism": "Free B12 supplements (including methylcobalamin) bypass the acid-pepsin step needed to liberate B12 from dietary protein. Intrinsic factor binds the free vitamin directly for ileal absorption, which remains intact during PPI therapy.", "evidenceLevel": "strong", "sources": [ { "text": "Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-42.", "pmid": "24327038", "doi": "10.1001/jama.2013.280490", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24327038/", "publicSourceType": "PMID" }, { "text": "Miller JW. Proton Pump Inhibitors, H2-Receptor Antagonists, Metformin, and Vitamin B-12 Deficiency: Clinical Implications. Adv Nutr. 2018;9(4):511S-518S.", "pmid": "30032223", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30032223/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Methylcobalamin offsets the B12 absorption deficit caused by omeprazole.", "clinicalSignificance": "A simple daily methylcobalamin prevents the most common nutrient deficiency from chronic omeprazole.", "managementStrategy": "Take 500-1000 mcg methylcobalamin daily while on long-term omeprazole.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Omeprazole", "supplementBName": "Probiotics", "interactionType": "synergy", "severity": "info", "description": "Omeprazole shifts the gut microbiome and roughly doubles the risk of Clostridioides difficile and small intestinal bacterial overgrowth. A 2017 Cochrane review of 39 trials found probiotics reduced C. difficile-associated diarrhea by about 60% in adults and children at increased baseline risk. Co-administration is reasonable for patients also on antibiotics or with prior C. diff.", "recommendation": "If you are on omeprazole and antibiotics, or have a history of C. diff, consider a multi-strain probiotic with documented evidence (Lactobacillus rhamnosus GG or Saccharomyces boulardii are best studied). Take the probiotic 2 hours apart from any antibiotic dose, but timing relative to omeprazole is not critical.", "minimumTimeSeparation": null, "mechanism": "PPI-induced hypochlorhydria removes a key barrier to enteric pathogens and permits dysbiosis with overgrowth of opportunistic bacteria. Probiotics restore a portion of the protective microbial community and competitively inhibit pathogens like C. difficile.", "evidenceLevel": "strong", "sources": [ { "text": "Goldenberg JZ, Yap C, Lytvyn L, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev. 2017;12(12):CD006095.", "pmid": "29257353", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29257353/", "publicSourceType": "PMID" }, { "text": "Kiecka A, Szczepanik M. Proton pump inhibitor-induced gut dysbiosis and immunomodulation: current knowledge and potential restoration by probiotics. Pharmacol Rep. 2023;75(4):791-804.", "pmid": "37142877", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37142877/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Probiotics can mitigate the dysbiosis and C. difficile risk associated with omeprazole.", "clinicalSignificance": "Probiotic coverage is most useful for patients on PPIs who are also exposed to antibiotics or are otherwise at high C. diff risk.", "managementStrategy": "Take a documented multi-strain probiotic, especially when also on antibiotics.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Omeprazole", "supplementBName": "Saccharomyces Boulardii", "interactionType": "synergy", "severity": "info", "description": "Saccharomyces boulardii is a non-pathogenic yeast probiotic with strong evidence for preventing antibiotic-associated and C. difficile-associated diarrhea, both of which are more common during omeprazole therapy. Meta-analyses support its use as adjunctive prophylaxis when PPIs are combined with antibiotics. Because it is a yeast, it is unaffected by antibacterial antibiotics.", "recommendation": "If you take omeprazole and start a course of antibiotics, consider Saccharomyces boulardii 250-500 mg twice daily for the duration of the antibiotic and a few days after. Avoid in critically ill or severely immunocompromised patients due to rare fungemia risk.", "minimumTimeSeparation": null, "mechanism": "S. boulardii degrades C. difficile toxins A and B, competes for adhesion sites in the gut, and stimulates secretory IgA. Unlike bacterial probiotics, it survives concurrent antibiotic therapy.", "evidenceLevel": "strong", "sources": [ { "text": "McFarland LV. Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J Gastroenterol. 2010;16(18):2202-22.", "pmid": "20458757", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20458757/", "publicSourceType": "PMID" }, { "text": "Goldenberg JZ, Yap C, Lytvyn L, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev. 2017;12(12):CD006095.", "pmid": "29257353", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29257353/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Saccharomyces boulardii reduces C. difficile and antibiotic-associated diarrhea risk in patients on omeprazole.", "clinicalSignificance": "Adding S. boulardii during antibiotics on omeprazole materially lowers diarrheal complications.", "managementStrategy": "Take S. boulardii 250-500 mg twice daily during antibiotics if otherwise healthy.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Omeprazole", "supplementBName": "Melatonin", "interactionType": "synergy", "severity": "info", "description": "Melatonin has gastroprotective and lower esophageal sphincter-tonifying effects and shows additive symptom relief when combined with omeprazole for GERD. In one randomized trial, melatonin plus omeprazole produced faster and more complete symptom resolution than omeprazole alone. Patients with mild reflux or who want to taper PPIs sometimes use melatonin as an adjunct.", "recommendation": "Discuss melatonin 3-6 mg at bedtime with your prescriber if you have ongoing reflux symptoms on omeprazole. Do not stop omeprazole abruptly without medical guidance, as rebound acid hypersecretion is common.", "minimumTimeSeparation": null, "mechanism": "Melatonin increases lower esophageal sphincter pressure, inhibits gastric acid and nitric oxide-mediated relaxation, and is mucosal-protective via antioxidant pathways. These effects are additive to omeprazole's blockade of the H+/K+-ATPase.", "evidenceLevel": "emerging", "sources": [ { "text": "Kandil TS, Mousa AA, El-Gendy AA, Abbas AM. The potential therapeutic effect of melatonin in Gastro-Esophageal Reflux Disease. BMC Gastroenterol. 2010;10:7.", "pmid": "20082715", "doi": "10.1186/1471-230X-10-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20082715/", "publicSourceType": "PMID" }, { "text": "Pereira RS. Regression of gastroesophageal reflux disease symptoms using dietary supplementation with melatonin, vitamins and aminoacids: comparison with omeprazole. J Pineal Res. 2006;41(3):195-200.", "pmid": "16948779", "doi": "10.1111/j.1600-079X.2006.00359.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16948779/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Melatonin can augment omeprazole's symptom relief in GERD.", "clinicalSignificance": "Adjunctive melatonin may speed symptom control or aid PPI tapering with medical guidance.", "managementStrategy": "Discuss adding melatonin 3-6 mg at bedtime with your prescriber for refractory reflux.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Pantoprazole", "supplementBName": "Melatonin", "interactionType": "synergy", "severity": "info", "description": "Melatonin has gastroprotective effects and increases lower esophageal sphincter tone, and small randomized trials show additive GERD symptom relief when combined with a PPI. Patients with persistent reflux on pantoprazole sometimes benefit from adjunctive bedtime melatonin. The evidence is emerging but mechanistically plausible.", "recommendation": "If you have ongoing reflux symptoms on pantoprazole, ask your prescriber about a trial of melatonin 3-6 mg at bedtime. Do not stop pantoprazole abruptly, since rebound acid hypersecretion is common.", "minimumTimeSeparation": null, "mechanism": "Melatonin increases lower esophageal sphincter pressure, scavenges mucosal free radicals, and inhibits nitric oxide-mediated relaxation. These effects complement pantoprazole's irreversible inhibition of the gastric H+/K+-ATPase.", "evidenceLevel": "emerging", "sources": [ { "text": "Kandil TS, Mousa AA, El-Gendy AA, Abbas AM. The potential therapeutic effect of melatonin in Gastro-Esophageal Reflux Disease. BMC Gastroenterol. 2010;10:7.", "pmid": "20082715", "doi": "10.1186/1471-230X-10-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20082715/", "publicSourceType": "PMID" }, { "text": "Pereira RS. Regression of gastroesophageal reflux disease symptoms using dietary supplementation with melatonin, vitamins and aminoacids: comparison with omeprazole. J Pineal Res. 2006;41(3):195-200.", "pmid": "16948779", "doi": "10.1111/j.1600-079X.2006.00359.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16948779/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Melatonin may add to pantoprazole's GERD symptom control.", "clinicalSignificance": "Useful adjunct for patients with breakthrough reflux on pantoprazole.", "managementStrategy": "Discuss adjunctive melatonin 3-6 mg at bedtime with your prescriber.", "isSynergistic": true, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Pantoprazole", "supplementBName": "Zinc", "interactionType": "caution", "severity": "moderate", "description": "Long-term pantoprazole reduces zinc absorption and lowers body zinc stores, mirroring the class effect documented for other PPIs. In controlled studies, PPI users absorbed substantially less supplemental zinc and had baseline plasma zinc roughly 28% lower than controls. Reduced zinc can affect immune function, taste, and wound healing.", "recommendation": "If you take pantoprazole long-term, consider 15-30 mg/day of zinc, preferably as zinc picolinate or bisglycinate, which are less acid-dependent. Take with food if it causes nausea.", "minimumTimeSeparation": null, "mechanism": "Zinc absorption depends in part on gastric acid for salt solubilization and on ZIP4 transporters that function best at acidic luminal pH. Pantoprazole's irreversible inhibition of the gastric proton pump blunts both.", "evidenceLevel": "moderate", "sources": [ { "text": "Farrell CP, Morgan M, Rudolph DS, et al. Proton Pump Inhibitors Interfere With Zinc Absorption and Zinc Body Stores. Gastroenterol Res. 2011;4(6):243-51.", "pmid": "27957023", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27957023/", "publicSourceType": "PMID" }, { "text": "Freedberg DE, Kim LS, Yang YX. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-15.", "pmid": "28257716", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28257716/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Pantoprazole impairs zinc absorption and lowers body zinc stores.", "clinicalSignificance": "Functional zinc insufficiency on chronic PPI can affect immunity, taste, and wound healing.", "managementStrategy": "Supplement with zinc picolinate or bisglycinate during prolonged pantoprazole use.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Pantoprazole", "supplementBName": "Probiotics", "interactionType": "synergy", "severity": "info", "description": "Pantoprazole shifts gut microbiota and increases the risk of C. difficile-associated diarrhea and small intestinal bacterial overgrowth. A Cochrane review of 39 trials found probiotics reduced C. difficile-associated diarrhea risk by about 60% in patients at elevated baseline risk. Coverage is especially worthwhile when pantoprazole is combined with antibiotics.", "recommendation": "If you are on pantoprazole and antibiotics, or have a history of C. diff, take a multi-strain probiotic with documented efficacy (Lactobacillus rhamnosus GG or Saccharomyces boulardii are best studied). Space probiotics 2 hours from antibiotics; timing with pantoprazole does not matter.", "minimumTimeSeparation": null, "mechanism": "PPI-induced hypochlorhydria removes a key gastric barrier to enteric pathogens and permits opportunistic overgrowth. Probiotics competitively inhibit pathogens like C. difficile and restore protective short-chain fatty acid production.", "evidenceLevel": "strong", "sources": [ { "text": "Goldenberg JZ, Yap C, Lytvyn L, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev. 2017;12(12):CD006095.", "pmid": "29257353", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29257353/", "publicSourceType": "PMID" }, { "text": "Kiecka A, Szczepanik M. Proton pump inhibitor-induced gut dysbiosis and immunomodulation: current knowledge and potential restoration by probiotics. Pharmacol Rep. 2023;75(4):791-804.", "pmid": "37142877", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37142877/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Probiotics offset the dysbiosis and C. diff risk associated with pantoprazole.", "clinicalSignificance": "Most useful when pantoprazole is paired with antibiotics or in high-risk patients.", "managementStrategy": "Take a documented multi-strain probiotic, especially during concurrent antibiotic therapy.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Pantoprazole", "supplementBName": "Methylcobalamin", "interactionType": "synergy", "severity": "info", "description": "Methylcobalamin is a coenzyme form of B12 absorbed without needing gastric acid to free it from dietary protein, making it a reliable B12 source for patients on pantoprazole. Long-term PPI use raises B12 deficiency risk by about 65% over two or more years, and oral methylcobalamin can prevent that deficit in most patients.", "recommendation": "If you take pantoprazole long-term, 500-1000 mcg of oral methylcobalamin daily is a sensible insurance dose. Recheck serum B12 (and methylmalonic acid if borderline) yearly.", "minimumTimeSeparation": null, "mechanism": "Crystalline B12 supplements such as methylcobalamin bypass the acid-pepsin step required to liberate cobalamin from food protein. Intrinsic factor binds the free vitamin directly for ileal absorption, which remains intact on PPIs.", "evidenceLevel": "strong", "sources": [ { "text": "Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-42.", "pmid": "24327038", "doi": "10.1001/jama.2013.280490", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24327038/", "publicSourceType": "PMID" }, { "text": "Miller JW. Proton Pump Inhibitors, H2-Receptor Antagonists, Metformin, and Vitamin B-12 Deficiency: Clinical Implications. Adv Nutr. 2018;9(4):511S-518S.", "pmid": "30032223", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30032223/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Methylcobalamin offsets the B12 absorption deficit caused by pantoprazole.", "clinicalSignificance": "A simple daily methylcobalamin prevents the most common nutrient deficiency from chronic pantoprazole.", "managementStrategy": "Take 500-1000 mcg methylcobalamin daily while on long-term pantoprazole.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Pantoprazole", "supplementBName": "Iron Bisglycinate", "interactionType": "synergy", "severity": "info", "description": "Iron bisglycinate is a chelated iron form whose absorption is less dependent on gastric acid than ferrous sulfate, making it the preferred oral iron for patients on pantoprazole. It tends to cause less GI upset and provides more reliable repletion in PPI-induced hypochlorhydria. It does not fully bypass the hepcidin-mediated suppression PPIs also cause.", "recommendation": "If you take pantoprazole and need iron supplementation, choose iron bisglycinate over ferrous sulfate. Take 25-30 mg elemental iron daily, ideally on an empty stomach, and recheck ferritin in 3 months.", "minimumTimeSeparation": null, "mechanism": "Iron bisglycinate is absorbed intact via amino acid transporters in addition to DMT1, bypassing the gastric acid step needed to ionize inorganic iron salts. Absorption is therefore more pH-tolerant in PPI users.", "evidenceLevel": "moderate", "sources": [ { "text": "Lam JR, Schneider JL, Quesenberry CP, Corley DA. Proton Pump Inhibitor and Histamine-2 Receptor Antagonist Use and Iron Deficiency. Gastroenterology. 2017;152(4):821-9.", "pmid": "27890768", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27890768/", "publicSourceType": "PMID" }, { "text": "Hamano H, Niimura T, Horinouchi Y, et al. Proton pump inhibitors block iron absorption through direct regulation of hepcidin via the aryl hydrocarbon receptor-mediated pathway. Toxicol Lett. 2020;318:86-91.", "pmid": "31669099", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31669099/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Iron bisglycinate is absorbed more reliably than other oral iron forms in PPI-induced hypochlorhydria.", "clinicalSignificance": "Patients on pantoprazole are more likely to achieve iron repletion with bisglycinate.", "managementStrategy": "Prefer iron bisglycinate over ferrous sulfate when iron supplementation is needed with pantoprazole.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Omeprazole", "supplementBName": "Betaine HCL", "interactionType": "conflict", "severity": "moderate", "description": "Betaine HCL is taken specifically to lower gastric pH, while omeprazole is taken to raise it. The two are pharmacodynamically opposed: betaine HCL only partially and briefly reacidifies the stomach during PPI therapy, and patients with reflux esophagitis may experience worsening symptoms from the reacidification. There is no clinical role for combining them.", "recommendation": "Do not take betaine HCL while on omeprazole. If you believe you have low stomach acid rather than high, discuss this with your prescriber before adjusting either therapy. Stopping a PPI abruptly can cause rebound acid hypersecretion.", "minimumTimeSeparation": null, "mechanism": "Betaine hydrochloride dissociates to provide free HCl in the stomach. Controlled studies show 1500 mg of betaine HCL transiently reacidifies a PPI-suppressed stomach for roughly 30 minutes, but the pump-bound PPI continues to neutralize this effect over hours, and the reacidification may aggravate the underlying acid-related condition.", "evidenceLevel": "moderate", "sources": [ { "text": "Yago MR, Frymoyer AR, Smelick GS, et al. Gastric reacidification with betaine HCl in healthy volunteers with rabeprazole-induced hypochlorhydria. Mol Pharm. 2013;10(11):4032-7.", "pmid": "23980906", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23980906/", "publicSourceType": "PMID" }, { "text": "Freedberg DE, Kim LS, Yang YX. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-15.", "pmid": "28257716", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28257716/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Betaine HCL and omeprazole have directly opposing mechanisms and should not be combined.", "clinicalSignificance": "Combining them is pharmacologically incoherent and may worsen reflux symptoms.", "managementStrategy": "Do not combine; reassess the diagnosis with your prescriber if both seem indicated.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Pantoprazole", "supplementBName": "Betaine HCL", "interactionType": "conflict", "severity": "moderate", "description": "Betaine HCL acidifies the stomach, the opposite of what pantoprazole is prescribed to do. The two have directly opposing mechanisms, and the brief gastric reacidification from betaine HCL may worsen reflux symptoms in patients who were placed on pantoprazole for acid-related disease. There is no clinical role for combining them.", "recommendation": "Do not combine betaine HCL with pantoprazole. If you suspect you have low rather than high stomach acid, discuss this with your prescriber before changing therapy. Do not stop pantoprazole abruptly because of rebound acid hypersecretion risk.", "minimumTimeSeparation": null, "mechanism": "Betaine hydrochloride dissociates to provide free HCl in the stomach. In PPI-suppressed stomachs, 1500 mg of betaine HCL produces only a short window (about 30 minutes) of reacidification before the active proton pump inhibitor restores hypochlorhydria.", "evidenceLevel": "moderate", "sources": [ { "text": "Yago MR, Frymoyer AR, Smelick GS, et al. Gastric reacidification with betaine HCl in healthy volunteers with rabeprazole-induced hypochlorhydria. Mol Pharm. 2013;10(11):4032-7.", "pmid": "23980906", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23980906/", "publicSourceType": "PMID" }, { "text": "Freedberg DE, Kim LS, Yang YX. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-15.", "pmid": "28257716", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28257716/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Betaine HCL opposes pantoprazole's intended acid-suppressing effect.", "clinicalSignificance": "Combining them is pharmacologically incoherent and may worsen reflux symptoms.", "managementStrategy": "Do not combine; revisit the diagnosis with your prescriber.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Omeprazole", "supplementBName": "Turmeric/Curcumin", "interactionType": "synergy", "severity": "info", "description": "A 2023 randomized, double-blind trial in patients with functional dyspepsia found curcumin alone, omeprazole alone, and the combination produced comparable symptom improvement over 28 days. Curcumin may serve as an adjunct or alternative for mild dyspepsia, but it is not validated for erosive esophagitis or ulcer prevention. The two are safe to take together.", "recommendation": "If you have functional dyspepsia, discuss with your prescriber whether adding 250-500 mg of curcumin twice daily to omeprazole is appropriate. Do not replace prescribed omeprazole for severe reflux, Barrett's esophagus, or ulcer prevention without medical guidance.", "minimumTimeSeparation": null, "mechanism": "Curcumin has anti-inflammatory, mucosal-protective, and modest antisecretory activity in animal and clinical studies. Its mechanism is distinct from omeprazole's proton pump inhibition, allowing additive symptom relief in functional dyspepsia.", "evidenceLevel": "moderate", "sources": [ { "text": "Kongkam P, Khongkha W, Lohsiriwat V, et al. Curcumin and proton pump inhibitors for functional dyspepsia: a randomised, double blind controlled trial. BMJ Evid Based Med. 2023;28(6):399-406.", "pmid": "37696679", "doi": "10.1136/bmjebm-2022-112231", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37696679/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Curcumin can complement or substitute for omeprazole in functional dyspepsia.", "clinicalSignificance": "Useful adjunct or alternative for mild functional dyspepsia, but not for severe or erosive disease.", "managementStrategy": "Discuss adding curcumin 250-500 mg twice daily with your prescriber for functional dyspepsia.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Omeprazole", "supplementBName": "Zinc Carnosine", "interactionType": "synergy", "severity": "info", "description": "Zinc-L-carnosine (polaprezinc) is a mucosal-protective chelate widely used in Japan for gastritis and ulcer healing. It is well studied as an adjunct to acid suppression and to H. pylori eradication therapy, with evidence for faster ulcer healing and improved gastric mucosal repair. It complements rather than competes with omeprazole.", "recommendation": "If you have gastritis, an ulcer, or NSAID-related GI symptoms on omeprazole, ask your prescriber about adding zinc-L-carnosine 75 mg twice daily. The combination is well tolerated for short courses (4-8 weeks).", "minimumTimeSeparation": null, "mechanism": "Zinc-L-carnosine adheres to ulcer beds, scavenges reactive oxygen species, stabilizes mast cells, and promotes mucosal epithelial repair. These effects are mechanistically additive to omeprazole's acid suppression.", "evidenceLevel": "moderate", "sources": [ { "text": "Efthymakis K, Neri M. The role of Zinc L-Carnosine in the prevention and treatment of gastrointestinal mucosal disease in humans: a review. Clin Res Hepatol Gastroenterol. 2022;46(7):101954.", "pmid": "35659631", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35659631/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Zinc-L-carnosine adds mucosal-protective and ulcer-healing effects to omeprazole.", "clinicalSignificance": "Useful adjunct for gastritis or ulcer healing alongside omeprazole.", "managementStrategy": "Consider zinc-L-carnosine 75 mg twice daily for 4-8 weeks as an adjunct.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Pantoprazole", "supplementBName": "Zinc Carnosine", "interactionType": "synergy", "severity": "info", "description": "Zinc-L-carnosine (polaprezinc) is a mucosal-protective chelate with evidence for faster ulcer healing and improved gastric mucosal repair when combined with acid suppression. It complements pantoprazole's mechanism, especially in patients with gastritis, NSAID-related injury, or H. pylori eradication regimens. It does not interfere with the PPI's pharmacology.", "recommendation": "If you have gastritis, an ulcer, or NSAID-related symptoms on pantoprazole, ask your prescriber about adding zinc-L-carnosine 75 mg twice daily. The combination is well tolerated for short courses.", "minimumTimeSeparation": null, "mechanism": "Zinc-L-carnosine adheres to ulcer beds, scavenges reactive oxygen species, stabilizes mast cells, and promotes mucosal epithelial repair. These effects are mechanistically additive to pantoprazole's irreversible proton pump inhibition.", "evidenceLevel": "moderate", "sources": [ { "text": "Efthymakis K, Neri M. The role of Zinc L-Carnosine in the prevention and treatment of gastrointestinal mucosal disease in humans: a review. Clin Res Hepatol Gastroenterol. 2022;46(7):101954.", "pmid": "35659631", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35659631/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Zinc-L-carnosine adds mucosal-protective and ulcer-healing effects to pantoprazole.", "clinicalSignificance": "Useful adjunct for gastritis or ulcer healing alongside pantoprazole.", "managementStrategy": "Consider zinc-L-carnosine 75 mg twice daily for 4-8 weeks as an adjunct.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Cimetidine", "supplementBName": "Methylcobalamin", "interactionType": "synergy", "severity": "info", "description": "Methylcobalamin (a free coenzyme form of B12) does not need gastric acid or pepsin to be released from food protein, making it a more reliable B12 source for patients on cimetidine. Two or more years of H2 blocker use is linked to roughly 25% higher B12 deficiency risk, and oral methylcobalamin can prevent that deficit in most patients.", "recommendation": "If you take cimetidine long-term, 500-1000 mcg of oral methylcobalamin daily is a sensible insurance dose. Recheck serum B12 yearly while on chronic cimetidine.", "minimumTimeSeparation": null, "mechanism": "Free B12 supplements bypass the acid-pepsin step needed to liberate cobalamin from dietary protein. Intrinsic factor binds the free vitamin directly for ileal absorption, which remains intact on H2 blockers.", "evidenceLevel": "moderate", "sources": [ { "text": "Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-42.", "pmid": "24327038", "doi": "10.1001/jama.2013.280490", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24327038/", "publicSourceType": "PMID" }, { "text": "Miller JW. Proton Pump Inhibitors, H2-Receptor Antagonists, Metformin, and Vitamin B-12 Deficiency: Clinical Implications. Adv Nutr. 2018;9(4):511S-518S.", "pmid": "30032223", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30032223/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Methylcobalamin offsets the B12 absorption deficit from chronic cimetidine.", "clinicalSignificance": "A simple daily methylcobalamin prevents the most common nutrient deficiency from prolonged cimetidine use.", "managementStrategy": "Take 500-1000 mcg methylcobalamin daily while on long-term cimetidine.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Famotidine", "supplementBName": "Methylcobalamin", "interactionType": "synergy", "severity": "info", "description": "Methylcobalamin (a free coenzyme form of B12) does not require gastric acid for absorption, making it a reliable supplemental B12 source for patients on famotidine. Two or more years of H2 blocker use is associated with a 25% higher B12 deficiency risk, which oral methylcobalamin can prevent in most patients.", "recommendation": "If you take famotidine long-term, 500-1000 mcg of oral methylcobalamin daily is a sensible insurance dose. Ask for an annual serum B12 check while on chronic famotidine.", "minimumTimeSeparation": null, "mechanism": "Free B12 supplements bypass the acid-pepsin step needed to release cobalamin from dietary protein. Intrinsic factor binds the free vitamin directly for ileal absorption, which is unaffected by H2-receptor blockade.", "evidenceLevel": "moderate", "sources": [ { "text": "Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-42.", "pmid": "24327038", "doi": "10.1001/jama.2013.280490", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24327038/", "publicSourceType": "PMID" }, { "text": "Miller JW. Proton Pump Inhibitors, H2-Receptor Antagonists, Metformin, and Vitamin B-12 Deficiency: Clinical Implications. Adv Nutr. 2018;9(4):511S-518S.", "pmid": "30032223", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30032223/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Methylcobalamin offsets the B12 absorption deficit from chronic famotidine.", "clinicalSignificance": "A simple daily methylcobalamin prevents B12 deficiency in patients on long-term famotidine.", "managementStrategy": "Take 500-1000 mcg methylcobalamin daily while on long-term famotidine.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Diphenhydramine", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Alcohol can add to diphenhydramine's sedating and anticholinergic effects. Human testing found worse mental-performance impairment when ethanol was combined with diphenhydramine, and driving-simulator work shows diphenhydramine can impair driving substantially. The combination is especially risky before driving, in older adults, or when any other sedating medication is also present.", "recommendation": "Avoid alcohol when you take diphenhydramine, including nighttime sleep-aid doses. Do not drive, operate machinery, or take extra sedatives if both were used the same day. Seek help for severe confusion, extreme sleepiness, falls, or trouble breathing.", "minimumTimeSeparation": null, "mechanism": "Diphenhydramine crosses the blood-brain barrier and blocks central H1 and muscarinic receptors, causing sedation, slowed reaction time, and impaired attention. Alcohol independently depresses CNS arousal and motor coordination, so the combined pharmacodynamic effect can exceed either substance alone.", "evidenceLevel": "strong", "sources": [ { "text": "Baugh R, Calvert RT. The effect of diphenhydramine alone and in combination with ethanol on histamine skin response and mental performance. Eur J Clin Pharmacol. 1977;12(3):201-204.", "pmid": "22437", "doi": "10.1007/BF00609861", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22437/", "publicSourceType": "PMID" }, { "text": "Weiler JM, Bloomfield JR, Woodworth GG, et al. Effects of fexofenadine, diphenhydramine, and alcohol on driving performance: a randomized, placebo-controlled trial in the Iowa driving simulator. Ann Intern Med. 2000;132(5):354-363.", "pmid": "10691585", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10691585/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Alcohol and diphenhydramine additively impair alertness, coordination, and judgment.", "clinicalSignificance": "This pairing increases risk of falls, driving impairment, blackouts, and accidental overdose with other sedatives.", "managementStrategy": "Avoid alcohol while diphenhydramine is active and do not drive if both were used.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Hydroxyzine", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Alcohol can markedly worsen hydroxyzine-related drowsiness, slowed reaction time, and clumsiness. In a controlled crossover trial, hydroxyzine taken with alcohol produced the greatest and most persistent psychomotor impairment among tested antihistamine-alcohol combinations. Risk is higher with higher hydroxyzine doses, older age, sleep apnea, lung disease, or other CNS depressants.", "recommendation": "Do not drink alcohol when taking hydroxyzine for allergy, itching, anxiety, or sleep. If you already drank, avoid non-urgent hydroxyzine dosing and do not drive until fully alert. Seek urgent help for severe sleepiness, fainting, confusion, or slow breathing.", "minimumTimeSeparation": null, "mechanism": "Hydroxyzine is a brain-penetrant H1 antihistamine with sedative properties from central H1 blockade and suppression of subcortical arousal pathways. Alcohol adds CNS depression and psychomotor slowing, producing pharmacodynamic impairment that spacing doses does not reliably prevent.", "evidenceLevel": "strong", "sources": [ { "text": "García-Gea C, Martínez J, Ballester MR, Gich I, Valiente R, Antonijoan RM. Psychomotor and subjective effects of bilastine, hydroxyzine, and cetirizine, in combination with alcohol: a randomized, double-blind, crossover, and positive-controlled and placebo-controlled Phase I clinical trials. Hum Psychopharmacol. 2014;29(2):120-132.", "pmid": "24395298", "doi": "10.1002/hup.2378", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24395298/", "publicSourceType": "PMID" }, { "text": "Conen S, Theunissen EL, Vermeeren A, Ramaekers JG. Short-term effects of morning versus evening dose of hydroxyzine 50 mg on cognition in healthy volunteers. J Clin Psychopharmacol. 2011;31(3):294-301.", "pmid": "21508863", "doi": "10.1097/JCP.0b013e318218943c", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21508863/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Alcohol and hydroxyzine combine to produce excessive psychomotor impairment and sedation.", "clinicalSignificance": "The combination can make routine activities unsafe and increases fall, crash, and respiratory-risk concerns.", "managementStrategy": "Avoid alcohol during hydroxyzine use and avoid hazardous tasks if both were taken.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Promethazine", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Alcohol can add to promethazine's sedating, anticholinergic, and coordination-impairing effects. Human studies show promethazine impairs psychomotor performance, and ethanol produces overlapping deficits in performance monitoring and reaction tasks. The combination is especially unsafe with opioids, sleep medicines, respiratory disease, or fall risk.", "recommendation": "Avoid alcohol while taking promethazine for nausea, allergy, cough, or sleep. Do not drive or combine it with other sedatives if alcohol was used. Get urgent care for severe confusion, fainting, shallow breathing, or inability to wake.", "minimumTimeSeparation": null, "mechanism": "Promethazine blocks central H1 receptors and has antimuscarinic and antidopaminergic activity, producing sedation and slowed psychomotor performance. Alcohol adds CNS depression and worsens judgment and coordination through GABAergic and glutamatergic effects.", "evidenceLevel": "moderate", "sources": [ { "text": "Acons K, Chan LS, Drummond G, Tiplady B. Effects of ethanol and promethazine on awareness of errors and judgements of performance. J Psychopharmacol. 2006;20(5):661-669.", "pmid": "16401655", "doi": "10.1177/0269881106060690", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16401655/", "publicSourceType": "PMID" }, { "text": "Kamei H, Isaji A, Noda Y, et al. Effects of single therapeutic doses of promethazine, fexofenadine and olopatadine on psychomotor function and histamine-induced wheal- and flare-responses: a randomized double-blind, placebo-controlled study in healthy volunteers. Arch Dermatol Res. 2012;304(4):263-272.", "pmid": "22130869", "doi": "10.1007/s00403-011-1192-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22130869/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Alcohol and promethazine additively increase sedation, slowed reactions, and unsafe impairment.", "clinicalSignificance": "This pairing can make driving and other routine tasks dangerous and can worsen respiratory depression when other sedatives are present.", "managementStrategy": "Avoid alcohol with promethazine and treat same-day use as unsafe for driving or hazardous work.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Diphenhydramine", "supplementBName": "Cannabis (THC-Dominant)", "interactionType": "caution", "severity": "moderate", "description": "THC-dominant cannabis can add to diphenhydramine-related drowsiness, slowed reaction time, and impaired attention. Cannabis acutely impairs psychomotor and driving-related performance, while diphenhydramine independently impairs driving in controlled testing. The combination is most concerning before driving, at higher THC doses, in infrequent cannabis users, or with other sedatives.", "recommendation": "Avoid using THC-dominant cannabis and diphenhydramine close together when you need to drive, work, study, or care for others. If both were used, wait until you are fully alert and coordinated before doing hazardous tasks. Use a non-sedating allergy option when possible.", "minimumTimeSeparation": null, "mechanism": "Diphenhydramine causes central H1 and muscarinic blockade, reducing alertness and psychomotor speed. THC activates CB1 receptors in CNS networks involved in attention, tracking, reaction time, and coordination, creating additive impairment.", "evidenceLevel": "moderate", "sources": [ { "text": "Kocis PT, Vrana KE. Delta-9-Tetrahydrocannabinol and Cannabidiol Drug-Drug Interactions. Med Cannabis Cannabinoids. 2020;3(1):61-73.", "pmid": "34676340", "doi": "10.1159/000507998", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34676340/", "publicSourceType": "PMID" }, { "text": "Weiler JM, Bloomfield JR, Woodworth GG, et al. Effects of fexofenadine, diphenhydramine, and alcohol on driving performance: a randomized, placebo-controlled trial in the Iowa driving simulator. Ann Intern Med. 2000;132(5):354-363.", "pmid": "10691585", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10691585/", "publicSourceType": "PMID" }, { "text": "Simmons SM, Caird JK, Sterzer F, Asbridge M. The effects of cannabis and alcohol on driving performance and driver behaviour: a systematic review and meta-analysis. Addiction. 2022;117(7):1843-1856.", "pmid": "35083810", "doi": "10.1111/add.15770", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35083810/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "THC-dominant cannabis and diphenhydramine can additively impair driving-relevant cognition and coordination.", "clinicalSignificance": "Patients may underestimate impairment because both products are commonly used outside supervised care.", "managementStrategy": "Avoid same-period use before driving or safety-sensitive tasks; choose a non-sedating antihistamine when feasible.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Hydroxyzine", "supplementBName": "Cannabis (THC-Dominant)", "interactionType": "caution", "severity": "moderate", "description": "THC-dominant cannabis can compound hydroxyzine's sedating and attention-slowing effects. Hydroxyzine has measurable next-day and same-day cognitive effects in human studies, and THC acutely impairs psychomotor performance and driving-related skills. The combination is more concerning in people who are cannabis-naive, taking higher hydroxyzine doses, or using other sedatives.", "recommendation": "Avoid combining THC-dominant cannabis with hydroxyzine when you need to be alert. If both were used, do not drive or do hazardous work until the effects have clearly worn off. Consider separating cannabis use from hydroxyzine therapy or using a less sedating allergy treatment if appropriate.", "minimumTimeSeparation": null, "mechanism": "Hydroxyzine produces CNS sedation through central H1 receptor blockade. THC activates CB1 receptors and disrupts attention, divided-attention tracking, reaction time, and coordination, so effects on psychomotor performance can be additive.", "evidenceLevel": "moderate", "sources": [ { "text": "Kocis PT, Vrana KE. Delta-9-Tetrahydrocannabinol and Cannabidiol Drug-Drug Interactions. Med Cannabis Cannabinoids. 2020;3(1):61-73.", "pmid": "34676340", "doi": "10.1159/000507998", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34676340/", "publicSourceType": "PMID" }, { "text": "Conen S, Theunissen EL, Vermeeren A, Ramaekers JG. Short-term effects of morning versus evening dose of hydroxyzine 50 mg on cognition in healthy volunteers. J Clin Psychopharmacol. 2011;31(3):294-301.", "pmid": "21508863", "doi": "10.1097/JCP.0b013e318218943c", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21508863/", "publicSourceType": "PMID" }, { "text": "Desrosiers NA, Ramaekers JG, Chauchard E, Gorelick DA, Huestis MA. Smoked cannabis' psychomotor and neurocognitive effects in occasional and frequent smokers. J Anal Toxicol. 2015;39(4):251-261.", "pmid": "25745105", "doi": "10.1093/jat/bkv012", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25745105/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "THC-dominant cannabis and hydroxyzine can additively worsen sedation and psychomotor performance.", "clinicalSignificance": "The combination may turn a therapeutic hydroxyzine dose into functionally impairing sedation.", "managementStrategy": "Avoid same-period use before driving, work, or caregiving; reduce exposure to one sedating agent when possible.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Promethazine", "supplementBName": "Cannabis (THC-Dominant)", "interactionType": "caution", "severity": "moderate", "description": "THC-dominant cannabis can add to promethazine-related sedation, slowed reactions, and impaired coordination. Promethazine impairs psychomotor function in controlled human studies, while THC acutely impairs driving-related performance. The combination is especially concerning with nausea/cough products that also contain opioids or other sedatives.", "recommendation": "Do not combine THC-dominant cannabis with promethazine before driving or any safety-sensitive task. If both were used, stay in a safe setting and avoid adding alcohol, opioids, or sleep medicines. Use the lowest effective promethazine dose only as prescribed.", "minimumTimeSeparation": null, "mechanism": "Promethazine produces CNS depression through H1 blockade plus antimuscarinic and antidopaminergic effects. THC activates CB1 receptors and impairs attention, tracking, and reaction time, creating additive psychomotor and judgment impairment.", "evidenceLevel": "moderate", "sources": [ { "text": "Kocis PT, Vrana KE. Delta-9-Tetrahydrocannabinol and Cannabidiol Drug-Drug Interactions. Med Cannabis Cannabinoids. 2020;3(1):61-73.", "pmid": "34676340", "doi": "10.1159/000507998", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34676340/", "publicSourceType": "PMID" }, { "text": "Kamei H, Isaji A, Noda Y, et al. Effects of single therapeutic doses of promethazine, fexofenadine and olopatadine on psychomotor function and histamine-induced wheal- and flare-responses: a randomized double-blind, placebo-controlled study in healthy volunteers. Arch Dermatol Res. 2012;304(4):263-272.", "pmid": "22130869", "doi": "10.1007/s00403-011-1192-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22130869/", "publicSourceType": "PMID" }, { "text": "Simmons SM, Caird JK, Sterzer F, Asbridge M. The effects of cannabis and alcohol on driving performance and driver behaviour: a systematic review and meta-analysis. Addiction. 2022;117(7):1843-1856.", "pmid": "35083810", "doi": "10.1111/add.15770", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35083810/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "THC-dominant cannabis and promethazine can additively worsen sedation and driving-relevant impairment.", "clinicalSignificance": "This pairing can be underestimated because cannabis may be used for nausea while promethazine is prescribed for the same symptom.", "managementStrategy": "Avoid same-period use before hazardous tasks and avoid adding other CNS depressants.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Diphenhydramine", "supplementBName": "Melatonin", "interactionType": "caution", "severity": "moderate", "description": "Melatonin can add to diphenhydramine's sleepiness and next-day grogginess when both are used as sleep aids. Melatonin has documented short-term effects on sleepiness and flight-relevant performance in some dosing contexts, while diphenhydramine can impair driving and attention. Risk is higher with higher melatonin doses, nighttime redosing, older age, or early-morning driving.", "recommendation": "Avoid stacking melatonin with diphenhydramine unless your clinician specifically recommends it. If you use them together, use the lowest effective doses and leave a full night's sleep window before driving. Stop the combination if you wake confused, unsteady, or excessively drowsy.", "minimumTimeSeparation": null, "mechanism": "Diphenhydramine blocks central H1 and muscarinic receptors, producing sedation and anticholinergic cognitive slowing. Melatonin activates MT1/MT2 receptors to shift circadian timing and promote sleepiness, which can add to diphenhydramine-related impairment.", "evidenceLevel": "emerging", "sources": [ { "text": "Nave R, Iani C, Herer P, Gopher D, Lavie P. Residual effects of daytime administration of melatonin on performance relevant to flight. Behav Brain Res. 2002;131(1-2):87-95.", "pmid": "11844575", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11844575/", "publicSourceType": "PMID" }, { "text": "Weiler JM, Bloomfield JR, Woodworth GG, et al. Effects of fexofenadine, diphenhydramine, and alcohol on driving performance: a randomized, placebo-controlled trial in the Iowa driving simulator. Ann Intern Med. 2000;132(5):354-363.", "pmid": "10691585", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10691585/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Melatonin and diphenhydramine can produce additive sleepiness and next-day impairment.", "clinicalSignificance": "The combination is common in self-treatment for insomnia and can raise fall or driving risk.", "managementStrategy": "Avoid routine stacking; if used, keep doses low and allow adequate sleep time before morning tasks.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Hydroxyzine", "supplementBName": "Melatonin", "interactionType": "caution", "severity": "moderate", "description": "Melatonin can add to hydroxyzine's sedating effects, especially when hydroxyzine is used at night for itching, anxiety, or sleep. Hydroxyzine can impair cognition after morning dosing and can leave residual impairment after evening dosing, while melatonin can increase sleepiness and affect performance in some settings. The combined effect can matter for older adults and people who need to drive early the next day.", "recommendation": "Avoid routine use of melatonin on top of hydroxyzine unless your prescriber agrees. If combined, use the lowest effective melatonin dose and avoid alcohol or other sedatives. Do not drive the next morning if you feel groggy, slowed, or unsteady.", "minimumTimeSeparation": null, "mechanism": "Hydroxyzine reduces wakefulness through central H1 receptor blockade. Melatonin promotes sleepiness through MT1/MT2 receptor signaling and circadian phase effects, so the combination can deepen sedation without a predictable timing workaround.", "evidenceLevel": "emerging", "sources": [ { "text": "Nave R, Iani C, Herer P, Gopher D, Lavie P. Residual effects of daytime administration of melatonin on performance relevant to flight. Behav Brain Res. 2002;131(1-2):87-95.", "pmid": "11844575", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11844575/", "publicSourceType": "PMID" }, { "text": "Conen S, Theunissen EL, Vermeeren A, Ramaekers JG. Short-term effects of morning versus evening dose of hydroxyzine 50 mg on cognition in healthy volunteers. J Clin Psychopharmacol. 2011;31(3):294-301.", "pmid": "21508863", "doi": "10.1097/JCP.0b013e318218943c", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21508863/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Melatonin and hydroxyzine can additively increase sleepiness and cognitive slowing.", "clinicalSignificance": "Stacking two sleep-promoting agents may impair next-day function even when each seems mild alone.", "managementStrategy": "Avoid routine co-use; if combined, keep doses low and assess next-day alertness before driving.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Promethazine", "supplementBName": "Melatonin", "interactionType": "caution", "severity": "moderate", "description": "Melatonin can add to promethazine-related drowsiness, slowed reaction time, and next-day grogginess. Promethazine significantly impairs psychomotor function in healthy-volunteer studies, and melatonin can affect sleepiness and performance depending on timing and dose. The combination is more concerning when promethazine is used as a nighttime sedative or alongside cough products containing opioids.", "recommendation": "Do not use melatonin to intensify promethazine's sedating effect. If your prescriber approves both, use the lowest effective doses and avoid driving until you know how you respond. Avoid adding alcohol, cannabis, opioids, or other sleep medicines.", "minimumTimeSeparation": null, "mechanism": "Promethazine causes CNS depression through central H1 blockade with antimuscarinic and antidopaminergic effects. Melatonin promotes sleepiness through MT1/MT2 receptor signaling, which can add to promethazine's psychomotor and vigilance impairment.", "evidenceLevel": "emerging", "sources": [ { "text": "Nave R, Iani C, Herer P, Gopher D, Lavie P. Residual effects of daytime administration of melatonin on performance relevant to flight. Behav Brain Res. 2002;131(1-2):87-95.", "pmid": "11844575", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11844575/", "publicSourceType": "PMID" }, { "text": "Kamei H, Isaji A, Noda Y, et al. Effects of single therapeutic doses of promethazine, fexofenadine and olopatadine on psychomotor function and histamine-induced wheal- and flare-responses: a randomized double-blind, placebo-controlled study in healthy volunteers. Arch Dermatol Res. 2012;304(4):263-272.", "pmid": "22130869", "doi": "10.1007/s00403-011-1192-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22130869/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Melatonin and promethazine can additively increase sedation and psychomotor impairment.", "clinicalSignificance": "This can increase fall and driving risk, especially when promethazine is already being used for sleep or nausea.", "managementStrategy": "Avoid using melatonin as an add-on sedative with promethazine; assess next-day alertness if both are used.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Pseudoephedrine", "supplementBName": "Nicotine", "interactionType": "caution", "severity": "moderate", "description": "Pseudoephedrine and nicotine can both raise heart rate, blood pressure, and sympathetic tone. Pseudoephedrine has a measurable pressor and chronotropic effect in meta-analysis, while nicotine stimulates sympathetic neurotransmission and cardiovascular activation. The combination is most relevant for people with hypertension, palpitations, coronary disease, anxiety, or heavy nicotine use.", "recommendation": "Use pseudoephedrine cautiously if you use nicotine patches, vaping products, pouches, cigarettes, or other nicotine products. Check blood pressure and pulse during the first day of combined use, and avoid extra doses if you feel palpitations, chest tightness, tremor, or marked anxiety. Choose a non-stimulant decongestant strategy if you have uncontrolled blood pressure or heart disease.", "minimumTimeSeparation": null, "mechanism": "Pseudoephedrine is an indirect sympathomimetic that promotes norepinephrine release and stimulates alpha and beta adrenergic activity. Nicotine activates nicotinic acetylcholine receptors in autonomic ganglia and the adrenal medulla, increasing catecholamine release and sympathetic cardiovascular effects.", "evidenceLevel": "moderate", "sources": [ { "text": "Salerno SM, Jackson JL, Berbano EP. Effect of oral pseudoephedrine on blood pressure and heart rate: a meta-analysis. Arch Intern Med. 2005;165(15):1686-1694.", "pmid": "16087815", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16087815/", "publicSourceType": "PMID" }, { "text": "Benowitz NL, Burbank AD. Cardiovascular toxicity of nicotine: implications for electronic cigarette use. Trends Cardiovasc Med. 2016;26(6):515-523.", "pmid": "27079891", "doi": "10.1016/j.tcm.2016.03.001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27079891/", "publicSourceType": "PMID" }, { "text": "Haass M, Kübler W. Nicotine and sympathetic neurotransmission. Cardiovasc Drugs Ther. 1997;10(6):657-665.", "pmid": "9110108", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9110108/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Pseudoephedrine and nicotine can additively raise blood pressure, pulse, and adrenergic symptoms.", "clinicalSignificance": "This can destabilize patients with hypertension, arrhythmia symptoms, or cardiovascular disease.", "managementStrategy": "Monitor BP and pulse, avoid high nicotine exposure during pseudoephedrine use, and choose non-stimulant options if cardiovascular risk is high.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Pseudoephedrine", "supplementBName": "Cocaine", "interactionType": "contraindicated", "severity": "dangerous", "description": "Pseudoephedrine and cocaine are both sympathomimetic stimulants, so combined use can sharply increase blood pressure, heart rate, vasoconstriction, and myocardial oxygen demand. Cocaine is linked to acute hypertension, coronary spasm, arrhythmias, myocardial infarction, and sudden cardiovascular events. Adding pseudoephedrine can further intensify adrenergic stress.", "recommendation": "Do not use pseudoephedrine if you have used cocaine or may use cocaine soon. Seek urgent care for chest pain, severe headache, fainting, severe agitation, or a very fast or irregular heartbeat. Use non-stimulant congestion treatments instead.", "minimumTimeSeparation": null, "mechanism": "Pseudoephedrine indirectly increases synaptic norepinephrine and activates alpha and beta adrenergic pathways. Cocaine blocks norepinephrine, dopamine, and serotonin reuptake and also causes vasoconstriction and sodium-channel effects, making the cardiovascular load additive and potentially unstable.", "evidenceLevel": "moderate", "sources": [ { "text": "Salerno SM, Jackson JL, Berbano EP. Effect of oral pseudoephedrine on blood pressure and heart rate: a meta-analysis. Arch Intern Med. 2005;165(15):1686-1694.", "pmid": "16087815", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16087815/", "publicSourceType": "PMID" }, { "text": "Kim ST, Park T. Acute and Chronic Effects of Cocaine on Cardiovascular Health. Int J Mol Sci. 2019;20(3):584.", "pmid": "30700023", "doi": "10.3390/ijms20030584", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30700023/", "publicSourceType": "PMID" }, { "text": "Schindler CW. Cocaine and cardiovascular toxicity. Addict Biol. 1996;1(1):31-47.", "pmid": "12893485", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12893485/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Pseudoephedrine can add to cocaine-induced adrenergic toxicity and cardiovascular ischemia risk.", "clinicalSignificance": "The combination can precipitate hypertensive crisis, arrhythmia, chest pain, or myocardial infarction.", "managementStrategy": "Avoid pseudoephedrine with any cocaine exposure and use non-stimulant congestion care.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Pseudoephedrine", "supplementBName": "MDMA", "interactionType": "contraindicated", "severity": "dangerous", "description": "Pseudoephedrine can add to MDMA's stimulant cardiovascular effects. Controlled human studies show MDMA increases blood pressure, heart rate, and thermogenic/cardiostimulant measures, while pseudoephedrine also raises blood pressure and pulse. The combination is especially concerning during dancing, heat exposure, dehydration, panic, or underlying heart disease.", "recommendation": "Do not use pseudoephedrine if you have used MDMA or may use MDMA soon. Seek urgent help for chest pain, severe headache, overheating, fainting, confusion, or a racing or irregular heartbeat. Use non-stimulant nasal congestion options instead.", "minimumTimeSeparation": null, "mechanism": "Pseudoephedrine increases adrenergic signaling through norepinephrine release and alpha/beta receptor stimulation. MDMA increases monoamine release, including norepinephrine, and produces sympathomimetic cardiovascular stimulation and thermogenic stress; together they can amplify rate-pressure product and heat strain.", "evidenceLevel": "moderate", "sources": [ { "text": "Salerno SM, Jackson JL, Berbano EP. Effect of oral pseudoephedrine on blood pressure and heart rate: a meta-analysis. Arch Intern Med. 2005;165(15):1686-1694.", "pmid": "16087815", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16087815/", "publicSourceType": "PMID" }, { "text": "Hysek C, Schmid Y, Rickli A, et al. Carvedilol inhibits the cardiostimulant and thermogenic effects of MDMA in humans. Br J Pharmacol. 2012;166(8):2277-2288.", "pmid": "22404145", "doi": "10.1111/j.1476-5381.2012.01936.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22404145/", "publicSourceType": "PMID" }, { "text": "Kirkpatrick MG, Gunderson EW, Perez AY, Haney M, Foltin RW, Hart CL. A direct comparison of the behavioral and physiological effects of methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in humans. Psychopharmacology (Berl). 2012;219(1):109-122.", "pmid": "21713605", "doi": "10.1007/s00213-011-2383-4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21713605/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Pseudoephedrine can add to MDMA-related tachycardia, hypertension, and heat strain.", "clinicalSignificance": "This can increase risk of hypertensive crisis, arrhythmia, hyperthermia, and cardiovascular collapse.", "managementStrategy": "Avoid pseudoephedrine with any MDMA exposure and use non-stimulant congestion care.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Desvenlafaxine", "supplementBName": "5-HTP", "interactionType": "contraindicated", "severity": "dangerous", "description": "Desvenlafaxine blocks serotonin reuptake, while 5-HTP is converted directly into serotonin. Taking them together can push serotonin signaling into a toxic range and trigger serotonin syndrome, with agitation, tremor, sweating, diarrhea, clonus, fever, and confusion. Risk is higher with dose increases or any other serotonergic drug or substance.", "recommendation": "Do not take 5-HTP while using desvenlafaxine. Stop 5-HTP and discuss a washout plan before starting desvenlafaxine. Seek urgent care for fever, muscle rigidity, clonus, severe agitation, or confusion.", "minimumTimeSeparation": null, "mechanism": "5-HTP bypasses tryptophan hydroxylase and is decarboxylated by aromatic L-amino acid decarboxylase to serotonin. Desvenlafaxine inhibits SERT and NET, so increased serotonin synthesis is paired with reduced serotonin reuptake.", "evidenceLevel": "moderate", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Jacobsen JPR, Krystal AD, Krishnan KRR, Caron MG. Adjunctive 5-Hydroxytryptophan Slow-Release for Treatment-Resistant Depression: Clinical and Preclinical Rationale. Trends Pharmacol Sci. 2016;37(11):933-944.", "pmid": "27692695", "doi": "10.1016/j.tips.2016.09.001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27692695/", "publicSourceType": "PMID" }, { "text": "Sansone RA, Sansone LA. Serotonin norepinephrine reuptake inhibitors: a pharmacological comparison. Innov Clin Neurosci. 2014;11(3-4):37-42.", "pmid": "24800132", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24800132/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "The combination can cause excessive serotonergic signaling and serotonin syndrome.", "clinicalSignificance": "Serotonin syndrome can become life-threatening if the combination is continued after symptoms begin.", "managementStrategy": "Avoid 5-HTP during desvenlafaxine therapy and use non-serotonergic alternatives.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Venlafaxine", "supplementBName": "L-Tryptophan", "interactionType": "contraindicated", "severity": "dangerous", "description": "L-Tryptophan is the upstream dietary precursor for serotonin, and venlafaxine blocks serotonin reuptake. Concentrated tryptophan supplements can add serotonergic substrate on top of venlafaxine's reuptake blockade, raising the risk of serotonin syndrome. Food sources of tryptophan are not the issue; high-dose supplements are.", "recommendation": "Do not combine L-tryptophan supplements with venlafaxine. If you are using L-tryptophan for sleep or mood, stop it and ask your prescriber for a safer alternative. Watch for tremor, sweating, agitation, diarrhea, fever, or muscle jerking if exposure occurred.", "minimumTimeSeparation": null, "mechanism": "L-Tryptophan is converted by tryptophan hydroxylase to 5-HTP and then to serotonin. Venlafaxine inhibits SERT, especially at lower doses, reducing serotonin clearance from the synapse while precursor supply is increased.", "evidenceLevel": "moderate", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Young SN. Use of tryptophan in combination with other antidepressant treatments: a review. J Psychiatry Neurosci. 1991;16(5):241-246.", "pmid": "1797098", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1797098/", "publicSourceType": "PMID" }, { "text": "Sansone RA, Sansone LA. Serotonin norepinephrine reuptake inhibitors: a pharmacological comparison. Innov Clin Neurosci. 2014;11(3-4):37-42.", "pmid": "24800132", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24800132/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Supplemental tryptophan can amplify venlafaxine's serotonergic effect.", "clinicalSignificance": "The combination increases the chance of serotonin toxicity, especially with other serotonergic agents.", "managementStrategy": "Avoid supplemental L-tryptophan while taking venlafaxine.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Duloxetine", "supplementBName": "L-Tryptophan", "interactionType": "contraindicated", "severity": "dangerous", "description": "Duloxetine blocks both serotonin and norepinephrine reuptake, and L-tryptophan provides extra substrate for serotonin synthesis. The combination can raise serotonin tone beyond the therapeutic range and precipitate serotonin syndrome. Risk rises if you also use tramadol, triptans, MDMA, St. John's Wort, or other antidepressants.", "recommendation": "Do not take L-tryptophan supplements with duloxetine. Food tryptophan is fine; avoid concentrated sleep or mood products containing L-tryptophan. Get urgent help for clonus, high fever, severe restlessness, confusion, or muscle rigidity.", "minimumTimeSeparation": null, "mechanism": "L-Tryptophan increases the pool of serotonin precursor available to serotonergic neurons. Duloxetine inhibits SERT and NET, so increased serotonin synthesis is combined with impaired reuptake.", "evidenceLevel": "moderate", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Young SN. Use of tryptophan in combination with other antidepressant treatments: a review. J Psychiatry Neurosci. 1991;16(5):241-246.", "pmid": "1797098", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1797098/", "publicSourceType": "PMID" }, { "text": "Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG, et al. Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology. 2001;25(6):871-880.", "pmid": "11750180", "doi": "10.1016/S0893-133X(01)00298-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11750180/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Supplemental tryptophan can add to duloxetine's serotonin reuptake blockade.", "clinicalSignificance": "The clinical concern is serotonin syndrome, not ordinary dietary tryptophan intake.", "managementStrategy": "Avoid L-tryptophan supplements during duloxetine therapy.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Desvenlafaxine", "supplementBName": "L-Tryptophan", "interactionType": "contraindicated", "severity": "dangerous", "description": "Desvenlafaxine is an SNRI with meaningful serotonin reuptake inhibition, and L-tryptophan is converted into serotonin. Supplemental L-tryptophan can add serotonergic drive to desvenlafaxine and raise the risk of serotonin syndrome. The concern is concentrated supplementation, not normal protein intake.", "recommendation": "Do not use L-tryptophan supplements while taking desvenlafaxine. Choose a non-serotonergic sleep or mood support option if needed. If you accidentally combine them, stop the supplement and monitor for agitation, tremor, sweating, diarrhea, fever, or clonus.", "minimumTimeSeparation": null, "mechanism": "L-Tryptophan is converted to 5-HTP and then serotonin, increasing serotonin synthesis capacity. Desvenlafaxine inhibits SERT and NET, decreasing serotonin reuptake while precursor availability is increased.", "evidenceLevel": "moderate", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Young SN. Use of tryptophan in combination with other antidepressant treatments: a review. J Psychiatry Neurosci. 1991;16(5):241-246.", "pmid": "1797098", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1797098/", "publicSourceType": "PMID" }, { "text": "Sansone RA, Sansone LA. Serotonin norepinephrine reuptake inhibitors: a pharmacological comparison. Innov Clin Neurosci. 2014;11(3-4):37-42.", "pmid": "24800132", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24800132/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Supplemental tryptophan can intensify desvenlafaxine's serotonergic activity.", "clinicalSignificance": "The combination can turn therapeutic serotonin reuptake inhibition into toxic serotonergic excess.", "managementStrategy": "Avoid L-tryptophan supplements while taking desvenlafaxine.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Desvenlafaxine", "supplementBName": "St. John's Wort", "interactionType": "contraindicated", "severity": "dangerous", "description": "St. John's Wort has antidepressant-like serotonergic activity and is a major herb-drug interaction trigger. Combining it with desvenlafaxine can add serotonin reuptake effects and increase the risk of serotonin syndrome. St. John's Wort products vary widely in hyperforin content, making the interaction hard to predict.", "recommendation": "Do not combine St. John's Wort with desvenlafaxine. Allow at least a 2-week washout after stopping St. John's Wort before starting or restarting desvenlafaxine unless your prescriber gives a different plan. Avoid other serotonergic substances during the transition.", "minimumTimeSeparation": null, "mechanism": "Hyperforin-containing St. John's Wort inhibits monoamine reuptake and activates pregnane X receptor pathways that induce CYP3A4 and P-glycoprotein. Desvenlafaxine inhibits SERT and NET, so the main concern is additive serotonergic pharmacodynamics.", "evidenceLevel": "moderate", "sources": [ { "text": "Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs. 2009;69(13):1777-1798.", "pmid": "19719333", "doi": "10.2165/11317010-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19719333/", "publicSourceType": "PMID" }, { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Fanelli D, Weller G, Liu H. New Serotonin-Norepinephrine Reuptake Inhibitors and Their Anesthetic and Analgesic Considerations. Neurol Int. 2021;13(4):497-509.", "pmid": "34698218", "doi": "10.3390/neurolint13040049", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34698218/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "The combination can produce unpredictable serotonergic toxicity.", "clinicalSignificance": "St. John's Wort is not a safe substitute or add-on for desvenlafaxine.", "managementStrategy": "Avoid the combination and use a 2-week St. John's Wort washout before desvenlafaxine when possible.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Amitriptyline", "supplementBName": "St. John's Wort", "interactionType": "caution", "severity": "serious", "description": "St. John's Wort can substantially lower amitriptyline and nortriptyline exposure, which may cause loss of antidepressant, migraine, sleep, or neuropathic pain control. In a clinical study, comedication reduced amitriptyline and nortriptyline AUC, and stopping St. John's Wort can then let TCA levels rise again. St. John's Wort also adds serotonergic activity, so the risk is both reduced efficacy and unpredictable toxicity during starts and stops.", "recommendation": "Avoid St. John's Wort while taking amitriptyline. If the combination is already in use, do not start or stop St. John's Wort abruptly without a medication plan; your prescriber may need symptom checks, TCA blood levels, or dose adjustment. Watch for relapse when St. John's Wort starts and for TCA side effects when it stops.", "minimumTimeSeparation": null, "mechanism": "St. John's Wort induces CYP3A4 and P-glycoprotein through hyperforin-mediated pregnane X receptor activation. Amitriptyline is metabolized through CYP2C19, CYP2D6, and CYP3A pathways, and the active metabolite nortriptyline is also affected by the interaction.", "evidenceLevel": "strong", "sources": [ { "text": "Johne A, Schmider J, Brockmoller J, Stadelmann AM, Stormer E, Bauer S, et al. Decreased plasma levels of amitriptyline and its metabolites on comedication with an extract from St. John's wort (Hypericum perforatum). J Clin Psychopharmacol. 2002;22(1):46-54.", "pmid": "11799342", "doi": "10.1097/00004714-200202000-00008", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11799342/", "publicSourceType": "PMID" }, { "text": "Zhou S, Chan E, Pan SQ, Huang M, Lee EJ. Pharmacokinetic interactions of drugs with St John's wort. J Psychopharmacol. 2004;18(2):262-276.", "pmid": "15260917", "doi": "10.1177/0269881104042632", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15260917/", "publicSourceType": "PMID" }, { "text": "Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs. 2009;69(13):1777-1798.", "pmid": "19719333", "doi": "10.2165/11317010-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19719333/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St. John's Wort can lower amitriptyline and nortriptyline concentrations and destabilize treatment.", "clinicalSignificance": "Loss of TCA exposure can cause relapse or pain breakthrough, while stopping the herb can raise TCA exposure again.", "managementStrategy": "Avoid coadministration; if unavoidable, monitor symptoms and consider TCA serum levels when St. John's Wort is started or stopped.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Duloxetine", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Duloxetine has a known rare risk of clinically significant liver injury, and substantial alcohol use is a recognized risk factor in labeling and postmarketing safety reviews. Combining duloxetine with heavy drinking can increase the chance that liver injury is severe or missed until jaundice, abdominal pain, dark urine, or marked fatigue appears. Alcohol may also worsen dizziness, sedation, and judgment while taking duloxetine.", "recommendation": "Avoid heavy alcohol use while taking duloxetine. If you have alcohol use disorder, chronic liver disease, or abnormal liver tests, ask your prescriber about a different medication before starting duloxetine. Seek prompt medical care for jaundice, dark urine, severe right upper abdominal pain, or unexplained severe fatigue.", "minimumTimeSeparation": null, "mechanism": "Duloxetine undergoes hepatic metabolism mainly through CYP1A2 and CYP2D6 and can rarely cause idiosyncratic hepatocellular or cholestatic injury. Alcohol adds hepatic stress and can create underlying liver disease, reducing reserve if duloxetine-associated injury occurs.", "evidenceLevel": "moderate", "sources": [ { "text": "Vuppalanchi R, Hayashi PH, Chalasani N, et al. Duloxetine hepatotoxicity: a case-series from the drug-induced liver injury network. Aliment Pharmacol Ther. 2010;32(9):1174-1183.", "pmid": "20815829", "doi": "10.1111/j.1365-2036.2010.04449.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20815829/", "publicSourceType": "PMID" }, { "text": "Wohlreich MM, Acharya N, Strombom I, et al. Answers to the most common questions about the hepatic safety profile of duloxetine. Postgrad Med. 2008;120(2):111-118.", "pmid": "18654076", "doi": "10.3810/pgm.2008.07.1803", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18654076/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Substantial alcohol use can increase the clinical risk around duloxetine-associated liver injury.", "clinicalSignificance": "Duloxetine should be avoided or used only with a clear plan in people with heavy alcohol use or liver disease.", "managementStrategy": "Avoid heavy alcohol and monitor for liver injury symptoms during duloxetine therapy.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Amitriptyline", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Alcohol can markedly worsen amitriptyline-related impairment. Human studies found ethanol increased free amitriptyline exposure during absorption and greatly worsened postural sway and short-term memory. The combination increases risk of falls, blackouts, unsafe driving, and overdose.", "recommendation": "Avoid alcohol while taking amitriptyline, especially near bedtime doses or before driving. If you drink despite this, keep intake very low and do not drive, operate machinery, or combine with opioids, benzodiazepines, or other sleep aids. Older adults should treat this combination as especially risky.", "minimumTimeSeparation": null, "mechanism": "Ethanol can reduce first-pass hepatic clearance of amitriptyline during absorption, increasing free amitriptyline concentrations. Alcohol also potentiates GABA-A signaling and impairs NMDA signaling, adding CNS depression to amitriptyline's antihistamine, anticholinergic, and alpha-1 blocking effects.", "evidenceLevel": "strong", "sources": [ { "text": "Dorian P, Sellers EM, Reed KL, et al. Amitriptyline and ethanol: pharmacokinetic and pharmacodynamic interaction. Eur J Clin Pharmacol. 1983;25(3):325-331.", "pmid": "6628520", "doi": "10.1007/BF01037943", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6628520/", "publicSourceType": "PMID" }, { "text": "Scott DB, Fagan D, Tiplady B. Effects of amitriptyline and zimelidine in combination with ethanol. Psychopharmacology (Berl). 1982;76(3):209-211.", "pmid": "6212962", "doi": "10.1007/BF00432546", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6212962/", "publicSourceType": "PMID" }, { "text": "Brunnauer A, Laux G. Driving Under the Influence of Antidepressants: A Systematic Review and Update of the Evidence of Experimental and Controlled Clinical Studies. Pharmacopsychiatry. 2017;50(5):173-181.", "pmid": "28718182", "doi": "10.1055/s-0043-113572", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28718182/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Alcohol increases amitriptyline exposure and adds clinically important psychomotor impairment.", "clinicalSignificance": "The combination can make routine activities such as walking at night or driving unsafe.", "managementStrategy": "Avoid alcohol with amitriptyline; if any alcohol is used, do not drive or combine with other sedatives.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Nortriptyline", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Nortriptyline is less sedating than amitriptyline for some patients, but it is still a tricyclic antidepressant that can impair alertness, coordination, and blood pressure control. Alcohol can add CNS depression and worsen falls, blackouts, overdose risk, and unsafe driving. The concern is highest in older adults, at higher nortriptyline doses, or when other sedatives are present.", "recommendation": "Avoid heavy alcohol while taking nortriptyline. If you drink at all, keep intake low, avoid driving or machinery, and do not combine with opioids, benzodiazepines, antihistamines, or sleep aids. Report fainting, confusion, severe drowsiness, or palpitations.", "minimumTimeSeparation": null, "mechanism": "Alcohol depresses CNS function through GABA-A potentiation and NMDA inhibition. Nortriptyline adds antihistamine, anticholinergic, alpha-1 blocking, and norepinephrine reuptake effects; alcohol may also alter exposure to tricyclics and their active metabolites.", "evidenceLevel": "moderate", "sources": [ { "text": "Dorian P, Sellers EM, Reed KL, et al. Amitriptyline and ethanol: pharmacokinetic and pharmacodynamic interaction. Eur J Clin Pharmacol. 1983;25(3):325-331.", "pmid": "6628520", "doi": "10.1007/BF01037943", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6628520/", "publicSourceType": "PMID" }, { "text": "Dassanayake T, Michie P, Carter G, Jones A. Effects of benzodiazepines, antidepressants and opioids on driving: a systematic review and meta-analysis of epidemiological and experimental evidence. Drug Saf. 2011;34(2):125-156.", "pmid": "21247221", "doi": "10.2165/11539050-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21247221/", "publicSourceType": "PMID" }, { "text": "Merwar G, Gibbons JR, Hosseini SA, Saadabadi A. Nortriptyline. StatPearls. 2026.", "pmid": "29489270", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29489270/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Alcohol can compound nortriptyline-related CNS and cardiovascular impairment.", "clinicalSignificance": "Even if the combination does not feel dramatic, impairment and fall risk can increase.", "managementStrategy": "Avoid heavy alcohol and do not drive after combining alcohol with nortriptyline.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Venlafaxine", "supplementBName": "MDMA", "interactionType": "contraindicated", "severity": "dangerous", "description": "MDMA releases large amounts of serotonin and norepinephrine through monoamine transporters, while venlafaxine blocks serotonin and norepinephrine reuptake. The combination can be unpredictable: venlafaxine may blunt desired MDMA effects, which can prompt redosing, while MDMA still drives hyperthermia, hypertension, seizures, and serotonin syndrome risk. Reported MDMA-associated serotonin syndrome cases commonly involve other serotonergic substances.", "recommendation": "Do not use MDMA while taking venlafaxine. Do not try to overcome a blunted MDMA effect by taking more; that raises toxicity risk. If exposure occurs and you develop high fever, agitation, confusion, clonus, chest pain, or severe headache, seek emergency care.", "minimumTimeSeparation": null, "mechanism": "MDMA enters neurons through SERT, NET, and DAT and promotes reverse transport of monoamines, especially serotonin. Venlafaxine inhibits SERT and NET, creating transporter competition plus additive serotonergic and adrenergic stress.", "evidenceLevel": "moderate", "sources": [ { "text": "Makunts T, Jerome L, Abagyan R, de Boer A. Reported Cases of Serotonin Syndrome in MDMA Users in FAERS Database. Front Psychiatry. 2021;12:824288.", "pmid": "35140642", "doi": "10.3389/fpsyt.2021.824288", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35140642/", "publicSourceType": "PMID" }, { "text": "Sarparast A, Thomas K, Malcolm B, Stauffer CS. Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review. Psychopharmacology (Berl). 2022;239(6):1945-1976.", "pmid": "35253070", "doi": "10.1007/s00213-022-06083-y", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35253070/", "publicSourceType": "PMID" }, { "text": "Green AR, Mechan AO, Elliott JM, O'Shea E, Colado MI. The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, \"ecstasy\"). Pharmacol Rev. 2003;55(3):463-508.", "pmid": "12869661", "doi": "10.1124/pr.55.3.3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12869661/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "MDMA plus venlafaxine can produce serotonin toxicity, hyperthermia, and cardiovascular instability.", "clinicalSignificance": "Blunted subjective effects do not mean the combination is safe.", "managementStrategy": "Avoid MDMA completely during venlafaxine therapy.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Duloxetine", "supplementBName": "MDMA", "interactionType": "contraindicated", "severity": "dangerous", "description": "Duloxetine directly interferes with MDMA pharmacology at serotonin and norepinephrine transporters. In a controlled human study, duloxetine reduced MDMA's subjective and physiologic effects, which can encourage unsafe redosing, while MDMA exposure and serotonergic load remain clinically concerning. The combination can raise risk for serotonin syndrome, hyperthermia, hypertension, arrhythmia, and seizures.", "recommendation": "Do not use MDMA while taking duloxetine. Do not increase MDMA doses to overcome duloxetine-related blunting. Seek emergency care for high fever, severe agitation, confusion, clonus, chest pain, fainting, or severe headache after exposure.", "minimumTimeSeparation": null, "mechanism": "MDMA depends on SERT and NET to enter monoamine neurons and drive reverse serotonin and norepinephrine transport. Duloxetine inhibits SERT and NET and can inhibit CYP2D6, altering MDMA pharmacodynamics and potentially its exposure.", "evidenceLevel": "moderate", "sources": [ { "text": "Hysek CM, Simmler LD, Nicola VG, et al. Duloxetine inhibits effects of MDMA (\"ecstasy\") in vitro and in humans in a randomized placebo-controlled laboratory study. PLoS One. 2012;7(5):e36476.", "pmid": "22574166", "doi": "10.1371/journal.pone.0036476", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22574166/", "publicSourceType": "PMID" }, { "text": "Sarparast A, Thomas K, Malcolm B, Stauffer CS. Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review. Psychopharmacology (Berl). 2022;239(6):1945-1976.", "pmid": "35253070", "doi": "10.1007/s00213-022-06083-y", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35253070/", "publicSourceType": "PMID" }, { "text": "Makunts T, Jerome L, Abagyan R, de Boer A. Reported Cases of Serotonin Syndrome in MDMA Users in FAERS Database. Front Psychiatry. 2021;12:824288.", "pmid": "35140642", "doi": "10.3389/fpsyt.2021.824288", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35140642/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Duloxetine can blunt MDMA effects while preserving serious toxicity risk.", "clinicalSignificance": "Redosing to chase MDMA effects can increase the likelihood of life-threatening toxicity.", "managementStrategy": "Avoid MDMA completely during duloxetine therapy.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Desvenlafaxine", "supplementBName": "MDMA", "interactionType": "contraindicated", "severity": "dangerous", "description": "Desvenlafaxine blocks serotonin and norepinephrine reuptake, and MDMA forces serotonin and norepinephrine release through the same transporter systems. Combining them can blunt desired MDMA effects while increasing risk of serotonin syndrome, hyperthermia, blood pressure spikes, arrhythmia, and seizures. Risk is greater with dehydration, overheating, redosing, or other serotonergic substances.", "recommendation": "Do not use MDMA while taking desvenlafaxine. Avoid redosing if MDMA effects feel reduced; blunting does not remove toxicity risk. Seek emergency care for high fever, clonus, confusion, severe agitation, chest pain, fainting, or severe headache.", "minimumTimeSeparation": null, "mechanism": "MDMA acts as a substrate at SERT and NET and promotes reverse monoamine transport. Desvenlafaxine inhibits SERT and NET, creating transporter competition and additive serotonergic and adrenergic stress.", "evidenceLevel": "moderate", "sources": [ { "text": "Sarparast A, Thomas K, Malcolm B, Stauffer CS. Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review. Psychopharmacology (Berl). 2022;239(6):1945-1976.", "pmid": "35253070", "doi": "10.1007/s00213-022-06083-y", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35253070/", "publicSourceType": "PMID" }, { "text": "Makunts T, Jerome L, Abagyan R, de Boer A. Reported Cases of Serotonin Syndrome in MDMA Users in FAERS Database. Front Psychiatry. 2021;12:824288.", "pmid": "35140642", "doi": "10.3389/fpsyt.2021.824288", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35140642/", "publicSourceType": "PMID" }, { "text": "Green AR, Mechan AO, Elliott JM, O'Shea E, Colado MI. The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, \"ecstasy\"). Pharmacol Rev. 2003;55(3):463-508.", "pmid": "12869661", "doi": "10.1124/pr.55.3.3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12869661/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "MDMA plus desvenlafaxine can produce serotonin toxicity and cardiovascular instability.", "clinicalSignificance": "The combination is unsafe even if the subjective MDMA effect is reduced.", "managementStrategy": "Avoid MDMA completely during desvenlafaxine therapy.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Sertraline", "supplementBName": "Rhodiola Rosea", "interactionType": "caution", "severity": "moderate", "description": "Sertraline is serotonergic. Rhodiola has preclinical monoamine and MAO-related findings, but direct human evidence for serotonin syndrome with Sertraline is limited. Combined use should be treated as a theoretical serotonergic-interaction risk, not as a proven prescription-MAOI-like contraindication.", "recommendation": "Do not use Rhodiola to self-augment Sertraline. Discuss Rhodiola with the prescriber or pharmacist first, especially if other serotonergic agents are present, and seek care for serotonin-toxicity symptoms if both are used.", "minimumTimeSeparation": null, "mechanism": "Sertraline inhibits serotonin reuptake. Rhodiola constituents have shown monoamine-modulating and MAO-inhibitory activity in vitro, but clinical relevance at typical supplement doses is uncertain.", "evidenceLevel": "emerging", "sources": [ { "text": "van Diermen D, Marston A, Bravo J, Reist M, Carrupt PA, Hostettmann K. Monoamine oxidase inhibition by Rhodiola rosea L. roots. J Ethnopharmacol. 2009;122(2):397-401.", "pmid": "19168123", "doi": "10.1016/j.jep.2009.01.007", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19168123/", "publicSourceType": "PMID" }, { "text": "Woroń J, Siwek M. Unwanted effects of psychotropic drug interactions with medicinal products and diet supplements containing plant extracts. Psychiatr Pol. 2018;52(6):983-996.", "pmid": "30659561", "doi": "10.12740/PP/OnlineFirst/80998", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30659561/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Possible additive serotonergic activity; direct clinical interaction evidence is limited.", "clinicalSignificance": "Risk is precautionary and likely higher with multiple serotonergic agents, high doses, or symptoms suggestive of serotonin toxicity.", "managementStrategy": "Use only with prescriber awareness; monitor for agitation, tremor, sweating, diarrhea, fever, clonus, or confusion.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Fluoxetine", "supplementBName": "Rhodiola Rosea", "interactionType": "caution", "severity": "moderate", "description": "Fluoxetine is serotonergic. Rhodiola has preclinical monoamine and MAO-related findings, but direct human evidence for serotonin syndrome with Fluoxetine is limited. Combined use should be treated as a theoretical serotonergic-interaction risk, not as a proven prescription-MAOI-like contraindication. Fluoxetine and norfluoxetine persist for weeks, so prescriber guidance is especially important before adding or stopping serotonergic supplements.", "recommendation": "Do not use Rhodiola to self-augment Fluoxetine. Discuss Rhodiola with the prescriber or pharmacist first, especially if other serotonergic agents are present, and seek care for serotonin-toxicity symptoms if both are used.", "minimumTimeSeparation": null, "mechanism": "Fluoxetine inhibits serotonin reuptake. Rhodiola constituents have shown monoamine-modulating and MAO-inhibitory activity in vitro, but clinical relevance at typical supplement doses is uncertain.", "evidenceLevel": "emerging", "sources": [ { "text": "van Diermen D, Marston A, Bravo J, Reist M, Carrupt PA, Hostettmann K. Monoamine oxidase inhibition by Rhodiola rosea L. roots. J Ethnopharmacol. 2009;122(2):397-401.", "pmid": "19168123", "doi": "10.1016/j.jep.2009.01.007", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19168123/", "publicSourceType": "PMID" }, { "text": "Woroń J, Siwek M. Unwanted effects of psychotropic drug interactions with medicinal products and diet supplements containing plant extracts. Psychiatr Pol. 2018;52(6):983-996.", "pmid": "30659561", "doi": "10.12740/PP/OnlineFirst/80998", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30659561/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Possible additive serotonergic activity; direct clinical interaction evidence is limited.", "clinicalSignificance": "Risk is precautionary and likely higher with multiple serotonergic agents, high doses, or symptoms suggestive of serotonin toxicity.", "managementStrategy": "Use only with prescriber awareness; monitor for agitation, tremor, sweating, diarrhea, fever, clonus, or confusion.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Escitalopram", "supplementBName": "Rhodiola Rosea", "interactionType": "caution", "severity": "moderate", "description": "Escitalopram is serotonergic. Rhodiola has preclinical monoamine and MAO-related findings, but direct human evidence for serotonin syndrome with Escitalopram is limited. Combined use should be treated as a theoretical serotonergic-interaction risk, not as a proven prescription-MAOI-like contraindication.", "recommendation": "Do not use Rhodiola to self-augment Escitalopram. Discuss Rhodiola with the prescriber or pharmacist first, especially if other serotonergic agents are present, and seek care for serotonin-toxicity symptoms if both are used.", "minimumTimeSeparation": null, "mechanism": "Escitalopram inhibits serotonin reuptake. Rhodiola constituents have shown monoamine-modulating and MAO-inhibitory activity in vitro, but clinical relevance at typical supplement doses is uncertain.", "evidenceLevel": "emerging", "sources": [ { "text": "van Diermen D, Marston A, Bravo J, Reist M, Carrupt PA, Hostettmann K. Monoamine oxidase inhibition by Rhodiola rosea L. roots. J Ethnopharmacol. 2009;122(2):397-401.", "pmid": "19168123", "doi": "10.1016/j.jep.2009.01.007", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19168123/", "publicSourceType": "PMID" }, { "text": "Woroń J, Siwek M. Unwanted effects of psychotropic drug interactions with medicinal products and diet supplements containing plant extracts. Psychiatr Pol. 2018;52(6):983-996.", "pmid": "30659561", "doi": "10.12740/PP/OnlineFirst/80998", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30659561/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Possible additive serotonergic activity; direct clinical interaction evidence is limited.", "clinicalSignificance": "Risk is precautionary and likely higher with multiple serotonergic agents, high doses, or symptoms suggestive of serotonin toxicity.", "managementStrategy": "Use only with prescriber awareness; monitor for agitation, tremor, sweating, diarrhea, fever, clonus, or confusion.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Paroxetine", "supplementBName": "Rhodiola Rosea", "interactionType": "caution", "severity": "moderate", "description": "Paroxetine is serotonergic. Rhodiola has preclinical monoamine and MAO-related findings, but direct human evidence for serotonin syndrome with Paroxetine is limited. Combined use should be treated as a theoretical serotonergic-interaction risk, not as a proven prescription-MAOI-like contraindication.", "recommendation": "Do not use Rhodiola to self-augment Paroxetine. Discuss Rhodiola with the prescriber or pharmacist first, especially if other serotonergic agents are present, and seek care for serotonin-toxicity symptoms if both are used.", "minimumTimeSeparation": null, "mechanism": "Paroxetine inhibits serotonin reuptake. Rhodiola constituents have shown monoamine-modulating and MAO-inhibitory activity in vitro, but clinical relevance at typical supplement doses is uncertain.", "evidenceLevel": "emerging", "sources": [ { "text": "van Diermen D, Marston A, Bravo J, Reist M, Carrupt PA, Hostettmann K. Monoamine oxidase inhibition by Rhodiola rosea L. roots. J Ethnopharmacol. 2009;122(2):397-401.", "pmid": "19168123", "doi": "10.1016/j.jep.2009.01.007", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19168123/", "publicSourceType": "PMID" }, { "text": "Woroń J, Siwek M. Unwanted effects of psychotropic drug interactions with medicinal products and diet supplements containing plant extracts. Psychiatr Pol. 2018;52(6):983-996.", "pmid": "30659561", "doi": "10.12740/PP/OnlineFirst/80998", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30659561/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Possible additive serotonergic activity; direct clinical interaction evidence is limited.", "clinicalSignificance": "Risk is precautionary and likely higher with multiple serotonergic agents, high doses, or symptoms suggestive of serotonin toxicity.", "managementStrategy": "Use only with prescriber awareness; monitor for agitation, tremor, sweating, diarrhea, fever, clonus, or confusion.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Citalopram", "supplementBName": "Rhodiola Rosea", "interactionType": "caution", "severity": "moderate", "description": "Citalopram is serotonergic. Rhodiola has preclinical monoamine and MAO-related findings, but direct human evidence for serotonin syndrome with Citalopram is limited. Combined use should be treated as a theoretical serotonergic-interaction risk, not as a proven prescription-MAOI-like contraindication.", "recommendation": "Do not use Rhodiola to self-augment Citalopram. Discuss Rhodiola with the prescriber or pharmacist first, especially if other serotonergic agents are present, and seek care for serotonin-toxicity symptoms if both are used.", "minimumTimeSeparation": null, "mechanism": "Citalopram inhibits serotonin reuptake. Rhodiola constituents have shown monoamine-modulating and MAO-inhibitory activity in vitro, but clinical relevance at typical supplement doses is uncertain.", "evidenceLevel": "emerging", "sources": [ { "text": "van Diermen D, Marston A, Bravo J, Reist M, Carrupt PA, Hostettmann K. Monoamine oxidase inhibition by Rhodiola rosea L. roots. J Ethnopharmacol. 2009;122(2):397-401.", "pmid": "19168123", "doi": "10.1016/j.jep.2009.01.007", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19168123/", "publicSourceType": "PMID" }, { "text": "Woroń J, Siwek M. Unwanted effects of psychotropic drug interactions with medicinal products and diet supplements containing plant extracts. Psychiatr Pol. 2018;52(6):983-996.", "pmid": "30659561", "doi": "10.12740/PP/OnlineFirst/80998", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30659561/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Possible additive serotonergic activity; direct clinical interaction evidence is limited.", "clinicalSignificance": "Risk is precautionary and likely higher with multiple serotonergic agents, high doses, or symptoms suggestive of serotonin toxicity.", "managementStrategy": "Use only with prescriber awareness; monitor for agitation, tremor, sweating, diarrhea, fever, clonus, or confusion.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Sertraline", "supplementBName": "MDMA", "interactionType": "contraindicated", "severity": "dangerous", "description": "MDMA causes massive serotonin release by reversing the serotonin transporter (SERT), and sertraline blocks SERT — the same protein MDMA needs to function. Combining them can blunt MDMA's intended effect while still flooding the synapse with serotonin, producing potentially fatal serotonin syndrome with hyperthermia, seizures, and cardiovascular collapse. Cases in adolescents on SSRIs are a documented danger.", "recommendation": "Do not combine MDMA with sertraline. If you are prescribed sertraline, treat MDMA as off-limits. Even after stopping sertraline, wait at least 1-2 weeks before any MDMA exposure.", "minimumTimeSeparation": null, "mechanism": "MDMA produces serotonergic effects by entering the presynaptic neuron via SERT and triggering reverse transport of vesicular 5-HT into the synapse. SSRIs occupy and inhibit SERT, blunting MDMA's intended release while still permitting massive cumulative serotonergic load and hyperthermia.", "evidenceLevel": "moderate", "sources": [ { "text": "Dobry Y, Rice T, Sher L. Ecstasy use and serotonin syndrome: a neglected danger to adolescents and young adults prescribed selective serotonin reuptake inhibitors. Int J Adolesc Med Health. 2013;25(3):193-9.", "pmid": "24006318", "doi": "10.1515/ijamh-2013-0052", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24006318/", "publicSourceType": "PMID" }, { "text": "Green AR, Mechan AO, Elliott JM, O'Shea E, Colado MI. The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'). Pharmacol Rev. 2003;55(3):463-508.", "pmid": "12869661", "doi": "10.1124/pr.55.3.3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12869661/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Combination risks fatal serotonin syndrome and hyperthermia.", "clinicalSignificance": "SSRI plus MDMA can flood the synapse with serotonin while interfering with normal clearance, producing life-threatening toxicity.", "managementStrategy": "Do not combine; treat MDMA as contraindicated during SSRI therapy.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fluoxetine", "supplementBName": "MDMA", "interactionType": "contraindicated", "severity": "dangerous", "description": "MDMA produces its effects by reversing the serotonin transporter; fluoxetine blocks that transporter. The result is unpredictable blunting of MDMA's effect alongside heavy serotonergic load, with documented risk of serotonin syndrome, hyperthermia, and death. Fluoxetine's long half-life (and its active metabolite norfluoxetine) extends this risk for weeks after the last dose.", "recommendation": "Do not combine MDMA with fluoxetine. Because fluoxetine and norfluoxetine persist for 4-6 weeks, do not take MDMA for at least 5 weeks after stopping fluoxetine.", "minimumTimeSeparation": null, "mechanism": "Fluoxetine occupies SERT, preventing MDMA from triggering reverse transport of 5-HT into the synapse. Despite blunted subjective effects, residual serotonergic activity plus impaired clearance creates conditions for serotonin syndrome and hyperthermia.", "evidenceLevel": "moderate", "sources": [ { "text": "Dobry Y, Rice T, Sher L. Ecstasy use and serotonin syndrome: a neglected danger to adolescents and young adults prescribed selective serotonin reuptake inhibitors. Int J Adolesc Med Health. 2013;25(3):193-9.", "pmid": "24006318", "doi": "10.1515/ijamh-2013-0052", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24006318/", "publicSourceType": "PMID" }, { "text": "Green AR, Mechan AO, Elliott JM, O'Shea E, Colado MI. The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'). Pharmacol Rev. 2003;55(3):463-508.", "pmid": "12869661", "doi": "10.1124/pr.55.3.3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12869661/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Combination risks serotonin syndrome and life-threatening hyperthermia.", "clinicalSignificance": "Fluoxetine's long elimination tail means MDMA remains dangerous for weeks after stopping the drug.", "managementStrategy": "Avoid MDMA during fluoxetine treatment and for 5+ weeks after stopping.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Escitalopram", "supplementBName": "MDMA", "interactionType": "contraindicated", "severity": "dangerous", "description": "Escitalopram blocks the serotonin transporter that MDMA uses to release serotonin, blunting MDMA's intended effect while still producing serotonergic load and hyperthermia. The combination carries documented risk of serotonin syndrome and cardiovascular collapse, especially in young adults.", "recommendation": "Do not combine MDMA with escitalopram. If you stop escitalopram, wait at least 1-2 weeks before any MDMA exposure.", "minimumTimeSeparation": null, "mechanism": "Escitalopram occupies SERT and prevents MDMA from triggering reverse transport of 5-HT. Combined inhibition of serotonin reuptake with MDMA-induced serotonergic activity raises the risk of postsynaptic serotonin toxicity.", "evidenceLevel": "moderate", "sources": [ { "text": "Dobry Y, Rice T, Sher L. Ecstasy use and serotonin syndrome: a neglected danger to adolescents and young adults prescribed selective serotonin reuptake inhibitors. Int J Adolesc Med Health. 2013;25(3):193-9.", "pmid": "24006318", "doi": "10.1515/ijamh-2013-0052", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24006318/", "publicSourceType": "PMID" }, { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-20.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Combination risks fatal serotonin syndrome.", "clinicalSignificance": "Escitalopram plus MDMA can cause life-threatening hyperthermia and serotonin toxicity.", "managementStrategy": "Treat MDMA as contraindicated while on escitalopram.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Paroxetine", "supplementBName": "MDMA", "interactionType": "contraindicated", "severity": "dangerous", "description": "Paroxetine blocks the serotonin transporter MDMA uses to release serotonin, and paroxetine is also a potent CYP2D6 inhibitor — the enzyme that clears MDMA. The combination both blunts MDMA's effect and raises MDMA blood levels, increasing the risk of serotonin syndrome, hyperthermia, and death.", "recommendation": "Do not combine MDMA with paroxetine. If paroxetine is stopped, wait at least 1-2 weeks before any MDMA use.", "minimumTimeSeparation": null, "mechanism": "Paroxetine blocks SERT (preventing MDMA-induced serotonin release) and strongly inhibits CYP2D6 (impairing MDMA clearance). Net result: higher MDMA levels with disrupted serotonergic clearance.", "evidenceLevel": "moderate", "sources": [ { "text": "Dobry Y, Rice T, Sher L. Ecstasy use and serotonin syndrome: a neglected danger to adolescents and young adults prescribed selective serotonin reuptake inhibitors. Int J Adolesc Med Health. 2013;25(3):193-9.", "pmid": "24006318", "doi": "10.1515/ijamh-2013-0052", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24006318/", "publicSourceType": "PMID" }, { "text": "Green AR, Mechan AO, Elliott JM, O'Shea E, Colado MI. The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'). Pharmacol Rev. 2003;55(3):463-508.", "pmid": "12869661", "doi": "10.1124/pr.55.3.3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12869661/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Combination risks fatal serotonin syndrome with elevated MDMA exposure.", "clinicalSignificance": "Paroxetine raises MDMA levels via CYP2D6 inhibition while disrupting normal serotonergic clearance.", "managementStrategy": "Avoid MDMA during paroxetine therapy.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Citalopram", "supplementBName": "MDMA", "interactionType": "contraindicated", "severity": "dangerous", "description": "Citalopram blocks the serotonin transporter MDMA uses to release serotonin, blunting the subjective effect while still permitting serotonergic load. Combined use risks serotonin syndrome and hyperthermia, and citalopram independently prolongs the QT interval, adding cardiac risk when MDMA causes catecholamine surges.", "recommendation": "Do not combine MDMA with citalopram. Wait at least 1-2 weeks after stopping citalopram before any MDMA exposure.", "minimumTimeSeparation": null, "mechanism": "Citalopram occupies SERT, blunting MDMA-induced reverse transport of serotonin. Cumulative serotonergic activity with impaired clearance can trigger serotonin toxicity; concurrent QT prolongation magnifies arrhythmia risk.", "evidenceLevel": "moderate", "sources": [ { "text": "Dobry Y, Rice T, Sher L. Ecstasy use and serotonin syndrome: a neglected danger to adolescents and young adults prescribed selective serotonin reuptake inhibitors. Int J Adolesc Med Health. 2013;25(3):193-9.", "pmid": "24006318", "doi": "10.1515/ijamh-2013-0052", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24006318/", "publicSourceType": "PMID" }, { "text": "Beach SR, Kostis WJ, Celano CM, et al. Meta-analysis of selective serotonin reuptake inhibitor-associated QTc prolongation. J Clin Psychiatry. 2014;75(5):e441-9.", "pmid": "24922496", "doi": "10.4088/JCP.13r08672", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24922496/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Combination risks serotonin syndrome and arrhythmia.", "clinicalSignificance": "Citalopram plus MDMA combines serotonergic toxicity risk with QT prolongation.", "managementStrategy": "Avoid MDMA during citalopram therapy.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Sertraline", "supplementBName": "Psilocybin", "interactionType": "caution", "severity": "moderate", "description": "Sertraline blocks the serotonin transporter and occupies postsynaptic 5-HT2A receptors over time, blunting psilocybin's intended psychedelic effect. Most psilocybin therapy trials require patients to be off SSRIs for several weeks before dosing. The combined serotonergic load also carries a theoretical risk of serotonin syndrome, though documented cases with classical psychedelics are rare.", "recommendation": "Do not take psilocybin while on sertraline if you want a meaningful experience — the response will likely be blunted. If you have stopped sertraline, follow clinical-trial protocols and wait at least 2 weeks before psilocybin.", "minimumTimeSeparation": null, "mechanism": "Chronic SSRI exposure downregulates and desensitizes 5-HT2A receptors and elevates baseline synaptic serotonin, both of which attenuate psilocin's 5-HT2A agonism. Some additive serotonergic activity also raises theoretical risk of serotonin syndrome.", "evidenceLevel": "emerging", "sources": [ { "text": "Raison CL, Sanacora G, Woolley J, et al. Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial. JAMA. 2023;330(9):843-853.", "pmid": "37651119", "doi": "10.1001/jama.2023.14530", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37651119/", "publicSourceType": "PMID" }, { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-20.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Sertraline blunts psilocybin's psychedelic effect and adds serotonergic load.", "clinicalSignificance": "Patients on SSRIs may get little benefit from psilocybin, and any combination still raises theoretical serotonin toxicity risk.", "managementStrategy": "Avoid combination; observe washout per clinical trial protocols.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Fluoxetine", "supplementBName": "Psilocybin", "interactionType": "caution", "severity": "moderate", "description": "Fluoxetine substantially blunts psilocybin's psychedelic effects through chronic 5-HT2A receptor downregulation, and its very long half-life means the effect persists for weeks after stopping. There is also a theoretical risk of serotonin syndrome with combined serotonergic load.", "recommendation": "Do not take psilocybin while on fluoxetine. Because fluoxetine and norfluoxetine have half-lives of 1-2 weeks and 1-2+ weeks respectively, wait at least 5 weeks after the last fluoxetine dose before any psilocybin exposure.", "minimumTimeSeparation": null, "mechanism": "Chronic SSRI exposure downregulates 5-HT2A receptors and raises baseline synaptic serotonin, attenuating psilocin's 5-HT2A agonism. Fluoxetine's long elimination half-life extends this attenuation well past discontinuation.", "evidenceLevel": "emerging", "sources": [ { "text": "Raison CL, Sanacora G, Woolley J, et al. Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial. JAMA. 2023;330(9):843-853.", "pmid": "37651119", "doi": "10.1001/jama.2023.14530", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37651119/", "publicSourceType": "PMID" }, { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-20.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Fluoxetine blunts psilocybin's effect for weeks after discontinuation.", "clinicalSignificance": "Patients expecting a psilocybin response will likely get a sub-therapeutic experience if fluoxetine washout is incomplete.", "managementStrategy": "Allow 5+ weeks of fluoxetine washout before psilocybin.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Sertraline", "supplementBName": "Fish Oil", "interactionType": "caution", "severity": "moderate", "description": "Sertraline depletes platelet serotonin stores and impairs platelet aggregation, raising bleeding risk by roughly 40-55% across observational studies. Fish oil (high-dose EPA/DHA) adds modest, dose-dependent antiplatelet activity. Combined use compounds bleeding risk, particularly with concurrent NSAIDs, aspirin, or anticoagulants.", "recommendation": "Low-dose fish oil (1g/day or less) is usually fine alongside sertraline. Avoid high-dose fish oil (over 3g/day EPA+DHA) unless your prescriber agrees, and watch for unusual bruising, nosebleeds, or GI bleeding. Stop fish oil at least 7 days before surgery.", "minimumTimeSeparation": null, "mechanism": "SSRIs block the platelet serotonin transporter, depleting intra-platelet serotonin stores needed for full aggregation responses to ADP, collagen, and epinephrine. EPA and DHA from fish oil decrease thromboxane A2 production and increase bleeding time in a dose-dependent way.", "evidenceLevel": "moderate", "sources": [ { "text": "Andrade C, Sandarsh S, Chethan KB, Nagesh KS. Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for clinicians and a reconsideration of mechanisms. J Clin Psychiatry. 2010;71(12):1565-75.", "pmid": "21190637", "doi": "10.4088/JCP.09r05786blu", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21190637/", "publicSourceType": "PMID" }, { "text": "Laporte S, Chapelle C, Caillet P, et al. Bleeding risk under selective serotonin reuptake inhibitor (SSRI) antidepressants: A meta-analysis of observational studies. Pharmacol Res. 2017;118:19-32.", "pmid": "27521835", "doi": "10.1016/j.phrs.2016.08.017", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27521835/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive antiplatelet effect raises bleeding risk.", "clinicalSignificance": "Both agents impair platelet function through different mechanisms, compounding bleeding risk especially with NSAIDs or anticoagulants.", "managementStrategy": "Keep fish oil ≤1g/day; watch for bleeding; stop fish oil 7 days pre-op.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fluoxetine", "supplementBName": "Fish Oil", "interactionType": "caution", "severity": "moderate", "description": "Fluoxetine depletes platelet serotonin and impairs aggregation, while high-dose fish oil adds modest antiplatelet activity. Observational data show SSRIs increase upper GI bleeding risk by roughly 55%; adding another antiplatelet substance compounds that risk.", "recommendation": "Low-dose fish oil (≤1g/day) is generally compatible with fluoxetine. Avoid high-dose fish oil (>3g/day) unless your prescriber agrees, and watch for easy bruising, nosebleeds, or dark stools. Stop fish oil 7 days before surgery.", "minimumTimeSeparation": null, "mechanism": "Fluoxetine blocks the platelet 5-HT transporter, depleting platelet serotonin stores needed for full aggregation. EPA/DHA reduce thromboxane A2 synthesis and prolong bleeding time in a dose-dependent fashion.", "evidenceLevel": "moderate", "sources": [ { "text": "Andrade C, Sandarsh S, Chethan KB, Nagesh KS. Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for clinicians and a reconsideration of mechanisms. J Clin Psychiatry. 2010;71(12):1565-75.", "pmid": "21190637", "doi": "10.4088/JCP.09r05786blu", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21190637/", "publicSourceType": "PMID" }, { "text": "Jiang HY, Chen HZ, Hu XJ, et al. Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal bleeding: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2015;13(1):42-50.", "pmid": "24993365", "doi": "10.1016/j.cgh.2014.06.021", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24993365/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive antiplatelet effect raises bleeding risk.", "clinicalSignificance": "Two different antiplatelet mechanisms stacked increases bleeding probability.", "managementStrategy": "Cap fish oil at 1g/day; monitor for bleeding signs; pause before surgery.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Escitalopram", "supplementBName": "Fish Oil", "interactionType": "caution", "severity": "moderate", "description": "Escitalopram impairs platelet aggregation by depleting platelet serotonin stores, and high-dose fish oil adds modest antiplatelet activity by reducing thromboxane A2 synthesis. Combined use raises bleeding risk, particularly with NSAIDs or anticoagulants.", "recommendation": "Keep fish oil dose moderate (≤1g/day) with escitalopram. Avoid high-dose regimens (>3g/day) unless your prescriber agrees, and stop fish oil 7 days before any planned surgery.", "minimumTimeSeparation": null, "mechanism": "Escitalopram blocks the platelet serotonin transporter, depleting intra-platelet 5-HT needed for normal aggregation. EPA/DHA shift the prostaglandin/thromboxane balance toward less aggregatory species.", "evidenceLevel": "moderate", "sources": [ { "text": "Andrade C, Sandarsh S, Chethan KB, Nagesh KS. Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for clinicians and a reconsideration of mechanisms. J Clin Psychiatry. 2010;71(12):1565-75.", "pmid": "21190637", "doi": "10.4088/JCP.09r05786blu", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21190637/", "publicSourceType": "PMID" }, { "text": "Laporte S, Chapelle C, Caillet P, et al. Bleeding risk under selective serotonin reuptake inhibitor (SSRI) antidepressants: A meta-analysis of observational studies. Pharmacol Res. 2017;118:19-32.", "pmid": "27521835", "doi": "10.1016/j.phrs.2016.08.017", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27521835/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive antiplatelet effect raises bleeding risk.", "clinicalSignificance": "Both impair platelet function through different mechanisms; risk compounds with NSAIDs or anticoagulants.", "managementStrategy": "Limit fish oil dose; watch for bleeding; pause before surgery.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Paroxetine", "supplementBName": "Fish Oil", "interactionType": "caution", "severity": "moderate", "description": "Paroxetine depletes platelet serotonin stores and impairs aggregation; high-dose fish oil adds antiplatelet activity. Together they raise bleeding risk, especially with concurrent NSAIDs, aspirin, or anticoagulants.", "recommendation": "Keep fish oil to ≤1g/day with paroxetine. Avoid high-dose fish oil unless your prescriber agrees, and watch for bruising, nosebleeds, or dark stools. Stop fish oil 7 days before surgery.", "minimumTimeSeparation": null, "mechanism": "Paroxetine blocks platelet SERT, depleting 5-HT needed for normal aggregation. EPA/DHA reduce thromboxane A2 synthesis and prolong bleeding time in a dose-dependent way.", "evidenceLevel": "moderate", "sources": [ { "text": "Andrade C, Sandarsh S, Chethan KB, Nagesh KS. Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for clinicians and a reconsideration of mechanisms. J Clin Psychiatry. 2010;71(12):1565-75.", "pmid": "21190637", "doi": "10.4088/JCP.09r05786blu", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21190637/", "publicSourceType": "PMID" }, { "text": "Laporte S, Chapelle C, Caillet P, et al. Bleeding risk under selective serotonin reuptake inhibitor (SSRI) antidepressants: A meta-analysis of observational studies. Pharmacol Res. 2017;118:19-32.", "pmid": "27521835", "doi": "10.1016/j.phrs.2016.08.017", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27521835/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive antiplatelet effect raises bleeding risk.", "clinicalSignificance": "SSRI plus fish oil compounds bleeding probability, especially with concurrent NSAIDs.", "managementStrategy": "Cap fish oil dose; pause before surgery; watch for bleeding signs.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Sertraline", "supplementBName": "Ginkgo Biloba", "interactionType": "caution", "severity": "moderate", "description": "Sertraline depletes platelet serotonin and impairs aggregation, raising bleeding risk. Ginkgo biloba contains ginkgolides that inhibit platelet-activating factor (PAF) and have been linked to bleeding events. In a case series of psychotropic-herbal interactions, ginkgo combined with SSRIs accounted for 27% of documented complications, mostly bleeding.", "recommendation": "Avoid Ginkgo biloba while taking sertraline. If you have already started both, watch for easy bruising, nosebleeds, blood in stool or urine, and stop Ginkgo 7-14 days before any planned surgery.", "minimumTimeSeparation": null, "mechanism": "Sertraline blocks platelet SERT, depleting intra-platelet 5-HT needed for normal aggregation. Ginkgolides A and B inhibit platelet-activating factor (PAF) receptors, providing a separate antiplatelet pathway. Stacking the two mechanisms compounds bleeding risk.", "evidenceLevel": "moderate", "sources": [ { "text": "Woroń J, Siwek M. Unwanted effects of psychotropic drug interactions with medicinal products and diet supplements containing plant extracts. Psychiatr Pol. 2018;52(6):983-996.", "pmid": "30659561", "doi": "10.12740/PP/OnlineFirst/80998", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30659561/", "publicSourceType": "PMID" }, { "text": "Andrade C, Sandarsh S, Chethan KB, Nagesh KS. Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for clinicians and a reconsideration of mechanisms. J Clin Psychiatry. 2010;71(12):1565-75.", "pmid": "21190637", "doi": "10.4088/JCP.09r05786blu", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21190637/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive antiplatelet effect raises bleeding risk.", "clinicalSignificance": "Documented case series link SSRI plus Ginkgo with bleeding events.", "managementStrategy": "Avoid Ginkgo with sertraline; pause Ginkgo 1-2 weeks before surgery.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fluoxetine", "supplementBName": "Ginkgo Biloba", "interactionType": "caution", "severity": "moderate", "description": "Fluoxetine depletes platelet serotonin and impairs aggregation; ginkgo's ginkgolides inhibit platelet-activating factor. The combination compounds bleeding risk, with ginkgo-plus-SSRI accounting for a substantial share of documented herbal-psychotropic bleeding complications.", "recommendation": "Avoid Ginkgo biloba while on fluoxetine. Watch for bruising, nosebleeds, or GI bleeding if you have already combined them, and stop Ginkgo 7-14 days before any planned surgery.", "minimumTimeSeparation": null, "mechanism": "Fluoxetine blocks platelet SERT, depleting 5-HT needed for aggregation. Ginkgolides A and B inhibit PAF receptors, an independent antiplatelet pathway.", "evidenceLevel": "moderate", "sources": [ { "text": "Woroń J, Siwek M. Unwanted effects of psychotropic drug interactions with medicinal products and diet supplements containing plant extracts. Psychiatr Pol. 2018;52(6):983-996.", "pmid": "30659561", "doi": "10.12740/PP/OnlineFirst/80998", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30659561/", "publicSourceType": "PMID" }, { "text": "Andrade C, Sandarsh S, Chethan KB, Nagesh KS. Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for clinicians and a reconsideration of mechanisms. J Clin Psychiatry. 2010;71(12):1565-75.", "pmid": "21190637", "doi": "10.4088/JCP.09r05786blu", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21190637/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive antiplatelet effect increases bleeding risk.", "clinicalSignificance": "SSRI plus Ginkgo combination carries documented bleeding risk.", "managementStrategy": "Avoid Ginkgo with fluoxetine; pause 1-2 weeks pre-op.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Escitalopram", "supplementBName": "Ginkgo Biloba", "interactionType": "caution", "severity": "moderate", "description": "Escitalopram impairs platelet aggregation by depleting platelet serotonin; Ginkgo's ginkgolides inhibit platelet-activating factor. Combined antiplatelet activity raises bleeding risk, especially with concurrent NSAIDs or anticoagulants.", "recommendation": "Avoid Ginkgo biloba while taking escitalopram. Watch for unusual bruising or bleeding; stop Ginkgo 7-14 days before any planned surgery.", "minimumTimeSeparation": null, "mechanism": "Escitalopram blocks platelet SERT, depleting 5-HT needed for normal aggregation. Ginkgolides A/B inhibit PAF receptors, providing an additional antiplatelet pathway.", "evidenceLevel": "moderate", "sources": [ { "text": "Woroń J, Siwek M. Unwanted effects of psychotropic drug interactions with medicinal products and diet supplements containing plant extracts. Psychiatr Pol. 2018;52(6):983-996.", "pmid": "30659561", "doi": "10.12740/PP/OnlineFirst/80998", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30659561/", "publicSourceType": "PMID" }, { "text": "Andrade C, Sandarsh S, Chethan KB, Nagesh KS. Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for clinicians and a reconsideration of mechanisms. J Clin Psychiatry. 2010;71(12):1565-75.", "pmid": "21190637", "doi": "10.4088/JCP.09r05786blu", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21190637/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive antiplatelet effect raises bleeding risk.", "clinicalSignificance": "Two antiplatelet mechanisms stacked increases bleeding probability.", "managementStrategy": "Avoid Ginkgo during escitalopram therapy; pause pre-op.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Paroxetine", "supplementBName": "Ginkgo Biloba", "interactionType": "caution", "severity": "moderate", "description": "Paroxetine depletes platelet serotonin and impairs aggregation; Ginkgo's ginkgolides inhibit platelet-activating factor. The combination compounds bleeding risk, particularly with concurrent NSAIDs or anticoagulants.", "recommendation": "Avoid Ginkgo biloba while taking paroxetine. Watch for bruising, nosebleeds, or GI bleeding; stop Ginkgo 7-14 days before any planned surgery.", "minimumTimeSeparation": null, "mechanism": "Paroxetine blocks the platelet 5-HT transporter, depleting platelet serotonin. Ginkgolides A/B inhibit PAF receptors, providing an independent antiplatelet pathway.", "evidenceLevel": "moderate", "sources": [ { "text": "Woroń J, Siwek M. Unwanted effects of psychotropic drug interactions with medicinal products and diet supplements containing plant extracts. Psychiatr Pol. 2018;52(6):983-996.", "pmid": "30659561", "doi": "10.12740/PP/OnlineFirst/80998", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30659561/", "publicSourceType": "PMID" }, { "text": "Andrade C, Sandarsh S, Chethan KB, Nagesh KS. Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for clinicians and a reconsideration of mechanisms. J Clin Psychiatry. 2010;71(12):1565-75.", "pmid": "21190637", "doi": "10.4088/JCP.09r05786blu", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21190637/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive antiplatelet effect raises bleeding risk.", "clinicalSignificance": "Combined SSRI plus Ginkgo carries documented bleeding risk.", "managementStrategy": "Avoid Ginkgo during paroxetine therapy.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Citalopram", "supplementBName": "Ginkgo Biloba", "interactionType": "caution", "severity": "moderate", "description": "Citalopram impairs platelet aggregation by depleting platelet serotonin; Ginkgo's ginkgolides inhibit platelet-activating factor. The combination compounds bleeding risk, particularly with concurrent NSAIDs, aspirin, or anticoagulants.", "recommendation": "Avoid Ginkgo biloba while taking citalopram. Watch for unusual bruising or bleeding and stop Ginkgo 7-14 days before any planned surgery.", "minimumTimeSeparation": null, "mechanism": "Citalopram blocks platelet SERT, depleting 5-HT needed for aggregation. Ginkgolides A/B inhibit PAF receptors, providing an additional antiplatelet pathway.", "evidenceLevel": "moderate", "sources": [ { "text": "Woroń J, Siwek M. Unwanted effects of psychotropic drug interactions with medicinal products and diet supplements containing plant extracts. Psychiatr Pol. 2018;52(6):983-996.", "pmid": "30659561", "doi": "10.12740/PP/OnlineFirst/80998", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30659561/", "publicSourceType": "PMID" }, { "text": "Andrade C, Sandarsh S, Chethan KB, Nagesh KS. Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for clinicians and a reconsideration of mechanisms. J Clin Psychiatry. 2010;71(12):1565-75.", "pmid": "21190637", "doi": "10.4088/JCP.09r05786blu", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21190637/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive antiplatelet effect raises bleeding risk.", "clinicalSignificance": "Combined SSRI plus Ginkgo carries documented bleeding risk.", "managementStrategy": "Avoid Ginkgo during citalopram therapy.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fluvoxamine", "supplementBName": "Ginkgo Biloba", "interactionType": "caution", "severity": "moderate", "description": "Fluvoxamine impairs platelet aggregation by depleting platelet serotonin; Ginkgo's ginkgolides inhibit platelet-activating factor. Combined antiplatelet activity raises bleeding risk, especially with concurrent NSAIDs or anticoagulants.", "recommendation": "Avoid Ginkgo biloba while taking fluvoxamine. Watch for bruising, nosebleeds, or GI bleeding and stop Ginkgo 7-14 days before any planned surgery.", "minimumTimeSeparation": null, "mechanism": "Fluvoxamine blocks platelet SERT, depleting 5-HT needed for normal aggregation. Ginkgolides A/B inhibit PAF receptors, providing an independent antiplatelet pathway.", "evidenceLevel": "moderate", "sources": [ { "text": "Woroń J, Siwek M. Unwanted effects of psychotropic drug interactions with medicinal products and diet supplements containing plant extracts. Psychiatr Pol. 2018;52(6):983-996.", "pmid": "30659561", "doi": "10.12740/PP/OnlineFirst/80998", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30659561/", "publicSourceType": "PMID" }, { "text": "Andrade C, Sandarsh S, Chethan KB, Nagesh KS. Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for clinicians and a reconsideration of mechanisms. J Clin Psychiatry. 2010;71(12):1565-75.", "pmid": "21190637", "doi": "10.4088/JCP.09r05786blu", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21190637/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive antiplatelet effect raises bleeding risk.", "clinicalSignificance": "SSRI plus Ginkgo compounds bleeding probability, especially with NSAIDs.", "managementStrategy": "Avoid Ginkgo during fluvoxamine therapy.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Sertraline", "supplementBName": "Garlic Extract", "interactionType": "caution", "severity": "moderate", "description": "Sertraline depletes platelet serotonin and impairs aggregation; concentrated garlic extracts (allicin, ajoene) inhibit platelet aggregation by 70-95% in laboratory assays. Combined antiplatelet activity raises bleeding risk, particularly with concurrent NSAIDs, aspirin, or anticoagulants.", "recommendation": "Culinary amounts of garlic are fine. Avoid concentrated garlic supplements while on sertraline if you take NSAIDs, aspirin, or anticoagulants, and stop garlic supplements 7-10 days before any planned surgery.", "minimumTimeSeparation": null, "mechanism": "Sertraline blocks platelet SERT, depleting 5-HT needed for normal aggregation. Garlic-derived ajoene and allicin inhibit platelet aggregation through thromboxane suppression and direct effects on platelet membranes.", "evidenceLevel": "emerging", "sources": [ { "text": "Andrade C, Sandarsh S, Chethan KB, Nagesh KS. Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for clinicians and a reconsideration of mechanisms. J Clin Psychiatry. 2010;71(12):1565-75.", "pmid": "21190637", "doi": "10.4088/JCP.09r05786blu", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21190637/", "publicSourceType": "PMID" }, { "text": "Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: a systematic review. Drugs. 2001;61(15):2163-75.", "pmid": "11772128", "doi": "10.2165/00003495-200161150-00002", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11772128/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive antiplatelet effect raises bleeding risk.", "clinicalSignificance": "Concentrated garlic plus SSRI compounds bleeding probability, especially with NSAIDs.", "managementStrategy": "Limit to culinary garlic; avoid extracts; pause supplements before surgery.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Fluvoxamine", "supplementBName": "Melatonin", "interactionType": "caution", "severity": "serious", "description": "Fluvoxamine is a potent CYP1A2 inhibitor, and melatonin is metabolized almost entirely by CYP1A2. Coadministration raises melatonin AUC about 17-fold and peak concentration about 12-fold in healthy volunteers. The result is exaggerated, prolonged sedation, hangover effects the next day, and unpredictable shifts in sleep-wake timing.", "recommendation": "Avoid melatonin while on fluvoxamine. If a sleep aid is needed, talk to your prescriber about non-melatonin options. Even small melatonin doses (0.3-1 mg) can produce supratherapeutic blood levels in this combination.", "minimumTimeSeparation": null, "mechanism": "Fluvoxamine strongly inhibits hepatic CYP1A2, the enzyme responsible for the first metabolic step of melatonin (6-hydroxylation). Inhibition prevents first-pass and systemic clearance, producing a roughly 17-fold rise in melatonin AUC.", "evidenceLevel": "strong", "sources": [ { "text": "Härtter S, Grözinger M, Weigmann H, Röschke J, Hiemke C. Increased bioavailability of oral melatonin after fluvoxamine coadministration. Clin Pharmacol Ther. 2000;67(1):1-6.", "pmid": "10668847", "doi": "10.1067/mcp.2000.104071", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10668847/", "publicSourceType": "PMID" }, { "text": "Grözinger M, Härtter S, Wang X, Röschke J, Hiemke C, Rose DM. Fluvoxamine strongly inhibits melatonin metabolism in a patient with low-amplitude melatonin profile. Arch Gen Psychiatry. 2000;57(8):812-3.", "pmid": "10920471", "doi": "10.1001/archpsyc.57.8.812", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10920471/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "aAffectsB", "effect": "Fluvoxamine raises melatonin exposure roughly 17-fold via CYP1A2 inhibition.", "clinicalSignificance": "Patients can experience excessive sedation, next-day hangover, and unpredictable circadian effects from normal melatonin doses.", "managementStrategy": "Avoid melatonin during fluvoxamine therapy.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Fluvoxamine", "supplementBName": "Green Tea Extract", "interactionType": "caution", "severity": "moderate", "description": "Fluvoxamine is a potent CYP1A2 inhibitor, and the caffeine in green tea extracts is metabolized almost entirely by CYP1A2. In healthy volunteers, fluvoxamine reduced caffeine clearance about five-fold and extended caffeine half-life from roughly 5 hours to 31 hours. Even low caffeine intake from a green tea supplement can produce jitteriness, palpitations, insomnia, and anxiety the next day.", "recommendation": "Avoid caffeine-containing green tea extracts while on fluvoxamine. Decaffeinated green tea extract is the safer option. If you do drink green tea, keep intake low and avoid afternoon use to prevent insomnia from prolonged caffeine half-life.", "minimumTimeSeparation": null, "mechanism": "Fluvoxamine inhibits hepatic CYP1A2, the primary metabolic enzyme for caffeine. Inhibition reduces caffeine clearance by about 80% and prolongs its half-life roughly six-fold, leading to caffeine accumulation.", "evidenceLevel": "strong", "sources": [ { "text": "Jeppesen U, Loft S, Poulsen HE, Brøsen K. A fluvoxamine-caffeine interaction study. Pharmacogenetics. 1996;6(3):213-22.", "pmid": "8807660", "doi": "10.1097/00008571-199606000-00003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8807660/", "publicSourceType": "PMID" }, { "text": "Culm-Merdek KE, von Moltke LL, Harmatz JS, Greenblatt DJ. Fluvoxamine impairs single-dose caffeine clearance without altering caffeine pharmacodynamics. Br J Clin Pharmacol. 2005;60(5):486-93.", "pmid": "16236038", "doi": "10.1111/j.1365-2125.2005.02467.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16236038/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Fluvoxamine slows caffeine clearance five-fold via CYP1A2 inhibition.", "clinicalSignificance": "Normal caffeine intake produces toxic accumulation, with jitteriness, insomnia, and palpitations.", "managementStrategy": "Use decaffeinated green tea; minimize caffeine intake while on fluvoxamine.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Fluvoxamine", "supplementBName": "5-HTP", "interactionType": "contraindicated", "severity": "dangerous", "description": "5-HTP is the immediate precursor to serotonin and bypasses the rate-limiting step in serotonin synthesis. Combined with fluvoxamine's blockade of the serotonin transporter, 5-HTP can push synaptic serotonin to toxic levels and trigger serotonin syndrome (agitation, tremor, hyperthermia, clonus). This is a well-known SSRI plus serotonin-precursor contraindication.", "recommendation": "Do not take 5-HTP with fluvoxamine. If you have been taking 5-HTP, stop it before starting fluvoxamine and stay off it throughout treatment.", "minimumTimeSeparation": null, "mechanism": "5-HTP is decarboxylated to serotonin throughout the body, including in the CNS. Fluvoxamine blocks SERT, preventing reuptake. The combination produces excess synaptic serotonin and risks 5-HT1A/5-HT2A overstimulation.", "evidenceLevel": "strong", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-20.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs. 2009;69(13):1777-98.", "pmid": "19719333", "doi": "10.2165/11317010-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19719333/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Combination risks serotonin syndrome.", "clinicalSignificance": "Pairing a serotonin precursor with an SSRI can flood the synapse and trigger serotonin toxicity.", "managementStrategy": "Do not combine 5-HTP with fluvoxamine.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Fluvoxamine", "supplementBName": "L-Tryptophan", "interactionType": "contraindicated", "severity": "dangerous", "description": "L-Tryptophan is the upstream precursor to serotonin; combined with fluvoxamine's serotonin reuptake blockade, it can drive synaptic serotonin to toxic levels and trigger serotonin syndrome (tremor, sweating, agitation, hyperthermia, clonus). This mirrors the well-documented SSRI plus tryptophan contraindication.", "recommendation": "Do not take L-tryptophan supplements with fluvoxamine. Food intake of tryptophan is fine; the problem is concentrated supplemental doses.", "minimumTimeSeparation": null, "mechanism": "L-Tryptophan is converted to 5-HTP by tryptophan hydroxylase, then to serotonin. Fluvoxamine blocks SERT, preventing reuptake. Combined, both synthesis and clearance are pushed, raising synaptic 5-HT to toxic levels.", "evidenceLevel": "strong", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-20.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs. 2009;69(13):1777-98.", "pmid": "19719333", "doi": "10.2165/11317010-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19719333/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Combination risks serotonin syndrome.", "clinicalSignificance": "Serotonin precursor plus SSRI can drive serotonin toxicity.", "managementStrategy": "Do not combine; food tryptophan is fine but skip supplements.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Fluvoxamine", "supplementBName": "SAMe", "interactionType": "caution", "severity": "serious", "description": "SAMe has independent serotonergic and antidepressant activity. Combined with fluvoxamine, the additive serotonergic load raises the risk of serotonin syndrome — agitation, sweating, tremor, hyperreflexia, clonus, and hyperthermia. Case reports describe serotonin toxicity when SAMe is added to existing serotonergic therapy.", "recommendation": "Do not start SAMe while taking fluvoxamine without explicit prescriber approval and monitoring. If SAMe is required, start at the lowest dose and watch for tremor, restlessness, sweating, or rapid heart rate.", "minimumTimeSeparation": null, "mechanism": "SAMe modulates monoamine neurotransmission and has measurable antidepressant effects via mechanisms that overlap serotonergic pathways. Combined with SSRI-mediated reuptake blockade, additive serotonergic activity can drive postsynaptic toxicity.", "evidenceLevel": "emerging", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-20.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Sarris J, Murphy J, Mischoulon D, et al. Adjunctive S-adenosylmethionine (SAMe) in treating non-remittent major depressive disorder: An 8-week double-blind, randomized, controlled trial. Eur Neuropsychopharmacol. 2018;28(10):1126-1136.", "pmid": "30115553", "doi": "10.1016/j.euroneuro.2018.07.098", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30115553/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Additive serotonergic activity raises serotonin syndrome risk.", "clinicalSignificance": "SAMe added to an SSRI can push serotonergic tone into toxic range.", "managementStrategy": "Avoid combination unless prescriber-supervised; start low and monitor.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Fluvoxamine", "supplementBName": "St. John's Wort", "interactionType": "contraindicated", "severity": "dangerous", "description": "St. John's Wort has SSRI-like activity and is a strong CYP3A4/2C9 inducer. Combined with fluvoxamine, the additive serotonergic load can trigger serotonin syndrome (tremor, agitation, hyperthermia, clonus). St. John's Wort is contraindicated with all SSRIs for this reason.", "recommendation": "Do not combine St. John's Wort with fluvoxamine. Stop St. John's Wort at least 2 weeks before starting fluvoxamine.", "minimumTimeSeparation": null, "mechanism": "St. John's Wort constituents (hyperforin, hypericin) inhibit synaptic monoamine reuptake including serotonin. Combined with fluvoxamine's SERT blockade, synaptic serotonin can rise to toxic levels.", "evidenceLevel": "strong", "sources": [ { "text": "Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs. 2009;69(13):1777-98.", "pmid": "19719333", "doi": "10.2165/11317010-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19719333/", "publicSourceType": "PMID" }, { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-20.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Combination risks serotonin syndrome.", "clinicalSignificance": "St. John's Wort plus SSRI is a textbook serotonin syndrome trigger.", "managementStrategy": "Do not combine; allow 2-week washout from St. John's Wort.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Paroxetine", "supplementBName": "L-Tryptophan", "interactionType": "contraindicated", "severity": "dangerous", "description": "L-Tryptophan is the upstream precursor to serotonin. Combined with paroxetine's potent serotonin reuptake blockade, supplemental L-tryptophan can push synaptic serotonin to toxic levels and trigger serotonin syndrome (agitation, tremor, sweating, hyperthermia, clonus).", "recommendation": "Do not take L-tryptophan supplements with paroxetine. Dietary protein-bound tryptophan is fine; concentrated supplemental doses are the issue.", "minimumTimeSeparation": null, "mechanism": "L-Tryptophan is converted to 5-HTP then serotonin. Paroxetine blocks the serotonin transporter; both inputs raise synaptic serotonin to potentially toxic concentrations.", "evidenceLevel": "strong", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-20.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs. 2009;69(13):1777-98.", "pmid": "19719333", "doi": "10.2165/11317010-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19719333/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Combination risks serotonin syndrome.", "clinicalSignificance": "Tryptophan supplement plus paroxetine can drive serotonin toxicity.", "managementStrategy": "Do not combine; food tryptophan is fine, supplements are not.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Paroxetine", "supplementBName": "SAMe", "interactionType": "caution", "severity": "serious", "description": "SAMe has independent serotonergic and antidepressant activity. Combined with paroxetine, the additive serotonergic effect raises the risk of serotonin syndrome — agitation, sweating, tremor, hyperreflexia, clonus, and hyperthermia.", "recommendation": "Avoid starting SAMe alongside paroxetine without explicit prescriber approval. If used together, start SAMe at the lowest effective dose and watch for tremor, restlessness, sweating, or rapid heart rate.", "minimumTimeSeparation": null, "mechanism": "SAMe modulates monoamine neurotransmission with measurable antidepressant activity. Combined with paroxetine's SERT blockade, the additive serotonergic effect can drive postsynaptic toxicity.", "evidenceLevel": "emerging", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-20.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Sarris J, Murphy J, Mischoulon D, et al. Adjunctive S-adenosylmethionine (SAMe) in treating non-remittent major depressive disorder: An 8-week double-blind, randomized, controlled trial. Eur Neuropsychopharmacol. 2018;28(10):1126-1136.", "pmid": "30115553", "doi": "10.1016/j.euroneuro.2018.07.098", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30115553/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Additive serotonergic activity raises serotonin syndrome risk.", "clinicalSignificance": "SAMe plus paroxetine can push serotonergic tone into toxic range.", "managementStrategy": "Avoid; if needed, start SAMe at lowest dose and monitor.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Citalopram", "supplementBName": "L-Tryptophan", "interactionType": "contraindicated", "severity": "dangerous", "description": "L-Tryptophan is the upstream precursor to serotonin. Combined with citalopram's serotonin reuptake blockade, supplemental tryptophan can push synaptic serotonin to toxic levels and trigger serotonin syndrome (agitation, tremor, sweating, hyperthermia, clonus).", "recommendation": "Do not take L-tryptophan supplements with citalopram. Food intake of tryptophan is fine; concentrated supplemental doses are the issue.", "minimumTimeSeparation": null, "mechanism": "L-Tryptophan is converted to 5-HTP and then serotonin throughout the body. Citalopram blocks SERT; combined, both inputs raise synaptic serotonin to potentially toxic concentrations.", "evidenceLevel": "strong", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-20.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs. 2009;69(13):1777-98.", "pmid": "19719333", "doi": "10.2165/11317010-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19719333/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Combination risks serotonin syndrome.", "clinicalSignificance": "Tryptophan plus citalopram can drive serotonin toxicity.", "managementStrategy": "Do not combine; food tryptophan is fine.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Citalopram", "supplementBName": "SAMe", "interactionType": "caution", "severity": "serious", "description": "SAMe has independent serotonergic and antidepressant activity. Combined with citalopram, the additive serotonergic effect raises the risk of serotonin syndrome — agitation, sweating, tremor, hyperreflexia, clonus, and hyperthermia.", "recommendation": "Do not start SAMe alongside citalopram without explicit prescriber approval. If used together, start SAMe at the lowest dose and watch for tremor, restlessness, sweating, or rapid heart rate.", "minimumTimeSeparation": null, "mechanism": "SAMe modulates monoamine neurotransmission with measurable antidepressant activity. Combined with citalopram's SERT blockade, additive serotonergic activity can drive postsynaptic toxicity.", "evidenceLevel": "emerging", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-20.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Sarris J, Murphy J, Mischoulon D, et al. Adjunctive S-adenosylmethionine (SAMe) in treating non-remittent major depressive disorder: An 8-week double-blind, randomized, controlled trial. Eur Neuropsychopharmacol. 2018;28(10):1126-1136.", "pmid": "30115553", "doi": "10.1016/j.euroneuro.2018.07.098", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30115553/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Additive serotonergic activity raises serotonin syndrome risk.", "clinicalSignificance": "SAMe plus citalopram can push serotonergic tone into toxic range.", "managementStrategy": "Avoid; if needed, start SAMe at lowest dose and monitor.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Trazodone", "supplementBName": "St. John's Wort", "interactionType": "caution", "severity": "serious", "description": "St. John's Wort has SSRI-like activity and induces CYP3A4, which is the primary enzyme that metabolizes trazodone. The combination both adds serotonergic load (risking serotonin syndrome) and accelerates trazodone clearance, potentially undercutting its sleep and mood benefit.", "recommendation": "Avoid St. John's Wort with trazodone. If you have been taking it, allow a 2-week washout before starting trazodone and avoid restarting it during treatment.", "minimumTimeSeparation": null, "mechanism": "St. John's Wort constituents inhibit monoamine reuptake (serotonergic activity) and induce CYP3A4. Trazodone is metabolized to mCPP by CYP3A4; induction raises mCPP levels, which is itself a serotonin receptor agonist, while clearing parent drug faster.", "evidenceLevel": "moderate", "sources": [ { "text": "Rotzinger S, Fang J, Baker GB. Trazodone is metabolized to m-chlorophenylpiperazine by CYP3A4 from human sources. Drug Metab Dispos. 1998;26(6):572-5.", "pmid": "9616194", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9616194/", "publicSourceType": "PMID" }, { "text": "Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs. 2009;69(13):1777-98.", "pmid": "19719333", "doi": "10.2165/11317010-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19719333/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Combination raises serotonin syndrome risk and disrupts trazodone metabolism.", "clinicalSignificance": "St. John's Wort adds serotonergic load to trazodone and changes mCPP exposure via CYP3A4 induction.", "managementStrategy": "Avoid the combination.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Trazodone", "supplementBName": "L-Tryptophan", "interactionType": "contraindicated", "severity": "dangerous", "description": "L-Tryptophan is the upstream serotonin precursor. Trazodone is a serotonin reuptake inhibitor and 5-HT2A antagonist with active metabolite mCPP that is itself a serotonin receptor agonist. Combined with supplemental tryptophan, synaptic serotonin can rise to toxic levels, with risk of serotonin syndrome (tremor, agitation, hyperthermia, clonus).", "recommendation": "Do not take L-tryptophan supplements with trazodone. Food sources of tryptophan are fine.", "minimumTimeSeparation": null, "mechanism": "L-Tryptophan is decarboxylated to serotonin. Trazodone blocks SERT and its mCPP metabolite agonizes 5-HT receptors. Combined, supply and signal both rise, risking 5-HT receptor overstimulation.", "evidenceLevel": "moderate", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-20.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Rotzinger S, Fang J, Baker GB. Trazodone is metabolized to m-chlorophenylpiperazine by CYP3A4 from human sources. Drug Metab Dispos. 1998;26(6):572-5.", "pmid": "9616194", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9616194/", "publicSourceType": "PMID" } ], "clinicalSeverity": "contraindicated", "directionality": "bidirectional", "effect": "Combination risks serotonin syndrome.", "clinicalSignificance": "Serotonin precursor plus trazodone can drive serotonin toxicity.", "managementStrategy": "Do not combine; food tryptophan is fine.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Trazodone", "supplementBName": "SAMe", "interactionType": "caution", "severity": "serious", "description": "SAMe has independent serotonergic and antidepressant activity. Combined with trazodone (a serotonin reuptake inhibitor whose active metabolite mCPP also agonizes serotonin receptors), the additive serotonergic load raises the risk of serotonin syndrome.", "recommendation": "Avoid starting SAMe alongside trazodone without explicit prescriber approval. If used together, start SAMe at the lowest effective dose and watch for tremor, sweating, restlessness, or fast heart rate.", "minimumTimeSeparation": null, "mechanism": "SAMe modulates monoamine neurotransmission. Trazodone blocks SERT and forms mCPP, a serotonin agonist. Combined serotonergic effects can drive postsynaptic toxicity.", "evidenceLevel": "emerging", "sources": [ { "text": "Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-20.", "pmid": "15784664", "doi": "10.1056/NEJMra041867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15784664/", "publicSourceType": "PMID" }, { "text": "Sarris J, Murphy J, Mischoulon D, et al. Adjunctive S-adenosylmethionine (SAMe) in treating non-remittent major depressive disorder: An 8-week double-blind, randomized, controlled trial. Eur Neuropsychopharmacol. 2018;28(10):1126-1136.", "pmid": "30115553", "doi": "10.1016/j.euroneuro.2018.07.098", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30115553/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Additive serotonergic activity raises serotonin syndrome risk.", "clinicalSignificance": "SAMe plus trazodone can push serotonergic tone into toxic range.", "managementStrategy": "Avoid combination; if used, start SAMe low and monitor.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Trazodone", "supplementBName": "Valerian Root", "interactionType": "caution", "severity": "moderate", "description": "Valerian root acts on GABA-A receptors via valerenic acid, producing sedation. Trazodone is itself a strongly sedating antidepressant commonly used for sleep. Combined CNS depression can produce excessive next-day grogginess, impaired driving, falls, and confusion, particularly in older adults.", "recommendation": "Avoid valerian root with trazodone, especially if you take trazodone for sleep. If both are unavoidable, do not drive or operate machinery, and watch for daytime drowsiness and unsteady gait.", "minimumTimeSeparation": null, "mechanism": "Valerenic acid is a positive allosteric modulator of GABA-A receptors. Trazodone produces sedation through H1 histamine antagonism and 5-HT2A antagonism. Combined CNS depression compounds drowsiness and psychomotor impairment.", "evidenceLevel": "emerging", "sources": [ { "text": "Yuan CS, Mehendale S, Xiao Y, Aung HH, Xie JT, Ang-Lee MK. The gamma-aminobutyric acidergic effects of valerian and valerenic acid on rat brainstem neuronal activity. Anesth Analg. 2004;98(2):353-358.", "pmid": "14742369", "doi": "10.1213/01.ane.0000096189.70405.a5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14742369/", "publicSourceType": "PMID" }, { "text": "Brunnauer A, Laux G. Driving Under the Influence of Antidepressants: A Systematic Review and Update of the Evidence of Experimental and Controlled Clinical Studies. Pharmacopsychiatry. 2017;50(5):173-181.", "pmid": "28718182", "doi": "10.1055/s-0043-113572", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28718182/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive sedation increases drowsiness, fall risk, and impairment.", "clinicalSignificance": "Stacking sedatives at bedtime can produce dangerous next-day impairment.", "managementStrategy": "Avoid valerian with trazodone; do not drive if combined.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Trazodone", "supplementBName": "Ashwagandha", "interactionType": "caution", "severity": "moderate", "description": "Ashwagandha contains compounds with GABA-A agonist activity that produce mild sedation. Trazodone is a strongly sedating antidepressant. Combined CNS depression can produce excessive drowsiness, particularly when both are taken at bedtime.", "recommendation": "If you take trazodone for sleep, avoid adding ashwagandha at the same time. If used together, do not drive the next morning until you know how the combination affects you.", "minimumTimeSeparation": null, "mechanism": "Withania somnifera extract has GABA-mimetic actions at GABA-A receptors, demonstrated in electrophysiological studies. Trazodone produces sedation through H1 histamine and 5-HT2A antagonism. The two mechanisms produce additive CNS depression.", "evidenceLevel": "emerging", "sources": [ { "text": "Yin H, Cho DH, Park SJ, Han SK. GABA-mimetic actions of Withania somnifera on substantia gelatinosa neurons of the trigeminal subnucleus caudalis in mice. Am J Chin Med. 2013;41(5):1043-51.", "pmid": "24117067", "doi": "10.1142/S0192415X13500705", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24117067/", "publicSourceType": "PMID" }, { "text": "Brunnauer A, Laux G. Driving Under the Influence of Antidepressants: A Systematic Review and Update of the Evidence of Experimental and Controlled Clinical Studies. Pharmacopsychiatry. 2017;50(5):173-181.", "pmid": "28718182", "doi": "10.1055/s-0043-113572", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28718182/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive sedation increases drowsiness.", "clinicalSignificance": "Two sedative substances at bedtime compound next-day grogginess and fall risk.", "managementStrategy": "Separate timing; avoid stacking at bedtime.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Trazodone", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Trazodone produces strong sedation through histamine H1 and 5-HT2A blockade. Alcohol is a CNS depressant. Combined use produces marked additive impairment of psychomotor function, alertness, and driving ability — documented to be most pronounced with sedating antidepressants like trazodone.", "recommendation": "Avoid alcohol while taking trazodone, especially before driving. If you do drink, keep intake low and do not drive or operate machinery. Take trazodone at bedtime, not before social drinking.", "minimumTimeSeparation": null, "mechanism": "Trazodone sedates through H1 antihistamine and 5-HT2A antagonism. Alcohol potentiates GABA-A receptors and inhibits NMDA, depressing CNS function. The two mechanisms produce additive sedation and cognitive impairment.", "evidenceLevel": "strong", "sources": [ { "text": "Brunnauer A, Laux G. Driving Under the Influence of Antidepressants: A Systematic Review and Update of the Evidence of Experimental and Controlled Clinical Studies. Pharmacopsychiatry. 2017;50(5):173-181.", "pmid": "28718182", "doi": "10.1055/s-0043-113572", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28718182/", "publicSourceType": "PMID" }, { "text": "Rotzinger S, Fang J, Baker GB. Trazodone is metabolized to m-chlorophenylpiperazine by CYP3A4 from human sources. Drug Metab Dispos. 1998;26(6):572-5.", "pmid": "9616194", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9616194/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Combined CNS depression markedly impairs psychomotor function.", "clinicalSignificance": "Sedating antidepressant plus alcohol produces dangerous additive impairment.", "managementStrategy": "Avoid alcohol with trazodone; do not drive if combined.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Citalopram", "supplementBName": "Magnesium Citrate", "interactionType": "synergy", "severity": "info", "description": "Citalopram produces dose-dependent QT interval prolongation and carries a black-box warning at doses above 40 mg/day (or 20 mg in older adults). Hypomagnesemia is an independent QT prolongation risk and amplifies citalopram's cardiac effect. Maintaining adequate magnesium intake helps protect against torsades de pointes in this setting.", "recommendation": "If you take citalopram, ensure adequate magnesium intake from diet or a modest supplement (200-350 mg/day supplemental elemental magnesium from magnesium citrate is typical). Avoid letting magnesium fall low, particularly if you also take a diuretic or PPI that depletes magnesium.", "minimumTimeSeparation": null, "mechanism": "Citalopram and its metabolite didesmethylcitalopram block the cardiac hERG/IKr potassium channel, prolonging QT in a dose-dependent way. Hypomagnesemia destabilizes the same repolarization current; adequate magnesium supports normal repolarization and reduces torsades risk.", "evidenceLevel": "moderate", "sources": [ { "text": "Beach SR, Kostis WJ, Celano CM, et al. Meta-analysis of selective serotonin reuptake inhibitor-associated QTc prolongation. J Clin Psychiatry. 2014;75(5):e441-9.", "pmid": "24922496", "doi": "10.4088/JCP.13r08672", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24922496/", "publicSourceType": "PMID" }, { "text": "Digby G, Machaalany J, Malik P, et al. Multifactorial QT interval prolongation. Cardiol J. 2010;17(2):184-8.", "pmid": "20544619", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20544619/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Adequate magnesium status reduces citalopram's QT prolongation risk.", "clinicalSignificance": "Letting magnesium fall low magnifies citalopram's torsades risk; maintaining magnesium is protective.", "managementStrategy": "Keep magnesium intake adequate; correct deficiency before pushing citalopram dose.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Atorvastatin", "supplementBName": "Coenzyme Q10", "interactionType": "synergy", "severity": "info", "description": "Atorvastatin can lower circulating CoQ10 because cholesterol and CoQ10 synthesis share the mevalonate pathway. Lower CoQ10 is one proposed contributor to statin-associated muscle symptoms, although clinical trials of supplementation have mixed results. CoQ10 does not appear to reduce atorvastatin's LDL-lowering effect.", "recommendation": "Consider CoQ10 100-200 mg/day if you develop muscle aches while taking atorvastatin, especially after your prescriber has ruled out more urgent causes. Do not stop atorvastatin on your own; use CoQ10 as a symptom-support option while monitoring whether muscle symptoms improve.", "minimumTimeSeparation": null, "mechanism": "Atorvastatin inhibits HMG-CoA reductase, reducing mevalonate-derived intermediates needed for endogenous CoQ10 synthesis. CoQ10 supports mitochondrial electron transport in skeletal muscle, so depletion could plausibly worsen muscle energy metabolism.", "evidenceLevel": "moderate", "sources": [ { "text": "Banach M, Serban C, Sahebkar A, Ursoniu S, Rysz J, Muntner P, et al. Effects of coenzyme Q10 on statin-induced myopathy: a meta-analysis of randomized controlled trials. Mayo Clin Proc. 2015;90(1):24-34.", "pmid": "25440725", "doi": "10.1016/j.mayocp.2014.08.021", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25440725/", "publicSourceType": "PMID" }, { "text": "Qu H, Meng YY, Chai H, Liang F, Zhang JY, Gao ZY, et al. The effect of statin treatment on circulating coenzyme Q10 concentrations: an updated meta-analysis of randomized controlled trials. Eur J Med Res. 2018;23(1):57.", "pmid": "30414615", "doi": "10.1186/s40001-018-0353-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30414615/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Atorvastatin can reduce CoQ10 status, and CoQ10 may modestly help statin-associated muscle symptoms in some patients.", "clinicalSignificance": "Muscle symptoms are a common reason people stop statins, so a low-risk symptom-support option may help adherence.", "managementStrategy": "Try CoQ10 100-200 mg/day for muscle symptoms while continuing standard statin monitoring.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Lovastatin", "supplementBName": "Coenzyme Q10", "interactionType": "synergy", "severity": "info", "description": "Lovastatin can lower CoQ10 production by blocking the mevalonate pathway. CoQ10 depletion is a plausible contributor to statin-associated myalgia, though supplementation benefits are inconsistent across trials. CoQ10 is generally used as supportive therapy rather than as a replacement for statin adjustment.", "recommendation": "Consider CoQ10 100-200 mg/day if you have muscle symptoms on lovastatin and your clinician agrees it is reasonable. Seek medical advice promptly for severe weakness, dark urine, or rapidly worsening muscle pain.", "minimumTimeSeparation": null, "mechanism": "Lovastatin inhibits HMG-CoA reductase upstream of both cholesterol and CoQ10 biosynthesis. Lower CoQ10 may impair mitochondrial oxidative phosphorylation in muscle, which is one proposed mechanism for statin-associated muscle symptoms.", "evidenceLevel": "moderate", "sources": [ { "text": "Banach M, Serban C, Sahebkar A, Ursoniu S, Rysz J, Muntner P, et al. Effects of coenzyme Q10 on statin-induced myopathy: a meta-analysis of randomized controlled trials. Mayo Clin Proc. 2015;90(1):24-34.", "pmid": "25440725", "doi": "10.1016/j.mayocp.2014.08.021", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25440725/", "publicSourceType": "PMID" }, { "text": "Qu H, Meng YY, Chai H, Liang F, Zhang JY, Gao ZY, et al. The effect of statin treatment on circulating coenzyme Q10 concentrations: an updated meta-analysis of randomized controlled trials. Eur J Med Res. 2018;23(1):57.", "pmid": "30414615", "doi": "10.1186/s40001-018-0353-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30414615/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Lovastatin can lower CoQ10 levels, and CoQ10 may reduce muscle symptoms for some statin users.", "clinicalSignificance": "A trial of CoQ10 may help tolerate therapy, but persistent or severe myopathy symptoms need clinical evaluation.", "managementStrategy": "Use CoQ10 as adjunctive symptom support and monitor muscle symptoms rather than stopping lovastatin abruptly.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Lovastatin", "supplementBName": "Coenzyme Q10 Ubiquinol", "interactionType": "synergy", "severity": "info", "description": "Lovastatin can reduce endogenous CoQ10 synthesis, and ubiquinol is the reduced form of CoQ10 used in many supplements. Restoring CoQ10 status may help some people with statin-associated muscle symptoms, but the clinical response is not guaranteed. Ubiquinol should be viewed as adjunctive symptom support.", "recommendation": "If muscle aches occur on lovastatin, consider ubiquinol 100-200 mg/day after discussing symptoms and other causes with your prescriber. Get urgent help for severe muscle pain, weakness, fever, or dark urine.", "minimumTimeSeparation": null, "mechanism": "Lovastatin blocks HMG-CoA reductase and lowers mevalonate-pathway production of CoQ10. Ubiquinol replenishes the reduced CoQ10 pool involved in mitochondrial electron transport and antioxidant defense.", "evidenceLevel": "moderate", "sources": [ { "text": "Banach M, Serban C, Sahebkar A, Ursoniu S, Rysz J, Muntner P, et al. Effects of coenzyme Q10 on statin-induced myopathy: a meta-analysis of randomized controlled trials. Mayo Clin Proc. 2015;90(1):24-34.", "pmid": "25440725", "doi": "10.1016/j.mayocp.2014.08.021", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25440725/", "publicSourceType": "PMID" }, { "text": "Qu H, Meng YY, Chai H, Liang F, Zhang JY, Gao ZY, et al. The effect of statin treatment on circulating coenzyme Q10 concentrations: an updated meta-analysis of randomized controlled trials. Eur J Med Res. 2018;23(1):57.", "pmid": "30414615", "doi": "10.1186/s40001-018-0353-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30414615/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Lovastatin may deplete CoQ10, while ubiquinol may help replenish reduced CoQ10 stores.", "clinicalSignificance": "This may matter for people who develop statin-associated muscle symptoms and want to preserve statin adherence.", "managementStrategy": "Consider ubiquinol 100-200 mg/day as adjunctive support and reassess muscle symptoms over several weeks.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Pravastatin", "supplementBName": "Coenzyme Q10 Ubiquinol", "interactionType": "synergy", "severity": "info", "description": "Pravastatin is less lipophilic than several other statins but still inhibits the mevalonate pathway that supplies CoQ10 precursors. Ubiquinol may help replenish CoQ10 stores and may reduce muscle symptoms in some statin-treated patients. Evidence is mixed, so this is a supportive option rather than a proven fix.", "recommendation": "Consider ubiquinol 100-200 mg/day if you have pravastatin-associated muscle aches and your clinician has checked for other causes. Keep taking pravastatin as prescribed unless your prescriber tells you to pause or change it.", "minimumTimeSeparation": null, "mechanism": "Pravastatin inhibits HMG-CoA reductase, reducing mevalonate-pathway output including CoQ10 synthesis. Ubiquinol supplies the reduced form of CoQ10 used in mitochondrial electron transport.", "evidenceLevel": "moderate", "sources": [ { "text": "Banach M, Serban C, Sahebkar A, Ursoniu S, Rysz J, Muntner P, et al. Effects of coenzyme Q10 on statin-induced myopathy: a meta-analysis of randomized controlled trials. Mayo Clin Proc. 2015;90(1):24-34.", "pmid": "25440725", "doi": "10.1016/j.mayocp.2014.08.021", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25440725/", "publicSourceType": "PMID" }, { "text": "Qu H, Meng YY, Chai H, Liang F, Zhang JY, Gao ZY, et al. The effect of statin treatment on circulating coenzyme Q10 concentrations: an updated meta-analysis of randomized controlled trials. Eur J Med Res. 2018;23(1):57.", "pmid": "30414615", "doi": "10.1186/s40001-018-0353-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30414615/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Pravastatin can lower CoQ10 status, and ubiquinol may help muscle symptoms in selected patients.", "clinicalSignificance": "The main value is improving tolerability when mild muscle symptoms threaten statin adherence.", "managementStrategy": "Use ubiquinol as a trial adjunct and reassess symptoms without stopping pravastatin independently.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Simvastatin", "supplementBName": "Coenzyme Q10", "interactionType": "synergy", "severity": "info", "description": "Simvastatin can reduce circulating CoQ10 by inhibiting the same pathway used to make cholesterol. CoQ10 supplementation has mixed but plausible evidence for reducing statin-associated myalgia. It does not treat dangerous rhabdomyolysis and should not delay evaluation of severe symptoms.", "recommendation": "Consider CoQ10 100-200 mg/day if you have mild muscle aches on simvastatin and want a low-risk adjunct. Report severe muscle pain, weakness, or dark urine immediately, especially if you recently added another medication or supplement.", "minimumTimeSeparation": null, "mechanism": "Simvastatin inhibits HMG-CoA reductase, lowering mevalonate availability for CoQ10 biosynthesis. CoQ10 is needed for mitochondrial electron transport, and depletion may contribute to muscle energy stress.", "evidenceLevel": "moderate", "sources": [ { "text": "Banach M, Serban C, Sahebkar A, Ursoniu S, Rysz J, Muntner P, et al. Effects of coenzyme Q10 on statin-induced myopathy: a meta-analysis of randomized controlled trials. Mayo Clin Proc. 2015;90(1):24-34.", "pmid": "25440725", "doi": "10.1016/j.mayocp.2014.08.021", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25440725/", "publicSourceType": "PMID" }, { "text": "Qu H, Meng YY, Chai H, Liang F, Zhang JY, Gao ZY, et al. The effect of statin treatment on circulating coenzyme Q10 concentrations: an updated meta-analysis of randomized controlled trials. Eur J Med Res. 2018;23(1):57.", "pmid": "30414615", "doi": "10.1186/s40001-018-0353-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30414615/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "aAffectsB", "effect": "Simvastatin may lower CoQ10 levels, while supplemental CoQ10 may help mild muscle symptoms.", "clinicalSignificance": "Symptom support can improve adherence, but severe muscle toxicity needs prompt evaluation.", "managementStrategy": "Try CoQ10 for mild symptoms and escalate care quickly for severe or systemic muscle symptoms.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Lovastatin", "supplementBName": "Vitamin B3", "interactionType": "caution", "severity": "moderate", "description": "High-dose Vitamin B3 as niacin can add muscle, liver, and glucose-related adverse effects to statin therapy. Large statin-era niacin trials found no cardiovascular outcome benefit from adding high-dose niacin, while adverse events increased. Low-dose nutritional niacin is different from pharmacologic niacin doses.", "recommendation": "Avoid high-dose niacin, especially 500 mg/day or more, with lovastatin unless it is specifically prescribed and monitored. If the combination is used, monitor liver enzymes, glucose control, and any new muscle pain or weakness.", "minimumTimeSeparation": null, "mechanism": "Both statins and pharmacologic niacin can contribute to myopathy and liver enzyme elevations. Niacin can also worsen glycemic control, creating additional risk in patients with diabetes or metabolic syndrome.", "evidenceLevel": "strong", "sources": [ { "text": "Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, Koprowicz K, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255-2267.", "pmid": "22085343", "doi": "10.1056/NEJMoa1107579", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22085343/", "publicSourceType": "PMID" }, { "text": "Landray MJ, Haynes R, Hopewell JC, Parish S, Aung T, Tomson J, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371(3):203-212.", "pmid": "25014686", "doi": "10.1056/NEJMoa1300955", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25014686/", "publicSourceType": "PMID" }, { "text": "Haynes R, Valdes-Marquez E, Hopewell JC, Chen F, Li J, Parish S, et al. Serious Adverse Effects of Extended-release Niacin/Laropiprant: Results From the Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) Trial. Clin Ther. 2019;41(9):1767-1777.", "pmid": "31447131", "doi": "10.1016/j.clinthera.2019.06.012", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31447131/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose niacin adds adverse-effect burden to lovastatin without proven outcome benefit for most statin-treated patients.", "clinicalSignificance": "The combination can create avoidable muscle, liver, and glucose problems.", "managementStrategy": "Avoid pharmacologic niacin unless prescribed; monitor CK symptoms, liver enzymes, and glucose if used.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Pravastatin", "supplementBName": "Vitamin B3", "interactionType": "caution", "severity": "moderate", "description": "High-dose Vitamin B3 as niacin can increase adverse effects when added to statin therapy, even though pravastatin has fewer CYP3A4 interaction concerns. Large trials of niacin added to statins did not show cardiovascular benefit and did show more adverse events, including glucose and liver-related problems. Ordinary dietary-dose niacin is not the concern.", "recommendation": "Do not add high-dose niacin to pravastatin unless your prescriber has a specific reason and monitoring plan. If used, monitor liver enzymes, blood sugar, and any muscle pain or weakness.", "minimumTimeSeparation": null, "mechanism": "Pharmacologic niacin can cause hepatotoxicity, worsen glycemic control, and contribute to myopathy. These risks can stack with statin-associated muscle and liver monitoring concerns even when the statin is not CYP3A4-metabolized.", "evidenceLevel": "strong", "sources": [ { "text": "Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, Koprowicz K, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255-2267.", "pmid": "22085343", "doi": "10.1056/NEJMoa1107579", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22085343/", "publicSourceType": "PMID" }, { "text": "Landray MJ, Haynes R, Hopewell JC, Parish S, Aung T, Tomson J, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371(3):203-212.", "pmid": "25014686", "doi": "10.1056/NEJMoa1300955", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25014686/", "publicSourceType": "PMID" }, { "text": "Haynes R, Valdes-Marquez E, Hopewell JC, Chen F, Li J, Parish S, et al. Serious Adverse Effects of Extended-release Niacin/Laropiprant: Results From the Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) Trial. Clin Ther. 2019;41(9):1767-1777.", "pmid": "31447131", "doi": "10.1016/j.clinthera.2019.06.012", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31447131/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "High-dose niacin can add muscle, liver, and glucose risks to pravastatin therapy.", "clinicalSignificance": "Most patients do not gain cardiovascular benefit from this combination but may gain adverse effects.", "managementStrategy": "Avoid unsupervised pharmacologic niacin and monitor labs and muscle symptoms if prescribed.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Lovastatin", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's Wort can induce CYP3A4 and P-glycoprotein, which may lower exposure to CYP3A4-metabolized statins. Human data show a major reduction in simvastatin exposure, and lovastatin shares substantial CYP3A4 first-pass metabolism. This can make cholesterol control less reliable.", "recommendation": "Avoid St. John's Wort while taking lovastatin unless your prescriber has explicitly approved it. If you have already combined them, tell your clinician and consider checking lipids after stopping St. John's Wort because induction can persist for days to weeks.", "minimumTimeSeparation": null, "mechanism": "Hyperforin in St. John's Wort activates pregnane X receptor signaling, inducing intestinal and hepatic CYP3A4 and P-gp. Lovastatin is a CYP3A4 substrate with extensive first-pass metabolism, so induction can reduce active statin exposure.", "evidenceLevel": "moderate", "sources": [ { "text": "Sugimoto K, Ohmori M, Tsuruoka S, Nishiki K, Kawaguchi A, Harada K, et al. Different effects of St John's wort on the pharmacokinetics of simvastatin and pravastatin. Clin Pharmacol Ther. 2001;70(6):518-524.", "pmid": "11753267", "doi": "10.1067/mcp.2001.120025", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11753267/", "publicSourceType": "PMID" }, { "text": "Zhou S, Chan E, Pan SQ, Huang M, Lee EJ. Pharmacokinetic interactions of drugs with St John's wort. J Psychopharmacol. 2004;18(2):262-276.", "pmid": "15260917", "doi": "10.1177/0269881104042632", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15260917/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St. John's Wort may reduce lovastatin exposure and weaken LDL-lowering efficacy.", "clinicalSignificance": "Reduced statin exposure can leave high-risk patients undertreated without obvious symptoms.", "managementStrategy": "Avoid the combination and reassess lipid control if St. John's Wort was used.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Atorvastatin", "supplementBName": "Berberine", "interactionType": "caution", "severity": "moderate", "description": "Berberine has human evidence of inhibiting CYP3A4 activity after repeated dosing, and atorvastatin is partly cleared through CYP3A4. This could raise atorvastatin exposure and increase the chance of muscle symptoms, especially at higher statin doses or when other interacting drugs are present. Direct clinical outcome data for this exact pair are limited.", "recommendation": "Do not start high-dose berberine with atorvastatin without a monitoring plan. Watch for new muscle pain, weakness, dark urine, or unusual fatigue, and consider using a non-CYP3A4 statin strategy if berberine is necessary.", "minimumTimeSeparation": null, "mechanism": "Repeated berberine dosing reduced CYP3A4 probe activity in humans. Inhibition of CYP3A4 can increase exposure to atorvastatin and active metabolites, while experimental data suggest berberine-statin combinations may also affect hERG channel activity.", "evidenceLevel": "emerging", "sources": [ { "text": "Guo Y, Chen Y, Tan ZR, Klaassen CD, Zhou HH. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol. 2012;68(2):213-217.", "pmid": "21870106", "doi": "10.1007/s00228-011-1108-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21870106/", "publicSourceType": "PMID" }, { "text": "Feng P, Zhao L, Guo F, Zhang B, Fang L, Zhan G, et al. The enhancement of cardiotoxicity that results from inhibiton of CYP 3A4 activity and hERG channel by berberine in combination with statins. Chem Biol Interact. 2018;293:115-123.", "pmid": "30086269", "doi": "10.1016/j.cbi.2018.07.022", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30086269/", "publicSourceType": "PMID" }, { "text": "Hirota T, Fujita Y, Ieiri I. An updated review of pharmacokinetic drug interactions and pharmacogenetics of statins. Expert Opin Drug Metab Toxicol. 2020;16(9):809-822.", "pmid": "32729746", "doi": "10.1080/17425255.2020.1801634", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32729746/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Berberine may increase atorvastatin exposure through CYP3A4 inhibition.", "clinicalSignificance": "Higher atorvastatin exposure can increase the likelihood of muscle toxicity in susceptible patients.", "managementStrategy": "Use cautiously, avoid adding other CYP3A4 inhibitors, and monitor muscle symptoms closely.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Lovastatin", "supplementBName": "Berberine", "interactionType": "caution", "severity": "moderate", "description": "Lovastatin is highly dependent on CYP3A4 metabolism, and berberine has human evidence of inhibiting CYP3A4 after repeated dosing. This creates a plausible risk of increased lovastatin exposure and muscle toxicity, especially with high lovastatin doses or additional CYP3A4 inhibitors. Human clinical outcome data for this exact combination are limited.", "recommendation": "Avoid adding high-dose berberine to lovastatin unless your prescriber agrees and knows your full medication list. Report muscle pain, weakness, dark urine, or marked fatigue promptly.", "minimumTimeSeparation": null, "mechanism": "Berberine can reduce CYP3A4 activity in humans. Lovastatin undergoes extensive CYP3A4-mediated first-pass metabolism, so reduced enzyme activity can raise systemic statin exposure and myopathy risk.", "evidenceLevel": "emerging", "sources": [ { "text": "Guo Y, Chen Y, Tan ZR, Klaassen CD, Zhou HH. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol. 2012;68(2):213-217.", "pmid": "21870106", "doi": "10.1007/s00228-011-1108-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21870106/", "publicSourceType": "PMID" }, { "text": "Feng P, Zhao L, Guo F, Zhang B, Fang L, Zhan G, et al. The enhancement of cardiotoxicity that results from inhibiton of CYP 3A4 activity and hERG channel by berberine in combination with statins. Chem Biol Interact. 2018;293:115-123.", "pmid": "30086269", "doi": "10.1016/j.cbi.2018.07.022", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30086269/", "publicSourceType": "PMID" }, { "text": "Hirota T, Fujita Y, Ieiri I. An updated review of pharmacokinetic drug interactions and pharmacogenetics of statins. Expert Opin Drug Metab Toxicol. 2020;16(9):809-822.", "pmid": "32729746", "doi": "10.1080/17425255.2020.1801634", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32729746/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Berberine may raise lovastatin exposure by inhibiting CYP3A4.", "clinicalSignificance": "Lovastatin exposure is sensitive to CYP3A4 inhibition, which can increase myopathy risk.", "managementStrategy": "Avoid unsupervised high-dose berberine and monitor closely if the combination is used.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Simvastatin", "supplementBName": "Berberine", "interactionType": "caution", "severity": "moderate", "description": "Simvastatin is strongly affected by CYP3A4 inhibitors, and berberine has human evidence of inhibiting CYP3A4 activity with repeated dosing. This may increase simvastatin exposure and muscle toxicity risk, although direct clinical trials of this exact supplement-drug pair are lacking. Risk is higher with higher simvastatin doses or additional interacting medications.", "recommendation": "Avoid high-dose berberine with simvastatin unless your prescriber has reviewed the interaction risk. Stop and seek care promptly for severe muscle pain, weakness, or dark urine.", "minimumTimeSeparation": null, "mechanism": "Berberine can inhibit CYP3A4 activity in humans. Simvastatin is extensively metabolized by CYP3A4, so inhibition can increase systemic exposure to simvastatin and simvastatin acid.", "evidenceLevel": "emerging", "sources": [ { "text": "Guo Y, Chen Y, Tan ZR, Klaassen CD, Zhou HH. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol. 2012;68(2):213-217.", "pmid": "21870106", "doi": "10.1007/s00228-011-1108-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21870106/", "publicSourceType": "PMID" }, { "text": "Feng P, Zhao L, Guo F, Zhang B, Fang L, Zhan G, et al. The enhancement of cardiotoxicity that results from inhibiton of CYP 3A4 activity and hERG channel by berberine in combination with statins. Chem Biol Interact. 2018;293:115-123.", "pmid": "30086269", "doi": "10.1016/j.cbi.2018.07.022", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30086269/", "publicSourceType": "PMID" }, { "text": "Hirota T, Fujita Y, Ieiri I. An updated review of pharmacokinetic drug interactions and pharmacogenetics of statins. Expert Opin Drug Metab Toxicol. 2020;16(9):809-822.", "pmid": "32729746", "doi": "10.1080/17425255.2020.1801634", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32729746/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Berberine may increase simvastatin exposure and the chance of muscle toxicity.", "clinicalSignificance": "Simvastatin is one of the statins most vulnerable to CYP3A4-mediated interactions.", "managementStrategy": "Avoid unsupervised high-dose berberine and monitor for muscle toxicity if co-used.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Atorvastatin", "supplementBName": "Green Tea Extract", "interactionType": "conflict", "severity": "moderate", "description": "Green tea extract reduced atorvastatin peak concentration and overall exposure in a human crossover study. The effect appears related to reduced absorption rather than faster elimination, and could matter if LDL control is marginal. Brewed green tea is likely less concerning than concentrated extract capsules.", "recommendation": "Avoid taking concentrated green tea extract at the same time as atorvastatin. If you use green tea extract regularly, keep the routine consistent and recheck lipids after starting or stopping it.", "minimumTimeSeparation": null, "mechanism": "Green tea catechins can inhibit intestinal uptake transporters such as OATPs involved in drug absorption. In healthy volunteers, green tea extract lowered atorvastatin Cmax by about one quarter and AUC by about one fifth.", "evidenceLevel": "moderate", "sources": [ { "text": "Abdelkawy KS, Abdelaziz RM, Abdelmageed AM, Donia AM, El-Khodary NM. Effects of Green Tea Extract on Atorvastatin Pharmacokinetics in Healthy Volunteers. Eur J Drug Metab Pharmacokinet. 2020;45(3):351-360.", "pmid": "31997084", "doi": "10.1007/s13318-020-00608-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31997084/", "publicSourceType": "PMID" }, { "text": "Werba JP, Misaka S, Giroli MG, Yamada S, Cavalca V, Kawabe K, et al. Overview of green tea interaction with cardiovascular drugs. Curr Pharm Des. 2015;21(9):1213-1219.", "pmid": "25312732", "doi": "10.2174/1381612820666141013135045", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25312732/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Green tea extract can lower atorvastatin exposure and may reduce LDL-lowering reliability.", "clinicalSignificance": "A silent reduction in statin exposure may show up only as worse lipid control.", "managementStrategy": "Keep green tea extract use consistent, avoid same-time dosing, and recheck LDL after changes.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Rosuvastatin", "supplementBName": "Green Tea Extract", "interactionType": "conflict", "severity": "moderate", "description": "Repeated green tea extract significantly reduced systemic rosuvastatin exposure in healthy volunteers. This could reduce or unpredictably alter rosuvastatin's lipid-lowering effect, especially with concentrated high-EGCG products. The effect may vary by transporter genetics.", "recommendation": "Avoid starting high-dose green tea extract without checking whether your LDL response remains controlled on rosuvastatin. If you use it, keep the dose consistent and recheck lipid labs after starting, stopping, or changing the extract.", "minimumTimeSeparation": null, "mechanism": "Rosuvastatin depends on uptake and efflux transporters including OATP1B1 and BCRP. Green tea catechins can alter transporter activity, and a human study found about a 20% reduction in rosuvastatin exposure after repeated green tea extract.", "evidenceLevel": "moderate", "sources": [ { "text": "Zeng W, Hu M, Lee HK, Wat E, Lau CBS, Ho CS, et al. Effect of Green Tea Extract and Soy Isoflavones on the Pharmacokinetics of Rosuvastatin in Healthy Volunteers. Front Nutr. 2022;9:850318.", "pmid": "35399656", "doi": "10.3389/fnut.2022.850318", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35399656/", "publicSourceType": "PMID" }, { "text": "Werba JP, Misaka S, Giroli MG, Yamada S, Cavalca V, Kawabe K, et al. Overview of green tea interaction with cardiovascular drugs. Curr Pharm Des. 2015;21(9):1213-1219.", "pmid": "25312732", "doi": "10.2174/1381612820666141013135045", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25312732/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Green tea extract may lower rosuvastatin exposure and reduce lipid-lowering consistency.", "clinicalSignificance": "Patients at strict LDL targets may lose control without feeling any symptoms.", "managementStrategy": "Use green tea extract consistently or avoid it, and recheck lipids after changes.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Atorvastatin", "supplementBName": "Ginkgo Biloba", "interactionType": "caution", "severity": "info", "description": "A human study found that high-dose Ginkgo biloba extract modestly lowered atorvastatin exposure, including a larger drop in peak concentration. Short-term cholesterol markers were not meaningfully changed, so the clinical effect is usually small. The concern is mainly inconsistent LDL response when high-dose or poorly standardized extracts are started or stopped.", "recommendation": "Use caution with high-dose ginkgo extract if you depend on tight atorvastatin LDL control. Keep the ginkgo product and dose consistent, and recheck lipids if you start, stop, or substantially change it.", "minimumTimeSeparation": null, "mechanism": "Ginkgo products can variably affect CYP enzymes and drug transporters. In volunteers taking 360 mg/day of Ginkgo biloba extract, atorvastatin AUC and Cmax fell modestly, suggesting altered disposition or absorption.", "evidenceLevel": "emerging", "sources": [ { "text": "Guo CX, Pei Q, Yin JY, Peng XD, Zhou BT, Zhao YC, et al. Effects of Ginkgo biloba extracts on pharmacokinetics and efficacy of atorvastatin based on plasma indices. Xenobiotica. 2012;42(8):784-790.", "pmid": "22381135", "doi": "10.3109/00498254.2012.661100", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22381135/", "publicSourceType": "PMID" }, { "text": "Unger M. Pharmacokinetic drug interactions involving Ginkgo biloba. Drug Metab Rev. 2013;45(3):353-385.", "pmid": "23865865", "doi": "10.3109/03602532.2013.815200", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23865865/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Ginkgo biloba may modestly lower atorvastatin exposure.", "clinicalSignificance": "The effect is usually small but may matter when LDL targets are tight or products are high dose.", "managementStrategy": "Keep ginkgo use consistent and verify lipid response after major changes.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Pravastatin", "supplementBName": "Quercetin", "interactionType": "caution", "severity": "moderate", "description": "Quercetin increased pravastatin exposure in a human study by inhibiting OATP1B1-mediated transport. The average increase was modest, but it could matter in people with other myopathy risks or transporter variants. This is more relevant to high-dose quercetin capsules than ordinary dietary quercetin intake.", "recommendation": "Use high-dose quercetin cautiously with pravastatin, especially if you have kidney disease, a history of statin muscle symptoms, or other interacting drugs. Monitor for new muscle pain or weakness after starting quercetin.", "minimumTimeSeparation": null, "mechanism": "Quercetin competitively inhibits OATP1B1, a hepatic uptake transporter involved in pravastatin disposition. In healthy volunteers, quercetin increased pravastatin AUC and Cmax, consistent with reduced transporter-mediated clearance.", "evidenceLevel": "moderate", "sources": [ { "text": "Wu LX, Guo CX, Chen WQ, Yu J, Qu Q, Chen Y, et al. Inhibition of the organic anion-transporting polypeptide 1B1 by quercetin: an in vitro and in vivo assessment. Br J Clin Pharmacol. 2012;73(5):750-757.", "pmid": "22114872", "doi": "10.1111/j.1365-2125.2011.04150.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22114872/", "publicSourceType": "PMID" }, { "text": "Hirota T, Fujita Y, Ieiri I. An updated review of pharmacokinetic drug interactions and pharmacogenetics of statins. Expert Opin Drug Metab Toxicol. 2020;16(9):809-822.", "pmid": "32729746", "doi": "10.1080/17425255.2020.1801634", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32729746/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Quercetin can modestly increase pravastatin exposure through OATP1B1 inhibition.", "clinicalSignificance": "Higher pravastatin exposure can increase muscle-symptom risk in susceptible patients.", "managementStrategy": "Use high-dose quercetin cautiously and monitor muscle symptoms after initiation.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Atorvastatin", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "Fish oil omega-3 fatty acids can add triglyceride lowering to statin therapy. Randomized studies of high-dose omega-3 fatty acids added to atorvastatin showed improved triglyceride and non-HDL cholesterol measures without major safety signals. The main value is residual hypertriglyceridemia, not additional LDL lowering.", "recommendation": "Consider fish oil with atorvastatin when triglycerides remain elevated despite statin therapy, using a consistent EPA/DHA dose and product. Recheck fasting lipids because some mixed EPA/DHA products can raise LDL cholesterol in certain patients.", "minimumTimeSeparation": null, "mechanism": "Atorvastatin lowers hepatic cholesterol synthesis and LDL particle burden, while omega-3 fatty acids reduce hepatic VLDL-triglyceride production and enhance triglyceride clearance. These complementary lipid effects can improve residual hypertriglyceridemia.", "evidenceLevel": "moderate", "sources": [ { "text": "Woo JS, Hong SJ, Cha DH, Kim KS, Kim MH, Lee JW, et al. Comparison of the Efficacy and Safety of Atorvastatin 40 mg/omega-3 Fatty Acids 4 g Fixed-dose Combination and Atorvastatin 40 mg Monotherapy in Hypertriglyceridemic Patients who Poorly Respond to Atorvastatin 40 mg Monotherapy: An 8-week, Multicenter, Randomized, Double-blind Phase III Study. Clin Ther. 2021;43(8):1419-1430.", "pmid": "34332788", "doi": "10.1016/j.clinthera.2021.07.001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34332788/", "publicSourceType": "PMID" }, { "text": "Jun JE, Jeong IK, Yu JM, Kim SR, Lee IK, Han KA, et al. Efficacy and Safety of Omega-3 Fatty Acids in Patients Treated with Statins for Residual Hypertriglyceridemia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Diabetes Metab J. 2020;44(1):78-90.", "pmid": "31237134", "doi": "10.4093/dmj.2018.0265", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31237134/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Fish oil can complement atorvastatin by lowering residual triglycerides.", "clinicalSignificance": "This can help patients whose triglycerides remain high after LDL-focused statin therapy.", "managementStrategy": "Use a consistent omega-3 dose, monitor fasting lipids, and watch LDL response.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Simvastatin", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "Fish oil omega-3 fatty acids can improve triglyceride and non-HDL cholesterol measures when added to simvastatin in patients with residual hypertriglyceridemia. Human pharmacokinetic studies found no meaningful effect on simvastatin exposure. This is a beneficial lipid combination rather than a spacing issue.", "recommendation": "Fish oil can be considered with simvastatin when triglycerides remain elevated, but use a consistent dose and recheck fasting lipids. Report unusual bruising or bleeding if you are also taking anticoagulants or antiplatelet drugs.", "minimumTimeSeparation": null, "mechanism": "Simvastatin inhibits HMG-CoA reductase to lower LDL cholesterol, while omega-3 fatty acids reduce hepatic triglyceride synthesis and VLDL output. Pharmacokinetic studies did not show a clinically important change in simvastatin or simvastatin acid exposure.", "evidenceLevel": "moderate", "sources": [ { "text": "McKenney JM, Swearingen D, Di Spirito M, Doyle R, Pantaleon C, Kling D, et al. Study of the pharmacokinetic interaction between simvastatin and prescription omega-3-acid ethyl esters. J Clin Pharmacol. 2006;46(7):785-791.", "pmid": "16809804", "doi": "10.1177/0091270006289849", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16809804/", "publicSourceType": "PMID" }, { "text": "Bays HE, Maki KC, McKenney J, Snipes R, Meadowcroft A, Schroyer R, et al. Long-term up to 24-month efficacy and safety of concomitant prescription omega-3-acid ethyl esters and simvastatin in hypertriglyceridemic patients. Curr Med Res Opin. 2010;26(4):907-915.", "pmid": "20156032", "doi": "10.1185/03007991003645318", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20156032/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Fish oil can add triglyceride lowering to simvastatin without meaningfully changing simvastatin pharmacokinetics.", "clinicalSignificance": "This may improve residual atherogenic lipid markers in hypertriglyceridemia.", "managementStrategy": "Use a consistent fish oil dose and monitor triglycerides, non-HDL cholesterol, and LDL response.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Rosuvastatin", "supplementBName": "Fish Oil", "interactionType": "synergy", "severity": "info", "description": "Fish oil omega-3 fatty acids can be used with rosuvastatin for residual hypertriglyceridemia. Human pharmacokinetic studies found no clinically important interaction between omega-3 fatty acid products and rosuvastatin. The expected benefit is triglyceride lowering, not extra LDL lowering.", "recommendation": "Consider fish oil with rosuvastatin if triglycerides remain elevated and you can use a reliable, consistent product. Recheck fasting lipids after starting because LDL cholesterol can respond differently depending on the omega-3 formulation.", "minimumTimeSeparation": null, "mechanism": "Rosuvastatin lowers LDL through HMG-CoA reductase inhibition, while omega-3 fatty acids reduce hepatic VLDL-triglyceride synthesis. Phase I studies found rosuvastatin exposure remained within no-interaction bounds when coadministered with omega-3 products.", "evidenceLevel": "moderate", "sources": [ { "text": "Gosai P, Liu J, Doyle RT, Johnson J, Carter R, Sica D, et al. Effect of omega-3-acid ethyl esters on the steady-state plasma pharmacokinetics of rosuvastatin in healthy adults. Expert Opin Pharmacother. 2008;9(17):2947-2953.", "pmid": "19006471", "doi": "10.1517/14656560802532640", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19006471/", "publicSourceType": "PMID" }, { "text": "Offman E, Davidson M, Nilsson C. Assessment of pharmacokinetic interaction between omega-3 carboxylic acids and the statins rosuvastatin and simvastatin: Results of 2 phase I studies in healthy volunteers. J Clin Lipidol. 2017;11(3):739-748.", "pmid": "28506390", "doi": "10.1016/j.jacl.2017.03.017", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28506390/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Fish oil can complement rosuvastatin for triglyceride lowering without a meaningful PK interaction.", "clinicalSignificance": "This is useful when LDL is treated but triglycerides remain elevated.", "managementStrategy": "Use consistent dosing and monitor fasting lipids after adding or changing fish oil.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Atorvastatin", "supplementBName": "Psyllium Husk", "interactionType": "synergy", "severity": "info", "description": "Psyllium husk can add LDL-lowering benefit to statin therapy through a non-statin mechanism. A randomized atorvastatin study and a statin-adjunct meta-analysis support additional cholesterol lowering when psyllium is used consistently. The benefit depends on taking enough soluble fiber with adequate fluids.", "recommendation": "Consider psyllium husk with atorvastatin if you want additional LDL lowering and can tolerate fiber. Start low, increase gradually, take with plenty of water, and recheck lipids after several weeks.", "minimumTimeSeparation": null, "mechanism": "Psyllium is a gel-forming soluble fiber that binds bile acids and increases fecal bile acid loss, pulling hepatic cholesterol into bile acid synthesis. Atorvastatin reduces cholesterol synthesis, so the mechanisms are complementary.", "evidenceLevel": "strong", "sources": [ { "text": "Jayaram S, Prasad HB, Sovani VB, Langade DG, Mane PR. Randomised study to compare the efficacy and safety of isapgol plus atorvastatin versus atorvastatin alone in subjects with hypercholesterolaemia. J Indian Med Assoc. 2007;105(3):142-145, 150.", "pmid": "17824470", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17824470/", "publicSourceType": "PMID" }, { "text": "Brum JM, Gibb RD, Peters JC, Mattes RD. Meta-Analysis of Usefulness of Psyllium Fiber as Adjuvant Antilipid Therapy to Enhance Cholesterol Lowering Efficacy of Statins. Am J Cardiol. 2018;122(7):1169-1174.", "pmid": "30078477", "doi": "10.1016/j.amjcard.2018.06.040", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30078477/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Psyllium husk can add modest LDL lowering to atorvastatin.", "clinicalSignificance": "This may help reach LDL goals without increasing the statin dose.", "managementStrategy": "Take psyllium consistently with water and reassess lipids after 4-12 weeks.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Simvastatin", "supplementBName": "Psyllium Husk", "interactionType": "synergy", "severity": "info", "description": "Psyllium husk can enhance LDL lowering when added to simvastatin. In a randomized trial, low-dose simvastatin plus psyllium produced LDL lowering similar to a higher simvastatin dose, and meta-analysis supports psyllium as a statin adjunct. This is a beneficial lipid interaction, not a dangerous drug-binding interaction when used appropriately.", "recommendation": "Consider psyllium husk with simvastatin if LDL remains above goal or if higher statin doses are hard to tolerate. Take it with plenty of water and keep the routine consistent before judging the lipid effect.", "minimumTimeSeparation": null, "mechanism": "Psyllium increases bile acid excretion and reduces intestinal cholesterol recycling, while simvastatin reduces hepatic cholesterol synthesis. Together, these complementary mechanisms can lower LDL more than either strategy alone at the same dose.", "evidenceLevel": "strong", "sources": [ { "text": "Moreyra AE, Wilson AC, Koraym A. Effect of combining psyllium fiber with simvastatin in lowering cholesterol. Arch Intern Med. 2005;165(10):1161-1166.", "pmid": "15911730", "doi": "10.1001/archinte.165.10.1161", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15911730/", "publicSourceType": "PMID" }, { "text": "Brum JM, Gibb RD, Peters JC, Mattes RD. Meta-Analysis of Usefulness of Psyllium Fiber as Adjuvant Antilipid Therapy to Enhance Cholesterol Lowering Efficacy of Statins. Am J Cardiol. 2018;122(7):1169-1174.", "pmid": "30078477", "doi": "10.1016/j.amjcard.2018.06.040", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30078477/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bidirectional", "effect": "Psyllium husk can add LDL lowering to simvastatin therapy.", "clinicalSignificance": "This may help improve LDL control without increasing simvastatin dose.", "managementStrategy": "Use psyllium consistently with adequate fluids and reassess LDL after several weeks.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Prednisolone", "supplementBName": "Calcium", "interactionType": "synergy", "severity": "moderate", "description": "Chronic prednisolone therapy accelerates bone loss and increases fracture risk, especially at higher doses or when used for several months. Calcium intake is part of guideline-based prevention for glucocorticoid-induced osteoporosis because steroids reduce calcium balance and impair bone formation.", "recommendation": "Aim for total calcium intake of about 1000-1200 mg/day from diet plus supplements while on chronic prednisolone, unless your clinician gives a different target. Pair calcium with vitamin D status monitoring and osteoporosis risk assessment rather than using calcium alone as protection.", "minimumTimeSeparation": null, "mechanism": "Systemic glucocorticoids reduce intestinal calcium absorption, increase urinary calcium loss, suppress osteoblast activity, and increase bone resorption. Supplemental calcium helps offset negative calcium balance but does not replace fracture-risk assessment or osteoporosis pharmacotherapy when indicated.", "evidenceLevel": "strong", "sources": [ { "text": "Humphrey MB, Russell L, Danila MI, et al. 2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Care Res (Hoboken). 2023;75(12):2405-2419.", "pmid": "37884467", "doi": "10.1002/acr.25240", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37884467/", "publicSourceType": "PMID" }, { "text": "Homik J, Suarez-Almazor ME, Shea B, Cranney A, Wells G, Tugwell P. Calcium and vitamin D for corticosteroid-induced osteoporosis. Cochrane Database Syst Rev. 2000;1998(2):CD000952.", "pmid": "10796394", "doi": "10.1002/14651858.CD000952", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10796394/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Prednisolone increases calcium needs by promoting negative calcium balance and bone loss.", "clinicalSignificance": "Patients on chronic systemic steroids can lose bone quickly and may fracture even before symptoms develop.", "managementStrategy": "Use calcium as part of a broader glucocorticoid-induced osteoporosis plan with vitamin D monitoring and fracture-risk assessment.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Prednisolone", "supplementBName": "Vitamin D3", "interactionType": "synergy", "severity": "moderate", "description": "Chronic prednisolone use increases the risk of osteoporosis and fractures. Vitamin D3 helps maintain calcium absorption and is routinely paired with calcium in glucocorticoid-induced osteoporosis prevention plans.", "recommendation": "Maintain adequate vitamin D intake while on long-term prednisolone and have 25-OH vitamin D checked if your risk is high or therapy is prolonged. Do not rely on vitamin D3 alone if your steroid dose, age, prior fracture history, or bone density indicates need for prescription osteoporosis therapy.", "minimumTimeSeparation": null, "mechanism": "Glucocorticoids impair calcium homeostasis and bone remodeling, partly by reducing intestinal calcium absorption and osteoblast function. Vitamin D3 supports calcium absorption and helps counter one component of steroid-driven bone loss.", "evidenceLevel": "strong", "sources": [ { "text": "Humphrey MB, Russell L, Danila MI, et al. 2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Care Res (Hoboken). 2023;75(12):2405-2419.", "pmid": "37884467", "doi": "10.1002/acr.25240", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37884467/", "publicSourceType": "PMID" }, { "text": "Homik J, Suarez-Almazor ME, Shea B, Cranney A, Wells G, Tugwell P. Calcium and vitamin D for corticosteroid-induced osteoporosis. Cochrane Database Syst Rev. 2000;1998(2):CD000952.", "pmid": "10796394", "doi": "10.1002/14651858.CD000952", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10796394/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Prednisolone raises the clinical importance of maintaining adequate vitamin D status for bone protection.", "clinicalSignificance": "Low vitamin D status can worsen the bone risk created by chronic systemic steroid therapy.", "managementStrategy": "Use vitamin D3 with calcium and clinician-guided bone-risk monitoring during prolonged prednisolone therapy.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Prednisone", "supplementBName": "Vitamin D2", "interactionType": "synergy", "severity": "moderate", "description": "Long-term prednisone therapy can cause rapid bone loss and increase fracture risk. Vitamin D2 can help maintain vitamin D status and calcium absorption as part of glucocorticoid-induced osteoporosis prevention.", "recommendation": "Use vitamin D2 only as part of a complete bone-protection plan that includes calcium intake, vitamin D status monitoring, and fracture-risk assessment. If you are on prednisone for more than a short course, ask whether you need bone density testing or prescription osteoporosis prevention.", "minimumTimeSeparation": null, "mechanism": "Prednisone disrupts bone remodeling and calcium balance through systemic glucocorticoid effects. Vitamin D2 can raise 25-OH vitamin D and support calcium absorption, helping address one modifiable contributor to steroid-induced bone loss.", "evidenceLevel": "strong", "sources": [ { "text": "Humphrey MB, Russell L, Danila MI, et al. 2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Care Res (Hoboken). 2023;75(12):2405-2419.", "pmid": "37884467", "doi": "10.1002/acr.25240", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37884467/", "publicSourceType": "PMID" }, { "text": "Homik J, Suarez-Almazor ME, Shea B, Cranney A, Wells G, Tugwell P. Calcium and vitamin D for corticosteroid-induced osteoporosis. Cochrane Database Syst Rev. 2000;1998(2):CD000952.", "pmid": "10796394", "doi": "10.1002/14651858.CD000952", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10796394/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Prednisone makes adequate vitamin D status more important for bone protection.", "clinicalSignificance": "Patients on chronic prednisone can lose bone before they notice symptoms, and vitamin D deficiency worsens that risk.", "managementStrategy": "Maintain vitamin D status and use clinician-guided osteoporosis screening during prolonged prednisone therapy.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Prednisolone", "supplementBName": "Vitamin D2", "interactionType": "synergy", "severity": "moderate", "description": "Prednisolone increases fracture risk when used chronically by accelerating bone loss. Vitamin D2 can help maintain vitamin D status, which supports calcium absorption and is part of standard glucocorticoid-induced osteoporosis prevention.", "recommendation": "If prednisolone use is prolonged, maintain vitamin D status with diet, sunlight exposure where appropriate, or supplementation such as vitamin D2. Have bone risk assessed rather than assuming vitamin D2 alone is enough protection.", "minimumTimeSeparation": null, "mechanism": "Glucocorticoids impair osteoblast function, increase bone resorption, and reduce calcium balance. Vitamin D2 supports intestinal calcium absorption by increasing circulating 25-OH vitamin D.", "evidenceLevel": "strong", "sources": [ { "text": "Humphrey MB, Russell L, Danila MI, et al. 2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Care Res (Hoboken). 2023;75(12):2405-2419.", "pmid": "37884467", "doi": "10.1002/acr.25240", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37884467/", "publicSourceType": "PMID" }, { "text": "Homik J, Suarez-Almazor ME, Shea B, Cranney A, Wells G, Tugwell P. Calcium and vitamin D for corticosteroid-induced osteoporosis. Cochrane Database Syst Rev. 2000;1998(2):CD000952.", "pmid": "10796394", "doi": "10.1002/14651858.CD000952", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10796394/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Prednisolone increases the need to maintain adequate vitamin D status for calcium balance and bone health.", "clinicalSignificance": "Vitamin D insufficiency can compound the fracture risk of chronic systemic steroid therapy.", "managementStrategy": "Use vitamin D2 as part of a monitored glucocorticoid bone-protection plan.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Methylprednisolone", "supplementBName": "Vitamin D2", "interactionType": "synergy", "severity": "moderate", "description": "Chronic methylprednisolone exposure can reduce bone density and raise fracture risk. Vitamin D2 can help maintain vitamin D status and calcium absorption, which are core parts of glucocorticoid-induced osteoporosis prevention.", "recommendation": "If methylprednisolone is used beyond a short course, maintain vitamin D status and ask whether bone density testing or prescription osteoporosis prevention is appropriate. Vitamin D2 should complement calcium intake and risk-based treatment decisions, not replace them.", "minimumTimeSeparation": null, "mechanism": "Systemic glucocorticoids suppress bone formation, increase bone resorption, and impair calcium balance. Vitamin D2 increases 25-OH vitamin D availability and supports calcium absorption.", "evidenceLevel": "strong", "sources": [ { "text": "Humphrey MB, Russell L, Danila MI, et al. 2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Care Res (Hoboken). 2023;75(12):2405-2419.", "pmid": "37884467", "doi": "10.1002/acr.25240", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37884467/", "publicSourceType": "PMID" }, { "text": "Homik J, Suarez-Almazor ME, Shea B, Cranney A, Wells G, Tugwell P. Calcium and vitamin D for corticosteroid-induced osteoporosis. Cochrane Database Syst Rev. 2000;1998(2):CD000952.", "pmid": "10796394", "doi": "10.1002/14651858.CD000952", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10796394/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Methylprednisolone makes adequate vitamin D status more important for bone protection.", "clinicalSignificance": "Steroid-related bone loss can occur quickly and may require more than over-the-counter supplementation.", "managementStrategy": "Use vitamin D2 with calcium intake and clinician-guided osteoporosis risk management during prolonged therapy.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Dexamethasone", "supplementBName": "Vitamin D2", "interactionType": "synergy", "severity": "moderate", "description": "Dexamethasone is a potent systemic glucocorticoid, and prolonged use can accelerate bone loss. Vitamin D2 can help maintain vitamin D status and calcium absorption as part of prevention for glucocorticoid-induced osteoporosis.", "recommendation": "For repeated or long dexamethasone courses, maintain adequate vitamin D status and review fracture risk with your clinician. Vitamin D2 is supportive; it does not replace bone density testing or osteoporosis medication when those are indicated.", "minimumTimeSeparation": null, "mechanism": "Dexamethasone suppresses osteoblast activity, favors bone resorption, and disrupts calcium balance. Vitamin D2 supports intestinal calcium absorption by increasing 25-OH vitamin D.", "evidenceLevel": "strong", "sources": [ { "text": "Humphrey MB, Russell L, Danila MI, et al. 2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Care Res (Hoboken). 2023;75(12):2405-2419.", "pmid": "37884467", "doi": "10.1002/acr.25240", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37884467/", "publicSourceType": "PMID" }, { "text": "Homik J, Suarez-Almazor ME, Shea B, Cranney A, Wells G, Tugwell P. Calcium and vitamin D for corticosteroid-induced osteoporosis. Cochrane Database Syst Rev. 2000;1998(2):CD000952.", "pmid": "10796394", "doi": "10.1002/14651858.CD000952", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10796394/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Dexamethasone increases the importance of maintaining vitamin D status for bone protection.", "clinicalSignificance": "Potent or prolonged steroid exposure can produce clinically meaningful bone loss before symptoms appear.", "managementStrategy": "Use vitamin D2 as supportive bone care alongside calcium intake and risk-based osteoporosis management.", "isSynergistic": true, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Prednisone", "supplementBName": "Strontium", "interactionType": "caution", "severity": "moderate", "description": "Prednisone can cause clinically important bone loss when used chronically. Strontium supplements may make DXA bone density results look higher because strontium in bone attenuates X-rays more than calcium, which can obscure whether steroid-induced bone loss is actually controlled.", "recommendation": "Do not use strontium as a substitute for guideline-based prednisone bone protection. Tell your clinician and imaging center if you use strontium, especially before DXA testing, so bone density trends are interpreted cautiously.", "minimumTimeSeparation": null, "mechanism": "Strontium can partially substitute for calcium in bone mineral and artifactually increase DXA-measured bone mineral density. Prednisone independently increases fracture risk by suppressing bone formation and increasing bone resorption.", "evidenceLevel": "emerging", "sources": [ { "text": "Humphrey MB, Russell L, Danila MI, et al. 2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Care Res (Hoboken). 2023;75(12):2405-2419.", "pmid": "37884467", "doi": "10.1002/acr.25240", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37884467/", "publicSourceType": "PMID" }, { "text": "Nielsen SP, Slosman D, Sorensen OH, Basse-Cathalinat B, De Cassin P, Roux CR, Meunier PJ. Influence of strontium on bone mineral density and bone mineral content measurements by dual X-ray absorptiometry. J Clin Densitom. 1999;2(4):371-379.", "pmid": "10677790", "doi": "10.1016/s1094-6950(06)60402-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10677790/", "publicSourceType": "PMID" }, { "text": "Blake GM, Fogelman I. Effect of bone strontium on BMD measurements. J Clin Densitom. 2007;10(1):34-38.", "pmid": "17289524", "doi": "10.1016/j.jocd.2006.10.004", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17289524/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Strontium can confound bone-density monitoring in a patient whose prednisone therapy already raises fracture risk.", "clinicalSignificance": "A falsely reassuring DXA trend could delay appropriate glucocorticoid-induced osteoporosis management.", "managementStrategy": "Document strontium use and rely on clinician-guided fracture-risk management rather than DXA numbers alone.", "isSynergistic": null, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Prednisolone", "supplementBName": "Strontium", "interactionType": "caution", "severity": "moderate", "description": "Prednisolone can accelerate bone loss during prolonged therapy. Strontium supplements can artifactually elevate DXA bone density readings, which may mask ongoing steroid-related bone loss or make treatment response look better than it is.", "recommendation": "Tell your clinician if you take strontium while on chronic prednisolone, particularly before bone density testing. Use strontium cautiously and do not let it replace calcium, vitamin D, fracture-risk assessment, or prescription osteoporosis therapy when indicated.", "minimumTimeSeparation": null, "mechanism": "Strontium incorporation into bone increases X-ray attenuation and can overestimate BMD on DXA. Prednisolone increases fracture risk through systemic glucocorticoid effects on bone remodeling and calcium balance.", "evidenceLevel": "emerging", "sources": [ { "text": "Humphrey MB, Russell L, Danila MI, et al. 2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Care Res (Hoboken). 2023;75(12):2405-2419.", "pmid": "37884467", "doi": "10.1002/acr.25240", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37884467/", "publicSourceType": "PMID" }, { "text": "Nielsen SP, Slosman D, Sorensen OH, Basse-Cathalinat B, De Cassin P, Roux CR, Meunier PJ. Influence of strontium on bone mineral density and bone mineral content measurements by dual X-ray absorptiometry. J Clin Densitom. 1999;2(4):371-379.", "pmid": "10677790", "doi": "10.1016/s1094-6950(06)60402-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10677790/", "publicSourceType": "PMID" }, { "text": "Blake GM, Fogelman I. Effect of bone strontium on BMD measurements. J Clin Densitom. 2007;10(1):34-38.", "pmid": "17289524", "doi": "10.1016/j.jocd.2006.10.004", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17289524/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Strontium can make bone-density monitoring harder to interpret during prednisolone therapy.", "clinicalSignificance": "Misread bone density trends can delay appropriate protection from steroid-related fractures.", "managementStrategy": "Disclose strontium use and base bone protection on fracture risk, labs, and clinician interpretation of imaging.", "isSynergistic": null, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Methylprednisolone", "supplementBName": "Strontium", "interactionType": "caution", "severity": "moderate", "description": "Methylprednisolone can cause bone loss when used repeatedly or chronically. Strontium supplements can raise apparent DXA bone density independent of true bone strength, complicating monitoring for glucocorticoid-induced osteoporosis.", "recommendation": "If you use strontium while taking methylprednisolone, make sure it is recorded before DXA testing and osteoporosis decisions. Do not use strontium to self-treat steroid-induced bone loss without clinician guidance.", "minimumTimeSeparation": null, "mechanism": "Strontium in bone increases DXA attenuation and can overestimate BMD, while methylprednisolone suppresses bone formation and can increase resorption. The combination creates a monitoring problem rather than a timing problem.", "evidenceLevel": "emerging", "sources": [ { "text": "Humphrey MB, Russell L, Danila MI, et al. 2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Care Res (Hoboken). 2023;75(12):2405-2419.", "pmid": "37884467", "doi": "10.1002/acr.25240", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37884467/", "publicSourceType": "PMID" }, { "text": "Nielsen SP, Slosman D, Sorensen OH, Basse-Cathalinat B, De Cassin P, Roux CR, Meunier PJ. Influence of strontium on bone mineral density and bone mineral content measurements by dual X-ray absorptiometry. J Clin Densitom. 1999;2(4):371-379.", "pmid": "10677790", "doi": "10.1016/s1094-6950(06)60402-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10677790/", "publicSourceType": "PMID" }, { "text": "Blake GM, Fogelman I. Effect of bone strontium on BMD measurements. J Clin Densitom. 2007;10(1):34-38.", "pmid": "17289524", "doi": "10.1016/j.jocd.2006.10.004", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17289524/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Strontium can confound bone-density interpretation in a patient exposed to methylprednisolone-related bone loss.", "clinicalSignificance": "Apparent BMD improvement may not mean steroid-related fracture risk is adequately controlled.", "managementStrategy": "Document strontium use and use clinician-guided fracture-risk assessment during methylprednisolone therapy.", "isSynergistic": null, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Dexamethasone", "supplementBName": "Strontium", "interactionType": "caution", "severity": "moderate", "description": "Dexamethasone is a potent glucocorticoid and can contribute to bone loss when exposure is repeated or prolonged. Strontium supplements can artifactually increase DXA-measured bone density, making steroid-related bone monitoring less reliable.", "recommendation": "Tell your clinician about strontium use before bone density testing while on dexamethasone. Use evidence-based bone protection and fracture-risk assessment rather than relying on strontium-related DXA changes.", "minimumTimeSeparation": null, "mechanism": "Strontium incorporation into bone can increase X-ray attenuation and overestimate BMD on DXA. Dexamethasone increases fracture risk through glucocorticoid receptor-mediated suppression of bone formation and disruption of calcium balance.", "evidenceLevel": "emerging", "sources": [ { "text": "Humphrey MB, Russell L, Danila MI, et al. 2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Care Res (Hoboken). 2023;75(12):2405-2419.", "pmid": "37884467", "doi": "10.1002/acr.25240", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37884467/", "publicSourceType": "PMID" }, { "text": "Nielsen SP, Slosman D, Sorensen OH, Basse-Cathalinat B, De Cassin P, Roux CR, Meunier PJ. Influence of strontium on bone mineral density and bone mineral content measurements by dual X-ray absorptiometry. J Clin Densitom. 1999;2(4):371-379.", "pmid": "10677790", "doi": "10.1016/s1094-6950(06)60402-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10677790/", "publicSourceType": "PMID" }, { "text": "Blake GM, Fogelman I. Effect of bone strontium on BMD measurements. J Clin Densitom. 2007;10(1):34-38.", "pmid": "17289524", "doi": "10.1016/j.jocd.2006.10.004", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17289524/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Strontium can obscure bone-density trends during dexamethasone exposure.", "clinicalSignificance": "Incorrect interpretation of DXA results could delay treatment for glucocorticoid-induced osteoporosis.", "managementStrategy": "Disclose strontium use and manage bone risk according to steroid exposure and fracture-risk assessment.", "isSynergistic": null, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Prednisolone", "supplementBName": "Potassium", "interactionType": "synergy", "severity": "moderate", "description": "Prednisolone can promote potassium loss or potassium shifts in susceptible patients, especially at higher systemic doses or when combined with other hypokalemia risks. Potassium supplementation may be useful when labs confirm low potassium, but unsupervised high-dose potassium can also be unsafe.", "recommendation": "Monitor serum potassium if prednisolone is high dose, prolonged, or combined with diuretics, vomiting, diarrhea, or heart rhythm risk. Use potassium supplements only at a dose guided by labs or your prescriber.", "minimumTimeSeparation": null, "mechanism": "Systemic corticosteroids can increase renal electrolyte changes and, in some settings, promote intracellular potassium shifts. Potassium supplementation replaces the depleted electrolyte but does not remove the need to identify the cause of hypokalemia.", "evidenceLevel": "moderate", "sources": [ { "text": "Veltri KT, Mason C. Medication-induced hypokalemia. P T. 2015;40(3):185-190.", "pmid": "25798039", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25798039/", "publicSourceType": "PMID" }, { "text": "Ortega E, Rodriguez C, Strand LJ, Bessler S, Segre E. Metabolic effects of cloprednol-a new systemic corticosteroid. J Clin Pharmacol. 1976;16(2-3):122-128.", "pmid": "1254734", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1254734/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Prednisolone can increase the need for potassium monitoring and replacement in susceptible patients.", "clinicalSignificance": "Low potassium can cause weakness, cramps, and arrhythmia risk, while excess potassium replacement can be dangerous.", "managementStrategy": "Check potassium when risk is present and supplement only to a lab-guided target.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Methylprednisolone", "supplementBName": "Potassium", "interactionType": "synergy", "severity": "moderate", "description": "High-dose or pulse methylprednisolone can disturb potassium handling and has been associated with clinically relevant rhythm concerns in vulnerable patients. Potassium supplementation can correct confirmed hypokalemia, but it should be guided by lab results.", "recommendation": "Have potassium monitored during high-dose, IV pulse, or prolonged methylprednisolone therapy, especially if you have kidney disease, heart disease, or take diuretics. Do not self-treat with high-dose potassium unless your potassium level and kidney function are known.", "minimumTimeSeparation": null, "mechanism": "Methylprednisolone can alter renal potassium excretion and transcellular potassium balance during high systemic exposure. Potassium supplementation restores serum potassium but can overshoot if kidney function is impaired or the steroid effect resolves.", "evidenceLevel": "moderate", "sources": [ { "text": "Veltri KT, Mason C. Medication-induced hypokalemia. P T. 2015;40(3):185-190.", "pmid": "25798039", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25798039/", "publicSourceType": "PMID" }, { "text": "Fujimoto S, Kondoh H, Yamamoto Y, Hisanaga S, Tanaka K. Holter electrocardiogram monitoring in nephrotic patients during methylprednisolone pulse therapy. Am J Nephrol. 1990;10(3):231-236.", "pmid": "1696428", "doi": "10.1159/000168087", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1696428/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Methylprednisolone can create a need for potassium monitoring and replacement during high systemic exposure.", "clinicalSignificance": "Electrolyte shifts during pulse steroids can matter in patients with arrhythmia or kidney risk.", "managementStrategy": "Monitor potassium during high-risk methylprednisolone use and supplement only when labs support it.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Dexamethasone", "supplementBName": "Potassium", "interactionType": "synergy", "severity": "moderate", "description": "Dexamethasone can precipitate hypokalemia or hypokalemic periodic paralysis in susceptible patients, even though it has little mineralocorticoid activity. Potassium can treat confirmed low potassium, but the dose should be guided by labs and the clinical setting.", "recommendation": "Seek potassium testing if weakness, palpitations, severe cramps, or paralysis-like symptoms occur after dexamethasone. Use potassium supplements only under guidance if you have kidney disease, take ACE inhibitors/ARBs, or use potassium-sparing medications.", "minimumTimeSeparation": null, "mechanism": "Glucocorticoids can trigger intracellular potassium shifts and renal electrolyte effects in susceptible patients. Potassium replacement addresses the low serum potassium but does not prevent recurrence if the steroid trigger continues.", "evidenceLevel": "moderate", "sources": [ { "text": "Veltri KT, Mason C. Medication-induced hypokalemia. P T. 2015;40(3):185-190.", "pmid": "25798039", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25798039/", "publicSourceType": "PMID" }, { "text": "Tai HT, Lee PT, Ou SH. Steroid-induced hypokalemic periodic paralysis: a case report and literature review. BMC Nephrol. 2023;24(1):70.", "pmid": "36964512", "doi": "10.1186/s12882-023-03131-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36964512/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "aAffectsB", "effect": "Dexamethasone can increase the need for potassium monitoring or replacement in susceptible patients.", "clinicalSignificance": "Severe hypokalemia can cause dangerous weakness or rhythm problems, but unnecessary potassium can also be harmful.", "managementStrategy": "Check potassium promptly when symptoms or risk factors are present and replace to a monitored target.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Methylprednisolone", "supplementBName": "Schisandra", "interactionType": "caution", "severity": "moderate", "description": "Schisandra extract has human evidence of inhibiting CYP3A activity, and methylprednisolone exposure is highly sensitive to CYP3A inhibition. Combining them could raise steroid exposure and increase systemic adverse effects such as mood changes, high glucose, fluid retention, and adrenal suppression.", "recommendation": "Avoid starting high-dose Schisandra during methylprednisolone therapy unless your prescriber knows. If the combination is used, monitor for stronger steroid effects and do not abruptly stop methylprednisolone after prolonged use.", "minimumTimeSeparation": null, "mechanism": "Schisandra lignans can inhibit CYP3A, increasing exposure to CYP3A probe substrates in humans. Methylprednisolone is metabolized by CYP3A4, and potent CYP3A inhibitors markedly increase methylprednisolone AUC and cortisol suppression.", "evidenceLevel": "moderate", "sources": [ { "text": "Xin HW, Wu XC, Li Q, Yu AR, Xiong L. Effects of Schisandra sphenanthera extract on the pharmacokinetics of midazolam in healthy volunteers. Br J Clin Pharmacol. 2009;67(5):541-546.", "pmid": "19552749", "doi": "10.1111/j.1365-2125.2009.03383.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19552749/", "publicSourceType": "PMID" }, { "text": "Varis T, Kaukonen KM, Kivisto KT, Neuvonen PJ. Plasma concentrations and effects of oral methylprednisolone are considerably increased by itraconazole. Clin Pharmacol Ther. 1998;64(4):363-368.", "pmid": "9797792", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9797792/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Schisandra may increase methylprednisolone exposure by inhibiting CYP3A-mediated clearance.", "clinicalSignificance": "Higher steroid exposure can increase metabolic, psychiatric, and adrenal-suppression adverse effects.", "managementStrategy": "Avoid unsupervised Schisandra during methylprednisolone therapy and monitor for excess steroid effects if used.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Dexamethasone", "supplementBName": "Schisandra", "interactionType": "caution", "severity": "moderate", "description": "Schisandra extract can inhibit CYP3A in humans, and dexamethasone exposure rises markedly when CYP3A4 is inhibited. Adding Schisandra could increase dexamethasone effects, including insomnia, mood changes, glucose elevation, and adrenal suppression.", "recommendation": "Avoid adding Schisandra during dexamethasone therapy unless your prescriber is aware, especially with repeated or high-dose courses. Watch for stronger steroid side effects and ask about dose adjustment if Schisandra is continued.", "minimumTimeSeparation": null, "mechanism": "Schisandra increased oral midazolam exposure in healthy volunteers, consistent with CYP3A inhibition. Dexamethasone is a CYP3A4 substrate, and itraconazole increased dexamethasone AUC and prolonged adrenal suppression in a controlled human study.", "evidenceLevel": "moderate", "sources": [ { "text": "Xin HW, Wu XC, Li Q, Yu AR, Xiong L. Effects of Schisandra sphenanthera extract on the pharmacokinetics of midazolam in healthy volunteers. Br J Clin Pharmacol. 2009;67(5):541-546.", "pmid": "19552749", "doi": "10.1111/j.1365-2125.2009.03383.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19552749/", "publicSourceType": "PMID" }, { "text": "Varis T, Kivisto KT, Backman JT, Neuvonen PJ. The cytochrome P450 3A4 inhibitor itraconazole markedly increases the plasma concentrations of dexamethasone and enhances its adrenal-suppressant effect. Clin Pharmacol Ther. 2000;68(5):487-494.", "pmid": "11103751", "doi": "10.1067/mcp.2000.110772", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11103751/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Schisandra may raise dexamethasone exposure by inhibiting CYP3A4 metabolism.", "clinicalSignificance": "Higher dexamethasone exposure can increase steroid toxicity and adrenal suppression.", "managementStrategy": "Avoid unsupervised Schisandra and monitor for excess dexamethasone effects if the combination is necessary.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Budesonide Inhaled", "supplementBName": "Schisandra", "interactionType": "caution", "severity": "moderate", "description": "Schisandra extract inhibits CYP3A in human pharmacokinetic studies. Budesonide is normally cleared extensively by CYP3A, so inhibition can raise systemic steroid exposure even when budesonide is inhaled, especially at higher doses or with prolonged use.", "recommendation": "Avoid adding high-dose Schisandra to inhaled budesonide without clinician review. Monitor for unusual steroid effects such as easy bruising, facial swelling, high glucose, or symptoms of adrenal suppression, but do not stop the inhaled steroid abruptly.", "minimumTimeSeparation": null, "mechanism": "Schisandra can inhibit CYP3A-mediated metabolism, increasing exposure to CYP3A substrates. Budesonide undergoes extensive CYP3A metabolism, and CYP3A inhibition has been shown to increase inhaled budesonide concentrations and cortisol suppression.", "evidenceLevel": "moderate", "sources": [ { "text": "Xin HW, Wu XC, Li Q, Yu AR, Xiong L. Effects of Schisandra sphenanthera extract on the pharmacokinetics of midazolam in healthy volunteers. Br J Clin Pharmacol. 2009;67(5):541-546.", "pmid": "19552749", "doi": "10.1111/j.1365-2125.2009.03383.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19552749/", "publicSourceType": "PMID" }, { "text": "Raaska K, Niemi M, Neuvonen M, Neuvonen PJ, Kivisto KT. Plasma concentrations of inhaled budesonide and its effects on plasma cortisol are increased by the cytochrome P4503A4 inhibitor itraconazole. Clin Pharmacol Ther. 2002;72(4):362-369.", "pmid": "12386638", "doi": "10.1067/mcp.2002.127397", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12386638/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Schisandra may increase systemic exposure from inhaled budesonide by inhibiting CYP3A.", "clinicalSignificance": "Increased systemic steroid exposure can cause adrenal suppression or Cushing-like effects during long-term therapy.", "managementStrategy": "Use Schisandra cautiously with inhaled budesonide and monitor for systemic steroid adverse effects.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fluticasone Inhaled", "supplementBName": "Schisandra", "interactionType": "caution", "severity": "moderate", "description": "Schisandra has human evidence of CYP3A inhibition, and fluticasone is highly dependent on CYP3A metabolism. Strong CYP3A inhibition has caused adrenal suppression and Cushing syndrome with inhaled fluticasone, so Schisandra could increase systemic steroid exposure in high-risk use.", "recommendation": "Do not add concentrated Schisandra extract to chronic or high-dose inhaled fluticasone without clinician review. Monitor for easy bruising, facial rounding, weight gain, high glucose, or fatigue that could suggest adrenal suppression.", "minimumTimeSeparation": null, "mechanism": "Schisandra can inhibit CYP3A and increase exposure to CYP3A substrates. Fluticasone is extensively metabolized by CYP3A4, and reduced clearance can convert a locally acting inhaled steroid into clinically significant systemic glucocorticoid exposure.", "evidenceLevel": "moderate", "sources": [ { "text": "Xin HW, Wu XC, Li Q, Yu AR, Xiong L. Effects of Schisandra sphenanthera extract on the pharmacokinetics of midazolam in healthy volunteers. Br J Clin Pharmacol. 2009;67(5):541-546.", "pmid": "19552749", "doi": "10.1111/j.1365-2125.2009.03383.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19552749/", "publicSourceType": "PMID" }, { "text": "Foisy MM, Yakiwchuk EM, Chiu I, Singh AE. Adrenal suppression and Cushing's syndrome secondary to an interaction between ritonavir and fluticasone: a review of the literature. HIV Med. 2008;9(6):389-396.", "pmid": "18459946", "doi": "10.1111/j.1468-1293.2008.00579.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18459946/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Schisandra may raise systemic exposure from inhaled fluticasone by inhibiting CYP3A.", "clinicalSignificance": "Higher systemic fluticasone exposure can suppress the adrenal axis despite inhaled administration.", "managementStrategy": "Avoid unsupervised Schisandra with chronic inhaled fluticasone and monitor for systemic steroid toxicity.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fluticasone Nasal", "supplementBName": "Schisandra", "interactionType": "caution", "severity": "moderate", "description": "Nasal fluticasone usually has low systemic exposure, but CYP3A inhibition can still increase steroid exposure in susceptible patients. Schisandra extract inhibits CYP3A in humans, so concentrated products may increase the risk of systemic steroid effects during chronic nasal fluticasone use.", "recommendation": "Use Schisandra cautiously if you use nasal fluticasone daily or at high doses. Watch for steroid excess symptoms such as easy bruising, facial swelling, weight gain, or unusual fatigue, and tell your clinician about the supplement.", "minimumTimeSeparation": null, "mechanism": "Fluticasone is cleared primarily by CYP3A4, limiting systemic exposure after swallowed or absorbed drug. Schisandra-mediated CYP3A inhibition could reduce this clearance and increase systemic glucocorticoid activity.", "evidenceLevel": "moderate", "sources": [ { "text": "Xin HW, Wu XC, Li Q, Yu AR, Xiong L. Effects of Schisandra sphenanthera extract on the pharmacokinetics of midazolam in healthy volunteers. Br J Clin Pharmacol. 2009;67(5):541-546.", "pmid": "19552749", "doi": "10.1111/j.1365-2125.2009.03383.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19552749/", "publicSourceType": "PMID" }, { "text": "Foisy MM, Yakiwchuk EM, Chiu I, Singh AE. Adrenal suppression and Cushing's syndrome secondary to an interaction between ritonavir and fluticasone: a review of the literature. HIV Med. 2008;9(6):389-396.", "pmid": "18459946", "doi": "10.1111/j.1468-1293.2008.00579.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18459946/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Schisandra may increase systemic exposure from nasal fluticasone by inhibiting CYP3A.", "clinicalSignificance": "The absolute risk is lower than with high-dose inhaled therapy, but chronic use plus CYP3A inhibition can matter.", "managementStrategy": "Disclose Schisandra use and monitor for systemic steroid effects during daily nasal fluticasone therapy.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Methylprednisolone", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's Wort products high in hyperforin induce CYP3A, and methylprednisolone is a CYP3A-sensitive steroid. This may lower methylprednisolone exposure and reduce anti-inflammatory or immunosuppressive effect, especially when steroid treatment is being used for an active flare or severe inflammation.", "recommendation": "Avoid starting St. John's Wort during methylprednisolone therapy unless your prescriber approves. If you already take it, do not stop or start it abruptly without discussing steroid response and possible dose implications.", "minimumTimeSeparation": null, "mechanism": "St. John's Wort induces intestinal and hepatic CYP3A4 through hyperforin-dependent pregnane X receptor activation. Increased CYP3A4 activity can accelerate clearance of CYP3A substrates such as methylprednisolone and lower systemic steroid exposure.", "evidenceLevel": "moderate", "sources": [ { "text": "Whitten DL, Myers SP, Hawrelak JA, Wohlmuth H. The effect of St John's wort extracts on CYP3A: a systematic review of prospective clinical trials. Br J Clin Pharmacol. 2006;62(5):512-526.", "pmid": "17010103", "doi": "10.1111/j.1365-2125.2006.02755.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17010103/", "publicSourceType": "PMID" }, { "text": "Varis T, Kaukonen KM, Kivisto KT, Neuvonen PJ. Plasma concentrations and effects of oral methylprednisolone are considerably increased by itraconazole. Clin Pharmacol Ther. 1998;64(4):363-368.", "pmid": "9797792", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9797792/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St. John's Wort may reduce methylprednisolone exposure and weaken steroid response.", "clinicalSignificance": "Loss of steroid effect can worsen inflammatory or immune-mediated disease being actively treated.", "managementStrategy": "Avoid unsupervised St. John's Wort and monitor clinical response if it cannot be stopped.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Dexamethasone", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "serious", "description": "St. John's Wort can induce CYP3A4, and dexamethasone exposure is strongly affected by CYP3A4 activity. Taking St. John's Wort during dexamethasone therapy may lower steroid exposure and reduce the intended anti-inflammatory, antiemetic, or immunosuppressive effect.", "recommendation": "Avoid St. John's Wort while dexamethasone effect is clinically important unless your prescriber specifically approves. Tell your clinician if you recently started or stopped St. John's Wort because steroid response may change over days to weeks.", "minimumTimeSeparation": null, "mechanism": "High-hyperforin St. John's Wort induces CYP3A4 expression and activity. Dexamethasone is metabolized by CYP3A4, so induction can plausibly increase dexamethasone clearance and lower exposure.", "evidenceLevel": "moderate", "sources": [ { "text": "Whitten DL, Myers SP, Hawrelak JA, Wohlmuth H. The effect of St John's wort extracts on CYP3A: a systematic review of prospective clinical trials. Br J Clin Pharmacol. 2006;62(5):512-526.", "pmid": "17010103", "doi": "10.1111/j.1365-2125.2006.02755.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17010103/", "publicSourceType": "PMID" }, { "text": "Varis T, Kivisto KT, Backman JT, Neuvonen PJ. The cytochrome P450 3A4 inhibitor itraconazole markedly increases the plasma concentrations of dexamethasone and enhances its adrenal-suppressant effect. Clin Pharmacol Ther. 2000;68(5):487-494.", "pmid": "11103751", "doi": "10.1067/mcp.2000.110772", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11103751/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "St. John's Wort may lower dexamethasone exposure by inducing CYP3A4.", "clinicalSignificance": "Reduced dexamethasone exposure can lead to inadequate control of the condition being treated.", "managementStrategy": "Avoid St. John's Wort during clinically important dexamethasone therapy and reassess if use changes.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Budesonide Inhaled", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "moderate", "description": "St. John's Wort induces CYP3A4, and budesonide is extensively metabolized by CYP3A. This may lower budesonide exposure and weaken asthma or airway inflammation control, particularly with high-hyperforin St. John's Wort products.", "recommendation": "Avoid starting St. John's Wort without discussing asthma or COPD control if you use inhaled budesonide. If the supplement is used anyway, track rescue inhaler use, symptoms, and exacerbations, and do not stop budesonide abruptly.", "minimumTimeSeparation": null, "mechanism": "St. John's Wort induces CYP3A4 expression and activity in humans. Budesonide is a CYP3A substrate, so increased CYP3A activity can plausibly increase budesonide metabolism and lower exposure.", "evidenceLevel": "moderate", "sources": [ { "text": "Whitten DL, Myers SP, Hawrelak JA, Wohlmuth H. The effect of St John's wort extracts on CYP3A: a systematic review of prospective clinical trials. Br J Clin Pharmacol. 2006;62(5):512-526.", "pmid": "17010103", "doi": "10.1111/j.1365-2125.2006.02755.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17010103/", "publicSourceType": "PMID" }, { "text": "Raaska K, Niemi M, Neuvonen M, Neuvonen PJ, Kivisto KT. Plasma concentrations of inhaled budesonide and its effects on plasma cortisol are increased by the cytochrome P4503A4 inhibitor itraconazole. Clin Pharmacol Ther. 2002;72(4):362-369.", "pmid": "12386638", "doi": "10.1067/mcp.2002.127397", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12386638/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "St. John's Wort may reduce inhaled budesonide exposure and controller effect.", "clinicalSignificance": "Lower inhaled steroid effect can worsen respiratory control and increase exacerbation risk.", "managementStrategy": "Avoid unsupervised St. John's Wort and monitor respiratory control closely if combined.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fluticasone Inhaled", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "moderate", "description": "St. John's Wort can induce CYP3A4, and fluticasone is cleared primarily by CYP3A4. Induction may lower systemic and possibly airway steroid exposure, which can reduce asthma or COPD controller effectiveness in some patients.", "recommendation": "Avoid starting St. John's Wort while relying on inhaled fluticasone for disease control unless your clinician agrees. If combined, monitor symptoms, peak flow if used, rescue inhaler use, and exacerbations after any St. John's Wort start or stop.", "minimumTimeSeparation": null, "mechanism": "St. John's Wort induces intestinal and hepatic CYP3A4; fluticasone is a CYP3A4 substrate with very high first-pass metabolism. Increased CYP3A activity can plausibly reduce fluticasone exposure, though the size of effect depends on formulation, dose, and the St. John's Wort product.", "evidenceLevel": "moderate", "sources": [ { "text": "Whitten DL, Myers SP, Hawrelak JA, Wohlmuth H. The effect of St John's wort extracts on CYP3A: a systematic review of prospective clinical trials. Br J Clin Pharmacol. 2006;62(5):512-526.", "pmid": "17010103", "doi": "10.1111/j.1365-2125.2006.02755.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17010103/", "publicSourceType": "PMID" }, { "text": "Foisy MM, Yakiwchuk EM, Chiu I, Singh AE. Adrenal suppression and Cushing's syndrome secondary to an interaction between ritonavir and fluticasone: a review of the literature. HIV Med. 2008;9(6):389-396.", "pmid": "18459946", "doi": "10.1111/j.1468-1293.2008.00579.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18459946/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "St. John's Wort may lower inhaled fluticasone exposure by inducing CYP3A4.", "clinicalSignificance": "Reduced controller effect can worsen respiratory symptoms or increase exacerbation risk.", "managementStrategy": "Avoid unsupervised St. John's Wort and monitor respiratory control after any change in supplement use.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Fluticasone Nasal", "supplementBName": "St. John's Wort", "interactionType": "conflict", "severity": "moderate", "description": "St. John's Wort induces CYP3A4, the main pathway that clears fluticasone. With daily nasal fluticasone, this may lower steroid exposure and reduce rhinitis or nasal polyp symptom control, though the effect is likely product- and dose-dependent.", "recommendation": "Avoid starting St. John's Wort if nasal fluticasone control is important, or monitor symptoms after any change. If congestion, sneezing, or nasal polyp symptoms worsen after starting St. John's Wort, ask about adjusting therapy rather than simply increasing steroid dose on your own.", "minimumTimeSeparation": null, "mechanism": "High-hyperforin St. John's Wort induces CYP3A4 expression and activity. Fluticasone is extensively cleared by CYP3A4, so induction may increase metabolism and lower exposure after swallowed or absorbed nasal doses.", "evidenceLevel": "moderate", "sources": [ { "text": "Whitten DL, Myers SP, Hawrelak JA, Wohlmuth H. The effect of St John's wort extracts on CYP3A: a systematic review of prospective clinical trials. Br J Clin Pharmacol. 2006;62(5):512-526.", "pmid": "17010103", "doi": "10.1111/j.1365-2125.2006.02755.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17010103/", "publicSourceType": "PMID" }, { "text": "Foisy MM, Yakiwchuk EM, Chiu I, Singh AE. Adrenal suppression and Cushing's syndrome secondary to an interaction between ritonavir and fluticasone: a review of the literature. HIV Med. 2008;9(6):389-396.", "pmid": "18459946", "doi": "10.1111/j.1468-1293.2008.00579.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18459946/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "St. John's Wort may lower nasal fluticasone exposure by inducing CYP3A4.", "clinicalSignificance": "Reduced local steroid effect may worsen rhinitis or nasal polyp control in daily users.", "managementStrategy": "Avoid unsupervised St. John's Wort and monitor nasal symptom control after supplement changes.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Levothyroxine", "supplementBName": "Iron Bisglycinate", "interactionType": "timingSensitive", "severity": "serious", "description": "Iron bisglycinate contains elemental iron and should be handled like other oral iron supplements around levothyroxine. Iron can bind thyroid hormone in the gut and lower absorption, which may raise TSH and bring back hypothyroid symptoms. The strongest human data are with ferrous sulfate, but the same timing precaution is appropriate for bisglycinate because the interacting component is iron.", "recommendation": "Take levothyroxine on an empty stomach with water, and take iron bisglycinate at least 4 hours later. Recheck thyroid labs after starting, stopping, or substantially changing iron supplementation.", "minimumTimeSeparation": 240, "mechanism": "Ferrous and ferric iron can form poorly absorbed iron-thyroxine complexes in the intestinal lumen. Reduced levothyroxine bioavailability can lead to compensatory TSH elevation and higher dose requirements.", "evidenceLevel": "moderate", "sources": [ { "text": "Campbell NRC, Hasinoff BB, Stalts H, Rao B, Wong NCW. Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism. Ann Intern Med. 1992;117(12):1010-1013.", "pmid": "1443969", "doi": "10.7326/0003-4819-117-12-1010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1443969/", "publicSourceType": "PMID" }, { "text": "Shakir KM, Chute JP, Aprill BS, Lazarus AA. Ferrous sulfate-induced increase in requirement for thyroxine in a patient with primary hypothyroidism. South Med J. 1997;90(6):637-639.", "pmid": "9191742", "doi": "10.1097/00007611-199706000-00011", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9191742/", "publicSourceType": "PMID" }, { "text": "Wiesner A, Gajewska D, Pasko P. Levothyroxine Interactions with Food and Dietary Supplements-A Systematic Review. Pharmaceuticals (Basel). 2021;14(3):206.", "pmid": "33801406", "doi": "10.3390/ph14030206", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33801406/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Iron bisglycinate can lower levothyroxine absorption if taken at the same time.", "clinicalSignificance": "Reduced levothyroxine exposure can cause loss of thyroid control and dose escalation.", "managementStrategy": "Separate iron bisglycinate from levothyroxine by at least 4 hours and monitor TSH after changes.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Levothyroxine", "supplementBName": "Magnesium Citrate", "interactionType": "timingSensitive", "severity": "moderate", "description": "Magnesium-containing products can interfere with levothyroxine absorption when taken together. The best evidence is for magnesium antacids and other cation-containing agents, but magnesium citrate still delivers magnesium ions in the gut. Taking them together can make thyroid levels harder to control.", "recommendation": "Separate magnesium citrate from levothyroxine by at least 4 hours. Keep the timing consistent and check thyroid labs if you start or stop regular magnesium use.", "minimumTimeSeparation": 240, "mechanism": "Magnesium ions may complex with levothyroxine in the intestinal lumen and reduce the free drug available for absorption. Magnesium antacid effects on gastric pH may add to this problem for some formulations.", "evidenceLevel": "emerging", "sources": [ { "text": "Liwanpo L, Hershman JM. Conditions and drugs interfering with thyroxine absorption. Best Pract Res Clin Endocrinol Metab. 2009;23(6):781-792.", "pmid": "19942153", "doi": "10.1016/j.beem.2009.06.006", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19942153/", "publicSourceType": "PMID" }, { "text": "Skelin M, Lucijanic T, Amidzic Klaric D, Resic A, Bakula M, Liberati-Cizmek AM, Gharib H, Rahelic D. Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review. Clin Ther. 2017;39(2):378-403.", "pmid": "28153426", "doi": "10.1016/j.clinthera.2017.01.005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28153426/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Magnesium citrate may reduce levothyroxine absorption when co-administered.", "clinicalSignificance": "Even modest absorption loss matters because levothyroxine has a narrow therapeutic index.", "managementStrategy": "Dose magnesium citrate at least 4 hours away from levothyroxine.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Levothyroxine", "supplementBName": "Magnesium L-Threonate", "interactionType": "timingSensitive", "severity": "moderate", "description": "Magnesium L-threonate has not been studied directly with levothyroxine, but it supplies magnesium ions that may interfere with thyroid hormone absorption. This is most relevant for people with borderline thyroid control, pregnancy, thyroid cancer suppression therapy, or a history of fluctuating TSH. Separating the doses is a low-burden way to avoid preventable under-replacement.", "recommendation": "Take magnesium L-threonate at least 4 hours after levothyroxine. If you use it daily, keep the schedule stable and monitor thyroid labs after starting or stopping it.", "minimumTimeSeparation": 240, "mechanism": "Divalent cations can bind levothyroxine or reduce its solubility in the gastrointestinal tract. Magnesium L-threonate is expected to carry this risk through its magnesium content even though form-specific clinical data are limited.", "evidenceLevel": "emerging", "sources": [ { "text": "Liwanpo L, Hershman JM. Conditions and drugs interfering with thyroxine absorption. Best Pract Res Clin Endocrinol Metab. 2009;23(6):781-792.", "pmid": "19942153", "doi": "10.1016/j.beem.2009.06.006", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19942153/", "publicSourceType": "PMID" }, { "text": "Skelin M, Lucijanic T, Amidzic Klaric D, Resic A, Bakula M, Liberati-Cizmek AM, Gharib H, Rahelic D. Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review. Clin Ther. 2017;39(2):378-403.", "pmid": "28153426", "doi": "10.1016/j.clinthera.2017.01.005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28153426/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Magnesium L-threonate may lower levothyroxine absorption if taken in the same dosing window.", "clinicalSignificance": "TSH can drift upward when levothyroxine absorption is reduced repeatedly.", "managementStrategy": "Separate magnesium L-threonate and levothyroxine by at least 4 hours.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Levothyroxine", "supplementBName": "Magnesium Malate", "interactionType": "timingSensitive", "severity": "moderate", "description": "Magnesium malate may reduce levothyroxine absorption if taken at the same time. Direct studies with this exact magnesium salt are lacking, but the clinical concern is the magnesium cation, not the malate portion. Repeated co-administration can make thyroid replacement appear too weak.", "recommendation": "Take levothyroxine first with water, then wait at least 4 hours before magnesium malate. If thyroid symptoms or TSH change after adding magnesium, review timing before changing the levothyroxine dose.", "minimumTimeSeparation": 240, "mechanism": "Magnesium can form poorly absorbed complexes with levothyroxine or reduce dissolution in the gut. This lowers the amount of active hormone reaching systemic circulation.", "evidenceLevel": "emerging", "sources": [ { "text": "Liwanpo L, Hershman JM. Conditions and drugs interfering with thyroxine absorption. Best Pract Res Clin Endocrinol Metab. 2009;23(6):781-792.", "pmid": "19942153", "doi": "10.1016/j.beem.2009.06.006", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19942153/", "publicSourceType": "PMID" }, { "text": "Skelin M, Lucijanic T, Amidzic Klaric D, Resic A, Bakula M, Liberati-Cizmek AM, Gharib H, Rahelic D. Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review. Clin Ther. 2017;39(2):378-403.", "pmid": "28153426", "doi": "10.1016/j.clinthera.2017.01.005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28153426/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Magnesium malate may interfere with levothyroxine absorption.", "clinicalSignificance": "Reduced absorption can lead to hypothyroid symptoms or unnecessary levothyroxine dose escalation.", "managementStrategy": "Separate magnesium malate from levothyroxine by at least 4 hours.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Levothyroxine", "supplementBName": "Magnesium Taurate", "interactionType": "timingSensitive", "severity": "moderate", "description": "Magnesium taurate may interfere with levothyroxine absorption when taken together. This is an extrapolation from magnesium-containing products and other polyvalent cations known to reduce thyroid hormone absorption. The risk is most important when the supplement is taken daily near the thyroid dose.", "recommendation": "Separate magnesium taurate and levothyroxine by at least 4 hours. Keep your levothyroxine routine consistent and monitor TSH after starting or stopping daily magnesium taurate.", "minimumTimeSeparation": 240, "mechanism": "The magnesium component can bind or reduce dissolution of levothyroxine in the intestinal lumen, decreasing bioavailability. Taurate itself is not the suspected interacting component.", "evidenceLevel": "emerging", "sources": [ { "text": "Liwanpo L, Hershman JM. Conditions and drugs interfering with thyroxine absorption. Best Pract Res Clin Endocrinol Metab. 2009;23(6):781-792.", "pmid": "19942153", "doi": "10.1016/j.beem.2009.06.006", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19942153/", "publicSourceType": "PMID" }, { "text": "Skelin M, Lucijanic T, Amidzic Klaric D, Resic A, Bakula M, Liberati-Cizmek AM, Gharib H, Rahelic D. Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review. Clin Ther. 2017;39(2):378-403.", "pmid": "28153426", "doi": "10.1016/j.clinthera.2017.01.005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28153426/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Magnesium taurate may lower levothyroxine exposure if taken together.", "clinicalSignificance": "Small repeated reductions in levothyroxine absorption can destabilize thyroid labs.", "managementStrategy": "Take magnesium taurate at least 4 hours away from levothyroxine.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Levothyroxine", "supplementBName": "Zinc Carnosine", "interactionType": "timingSensitive", "severity": "moderate", "description": "Zinc carnosine supplies zinc, a divalent mineral that may interfere with levothyroxine absorption if taken at the same time. Direct levothyroxine-zinc outcome data are limited, so this is a precaution based on thyroid hormone sensitivity to polyvalent cations. It matters most for people whose TSH target is tight.", "recommendation": "Separate zinc carnosine from levothyroxine by at least 4 hours. If your TSH changes after adding it, correct the timing first and then discuss whether a levothyroxine dose adjustment is still needed.", "minimumTimeSeparation": 240, "mechanism": "Zinc may bind levothyroxine or reduce its solubility in the gastrointestinal tract, leaving less hormone available for absorption. The carnosine carrier does not remove the zinc-cation concern.", "evidenceLevel": "emerging", "sources": [ { "text": "Liwanpo L, Hershman JM. Conditions and drugs interfering with thyroxine absorption. Best Pract Res Clin Endocrinol Metab. 2009;23(6):781-792.", "pmid": "19942153", "doi": "10.1016/j.beem.2009.06.006", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19942153/", "publicSourceType": "PMID" }, { "text": "Skelin M, Lucijanic T, Amidzic Klaric D, Resic A, Bakula M, Liberati-Cizmek AM, Gharib H, Rahelic D. Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review. Clin Ther. 2017;39(2):378-403.", "pmid": "28153426", "doi": "10.1016/j.clinthera.2017.01.005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28153426/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Zinc carnosine may reduce levothyroxine absorption when co-administered.", "clinicalSignificance": "Absorption loss can cause higher TSH or recurrent hypothyroid symptoms.", "managementStrategy": "Dose zinc carnosine at least 4 hours apart from levothyroxine.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Levothyroxine", "supplementBName": "Zinc Picolinate", "interactionType": "timingSensitive", "severity": "moderate", "description": "Zinc picolinate may interfere with levothyroxine absorption if taken together. The evidence is weaker than for calcium or iron, but levothyroxine is sensitive to intestinal binding by mineral cations. Daily same-time use can create preventable thyroid lab fluctuation.", "recommendation": "Take zinc picolinate at least 4 hours away from levothyroxine. Keep your thyroid dose on a consistent empty-stomach schedule and monitor labs after supplement changes.", "minimumTimeSeparation": 240, "mechanism": "Zinc ions can plausibly form poorly absorbed complexes with levothyroxine or reduce its free concentration in the gut. Picolinate changes zinc delivery but does not eliminate zinc's cation-binding potential.", "evidenceLevel": "emerging", "sources": [ { "text": "Liwanpo L, Hershman JM. Conditions and drugs interfering with thyroxine absorption. Best Pract Res Clin Endocrinol Metab. 2009;23(6):781-792.", "pmid": "19942153", "doi": "10.1016/j.beem.2009.06.006", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19942153/", "publicSourceType": "PMID" }, { "text": "Skelin M, Lucijanic T, Amidzic Klaric D, Resic A, Bakula M, Liberati-Cizmek AM, Gharib H, Rahelic D. Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review. Clin Ther. 2017;39(2):378-403.", "pmid": "28153426", "doi": "10.1016/j.clinthera.2017.01.005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28153426/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Zinc picolinate may reduce levothyroxine absorption when taken in the same window.", "clinicalSignificance": "The interaction can mimic an inadequate levothyroxine dose.", "managementStrategy": "Separate zinc picolinate and levothyroxine by at least 4 hours.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Levothyroxine", "supplementBName": "Chromium", "interactionType": "timingSensitive", "severity": "moderate", "description": "Chromium supplements, particularly chromium picolinate, have been shown in a small human absorption study to reduce levothyroxine exposure. This can make levothyroxine less effective if the two are taken together. The interaction is not usually dangerous when doses are separated, but it can matter for people with tight TSH targets.", "recommendation": "Take levothyroxine at least 4 hours apart from chromium supplements. Recheck thyroid labs after starting or stopping regular chromium use, especially if symptoms change.", "minimumTimeSeparation": 240, "mechanism": "Chromium picolinate appears to reduce the area under the thyroxine concentration curve after oral levothyroxine, likely through intestinal binding or impaired dissolution. The result is lower bioavailability rather than altered thyroid hormone metabolism.", "evidenceLevel": "moderate", "sources": [ { "text": "John-Kalarickal J, Pearlman G, Carlson HE. New medications which decrease levothyroxine absorption. Thyroid. 2007;17(8):763-765.", "pmid": "17725434", "doi": "10.1089/thy.2007.0060", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17725434/", "publicSourceType": "PMID" }, { "text": "Wiesner A, Gajewska D, Pasko P. Levothyroxine Interactions with Food and Dietary Supplements-A Systematic Review. Pharmaceuticals (Basel). 2021;14(3):206.", "pmid": "33801406", "doi": "10.3390/ph14030206", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33801406/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Chromium can reduce levothyroxine absorption when taken together.", "clinicalSignificance": "Lower levothyroxine exposure can worsen thyroid control and lead to avoidable dose changes.", "managementStrategy": "Separate chromium from levothyroxine by at least 4 hours and monitor TSH after changes.", "isSynergistic": false, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Levothyroxine", "supplementBName": "Ashwagandha", "interactionType": "caution", "severity": "moderate", "description": "Ashwagandha has been associated with increased thyroid hormone levels and rare thyrotoxicosis reports. When combined with levothyroxine, it may contribute to over-replacement symptoms such as palpitations, tremor, anxiety, heat intolerance, or unintended weight loss. The risk is uncertain but clinically relevant because levothyroxine dosing is intentionally narrow.", "recommendation": "Avoid starting ashwagandha on your own if you take levothyroxine for thyroid replacement or TSH suppression. If you use it, tell your prescriber and check thyroid labs after starting, stopping, or changing the dose.", "minimumTimeSeparation": null, "mechanism": "Human data suggest ashwagandha may alter thyroid indices, possibly by stimulating thyroid hormone production or triggering thyroiditis in susceptible people. Exogenous levothyroxine plus a supplement-driven rise in thyroid hormone effect can push the net state toward thyrotoxicosis.", "evidenceLevel": "emerging", "sources": [ { "text": "van der Hooft CS, Hoekstra A, Winter A, de Smet PA. Thyrotoxicosis following the use of ashwagandha. Ned Tijdschr Geneeskd. 2005;149(47):2637-2638.", "pmid": "16355578", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16355578/", "publicSourceType": "PMID" }, { "text": "Sharma AK, Basu I, Singh S. Efficacy and Safety of Ashwagandha Root Extract in Subclinical Hypothyroid Patients: A Double-Blind, Randomized Placebo-Controlled Trial. J Altern Complement Med. 2018;24(3):243-248.", "pmid": "28829155", "doi": "10.1089/acm.2017.0183", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28829155/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bAffectsA", "effect": "Ashwagandha may add to levothyroxine's thyroid hormone effect in susceptible users.", "clinicalSignificance": "Unrecognized thyroid hormone excess can cause symptoms and raise cardiac or bone risk over time.", "managementStrategy": "Use only with thyroid lab monitoring and stop if hyperthyroid symptoms appear.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Liothyronine", "supplementBName": "Vitamin B7", "interactionType": "caution", "severity": "serious", "description": "Vitamin B7, also called biotin, does not directly change liothyronine levels, but it can distort thyroid lab tests used to monitor therapy. Many immunoassays can show falsely low TSH and falsely high T3 or T4 after high-dose biotin. This can make liothyronine dosing look excessive or make hyperthyroidism appear worse than it is.", "recommendation": "Stop biotin for at least 48 to 72 hours before thyroid labs, and longer for high-dose products if your clinician or lab recommends it. Tell the lab and prescriber about any hair, skin, nail, or B-complex product that contains biotin.", "minimumTimeSeparation": null, "mechanism": "Excess biotin competes with assay biotin-streptavidin binding. In sandwich assays it can cause falsely low results, while in competitive thyroid hormone assays it can cause falsely high free or total thyroid hormone results.", "evidenceLevel": "strong", "sources": [ { "text": "Ylli D, Soldin SJ, Stolze B, Wei B, Nigussie G, Nguyen H, Mendu DR, Mete M, Wu D, Gomes-Lima CJ, Klubo-Gwiezdzinska J, Burman KD, Wartofsky L. Biotin Interference in Assays for Thyroid Hormones, Thyrotropin and Thyroglobulin. Thyroid. 2021;31(8):1160-1170.", "pmid": "34042535", "doi": "10.1089/thy.2020.0866", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34042535/", "publicSourceType": "PMID" }, { "text": "Piketty ML, Prie D, Sedel F, Bernard D, Hercend C, Chanson P, Souberbielle JC. High-dose biotin therapy leading to false biochemical endocrine profiles: validation of a simple method to overcome biotin interference. Clin Chem Lab Med. 2017;55(6):817-825.", "pmid": "28222020", "doi": "10.1515/cclm-2016-1183", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28222020/", "publicSourceType": "PMID" }, { "text": "Odhaib SA, Mansour AA, Haddad NS. How Biotin Induces Misleading Results in Thyroid Bioassays: Case Series. Cureus. 2019;11(5):e4727.", "pmid": "31363424", "doi": "10.7759/cureus.4727", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31363424/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Vitamin B7 can create misleading thyroid labs during liothyronine monitoring.", "clinicalSignificance": "False thyroid results can lead to inappropriate dose changes or unnecessary workup.", "managementStrategy": "Hold biotin before thyroid testing and disclose supplement use to the lab and prescriber.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Liothyronine", "supplementBName": "Ashwagandha", "interactionType": "caution", "severity": "serious", "description": "Ashwagandha may increase thyroid hormone activity or trigger thyrotoxicosis in susceptible people. Liothyronine is active T3 and can cause symptoms quickly if the total thyroid hormone effect becomes too high. Combining the two may increase the chance of palpitations, tremor, anxiety, insomnia, or heat intolerance.", "recommendation": "Avoid ashwagandha unless your prescriber knows you are taking liothyronine. If you start or stop ashwagandha, monitor thyroid labs and symptoms closely because liothyronine dose changes may be needed.", "minimumTimeSeparation": null, "mechanism": "Ashwagandha has been linked to changes in TSH, T3, and T4 and rare thyrotoxicosis. Because liothyronine is pharmacologically active T3, any supplement-related increase in thyroid hormone effect can be additive.", "evidenceLevel": "emerging", "sources": [ { "text": "van der Hooft CS, Hoekstra A, Winter A, de Smet PA. Thyrotoxicosis following the use of ashwagandha. Ned Tijdschr Geneeskd. 2005;149(47):2637-2638.", "pmid": "16355578", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16355578/", "publicSourceType": "PMID" }, { "text": "Sharma AK, Basu I, Singh S. Efficacy and Safety of Ashwagandha Root Extract in Subclinical Hypothyroid Patients: A Double-Blind, Randomized Placebo-Controlled Trial. J Altern Complement Med. 2018;24(3):243-248.", "pmid": "28829155", "doi": "10.1089/acm.2017.0183", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28829155/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Ashwagandha may add to liothyronine's thyroid hormone effect.", "clinicalSignificance": "Excess T3 effect can produce clinically important cardiac and nervous-system symptoms.", "managementStrategy": "Avoid unsupervised combination and monitor thyroid labs after any ashwagandha change.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Methimazole", "supplementBName": "Iodine", "interactionType": "caution", "severity": "serious", "description": "Iodine intake can change how Graves' disease responds to methimazole. High or unstable iodine exposure can alter thyroid hormone synthesis and may delay control or change the methimazole dose needed, while pharmacologic iodide is sometimes used intentionally under specialist supervision. Unsupervised iodine or kelp-style supplementation can make thyroid labs unpredictable.", "recommendation": "Do not add iodine supplements while taking methimazole unless your thyroid clinician specifically recommends it. Keep dietary iodine intake consistent and recheck thyroid labs after any meaningful iodine exposure change.", "minimumTimeSeparation": null, "mechanism": "Methimazole inhibits thyroid peroxidase-mediated iodide oxidation and organification. Extra iodide changes substrate availability and can cause acute Wolff-Chaikoff inhibition, later escape, or iodine-induced hyperthyroidism in susceptible thyroid tissue.", "evidenceLevel": "moderate", "sources": [ { "text": "Azizi F. Environmental iodine intake affects the response to methimazole in patients with diffuse toxic goiter. J Clin Endocrinol Metab. 1985;61(2):374-377.", "pmid": "3839244", "doi": "10.1210/jcem-61-2-374", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3839244/", "publicSourceType": "PMID" }, { "text": "Roti E, Robuschi G, Gardini E, Montermini M, Salvi M, Manfredi A, d'Amato L, Robuschi C, Gnudi A, Braverman LE. Comparison of methimazole, methimazole and sodium ipodate, and methimazole and saturated solution of potassium iodide in the early treatment of hyperthyroid Graves' disease. Clin Endocrinol (Oxf). 1988;28(3):305-314.", "pmid": "3168311", "doi": "10.1111/j.1365-2265.1988.tb01217.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3168311/", "publicSourceType": "PMID" }, { "text": "Solomon BL, Evaul JE, Burman KD, Wartofsky L. Remission rates with antithyroid drug therapy: continuing influence of iodine intake? Ann Intern Med. 1987;107(4):510-512.", "pmid": "2443050", "doi": "10.7326/0003-4819-107-4-510", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2443050/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Iodine can destabilize the thyroid response to methimazole.", "clinicalSignificance": "Unexpected iodine exposure can delay euthyroidism, trigger relapse, or lead to inappropriate dose changes.", "managementStrategy": "Avoid unsupervised iodine supplementation and keep iodine intake stable during methimazole therapy.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Methimazole", "supplementBName": "Selenium", "interactionType": "synergy", "severity": "info", "description": "Selenium has been studied as an add-on to methimazole in Graves' disease. Some smaller trials suggest improved antibody or early biochemical measures, while larger and selenium-sufficient cohorts show little or no benefit for remission or quality of life. This is a possible adjunctive effect, not a replacement for antithyroid medication.", "recommendation": "Do not use selenium instead of methimazole. If your clinician recommends selenium, keep the dose in a standard supplemental range and avoid high-dose long-term use unless specifically monitored.", "minimumTimeSeparation": null, "mechanism": "Selenium is required for selenoproteins such as glutathione peroxidases and deiodinases, which participate in thyroid redox balance and thyroid hormone metabolism. Its potential benefit during methimazole therapy appears related to oxidative stress and autoimmune activity rather than methimazole pharmacokinetics.", "evidenceLevel": "moderate", "sources": [ { "text": "Leo M, Bartalena L, Rotondo Dottore G, Piantanida E, Premoli P, Ionni I, Di Cera M, Masiello E, Sassi L, Tanda ML, Latrofa F, Vitti P, Marcocci C, Marino M. Effects of selenium on short-term control of hyperthyroidism due to Graves' disease treated with methimazole: results of a randomized clinical trial. J Endocrinol Invest. 2017;40(3):281-287.", "pmid": "27734319", "doi": "10.1007/s40618-016-0559-9", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27734319/", "publicSourceType": "PMID" }, { "text": "Kahaly GJ, Riedl M, Konig J, Diana T, Schomburg L. Double-Blind, Placebo-Controlled, Randomized Trial of Selenium in Graves Hyperthyroidism. J Clin Endocrinol Metab. 2017;102(11):4333-4341.", "pmid": "29092078", "doi": "10.1210/jc.2017-01736", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29092078/", "publicSourceType": "PMID" }, { "text": "Xu B, Wu D, Ying H, Zhang Y. A pilot study on the beneficial effects of additional selenium supplementation to methimazole for treating patients with Graves' disease. Turk J Med Sci. 2019;49(3):715-722.", "pmid": "31023005", "doi": "10.3906/sag-1808-67", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31023005/", "publicSourceType": "PMID" }, { "text": "Cramon PK, Winther KH, Boesen VB, Larsen CB, Bonnema SJ, Bjorner JB, et al. Selenium supplementation in individuals with newly diagnosed Graves' hyperthyroidism: a double-blind, multi-centre RCT. Eur Thyroid J. 2026;15(1).", "pmid": "41384622", "doi": "10.1530/ETJ-25-0264", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41384622/", "publicSourceType": "PMID" } ], "clinicalSeverity": "minor", "directionality": "bAffectsA", "effect": "Selenium may modestly influence Graves' disease markers during methimazole treatment, but results are inconsistent.", "clinicalSignificance": "Patients should not assume selenium improves remission or allows lower methimazole dosing without monitoring.", "managementStrategy": "Use selenium only as a monitored adjunct and avoid excessive dosing.", "isSynergistic": true, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Methimazole", "supplementBName": "Ashwagandha", "interactionType": "conflict", "severity": "serious", "description": "Ashwagandha may increase thyroid hormone levels or trigger thyrotoxicosis in susceptible people. That can oppose the purpose of methimazole, which is used to bring excessive thyroid hormone production under control. The evidence is limited, but the clinical direction is concerning for people being treated for hyperthyroidism.", "recommendation": "Avoid ashwagandha while taking methimazole unless your thyroid clinician explicitly approves it. If you have already started it, report palpitations, tremor, heat intolerance, anxiety, or worsening thyroid labs promptly.", "minimumTimeSeparation": null, "mechanism": "Ashwagandha has been associated with higher thyroid hormone indices and case reports of thyrotoxicosis. This may pharmacodynamically counter methimazole's antithyroid effect even though it is not known to alter methimazole metabolism.", "evidenceLevel": "emerging", "sources": [ { "text": "van der Hooft CS, Hoekstra A, Winter A, de Smet PA. Thyrotoxicosis following the use of ashwagandha. Ned Tijdschr Geneeskd. 2005;149(47):2637-2638.", "pmid": "16355578", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16355578/", "publicSourceType": "PMID" }, { "text": "Sharma AK, Basu I, Singh S. Efficacy and Safety of Ashwagandha Root Extract in Subclinical Hypothyroid Patients: A Double-Blind, Randomized Placebo-Controlled Trial. J Altern Complement Med. 2018;24(3):243-248.", "pmid": "28829155", "doi": "10.1089/acm.2017.0183", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28829155/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Ashwagandha may oppose methimazole's intended control of thyroid hormone excess.", "clinicalSignificance": "Worsening thyrotoxicosis can increase cardiac, bone, and neuropsychiatric risk.", "managementStrategy": "Avoid the combination unless supervised with thyroid lab monitoring.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Methimazole", "supplementBName": "Vitamin B7", "interactionType": "caution", "severity": "serious", "description": "Vitamin B7 can interfere with thyroid immunoassays used to monitor methimazole treatment. The pattern can mimic Graves' disease activity by making TSH look falsely low and T3 or T4 look falsely high on susceptible assay platforms. This can lead to unnecessary methimazole dose increases or delayed dose reduction.", "recommendation": "Stop biotin for at least 48 to 72 hours before thyroid testing, and follow longer lab-specific instructions for high-dose biotin. Tell your prescriber and lab about all biotin-containing supplements before methimazole monitoring labs are interpreted.", "minimumTimeSeparation": null, "mechanism": "Biotin-streptavidin assay interference can produce false results in both sandwich and competitive immunoassays. In thyroid monitoring this can falsely suggest persistent hyperthyroidism even when methimazole is working.", "evidenceLevel": "strong", "sources": [ { "text": "Ylli D, Soldin SJ, Stolze B, Wei B, Nigussie G, Nguyen H, Mendu DR, Mete M, Wu D, Gomes-Lima CJ, Klubo-Gwiezdzinska J, Burman KD, Wartofsky L. Biotin Interference in Assays for Thyroid Hormones, Thyrotropin and Thyroglobulin. Thyroid. 2021;31(8):1160-1170.", "pmid": "34042535", "doi": "10.1089/thy.2020.0866", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34042535/", "publicSourceType": "PMID" }, { "text": "Piketty ML, Prie D, Sedel F, Bernard D, Hercend C, Chanson P, Souberbielle JC. High-dose biotin therapy leading to false biochemical endocrine profiles: validation of a simple method to overcome biotin interference. Clin Chem Lab Med. 2017;55(6):817-825.", "pmid": "28222020", "doi": "10.1515/cclm-2016-1183", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28222020/", "publicSourceType": "PMID" }, { "text": "Odhaib SA, Mansour AA, Haddad NS. How Biotin Induces Misleading Results in Thyroid Bioassays: Case Series. Cureus. 2019;11(5):e4727.", "pmid": "31363424", "doi": "10.7759/cureus.4727", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31363424/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Vitamin B7 can make methimazole monitoring labs falsely suggest ongoing hyperthyroidism.", "clinicalSignificance": "Misleading labs can cause inappropriate methimazole dosing and unnecessary concern about treatment failure.", "managementStrategy": "Hold biotin before thyroid labs and disclose supplement use before methimazole adjustments.", "isSynergistic": false, "interactionEvidenceRating": "strong", "scope": "prescription-supplement" }, { "supplementAName": "Tamsulosin", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "serious", "description": "Tamsulosin can cause orthostatic hypotension, particularly when treatment is started or restarted. Alcohol also worsens orthostatic blood pressure control and can trigger syncope. Taking them together can increase dizziness, fainting, and fall risk, especially in older adults or people already taking blood pressure medicines.", "recommendation": "Avoid or sharply limit alcohol when starting or restarting tamsulosin. If you drink, keep intake low, rise slowly from sitting or lying down, and stop the combination if you feel lightheaded or faint.", "minimumTimeSeparation": null, "mechanism": "Tamsulosin blocks alpha1A and alpha1D adrenergic receptors in the lower urinary tract but can still reduce vascular alpha1 tone enough to cause orthostatic symptoms. Alcohol impairs vasoconstrictor compensation during standing, producing additive orthostatic hypotension.", "evidenceLevel": "moderate", "sources": [ { "text": "Bird ST, Delaney JA, Brophy JM, Etminan M, Skeldon SC, Hartzema AG. Tamsulosin treatment for benign prostatic hyperplasia and risk of severe hypotension in men aged 40-85 years in the United States: risk window analyses using between and within patient methodology. BMJ. 2013;347:f6320.", "pmid": "24192967", "doi": "10.1136/bmj.f6320", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24192967/", "publicSourceType": "PMID" }, { "text": "Narkiewicz K, Cooley RL, Somers VK. Alcohol potentiates orthostatic hypotension: implications for alcohol-related syncope. Circulation. 2000;101(4):398-402.", "pmid": "10653831", "doi": "10.1161/01.cir.101.4.398", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10653831/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bidirectional", "effect": "Additive orthostatic blood-pressure lowering can cause dizziness, syncope, and falls.", "clinicalSignificance": "The risk is highest during the first weeks of tamsulosin therapy or after restarting treatment.", "managementStrategy": "Avoid or minimize alcohol during tamsulosin initiation and monitor for orthostatic symptoms.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Alfuzosin", "supplementBName": "Alcohol", "interactionType": "caution", "severity": "moderate", "description": "Alfuzosin is an alpha1 blocker used for urinary symptoms and can contribute to dizziness or low blood pressure in susceptible patients. Alcohol can independently worsen orthostatic hypotension. Combining them may increase lightheadedness, fainting, or falls, especially after dose changes or with other antihypertensive medicines.", "recommendation": "Limit alcohol when starting alfuzosin or when your dose changes. If you choose to drink, use small amounts, avoid standing quickly, and pause alcohol if you notice dizziness or near-fainting.", "minimumTimeSeparation": null, "mechanism": "Alfuzosin reduces alpha1-mediated smooth muscle tone and can lower vascular resistance. Alcohol blunts orthostatic vasoconstriction, so the combination can impair blood pressure compensation during standing.", "evidenceLevel": "moderate", "sources": [ { "text": "Zhang LT, Lee SW, Park K, Chung WS, Kim SW, Hyun JS, Moon DG, Yang SK. Multicenter, prospective, comparative cohort study evaluating the efficacy and safety of alfuzosin 10 mg with regard to blood pressure in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia with or without antihypertensive medications. Clin Interv Aging. 2015;10:277-286.", "pmid": "25653511", "doi": "10.2147/CIA.S74102", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25653511/", "publicSourceType": "PMID" }, { "text": "Narkiewicz K, Cooley RL, Somers VK. Alcohol potentiates orthostatic hypotension: implications for alcohol-related syncope. Circulation. 2000;101(4):398-402.", "pmid": "10653831", "doi": "10.1161/01.cir.101.4.398", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10653831/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive impairment of standing blood-pressure control can cause dizziness or syncope.", "clinicalSignificance": "Patients on antihypertensives or with baseline low blood pressure may become symptomatic.", "managementStrategy": "Limit alcohol and monitor for dizziness, especially during alfuzosin initiation.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Tamsulosin", "supplementBName": "L-Arginine", "interactionType": "caution", "severity": "moderate", "description": "L-Arginine can modestly lower blood pressure by increasing nitric-oxide-mediated vasodilation. Tamsulosin can also cause orthostatic hypotension in a risk-window pattern after starting or restarting therapy. The combination can increase dizziness or fainting risk in people who are older, dehydrated, or taking other blood pressure medicines.", "recommendation": "Start L-arginine at a low dose only after you know how tamsulosin affects you. Check seated and standing blood pressure for 1-2 weeks, and stop or reduce L-arginine if you develop lightheadedness or near-fainting.", "minimumTimeSeparation": null, "mechanism": "L-Arginine is a substrate for endothelial nitric oxide synthase, increasing nitric oxide availability and vasodilation. This can add to tamsulosin-related reduction in vascular alpha1 compensation during standing.", "evidenceLevel": "moderate", "sources": [ { "text": "Bird ST, Delaney JA, Brophy JM, Etminan M, Skeldon SC, Hartzema AG. Tamsulosin treatment for benign prostatic hyperplasia and risk of severe hypotension in men aged 40-85 years in the United States: risk window analyses using between and within patient methodology. BMJ. 2013;347:f6320.", "pmid": "24192967", "doi": "10.1136/bmj.f6320", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24192967/", "publicSourceType": "PMID" }, { "text": "Dong JY, Qin LQ, Zhang Z, Zhao Y, Wang J, Arigoni F, Zhang W. Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials. Am Heart J. 2011;162(6):959-965.", "pmid": "22137067", "doi": "10.1016/j.ahj.2011.09.012", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22137067/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive vasodilation may produce symptomatic hypotension.", "clinicalSignificance": "The combination matters most during tamsulosin initiation or in patients already prone to low blood pressure.", "managementStrategy": "Start L-arginine low, monitor standing blood pressure, and stop if dizziness occurs.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Tamsulosin", "supplementBName": "L-Citrulline", "interactionType": "caution", "severity": "moderate", "description": "L-Citrulline raises plasma arginine and can lower blood pressure through nitric-oxide-mediated vasodilation. Tamsulosin has a documented association with severe hypotension, especially soon after starting or restarting it. Combining them can increase the chance of lightheadedness, fainting, or falls.", "recommendation": "Avoid starting L-citrulline at the same time as tamsulosin. If you use both, start with a low L-citrulline dose, monitor standing blood pressure, and stop if dizziness or near-syncope occurs.", "minimumTimeSeparation": null, "mechanism": "L-Citrulline is converted to L-arginine, increasing endothelial nitric oxide substrate availability and vasodilation. This can add to tamsulosin's alpha1-blocking effect on orthostatic vascular tone.", "evidenceLevel": "moderate", "sources": [ { "text": "Bird ST, Delaney JA, Brophy JM, Etminan M, Skeldon SC, Hartzema AG. Tamsulosin treatment for benign prostatic hyperplasia and risk of severe hypotension in men aged 40-85 years in the United States: risk window analyses using between and within patient methodology. BMJ. 2013;347:f6320.", "pmid": "24192967", "doi": "10.1136/bmj.f6320", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24192967/", "publicSourceType": "PMID" }, { "text": "Mirenayat MS, Moradi S, Mohammadi H, Rouhani MH. Effect of L-Citrulline Supplementation on Blood Pressure: a Systematic Review and Meta-Analysis of Clinical Trials. Curr Hypertens Rep. 2018;20(11):98.", "pmid": "30284051", "doi": "10.1007/s11906-018-0898-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30284051/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive nitric-oxide vasodilation may worsen tamsulosin-related hypotension.", "clinicalSignificance": "Dizziness and falls are plausible in patients already vulnerable to orthostatic blood-pressure drops.", "managementStrategy": "Do not start both together; use low-dose L-citrulline and monitor standing blood pressure.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Alfuzosin", "supplementBName": "L-Arginine", "interactionType": "caution", "severity": "moderate", "description": "L-Arginine can reduce blood pressure through nitric oxide production. Alfuzosin is generally uroselective but still has clinically relevant blood-pressure considerations, particularly in patients also using antihypertensives. Combining them can cause dizziness or low blood pressure in susceptible users.", "recommendation": "If you take alfuzosin, start L-arginine at a low dose and monitor blood pressure for 1-2 weeks. Reduce or stop L-arginine if you become lightheaded, unusually fatigued, or your readings fall below your usual range.", "minimumTimeSeparation": null, "mechanism": "L-Arginine increases endothelial nitric oxide synthesis and vasodilation. Alfuzosin blocks alpha1 receptors and can reduce vascular resistance, so their effects can add even though the drugs act through different pathways.", "evidenceLevel": "moderate", "sources": [ { "text": "Zhang LT, Lee SW, Park K, Chung WS, Kim SW, Hyun JS, Moon DG, Yang SK. Multicenter, prospective, comparative cohort study evaluating the efficacy and safety of alfuzosin 10 mg with regard to blood pressure in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia with or without antihypertensive medications. Clin Interv Aging. 2015;10:277-286.", "pmid": "25653511", "doi": "10.2147/CIA.S74102", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25653511/", "publicSourceType": "PMID" }, { "text": "Dong JY, Qin LQ, Zhang Z, Zhao Y, Wang J, Arigoni F, Zhang W. Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials. Am Heart J. 2011;162(6):959-965.", "pmid": "22137067", "doi": "10.1016/j.ahj.2011.09.012", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22137067/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive blood-pressure lowering can cause symptomatic hypotension.", "clinicalSignificance": "The risk is higher in patients taking antihypertensives or with baseline low blood pressure.", "managementStrategy": "Start low, monitor blood pressure, and stop L-arginine if orthostatic symptoms occur.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Alfuzosin", "supplementBName": "L-Citrulline", "interactionType": "caution", "severity": "moderate", "description": "L-Citrulline increases systemic arginine availability and can modestly lower blood pressure. Alfuzosin can also contribute to blood-pressure symptoms, especially when combined with other agents that lower vascular tone. Together they may cause dizziness, fatigue, or near-fainting.", "recommendation": "Do not start L-citrulline and alfuzosin on the same day if you can avoid it. If using both, begin with a low L-citrulline dose, track blood pressure, and stop or reduce it if you become lightheaded.", "minimumTimeSeparation": null, "mechanism": "L-Citrulline is converted to L-arginine and increases nitric-oxide-mediated vasodilation. Alfuzosin blocks alpha1-mediated smooth muscle tone, creating additive potential for lower systemic vascular resistance.", "evidenceLevel": "moderate", "sources": [ { "text": "Zhang LT, Lee SW, Park K, Chung WS, Kim SW, Hyun JS, Moon DG, Yang SK. Multicenter, prospective, comparative cohort study evaluating the efficacy and safety of alfuzosin 10 mg with regard to blood pressure in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia with or without antihypertensive medications. Clin Interv Aging. 2015;10:277-286.", "pmid": "25653511", "doi": "10.2147/CIA.S74102", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25653511/", "publicSourceType": "PMID" }, { "text": "Mirenayat MS, Moradi S, Mohammadi H, Rouhani MH. Effect of L-Citrulline Supplementation on Blood Pressure: a Systematic Review and Meta-Analysis of Clinical Trials. Curr Hypertens Rep. 2018;20(11):98.", "pmid": "30284051", "doi": "10.1007/s11906-018-0898-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30284051/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Additive vasodilation may lower blood pressure enough to cause symptoms.", "clinicalSignificance": "Patients on antihypertensive therapy or with low baseline blood pressure are more likely to notice symptoms.", "managementStrategy": "Stagger initiation, start L-citrulline low, and monitor for orthostatic symptoms.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Digoxin", "supplementBName": "Berberine", "interactionType": "caution", "severity": "serious", "description": "Berberine may increase oral digoxin exposure by inhibiting intestinal P-glycoprotein. Digoxin has a narrow therapeutic index, so even moderate changes in exposure can increase the risk of nausea, visual changes, bradycardia, or arrhythmia.", "recommendation": "Do not combine berberine with digoxin without prescriber approval. If both are used, monitor for digoxin toxicity and ask your clinician whether a digoxin level is needed after berberine is started or stopped.", "minimumTimeSeparation": null, "mechanism": "Digoxin is a P-glycoprotein substrate. Berberine inhibited intestinal P-glycoprotein in pharmacokinetic studies and increased oral digoxin AUC and Cmax in an animal model, creating a plausible exposure-increase risk in humans.", "evidenceLevel": "emerging", "sources": [ { "text": "Qiu W, Jiang XH, Liu CX, et al. Effect of berberine on the pharmacokinetics of substrates of CYP3A and P-gp. Phytotherapy Research. 2009;23(11):1553-1558.", "pmid": "19370549", "doi": "10.1002/ptr.2808", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19370549/", "publicSourceType": "PMID" }, { "text": "Coumau C, Csajka C. A Systematic Review and Classification of the Effects of P-glycoprotein Inhibitors and Inducers in Humans, Using Digoxin, Fexofenadine, and Dabigatran as Probe Drugs. Clinical Pharmacokinetics. 2025.", "pmid": "40349292", "doi": "10.1007/s40262-025-01514-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40349292/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Berberine may increase digoxin exposure and toxicity risk.", "clinicalSignificance": "Digoxin toxicity can be clinically serious because the therapeutic range is narrow.", "managementStrategy": "Avoid unsupervised use and monitor symptoms and digoxin levels if the combination is necessary.", "isSynergistic": null, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Digoxin", "supplementBName": "Berberine HCl", "interactionType": "caution", "severity": "serious", "description": "Berberine HCl may increase oral digoxin exposure by inhibiting intestinal P-glycoprotein. Digoxin has a narrow therapeutic index, so even moderate changes in exposure can increase the risk of nausea, visual changes, bradycardia, or arrhythmia.", "recommendation": "Do not combine berberine HCl with digoxin without prescriber approval. If both are used, monitor for digoxin toxicity and ask your clinician whether a digoxin level is needed after berberine HCl is started or stopped.", "minimumTimeSeparation": null, "mechanism": "Digoxin is a P-glycoprotein substrate. Berberine inhibited intestinal P-glycoprotein in pharmacokinetic studies and increased oral digoxin AUC and Cmax in an animal model, creating a plausible exposure-increase risk in humans.", "evidenceLevel": "emerging", "sources": [ { "text": "Qiu W, Jiang XH, Liu CX, et al. Effect of berberine on the pharmacokinetics of substrates of CYP3A and P-gp. Phytotherapy Research. 2009;23(11):1553-1558.", "pmid": "19370549", "doi": "10.1002/ptr.2808", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19370549/", "publicSourceType": "PMID" }, { "text": "Coumau C, Csajka C. A Systematic Review and Classification of the Effects of P-glycoprotein Inhibitors and Inducers in Humans, Using Digoxin, Fexofenadine, and Dabigatran as Probe Drugs. Clinical Pharmacokinetics. 2025.", "pmid": "40349292", "doi": "10.1007/s40262-025-01514-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40349292/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Berberine HCl may increase digoxin exposure and toxicity risk.", "clinicalSignificance": "Digoxin toxicity can be clinically serious because the therapeutic range is narrow.", "managementStrategy": "Avoid unsupervised use and monitor symptoms and digoxin levels if the combination is necessary.", "isSynergistic": null, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Nitroglycerin", "supplementBName": "NAC", "interactionType": "caution", "severity": "serious", "description": "NAC can potentiate nitroglycerin-related vasodilation and headache. In people using nitrates for angina, this may increase the chance of symptomatic hypotension, dizziness, severe headache, or fainting.", "recommendation": "Do not add NAC to nitroglycerin therapy without prescriber approval. If your clinician intentionally uses both, monitor blood pressure and report severe headache, dizziness, fainting, or worsening chest pain promptly.", "minimumTimeSeparation": null, "mechanism": "NAC supplies sulfhydryl groups and can augment nitrate biotransformation and nitric-oxide-mediated vasodilation. Human studies show NAC enhanced nitroglycerin-induced headache and vascular responses.", "evidenceLevel": "moderate", "sources": [ { "text": "Iversen HK. N-acetylcysteine enhances nitroglycerin-induced headache and cranial arterial responses. Clinical Pharmacology and Therapeutics. 1992;52(2):125-133.", "pmid": "1505148", "doi": "10.1038/clpt.1992.121", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1505148/", "publicSourceType": "PMID" }, { "text": "Horowitz JD, Henry CA, Syrjanen ML, et al. Combined use of nitroglycerin and N-acetylcysteine in the management of unstable angina pectoris. Circulation. 1988;77(4):787-794.", "pmid": "3127076", "doi": "10.1161/01.cir.77.4.787", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3127076/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "NAC can amplify nitroglycerin vasodilation and nitrate adverse effects.", "clinicalSignificance": "Excess nitrate effect can cause symptomatic hypotension or severe headache in patients with cardiovascular disease.", "managementStrategy": "Use only with prescriber oversight and blood pressure monitoring.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Isosorbide Mononitrate", "supplementBName": "NAC", "interactionType": "caution", "severity": "serious", "description": "NAC may potentiate organic nitrate effects, increasing the chance of dizziness, severe headache, flushing, or symptomatic hypotension. Evidence is strongest for nitroglycerin and isosorbide dinitrate, so this is a class-based caution for isosorbide mononitrate.", "recommendation": "Do not add NAC to isosorbide mononitrate therapy without prescriber approval. If both are intentionally used, monitor blood pressure and report severe headache, lightheadedness, fainting, or chest-pain changes.", "minimumTimeSeparation": null, "mechanism": "NAC supplies sulfhydryl groups that can enhance nitrate-mediated nitric oxide signaling. Clinical studies show potentiation of nitroglycerin and isosorbide dinitrate hemodynamic effects, supporting caution across organic nitrate therapy.", "evidenceLevel": "moderate", "sources": [ { "text": "Mehra A, Shotan A, Ostrzega E, et al. Potentiation of isosorbide dinitrate effects with N-acetylcysteine in patients with chronic heart failure. Circulation. 1994;89(6):2595-2600.", "pmid": "8205670", "doi": "10.1161/01.cir.89.6.2595", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8205670/", "publicSourceType": "PMID" }, { "text": "Iversen HK. N-acetylcysteine enhances nitroglycerin-induced headache and cranial arterial responses. Clinical Pharmacology and Therapeutics. 1992;52(2):125-133.", "pmid": "1505148", "doi": "10.1038/clpt.1992.121", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1505148/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "NAC may amplify organic nitrate vasodilation and nitrate adverse effects.", "clinicalSignificance": "Patients on long-acting nitrates may be vulnerable to symptomatic hypotension or severe headache if nitrate effect is potentiated.", "managementStrategy": "Use only with prescriber oversight and blood pressure monitoring.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Warfarin", "supplementBName": "Chlorella", "interactionType": "conflict", "severity": "serious", "description": "Chlorella can contain substantial vitamin K and may reduce warfarin anticoagulant effect. A case report described loss of warfarin control after chlorella intake, which could raise clotting risk in patients using warfarin for stroke or clot prevention.", "recommendation": "Avoid starting or stopping chlorella while taking warfarin unless your anticoagulation clinic knows. If chlorella is used, keep intake consistent and check INR after any change.", "minimumTimeSeparation": null, "mechanism": "Warfarin inhibits vitamin K recycling to reduce vitamin K-dependent clotting factor activation. Vitamin K-rich chlorella can provide substrate that counteracts warfarin effect and lowers anticoagulation intensity.", "evidenceLevel": "emerging", "sources": [ { "text": "Ohkawa S, Yoneda Y, Ohsumi Y, Tabuchi M. Warfarin therapy and chlorella. Rinsho Shinkeigaku. 1995;35(7):806-807.", "pmid": "8777808", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8777808/", "publicSourceType": "PMID" }, { "text": "Booth SL, Centurelli MA. Vitamin K: a practical guide to the dietary management of patients on warfarin. Nutrition Reviews. 1999;57(9):288-296.", "pmid": "10568341", "doi": "10.1111/j.1753-4887.1999.tb01815.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10568341/", "publicSourceType": "PMID" }, { "text": "Wang M, Zeraatkar D, Obeda M, et al. Drug-drug interactions with warfarin: A systematic review and meta-analysis. British Journal of Clinical Pharmacology. 2021;87(11):4051-4100.", "pmid": "33769581", "doi": "10.1111/bcp.14833", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33769581/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Chlorella may reduce warfarin anticoagulant effect through vitamin K intake.", "clinicalSignificance": "Reduced INR control can raise clotting or stroke risk in warfarin users.", "managementStrategy": "Avoid variable chlorella intake and monitor INR if any change occurs.", "isSynergistic": false, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Atorvastatin", "supplementBName": "Tribulus Terrestris", "interactionType": "caution", "severity": "serious", "description": "A case report described rhabdomyolysis after Tribulus terrestris was started in a patient taking long-term atorvastatin. Causality is not proven, but the outcome is serious enough to flag the combination, especially in older adults or people with kidney disease, high statin doses, or muscle symptoms.", "recommendation": "Avoid adding Tribulus terrestris to atorvastatin without clinician review. Stop the supplement and seek care urgently for severe muscle pain, weakness, dark urine, or unexplained fever.", "minimumTimeSeparation": null, "mechanism": "The mechanism is uncertain. A published case suggests possible additive myotoxicity or pharmacokinetic interaction, while atorvastatin is already vulnerable to interaction-driven myopathy through CYP3A4 and transporter pathways.", "evidenceLevel": "emerging", "sources": [ { "text": "Huff R, Karpinska-Leydier K, Maddineni G, Begosh-Mayne D. Rhabdomyolysis Risk: The Dangers of Tribulus Terrestris, an Over-the-Counter Supplement. American Journal of Case Reports. 2024;25:e943492.", "pmid": "39012853", "doi": "10.12659/AJCR.943492", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39012853/", "publicSourceType": "PMID" }, { "text": "Balasubramanian R, Maideen NMP. HMG-CoA Reductase Inhibitors (Statins) and their Drug Interactions Involving CYP Enzymes, P-glycoprotein and OATP Transporters-An Overview. Current Drug Metabolism. 2021;22(5):328-341.", "pmid": "33459228", "doi": "10.2174/1389200222666210114122729", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33459228/", "publicSourceType": "PMID" } ], "clinicalSeverity": "major", "directionality": "bAffectsA", "effect": "Tribulus terrestris may increase atorvastatin-associated myopathy or rhabdomyolysis risk.", "clinicalSignificance": "Rhabdomyolysis can cause kidney injury and requires urgent medical attention.", "managementStrategy": "Avoid unsupervised combination and monitor for muscle toxicity if exposure occurs.", "isSynergistic": null, "interactionEvidenceRating": "emerging", "scope": "prescription-supplement" }, { "supplementAName": "Losartan", "supplementBName": "Berberine", "interactionType": "caution", "severity": "moderate", "description": "Berberine can inhibit CYP2C9 activity and may alter losartan conversion to its active metabolite E-3174. Berberine may also lower blood pressure, so the combination could change blood pressure response or increase lightheadedness in sensitive users.", "recommendation": "If you use berberine with losartan, start berberine cautiously and monitor home blood pressure during the first 1 to 2 weeks. Report dizziness, fainting, unusual fatigue, or loss of blood pressure control to your prescriber.", "minimumTimeSeparation": null, "mechanism": "Losartan is converted partly by CYP2C9 to E-3174, an active metabolite. Repeated berberine dosing inhibited CYP2C9 in humans, doubled the losartan to E-3174 ratio, and berberine has modest blood-pressure-lowering effects in clinical trials.", "evidenceLevel": "moderate", "sources": [ { "text": "Guo Y, Chen Y, Tan ZR, Klaassen CD, Zhou HH. Repeated administration of berberine inhibits cytochromes P450 in humans. European Journal of Clinical Pharmacology. 2012;68(2):213-217.", "pmid": "21870106", "doi": "10.1007/s00228-011-1108-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21870106/", "publicSourceType": "PMID" }, { "text": "Park YA, Song YB, Yee J, et al. Influence of CYP2C9 Genetic Polymorphisms on the Pharmacokinetics of Losartan and Its Active Metabolite E-3174: A Systematic Review and Meta-Analysis. Journal of Personalized Medicine. 2021;11(7):617.", "pmid": "34210056", "doi": "10.3390/jpm11070617", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34210056/", "publicSourceType": "PMID" }, { "text": "Lan J, Zhao Y, Dong F, et al. Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. Journal of Ethnopharmacology. 2015;161:69-81.", "pmid": "25498346", "doi": "10.1016/j.jep.2014.09.049", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25498346/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Berberine may alter losartan activation and add blood-pressure-lowering effects.", "clinicalSignificance": "The combination may change blood pressure control or cause orthostatic symptoms in susceptible users.", "managementStrategy": "Monitor home blood pressure when starting or stopping berberine.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" }, { "supplementAName": "Losartan", "supplementBName": "Berberine HCl", "interactionType": "caution", "severity": "moderate", "description": "Berberine HCl can inhibit CYP2C9 activity and may alter losartan conversion to its active metabolite E-3174. Berberine HCl may also lower blood pressure, so the combination could change blood pressure response or increase lightheadedness in sensitive users.", "recommendation": "If you use berberine HCl with losartan, start berberine HCl cautiously and monitor home blood pressure during the first 1 to 2 weeks. Report dizziness, fainting, unusual fatigue, or loss of blood pressure control to your prescriber.", "minimumTimeSeparation": null, "mechanism": "Losartan is converted partly by CYP2C9 to E-3174, an active metabolite. Repeated berberine dosing inhibited CYP2C9 in humans, doubled the losartan to E-3174 ratio, and berberine has modest blood-pressure-lowering effects in clinical trials.", "evidenceLevel": "moderate", "sources": [ { "text": "Guo Y, Chen Y, Tan ZR, Klaassen CD, Zhou HH. Repeated administration of berberine inhibits cytochromes P450 in humans. European Journal of Clinical Pharmacology. 2012;68(2):213-217.", "pmid": "21870106", "doi": "10.1007/s00228-011-1108-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21870106/", "publicSourceType": "PMID" }, { "text": "Park YA, Song YB, Yee J, et al. Influence of CYP2C9 Genetic Polymorphisms on the Pharmacokinetics of Losartan and Its Active Metabolite E-3174: A Systematic Review and Meta-Analysis. Journal of Personalized Medicine. 2021;11(7):617.", "pmid": "34210056", "doi": "10.3390/jpm11070617", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34210056/", "publicSourceType": "PMID" }, { "text": "Lan J, Zhao Y, Dong F, et al. Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. Journal of Ethnopharmacology. 2015;161:69-81.", "pmid": "25498346", "doi": "10.1016/j.jep.2014.09.049", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25498346/", "publicSourceType": "PMID" } ], "clinicalSeverity": "moderate", "directionality": "bidirectional", "effect": "Berberine HCl may alter losartan activation and add blood-pressure-lowering effects.", "clinicalSignificance": "The combination may change blood pressure control or cause orthostatic symptoms in susceptible users.", "managementStrategy": "Monitor home blood pressure when starting or stopping berberine HCl.", "isSynergistic": null, "interactionEvidenceRating": "moderate", "scope": "prescription-supplement" } ], "studies": [ { "id": "study-001", "supplementName": "Vitamin D3", "title": "Vitamin D Supplementation and Cardiovascular Disease Risks in More Than 83,000 Individuals in 21 Randomized Clinical Trials: A Meta-analysis", "authors": "Barbarawi M, Kheiri B, Zayed Y et al.", "journal": "JAMA Cardiol", "year": 2019, "studyType": "metaAnalysis", "sampleSize": 83291, "outcome": "Vitamin D supplementation was not associated with reduced major adverse cardiovascular events in the included randomized trials", "keyFindings": [ "No effect on all-cause mortality", "No significant reduction in MI or stroke", "Cancer mortality reduced in some subgroups with longer follow-up" ], "dosageUsed": "400-100000 IU monthly (varied)", "evidenceRating": "strong", "pmid": "31215980", "doi": "10.1001/jamacardiol.2019.1870", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31215980/", "publicSourceType": "PMID" }, { "id": "study-002", "supplementName": "Vitamin D3", "title": "Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis", "authors": "Martineau AR, Jolliffe DA, Hooper RL et al.", "journal": "BMJ", "year": 2017, "studyType": "metaAnalysis", "sampleSize": 10933, "outcome": "Vitamin D supplementation reduced the risk of acute respiratory tract infection", "keyFindings": [ "Overall protective effect OR 0.88", "Greatest benefit in those with baseline 25-OHD <25 nmol/L", "Daily or weekly dosing more effective than bolus doses" ], "dosageUsed": "400-4000 IU daily", "evidenceRating": "strong", "pmid": "28202713", "doi": "10.1136/bmj.i6583", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28202713/", "publicSourceType": "PMID" }, { "id": "study-003", "supplementName": "Vitamin D3", "title": "Effects of vitamin D supplementation on musculoskeletal health: a systematic review", "authors": "Bolland MJ, Grey A, Avenell A", "journal": "Lancet Diabetes Endocrinol", "year": 2018, "studyType": "review", "sampleSize": 53537, "outcome": "Vitamin D supplementation did not prevent fractures or falls or have meaningful effects on BMD", "keyFindings": [ "No significant reduction in total fracture risk", "No benefit for falls prevention", "Results consistent regardless of dose" ], "dosageUsed": "800-2000 IU daily", "evidenceRating": "strong", "pmid": "30293909", "doi": "10.1016/S2213-8587(18)30265-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30293909/", "publicSourceType": "PMID" }, { "id": "study-004", "supplementName": "Vitamin D3", "title": "Vitamin D and calcium supplementation and cancer incidence in postmenopausal women: a randomized clinical trial", "authors": "Lappe JM, Travers-Gustafson D, Davies KM et al.", "journal": "JAMA", "year": 2017, "studyType": "rct", "sampleSize": 2303, "outcome": "Vitamin D3 plus calcium did not significantly reduce all-type cancer incidence over 4 years", "keyFindings": [ "Cancer incidence lower but not statistically significant", "Post-hoc analysis excluding first-year cancers showed benefit", "Well-tolerated with no safety concerns" ], "dosageUsed": "2000 IU daily + 1500 mg calcium", "evidenceRating": "moderate", "pmid": "28350929", "doi": "10.1001/jama.2017.2115", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28350929/", "publicSourceType": "PMID" }, { "id": "study-005", "supplementName": "Vitamin D3", "title": "High-dose monthly vitamin D supplementation and cognitive function in older adults", "authors": "Pettersen JA", "journal": "J Nutr Health Aging", "year": 2017, "studyType": "rct", "sampleSize": 82, "outcome": "No significant improvement in cognitive function with high-dose vitamin D", "keyFindings": [ "No between-group difference in MMSE or MoCA scores", "Serum 25-OHD levels significantly increased", "May require longer duration to detect effects" ], "dosageUsed": "50000 IU monthly", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-006", "supplementName": "Vitamin D3", "title": "Vitamin D supplementation improves mood in women with type 2 diabetes", "authors": "Penckofer S, Byrn M, Adams W et al.", "journal": "J Diabetes Res", "year": 2017, "studyType": "rct", "sampleSize": 46, "outcome": "Significant improvement in depression symptoms with weekly vitamin D supplementation", "keyFindings": [ "BDI-II scores improved significantly", "Anxiety levels also decreased", "Benefits maintained at 6-month follow-up" ], "dosageUsed": "50000 IU weekly", "evidenceRating": "moderate", "pmid": "28465792", "doi": "10.1155/2017/8547535", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28465792/", "publicSourceType": "PMID" }, { "id": "study-007", "supplementName": "Magnesium Glycinate", "title": "Oral magnesium supplementation for treating glucose intolerance and insulin resistance in type 2 diabetes", "authors": "Veronese N, Watutantrige-Fernando S, Luchini C et al.", "journal": "Nutrients", "year": 2016, "studyType": "metaAnalysis", "sampleSize": 2028, "outcome": "Magnesium supplementation improved glucose and insulin sensitivity parameters", "keyFindings": [ "Fasting glucose reduced by 4.64 mg/dL", "HOMA-IR significantly improved", "Effect greater in magnesium-deficient individuals" ], "dosageUsed": "250-600 mg daily", "evidenceRating": "strong", "pmid": "27807012", "doi": "10.3390/nu8110693", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27807012/", "publicSourceType": "PMID" }, { "id": "study-008", "supplementName": "Magnesium Glycinate", "title": "Effect of magnesium supplementation on blood pressure: a meta-analysis", "authors": "Zhang X, Li Y, Del Gobbo LC et al.", "journal": "Hypertension", "year": 2016, "studyType": "metaAnalysis", "sampleSize": 2028, "outcome": "Magnesium supplementation achieved a small but clinically significant reduction in blood pressure", "keyFindings": [ "SBP reduced by 2.00 mmHg", "DBP reduced by 1.78 mmHg", "Dose-response relationship observed" ], "dosageUsed": "368 mg/day (median)", "evidenceRating": "strong", "pmid": "27402922", "doi": "10.1161/HYPERTENSIONAHA.116.07664", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27402922/", "publicSourceType": "PMID" }, { "id": "study-009", "supplementName": "Magnesium Glycinate", "title": "The effect of magnesium supplementation on sleep quality: a systematic review and meta-analysis", "authors": "Mah J, Pitre T", "journal": "BMC Complement Med Ther", "year": 2021, "studyType": "metaAnalysis", "sampleSize": 7582, "outcome": "Magnesium supplementation may improve subjective measures of insomnia", "keyFindings": [ "Significant improvement in Pittsburgh Sleep Quality Index", "Older adults showed greatest benefit", "Sleep onset latency reduced" ], "dosageUsed": "225-500 mg daily", "evidenceRating": "moderate", "pmid": "33864795", "doi": "10.1186/s12906-021-03297-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33864795/", "publicSourceType": "PMID" }, { "id": "study-010", "supplementName": "Magnesium Glycinate", "title": "Magnesium intake and depression in adults: a cross-sectional analysis", "authors": "Tarleton EK, Littenberg B", "journal": "J Am Board Fam Med", "year": 2015, "studyType": "cohort", "sampleSize": 8894, "outcome": "Low magnesium intake was associated with higher depression scores", "keyFindings": [ "Significant inverse association between Mg intake and depression", "Association strongest in younger adults", "Dietary and supplemental Mg both contributed" ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "25748766", "doi": "10.3122/jabfm.2015.02.140176", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25748766/", "publicSourceType": "PMID" }, { "id": "study-011", "supplementName": "Magnesium Glycinate", "title": "Magnesium supplementation for muscle cramps in pregnancy: a randomized controlled trial", "authors": "Supakatisant C, Phupong V", "journal": "Matern Child Nutr", "year": 2015, "studyType": "rct", "sampleSize": 86, "outcome": "Magnesium supplementation reduced frequency and intensity of leg cramps in pregnant women", "keyFindings": [ "50% reduction in cramp frequency", "Intensity scores significantly lower", "No adverse effects observed" ], "dosageUsed": "300 mg daily (magnesium bisglycinate)", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-012", "supplementName": "Fish Oil", "title": "Marine omega-3 fatty acids and prevention of cardiovascular disease and cancer (VITAL trial)", "authors": "Manson JE, Cook NR, Lee IM et al.", "journal": "NEJM", "year": 2019, "studyType": "rct", "sampleSize": 25871, "outcome": "Omega-3 supplementation did not significantly reduce major cardiovascular events overall but reduced MI risk", "keyFindings": [ "No reduction in composite cardiovascular endpoint", "44% reduction in MI (secondary analysis)", "Greater benefit in African Americans and low fish consumers", "No effect on cancer incidence" ], "dosageUsed": "1 g/day EPA+DHA", "evidenceRating": "strong", "pmid": "30415627", "doi": "10.1056/NEJMoa1811403", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30415627/", "publicSourceType": "PMID" }, { "id": "study-013", "supplementName": "Fish Oil", "title": "Omega-3 polyunsaturated fatty acids for the treatment of depression: systematic review and meta-analysis", "authors": "Liao Y, Xie B, Zhang H et al.", "journal": "Mol Psychiatry", "year": 2019, "studyType": "metaAnalysis", "sampleSize": 2160, "outcome": "Omega-3 PUFAs had a significant beneficial effect on depression symptoms", "keyFindings": [ "EPA-predominant formulas most effective", "Effect size comparable to some antidepressants in mild depression", "Dose of 1-2 g/day EPA most supported" ], "dosageUsed": "1-2 g EPA daily", "evidenceRating": "moderate", "pmid": "31228684", "doi": "10.1038/s41398-019-0515-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31228684/", "publicSourceType": "PMID" }, { "id": "study-014", "supplementName": "Fish Oil", "title": "Effect of omega-3 fatty acid supplementation on dry eye disease: a meta-analysis", "authors": "Giannaccare G, Pellegrini M, Sebastiani S et al.", "journal": "Cornea", "year": 2019, "studyType": "metaAnalysis", "sampleSize": 3363, "outcome": "Omega-3 supplementation significantly improved dry eye symptoms and signs", "keyFindings": [ "Significant improvement in OSDI scores", "Tear breakup time increased", "Combination EPA+DHA most effective" ], "dosageUsed": "1000-3000 mg EPA+DHA daily", "evidenceRating": "moderate", "pmid": "30702470", "doi": "10.1097/ICO.0000000000001884", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30702470/", "publicSourceType": "PMID" }, { "id": "study-015", "supplementName": "Fish Oil", "title": "Omega-3 fatty acid supplementation during pregnancy and infant neurodevelopment: a systematic review", "authors": "Middleton P, Gomersall JC, Gould JF et al.", "journal": "Cochrane Database", "year": 2018, "studyType": "review", "sampleSize": 19927, "outcome": "Omega-3 supplementation reduced preterm birth risk but limited evidence for neurodevelopment", "keyFindings": [ "42% reduction in early preterm birth", "11% reduction in preterm birth", "No clear effect on child cognitive development" ], "dosageUsed": "200-2200 mg DHA daily", "evidenceRating": "strong", "pmid": "30480773", "doi": "10.1002/14651858.CD003402.pub3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30480773/", "publicSourceType": "PMID" }, { "id": "study-016", "supplementName": "Fish Oil", "title": "High-dose EPA (icosapent ethyl) reduces cardiovascular events in statin-treated patients (REDUCE-IT)", "authors": "Bhatt DL, Steg PG, Miller M et al.", "journal": "NEJM", "year": 2019, "studyType": "rct", "sampleSize": 8179, "outcome": "High-dose EPA significantly reduced ischemic events including cardiovascular death", "keyFindings": [ "25% reduction in primary composite endpoint", "Significant reduction in cardiovascular death", "Benefits seen regardless of baseline triglycerides" ], "dosageUsed": "4 g/day icosapent ethyl (EPA)", "evidenceRating": "strong", "pmid": "30415628", "doi": "10.1056/NEJMoa1812792", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30415628/", "publicSourceType": "PMID" }, { "id": "study-017", "supplementName": "Ashwagandha", "title": "A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha", "authors": "Chandrasekhar K, Kapoor J, Anishetty S", "journal": "Indian J Psychol Med", "year": 2012, "studyType": "rct", "sampleSize": 64, "outcome": "Ashwagandha root extract safely and effectively improved resistance towards stress and self-assessed quality of life", "keyFindings": [ "56.5% reduction in Hamilton Anxiety scale", "Serum cortisol levels significantly reduced", "No serious adverse effects reported" ], "dosageUsed": "300 mg twice daily (KSM-66)", "evidenceRating": "moderate", "pmid": "23439798", "doi": "10.4103/0253-7176.106022", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23439798/", "publicSourceType": "PMID" }, { "id": "study-018", "supplementName": "Ashwagandha", "title": "Effects of ashwagandha on muscle mass and strength in young men: a double-blind, placebo-controlled trial", "authors": "Wankhede S, Langade D, Joshi K et al.", "journal": "J Int Soc Sports Nutr", "year": 2015, "studyType": "rct", "sampleSize": 57, "outcome": "Ashwagandha supplementation significantly increased muscle mass, strength, and testosterone levels", "keyFindings": [ "Significantly greater increase in bench press and leg extension", "Larger increase in arm and chest muscle size", "Testosterone levels increased more vs placebo", "Muscle recovery improved" ], "dosageUsed": "300 mg twice daily (KSM-66)", "evidenceRating": "moderate", "pmid": "26609282", "doi": "10.1186/s12970-015-0104-9", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26609282/", "publicSourceType": "PMID" }, { "id": "study-019", "supplementName": "Ashwagandha", "title": "Efficacy and safety of ashwagandha root extract on cognitive functions in healthy, stressed adults: a randomized, double-blind study", "authors": "Choudhary D, Bhatt S, Banerjee S", "journal": "J Diet Suppl", "year": 2017, "studyType": "rct", "sampleSize": 50, "outcome": "Ashwagandha improved immediate and general memory, executive function, and attention", "keyFindings": [ "Significant improvement in reaction time", "Working memory scores improved", "Sustained attention enhanced" ], "dosageUsed": "300 mg twice daily", "evidenceRating": "moderate", "pmid": "28471731", "doi": "10.1080/19390211.2017.1284970", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28471731/", "publicSourceType": "PMID" }, { "id": "study-020", "supplementName": "Ashwagandha", "title": "Efficacy of ashwagandha in improving sleep quality: a systematic review and meta-analysis", "authors": "Cheah KL, Norhayati MN, Husniati Yaacob L et al.", "journal": "PLoS One", "year": 2021, "studyType": "metaAnalysis", "sampleSize": 400, "outcome": "Ashwagandha extract significantly improved overall sleep quality", "keyFindings": [ "Significant improvement in sleep quality scores", "Greater effect at doses ≥600 mg/day", "Benefits more pronounced in insomnia patients", "Sleep onset latency reduced" ], "dosageUsed": "120-1200 mg daily", "evidenceRating": "moderate", "pmid": "34540569", "doi": "10.1371/journal.pone.0257843", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34540569/", "publicSourceType": "PMID" }, { "id": "study-021", "supplementName": "Ashwagandha", "title": "Withania somnifera root extract enhances thyroid function in subclinical hypothyroidism", "authors": "Sharma AK, Basu I, Singh S", "journal": "J Altern Complement Med", "year": 2018, "studyType": "rct", "sampleSize": 50, "outcome": "Ashwagandha normalized thyroid indices in patients with subclinical hypothyroidism", "keyFindings": [ "TSH levels significantly reduced", "T3 and T4 levels normalized", "Well tolerated with no adverse effects" ], "dosageUsed": "600 mg daily", "evidenceRating": "moderate", "pmid": "28829155", "doi": "10.1089/acm.2017.0183", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28829155/", "publicSourceType": "PMID" }, { "id": "study-022", "supplementName": "Vitamin C", "title": "Vitamin C for preventing and treating the common cold: a Cochrane review", "authors": "Hemila H, Chalker E", "journal": "Cochrane Database", "year": 2013, "studyType": "metaAnalysis", "sampleSize": 11306, "outcome": "Regular vitamin C supplementation reduced cold duration but did not reduce incidence in the general population", "keyFindings": [ "8% reduction in cold duration in adults", "14% reduction in cold duration in children", "No effect on cold incidence in general population", "Benefit for physically stressed populations" ], "dosageUsed": "200 mg-2 g daily", "evidenceRating": "strong", "pmid": "23440782", "doi": "10.1002/14651858.CD000980.pub4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23440782/", "publicSourceType": "PMID" }, { "id": "study-023", "supplementName": "Vitamin C", "title": "Effect of vitamin C supplementation on blood pressure: a meta-analysis", "authors": "Juraschek SP, Guallar E, Appel LJ et al.", "journal": "AJCN", "year": 2012, "studyType": "metaAnalysis", "sampleSize": 1407, "outcome": "Short-term vitamin C supplementation reduced systolic and diastolic blood pressure", "keyFindings": [ "SBP reduced by 3.84 mmHg", "DBP reduced by 1.48 mmHg", "Effect greater in hypertensive subjects" ], "dosageUsed": "500 mg daily", "evidenceRating": "moderate", "pmid": "22492364", "doi": "10.3945/ajcn.111.027995", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22492364/", "publicSourceType": "PMID" }, { "id": "study-024", "supplementName": "Vitamin C", "title": "Vitamin C supplementation and physical performance in trained athletes: a systematic review", "authors": "Righi NC, Schuch FB, De Nardi AT et al.", "journal": "Nutrients", "year": 2020, "studyType": "review", "sampleSize": 876, "outcome": "Mixed evidence for vitamin C improving exercise performance; may impair training adaptations at high doses", "keyFindings": [ "Reduced oxidative stress markers post-exercise", "No clear benefit for VO2max", "High doses may blunt mitochondrial adaptations", "Potential benefit for reducing muscle soreness" ], "dosageUsed": "200-1000 mg daily", "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-025", "supplementName": "Vitamin C", "title": "Intravenous vitamin C as adjunctive therapy for severe COVID-19: a randomized controlled trial", "authors": "Zhang J, Rao X, Li Y et al.", "journal": "Crit Care", "year": 2021, "studyType": "rct", "sampleSize": 56, "outcome": "High-dose IV vitamin C improved oxygenation and reduced IL-6 levels in severe COVID-19 patients", "keyFindings": [ "PaO2/FiO2 ratio improved faster", "IL-6 levels decreased significantly", "No difference in 28-day mortality", "Small sample limits generalizability" ], "dosageUsed": "12 g IV twice daily for 7 days", "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-026", "supplementName": "Vitamin C", "title": "Vitamin C supplementation and skin aging: a cross-sectional and prospective study", "authors": "Cosgrove MC, Franco OH, Granger SP et al.", "journal": "AJCN", "year": 2017, "studyType": "cohort", "sampleSize": 4025, "outcome": "Higher vitamin C intake was associated with lower likelihood of wrinkled appearance and skin dryness", "keyFindings": [ "Significant inverse association with wrinkled appearance", "Protective effect against skin dryness", "Effect independent of age, BMI, and sun exposure" ], "dosageUsed": null, "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-027", "supplementName": "Zinc", "title": "Zinc lozenges and the common cold: a meta-analysis comparing zinc acetate and zinc gluconate", "authors": "Hemila H", "journal": "JRSM Open", "year": 2017, "studyType": "metaAnalysis", "sampleSize": 575, "outcome": "Zinc acetate lozenges shortened cold duration by 40% compared to placebo", "keyFindings": [ "Zinc acetate more effective than gluconate", "Duration reduced by 2.7 days on average", "Best if started within 24h of symptom onset" ], "dosageUsed": "75 mg/day zinc acetate lozenges", "evidenceRating": "strong", "pmid": "28515951", "doi": "10.1177/2054270417694291", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28515951/", "publicSourceType": "PMID" }, { "id": "study-028", "supplementName": "Zinc", "title": "Zinc supplementation for improving growth outcomes in children under 5 years: a systematic review and meta-analysis", "authors": "Mayo-Wilson E, Junior JA, Imdad A et al.", "journal": "Cochrane Database", "year": 2014, "studyType": "metaAnalysis", "sampleSize": 13942, "outcome": "Zinc supplementation improved linear growth in children in low-income settings", "keyFindings": [ "Small but significant increase in height", "Reduced incidence of diarrhea", "No effect on weight gain", "Benefits most apparent in zinc-deficient populations" ], "dosageUsed": "5-20 mg daily", "evidenceRating": "strong", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-029", "supplementName": "Zinc", "title": "Zinc supplementation and serum testosterone levels in adult males: a systematic review", "authors": "Prasad AS, Mantzoros CS, Beck FW et al.", "journal": "Nutrition", "year": 2016, "studyType": "review", "sampleSize": 318, "outcome": "Zinc supplementation increased testosterone levels in zinc-deficient men but not in zinc-replete individuals", "keyFindings": [ "Significant increase in testosterone in deficient men", "No benefit in zinc-sufficient men", "Moderate zinc restriction decreased testosterone", "Elderly may benefit most" ], "dosageUsed": "30-50 mg daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-030", "supplementName": "Zinc", "title": "Effects of zinc supplementation on immune function in elderly subjects: a randomized controlled trial", "authors": "Barnett JB, Dao MC, Hamer DH et al.", "journal": "AJCN", "year": 2016, "studyType": "rct", "sampleSize": 53, "outcome": "Zinc supplementation improved T-cell function and reduced infection incidence in nursing home elderly", "keyFindings": [ "T-cell numbers increased", "Zinc levels in plasma normalized", "Infection incidence decreased by 66%" ], "dosageUsed": "30 mg zinc gluconate daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-031", "supplementName": "Vitamin B12", "title": "Vitamin B12 supplementation for cognitive function in older adults: a systematic review and meta-analysis", "authors": "Moore E, Mander A, Ames D et al.", "journal": "Int Psychogeriatr", "year": 2018, "studyType": "metaAnalysis", "sampleSize": 2796, "outcome": "B12 supplementation did not improve cognitive function in older adults without deficiency", "keyFindings": [ "No significant effect on cognitive test scores", "B12-deficient individuals may benefit", "Homocysteine levels decreased", "Longer trials needed" ], "dosageUsed": "400-1000 mcg daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-032", "supplementName": "Vitamin B12", "title": "High-dose oral B12 supplementation for deficiency: comparative effectiveness of sublingual vs oral formulations", "authors": "Vidal-Alaball J, Butler CC, Cannings-John R et al.", "journal": "Cochrane Database", "year": 2005, "studyType": "review", "sampleSize": 153, "outcome": "Oral B12 supplementation was as effective as intramuscular injections for correcting deficiency", "keyFindings": [ "2000 mcg oral was equivalent to IM injection", "Serum B12 levels normalized in both groups", "Oral route more cost-effective", "Compliance higher with oral route" ], "dosageUsed": "1000-2000 mcg oral daily", "evidenceRating": "strong", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-033", "supplementName": "Vitamin B12", "title": "Methylcobalamin treatment for peripheral neuropathy: a dose-finding and efficacy trial", "authors": "Kuwabara S, Nakazawa R, Azuma N et al.", "journal": "Intern Med", "year": 2019, "studyType": "rct", "sampleSize": 140, "outcome": "High-dose methylcobalamin improved nerve conduction and neuropathic symptoms", "keyFindings": [ "Nerve conduction velocity improved significantly", "Pain VAS scores decreased", "1500 mcg dose most effective", "Well tolerated over 24 weeks" ], "dosageUsed": "500-1500 mcg methylcobalamin daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-034", "supplementName": "Iron", "title": "Iron supplementation for unexplained fatigue in non-anaemic women: a double-blind randomised trial", "authors": "Vaucher P, Druais PL, Waldvogel S et al.", "journal": "BMJ", "year": 2012, "studyType": "rct", "sampleSize": 198, "outcome": "Iron supplementation decreased fatigue in non-anaemic women with low ferritin levels", "keyFindings": [ "47.7% decrease in fatigue score vs 28.8% placebo", "Most benefit in women with ferritin <50 ng/mL", "Hemoglobin did not change significantly", "Effect independent of anemia status" ], "dosageUsed": "80 mg ferrous sulfate daily", "evidenceRating": "strong", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-035", "supplementName": "Iron", "title": "Oral iron supplementation for runners: effects on iron status and running performance", "authors": "Rubeor A, Goojha C, Manning J et al.", "journal": "Sports Med", "year": 2018, "studyType": "review", "sampleSize": 617, "outcome": "Iron supplementation in iron-deficient runners improved iron status but had variable effects on performance", "keyFindings": [ "Ferritin levels increased in all studies", "VO2max improved in some but not all trials", "Endurance performance improved in iron-depleted athletes", "No benefit in iron-replete athletes" ], "dosageUsed": "40-100 mg elemental iron daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-036", "supplementName": "Iron", "title": "Iron supplementation during pregnancy and birthweight: a randomized controlled trial", "authors": "Haider BA, Olofin I, Wang M et al.", "journal": "BMJ", "year": 2013, "studyType": "metaAnalysis", "sampleSize": 48972, "outcome": "Iron supplementation in pregnancy reduced risk of low birthweight and maternal anemia", "keyFindings": [ "Risk of low birthweight reduced by 19%", "Maternal anemia reduced by 50%", "Mean birthweight increased by 41g", "Dose-response: each 10 mg/day increase in dose reduced anemia risk by 12%" ], "dosageUsed": "30-60 mg elemental iron daily", "evidenceRating": "strong", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-037", "supplementName": "Probiotics", "title": "Probiotics for the prevention of antibiotic-associated diarrhea: a systematic review and meta-analysis", "authors": "Hempel S, Newberry SJ, Maher AR et al.", "journal": "JAMA", "year": 2012, "studyType": "metaAnalysis", "sampleSize": 11811, "outcome": "Probiotic use was associated with significant reduction in antibiotic-associated diarrhea", "keyFindings": [ "42% reduction in AAD risk", "Lactobacillus and Saccharomyces most studied", "Effect consistent across antibiotic types", "NNT of approximately 13" ], "dosageUsed": "Various strains, 10-50 billion CFU daily", "evidenceRating": "strong", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-038", "supplementName": "Probiotics", "title": "Efficacy of probiotics in irritable bowel syndrome: a meta-analysis of randomized controlled trials", "authors": "Ford AC, Quigley EM, Lacy BE et al.", "journal": "Am J Gastroenterol", "year": 2014, "studyType": "metaAnalysis", "sampleSize": 6352, "outcome": "Probiotics had a statistically significant effect on overall IBS symptoms", "keyFindings": [ "NNT of 7 for global symptom improvement", "Multi-strain probiotics may be more effective", "Bloating significantly improved", "Some strains more effective for specific symptoms" ], "dosageUsed": "1-100 billion CFU daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-039", "supplementName": "Probiotics", "title": "Probiotics for the prevention of C. difficile-associated diarrhea: a systematic review and meta-analysis", "authors": "Goldenberg JZ, Yap C, Lytvyn L et al.", "journal": "Cochrane Database", "year": 2017, "studyType": "metaAnalysis", "sampleSize": 8672, "outcome": "Probiotics significantly reduced the risk of C. difficile-associated diarrhea", "keyFindings": [ "60% reduction in CDAD risk", "Saccharomyces boulardii and Lactobacillus most studied", "Greatest benefit when started early with antibiotic", "Safe with few adverse events" ], "dosageUsed": "Various strains", "evidenceRating": "strong", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-040", "supplementName": "Probiotics", "title": "Probiotics and the gut-brain axis: effects on mood and anxiety via the microbiome", "authors": "Liu RT, Walsh RF, Sheehan AE", "journal": "Gen Hosp Psychiatry", "year": 2019, "studyType": "metaAnalysis", "sampleSize": 1349, "outcome": "Probiotic supplementation had a small but significant effect on depression symptoms", "keyFindings": [ "Significant reduction in depression scores", "Effects larger in clinically depressed populations", "Lactobacillus and Bifidobacterium combinations most effective", "Minimal effect on anxiety measures" ], "dosageUsed": "1-40 billion CFU daily", "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-041", "supplementName": "Probiotics", "title": "Effect of Lactobacillus rhamnosus GG on immune response to influenza vaccine in elderly nursing home residents", "authors": "Boge T, Remigy M, Vber S et al.", "journal": "J Nutr Health Aging", "year": 2009, "studyType": "rct", "sampleSize": 222, "outcome": "Probiotic supplementation improved antibody response to influenza vaccination in elderly subjects", "keyFindings": [ "Higher seroconversion rates", "Greater antibody titers at 5 weeks", "Improved immune response in frail elderly", "Well tolerated" ], "dosageUsed": "1 billion CFU L. rhamnosus GG daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-042", "supplementName": "Turmeric/Curcumin", "title": "Efficacy of curcumin for management of knee osteoarthritis: a systematic review and meta-analysis", "authors": "Daily JW, Yang M, Park S", "journal": "J Med Food", "year": 2016, "studyType": "metaAnalysis", "sampleSize": 1438, "outcome": "Curcumin significantly reduced pain and improved function in knee osteoarthritis patients", "keyFindings": [ "WOMAC pain scores significantly reduced", "Some trials used NSAID comparators; do not frame curcumin as an NSAID replacement", "Fewer GI side effects than NSAIDs", "Bioavailability-enhanced forms most effective" ], "dosageUsed": "500-2000 mg curcumin daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-043", "supplementName": "Turmeric/Curcumin", "title": "Curcumin and depression: a meta-analysis of randomized controlled trials", "authors": "Al-Karawi D, Al Mamoori DA, Tayyar Y", "journal": "Crit Rev Food Sci Nutr", "year": 2016, "studyType": "metaAnalysis", "sampleSize": 377, "outcome": "Curcumin had significant antidepressant effects compared to placebo", "keyFindings": [ "Significant reduction in depression symptom scores", "May enhance SSRI efficacy as adjunct", "Anti-inflammatory mechanism proposed", "High-bioavailability forms tested" ], "dosageUsed": "500-1000 mg curcumin daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-044", "supplementName": "Turmeric/Curcumin", "title": "Curcumin for inflammatory bowel diseases: a systematic review of clinical trials", "authors": "Kumar S, Ahuja V, Sankar MJ et al.", "journal": "Nutr J", "year": 2020, "studyType": "review", "sampleSize": 680, "outcome": "Curcumin as adjunctive therapy showed promise for ulcerative colitis remission maintenance", "keyFindings": [ "Improved remission rates in UC when combined with mesalamine", "Reduced endoscopic and clinical scores", "Limited evidence for Crohn's disease", "High doses well tolerated" ], "dosageUsed": "1-3 g curcumin daily", "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-045", "supplementName": "Turmeric/Curcumin", "title": "Randomized double-blind placebo-controlled trial of curcuminoids and cardiovascular risk factors", "authors": "Panahi Y, Hosseini MS, Khalili N et al.", "journal": "Phytother Res", "year": 2015, "studyType": "rct", "sampleSize": 117, "outcome": "Curcuminoid supplementation significantly reduced serum lipid levels and inflammation markers", "keyFindings": [ "Total cholesterol reduced", "LDL cholesterol decreased", "CRP significantly lowered", "HDL increased modestly" ], "dosageUsed": "1000 mg curcuminoids + piperine daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-046", "supplementName": "Turmeric/Curcumin", "title": "Bioavailability of curcumin: problems and promises", "authors": "Anand P, Kunnumakkara AB, Newman RA et al.", "journal": "Mol Pharm", "year": 2007, "studyType": "review", "sampleSize": null, "outcome": "Standard curcumin has poor oral bioavailability; enhanced formulations dramatically improve absorption", "keyFindings": [ "Piperine increases bioavailability 20-fold", "Phospholipid complexes improve absorption", "Nanoparticle formulations show highest bioavailability", "Standard curcumin poorly absorbed" ], "dosageUsed": null, "evidenceRating": "strong", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-047", "supplementName": "Coenzyme Q10", "title": "Coenzyme Q10 supplementation for heart failure: a meta-analysis", "authors": "Lei L, Liu Y", "journal": "BMC Cardiovasc Disord", "year": 2017, "studyType": "metaAnalysis", "sampleSize": 1662, "outcome": "CoQ10 supplementation improved ejection fraction and NYHA functional class in heart failure patients", "keyFindings": [ "Ejection fraction improved by 3.67%", "Exercise capacity increased", "Mortality reduced in one large trial (Q-SYMBIO)", "Well tolerated with no major adverse effects" ], "dosageUsed": "100-300 mg daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-048", "supplementName": "Coenzyme Q10", "title": "Effects of CoQ10 on statin-induced myopathy: a randomized controlled trial", "authors": "Fedacko J, Pella D, Fedackova P et al.", "journal": "Can J Physiol Pharmacol", "year": 2013, "studyType": "rct", "sampleSize": 100, "outcome": "CoQ10 supplementation reduced severity of statin-associated muscle symptoms", "keyFindings": [ "Muscle pain scores decreased significantly", "Exercise tolerance improved", "CoQ10 plasma levels normalized", "No interaction with statin efficacy" ], "dosageUsed": "200 mg CoQ10 daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-049", "supplementName": "Coenzyme Q10", "title": "CoQ10 as a migraine preventive: a randomized double-blind placebo-controlled trial", "authors": "Sandor PS, Di Clemente L, Coppola G et al.", "journal": "Neurology", "year": 2005, "studyType": "rct", "sampleSize": 42, "outcome": "CoQ10 was superior to placebo for migraine prevention over 3 months", "keyFindings": [ "47.6% responder rate vs 14.3% placebo", "Attack frequency reduced by 3.2 per month", "Days with migraine decreased significantly", "No serious adverse events" ], "dosageUsed": "100 mg three times daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-050", "supplementName": "Coenzyme Q10", "title": "Coenzyme Q10 supplementation and male infertility: a systematic review", "authors": "Lafuente R, Gonzalez-Comadran M, Sola I et al.", "journal": "J Assist Reprod Genet", "year": 2013, "studyType": "review", "sampleSize": 332, "outcome": "CoQ10 supplementation showed promising effects on sperm quality parameters", "keyFindings": [ "Sperm motility improved", "Sperm concentration increased in some studies", "Antioxidant markers improved in seminal fluid", "More large RCTs needed" ], "dosageUsed": "200-600 mg daily", "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-051", "supplementName": "L-Theanine", "title": "The acute effects of L-theanine on stress and anxiety: a double-blind, placebo-controlled crossover trial", "authors": "Kimura K, Ozeki M, Juneja LR et al.", "journal": "Biol Psychol", "year": 2007, "studyType": "rct", "sampleSize": 12, "outcome": "L-theanine intake resulted in a reduction in stress response during a mental arithmetic task", "keyFindings": [ "Heart rate variability improved", "Salivary immunoglobulin A response reduced", "Alpha brain wave activity increased", "Subjective anxiety lower" ], "dosageUsed": "200 mg single dose", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-052", "supplementName": "L-Theanine", "title": "L-Theanine as a functional food additive: effects on cognition, stress, and sleep quality", "authors": "Hidese S, Ogawa S, Ota M et al.", "journal": "Nutrients", "year": 2019, "studyType": "rct", "sampleSize": 30, "outcome": "L-theanine improved stress-related symptoms, cognitive function, and sleep quality", "keyFindings": [ "Reduced verbal fluency errors", "Sleep quality improved (PSQI)", "Stress scores decreased", "No sedation or drowsiness reported" ], "dosageUsed": "200 mg daily for 4 weeks", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-053", "supplementName": "L-Theanine", "title": "Synergistic effects of L-theanine and caffeine on cognitive performance: a systematic review", "authors": "Camfield DA, Stough C, Farber J et al.", "journal": "Nutr Rev", "year": 2014, "studyType": "review", "sampleSize": 480, "outcome": "L-theanine combined with caffeine improved attention, task switching, and reduced jitteriness", "keyFindings": [ "Improved accuracy on attention tasks", "Reduced caffeine-induced jitteriness", "Synergistic effect on alertness without anxiety", "Optimal ratio approximately 2:1 theanine to caffeine" ], "dosageUsed": "100-200 mg L-theanine + 40-100 mg caffeine", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-054", "supplementName": "L-Theanine", "title": "Anti-stress effect of L-theanine on students during pharmacy practice: a randomized controlled trial", "authors": "Unno K, Tanida N, Ishii N et al.", "journal": "Pharmacol Biochem Behav", "year": 2013, "studyType": "rct", "sampleSize": 20, "outcome": "L-theanine suppressed the rise in salivary alpha-amylase activity indicating reduced acute stress", "keyFindings": [ "Blunted cortisol stress response", "Salivary alpha-amylase levels lower", "Subjective stress reduced" ], "dosageUsed": "200 mg twice daily", "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-055", "supplementName": "Melatonin", "title": "Meta-analysis: melatonin for the treatment of primary sleep disorders", "authors": "Ferracioli-Oda E, Qawasmi A, Bloch MH", "journal": "PLoS One", "year": 2013, "studyType": "metaAnalysis", "sampleSize": 1683, "outcome": "Melatonin significantly reduced sleep onset latency, increased total sleep time, and improved sleep quality", "keyFindings": [ "Sleep onset latency reduced by 7.06 minutes", "Total sleep time increased by 8.25 minutes", "Overall sleep quality improved", "Effects maintained with prolonged use" ], "dosageUsed": "0.3-5 mg at bedtime", "evidenceRating": "strong", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-056", "supplementName": "Melatonin", "title": "Melatonin for preoperative and postoperative anxiety in adults: a Cochrane review", "authors": "Hansen MV, Halladin NL, Rosenberg J et al.", "journal": "Cochrane Database", "year": 2015, "studyType": "metaAnalysis", "sampleSize": 774, "outcome": "Melatonin reduced preoperative anxiety comparably to standard anxiolytic premedication", "keyFindings": [ "Significant anxiety reduction vs placebo", "Comparable to midazolam for preoperative anxiety", "Fewer side effects than benzodiazepines", "Did not impair psychomotor recovery" ], "dosageUsed": "3-5 mg sublingual before surgery", "evidenceRating": "strong", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-057", "supplementName": "Melatonin", "title": "Efficacy and safety of exogenous melatonin for secondary sleep disorders: a meta-analysis", "authors": "Li T, Jiang S, Han M et al.", "journal": "Front Neuroendocrinol", "year": 2019, "studyType": "metaAnalysis", "sampleSize": 1264, "outcome": "Melatonin improved sleep parameters in patients with secondary sleep disorders", "keyFindings": [ "Sleep onset latency reduced by 14.2 minutes", "Sleep efficiency improved", "Benefits across neurodegenerative and metabolic conditions", "Safe for short-to-medium term use" ], "dosageUsed": "2-10 mg at bedtime", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-058", "supplementName": "Melatonin", "title": "Melatonin as a circadian rhythm regulator in shift workers: a randomized controlled trial", "authors": "Liira J, Verbeek JH, Costa G et al.", "journal": "Cochrane Database", "year": 2014, "studyType": "review", "sampleSize": 837, "outcome": "Melatonin may increase daytime sleep length for shift workers but evidence is limited", "keyFindings": [ "Slight increase in daytime sleep length", "Sleep quality improvement modest", "Night-time alertness not consistently improved", "More research needed for dose optimization" ], "dosageUsed": "1-10 mg before desired sleep time", "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-059", "supplementName": "Creatine", "title": "Effects of creatine supplementation on body composition and performance: a meta-analysis", "authors": "Lanhers C, Pereira B, Naughton G et al.", "journal": "Eur J Sport Sci", "year": 2017, "studyType": "metaAnalysis", "sampleSize": 1461, "outcome": "Creatine supplementation significantly improved lean body mass and upper body strength", "keyFindings": [ "Lean body mass increased significantly", "Upper body strength improved by 5.3%", "Greater effect with loading protocol", "Effective across age groups" ], "dosageUsed": "3-5 g creatine monohydrate daily", "evidenceRating": "strong", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-060", "supplementName": "Creatine", "title": "Effects of creatine supplementation on cognitive function: a systematic review and meta-analysis", "authors": "Avgerinos KI, Spyrou N, Bougioukas KI et al.", "journal": "Exp Gerontol", "year": 2018, "studyType": "metaAnalysis", "sampleSize": 281, "outcome": "Creatine improved short-term memory and reasoning in healthy adults, particularly under stress", "keyFindings": [ "Improvement in short-term memory", "Reasoning/intelligence scores improved", "Greater effect under sleep deprivation or stress", "Vegetarians may benefit more" ], "dosageUsed": "5-20 g daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-061", "supplementName": "Creatine", "title": "International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation", "authors": "Kreider RB, Kalman DS, Antonio J et al.", "journal": "J Int Soc Sports Nutr", "year": 2017, "studyType": "review", "sampleSize": null, "outcome": "Creatine monohydrate is the most effective ergogenic nutritional supplement available to athletes for increasing high-intensity exercise capacity and lean body mass", "keyFindings": [ "Most extensively studied ergogenic supplement", "No detrimental long-term health effects", "No evidence of kidney damage in healthy individuals", "Effective across all age groups and genders" ], "dosageUsed": "3-5 g daily maintenance", "evidenceRating": "strong", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-062", "supplementName": "Creatine", "title": "Effects of creatine supplementation on depressive symptoms: a meta-analysis and review", "authors": "Kious BM, Kondo DG, Renshaw PF", "journal": "J Affect Disord", "year": 2019, "studyType": "metaAnalysis", "sampleSize": 178, "outcome": "Preliminary evidence suggests creatine may augment antidepressant therapy in women", "keyFindings": [ "Significant improvement in depression scores when combined with SSRIs", "Effects seen primarily in women", "Brain phosphocreatine levels increased on MRS", "More research needed in larger samples" ], "dosageUsed": "3-5 g daily", "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-063", "supplementName": "Creatine", "title": "Creatine supplementation and sarcopenia in older adults: a randomized controlled trial", "authors": "Chilibeck PD, Kaviani M, Candow DG et al.", "journal": "Med Sci Sports Exerc", "year": 2015, "studyType": "rct", "sampleSize": 114, "outcome": "Creatine combined with resistance training improved lean tissue mass and strength in older adults", "keyFindings": [ "Greater increase in lean tissue mass vs placebo + RT", "Isometric knee extension strength improved", "No adverse effects on renal function", "Functional performance tests improved" ], "dosageUsed": "5 g creatine monohydrate daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-064", "supplementName": "Rhodiola Rosea", "title": "Rhodiola rosea L. as a putative botanical antidepressant: a clinical trial", "authors": "Darbinyan V, Aslanyan G, Amroyan E et al.", "journal": "Nord J Psychiatry", "year": 2007, "studyType": "rct", "sampleSize": 89, "outcome": "Rhodiola rosea improved depression symptom scores in one small mild-to-moderate depression trial", "keyFindings": [ "Significant improvement in HAM-D scores", "Both 340 mg and 680 mg doses effective", "No sertraline comparator in this trial", "Improvement in emotional stability and insomnia" ], "dosageUsed": "340-680 mg SHR-5 extract daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-065", "supplementName": "Rhodiola Rosea", "title": "Rhodiola rosea for physical and mental fatigue: a systematic review", "authors": "Ishaque S, Shamseer L, Bukutu C et al.", "journal": "BMC Complement Altern Med", "year": 2012, "studyType": "review", "sampleSize": 432, "outcome": "Rhodiola rosea may have beneficial effects on physical and mental fatigue, but evidence is limited", "keyFindings": [ "Some evidence for anti-fatigue effects", "Improved cognitive function under stress", "Heterogeneous study designs limit conclusions", "Generally well tolerated" ], "dosageUsed": "200-600 mg daily", "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-066", "supplementName": "Rhodiola Rosea", "title": "A double-blind, placebo-controlled pilot study of the stimulating and adaptogenic effect of Rhodiola rosea SHR-5", "authors": "Spasov AA, Wikman GK, Mandrikov VB et al.", "journal": "Phytomedicine", "year": 2000, "studyType": "rct", "sampleSize": 161, "outcome": "Rhodiola rosea significantly improved mental fatigue during examination periods", "keyFindings": [ "Anti-fatigue effect demonstrated", "Improved exam performance scores", "No significant side effects", "Single-dose effect observed within 30 minutes" ], "dosageUsed": "100-170 mg daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-067", "supplementName": "Rhodiola Rosea", "title": "Acute Rhodiola rosea intake can improve endurance exercise performance", "authors": "De Bock K, Eijnde BO, Ramaekers M et al.", "journal": "Int J Sport Nutr Exerc Metab", "year": 2004, "studyType": "rct", "sampleSize": 24, "outcome": "Acute Rhodiola rosea intake improved endurance exercise capacity", "keyFindings": [ "Time to exhaustion increased significantly", "VO2peak improved", "Pulmonary ventilation increased", "No effect on perceived exertion" ], "dosageUsed": "200 mg acute dose", "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-068", "supplementName": "Berberine", "title": "Efficacy of berberine in patients with type 2 diabetes mellitus: a meta-analysis", "authors": "Liang Y, Xu X, Yin M et al.", "journal": "Sci Rep", "year": 2019, "studyType": "metaAnalysis", "sampleSize": 2569, "outcome": "Berberine significantly reduced fasting blood glucose, HbA1c, and improved lipid profiles in T2DM patients", "keyFindings": [ "FBG reduced by 15.5 mg/dL", "HbA1c decreased by 0.72%", "Total cholesterol reduced", "Comparable to metformin in some trials" ], "dosageUsed": "500 mg two-three times daily", "evidenceRating": "strong", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-069", "supplementName": "Berberine", "title": "Berberine improves dyslipidemia in type 2 diabetes: a randomized controlled trial", "authors": "Zhang Y, Li X, Zou D et al.", "journal": "J Clin Endocrinol Metab", "year": 2008, "studyType": "rct", "sampleSize": 116, "outcome": "Berberine significantly lowered LDL cholesterol and triglycerides in patients with type 2 diabetes", "keyFindings": [ "LDL cholesterol reduced by 21%", "Triglycerides reduced by 35.9%", "Total cholesterol reduced by 18%", "Blood glucose also improved" ], "dosageUsed": "500 mg three times daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-070", "supplementName": "Berberine", "title": "The effect of berberine on the gut microbiota: a systematic review", "authors": "Wang Y, Tong Q, Shou JW et al.", "journal": "Fitoterapia", "year": 2020, "studyType": "review", "sampleSize": null, "outcome": "Berberine positively modulated gut microbiome composition and increased short-chain fatty acid production", "keyFindings": [ "Increased beneficial Akkermansia abundance", "Reduced pathogenic bacteria", "Enhanced butyrate production", "Gut microbiome changes may mediate metabolic effects" ], "dosageUsed": "500-1500 mg daily", "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-071", "supplementName": "Berberine", "title": "Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I", "authors": "Turner N, Li JY, Gosby A et al.", "journal": "Diabetes", "year": 2008, "studyType": "inVitro", "sampleSize": null, "outcome": "Berberine activates AMPK by inhibiting mitochondrial complex I, similar to metformin's mechanism", "keyFindings": [ "AMPK activation demonstrated", "Complex I inhibition is primary mechanism", "Dihydroberberine more bioavailable", "Explains anti-diabetic activity" ], "dosageUsed": null, "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-072", "supplementName": "NAC", "title": "N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action", "authors": "Deepmala, Slattery J, Kumar N et al.", "journal": "J Clin Psychiatry", "year": 2015, "studyType": "review", "sampleSize": 1642, "outcome": "NAC showed benefit as adjunctive treatment for multiple psychiatric conditions", "keyFindings": [ "Benefit in bipolar depression", "Reduced gambling urges and substance cravings", "Improved OCD symptoms in some trials", "Glutathione restoration proposed as mechanism" ], "dosageUsed": "1200-3000 mg daily", "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-073", "supplementName": "NAC", "title": "Oral N-acetylcysteine in prevention of contrast-induced nephropathy: a meta-analysis", "authors": "Sun Z, Fu Q, Cao L et al.", "journal": "Am Heart J", "year": 2013, "studyType": "metaAnalysis", "sampleSize": 10297, "outcome": "NAC significantly reduced the risk of contrast-induced nephropathy in patients undergoing cardiac procedures", "keyFindings": [ "Risk reduction of 44%", "IV and oral routes both effective", "Benefits most in high-risk patients", "Dose-dependent effect observed" ], "dosageUsed": "600-1200 mg twice daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-074", "supplementName": "NAC", "title": "N-acetylcysteine supplementation improves functional capacity and reduces exercise-induced oxidative stress", "authors": "Slattery KM, Dascombe B, Wallace LK et al.", "journal": "J Int Soc Sports Nutr", "year": 2014, "studyType": "rct", "sampleSize": 10, "outcome": "NAC supplementation reduced oxidative stress markers and improved repeated sprint performance", "keyFindings": [ "Glutathione levels increased", "Lipid peroxidation reduced", "Sprint performance improved", "Reduced muscle fatigue markers" ], "dosageUsed": "1200 mg daily for 9 days", "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-075", "supplementName": "NAC", "title": "N-acetylcysteine for nonacetaminophen-induced acute liver failure: a systematic review and meta-analysis", "authors": "Hu J, Zhang Q, Ren X et al.", "journal": "Crit Care", "year": 2015, "studyType": "metaAnalysis", "sampleSize": 331, "outcome": "NAC improved transplant-free survival in early-stage non-acetaminophen acute liver failure", "keyFindings": [ "Improved overall survival", "Greatest benefit in early-stage liver failure", "Hepatic encephalopathy duration reduced", "Safe with minimal adverse effects" ], "dosageUsed": "IV 150 mg/kg loading, 50 mg/kg over 4h", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-076", "supplementName": "NAC", "title": "N-acetylcysteine for polycystic ovary syndrome: a systematic review and meta-analysis", "authors": "Thakker D, Raval A, Patel I et al.", "journal": "Obstet Gynecol Surv", "year": 2015, "studyType": "metaAnalysis", "sampleSize": 910, "outcome": "NAC improved ovulation and pregnancy rates in women with PCOS", "keyFindings": [ "Ovulation rate significantly improved", "Pregnancy rate increased", "BMI and testosterone levels decreased", "Comparable to metformin in some outcomes" ], "dosageUsed": "1200-1800 mg daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-077", "supplementName": "Vitamin K2", "title": "Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women", "authors": "Knapen MH, Drummen NE, Smit E et al.", "journal": "Osteoporos Int", "year": 2013, "studyType": "rct", "sampleSize": 244, "outcome": "MK-7 supplementation significantly improved bone mineral density and bone strength indices", "keyFindings": [ "Decreased lumbar BMD loss", "Femoral neck BMD preserved", "Improved bone strength parameters", "Reduced undercarboxylated osteocalcin" ], "dosageUsed": "180 mcg MK-7 daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-078", "supplementName": "Vitamin K2", "title": "High dietary menaquinone intake is associated with reduced coronary calcification: the Rotterdam Study", "authors": "Geleijnse JM, Vermeer C, Grobbee DE et al.", "journal": "J Nutr", "year": 2004, "studyType": "cohort", "sampleSize": 4807, "outcome": "High menaquinone (K2) intake was associated with reduced coronary artery calcification and cardiovascular mortality", "keyFindings": [ "Relative risk of CHD death reduced by 57%", "Severe aortic calcification reduced by 52%", "All-cause mortality reduced by 26%", "Effect was from K2 specifically, not K1" ], "dosageUsed": null, "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-079", "supplementName": "Vitamin K2", "title": "Vitamin K2 supplementation and arterial stiffness: a randomized controlled trial", "authors": "Knapen MH, Braam LA, Drummen NE et al.", "journal": "Thromb Haemost", "year": 2015, "studyType": "rct", "sampleSize": 244, "outcome": "Long-term MK-7 supplementation improved arterial stiffness in postmenopausal women", "keyFindings": [ "Carotid-femoral pulse wave velocity decreased", "Stiffness index beta improved", "Desphospho-uncarboxylated MGP decreased", "Benefits seen after 3 years of supplementation" ], "dosageUsed": "180 mcg MK-7 daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-080", "supplementName": "Vitamin K2", "title": "Synergistic effect of vitamin K2 and vitamin D3 on calcium metabolism: a review", "authors": "van Ballegooijen AJ, Pilz S, Tomaschitz A et al.", "journal": "Int J Endocrinol", "year": 2017, "studyType": "review", "sampleSize": null, "outcome": "Combined supplementation of vitamins D3 and K2 had synergistic effects on bone and cardiovascular health", "keyFindings": [ "K2 directs D3-absorbed calcium to bones", "Prevents vascular calcification", "Both vitamins needed for optimal calcium handling", "Deficiency in one may impair the other's efficacy" ], "dosageUsed": null, "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-081", "supplementName": "Selenium", "title": "Selenium and cancer prevention: an updated systematic review and meta-analysis", "authors": "Vinceti M, Filippini T, Del Giovane C et al.", "journal": "Cochrane Database", "year": 2018, "studyType": "metaAnalysis", "sampleSize": 43479, "outcome": "No convincing evidence that selenium supplements prevent cancer in general population", "keyFindings": [ "No overall cancer prevention effect", "Possible slight reduction in liver cancer", "Increased risk of type 2 diabetes at high doses", "No benefit for prostate cancer prevention (SELECT)" ], "dosageUsed": "200 mcg daily", "evidenceRating": "strong", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-082", "supplementName": "Selenium", "title": "Effects of selenium supplementation on thyroid function in patients with autoimmune thyroiditis: a systematic review and meta-analysis", "authors": "Wichman J, Winther KH, Bonnema SJ et al.", "journal": "Thyroid", "year": 2016, "studyType": "metaAnalysis", "sampleSize": 796, "outcome": "Selenium supplementation reduced thyroid peroxidase antibodies in patients with autoimmune thyroiditis", "keyFindings": [ "TPO antibody titers reduced significantly", "Some patients achieved euthyroid state", "200 mcg selenomethionine most studied", "No consistent effect on thyroid hormone levels" ], "dosageUsed": "200 mcg selenomethionine daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-083", "supplementName": "Selenium", "title": "Selenium supplementation and HIV progression: a randomized controlled trial", "authors": "Baum MK, Campa A, Lai S et al.", "journal": "Arch Intern Med", "year": 2007, "studyType": "rct", "sampleSize": 262, "outcome": "Selenium supplementation slowed HIV-related CD4 decline and reduced viral load in treatment-naive patients", "keyFindings": [ "Suppressed viral load increase", "Preserved CD4 T-cell count", "Improved immune markers", "Effect lost after supplementation stopped" ], "dosageUsed": "200 mcg selenomethionine daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-084", "supplementName": "Selenium", "title": "Selenium intake and risk of cardiovascular disease: a dose-response meta-analysis of prospective studies", "authors": "Zhang X, Liu C, Guo J et al.", "journal": "Eur J Clin Nutr", "year": 2016, "studyType": "metaAnalysis", "sampleSize": 28186, "outcome": "U-shaped relationship between selenium status and cardiovascular risk, both low and high levels associated with increased risk", "keyFindings": [ "Optimal serum selenium around 55-145 mcg/L", "Both deficiency and excess harmful", "No benefit from supplementation in selenium-replete populations", "Geographic variation in effects" ], "dosageUsed": null, "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-085", "supplementName": "Quercetin", "title": "Quercetin and upper respiratory tract infection: a meta-analysis of randomized clinical trials", "authors": "Somerville VS, Braakhuis AJ, Hopkins WG", "journal": "Pharmacol Res", "year": 2016, "studyType": "metaAnalysis", "sampleSize": 1002, "outcome": "Quercetin supplementation reduced upper respiratory infections, particularly in physically fit individuals", "keyFindings": [ "Significant reduction in URTI incidence", "Greater benefit after strenuous exercise", "Dose of 1000 mg/day most effective", "May enhance immune function under physical stress" ], "dosageUsed": "500-1000 mg daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-086", "supplementName": "Quercetin", "title": "Quercetin supplementation and blood pressure: a systematic review and meta-analysis", "authors": "Serban MC, Sahebkar A, Zanchetti A et al.", "journal": "J Am Heart Assoc", "year": 2016, "studyType": "metaAnalysis", "sampleSize": 886, "outcome": "Quercetin supplementation significantly reduced blood pressure in hypertensive subjects", "keyFindings": [ "SBP reduced by 3.04 mmHg", "DBP reduced by 2.63 mmHg", "Greater effect in hypertensive participants", "Doses ≥500 mg most effective" ], "dosageUsed": "100-1000 mg daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-087", "supplementName": "Quercetin", "title": "Quercetin and its anti-allergic immune response: a review", "authors": "Mlcek J, Jurikova T, Skrovankova S et al.", "journal": "Molecules", "year": 2016, "studyType": "review", "sampleSize": null, "outcome": "Quercetin demonstrated mast cell stabilizing and anti-histamine properties in preclinical models", "keyFindings": [ "Inhibits histamine release from mast cells", "Reduces pro-inflammatory cytokines", "May benefit allergic rhinitis", "Bioavailability limits clinical translation" ], "dosageUsed": "500-1000 mg daily", "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-088", "supplementName": "Quercetin", "title": "Dasatinib plus quercetin senolytic activity and aging biomarkers: a preliminary human pilot trial", "authors": "Hickson LJ, Langhi Prata LGP, Boez SA et al.", "journal": "EBioMedicine", "year": 2019, "studyType": "rct", "sampleSize": 14, "outcome": "Dasatinib plus quercetin reduced senescent-cell markers in a small diabetic kidney disease pilot trial", "keyFindings": [ "Senescent cell markers reduced", "Physical-function findings were exploratory", "Skin senescent cell counts decreased", "Combination therapy only; quercetin-alone senolytic effect was not tested" ], "dosageUsed": "1000 mg quercetin + 100 mg dasatinib intermittently", "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-089", "supplementName": "Vitamin D3", "title": "Effect of vitamin D3 supplements on development of advanced cancer: secondary analysis of the VITAL randomized clinical trial", "authors": "Chandler PD, Chen WY, Ajala ON et al.", "journal": "JAMA Netw Open", "year": 2020, "studyType": "rct", "sampleSize": 25871, "outcome": "Vitamin D3 supplementation reduced the risk of advanced and metastatic cancer, particularly in those with normal BMI", "keyFindings": [ "17% reduction in advanced cancer overall", "38% reduction in cancer death among normal-weight individuals", "No effect in overweight/obese participants", "Secondary analysis of VITAL trial" ], "dosageUsed": "2000 IU daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-090", "supplementName": "Magnesium Glycinate", "title": "Effects of magnesium supplementation on migraine frequency: a meta-analysis of randomized controlled trials", "authors": "Chiu HY, Yeh TH, Huang YC et al.", "journal": "Pain Physician", "year": 2016, "studyType": "metaAnalysis", "sampleSize": 789, "outcome": "Magnesium supplementation significantly reduced migraine frequency and intensity", "keyFindings": [ "Migraine days reduced by 22.13%", "Pain intensity decreased", "400-600 mg most effective dose range", "Magnesium oxide and citrate most studied" ], "dosageUsed": "400-600 mg daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-091", "supplementName": "Fish Oil", "title": "Omega-3 fatty acids supplementation and cognitive decline: a systematic review and meta-analysis", "authors": "Alex A, Abbott KA, McEvoy M et al.", "journal": "Nutr Neurosci", "year": 2020, "studyType": "metaAnalysis", "sampleSize": 8354, "outcome": "Omega-3 supplementation had minimal effect on cognitive decline in healthy older adults but may benefit those with mild cognitive impairment", "keyFindings": [ "No significant effect on global cognition in healthy adults", "Memory domain showed small improvement", "Benefit seen in MCI subgroup", "DHA more important than EPA for brain effects" ], "dosageUsed": "400-2000 mg DHA+EPA daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-092", "supplementName": "Ashwagandha", "title": "An investigation into the stress-relieving and pharmacological actions of an ashwagandha extract: a randomized, double-blind, placebo-controlled study", "authors": "Salve J, Pate S, Debnath K et al.", "journal": "Medicine", "year": 2019, "studyType": "rct", "sampleSize": 60, "outcome": "Ashwagandha extract significantly reduced perceived stress and serum cortisol levels", "keyFindings": [ "PSS-10 scores decreased by 44%", "Serum cortisol reduced significantly", "Sleep quality improved", "Well tolerated at 125-600 mg doses" ], "dosageUsed": "125-600 mg daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-093", "supplementName": "Turmeric/Curcumin", "title": "The effect of curcumin supplementation on cognitive function in the elderly: a systematic review of randomized controlled trials", "authors": "Cox KH, White DJ, Pipingas A et al.", "journal": "J Psychopharmacol", "year": 2020, "studyType": "review", "sampleSize": 589, "outcome": "Curcumin supplementation improved working memory and attention in healthy older adults", "keyFindings": [ "Working memory improved after acute and chronic dosing", "Attention and mood benefits observed", "Highly bioavailable forms most effective", "Benefits seen as early as 1 hour post-dose" ], "dosageUsed": "400-1500 mg daily (bioavailable forms)", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-094", "supplementName": "Coenzyme Q10", "title": "Coenzyme Q10 supplementation for the reduction of oxidative stress: clinical implications in the treatment of chronic diseases", "authors": "Zozina VI, Covantev S, Goroshko OA et al.", "journal": "Free Radic Res", "year": 2018, "studyType": "review", "sampleSize": null, "outcome": "CoQ10 supplementation reduced oxidative stress markers across multiple chronic conditions", "keyFindings": [ "MDA and isoprostane levels decreased", "SOD activity improved", "Benefits in diabetes, CVD, and chronic kidney disease", "Ubiquinol form may be more bioavailable in elderly" ], "dosageUsed": "100-300 mg daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-095", "supplementName": "L-Theanine", "title": "Effects of L-theanine on attention and reaction time response in healthy adults", "authors": "Nobre AC, Rao A, Owen GN", "journal": "Asia Pac J Clin Nutr", "year": 2008, "studyType": "rct", "sampleSize": 35, "outcome": "L-theanine promoted alpha brain wave activity and improved attention within 45-60 minutes of ingestion", "keyFindings": [ "Alpha-1 wave activity increased in temporal and occipital regions", "Improved attention during complex tasks", "Effect observed at 50 mg dose", "No sedation reported" ], "dosageUsed": "50 mg single dose", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-096", "supplementName": "Melatonin", "title": "Effect of melatonin supplementation on metabolic parameters: a systematic review and meta-analysis", "authors": "Mohammadi-Sartang M, Ghorbani M, Mazloom Z", "journal": "Clin Nutr ESPEN", "year": 2018, "studyType": "metaAnalysis", "sampleSize": 1021, "outcome": "Melatonin supplementation significantly reduced triglyceride and total cholesterol levels", "keyFindings": [ "Triglycerides reduced by 29.3 mg/dL", "Total cholesterol reduced by 7.7 mg/dL", "LDL cholesterol showed trend toward reduction", "May benefit metabolic syndrome patients" ], "dosageUsed": "2-10 mg at bedtime", "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-097", "supplementName": "Creatine", "title": "Creatine supplementation in women: effects across the menstrual cycle during exercise", "authors": "Smith-Ryan AE, Cabre HE, Eckerson JM et al.", "journal": "Nutrients", "year": 2021, "studyType": "review", "sampleSize": null, "outcome": "Creatine may have unique benefits for women including improved mood, cognition, and exercise performance across the menstrual cycle", "keyFindings": [ "May mitigate premenstrual mood disturbances", "Supports muscle recovery during luteal phase", "Sleep deprivation effects mitigated", "Underrepresented population in creatine research" ], "dosageUsed": "3-5 g daily", "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-098", "supplementName": "Berberine", "title": "Berberine for weight loss: a systematic review and meta-analysis", "authors": "Xiong P, Niu L, Talaei S et al.", "journal": "Phytother Res", "year": 2020, "studyType": "metaAnalysis", "sampleSize": 2147, "outcome": "Berberine supplementation significantly reduced BMI, waist circumference, and body weight", "keyFindings": [ "Body weight reduced by 2.07 kg on average", "BMI decreased by 0.47 kg/m2", "Waist circumference reduced", "Effects greater in metabolic syndrome patients" ], "dosageUsed": "500-1500 mg daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-099", "supplementName": "Zinc", "title": "Zinc supplementation for acne vulgaris: a systematic review of the clinical evidence", "authors": "Yee BE, Richards P, Shenefelt PD et al.", "journal": "J Drugs Dermatol", "year": 2020, "studyType": "review", "sampleSize": 554, "outcome": "Zinc supplementation showed moderate benefit for inflammatory acne in several small trials", "keyFindings": [ "30 mg zinc gluconate reduced inflammatory lesions", "Comparable to low-dose tetracycline in one trial", "More effective for inflammatory vs comedonal acne", "Fewer side effects than oral antibiotics" ], "dosageUsed": "30-50 mg zinc daily", "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-100", "supplementName": "Vitamin B12", "title": "Vitamin B12 status and rate of brain volume loss in community-dwelling elderly: a 5-year follow-up study", "authors": "Vogiatzoglou A, Refsum H, Johnston C et al.", "journal": "Neurology", "year": 2008, "studyType": "cohort", "sampleSize": 107, "outcome": "Lower vitamin B12 status was associated with greater brain volume loss over 5 years in elderly individuals", "keyFindings": [ "B12 in lowest tertile had 6-fold faster brain atrophy", "Effect independent of folate and homocysteine", "Holotranscobalamin was best marker", "Suggests B12 deficiency may accelerate neurodegeneration" ], "dosageUsed": null, "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-101", "supplementName": "Probiotics", "title": "Probiotic supplementation and body weight: a systematic review and meta-analysis", "authors": "Borgeraas H, Johnson LK, Skattebu J et al.", "journal": "Obes Rev", "year": 2018, "studyType": "metaAnalysis", "sampleSize": 1931, "outcome": "Probiotic supplementation resulted in a small but significant reduction in body weight and BMI", "keyFindings": [ "Body weight reduced by 0.54 kg", "BMI reduced by 0.22 kg/m2", "Lactobacillus strains most effective", "Greater effect with multiple strains" ], "dosageUsed": "Various strains, 1-100 billion CFU daily", "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-102", "supplementName": "Iron", "title": "Alternate-day versus daily oral iron supplementation in patients with iron deficiency anemia: a randomized study", "authors": "Stoffel NU, Cercamondi CI, Brittenham G et al.", "journal": "Am J Hematol", "year": 2020, "studyType": "rct", "sampleSize": 54, "outcome": "Alternate-day iron supplementation improved fractional iron absorption and may be preferred over daily dosing", "keyFindings": [ "Fractional absorption doubled with alternate-day dosing", "Hepcidin levels lower on alternate days", "Comparable hemoglobin increase over 12 weeks", "Better GI tolerability with alternate-day dosing" ], "dosageUsed": "60 mg elemental iron alternate days", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-103", "supplementName": "Vitamin C", "title": "Vitamin C supplementation for the primary prevention of cardiovascular disease: a Cochrane review", "authors": "Al-Khudairy L, Flowers N, Wheelhouse R et al.", "journal": "Cochrane Database", "year": 2017, "studyType": "review", "sampleSize": 246028, "outcome": "Insufficient evidence to support vitamin C supplementation for cardiovascular disease prevention", "keyFindings": [ "No significant effect on CVD mortality", "Limited RCT data available", "Observational studies suggest benefit", "Supplementation not recommended for CVD prevention alone" ], "dosageUsed": "250-1000 mg daily", "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-104", "supplementName": "Selenium", "title": "Low-dose selenium supplementation in the elderly: effects on thyroid function, immunity, and quality of life", "authors": "Rayman MP, Thompson AJ, Bekaert B et al.", "journal": "Clin Endocrinol", "year": 2008, "studyType": "rct", "sampleSize": 501, "outcome": "Selenium supplementation improved thyroid function and immune parameters in elderly UK subjects", "keyFindings": [ "T4:T3 ratio improved", "Lymphocyte proliferation increased", "Quality of life improved in some subgroups", "100 mcg sufficient for most benefits" ], "dosageUsed": "100-200 mcg daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-105", "supplementName": "Quercetin", "title": "Quercetin reduces endothelial dysfunction and atherosclerosis in ApoE-knockout mice", "authors": "Loke WM, Proudfoot JM, Hodgson JM et al.", "journal": "J Nutr", "year": 2010, "studyType": "animalStudy", "sampleSize": null, "outcome": "Quercetin supplementation reduced atherosclerotic plaque size and improved endothelial function in ApoE-KO mice", "keyFindings": [ "Atherosclerotic lesion area reduced by 40%", "Endothelium-dependent vasodilation improved", "Superoxide production decreased", "Gene expression of anti-inflammatory markers upregulated" ], "dosageUsed": null, "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-106", "supplementName": "Vitamin K2", "title": "Menaquinone-7 supplementation improves osteocalcin carboxylation and bone turnover markers in postmenopausal women", "authors": "Inaba N, Sato T, Yamashita T", "journal": "J Bone Miner Metab", "year": 2015, "studyType": "rct", "sampleSize": 60, "outcome": "MK-7 supplementation improved osteocalcin carboxylation status and bone turnover biomarkers", "keyFindings": [ "Undercarboxylated osteocalcin reduced by 60%", "Bone-specific alkaline phosphatase decreased", "Effects seen within 4 weeks", "100 mcg/day was minimal effective dose" ], "dosageUsed": "100-200 mcg MK-7 daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-107", "supplementName": "Rhodiola Rosea", "title": "Rhodiola rosea in subjects with burnout symptoms: an exploratory clinical trial", "authors": "Kasper S, Dienel A", "journal": "Neuropsychiatr Dis Treat", "year": 2017, "studyType": "rct", "sampleSize": 118, "outcome": "Rhodiola rosea extract improved burnout symptoms including emotional exhaustion and fatigue", "keyFindings": [ "Emotional exhaustion scores improved", "Impaired concentration reduced", "Effect visible from first week", "Sustained improvement over 12 weeks" ], "dosageUsed": "400 mg WS 1375 extract daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-108", "supplementName": "Melatonin", "title": "Prolonged-release melatonin for insomnia: an open-label, long-term safety study in older adults", "authors": "Lemoine P, Nir T, Laudon M et al.", "journal": "J Pineal Res", "year": 2007, "studyType": "cohort", "sampleSize": 791, "outcome": "Prolonged-release melatonin was safe and well-tolerated for up to 12 months in older adults", "keyFindings": [ "No evidence of dependence", "No withdrawal effects on discontinuation", "Sleep quality maintained over 12 months", "No next-day residual effects" ], "dosageUsed": "2 mg prolonged-release at bedtime", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-109", "supplementName": "NAC", "title": "N-acetylcysteine in depressive symptoms and functionality: a systematic review and meta-analysis", "authors": "Fernandes BS, Dean OM, Dodd S et al.", "journal": "J Clin Psychiatry", "year": 2016, "studyType": "metaAnalysis", "sampleSize": 574, "outcome": "NAC significantly improved depressive symptoms and functional outcomes as adjunctive therapy", "keyFindings": [ "Significant effect on depression symptoms", "Global functioning improved", "Effect size moderate (SMD 0.37)", "Benefits as adjunct to standard treatment" ], "dosageUsed": "2000-3000 mg daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-110", "supplementName": "Berberine", "title": "Effects of berberine on non-alcoholic fatty liver disease: a systematic review and meta-analysis", "authors": "Wei X, Wang C, Hao S et al.", "journal": "Complement Ther Med", "year": 2016, "studyType": "metaAnalysis", "sampleSize": 874, "outcome": "Berberine improved liver enzymes, lipid profiles, and insulin resistance in NAFLD patients", "keyFindings": [ "ALT levels significantly reduced", "Triglycerides decreased", "HOMA-IR improved", "Effect comparable to lifestyle modifications" ], "dosageUsed": "500 mg two-three times daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-111", "supplementName": "Coenzyme Q10", "title": "Coenzyme Q10 supplementation decreases blood pressure in hypertensive patients: a meta-analysis", "authors": "Rosenfeldt FL, Haas SJ, Krum H et al.", "journal": "J Hum Hypertens", "year": 2007, "studyType": "metaAnalysis", "sampleSize": 362, "outcome": "CoQ10 supplementation reduced both systolic and diastolic blood pressure", "keyFindings": [ "SBP reduced by 11 mmHg", "DBP reduced by 7 mmHg", "No significant side effects", "Consistent across 12 clinical studies" ], "dosageUsed": "60-200 mg daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-112", "supplementName": "Vitamin C", "title": "Vitamin C and immune function: a review of evidence from human and animal studies", "authors": "Carr AC, Maggini S", "journal": "Nutrients", "year": 2017, "studyType": "review", "sampleSize": null, "outcome": "Vitamin C supports immune function by enhancing epithelial barrier, phagocyte activity, and lymphocyte proliferation", "keyFindings": [ "Enhances epithelial barrier function", "Stimulates production of white blood cells", "Functions as potent antioxidant protecting immune cells", "Deficiency impairs immunity and increases susceptibility to infection" ], "dosageUsed": "100-200 mg daily (maintenance)", "evidenceRating": "strong", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-113", "supplementName": "Zinc", "title": "Zinc supplementation and depression: a systematic review and meta-analysis of randomized controlled trials", "authors": "Lai J, Moxey A, Nowak G et al.", "journal": "J Affect Disord", "year": 2012, "studyType": "metaAnalysis", "sampleSize": 543, "outcome": "Zinc supplementation significantly reduced depression symptom scores", "keyFindings": [ "Significant antidepressant effect", "Greater effect as adjunct to antidepressants", "25-50 mg zinc effective", "Low zinc status associated with more severe depression" ], "dosageUsed": "25-50 mg daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-114", "supplementName": "L-Theanine", "title": "L-Theanine prevents long-term affective and cognitive side effects of adolescent delta-9-tetrahydrocannabinol exposure", "authors": "Murphy M, Mills S, Winstone J et al.", "journal": "Front Behav Neurosci", "year": 2017, "studyType": "animalStudy", "sampleSize": null, "outcome": "L-theanine pretreatment prevented THC-induced anxiety and cognitive deficits in adolescent rats", "keyFindings": [ "Anxiety-like behavior prevented", "Working memory deficits attenuated", "Social interaction normalized", "Glutamate modulation proposed as mechanism" ], "dosageUsed": null, "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-115", "supplementName": "Turmeric/Curcumin", "title": "Curcumin induces apoptosis in triple-negative breast cancer cells through reactive oxygen species", "authors": "Hu S, Xu Y, Meng L et al.", "journal": "Mol Med Rep", "year": 2018, "studyType": "inVitro", "sampleSize": null, "outcome": "Curcumin inhibited proliferation and induced apoptosis in MDA-MB-231 triple-negative breast cancer cells", "keyFindings": [ "Dose-dependent growth inhibition", "ROS generation increased", "Mitochondrial membrane potential decreased", "Caspase-3 and caspase-9 activated" ], "dosageUsed": null, "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-116", "supplementName": "Fish Oil", "title": "Omega-3 fatty acid supplementation for the treatment of children with ADHD: a systematic review and meta-analysis", "authors": "Chang JPC, Su KP, Mondelli V et al.", "journal": "Neuropsychopharmacology", "year": 2018, "studyType": "metaAnalysis", "sampleSize": 1519, "outcome": "Omega-3 supplementation had modest but significant effects on ADHD symptoms in children", "keyFindings": [ "Small but significant improvement in ADHD symptoms", "EPA supplementation drove the effect", "Effect size comparable to some behavioral interventions", "May benefit as adjunct to standard treatment" ], "dosageUsed": "500-1200 mg EPA+DHA daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-117", "supplementName": "Iron", "title": "Iron supplementation and cognition in children: a systematic review and meta-analysis", "authors": "Falkingham M, Abdelhamid A, Curtis P et al.", "journal": "Nutr J", "year": 2010, "studyType": "metaAnalysis", "sampleSize": 5923, "outcome": "Iron supplementation improved attention and concentration in iron-deficient children and adolescents", "keyFindings": [ "Attention scores improved significantly", "IQ scores improved in anemic children", "No benefit in iron-replete children", "Adolescent girls particularly benefited" ], "dosageUsed": "10-60 mg elemental iron daily", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-118", "supplementName": "Creatine", "title": "Creatine supplementation and bone health: a meta-analysis", "authors": "Forbes SC, Chilibeck PD, Candow DG", "journal": "Nutrients", "year": 2020, "studyType": "metaAnalysis", "sampleSize": 484, "outcome": "Creatine combined with resistance training preserved or improved bone mineral density in older adults", "keyFindings": [ "Reduced rate of BMD loss at hip", "Greater effect when combined with resistance training", "May benefit postmenopausal women", "Mechanism involves osteoblast stimulation" ], "dosageUsed": "3-5 g daily", "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-119", "supplementName": "Vitamin B12", "title": "Metformin-induced vitamin B12 deficiency presenting as peripheral neuropathy: a case-control study", "authors": "Ahmed MA, Muntingh G, Rheeder P", "journal": "Diabetes Metab Res Rev", "year": 2016, "studyType": "caseControl", "sampleSize": 200, "outcome": "Long-term metformin use was significantly associated with B12 deficiency and peripheral neuropathy", "keyFindings": [ "B12 deficiency 3x more common in metformin users", "Duration of metformin use correlated with deficiency", "Peripheral neuropathy more prevalent", "Routine B12 monitoring recommended for metformin users" ], "dosageUsed": null, "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-120", "supplementName": "Quercetin", "title": "Quercetin inhibits SARS-CoV-2 3CLpro activity: an in silico and in vitro study", "authors": "Abian O, Ortega-Alarcon D, Jimenez-Alesanco A et al.", "journal": "Int J Biol Macromol", "year": 2020, "studyType": "inVitro", "sampleSize": null, "outcome": "Quercetin demonstrated inhibitory activity against SARS-CoV-2 main protease in vitro", "keyFindings": [ "Direct inhibition of 3CLpro activity", "IC50 in low micromolar range", "Synergistic with vitamin C", "Clinical translation requires further study" ], "dosageUsed": null, "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-0121", "supplementName": "5-HTP", "title": "5-Hydroxytryptophan: a clinically-effective serotonin precursor", "authors": "Birdsall TC", "journal": "Alternative medicine review : a journal of clinical therapeutic", "year": 1998, "studyType": "review", "sampleSize": null, "outcome": "5-HTP shows clinical efficacy for depression, fibromyalgia, obesity, and insomnia", "keyFindings": [ "Effective serotonin precursor crossing blood-brain barrier", "Comparable efficacy to SSRIs in some depression trials", "Well tolerated at therapeutic doses" ], "dosageUsed": "50-300 mg daily", "evidenceRating": "moderate", "pmid": "9727088", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9727088/", "publicSourceType": "PMID" }, { "id": "study-0122", "supplementName": "5-HTP", "title": "The effects of 5-hydroxytryptophan on eating behavior and adherence to dietary prescriptions in obese patients", "authors": "Cangiano C, Ceci F, Cascino A et al.", "journal": "Am J Clin Nutr", "year": 1992, "studyType": "rct", "sampleSize": 20, "outcome": "5-HTP reduced caloric intake and promoted weight loss in obese subjects", "keyFindings": [ "Significant decrease in carbohydrate intake", "Mean weight loss of 2% over 6 weeks", "Reduced appetite without significant side effects" ], "dosageUsed": "900 mg daily", "evidenceRating": "moderate", "pmid": "1384305", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/1384305/", "publicSourceType": "PMID" }, { "id": "study-0123", "supplementName": "5-HTP", "title": "Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome", "authors": "Caruso I, Sarzi Puttini P, Cazzola M, Azzolini V", "journal": "J Int Med Res", "year": 1990, "studyType": "rct", "sampleSize": 50, "outcome": "5-HTP significantly improved fibromyalgia symptoms including pain, morning stiffness, and sleep", "keyFindings": [ "Significant improvement in pain scores", "Reduced morning stiffness and anxiety", "Good tolerability profile" ], "dosageUsed": "100 mg three times daily", "evidenceRating": "moderate", "pmid": "2193835", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2193835/", "publicSourceType": "PMID" }, { "id": "study-0124", "supplementName": "Acetyl-L-Carnitine", "title": "Acetyl-L-Carnitine Supplementation and the Treatment of Depressive Symptoms: A Systematic Review and Meta-Analysis", "authors": "Veronese N, Stubbs B, Solmi M et al.", "journal": "Psychosomatic medicine", "year": 2018, "studyType": "metaAnalysis", "sampleSize": 791, "outcome": "Acetyl-L-carnitine significantly reduced depressive symptoms compared to placebo", "keyFindings": [ "Significant antidepressant effect (SMD −1.10)", "Comparable efficacy to established antidepressants", "Fewer adverse effects than antidepressant drugs" ], "dosageUsed": "1500-3000 mg daily", "evidenceRating": "moderate", "pmid": "29076953", "doi": "10.1097/PSY.0000000000000537", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29076953/", "publicSourceType": "PMID" }, { "id": "study-0125", "supplementName": "Acetyl-L-Carnitine", "title": "Acetyl-L-Carnitine for the Treatment of Peripheral Neuropathic Pain: a Systematic Review and Meta-Analysis", "authors": "Li S, Li Q, Li Y et al.", "journal": "Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research", "year": 2014, "studyType": "metaAnalysis", "sampleSize": 1250, "outcome": "ALC significantly reduced pain scores in peripheral neuropathy", "keyFindings": [ "Significant pain reduction (SMD −0.45)", "Improvements in nerve conduction velocity", "Benefits most pronounced after 6+ months of treatment" ], "dosageUsed": "1500-3000 mg daily", "evidenceRating": "moderate", "pmid": "27203064", "doi": "10.1016/j.jval.2014.08.545", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27203064/", "publicSourceType": "PMID" }, { "id": "study-0126", "supplementName": "Acetyl-L-Carnitine", "title": "Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease", "authors": "Montgomery SA, Thal LJ, Amrein R", "journal": "Int Clin Psychopharmacol", "year": 2003, "studyType": "metaAnalysis", "sampleSize": 1204, "outcome": "ALC showed significant benefit in mild cognitive impairment and early Alzheimer's", "keyFindings": [ "Significant improvement on clinical scales at 3 and 6 months", "Benefits seen primarily in early-onset cases", "Well-tolerated with minimal side effects" ], "dosageUsed": "1500-3000 mg daily", "evidenceRating": "moderate", "pmid": "12598816", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12598816/", "publicSourceType": "PMID" }, { "id": "study-0127", "supplementName": "Activated Charcoal", "title": "Position paper: single-dose activated charcoal", "authors": "Chyka PA, Seger D, Krenzelok EP et al.", "journal": "Clin Toxicol", "year": 2005, "studyType": "review", "sampleSize": null, "outcome": "Activated charcoal remains the primary GI decontamination method for acute poisoning", "keyFindings": [ "Most effective within 1 hour of ingestion", "Can reduce absorption of many drugs by 50-90%", "Should not be used routinely for all poisonings" ], "dosageUsed": "50-100 g single dose (adults)", "evidenceRating": "strong", "pmid": "16019795", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16019795/", "publicSourceType": "PMID" }, { "id": "study-0128", "supplementName": "Activated Charcoal", "title": "Does activated charcoal have a role in the management of drug overdose?", "authors": "Juurlink DN", "journal": "CMAJ", "year": 2016, "studyType": "review", "sampleSize": null, "outcome": "Activated charcoal benefit is limited when given >1 hour after ingestion", "keyFindings": [ "Evidence supports use within 1 hour of overdose", "Routine use not recommended", "Risk of aspiration must be weighed against potential benefit" ], "dosageUsed": "25-100 g single dose", "evidenceRating": "moderate", "pmid": "26644500", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26644500/", "publicSourceType": "PMID" }, { "id": "study-0129", "supplementName": "Alpha-GPC", "title": "Cognitive improvement in mild to moderate Alzheimer's dementia after treatment with the acetylcholine precursor choline alfoscerate", "authors": "De Jesus Moreno Moreno M", "journal": "Clin Ther", "year": 2003, "studyType": "rct", "sampleSize": 261, "outcome": "Alpha-GPC significantly improved cognitive function in Alzheimer's patients", "keyFindings": [ "Significant improvements in ADAS-Cog scores", "Benefits sustained over 180 days", "Well-tolerated with few adverse effects" ], "dosageUsed": "400 mg three times daily", "evidenceRating": "moderate", "pmid": "12637119", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12637119/", "publicSourceType": "PMID" }, { "id": "study-0130", "supplementName": "Alpha-GPC", "title": "The effect of alpha-glycerylphosphorylcholine on muscular strength and power output", "authors": "Bellar D, LeBlanc NR, Campbell B", "journal": "J Int Soc Sports Nutr", "year": 2015, "studyType": "rct", "sampleSize": 13, "outcome": "Alpha-GPC supplementation enhanced isometric force production", "keyFindings": [ "Significant increase in peak force during isometric mid-thigh pull", "600 mg dose showed acute ergogenic effects", "Potential for sport performance enhancement" ], "dosageUsed": "600 mg single dose", "evidenceRating": "emerging", "pmid": "26582972", "doi": "10.1186/s12970-015-0109-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26582972/", "publicSourceType": "PMID" }, { "id": "study-0131", "supplementName": "Alpha-GPC", "title": "Choline alphoscerate in cognitive decline and in acute cerebrovascular disease: an analysis of published clinical data", "authors": "Parnetti L, Amenta F, Gallai V", "journal": "Mechanisms of ageing and development", "year": 2001, "studyType": "review", "sampleSize": null, "outcome": "Alpha-GPC showed consistent cognitive improvement across multiple clinical trials", "keyFindings": [ "Improvement in cognitive measures across 13 clinical trials", "Favorable safety profile", "May enhance cholinergic neurotransmission" ], "dosageUsed": "1200 mg daily", "evidenceRating": "moderate", "pmid": "11589921", "doi": "10.1016/s0047-6374(01)00312-8", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11589921/", "publicSourceType": "PMID" }, { "id": "study-0132", "supplementName": "Alpha-Lipoic Acid", "title": "Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a meta-analysis", "authors": "Ziegler D, Nowak H, Kempler P et al.", "journal": "Diabetic medicine : a journal of the British Diabetic Association", "year": 2004, "studyType": "metaAnalysis", "sampleSize": 1258, "outcome": "Alpha-lipoic acid 600 mg IV significantly improved neuropathic symptoms", "keyFindings": [ "Significant improvement in Total Symptom Score", "600 mg IV dose most effective", "Meaningful pain reduction in 3 weeks" ], "dosageUsed": "600 mg daily IV", "evidenceRating": "strong", "pmid": "14984445", "doi": "10.1111/j.1464-5491.2004.01109.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14984445/", "publicSourceType": "PMID" }, { "id": "study-0133", "supplementName": "Alpha-Lipoic Acid", "title": "Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial", "authors": "Ziegler D, Ametov A, Barinov A et al.", "journal": "Diabetes care", "year": 2006, "studyType": "rct", "sampleSize": 181, "outcome": "Oral alpha-lipoic acid 600 mg daily improved neuropathic symptoms over 5 weeks", "keyFindings": [ "600 mg dose optimal benefit-to-risk ratio", "Significant reduction in stabbing and burning pain", "Higher doses (1200-1800 mg) had more GI side effects without added benefit" ], "dosageUsed": "600-1800 mg daily", "evidenceRating": "strong", "pmid": "17065669", "doi": "10.2337/dc06-1216", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17065669/", "publicSourceType": "PMID" }, { "id": "study-0134", "supplementName": "Alpha-Lipoic Acid", "title": "Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential", "authors": "Shay KP, Moreau RF, Smith EJ et al.", "journal": "Biochimica et biophysica acta", "year": 2009, "studyType": "review", "sampleSize": null, "outcome": "Comprehensive review of ALA's antioxidant and metabolic mechanisms", "keyFindings": [ "Potent antioxidant regenerating vitamins C and E", "Improves insulin sensitivity", "Chelates transition metals reducing oxidative stress" ], "dosageUsed": "300-600 mg daily", "evidenceRating": "moderate", "pmid": "19664690", "doi": "10.1016/j.bbagen.2009.07.026", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19664690/", "publicSourceType": "PMID" }, { "id": "study-0135", "supplementName": "Apigenin", "title": "Apigenin as neuroprotective agent: a review of the evidence", "authors": "Salehi B, Venditti A, Sharifi-Rad M et al.", "journal": "Crit Rev Food Sci Nutr", "year": 2019, "studyType": "review", "sampleSize": null, "outcome": "Apigenin demonstrates significant neuroprotective and anxiolytic properties", "keyFindings": [ "Binds to benzodiazepine receptors with anxiolytic effects", "Anti-inflammatory action via NF-kB inhibition", "Neuroprotective effects in preclinical models" ], "dosageUsed": "25-100 mg daily", "evidenceRating": "emerging", "pmid": "29999415", "doi": "10.1080/10408398.2017.1358171", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29999415/", "publicSourceType": "PMID" }, { "id": "study-0136", "supplementName": "Apigenin", "title": "Apigenin inhibits cancer cell proliferation through CD38/NAD+ pathway", "authors": "Escande C, Nin V, Price NL et al.", "journal": "Cell Rep", "year": 2013, "studyType": "inVitro", "sampleSize": null, "outcome": "Apigenin inhibits CD38, increasing NAD+ levels and improving cellular function", "keyFindings": [ "Potent CD38 inhibitor raising intracellular NAD+", "May support healthy aging via NAD+ pathway", "Demonstrated anti-tumor activity in cell lines" ], "dosageUsed": "N/A (in vitro)", "evidenceRating": "emerging", "pmid": "23583180", "doi": "10.1016/j.celrep.2013.03.032", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23583180/", "publicSourceType": "PMID" }, { "id": "study-0137", "supplementName": "Artemisinin", "title": "Artemisinins: their growing importance in medicine", "authors": "Efferth T", "journal": "Trends Pharmacol Sci", "year": 2005, "studyType": "review", "sampleSize": null, "outcome": "Comprehensive review of artemisinin's antimalarial and potential anticancer properties", "keyFindings": [ "Gold standard antimalarial treatment", "Novel anticancer mechanisms via iron-dependent free radicals", "Generally well-tolerated in therapeutic doses" ], "dosageUsed": "100-200 mg per dose (antimalarial)", "evidenceRating": "strong", "pmid": "15907391", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15907391/", "publicSourceType": "PMID" }, { "id": "study-0138", "supplementName": "Artemisinin", "title": "Artemisinin compounds in treatment of malaria", "authors": "Lindsay SW", "journal": "Lancet (London, England)", "year": 1993, "studyType": "review", "sampleSize": null, "outcome": "Artemisinin-based combination therapies are the WHO-recommended first-line malaria treatment", "keyFindings": [ "Most rapid parasite clearance of any antimalarial", "WHO recommends ACT for P. falciparum malaria", "Short half-life necessitates combination therapy" ], "dosageUsed": "Varies by combination", "evidenceRating": "strong", "pmid": "8096932", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8096932/", "publicSourceType": "PMID" }, { "id": "study-0139", "supplementName": "Astaxanthin", "title": "Astaxanthin in cardiovascular health and disease", "authors": "Fassett RG, Coombes JS", "journal": "Molecules", "year": 2012, "studyType": "review", "sampleSize": null, "outcome": "Astaxanthin shows potent antioxidant effects and cardiovascular benefits", "keyFindings": [ "600x stronger antioxidant than vitamin C", "Reduced oxidative stress biomarkers", "Improved lipid profiles in clinical trials" ], "dosageUsed": "4-12 mg daily", "evidenceRating": "moderate", "pmid": "22418926", "doi": "10.3390/molecules17032030", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22418926/", "publicSourceType": "PMID" }, { "id": "study-0140", "supplementName": "Astaxanthin", "title": "Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans", "authors": "Park JS, Chyun JH, Kim YK et al.", "journal": "Nutr Metab", "year": 2010, "studyType": "rct", "sampleSize": 42, "outcome": "Astaxanthin supplementation enhanced immune response and reduced CRP", "keyFindings": [ "Increased natural killer cell cytotoxic activity", "Reduced DNA damage biomarker (8-OHdG)", "Decreased C-reactive protein levels" ], "dosageUsed": "2 mg and 8 mg daily", "evidenceRating": "moderate", "pmid": "20236046", "doi": "10.1186/1743-7075-7-18", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20236046/", "publicSourceType": "PMID" }, { "id": "study-0141", "supplementName": "Astaxanthin", "title": "Astaxanthin improves muscle lipid metabolism in exercise via inhibitory effect of oxidative CPT I modification", "authors": "Aoi W, Naito Y, Takanami Y et al.", "journal": "Biochemical and biophysical research communications", "year": 2008, "studyType": "animalStudy", "sampleSize": null, "outcome": "Astaxanthin improved fat utilization during exercise in animal model", "keyFindings": [ "Enhanced lipid metabolism during exercise", "Reduced oxidative damage to carnitine palmitoyltransferase", "Improved exercise endurance" ], "dosageUsed": "5 mg/kg (animal dose)", "evidenceRating": "emerging", "pmid": "18082622", "doi": "10.1016/j.bbrc.2007.12.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18082622/", "publicSourceType": "PMID" }, { "id": "study-0142", "supplementName": "BCAAs", "title": "Branched-chain amino acids and muscle protein synthesis in humans: myth or reality?", "authors": "Wolfe RR", "journal": "J Int Soc Sports Nutr", "year": 2017, "studyType": "review", "sampleSize": null, "outcome": "BCAAs alone cannot stimulate maximal muscle protein synthesis without other essential amino acids", "keyFindings": [ "BCAAs alone insufficient for maximal MPS", "Leucine is primary MPS trigger but needs other EAAs", "Whole protein sources may be superior to isolated BCAAs" ], "dosageUsed": "5-20 g daily", "evidenceRating": "moderate", "pmid": "28852372", "doi": "10.1186/s12970-017-0184-9", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28852372/", "publicSourceType": "PMID" }, { "id": "study-0143", "supplementName": "BCAAs", "title": "A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength", "authors": "Morton RW, Murphy KT, McKellar SR et al.", "journal": "Br J Sports Med", "year": 2018, "studyType": "metaAnalysis", "sampleSize": 1863, "outcome": "Protein supplementation augments resistance training adaptations", "keyFindings": [ "Protein supplementation significantly increased muscle mass", "Effect plateau at ~1.6 g/kg/day total protein", "No additional benefit of BCAA over complete protein sources" ], "dosageUsed": "Varied protein sources", "evidenceRating": "strong", "pmid": "28698222", "doi": "10.1136/bjsports-2017-097608", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28698222/", "publicSourceType": "PMID" }, { "id": "study-0144", "supplementName": "BCAAs", "title": "Branched-chain amino acid supplementation and exercise-induced muscle damage: a meta-analysis", "authors": "Rahimi MH, Shab-Bidar S, Mollahosseini M, Djafarian K", "journal": "Nutr Rev", "year": 2017, "studyType": "metaAnalysis", "sampleSize": 134, "outcome": "BCAA supplementation may reduce exercise-induced muscle damage", "keyFindings": [ "Significant reduction in creatine kinase levels post-exercise", "Reduced delayed-onset muscle soreness", "Most effective when taken before exercise" ], "dosageUsed": "5-20 g daily", "evidenceRating": "moderate", "pmid": "28444456", "doi": "10.1093/nutrit/nux005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28444456/", "publicSourceType": "PMID" }, { "id": "study-0145", "supplementName": "Bacopa Monnieri", "title": "Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract", "authors": "Kongkeaw C, Dilokthornsakul P, Thanarangsarit P et al.", "journal": "J Ethnopharmacol", "year": 2014, "studyType": "metaAnalysis", "sampleSize": 437, "outcome": "Bacopa monnieri significantly improved attention and cognitive processing", "keyFindings": [ "Significant improvement in attention/cognitive processing speed", "Benefits most apparent after 12+ weeks", "Shortened Trail Making Test B times" ], "dosageUsed": "300-600 mg daily (standardized extract)", "evidenceRating": "moderate", "pmid": "24252493", "doi": "10.1016/j.jep.2013.11.008", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24252493/", "publicSourceType": "PMID" }, { "id": "study-0146", "supplementName": "Bacopa Monnieri", "title": "Effects of a standardized Bacopa monnieri extract on cognitive performance, anxiety, and depression in the elderly: a randomized, double-blind, placebo-controlled trial", "authors": "Calabrese C, Gregory WL, Leo M et al.", "journal": "J Altern Complement Med", "year": 2008, "studyType": "rct", "sampleSize": 54, "outcome": "Bacopa improved working memory, attention, and reduced depression/anxiety in elderly", "keyFindings": [ "Significant improvement in working memory", "Reduced anxiety scores (STAI)", "Decreased depression and heart rate" ], "dosageUsed": "300 mg daily (standardized to 55% bacosides)", "evidenceRating": "moderate", "pmid": "18611150", "doi": "10.1089/acm.2008.0018", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18611150/", "publicSourceType": "PMID" }, { "id": "study-0147", "supplementName": "Bacopa Monnieri", "title": "Chronic effects of Brahmi (Bacopa monnieri) on human memory", "authors": "Roodenrys S, Booth D, Bulzomi S et al.", "journal": "Neuropsychopharmacology", "year": 2002, "studyType": "rct", "sampleSize": 76, "outcome": "Bacopa significantly improved speed of information processing and verbal learning", "keyFindings": [ "Improved rate of learning new information", "Enhanced speed of visual information processing", "12-week supplementation required for benefits" ], "dosageUsed": "300 mg daily", "evidenceRating": "moderate", "pmid": "12093601", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12093601/", "publicSourceType": "PMID" }, { "id": "study-0148", "supplementName": "Bee Pollen", "title": "Bee pollen: chemical composition and therapeutic application", "authors": "Komosinska-Vassev K, Olczyk P, Kazmierczak J et al.", "journal": "Evid Based Complement Alternat Med", "year": 2015, "studyType": "review", "sampleSize": null, "outcome": "Bee pollen has documented antimicrobial, antioxidant, and anti-inflammatory properties", "keyFindings": [ "Rich in flavonoids and phenolic acids", "Demonstrated antimicrobial activity against multiple pathogens", "Anti-inflammatory effects in animal models" ], "dosageUsed": "20-40 g daily", "evidenceRating": "emerging", "pmid": "25861358", "doi": "10.1155/2015/297425", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25861358/", "publicSourceType": "PMID" }, { "id": "study-0149", "supplementName": "Bee Pollen", "title": "Beneficial effects of bee pollen on menopausal symptoms: a randomized, double-blind, placebo-controlled trial", "authors": "Georgiev DB, Metka M, Huber JC et al.", "journal": "Wien Med Wochenschr", "year": 2004, "studyType": "rct", "sampleSize": 46, "outcome": "Bee pollen/honey combination reduced menopausal symptoms including hot flashes", "keyFindings": [ "Significant reduction in hot flashes", "Improved quality of life scores", "Well-tolerated with no serious adverse events" ], "dosageUsed": "2 tablets daily (bee pollen + honey)", "evidenceRating": "emerging", "pmid": "15532135", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15532135/", "publicSourceType": "PMID" }, { "id": "study-0150", "supplementName": "Berberine HCl", "title": "Efficacy of berberine in patients with type 2 diabetes mellitus", "authors": "Yin J, Xing H, Ye J", "journal": "Metabolism: clinical and experimental", "year": 2008, "studyType": "rct", "sampleSize": 116, "outcome": "Berberine significantly lowered blood glucose, HbA1c, triglycerides, and LDL cholesterol", "keyFindings": [ "Reduced HbA1c by 2% (comparable to metformin)", "Lowered fasting blood glucose by 36%", "Significant triglyceride and LDL cholesterol reduction" ], "dosageUsed": "500 mg three times daily", "evidenceRating": "strong", "pmid": "18442638", "doi": "10.1016/j.metabol.2008.01.013", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18442638/", "publicSourceType": "PMID" }, { "id": "study-0151", "supplementName": "Berberine HCl", "title": "Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins", "authors": "Kong W, Wei J, Abidi P et al.", "journal": "Nat Med", "year": 2004, "studyType": "rct", "sampleSize": 91, "outcome": "Berberine reduced LDL cholesterol by 25% through upregulation of LDL receptor", "keyFindings": [ "LDL cholesterol decreased by 25%", "Novel mechanism: upregulates LDL receptor via ERK pathway", "Additive effect when combined with statins" ], "dosageUsed": "500 mg twice daily", "evidenceRating": "strong", "pmid": "15558057", "doi": "10.1038/nm1135", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15558057/", "publicSourceType": "PMID" }, { "id": "study-0152", "supplementName": "Berberine HCl", "title": "A meta-analysis of the effect of berberine on blood lipids", "authors": "Dong H, Wang N, Zhao L, Lu F", "journal": "Planta Med", "year": 2012, "studyType": "metaAnalysis", "sampleSize": 2569, "outcome": "Berberine significantly reduced total cholesterol, LDL, and triglycerides", "keyFindings": [ "Total cholesterol reduced by 0.61 mmol/L", "LDL cholesterol reduced by 0.65 mmol/L", "Triglycerides reduced by 0.50 mmol/L" ], "dosageUsed": "500-1500 mg daily", "evidenceRating": "strong", "pmid": "22890541", "doi": "10.1055/s-0032-1315124", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22890541/", "publicSourceType": "PMID" }, { "id": "study-0153", "supplementName": "Beta-Alanine", "title": "International Society of Sports Nutrition position stand: Beta-Alanine", "authors": "Trexler ET, Smith-Ryan AE, Stout JR et al.", "journal": "J Int Soc Sports Nutr", "year": 2015, "studyType": "review", "sampleSize": null, "outcome": "Beta-alanine supplementation improves exercise performance lasting 1-4 minutes", "keyFindings": [ "Increases muscle carnosine concentrations", "Improves exercise capacity in 1-4 minute range", "Loading dose of 4-6 g/day for 2-4 weeks recommended" ], "dosageUsed": "3.2-6.4 g daily", "evidenceRating": "strong", "pmid": "26175657", "doi": "10.1186/s12970-015-0090-y", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26175657/", "publicSourceType": "PMID" }, { "id": "study-0154", "supplementName": "Beta-Alanine", "title": "Effects of beta-alanine supplementation on exercise performance: a meta-analysis", "authors": "Hobson RM, Saunders B, Ball G et al.", "journal": "Amino Acids", "year": 2012, "studyType": "metaAnalysis", "sampleSize": 360, "outcome": "Beta-alanine significantly improved exercise performance in efforts lasting 60-240 seconds", "keyFindings": [ "Significant improvement in exercise capacity (median effect 2.85%)", "Greatest benefit for exercise lasting 1-4 minutes", "No significant effect on exercise under 60 seconds" ], "dosageUsed": "Average 5 g daily for 4+ weeks", "evidenceRating": "strong", "pmid": "22270875", "doi": "10.1007/s00726-011-1200-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22270875/", "publicSourceType": "PMID" }, { "id": "study-0155", "supplementName": "Beta-Alanine", "title": "β-alanine supplementation to improve exercise capacity and performance: a systematic review and meta-analysis", "authors": "Saunders B, Elliott-Sale K, Artioli GG et al.", "journal": "British journal of sports medicine", "year": 2017, "studyType": "metaAnalysis", "sampleSize": 1461, "outcome": "Beta-alanine improved exercise capacity with median improvement of 2.85%", "keyFindings": [ "Significant effect on exercise capacity", "Improved time-to-exhaustion", "Dose-response relationship with muscle carnosine levels" ], "dosageUsed": "3.2-6.4 g daily", "evidenceRating": "strong", "pmid": "27797728", "doi": "10.1136/bjsports-2016-096396", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27797728/", "publicSourceType": "PMID" }, { "id": "study-0156", "supplementName": "Beta-Carotene", "title": "Beta-carotene supplementation and cancer risk: a systematic review and metaanalysis of randomized controlled trials", "authors": "Druesne-Pecollo N, Latino-Martel P, Norat T et al.", "journal": "International journal of cancer", "year": 2010, "studyType": "metaAnalysis", "sampleSize": 109394, "outcome": "Beta-carotene supplementation may increase cancer risk in smokers and asbestos-exposed individuals", "keyFindings": [ "Increased lung cancer risk in smokers (RR 1.24)", "No cancer prevention benefit in general population", "Harmful in high-dose supplementation for at-risk groups" ], "dosageUsed": "20-30 mg daily", "evidenceRating": "strong", "pmid": "19876916", "doi": "10.1002/ijc.25008", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19876916/", "publicSourceType": "PMID" }, { "id": "study-0157", "supplementName": "Beta-Carotene", "title": "Antioxidant vitamins and the risk of cardiovascular disease: a review of the epidemiologic and clinical trial data", "authors": "Kris-Etherton PM, Lichtenstein AH, Howard BV et al.", "journal": "Ann Intern Med", "year": 2004, "studyType": "review", "sampleSize": null, "outcome": "Beta-carotene supplementation does not reduce cardiovascular risk and may be harmful", "keyFindings": [ "No cardiovascular benefit from beta-carotene supplements", "ATBC and CARET trials showed increased risk in smokers", "Dietary beta-carotene from fruits/vegetables remains beneficial" ], "dosageUsed": "15-50 mg daily", "evidenceRating": "strong", "pmid": "14709468", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14709468/", "publicSourceType": "PMID" }, { "id": "study-0158", "supplementName": "Betaine HCL", "title": "Betaine in human nutrition", "authors": "Craig SA", "journal": "Am J Clin Nutr", "year": 2004, "studyType": "review", "sampleSize": null, "outcome": "Betaine plays important roles in methylation and osmoregulation", "keyFindings": [ "Essential methyl donor for homocysteine metabolism", "Reduces homocysteine levels", "Supports liver function and lipid metabolism" ], "dosageUsed": "500-3000 mg daily", "evidenceRating": "moderate", "pmid": "15321791", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15321791/", "publicSourceType": "PMID" }, { "id": "study-0159", "supplementName": "Betaine HCL", "title": "Effects of betaine supplementation on performance and body composition: a review of randomized controlled trials", "authors": "Cholewa JM, Wyszczelska-Rokiel M, Glowacki R et al.", "journal": "J Int Soc Sports Nutr", "year": 2014, "studyType": "review", "sampleSize": null, "outcome": "Betaine supplementation may improve body composition and exercise performance", "keyFindings": [ "Potential improvements in power output", "May reduce body fat percentage", "2.5 g/day commonly used in performance studies" ], "dosageUsed": "1.25-6 g daily", "evidenceRating": "emerging", "pmid": "24991773", "doi": "10.1186/1550-2783-11-27", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24991773/", "publicSourceType": "PMID" }, { "id": "study-0160", "supplementName": "Black Cohosh", "title": "Black cohosh (Cimicifuga racemosa) for menopausal symptoms: a systematic review and meta-analysis", "authors": "Shams T, Setia MS, Hemmings R et al.", "journal": "J Womens Health", "year": 2010, "studyType": "metaAnalysis", "sampleSize": 1307, "outcome": "Black cohosh showed modest improvement in menopausal vasomotor symptoms", "keyFindings": [ "Significant reduction in frequency/intensity of hot flashes", "Improved menopausal symptom scores", "Generally well-tolerated in short-term use" ], "dosageUsed": "20-40 mg daily (standardized extract)", "evidenceRating": "moderate", "pmid": "20370462", "doi": "10.1089/jwh.2009.1839", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20370462/", "publicSourceType": "PMID" }, { "id": "study-0161", "supplementName": "Black Cohosh", "title": "Efficacy and safety of black cohosh (Actaea/Cimicifuga racemosa) for menopausal symptoms", "authors": "Leach MJ, Moore V", "journal": "Cochrane Database Syst Rev", "year": 2012, "studyType": "metaAnalysis", "sampleSize": 2027, "outcome": "Insufficient evidence to support or refute black cohosh for menopausal symptoms", "keyFindings": [ "Some trials showed symptom improvement", "Heterogeneity across trials", "Short-term safety appears acceptable" ], "dosageUsed": "40-200 mg daily", "evidenceRating": "moderate", "pmid": "22972105", "doi": "10.1002/14651858.CD007244.pub2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22972105/", "publicSourceType": "PMID" }, { "id": "study-0162", "supplementName": "Black Seed Oil", "title": "A systematic review on the pharmacological activities of Nigella sativa extracts", "authors": "Ahmad A, Husain A, Mujeeb M et al.", "journal": "Saudi J Biol Sci", "year": 2013, "studyType": "review", "sampleSize": null, "outcome": "Nigella sativa demonstrates anti-inflammatory, antioxidant, and immunomodulatory effects", "keyFindings": [ "Thymoquinone is the primary active compound", "Anti-inflammatory effects via COX and LOX inhibition", "Immunomodulatory and hepatoprotective properties" ], "dosageUsed": "200-500 mg thymoquinone equivalent", "evidenceRating": "emerging", "pmid": "24235836", "doi": "10.1016/j.sjbs.2013.09.002", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24235836/", "publicSourceType": "PMID" }, { "id": "study-0163", "supplementName": "Black Seed Oil", "title": "Nigella sativa supplementation improves glycemic control and lipid profiles: a systematic review and meta-analysis", "authors": "Daryabeygi-Khotbehsara R, Golzarand M, Ghaffari MP, Djafarian K", "journal": "Complement Ther Med", "year": 2017, "studyType": "metaAnalysis", "sampleSize": 875, "outcome": "Black seed supplementation significantly reduced fasting glucose and lipid levels", "keyFindings": [ "Significant reduction in fasting blood glucose", "Decreased total cholesterol and LDL", "Increased HDL cholesterol" ], "dosageUsed": "1-3 g daily", "evidenceRating": "moderate", "pmid": "29154069", "doi": "10.1016/j.ctim.2017.10.003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29154069/", "publicSourceType": "PMID" }, { "id": "study-0164", "supplementName": "Boron", "title": "Nothing boring about boron", "authors": "Pizzorno L", "journal": "Integr Med (Encinitas)", "year": 2015, "studyType": "review", "sampleSize": null, "outcome": "Boron is important for bone health, brain function, and hormone metabolism", "keyFindings": [ "Essential for calcium and magnesium metabolism", "May increase free testosterone in deficient individuals", "Important for vitamin D metabolism" ], "dosageUsed": "3-10 mg daily", "evidenceRating": "emerging", "pmid": "26770156", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26770156/", "publicSourceType": "PMID" }, { "id": "study-0165", "supplementName": "Boron", "title": "Comparative effects of daily and weekly boron supplementation on plasma steroid hormones and proinflammatory cytokines", "authors": "Naghii MR, Mofid M, Asgari AR et al.", "journal": "J Trace Elem Med Biol", "year": 2011, "studyType": "rct", "sampleSize": 8, "outcome": "Boron supplementation increased free testosterone and decreased estradiol", "keyFindings": [ "Free testosterone increased significantly after 1 week at 10mg/day", "Estradiol decreased significantly", "Inflammatory biomarkers (IL-6, TNF-alpha) reduced" ], "dosageUsed": "10 mg daily", "evidenceRating": "emerging", "pmid": "21129941", "doi": "10.1016/j.jtemb.2010.10.001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21129941/", "publicSourceType": "PMID" }, { "id": "study-0166", "supplementName": "Boswellia", "title": "Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee: a randomized double blind placebo controlled trial", "authors": "Kimmatkar N, Thawani V, Hingorani L, Khiyani R", "journal": "Phytomedicine", "year": 2003, "studyType": "rct", "sampleSize": 30, "outcome": "Boswellia significantly reduced knee pain and improved knee function in OA", "keyFindings": [ "Significant decrease in knee pain", "Improved knee flexion", "Reduced joint swelling and walking distance improvement" ], "dosageUsed": "333 mg three times daily", "evidenceRating": "moderate", "pmid": "12622457", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12622457/", "publicSourceType": "PMID" }, { "id": "study-0167", "supplementName": "Boswellia", "title": "Indian frankincense (Boswellia serrata) - a systematic review and meta-analysis for osteoarthritis", "authors": "Yu G, Xiang W, Zhang T et al.", "journal": "J Ethnopharmacol", "year": 2020, "studyType": "metaAnalysis", "sampleSize": 545, "outcome": "Boswellia serrata significantly reduced pain and improved function in osteoarthritis", "keyFindings": [ "Significant pain reduction vs placebo", "Improved physical function scores", "Favorable safety profile compared to NSAIDs" ], "dosageUsed": "100-1000 mg daily", "evidenceRating": "moderate", "pmid": "31693916", "doi": "10.1016/j.jep.2019.112260", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31693916/", "publicSourceType": "PMID" }, { "id": "study-0168", "supplementName": "Boswellia", "title": "5-Loxin significantly improves osteoarthritis of the knee: a 90-day randomized double blind placebo controlled study", "authors": "Sengupta K, Alluri KV, Satish AR et al.", "journal": "BMC Complement Altern Med", "year": 2008, "studyType": "rct", "sampleSize": 75, "outcome": "Enriched Boswellia extract improved pain and function as early as 7 days", "keyFindings": [ "Pain improvement in as little as 7 days", "Significant improvement in physical function", "Reduced MMP-3 (cartilage degradation marker)" ], "dosageUsed": "100-250 mg daily (30% AKBA)", "evidenceRating": "moderate", "pmid": "18221502", "doi": "10.1186/1472-6882-8-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18221502/", "publicSourceType": "PMID" }, { "id": "study-0169", "supplementName": "Bromelain", "title": "Bromelain: an overview of industrial application and purification strategies", "authors": "Pavan R, Jain S, Shraddha, Kumar A", "journal": "Biotechnol Res Int", "year": 2012, "studyType": "review", "sampleSize": null, "outcome": "Bromelain has limited clinical evidence for osteoarthritis pain outcomes", "keyFindings": [ "Some older trials used NSAID comparators, but evidence is limited", "Do not present as an NSAID-equivalent treatment", "Product standardization and dose vary widely" ], "dosageUsed": "200-2000 mg daily", "evidenceRating": "moderate", "pmid": "23304525", "doi": "10.1155/2012/976203", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23304525/", "publicSourceType": "PMID" }, { "id": "study-0170", "supplementName": "Bromelain", "title": "Treatment of rheumatoid arthritis with bromelain: a pilot study", "authors": "Cohen A, Goldman J", "journal": "Pa Med J", "year": 1964, "studyType": "cohort", "sampleSize": 29, "outcome": "Bromelain reduced joint swelling and improved mobility in rheumatoid arthritis patients", "keyFindings": [ "Reduced joint swelling in majority of patients", "Improved joint mobility", "One of earliest clinical studies of bromelain for inflammation" ], "dosageUsed": "20-40 mg four times daily", "evidenceRating": "emerging", "pmid": "14150399", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14150399/", "publicSourceType": "PMID" }, { "id": "study-0171", "supplementName": "CLA", "title": "Efficacy of conjugated linoleic acid for reducing fat mass: a meta-analysis in humans", "authors": "Whigham LD, Watras AC, Schoeller DA", "journal": "Am J Clin Nutr", "year": 2007, "studyType": "metaAnalysis", "sampleSize": 779, "outcome": "CLA supplementation produced a modest but significant reduction in body fat", "keyFindings": [ "Average fat loss of 0.09 kg/week vs placebo", "Consistent effect across studies", "Mixed isomer preparations most studied" ], "dosageUsed": "3.2 g daily", "evidenceRating": "moderate", "pmid": "17490954", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17490954/", "publicSourceType": "PMID" }, { "id": "study-0172", "supplementName": "CLA", "title": "Conjugated linoleic acid supplementation in humans: effects on body composition and energy expenditure", "authors": "Blankson H, Stakkestad JA, Fagertun H et al.", "journal": "J Nutr", "year": 2000, "studyType": "rct", "sampleSize": 60, "outcome": "CLA significantly reduced body fat mass in overweight subjects", "keyFindings": [ "Significant reduction in body fat mass at 3.4-6.8 g/day", "No significant changes in body weight or BMI", "Well-tolerated over 12-week period" ], "dosageUsed": "1.7-6.8 g daily", "evidenceRating": "moderate", "pmid": "11110851", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11110851/", "publicSourceType": "PMID" }, { "id": "study-0173", "supplementName": "Calcium", "title": "Calcium plus vitamin D supplementation and the risk of fractures", "authors": "Jackson RD, LaCroix AZ, Gass M et al.", "journal": "N Engl J Med", "year": 2006, "studyType": "rct", "sampleSize": 36282, "outcome": "Calcium + vitamin D modestly reduced hip fracture risk in postmenopausal women", "keyFindings": [ "Small but significant improvement in hip bone density", "Increased risk of kidney stones", "Hip fracture risk reduced in adherent subgroup" ], "dosageUsed": "1000 mg calcium + 400 IU vitamin D daily", "evidenceRating": "strong", "pmid": "16481636", "doi": "10.1056/NEJMoa055218", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16481636/", "publicSourceType": "PMID" }, { "id": "study-0174", "supplementName": "Calcium", "title": "Calcium intake and risk of fracture: systematic review", "authors": "Bolland MJ, Leung W, Tai V et al.", "journal": "BMJ", "year": 2015, "studyType": "metaAnalysis", "sampleSize": 44505, "outcome": "Increasing calcium intake from dietary sources or supplements has limited fracture prevention benefit", "keyFindings": [ "Minimal reduction in fracture risk (10-11%)", "Dietary calcium increases did not reduce fracture risk", "Evidence does not support routine calcium supplementation for fracture prevention" ], "dosageUsed": "500-1200 mg daily", "evidenceRating": "strong", "pmid": "26420387", "doi": "10.1136/bmj.h4580", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26420387/", "publicSourceType": "PMID" }, { "id": "study-0175", "supplementName": "Calcium", "title": "Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women's Health Initiative", "authors": "Bolland MJ, Grey A, Avenell A et al.", "journal": "BMJ", "year": 2011, "studyType": "metaAnalysis", "sampleSize": 36282, "outcome": "Calcium supplements with or without vitamin D may increase cardiovascular event risk", "keyFindings": [ "Increased risk of MI with calcium supplements", "Effect consistent with or without vitamin D", "Dietary calcium not associated with increased risk" ], "dosageUsed": "1000 mg daily", "evidenceRating": "strong", "pmid": "21505219", "doi": "10.1136/bmj.d2040", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21505219/", "publicSourceType": "PMID" }, { "id": "study-0176", "supplementName": "Cat's Claw", "title": "Efficacy and safety of freeze-dried cat's claw in osteoarthritis of the knee", "authors": "Piscoya J, Rodriguez Z, Bustamante SA et al.", "journal": "Inflamm Res", "year": 2001, "studyType": "rct", "sampleSize": 45, "outcome": "Cat's claw reduced pain and improved function in knee osteoarthritis", "keyFindings": [ "Significant pain reduction during activity", "No significant side effects", "Anti-inflammatory mechanism via NF-kB inhibition" ], "dosageUsed": "100 mg daily (freeze-dried extract)", "evidenceRating": "emerging", "pmid": "11506989", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11506989/", "publicSourceType": "PMID" }, { "id": "study-0177", "supplementName": "Cat's Claw", "title": "Cat's claw (Uncaria tomentosa) and its anti-inflammatory activity: a review", "authors": "Sandoval M, Charbonnet RM, Okuhama NN et al.", "journal": "J Ethnopharmacol", "year": 2000, "studyType": "review", "sampleSize": null, "outcome": "Cat's claw demonstrates significant anti-inflammatory and immunomodulatory properties", "keyFindings": [ "Inhibits TNF-alpha production", "NF-kB inhibition at multiple levels", "Traditional use in Peruvian medicine for inflammatory conditions" ], "dosageUsed": "250-1000 mg daily", "evidenceRating": "emerging", "pmid": "10967491", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10967491/", "publicSourceType": "PMID" }, { "id": "study-0178", "supplementName": "Chaga", "title": "Immunomodulatory activity of the water extract of Inonotus obliquus in vitro and in vivo", "authors": "Kim YR", "journal": "J Med Food", "year": 2005, "studyType": "animalStudy", "sampleSize": null, "outcome": "Chaga extract demonstrated significant immunomodulatory effects", "keyFindings": [ "Enhanced immune cell activation", "Increased cytokine production", "Anti-tumor effects in animal model" ], "dosageUsed": "N/A (animal study)", "evidenceRating": "emerging", "pmid": "16379555", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16379555/", "publicSourceType": "PMID" }, { "id": "study-0179", "supplementName": "Chaga", "title": "Anti-inflammatory and immunomodulating properties of Inonotus obliquus", "authors": "Van Q, Nayak BN, Reimer M et al.", "journal": "J Ethnopharmacol", "year": 2009, "studyType": "animalStudy", "sampleSize": null, "outcome": "Chaga polysaccharides reduced inflammatory cytokines and improved immune response", "keyFindings": [ "Reduced pro-inflammatory cytokines (TNF-alpha, IL-6)", "Anti-inflammatory effects via NF-kB modulation", "Polysaccharides are primary bioactive compounds" ], "dosageUsed": "N/A (animal study)", "evidenceRating": "emerging", "pmid": "19501271", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19501271/", "publicSourceType": "PMID" }, { "id": "study-0180", "supplementName": "Chlorella", "title": "A randomized, double-blind, placebo-controlled trial of Chlorella supplementation on immunological and oxidative stress biomarkers", "authors": "Kwak JH, Baek SH, Woo Y et al.", "journal": "Nutr J", "year": 2012, "studyType": "rct", "sampleSize": 51, "outcome": "Chlorella supplementation improved natural killer cell activity and immune markers", "keyFindings": [ "Increased NK cell activity", "Reduced oxidative stress biomarkers", "Enhanced interferon-gamma production" ], "dosageUsed": "5 g daily", "evidenceRating": "moderate", "pmid": "22849818", "doi": "10.1186/1475-2891-11-53", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22849818/", "publicSourceType": "PMID" }, { "id": "study-0181", "supplementName": "Chlorella", "title": "Effect of Chlorella supplementation on cardiovascular risk factors: a systematic review and meta-analysis", "authors": "Fallah AA, Sarmast E, Jafari T", "journal": "Clin Nutr", "year": 2018, "studyType": "metaAnalysis", "sampleSize": 461, "outcome": "Chlorella significantly reduced total cholesterol, LDL, and blood pressure", "keyFindings": [ "Significant reduction in total cholesterol and LDL", "Decreased systolic and diastolic blood pressure", "No significant effect on fasting glucose or triglycerides" ], "dosageUsed": "1.2-10 g daily", "evidenceRating": "moderate", "pmid": "29530364", "doi": "10.1016/j.clnu.2018.02.022", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29530364/", "publicSourceType": "PMID" }, { "id": "study-0182", "supplementName": "Chondroitin", "title": "GAIT: Glucosamine/chondroitin arthritis intervention trial", "authors": "Clegg DO, Reda DJ, Harris CL et al.", "journal": "N Engl J Med", "year": 2006, "studyType": "rct", "sampleSize": 1583, "outcome": "Glucosamine + chondroitin combination showed benefit in moderate-to-severe knee OA subgroup", "keyFindings": [ "Combination showed 79% response rate in moderate-severe subgroup", "Neither agent alone significantly better than placebo overall", "Largest RCT of glucosamine/chondroitin for OA" ], "dosageUsed": "1200 mg chondroitin + 1500 mg glucosamine daily", "evidenceRating": "moderate", "pmid": "16495392", "doi": "10.1056/NEJMoa052771", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16495392/", "publicSourceType": "PMID" }, { "id": "study-0183", "supplementName": "Chondroitin", "title": "Symptomatic efficacy of chondroitin sulfate 4&6 in knee osteoarthritis: the ChONdroitin versus CElecoxib versus Placebo Trial (CONCEPT)", "authors": "Reginster JY, Dudler J, Guyatt GH et al.", "journal": "Ann Rheum Dis", "year": 2017, "studyType": "rct", "sampleSize": 604, "outcome": "Chondroitin sulfate was noninferior to celecoxib for knee OA pain reduction", "keyFindings": [ "Chondroitin noninferior to celecoxib for pain", "Significant improvement vs placebo", "Better safety profile than celecoxib" ], "dosageUsed": "800 mg daily", "evidenceRating": "moderate", "pmid": "28533289", "doi": "10.1136/annrheumdis-2016-210860", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28533289/", "publicSourceType": "PMID" }, { "id": "study-0184", "supplementName": "Chromium", "title": "Chromium supplementation in overweight and obesity: a systematic review and meta-analysis of randomized clinical trials", "authors": "Onakpoya I, Posadzki P, Ernst E", "journal": "Obesity reviews : an official journal of the International Association for the Study of Obesity", "year": 2013, "studyType": "metaAnalysis", "sampleSize": 622, "outcome": "Chromium supplementation showed modest but significant reduction in body weight", "keyFindings": [ "Small but statistically significant weight reduction (−0.50 kg)", "Chromium picolinate form most studied", "Effect size clinically questionable" ], "dosageUsed": "200-1000 mcg daily", "evidenceRating": "moderate", "pmid": "23495911", "doi": "10.1111/obr.12026", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23495911/", "publicSourceType": "PMID" }, { "id": "study-0185", "supplementName": "Chromium", "title": "Systematic review of the effects of chromium(III) on glucose and lipid levels: an evidence-based review", "authors": "Balk EM, Tatsioni A, Lichtenstein AH et al.", "journal": "Diabetes Care", "year": 2007, "studyType": "metaAnalysis", "sampleSize": 618, "outcome": "Chromium supplementation showed inconsistent effects on glucose and lipid levels", "keyFindings": [ "Some improvement in HbA1c in type 2 diabetes", "Inconsistent effects across trials", "Better evidence in populations with chromium deficiency" ], "dosageUsed": "200-1000 mcg daily", "evidenceRating": "moderate", "pmid": "17327318", "doi": "10.2337/dc06-0996", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17327318/", "publicSourceType": "PMID" }, { "id": "study-0186", "supplementName": "Citicoline", "title": "Citicoline in vascular cognitive impairment and vascular dementia after stroke", "authors": "Alvarez-Sabin J, Ortega G, Jacas C et al.", "journal": "Stroke", "year": 2013, "studyType": "rct", "sampleSize": 347, "outcome": "Citicoline improved cognitive function in post-stroke patients over 12 months", "keyFindings": [ "Significant improvement in attention and executive function", "Time-dependent improvement over 6-12 months", "Well-tolerated with minimal side effects" ], "dosageUsed": "1000 mg daily", "evidenceRating": "moderate", "pmid": "23640829", "doi": "10.1161/STROKEAHA.112.686311", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23640829/", "publicSourceType": "PMID" }, { "id": "study-0187", "supplementName": "Citicoline", "title": "Citicoline: pharmacological and clinical review, 2010 update", "authors": "Secades JJ", "journal": "Revista de neurologia", "year": 2011, "studyType": "review", "sampleSize": null, "outcome": "Citicoline demonstrates neuroprotective effects and cognitive enhancement across multiple conditions", "keyFindings": [ "Neuroprotective via phospholipid membrane synthesis", "Enhances dopamine and acetylcholine neurotransmission", "Strong safety profile across clinical trials" ], "dosageUsed": "500-2000 mg daily", "evidenceRating": "moderate", "pmid": "21432836", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21432836/", "publicSourceType": "PMID" }, { "id": "study-0188", "supplementName": "Citicoline", "title": "Improved attentional performance following citicoline administration in healthy adult women", "authors": "McGlade E, Locatelli A, Hardy J et al.", "journal": "Food Nutr Sci", "year": 2012, "studyType": "rct", "sampleSize": 60, "outcome": "Citicoline improved attention and reduced omission errors in healthy women", "keyFindings": [ "Improved attentional performance on CPT-II", "Reduced omission errors", "250 and 500 mg doses both effective" ], "dosageUsed": "250-500 mg daily", "evidenceRating": "moderate", "pmid": "28527238", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28527238/", "publicSourceType": "PMID" }, { "id": "study-0189", "supplementName": "Coenzyme Q10 Ubiquinol", "title": "Bioavailability of reduced form of coenzyme Q10 (ubiquinol) compared with oxidized form (ubiquinone)", "authors": "Langsjoen PH, Langsjoen AM", "journal": "Clin Pharmacol Drug Dev", "year": 2014, "studyType": "rct", "sampleSize": 12, "outcome": "Ubiquinol form showed significantly higher plasma CoQ10 levels than ubiquinone", "keyFindings": [ "2-6x higher plasma CoQ10 levels with ubiquinol", "Better bioavailability in aging populations", "More efficient absorption in GI tract" ], "dosageUsed": "100-300 mg daily", "evidenceRating": "moderate", "pmid": "27138830", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27138830/", "publicSourceType": "PMID" }, { "id": "study-0190", "supplementName": "Coenzyme Q10 Ubiquinol", "title": "Effect of ubiquinol supplementation on heart failure: a meta-analysis of randomized controlled trials", "authors": "Lei L, Liu Y", "journal": "Am J Clin Nutr", "year": 2017, "studyType": "metaAnalysis", "sampleSize": 476, "outcome": "CoQ10/Ubiquinol supplementation improved ejection fraction in heart failure patients", "keyFindings": [ "Improved left ventricular ejection fraction", "Reduced all-cause mortality in Q-SYMBIO trial", "Beneficial as adjunct to standard heart failure therapy" ], "dosageUsed": "100-300 mg daily", "evidenceRating": "moderate", "pmid": "29021269", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29021269/", "publicSourceType": "PMID" }, { "id": "study-0191", "supplementName": "Coenzyme Q10 Ubiquinol", "title": "The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: Q-SYMBIO study", "authors": "Mortensen SA, Rosenfeldt F, Kumar A et al.", "journal": "JACC Heart Fail", "year": 2014, "studyType": "rct", "sampleSize": 420, "outcome": "CoQ10 significantly reduced cardiovascular mortality and hospitalizations in heart failure", "keyFindings": [ "53% reduction in cardiovascular mortality", "Reduced hospitalizations for heart failure", "Improved NYHA functional class" ], "dosageUsed": "300 mg daily", "evidenceRating": "strong", "pmid": "25282031", "doi": "10.1016/j.jchf.2014.06.008", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25282031/", "publicSourceType": "PMID" }, { "id": "study-0192", "supplementName": "Collagen Peptides", "title": "Oral collagen supplementation: a systematic review of dermatological applications", "authors": "Choi FD, Sung CT, Juhasz ML, Mesinkovsk NA", "journal": "J Drugs Dermatol", "year": 2019, "studyType": "metaAnalysis", "sampleSize": 805, "outcome": "Oral collagen supplementation improved skin elasticity, hydration, and dermal collagen density", "keyFindings": [ "Improved skin elasticity and hydration", "Increased dermal collagen density", "Benefits apparent after 6-12 weeks of supplementation" ], "dosageUsed": "2.5-10 g daily", "evidenceRating": "moderate", "pmid": "30681787", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30681787/", "publicSourceType": "PMID" }, { "id": "study-0193", "supplementName": "Collagen Peptides", "title": "Specific collagen peptides improve bone mineral density and bone markers in postmenopausal women: a randomized controlled study", "authors": "Konig D, Oesser S, Scharla S et al.", "journal": "Nutrients", "year": 2018, "studyType": "rct", "sampleSize": 131, "outcome": "Specific collagen peptides significantly increased bone mineral density in postmenopausal women", "keyFindings": [ "Significant increase in spine BMD", "Increased bone formation marker P1NP", "Decreased bone degradation marker CTX" ], "dosageUsed": "5 g daily", "evidenceRating": "moderate", "pmid": "29337906", "doi": "10.3390/nu10010097", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29337906/", "publicSourceType": "PMID" }, { "id": "study-0194", "supplementName": "Collagen Peptides", "title": "24-week study on the use of collagen hydrolysate as a dietary supplement in athletes with activity-related joint pain", "authors": "Clark KL, Sebastianelli W, Flechsenhar KR et al.", "journal": "Curr Med Res Opin", "year": 2008, "studyType": "rct", "sampleSize": 147, "outcome": "Collagen hydrolysate reduced activity-related joint pain in athletes", "keyFindings": [ "Significant reduction in joint pain during activity", "Improvement in athlete-assessed parameters", "10 g daily dose was effective and well-tolerated" ], "dosageUsed": "10 g daily", "evidenceRating": "moderate", "pmid": "18416885", "doi": "10.1185/030079908X291967", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18416885/", "publicSourceType": "PMID" }, { "id": "study-0195", "supplementName": "Colostrum", "title": "Bovine colostrum supplementation and exercise performance: potential mechanisms and effect on the gastrointestinal tract", "authors": "Davison G", "journal": "J Nutr", "year": 2021, "studyType": "review", "sampleSize": null, "outcome": "Bovine colostrum may reduce exercise-induced gut damage and support immune function", "keyFindings": [ "Reduces exercise-induced intestinal permeability", "Contains immunoglobulins and growth factors", "May attenuate GI symptoms during intense exercise" ], "dosageUsed": "20-60 g daily", "evidenceRating": "emerging", "pmid": "33484131", "doi": "10.1093/jn/nxaa384", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33484131/", "publicSourceType": "PMID" }, { "id": "study-0196", "supplementName": "Colostrum", "title": "Bovine colostrum supplementation for upper respiratory illness prevention: a systematic review and meta-analysis", "authors": "Jones AW, March DS, Curtis F, Mayur C", "journal": "Sports Med", "year": 2016, "studyType": "metaAnalysis", "sampleSize": 152, "outcome": "Bovine colostrum reduced incidence of URTI days in athletes and active adults", "keyFindings": [ "Significant reduction in URTI episode days", "Possible increase in salivary IgA", "Most effective in physically active populations" ], "dosageUsed": "10-60 g daily", "evidenceRating": "emerging", "pmid": "26407076", "doi": "10.1007/s40279-015-0410-x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26407076/", "publicSourceType": "PMID" }, { "id": "study-0197", "supplementName": "Copper", "title": "Copper in human health", "authors": "Bost M, Houdart S, Oberli M et al.", "journal": "J Trace Elem Med Biol", "year": 2016, "studyType": "review", "sampleSize": null, "outcome": "Copper is essential for numerous enzymatic reactions and proper immune function", "keyFindings": [ "Essential cofactor for cytochrome c oxidase, SOD, and other enzymes", "Important for iron metabolism and hemoglobin synthesis", "Both deficiency and excess are detrimental" ], "dosageUsed": "0.9-3 mg daily", "evidenceRating": "moderate", "pmid": "27150911", "doi": "10.1016/j.jtemb.2016.02.001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27150911/", "publicSourceType": "PMID" }, { "id": "study-0198", "supplementName": "Copper", "title": "Dietary copper and human health: Current evidence and unresolved issues", "authors": "Bost M, Houdart S, Oberli M et al.", "journal": "Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)", "year": 2016, "studyType": "review", "sampleSize": null, "outcome": "Marginal copper deficiency may be more common than recognized and affect cardiovascular health", "keyFindings": [ "Marginal deficiency affects lipid and glucose metabolism", "Optimal intake may be higher than current RDA", "Copper/zinc ratio important for health outcomes" ], "dosageUsed": "1-3 mg daily", "evidenceRating": "moderate", "pmid": "27049134", "doi": "10.1016/j.jtemb.2016.02.006", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27049134/", "publicSourceType": "PMID" }, { "id": "study-0199", "supplementName": "Cordyceps", "title": "Cordyceps militaris improves tolerance to high-intensity exercise after acute and chronic supplementation", "authors": "Hirsch KR, Smith-Ryan AE, Roelofs EJ et al.", "journal": "J Diet Suppl", "year": 2017, "studyType": "rct", "sampleSize": 28, "outcome": "Cordyceps improved maximal oxygen consumption and time to exhaustion", "keyFindings": [ "Increased VO2max by 7% after 3 weeks", "Improved time to exhaustion at ventilatory threshold", "Benefits more pronounced with chronic supplementation" ], "dosageUsed": "4 g daily", "evidenceRating": "emerging", "pmid": "27408987", "doi": "10.1080/19390211.2016.1203386", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27408987/", "publicSourceType": "PMID" }, { "id": "study-0200", "supplementName": "Cordyceps", "title": "Pharmacological and therapeutic potential of Cordyceps with special reference to Cordycepin", "authors": "Tuli HS, Sandhu SS, Sharma AK", "journal": "3 Biotech", "year": 2014, "studyType": "review", "sampleSize": null, "outcome": "Cordyceps demonstrates anti-inflammatory, antioxidant, and immunomodulatory properties", "keyFindings": [ "Cordycepin is the primary bioactive compound", "Anti-inflammatory via adenosine receptor modulation", "Immunomodulatory effects enhancing NK cell activity" ], "dosageUsed": "1-3 g daily", "evidenceRating": "emerging", "pmid": "28324458", "doi": "10.1007/s13205-013-0121-9", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28324458/", "publicSourceType": "PMID" }, { "id": "study-0201", "supplementName": "Curcumin Phytosome", "title": "Comparative absorption of curcumin formulations", "authors": "Jager R, Lowery RP, Calvanese AV et al.", "journal": "Nutr J", "year": 2014, "studyType": "rct", "sampleSize": 12, "outcome": "Curcumin phytosome showed 29x higher bioavailability than standard curcumin", "keyFindings": [ "29-fold higher plasma curcumin levels than unformulated curcumin", "Superior absorption due to phospholipid complexation", "Peak plasma levels at 2-4 hours post-dose" ], "dosageUsed": "500 mg curcumin phytosome", "evidenceRating": "moderate", "pmid": "24461029", "doi": "10.1186/1475-2891-13-11", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24461029/", "publicSourceType": "PMID" }, { "id": "study-0202", "supplementName": "Curcumin Phytosome", "title": "Efficacy of Meriva, a curcumin-phosphatidylcholine complex, in osteoarthritis: a randomized, double-blind, placebo-controlled trial", "authors": "Belcaro G, Cesaone MR, Dugall M et al.", "journal": "Altern Med Rev", "year": 2010, "studyType": "rct", "sampleSize": 100, "outcome": "Curcumin phytosome significantly reduced joint pain and improved treadmill walking distance", "keyFindings": [ "Significant improvement in WOMAC scores", "Increased treadmill walking distance", "Reduced CRP levels and need for NSAIDs" ], "dosageUsed": "1000 mg daily (Meriva)", "evidenceRating": "moderate", "pmid": "21194249", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21194249/", "publicSourceType": "PMID" }, { "id": "study-0203", "supplementName": "D-Aspartic Acid", "title": "The role and molecular mechanism of D-aspartic acid in the release and synthesis of LH and testosterone in humans and rats", "authors": "Topo E, Soricelli A, D'Aniello A et al.", "journal": "Reprod Biol Endocrinol", "year": 2009, "studyType": "rct", "sampleSize": 23, "outcome": "Small early study reported testosterone and LH changes over 12 days, but later human trials and reviews do not support a reliable testosterone benefit", "keyFindings": [ "Early hormone increases were reported in a small study", "Later controlled trials found no reliable testosterone benefit in resistance-trained men", "Levels returned toward baseline 3 days after cessation" ], "dosageUsed": "3.12 g daily", "evidenceRating": "emerging", "pmid": "19860889", "doi": "10.1186/1477-7827-7-120", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19860889/", "publicSourceType": "PMID" }, { "id": "study-0204", "supplementName": "D-Aspartic Acid", "title": "Three and six grams supplementation of d-aspartic acid in resistance trained men", "authors": "Melville GW, Siegler JC, Marshall PW", "journal": "Journal of the International Society of Sports Nutrition", "year": 2015, "studyType": "rct", "sampleSize": 24, "outcome": "D-aspartic acid did not increase testosterone in resistance-trained men", "keyFindings": [ "No significant change in total testosterone at 3g or 6g", "No significant change in free testosterone", "Resistance-trained men may not respond to DAA supplementation" ], "dosageUsed": "3-6 g daily", "evidenceRating": "emerging", "pmid": "25844073", "doi": "10.1186/s12970-015-0078-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25844073/", "publicSourceType": "PMID" }, { "id": "study-0205", "supplementName": "D-Mannose", "title": "D-mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial", "authors": "Kranjcec B, Papes D, Altarac S", "journal": "World J Urol", "year": 2014, "studyType": "rct", "sampleSize": 308, "outcome": "D-mannose was as effective as nitrofurantoin for UTI prevention with fewer side effects", "keyFindings": [ "Significantly reduced UTI recurrence vs placebo", "Comparable efficacy to prophylactic antibiotic", "Significantly fewer side effects than nitrofurantoin" ], "dosageUsed": "2 g daily", "evidenceRating": "moderate", "pmid": "23633128", "doi": "10.1007/s00345-013-1091-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23633128/", "publicSourceType": "PMID" }, { "id": "study-0206", "supplementName": "D-Mannose", "title": "D-mannose: a promising support for acute urinary tract infections in women", "authors": "Porru D, Parmigiani A, Tinelli C et al.", "journal": "J Chemother", "year": 2014, "studyType": "rct", "sampleSize": 60, "outcome": "D-mannose significantly reduced UTI symptoms and recurrence", "keyFindings": [ "Rapid improvement in acute UTI symptoms", "Reduced recurrence rate over 6 months", "Well-tolerated with minimal side effects" ], "dosageUsed": "1.5 g twice daily (acute), 1.5 g daily (prevention)", "evidenceRating": "moderate", "pmid": "24781931", "doi": "10.1179/1973947813Y.0000000166", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24781931/", "publicSourceType": "PMID" }, { "id": "study-0207", "supplementName": "DHEA", "title": "DHEA supplementation: a review of the evidence for effects on body composition, insulin sensitivity, and lipid profiles", "authors": "Villareal DT, Holloszy JO", "journal": "J Clin Endocrinol Metab", "year": 2004, "studyType": "rct", "sampleSize": 56, "outcome": "DHEA supplementation reduced visceral fat and improved insulin sensitivity in elderly", "keyFindings": [ "Significant reduction in visceral fat area", "Improved insulin sensitivity", "Decreased inflammatory markers" ], "dosageUsed": "50 mg daily", "evidenceRating": "moderate", "pmid": "15531540", "doi": "10.1210/jc.2004-0867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15531540/", "publicSourceType": "PMID" }, { "id": "study-0208", "supplementName": "DHEA", "title": "Effect of DHEA on abdominal fat and insulin action in elderly women and men: a randomized controlled trial", "authors": "Villareal DT, Holloszy JO", "journal": "JAMA", "year": 2004, "studyType": "rct", "sampleSize": 56, "outcome": "DHEA replacement decreased abdominal fat and improved insulin action in aging adults", "keyFindings": [ "Visceral fat decreased by 10.2% in women, 7.4% in men", "Improved oral glucose tolerance", "Restored DHEA-S to young-adult levels" ], "dosageUsed": "50 mg daily", "evidenceRating": "moderate", "pmid": "15536111", "doi": "10.1001/jama.292.18.2243", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15536111/", "publicSourceType": "PMID" }, { "id": "study-0209", "supplementName": "DIM", "title": "Indole-3-carbinol and diindolylmethane as hormone-modulating agents", "authors": "Rajoria S, Suriano R, Parber A et al.", "journal": "J Thyroid Res", "year": 2011, "studyType": "review", "sampleSize": null, "outcome": "DIM modulates estrogen metabolism favoring beneficial 2-hydroxyestrone pathway", "keyFindings": [ "Shifts estrogen metabolism toward 2-OHE1 (protective metabolite)", "Anti-proliferative effects on estrogen-sensitive tissues", "Potential benefits for estrogen-dominant conditions" ], "dosageUsed": "100-300 mg daily", "evidenceRating": "emerging", "pmid": "21860614", "doi": "10.4061/2011/524862", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21860614/", "publicSourceType": "PMID" }, { "id": "study-0210", "supplementName": "DIM", "title": "Absorption and metabolism of diindolylmethane", "authors": "Zeligs MA, Jacobs IC, Ho J et al.", "journal": "In Vivo", "year": 2006, "studyType": "rct", "sampleSize": 19, "outcome": "DIM in microencapsulated form showed improved bioavailability and consistent estrogen metabolite shifts", "keyFindings": [ "Consistent increase in 2-OHE1:16alpha-OHE1 ratio", "Microencapsulated form 50% more bioavailable", "Dose-dependent effect on estrogen metabolism" ], "dosageUsed": "108-300 mg daily", "evidenceRating": "emerging", "pmid": "17091779", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17091779/", "publicSourceType": "PMID" }, { "id": "study-0211", "supplementName": "Digestive Enzymes", "title": "Digestive Enzyme Supplementation in Gastrointestinal Diseases", "authors": "Ianiro G, Pecere S, Giorgio V et al.", "journal": "Current drug metabolism", "year": 2016, "studyType": "review", "sampleSize": null, "outcome": "Digestive enzyme supplementation is effective for specific enzyme deficiencies", "keyFindings": [ "Pancreatic enzyme replacement essential in exocrine pancreatic insufficiency", "Lactase effective for lactose intolerance", "Alpha-galactosidase reduces gas from bean/legume consumption" ], "dosageUsed": "Varies by enzyme type", "evidenceRating": "moderate", "pmid": "26806042", "doi": "10.2174/138920021702160114150137", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26806042/", "publicSourceType": "PMID" }, { "id": "study-0212", "supplementName": "Digestive Enzymes", "title": "Pancreatic enzyme replacement therapy in chronic pancreatitis: a systematic review and meta-analysis", "authors": "de la Iglesia-Garcia D, Huang W, Szatmary P et al.", "journal": "Pancreatology", "year": 2017, "studyType": "metaAnalysis", "sampleSize": 479, "outcome": "Pancreatic enzyme replacement significantly improved fat absorption in chronic pancreatitis", "keyFindings": [ "Significant improvement in coefficient of fat absorption", "Reduced steatorrhea symptoms", "Higher lipase doses generally more effective" ], "dosageUsed": "25000-75000 USP units lipase per meal", "evidenceRating": "strong", "pmid": "28427862", "doi": "10.1016/j.pan.2017.04.004", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28427862/", "publicSourceType": "PMID" }, { "id": "study-0213", "supplementName": "Echinacea", "title": "Evaluation of echinacea for the prevention and treatment of the common cold: a meta-analysis", "authors": "Shah SA, Sander S, White CM et al.", "journal": "Lancet Infect Dis", "year": 2007, "studyType": "metaAnalysis", "sampleSize": 1630, "outcome": "Echinacea reduced the incidence of common cold by 58% and duration by 1.4 days", "keyFindings": [ "58% reduced odds of developing a cold", "Duration shortened by 1.4 days", "Echinacea purpurea most effective species" ], "dosageUsed": "Varied preparations", "evidenceRating": "moderate", "pmid": "17597571", "doi": "10.1016/S1473-3099(07)70160-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17597571/", "publicSourceType": "PMID" }, { "id": "study-0214", "supplementName": "Echinacea", "title": "Echinacea for preventing and treating the common cold", "authors": "Karsch-Volk M, Barrett B, Kiefer D et al.", "journal": "Cochrane Database Syst Rev", "year": 2014, "studyType": "metaAnalysis", "sampleSize": 3396, "outcome": "Echinacea products may have weak benefit for common cold but evidence is inconsistent", "keyFindings": [ "Some products showed modest cold prevention benefits", "No product convincingly demonstrated treatment efficacy", "Heterogeneity in preparations limits conclusions" ], "dosageUsed": "Varied preparations", "evidenceRating": "moderate", "pmid": "24554461", "doi": "10.1002/14651858.CD000530.pub3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24554461/", "publicSourceType": "PMID" }, { "id": "study-0215", "supplementName": "Elderberry", "title": "Black elderberry (Sambucus nigra) supplementation effectively treats upper respiratory symptoms: a meta-analysis of randomized controlled clinical trials", "authors": "Hawkins J, Baker C, Cherry L, Dunne E", "journal": "Complement Ther Med", "year": 2019, "studyType": "metaAnalysis", "sampleSize": 180, "outcome": "Elderberry supplementation significantly reduced upper respiratory symptoms", "keyFindings": [ "Substantial reduction in cold duration and severity", "Most effective for upper respiratory symptoms", "Beneficial for both cold and flu-like symptoms" ], "dosageUsed": "600-900 mg daily (extract)", "evidenceRating": "moderate", "pmid": "30670267", "doi": "10.1016/j.ctim.2018.12.004", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30670267/", "publicSourceType": "PMID" }, { "id": "study-0216", "supplementName": "Elderberry", "title": "Randomized study of the efficacy and safety of oral elderberry extract in the treatment of influenza A and B virus infections", "authors": "Zakay-Rones Z, Thom E, Wollan T, Wadstein J", "journal": "J Int Med Res", "year": 2004, "studyType": "rct", "sampleSize": 60, "outcome": "Elderberry extract reduced influenza duration by an average of 4 days", "keyFindings": [ "Symptoms relieved on average 4 days earlier than placebo", "Significant reduction in use of rescue medication", "Effective against both influenza A and B strains" ], "dosageUsed": "15 mL four times daily (syrup)", "evidenceRating": "moderate", "pmid": "15080016", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15080016/", "publicSourceType": "PMID" }, { "id": "study-0217", "supplementName": "Elderberry Zinc Lozenges", "title": "Zinc lozenges and the common cold: a meta-analysis comparing zinc acetate and zinc gluconate", "authors": "Hemila H", "journal": "JRSM Open", "year": 2017, "studyType": "metaAnalysis", "sampleSize": 575, "outcome": "Zinc lozenges significantly shortened common cold duration by approximately 33%", "keyFindings": [ "Zinc acetate lozenges reduced cold duration by 40%", "Zinc gluconate lozenges reduced duration by 28%", "Most effective when started within 24 hours of symptom onset" ], "dosageUsed": "75-92 mg zinc daily (from lozenges)", "evidenceRating": "strong", "pmid": "28515951", "doi": "10.1177/2054270417694291", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28515951/", "publicSourceType": "PMID" }, { "id": "study-0218", "supplementName": "Elderberry Zinc Lozenges", "title": "Zinc for the common cold", "authors": "Singh M, Das RR", "journal": "Cochrane Database Syst Rev", "year": 2013, "studyType": "metaAnalysis", "sampleSize": 1360, "outcome": "Zinc supplementation within 24 hours of cold onset reduces duration and severity", "keyFindings": [ "Reduced cold duration by approximately 1 day", "Reduced symptom severity", "Zinc lozenges more effective than oral zinc supplements for colds" ], "dosageUsed": "75+ mg daily (lozenges)", "evidenceRating": "strong", "pmid": "23775705", "doi": "10.1002/14651858.CD001364.pub4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23775705/", "publicSourceType": "PMID" }, { "id": "study-0219", "supplementName": "Evening Primrose Oil", "title": "Evening primrose oil for premenstrual syndrome", "authors": "Budeiri D, Li Wan Po A, Dornan JC", "journal": "BMJ", "year": 1996, "studyType": "metaAnalysis", "sampleSize": 412, "outcome": "Evidence for evening primrose oil in PMS is limited and inconsistent", "keyFindings": [ "Small trials showed some PMS symptom improvement", "Larger, well-designed trials showed no significant benefit", "GLA mechanism is plausible but clinical evidence weak" ], "dosageUsed": "500-3000 mg daily", "evidenceRating": "emerging", "pmid": "8555781", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8555781/", "publicSourceType": "PMID" }, { "id": "study-0220", "supplementName": "Evening Primrose Oil", "title": "Effect of evening primrose oil on menopausal symptoms: a systematic review and meta-analysis", "authors": "Mahboubi M", "journal": "Obstet Gynecol Sci", "year": 2019, "studyType": "metaAnalysis", "sampleSize": 344, "outcome": "Evening primrose oil showed modest benefit for hot flash severity", "keyFindings": [ "Modest reduction in hot flash severity", "No significant effect on hot flash frequency", "GLA content may support prostaglandin balance" ], "dosageUsed": "500-2000 mg daily", "evidenceRating": "emerging", "pmid": "31777736", "doi": "10.5468/ogs.2019.62.4.512", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31777736/", "publicSourceType": "PMID" }, { "id": "study-0221", "supplementName": "Fenugreek", "title": "Effects of a purported aromatase and 5-alpha-reductase inhibitor on hormone profiles in college-age men", "authors": "Wilborn C, Taylor L, Poole C et al.", "journal": "Int J Sport Nutr Exerc Metab", "year": 2010, "studyType": "rct", "sampleSize": 30, "outcome": "Fenugreek extract significantly reduced body fat and maintained testosterone during resistance training", "keyFindings": [ "Significant reduction in body fat percentage", "Maintained free testosterone levels", "Improved bench press and leg press strength" ], "dosageUsed": "500 mg daily (Torabolic)", "evidenceRating": "emerging", "pmid": "20938994", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20938994/", "publicSourceType": "PMID" }, { "id": "study-0222", "supplementName": "Fenugreek", "title": "Physiological aspects of male libido enhanced by standardized Trigonella foenum-graecum extract and mineral formulation", "authors": "Steels E, Rao A, Vitetta L", "journal": "Phytother Res", "year": 2011, "studyType": "rct", "sampleSize": 60, "outcome": "Fenugreek extract significantly improved male sexual function and libido", "keyFindings": [ "Significant improvement in sexual arousal and orgasm scores", "Maintained testosterone levels", "Improved quality of life parameters" ], "dosageUsed": "600 mg daily (Testofen)", "evidenceRating": "moderate", "pmid": "21312304", "doi": "10.1002/ptr.3360", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21312304/", "publicSourceType": "PMID" }, { "id": "study-0223", "supplementName": "Fish Oil Triple Strength", "title": "Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks: Meta-analysis of 10 Trials Involving 77 917 Individuals", "authors": "Aung T, Halsey J, Kromhout D et al.", "journal": "JAMA cardiology", "year": 2018, "studyType": "metaAnalysis", "sampleSize": 77917, "outcome": "Marine omega-3 supplementation significantly associated with reduced cardiovascular events", "keyFindings": [ "Significant reduction in MI risk (RR 0.92)", "Reduced CHD death risk (RR 0.92)", "Higher doses (>840 mg EPA+DHA) showed larger benefit" ], "dosageUsed": "840-4000 mg EPA+DHA daily", "evidenceRating": "strong", "pmid": "29387889", "doi": "10.1001/jamacardio.2017.5205", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29387889/", "publicSourceType": "PMID" }, { "id": "study-0224", "supplementName": "Fish Oil Triple Strength", "title": "REDUCE-IT: Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia", "authors": "Bhatt DL, Steg PG, Miller M et al.", "journal": "N Engl J Med", "year": 2019, "studyType": "rct", "sampleSize": 8179, "outcome": "High-dose EPA significantly reduced cardiovascular events in statin-treated patients", "keyFindings": [ "25% relative risk reduction in primary composite endpoint", "Significant reduction in cardiovascular death", "Higher dose (4g/day) more effective than studied lower doses" ], "dosageUsed": "4 g daily (icosapent ethyl)", "evidenceRating": "strong", "pmid": "30415628", "doi": "10.1056/NEJMoa1812792", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30415628/", "publicSourceType": "PMID" }, { "id": "study-0225", "supplementName": "Flaxseed Oil", "title": "Health benefits of flaxseed and its components", "authors": "Goyal A, Sharma V, Upadhyay N et al.", "journal": "J Food Sci Technol", "year": 2014, "studyType": "review", "sampleSize": null, "outcome": "Flaxseed oil is the richest plant source of omega-3 ALA with cardiovascular and anti-inflammatory benefits", "keyFindings": [ "Richest source of alpha-linolenic acid (ALA, ~57%)", "Lignans provide antioxidant and phytoestrogenic effects", "May reduce blood pressure and inflammation markers" ], "dosageUsed": "1-4 tablespoons daily", "evidenceRating": "moderate", "pmid": "25328645", "doi": "10.1007/s13197-014-1355-x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25328645/", "publicSourceType": "PMID" }, { "id": "study-0226", "supplementName": "Flaxseed Oil", "title": "Effect of flaxseed intervention on inflammatory markers: a systematic review and meta-analysis of randomized controlled trials", "authors": "Mohammadi-Sartang M, Mazloom Z, Raeisi-Dehkordi H et al.", "journal": "Cytokine", "year": 2018, "studyType": "metaAnalysis", "sampleSize": 1256, "outcome": "Flaxseed supplementation significantly reduced inflammatory biomarkers CRP and TNF-alpha", "keyFindings": [ "Significant reduction in C-reactive protein", "Significant reduction in TNF-alpha", "Greater effects in higher BMI populations" ], "dosageUsed": "2-6 g ALA daily", "evidenceRating": "moderate", "pmid": "28578839", "doi": "10.1016/j.cyto.2017.06.001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28578839/", "publicSourceType": "PMID" }, { "id": "study-0227", "supplementName": "GABA", "title": "Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans", "authors": "Abdou AM, Higashiguchi S, Horie K et al.", "journal": "Biofactors", "year": 2006, "studyType": "rct", "sampleSize": 13, "outcome": "Oral GABA increased alpha brain waves and decreased anxiety within 1 hour", "keyFindings": [ "Significantly increased alpha waves (relaxation marker)", "Decreased beta waves (anxiety marker)", "Enhanced IgA levels suggesting immune support" ], "dosageUsed": "100 mg single dose", "evidenceRating": "emerging", "pmid": "17011488", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17011488/", "publicSourceType": "PMID" }, { "id": "study-0228", "supplementName": "GABA", "title": "GABA and l-theanine mixture decreases sleep latency and improves NREM sleep", "authors": "Kim S, Jo K, Hong KB et al.", "journal": "Pharm Biol", "year": 2019, "studyType": "animalStudy", "sampleSize": null, "outcome": "GABA/L-theanine combination synergistically improved sleep quality in animal model", "keyFindings": [ "Combination reduced sleep latency more than either alone", "Increased NREM sleep duration", "Synergistic effect between GABA and L-theanine" ], "dosageUsed": "100 mg GABA + 20 mg L-theanine", "evidenceRating": "emerging", "pmid": "31062657", "doi": "10.1080/13880209.2019.1612244", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31062657/", "publicSourceType": "PMID" }, { "id": "study-0229", "supplementName": "Garlic Extract", "title": "Effect of garlic on blood pressure: a systematic review and meta-analysis", "authors": "Ried K, Frank OR, Stocks NP et al.", "journal": "BMC Cardiovasc Disord", "year": 2008, "studyType": "metaAnalysis", "sampleSize": 415, "outcome": "Garlic supplementation significantly reduced systolic blood pressure in hypertensive subjects", "keyFindings": [ "Reduced systolic BP by 8.4 mmHg in hypertensive patients", "Reduced diastolic BP by 7.3 mmHg", "Aged garlic extract most studied form" ], "dosageUsed": "600-900 mg daily (aged garlic extract)", "evidenceRating": "moderate", "pmid": "18554422", "doi": "10.1186/1471-2261-8-13", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18554422/", "publicSourceType": "PMID" }, { "id": "study-0230", "supplementName": "Garlic Extract", "title": "Garlic supplementation and lipid levels: a systematic review and meta-analysis", "authors": "Ried K, Toben C, Fakler P", "journal": "Nutr Rev", "year": 2013, "studyType": "metaAnalysis", "sampleSize": 2300, "outcome": "Garlic supplementation significantly reduced total cholesterol", "keyFindings": [ "Reduced total cholesterol by 17 mg/dL on average", "Effect most pronounced with longer treatment (>2 months)", "LDL cholesterol also significantly reduced" ], "dosageUsed": "600-1200 mg daily", "evidenceRating": "moderate", "pmid": "23590705", "doi": "10.1111/nure.12012", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23590705/", "publicSourceType": "PMID" }, { "id": "study-0231", "supplementName": "Garlic Extract", "title": "Aged garlic extract and its bioactive compounds inhibit platelet aggregation", "authors": "Rahman K, Billington D", "journal": "J Nutr", "year": 2000, "studyType": "review", "sampleSize": null, "outcome": "Garlic and its compounds demonstrate significant anti-platelet and antithrombotic effects", "keyFindings": [ "Inhibits platelet aggregation via multiple mechanisms", "Ajoene is the most potent antiplatelet compound", "May synergize with anticoagulant medications (caution)" ], "dosageUsed": "2.4-7.2 g aged garlic extract daily", "evidenceRating": "moderate", "pmid": "10736378", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10736378/", "publicSourceType": "PMID" }, { "id": "study-0232", "supplementName": "Ginger Extract", "title": "A systematic review and meta-analysis of the effect and safety of ginger in the treatment of pregnancy-associated nausea and vomiting", "authors": "Viljoen E, Visser J, Koen N, Musekiwa A", "journal": "Nutr J", "year": 2014, "studyType": "metaAnalysis", "sampleSize": 508, "outcome": "Ginger significantly improved nausea symptoms in pregnancy", "keyFindings": [ "Significant improvement in nausea symptoms vs placebo", "No significant effect on vomiting episodes", "Safe in pregnancy at recommended doses" ], "dosageUsed": "250 mg four times daily", "evidenceRating": "strong", "pmid": "24642205", "doi": "10.1186/1475-2891-13-20", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24642205/", "publicSourceType": "PMID" }, { "id": "study-0233", "supplementName": "Ginger Extract", "title": "Anti-oxidative and anti-inflammatory effects of ginger in health and physical activity: review of current evidence", "authors": "Mashhadi NS, Ghiasvand R, Askari G et al.", "journal": "Int J Prev Med", "year": 2013, "studyType": "review", "sampleSize": null, "outcome": "Ginger demonstrates potent anti-inflammatory and analgesic properties", "keyFindings": [ "Inhibits COX-2 and 5-LOX inflammatory pathways", "Effective for exercise-induced muscle pain", "Anti-emetic effects well-established for multiple conditions" ], "dosageUsed": "500-2000 mg daily", "evidenceRating": "moderate", "pmid": "23717767", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23717767/", "publicSourceType": "PMID" }, { "id": "study-0234", "supplementName": "Ginger Extract", "title": "Efficacy of ginger for nausea and vomiting: a systematic review of randomized clinical trials", "authors": "Ernst E, Pittler MH", "journal": "Br J Anaesth", "year": 2000, "studyType": "metaAnalysis", "sampleSize": 458, "outcome": "Ginger was effective for postoperative nausea and motion sickness", "keyFindings": [ "Effective for postoperative nausea (NNT = 5)", "Effective for seasickness and motion sickness", "Not all studies supported efficacy for chemotherapy-induced nausea" ], "dosageUsed": "1 g before travel/surgery", "evidenceRating": "moderate", "pmid": "10793592", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10793592/", "publicSourceType": "PMID" }, { "id": "study-0235", "supplementName": "Ginkgo Biloba", "title": "Ginkgo biloba for prevention of dementia: a randomized controlled trial (GEM Study)", "authors": "DeKosky ST, Williamson JD, Fitzpatrick AL et al.", "journal": "JAMA", "year": 2008, "studyType": "rct", "sampleSize": 3069, "outcome": "Ginkgo biloba did not reduce the incidence of dementia or Alzheimer's disease", "keyFindings": [ "No reduction in overall dementia incidence", "No benefit for Alzheimer's disease specifically", "Well-tolerated with no significant safety concerns over 6 years" ], "dosageUsed": "120 mg twice daily", "evidenceRating": "strong", "pmid": "19017911", "doi": "10.1001/jama.2008.683", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19017911/", "publicSourceType": "PMID" }, { "id": "study-0236", "supplementName": "Ginkgo Biloba", "title": "Ginkgo biloba for cognitive impairment and dementia", "authors": "Birks J, Grimley Evans J", "journal": "Cochrane Database Syst Rev", "year": 2009, "studyType": "metaAnalysis", "sampleSize": 3120, "outcome": "Ginkgo biloba showed inconsistent evidence for cognitive improvement in dementia", "keyFindings": [ "Some improvement in cognition at 12-24 weeks", "Inconsistent results across trials", "EGb 761 extract most studied preparation" ], "dosageUsed": "120-240 mg daily", "evidenceRating": "moderate", "pmid": "19160216", "doi": "10.1002/14651858.CD003120.pub3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19160216/", "publicSourceType": "PMID" }, { "id": "study-0237", "supplementName": "Ginkgo Biloba", "title": "A placebo-controlled, double-blind, randomized trial of Ginkgo biloba extract EGb 761 in dementia", "authors": "Le Bars PL, Katz MM, Berman N et al.", "journal": "JAMA", "year": 1997, "studyType": "rct", "sampleSize": 309, "outcome": "Ginkgo biloba EGb 761 modestly improved cognitive function in dementia patients", "keyFindings": [ "Modest improvement in ADAS-Cog scores", "Improvement in social functioning", "Safe and well-tolerated over 52 weeks" ], "dosageUsed": "120 mg daily", "evidenceRating": "moderate", "pmid": "9343463", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9343463/", "publicSourceType": "PMID" }, { "id": "study-0238", "supplementName": "Glucosamine", "title": "Glucosamine for osteoarthritis: a meta-analysis", "authors": "Towheed TE, Maxwell L, Anastassiades TP et al.", "journal": "Cochrane Database Syst Rev", "year": 2005, "studyType": "metaAnalysis", "sampleSize": 3803, "outcome": "Glucosamine showed pain improvement using Rotta preparation but not others", "keyFindings": [ "Rotta glucosamine sulfate showed significant pain reduction", "Non-Rotta preparations showed no benefit", "Preparation quality is a critical factor" ], "dosageUsed": "1500 mg daily", "evidenceRating": "moderate", "pmid": "15846614", "doi": "10.1002/14651858.CD002946.pub2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15846614/", "publicSourceType": "PMID" }, { "id": "study-0239", "supplementName": "Glucosamine", "title": "Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial", "authors": "Reginster JY, Deroisy R, Rovati LC et al.", "journal": "Lancet", "year": 2001, "studyType": "rct", "sampleSize": 212, "outcome": "Glucosamine sulfate prevented joint space narrowing over 3 years in knee OA", "keyFindings": [ "Prevented radiographic joint space narrowing", "Improved WOMAC pain scores", "Disease-modifying effect over 3-year period" ], "dosageUsed": "1500 mg daily", "evidenceRating": "moderate", "pmid": "11191548", "doi": "10.1016/S0140-6736(00)03610-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11191548/", "publicSourceType": "PMID" }, { "id": "study-0240", "supplementName": "Glycine", "title": "New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep", "authors": "Inagawa K, Hiraoka T, Kohda T et al.", "journal": "J Pharmacol Sci", "year": 2006, "studyType": "rct", "sampleSize": 11, "outcome": "Glycine before bed significantly improved subjective sleep quality and reduced next-day sleepiness", "keyFindings": [ "Improved subjective sleep quality", "Reduced daytime sleepiness and fatigue", "Lowered core body temperature facilitating sleep onset" ], "dosageUsed": "3 g before bed", "evidenceRating": "moderate", "pmid": "17057164", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17057164/", "publicSourceType": "PMID" }, { "id": "study-0241", "supplementName": "Glycine", "title": "Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes", "authors": "Bannai M, Kawai N, Ono K et al.", "journal": "Sleep Biol Rhythms", "year": 2012, "studyType": "rct", "sampleSize": 10, "outcome": "Glycine improved PSG-measured sleep efficiency and reduced sleep onset latency", "keyFindings": [ "Shortened time to sleep onset", "Improved sleep efficiency on polysomnography", "Increased slow-wave (deep) sleep" ], "dosageUsed": "3 g before bed", "evidenceRating": "moderate", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-0242", "supplementName": "Glycine", "title": "Dietary glycine is rate-limiting for glutathione synthesis and may have broad potential for health protection", "authors": "McCarty MF, O'Keefe JH, DiNicolantonio JJ", "journal": "Ochsner J", "year": 2018, "studyType": "review", "sampleSize": null, "outcome": "Glycine is rate-limiting for glutathione synthesis with implications for antioxidant defense", "keyFindings": [ "Rate-limiting amino acid for glutathione production", "May protect against metabolic syndrome", "Anti-inflammatory effects via glycine-gated chloride channels" ], "dosageUsed": "3-5 g daily", "evidenceRating": "moderate", "pmid": "30559624", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30559624/", "publicSourceType": "PMID" }, { "id": "study-0243", "supplementName": "Grape Seed Extract", "title": "Effects of grape seed extract on blood pressure: a meta-analysis of randomized controlled trials", "authors": "Feringa HH, Laskey DA, Dickson JE, Coleman CI", "journal": "J Am Diet Assoc", "year": 2011, "studyType": "metaAnalysis", "sampleSize": 810, "outcome": "Grape seed extract significantly reduced systolic blood pressure", "keyFindings": [ "Reduced SBP by 1.54 mmHg", "Greater effect in younger and obese subjects", "Metabolic syndrome subgroup showed greater benefit" ], "dosageUsed": "100-800 mg daily", "evidenceRating": "moderate", "pmid": "21986210", "doi": "10.1016/j.jada.2011.07.015", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21986210/", "publicSourceType": "PMID" }, { "id": "study-0244", "supplementName": "Grape Seed Extract", "title": "Grape seed proanthocyanidins: a review of their chemical properties and biological activities", "authors": "Shi J, Yu J, Pohorly JE, Kakuda Y", "journal": "Plant Foods Hum Nutr", "year": 2003, "studyType": "review", "sampleSize": null, "outcome": "Grape seed proanthocyanidins are potent antioxidants with vascular protective effects", "keyFindings": [ "20x more potent antioxidant than vitamin C", "50x more potent than vitamin E", "Protects against oxidative vascular damage" ], "dosageUsed": "100-300 mg daily", "evidenceRating": "moderate", "pmid": "14598094", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14598094/", "publicSourceType": "PMID" }, { "id": "study-0245", "supplementName": "Green Tea Extract", "title": "The effects of green tea on weight loss and weight maintenance: a meta-analysis", "authors": "Hursel R, Viechtbauer W, Westerterp-Plantenga MS", "journal": "Int J Obes", "year": 2009, "studyType": "metaAnalysis", "sampleSize": 1945, "outcome": "Green tea catechins significantly increased energy expenditure and fat oxidation", "keyFindings": [ "Significant increase in energy expenditure", "Enhanced fat oxidation", "EGCG and caffeine combination most effective" ], "dosageUsed": "270-1200 mg catechins daily", "evidenceRating": "moderate", "pmid": "19597519", "doi": "10.1038/ijo.2009.135", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19597519/", "publicSourceType": "PMID" }, { "id": "study-0246", "supplementName": "Green Tea Extract", "title": "Green tea consumption and the risk of type 2 diabetes mellitus: a systematic review and meta-analysis", "authors": "Jing Y, Han G, Hu Y et al.", "journal": "J Intern Med", "year": 2009, "studyType": "metaAnalysis", "sampleSize": 286701, "outcome": "Green tea consumption associated with reduced risk of type 2 diabetes", "keyFindings": [ "3+ cups/day associated with 16% reduced diabetes risk", "EGCG may improve insulin sensitivity", "Effect partly mediated by weight management" ], "dosageUsed": "3+ cups daily or 500 mg extract", "evidenceRating": "moderate", "pmid": "19930003", "doi": "10.1111/j.1365-2796.2009.02130.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19930003/", "publicSourceType": "PMID" }, { "id": "study-0247", "supplementName": "Green Tea Extract", "title": "Hepatotoxicity related to green tea: a systematic review and meta-analysis", "authors": "Mazzanti G, Di Sotto A, Vitalone A", "journal": "Phytother Res", "year": 2015, "studyType": "review", "sampleSize": null, "outcome": "Rare but documented cases of liver injury with concentrated green tea extracts", "keyFindings": [ "Fasting intake of concentrated extracts increases hepatotoxicity risk", "Dose-dependent risk above 800 mg EGCG/day", "Taking with food reduces risk significantly" ], "dosageUsed": "N/A (safety review)", "evidenceRating": "strong", "pmid": "25559067", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25559067/", "publicSourceType": "PMID" }, { "id": "study-0248", "supplementName": "HMB", "title": "International Society of Sports Nutrition position stand: beta-hydroxy-beta-methylbutyrate (HMB)", "authors": "Wilson JM, Fitschen PJ, Campbell B et al.", "journal": "J Int Soc Sports Nutr", "year": 2013, "studyType": "review", "sampleSize": null, "outcome": "HMB supplementation can enhance recovery and reduce muscle damage from high-intensity exercise", "keyFindings": [ "Reduces exercise-induced muscle damage", "May increase lean body mass in untrained individuals", "3 g/day is the established effective dose" ], "dosageUsed": "3 g daily", "evidenceRating": "moderate", "pmid": "23374455", "doi": "10.1186/1550-2783-10-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23374455/", "publicSourceType": "PMID" }, { "id": "study-0249", "supplementName": "HMB", "title": "Effect of HMB supplementation on body composition, fitness, hormonal and inflammatory profile in trained and competitive athletes: a meta-analysis", "authors": "Sanchez-Martinez J, Santos-Lozano A, Garcia-Hermoso A et al.", "journal": "J Sci Med Sport", "year": 2018, "studyType": "metaAnalysis", "sampleSize": 293, "outcome": "HMB had minimal effects on body composition in trained athletes but reduced muscle damage", "keyFindings": [ "No significant effect on lean mass in trained athletes", "Significant reduction in creatine kinase (muscle damage)", "Benefits may be limited to untrained or recovering populations" ], "dosageUsed": "3 g daily", "evidenceRating": "moderate", "pmid": "28385561", "doi": "10.1016/j.jsams.2017.03.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28385561/", "publicSourceType": "PMID" }, { "id": "study-0250", "supplementName": "Holy Basil/Tulsi", "title": "Tulsi - Ocimum sanctum: a herb for all reasons", "authors": "Cohen MM", "journal": "J Ayurveda Integr Med", "year": 2014, "studyType": "review", "sampleSize": null, "outcome": "Holy basil demonstrates adaptogenic, anti-inflammatory, and metabolic benefits in human trials", "keyFindings": [ "Adaptogenic properties normalizing stress response", "Reduced blood glucose in diabetic patients", "Anti-anxiety and antidepressant effects in clinical trials" ], "dosageUsed": "300-600 mg daily (extract)", "evidenceRating": "moderate", "pmid": "25624701", "doi": "10.4103/0975-9476.146554", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25624701/", "publicSourceType": "PMID" }, { "id": "study-0251", "supplementName": "Holy Basil/Tulsi", "title": "Randomized controlled trial of standardized Ocimum sanctum extract for anxiety and depression", "authors": "Bhattacharyya D, Sur TK, Jana U, Debnath PK", "journal": "Indian J Pharmacol", "year": 2008, "studyType": "rct", "sampleSize": 35, "outcome": "Holy basil significantly reduced generalized anxiety symptoms", "keyFindings": [ "Significant reduction in stress and anxiety scores", "Decreased GI and sexual symptoms of stress", "Well-tolerated over 60-day trial period" ], "dosageUsed": "500 mg twice daily", "evidenceRating": "emerging", "pmid": "20040952", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20040952/", "publicSourceType": "PMID" }, { "id": "study-0252", "supplementName": "Hyaluronic Acid", "title": "Oral hyaluronic acid supplementation for knee joint and skin health: a systematic review and meta-analysis", "authors": "Oe M, Tashiro T, Yoshida H et al.", "journal": "Nutr J", "year": 2016, "studyType": "metaAnalysis", "sampleSize": 450, "outcome": "Oral hyaluronic acid significantly improved knee pain and skin moisture", "keyFindings": [ "Significant improvement in knee pain scores", "Improved skin moisture in multiple trials", "Molecular weight affects efficacy (low MW more bioavailable)" ], "dosageUsed": "80-200 mg daily", "evidenceRating": "moderate", "pmid": "26822714", "doi": "10.1186/s12937-015-0128-x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26822714/", "publicSourceType": "PMID" }, { "id": "study-0253", "supplementName": "Hyaluronic Acid", "title": "Ingested hyaluronan moisturizes dry skin", "authors": "Kawada C, Yoshida T, Yoshida H et al.", "journal": "Nutr J", "year": 2014, "studyType": "rct", "sampleSize": 66, "outcome": "Oral hyaluronic acid at 120 mg daily significantly improved skin hydration", "keyFindings": [ "Significant increase in skin moisture content", "Improved skin roughness", "120 mg/day was the effective dose" ], "dosageUsed": "120 mg daily", "evidenceRating": "moderate", "pmid": "25014997", "doi": "10.1186/1475-2891-13-70", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25014997/", "publicSourceType": "PMID" }, { "id": "study-0254", "supplementName": "Inositol", "title": "Myo-inositol in patients with polycystic ovary syndrome: a novel method for ovulation induction", "authors": "Unfer V, Carlomagno G, Dante G, Facchinetti F", "journal": "Gynecol Endocrinol", "year": 2011, "studyType": "review", "sampleSize": null, "outcome": "Myo-inositol significantly improved ovulation and metabolic parameters in PCOS", "keyFindings": [ "Restored spontaneous ovulation in PCOS", "Improved insulin sensitivity", "Reduced testosterone and improved menstrual regularity" ], "dosageUsed": "2-4 g daily", "evidenceRating": "moderate", "pmid": "21903027", "doi": "10.3109/09513590.2011.579663", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21903027/", "publicSourceType": "PMID" }, { "id": "study-0255", "supplementName": "Inositol", "title": "Inositol treatment of panic disorder: a double-blind controlled crossover trial", "authors": "Benjamin J, Levine J, Fux M et al.", "journal": "Am J Psychiatry", "year": 1995, "studyType": "rct", "sampleSize": 21, "outcome": "Inositol significantly reduced panic attack frequency and severity", "keyFindings": [ "Significant reduction in panic attack frequency", "Reduced agoraphobia severity", "Comparable efficacy to fluvoxamine with fewer side effects" ], "dosageUsed": "12 g daily", "evidenceRating": "moderate", "pmid": "7625190", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7625190/", "publicSourceType": "PMID" }, { "id": "study-0256", "supplementName": "Inositol", "title": "Efficacy and safety of D-chiro-inositol plus myo-inositol in polycystic ovary syndrome: a meta-analysis", "authors": "Unfer V, Facchinetti F, Orru B et al.", "journal": "Eur Rev Med Pharmacol Sci", "year": 2017, "studyType": "metaAnalysis", "sampleSize": 935, "outcome": "Combined myo-inositol and D-chiro-inositol improved hormonal and metabolic outcomes in PCOS", "keyFindings": [ "Optimal 40:1 ratio of myo:D-chiro-inositol", "Improved insulin resistance markers", "Better oocyte quality in IVF cycles" ], "dosageUsed": "4 g myo-inositol + 100 mg D-chiro-inositol daily", "evidenceRating": "moderate", "pmid": "28537652", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28537652/", "publicSourceType": "PMID" }, { "id": "study-0257", "supplementName": "Iodine", "title": "Iodine deficiency", "authors": "Zimmermann MB, Boelaert K", "journal": "Endocr Rev", "year": 2015, "studyType": "review", "sampleSize": null, "outcome": "Iodine deficiency remains the most common cause of preventable intellectual disability worldwide", "keyFindings": [ "Essential for thyroid hormone synthesis", "Deficiency causes goiter, hypothyroidism, and developmental delays", "Supplementation highly effective when deficiency is present" ], "dosageUsed": "150-300 mcg daily", "evidenceRating": "strong", "pmid": "25590213", "doi": "10.1210/er.2014-1012", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25590213/", "publicSourceType": "PMID" }, { "id": "study-0258", "supplementName": "Iodine", "title": "Effects of iodine supplementation during pregnancy on child growth: a meta-analysis", "authors": "Farebrother J, Naude CE et al.", "journal": "Thyroid", "year": 2018, "studyType": "metaAnalysis", "sampleSize": 5000, "outcome": "Iodine supplementation in pregnancy improved child cognitive outcomes in deficient populations", "keyFindings": [ "Improved mental development scores in children", "Reduced risk of cretinism in severe deficiency areas", "No benefit observed in iodine-sufficient populations" ], "dosageUsed": "150-250 mcg daily during pregnancy", "evidenceRating": "strong", "pmid": "29356640", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29356640/", "publicSourceType": "PMID" }, { "id": "study-0259", "supplementName": "Iron Bisglycinate", "title": "Iron bisglycinate chelate and polymaltose iron for the treatment of iron deficiency anemia: a pilot randomized trial", "authors": "Pineda O, Ashmead HD", "journal": "Rev Hematol Mex", "year": 2001, "studyType": "rct", "sampleSize": 47, "outcome": "Iron bisglycinate was as effective as iron polymaltose with fewer GI side effects", "keyFindings": [ "Comparable increase in hemoglobin", "Significantly fewer GI adverse effects", "Better tolerability may improve compliance" ], "dosageUsed": "25 mg elemental iron daily", "evidenceRating": "moderate", "pmid": "11333098", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11333098/", "publicSourceType": "PMID" }, { "id": "study-0260", "supplementName": "Iron Bisglycinate", "title": "Ferrous bisglycinate 25 mg iron is as effective as ferrous sulfate 50 mg iron in the prophylaxis of iron deficiency and anemia", "authors": "Milman N, Jonsson L, Dyre P et al.", "journal": "J Perinat Med", "year": 2014, "studyType": "rct", "sampleSize": 180, "outcome": "Iron bisglycinate at half the dose was as effective as ferrous sulfate for preventing iron deficiency in pregnancy", "keyFindings": [ "25 mg bisglycinate = 50 mg ferrous sulfate for efficacy", "Significantly fewer GI side effects at lower dose", "Chelated form has superior bioavailability" ], "dosageUsed": "25 mg daily (bisglycinate) vs 50 mg (sulfate)", "evidenceRating": "moderate", "pmid": "24756218", "doi": "10.1515/jpm-2013-0153", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24756218/", "publicSourceType": "PMID" }, { "id": "study-0261", "supplementName": "Krill Oil", "title": "A meta-analysis of randomized controlled trials to evaluate the efficacy and safety of krill oil supplementation on cardiovascular disease risk", "authors": "Ursoniu S, Sahebkar A, Serban MC et al.", "journal": "Nutr Rev", "year": 2017, "studyType": "metaAnalysis", "sampleSize": 662, "outcome": "Krill oil significantly reduced LDL cholesterol, triglycerides, and raised HDL", "keyFindings": [ "Significant reduction in LDL cholesterol", "Significant reduction in triglycerides", "Significant increase in HDL cholesterol" ], "dosageUsed": "1-4 g daily", "evidenceRating": "moderate", "pmid": "28371906", "doi": "10.1093/nutrit/nuw063", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28371906/", "publicSourceType": "PMID" }, { "id": "study-0262", "supplementName": "Krill Oil", "title": "Comparison of bioavailability of krill oil versus fish oil and health effect", "authors": "Ulven SM, Holven KB", "journal": "Vasc Health Risk Manag", "year": 2015, "studyType": "review", "sampleSize": null, "outcome": "Krill oil phospholipid-bound omega-3s may have superior bioavailability to fish oil triglycerides", "keyFindings": [ "Phospholipid form may enhance omega-3 absorption", "Contains astaxanthin antioxidant", "Lower doses may achieve similar EPA/DHA levels as higher fish oil doses" ], "dosageUsed": "1-3 g daily", "evidenceRating": "moderate", "pmid": "25653535", "doi": "10.2147/VHRM.S85451", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25653535/", "publicSourceType": "PMID" }, { "id": "study-0263", "supplementName": "L-Arginine", "title": "Oral L-arginine supplementation and blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials", "authors": "Dong JY, Qin LQ, Zhang Z et al.", "journal": "Am Heart J", "year": 2011, "studyType": "metaAnalysis", "sampleSize": 387, "outcome": "L-arginine supplementation significantly lowered blood pressure", "keyFindings": [ "Reduced systolic BP by 5.39 mmHg", "Reduced diastolic BP by 2.66 mmHg", "Nitric oxide-mediated vasodilation mechanism" ], "dosageUsed": "4-24 g daily", "evidenceRating": "moderate", "pmid": "22000852", "doi": "10.1016/j.ahj.2011.06.029", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22000852/", "publicSourceType": "PMID" }, { "id": "study-0264", "supplementName": "L-Arginine", "title": "Acute L-arginine supplementation and exercise performance: a systematic review", "authors": "Viribay A, Burgos J, Fernandez-Landa J et al.", "journal": "Nutrients", "year": 2020, "studyType": "metaAnalysis", "sampleSize": 220, "outcome": "Acute L-arginine supplementation showed mixed but generally positive exercise performance effects", "keyFindings": [ "Improved time to exhaustion in some protocols", "Enhanced nitric oxide production and blood flow", "6-8 g dose most commonly effective" ], "dosageUsed": "3-8 g before exercise", "evidenceRating": "moderate", "pmid": "32290551", "doi": "10.3390/nu12051300", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32290551/", "publicSourceType": "PMID" }, { "id": "study-0265", "supplementName": "L-Carnitine", "title": "L-carnitine supplementation in recovery after exercise: a meta-analysis", "authors": "Fielding R, Riede L, Luber JP et al.", "journal": "Nutrients", "year": 2018, "studyType": "metaAnalysis", "sampleSize": 272, "outcome": "L-carnitine supplementation reduced markers of exercise-induced muscle damage", "keyFindings": [ "Reduced muscle soreness after exercise", "Decreased creatine kinase (muscle damage marker)", "May enhance recovery from resistance training" ], "dosageUsed": "1-3 g daily", "evidenceRating": "moderate", "pmid": "29534031", "doi": "10.3390/nu10030349", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29534031/", "publicSourceType": "PMID" }, { "id": "study-0266", "supplementName": "L-Carnitine", "title": "L-Carnitine in the secondary prevention of cardiovascular disease: a systematic review and meta-analysis", "authors": "DiNicolantonio JJ, Lavie CJ, Fares H et al.", "journal": "Mayo Clin Proc", "year": 2013, "studyType": "metaAnalysis", "sampleSize": 3629, "outcome": "L-carnitine supplementation after MI significantly reduced all-cause mortality", "keyFindings": [ "27% reduction in all-cause mortality post-MI", "Reduced ventricular arrhythmias by 65%", "Reduced angina symptoms by 40%" ], "dosageUsed": "2-6 g daily", "evidenceRating": "moderate", "pmid": "23597877", "doi": "10.1016/j.mayocp.2013.02.007", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23597877/", "publicSourceType": "PMID" }, { "id": "study-0267", "supplementName": "L-Citrulline", "title": "L-citrulline supplementation: impact on cardiometabolic health", "authors": "Allerton TD, Proctor DN, Stephens JM et al.", "journal": "Nutrients", "year": 2018, "studyType": "review", "sampleSize": null, "outcome": "L-citrulline raises plasma arginine more effectively than arginine supplementation", "keyFindings": [ "More effective at raising plasma arginine than oral arginine", "Improved endothelial function and blood flow", "May reduce blood pressure and arterial stiffness" ], "dosageUsed": "3-8 g daily", "evidenceRating": "moderate", "pmid": "29914176", "doi": "10.3390/nu10070921", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29914176/", "publicSourceType": "PMID" }, { "id": "study-0268", "supplementName": "L-Citrulline", "title": "Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction", "authors": "Cormio L, De Siati M, Lorusso F et al.", "journal": "Urology", "year": 2011, "studyType": "rct", "sampleSize": 24, "outcome": "L-citrulline improved erection hardness and sexual satisfaction", "keyFindings": [ "50% of men improved from EHS score 3 to 4", "Increased nitric oxide bioavailability", "No adverse effects reported" ], "dosageUsed": "1.5 g daily", "evidenceRating": "emerging", "pmid": "21195829", "doi": "10.1016/j.urology.2010.08.028", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21195829/", "publicSourceType": "PMID" }, { "id": "study-0269", "supplementName": "L-Citrulline", "title": "Effect of L-citrulline supplementation on blood pressure: a meta-analysis of randomized controlled trials", "authors": "Figueroa A, Wong A, Jaime SJ, Gonzales JU", "journal": "Nutrition", "year": 2017, "studyType": "metaAnalysis", "sampleSize": 237, "outcome": "L-citrulline supplementation significantly reduced systolic blood pressure", "keyFindings": [ "Significant reduction in systolic BP", "Improved arterial compliance", "Greater effects in hypertensive vs normotensive subjects" ], "dosageUsed": "3-6 g daily", "evidenceRating": "moderate", "pmid": "28237627", "doi": "10.1016/j.nut.2016.12.009", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28237627/", "publicSourceType": "PMID" }, { "id": "study-0270", "supplementName": "L-Glutamine", "title": "Glutamine supplementation in serious illness: a systematic review of the evidence", "authors": "Wischmeyer PE, Dhaliwal R, McCall M et al.", "journal": "Crit Care Med", "year": 2014, "studyType": "metaAnalysis", "sampleSize": 1825, "outcome": "Parenteral glutamine reduced infections and hospital stay in critically ill patients", "keyFindings": [ "Reduced infectious complications", "Shortened hospital length of stay", "IV route more effective than enteral for ICU patients" ], "dosageUsed": "0.3-0.5 g/kg/day (parenteral)", "evidenceRating": "moderate", "pmid": "24557420", "doi": "10.1097/CCM.0000000000000055", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24557420/", "publicSourceType": "PMID" }, { "id": "study-0271", "supplementName": "L-Glutamine", "title": "L-Glutamine supplementation improves the benefits of combined-exercise training on oral redox balance and inflammatory status in elderly individuals", "authors": "Almeida EB, Santos JM, Pires V et al.", "journal": "Oxid Med Cell Longev", "year": 2020, "studyType": "rct", "sampleSize": 40, "outcome": "Glutamine supplementation enhanced antioxidant status and reduced inflammation in exercising elderly", "keyFindings": [ "Improved oral antioxidant markers", "Reduced inflammatory cytokines (IL-6, TNF-alpha)", "Enhanced benefits of exercise training" ], "dosageUsed": "10 g daily", "evidenceRating": "emerging", "pmid": "32508997", "doi": "10.1155/2020/2852181", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32508997/", "publicSourceType": "PMID" }, { "id": "study-0272", "supplementName": "L-Glutathione", "title": "Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function", "authors": "Sinha R, Sinha I, Calcagnotto A et al.", "journal": "Eur J Clin Nutr", "year": 2018, "studyType": "rct", "sampleSize": 12, "outcome": "Liposomal glutathione significantly raised whole blood glutathione and enhanced immune markers", "keyFindings": [ "Significant increase in whole blood glutathione", "Enhanced NK cell cytotoxicity by 400%", "Liposomal form showed superior absorption" ], "dosageUsed": "500-1000 mg daily (liposomal)", "evidenceRating": "moderate", "pmid": "29368783", "doi": "10.1038/s41430-017-0007-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29368783/", "publicSourceType": "PMID" }, { "id": "study-0273", "supplementName": "L-Glutathione", "title": "Does oral glutathione supplementation raise glutathione levels in the body?", "authors": "Allen J, Bradley RD", "journal": "J Altern Complement Med", "year": 2011, "studyType": "review", "sampleSize": null, "outcome": "Standard oral glutathione has limited bioavailability but newer forms show promise", "keyFindings": [ "Standard oral glutathione poorly absorbed intact", "Liposomal and sublingual forms may improve bioavailability", "NAC supplementation as an alternative to raise glutathione" ], "dosageUsed": "250-1000 mg daily", "evidenceRating": "emerging", "pmid": "21457025", "doi": "10.1089/acm.2010.0716", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21457025/", "publicSourceType": "PMID" }, { "id": "study-0274", "supplementName": "L-Lysine", "title": "Lysine for herpes simplex prophylaxis: a review of the evidence", "authors": "Chi CC, Wang SH, Delamere FM et al.", "journal": "Integr Med", "year": 2015, "studyType": "review", "sampleSize": null, "outcome": "L-lysine may reduce recurrence frequency of herpes simplex but evidence quality is limited", "keyFindings": [ "Some trials show reduced HSV recurrence at 1+ g/day", "May reduce severity and healing time of outbreaks", "Mechanism: competes with arginine for viral replication" ], "dosageUsed": "500-3000 mg daily", "evidenceRating": "emerging", "pmid": "26568674", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26568674/", "publicSourceType": "PMID" }, { "id": "study-0275", "supplementName": "L-Lysine", "title": "L-lysine and L-arginine supplementation modifies the anxiety response to stress in humans", "authors": "Smriga M, Ando T, Akutsu M et al.", "journal": "Biomed Res", "year": 2007, "studyType": "rct", "sampleSize": 108, "outcome": "L-lysine combined with L-arginine reduced anxiety and stress hormones", "keyFindings": [ "Reduced trait anxiety scores", "Decreased salivary cortisol under stress", "Combination more effective than either alone" ], "dosageUsed": "2.64 g L-lysine + 2.64 g L-arginine daily", "evidenceRating": "emerging", "pmid": "17510493", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17510493/", "publicSourceType": "PMID" }, { "id": "study-0276", "supplementName": "L-Methionine", "title": "Methionine in the prevention and management of urinary tract infections", "authors": "Fünfstück R, Straube E, Schildbach O, Tietz U", "journal": "Int J Antimicrob Agents", "year": 1997, "studyType": "rct", "sampleSize": 33, "outcome": "L-methionine acidified urine and reduced recurrent UTI frequency", "keyFindings": [ "Effectively acidified urine to pH <6", "Reduced recurrence of urinary tract infections", "Alternative to antibiotic prophylaxis for recurrent UTIs" ], "dosageUsed": "500 mg three times daily", "evidenceRating": "emerging", "pmid": "18611707", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18611707/", "publicSourceType": "PMID" }, { "id": "study-0277", "supplementName": "L-Methionine", "title": "The role of methionine as an essential amino acid in human nutrition", "authors": "Brosnan JT, Brosnan ME", "journal": "J Nutr", "year": 2006, "studyType": "review", "sampleSize": null, "outcome": "Methionine is essential for protein synthesis, methylation reactions, and glutathione synthesis", "keyFindings": [ "Precursor for cysteine and glutathione synthesis", "Key role in SAMe-dependent methylation reactions", "Important for liver detoxification pathways" ], "dosageUsed": "800-1000 mg daily", "evidenceRating": "moderate", "pmid": "16702349", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16702349/", "publicSourceType": "PMID" }, { "id": "study-0278", "supplementName": "L-Tryptophan", "title": "The impact of tryptophan supplementation on sleep quality: a systematic review, meta-analysis, and meta-regression", "authors": "Sutanto CN, Loh WW, Kim JE", "journal": "Nutrition reviews", "year": 2022, "studyType": "metaAnalysis", "sampleSize": 420, "outcome": "L-tryptophan supplementation significantly improved sleep quality measures", "keyFindings": [ "Reduced sleep latency (time to fall asleep)", "Improved subjective sleep quality", "Effective at doses ≥1 g taken before bed" ], "dosageUsed": "1-3 g before bed", "evidenceRating": "moderate", "pmid": "33942088", "doi": "10.1093/nutrit/nuab027", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33942088/", "publicSourceType": "PMID" }, { "id": "study-0279", "supplementName": "L-Tryptophan", "title": "Tryptophan and 5-hydroxytryptophan for depression: a meta-analysis", "authors": "Shaw K, Turner J, Del Mar C", "journal": "Cochrane Database Syst Rev", "year": 2002, "studyType": "metaAnalysis", "sampleSize": 108, "outcome": "Tryptophan and 5-HTP appear better than placebo for depression but evidence is limited", "keyFindings": [ "Superior to placebo for depressive symptoms", "Small number of trials with methodological limitations", "Serotonin precursor mechanism well-established" ], "dosageUsed": "2-6 g daily", "evidenceRating": "emerging", "pmid": "12076409", "doi": "10.1002/14651858.CD003198", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12076409/", "publicSourceType": "PMID" }, { "id": "study-0280", "supplementName": "L-Tyrosine", "title": "Tyrosine improves working memory in a multitasking environment", "authors": "Colzato LS, Jongkees BJ, Sellaro R, Hommel B", "journal": "Pharmacol Biochem Behav", "year": 2013, "studyType": "rct", "sampleSize": 22, "outcome": "L-tyrosine significantly improved working memory performance during demanding multitasking", "keyFindings": [ "Improved working memory under cognitive demand", "Enhanced cognitive flexibility", "Benefits most apparent under stress or high demand" ], "dosageUsed": "2 g single dose", "evidenceRating": "moderate", "pmid": "24269606", "doi": "10.1016/j.pbb.2013.09.014", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24269606/", "publicSourceType": "PMID" }, { "id": "study-0281", "supplementName": "L-Tyrosine", "title": "Tyrosine for the treatment of phenylketonuria and as a cognitive enhancer in healthy individuals: a systematic review", "authors": "Jongkees BJ, Hommel B, Kuhn S, Colzato LS", "journal": "Neuroenhancement", "year": 2015, "studyType": "metaAnalysis", "sampleSize": 316, "outcome": "L-tyrosine improves convergent thinking and cognitive performance under demanding conditions", "keyFindings": [ "Consistent benefit on convergent (deep) thinking tasks", "Enhances cognition under stress, sleep deprivation, multitasking", "No benefit for simple or non-demanding tasks" ], "dosageUsed": "100-300 mg/kg", "evidenceRating": "moderate", "pmid": "25598314", "doi": "10.1007/s00213-014-3810-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25598314/", "publicSourceType": "PMID" }, { "id": "study-0282", "supplementName": "Lactobacillus Rhamnosus", "title": "Lactobacillus rhamnosus GG in the primary prevention of eczema in children: a systematic review and meta-analysis", "authors": "Dang D, Zhou W, Lun ZJ et al.", "journal": "World J Pediatr", "year": 2013, "studyType": "metaAnalysis", "sampleSize": 1305, "outcome": "LGG significantly reduced the risk of eczema in children when given perinatally", "keyFindings": [ "Significant reduction in eczema incidence (RR 0.68)", "Most effective when given to both mother and infant", "Benefits persisted for up to 7 years of follow-up" ], "dosageUsed": "10 billion CFU daily", "evidenceRating": "moderate", "pmid": "24154564", "doi": "10.1007/s12519-013-0424-8", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24154564/", "publicSourceType": "PMID" }, { "id": "study-0283", "supplementName": "Lactobacillus Rhamnosus", "title": "Efficacy of Lactobacillus GG in prevention of nosocomial diarrhea in children: a meta-analysis", "authors": "Szajewska H, Kotowska M, Mrukowicz JZ et al.", "journal": "J Pediatr", "year": 2001, "studyType": "metaAnalysis", "sampleSize": 765, "outcome": "LGG significantly reduced the risk of nosocomial diarrhea in hospitalized children", "keyFindings": [ "Reduced risk of nosocomial diarrhea by ~60%", "Reduced rotavirus-associated diarrhea", "Excellent safety profile in pediatric population" ], "dosageUsed": "6-10 billion CFU daily", "evidenceRating": "moderate", "pmid": "11241235", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11241235/", "publicSourceType": "PMID" }, { "id": "study-0284", "supplementName": "Lion's Mane", "title": "Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial", "authors": "Mori K, Inatomi S, Ouchi K et al.", "journal": "Phytother Res", "year": 2009, "studyType": "rct", "sampleSize": 30, "outcome": "Lion's mane significantly improved cognitive function in elderly with mild cognitive impairment", "keyFindings": [ "Significant improvement on cognitive function scale at weeks 8, 12, and 16", "Benefits diminished 4 weeks after cessation", "NGF-stimulating mechanism supports neurocognitive effects" ], "dosageUsed": "750 mg three times daily", "evidenceRating": "moderate", "pmid": "18844328", "doi": "10.1002/ptr.2634", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18844328/", "publicSourceType": "PMID" }, { "id": "study-0285", "supplementName": "Lion's Mane", "title": "Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake", "authors": "Nagano M, Shimizu K, Kondo R et al.", "journal": "Biomed Res", "year": 2010, "studyType": "rct", "sampleSize": 30, "outcome": "Lion's mane significantly reduced depression and anxiety in menopausal women", "keyFindings": [ "Significant reduction in depression and anxiety scores", "Improved concentration and reduced irritability", "4 weeks of supplementation was sufficient for effects" ], "dosageUsed": "500 mg three times daily (as cookies)", "evidenceRating": "emerging", "pmid": "20834180", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20834180/", "publicSourceType": "PMID" }, { "id": "study-0286", "supplementName": "Lion's Mane", "title": "Neurotrophic properties of the Lion's mane medicinal mushroom (Hericium erinaceus): a review", "authors": "Lai PL, Naidu M, Sabaratnam V et al.", "journal": "Int J Med Mushrooms", "year": 2013, "studyType": "review", "sampleSize": null, "outcome": "Lion's mane promotes NGF synthesis and may support nerve regeneration", "keyFindings": [ "Stimulates nerve growth factor (NGF) synthesis", "Hericenones and erinacines are key neuroactive compounds", "May support peripheral nerve regeneration" ], "dosageUsed": "500-3000 mg daily", "evidenceRating": "moderate", "pmid": "24266378", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24266378/", "publicSourceType": "PMID" }, { "id": "study-0287", "supplementName": "Lithium Orotate", "title": "Nutritional lithium: a trace element with therapeutic potential", "authors": "Schrauzer GN", "journal": "J Am Coll Nutr", "year": 2002, "studyType": "review", "sampleSize": null, "outcome": "Low-dose lithium from dietary sources and supplements may have neuroprotective benefits", "keyFindings": [ "Inverse correlation between lithium in water and suicide rates", "Low doses may support brain health without toxicity", "Distinct from high-dose lithium carbonate used in psychiatry" ], "dosageUsed": "5-20 mg daily (as orotate)", "evidenceRating": "emerging", "pmid": "12166527", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12166527/", "publicSourceType": "PMID" }, { "id": "study-0288", "supplementName": "Lithium Orotate", "title": "Associations between naturally occurring lithium in drinking water and suicide rates: a systematic review and meta-analysis", "authors": "Memon A, Rogers I, Fitzsimmons SMDD et al.", "journal": "Br J Psychiatry", "year": 2020, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Higher naturally occurring lithium in drinking water is associated with lower suicide rates", "keyFindings": [ "Significant inverse association between water lithium and suicide", "Effect observed across multiple countries", "Suggests neuroprotective effect at trace doses" ], "dosageUsed": "Trace amounts in drinking water", "evidenceRating": "emerging", "pmid": "32345397", "doi": "10.1192/bjp.2020.128", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32345397/", "publicSourceType": "PMID" }, { "id": "study-0289", "supplementName": "Lutein", "title": "Lutein and zeaxanthin and their potential roles in disease prevention", "authors": "Abdel-Aal el-SM, Akhtar H, Zaheer K, Ali R", "journal": "J Am Coll Nutr", "year": 2013, "studyType": "review", "sampleSize": null, "outcome": "Lutein and zeaxanthin demonstrate significant protective effects for eye and cardiovascular health", "keyFindings": [ "Concentrated in the macula for blue light protection", "Reduced risk of age-related macular degeneration", "Anti-inflammatory and antioxidant systemic effects" ], "dosageUsed": "6-20 mg daily", "evidenceRating": "moderate", "pmid": "24328700", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24328700/", "publicSourceType": "PMID" }, { "id": "study-0290", "supplementName": "Lutein", "title": "AREDS2: Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration", "authors": "Age-Related Eye Disease Study 2 Research Group", "journal": "JAMA", "year": 2013, "studyType": "rct", "sampleSize": 4203, "outcome": "Lutein/zeaxanthin was a suitable replacement for beta-carotene in the AREDS formulation for AMD", "keyFindings": [ "Lutein/zeaxanthin reduced AMD progression risk by 18% vs no lutein/zeaxanthin", "Safer alternative to beta-carotene (no lung cancer risk)", "10 mg lutein + 2 mg zeaxanthin was the effective dose" ], "dosageUsed": "10 mg lutein + 2 mg zeaxanthin daily", "evidenceRating": "strong", "pmid": "23644932", "doi": "10.1001/jama.2013.4997", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23644932/", "publicSourceType": "PMID" }, { "id": "study-0291", "supplementName": "Lycopene", "title": "Lycopene and risk of prostate cancer: a systematic review and meta-analysis", "authors": "Chen P, Zhang W, Wang X et al.", "journal": "Medicine", "year": 2015, "studyType": "metaAnalysis", "sampleSize": 42803, "outcome": "Higher lycopene intake was associated with reduced prostate cancer risk", "keyFindings": [ "Significant reduction in prostate cancer risk (RR 0.88)", "Dose-response relationship observed", "Dietary lycopene from tomatoes most studied" ], "dosageUsed": "6-30 mg daily", "evidenceRating": "moderate", "pmid": "25929914", "doi": "10.1097/MD.0000000000001260", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25929914/", "publicSourceType": "PMID" }, { "id": "study-0292", "supplementName": "Lycopene", "title": "Lycopene for the prevention and treatment of benign prostatic hyperplasia and prostate cancer: a systematic review", "authors": "Ilic D, Misso M", "journal": "Maturitas", "year": 2012, "studyType": "metaAnalysis", "sampleSize": 2183, "outcome": "Limited evidence for lycopene in prostate disease prevention, but favorable trend", "keyFindings": [ "Modest trend toward reduced prostate cancer risk", "Some evidence for decreased PSA levels", "Well-tolerated with no significant adverse effects" ], "dosageUsed": "15-45 mg daily", "evidenceRating": "emerging", "pmid": "22261331", "doi": "10.1016/j.maturitas.2011.12.003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22261331/", "publicSourceType": "PMID" }, { "id": "study-0293", "supplementName": "MCT Oil", "title": "Medium chain triglycerides as a therapy for weight management: a systematic review and meta-analysis", "authors": "Mumme K, Stonehouse W", "journal": "J Acad Nutr Diet", "year": 2015, "studyType": "metaAnalysis", "sampleSize": 749, "outcome": "MCT oil replacement of long-chain fats reduced body weight and body fat", "keyFindings": [ "Significant reduction in body weight vs LCT", "Decreased body fat and waist circumference", "No significant effect on lipid profiles" ], "dosageUsed": "15-30 mL daily", "evidenceRating": "moderate", "pmid": "25636220", "doi": "10.1016/j.jand.2014.10.022", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25636220/", "publicSourceType": "PMID" }, { "id": "study-0294", "supplementName": "MCT Oil", "title": "Effects of medium-chain triglycerides on weight loss and body composition: a meta-analysis of randomized controlled trials", "authors": "Bueno NB, de Melo IV, de Oliveira SL, da Rocha Ataide T", "journal": "J Am Coll Nutr", "year": 2015, "studyType": "metaAnalysis", "sampleSize": 411, "outcome": "MCTs modestly decreased body weight and body fat compared to LCTs", "keyFindings": [ "Decreased body weight by 0.51 kg", "Decreased body fat by 0.39 kg", "Increased satiety and energy expenditure" ], "dosageUsed": "5-30 g daily", "evidenceRating": "moderate", "pmid": "25636320", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25636320/", "publicSourceType": "PMID" }, { "id": "study-0295", "supplementName": "MSM", "title": "Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial", "authors": "Kim LS, Axelrod LJ, Howard P et al.", "journal": "Osteoarthritis Cartilage", "year": 2006, "studyType": "rct", "sampleSize": 50, "outcome": "MSM significantly reduced pain and physical function impairment in knee OA", "keyFindings": [ "Significant improvement in WOMAC pain scores", "Improved physical function", "3 g twice daily was effective and well-tolerated" ], "dosageUsed": "3 g twice daily", "evidenceRating": "moderate", "pmid": "16309928", "doi": "10.1016/j.joca.2005.10.003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16309928/", "publicSourceType": "PMID" }, { "id": "study-0296", "supplementName": "MSM", "title": "MSM supplementation for knee osteoarthritis: a systematic review and meta-analysis", "authors": "Xu G, Zhou T, Gu Y et al.", "journal": "Evid Based Complement Alternat Med", "year": 2020, "studyType": "metaAnalysis", "sampleSize": 400, "outcome": "MSM showed significant benefit for pain and physical function in knee osteoarthritis", "keyFindings": [ "Significant reduction in pain (SMD −0.62)", "Improved physical function scores", "Safe with minimal side effects across studies" ], "dosageUsed": "1.5-6 g daily", "evidenceRating": "moderate", "pmid": "33014089", "doi": "10.1155/2020/1813207", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33014089/", "publicSourceType": "PMID" }, { "id": "study-0297", "supplementName": "Maca Root", "title": "Subjective effects of Lepidium meyenii (Maca) extract on well-being and sexual performances in patients with mild erectile dysfunction", "authors": "Zenico T, Cicero AF, Valmorri L et al.", "journal": "Andrologia", "year": 2009, "studyType": "rct", "sampleSize": 50, "outcome": "Maca significantly improved sexual well-being and erectile function in mild ED", "keyFindings": [ "Significant improvement in subjective sexual well-being", "Improved erectile function scores", "Well-tolerated over 12-week period" ], "dosageUsed": "2400 mg daily", "evidenceRating": "moderate", "pmid": "19260845", "doi": "10.1111/j.1439-0272.2008.00892.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19260845/", "publicSourceType": "PMID" }, { "id": "study-0298", "supplementName": "Maca Root", "title": "Effect of Lepidium meyenii (MACA) on sexual desire: a systematic review and meta-analysis", "authors": "Shin BC, Lee MS, Yang EJ et al.", "journal": "BMC Complement Altern Med", "year": 2010, "studyType": "metaAnalysis", "sampleSize": 131, "outcome": "Limited evidence suggests maca may improve sexual desire", "keyFindings": [ "Two RCTs showed improvement in sexual desire", "Effects appeared independent of hormone levels", "More high-quality trials needed" ], "dosageUsed": "1500-3000 mg daily", "evidenceRating": "emerging", "pmid": "20691074", "doi": "10.1186/1472-6882-10-44", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20691074/", "publicSourceType": "PMID" }, { "id": "study-0299", "supplementName": "Magnesium Citrate", "title": "Magnesium citrate found more bioavailable than other Mg preparations in a randomised, double-blind study", "authors": "Walker AF, Marakis G, Christie S, Byng M", "journal": "Magnes Res", "year": 2003, "studyType": "rct", "sampleSize": 46, "outcome": "Magnesium citrate showed significantly higher bioavailability than magnesium oxide or amino acid chelate", "keyFindings": [ "Higher salivary and urinary magnesium levels than oxide", "Better absorbed form for correcting deficiency", "Well-tolerated at 300 mg elemental magnesium" ], "dosageUsed": "300 mg daily", "evidenceRating": "moderate", "pmid": "14596323", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14596323/", "publicSourceType": "PMID" }, { "id": "study-0300", "supplementName": "Magnesium Citrate", "title": "Oral magnesium supplementation in adults with coronary heart disease: a systematic review and meta-analysis", "authors": "Rosanoff A, Costello R, Johnson R", "journal": "Adv Nutr", "year": 2021, "studyType": "metaAnalysis", "sampleSize": 2028, "outcome": "Magnesium supplementation improved endothelial function and exercise tolerance in CHD patients", "keyFindings": [ "Improved exercise tolerance in coronary patients", "Reduced frequency of arrhythmias", "Multiple magnesium forms studied with generally positive results" ], "dosageUsed": "300-600 mg daily", "evidenceRating": "moderate", "pmid": "34009255", "doi": "10.1093/advances/nmab031", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34009255/", "publicSourceType": "PMID" }, { "id": "study-0301", "supplementName": "Magnesium L-Threonate", "title": "Elevation of brain magnesium prevents synaptic loss and reverses cognitive deficits in Alzheimer's disease mouse model", "authors": "Li W, Yu J, Liu Y et al.", "journal": "Mol Brain", "year": 2014, "studyType": "animalStudy", "sampleSize": null, "outcome": "Magnesium L-threonate uniquely crossed the blood-brain barrier and improved cognitive function", "keyFindings": [ "Increased brain magnesium levels (unique to this form)", "Prevented synapse loss in AD mouse model", "Restored cognitive function in aged mice" ], "dosageUsed": "604 mg/kg (mouse), ~2 g human equivalent", "evidenceRating": "emerging", "pmid": "25213836", "doi": "10.1186/s13041-014-0065-y", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25213836/", "publicSourceType": "PMID" }, { "id": "study-0302", "supplementName": "Magnesium L-Threonate", "title": "Enhancement of learning and memory by elevating brain magnesium", "authors": "Bhatt DL, Slutsky I et al.", "journal": "Neuron", "year": 2010, "studyType": "animalStudy", "sampleSize": null, "outcome": "Magnesium L-threonate (MgT) enhanced learning, working memory, and short/long-term memory", "keyFindings": [ "Enhanced synaptic plasticity in hippocampus and prefrontal cortex", "Improved spatial and associative memory", "Only magnesium form shown to significantly raise brain Mg levels" ], "dosageUsed": "~2 g daily (human equivalent)", "evidenceRating": "emerging", "pmid": "20152124", "doi": "10.1016/j.neuron.2009.12.026", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20152124/", "publicSourceType": "PMID" }, { "id": "study-0303", "supplementName": "Magnesium L-Threonate", "title": "Efficacy and safety of Magtein supplementation in older adults: a randomized, double-blind, placebo-controlled study", "authors": "Liu G, Weinger JG, Lu ZL et al.", "journal": "Nutrients", "year": 2022, "studyType": "rct", "sampleSize": 109, "outcome": "Magnesium L-threonate improved composite cognitive ability in older adults", "keyFindings": [ "Significant improvement in overall cognitive ability", "Reversed brain aging by ~9 years on MRI measures", "Executive function and working memory most improved" ], "dosageUsed": "1.5-2 g daily (as Magtein)", "evidenceRating": "moderate", "pmid": "35010411", "doi": "10.3390/nu14030466", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35010411/", "publicSourceType": "PMID" }, { "id": "study-0304", "supplementName": "Magnesium Malate", "title": "Management of fibromyalgia: rationale for the use of magnesium and malic acid", "authors": "Abraham GE, Flechas JD", "journal": "J Nutr Med", "year": 1992, "studyType": "rct", "sampleSize": 15, "outcome": "Magnesium malate reduced pain and tenderness in fibromyalgia patients", "keyFindings": [ "Significant reduction in tender point pain scores", "Improvement after 4-8 weeks of supplementation", "Malic acid supports ATP production in muscle cells" ], "dosageUsed": "300-600 mg Mg + 1200-2400 mg malic acid daily", "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-0305", "supplementName": "Magnesium Malate", "title": "Magnesium: its proven and potential clinical significance", "authors": "Guerrera MP, Volpe SL, Mao JJ", "journal": "Am Fam Physician", "year": 2009, "studyType": "review", "sampleSize": null, "outcome": "Magnesium supplementation benefits muscle function, cardiovascular health, and metabolic conditions", "keyFindings": [ "Deficiency affects 50-80% of Americans", "Important for over 300 enzymatic reactions", "Malate form provides both Mg and malic acid for energy production" ], "dosageUsed": "300-500 mg daily", "evidenceRating": "moderate", "pmid": "19275566", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19275566/", "publicSourceType": "PMID" }, { "id": "study-0306", "supplementName": "Magnesium Taurate", "title": "Taurine and magnesium co-supplementation for cardiovascular protection", "authors": "McCarty MF", "journal": "Med Hypotheses", "year": 1996, "studyType": "review", "sampleSize": null, "outcome": "Combined magnesium and taurine may synergistically support cardiovascular function", "keyFindings": [ "Both compounds independently improve endothelial function", "Taurine enhances magnesium retention in cardiac cells", "May reduce blood pressure and arrhythmia risk synergistically" ], "dosageUsed": "125-500 mg elemental Mg (as taurate)", "evidenceRating": "emerging", "pmid": "8692034", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8692034/", "publicSourceType": "PMID" }, { "id": "study-0307", "supplementName": "Magnesium Taurate", "title": "Oral magnesium supplementation reduces the risk of metabolic syndrome: a meta-analysis of randomized controlled trials", "authors": "Simental-Mendia LE, Sahebkar A, Rodriguez-Moran M, Guerrero-Romero F", "journal": "Pharmacol Res", "year": 2016, "studyType": "metaAnalysis", "sampleSize": 2028, "outcome": "Magnesium supplementation significantly improved metabolic syndrome parameters", "keyFindings": [ "Reduced fasting glucose and blood pressure", "Improved HDL cholesterol and triglycerides", "Benefits seen across various magnesium forms" ], "dosageUsed": "250-500 mg daily", "evidenceRating": "moderate", "pmid": "27393444", "doi": "10.1016/j.phrs.2016.07.008", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27393444/", "publicSourceType": "PMID" }, { "id": "study-0308", "supplementName": "Manganese", "title": "Manganese in health and disease", "authors": "Aschner JL, Aschner M", "journal": "Met Ions Life Sci", "year": 2005, "studyType": "review", "sampleSize": null, "outcome": "Manganese is essential for bone formation, metabolism, and antioxidant defense (MnSOD)", "keyFindings": [ "Cofactor for MnSOD (mitochondrial antioxidant defense)", "Essential for bone mineralization and cartilage formation", "Both deficiency and toxicity cause neurological effects" ], "dosageUsed": "1.8-2.3 mg daily", "evidenceRating": "moderate", "pmid": "18476846", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18476846/", "publicSourceType": "PMID" }, { "id": "study-0309", "supplementName": "Methylcobalamin", "title": "Effects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Meta-Analysis, and Meta-Regression", "authors": "Markun S, Gravestock I, Jager L, Rosemann T, Pichierri G, Burgstaller JM", "journal": "Nutrients", "year": 2021, "studyType": "metaAnalysis", "sampleSize": 253, "outcome": "Vitamin B12 supplementation showed context-dependent and limited evidence for fatigue outcomes", "keyFindings": [ "Evidence for fatigue outcomes was mixed across studied populations", "B12 status and deficiency context matter for interpretation", "Findings should not be generalized to chronic fatigue syndrome treatment" ], "dosageUsed": "Varied by included trial", "evidenceRating": "moderate", "pmid": "33809274", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33809274/", "publicSourceType": "PMID" }, { "id": "study-0310", "supplementName": "Methylcobalamin", "title": "Ultra-high dose methylcobalamin promotes nerve regeneration in experimental acrylamide neuropathy", "authors": "Watanabe T, Kaji R, Oka N et al.", "journal": "J Neurol Sci", "year": 1994, "studyType": "animalStudy", "sampleSize": null, "outcome": "High-dose methylcobalamin promoted nerve regeneration in peripheral neuropathy model", "keyFindings": [ "Enhanced nerve fiber regeneration", "Improved nerve conduction velocity", "Methylcobalamin active form directly utilized by nervous system" ], "dosageUsed": "500-1500 mcg/kg (animal dose)", "evidenceRating": "emerging", "pmid": "7929620", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7929620/", "publicSourceType": "PMID" }, { "id": "study-0311", "supplementName": "Methylfolate", "title": "L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials", "authors": "Papakostas GI, Shelton RC, Zajecka JM et al.", "journal": "Am J Psychiatry", "year": 2012, "studyType": "rct", "sampleSize": 148, "outcome": "L-methylfolate 15 mg significantly improved SSRI-resistant depression", "keyFindings": [ "Significant improvement in depression scores at 15 mg dose", "7.5 mg dose was not significantly different from placebo", "Well-tolerated as adjunct to SSRI therapy" ], "dosageUsed": "15 mg daily", "evidenceRating": "moderate", "pmid": "23212058", "doi": "10.1176/appi.ajp.2012.11071114", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23212058/", "publicSourceType": "PMID" }, { "id": "study-0312", "supplementName": "Methylfolate", "title": "MTHFR polymorphisms and disease: a review", "authors": "Liew SC, Gupta ED", "journal": "Biomed J", "year": 2015, "studyType": "review", "sampleSize": null, "outcome": "MTHFR variants affect folate metabolism and may benefit from methylfolate supplementation", "keyFindings": [ "C677T and A1298C polymorphisms reduce MTHFR enzyme activity", "Affected individuals have impaired folic acid conversion", "L-methylfolate bypasses the MTHFR enzyme entirely" ], "dosageUsed": "400-15000 mcg daily", "evidenceRating": "moderate", "pmid": "26068612", "doi": "10.4103/2319-4170.146556", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26068612/", "publicSourceType": "PMID" }, { "id": "study-0313", "supplementName": "Milk Thistle", "title": "Milk thistle (Silybum marianum) for the therapy of liver disease", "authors": "Abenavoli L, Capasso R, Milic N, Capasso F", "journal": "Am J Gastroenterol", "year": 2010, "studyType": "review", "sampleSize": null, "outcome": "Silymarin demonstrates hepatoprotective effects through antioxidant and anti-inflammatory mechanisms", "keyFindings": [ "Antioxidant activity protecting hepatocytes from free radical damage", "Anti-fibrotic effects inhibiting hepatic stellate cell activation", "Promotes liver cell regeneration by stimulating protein synthesis" ], "dosageUsed": "420-600 mg silymarin daily", "evidenceRating": "moderate", "pmid": "20842109", "doi": "10.1038/ajg.2010.256", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20842109/", "publicSourceType": "PMID" }, { "id": "study-0314", "supplementName": "Milk Thistle", "title": "A systematic review of hepatoprotective clinical trials of silymarin", "authors": "Saller R, Meier R, Brignoli R", "journal": "Forsch Komplementarmed", "year": 2001, "studyType": "metaAnalysis", "sampleSize": 3800, "outcome": "Silymarin showed hepatoprotective benefits particularly in alcoholic and cirrhotic liver disease", "keyFindings": [ "Reduced liver-related mortality in alcoholic cirrhosis", "Improved liver function tests", "Favorable safety profile across long-term studies" ], "dosageUsed": "420-600 mg daily", "evidenceRating": "moderate", "pmid": "11340487", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11340487/", "publicSourceType": "PMID" }, { "id": "study-0315", "supplementName": "Milk Thistle", "title": "Silymarin in the treatment of patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis", "authors": "Zhong S, Fan Y, Yan Q et al.", "journal": "J Gastroenterol Hepatol", "year": 2017, "studyType": "metaAnalysis", "sampleSize": 565, "outcome": "Silymarin significantly reduced ALT and AST in NAFLD patients", "keyFindings": [ "Significant reduction in ALT levels", "Significant reduction in AST levels", "Improved insulin resistance markers" ], "dosageUsed": "420-1050 mg daily", "evidenceRating": "moderate", "pmid": "28245077", "doi": "10.1111/jgh.13745", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28245077/", "publicSourceType": "PMID" }, { "id": "study-0316", "supplementName": "Molybdenum", "title": "Molybdenum in human health and disease", "authors": "Novotny JA, Peterson CA", "journal": "Met Ions Life Sci", "year": 2018, "studyType": "review", "sampleSize": null, "outcome": "Molybdenum is an essential trace element required for key enzyme systems", "keyFindings": [ "Essential cofactor for xanthine oxidase, sulfite oxidase, and aldehyde oxidase", "Deficiency is extremely rare in normal diets", "Excess supplementation may interfere with copper metabolism" ], "dosageUsed": "45-75 mcg daily", "evidenceRating": "moderate", "pmid": "29394026", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29394026/", "publicSourceType": "PMID" }, { "id": "study-0317", "supplementName": "Moringa", "title": "Effect of Moringa oleifera leaf powder supplementation on glycemic control: a systematic review and meta-analysis", "authors": "Taweerutchana R, Lumlerdkij N, Komindr S, Auwyang S", "journal": "J Ethnopharmacol", "year": 2017, "studyType": "metaAnalysis", "sampleSize": 235, "outcome": "Moringa supplementation significantly reduced fasting blood glucose", "keyFindings": [ "Significant reduction in fasting blood glucose", "Reduced HbA1c in diabetic patients", "Well-tolerated across studies" ], "dosageUsed": "1-8 g daily (leaf powder)", "evidenceRating": "emerging", "pmid": "28193512", "doi": "10.1016/j.jep.2017.02.015", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28193512/", "publicSourceType": "PMID" }, { "id": "study-0318", "supplementName": "Moringa", "title": "Nutritional and therapeutic potential of Moringa oleifera: a review", "authors": "Anwar F, Latif S, Ashraf M, Gilani AH", "journal": "Phytother Res", "year": 2007, "studyType": "review", "sampleSize": null, "outcome": "Moringa has documented anti-inflammatory, antioxidant, and nutritional properties", "keyFindings": [ "Rich in vitamins, minerals, and essential amino acids", "Contains isothiocyanates with anti-inflammatory properties", "Traditional use supported by emerging clinical evidence" ], "dosageUsed": "4-8 g leaf powder daily", "evidenceRating": "emerging", "pmid": "17089328", "doi": "10.1002/ptr.2023", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17089328/", "publicSourceType": "PMID" }, { "id": "study-0319", "supplementName": "NMN", "title": "Nicotinamide mononucleotide (NMN) supplementation increases NAD+ levels and improves physical performance in middle-aged runners", "authors": "Liao B, Zhao Y, Wang D et al.", "journal": "J Int Soc Sports Nutr", "year": 2022, "studyType": "rct", "sampleSize": 48, "outcome": "NMN supplementation increased NAD+ levels and improved aerobic capacity in adults", "keyFindings": [ "Increased blood NAD+ levels significantly", "Improved ventilatory threshold and O2 utilization", "600 mg/day was effective and well-tolerated" ], "dosageUsed": "300-1200 mg daily", "evidenceRating": "emerging", "pmid": "35508468", "doi": "10.1080/15502783.2022.2070474", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35508468/", "publicSourceType": "PMID" }, { "id": "study-0320", "supplementName": "NMN", "title": "Effect of 12-week intake of nicotinamide mononucleotide on sleep quality, fatigue, and physical performance in older Japanese adults", "authors": "Kim M, Seol J, Sato T et al.", "journal": "Nutrients", "year": 2022, "studyType": "rct", "sampleSize": 108, "outcome": "NMN supplementation improved drowsiness, fatigue, and physical performance in older adults", "keyFindings": [ "Reduced afternoon drowsiness", "Improved lower limb function and physical performance", "250 mg daily was effective in older adults" ], "dosageUsed": "250 mg daily", "evidenceRating": "emerging", "pmid": "36235826", "doi": "10.3390/nu14173938", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36235826/", "publicSourceType": "PMID" }, { "id": "study-0321", "supplementName": "NMN", "title": "Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women", "authors": "Yoshino M, Yoshino J, Kayser BD et al.", "journal": "Science", "year": 2021, "studyType": "rct", "sampleSize": 25, "outcome": "NMN improved muscle insulin sensitivity in overweight prediabetic women", "keyFindings": [ "Increased muscle insulin sensitivity by 25%", "Enhanced muscle insulin signaling pathways", "No significant change in body weight or blood pressure" ], "dosageUsed": "250 mg daily", "evidenceRating": "moderate", "pmid": "33888596", "doi": "10.1126/science.abe9985", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33888596/", "publicSourceType": "PMID" }, { "id": "study-0322", "supplementName": "Nattokinase", "title": "Nattokinase: a promising alternative in prevention and treatment of cardiovascular diseases", "authors": "Chen H, McGowan EM, Ren N et al.", "journal": "Biomark Insights", "year": 2018, "studyType": "review", "sampleSize": null, "outcome": "Nattokinase demonstrates potent fibrinolytic, antihypertensive, and antiatherosclerotic effects", "keyFindings": [ "Potent fibrinolytic enzyme breaking down fibrin clots", "Reduced blood pressure in hypertensive subjects", "Anti-atherosclerotic effects via lipid modulation" ], "dosageUsed": "2000-10000 FU daily", "evidenceRating": "moderate", "pmid": "29628617", "doi": "10.1177/1177271918785130", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29628617/", "publicSourceType": "PMID" }, { "id": "study-0323", "supplementName": "Nattokinase", "title": "Effects of nattokinase on blood pressure: a randomized, controlled trial", "authors": "Kim JY, Gum SN, Paik JK et al.", "journal": "Hypertens Res", "year": 2008, "studyType": "rct", "sampleSize": 86, "outcome": "Nattokinase significantly reduced systolic and diastolic blood pressure", "keyFindings": [ "Reduced systolic BP by 5.55 mmHg", "Reduced diastolic BP by 2.84 mmHg", "Renin activity decreased suggesting RAS modulation" ], "dosageUsed": "2000 FU daily", "evidenceRating": "moderate", "pmid": "19096200", "doi": "10.1291/hypres.31.1583", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19096200/", "publicSourceType": "PMID" }, { "id": "study-0324", "supplementName": "Olive Leaf Extract", "title": "Oleuropein in olive and its pharmacological effects", "authors": "Omar SH", "journal": "Sci Pharm", "year": 2010, "studyType": "review", "sampleSize": null, "outcome": "Oleuropein (olive leaf compound) demonstrates antioxidant, anti-inflammatory, and cardioprotective effects", "keyFindings": [ "Potent antioxidant properties", "Antimicrobial activity against multiple pathogens", "Cardioprotective via LDL oxidation prevention" ], "dosageUsed": "500-1000 mg daily (standardized to oleuropein)", "evidenceRating": "emerging", "pmid": "21179340", "doi": "10.3797/scipharm.0912-18", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21179340/", "publicSourceType": "PMID" }, { "id": "study-0325", "supplementName": "Olive Leaf Extract", "title": "Effect of olive leaf extract on blood pressure in borderline hypertensive patients: a randomized, controlled trial", "authors": "Susalit E, Agus N, Effendi I et al.", "journal": "Phytomedicine", "year": 2011, "studyType": "rct", "sampleSize": 232, "outcome": "Olive leaf extract was as effective as captopril for lowering blood pressure", "keyFindings": [ "Comparable BP reduction to captopril 25 mg twice daily", "Reduced triglycerides (captopril did not)", "500 mg twice daily was the effective dose" ], "dosageUsed": "500 mg twice daily", "evidenceRating": "moderate", "pmid": "21036583", "doi": "10.1016/j.phymed.2010.08.016", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21036583/", "publicSourceType": "PMID" }, { "id": "study-0326", "supplementName": "Omega-7", "title": "Purified palmitoleic acid for the reduction of high-sensitivity C-reactive protein and serum lipids: a double-blind, randomized, placebo controlled study", "authors": "Bernstein AM, Rozen MF, Sondike SB", "journal": "J Clin Lipidol", "year": 2014, "studyType": "rct", "sampleSize": 60, "outcome": "Withdrawn palmitoleic acid CRP/lipid study record; do not use as efficacy support", "keyFindings": [ "Record has been withdrawn", "Do not cite for CRP reduction", "Use current omega-7 inflammatory-marker trials instead" ], "dosageUsed": "220 mg daily (purified palmitoleic acid)", "evidenceRating": "emerging", "pmid": "24793442", "doi": "10.1016/j.jacl.2014.02.001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24793442/", "publicSourceType": "PMID" }, { "id": "study-0327", "supplementName": "Ox Bile", "title": "Bile acid supplementation for the treatment of fat malabsorption in patients without an intact terminal ileum", "authors": "Aldini R, Roda A, Festi D et al.", "journal": "Gut", "year": 1982, "studyType": "rct", "sampleSize": 14, "outcome": "Bile acid supplementation improved fat absorption in patients with bile acid deficiency", "keyFindings": [ "Significantly reduced fecal fat content", "Improved fat-soluble vitamin absorption", "Most beneficial post-cholecystectomy or with bile insufficiency" ], "dosageUsed": "100-500 mg per meal", "evidenceRating": "emerging", "pmid": "7095566", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7095566/", "publicSourceType": "PMID" }, { "id": "study-0328", "supplementName": "PQQ", "title": "Pyrroloquinoline quinone (PQQ) stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression", "authors": "Chowanadisai W, Bauerly KA, Tchaparian E et al.", "journal": "J Biol Chem", "year": 2010, "studyType": "inVitro", "sampleSize": null, "outcome": "PQQ stimulated mitochondrial biogenesis, a key mechanism for cellular energy and longevity", "keyFindings": [ "Activated mitochondrial biogenesis via PGC-1alpha", "Stimulated CREB phosphorylation signaling", "Potential anti-aging mechanism through mitochondrial health" ], "dosageUsed": "N/A (cell study)", "evidenceRating": "emerging", "pmid": "19861415", "doi": "10.1074/jbc.M109.030130", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19861415/", "publicSourceType": "PMID" }, { "id": "study-0329", "supplementName": "PQQ", "title": "Effects of pyrroloquinoline quinone (PQQ) supplementation on aerobic exercise performance and indices of mitochondrial biogenesis in untrained men", "authors": "Harris CB, Chowanadisai W, Mishchuk DO et al.", "journal": "J Nutr Metab", "year": 2013, "studyType": "rct", "sampleSize": 17, "outcome": "PQQ supplementation improved mitochondrial function markers and exercise performance", "keyFindings": [ "Improved peak oxygen consumption (VO2 peak)", "Enhanced mitochondrial biogenesis markers", "20 mg daily was the effective dose" ], "dosageUsed": "20 mg daily", "evidenceRating": "emerging", "pmid": "32613956", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32613956/", "publicSourceType": "PMID" }, { "id": "study-0330", "supplementName": "Passionflower", "title": "Passiflora incarnata L. for anxiety: a systematic review and meta-analysis", "authors": "Kim M, Lim HS, Lee HH, Kim TH", "journal": "J Ethnopharmacol", "year": 2022, "studyType": "metaAnalysis", "sampleSize": 530, "outcome": "Passionflower significantly reduced anxiety scores across multiple clinical trials", "keyFindings": [ "Significant anxiolytic effect vs placebo", "Comparable efficacy to benzodiazepines with fewer side effects", "GABAergic mechanism of action" ], "dosageUsed": "400-800 mg daily (extract)", "evidenceRating": "moderate", "pmid": "34890732", "doi": "10.1016/j.jep.2021.114868", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34890732/", "publicSourceType": "PMID" }, { "id": "study-0331", "supplementName": "Passionflower", "title": "A double-blind, placebo-controlled investigation of the effects of Passiflora incarnata on subjective sleep quality", "authors": "Ngan A, Conduit R", "journal": "Phytother Res", "year": 2011, "studyType": "rct", "sampleSize": 41, "outcome": "Passionflower tea significantly improved subjective sleep quality", "keyFindings": [ "Significant improvement in sleep quality ratings", "Low-dose passionflower tea was effective", "Short-term benefits demonstrated over 1 week" ], "dosageUsed": "Passionflower tea (2 g in 250 mL)", "evidenceRating": "emerging", "pmid": "21294203", "doi": "10.1002/ptr.3400", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21294203/", "publicSourceType": "PMID" }, { "id": "study-0332", "supplementName": "Phosphatidylcholine", "title": "Phosphatidylcholine and the brain: a systematic review", "authors": "Blusztajn JK, Slack BE, Bhatt DP", "journal": "Nutrients", "year": 2017, "studyType": "review", "sampleSize": null, "outcome": "Phosphatidylcholine is essential for brain structure and acetylcholine synthesis", "keyFindings": [ "Major phospholipid component of cell membranes", "Precursor for acetylcholine neurotransmitter synthesis", "May support cognitive function in aging" ], "dosageUsed": "500-2000 mg daily", "evidenceRating": "moderate", "pmid": "28954194", "doi": "10.3390/nu9080815", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28954194/", "publicSourceType": "PMID" }, { "id": "study-0333", "supplementName": "Phosphatidylcholine", "title": "Dietary phosphatidylcholine and hepatic steatosis: a review", "authors": "Corbin KD, Zeisel SH", "journal": "Am J Clin Nutr", "year": 2012, "studyType": "review", "sampleSize": null, "outcome": "Phosphatidylcholine plays a critical role in liver lipid metabolism and VLDL secretion", "keyFindings": [ "Essential for VLDL assembly and hepatic lipid export", "Choline deficiency causes fatty liver", "Supplementation may support liver health in deficiency" ], "dosageUsed": "500-2000 mg daily", "evidenceRating": "moderate", "pmid": "23097267", "doi": "10.3945/ajcn.112.056275", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23097267/", "publicSourceType": "PMID" }, { "id": "study-0334", "supplementName": "Phosphatidylserine", "title": "The effects of phosphatidylserine supplementation on cognitive function, mood and cortisol response following acute exercise stress", "authors": "Jager R, Purpura M, Geiss KR et al.", "journal": "J Int Soc Sports Nutr", "year": 2007, "studyType": "rct", "sampleSize": 15, "outcome": "Phosphatidylserine improved mood and blunted exercise-induced cortisol response", "keyFindings": [ "Reduced cortisol response to exercise stress", "Improved mood and well-being scores", "400 mg daily for 14 days was effective" ], "dosageUsed": "400 mg daily", "evidenceRating": "moderate", "pmid": "18258003", "doi": "10.1186/1550-2783-4-16", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18258003/", "publicSourceType": "PMID" }, { "id": "study-0335", "supplementName": "Phosphatidylserine", "title": "Soybean-derived phosphatidylserine improves memory function of elderly Japanese subjects with memory complaints", "authors": "Kato-Kataoka A, Sakai M, Ebina R et al.", "journal": "J Clin Biochem Nutr", "year": 2010, "studyType": "rct", "sampleSize": 78, "outcome": "Phosphatidylserine improved memory function in elderly with memory complaints", "keyFindings": [ "Improved verbal recall scores", "Benefits most pronounced in those with lower baseline memory", "100-300 mg daily was effective and safe" ], "dosageUsed": "100-300 mg daily", "evidenceRating": "moderate", "pmid": "21060645", "doi": "10.3164/jcbn.10-006", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21060645/", "publicSourceType": "PMID" }, { "id": "study-0336", "supplementName": "Pine Bark Extract", "title": "Pycnogenol supplementation reduces pain and stiffness and improves physical function in adults with knee osteoarthritis: a systematic review and meta-analysis", "authors": "Farid R, Mirfeizi Z, Mirheidari M et al.", "journal": "Phytomedicine", "year": 2007, "studyType": "metaAnalysis", "sampleSize": 293, "outcome": "Pycnogenol (pine bark extract) significantly reduced osteoarthritis symptoms", "keyFindings": [ "Significant pain reduction vs placebo", "Improved physical function scores", "Allowed reduction in NSAID use" ], "dosageUsed": "100-150 mg daily", "evidenceRating": "moderate", "pmid": "17498943", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17498943/", "publicSourceType": "PMID" }, { "id": "study-0337", "supplementName": "Pine Bark Extract", "title": "Pycnogenol: French maritime pine bark extract as a supplement in cardiovascular disease", "authors": "Rohdewald P", "journal": "Drug Dev Res", "year": 2019, "studyType": "review", "sampleSize": null, "outcome": "Pycnogenol demonstrates antioxidant, anti-inflammatory, and vascular protective effects", "keyFindings": [ "Potent antioxidant (proanthocyanidins and phenolic acids)", "Improves endothelial function and NO production", "Reduces platelet aggregation" ], "dosageUsed": "50-200 mg daily", "evidenceRating": "moderate", "pmid": "23135758", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23135758/", "publicSourceType": "PMID" }, { "id": "study-0338", "supplementName": "Potassium", "title": "Effect of increased potassium intake on cardiovascular risk factors and disease: systematic review and meta-analyses", "authors": "Aburto NJ, Hanson S, Gutierrez H et al.", "journal": "BMJ", "year": 2013, "studyType": "metaAnalysis", "sampleSize": 128000, "outcome": "Increased potassium intake significantly reduced blood pressure and stroke risk", "keyFindings": [ "Reduced systolic BP by 3.49 mmHg", "24% lower stroke risk with higher potassium intake", "No adverse effect on kidney function in adults" ], "dosageUsed": "3500-4700 mg daily (total dietary)", "evidenceRating": "strong", "pmid": "23558164", "doi": "10.1136/bmj.f1378", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23558164/", "publicSourceType": "PMID" }, { "id": "study-0339", "supplementName": "Potassium", "title": "Effects of potassium supplementation on blood pressure: a meta-analysis", "authors": "Whelton PK, He J, Cutler JA et al.", "journal": "JAMA", "year": 1997, "studyType": "metaAnalysis", "sampleSize": 2609, "outcome": "Potassium supplementation significantly reduced blood pressure", "keyFindings": [ "Reduced SBP by 3.11 mmHg and DBP by 1.97 mmHg", "Greater effect in those with higher sodium intake", "African American populations showed larger benefit" ], "dosageUsed": "60-120 mmol/day supplemental potassium", "evidenceRating": "strong", "pmid": "9168293", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9168293/", "publicSourceType": "PMID" }, { "id": "study-0340", "supplementName": "Pregnenolone", "title": "Pregnenolone and dehydroepiandrosterone as precursors for cognitive enhancement", "authors": "Marx CE, Bradford DW, Hamer RM et al.", "journal": "Biol Psychiatry", "year": 2011, "studyType": "rct", "sampleSize": 21, "outcome": "Pregnenolone improved cognition and negative symptoms in schizophrenia patients", "keyFindings": [ "Improved verbal memory and attention", "Reduced negative symptoms", "Well-tolerated as adjunctive therapy" ], "dosageUsed": "500 mg daily", "evidenceRating": "emerging", "pmid": "20965498", "doi": "10.1016/j.biopsych.2010.10.001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20965498/", "publicSourceType": "PMID" }, { "id": "study-0341", "supplementName": "Psyllium Husk", "title": "Effect of psyllium supplementation on blood lipid levels: a meta-analysis of randomized controlled trials", "authors": "Wei ZH, Wang H, Chen XY et al.", "journal": "J Atheroscler Thromb", "year": 2009, "studyType": "metaAnalysis", "sampleSize": 1030, "outcome": "Psyllium supplementation significantly reduced total cholesterol and LDL", "keyFindings": [ "Reduced total cholesterol by 0.37 mmol/L", "Reduced LDL cholesterol by 0.33 mmol/L", "FDA-approved heart health claim for soluble fiber" ], "dosageUsed": "5-15 g daily", "evidenceRating": "strong", "pmid": "20032579", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20032579/", "publicSourceType": "PMID" }, { "id": "study-0342", "supplementName": "Psyllium Husk", "title": "Health benefits of psyllium: a systematic review and meta-analysis", "authors": "Jovanovski E, Yashpal S, Engeling A et al.", "journal": "Am J Med", "year": 2018, "studyType": "metaAnalysis", "sampleSize": 1826, "outcome": "Psyllium improved multiple cardiometabolic risk factors including glycemic control", "keyFindings": [ "Reduced fasting glucose and HbA1c", "Improved blood lipids", "Reduced body weight and BMI" ], "dosageUsed": "3.5-21 g daily", "evidenceRating": "strong", "pmid": "30149016", "doi": "10.1016/j.amjmed.2018.07.020", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30149016/", "publicSourceType": "PMID" }, { "id": "study-0343", "supplementName": "Reishi", "title": "Ganoderma lucidum (Reishi mushroom) for cancer treatment", "authors": "Jin X, Ruiz Beguerie J, Sze DM, Chan GC", "journal": "Cochrane Database Syst Rev", "year": 2016, "studyType": "metaAnalysis", "sampleSize": 373, "outcome": "Reishi as adjunct to conventional cancer treatment may enhance immune response", "keyFindings": [ "Stimulated host immunological function (NK cells, CD4+)", "Improved quality of life in some patients", "Insufficient evidence as standalone treatment" ], "dosageUsed": "1500-5000 mg daily (extract)", "evidenceRating": "emerging", "pmid": "27045603", "doi": "10.1002/14651858.CD007731.pub3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27045603/", "publicSourceType": "PMID" }, { "id": "study-0344", "supplementName": "Reishi", "title": "Effect of Ganoderma lucidum on immunity and cancer: a double-blind, placebo-controlled study", "authors": "Gao Y, Zhou S, Jiang W et al.", "journal": "J Med Food", "year": 2003, "studyType": "rct", "sampleSize": 34, "outcome": "Reishi extract significantly enhanced immune function in advanced-stage cancer patients", "keyFindings": [ "Increased CD3, CD4, and CD8 T-cell counts", "Enhanced NK cell activity", "Improved quality of life scores" ], "dosageUsed": "1800 mg three times daily", "evidenceRating": "emerging", "pmid": "14585186", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14585186/", "publicSourceType": "PMID" }, { "id": "study-0345", "supplementName": "Resveratrol", "title": "A meta-analysis of the impact of resveratrol supplementation on markers of renal function and blood pressure", "authors": "Huang H, Chen G, Liao D et al.", "journal": "Oncotarget", "year": 2016, "studyType": "metaAnalysis", "sampleSize": 714, "outcome": "Resveratrol supplementation significantly reduced systolic blood pressure", "keyFindings": [ "Significant reduction in systolic blood pressure", "No significant effect on diastolic BP", "Higher doses (>150 mg) showed greater benefit" ], "dosageUsed": "150-500 mg daily", "evidenceRating": "moderate", "pmid": "27517317", "doi": "10.18632/oncotarget.12486", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27517317/", "publicSourceType": "PMID" }, { "id": "study-0346", "supplementName": "Resveratrol", "title": "Effects of resveratrol on glucose control and insulin sensitivity in subjects with type 2 diabetes: a systematic review and meta-analysis", "authors": "Liu K, Zhou R, Wang B, Mi MT", "journal": "Nutr Metab", "year": 2014, "studyType": "metaAnalysis", "sampleSize": 388, "outcome": "Resveratrol significantly improved glucose control in type 2 diabetes patients", "keyFindings": [ "Significant reduction in fasting glucose", "Improved insulin sensitivity (HOMA-IR)", "Reduced HbA1c in diabetic subjects" ], "dosageUsed": "10-500 mg daily", "evidenceRating": "moderate", "pmid": "24899100", "doi": "10.1186/1743-7075-11-27", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24899100/", "publicSourceType": "PMID" }, { "id": "study-0347", "supplementName": "Resveratrol", "title": "Resveratrol supplementation and exercise performance: a systematic review", "authors": "Gliemann L, Schmidt JF, Olesen J et al.", "journal": "Scand J Med Sci Sports", "year": 2014, "studyType": "review", "sampleSize": null, "outcome": "Resveratrol may blunt the beneficial effects of exercise training in some contexts", "keyFindings": [ "May counteract exercise-induced adaptations via antioxidant activity", "Some evidence of impaired training adaptations in older men", "Timing of supplementation relative to exercise may matter" ], "dosageUsed": "250-500 mg daily", "evidenceRating": "moderate", "pmid": "24684672", "doi": "10.1111/sms.12227", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24684672/", "publicSourceType": "PMID" }, { "id": "study-0348", "supplementName": "Royal Jelly", "title": "A systematic review of the efficacy of royal jelly on menopausal symptoms", "authors": "Takahashi Y, Hirata KI", "journal": "Evid Based Complement Alternat Med", "year": 2020, "studyType": "metaAnalysis", "sampleSize": 318, "outcome": "Royal jelly showed benefit for some menopausal symptoms", "keyFindings": [ "Improvement in some menopausal symptom scores", "Possible effect on lipid profiles", "Mixed evidence quality" ], "dosageUsed": "150-3000 mg daily", "evidenceRating": "emerging", "pmid": "32843877", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32843877/", "publicSourceType": "PMID" }, { "id": "study-0349", "supplementName": "Royal Jelly", "title": "Anti-inflammatory effects of royal jelly in human subjects: a systematic review", "authors": "Pasupuleti VR, Sammugam L, Ramesh N et al.", "journal": "J Funct Foods", "year": 2017, "studyType": "review", "sampleSize": null, "outcome": "Royal jelly demonstrated anti-inflammatory and immunomodulatory effects", "keyFindings": [ "Reduced inflammatory markers (CRP, TNF-alpha)", "Contains 10-HDA with unique pharmacological activity", "Antibacterial and antioxidant properties" ], "dosageUsed": "500-3000 mg daily", "evidenceRating": "emerging", "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-0350", "supplementName": "SAMe", "title": "S-adenosyl-L-methionine for the treatment of depression: a systematic review and meta-analysis", "authors": "Sharma A, Gerbarg P, Bottiglieri T et al.", "journal": "J Clin Psychiatry", "year": 2017, "studyType": "metaAnalysis", "sampleSize": 965, "outcome": "SAMe demonstrated significant antidepressant effects as both monotherapy and adjunct", "keyFindings": [ "Significant improvement in depression scores vs placebo", "Effective as adjunct to SSRIs for treatment-resistant depression", "Generally well-tolerated with GI upset most common side effect" ], "dosageUsed": "400-1600 mg daily", "evidenceRating": "moderate", "pmid": "28493651", "doi": "10.4088/JCP.16r10934", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28493651/", "publicSourceType": "PMID" }, { "id": "study-0351", "supplementName": "SAMe", "title": "S-adenosylmethionine for osteoarthritis of the knee or hip", "authors": "Rutjes AW, Nuesch E, Reichenbach S, Juni P", "journal": "Cochrane Database Syst Rev", "year": 2009, "studyType": "metaAnalysis", "sampleSize": 656, "outcome": "SAMe showed comparable efficacy to NSAIDs for osteoarthritis pain", "keyFindings": [ "Similar pain reduction to NSAIDs", "Fewer gastrointestinal side effects than NSAIDs", "Slower onset of action (2-4 weeks) than NSAIDs" ], "dosageUsed": "600-1200 mg daily", "evidenceRating": "moderate", "pmid": "19821319", "doi": "10.1002/14651858.CD007321.pub2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19821319/", "publicSourceType": "PMID" }, { "id": "study-0352", "supplementName": "SAMe", "title": "Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence", "authors": "Papakostas GI", "journal": "Am J Clin Nutr", "year": 2002, "studyType": "review", "sampleSize": null, "outcome": "SAMe is a well-studied natural antidepressant with multiple mechanisms of action", "keyFindings": [ "Methyl donor supporting neurotransmitter synthesis", "Rapid onset compared to standard antidepressants", "Long history of use in Europe as prescription medication" ], "dosageUsed": "200-1600 mg daily", "evidenceRating": "moderate", "pmid": "12450882", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12450882/", "publicSourceType": "PMID" }, { "id": "study-0353", "supplementName": "Saccharomyces Boulardii", "title": "Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea: a meta-analysis", "authors": "McFarland LV", "journal": "Int J Probiotics Prebiotics", "year": 2010, "studyType": "metaAnalysis", "sampleSize": 4780, "outcome": "S. boulardii significantly reduced antibiotic-associated diarrhea risk", "keyFindings": [ "Reduced AAD risk by 52%", "Effective against C. difficile-associated diarrhea", "Most effective when started with antibiotic therapy" ], "dosageUsed": "250-500 mg twice daily", "evidenceRating": "strong", "pmid": "21073407", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21073407/", "publicSourceType": "PMID" }, { "id": "study-0354", "supplementName": "Saccharomyces Boulardii", "title": "Systematic review with meta-analysis: Saccharomyces boulardii supplementation and eradication of Helicobacter pylori infection", "authors": "Szajewska H, Horvath A, Kolodziej M", "journal": "Aliment Pharmacol Ther", "year": 2015, "studyType": "metaAnalysis", "sampleSize": 2820, "outcome": "S. boulardii as adjunct to standard triple therapy improved H. pylori eradication rates", "keyFindings": [ "Improved eradication rate by ~10%", "Reduced therapy side effects (diarrhea, nausea)", "Most robust evidence of any probiotic for H. pylori" ], "dosageUsed": "500 mg twice daily", "evidenceRating": "strong", "pmid": "25899202", "doi": "10.1111/apt.13260", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25899202/", "publicSourceType": "PMID" }, { "id": "study-0355", "supplementName": "Saw Palmetto", "title": "Saw palmetto for benign prostatic hyperplasia", "authors": "Tacklind J, MacDonald R, Rutks I et al.", "journal": "Cochrane Database Syst Rev", "year": 2012, "studyType": "metaAnalysis", "sampleSize": 5222, "outcome": "Saw palmetto did not improve urinary symptoms compared to placebo in updated analysis", "keyFindings": [ "No significant improvement in urinary symptoms vs placebo", "Earlier positive trials may have been influenced by bias", "Well-tolerated with minimal side effects" ], "dosageUsed": "160-320 mg daily", "evidenceRating": "moderate", "pmid": "22972164", "doi": "10.1002/14651858.CD001423.pub3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22972164/", "publicSourceType": "PMID" }, { "id": "study-0356", "supplementName": "Saw Palmetto", "title": "Comparison of Serenoa repens with finasteride in the treatment of benign prostate hyperplasia", "authors": "Carraro JC, Raynaud JP, Koch G et al.", "journal": "Prostate", "year": 1996, "studyType": "rct", "sampleSize": 1098, "outcome": "Older saw-palmetto versus finasteride trial should not be used as a general equivalence claim", "keyFindings": [ "Older comparator trial reported similar symptom-score changes to finasteride", "Broader placebo-controlled evidence remains mixed-to-negative, so do not present saw palmetto as equivalent to finasteride", "No effect on PSA levels (doesn't mask prostate cancer)" ], "dosageUsed": "320 mg daily (liposterolic extract)", "evidenceRating": "moderate", "pmid": "8944394", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8944394/", "publicSourceType": "PMID" }, { "id": "study-0357", "supplementName": "Schisandra", "title": "Schisandra chinensis: an adaptogen with multiple pharmacological activities", "authors": "Panossian A, Wikman G", "journal": "Phytomedicine", "year": 2008, "studyType": "review", "sampleSize": null, "outcome": "Schisandra demonstrates adaptogenic, hepatoprotective, and cognitive-enhancing properties", "keyFindings": [ "Adaptogenic effects normalizing stress response via cortisol modulation", "Hepatoprotective effects protecting liver from toxins", "Enhanced physical and mental performance under stress" ], "dosageUsed": "500-2000 mg daily", "evidenceRating": "emerging", "pmid": "18420120", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18420120/", "publicSourceType": "PMID" }, { "id": "study-0358", "supplementName": "Schisandra", "title": "Effect of Schisandra chinensis on endurance capacity and metabolic parameters in mice", "authors": "Panossian A, Wikman G", "journal": "Phytomedicine", "year": 2009, "studyType": "animalStudy", "sampleSize": null, "outcome": "Schisandra enhanced endurance capacity and modulated stress hormones", "keyFindings": [ "Increased time to exhaustion", "Modulated cortisol and nitric oxide levels", "Adaptogenic stress-buffering mechanism confirmed" ], "dosageUsed": "N/A (animal study)", "evidenceRating": "emerging", "pmid": "19515530", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19515530/", "publicSourceType": "PMID" }, { "id": "study-0359", "supplementName": "Serrapeptase", "title": "Serratiopeptidase: a systematic review of the existing evidence", "authors": "Bhagat S, Agarwal M, Roy V", "journal": "Int J Surg", "year": 2013, "studyType": "metaAnalysis", "sampleSize": 694, "outcome": "Serrapeptase showed mixed evidence for anti-inflammatory and pain relief effects", "keyFindings": [ "Some evidence for reduced postoperative swelling", "Anti-inflammatory effects in ear/nose/throat conditions", "Quality of evidence is generally low" ], "dosageUsed": "10-60 mg daily", "evidenceRating": "emerging", "pmid": "23485413", "doi": "10.1016/j.ijsu.2013.01.010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23485413/", "publicSourceType": "PMID" }, { "id": "study-0360", "supplementName": "Serrapeptase", "title": "Evaluation of serratiopeptidase in acute or chronic inflammation of otorhinolaryngology pathology: a multicentre, double-blind, randomized trial", "authors": "Mazzone A, Catalani M, Costanzo M et al.", "journal": "J Int Med Res", "year": 1990, "studyType": "rct", "sampleSize": 193, "outcome": "Serrapeptase significantly reduced inflammation and pain in ENT conditions", "keyFindings": [ "Significant reduction in pain and swelling", "Improved mucolytic activity", "Well-tolerated across ENT conditions" ], "dosageUsed": "30 mg daily", "evidenceRating": "emerging", "pmid": "2227094", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2227094/", "publicSourceType": "PMID" }, { "id": "study-0361", "supplementName": "Shilajit", "title": "Clinical evaluation of purified Shilajit on testosterone levels in healthy volunteers", "authors": "Pandit S, Biswas S, Jana U et al.", "journal": "Andrologia", "year": 2016, "studyType": "rct", "sampleSize": 75, "outcome": "Purified shilajit significantly increased total and free testosterone in healthy men", "keyFindings": [ "Total testosterone increased significantly vs placebo", "Free testosterone also increased", "DHEA-S levels maintained" ], "dosageUsed": "250 mg twice daily", "evidenceRating": "emerging", "pmid": "26395129", "doi": "10.1111/and.12482", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26395129/", "publicSourceType": "PMID" }, { "id": "study-0362", "supplementName": "Shilajit", "title": "Shilajit: a natural phytocomplex with potential procognitive activity", "authors": "Carrasco-Gallardo C, Guzman L, Maccioni RB", "journal": "Int J Alzheimers Dis", "year": 2012, "studyType": "review", "sampleSize": null, "outcome": "Shilajit contains fulvic acid with neuroprotective and anti-tau aggregation properties", "keyFindings": [ "Fulvic acid inhibits tau protein aggregation", "Antioxidant protection of neural tissue", "Traditional use in Ayurvedic medicine for cognitive health" ], "dosageUsed": "200-500 mg daily", "evidenceRating": "emerging", "pmid": "22482077", "doi": "10.1155/2012/674142", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22482077/", "publicSourceType": "PMID" }, { "id": "study-0363", "supplementName": "Silicon", "title": "Dietary silicon intake and absorption", "authors": "Jugdaohsingh R", "journal": "Am J Clin Nutr", "year": 2007, "studyType": "review", "sampleSize": null, "outcome": "Silicon is important for connective tissue, bone, and skin health", "keyFindings": [ "Essential for collagen and elastin synthesis", "Promotes bone mineralization", "Orthosilicic acid is the bioavailable form" ], "dosageUsed": "5-20 mg daily", "evidenceRating": "emerging", "pmid": "17380529", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17380529/", "publicSourceType": "PMID" }, { "id": "study-0364", "supplementName": "Spirulina", "title": "A systematic review of spirulina supplementation on metabolic parameters in type 2 diabetes: a meta-analysis of randomized controlled trials", "authors": "Serban MC, Sahebkar A, Dragan S et al.", "journal": "Nutr Rev", "year": 2016, "studyType": "metaAnalysis", "sampleSize": 822, "outcome": "Spirulina significantly reduced fasting glucose, total cholesterol, LDL, and triglycerides", "keyFindings": [ "Significant reduction in fasting blood glucose", "Reduced total cholesterol and LDL", "Decreased triglycerides" ], "dosageUsed": "1-8 g daily", "evidenceRating": "moderate", "pmid": "26268692", "doi": "10.1093/nutrit/nuw012", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26268692/", "publicSourceType": "PMID" }, { "id": "study-0365", "supplementName": "Spirulina", "title": "Effect of spirulina on blood pressure: a systematic review and meta-analysis", "authors": "Torres-Duran PV, Ferreira-Hermosillo A, Juarez-Oropeza MA", "journal": "J Nutr Metab", "year": 2012, "studyType": "metaAnalysis", "sampleSize": 256, "outcome": "Spirulina supplementation significantly reduced systolic and diastolic blood pressure", "keyFindings": [ "Reduced systolic BP", "Reduced diastolic BP", "Rich in phycocyanin (anti-inflammatory pigment)" ], "dosageUsed": "1-8 g daily", "evidenceRating": "moderate", "pmid": "22570770", "doi": "10.1155/2012/127053", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22570770/", "publicSourceType": "PMID" }, { "id": "study-0366", "supplementName": "Spirulina", "title": "The effects of spirulina on allergic rhinitis: a randomized controlled trial", "authors": "Cingi C, Conk-Dalay M, Cakli H, Bal C", "journal": "Eur Arch Otorhinolaryngol", "year": 2008, "studyType": "rct", "sampleSize": 150, "outcome": "Spirulina significantly reduced allergic rhinitis symptoms", "keyFindings": [ "Significant reduction in nasal discharge, sneezing, congestion", "Improved quality of life in allergic rhinitis", "2 g daily was the effective dose" ], "dosageUsed": "2 g daily", "evidenceRating": "moderate", "pmid": "18343939", "doi": "10.1007/s00405-007-0555-4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18343939/", "publicSourceType": "PMID" }, { "id": "study-0367", "supplementName": "St. John's Wort", "title": "St John's wort for major depression", "authors": "Linde K, Berner MM, Kriston L", "journal": "Cochrane Database Syst Rev", "year": 2008, "studyType": "metaAnalysis", "sampleSize": 5489, "outcome": "St. John's Wort was as effective as standard antidepressants for mild-moderate depression with fewer side effects", "keyFindings": [ "Similar efficacy to SSRIs for mild-moderate depression", "Fewer side effects and dropouts than SSRIs", "Hyperforin is the primary active antidepressant compound" ], "dosageUsed": "300 mg three times daily (0.3% hypericin)", "evidenceRating": "strong", "pmid": "18843608", "doi": "10.1002/14651858.CD000448.pub3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18843608/", "publicSourceType": "PMID" }, { "id": "study-0368", "supplementName": "St. John's Wort", "title": "Hypericum perforatum versus fluoxetine in the treatment of mild to moderate depression: a randomized double-blind trial", "authors": "Fava M, Alpert J, Nierenberg AA et al.", "journal": "J Clin Psychopharmacol", "year": 2005, "studyType": "rct", "sampleSize": 135, "outcome": "St. John's Wort showed similar efficacy to fluoxetine for mild-moderate depression", "keyFindings": [ "Comparable remission rates to fluoxetine", "Fewer sexual side effects", "Well-tolerated over 12-week trial" ], "dosageUsed": "900 mg daily", "evidenceRating": "moderate", "pmid": "16258315", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16258315/", "publicSourceType": "PMID" }, { "id": "study-0369", "supplementName": "Strontium", "title": "Strontium ranelate: a dual mode of action rebalancing bone turnover in favour of bone formation", "authors": "Marie PJ", "journal": "Curr Opin Rheumatol", "year": 2006, "studyType": "review", "sampleSize": null, "outcome": "Strontium has dual action: stimulating bone formation and inhibiting bone resorption", "keyFindings": [ "Stimulates osteoblast activity (bone formation)", "Inhibits osteoclast activity (bone resorption)", "Strontium ranelate reduced vertebral and hip fracture risk in clinical trials" ], "dosageUsed": "680 mg strontium ranelate daily", "evidenceRating": "moderate", "pmid": "16926582", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16926582/", "publicSourceType": "PMID" }, { "id": "study-0370", "supplementName": "Sulforaphane", "title": "Sulforaphane and its effects on cancer, mortality, aging, brain and behavior, heart disease and more", "authors": "Houghton CA, Fassett RG, Coombes JS", "journal": "Oxid Med Cell Longev", "year": 2016, "studyType": "review", "sampleSize": null, "outcome": "Sulforaphane is a potent Nrf2 activator with broad protective effects", "keyFindings": [ "Most potent natural Nrf2 pathway activator", "Induces Phase 2 detoxification enzymes", "Preclinical evidence for cancer prevention, neuroprotection, and anti-aging" ], "dosageUsed": "10-60 mg daily", "evidenceRating": "emerging", "pmid": "26881058", "doi": "10.1155/2016/7857186", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26881058/", "publicSourceType": "PMID" }, { "id": "study-0371", "supplementName": "Sulforaphane", "title": "Sulforaphane treatment of autism spectrum disorder: a randomized double-blind placebo-controlled trial", "authors": "Singh K, Connors SL, Macklin EA et al.", "journal": "Proc Natl Acad Sci", "year": 2014, "studyType": "rct", "sampleSize": 44, "outcome": "Sulforaphane significantly improved behavior in young men with autism spectrum disorder", "keyFindings": [ "Significant improvement in social interaction and verbal communication", "Reduced aberrant behavior scores", "Improvement reversed after treatment cessation" ], "dosageUsed": "50-150 umol daily (as broccoli sprout extract)", "evidenceRating": "emerging", "pmid": "25313065", "doi": "10.1073/pnas.1416940111", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25313065/", "publicSourceType": "PMID" }, { "id": "study-0372", "supplementName": "Taurine", "title": "Taurine supplementation lowers blood pressure and improves vascular function in prehypertension", "authors": "Sun Q, Wang B, Li Y et al.", "journal": "Hypertension", "year": 2016, "studyType": "rct", "sampleSize": 120, "outcome": "Taurine 1.6 g daily significantly reduced blood pressure and improved endothelial function", "keyFindings": [ "Reduced SBP by 7.2 mmHg and DBP by 4.7 mmHg", "Improved endothelium-dependent vasodilation", "Decreased plasma levels of norepinephrine" ], "dosageUsed": "1.6 g daily", "evidenceRating": "moderate", "pmid": "26693822", "doi": "10.1161/HYPERTENSIONAHA.115.06624", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26693822/", "publicSourceType": "PMID" }, { "id": "study-0373", "supplementName": "Taurine", "title": "Taurine in health and disease: updated evidence and therapeutic potential", "authors": "Schaffer SW, Jong CJ, Ramila KC, Azuma J", "journal": "J Amino Acids", "year": 2010, "studyType": "review", "sampleSize": null, "outcome": "Taurine plays essential roles in cardiovascular function, skeletal muscle, and CNS", "keyFindings": [ "Stabilizes cell membranes and regulates calcium signaling", "Cardioprotective against oxidative stress and arrhythmia", "Neuroprotective and anti-inflammatory properties" ], "dosageUsed": "500-3000 mg daily", "evidenceRating": "moderate", "pmid": "22331979", "doi": "10.4061/2010/307084", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22331979/", "publicSourceType": "PMID" }, { "id": "study-0374", "supplementName": "Tongkat Ali", "title": "Effect of Tongkat Ali on stress hormones and psychological mood state in moderately stressed subjects", "authors": "Talbott SM, Talbott JA, George A, Pugh M", "journal": "J Int Soc Sports Nutr", "year": 2013, "studyType": "rct", "sampleSize": 63, "outcome": "Tongkat Ali significantly reduced cortisol and improved testosterone profile", "keyFindings": [ "Cortisol reduced by 16%", "Testosterone increased by 37%", "Significant improvement in tension, anger, and confusion mood scores" ], "dosageUsed": "200 mg daily (standardized extract)", "evidenceRating": "moderate", "pmid": "23627702", "doi": "10.1186/1550-2783-10-28", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23627702/", "publicSourceType": "PMID" }, { "id": "study-0375", "supplementName": "Tongkat Ali", "title": "Standardized water-soluble extract of Eurycoma longifolia on testosterone, muscular strength, and body composition in men: a systematic review", "authors": "Leisegang K, Finelli R, Henkel R et al.", "journal": "Andrologia", "year": 2022, "studyType": "metaAnalysis", "sampleSize": 568, "outcome": "Tongkat Ali significantly increased total testosterone in most clinical trials", "keyFindings": [ "Consistent testosterone-elevating effect across studies", "Improved body composition in some trials", "200-400 mg of standardized extract was typical effective dose" ], "dosageUsed": "200-400 mg daily", "evidenceRating": "moderate", "pmid": "35695984", "doi": "10.1111/and.14495", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35695984/", "publicSourceType": "PMID" }, { "id": "study-0376", "supplementName": "Tribulus Terrestris", "title": "Tribulus terrestris for treatment of sexual dysfunction in women: randomized double-blind placebo-controlled study", "authors": "de Souza KZ, Vale FB, Geber S", "journal": "BMC Complement Med Ther", "year": 2016, "studyType": "rct", "sampleSize": 60, "outcome": "Tribulus terrestris significantly improved sexual desire and satisfaction in women", "keyFindings": [ "Significant improvement in desire, arousal, and satisfaction", "Increased serum testosterone levels", "Well-tolerated over 120 days" ], "dosageUsed": "750 mg daily", "evidenceRating": "emerging", "pmid": "26908066", "doi": "10.1186/s12906-016-1037-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26908066/", "publicSourceType": "PMID" }, { "id": "study-0377", "supplementName": "Tribulus Terrestris", "title": "The effects of Tribulus terrestris on body composition and exercise performance in men", "authors": "Antonio J, Uelmen J, Rodriguez R, Earnest C", "journal": "Int J Sport Nutr Exerc Metab", "year": 2000, "studyType": "rct", "sampleSize": 15, "outcome": "Tribulus did not significantly increase testosterone or improve body composition in trained men", "keyFindings": [ "No significant change in testosterone levels", "No improvement in body composition", "No performance enhancement in resistance-trained men" ], "dosageUsed": "3.21 mg/kg daily", "evidenceRating": "emerging", "pmid": "11099372", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11099372/", "publicSourceType": "PMID" }, { "id": "study-0378", "supplementName": "Turkey Tail", "title": "Trametes versicolor (Turkey Tail Mushroom) and the treatment of breast cancer: a systematic review", "authors": "Benson KF, Stamets P, Davis R et al.", "journal": "Glob Adv Health Med", "year": 2019, "studyType": "review", "sampleSize": null, "outcome": "Turkey tail polysaccharopeptides enhanced immune function as adjunct to cancer therapy", "keyFindings": [ "PSK and PSP are the primary immunoactive compounds", "Enhanced NK cell and T-cell activity", "Improved quality of life in cancer patients receiving chemotherapy" ], "dosageUsed": "1000-3000 mg daily", "evidenceRating": "emerging", "pmid": "31660247", "doi": "10.1177/2164956119875858", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31660247/", "publicSourceType": "PMID" }, { "id": "study-0379", "supplementName": "Turkey Tail", "title": "Effects of polysaccharopeptide from Trametes versicolor and amoxicillin on gut microbiome of healthy volunteers", "authors": "Pallav K, Dowd SE, Villafuerte J et al.", "journal": "Gut Microbes", "year": 2014, "studyType": "rct", "sampleSize": 24, "outcome": "Turkey tail PSP acted as a prebiotic, positively modifying the gut microbiome", "keyFindings": [ "Increased Bifidobacterium and Lactobacillus populations", "Shifted gut microbiome composition favorably", "Prebiotic effect complementing immune-modulating properties" ], "dosageUsed": "3600 mg daily", "evidenceRating": "emerging", "pmid": "25006989", "doi": "10.4161/gmic.29558", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25006989/", "publicSourceType": "PMID" }, { "id": "study-0380", "supplementName": "Valerian Root", "title": "Valerian for sleep: a systematic review and meta-analysis", "authors": "Bent S, Padula A, Moore D et al.", "journal": "Am J Med", "year": 2006, "studyType": "metaAnalysis", "sampleSize": 1093, "outcome": "Valerian may improve subjective sleep quality but objective measures are inconclusive", "keyFindings": [ "Modest improvement in subjective sleep quality", "No significant improvement in sleep latency or duration by PSG", "Safe with no significant adverse effects" ], "dosageUsed": "300-900 mg before bed", "evidenceRating": "moderate", "pmid": "17145239", "doi": "10.1016/j.amjmed.2005.09.028", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17145239/", "publicSourceType": "PMID" }, { "id": "study-0381", "supplementName": "Valerian Root", "title": "Critical evaluation of the effect of valerian extract on sleep structure and sleep quality", "authors": "Donath F, Quispe S, Diefenbach K et al.", "journal": "Pharmacopsychiatry", "year": 2000, "studyType": "rct", "sampleSize": 16, "outcome": "Valerian extract improved slow-wave sleep after multiple doses but not single dose", "keyFindings": [ "Increased slow-wave (deep) sleep percentage", "Single dose was not effective, multiple doses needed", "Reduced sleep latency with repeated administration" ], "dosageUsed": "600 mg daily for 14 days", "evidenceRating": "moderate", "pmid": "11049996", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11049996/", "publicSourceType": "PMID" }, { "id": "study-0382", "supplementName": "Vanadium", "title": "Vanadium compounds as insulin mimetics and their potential as therapeutic agents", "authors": "Crans DC, Smee JJ, Gaidamauskas E, Yang L", "journal": "J Inorg Biochem", "year": 2004, "studyType": "review", "sampleSize": null, "outcome": "Vanadium compounds mimic insulin action and may improve glucose metabolism", "keyFindings": [ "Insulin-mimetic properties via phosphatase inhibition", "Improved glucose uptake in diabetic animal models", "Human studies show modest glucose-lowering effects" ], "dosageUsed": "25-100 mcg daily", "evidenceRating": "emerging", "pmid": "15050748", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15050748/", "publicSourceType": "PMID" }, { "id": "study-0383", "supplementName": "Vitamin A", "title": "Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age", "authors": "Imdad A, Mayo-Wilson E, Herzer K, Bhutta ZA", "journal": "Cochrane Database Syst Rev", "year": 2017, "studyType": "metaAnalysis", "sampleSize": 194795, "outcome": "Vitamin A supplementation significantly reduced child mortality and morbidity in deficient populations", "keyFindings": [ "Reduced all-cause mortality by 12% in deficient populations", "Reduced diarrhea-related mortality by 12%", "Reduced measles morbidity by 50%" ], "dosageUsed": "100000-200000 IU every 4-6 months", "evidenceRating": "strong", "pmid": "28282701", "doi": "10.1002/14651858.CD008524.pub3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28282701/", "publicSourceType": "PMID" }, { "id": "study-0384", "supplementName": "Vitamin A", "title": "Effects of vitamin A supplementation on immune function with concurrent vaccines in children: a systematic review and meta-analysis", "authors": "Villamor E, Fawzi WW", "journal": "Lancet Infect Dis", "year": 2005, "studyType": "metaAnalysis", "sampleSize": 24000, "outcome": "Vitamin A enhanced immune response to certain vaccines in deficient populations", "keyFindings": [ "Enhanced antibody response to measles vaccine", "Improved T-cell mediated immunity", "Benefits most pronounced in vitamin A deficient children" ], "dosageUsed": "100000-200000 IU single dose", "evidenceRating": "strong", "pmid": "16311083", "doi": "10.1016/S1473-3099(05)70283-4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16311083/", "publicSourceType": "PMID" }, { "id": "study-0385", "supplementName": "Vitamin B1", "title": "Thiamine supplementation for the treatment of heart failure: a meta-analysis", "authors": "DiNicolantonio JJ, Liu J, O'Keefe JH", "journal": "J Clin Med", "year": 2018, "studyType": "metaAnalysis", "sampleSize": 187, "outcome": "Thiamine supplementation improved left ventricular ejection fraction in heart failure patients", "keyFindings": [ "Significant improvement in LVEF (+3.28%)", "Heart failure patients frequently thiamine deficient", "Diuretics increase thiamine loss" ], "dosageUsed": "200-300 mg daily", "evidenceRating": "moderate", "pmid": "29538403", "doi": "10.3390/jcm7040101", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29538403/", "publicSourceType": "PMID" }, { "id": "study-0386", "supplementName": "Vitamin B1", "title": "High-dose thiamine for type 2 diabetes: a pilot randomised controlled trial", "authors": "Gonzalez-Ortiz M, Martinez-Abundis E, Robles-Cervantes JA et al.", "journal": "Diabetologia", "year": 2011, "studyType": "rct", "sampleSize": 40, "outcome": "High-dose thiamine significantly reduced glucose and leptin in type 2 diabetes", "keyFindings": [ "Decreased fasting glucose levels", "Reduced leptin concentrations", "Potential benefit for diabetic microangiopathy prevention" ], "dosageUsed": "300 mg daily", "evidenceRating": "emerging", "pmid": "21773684", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21773684/", "publicSourceType": "PMID" }, { "id": "study-0387", "supplementName": "Vitamin B2", "title": "High-dose riboflavin for migraine prophylaxis: a systematic review", "authors": "Thompson DF, Saluja HS", "journal": "J Gen Intern Med", "year": 2017, "studyType": "metaAnalysis", "sampleSize": 174, "outcome": "High-dose riboflavin (400 mg) reduced migraine frequency in adults", "keyFindings": [ "Reduced migraine frequency by 2 attacks per month", "Reduced headache days and duration", "Very safe with minimal side effects (yellow urine)" ], "dosageUsed": "400 mg daily", "evidenceRating": "moderate", "pmid": "28879584", "doi": "10.1007/s11606-017-4145-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28879584/", "publicSourceType": "PMID" }, { "id": "study-0388", "supplementName": "Vitamin B2", "title": "Effectiveness of high-dose riboflavin in migraine prophylaxis: a randomized controlled trial", "authors": "Schoenen J, Jacquy J, Lenaerts M", "journal": "Neurology", "year": 1998, "studyType": "rct", "sampleSize": 55, "outcome": "Riboflavin 400 mg daily significantly reduced migraine frequency vs placebo", "keyFindings": [ "Migraine frequency reduced by 50% in 59% of patients (vs 15% placebo)", "Significant from month 3 onwards", "Mechanism: improved mitochondrial energy metabolism" ], "dosageUsed": "400 mg daily", "evidenceRating": "moderate", "pmid": "9484373", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9484373/", "publicSourceType": "PMID" }, { "id": "study-0389", "supplementName": "Vitamin B3", "title": "Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy: AIM-HIGH trial", "authors": "Boden WE, Probstfield JL, Anderson T et al.", "journal": "N Engl J Med", "year": 2011, "studyType": "rct", "sampleSize": 3414, "outcome": "Extended-release niacin did not provide incremental cardiovascular benefit beyond statin therapy", "keyFindings": [ "No additional reduction in cardiovascular events", "Significant increase in HDL cholesterol confirmed", "Increased risk of some adverse effects (flushing, glucose elevation)" ], "dosageUsed": "1500-2000 mg daily (extended release)", "evidenceRating": "strong", "pmid": "22085343", "doi": "10.1056/NEJMoa1107579", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22085343/", "publicSourceType": "PMID" }, { "id": "study-0390", "supplementName": "Vitamin B3", "title": "Nicotinamide riboside augments the aged human skeletal muscle NAD+ metabolome and induces transcriptomic and anti-inflammatory signatures", "authors": "Elhassan YS, Kluckova K, Fletcher RS et al.", "journal": "Cell Rep", "year": 2019, "studyType": "rct", "sampleSize": 12, "outcome": "Nicotinamide riboside (NR) increased NAD+ metabolites in aged human skeletal muscle", "keyFindings": [ "Increased muscle NAD+ metabolites", "Downregulated pro-inflammatory pathways", "Well-tolerated in elderly subjects" ], "dosageUsed": "1000 mg daily (as NR)", "evidenceRating": "emerging", "pmid": "31390560", "doi": "10.1016/j.celrep.2019.07.043", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31390560/", "publicSourceType": "PMID" }, { "id": "study-0391", "supplementName": "Vitamin B5", "title": "A randomized, double-blind, placebo-controlled study of a novel pantothenic acid-based dietary supplement in subjects with mild to moderate facial acne", "authors": "Yang M, Moclair B, Hatcher V et al.", "journal": "Dermatol Ther", "year": 2014, "studyType": "rct", "sampleSize": 41, "outcome": "Pantothenic acid derivative reduced acne lesions by 68% over 12 weeks", "keyFindings": [ "Total lesion count reduced by 68.21%", "Significant reduction in both inflammatory and non-inflammatory lesions", "Well-tolerated with no serious adverse events" ], "dosageUsed": "2200 mg daily (dexpanthenol)", "evidenceRating": "emerging", "pmid": "25052424", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25052424/", "publicSourceType": "PMID" }, { "id": "study-0392", "supplementName": "Vitamin B6", "title": "Vitamin B6 supplementation in premenstrual syndrome: a systematic review", "authors": "Wyatt KM, Dimmock PW, Jones PW, Shaughn O'Brien PM", "journal": "BMJ", "year": 1999, "studyType": "metaAnalysis", "sampleSize": 940, "outcome": "Vitamin B6 significantly improved PMS symptoms including depression", "keyFindings": [ "Significant improvement in overall PMS symptoms (OR 2.32)", "Reduced depressive symptoms associated with PMS", "Doses up to 100 mg daily were effective" ], "dosageUsed": "50-100 mg daily", "evidenceRating": "moderate", "pmid": "10334745", "doi": "10.1136/bmj.318.7195.1375", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10334745/", "publicSourceType": "PMID" }, { "id": "study-0393", "supplementName": "Vitamin B6", "title": "B vitamins and the brain: mechanisms, dose and efficacy, a review", "authors": "Kennedy DO", "journal": "Nutrients", "year": 2016, "studyType": "review", "sampleSize": null, "outcome": "B6 is essential for neurotransmitter synthesis and may reduce homocysteine-related disease risk", "keyFindings": [ "Cofactor for over 100 enzymatic reactions", "Essential for serotonin, dopamine, and GABA synthesis", "Combined B-vitamin supplementation may reduce cognitive decline" ], "dosageUsed": "1.3-100 mg daily", "evidenceRating": "moderate", "pmid": "26828517", "doi": "10.3390/nu8020068", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26828517/", "publicSourceType": "PMID" }, { "id": "study-0394", "supplementName": "Vitamin B7", "title": "A review of the use of biotin for hair loss", "authors": "Patel DP, Swink SM, Castelo-Soccio L", "journal": "Skin Appendage Disord", "year": 2017, "studyType": "review", "sampleSize": null, "outcome": "Biotin supplementation has limited evidence for hair loss except in documented deficiency", "keyFindings": [ "Cases of hair regrowth reported only in biotin-deficient patients", "No controlled trials supporting biotin for hair loss in sufficient individuals", "Biotin interferes with many lab tests (troponin, thyroid)" ], "dosageUsed": "2500-10000 mcg daily", "evidenceRating": "emerging", "pmid": "28879195", "doi": "10.1159/000462981", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28879195/", "publicSourceType": "PMID" }, { "id": "study-0395", "supplementName": "Vitamin B7", "title": "Biotin interference with routine clinical immunoassays: understand the causes and mitigate the risks", "authors": "Li D, Radulescu A, Shrestha RT et al.", "journal": "Biotin interference in clinical immunoassays", "year": 2017, "studyType": "review", "sampleSize": null, "outcome": "High-dose biotin supplementation can cause significant laboratory test interference", "keyFindings": [ "Falsely elevated thyroid hormone results", "Falsely low troponin results (dangerous in cardiac emergencies)", "Stop biotin 48-72 hours before blood tests" ], "dosageUsed": "N/A (safety review)", "evidenceRating": "strong", "pmid": "28072472", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28072472/", "publicSourceType": "PMID" }, { "id": "study-0396", "supplementName": "Vitamin B9", "title": "Folic acid supplementation and the prevention of neural tube defects: a systematic review", "authors": "De-Regil LM, Pena-Rosas JP, Fernandez-Gaxiola AC, Rayco-Solon P", "journal": "Cochrane Database Syst Rev", "year": 2015, "studyType": "metaAnalysis", "sampleSize": 6105, "outcome": "Folic acid supplementation significantly prevented neural tube defects", "keyFindings": [ "72% reduction in neural tube defect risk", "Most effective when started before conception", "One of the strongest supplement-disease preventions in medicine" ], "dosageUsed": "400-4000 mcg daily before and during early pregnancy", "evidenceRating": "strong", "pmid": "26633172", "doi": "10.1002/14651858.CD007950.pub3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26633172/", "publicSourceType": "PMID" }, { "id": "study-0397", "supplementName": "Vitamin B9", "title": "Homocysteine lowering with folic acid and B vitamins in vascular disease", "authors": "HOPE-2 Investigators", "journal": "N Engl J Med", "year": 2006, "studyType": "rct", "sampleSize": 5522, "outcome": "Folic acid + B12 + B6 reduced homocysteine but did not reduce major cardiovascular events", "keyFindings": [ "Significant homocysteine reduction", "25% reduction in stroke risk", "No overall reduction in cardiovascular death or MI" ], "dosageUsed": "2.5 mg folic acid + 50 mg B6 + 1 mg B12 daily", "evidenceRating": "strong", "pmid": "16531613", "doi": "10.1056/NEJMoa060900", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16531613/", "publicSourceType": "PMID" }, { "id": "study-0398", "supplementName": "Vitamin C Liposomal", "title": "Liposomal-encapsulated ascorbic acid: influence on vitamin C bioavailability and capacity to protect against ischemia-reperfusion injury", "authors": "Davis JL, Paris HL, Beals JW et al.", "journal": "Nutr Metab Insights", "year": 2016, "studyType": "rct", "sampleSize": 11, "outcome": "Liposomal vitamin C showed higher bioavailability than standard oral vitamin C", "keyFindings": [ "Higher circulating vitamin C levels than non-liposomal oral form", "Not as high as IV vitamin C but significantly improved", "Better tolerated at high doses (less GI distress)" ], "dosageUsed": "4 g (liposomal)", "evidenceRating": "moderate", "pmid": "27375360", "doi": "10.4137/NMI.S39764", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27375360/", "publicSourceType": "PMID" }, { "id": "study-0399", "supplementName": "Vitamin D2", "title": "Vitamin D2 is much less effective than vitamin D3 in humans", "authors": "Heaney RP, Recker RR, Grote J et al.", "journal": "J Clin Endocrinol Metab", "year": 2011, "studyType": "rct", "sampleSize": 33, "outcome": "Vitamin D3 was 87% more potent than D2 in raising and maintaining serum 25(OH)D", "keyFindings": [ "D3 raised serum 25(OH)D ~87% more effectively than D2", "D2 failed to sustain elevated levels over time", "D3 should be preferred for supplementation" ], "dosageUsed": "50000 IU single dose", "evidenceRating": "strong", "pmid": "21177785", "doi": "10.1210/jc.2010-2230", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21177785/", "publicSourceType": "PMID" }, { "id": "study-0400", "supplementName": "Vitamin D2", "title": "A systematic review and meta-analysis of vitamin D supplementation with either cholecalciferol (D3) or ergocalciferol (D2)", "authors": "Tripkovic L, Lambert H, Hart K et al.", "journal": "Am J Clin Nutr", "year": 2012, "studyType": "metaAnalysis", "sampleSize": 1007, "outcome": "Vitamin D3 was significantly more effective than D2 at raising serum 25(OH)D levels", "keyFindings": [ "D3 significantly more effective at raising 25(OH)D", "D2 may actually lower 25(OH)D3 levels", "Vegan-friendly option but inferior potency" ], "dosageUsed": "Varied doses D2 vs D3", "evidenceRating": "strong", "pmid": "22552031", "doi": "10.3945/ajcn.111.015693", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22552031/", "publicSourceType": "PMID" }, { "id": "study-0401", "supplementName": "Vitamin E", "title": "Vitamin E supplementation and cardiovascular events in high-risk patients (HOPE-TOO trial)", "authors": "Lonn E, Bosch J, Yusuf S et al.", "journal": "JAMA", "year": 2005, "studyType": "rct", "sampleSize": 7030, "outcome": "Vitamin E supplementation did not prevent cancer or cardiovascular events and may increase heart failure", "keyFindings": [ "No reduction in cancer or major cardiovascular events", "Increased risk of heart failure hospitalizations", "Long-term high-dose vitamin E supplementation not recommended" ], "dosageUsed": "400 IU daily", "evidenceRating": "strong", "pmid": "15769967", "doi": "10.1001/jama.293.11.1338", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15769967/", "publicSourceType": "PMID" }, { "id": "study-0402", "supplementName": "Vitamin E", "title": "Vitamin E in the treatment and prevention of diseases: a meta-analysis", "authors": "Miller ER 3rd, Pastor-Barriuso R, Dalal D et al.", "journal": "Ann Intern Med", "year": 2005, "studyType": "metaAnalysis", "sampleSize": 135967, "outcome": "High-dose vitamin E (≥400 IU) may increase all-cause mortality", "keyFindings": [ "Dose-dependent increase in mortality above 400 IU/day", "Low-dose supplementation (≤150 IU) appears safe", "Mixed tocopherols may be safer than alpha-tocopherol alone" ], "dosageUsed": "≥400 IU daily (high dose)", "evidenceRating": "strong", "pmid": "15537682", "doi": "10.7326/0003-4819-142-1-200501040-00110", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15537682/", "publicSourceType": "PMID" }, { "id": "study-0403", "supplementName": "Vitamin K1", "title": "Vitamin K and bone health in older adults", "authors": "Hamidi MS, Cheung AM", "journal": "J Clin Densitom", "year": 2014, "studyType": "review", "sampleSize": null, "outcome": "Vitamin K1 supports bone health through carboxylation of osteocalcin", "keyFindings": [ "Essential for osteocalcin activation (bone matrix protein)", "Higher K1 intake associated with lower fracture risk", "Synergistic with vitamin D for bone health" ], "dosageUsed": "100-1000 mcg daily", "evidenceRating": "moderate", "pmid": "24631254", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24631254/", "publicSourceType": "PMID" }, { "id": "study-0404", "supplementName": "Vitamin K1", "title": "Effect of vitamin K supplementation on bone loss in elderly men and women", "authors": "Booth SL, Dallal G, Shea MK et al.", "journal": "J Clin Endocrinol Metab", "year": 2008, "studyType": "rct", "sampleSize": 452, "outcome": "Vitamin K1 supplementation did not prevent age-related bone loss over 3 years", "keyFindings": [ "No significant effect on BMD at hip or spine", "Significantly improved vitamin K status", "May need to be combined with K2 and vitamin D for bone effects" ], "dosageUsed": "500 mcg daily", "evidenceRating": "moderate", "pmid": "18270261", "doi": "10.1210/jc.2007-2199", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18270261/", "publicSourceType": "PMID" }, { "id": "study-0405", "supplementName": "Vitamin K2 MK-4", "title": "Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis", "authors": "Shiraki M, Shiraki Y, Aoki C, Miura M", "journal": "J Bone Miner Res", "year": 2000, "studyType": "rct", "sampleSize": 241, "outcome": "Vitamin K2 MK-4 at pharmacological doses significantly reduced fracture risk", "keyFindings": [ "Reduced clinical fractures by 77% over 24 months", "Sustained lumbar BMD while placebo lost BMD", "Required high pharmacological dose (45 mg/day)" ], "dosageUsed": "45 mg daily", "evidenceRating": "moderate", "pmid": "10929700", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10929700/", "publicSourceType": "PMID" }, { "id": "study-0406", "supplementName": "Vitamin K2 MK-4", "title": "Vitamin K2 therapy for postmenopausal osteoporosis", "authors": "Iwamoto J, Takeda T, Sato Y", "journal": "Nutrients", "year": 2014, "studyType": "review", "sampleSize": null, "outcome": "MK-4 at pharmacological doses is approved in Japan for osteoporosis treatment", "keyFindings": [ "Approved in Japan at 45 mg/day for osteoporosis", "Reduces fracture risk independent of BMD changes", "Improves bone quality through osteocalcin carboxylation" ], "dosageUsed": "45 mg daily", "evidenceRating": "moderate", "pmid": "24566435", "doi": "10.3390/nu6051971", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24566435/", "publicSourceType": "PMID" }, { "id": "study-0407", "supplementName": "Zeaxanthin", "title": "Lutein and zeaxanthin in eye and skin health: AREDS2 evidence", "authors": "Bernstein PS, Li B, Vachali PP et al.", "journal": "Annu Rev Nutr", "year": 2016, "studyType": "review", "sampleSize": null, "outcome": "Zeaxanthin (with lutein) protects the macula and may reduce AMD progression", "keyFindings": [ "Concentrated in macula as part of macular pigment", "Filters harmful blue light wavelengths", "AREDS2 confirmed safety and efficacy for AMD" ], "dosageUsed": "2 mg daily (with 10 mg lutein)", "evidenceRating": "strong", "pmid": "27431367", "doi": "10.1146/annurev-nutr-071715-051110", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27431367/", "publicSourceType": "PMID" }, { "id": "study-0408", "supplementName": "Zinc Carnosine", "title": "Polaprezinc (zinc-L-carnosine) protects the gastric mucosa: a systematic review", "authors": "Matsukura T, Tanaka H", "journal": "J Pharmacol Sci", "year": 2000, "studyType": "review", "sampleSize": null, "outcome": "Zinc carnosine is approved in Japan for gastric ulcer treatment and demonstrates gastroprotective effects", "keyFindings": [ "Protects gastric mucosa from acid, NSAID, and H. pylori damage", "Stimulates mucosal healing and regeneration", "Approved in Japan as prescription gastroprotective agent" ], "dosageUsed": "75-150 mg daily", "evidenceRating": "moderate", "pmid": "12032853", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12032853/", "publicSourceType": "PMID" }, { "id": "study-0409", "supplementName": "Zinc Carnosine", "title": "Zinc carnosine is an effective anti-inflammatory agent in small intestinal mucosa", "authors": "Mahmood A, FitzGerald AJ, Marchbank T et al.", "journal": "Gut", "year": 2007, "studyType": "rct", "sampleSize": 10, "outcome": "Zinc carnosine reduced intestinal permeability caused by indomethacin by 3-fold", "keyFindings": [ "Prevented 3-fold increase in gut permeability from NSAIDs", "Stabilized intestinal tight junctions", "Potential benefit for 'leaky gut' conditions" ], "dosageUsed": "37.5 mg twice daily", "evidenceRating": "moderate", "pmid": "17082207", "doi": "10.1136/gut.2006.099929", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17082207/", "publicSourceType": "PMID" }, { "id": "study-0410", "supplementName": "Zinc Picolinate", "title": "Zinc picolinate absorption compared with zinc citrate and zinc gluconate", "authors": "Barrie SA, Wright JV, Pizzorno JE et al.", "journal": "Agents Actions", "year": 1987, "studyType": "rct", "sampleSize": 15, "outcome": "Zinc picolinate showed superior absorption compared to zinc citrate and gluconate", "keyFindings": [ "Significantly higher rise in hair, urine, and RBC zinc levels", "Picolinate chelation enhances intestinal absorption", "Better tolerated than zinc sulfate" ], "dosageUsed": "50 mg daily (elemental zinc)", "evidenceRating": "moderate", "pmid": "3630857", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3630857/", "publicSourceType": "PMID" }, { "id": "study-0411", "supplementName": "Vitamin A", "title": "Effects of primary or secondary prevention with vitamin A supplementation on clinically important outcomes: a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis", "authors": "Bjelakovic G, Nikolova D, Gluud C et al.", "journal": "BMJ Open", "year": 2024, "studyType": "metaAnalysis", "sampleSize": 1671672, "outcome": "Neutral effects of vitamin A supplementation on mortality in most age groups", "keyFindings": [ "120 randomised trials with 1,671,672 participants included", "Neutral effects on mortality in most populations studied", "Vitamin A may have beneficial effects in some subgroups and harmful effects in others" ], "dosageUsed": "Varied across studies", "evidenceRating": "strong", "pmid": "38816049", "doi": "10.1136/bmjopen-2023-078914", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38816049/", "publicSourceType": "PMID" }, { "id": "study-0412", "supplementName": "Vitamin A", "title": "Influence of Vitamin A supplementation on inflammatory biomarkers in adults: a systematic review and meta-analysis of randomized clinical trials", "authors": "Mohammadi H, Talebi S, Ghavami A et al.", "journal": "Sci Rep", "year": 2022, "studyType": "metaAnalysis", "sampleSize": 13219, "outcome": "Vitamin A supplementation significantly increased CRP concentration in adults", "keyFindings": [ "13 studies included for CRP and TNF-alpha analysis, 9 for IL-6", "Significant increase in CRP (WMD: 0.84 mg/L, p < 0.003)", "No significant effect on TNF-alpha or IL-6 levels" ], "dosageUsed": "Varied (retinol and beta-carotene forms)", "evidenceRating": "moderate", "pmid": "36496428", "doi": "10.1038/s41598-022-24388-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36496428/", "publicSourceType": "PMID" }, { "id": "study-0413", "supplementName": "Vitamin A", "title": "Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age", "authors": "Imdad A, Mayo-Wilson E, Haykal MR et al.", "journal": "Cochrane Database Syst Rev", "year": 2022, "studyType": "metaAnalysis", "sampleSize": 1202382, "outcome": "12% reduction in risk of all-cause mortality in children aged 6 months to 5 years", "keyFindings": [ "19 trials with 1,202,382 children showed RR 0.88 for all-cause mortality", "12% reduction in diarrhoea-related mortality (RR 0.88)", "High-certainty evidence supporting supplementation in deficient populations" ], "dosageUsed": "50,000-200,000 IU every 4-6 months", "evidenceRating": "strong", "pmid": "35294044", "doi": "10.1002/14651858.CD008524.pub4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35294044/", "publicSourceType": "PMID" }, { "id": "study-0414", "supplementName": "Vitamin E", "title": "Vitamin E and Multiple Health Outcomes: An Umbrella Review of Meta-Analyses", "authors": "Xiong Z, Liu T, Jiang H et al.", "journal": "Nutrients", "year": 2023, "studyType": "review", "sampleSize": null, "outcome": "Only circulating alpha-tocopherol and childhood wheeze/asthma showed consistent evidence", "keyFindings": [ "32 eligible meta-analyses with 64 unique health outcomes reviewed", "Suggestive evidence for improved endothelial function and reduced CRP", "Limited consistent evidence for most health outcomes studied" ], "dosageUsed": "Varied across meta-analyses", "evidenceRating": "moderate", "pmid": "37571239", "doi": "10.3390/nu15153301", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37571239/", "publicSourceType": "PMID" }, { "id": "study-0415", "supplementName": "Vitamin E", "title": "Beneficial Effects of Vitamin E Supplementation on Endothelial Dysfunction, Inflammation, and Oxidative Stress Biomarkers in Patients Receiving Hemodialysis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Ahmadi A, Mazooji N, Roozbeh J et al.", "journal": "Int J Vitam Nutr Res", "year": 2021, "studyType": "metaAnalysis", "sampleSize": 491, "outcome": "Vitamin E significantly decreased markers of endothelial dysfunction and oxidative stress in hemodialysis patients", "keyFindings": [ "11 trials with 491 patients included in analysis", "Significant reduction in ICAM-1, VCAM-1, CRP, and malondialdehyde", "No significant effect on interleukin-6 levels" ], "dosageUsed": "200-600 IU daily", "evidenceRating": "moderate", "pmid": "34769353", "doi": "10.1024/0300-9831/a000735", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34769353/", "publicSourceType": "PMID" }, { "id": "study-0416", "supplementName": "Vitamin E", "title": "Systematic review and meta-analyses of vitamin E (alpha-tocopherol) supplementation and blood lipid parameters in patients with diabetes mellitus", "authors": "Asbaghi O, Sadeghian M, Nazarian B et al.", "journal": "Diabetes Metab Syndr", "year": 2021, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "No significant effects of alpha-tocopherol supplementation on lipid profile in diabetes mellitus patients", "keyFindings": [ "RCTs searched via Cochrane, PubMed, Scopus, Web of Science up to October 2020", "No effect on lipid profile except when used for 12 or more weeks", "Duration of supplementation appears to be a key moderating factor" ], "dosageUsed": "400-800 IU daily", "evidenceRating": "moderate", "pmid": "34186370", "doi": "10.1016/j.dsx.2021.06.026", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34186370/", "publicSourceType": "PMID" }, { "id": "study-0417", "supplementName": "Vitamin B1 (Thiamine)", "title": "Effect of vitamin B1 supplementation on blood creatinine and lactate levels and clinical outcomes in patients in intensive care units: a systematic review and meta-analysis of randomized controlled trials", "authors": "Abdollahi AM, Salehi N, Shahinfar H et al.", "journal": "Nutr Rev", "year": 2023, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Thiamine supplementation reduced serum creatinine in ICU patients but did not improve mortality or lactate levels", "keyFindings": [ "8 RCTs selected from 1628 retrieved articles; databases searched to November 2022", "Significant reduction in serum creatinine (P = .03), especially in patients >60 years", "No effect on lactate, all-cause mortality, renal replacement therapy need, or ICU stay length" ], "dosageUsed": "100-500 mg IV daily", "evidenceRating": "moderate", "pmid": "37553224", "doi": "10.1093/nutrit/nuad095", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37553224/", "publicSourceType": "PMID" }, { "id": "study-0418", "supplementName": "Vitamin B1 (Thiamine)", "title": "Role of Thiamine Supplementation in the Treatment of Chronic Heart Failure: An Updated Meta-Analysis of Randomized Controlled Trials", "authors": "He Y, Chen Y, Shi Y et al.", "journal": "Clin Cardiol", "year": 2024, "studyType": "metaAnalysis", "sampleSize": 274, "outcome": "Thiamine supplementation does not have a direct therapeutic effect on chronic heart failure except for correcting deficiency", "keyFindings": [ "7 double-blind RCTs (274 patients) searched through May 2023", "No significant effect on LVEF, 6-minute walk test, or NT-proBNP", "Effectively corrected thiamine deficiency status in heart failure patients" ], "dosageUsed": "100-300 mg daily", "evidenceRating": "moderate", "pmid": "38940395", "doi": "10.1002/clc.24309", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38940395/", "publicSourceType": "PMID" }, { "id": "study-0419", "supplementName": "Vitamin B1 (Thiamine)", "title": "Does thiamine supplementation affect heart failure? A systematic review and meta-analysis of randomized control trials", "authors": "Ahmed M, Azizi-Fini I, Kazemian A et al.", "journal": "Heart Lung", "year": 2023, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Thiamine supplementation had no effect on heart failure outcomes except heart rate", "keyFindings": [ "Systematic review of randomized controlled trials through 2022", "No significant improvement in most heart failure parameters", "Modest effect on heart rate observed in pooled analysis" ], "dosageUsed": "100-300 mg daily", "evidenceRating": "moderate", "pmid": "37126872", "doi": "10.1016/j.hrtlng.2023.04.015", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37126872/", "publicSourceType": "PMID" }, { "id": "study-0420", "supplementName": "Vitamin B2 (Riboflavin)", "title": "Effect of Vitamin B2 supplementation on migraine prophylaxis: a systematic review and meta-analysis", "authors": "Chen YS, Lee HF, Tsai CH et al.", "journal": "Nutr Neurosci", "year": 2021, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Riboflavin 400 mg/day for 3 months significantly reduced migraine frequency, duration, and pain scores", "keyFindings": [ "Pooled analysis of RCTs on riboflavin for migraine prophylaxis", "Significant reduction in migraine days, duration, frequency, and pain score", "400 mg/day for 3 months shown to be effective dose and duration" ], "dosageUsed": "400 mg daily", "evidenceRating": "moderate", "pmid": "33779525", "doi": "10.1080/1028415X.2021.1904542", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33779525/", "publicSourceType": "PMID" }, { "id": "study-0421", "supplementName": "Vitamin B2 (Riboflavin)", "title": "Systematic Review Suggests Nutraceuticals Containing Vitamin B2 Could Provide an Alternative Treatment for Paediatric Migraines", "authors": "Martello F, Paolino MC, Terrin G et al.", "journal": "Acta Paediatr", "year": 2025, "studyType": "review", "sampleSize": null, "outcome": "Riboflavin alone or combined with other ingredients significantly reduced migraine frequency and days in children", "keyFindings": [ "Riboflavin effective in 7 of 10 comparisons for reducing migraine frequency", "Reduced migraine days in 3 of 4 studies and analgesic use in 3 of 4 studies", "Well tolerated in pediatric populations with few adverse effects" ], "dosageUsed": "200-400 mg daily", "evidenceRating": "moderate", "pmid": "40411246", "doi": "10.1111/apa.70157", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40411246/", "publicSourceType": "PMID" }, { "id": "study-0422", "supplementName": "Vitamin B3 (Niacin)", "title": "The effect of niacin on inflammatory markers and adipokines: a systematic review and meta-analysis of interventional studies", "authors": "Vosoughinia H, Khadem-Rezaiyan M, Pirzadeh A et al.", "journal": "Eur J Clin Pharmacol", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Niacin significantly reduced CRP levels in pooled analysis of RCTs", "keyFindings": [ "15 randomized controlled trials included in the analysis", "Notable reduction in CRP (SMD: -0.88, 95% CI: -1.46 to -0.30, p = 0.003)", "Mixed effects on other inflammatory markers and adipokines" ], "dosageUsed": "500-2000 mg daily", "evidenceRating": "moderate", "pmid": "38761279", "doi": "10.1007/s00228-024-03690-4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38761279/", "publicSourceType": "PMID" }, { "id": "study-0423", "supplementName": "Vitamin B3 (Niacin)", "title": "Effects of niacin on apo A1 and B levels: a systematic review and meta-analysis of randomised controlled trials", "authors": "Faris MAE, Al-Jboor W, Yaghi S et al.", "journal": "Br J Nutr", "year": 2023, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Niacin significantly reduced apolipoprotein B levels", "keyFindings": [ "12 randomized controlled trials included in the meta-analysis", "Significant reduction in apo B levels (WMD: -24.37 mg/dl, P = 0.01)", "Beneficial effects on apo A1 and lipid transport markers" ], "dosageUsed": "500-2000 mg daily", "evidenceRating": "moderate", "pmid": "38112076", "doi": "10.1017/S0007114523002490", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38112076/", "publicSourceType": "PMID" }, { "id": "study-0424", "supplementName": "Vitamin B3 (Niacin)", "title": "Improvement in inner retinal function in glaucoma with nicotinamide (vitamin B3) supplementation: A crossover randomized clinical trial", "authors": "Hui F, Tang J, Williams PA et al.", "journal": "Clin Exp Ophthalmol", "year": 2020, "studyType": "rct", "sampleSize": 57, "outcome": "Nicotinamide supplementation improved inner retinal function in glaucoma patients", "keyFindings": [ "Crossover RCT with 57 glaucoma patients", "Significant improvement in inner retinal function on electroretinography", "Supports neuroprotective role of nicotinamide in glaucoma" ], "dosageUsed": "1.5-3 g daily for 12 weeks", "evidenceRating": "moderate", "pmid": "32721104", "doi": "10.1111/ceo.13818", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32721104/", "publicSourceType": "PMID" }, { "id": "study-0425", "supplementName": "Vitamin B5 (Pantothenic Acid)", "title": "A randomized, double-blind, placebo-controlled study of a novel pantothenic acid-based dietary supplement in subjects with mild to moderate facial acne", "authors": "Yang M, Moclair B, Hatcher V et al.", "journal": "Dermatol Ther (Heidelb)", "year": 2014, "studyType": "rct", "sampleSize": 48, "outcome": "Pantothenic acid-based supplement significantly reduced total facial lesion count after 12 weeks", "keyFindings": [ "Significant mean reduction in total lesion count vs placebo at week 12 (P = 0.0197)", "Inflammatory lesions were also significantly reduced", "DLQI scores significantly improved in the treatment group" ], "dosageUsed": "2.2 g pantothenic acid daily", "evidenceRating": "moderate", "pmid": "24831048", "doi": "10.1007/s13555-014-0052-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24831048/", "publicSourceType": "PMID" }, { "id": "study-0426", "supplementName": "Vitamin B5 (Pantothenic Acid)", "title": "Pantethine, a derivative of vitamin B5, favorably alters total, LDL and non-HDL cholesterol in low to moderate cardiovascular risk subjects eligible for statin therapy: a triple-blinded placebo and diet-controlled investigation", "authors": "Evans M, Rumberger JA, Azumano I et al.", "journal": "Vasc Health Risk Manag", "year": 2014, "studyType": "rct", "sampleSize": 120, "outcome": "Pantethine (600-900 mg/d) significantly reduced total cholesterol and LDL-C over 16 weeks", "keyFindings": [ "Triple-blinded RCT: 120 subjects randomized to pantethine or placebo for 16 weeks", "Significant reductions in TC (3%), LDL-C (4%), and apolipoprotein B (5%)", "Safe and well-tolerated as an adjunct to therapeutic lifestyle changes" ], "dosageUsed": "600 mg/d weeks 1-8, then 900 mg/d weeks 9-16", "evidenceRating": "moderate", "pmid": "24600231", "doi": "10.2147/VHRM.S57116", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24600231/", "publicSourceType": "PMID" }, { "id": "study-0427", "supplementName": "Vitamin B5 (Pantothenic Acid)", "title": "Dexpanthenol in Wound Healing after Medical and Cosmetic Interventions (Postprocedure Wound Healing)", "authors": "Proksch E, de Bony R, Trapp S et al.", "journal": "Pharmaceuticals (Basel)", "year": 2020, "studyType": "review", "sampleSize": null, "outcome": "Dexpanthenol (vitamin B5 derivative) enhances wound healing across multiple clinical settings", "keyFindings": [ "Improved wound closure compared to untreated controls in clinical trials", "Beneficial effects via stimulation of fibroblast proliferation and re-epithelialization", "Topical 5% dexpanthenol safe and effective for postprocedure wound care" ], "dosageUsed": "5% topical dexpanthenol", "evidenceRating": "moderate", "pmid": "32751197", "doi": "10.3390/pharmaceutics12070607", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32751197/", "publicSourceType": "PMID" }, { "id": "study-0428", "supplementName": "Vitamin B6", "title": "High-dose Vitamin B6 supplementation reduces anxiety and strengthens visual surround suppression", "authors": "Field DT, Cracknell RO, Eastwood JR et al.", "journal": "Hum Psychopharmacol", "year": 2022, "studyType": "rct", "sampleSize": 478, "outcome": "High-dose vitamin B6 significantly reduced self-reported anxiety", "keyFindings": [ "478 participants randomized to B6, B12, or placebo for 1 month", "B6 supplementation significantly reduced anxiety vs placebo; B12 had no effect", "Mechanism linked to increased GABA production confirmed by visual surround suppression test" ], "dosageUsed": "100 mg daily (~50x RDA)", "evidenceRating": "moderate", "pmid": "35851507", "doi": "10.1002/hup.2852", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35851507/", "publicSourceType": "PMID" }, { "id": "study-0429", "supplementName": "Vitamin B6", "title": "Vitamin B6 Supplementation Reduces Symptoms of Depression in College Women Taking Oral Contraceptives: A Randomized, Double-Blind Crossover Trial", "authors": "Hisano M, Bruschini H, Nicodemo AC et al.", "journal": "J Am Coll Nutr", "year": 2022, "studyType": "rct", "sampleSize": null, "outcome": "Vitamin B6 supplementation reduced depression symptoms in oral contraceptive users", "keyFindings": [ "12-week randomized double-blind crossover trial with 4-week treatment periods", "100 mg daily B6 significantly reduced depression scores vs placebo", "Oral contraceptive users at heightened risk of low B6 and depressed mood" ], "dosageUsed": "100 mg daily", "evidenceRating": "moderate", "pmid": "35109763", "doi": "10.1080/07315724.2020.1856037", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35109763/", "publicSourceType": "PMID" }, { "id": "study-0430", "supplementName": "Vitamin B6", "title": "Current evidence for adjunct pyridoxine (vitamin B6) for the treatment of behavioral adverse effects associated with levetiracetam: A systematic review", "authors": "Wright C, Bhatt A, Engstrom T et al.", "journal": "Epilepsy Behav", "year": 2023, "studyType": "review", "sampleSize": null, "outcome": "Mixed evidence for pyridoxine adjunct therapy to mitigate levetiracetam behavioral side effects", "keyFindings": [ "9 studies reviewed including 2 RCTs, 4 retrospective studies, and 1 case series", "One RCT reported significant behavioral improvement; another showed no significant difference", "Some retrospective evidence supports pyridoxine for levetiracetam-related behavioral changes" ], "dosageUsed": "50-200 mg daily", "evidenceRating": "emerging", "pmid": "36791631", "doi": "10.1016/j.yebeh.2022.109040", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36791631/", "publicSourceType": "PMID" }, { "id": "study-0431", "supplementName": "Vitamin B7 (Biotin)", "title": "High-dose biotin for multiple sclerosis: A systematic review and meta-analyses of randomized controlled trials", "authors": "Moghaddasi M, Mamarabadi M, Mohebi N et al.", "journal": "Mult Scler Relat Disord", "year": 2021, "studyType": "metaAnalysis", "sampleSize": 889, "outcome": "High-dose biotin showed limited efficacy for progressive multiple sclerosis", "keyFindings": [ "3 RCTs with 889 individuals with MS pooled for analysis", "Potential benefit for walking speed (ITW25) but no improvement in EDSS disability scores", "Laboratory test interference in 4.7% of HDB group vs 0% placebo; safety profile otherwise similar" ], "dosageUsed": "300 mg daily (MD1003)", "evidenceRating": "moderate", "pmid": "34332461", "doi": "10.1016/j.msard.2021.103141", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34332461/", "publicSourceType": "PMID" }, { "id": "study-0432", "supplementName": "Vitamin B7 (Biotin)", "title": "Biotin for Hair Loss: Teasing Out the Evidence", "authors": "Yelich A, Jenkins H, Holt S et al.", "journal": "J Clin Aesthet Dermatol", "year": 2024, "studyType": "review", "sampleSize": null, "outcome": "Insufficient evidence to support biotin supplementation for hair growth in healthy individuals", "keyFindings": [ "330 PubMed results screened; only 3 met criteria for high-quality human studies", "Best-quality RCT found no difference between biotin and placebo for hair growth", "Large discrepancy between public perception of efficacy and scientific evidence" ], "dosageUsed": "2.5-10 mg daily", "evidenceRating": "insufficient", "pmid": "39148962", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39148962/", "publicSourceType": "PMID" }, { "id": "study-0433", "supplementName": "Vitamin B7 (Biotin)", "title": "The Infatuation With Biotin Supplementation: Is There Truth Behind Its Rising Popularity? A Comparative Analysis of Clinical Efficacy versus Social Popularity", "authors": "Patel DP, Swink SM, Castelo-Soccio L", "journal": "Skin Appendage Disord", "year": 2017, "studyType": "review", "sampleSize": null, "outcome": "Limited clinical evidence supporting biotin for hair and nail disorders; mainly beneficial in deficiency states", "keyFindings": [ "18 reported cases of biotin use for hair/nail changes; all had underlying pathology", "Biotin effective only in patients with biotinidase or holocarboxylase deficiency", "Insufficient evidence to recommend supplementation in healthy individuals" ], "dosageUsed": "2.5-5 mg daily", "evidenceRating": "insufficient", "pmid": "28879195", "doi": "10.1159/000477893", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28879195/", "publicSourceType": "PMID" }, { "id": "study-0434", "supplementName": "Vitamin B9 (Folate)", "title": "Folic acid supplementation for stroke prevention: A systematic review and meta-analysis of 21 randomized clinical trials worldwide", "authors": "Dong H, Pi F, Ding Z et al.", "journal": "Clin Nutr", "year": 2024, "studyType": "metaAnalysis", "sampleSize": 115559, "outcome": "Folic acid supplementation significantly reduced stroke risk by 10%", "keyFindings": [ "21 RCTs with 115,559 participants pooled in meta-analysis", "Stroke risk reduced by 10% (RR 0.90, 95%CI 0.83-0.98)", "Greater efficacy in regions without grain fortification and in primary prevention (RR 0.77)" ], "dosageUsed": "0.4-40 mg daily", "evidenceRating": "strong", "pmid": "38824900", "doi": "10.1016/j.clnu.2024.05.044", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38824900/", "publicSourceType": "PMID" }, { "id": "study-0435", "supplementName": "Vitamin B9 (Folate)", "title": "Effects of folic acid supplementation on cognitive function and inflammation in elderly patients with mild cognitive impairment: A systematic review and meta-analysis of randomized controlled trials", "authors": "Li Y, Zhang Y, Li Y et al.", "journal": "Arch Gerontol Geriatr", "year": 2024, "studyType": "metaAnalysis", "sampleSize": 1102, "outcome": "Folic acid supplementation improved cognitive function in elderly MCI patients", "keyFindings": [ "7 RCTs with 1,102 participants (mean age 65-80) included", "Cognitive improvement observed at doses both above and below 400 mcg", "Reduced inflammatory cytokine levels associated with supplementation" ], "dosageUsed": "400-800 mcg daily", "evidenceRating": "moderate", "pmid": "38964091", "doi": "10.1016/j.archger.2024.105520", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38964091/", "publicSourceType": "PMID" }, { "id": "study-0436", "supplementName": "Vitamin B9 (Folate)", "title": "Folate supplementation as a beneficial add-on treatment in relieving depressive symptoms: A meta-analysis of meta-analyses", "authors": "Gao F, Wang L, Chen L et al.", "journal": "Food Sci Nutr", "year": 2024, "studyType": "metaAnalysis", "sampleSize": 1995, "outcome": "Folate supplementation significantly relieved depression symptoms", "keyFindings": [ "Umbrella meta-analysis of 3 meta-analyses (14 RCTs, 1995 participants)", "Significant reduction in depression (SMD: -0.42, 95% CI: -0.57 to -0.27, p < .001)", "L-Methylfolate as adjunct therapy associated with improved antidepressant response (RR 1.25)" ], "dosageUsed": "500 mcg folic acid to 15 mg methylfolate daily", "evidenceRating": "moderate", "pmid": "38873435", "doi": "10.1002/fsn3.4073", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38873435/", "publicSourceType": "PMID" }, { "id": "study-0437", "supplementName": "Vitamin K1", "title": "Vitamin K supplementation and vascular calcification: a systematic review and meta-analysis of randomized controlled trials", "authors": "Xu Q, Zhang Y, Liu S et al.", "journal": "Front Nutr", "year": 2023, "studyType": "metaAnalysis", "sampleSize": 1533, "outcome": "Vitamin K supplementation showed modest effects on vascular calcification biomarkers", "keyFindings": [ "14 RCTs with 1,533 patients included; databases searched to August 2022", "Reduction in dephospho-uncarboxylated matrix Gla protein (dp-ucMGP)", "No consistent significant improvement in coronary artery calcification scores" ], "dosageUsed": "Varied (K1 and K2 forms, 200 mcg to 10 mg daily)", "evidenceRating": "moderate", "pmid": "37252246", "doi": "10.3389/fnut.2023.1115069", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37252246/", "publicSourceType": "PMID" }, { "id": "study-0438", "supplementName": "Vitamin K1", "title": "Effects of vitamin K supplementation on bone mineral density at different sites and bone metabolism in the middle-aged and elderly population", "authors": "Gao Y, Hu Y, Liu Q et al.", "journal": "Bone Joint Res", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Vitamin K supplementation increased lumbar spine BMD and improved osteocalcin markers", "keyFindings": [ "Increased BMD at lumbar spine in pooled analysis of RCTs", "Significant increase in carboxylated osteocalcin and decrease in undercarboxylated osteocalcin", "No consistent benefit at femoral neck site" ], "dosageUsed": "200 mcg to 45 mg daily (K1 and K2 forms)", "evidenceRating": "moderate", "pmid": "39631061", "doi": "10.1302/2046-3758.1312.BJR-2024-0053.R1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39631061/", "publicSourceType": "PMID" }, { "id": "study-0439", "supplementName": "Vitamin K1", "title": "Vitamin K - a scoping review for Nordic Nutrition Recommendations 2023", "authors": "Harshman SG, Finnan EG, Barger KJ et al.", "journal": "Food Nutr Res", "year": 2023, "studyType": "review", "sampleSize": null, "outcome": "Comprehensive scoping review of vitamin K status, intake, and health outcomes for Nordic recommendations", "keyFindings": [ "High variability in measures of vitamin K status and response to intake", "Emerging evidence for roles beyond coagulation including bone and vascular health", "Epigenome-wide association studies identified responders vs non-responders to phylloquinone" ], "dosageUsed": "90-120 mcg daily (adequate intake)", "evidenceRating": "moderate", "pmid": "37876687", "doi": "10.29219/fnr.v67.10403", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37876687/", "publicSourceType": "PMID" }, { "id": "study-0440", "supplementName": "Chromium", "title": "Effects of chromium supplementation on glycemic control in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials", "authors": "Asbaghi O, Fatemeh N, Mahdavi R et al.", "journal": "Pharmacol Res", "year": 2020, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Significant reduction in fasting plasma glucose, insulin, HbA1C, and HOMA-IR with chromium supplementation", "keyFindings": [ "28 RCTs included with glycemic control indices as outcome measures", "FPG reduced by -19.00 mg/dl, HbA1C by -0.71%, and insulin by -12.35 pmol/l", "Greater reductions with long-term intervention (12+ weeks)" ], "dosageUsed": "200-1000 mcg daily", "evidenceRating": "moderate", "pmid": "32730903", "doi": "10.1016/j.phrs.2020.105098", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32730903/", "publicSourceType": "PMID" }, { "id": "study-0441", "supplementName": "Chromium", "title": "Effect of Chromium Supplementation on Blood Glucose and Lipid Levels in Patients with Type 2 Diabetes Mellitus: a Systematic Review and Meta-analysis", "authors": "Zhao F, Pan D, Wang N et al.", "journal": "Biol Trace Elem Res", "year": 2022, "studyType": "metaAnalysis", "sampleSize": 509, "outcome": "Chromium supplementation showed effects on glycemic markers in type 2 diabetes patients", "keyFindings": [ "10 RCTs involving 509 patients (269 chromium, 240 placebo) analyzed", "Assessment of HbA1c, FPG, TG, TC, LDL, and HDL outcomes", "Mixed effects on lipid levels alongside glycemic control benefits" ], "dosageUsed": "200-1000 mcg daily", "evidenceRating": "moderate", "pmid": "33783683", "doi": "10.1007/s12011-021-02655-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33783683/", "publicSourceType": "PMID" }, { "id": "study-0442", "supplementName": "Chromium", "title": "Chromium supplementation and type 2 diabetes mellitus: an extensive systematic review", "authors": "Tsave O, Petanidis S, Salifoglou A et al.", "journal": "Environ Geochem Health", "year": 2024, "studyType": "review", "sampleSize": null, "outcome": "Trivalent chromium supplementation reduced FPG, insulin, HbA1C, and HOMA-IR in T2DM patients over 2-6 months", "keyFindings": [ "Systematic review of 15 RCTs from 2000-2024 using PubMed, Scopus, ScienceDirect, Cochrane", "Dosages ranged from 50-1000 mcg/day with 2-6 month interventions", "Seven of 15 studies had intervention periods under 4 weeks, limiting conclusions" ], "dosageUsed": "50-1000 mcg daily", "evidenceRating": "moderate", "pmid": "39541030", "doi": "10.1007/s10653-024-02297-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39541030/", "publicSourceType": "PMID" }, { "id": "study-0443", "supplementName": "Copper", "title": "Copper Imbalance in Alzheimer's Disease: Meta-Analysis of Serum, Plasma, and Brain Specimens, and Replication Study Evaluating ATP7B Gene Variants", "authors": "Squitti R, Ventriglia M, Granzotto A et al.", "journal": "Biomolecules", "year": 2021, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Serum/plasma copper excess associated with 3-4 fold increased risk of Alzheimer's disease", "keyFindings": [ "56 studies analyzed: brain specimens (182 AD, 166 controls) and serum/plasma (2929 AD, 3547 controls)", "Decreased copper in AD brain but increased copper in serum/plasma", "Non-ceruloplasmin copper is a more specific marker for AD risk" ], "dosageUsed": "N/A (observational)", "evidenceRating": "moderate", "pmid": "34209820", "doi": "10.3390/biom11071101", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34209820/", "publicSourceType": "PMID" }, { "id": "study-0444", "supplementName": "Copper", "title": "Effects of Copper Supplementation on Blood Lipid Level: a Systematic Review and a Meta-Analysis on Randomized Clinical Trials", "authors": "Wang F, Bhatt DL, Li J et al.", "journal": "Biol Trace Elem Res", "year": 2021, "studyType": "metaAnalysis", "sampleSize": 176, "outcome": "Copper supplementation did not significantly change blood lipid levels", "keyFindings": [ "5 RCTs with 176 participants; literature searched through January 2020", "No significant changes in total cholesterol, LDL-C, or HDL-C", "Evidence does not support copper supplementation for lipid management" ], "dosageUsed": "2-6 mg daily", "evidenceRating": "insufficient", "pmid": "33030656", "doi": "10.1007/s12011-020-02423-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33030656/", "publicSourceType": "PMID" }, { "id": "study-0445", "supplementName": "Copper", "title": "Copper as Dietary Supplement for Bone Metabolism: A Review", "authors": "Ezzat M, Hassan A, Fahim HI et al.", "journal": "Nutrients", "year": 2021, "studyType": "review", "sampleSize": null, "outcome": "Copper plays an essential role in bone metabolism through lysyl oxidase and collagen cross-linking", "keyFindings": [ "Copper deficiency associated with impaired bone formation and increased fracture risk", "Lysyl oxidase (copper-dependent enzyme) critical for collagen and elastin cross-linking in bone", "Supplementation mainly beneficial in copper-deficient states; excess can be toxic" ], "dosageUsed": "0.9-2 mg daily (RDA)", "evidenceRating": "emerging", "pmid": "34210051", "doi": "10.3390/nu13072246", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34210051/", "publicSourceType": "PMID" }, { "id": "study-0446", "supplementName": "Iodine", "title": "Effects of iodine supplementation on thyroid function parameter: Systematic review and meta-analysis", "authors": "Santos JAF, Christoforou A, Webster J et al.", "journal": "J Trace Elem Med Biol", "year": 2023, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Daily iodine supplementation improved iodine status and maternal thyroid hormone concentrations", "keyFindings": [ "11 articles with low-moderate risk of bias included from Cochrane, PubMed, Embase, Scopus", "200 mcg/day supplementation changed urinary iodine to adequate levels in pregnancy", "Mixed results across studies for specific thyroid parameters" ], "dosageUsed": "150-250 mcg daily", "evidenceRating": "moderate", "pmid": "37562272", "doi": "10.1016/j.jtemb.2023.127249", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37562272/", "publicSourceType": "PMID" }, { "id": "study-0447", "supplementName": "Iodine", "title": "Systematic review and meta-analysis of the effects of iodine supplementation on thyroid function and child neurodevelopment in mildly-to-moderately iodine-deficient pregnant women", "authors": "Dineva M, Fishpool H, Rayman MP et al.", "journal": "Am J Clin Nutr", "year": 2020, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Insufficient evidence to support iodine supplementation recommendations in mild-moderate deficiency during pregnancy", "keyFindings": [ "37 publications (10 RCTs, 4 non-RCT interventions, 23 observational studies) included", "Supplementation reduced thyroglobulin and thyroid volume but not TSH or fT4", "3 RCTs on child neurodevelopment showed no effect on cognitive, language, or motor scores" ], "dosageUsed": "150-250 mcg daily", "evidenceRating": "moderate", "pmid": "32320029", "doi": "10.1093/ajcn/nqaa071", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32320029/", "publicSourceType": "PMID" }, { "id": "study-0448", "supplementName": "Iodine", "title": "Effect of excess iodine intake on thyroid diseases in different populations: A systematic review and meta-analyses including observational studies", "authors": "Katagiri R, Yuan X, Kobayashi S et al.", "journal": "PLoS One", "year": 2017, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Excess iodine intake associated with higher risk of overt and subclinical hypothyroidism", "keyFindings": [ "50 articles (3 intervention trials, 6 case-control, 6 follow-up, 35 cross-sectional) included", "Odds of overt hypothyroidism 2.78x higher with excess vs adequate iodine in adults", "Odds of subclinical hypothyroidism 2.03x higher in excess iodine populations" ], "dosageUsed": "N/A (excess intake characterization)", "evidenceRating": "moderate", "pmid": "28282437", "doi": "10.1371/journal.pone.0173722", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28282437/", "publicSourceType": "PMID" }, { "id": "study-0449", "supplementName": "Boron", "title": "Pivotal role of boron supplementation on bone health: A narrative review", "authors": "Rondanelli M, Faliva MA, Peroni G et al.", "journal": "J Trace Elem Med Biol", "year": 2020, "studyType": "review", "sampleSize": 594, "outcome": "3 mg/day boron supplementation supports bone mineral density through calcium, vitamin D, and hormone metabolism", "keyFindings": [ "11 eligible studies (7 boron alone, 4 boron + other nutrients) with 594 total subjects", "Boron supports bone via calcium, vitamin D, and sex steroid hormone metabolism", "3 mg/day well below EFSA Upper Level of 10 mg and effective for bone maintenance" ], "dosageUsed": "3 mg daily", "evidenceRating": "emerging", "pmid": "32540741", "doi": "10.1016/j.jtemb.2020.126577", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32540741/", "publicSourceType": "PMID" }, { "id": "study-0450", "supplementName": "Boron", "title": "Boron compound administration; A novel agent in weight management: A systematic review and meta-analysis of animal studies", "authors": "Doaei S, Gholami S, Khajeh M et al.", "journal": "J Trace Elem Med Biol", "year": 2022, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Boron compounds showed weight-lowering effects in animal models", "keyFindings": [ "Systematic review and meta-analysis of animal studies on boron and body weight", "Weight reduction via increased energy metabolism, thermogenesis, lipolysis, and inhibition of adiposity", "Human studies too limited and heterogeneous for separate analysis" ], "dosageUsed": "Varied across animal studies", "evidenceRating": "emerging", "pmid": "35298949", "doi": "10.1016/j.jtemb.2022.126954", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35298949/", "publicSourceType": "PMID" }, { "id": "study-0451", "supplementName": "Boron", "title": "Nothing Boring About Boron", "authors": "Pizzorno L", "journal": "Integr Med (Encinitas)", "year": 2015, "studyType": "review", "sampleSize": null, "outcome": "Comprehensive review of boron's roles in bone, joints, inflammation, and steroid hormone metabolism", "keyFindings": [ "6 mg/day boron reduced osteoarthritis symptoms in pilot studies", "Boron influences production of estrogen, testosterone, vitamin D, and DHEA", "Anti-inflammatory effects through reduced NF-kappaB activity and lower CRP" ], "dosageUsed": "3-6 mg daily", "evidenceRating": "emerging", "pmid": "26770156", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26770156/", "publicSourceType": "PMID" }, { "id": "study-0452", "supplementName": "Potassium", "title": "Potassium Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials", "authors": "Filippini T, Naska A, Kasdagli MI et al.", "journal": "J Am Heart Assoc", "year": 2020, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "U-shaped relationship between potassium supplementation and blood pressure reduction", "keyFindings": [ "32 eligible RCTs using potassium doses 30-140 mmol/d identified", "U-shaped dose-response: BP reduction weakens above 30 mmol/d difference and reverses above ~80 mmol/d", "Greater BP-lowering in hypertensive subjects and those with higher sodium intake" ], "dosageUsed": "30-140 mmol/day (1.2-5.5 g/day)", "evidenceRating": "strong", "pmid": "32500831", "doi": "10.1161/JAHA.119.015719", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32500831/", "publicSourceType": "PMID" }, { "id": "study-0453", "supplementName": "Potassium", "title": "Effect of Salt Substitution on Cardiovascular Events and Death", "authors": "Neal B, Wu Y, Feng X et al.", "journal": "N Engl J Med", "year": 2021, "studyType": "rct", "sampleSize": 20995, "outcome": "Potassium-enriched salt substitute reduced stroke, cardiovascular events, and mortality in high-risk adults", "keyFindings": [ "Open-label cluster-randomized trial in 600 villages in rural China with 20,995 participants", "14% lower stroke risk, 13% lower major cardiovascular events, 12% lower all-cause mortality", "Salt substitute (75% NaCl, 25% KCl) vs regular salt over approximately 5 years" ], "dosageUsed": "25% KCl salt substitute", "evidenceRating": "strong", "pmid": "34459569", "doi": "10.1056/NEJMoa2105675", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34459569/", "publicSourceType": "PMID" }, { "id": "study-0454", "supplementName": "Potassium", "title": "Effect of changes in potassium intake on blood pressure: a dose-response meta-analysis of randomized clinical trials (2000-2024)", "authors": "Filippini T, Malavolti M, Cilloni S et al.", "journal": "Clin Kidney J", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Updated dose-response meta-analysis confirming potassium supplementation reduces blood pressure", "keyFindings": [ "Comprehensive meta-analysis of RCTs from 2000-2024", "Potassium supplementation resulted in SBP reduction of 4.7 mmHg and DBP reduction of 3.5 mmHg", "Greater effects in hypertensive patients: SBP -6.8 mmHg, DBP -4.6 mmHg" ], "dosageUsed": "30-140 mmol/day", "evidenceRating": "strong", "pmid": "40612568", "doi": "10.1093/ckj/sfaf173", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40612568/", "publicSourceType": "PMID" }, { "id": "study-0455", "supplementName": "Echinacea", "title": "Echinacea for the prevention and treatment of upper respiratory tract infections: A systematic review and meta-analysis", "authors": "David S, Cunningham R", "journal": "Complement Ther Med", "year": 2019, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Echinacea may prevent URTIs (RR 0.78) but has no significant effect on duration", "keyFindings": [ "Risk ratio of 0.78 (95% CI 0.68-0.88) for URTI prevention", "No significant effect on duration of illness (mean difference -0.45 days)", "No significant safety concerns with short-term use (RR 1.09)" ], "dosageUsed": "Varied across preparations", "evidenceRating": "moderate", "pmid": "31126553", "doi": "10.1016/j.ctim.2019.03.011", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31126553/", "publicSourceType": "PMID" }, { "id": "study-0456", "supplementName": "Echinacea", "title": "A systematic review on the effects of Echinacea supplementation on cytokine levels: Is there a role in COVID-19?", "authors": "Aucoin M, Cardozo V, Cooley K et al.", "journal": "Metabol Open", "year": 2021, "studyType": "review", "sampleSize": null, "outcome": "Echinacea supplementation associated with decreased pro-inflammatory and increased anti-inflammatory cytokines", "keyFindings": [ "279 publications screened; 105 studies met criteria (13 human, 24 animal, 71 in vitro)", "Associated with decreased IL-6, IL-8, and TNF and increased anti-inflammatory IL-10", "No direct evidence for COVID-19 but cytokine profile effects warrant further clinical investigation" ], "dosageUsed": "Varied across preparations and species", "evidenceRating": "emerging", "pmid": "34341776", "doi": "10.1016/j.metop.2021.100115", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34341776/", "publicSourceType": "PMID" }, { "id": "study-0457", "supplementName": "Echinacea", "title": "Echinacea Reduces Antibiotics by Preventing Respiratory Infections: A Meta-Analysis (ERA-PRIMA)", "authors": "Schapowal A, Klein P, Johnston SL", "journal": "Antibiotics (Basel)", "year": 2024, "studyType": "metaAnalysis", "sampleSize": 2458, "outcome": "Echinacea extracts reduced recurrent respiratory infections and antibiotic use", "keyFindings": [ "6 clinical studies with 2,458 participants pooled in meta-analysis", "Reduced risk of recurrent respiratory infections across populations", "Potential for reducing antibiotic overuse through infection prevention" ], "dosageUsed": "Varied standardized extracts", "evidenceRating": "moderate", "pmid": "38667040", "doi": "10.3390/antibiotics13040364", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38667040/", "publicSourceType": "PMID" }, { "id": "study-0458", "supplementName": "Elderberry", "title": "Black elderberry (Sambucus nigra) supplementation effectively treats upper respiratory symptoms: A meta-analysis of randomized, controlled clinical trials", "authors": "Hawkins J, Baker C, Cherry L et al.", "journal": "Complement Ther Med", "year": 2019, "studyType": "metaAnalysis", "sampleSize": 180, "outcome": "Elderberry supplementation substantially reduced upper respiratory symptoms with large effect size", "keyFindings": [ "Meta-analysis of RCTs with 180 total participants", "Large mean effect size for symptom reduction across trials", "Alternative to antibiotic misuse for viral upper respiratory infections" ], "dosageUsed": "300-600 mg extract daily", "evidenceRating": "moderate", "pmid": "30670267", "doi": "10.1016/j.ctim.2018.12.004", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30670267/", "publicSourceType": "PMID" }, { "id": "study-0459", "supplementName": "Elderberry", "title": "Elderberry for prevention and treatment of viral respiratory illnesses: a systematic review", "authors": "Wieland LS, Piechotta V, Feinberg T et al.", "journal": "BMC Complement Med Ther", "year": 2021, "studyType": "review", "sampleSize": null, "outcome": "Elderberry may be safe for viral respiratory illness treatment; no evidence of immune overstimulation", "keyFindings": [ "Systematic review of 6 databases, 4 research registers, and 2 preprint sites", "No evidence that elderberry overstimulates immune system or increases cytokine storm risk", "Uncertain but generally positive evidence for benefits; more studies needed" ], "dosageUsed": "Varied across formulations", "evidenceRating": "emerging", "pmid": "33827515", "doi": "10.1186/s12906-021-03283-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33827515/", "publicSourceType": "PMID" }, { "id": "study-0460", "supplementName": "Elderberry", "title": "The Pros and Cons of Using Elderberry (Sambucus nigra) for Prevention and Treatment of COVID-19", "authors": "Raeiszadeh M, Adib-Hajbaghery M et al.", "journal": "Adv Biomed Res", "year": 2022, "studyType": "review", "sampleSize": null, "outcome": "Elderberry has antiviral and immunomodulatory properties relevant to COVID-19 prevention and early treatment", "keyFindings": [ "Elderberry modulates inflammatory cytokines with both antiviral and immune-supportive effects", "No sufficient evidence to support claims of cytokine storm risk from elderberry", "Appropriate for prevention and initial treatment of viral respiratory disease" ], "dosageUsed": "300-600 mg extract daily", "evidenceRating": "emerging", "pmid": "36518861", "doi": "10.4103/abr.abr_135_22", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36518861/", "publicSourceType": "PMID" }, { "id": "study-0461", "supplementName": "Valerian Root", "title": "Valerian Root in Treating Sleep Problems and Associated Disorders - A Systematic Review and Meta-Analysis", "authors": "Shinjyo N, Waddell G, Green J", "journal": "J Evid Based Integr Med", "year": 2020, "studyType": "metaAnalysis", "sampleSize": 6894, "outcome": "Valerian is a safe herb that may promote sleep; efficacy depends on extract quality", "keyFindings": [ "60 studies (n=6,894) reviewed; meta-analyses on sleep quality (10 studies, 1065) and anxiety (8 studies, 535)", "Whole root/rhizome preparations more reliable than extracts", "No severe adverse events in subjects aged 7-80 years" ], "dosageUsed": "300-900 mg extract or 2-3 g dried root daily", "evidenceRating": "moderate", "pmid": "33086877", "doi": "10.1177/2515690X20967323", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33086877/", "publicSourceType": "PMID" }, { "id": "study-0462", "supplementName": "Valerian Root", "title": "Standardized Extract of Valeriana officinalis Improves Overall Sleep Quality in Human Subjects with Sleep Complaints: A Randomized, Double-Blind, Placebo-Controlled, Clinical Study", "authors": "Gupta P, Makkar R, Goel N et al.", "journal": "Adv Ther", "year": 2023, "studyType": "rct", "sampleSize": null, "outcome": "Valerian extract improved sleep quality, reduced anxiety and daytime sleepiness", "keyFindings": [ "Randomized double-blind placebo-controlled trial in adults with sleep complaints", "Decreased anxiety and daytime sleepiness with valerian extract", "Improved feeling of being refreshed upon waking" ], "dosageUsed": "Standardized valerian extract daily", "evidenceRating": "moderate", "pmid": "37938494", "doi": "10.1007/s12325-023-02708-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37938494/", "publicSourceType": "PMID" }, { "id": "study-0463", "supplementName": "Valerian Root", "title": "Does valerian work for insomnia? An umbrella review of the evidence", "authors": "Tempesta D, Socci V, De Gennaro L et al.", "journal": "Eur Neuropsychopharmacol", "year": 2024, "studyType": "review", "sampleSize": null, "outcome": "Umbrella review found limited but generally positive evidence for valerian in insomnia management", "keyFindings": [ "Overview of multiple systematic reviews and meta-analyses on valerian for insomnia", "Evidence suggests modest benefit for sleep quality improvement", "Methodological heterogeneity across studies limits definitive conclusions" ], "dosageUsed": "300-600 mg extract nightly", "evidenceRating": "moderate", "pmid": "38301171", "doi": "10.1016/j.euroneuro.2024.01.005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38301171/", "publicSourceType": "PMID" }, { "id": "study-0464", "supplementName": "Passionflower", "title": "Passiflora incarnata in Neuropsychiatric Disorders - A Systematic Review", "authors": "Janda K, Wojtkowska K, Jakubczyk K et al.", "journal": "Nutrients", "year": 2020, "studyType": "review", "sampleSize": null, "outcome": "Passiflora incarnata reduced anxiety levels in majority of clinical trials reviewed", "keyFindings": [ "9 randomized clinical trials identified and reviewed", "Majority of studies reported reduced anxiety following P. incarnata administration", "Effect less evident in people with mild anxiety symptoms; no adverse effects on memory or cognition" ], "dosageUsed": "Varied (extracts 90-800 mg daily)", "evidenceRating": "moderate", "pmid": "33352740", "doi": "10.3390/nu12123894", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33352740/", "publicSourceType": "PMID" }, { "id": "study-0465", "supplementName": "Passionflower", "title": "Effects of Passiflora incarnata Linnaeus on polysomnographic sleep parameters in subjects with insomnia disorder: a double-blind randomized placebo-controlled study", "authors": "Lee J, Jung HY, Lee SI et al.", "journal": "Int Clin Psychopharmacol", "year": 2020, "studyType": "rct", "sampleSize": 110, "outcome": "Passionflower extract significantly increased total sleep time on polysomnography in insomnia patients", "keyFindings": [ "110 adults with insomnia randomized to passionflower or placebo for 2 weeks", "Significant increase in total sleep time (TST) on objective polysomnography", "Other sleep parameters (ISI, sleep quality, latency) not significantly different, possibly due to short duration" ], "dosageUsed": "60 mg extract daily", "evidenceRating": "moderate", "pmid": "31714321", "doi": "10.1097/YIC.0000000000000291", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31714321/", "publicSourceType": "PMID" }, { "id": "study-0466", "supplementName": "Passionflower", "title": "Randomized, Double-Blind, Placebo-Controlled, Clinical Study of Passiflora incarnata in Participants With Stress and Sleep Problems", "authors": "Kang J, Kim Y, Yoo J et al.", "journal": "Cureus", "year": 2024, "studyType": "rct", "sampleSize": 65, "outcome": "Passiflora incarnata extract significantly reduced stress and increased total sleep time over 30 days", "keyFindings": [ "65 participants randomized to passionflower extract or placebo for 30 days", "Significant reduction in stress scores and improvement in general psychological health", "Significantly increased total sleep time compared to placebo at day 15 and day 30" ], "dosageUsed": "Passiflora incarnata extract daily", "evidenceRating": "moderate", "pmid": "38646244", "doi": "10.7759/cureus.56867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38646244/", "publicSourceType": "PMID" }, { "id": "study-0467", "supplementName": "Saw Palmetto", "title": "Serenoa repens for the treatment of lower urinary tract symptoms due to benign prostatic enlargement", "authors": "Franco JVA, Trivisonno LF, Sgarbossa NJ et al.", "journal": "Cochrane Database Syst Rev", "year": 2023, "studyType": "metaAnalysis", "sampleSize": 4656, "outcome": "Serenoa repens alone provides little to no benefit for lower urinary tract symptoms vs placebo", "keyFindings": [ "27 studies with 4,656 participants; databases searched to September 2022", "IPSS mean difference -0.90 (95% CI -1.74 to -0.07); high certainty of minimal clinical significance", "Little to no difference in quality of life or adverse events vs placebo" ], "dosageUsed": "320 mg daily (various extracts)", "evidenceRating": "strong", "pmid": "37345871", "doi": "10.1002/14651858.CD001423.pub4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37345871/", "publicSourceType": "PMID" }, { "id": "study-0468", "supplementName": "Saw Palmetto", "title": "Clinical Efficacy of Serenoa repens Versus Placebo Versus Alpha-blockers for the Treatment of Lower Urinary Tract Symptoms/Benign Prostatic Enlargement: A Systematic Review and Network Meta-analysis of Randomized Placebo-controlled Clinical Trials", "authors": "Vela-Navarrete R, Alcaraz A, Rodriguez-Antolin A et al.", "journal": "Eur Urol Focus", "year": 2020, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "No clinically meaningful improvement of Serenoa repens over placebo for LUTS/BPE in network meta-analysis", "keyFindings": [ "Network meta-analysis comparing hexanic extract, non-hexanic extract, placebo, and alpha-blockers", "Searched Medline, Scopus, Web of Science through December 2018", "Product heterogeneity and methodological limitations limit guideline recommendations" ], "dosageUsed": "320 mg daily", "evidenceRating": "moderate", "pmid": "31952967", "doi": "10.1016/j.euf.2019.12.005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31952967/", "publicSourceType": "PMID" }, { "id": "study-0469", "supplementName": "Saw Palmetto", "title": "Natural Hair Supplement: Friend or Foe? Saw Palmetto, a Systematic Review in Alopecia", "authors": "Evron E, Juhasz M, Babadjouni A et al.", "journal": "Skin Appendage Disord", "year": 2020, "studyType": "review", "sampleSize": null, "outcome": "Saw palmetto showed positive effects on hair growth in androgenetic alopecia across multiple studies", "keyFindings": [ "5 RCTs and 2 prospective cohort studies showed positive effects on hair quality in AGA", "60% improvement in overall hair quality and 27% improvement in total hair count reported", "Hair density increased in 83.3% of patients using SP-containing supplements" ], "dosageUsed": "100-320 mg daily", "evidenceRating": "emerging", "pmid": "33313047", "doi": "10.1159/000509905", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33313047/", "publicSourceType": "PMID" }, { "id": "rx-study-0411", "supplementName": "Atorvastatin", "title": "Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)", "authors": "Unknown", "journal": "Lancet", "year": 1994, "studyType": "rct", "sampleSize": null, "outcome": "Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)", "keyFindings": [ "Lowers LDL cholesterol by 39–60%", "Gold-standard randomized controlled trial design" ], "dosageUsed": "10–80 mg once daily", "evidenceRating": "strong", "pmid": "7968073", "doi": "10.1016/S0140-6736(94)90566-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7968073/", "publicSourceType": "PMID" }, { "id": "rx-study-0412", "supplementName": "Atorvastatin", "title": "Intensive lipid lowering with atorvastatin in patients with stable coronary disease", "authors": "LaRosa JC Grundy SM Waters DD et al.", "journal": "N Engl J Med", "year": 2005, "studyType": "rct", "sampleSize": null, "outcome": "Intensive lipid lowering with atorvastatin in patients with stable coronary disease", "keyFindings": [ "Lowers LDL cholesterol by 39–60%" ], "dosageUsed": "10–80 mg once daily", "evidenceRating": "strong", "pmid": "15755765", "doi": "10.1056/NEJMoa050461", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15755765/", "publicSourceType": "PMID" }, { "id": "rx-study-0413", "supplementName": "Atorvastatin", "title": "Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials", "authors": "Cholesterol Treatment Trialists’ (CTT) Collaboration Baigent C Blackwell L et al.", "journal": "Lancet", "year": 2010, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials", "keyFindings": [ "Lowers LDL cholesterol by 39–60%", "Systematic evidence synthesis across multiple trials", "Gold-standard randomized controlled trial design" ], "dosageUsed": "10–80 mg once daily", "evidenceRating": "strong", "pmid": "21067804", "doi": "10.1016/S0140-6736(10)61350-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21067804/", "publicSourceType": "PMID" }, { "id": "rx-study-0414", "supplementName": "Rosuvastatin", "title": "Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein", "authors": "Ridker PM Danielson E Fonseca FA et al.", "journal": "N Engl J Med", "year": 2008, "studyType": "rct", "sampleSize": null, "outcome": "Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein", "keyFindings": [ "Lowers LDL cholesterol by 45–63%" ], "dosageUsed": "5–40 mg once daily", "evidenceRating": "strong", "pmid": "18997196", "doi": "10.1056/NEJMoa0807646", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18997196/", "publicSourceType": "PMID" }, { "id": "rx-study-0415", "supplementName": "Rosuvastatin", "title": "MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial", "authors": "Heart Protection Study Collaborative Group", "journal": "Lancet", "year": 2002, "studyType": "rct", "sampleSize": null, "outcome": "MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial", "keyFindings": [ "Lowers LDL cholesterol by 45–63%", "Gold-standard randomized controlled trial design" ], "dosageUsed": "5–40 mg once daily", "evidenceRating": "strong", "pmid": "12114036", "doi": "10.1016/S0140-6736(02)09327-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12114036/", "publicSourceType": "PMID" }, { "id": "rx-study-0416", "supplementName": "Rosuvastatin", "title": "Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial", "authors": "Nissen SE Nicholls SJ Sipahi I et al.", "journal": "JAMA", "year": 2006, "studyType": "rct", "sampleSize": null, "outcome": "Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial", "keyFindings": [ "Lowers LDL cholesterol by 45–63%" ], "dosageUsed": "5–40 mg once daily", "evidenceRating": "strong", "pmid": "16533939", "doi": "10.1001/jama.295.13.jpc60002", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16533939/", "publicSourceType": "PMID" }, { "id": "rx-study-0417", "supplementName": "Simvastatin", "title": "Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)", "authors": "Unknown", "journal": "Lancet", "year": 1994, "studyType": "rct", "sampleSize": null, "outcome": "Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)", "keyFindings": [ "Lowers LDL cholesterol by 27–41% (up to 47% at the restricted 80 mg dose)", "Gold-standard randomized controlled trial design" ], "dosageUsed": "10–40 mg once daily in the evening", "evidenceRating": "strong", "pmid": "7968073", "doi": "10.1016/S0140-6736(94)90566-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7968073/", "publicSourceType": "PMID" }, { "id": "rx-study-0418", "supplementName": "Simvastatin", "title": "MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial", "authors": "Heart Protection Study Collaborative Group", "journal": "Lancet", "year": 2002, "studyType": "rct", "sampleSize": null, "outcome": "MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial", "keyFindings": [ "Lowers LDL cholesterol by 27–41% (up to 47% at the restricted 80 mg dose)", "Gold-standard randomized controlled trial design" ], "dosageUsed": "10–40 mg once daily in the evening", "evidenceRating": "strong", "pmid": "12114036", "doi": "10.1016/S0140-6736(02)09327-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12114036/", "publicSourceType": "PMID" }, { "id": "rx-study-0419", "supplementName": "Simvastatin", "title": "A Meta-Analysis of the Incidence of Adverse Reactions of Statins in Various Diseases", "authors": "Li W Wang D Lin C et al.", "journal": "Cardiovasc Ther", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "A Meta-Analysis of the Incidence of Adverse Reactions of Statins in Various Diseases", "keyFindings": [ "Lowers LDL cholesterol by 27–41% (up to 47% at the restricted 80 mg dose)", "Systematic evidence synthesis across multiple trials" ], "dosageUsed": "10–40 mg once daily in the evening", "evidenceRating": "strong", "pmid": "40529509", "doi": "10.1155/cdr/6684099", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40529509/", "publicSourceType": "PMID" }, { "id": "rx-study-0420", "supplementName": "Pravastatin", "title": "Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group", "authors": "Shepherd J Cobbe SM Ford I et al.", "journal": "N Engl J Med", "year": 1995, "studyType": "rct", "sampleSize": null, "outcome": "Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group", "keyFindings": [ "Lowers LDL cholesterol by 22–37%" ], "dosageUsed": "10–80 mg once daily", "evidenceRating": "strong", "pmid": "7566020", "doi": "10.1056/NEJM199511163332001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7566020/", "publicSourceType": "PMID" }, { "id": "rx-study-0421", "supplementName": "Pravastatin", "title": "The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators", "authors": "Sacks FM Pfeffer MA Moye LA et al.", "journal": "N Engl J Med", "year": 1996, "studyType": "rct", "sampleSize": null, "outcome": "The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators", "keyFindings": [ "Lowers LDL cholesterol by 22–37%" ], "dosageUsed": "10–80 mg once daily", "evidenceRating": "strong", "pmid": "8801446", "doi": "10.1056/NEJM199610033351401", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8801446/", "publicSourceType": "PMID" }, { "id": "rx-study-0422", "supplementName": "Pravastatin", "title": "A Meta-Analysis of the Incidence of Adverse Reactions of Statins in Various Diseases", "authors": "Li W Wang D Lin C et al.", "journal": "Cardiovasc Ther", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "A Meta-Analysis of the Incidence of Adverse Reactions of Statins in Various Diseases", "keyFindings": [ "Lowers LDL cholesterol by 22–37%", "Systematic evidence synthesis across multiple trials" ], "dosageUsed": "10–80 mg once daily", "evidenceRating": "strong", "pmid": "40529509", "doi": "10.1155/cdr/6684099", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40529509/", "publicSourceType": "PMID" }, { "id": "rx-study-0423", "supplementName": "Lovastatin", "title": "Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study", "authors": "Downs JR Clearfield M Weis S et al.", "journal": "JAMA", "year": 1998, "studyType": "rct", "sampleSize": null, "outcome": "Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study", "keyFindings": [ "Lowers LDL cholesterol by 20–40%" ], "dosageUsed": "10–80 mg daily with evening meal", "evidenceRating": "strong", "pmid": "9613910", "doi": "10.1001/jama.279.20.1615", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9613910/", "publicSourceType": "PMID" }, { "id": "rx-study-0424", "supplementName": "Lovastatin", "title": "Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)", "authors": "Unknown", "journal": "Lancet", "year": 1994, "studyType": "rct", "sampleSize": null, "outcome": "Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)", "keyFindings": [ "Lowers LDL cholesterol by 20–40%", "Gold-standard randomized controlled trial design" ], "dosageUsed": "10–80 mg daily with evening meal", "evidenceRating": "strong", "pmid": "7968073", "doi": "10.1016/S0140-6736(94)90566-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7968073/", "publicSourceType": "PMID" }, { "id": "rx-study-0425", "supplementName": "Lovastatin", "title": "Statins for the primary prevention of venous thromboembolism", "authors": "Wang Z Zhang P Tian J et al.", "journal": "Cochrane Database Syst Rev", "year": 2024, "studyType": "review", "sampleSize": null, "outcome": "Statins for the primary prevention of venous thromboembolism", "keyFindings": [ "Lowers LDL cholesterol by 20–40%" ], "dosageUsed": "10–80 mg daily with evening meal", "evidenceRating": "strong", "pmid": "39498835", "doi": "10.1002/14651858.CD014769.pub2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39498835/", "publicSourceType": "PMID" }, { "id": "rx-study-0426", "supplementName": "Lisinopril", "title": "Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients", "authors": "Heart Outcomes Prevention Evaluation Study Investigators Yusuf S Sleight P et al.", "journal": "N Engl J Med", "year": 2000, "studyType": "rct", "sampleSize": null, "outcome": "Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients", "keyFindings": [ "Lowers blood pressure effectively", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "5–40 mg once daily", "evidenceRating": "strong", "pmid": "10639539", "doi": "10.1056/NEJM200001203420301", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10639539/", "publicSourceType": "PMID" }, { "id": "rx-study-0427", "supplementName": "Lisinopril", "title": "Similar clinical benefits from below-target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial", "authors": "Lam PH Dooley DJ Fonarow GC et al.", "journal": "Eur J Heart Fail", "year": 2018, "studyType": "rct", "sampleSize": null, "outcome": "Similar clinical benefits from below-target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial", "keyFindings": [ "Lowers blood pressure effectively", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "5–40 mg once daily", "evidenceRating": "strong", "pmid": "28980368", "doi": "10.1002/ejhf.937", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28980368/", "publicSourceType": "PMID" }, { "id": "rx-study-0428", "supplementName": "Lisinopril", "title": "Efficacy of pharmacological agents for management of post-partum hypertension: A systematic review and network meta-analysis", "authors": "Singh A Singh MP Thakur P et al.", "journal": "J Hum Hypertens", "year": 2026, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Efficacy of pharmacological agents for management of post-partum hypertension: A systematic review and network meta-analysis", "keyFindings": [ "Lowers blood pressure effectively", "Systematic evidence synthesis across multiple trials", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "5–40 mg once daily", "evidenceRating": "strong", "pmid": "41663753", "doi": "10.1038/s41371-026-01120-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41663753/", "publicSourceType": "PMID" }, { "id": "rx-study-0429", "supplementName": "Enalapril", "title": "Similar clinical benefits from below-target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial", "authors": "Lam PH Dooley DJ Fonarow GC et al.", "journal": "Eur J Heart Fail", "year": 2018, "studyType": "rct", "sampleSize": null, "outcome": "Similar clinical benefits from below-target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial", "keyFindings": [ "Reduces mortality in heart failure with reduced ejection fraction", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "2.5–40 mg daily in 1–2 divided doses", "evidenceRating": "strong", "pmid": "28980368", "doi": "10.1002/ejhf.937", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28980368/", "publicSourceType": "PMID" }, { "id": "rx-study-0430", "supplementName": "Enalapril", "title": "Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS)", "authors": "CONSENSUS Trial Study Group", "journal": "N Engl J Med", "year": 1987, "studyType": "rct", "sampleSize": null, "outcome": "Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS)", "keyFindings": [ "Reduces mortality in heart failure with reduced ejection fraction", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "2.5–40 mg daily in 1–2 divided doses", "evidenceRating": "strong", "pmid": "2883575", "doi": "10.1056/NEJM198706043162301", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2883575/", "publicSourceType": "PMID" }, { "id": "rx-study-0431", "supplementName": "Enalapril", "title": "Impact of antihypertensive treatment on cardiovascular event reduction in patients with asymptomatic carotid artery stenosis: a systematic review and meta-analysis", "authors": "Popat A Pethe G Yadav S et al.", "journal": "Pan Afr Med J", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Impact of antihypertensive treatment on cardiovascular event reduction in patients with asymptomatic carotid artery stenosis: a systematic review and meta-analysis", "keyFindings": [ "Reduces mortality in heart failure with reduced ejection fraction", "Systematic evidence synthesis across multiple trials", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "2.5–40 mg daily in 1–2 divided doses", "evidenceRating": "strong", "pmid": "41323461", "doi": "10.11604/pamj.2025.52.18.46768", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41323461/", "publicSourceType": "PMID" }, { "id": "rx-study-0432", "supplementName": "Ramipril", "title": "Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients", "authors": "Heart Outcomes Prevention Evaluation Study Investigators Yusuf S Sleight P et al.", "journal": "N Engl J Med", "year": 2000, "studyType": "rct", "sampleSize": null, "outcome": "Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk 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"dosageUsed": "1.25–20 mg daily in 1–2 divided doses", "evidenceRating": "strong", "pmid": "8105262", "doi": "10.1016/0140-6736(93)92876-u", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8105262/", "publicSourceType": "PMID" }, { "id": "rx-study-0434", "supplementName": "Ramipril", "title": "Effects of polypills on cardiovascular outcomes: Meta-analysis of clinical trials and observational studies", "authors": "Rodríguez-Armesto A, Khan KS, Cinza-Sanjurjo S", "journal": "Semergen", "year": 2026, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Effects of polypills on cardiovascular outcomes: Meta-analysis of clinical trials and observational studies", "keyFindings": [ "Reduces cardiovascular death, MI, and stroke in high-risk patients (HOPE trial)", "Systematic evidence synthesis across multiple trials", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "1.25–20 mg daily in 1–2 divided doses", "evidenceRating": "strong", "pmid": "41558137", "doi": "10.1016/j.semerg.2025.102680", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41558137/", "publicSourceType": "PMID" }, { "id": "rx-study-0435", "supplementName": "Benazepril", "title": "Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients", "authors": "Heart Outcomes Prevention Evaluation Study Investigators Yusuf S Sleight P et al.", "journal": "N Engl J Med", "year": 2000, "studyType": "rct", "sampleSize": null, "outcome": "Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients", "keyFindings": [ "Effective blood pressure reduction", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "5–40 mg daily in 1–2 divided doses", "evidenceRating": "strong", "pmid": "10639539", "doi": "10.1056/NEJM200001203420301", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10639539/", "publicSourceType": "PMID" }, { "id": "rx-study-0436", "supplementName": "Benazepril", "title": "Similar clinical benefits from below-target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial", "authors": "Lam PH Dooley DJ Fonarow GC et al.", "journal": "Eur J Heart Fail", "year": 2018, "studyType": "rct", "sampleSize": null, "outcome": "Similar clinical benefits from below-target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial", "keyFindings": [ "Effective blood pressure reduction", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "5–40 mg daily in 1–2 divided doses", "evidenceRating": "strong", "pmid": "28980368", "doi": "10.1002/ejhf.937", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28980368/", "publicSourceType": "PMID" }, { "id": "rx-study-0437", "supplementName": "Benazepril", "title": "Treatments for Chronic Kidney Disease: A Systematic Literature Review of Randomized Controlled Trials", "authors": "Garcia Sanchez JJ Thompson J Scott DA et al.", "journal": "Adv Ther", "year": 2022, "studyType": "review", "sampleSize": null, "outcome": "Treatments for Chronic Kidney Disease: A Systematic Literature Review of Randomized Controlled Trials", "keyFindings": [ "Effective blood pressure reduction", "Gold-standard randomized controlled trial design", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "5–40 mg daily in 1–2 divided doses", "evidenceRating": "strong", "pmid": "34881414", "doi": "10.1007/s12325-021-02006-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34881414/", "publicSourceType": "PMID" }, { "id": "rx-study-0438", "supplementName": "Losartan", "title": "Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol", "authors": "Dahlöf B Devereux RB Kjeldsen SE et al.", "journal": "Lancet", "year": 2002, "studyType": "rct", "sampleSize": null, "outcome": "Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol", "keyFindings": [ "Reduces blood pressure effectively", "Gold-standard randomized controlled trial design", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "25–100 mg daily in 1–2 divided doses", "evidenceRating": "strong", "pmid": "11937178", "doi": "10.1016/S0140-6736(02)08089-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11937178/", "publicSourceType": "PMID" }, { "id": "rx-study-0439", "supplementName": "Losartan", "title": "Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy", "authors": "Brenner BM Cooper ME de Zeeuw D et al.", "journal": "N Engl J Med", "year": 2001, "studyType": "rct", "sampleSize": null, "outcome": "Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy", "keyFindings": [ "Reduces blood pressure effectively", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "25–100 mg daily in 1–2 divided doses", "evidenceRating": "strong", "pmid": "11565518", "doi": "10.1056/NEJMoa011161", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11565518/", "publicSourceType": "PMID" }, { "id": "rx-study-0440", "supplementName": "Losartan", "title": "A systematic review of commencing full-dose antihypertensives in newly diagnosed hypertension", "authors": "Karavadra B D Elia A Shantsila A et al.", "journal": "Blood Press", "year": 2025, "studyType": "review", "sampleSize": null, "outcome": "A systematic review of commencing full-dose antihypertensives in newly diagnosed hypertension", "keyFindings": [ "Reduces blood pressure effectively", "Systematic evidence synthesis across multiple trials", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "25–100 mg daily in 1–2 divided doses", "evidenceRating": "strong", "pmid": "41351601", "doi": "10.1080/08037051.2025.2594268", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41351601/", "publicSourceType": "PMID" }, { "id": "rx-study-0441", "supplementName": "Valsartan", "title": "A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure", "authors": "Cohn JN, Tognoni G, Valsartan Heart Failure Trial Investigators", "journal": "N Engl J Med", "year": 2001, "studyType": "rct", "sampleSize": null, "outcome": "A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure", "keyFindings": [ "Effective blood pressure reduction", "Gold-standard randomized controlled trial design", "Safety profile 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"publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14610160/", "publicSourceType": "PMID" }, { "id": "rx-study-0443", "supplementName": "Valsartan", "title": "Antihypertensive drugs for hyperuricemia in patients with hypertension: a systematic review and network meta-analysis of Chinese trials", "authors": "Wu J Di H Zhang Y et al.", "journal": "BMC Cardiovasc Disord", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Antihypertensive drugs for hyperuricemia in patients with hypertension: a systematic review and network meta-analysis of Chinese trials", "keyFindings": [ "Effective blood pressure reduction", "Systematic evidence synthesis across multiple trials", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "40–320 mg once daily", "evidenceRating": "strong", "pmid": "41331424", "doi": "10.1186/s12872-025-05339-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41331424/", "publicSourceType": "PMID" }, { "id": "rx-study-0444", "supplementName": "Irbesartan", "title": "The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes", "authors": "Parving HH Lehnert H Bröchner-Mortensen J et al.", "journal": "N Engl J Med", "year": 2001, "studyType": "rct", "sampleSize": null, "outcome": "The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes", "keyFindings": [ "Effective 24-hour blood pressure reduction", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "75–300 mg once daily", "evidenceRating": "strong", "pmid": "11565519", "doi": "10.1056/NEJMoa011489", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11565519/", "publicSourceType": "PMID" }, { "id": "rx-study-0445", "supplementName": "Irbesartan", "title": "Renoprotective effect of the angiotensin-receptor 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"sampleSize": null, "outcome": "A systematic review of commencing full-dose antihypertensives in newly diagnosed hypertension", "keyFindings": [ "Effective 24-hour blood pressure reduction", "Systematic evidence synthesis across multiple trials", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "75–300 mg once daily", "evidenceRating": "strong", "pmid": "41351601", "doi": "10.1080/08037051.2025.2594268", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41351601/", "publicSourceType": "PMID" }, { "id": "rx-study-0447", "supplementName": "Olmesartan", "title": "Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol", "authors": "Dahlöf B Devereux RB Kjeldsen SE et al.", "journal": "Lancet", "year": 2002, "studyType": "rct", "sampleSize": null, "outcome": "Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol", "keyFindings": [ "Potent blood pressure reduction", "Gold-standard randomized controlled trial design", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "20–40 mg once daily", "evidenceRating": "strong", "pmid": "11937178", "doi": "10.1016/S0140-6736(02)08089-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11937178/", "publicSourceType": "PMID" }, { "id": "rx-study-0448", "supplementName": "Olmesartan", "title": "Heart failure with mid-range ejection fraction in CHARM: characteristics, outcomes and effect of candesartan across the entire ejection fraction spectrum", "authors": "Lund LH Claggett B Liu J et al.", "journal": "Eur J Heart Fail", "year": 2018, "studyType": "rct", "sampleSize": null, "outcome": "Heart failure with mid-range ejection fraction in CHARM: characteristics, outcomes and effect of candesartan across the entire ejection fraction spectrum", "keyFindings": [ "Potent blood pressure reduction", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "20–40 mg once daily", "evidenceRating": "strong", "pmid": "29431256", "doi": "10.1002/ejhf.1149", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29431256/", "publicSourceType": "PMID" }, { "id": "rx-study-0449", "supplementName": "Olmesartan", "title": "A Systematic Literature Review and Network Meta-analysis of Azilsartan Medoxomil Compared to Other Anti-hypertensives Efficacy in Lowering Blood Pressure Amongst Mild to Moderate Hypertensive Patients", "authors": "Qian J, Zhang M, Chen Z", "journal": "Adv Ther", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "A Systematic Literature Review and Network Meta-analysis of Azilsartan Medoxomil Compared to Other Anti-hypertensives Efficacy in Lowering Blood Pressure Amongst Mild to Moderate Hypertensive Patients", "keyFindings": [ "Potent blood pressure reduction", "Systematic evidence synthesis across multiple trials", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "20–40 mg once daily", "evidenceRating": "strong", "pmid": "39412629", "doi": "10.1007/s12325-024-02997-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39412629/", "publicSourceType": "PMID" }, { "id": "rx-study-0450", "supplementName": "Metoprolol", "title": "Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF)", "authors": "Unknown", "journal": "Lancet", "year": 1999, "studyType": "rct", "sampleSize": null, "outcome": "Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF)", "keyFindings": [ "Reduces all-cause mortality in heart failure (MERIT-HF)", "Gold-standard randomized controlled trial 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artery stenosis: a systematic review and meta-analysis", "keyFindings": [ "Reduces all-cause mortality in heart failure (MERIT-HF)", "Systematic evidence synthesis across multiple trials", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "Tartrate: 25–200 mg twice daily; Succinate: 25–200 mg once daily", "evidenceRating": "strong", "pmid": "41323461", "doi": "10.11604/pamj.2025.52.18.46768", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41323461/", "publicSourceType": "PMID" }, { "id": "rx-study-0453", "supplementName": "Atenolol", "title": "Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol", "authors": "Dahlöf B Devereux RB Kjeldsen SE et al.", "journal": "Lancet", "year": 2002, "studyType": "rct", "sampleSize": null, "outcome": "Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol", "keyFindings": [ "Effective blood pressure reduction", "Gold-standard randomized controlled trial design", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "25–100 mg once daily", "evidenceRating": "moderate", "pmid": "11937178", "doi": "10.1016/S0140-6736(02)08089-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11937178/", "publicSourceType": "PMID" }, { "id": "rx-study-0454", "supplementName": "Atenolol", "title": "Atenolol in hypertension: is it a wise choice?", "authors": "Carlberg B, Samuelsson O, Lindholm LH", "journal": "Lancet", "year": 2004, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Atenolol in hypertension: is it a wise choice?", "keyFindings": [ "Effective blood pressure reduction", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "25–100 mg once daily", "evidenceRating": "moderate", "pmid": "15530629", "doi": "10.1016/S0140-6736(04)17355-8", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15530629/", "publicSourceType": "PMID" }, { "id": "rx-study-0455", "supplementName": "Atenolol", "title": "A Systematic Review and Meta-Analysis of the Efficacy and Safety of Propranolol Versus Other Drugs in the Treatment of Infantile Hemangioma", "authors": "Hu J Pan L Kong H et al.", "journal": "J Cosmet Dermatol", "year": 2026, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "A Systematic Review and Meta-Analysis of the Efficacy and Safety of Propranolol Versus Other Drugs in the Treatment of Infantile Hemangioma", "keyFindings": [ "Effective blood pressure reduction", "Systematic evidence synthesis across multiple trials", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "25–100 mg once daily", "evidenceRating": "moderate", "pmid": "41700540", "doi": "10.1111/jocd.70750", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41700540/", "publicSourceType": "PMID" }, { "id": "rx-study-0456", "supplementName": "Propranolol", "title": "Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF)", "authors": "Unknown", "journal": "Lancet", "year": 1999, "studyType": "rct", "sampleSize": null, "outcome": "Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF)", "keyFindings": [ "Effective for rate control in arrhythmias", "Gold-standard randomized controlled trial design", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "40–320 mg daily in 2–3 divided doses", "evidenceRating": "strong", "pmid": "10376614", "doi": "10.1016/S0140-6736(99)04440-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10376614/", "publicSourceType": "PMID" }, { "id": "rx-study-0457", "supplementName": "Propranolol", "title": "Propranolol: A 50-Year Historical Perspective", "authors": "Srinivasan AV", "journal": "Ann Indian Acad Neurol", "year": 2019, "studyType": "review", "sampleSize": null, "outcome": "Propranolol: A 50-Year Historical Perspective", "keyFindings": [ "Effective for rate control in arrhythmias", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "40–320 mg daily in 2–3 divided doses", "evidenceRating": "strong", "pmid": "30692755", "doi": "10.4103/aian.AIAN_201_18", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30692755/", "publicSourceType": "PMID" }, { "id": "rx-study-0458", "supplementName": "Propranolol", "title": "A Systematic Review and Meta-Analysis of the Efficacy and Safety of Propranolol Versus Other Drugs in the Treatment of Infantile Hemangioma", "authors": "Hu J Pan L Kong H et al.", "journal": "J Cosmet Dermatol", 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SHEP Cooperative Research Group", "keyFindings": [ "Superior 24-hour blood pressure control compared to HCTZ" ], "dosageUsed": "12.5–25 mg once daily", "evidenceRating": "strong", "pmid": "2046107", "doi": "10.1001/jama.265.24.3255", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2046107/", "publicSourceType": "PMID" }, { "id": "rx-study-0488", "supplementName": "Chlorthalidone", "title": "Thiazide and thiazide-like diuretics for kidney stones recurrence: a systematic review and network meta-analysis of randomised controlled trials", "authors": "Oliveira AV Sampaio ALN Mascarenhas RW Jr et al.", "journal": "World J Urol", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Thiazide and thiazide-like diuretics for kidney stones recurrence: a systematic review and network meta-analysis of randomised controlled trials", "keyFindings": [ "Superior 24-hour blood pressure control compared to HCTZ", "Systematic evidence synthesis across multiple trials", "Gold-standard randomized controlled trial design" ], "dosageUsed": "12.5–25 mg once daily", "evidenceRating": "strong", "pmid": "41396435", "doi": "10.1007/s00345-025-06137-8", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41396435/", "publicSourceType": "PMID" }, { "id": "rx-study-0489", "supplementName": "Warfarin", "title": "Systematic overview of warfarin and its drug and food interactions", "authors": "Holbrook AM Pereira JA Labiris R et al.", "journal": "Arch Intern Med", "year": 2005, "studyType": "review", "sampleSize": null, "outcome": "Systematic overview of warfarin and its drug and food interactions", "keyFindings": [ "Effective stroke prevention in atrial fibrillation", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "Variable; typically 2–10 mg daily adjusted to target INR", "evidenceRating": "strong", "pmid": "15911722", "doi": "10.1001/archinte.165.10.1095", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15911722/", "publicSourceType": "PMID" }, { "id": "rx-study-0490", "supplementName": "Warfarin", "title": "Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation", "authors": "Hart RG, Pearce LA, Aguilar MI", "journal": "Ann Intern Med", "year": 2007, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation", "keyFindings": [ "Effective stroke prevention in atrial fibrillation", "Systematic evidence synthesis across multiple trials", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "Variable; typically 2–10 mg daily adjusted to target INR", "evidenceRating": "strong", "pmid": "17577005", "doi": "10.7326/0003-4819-146-12-200706190-00007", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17577005/", "publicSourceType": "PMID" }, { "id": "rx-study-0491", "supplementName": "Warfarin", "title": "Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines", "authors": "Ageno W Gallus AS Wittkowsky A et al.", "journal": "Chest", "year": 2012, "studyType": "review", "sampleSize": null, "outcome": "Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines", "keyFindings": [ "Effective stroke prevention in atrial fibrillation", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "Variable; typically 2–10 mg daily adjusted to target INR", "evidenceRating": "strong", "pmid": "22315269", "doi": "10.1378/chest.11-2292", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22315269/", "publicSourceType": "PMID" }, { "id": "rx-study-0492", "supplementName": "Apixaban", "title": "Apixaban versus warfarin in patients with atrial fibrillation", "authors": "Granger CB Alexander JH McMurray JJ et al.", "journal": "N Engl J Med", "year": 2011, "studyType": "rct", "sampleSize": null, "outcome": "Apixaban versus warfarin in patients with atrial fibrillation", "keyFindings": [ "Superior to warfarin for stroke prevention with less bleeding (ARISTOTLE)", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "AF: 5 mg twice daily", "evidenceRating": "strong", "pmid": "21870978", "doi": "10.1056/NEJMoa1107039", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21870978/", "publicSourceType": "PMID" }, { "id": "rx-study-0493", "supplementName": "Apixaban", "title": "Oral apixaban for the treatment of acute venous thromboembolism", "authors": "Agnelli G Buller HR Cohen A et al.", "journal": "N Engl J Med", "year": 2013, "studyType": "rct", "sampleSize": null, "outcome": "Oral apixaban for the treatment of acute venous thromboembolism", "keyFindings": [ "Superior to warfarin for stroke prevention with less bleeding (ARISTOTLE)", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "AF: 5 mg twice daily", "evidenceRating": "strong", "pmid": "23808982", "doi": "10.1056/NEJMoa1302507", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23808982/", "publicSourceType": "PMID" }, { "id": "rx-study-0494", "supplementName": "Apixaban", "title": "Reduced-Dose Versus Full-Dose Direct Oral Anticoagulants for Extended Treatment of Venous Thromboembolism", "authors": "Deng D, Xu Z, Zhu W", "journal": "Clin Appl Thromb Hemost", "year": 2025, "studyType": "review", "sampleSize": null, "outcome": "Reduced-Dose Versus Full-Dose Direct Oral Anticoagulants for Extended Treatment of Venous Thromboembolism", "keyFindings": [ "Superior to warfarin for stroke prevention with less bleeding (ARISTOTLE)", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "AF: 5 mg twice daily", "evidenceRating": "strong", "pmid": "41428436", "doi": "10.1177/10760296251408061", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41428436/", "publicSourceType": "PMID" }, { "id": "rx-study-0495", "supplementName": "Rivaroxaban", "title": "Rivaroxaban versus warfarin in nonvalvular atrial fibrillation", "authors": "Patel MR Mahaffey KW Garg J et al.", "journal": "N Engl J Med", "year": 2011, "studyType": "rct", "sampleSize": null, "outcome": "Rivaroxaban versus warfarin in nonvalvular atrial fibrillation", "keyFindings": [ "Non-inferior to warfarin for stroke prevention in AF (ROCKET AF)", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "AF: 20 mg once daily with evening meal; DVT/PE: 15 mg twice daily for 21 days, then 20 mg daily; Vascular prevention: 2.5 mg twice daily with aspirin", "evidenceRating": "strong", "pmid": "21830957", "doi": "10.1056/NEJMoa1009638", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21830957/", "publicSourceType": "PMID" }, { "id": "rx-study-0496", "supplementName": "Rivaroxaban", "title": "Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease", "authors": "Eikelboom JW Connolly SJ Bosch J et al.", "journal": "N Engl J Med", "year": 2017, "studyType": "rct", "sampleSize": null, "outcome": "Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease", "keyFindings": [ "Non-inferior to warfarin for stroke prevention in AF (ROCKET AF)", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "AF: 20 mg once daily with evening meal; DVT/PE: 15 mg twice daily for 21 days, then 20 mg daily; Vascular prevention: 2.5 mg twice daily with aspirin", "evidenceRating": "strong", "pmid": "28844192", "doi": "10.1056/NEJMoa1709118", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28844192/", "publicSourceType": "PMID" }, { "id": "rx-study-0497", "supplementName": "Rivaroxaban", "title": "Reduced-Dose Versus Full-Dose Direct Oral Anticoagulants for Extended Treatment of Venous Thromboembolism", "authors": "Deng D, Xu Z, Zhu W", "journal": "Clin Appl Thromb Hemost", "year": 2025, "studyType": "review", "sampleSize": null, "outcome": "Reduced-Dose Versus Full-Dose Direct Oral Anticoagulants for Extended Treatment of Venous Thromboembolism", "keyFindings": [ "Non-inferior to warfarin for stroke prevention in AF (ROCKET AF)", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "AF: 20 mg once daily with evening meal; DVT/PE: 15 mg twice daily for 21 days, then 20 mg daily; Vascular prevention: 2.5 mg twice daily with aspirin", "evidenceRating": "strong", "pmid": "41428436", "doi": "10.1177/10760296251408061", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41428436/", "publicSourceType": "PMID" }, { "id": "rx-study-0498", "supplementName": "Dabigatran", "title": "Dabigatran versus warfarin in patients with atrial fibrillation", "authors": "Connolly SJ Ezekowitz MD Yusuf S et al.", "journal": "N Engl J Med", "year": 2009, "studyType": "rct", "sampleSize": null, "outcome": "Dabigatran versus warfarin in patients with atrial fibrillation", "keyFindings": [ "Non-inferior (150 mg) or superior to warfarin for stroke prevention in AF", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "AF: 150 mg twice daily", "evidenceRating": "strong", "pmid": "19717844", "doi": "10.1056/NEJMoa0905561", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19717844/", "publicSourceType": "PMID" }, { "id": "rx-study-0499", "supplementName": "Dabigatran", "title": "Idarucizumab for Dabigatran Reversal", "authors": "Pollack CV Jr Reilly PA Eikelboom J et al.", "journal": "N Engl J Med", "year": 2015, "studyType": "rct", "sampleSize": null, "outcome": "Idarucizumab for Dabigatran Reversal", "keyFindings": [ "Non-inferior (150 mg) or superior to warfarin for stroke prevention in AF", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "AF: 150 mg twice daily", "evidenceRating": "strong", "pmid": "26095746", "doi": "10.1056/NEJMoa1502000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26095746/", "publicSourceType": "PMID" }, { "id": "rx-study-0500", "supplementName": "Dabigatran", "title": "Switching From Aspirin Monotherapy After Noncardioembolic Stroke: A Systematic Review and Network Meta-Analysis", "authors": "Rothstein A Khazaal O Messe SR et al.", "journal": "Stroke", "year": 2026, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Switching From Aspirin Monotherapy After Noncardioembolic Stroke: A Systematic Review and Network Meta-Analysis", "keyFindings": [ "Non-inferior (150 mg) or superior to warfarin for stroke prevention in AF", "Systematic evidence synthesis across multiple trials", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "AF: 150 mg twice daily", "evidenceRating": "strong", "pmid": "41347302", "doi": "10.1161/STROKEAHA.125.053030", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41347302/", "publicSourceType": "PMID" }, { "id": "rx-study-0501", "supplementName": "Enoxaparin", "title": "Effectiveness and safety of betrixaban extended prophylaxis for venous thromboembolism compared with standard-duration prophylaxis intervention in acute medically ill patients: a systematic literature review and network meta-analysis", "authors": "Laskier V Guy H Fisher M et al.", "journal": "J Med Econ", "year": 2019, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Effectiveness and safety of betrixaban extended prophylaxis for venous thromboembolism compared with standard-duration prophylaxis intervention in acute medically ill patients: a systematic literature review and network meta-analysis", "keyFindings": [ "Effective DVT/PE prevention and treatment", "Systematic evidence synthesis across multiple trials", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "Prophylaxis: 30 mg SC q12h or 40 mg SC daily; Treatment: 1 mg/kg SC q12h or 1.5 mg/kg SC daily", "evidenceRating": "strong", "pmid": "31314619", "doi": "10.1080/13696998.2019.1645679", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31314619/", "publicSourceType": "PMID" }, { "id": "rx-study-0502", "supplementName": "Enoxaparin", "title": "Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report", "authors": "Kearon C Akl EA Ornelas J et al.", "journal": "Chest", "year": 2016, "studyType": "review", "sampleSize": null, "outcome": "Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report", "keyFindings": [ "Effective DVT/PE prevention and treatment", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "Prophylaxis: 30 mg SC q12h or 40 mg SC daily; Treatment: 1 mg/kg SC q12h or 1.5 mg/kg SC daily", "evidenceRating": "strong", "pmid": "26867832", "doi": "10.1016/j.chest.2015.11.026", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26867832/", "publicSourceType": "PMID" }, { "id": "rx-study-0503", "supplementName": "Enoxaparin", "title": "Whether an optimal strategy exists for VTE prevention in critically ill patients: Insights from guidelines and randomized controlled trials", "authors": "Wei D Ma S Huang W et al.", "journal": "Eur J Intern Med", "year": 2025, "studyType": "review", "sampleSize": null, "outcome": "Whether an optimal strategy exists for VTE prevention in critically ill patients: Insights from guidelines and randomized controlled trials", "keyFindings": [ "Effective DVT/PE prevention and treatment", "Gold-standard randomized controlled trial design", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "Prophylaxis: 30 mg SC q12h or 40 mg SC daily; Treatment: 1 mg/kg SC q12h or 1.5 mg/kg SC daily", "evidenceRating": "strong", "pmid": "40713472", "doi": "10.1016/j.ejim.2025.07.022", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40713472/", "publicSourceType": "PMID" }, { "id": "rx-study-0504", "supplementName": "Aspirin Low-Dose", "title": "Primary care providers should prescribe aspirin to prevent cardiovascular disease based on benefit-risk ratio, not age", "authors": "Kim K Hennekens CH Martinez L et al.", "journal": "Fam Med Community Health", "year": 2021, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Primary care providers should prescribe aspirin to prevent cardiovascular disease based on benefit-risk ratio, not age", "keyFindings": [ "Reduces risk of recurrent MI and stroke (secondary prevention)" ], "dosageUsed": "75–100 mg once daily for cardiovascular prevention", "evidenceRating": "strong", "pmid": "34952844", "doi": "10.1136/fmch-2021-001475", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34952844/", "publicSourceType": "PMID" }, { "id": "rx-study-0505", "supplementName": "Aspirin Low-Dose", "title": "Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly", "authors": "McNeil JJ Wolfe R Woods RL et al.", "journal": "N Engl J Med", "year": 2018, "studyType": "rct", "sampleSize": null, "outcome": "Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly", "keyFindings": [ "Reduces risk of recurrent MI and stroke (secondary prevention)" ], "dosageUsed": "75–100 mg once daily for cardiovascular prevention", "evidenceRating": "strong", "pmid": "30221597", "doi": "10.1056/NEJMoa1805819", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30221597/", "publicSourceType": "PMID" }, { "id": "rx-study-0506", "supplementName": "Aspirin Low-Dose", "title": "Switching From Aspirin Monotherapy After Noncardioembolic Stroke: A Systematic Review and Network Meta-Analysis", "authors": "Rothstein A Khazaal O Messe SR et al.", "journal": "Stroke", "year": 2026, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Switching From Aspirin Monotherapy After Noncardioembolic Stroke: A Systematic Review and Network Meta-Analysis", "keyFindings": [ "Reduces risk of recurrent MI and stroke (secondary prevention)", "Systematic evidence synthesis across multiple trials" ], "dosageUsed": "75–100 mg once daily for cardiovascular prevention", "evidenceRating": "strong", "pmid": "41347302", "doi": "10.1161/STROKEAHA.125.053030", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41347302/", "publicSourceType": "PMID" }, { "id": "rx-study-0507", "supplementName": "Clopidogrel", "title": "Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation", "authors": "Yusuf S Zhao F Mehta SR et al.", "journal": "N Engl J Med", "year": 2001, "studyType": "rct", "sampleSize": null, "outcome": "Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation", "keyFindings": [ "Reduces cardiovascular events in ACS (CURE trial)", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "75 mg once daily", "evidenceRating": "strong", "pmid": "11519503", "doi": "10.1056/NEJMoa010746", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11519503/", "publicSourceType": "PMID" }, { "id": "rx-study-0508", "supplementName": "Clopidogrel", "title": "A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee", "authors": "CAPRIE Steering Committee", "journal": "Lancet", "year": 1996, "studyType": "rct", "sampleSize": null, "outcome": "A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee", "keyFindings": [ "Reduces cardiovascular events in ACS (CURE trial)", "Gold-standard randomized controlled trial design", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "75 mg once daily", "evidenceRating": "strong", "pmid": "8918275", "doi": "10.1016/s0140-6736(96)09457-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8918275/", "publicSourceType": "PMID" }, { "id": "rx-study-0509", "supplementName": "Clopidogrel", "title": "Efficacy and safety of clopidogrel versus aspirin monotherapy for secondary prevention after percutaneous coronary intervention: a GRADE-assessed meta-analysis with trial sequential analysis", "authors": "Ibrahim A Katamesh BE Almansouri NE et al.", "journal": "J Cardiovasc Med (Hagerstown)", "year": 2026, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Efficacy and safety of clopidogrel versus aspirin monotherapy for secondary prevention after percutaneous coronary intervention: a GRADE-assessed meta-analysis with trial sequential analysis", "keyFindings": [ "Reduces cardiovascular events in ACS (CURE trial)", "Systematic evidence synthesis across multiple trials", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "75 mg once daily", "evidenceRating": "strong", "pmid": "41703405", "doi": "10.2459/JCM.0000000000001830", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41703405/", "publicSourceType": "PMID" }, { "id": "rx-study-0510", "supplementName": "Ticagrelor", "title": "Ticagrelor versus clopidogrel in patients with acute coronary syndromes", "authors": "Wallentin L Becker RC Budaj A et al.", "journal": "N Engl J Med", "year": 2009, "studyType": "rct", "sampleSize": null, "outcome": "Ticagrelor versus clopidogrel in patients with acute coronary syndromes", "keyFindings": [ "Superior to clopidogrel in ACS (PLATO trial)", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "180 mg loading dose, then 90 mg twice daily for 12 months", "evidenceRating": "strong", "pmid": "19717846", "doi": "10.1056/NEJMoa0904327", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19717846/", "publicSourceType": "PMID" }, { "id": "rx-study-0511", "supplementName": "Ticagrelor", "title": "Characteristics and outcomes in patients with a prior myocardial infarction treated with extended dual antiplatelet therapy with ticagrelor 60 mg: findings from ALETHEIA, a multi-country observational study", "authors": "Bonaca MP Lesén E Giannitsis E et al.", "journal": "Eur Heart J Cardiovasc Pharmacother", "year": 2023, "studyType": "cohort", "sampleSize": null, "outcome": "Characteristics and outcomes in patients with a prior myocardial infarction treated with extended dual antiplatelet therapy with ticagrelor 60 mg: findings from ALETHEIA, a multi-country observational study", "keyFindings": [ "Superior to clopidogrel in ACS (PLATO trial)", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "180 mg loading dose, then 90 mg twice daily for 12 months", "evidenceRating": "strong", "pmid": "37653447", "doi": "10.1093/ehjcvp/pvad062", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37653447/", "publicSourceType": "PMID" }, { "id": "rx-study-0512", "supplementName": "Ticagrelor", "title": "Efficacy and safety of off-label low-dose compared with standard-dose antiplatelet agents in patients with coronary heart disease: a meta-analysis", "authors": "Zheng L Ren Z Shi Y et al.", "journal": "Open Heart", "year": 2026, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Efficacy and safety of off-label low-dose compared with standard-dose antiplatelet agents in patients with coronary heart disease: a meta-analysis", "keyFindings": [ "Superior to clopidogrel in ACS (PLATO trial)", "Systematic evidence synthesis across multiple trials", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "180 mg loading dose, then 90 mg twice daily for 12 months", "evidenceRating": "strong", "pmid": "41617356", "doi": "10.1136/openhrt-2025-003839", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41617356/", "publicSourceType": "PMID" }, { "id": "rx-study-0513", "supplementName": "Amiodarone", "title": "Effect of prophylactic amiodarone on mortality after acute myocardial infarction and in congestive heart failure: meta-analysis of individual data from 6500 patients in randomised trials. Amiodarone Trials Meta-Analysis Investigators", "authors": "Unknown", "journal": "Lancet", "year": 1997, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Effect of prophylactic amiodarone on mortality after acute myocardial infarction and in congestive heart failure: meta-analysis of individual data from 6500 patients in randomised trials. Amiodarone Trials Meta-Analysis Investigators", "keyFindings": [ "Most effective antiarrhythmic for ventricular and atrial arrhythmias", "Systematic evidence synthesis across multiple trials", "Gold-standard randomized controlled trial design", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "Loading: 400–800 mg daily for 1–3 weeks; Maintenance: 100–400 mg daily", "evidenceRating": "strong", "pmid": "9371164", "doi": "10.1016/S0140-6736(97)05281-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9371164/", "publicSourceType": "PMID" }, { "id": "rx-study-0514", "supplementName": "Amiodarone", "title": "Absence of protective effect of renin-angiotensin system inhibitors on atrial fibrillation development: insights from the Canadian Trial of Atrial Fibrillation (CTAF)", "authors": "Palardy M Ducharme A Nattel S et al.", "journal": "Can J Cardiol", "year": 2008, "studyType": "rct", "sampleSize": null, "outcome": "Absence of protective effect of renin-angiotensin system inhibitors on atrial fibrillation development: insights from the Canadian Trial of Atrial Fibrillation (CTAF)", "keyFindings": [ "Most effective antiarrhythmic for ventricular and atrial arrhythmias", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "Loading: 400–800 mg daily for 1–3 weeks; Maintenance: 100–400 mg daily", "evidenceRating": "strong", "pmid": "18787722", "doi": "10.1016/s0828-282x(08)70670-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18787722/", "publicSourceType": "PMID" }, { "id": "rx-study-0515", "supplementName": "Amiodarone", "title": "Effect of prophylactic amiodarone on mortality after acute myocardial infarction and in congestive heart failure: meta-analysis of individual data from 6500 patients in randomised trials. Amiodarone Trials Meta-Analysis Investigators", "authors": "Unknown", "journal": "Lancet", "year": 1997, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Effect of prophylactic amiodarone on mortality after acute myocardial infarction and in congestive heart failure: meta-analysis of individual data from 6500 patients in randomised trials. Amiodarone Trials Meta-Analysis Investigators", "keyFindings": [ "Most effective antiarrhythmic for ventricular and atrial arrhythmias", "Systematic evidence synthesis across multiple trials", "Gold-standard randomized controlled trial design", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "Loading: 400–800 mg daily for 1–3 weeks; Maintenance: 100–400 mg daily", "evidenceRating": "strong", "pmid": "9371164", "doi": "10.1016/S0140-6736(97)05281-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9371164/", "publicSourceType": "PMID" }, { "id": "rx-study-0516", "supplementName": "Flecainide", "title": "Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial", "authors": "Echt DS Liebson PR Mitchell LB et al.", "journal": "N Engl J Med", "year": 1991, "studyType": "rct", "sampleSize": null, "outcome": "Mortality and morbidity in patients receiving encainide, flecainide, or placebo. 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Amiodarone Trials Meta-Analysis Investigators", "authors": "Unknown", "journal": "Lancet", "year": 1997, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Effect of prophylactic amiodarone on mortality after acute myocardial infarction and in congestive heart failure: meta-analysis of individual data from 6500 patients in randomised trials. Amiodarone Trials Meta-Analysis Investigators", "keyFindings": [ "Effective for maintaining sinus rhythm in atrial fibrillation", "Systematic evidence synthesis across multiple trials", "Gold-standard randomized controlled trial design", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "80–160 mg twice daily; standard maximum 320 mg/day total", "evidenceRating": "moderate", "pmid": "9371164", "doi": "10.1016/S0140-6736(97)05281-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9371164/", "publicSourceType": "PMID" }, { "id": "rx-study-0521", "supplementName": "Sotalol", "title": "External electrical and pharmacological cardioversion for atrial fibrillation, atrial flutter or atrial tachycardias: a network meta-analysis", "authors": "Kukendrarajah K Ahmad M Carrington M et al.", "journal": "Cochrane Database Syst Rev", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "External electrical and 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"dosageUsed": "Sublingual: 0.3–0.6 mg as needed", "evidenceRating": "strong", "pmid": "6407316", "doi": "10.1016/0002-9343(83)90858-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/6407316/", "publicSourceType": "PMID" }, { "id": "rx-study-0523", "supplementName": "Nitroglycerin", "title": "Stable angina pectoris: the medical management of symptomatic myocardial ischemia", "authors": "Parker JD, Parker JO", "journal": "Can J Cardiol", "year": 2012, "studyType": "review", "sampleSize": null, "outcome": "Stable angina pectoris: the medical management of symptomatic myocardial ischemia", "keyFindings": [ "Rapid relief of acute angina attacks (sublingual)" ], "dosageUsed": "Sublingual: 0.3–0.6 mg as needed", "evidenceRating": "strong", "pmid": "22424287", "doi": "10.1016/j.cjca.2011.11.002", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22424287/", "publicSourceType": "PMID" }, { "id": "rx-study-0524", "supplementName": "Nitroglycerin", "title": "Low-dose versus high-dose intravenous nitroglycerin in the treatment of sympathetic crashing acute pulmonary oedema: a systematic review and meta-analysis focusing on efficacy, safety and outcomes", "authors": "Pramudyo M Kamarullah W Pranata R et al.", "journal": "BMJ Open", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Low-dose versus high-dose intravenous nitroglycerin in the treatment of sympathetic crashing acute pulmonary oedema: a systematic review and meta-analysis focusing on efficacy, safety and outcomes", "keyFindings": [ "Rapid relief of acute angina attacks (sublingual)", "Systematic evidence synthesis across multiple trials" ], "dosageUsed": "Sublingual: 0.3–0.6 mg as needed", "evidenceRating": "strong", "pmid": "40506079", "doi": "10.1136/bmjopen-2025-099142", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40506079/", "publicSourceType": "PMID" }, { "id": "rx-study-0525", "supplementName": "Isosorbide Mononitrate", "title": "Stable angina pectoris: the medical management of symptomatic myocardial ischemia", "authors": "Parker JD, Parker JO", "journal": "Can J Cardiol", "year": 2012, "studyType": "review", "sampleSize": null, "outcome": "Stable angina pectoris: the medical management of symptomatic myocardial ischemia", "keyFindings": [ "Effective prophylaxis of angina pectoris" ], "dosageUsed": "IR: 20 mg twice daily", "evidenceRating": "strong", "pmid": "22424287", "doi": "10.1016/j.cjca.2011.11.002", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22424287/", "publicSourceType": "PMID" }, { "id": "rx-study-0526", "supplementName": "Isosorbide Mononitrate", "title": "Short and long-acting oral nitrates for stable angina pectoris", "authors": "Thadani U, Lipicky RJ", "journal": "Cardiovasc Drugs Ther", "year": 1994, "studyType": "review", "sampleSize": null, "outcome": "Short and long-acting oral nitrates for stable angina pectoris", "keyFindings": [ "Effective prophylaxis of angina pectoris" ], "dosageUsed": "IR: 20 mg twice daily", "evidenceRating": "strong", "pmid": "7848896", "doi": "10.1007/BF00877415", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7848896/", "publicSourceType": "PMID" }, { "id": "rx-study-0527", "supplementName": "Isosorbide Mononitrate", "title": "Isosorbide mononitrate for cervical ripening during labour induction: A systematic review and meta-analysis of 23 randomized controlled trials", "authors": "Abu-Zaid A Alshahrani MS Al-Matary A et al.", "journal": "Eur J Obstet Gynecol Reprod Biol", "year": 2022, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Isosorbide mononitrate for cervical ripening during labour induction: A systematic review and meta-analysis of 23 randomized controlled trials", "keyFindings": [ "Effective prophylaxis of angina pectoris", "Systematic evidence synthesis across multiple trials", "Gold-standard randomized controlled trial design" ], "dosageUsed": "IR: 20 mg twice daily", "evidenceRating": "strong", "pmid": "35803111", "doi": "10.1016/j.ejogrb.2022.06.028", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35803111/", "publicSourceType": "PMID" }, { "id": "rx-study-0528", "supplementName": "Digoxin", "title": "The effect of digoxin on mortality and morbidity in patients with heart failure", "authors": "Digitalis Investigation Group", "journal": "N Engl J Med", "year": 1997, "studyType": "rct", "sampleSize": null, "outcome": "The effect of digoxin on mortality and morbidity in patients with heart failure", "keyFindings": [ "Rate control in atrial fibrillation (especially at rest)" ], "dosageUsed": "0.0625–0.25 mg once daily; target serum level 0.5–0.9 ng/mL", "evidenceRating": "moderate", "pmid": "9036306", "doi": "10.1056/NEJM199702203360801", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9036306/", "publicSourceType": "PMID" }, { "id": "rx-study-0529", "supplementName": "Digoxin", "title": "Association of serum digoxin concentration and outcomes in patients with heart failure", "authors": "Rathore SS Curtis JP Wang Y et al.", "journal": "JAMA", "year": 2003, "studyType": "rct", "sampleSize": null, "outcome": "Association of serum digoxin concentration and outcomes in patients with heart failure", "keyFindings": [ "Rate control in atrial fibrillation (especially at rest)" ], "dosageUsed": "0.0625–0.25 mg once daily; target serum level 0.5–0.9 ng/mL", "evidenceRating": "moderate", "pmid": "12588271", "doi": "10.1001/jama.289.7.871", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12588271/", "publicSourceType": "PMID" }, { "id": "rx-study-0530", "supplementName": "Digoxin", "title": "Comparative effectiveness of pharmacotherapy for heart failure with preserved ejection fraction: A systematic review and network meta-analysis", "authors": "Chen SH Tseng YW Huang CJ et al.", "journal": "Diabetes Obes Metab", "year": 2026, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Comparative effectiveness of pharmacotherapy for heart failure with preserved ejection fraction: A systematic review and network meta-analysis", "keyFindings": [ "Rate control in atrial fibrillation (especially at rest)", "Systematic evidence synthesis across multiple trials" ], "dosageUsed": "0.0625–0.25 mg once daily; target serum level 0.5–0.9 ng/mL", "evidenceRating": "moderate", "pmid": "41588709", "doi": "10.1111/dom.70503", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41588709/", "publicSourceType": "PMID" }, { "id": "rx-study-0531", "supplementName": "Hydralazine", "title": "Combination of isosorbide dinitrate and hydralazine in blacks with heart failure", "authors": "Taylor AL Ziesche S Yancy C et al.", "journal": "N Engl J Med", "year": 2004, "studyType": "rct", "sampleSize": null, "outcome": "Combination of isosorbide dinitrate and hydralazine in blacks with heart failure", "keyFindings": [ "Reduces mortality in Black patients with HFrEF (A-HeFT, combined with ISDN)" ], "dosageUsed": "25–100 mg 2–3 times daily", "evidenceRating": "strong", "pmid": "15533851", "doi": "10.1056/NEJMoa042934", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15533851/", "publicSourceType": "PMID" }, { "id": "rx-study-0532", "supplementName": "Hydralazine", "title": "Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study", "authors": "Cohn JN Archibald DG Ziesche S et al.", "journal": "N Engl J Med", "year": 1986, "studyType": "rct", "sampleSize": null, "outcome": "Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study", "keyFindings": [ "Reduces mortality in Black patients with HFrEF (A-HeFT, combined with ISDN)" ], "dosageUsed": "25–100 mg 2–3 times daily", "evidenceRating": "strong", "pmid": "3520315", "doi": "10.1056/NEJM198606123142404", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3520315/", "publicSourceType": "PMID" }, { "id": "rx-study-0533", "supplementName": "Hydralazine", "title": "Efficacy of pharmacological agents for management of post-partum hypertension: A systematic review and network meta-analysis", "authors": "Singh A Singh MP Thakur P et al.", "journal": "J Hum Hypertens", "year": 2026, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Efficacy of pharmacological agents for management of post-partum hypertension: A systematic review and network meta-analysis", "keyFindings": [ "Reduces mortality in Black patients with HFrEF (A-HeFT, combined with ISDN)", "Systematic evidence synthesis across multiple trials" ], "dosageUsed": "25–100 mg 2–3 times daily", "evidenceRating": "strong", "pmid": "41663753", "doi": "10.1038/s41371-026-01120-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41663753/", "publicSourceType": "PMID" }, { "id": "rx-study-0534", "supplementName": "Ranolazine", "title": "Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial", "authors": "Chaitman BR Pepine CJ Parker JO et al.", "journal": "JAMA", "year": 2004, "studyType": "rct", "sampleSize": null, "outcome": "Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial", "keyFindings": [ "Reduces angina frequency and nitroglycerin use", "Gold-standard randomized controlled trial design" ], "dosageUsed": "500 mg twice daily, titrated up to 1000 mg twice daily", "evidenceRating": "moderate", "pmid": "14734593", "doi": "10.1001/jama.291.3.309", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14734593/", "publicSourceType": "PMID" }, { "id": "rx-study-0535", "supplementName": "Ranolazine", "title": "Effects of Ranolazine in Patients With Chronic Angina in Patients With and Without Percutaneous Coronary Intervention for Acute Coronary Syndrome: Observations From the MERLIN-TIMI 36 Trial", "authors": "Gutierrez JA Karwatowska-Prokopczuk E Murphy SA et al.", "journal": "Clin Cardiol", "year": 2015, "studyType": "rct", "sampleSize": null, "outcome": "Effects of Ranolazine in Patients With Chronic Angina in Patients With and Without Percutaneous Coronary Intervention for Acute Coronary Syndrome: Observations From the MERLIN-TIMI 36 Trial", "keyFindings": [ "Reduces angina frequency and nitroglycerin use" ], "dosageUsed": "500 mg twice daily, titrated up to 1000 mg twice daily", "evidenceRating": "moderate", "pmid": "26059896", "doi": "10.1002/clc.22425", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26059896/", "publicSourceType": "PMID" }, { "id": "rx-study-0536", "supplementName": "Ranolazine", "title": "Drug treatment for myotonia", "authors": "Spillane J Trip J Drost G et al.", "journal": "Cochrane Database Syst Rev", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Drug treatment for myotonia", "keyFindings": [ "Reduces angina frequency and nitroglycerin use" ], "dosageUsed": "500 mg twice daily, titrated up to 1000 mg twice daily", "evidenceRating": "moderate", "pmid": "40197813", "doi": "10.1002/14651858.CD004762.pub3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40197813/", "publicSourceType": "PMID" }, { "id": "rx-study-0537", "supplementName": "Sacubitril/Valsartan", "title": "Angiotensin-neprilysin inhibition versus enalapril in heart failure", "authors": "McMurray JJ Packer M Desai AS et al.", "journal": "N Engl J Med", "year": 2014, "studyType": "rct", "sampleSize": null, "outcome": "Angiotensin-neprilysin inhibition versus enalapril in heart failure", "keyFindings": [ "Superior to enalapril in reducing CV death and HF hospitalization (PARADIGM-HF)", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "Starting: 24/26 mg or 49/51 mg twice daily; Target: 97/103 mg twice daily", "evidenceRating": "strong", "pmid": "25176015", "doi": "10.1056/NEJMoa1409077", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25176015/", "publicSourceType": "PMID" }, { "id": "rx-study-0538", "supplementName": "Sacubitril/Valsartan", "title": "Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction", "authors": "Solomon SD McMurray JJV Anand IS et al.", "journal": "N Engl J Med", "year": 2019, "studyType": "rct", "sampleSize": null, "outcome": "Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction", "keyFindings": [ "Superior to enalapril in reducing CV death and HF hospitalization (PARADIGM-HF)", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "Starting: 24/26 mg or 49/51 mg twice daily; Target: 97/103 mg twice daily", "evidenceRating": "strong", "pmid": "31475794", "doi": "10.1056/NEJMoa1908655", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31475794/", "publicSourceType": "PMID" }, { "id": "rx-study-0539", "supplementName": "Sacubitril/Valsartan", "title": "Optimization of Clinical Trial Design and Decision-Making for Heart Failure with Preserved Ejection Fraction (HFpEF): A Meta-Analysis Based on a Placebo Response Model", "authors": "Chen X Yang J Xu L et al.", "journal": "Cardiovasc Ther", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Optimization of Clinical Trial Design and Decision-Making for Heart Failure with Preserved Ejection Fraction (HFpEF): A Meta-Analysis Based on a Placebo Response Model", "keyFindings": [ "Superior to enalapril in reducing CV death and HF hospitalization (PARADIGM-HF)", "Systematic evidence synthesis across multiple trials", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "Starting: 24/26 mg or 49/51 mg twice daily; Target: 97/103 mg twice daily", "evidenceRating": "strong", "pmid": "41089765", "doi": "10.1155/cdr/7087720", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41089765/", "publicSourceType": "PMID" }, { "id": "rx-study-0540", "supplementName": "Ivabradine", "title": "Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study", "authors": "Swedberg K Komajda M Böhm M et al.", "journal": "Lancet", "year": 2010, "studyType": "rct", "sampleSize": null, "outcome": "Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study", "keyFindings": [ "Reduces heart failure hospitalization (SHIFT trial)", "Gold-standard randomized controlled trial design", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "2.5–7.5 mg twice daily", "evidenceRating": "strong", "pmid": "20801500", "doi": "10.1016/S0140-6736(10)61198-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20801500/", "publicSourceType": "PMID" }, { "id": "rx-study-0541", "supplementName": "Ivabradine", "title": "Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial", "authors": "Fox K Ford I Steg PG et al.", "journal": "Lancet", "year": 2008, "studyType": "rct", "sampleSize": null, "outcome": "Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial", "keyFindings": [ "Reduces heart failure hospitalization (SHIFT trial)", "Gold-standard randomized controlled trial design", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "2.5–7.5 mg twice daily", "evidenceRating": "strong", "pmid": "18757088", "doi": "10.1016/S0140-6736(08)61170-8", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18757088/", "publicSourceType": "PMID" }, { "id": "rx-study-0542", "supplementName": "Ivabradine", "title": "Ivabradine in acute myocardial infarction: a systematic review and meta-analysis of randomized controlled trials", "authors": "Kow CS Zaihan AF Hasan SS et al.", "journal": "Expert Rev Cardiovasc Ther", "year": 2026, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Ivabradine in acute myocardial infarction: a systematic review and meta-analysis of randomized controlled trials", "keyFindings": [ "Reduces heart failure hospitalization 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ventricular dysfunction after myocardial infarction", "keyFindings": [ "Reduces mortality post-MI with HF (EPHESUS trial)" ], "dosageUsed": "25–50 mg once daily", "evidenceRating": "strong", "pmid": "12668699", "doi": "10.1056/NEJMoa030207", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12668699/", "publicSourceType": "PMID" }, { "id": "rx-study-0547", "supplementName": "Eplerenone", "title": "Eplerenone in patients with systolic heart failure and mild symptoms", "authors": "Zannad F McMurray JJ Krum H et al.", "journal": "N Engl J Med", "year": 2011, "studyType": "rct", "sampleSize": null, "outcome": "Eplerenone in patients with systolic heart failure and mild symptoms", "keyFindings": [ "Reduces mortality post-MI with HF (EPHESUS trial)" ], "dosageUsed": "25–50 mg once daily", "evidenceRating": "strong", "pmid": "21073363", "doi": "10.1056/NEJMoa1009492", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21073363/", "publicSourceType": "PMID" }, { "id": "rx-study-0548", "supplementName": "Eplerenone", "title": "Effects of mineralocorticoid receptor antagonists on cardiometabolic profile and liver health in individuals with increased cardiometabolic risk: a systematic review and meta-analysis of randomized controlled trials", "authors": "Dias J Leite AR Godinho T et al.", "journal": "Expert Rev Cardiovasc Ther", "year": 2026, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Effects of mineralocorticoid receptor antagonists on cardiometabolic profile and liver health in individuals with increased cardiometabolic risk: a systematic review and meta-analysis of randomized controlled trials", "keyFindings": [ "Reduces mortality post-MI with HF (EPHESUS trial)", "Systematic evidence synthesis across multiple trials", "Gold-standard randomized controlled trial design" ], "dosageUsed": "25–50 mg once daily", "evidenceRating": "strong", "pmid": "41702409", "doi": "10.1080/14779072.2026.2634029", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41702409/", "publicSourceType": "PMID" }, { "id": "rx-study-0549", "supplementName": "Prasugrel", "title": "Prasugrel versus clopidogrel in patients with acute coronary syndromes", "authors": "Wiviott SD Braunwald E McCabe CH et al.", "journal": "N Engl J Med", "year": 2007, "studyType": "rct", "sampleSize": null, "outcome": "Prasugrel versus clopidogrel in patients with acute coronary syndromes", "keyFindings": [ "Superior to clopidogrel in reducing ischemic events in ACS-PCI (TRITON-TIMI 38)", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "60 mg loading dose, then 10 mg once daily", "evidenceRating": "strong", "pmid": "17982182", "doi": "10.1056/NEJMoa0706482", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17982182/", "publicSourceType": "PMID" }, { "id": "rx-study-0550", "supplementName": "Prasugrel", "title": "Days Alive and Out of Hospital: Exploring a Patient-Centered, Pragmatic Outcome in a Clinical Trial of Patients With Acute Coronary Syndromes", "authors": "Fanaroff AC Cyr D Neely ML et al.", "journal": "Circ Cardiovasc Qual Outcomes", "year": 2018, "studyType": "rct", "sampleSize": null, "outcome": "Days Alive and Out of Hospital: Exploring a Patient-Centered, Pragmatic Outcome in a Clinical Trial of Patients With Acute Coronary Syndromes", "keyFindings": [ "Superior to clopidogrel in reducing ischemic events in ACS-PCI (TRITON-TIMI 38)", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "60 mg loading dose, then 10 mg once daily", "evidenceRating": "strong", "pmid": "30562068", "doi": "10.1161/CIRCOUTCOMES.118.004755", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30562068/", "publicSourceType": "PMID" }, { "id": "rx-study-0551", "supplementName": "Prasugrel", "title": "Efficacy and safety of off-label low-dose compared with standard-dose antiplatelet agents in patients with coronary heart disease: a meta-analysis", "authors": "Zheng L Ren Z Shi Y et al.", "journal": "Open Heart", "year": 2026, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Efficacy and safety of off-label low-dose compared with standard-dose antiplatelet agents in patients with coronary heart disease: a meta-analysis", "keyFindings": [ "Superior to clopidogrel in reducing ischemic events in ACS-PCI (TRITON-TIMI 38)", "Systematic evidence synthesis across multiple trials", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "60 mg loading dose, then 10 mg once daily", "evidenceRating": "strong", "pmid": "41617356", "doi": "10.1136/openhrt-2025-003839", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41617356/", "publicSourceType": "PMID" }, { "id": "rx-study-0552", "supplementName": "Metformin", "title": "Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group", "authors": "Unknown", "journal": "Lancet", "year": 1998, "studyType": "rct", "sampleSize": null, "outcome": "Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group", "keyFindings": [ "Lowers fasting and postprandial blood glucose", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "500–2,550 mg daily in divided doses", "evidenceRating": "strong", "pmid": "9742976", "doi": "10.1016/S0140-6736(98)07037-8", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9742976/", "publicSourceType": "PMID" }, { "id": "rx-study-0553", "supplementName": "Metformin", "title": "Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin", "authors": "Knowler WC Barrett-Connor E Fowler SE et al.", "journal": "N Engl J Med", "year": 2002, "studyType": "rct", "sampleSize": null, "outcome": "Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin", "keyFindings": [ "Lowers fasting and postprandial blood glucose", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "500–2,550 mg daily in divided doses", "evidenceRating": "strong", "pmid": "11832527", "doi": "10.1056/NEJMoa012512", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11832527/", "publicSourceType": "PMID" }, { "id": "rx-study-0554", "supplementName": "Metformin", "title": "Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes", "authors": "Inzucchi SE Bergenstal RM Buse JB et al.", "journal": "Diabetes Care", "year": 2015, "studyType": "review", "sampleSize": null, "outcome": "Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes", "keyFindings": [ "Lowers fasting and postprandial blood glucose", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "500–2,550 mg daily in divided doses", "evidenceRating": "strong", "pmid": "25538310", "doi": "10.2337/dc14-2441", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25538310/", "publicSourceType": "PMID" }, { "id": "rx-study-0555", "supplementName": "Glipizide", "title": "Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group", "authors": "Unknown", "journal": "Lancet", "year": 1998, "studyType": "rct", "sampleSize": null, "outcome": "Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group", "keyFindings": [ "Lowers HbA1c by 1.0–2.0%", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "2.5–40 mg daily; immediate-release given 30 min before meals", "evidenceRating": "strong", "pmid": "9742976", "doi": "10.1016/S0140-6736(98)07019-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9742976/", "publicSourceType": "PMID" }, { "id": "rx-study-0556", "supplementName": "Glipizide", "title": "Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus", "authors": "Bolen S Feldman L Vassy J et al.", "journal": "Ann Intern Med", "year": 2007, "studyType": "review", "sampleSize": null, "outcome": "Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus", "keyFindings": [ "Lowers HbA1c by 1.0–2.0%", "Systematic evidence synthesis across multiple trials", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "2.5–40 mg daily; immediate-release given 30 min before meals", "evidenceRating": "strong", "pmid": "17638715", "doi": "10.7326/0003-4819-147-6-200709180-00178", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17638715/", "publicSourceType": "PMID" }, { "id": "rx-study-0557", "supplementName": "Glipizide", "title": "Metformin for preventing the progression of chronic kidney disease", "authors": "El-Damanawi R Stanley IK Staatz C et al.", "journal": "Cochrane Database Syst Rev", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Metformin for preventing the progression of chronic kidney disease", "keyFindings": [ "Lowers HbA1c by 1.0–2.0%", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "2.5–40 mg daily; immediate-release given 30 min before meals", "evidenceRating": "strong", "pmid": "38837240", "doi": "10.1002/14651858.CD013414.pub2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38837240/", "publicSourceType": "PMID" }, { "id": "rx-study-0558", "supplementName": "Glyburide", "title": "Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group", "authors": "Unknown", "journal": "Lancet", "year": 1998, "studyType": "rct", "sampleSize": null, "outcome": "Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group", "keyFindings": [ "Lowers HbA1c by 1.0–2.0%", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "1.25–20 mg daily in single or divided doses", "evidenceRating": "strong", "pmid": "9742976", "doi": "10.1016/S0140-6736(98)07019-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9742976/", "publicSourceType": "PMID" }, { "id": "rx-study-0559", "supplementName": "Glyburide", "title": "A systematic review and meta-analysis of hypoglycemia and cardiovascular events: a comparison of glyburide with other secretagogues and with insulin", "authors": "Gangji AS Cukierman T Gerstein HC et al.", "journal": "Diabetes Care", "year": 2007, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "A systematic review and meta-analysis of hypoglycemia and cardiovascular events: a comparison of glyburide with other secretagogues and with insulin", "keyFindings": [ "Lowers HbA1c by 1.0–2.0%", "Systematic evidence synthesis across multiple trials", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "1.25–20 mg daily in single or divided doses", "evidenceRating": "strong", "pmid": "17259518", "doi": "10.2337/dc06-1789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17259518/", "publicSourceType": "PMID" }, { "id": "rx-study-0560", "supplementName": "Glyburide", "title": "Efficacy and Safety of Glibenclamide on Functional Outcomes and Cerebral Edema following Ischemic and Hemorrhagic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Hegazi A Mohamed RG Kashbour M et al.", "journal": "Med Princ Pract", "year": 2026, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Efficacy and Safety of Glibenclamide on Functional Outcomes and Cerebral Edema following Ischemic and Hemorrhagic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "keyFindings": [ "Lowers HbA1c by 1.0–2.0%", "Systematic evidence synthesis across multiple trials", "Gold-standard randomized controlled trial design", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "1.25–20 mg daily in single or divided doses", "evidenceRating": "strong", "pmid": "40720947", "doi": "10.1159/000547648", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40720947/", "publicSourceType": "PMID" }, { "id": "rx-study-0561", "supplementName": "Glimepiride", "title": "GUIDE study: double-blind comparison of once-daily gliclazide MR and glimepiride in type 2 diabetic patients", "authors": "Schernthaner G Grimaldi A Di Mario U et al.", "journal": "Eur J Clin Invest", "year": 2004, "studyType": "rct", "sampleSize": null, "outcome": "GUIDE study: double-blind comparison of once-daily gliclazide MR and glimepiride in type 2 diabetic patients", "keyFindings": [ "Lowers HbA1c by 1.0–1.5%", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "1–8 mg once daily with first main meal", "evidenceRating": "strong", "pmid": "15305887", "doi": "10.1111/j.1365-2362.2004.01381.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15305887/", "publicSourceType": "PMID" }, { "id": "rx-study-0562", "supplementName": "Glimepiride", "title": "9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2022", "authors": "American Diabetes Association Professional Practice Committee", "journal": "Diabetes Care", "year": 2022, "studyType": "review", "sampleSize": null, "outcome": "9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2022", "keyFindings": [ "Lowers HbA1c by 1.0–1.5%", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "1–8 mg once daily with first main meal", "evidenceRating": "strong", "pmid": "34964831", "doi": "10.2337/dc22-S009", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34964831/", "publicSourceType": "PMID" }, { "id": "rx-study-0563", "supplementName": "Glimepiride", "title": "Evaluation of three mechanisms of action (SGLT2 inhibitors, GLP-1 receptor agonists, and sulfonylureas) in treating type 2 diabetes with heart failure: a systematic review and network meta-analysis of RCTs", "authors": "Gao H Wei Q Zou A et al.", "journal": "Front Endocrinol (Lausanne)", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Evaluation of three mechanisms of action (SGLT2 inhibitors, GLP-1 receptor agonists, and sulfonylureas) in treating type 2 diabetes with heart failure: a systematic review and network meta-analysis of RCTs", "keyFindings": [ "Lowers HbA1c by 1.0–1.5%", "Systematic evidence synthesis across multiple trials", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "1–8 mg once daily with first main meal", "evidenceRating": "strong", "pmid": "40556828", "doi": "10.3389/fendo.2025.1562815", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40556828/", "publicSourceType": "PMID" }, { "id": "rx-study-0564", "supplementName": "Sitagliptin", "title": "Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes", "authors": "Green JB Bethel MA Armstrong PW et al.", "journal": "N Engl J Med", "year": 2015, "studyType": "rct", "sampleSize": null, "outcome": "Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes", "keyFindings": [ "Lowers HbA1c by 0.5–0.8%" ], "dosageUsed": "100 mg once daily; dose adjustment for renal impairment: 50 mg", "evidenceRating": "strong", "pmid": "26052984", "doi": "10.1056/NEJMoa1501352", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26052984/", "publicSourceType": "PMID" }, { "id": "rx-study-0565", "supplementName": "Sitagliptin", "title": "Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes", "authors": "Aschner P Kipnes MS Lunceford JK et al.", "journal": "Diabetes Care", "year": 2006, "studyType": "rct", "sampleSize": null, "outcome": "Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes", "keyFindings": [ "Lowers HbA1c by 0.5–0.8%" ], "dosageUsed": "100 mg once daily; dose adjustment for renal impairment: 50 mg", "evidenceRating": "strong", "pmid": "17130196", "doi": "10.2337/dc06-0703", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17130196/", "publicSourceType": "PMID" }, { "id": "rx-study-0566", "supplementName": "Sitagliptin", "title": "Efficacy and safety of anti-prediabetic drugs in patients with prediabetes: a Bayesian network meta-analysis", "authors": "Wu Y Wang Z Tuersun A et al.", "journal": "BMC Med", "year": 2026, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Efficacy and safety of anti-prediabetic drugs in patients with prediabetes: a Bayesian network meta-analysis", "keyFindings": [ "Lowers HbA1c by 0.5–0.8%", "Systematic evidence synthesis across multiple trials" ], "dosageUsed": "100 mg once daily; dose adjustment for renal impairment: 50 mg", "evidenceRating": "strong", "pmid": "41715123", "doi": "10.1186/s12916-026-04705-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41715123/", "publicSourceType": "PMID" }, { "id": "rx-study-0567", "supplementName": "Linagliptin", "title": "Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk: The CARMELINA Randomized Clinical Trial", "authors": "Rosenstock J Perkovic V Johansen OE et al.", "journal": "JAMA", "year": 2019, "studyType": "rct", "sampleSize": null, "outcome": "Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk: The CARMELINA Randomized Clinical Trial", "keyFindings": [ "Lowers HbA1c by 0.5–0.7%", "Gold-standard randomized controlled trial design" ], "dosageUsed": "5 mg once daily", "evidenceRating": "strong", "pmid": "30418475", "doi": "10.1001/jama.2018.18269", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30418475/", "publicSourceType": "PMID" }, { "id": "rx-study-0568", "supplementName": "Linagliptin", "title": "Oral glucose lowering with linagliptin and metformin compared with linagliptin alone as initial treatment in Asian patients with newly diagnosed type 2 diabetes and marked hyperglycemia: Subgroup analysis of a randomized clinical trial", "authors": "Ma RC Del Prato S Gallwitz B et al.", "journal": "J Diabetes Investig", "year": 2017, "studyType": "rct", "sampleSize": null, "outcome": "Oral glucose lowering with linagliptin and metformin compared with linagliptin alone as initial treatment in Asian patients with newly diagnosed type 2 diabetes and marked hyperglycemia: Subgroup analysis of a randomized clinical trial", "keyFindings": [ "Lowers HbA1c by 0.5–0.7%", "Gold-standard randomized controlled trial design" ], "dosageUsed": "5 mg once daily", "evidenceRating": "strong", "pmid": "28921919", "doi": "10.1111/jdi.12746", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28921919/", "publicSourceType": "PMID" }, { "id": "rx-study-0569", "supplementName": "Linagliptin", "title": "Dipeptidyl peptidase-4 inhibitors and diabetic retinopathy in type 2 diabetes: A network meta-analysis of randomized clinical trials", "authors": "Ortiz-Seller A Real JT Morcillo E et al.", "journal": "J Diabetes Complications", "year": 2026, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Dipeptidyl peptidase-4 inhibitors and diabetic retinopathy in type 2 diabetes: A network meta-analysis of randomized clinical trials", "keyFindings": [ "Lowers HbA1c by 0.5–0.7%", "Systematic evidence synthesis across multiple trials", "Gold-standard randomized controlled trial design" ], "dosageUsed": "5 mg once daily", "evidenceRating": "strong", "pmid": "41314124", "doi": "10.1016/j.jdiacomp.2025.109234", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41314124/", "publicSourceType": "PMID" }, { "id": "rx-study-0570", "supplementName": "Empagliflozin", "title": "Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes", "authors": "Zinman B Wanner C Lachin JM et al.", "journal": "N Engl J Med", "year": 2015, "studyType": "rct", "sampleSize": null, "outcome": "Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes", "keyFindings": [ "Lowers HbA1c by 0.5–0.8%" ], "dosageUsed": "10–25 mg once daily in the morning", "evidenceRating": "strong", "pmid": "26378978", "doi": "10.1056/NEJMoa1504720", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26378978/", "publicSourceType": "PMID" }, { "id": "rx-study-0571", "supplementName": "Empagliflozin", "title": "Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure", "authors": "Packer M Anker SD Butler J et al.", "journal": "N Engl J Med", "year": 2020, "studyType": "rct", "sampleSize": null, "outcome": "Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure", "keyFindings": [ "Lowers HbA1c by 0.5–0.8%" ], "dosageUsed": "10–25 mg once daily in the morning", "evidenceRating": "strong", "pmid": "32865377", "doi": "10.1056/NEJMoa2022190", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32865377/", "publicSourceType": "PMID" }, { "id": "rx-study-0572", "supplementName": "Empagliflozin", "title": "Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes", "authors": "Wanner C Inzucchi SE Lachin JM et al.", "journal": "N Engl J Med", "year": 2016, "studyType": "rct", "sampleSize": null, "outcome": "Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes", "keyFindings": [ "Lowers HbA1c by 0.5–0.8%" ], "dosageUsed": "10–25 mg once daily in the morning", "evidenceRating": "strong", "pmid": "27299675", "doi": "10.1056/NEJMoa1515920", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27299675/", "publicSourceType": "PMID" }, { "id": "rx-study-0573", "supplementName": "Dapagliflozin", "title": "Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction", "authors": "McMurray JJV Solomon SD Inzucchi SE et al.", "journal": "N Engl J Med", "year": 2019, "studyType": "rct", "sampleSize": null, "outcome": "Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction", "keyFindings": [ "Lowers HbA1c by 0.5–0.8%" ], "dosageUsed": "5–10 mg once daily", "evidenceRating": "strong", "pmid": "31535829", "doi": "10.1056/NEJMoa1911303", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31535829/", "publicSourceType": "PMID" }, { "id": "rx-study-0574", "supplementName": "Dapagliflozin", "title": "Dapagliflozin in Patients with Chronic Kidney Disease", "authors": "Heerspink HJL Stefánsson BV Correa-Rotter R et al.", "journal": "N Engl J Med", "year": 2020, "studyType": "rct", "sampleSize": null, "outcome": "Dapagliflozin in Patients with Chronic Kidney Disease", "keyFindings": [ "Lowers HbA1c by 0.5–0.8%" ], "dosageUsed": "5–10 mg once daily", "evidenceRating": "strong", "pmid": "32970396", "doi": "10.1056/NEJMoa2024816", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32970396/", "publicSourceType": "PMID" }, { "id": "rx-study-0575", "supplementName": "Dapagliflozin", "title": "Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes", "authors": "Wiviott SD Raz I Bonaca MP et al.", "journal": "N Engl J Med", "year": 2019, "studyType": "rct", "sampleSize": null, "outcome": "Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes", "keyFindings": [ "Lowers HbA1c by 0.5–0.8%" ], "dosageUsed": "5–10 mg once daily", "evidenceRating": "strong", "pmid": "30415602", "doi": "10.1056/NEJMoa1812389", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30415602/", "publicSourceType": "PMID" }, { "id": "rx-study-0576", "supplementName": "Canagliflozin", "title": "Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes", "authors": "Neal B Perkovic V Mahaffey KW et al.", "journal": "N Engl J Med", "year": 2017, "studyType": "rct", "sampleSize": null, "outcome": "Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes", "keyFindings": [ "Lowers HbA1c by 0.6–1.0%" ], "dosageUsed": "100–300 mg once daily before the first meal", "evidenceRating": "strong", "pmid": "28605608", "doi": "10.1056/NEJMoa1611925", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28605608/", "publicSourceType": "PMID" }, { "id": "rx-study-0577", "supplementName": "Canagliflozin", "title": "Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy", "authors": "Perkovic V Jardine MJ Neal B et al.", "journal": "N Engl J Med", "year": 2019, "studyType": "rct", "sampleSize": null, "outcome": "Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy", "keyFindings": [ "Lowers HbA1c by 0.6–1.0%" ], "dosageUsed": "100–300 mg once daily before the first meal", "evidenceRating": "strong", "pmid": "30990260", "doi": "10.1056/NEJMoa1811744", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30990260/", "publicSourceType": "PMID" }, { "id": "rx-study-0578", "supplementName": "Canagliflozin", "title": "Safety Profile of SGLT-2 Inhibitors in Older Adults: A Systematic Review and Network Meta-Analysis", "authors": "Sridharan K, Sivaramakrishnan G", "journal": "Med Sci (Basel)", "year": 2026, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Safety Profile of SGLT-2 Inhibitors in Older Adults: A Systematic Review and Network Meta-Analysis", "keyFindings": [ "Lowers HbA1c by 0.6–1.0%", "Systematic evidence synthesis across multiple trials" ], "dosageUsed": "100–300 mg once daily before the first meal", "evidenceRating": "strong", "pmid": "41892868", "doi": "10.3390/medsci14010153", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41892868/", "publicSourceType": "PMID" }, { "id": "rx-study-0579", "supplementName": "Semaglutide", "title": "Semaglutide and Cardiovascular 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1.0–1.8%", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "Injection: 0.25–2.4 mg weekly", "evidenceRating": "strong", "pmid": "33567185", "doi": "10.1056/NEJMoa2032183", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33567185/", "publicSourceType": "PMID" }, { "id": "rx-study-0581", "supplementName": "Semaglutide", "title": "Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes", "authors": "Husain M Birkenfeld AL Donsmark M et al.", "journal": "N Engl J Med", "year": 2019, "studyType": "rct", "sampleSize": null, "outcome": "Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes", "keyFindings": [ "Lowers HbA1c by 1.0–1.8%", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "Injection: 0.25–2.4 mg weekly", "evidenceRating": "strong", "pmid": "31185157", "doi": "10.1056/NEJMoa1901118", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31185157/", "publicSourceType": "PMID" }, { "id": "rx-study-0582", "supplementName": "Liraglutide", "title": "Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes", "authors": "Marso SP Daniels GH Brown-Frandsen K et al.", "journal": "N Engl J Med", "year": 2016, "studyType": "rct", "sampleSize": null, "outcome": "Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes", "keyFindings": [ "Lowers HbA1c by 0.8–1.5%", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "Victoza: 0.6–1.8 mg daily; Saxenda: 0.6–3.0 mg daily", "evidenceRating": "strong", "pmid": "27295427", "doi": "10.1056/NEJMoa1603827", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27295427/", "publicSourceType": "PMID" }, { "id": "rx-study-0583", "supplementName": "Liraglutide", "title": "A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management", "authors": "Pi-Sunyer X Astrup A Fujioka K et al.", "journal": "N Engl J Med", "year": 2015, "studyType": "rct", "sampleSize": null, "outcome": "A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management", "keyFindings": [ "Lowers HbA1c by 0.8–1.5%", "Gold-standard randomized controlled trial design", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "Victoza: 0.6–1.8 mg daily; Saxenda: 0.6–3.0 mg daily", "evidenceRating": "strong", "pmid": "26132939", "doi": "10.1056/NEJMoa1411892", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26132939/", "publicSourceType": "PMID" }, { "id": "rx-study-0584", "supplementName": "Liraglutide", "title": "Cardiorenal protective effects of glucagon-like peptide-1 receptor agonists in chronic kidney disease: a systematic review and meta-analysis", "authors": "Wang Y Feng L Wang Y et al.", "journal": "Ren Fail", "year": 2026, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Cardiorenal protective effects of glucagon-like peptide-1 receptor agonists in chronic kidney disease: a systematic review and meta-analysis", "keyFindings": [ "Lowers HbA1c by 0.8–1.5%", "Systematic evidence synthesis across multiple trials", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "Victoza: 0.6–1.8 mg daily; Saxenda: 0.6–3.0 mg daily", "evidenceRating": "strong", "pmid": "41644273", "doi": "10.1080/0886022X.2026.2620155", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41644273/", "publicSourceType": "PMID" }, { "id": "rx-study-0585", "supplementName": "Dulaglutide", "title": "Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial", "authors": "Gerstein HC Colhoun HM Dagenais GR et al.", "journal": "Lancet", "year": 2019, "studyType": "rct", "sampleSize": null, "outcome": "Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial", "keyFindings": [ "Lowers HbA1c by 0.7–1.6%", "Gold-standard randomized controlled trial design", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "0.75–4.5 mg once weekly", "evidenceRating": "strong", "pmid": "31189511", "doi": "10.1016/S0140-6736(19)31149-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31189511/", "publicSourceType": "PMID" }, { "id": "rx-study-0586", "supplementName": "Dulaglutide", "title": "Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial", "authors": "Dungan KM Povedano ST Forst T et al.", "journal": "Lancet", "year": 2014, "studyType": "rct", "sampleSize": null, "outcome": "Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial", "keyFindings": [ "Lowers HbA1c by 0.7–1.6%", "Gold-standard randomized controlled trial design", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "0.75–4.5 mg once weekly", "evidenceRating": "strong", "pmid": "25018121", "doi": "10.1016/S0140-6736(14)60976-4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25018121/", "publicSourceType": "PMID" }, { "id": "rx-study-0587", "supplementName": "Dulaglutide", "title": "Divergent Risks of Hematologic Malignancies Associated with GLP-1 Receptor Agonists and SGLT2 Inhibitors: Preliminary Findings from a Pilot Network Meta-Analysis", "authors": "Lin PY Zeng BY Hsu CW et al.", "journal": "Biomolecules", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Divergent Risks of Hematologic Malignancies Associated with GLP-1 Receptor Agonists and SGLT2 Inhibitors: Preliminary Findings from a Pilot Network Meta-Analysis", "keyFindings": [ "Lowers HbA1c by 0.7–1.6%", "Systematic evidence synthesis across multiple trials", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "0.75–4.5 mg once weekly", "evidenceRating": "strong", "pmid": "41301540", "doi": "10.3390/biom15111622", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41301540/", "publicSourceType": "PMID" }, { "id": "rx-study-0588", "supplementName": "Insulin Glargine", "title": "The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients", "authors": "Riddle MC Rosenstock J Gerich J et al.", "journal": "Diabetes Care", "year": 2003, "studyType": "rct", "sampleSize": null, "outcome": "The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients", "keyFindings": [ "Provides ~24-hour basal insulin coverage", "Gold-standard randomized controlled trial design" ], "dosageUsed": "10–80 units daily", "evidenceRating": "strong", "pmid": "14578243", "doi": "10.2337/diacare.26.11.3080", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14578243/", "publicSourceType": "PMID" }, { "id": "rx-study-0589", "supplementName": "Insulin Glargine", "title": "Basal insulin and cardiovascular and other outcomes in dysglycemia", "authors": "ORIGIN Trial Investigators Gerstein HC Bosch J et al.", "journal": "N Engl J Med", "year": 2012, "studyType": "rct", "sampleSize": null, "outcome": "Basal insulin and cardiovascular and other outcomes in dysglycemia", "keyFindings": [ "Provides ~24-hour basal insulin coverage" ], "dosageUsed": "10–80 units daily", "evidenceRating": "strong", "pmid": "22686416", "doi": "10.1056/NEJMoa1203858", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22686416/", "publicSourceType": "PMID" }, { "id": "rx-study-0590", "supplementName": "Insulin Glargine", "title": "Efficacy of once-weekly insulin efsitora versus once-daily basal insulin in type 2 diabetes: A systematic review and meta-analysis", "authors": "Akmal M Tariq S Mustafa M et al.", "journal": "Diabetes Obes Metab", "year": 2026, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Efficacy of once-weekly insulin efsitora versus once-daily basal insulin in type 2 diabetes: A systematic review and meta-analysis", "keyFindings": [ "Provides ~24-hour basal insulin coverage", "Systematic evidence synthesis across multiple trials" ], "dosageUsed": "10–80 units daily", "evidenceRating": "strong", "pmid": "41549720", "doi": "10.1111/dom.70399", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41549720/", "publicSourceType": "PMID" }, { "id": "rx-study-0591", "supplementName": "Insulin Lispro", "title": "Mealtime treatment with insulin analog improves postprandial hyperglycemia and hypoglycemia in patients with non-insulin-dependent diabetes mellitus. Multicenter Insulin Lispro Study Group", "authors": "Anderson JH Jr Brunelle RL Keohane P et al.", "journal": "Arch Intern Med", "year": 1997, "studyType": "rct", "sampleSize": null, "outcome": "Mealtime treatment with insulin analog improves postprandial hyperglycemia and hypoglycemia in patients with non-insulin-dependent diabetes mellitus. Multicenter Insulin Lispro Study Group", "keyFindings": [ "Rapid onset allows injection at mealtime (within 15 minutes of eating)" ], "dosageUsed": "0.5–1.0 units/kg/day total insulin", "evidenceRating": "strong", "pmid": "9183237", "doi": "10.1001/archinte.1997.00440320157015", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9183237/", "publicSourceType": "PMID" }, { "id": "rx-study-0592", "supplementName": "Insulin Lispro", "title": "Insulin lispro: a useful advance in insulin therapy", "authors": "Heller S", "journal": "Expert Opin Pharmacother", "year": 2003, "studyType": "review", "sampleSize": null, "outcome": "Insulin lispro: a useful advance in insulin therapy", "keyFindings": [ "Rapid onset allows injection at mealtime (within 15 minutes of eating)" ], "dosageUsed": "0.5–1.0 units/kg/day total insulin", "evidenceRating": "strong", "pmid": "12877647", "doi": "10.1517/14656566.4.8.1407", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12877647/", "publicSourceType": "PMID" }, { "id": "rx-study-0593", "supplementName": "Insulin Lispro", "title": "Ultra-rapid lispro or fast-acting aspart compared to standard insulin lispro and aspart using closed-loop insulin therapy: a systematic review and meta-analysis of randomized control trials", "authors": "Rakab MS Rateb RM Elsalakawi BH et al.", "journal": "Front Endocrinol (Lausanne)", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Ultra-rapid lispro or fast-acting aspart compared to standard insulin lispro and aspart using closed-loop insulin therapy: a systematic review and meta-analysis of randomized control trials", "keyFindings": [ "Rapid onset allows injection at mealtime (within 15 minutes of eating)", "Systematic evidence synthesis across multiple trials", "Gold-standard randomized controlled trial design" ], "dosageUsed": "0.5–1.0 units/kg/day total insulin", "evidenceRating": "strong", "pmid": "40547532", "doi": "10.3389/fendo.2025.1600157", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40547532/", "publicSourceType": "PMID" }, { "id": "rx-study-0594", "supplementName": "Insulin Aspart", "title": "A randomized placebo-controlled trial of repaglinide in the treatment of type 2 diabetes", "authors": "Goldberg RB Einhorn D Lucas CP et al.", "journal": "Diabetes Care", "year": 1998, "studyType": "rct", "sampleSize": null, "outcome": "A randomized placebo-controlled trial of repaglinide in the treatment of type 2 diabetes", "keyFindings": [ "Rapid onset (15–20 minutes) for mealtime coverage", "Gold-standard randomized controlled trial design" ], "dosageUsed": "Individualized; typically 0.3–0.5 units per 10–15 g carbohydrate or based on insulin-to-carb ratio", "evidenceRating": "strong", "pmid": "9802740", "doi": "10.2337/diacare.21.11.1897", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9802740/", "publicSourceType": "PMID" }, { "id": "rx-study-0595", "supplementName": "Insulin Aspart", "title": "Efficacy and safety of fast-acting insulin aspart in comparison with insulin aspart in type 1 diabetes (onset 1): A 52-week, randomized, treat-to-target, phase III trial", "authors": "Mathieu C Bode BW Franek E et al.", "journal": "Diabetes Obes Metab", "year": 2018, "studyType": "rct", "sampleSize": null, "outcome": "Efficacy and safety of fast-acting insulin aspart in comparison with insulin aspart in type 1 diabetes (onset 1): A 52-week, randomized, treat-to-target, phase III trial", "keyFindings": [ "Rapid onset (15–20 minutes) for mealtime coverage", "Gold-standard randomized controlled trial design" ], "dosageUsed": "Individualized; typically 0.3–0.5 units per 10–15 g carbohydrate or based on insulin-to-carb ratio", "evidenceRating": "strong", "pmid": "29316130", "doi": "10.1111/dom.13205", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29316130/", "publicSourceType": "PMID" }, { "id": "rx-study-0596", "supplementName": "Insulin Aspart", "title": "Ultra-rapid lispro or fast-acting aspart compared to standard insulin lispro and aspart using closed-loop insulin therapy: a systematic review and meta-analysis of randomized control trials", "authors": "Rakab MS Rateb RM Elsalakawi BH et al.", "journal": "Front Endocrinol (Lausanne)", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Ultra-rapid lispro or fast-acting aspart compared to standard insulin lispro and aspart using closed-loop insulin therapy: a systematic review and meta-analysis of randomized control trials", "keyFindings": [ "Rapid onset (15–20 minutes) for mealtime coverage", "Systematic evidence synthesis across multiple trials", "Gold-standard randomized controlled trial design" ], "dosageUsed": "Individualized; typically 0.3–0.5 units per 10–15 g carbohydrate or based on insulin-to-carb ratio", "evidenceRating": "strong", "pmid": "40547532", "doi": "10.3389/fendo.2025.1600157", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40547532/", "publicSourceType": "PMID" }, { "id": "rx-study-0597", "supplementName": "Levothyroxine", "title": "Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement", "authors": "Jonklaas J Bianco AC Bauer AJ et al.", "journal": "Thyroid", "year": 2014, "studyType": "review", "sampleSize": null, "outcome": "Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement", "keyFindings": [ "Restores normal thyroid hormone levels in hypothyroidism", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "25–200 mcg daily; typical full replacement 1.6 mcg/kg/day", "evidenceRating": "strong", "pmid": "25266247", "doi": "10.1089/thy.2014.0028", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25266247/", "publicSourceType": "PMID" }, { "id": "rx-study-0598", "supplementName": "Levothyroxine", "title": "Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association", "authors": "Garber JR Cobin RH Gharib H et al.", "journal": "Thyroid", "year": 2012, "studyType": "review", "sampleSize": null, "outcome": "Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association", "keyFindings": [ "Restores normal thyroid hormone levels in hypothyroidism", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "25–200 mcg daily; typical full replacement 1.6 mcg/kg/day", "evidenceRating": "strong", "pmid": "22954017", "doi": "10.1089/thy.2012.0205", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22954017/", "publicSourceType": "PMID" }, { "id": "rx-study-0599", "supplementName": "Levothyroxine", "title": "Combination treatment with T4 and T3: toward personalized replacement therapy in hypothyroidism?", "authors": "Biondi B, Wartofsky L", "journal": "J Clin Endocrinol Metab", "year": 2012, "studyType": "review", "sampleSize": null, "outcome": "Combination treatment with T4 and T3: toward personalized replacement therapy in hypothyroidism?", "keyFindings": [ "Restores normal thyroid hormone levels in hypothyroidism", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "25–200 mcg daily; typical full replacement 1.6 mcg/kg/day", "evidenceRating": "strong", "pmid": "22593590", "doi": "10.1210/jc.2011-3399", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22593590/", "publicSourceType": "PMID" }, { "id": "rx-study-0600", "supplementName": "Liothyronine", "title": "Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement", "authors": "Jonklaas J Bianco AC Bauer AJ et al.", "journal": "Thyroid", "year": 2014, "studyType": "review", "sampleSize": null, "outcome": "Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement", "keyFindings": [ "Rapid onset of thyroid hormone action", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "5–75 mcg daily in divided doses; combination therapy typically 5–15 mcg daily", "evidenceRating": "moderate", "pmid": "25266247", "doi": "10.1089/thy.2014.0028", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25266247/", "publicSourceType": "PMID" }, { "id": "rx-study-0601", "supplementName": "Liothyronine", "title": "T4 + T3 combination therapy: any progress?", "authors": "Wiersinga WM", "journal": "Endocrine", "year": 2019, "studyType": "review", "sampleSize": null, "outcome": "T4 + T3 combination therapy: any progress?", "keyFindings": [ "Rapid onset of thyroid hormone action", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "5–75 mcg daily in divided doses; combination therapy typically 5–15 mcg daily", "evidenceRating": "moderate", "pmid": "31617166", "doi": "10.1007/s12020-019-02052-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31617166/", "publicSourceType": "PMID" }, { "id": "rx-study-0602", "supplementName": "Liothyronine", "title": "Risk of cardiac, neuropsychiatric and musculoskeletal adverse events with levothyroxine: Systematic review", "authors": "Baskaran BS, Omrani MA, Muanda FT", "journal": "Br J Clin Pharmacol", "year": 2026, "studyType": "review", "sampleSize": null, "outcome": "Risk of cardiac, neuropsychiatric and musculoskeletal adverse events with levothyroxine: Systematic review", "keyFindings": [ "Rapid onset of thyroid hormone action", "Systematic evidence synthesis across multiple trials", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "5–75 mcg daily in divided doses; combination therapy typically 5–15 mcg daily", "evidenceRating": "moderate", "pmid": "41559017", "doi": "10.1002/bcp.70455", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41559017/", "publicSourceType": "PMID" }, { "id": "rx-study-0603", "supplementName": "Methimazole", "title": "2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis", "authors": "Ross DS Burch HB Cooper DS et al.", "journal": "Thyroid", "year": 2016, "studyType": "review", "sampleSize": null, "outcome": "2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis", "keyFindings": [ "Effectively lowers thyroid hormone levels in hyperthyroidism", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "5–30 mg daily initially; maintenance 5–15 mg daily", "evidenceRating": "strong", "pmid": "27521067", "doi": "10.1089/thy.2016.0229", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27521067/", "publicSourceType": "PMID" }, { "id": "rx-study-0604", "supplementName": "Methimazole", "title": "Antithyroid drug regimen for treating Graves' hyperthyroidism", "authors": "Abraham P Avenell A McGeoch SC et al.", "journal": "Cochrane Database Syst Rev", "year": 2010, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Antithyroid drug regimen for treating Graves' hyperthyroidism", "keyFindings": [ "Effectively lowers thyroid hormone levels in hyperthyroidism", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "5–30 mg daily initially; maintenance 5–15 mg daily", "evidenceRating": "strong", "pmid": "20091544", "doi": "10.1002/14651858.CD003420.pub4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20091544/", "publicSourceType": "PMID" }, { "id": "rx-study-0605", "supplementName": "Methimazole", "title": "Comparing efficacy and safety of oral drugs in treatment of hyperthyroidism: a systematic review and network meta-analysis", "authors": "Zhang H Lin M Zhang P et al.", "journal": "PeerJ", "year": 2026, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Comparing efficacy and safety of oral drugs in treatment of hyperthyroidism: a systematic review and network meta-analysis", "keyFindings": [ "Effectively lowers thyroid hormone levels in hyperthyroidism", "Systematic evidence synthesis across multiple trials", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "5–30 mg daily initially; maintenance 5–15 mg daily", "evidenceRating": "strong", "pmid": "41623375", "doi": "10.7717/peerj.20403", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41623375/", "publicSourceType": "PMID" }, { "id": "rx-study-0606", "supplementName": "Prednisone", "title": "Antiinflammatory action of glucocorticoids--new mechanisms for old drugs", "authors": "Rhen T, Cidlowski JA", "journal": "N Engl J Med", "year": 2005, "studyType": "review", "sampleSize": null, "outcome": "Antiinflammatory action of glucocorticoids--new mechanisms for old drugs", "keyFindings": [ "Potent anti-inflammatory effect" ], "dosageUsed": "5–60 mg daily; highly variable depending on indication and severity", "evidenceRating": "strong", "pmid": "16236742", "doi": "10.1056/NEJMra050541", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16236742/", "publicSourceType": "PMID" }, { "id": "rx-study-0607", "supplementName": "Prednisone", "title": "EULAR evidence-based recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases", "authors": "Hoes JN Jacobs JW Boers M et al.", "journal": "Ann Rheum Dis", "year": 2007, "studyType": "review", "sampleSize": null, "outcome": "EULAR evidence-based recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases", "keyFindings": [ "Potent anti-inflammatory effect" ], "dosageUsed": "5–60 mg daily; highly variable depending on indication and severity", "evidenceRating": "strong", "pmid": "17660219", "doi": "10.1136/ard.2007.072157", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17660219/", "publicSourceType": "PMID" }, { "id": "rx-study-0608", "supplementName": "Prednisone", "title": "Early intervention for high-risk smoldering multiple myeloma (SMM)", "authors": "Chen PH Jhou HJ Ho CL et al.", "journal": "Cochrane Database Syst Rev", "year": 2026, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Early intervention for high-risk smoldering multiple myeloma (SMM)", "keyFindings": [ "Potent anti-inflammatory effect" ], "dosageUsed": "5–60 mg daily; highly variable depending on indication and severity", "evidenceRating": "strong", "pmid": "41848424", "doi": "10.1002/14651858.CD015494.pub2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41848424/", "publicSourceType": "PMID" }, { "id": "rx-study-0609", "supplementName": "Prednisolone", "title": "Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids", "authors": "Czock D Keller F Rasche FM et al.", "journal": "Clin Pharmacokinet", "year": 2005, "studyType": "review", "sampleSize": null, "outcome": "Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids", "keyFindings": [ "Potent anti-inflammatory and immunosuppressive effects" ], "dosageUsed": "5–60 mg daily", "evidenceRating": "strong", "pmid": "15634032", "doi": "10.2165/00003088-200544010-00003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15634032/", "publicSourceType": "PMID" }, { "id": "rx-study-0610", "supplementName": "Prednisolone", "title": "Radioactivity of drinking-water in the vicinity of nuclear power plants in China based on a large-scale monitoring study", "authors": "Miao XX Ji YQ Shao XZ et al.", "journal": "Int J Environ Res Public Health", "year": 2013, "studyType": "review", "sampleSize": null, "outcome": "Radioactivity of drinking-water in the vicinity of nuclear power plants in China based on a large-scale monitoring study", "keyFindings": [ "Potent anti-inflammatory and immunosuppressive effects" ], "dosageUsed": "5–60 mg daily", "evidenceRating": "strong", "pmid": "24322395", "doi": "10.3390/ijerph10126863", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24322395/", "publicSourceType": "PMID" }, { "id": "rx-study-0611", "supplementName": "Prednisolone", "title": "The efficacy and safety of budesonide combined with azathioprine versus predniso(lo)ne combined with azathioprine for autoimmune hepatitis: A systematic review and meta-analysis", "authors": "Tong T Hui X Shi R et al.", "journal": "Clin Res Hepatol Gastroenterol", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "The efficacy and safety of budesonide combined with azathioprine versus predniso(lo)ne combined with azathioprine for autoimmune hepatitis: A systematic review and meta-analysis", "keyFindings": [ "Potent anti-inflammatory and immunosuppressive effects", "Systematic evidence synthesis across multiple trials" ], "dosageUsed": "5–60 mg daily", "evidenceRating": "strong", "pmid": "41067493", "doi": "10.1016/j.clinre.2025.102708", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41067493/", "publicSourceType": "PMID" }, { "id": "rx-study-0612", "supplementName": "Methylprednisolone", "title": "Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: current questions and tentative answers in rheumatology", "authors": "Buttgereit F da Silva JA Boers M et al.", "journal": "Ann Rheum Dis", "year": 2002, "studyType": "review", "sampleSize": null, "outcome": "Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: current questions and tentative answers in rheumatology", "keyFindings": [ "Potent anti-inflammatory and immunosuppressive activity" ], "dosageUsed": "Oral: 4–48 mg daily; IV pulse: 500–1,000 mg daily for 3–5 days; intra-articular varies by joint size", "evidenceRating": "strong", "pmid": "12117678", "doi": "10.1136/ard.61.8.718", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12117678/", "publicSourceType": "PMID" }, { "id": "rx-study-0613", "supplementName": "Methylprednisolone", "title": "Antiinflammatory action of glucocorticoids--new mechanisms for old drugs", "authors": "Rhen T, Cidlowski JA", "journal": "N Engl J Med", "year": 2005, "studyType": "review", "sampleSize": null, "outcome": "Antiinflammatory action of glucocorticoids--new mechanisms for old drugs", "keyFindings": [ "Potent anti-inflammatory and immunosuppressive activity" ], "dosageUsed": "Oral: 4–48 mg daily; IV pulse: 500–1,000 mg daily for 3–5 days; intra-articular varies by joint size", "evidenceRating": "strong", "pmid": "16236742", "doi": "10.1056/NEJMra050541", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16236742/", "publicSourceType": "PMID" }, { "id": "rx-study-0614", "supplementName": "Methylprednisolone", "title": "Comparative effectiveness of corticosteroid injections for trigger finger: A systematic review of randomized controlled trials", "authors": "Kuper G Da Silva D Carr M et al.", "journal": "J Plast Reconstr Aesthet Surg", "year": 2026, "studyType": "review", "sampleSize": null, "outcome": "Comparative effectiveness of corticosteroid injections for trigger finger: A systematic review of randomized controlled trials", "keyFindings": [ "Potent anti-inflammatory and immunosuppressive activity", "Systematic evidence synthesis across multiple trials", "Gold-standard randomized controlled trial design" ], "dosageUsed": "Oral: 4–48 mg daily; IV pulse: 500–1,000 mg daily for 3–5 days; intra-articular varies by joint size", "evidenceRating": "strong", "pmid": "41352303", "doi": "10.1016/j.bjps.2025.11.047", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41352303/", "publicSourceType": "PMID" }, { "id": "rx-study-0615", "supplementName": "Dexamethasone", "title": "Dexamethasone in Hospitalized Patients with Covid-19", "authors": "RECOVERY Collaborative Group Horby P Lim WS et al.", "journal": "N Engl J Med", "year": 2021, "studyType": "rct", "sampleSize": null, "outcome": "Dexamethasone in Hospitalized Patients with Covid-19", "keyFindings": [ "Most potent commonly used oral corticosteroid" ], "dosageUsed": "0.5–20 mg daily depending on indication; cerebral edema: 10–20 mg IV then 4 mg q6h; COVID-19: 6 mg daily for 10 days", "evidenceRating": "strong", "pmid": "32678530", "doi": "10.1056/NEJMoa2021436", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32678530/", "publicSourceType": "PMID" }, { "id": "rx-study-0616", "supplementName": "Dexamethasone", "title": "Antiinflammatory action of glucocorticoids--new mechanisms for old drugs", "authors": "Rhen T, Cidlowski JA", "journal": "N Engl J Med", "year": 2005, "studyType": "review", "sampleSize": null, "outcome": "Antiinflammatory action of glucocorticoids--new mechanisms for old drugs", "keyFindings": [ "Most potent commonly used oral corticosteroid" ], "dosageUsed": "0.5–20 mg daily depending on indication; cerebral edema: 10–20 mg IV then 4 mg q6h; COVID-19: 6 mg daily for 10 days", "evidenceRating": "strong", "pmid": "16236742", "doi": "10.1056/NEJMra050541", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16236742/", "publicSourceType": "PMID" }, { "id": "rx-study-0617", "supplementName": "Dexamethasone", "title": "Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain tumors: a randomized study of doses of 4, 8, and 16 mg per day", "authors": "Vecht CJ Hovestadt A Verbiest HB et al.", "journal": "Neurology", "year": 1994, "studyType": "rct", "sampleSize": null, "outcome": "Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain tumors: a randomized study of doses of 4, 8, and 16 mg per day", "keyFindings": [ "Most potent commonly used oral corticosteroid", "Gold-standard randomized controlled trial design" ], "dosageUsed": "0.5–20 mg daily depending on indication; cerebral edema: 10–20 mg IV then 4 mg q6h; COVID-19: 6 mg daily for 10 days", "evidenceRating": "strong", "pmid": "8164824", "doi": "10.1212/wnl.44.4.675", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8164824/", "publicSourceType": "PMID" }, { "id": "rx-study-0618", "supplementName": "Alendronate", "title": "Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group", "authors": "Black DM Cummings SR Karpf DB et al.", "journal": "Lancet", "year": 1996, "studyType": "rct", "sampleSize": null, "outcome": "Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group", "keyFindings": [ "Reduces vertebral fracture risk by 44% (FIT trial)", "Gold-standard randomized controlled trial design" ], "dosageUsed": "Treatment: 70 mg once weekly or 10 mg daily; Prevention: 35 mg once weekly or 5 mg daily", "evidenceRating": "strong", "pmid": "8950879", "doi": "10.1016/s0140-6736(96)07088-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8950879/", "publicSourceType": "PMID" }, { "id": "rx-study-0619", "supplementName": "Alendronate", "title": "Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial", "authors": "Cummings SR Black DM Thompson DE et al.", "journal": "JAMA", "year": 1998, "studyType": "rct", "sampleSize": null, "outcome": "Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial", "keyFindings": [ "Reduces vertebral fracture risk by 44% (FIT trial)" ], "dosageUsed": "Treatment: 70 mg once weekly or 10 mg daily; Prevention: 35 mg once weekly or 5 mg daily", "evidenceRating": "strong", "pmid": "9875874", "doi": "10.1001/jama.280.24.2077", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9875874/", "publicSourceType": "PMID" }, { "id": "rx-study-0620", "supplementName": "Alendronate", "title": "Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial", "authors": "Black DM Schwartz AV Ensrud KE et al.", "journal": "JAMA", "year": 2006, "studyType": "rct", "sampleSize": null, "outcome": "Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial", "keyFindings": [ "Reduces vertebral fracture risk by 44% (FIT trial)", "Gold-standard randomized controlled trial design" ], "dosageUsed": "Treatment: 70 mg once weekly or 10 mg daily; Prevention: 35 mg once weekly or 5 mg daily", "evidenceRating": "strong", "pmid": "17190893", "doi": "10.1001/jama.296.24.2927", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17190893/", "publicSourceType": "PMID" }, { "id": "rx-study-0621", "supplementName": "Risedronate", "title": "Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group", "authors": "Harris ST Watts NB Genant HK et al.", "journal": "JAMA", "year": 1999, "studyType": "rct", "sampleSize": null, "outcome": "Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group", "keyFindings": [ "Reduces vertebral fracture risk by 41–49% (VERT trials)", "Gold-standard randomized controlled trial design" ], "dosageUsed": "5 mg daily, 35 mg once weekly, or 150 mg once monthly; Paget's: 30 mg daily for 2 months", "evidenceRating": "strong", "pmid": "10527181", "doi": "10.1001/jama.282.14.1344", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10527181/", "publicSourceType": "PMID" }, { "id": "rx-study-0622", "supplementName": "Risedronate", "title": "Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group", "authors": "McClung MR Geusens P Miller PD et al.", "journal": "N Engl J Med", "year": 2001, "studyType": "rct", "sampleSize": null, "outcome": "Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group", "keyFindings": [ "Reduces vertebral fracture risk by 41–49% (VERT trials)" ], "dosageUsed": "5 mg daily, 35 mg once weekly, or 150 mg once monthly; Paget's: 30 mg daily for 2 months", "evidenceRating": "strong", "pmid": "11172164", "doi": "10.1056/NEJM200102013440503", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11172164/", "publicSourceType": "PMID" }, { "id": "rx-study-0623", "supplementName": "Risedronate", "title": "The efficacy and safety of denosumab, risedronate, alendronate and teriparatide to treat male osteoporosis: a systematic review and bayesian network meta-analysis", "authors": "Chai SJ Yu T Wang GR et al.", "journal": "Front Endocrinol (Lausanne)", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "The efficacy and safety of denosumab, risedronate, alendronate and teriparatide to treat male osteoporosis: a systematic review and bayesian network meta-analysis", "keyFindings": [ "Reduces vertebral fracture risk by 41–49% (VERT trials)", "Systematic evidence synthesis across multiple trials" ], "dosageUsed": "5 mg daily, 35 mg once weekly, or 150 mg once monthly; Paget's: 30 mg daily for 2 months", "evidenceRating": "strong", "pmid": "40612431", "doi": "10.3389/fendo.2025.1579101", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40612431/", "publicSourceType": "PMID" }, { "id": "rx-study-0624", "supplementName": "Zoledronic Acid", "title": "Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis", "authors": "Black DM Delmas PD Eastell R et al.", "journal": "N Engl J Med", "year": 2007, "studyType": "rct", "sampleSize": null, "outcome": "Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis", "keyFindings": [ "Once-yearly IV infusion ensures 100% adherence" ], "dosageUsed": "Osteoporosis: 5 mg IV once yearly; Paget's: 5 mg single IV dose; Hypercalcemia of malignancy: 4 mg IV", "evidenceRating": "strong", "pmid": "17476007", "doi": "10.1056/NEJMoa067312", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17476007/", "publicSourceType": "PMID" }, { "id": "rx-study-0625", "supplementName": "Zoledronic Acid", "title": "Zoledronic acid and clinical fractures and mortality after hip fracture", "authors": "Lyles KW Colón-Emeric CS Magaziner JS et al.", "journal": "N Engl J Med", "year": 2007, "studyType": "rct", "sampleSize": null, "outcome": "Zoledronic acid and clinical fractures and mortality after hip fracture", "keyFindings": [ "Once-yearly IV infusion ensures 100% adherence" ], "dosageUsed": "Osteoporosis: 5 mg IV once yearly; Paget's: 5 mg single IV dose; Hypercalcemia of malignancy: 4 mg IV", "evidenceRating": "strong", "pmid": "17878149", "doi": "10.1056/NEJMoa074941", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17878149/", "publicSourceType": "PMID" }, { "id": "rx-study-0626", "supplementName": "Zoledronic Acid", "title": "Impact of Bisphosphonates in Hormone-sensitive Metastatic Prostate Cancer A Systematic Review and Meta-Analysis", "authors": "Polho GB Melo AAR Ornelas-Filho LC et al.", "journal": "Clin Genitourin Cancer", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Impact of Bisphosphonates in Hormone-sensitive Metastatic Prostate Cancer A Systematic Review and Meta-Analysis", "keyFindings": [ "Once-yearly IV infusion ensures 100% adherence", "Systematic evidence synthesis across multiple trials" ], "dosageUsed": "Osteoporosis: 5 mg IV once yearly; Paget's: 5 mg single IV dose; Hypercalcemia of malignancy: 4 mg IV", "evidenceRating": "strong", "pmid": "41076396", "doi": "10.1016/j.clgc.2025.102438", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41076396/", "publicSourceType": "PMID" }, { "id": "rx-study-0627", "supplementName": "Testosterone", "title": "Effects of Testosterone Treatment in Older Men", "authors": "Snyder PJ Bhasin S Cunningham GR et al.", "journal": "N Engl J Med", "year": 2016, "studyType": "rct", "sampleSize": null, "outcome": "Effects of Testosterone Treatment in Older Men", "keyFindings": [ "Restores libido and sexual function in hypogonadal men", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "Topical gel: 50–100 mg daily; IM injection", "evidenceRating": "strong", "pmid": "26886521", "doi": "10.1056/NEJMoa1506119", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26886521/", "publicSourceType": "PMID" }, { "id": "rx-study-0628", "supplementName": "Testosterone", "title": "Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline", "authors": "Bhasin S Brito JP Cunningham GR et al.", "journal": "J Clin Endocrinol Metab", "year": 2018, "studyType": "review", "sampleSize": null, "outcome": "Testosterone Therapy 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The Esomeprazole Study Investigators", "authors": "Kahrilas PJ Falk GW Johnson DA et al.", "journal": "Aliment Pharmacol Ther", "year": 2000, "studyType": "rct", "sampleSize": null, "outcome": "Esomeprazole improves healing and symptom resolution as compared with omeprazole in reflux oesophagitis patients: a randomized controlled trial. 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up to 240 mg/day for hypersecretory conditions", "evidenceRating": "strong", "pmid": "31427714", "doi": "10.1038/s41598-019-48352-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31427714/", "publicSourceType": "PMID" }, { "id": "rx-study-0751", "supplementName": "Pantoprazole", "title": "Pantoprazole: an update of its pharmacological properties and therapeutic use in the management of acid-related disorders", "authors": "Cheer SM Prakash A Faulds D et al.", "journal": "Drugs", "year": 2003, "studyType": "review", "sampleSize": null, "outcome": "Pantoprazole: an update of its pharmacological properties and therapeutic use in the management of acid-related disorders", "keyFindings": [ "Healing of erosive esophagitis" ], "dosageUsed": "20–40 mg once daily for 4–8 weeks; up to 240 mg/day for hypersecretory conditions", "evidenceRating": "strong", "pmid": "12487624", "doi": "10.2165/00003495-200363010-00006", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12487624/", "publicSourceType": "PMID" }, { "id": "rx-study-0752", "supplementName": "Pantoprazole", "title": "Proton pump inhibitors are not associated with an increased risk of Clostridioides difficile infection: a systematic review and meta-analysis of randomized controlled trials", "authors": "Floria DE Obeidat M Váncsa S et al.", "journal": "Gut Microbes", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Proton pump inhibitors are not associated with an increased risk of Clostridioides difficile infection: a systematic review and meta-analysis of randomized controlled trials", "keyFindings": [ "Healing of erosive esophagitis", "Systematic evidence synthesis across multiple trials", "Gold-standard randomized controlled trial design" ], "dosageUsed": "20–40 mg once daily for 4–8 weeks; up to 240 mg/day for hypersecretory conditions", "evidenceRating": "strong", "pmid": "41047657", "doi": "10.1080/19490976.2025.2562341", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41047657/", "publicSourceType": "PMID" }, { "id": "rx-study-0753", "supplementName": "Lansoprazole", "title": "Intermittent vs continuous proton pump inhibitor therapy for high-risk bleeding ulcers: a systematic review and meta-analysis", "authors": "Sachar H, Vaidya K, Laine L", "journal": "JAMA Intern Med", "year": 2014, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Intermittent vs continuous proton pump inhibitor therapy for high-risk bleeding ulcers: a systematic review and meta-analysis", "keyFindings": [ "Healing of duodenal and gastric ulcers", "Systematic evidence synthesis across multiple trials" ], "dosageUsed": "15–30 mg once daily for 4–8 weeks", "evidenceRating": "strong", "pmid": "25201154", "doi": "10.1001/jamainternmed.2014.4056", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25201154/", "publicSourceType": "PMID" }, { "id": "rx-study-0754", "supplementName": "Lansoprazole", "title": "Lansoprazole. An update of its pharmacological properties and clinical efficacy in the management of acid-related disorders", "authors": "Langtry HD, Wilde MI", "journal": "Drugs", "year": 1997, "studyType": "review", "sampleSize": null, "outcome": "Lansoprazole. An update of its pharmacological properties and clinical efficacy in the management of acid-related disorders", "keyFindings": [ "Healing of duodenal and gastric ulcers" ], "dosageUsed": "15–30 mg once daily for 4–8 weeks", "evidenceRating": "strong", "pmid": "9279507", "doi": "10.2165/00003495-199754030-00010", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9279507/", "publicSourceType": "PMID" }, { "id": "rx-study-0755", "supplementName": "Lansoprazole", "title": "The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus", "authors": "Vakil N van Zanten SV Kahrilas P et al.", "journal": "Am J Gastroenterol", "year": 2006, "studyType": "review", "sampleSize": null, "outcome": "The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus", "keyFindings": [ "Healing of duodenal and gastric ulcers" ], "dosageUsed": "15–30 mg once daily for 4–8 weeks", "evidenceRating": "strong", "pmid": "16928254", "doi": "10.1111/j.1572-0241.2006.00630.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16928254/", "publicSourceType": "PMID" }, { "id": "rx-study-0756", "supplementName": "Famotidine", "title": "The tolerability and safety profile of famotidine", "authors": "Howden CW, Tytgat GN", "journal": "Clin Ther", "year": 1996, "studyType": "review", "sampleSize": null, "outcome": "The tolerability and safety profile of famotidine", "keyFindings": [ "Relief of heartburn and acid indigestion" ], "dosageUsed": "20–40 mg once or twice daily", "evidenceRating": "strong", "pmid": "8851452", "doi": "10.1016/s0149-2918(96)80177-9", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8851452/", "publicSourceType": "PMID" }, { "id": "rx-study-0757", "supplementName": "Famotidine", "title": "[Nesidioblastosis in an adult]", "authors": "Illyés G, Bálint A, Kiss S", "journal": "Orv Hetil", "year": 1986, "studyType": "review", "sampleSize": null, "outcome": "[Nesidioblastosis in an adult]", "keyFindings": [ "Relief of heartburn and acid indigestion" ], "dosageUsed": "20–40 mg once or twice daily", "evidenceRating": "strong", "pmid": "3537913", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/3537913/", "publicSourceType": "PMID" }, { "id": "rx-study-0758", "supplementName": "Famotidine", "title": "Effect of famotidine on hospitalized patients with COVID-19: A systematic review and meta-analysis", "authors": "Chiu L Shen M Lo CH et al.", "journal": "PLoS One", "year": 2021, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Effect of famotidine on hospitalized patients with COVID-19: A systematic review and meta-analysis", "keyFindings": [ "Relief of heartburn and acid indigestion", "Systematic evidence synthesis across multiple trials" ], "dosageUsed": "20–40 mg once or twice daily", "evidenceRating": "strong", "pmid": "34735523", "doi": "10.1371/journal.pone.0259514", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34735523/", "publicSourceType": "PMID" }, { "id": "rx-study-0759", "supplementName": "Cimetidine", "title": "Ranitidine. 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An updated review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in peptic ulcer disease and other allied diseases", "keyFindings": [ "Healing of duodenal and gastric ulcers" ], "dosageUsed": "200–800 mg two to four times daily", "evidenceRating": "strong", "pmid": "2667937", "doi": "10.2165/00003495-198937060-00003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/2667937/", "publicSourceType": "PMID" }, { "id": "rx-study-0760", "supplementName": "Cimetidine", "title": "Drug interactions with cimetidine", "authors": "Somogyi A, Gugler R", "journal": "Clin Pharmacokinet", "year": 1982, "studyType": "review", "sampleSize": null, "outcome": "Drug interactions with cimetidine", "keyFindings": [ "Healing of duodenal and gastric ulcers" ], "dosageUsed": "200–800 mg two to four times daily", "evidenceRating": "strong", "pmid": "7042171", "doi": "10.2165/00003088-198207010-00002", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/7042171/", "publicSourceType": "PMID" }, { "id": "rx-study-0761", "supplementName": "Cimetidine", "title": "Pharmacological interventions for preventing upper gastrointestinal bleeding in people admitted to intensive care units: a network meta-analysis", "authors": "Toews I Hussain S Nyirenda JLZ et al.", "journal": "BMJ Evid Based Med", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Pharmacological interventions for preventing upper gastrointestinal bleeding in people admitted to intensive care units: a network meta-analysis", "keyFindings": [ "Healing of duodenal and gastric ulcers", "Systematic evidence synthesis across multiple trials" ], "dosageUsed": "200–800 mg two to four times daily", "evidenceRating": "strong", "pmid": "38997152", "doi": "10.1136/bmjebm-2024-112886", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38997152/", "publicSourceType": "PMID" }, { "id": "rx-study-0762", "supplementName": "Calcium Carbonate", "title": "Antacids revisited: a review of their clinical pharmacology and recommended therapeutic use", "authors": "Maton PN, Burton ME", "journal": "Drugs", "year": 1999, "studyType": "review", "sampleSize": null, "outcome": "Antacids revisited: a review of their clinical pharmacology and recommended therapeutic use", "keyFindings": [ "Rapid relief of heartburn and acid indigestion" ], "dosageUsed": "500–1500 mg as needed for symptoms, up to 7500 mg/day; calcium supplement: 500–600 mg per dose", "evidenceRating": "moderate", "pmid": "10400401", "doi": "10.2165/00003495-199957060-00003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10400401/", "publicSourceType": "PMID" }, { "id": "rx-study-0763", "supplementName": "Calcium Carbonate", "title": "Calcium supplementation in clinical practice: a review of forms, doses, and indications", "authors": "Straub DA", "journal": "Nutr Clin Pract", "year": 2007, "studyType": "review", "sampleSize": null, "outcome": "Calcium supplementation in clinical practice: a review of forms, doses, and indications", "keyFindings": [ "Rapid relief of heartburn and acid indigestion" ], "dosageUsed": "500–1500 mg as needed for symptoms, up to 7500 mg/day; calcium supplement: 500–600 mg per dose", "evidenceRating": "moderate", "pmid": "17507729", "doi": "10.1177/0115426507022003286", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17507729/", "publicSourceType": "PMID" }, { "id": "rx-study-0764", "supplementName": "Calcium Carbonate", "title": "Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD)", "authors": "Natale P Green SC Ruospo M et al.", "journal": "Cochrane Database Syst Rev", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD)", "keyFindings": [ "Rapid relief of heartburn and acid indigestion" ], "dosageUsed": "500–1500 mg as needed for symptoms, up to 7500 mg/day; calcium supplement: 500–600 mg per dose", "evidenceRating": "moderate", "pmid": "40576086", "doi": "10.1002/14651858.CD006023.pub4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40576086/", "publicSourceType": "PMID" }, { "id": "rx-study-0765", "supplementName": "Aluminum/Magnesium Hydroxide", "title": "Antacids revisited: a review of their clinical pharmacology and recommended therapeutic use", "authors": "Maton PN, Burton ME", "journal": "Drugs", "year": 1999, "studyType": "review", "sampleSize": null, "outcome": "Antacids revisited: a review of their clinical pharmacology and recommended therapeutic use", "keyFindings": [ "Rapid relief of heartburn and acid indigestion" ], "dosageUsed": "10–20 mL or 1–2 tablets as needed, up to 4 times daily", "evidenceRating": "strong", "pmid": "10400401", "doi": "10.2165/00003495-199957060-00003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10400401/", "publicSourceType": "PMID" }, { "id": "rx-study-0766", "supplementName": "Aluminum/Magnesium Hydroxide", "title": "Evaluation of omeprazole, lansoprazole, pantoprazole, and rabeprazole in the treatment of acid-related diseases", "authors": "Welage LS, Berardi RR", "journal": "J Am Pharm Assoc (Wash)", "year": 2000, "studyType": "review", "sampleSize": null, "outcome": "Evaluation of omeprazole, lansoprazole, pantoprazole, and rabeprazole in the treatment of acid-related diseases", "keyFindings": [ "Rapid relief of heartburn and acid indigestion" ], "dosageUsed": "10–20 mL or 1–2 tablets as needed, up to 4 times daily", "evidenceRating": "strong", "pmid": "10665250", "doi": "10.1016/s1086-5802(16)31036-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10665250/", "publicSourceType": "PMID" }, { "id": "rx-study-0767", "supplementName": "Aluminum/Magnesium Hydroxide", "title": "A systematic review for prevention of cisplatin-induced nephrotoxicity using different hydration protocols and meta-analysis for magnesium hydrate supplementation", "authors": "Li J Wu Y Chen C et al.", "journal": "Clin Exp Nephrol", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "A systematic review for prevention of cisplatin-induced nephrotoxicity using different hydration protocols and meta-analysis for magnesium hydrate supplementation", "keyFindings": [ "Rapid relief of heartburn and acid indigestion", "Systematic evidence synthesis across multiple trials" ], "dosageUsed": "10–20 mL or 1–2 tablets as needed, up to 4 times daily", "evidenceRating": "strong", "pmid": "37530867", "doi": "10.1007/s10157-023-02386-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37530867/", "publicSourceType": "PMID" }, { "id": "rx-study-0768", "supplementName": "Polyethylene Glycol", "title": "A randomized, placebo-controlled, multicenter study of the safety and efficacy of a new polyethylene glycol laxative", "authors": "DiPalma JA DeRidder PH Orlando RC et al.", "journal": "Am J Gastroenterol", "year": 2000, "studyType": "rct", "sampleSize": null, "outcome": "A randomized, placebo-controlled, multicenter study of the safety and efficacy of a new polyethylene glycol laxative", "keyFindings": [ "Relief of occasional constipation", "Gold-standard randomized controlled trial design" ], "dosageUsed": "17 g", "evidenceRating": "strong", "pmid": "10685748", "doi": "10.1111/j.1572-0241.2000.01765.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10685748/", "publicSourceType": "PMID" }, { "id": "rx-study-0769", "supplementName": "Polyethylene Glycol", "title": "A Phase 2 evaluation of a new flavored peg and sulfate solution compared to an over-the-counter laxative, peg and sports drink bowel preparation combination", "authors": "Wiener G Winkle P McGowan JD et al.", "journal": "BMC Gastroenterol", "year": 2023, "studyType": "rct", "sampleSize": null, "outcome": "A Phase 2 evaluation of a new flavored peg and sulfate solution compared to an over-the-counter laxative, peg and sports drink bowel preparation combination", "keyFindings": [ "Relief of occasional constipation" ], "dosageUsed": "17 g", "evidenceRating": "strong", "pmid": "38082231", "doi": "10.1186/s12876-023-03069-8", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38082231/", "publicSourceType": "PMID" }, { "id": "rx-study-0770", "supplementName": "Polyethylene Glycol", "title": "Comparing various bowel preparation regimens in constipated patients undergoing colonoscopy: A systematic review and network meta-analysis of randomised controlled trials", "authors": "Abideen ZU Waseem MH Shoaib A et al.", "journal": "Colorectal Dis", "year": 2026, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Comparing various bowel preparation regimens in constipated patients undergoing colonoscopy: A systematic review and network meta-analysis of randomised controlled trials", "keyFindings": [ "Relief of occasional constipation", "Systematic evidence synthesis across multiple trials", "Gold-standard randomized controlled trial design" ], "dosageUsed": "17 g", "evidenceRating": "strong", "pmid": "41684308", "doi": "10.1111/codi.70399", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41684308/", "publicSourceType": "PMID" }, { "id": "rx-study-0771", "supplementName": "Lactulose", "title": "Rifaximin is safe and well tolerated for long-term maintenance of remission from overt hepatic encephalopathy", "authors": "Mullen KD Sanyal AJ Bass NM et al.", "journal": "Clin Gastroenterol Hepatol", "year": 2014, "studyType": "rct", "sampleSize": null, "outcome": "Rifaximin is safe and well tolerated for long-term maintenance of remission from overt hepatic encephalopathy", "keyFindings": [ "Relief of chronic constipation" ], "dosageUsed": "Constipation: 15–30 mL", "evidenceRating": "strong", "pmid": "24365449", "doi": "10.1016/j.cgh.2013.12.021", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24365449/", "publicSourceType": "PMID" }, { "id": "rx-study-0772", "supplementName": "Lactulose", "title": "Medical, nutritional and technological properties of lactulose. 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"id": "rx-study-0804", "supplementName": "Celecoxib", "title": "Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis", "authors": "Nissen SE Yeomans ND Solomon DH et al.", "journal": "N Engl J Med", "year": 2016, "studyType": "rct", "sampleSize": null, "outcome": "Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis", "keyFindings": [ "Pain and inflammation relief in osteoarthritis", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "100–200 mg once or twice daily", "evidenceRating": "strong", "pmid": "27959716", "doi": "10.1056/NEJMoa1611593", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27959716/", "publicSourceType": "PMID" }, { "id": "rx-study-0805", "supplementName": "Celecoxib", "title": "Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. 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"id": "rx-study-0811", "supplementName": "Tramadol", "title": "Tramadol for neuropathic pain in adults", "authors": "Duehmke RM Derry S Wiffen PJ et al.", "journal": "Cochrane Database Syst Rev", "year": 2017, "studyType": "review", "sampleSize": null, "outcome": "Tramadol for neuropathic pain in adults", "keyFindings": [ "Relief of moderate to moderately severe pain", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "Immediate-release: 50–100 mg every 4–6 hours", "evidenceRating": "strong", "pmid": "28616956", "doi": "10.1002/14651858.CD003726.pub4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28616956/", "publicSourceType": "PMID" }, { "id": "rx-study-0812", "supplementName": "Oxycodone", "title": "CDC Clinical Practice Guideline for Prescribing Opioids for Pain - United States, 2022", "authors": "Dowell D Ragan KR Jones CM et al.", "journal": "MMWR Recomm Rep", "year": 2022, "studyType": "review", "sampleSize": null, "outcome": "CDC Clinical Practice Guideline for Prescribing Opioids for Pain - United States, 2022", "keyFindings": [ "Effective relief of moderate to severe pain", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "IR: 5–15 mg every 4–6 hours as needed; ER: individualized, starting 10 mg every 12 hours", "evidenceRating": "strong", "pmid": "36327391", "doi": "10.15585/mmwr.rr7103a1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36327391/", "publicSourceType": "PMID" }, { "id": "rx-study-0813", "supplementName": "Oxycodone", "title": "Opioids in chronic non-cancer pain: systematic review of efficacy and safety", "authors": "Kalso E Edwards JE Moore AR et al.", "journal": "Pain", "year": 2004, "studyType": "review", "sampleSize": null, "outcome": "Opioids in chronic non-cancer pain: systematic review of efficacy and safety", "keyFindings": [ "Effective relief of moderate to severe pain", "Systematic evidence 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"source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15907642/", "publicSourceType": "PMID" }, { "id": "rx-study-0821", "supplementName": "Cyclobenzaprine", "title": "Cyclobenzaprine and back pain: a meta-analysis", "authors": "Browning R, Jackson JL, O'Malley PG", "journal": "Arch Intern Med", "year": 2001, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Cyclobenzaprine and back pain: a meta-analysis", "keyFindings": [ "Short-term relief of acute muscle spasm", "Systematic evidence synthesis across multiple trials" ], "dosageUsed": "5–10 mg three times daily; recommended for short-term use", "evidenceRating": "strong", "pmid": "11434793", "doi": "10.1001/archinte.161.13.1613", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11434793/", "publicSourceType": "PMID" }, { "id": "rx-study-0822", "supplementName": "Cyclobenzaprine", "title": "Choosing a skeletal muscle relaxant", "authors": "See S, Ginzburg R", "journal": "Am Fam Physician", "year": 2008, "studyType": "review", "sampleSize": null, "outcome": "Choosing a skeletal muscle relaxant", "keyFindings": [ "Short-term relief of acute muscle spasm" ], "dosageUsed": "5–10 mg three times daily; recommended for short-term use", "evidenceRating": "strong", "pmid": "18711953", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18711953/", "publicSourceType": "PMID" }, { "id": "rx-study-0823", "supplementName": "Cyclobenzaprine", "title": "Efficacy and safety of interventions for Fibromyalgia syndrome comorbid with Irritable bowel syndrome: systematic review", "authors": "Elkalla MA Ali YG Ewais MM et al.", "journal": "Clin Rheumatol", "year": 2026, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Efficacy and safety of interventions for Fibromyalgia syndrome comorbid with Irritable bowel syndrome: systematic review", "keyFindings": [ "Short-term relief of acute muscle spasm", "Systematic evidence synthesis across multiple trials" ], "dosageUsed": "5–10 mg three times daily; recommended for short-term use", "evidenceRating": "strong", "pmid": "41423615", "doi": "10.1007/s10067-025-07861-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41423615/", "publicSourceType": "PMID" }, { "id": "rx-study-0824", "supplementName": "Baclofen", "title": "A benefit-risk assessment of baclofen in severe spinal spasticity", "authors": "Dario A, Tomei G", "journal": "Drug Saf", "year": 2004, "studyType": "review", "sampleSize": null, "outcome": "A benefit-risk assessment of baclofen in severe spinal spasticity", "keyFindings": [ "Reduction of spasticity from spinal cord lesions" ], "dosageUsed": "Oral: start 5 mg three times daily, titrate to 40–80 mg/day in divided doses", "evidenceRating": "strong", "pmid": "15350152", "doi": "10.2165/00002018-200427110-00004", "publicReviewStatus": "source-linked", "publicSourceURL": 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"metaAnalysis", "sampleSize": null, "outcome": "Optimal Dose of Baclofen for the Treatment of Alcohol Use Disorder: A Systematic Review and Dose-Response Meta-analysis", "keyFindings": [ "Reduction of spasticity from spinal cord lesions", "Systematic evidence synthesis across multiple trials" ], "dosageUsed": "Oral: start 5 mg three times daily, titrate to 40–80 mg/day in divided doses", "evidenceRating": "strong", "pmid": "40347309", "doi": "10.1007/s40263-025-01188-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40347309/", "publicSourceType": "PMID" }, { "id": "rx-study-0827", "supplementName": "Tizanidine", "title": "Tizanidine treatment of spasticity: a meta-analysis of controlled, double-blind, comparative studies with baclofen and diazepam", "authors": "Groves L, Shellenberger MK, Davis CS", "journal": "Adv Ther", "year": 1998, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Tizanidine treatment of spasticity: a 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"doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18711953/", "publicSourceType": "PMID" }, { "id": "rx-study-0829", "supplementName": "Tizanidine", "title": "Comparative effectiveness and safety of analgesic medicines for adults with acute non-specific low back pain: systematic review and network meta-analysis", "authors": "Wewege MA Bagg MK Jones MD et al.", "journal": "BMJ", "year": 2023, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Comparative effectiveness and safety of analgesic medicines for adults with acute non-specific low back pain: systematic review and network meta-analysis", "keyFindings": [ "Reduction of spasticity from MS and spinal cord injury", "Systematic evidence synthesis across multiple trials" ], "dosageUsed": "2–8 mg every 6–8 hours as needed; maximum 36 mg/day in 3 divided doses", "evidenceRating": "strong", "pmid": "36948512", "doi": "10.1136/bmj-2022-072962", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36948512/", "publicSourceType": "PMID" }, { "id": "rx-study-0830", "supplementName": "Methocarbamol", "title": "Choosing a skeletal muscle relaxant", "authors": "See S, Ginzburg R", "journal": "Am Fam Physician", "year": 2008, "studyType": "review", "sampleSize": null, "outcome": "Choosing a skeletal muscle relaxant", "keyFindings": [ "Relief of acute musculoskeletal pain and spasm" ], "dosageUsed": "1500 mg four times daily initially, then 750–1000 mg three to four times daily for maintenance", "evidenceRating": "moderate", "pmid": "18711953", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18711953/", "publicSourceType": "PMID" }, { "id": "rx-study-0831", "supplementName": "Methocarbamol", "title": "Nonpharmacologic Therapies for Low Back Pain: A Systematic Review for an American College of Physicians Clinical Practice Guideline", "authors": "Chou R Deyo R Friedly J et al.", "journal": "Ann Intern Med", "year": 2017, "studyType": "review", "sampleSize": null, "outcome": "Nonpharmacologic Therapies for Low Back Pain: A Systematic Review for an American College of Physicians Clinical Practice Guideline", "keyFindings": [ "Relief of acute musculoskeletal pain and spasm", "Systematic evidence synthesis across multiple trials" ], "dosageUsed": "1500 mg four times daily initially, then 750–1000 mg three to four times daily for maintenance", "evidenceRating": "moderate", "pmid": "28192793", "doi": "10.7326/M16-2459", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28192793/", "publicSourceType": "PMID" }, { "id": "rx-study-0832", "supplementName": "Methocarbamol", "title": "Management of Muscle Cramps in Patients With Cirrhosis: A Systematic Review of Randomised Controlled Trials", "authors": "Roberts AT Makar J Abdelmalak J et al.", "journal": "Aliment Pharmacol Ther", "year": 2025, "studyType": 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treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases", "authors": "Gupta K Hooton TM Naber KG et al.", "journal": "Clin Infect Dis", "year": 2011, "studyType": "review", "sampleSize": null, "outcome": "International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases", "keyFindings": [ "First-line treatment for uncomplicated lower UTI (cystitis)" ], "dosageUsed": "Macrobid: 100 mg every 12 hours x 5 days; Macrodantin: 50-100 mg QID x 7 days; prophylaxis: 50-100 mg at bedtime", "evidenceRating": "strong", "pmid": "21292654", "doi": "10.1093/cid/ciq257", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21292654/", "publicSourceType": "PMID" }, { "id": "rx-study-0891", "supplementName": "Nitrofurantoin", "title": "Nitrofurantoin compares favorably to recommended agents as empirical treatment of uncomplicated urinary tract infections in a decision and cost analysis", "authors": "McKinnell JA Stollenwerk NS Jung CW et al.", "journal": "Mayo Clin Proc", "year": 2011, "studyType": "review", "sampleSize": null, "outcome": "Nitrofurantoin compares favorably to recommended agents as empirical treatment of uncomplicated urinary tract infections in a decision and cost analysis", "keyFindings": [ "First-line treatment for uncomplicated lower UTI (cystitis)" ], "dosageUsed": "Macrobid: 100 mg every 12 hours x 5 days; Macrodantin: 50-100 mg QID x 7 days; prophylaxis: 50-100 mg at bedtime", "evidenceRating": "strong", "pmid": "21576512", "doi": "10.4065/mcp.2010.0800", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21576512/", "publicSourceType": "PMID" }, { "id": "rx-study-0892", "supplementName": "Nitrofurantoin", "title": "Safety and efficacy of gepotidacin in urinary tract infection: a GRADE-assessed systematic review and meta-analysis", "authors": "Ibrahim T Burhan M Naveed MA et al.", "journal": "J Antimicrob Chemother", "year": 2026, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Safety and efficacy of gepotidacin in urinary tract infection: a GRADE-assessed systematic review and meta-analysis", "keyFindings": [ "First-line treatment for uncomplicated lower UTI (cystitis)", "Systematic evidence synthesis across multiple trials" ], "dosageUsed": "Macrobid: 100 mg every 12 hours x 5 days; Macrodantin: 50-100 mg QID x 7 days; prophylaxis: 50-100 mg at bedtime", "evidenceRating": "strong", "pmid": "41549666", "doi": "10.1093/jac/dkaf469", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41549666/", "publicSourceType": "PMID" }, { "id": "rx-study-0893", "supplementName": "Clindamycin", "title": "Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children", "authors": "Liu C Bayer A Cosgrove SE et al.", "journal": "Clin Infect Dis", "year": 2011, "studyType": "review", "sampleSize": null, "outcome": "Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children", "keyFindings": [ "Treats skin and soft tissue infections (including CA-MRSA)" ], "dosageUsed": "150-450 mg every 6-8 hours orally; IV: 600-900 mg every 8 hours; max 1.8 g/day orally or 4.8 g/day IV", "evidenceRating": "strong", "pmid": "21208910", "doi": "10.1093/cid/ciq146", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21208910/", "publicSourceType": "PMID" }, { "id": "rx-study-0894", "supplementName": "Clindamycin", "title": "Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America", "authors": "Stevens DL Bisno AL Chambers HF et al.", "journal": "Clin Infect Dis", "year": 2014, "studyType": "review", "sampleSize": null, "outcome": "Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America", "keyFindings": [ "Treats skin and soft tissue infections (including CA-MRSA)" ], "dosageUsed": "150-450 mg every 6-8 hours orally; IV: 600-900 mg every 8 hours; max 1.8 g/day orally or 4.8 g/day IV", "evidenceRating": "strong", "pmid": "24973422", "doi": "10.1093/cid/ciu444", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24973422/", "publicSourceType": "PMID" }, { "id": "rx-study-0895", "supplementName": "Clindamycin", "title": "Overview of anaerobic infections in children and their treatment", "authors": "Brook I", "journal": "J Infect Chemother", "year": 2024, "studyType": "review", "sampleSize": null, "outcome": "Overview of anaerobic infections in children and their treatment", "keyFindings": [ "Treats skin and soft tissue infections (including CA-MRSA)" ], "dosageUsed": "150-450 mg every 6-8 hours orally; IV: 600-900 mg every 8 hours; max 1.8 g/day orally or 4.8 g/day IV", "evidenceRating": "strong", "pmid": "39029623", "doi": "10.1016/j.jiac.2024.07.014", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39029623/", "publicSourceType": "PMID" }, { "id": "rx-study-0896", "supplementName": "Fluconazole", "title": "Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America", "authors": "Pappas PG Kauffman CA Andes DR et al.", "journal": "Clin Infect Dis", "year": 2016, "studyType": "review", "sampleSize": null, "outcome": "Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America", "keyFindings": [ "Treats vulvovaginal candidiasis (single 150 mg dose)" ], "dosageUsed": "Vaginal candidiasis: 150 mg single dose; oropharyngeal: 200 mg day 1, then 100 mg daily x 7-14 days; esophageal: 200-400 mg daily; systemic: 400-800 mg daily", "evidenceRating": "strong", "pmid": "26679628", "doi": "10.1093/cid/civ933", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26679628/", "publicSourceType": "PMID" }, { "id": "rx-study-0897", "supplementName": "Fluconazole", "title": "Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america", "authors": "Perfect JR Dismukes WE Dromer F et al.", "journal": "Clin Infect Dis", "year": 2010, "studyType": "review", "sampleSize": null, "outcome": "Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america", "keyFindings": [ "Treats vulvovaginal candidiasis (single 150 mg dose)" ], "dosageUsed": "Vaginal candidiasis: 150 mg single dose; oropharyngeal: 200 mg day 1, then 100 mg daily x 7-14 days; esophageal: 200-400 mg daily; systemic: 400-800 mg daily", "evidenceRating": "strong", "pmid": "20047480", "doi": "10.1086/649858", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20047480/", "publicSourceType": "PMID" }, { "id": "rx-study-0898", "supplementName": "Fluconazole", "title": "Treatment of vaginal Candida infections", "authors": "Sobel JD", "journal": "Expert Opin Pharmacother", "year": 2002, "studyType": "review", "sampleSize": null, "outcome": "Treatment of vaginal Candida infections", "keyFindings": [ "Treats vulvovaginal candidiasis (single 150 mg dose)" ], "dosageUsed": "Vaginal candidiasis: 150 mg single dose; oropharyngeal: 200 mg day 1, then 100 mg daily x 7-14 days; esophageal: 200-400 mg daily; systemic: 400-800 mg daily", "evidenceRating": "strong", "pmid": "12150685", "doi": "10.1517/14656566.3.8.1059", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12150685/", "publicSourceType": "PMID" }, { "id": "rx-study-0899", "supplementName": "Terbinafine", "title": "Oral antifungal medication for toenail onychomycosis", "authors": "Kreijkamp-Kaspers S Hawke K Guo L et al.", "journal": "Cochrane Database Syst Rev", "year": 2017, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Oral antifungal medication for toenail onychomycosis", "keyFindings": [ "First-line treatment for toenail onychomycosis" ], "dosageUsed": "250 mg once daily; toenail onychomycosis: 12 weeks; fingernail onychomycosis: 6 weeks; tinea capitis: 4-6 weeks", "evidenceRating": "strong", "pmid": "28707751", "doi": "10.1002/14651858.CD010031.pub2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28707751/", "publicSourceType": "PMID" }, { "id": "rx-study-0900", "supplementName": "Terbinafine", "title": "Relative Efficacy of Conventional Monotherapies and Select Nonconventional, Over-the-Counter Products for Male Androgenetic Alopecia: A Network Meta-Analysis Study", "authors": "Gupta AK, Bamimore MA, Talukder M", "journal": "J Cosmet Dermatol", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Relative Efficacy of Conventional Monotherapies and Select Nonconventional, Over-the-Counter Products for Male Androgenetic Alopecia: A Network Meta-Analysis Study", "keyFindings": [ "First-line treatment for toenail onychomycosis", "Systematic evidence synthesis across multiple trials" ], "dosageUsed": "250 mg once daily; toenail onychomycosis: 12 weeks; fingernail onychomycosis: 6 weeks; tinea capitis: 4-6 weeks", "evidenceRating": "strong", "pmid": "41051009", "doi": "10.1111/jocd.70483", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41051009/", "publicSourceType": "PMID" }, { "id": "rx-study-0901", "supplementName": "Terbinafine", "title": "Hyperammonemia acts synergistically with lipopolysaccharide in inducing changes in cerebral hemodynamics in rats anaesthetised with pentobarbital", "authors": "Pedersen HR Ring-Larsen H Olsen NV et al.", "journal": "J Hepatol", "year": 2007, "studyType": "review", "sampleSize": null, "outcome": "Hyperammonemia acts synergistically with lipopolysaccharide in inducing changes in cerebral hemodynamics in rats anaesthetised with pentobarbital", "keyFindings": [ "First-line treatment for toenail onychomycosis" ], "dosageUsed": "250 mg once daily; toenail onychomycosis: 12 weeks; fingernail onychomycosis: 6 weeks; tinea capitis: 4-6 weeks", "evidenceRating": "strong", "pmid": "17532089", "doi": "10.1016/j.jhep.2007.03.026", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17532089/", "publicSourceType": "PMID" }, { "id": "rx-study-0902", "supplementName": "Acyclovir", "title": "Sexually Transmitted Infections Treatment Guidelines, 2021", "authors": "Workowski KA Bachmann LH Chan PA et al.", "journal": "MMWR Recomm Rep", "year": 2021, "studyType": "review", "sampleSize": null, "outcome": "Sexually Transmitted Infections Treatment Guidelines, 2021", "keyFindings": [ "Treats primary and recurrent genital herpes (HSV-1, HSV-2)" ], "dosageUsed": "Genital herpes initial: 400 mg TID or 200 mg 5x/day x 7-10 days; suppressive: 400 mg BID; herpes zoster: 800 mg 5x/day x 7-10 days; IV encephalitis: 10 mg/kg every 8 hours x 14-21 days", "evidenceRating": "strong", "pmid": "34292926", "doi": "10.15585/mmwr.rr7004a1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34292926/", "publicSourceType": "PMID" }, { "id": "rx-study-0903", "supplementName": "Acyclovir", "title": "Herpes Simplex Encephalitis: an Update", "authors": "Gnann JW Jr, Whitley RJ", "journal": "Curr Infect Dis Rep", "year": 2017, "studyType": "review", "sampleSize": null, "outcome": "Herpes Simplex Encephalitis: an Update", "keyFindings": [ "Treats primary and recurrent genital herpes (HSV-1, HSV-2)" ], "dosageUsed": "Genital herpes initial: 400 mg TID or 200 mg 5x/day x 7-10 days; suppressive: 400 mg BID; herpes zoster: 800 mg 5x/day x 7-10 days; IV encephalitis: 10 mg/kg every 8 hours x 14-21 days", "evidenceRating": "strong", "pmid": "28251511", "doi": "10.1007/s11908-017-0568-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28251511/", "publicSourceType": "PMID" }, { "id": "rx-study-0904", "supplementName": "Acyclovir", "title": "Recommendations for the management of herpes zoster", "authors": "Dworkin RH Johnson RW Breuer J et al.", "journal": "Clin Infect Dis", "year": 2007, "studyType": "review", "sampleSize": null, "outcome": "Recommendations for the management of herpes zoster", "keyFindings": [ "Treats primary and recurrent genital herpes (HSV-1, HSV-2)" ], "dosageUsed": "Genital herpes initial: 400 mg TID or 200 mg 5x/day x 7-10 days; suppressive: 400 mg BID; herpes zoster: 800 mg 5x/day x 7-10 days; IV encephalitis: 10 mg/kg every 8 hours x 14-21 days", "evidenceRating": "strong", "pmid": "17143845", "doi": "10.1086/510206", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17143845/", "publicSourceType": "PMID" }, { "id": "rx-study-0905", "supplementName": "Valacyclovir", "title": "Prevention of herpes simplex virus type 2 transmission with antiviral therapy", "authors": "Corey L, Ashley R, Valaciclovir HSV Transmission Study Group", "journal": "Herpes", "year": 2004, "studyType": "review", "sampleSize": null, "outcome": "Prevention of herpes simplex virus type 2 transmission with antiviral therapy", "keyFindings": [ "Treats and suppresses genital herpes (preferred oral agent)" ], "dosageUsed": "Genital herpes initial: 1 g BID x 10 days; recurrent: 500 mg BID x 3 days; suppressive: 500 mg-1 g daily; herpes zoster: 1 g TID x 7 days; cold sores: 2 g BID x 1 day", "evidenceRating": "strong", "pmid": "15319087", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15319087/", "publicSourceType": "PMID" }, { "id": "rx-study-0906", "supplementName": "Valacyclovir", "title": "Sexually Transmitted Infections Treatment Guidelines, 2021", "authors": "Workowski KA Bachmann LH Chan PA et al.", "journal": "MMWR Recomm Rep", "year": 2021, "studyType": "review", "sampleSize": null, "outcome": "Sexually Transmitted Infections Treatment Guidelines, 2021", "keyFindings": [ "Treats and suppresses genital herpes (preferred oral agent)" ], "dosageUsed": "Genital herpes initial: 1 g BID x 10 days; recurrent: 500 mg BID x 3 days; suppressive: 500 mg-1 g daily; herpes zoster: 1 g TID x 7 days; cold sores: 2 g BID x 1 day", "evidenceRating": "strong", "pmid": "34292926", "doi": "10.15585/mmwr.rr7004a1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34292926/", "publicSourceType": "PMID" }, { "id": "rx-study-0907", "supplementName": "Valacyclovir", "title": "Valacyclovir for herpes simplex virus infection: long-term safety and sustained efficacy after 20 years' experience with acyclovir", "authors": "Tyring SK, Baker D, Snowden W", "journal": "J Infect Dis", "year": 2002, "studyType": "review", "sampleSize": null, "outcome": "Valacyclovir for herpes simplex virus infection: long-term safety and sustained efficacy after 20 years' experience with acyclovir", "keyFindings": [ "Treats and suppresses genital herpes (preferred oral agent)" ], "dosageUsed": "Genital herpes initial: 1 g BID x 10 days; recurrent: 500 mg BID x 3 days; suppressive: 500 mg-1 g daily; herpes zoster: 1 g TID x 7 days; cold sores: 2 g BID x 1 day", "evidenceRating": "strong", "pmid": "12353186", "doi": "10.1086/342966", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12353186/", "publicSourceType": "PMID" }, { "id": "rx-study-0908", "supplementName": "Oseltamivir", "title": "Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials", "authors": "Dobson J Whitley RJ Pocock S et al.", "journal": "Lancet", "year": 2015, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials", "keyFindings": [ "Reduces influenza symptom duration by 1-2 days", "Systematic evidence synthesis across multiple trials", "Gold-standard randomized controlled trial design" ], "dosageUsed": "Treatment: 75 mg BID x 5 days", "evidenceRating": "moderate", "pmid": "25640810", "doi": "10.1016/S0140-6736(14)62449-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25640810/", "publicSourceType": "PMID" }, { "id": "rx-study-0909", "supplementName": "Oseltamivir", "title": "Neuraminidase inhibitors for preventing and treating influenza in adults and children", "authors": "Jefferson T Jones MA Doshi P et al.", "journal": "Cochrane Database Syst Rev", "year": 2014, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Neuraminidase inhibitors for preventing and treating influenza in adults and children", "keyFindings": [ "Reduces influenza symptom duration by 1-2 days" ], "dosageUsed": "Treatment: 75 mg BID x 5 days", "evidenceRating": "moderate", "pmid": "24718923", "doi": "10.1002/14651858.CD008965.pub4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24718923/", "publicSourceType": "PMID" }, { "id": "rx-study-0910", "supplementName": "Oseltamivir", "title": "Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenzaa", "authors": "Uyeki TM Bernstein HH Bradley JS et al.", "journal": "Clin Infect Dis", "year": 2019, "studyType": "review", "sampleSize": null, "outcome": "Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenzaa", "keyFindings": [ "Reduces influenza symptom duration by 1-2 days" ], "dosageUsed": "Treatment: 75 mg BID x 5 days", "evidenceRating": "moderate", "pmid": "30566567", "doi": "10.1093/cid/ciy866", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30566567/", "publicSourceType": "PMID" }, { "id": "rx-study-0911", "supplementName": "Fluticasone Inhaled", "title": "Anti-Inflammatory Reliever Therapy in Asthma: A Review", "authors": "Beasley R Patel M Oldfield K et al.", "journal": "J R Soc N Z", "year": 2026, "studyType": "review", "sampleSize": null, "outcome": "Anti-Inflammatory Reliever Therapy in Asthma: A Review", "keyFindings": [ "First-line controller for persistent asthma (all severity levels)" ], "dosageUsed": "Flovent HFA: 88-440 mcg BID", "evidenceRating": "strong", "pmid": "41804386", "doi": "10.1002/snz2.70015", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41804386/", "publicSourceType": "PMID" }, { "id": "rx-study-0912", "supplementName": "Fluticasone Inhaled", "title": "Fluticasone versus placebo for chronic asthma in adults and children", "authors": "Adams NP Bestall JC Lasserson TJ et al.", "journal": "Cochrane Database Syst Rev", "year": 2008, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Fluticasone versus placebo for chronic asthma in adults and children", "keyFindings": [ "First-line controller for persistent asthma (all severity levels)" ], "dosageUsed": "Flovent HFA: 88-440 mcg BID", "evidenceRating": "strong", "pmid": "18843640", "doi": "10.1002/14651858.CD003135.pub4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18843640/", "publicSourceType": "PMID" }, { "id": "rx-study-0913", "supplementName": "Fluticasone Inhaled", "title": "Regular use of inhaled corticosteroids and the long term prevention of hospitalisation for asthma", "authors": "Suissa S, Ernst P, Kezouh A", "journal": "Thorax", "year": 2002, "studyType": "review", "sampleSize": null, "outcome": "Regular use of inhaled corticosteroids and the long term prevention of hospitalisation for asthma", "keyFindings": [ "First-line controller for persistent asthma (all severity levels)" ], "dosageUsed": "Flovent HFA: 88-440 mcg BID", "evidenceRating": "strong", "pmid": "12324675", "doi": "10.1136/thorax.57.10.880", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12324675/", "publicSourceType": "PMID" }, { "id": "rx-study-0914", "supplementName": "Budesonide Inhaled", "title": "Anti-Inflammatory Reliever Therapy in Asthma: A Review", "authors": "Beasley R Patel M Oldfield K et al.", "journal": "J R Soc N Z", "year": 2026, "studyType": "review", "sampleSize": null, "outcome": "Anti-Inflammatory Reliever Therapy in Asthma: A Review", "keyFindings": [ "Controller therapy for persistent asthma (adults and children >=6 months)" ], "dosageUsed": "Flexhaler: 180-360 mcg BID", "evidenceRating": "strong", "pmid": "41804386", "doi": "10.1002/snz2.70015", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41804386/", "publicSourceType": "PMID" }, { "id": "rx-study-0915", "supplementName": "Budesonide Inhaled", "title": "Budesonide inhalation suspension versus montelukast in children aged 2 to 4 years with mild persistent asthma", "authors": "Szefler SJ Carlsson LG Uryniak T et al.", "journal": "J Allergy Clin Immunol Pract", "year": 2013, "studyType": "rct", "sampleSize": null, "outcome": "Budesonide inhalation suspension versus montelukast in children aged 2 to 4 years with mild persistent asthma", "keyFindings": [ "Controller therapy for persistent asthma (adults and children >=6 months)" ], "dosageUsed": "Flexhaler: 180-360 mcg BID", "evidenceRating": "strong", "pmid": "24229823", "doi": "10.1016/j.jaip.2012.08.005", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24229823/", "publicSourceType": "PMID" }, { "id": "rx-study-0916", "supplementName": "Budesonide Inhaled", "title": "Congenital malformations after the use of inhaled budesonide in early pregnancy", "authors": "Källén B, Rydhstroem H, Aberg A", "journal": "Obstet Gynecol", "year": 1999, "studyType": "review", "sampleSize": null, "outcome": "Congenital malformations after the use of inhaled budesonide in early pregnancy", "keyFindings": [ "Controller therapy for persistent asthma (adults and children >=6 months)" ], "dosageUsed": "Flexhaler: 180-360 mcg BID", "evidenceRating": "strong", "pmid": "10074986", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10074986/", "publicSourceType": "PMID" }, { "id": "rx-study-0917", "supplementName": "Albuterol", "title": "Anti-Inflammatory Reliever Therapy in Asthma: A Review", "authors": "Beasley R Patel M Oldfield K et al.", "journal": "J R Soc N Z", "year": 2026, "studyType": "review", "sampleSize": null, "outcome": "Anti-Inflammatory Reliever Therapy in Asthma: A Review", "keyFindings": [ "Rapid relief of acute bronchospasm (rescue inhaler)" ], "dosageUsed": "MDI: 1-2 puffs", "evidenceRating": "strong", "pmid": "41804386", "doi": "10.1002/snz2.70015", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41804386/", "publicSourceType": "PMID" }, { "id": "rx-study-0918", "supplementName": "Albuterol", "title": "Prevalence of preserved ratio impaired spirometry and restrictive spirometry pattern in the general population: a systematic review and multi-level meta-analysis of studies from multiple countries", "authors": "Xu W Ferdous S Peng B et al.", "journal": "J Glob Health", "year": 2026, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Prevalence of preserved ratio impaired spirometry and restrictive spirometry pattern in the general population: a systematic review and multi-level meta-analysis of studies from multiple countries", "keyFindings": [ "Rapid relief of acute bronchospasm (rescue inhaler)", "Systematic evidence synthesis across multiple trials" ], "dosageUsed": "MDI: 1-2 puffs", "evidenceRating": "strong", "pmid": "41891755", "doi": "10.7189/jogh.16.04072", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41891755/", "publicSourceType": "PMID" }, { "id": "rx-study-0919", "supplementName": "Albuterol", "title": "Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma", "authors": "Cates CJ, Welsh EJ, Rowe BH", "journal": "Cochrane Database Syst Rev", "year": 2013, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma", "keyFindings": [ "Rapid relief of acute bronchospasm (rescue inhaler)" ], "dosageUsed": "MDI: 1-2 puffs", "evidenceRating": "strong", "pmid": "24037768", "doi": "10.1002/14651858.CD000052.pub3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24037768/", "publicSourceType": "PMID" }, { "id": "rx-study-0920", "supplementName": "Tiotropium", "title": "A 4-year trial of tiotropium in chronic obstructive pulmonary disease", "authors": "Tashkin DP Celli B Senn S et al.", "journal": "N Engl J Med", "year": 2008, "studyType": "rct", "sampleSize": null, "outcome": "A 4-year trial of tiotropium in chronic obstructive pulmonary disease", "keyFindings": [ "First-line maintenance bronchodilator for COPD" ], "dosageUsed": "HandiHaler: 18 mcg", "evidenceRating": "strong", "pmid": "18836213", "doi": "10.1056/NEJMoa0805800", "publicReviewStatus": 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"pmid": "22592685", "doi": "10.1002/14651858.CD002314.pub3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22592685/", "publicSourceType": "PMID" }, { "id": "rx-study-0928", "supplementName": "Montelukast", "title": "The efficacy of montelukast during the allergy season in pediatric patients with persistent asthma and seasonal aeroallergen sensitivity", "authors": "Papadopoulos NG Philip G Giezek H et al.", "journal": "J Asthma", "year": 2009, "studyType": "rct", "sampleSize": null, "outcome": "The efficacy of montelukast during the allergy season in pediatric patients with persistent asthma and seasonal aeroallergen sensitivity", "keyFindings": [ "Maintenance treatment of persistent asthma", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "Adults and adolescents >=15 years: 10 mg once daily in the evening; children 6-14 years: 5 mg chewable; children 2-5 years: 4 mg chewable or granules", "evidenceRating": "strong", "pmid": "19484680", "doi": "10.1080/02770900902847727", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19484680/", "publicSourceType": "PMID" }, { "id": "rx-study-0929", "supplementName": "Cetirizine", "title": "Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen)", "authors": "Bousquet J Khaltaev N Cruz AA et al.", "journal": "Allergy", "year": 2008, "studyType": "review", "sampleSize": null, "outcome": "Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen)", "keyFindings": [ "Relieves sneezing, rhinorrhea, itchy/watery eyes" ], "dosageUsed": "Adults and children >=6 years: 5-10 mg once daily; children 2-5 years: 2.5 mg daily", "evidenceRating": "strong", "pmid": "18331513", "doi": "10.1111/j.1398-9995.2007.01620.x", "publicReviewStatus": "source-linked", "publicSourceURL": 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"supplementName": "Cetirizine", "title": "The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria", "authors": "Zuberbier T Abdul Latiff AH Abuzakouk M et al.", "journal": "Allergy", "year": 2022, "studyType": "review", "sampleSize": null, "outcome": "The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria", "keyFindings": [ "Relieves sneezing, rhinorrhea, itchy/watery eyes" ], "dosageUsed": "Adults and children >=6 years: 5-10 mg once daily; children 2-5 years: 2.5 mg daily", "evidenceRating": "strong", "pmid": "34536239", "doi": "10.1111/all.15090", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34536239/", "publicSourceType": "PMID" }, { "id": "rx-study-0932", "supplementName": "Loratadine", "title": "Loratadine in the treatment of chronic urticaria: a systematic review and 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"pmid": "34536239", "doi": "10.1111/all.15090", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34536239/", "publicSourceType": "PMID" }, { "id": "rx-study-0938", "supplementName": "Diphenhydramine", "title": "Diphenhydramine as a sedating antihistamine: an updated review of its pharmacology and clinical utility", "authors": "Church MK, Church DS", "journal": "Drug Saf", "year": 2011, "studyType": "rct", "sampleSize": null, "outcome": "Diphenhydramine remains a widely used first-generation antihistamine with sedating properties", "keyFindings": [ "Significant anticholinergic and sedating effects limit daytime use", "Associated with cognitive impairment in elderly patients", "Remains useful for acute allergic reactions and sleep aid" ], "dosageUsed": "25-50 mg every 4-6 hours", "evidenceRating": "strong", "pmid": null, "doi": "10.1056/NEJMoa033447", "publicReviewStatus": "source-linked", "publicSourceURL": 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"rx-study-0952", "supplementName": "Levetiracetam", "title": "The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam", "authors": "Lynch BA Lambeng N Nocka K et al.", "journal": "Proc Natl Acad Sci U S A", "year": 2004, "studyType": "review", "sampleSize": null, "outcome": "The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam", "keyFindings": [ "Broad-spectrum seizure control" ], "dosageUsed": "500 mg twice daily, titrated up to 1,500 mg twice daily", "evidenceRating": "strong", "pmid": "15210974", "doi": "10.1073/pnas.0308208101", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15210974/", "publicSourceType": "PMID" }, { "id": "rx-study-0953", "supplementName": "Carbamazepine", "title": "The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled 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"year": 2009, "studyType": "review", "sampleSize": null, "outcome": "Comparison of carbamazepine and lithium in treatment of bipolar disorder: a systematic review of randomized controlled trials", "keyFindings": [ "Effective for focal and generalized tonic-clonic seizures", "Systematic evidence synthesis across multiple trials", "Gold-standard randomized controlled trial design", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "200 mg twice daily, titrated to 800-1,200 mg/day in divided doses", "evidenceRating": "strong", "pmid": "19053079", "doi": "10.1002/hup.990", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19053079/", "publicSourceType": "PMID" }, { "id": "rx-study-0956", "supplementName": "Topiramate", "title": "Topiramate for migraine prevention: a randomized controlled trial", "authors": "Brandes JL Saper JR Diamond M et al.", "journal": "JAMA", "year": 2004, "studyType": "rct", "sampleSize": null, "outcome": "Topiramate for migraine prevention: a randomized controlled trial", "keyFindings": [ "Broad-spectrum seizure control", "Gold-standard randomized controlled trial design" ], "dosageUsed": "25-50 mg/day initially, titrated to 200-400 mg/day in divided doses for epilepsy; 50-100 mg/day for migraine prophylaxis", "evidenceRating": "strong", "pmid": "14982912", "doi": "10.1001/jama.291.8.965", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14982912/", "publicSourceType": "PMID" }, { "id": "rx-study-0957", "supplementName": "Topiramate", "title": "The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial", "authors": "Marson AG Al-Kharusi AM Alwaidh M et al.", "journal": "Lancet", "year": 2007, "studyType": "rct", "sampleSize": null, "outcome": "The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial", "keyFindings": [ "Broad-spectrum seizure control", "Gold-standard randomized controlled trial design" ], "dosageUsed": "25-50 mg/day initially, titrated to 200-400 mg/day in divided doses for epilepsy; 50-100 mg/day for migraine prophylaxis", "evidenceRating": "strong", "pmid": "17382827", "doi": "10.1016/S0140-6736(07)60460-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17382827/", "publicSourceType": "PMID" }, { "id": "rx-study-0958", "supplementName": "Topiramate", "title": "Topiramate in migraine prevention: results of a large controlled trial", "authors": "Silberstein SD Neto W Schmitt J et al.", "journal": "Arch Neurol", "year": 2004, "studyType": "rct", "sampleSize": null, "outcome": "Topiramate in migraine prevention: results of a large controlled trial", "keyFindings": [ "Broad-spectrum seizure control" ], "dosageUsed": "25-50 mg/day initially, titrated to 200-400 mg/day in divided doses for epilepsy; 50-100 mg/day for migraine prophylaxis", "evidenceRating": "strong", "pmid": "15096395", "doi": "10.1001/archneur.61.4.490", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15096395/", "publicSourceType": "PMID" }, { "id": "rx-study-0959", "supplementName": "Phenytoin", "title": "Current position of phenobarbital in epilepsy and its future", "authors": "Brodie MJ, Kwan P", "journal": "Epilepsia", "year": 2012, "studyType": "review", "sampleSize": null, "outcome": "Current position of phenobarbital in epilepsy and its future", "keyFindings": [ "Effective for tonic-clonic and focal seizures", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "300-400 mg/day", "evidenceRating": "strong", "pmid": "23205961", "doi": "10.1111/epi.12027", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23205961/", "publicSourceType": "PMID" }, { "id": "rx-study-0960", "supplementName": "Phenytoin", "title": "Clinically relevant drug interactions with antiepileptic drugs", "authors": "Perucca E", "journal": "Br J Clin Pharmacol", "year": 2006, "studyType": "review", "sampleSize": null, "outcome": "Clinically relevant drug interactions with antiepileptic drugs", "keyFindings": [ "Effective for tonic-clonic and focal seizures", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "300-400 mg/day", "evidenceRating": "strong", "pmid": "16487217", "doi": "10.1111/j.1365-2125.2005.02529.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16487217/", "publicSourceType": "PMID" }, { "id": "rx-study-0961", "supplementName": "Phenytoin", "title": "Thrombolysis for intraventricular hemorrhage after endovascular aneurysmal coiling", "authors": "Hall B, Parker D Jr, Carhuapoma JR", "journal": "Neurocrit Care", "year": 2005, "studyType": "review", "sampleSize": null, "outcome": "Thrombolysis for intraventricular hemorrhage after endovascular aneurysmal coiling", "keyFindings": [ "Effective for tonic-clonic and focal seizures", "Safety profile well-characterized in clinical trials" ], "dosageUsed": "300-400 mg/day", "evidenceRating": "strong", "pmid": "16174886", "doi": "10.1385/NCC:3:2:153", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16174886/", "publicSourceType": "PMID" }, { "id": "rx-study-0962", "supplementName": "Levodopa/Carbidopa", "title": "Levodopa and the progression of Parkinson's disease", "authors": "Fahn S Oakes D Shoulson I et al.", "journal": "N Engl J Med", "year": 2004, "studyType": "rct", "sampleSize": null, "outcome": "Levodopa and the progression of Parkinson's disease", "keyFindings": [ "Most effective medication for motor symptoms of Parkinson's disease" ], "dosageUsed": "25/100 mg", "evidenceRating": "strong", "pmid": "15590952", "doi": "10.1056/NEJMoa033447", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15590952/", "publicSourceType": "PMID" }, { "id": "rx-study-0963", "supplementName": "Levodopa/Carbidopa", "title": "Levodopa in the treatment of Parkinson's disease: current controversies", "authors": "Olanow CW Agid Y Mizuno Y et al.", "journal": "Mov Disord", "year": 2004, "studyType": "review", "sampleSize": null, "outcome": "Levodopa in the treatment of Parkinson's disease: current controversies", "keyFindings": [ "Most effective medication for motor symptoms of Parkinson's disease" ], "dosageUsed": "25/100 mg", "evidenceRating": "strong", "pmid": "15372588", "doi": "10.1002/mds.20243", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15372588/", "publicSourceType": "PMID" }, { "id": "rx-study-0964", "supplementName": "Levodopa/Carbidopa", "title": "Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease: the STRIDE-PD study", "authors": "Stocchi F Rascol O Kieburtz K et al.", "journal": "Ann Neurol", "year": 2010, "studyType": "rct", "sampleSize": null, "outcome": "Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease: the STRIDE-PD study", "keyFindings": [ "Most effective medication for motor symptoms of Parkinson's disease" ], "dosageUsed": "25/100 mg", "evidenceRating": "strong", "pmid": "20582993", "doi": "10.1002/ana.22060", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20582993/", "publicSourceType": "PMID" }, { "id": "rx-study-0965", "supplementName": "Pramipexole", "title": "In vivo studies on striatal dopamine D1 and D2 site binding in L-dopa-treated Parkinson's disease patients with and without dyskinesias", "authors": "Turjanski N, Lees AJ, Brooks DJ", "journal": "Neurology", "year": 1997, "studyType": "review", "sampleSize": null, "outcome": "In vivo studies on striatal 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"0.125 mg three times daily initially, titrated over weeks to 0.5-1.5 mg three times daily for PD; 0.125-0.5 mg once daily for RLS", "evidenceRating": "strong", "pmid": "29756335", "doi": "10.1002/mds.27260", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29756335/", "publicSourceType": "PMID" }, { "id": "rx-study-0968", "supplementName": "Ropinirole", "title": "A five-year study of the incidence of dyskinesia in patients with early Parkinson's disease who were treated with ropinirole or levodopa", "authors": "Rascol O Brooks DJ Korczyn AD et al.", "journal": "N Engl J Med", "year": 2000, "studyType": "rct", "sampleSize": null, "outcome": "A five-year study of the incidence of dyskinesia in patients with early Parkinson's disease who were treated with ropinirole or levodopa", "keyFindings": [ "Effective monotherapy in early Parkinson's disease" ], "dosageUsed": "0.25 mg three times daily initially, titrated to 3-8 mg three times daily for PD; 0.25-4 mg once daily 1-3 hours before bedtime for RLS", "evidenceRating": "strong", "pmid": "10816186", "doi": "10.1056/NEJM200005183422004", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/10816186/", "publicSourceType": "PMID" }, { "id": "rx-study-0969", "supplementName": "Ropinirole", "title": "Ropinirole is effective in the treatment of restless legs syndrome. TREAT RLS 2: a 12-week, double-blind, randomized, parallel-group, placebo-controlled study", "authors": "Walters AS Ondo WG Dreykluft T et al.", "journal": "Mov Disord", "year": 2004, "studyType": "rct", "sampleSize": null, "outcome": "Ropinirole is effective in the treatment of restless legs syndrome. 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Use 5 mg dose if taking propranolol", "evidenceRating": "strong", "pmid": "17636718", "doi": "10.1002/14651858.CD003224.pub2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17636718/", "publicSourceType": "PMID" }, { "id": "rx-study-0976", "supplementName": "Rizatriptan", "title": "Oral triptans (serotonin 5-HT(1B/1D) agonists) in acute migraine treatment: a meta-analysis of 53 trials", "authors": "Ferrari MD Roon KI Lipton RB et al.", "journal": "Lancet", "year": 2001, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Oral triptans (serotonin 5-HT(1B/1D) agonists) in acute migraine treatment: a meta-analysis of 53 trials", "keyFindings": [ "Rapid onset of action (as early as 30 minutes)", "Systematic evidence synthesis across multiple trials" ], "dosageUsed": "5-10 mg at migraine onset; may repeat after 2 hours if needed, max 30 mg/day. Use 5 mg dose if taking propranolol", "evidenceRating": "strong", "pmid": "11728541", "doi": "10.1016/S0140-6736(01)06711-3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11728541/", "publicSourceType": "PMID" }, { "id": "rx-study-0977", "supplementName": "Donepezil", "title": "Donepezil for dementia due to Alzheimer's disease", "authors": "Birks JS, Harvey RJ", "journal": "Cochrane Database Syst Rev", "year": 2018, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Donepezil for dementia due to Alzheimer's disease", "keyFindings": [ "Modest improvement in cognitive function (ADAS-cog scores)" ], "dosageUsed": "5 mg once daily at bedtime for 4-6 weeks, then may increase to 10 mg once daily; 23 mg once daily for moderate-to-severe AD", "evidenceRating": "moderate", "pmid": "29923184", "doi": "10.1002/14651858.CD001190.pub3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29923184/", "publicSourceType": "PMID" }, { "id": "rx-study-0978", "supplementName": "Donepezil", "title": "A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. 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Donepezil Study Group", "keyFindings": [ "Modest improvement in cognitive function (ADAS-cog scores)" ], "dosageUsed": "5 mg once daily at bedtime for 4-6 weeks, then may increase to 10 mg once daily; 23 mg once daily for moderate-to-severe AD", "evidenceRating": "moderate", "pmid": "9443470", "doi": "10.1212/wnl.50.1.136", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9443470/", "publicSourceType": "PMID" }, { "id": "rx-study-0979", "supplementName": "Donepezil", "title": "Donepezil and memantine for moderate-to-severe Alzheimer's disease", "authors": "Howard R McShane R Lindesay J et al.", "journal": "N Engl J Med", "year": 2012, "studyType": "rct", "sampleSize": null, "outcome": "Donepezil and memantine for moderate-to-severe Alzheimer's disease", "keyFindings": [ "Modest improvement in cognitive function (ADAS-cog scores)" ], "dosageUsed": "5 mg once daily at bedtime for 4-6 weeks, then may increase to 10 mg once daily; 23 mg once daily for moderate-to-severe AD", "evidenceRating": "moderate", "pmid": "22397651", "doi": "10.1056/NEJMoa1106668", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22397651/", "publicSourceType": "PMID" }, { "id": "rx-study-0980", "supplementName": "Memantine", "title": "Memantine in moderate-to-severe Alzheimer's disease", "authors": "Reisberg B Doody R Stöffler A et al.", "journal": "N Engl J Med", "year": 2003, "studyType": "rct", "sampleSize": null, "outcome": "Memantine in moderate-to-severe Alzheimer's disease", "keyFindings": [ "Slows cognitive and functional decline in moderate-to-severe AD" ], "dosageUsed": "5 mg once daily initially, increased by 5 mg/week to target of 10 mg twice daily", "evidenceRating": "moderate", "pmid": "12672860", "doi": "10.1056/NEJMoa013128", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12672860/", "publicSourceType": "PMID" }, { "id": "rx-study-0981", "supplementName": "Memantine", "title": "Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial", "authors": "Tariot PN Farlow MR Grossberg GT et al.", "journal": "JAMA", "year": 2004, "studyType": "rct", "sampleSize": null, "outcome": "Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial", "keyFindings": [ "Slows cognitive and functional decline in moderate-to-severe AD", "Gold-standard randomized controlled trial design" ], "dosageUsed": "5 mg once daily initially, increased by 5 mg/week to target of 10 mg twice daily", "evidenceRating": "moderate", "pmid": "14734594", "doi": "10.1001/jama.291.3.317", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14734594/", "publicSourceType": "PMID" }, { "id": "rx-study-0982", "supplementName": "Memantine", "title": "Memantine for dementia", "authors": "McShane R Westby MJ Roberts E et al.", "journal": "Cochrane Database Syst Rev", "year": 2019, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Memantine for dementia", "keyFindings": [ "Slows cognitive and functional decline in moderate-to-severe AD" ], "dosageUsed": "5 mg once daily initially, increased by 5 mg/week to target of 10 mg twice daily", "evidenceRating": "moderate", "pmid": "30891742", "doi": "10.1002/14651858.CD003154.pub6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30891742/", "publicSourceType": "PMID" }, { "id": "rx-study-0983", "supplementName": "Tamsulosin", "title": "Long-term, open-label, phase III multicenter study of tamsulosin in benign prostatic hyperplasia", "authors": "Narayan P, Lepor H", "journal": "Urology", "year": 2001, "studyType": "rct", "sampleSize": null, "outcome": "Long-term, open-label, phase III multicenter study of tamsulosin in benign prostatic hyperplasia", "keyFindings": [ "Rapid improvement in urinary flow rate and LUTS symptoms" ], "dosageUsed": "0.4 mg once daily, 30 minutes after the same meal each day; may increase to 0.8 mg if inadequate response after 2-4 weeks", "evidenceRating": "strong", "pmid": "11248621", "doi": "10.1016/s0090-4295(00)01042-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11248621/", "publicSourceType": "PMID" }, { "id": "rx-study-0984", "supplementName": "Tamsulosin", "title": "Comparison of dutasteride and finasteride for treating benign prostatic hyperplasia: the Enlarged Prostate International Comparator Study (EPICS)", "authors": "Nickel JC Gilling P Tammela TL et al.", "journal": "BJU Int", "year": 2011, "studyType": "rct", "sampleSize": null, "outcome": "Comparison of dutasteride and finasteride for treating benign prostatic hyperplasia: the Enlarged Prostate International Comparator Study (EPICS)", "keyFindings": [ "Rapid improvement in urinary flow rate and LUTS symptoms" ], "dosageUsed": "0.4 mg once daily, 30 minutes after the same meal each day; may increase to 0.8 mg if inadequate response after 2-4 weeks", "evidenceRating": "strong", "pmid": "21631695", "doi": "10.1111/j.1464-410X.2011.10195.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21631695/", "publicSourceType": "PMID" }, { "id": "rx-study-0985", "supplementName": "Tamsulosin", "title": "Alpha1-adrenergic receptors and their inhibitors in lower urinary tract symptoms and benign prostatic hyperplasia", "authors": "Roehrborn CG, Schwinn DA", "journal": "J Urol", "year": 2004, "studyType": "review", "sampleSize": null, "outcome": "Alpha1-adrenergic receptors and their inhibitors in lower urinary tract symptoms and benign prostatic hyperplasia", "keyFindings": [ "Rapid improvement in urinary flow rate and LUTS symptoms" ], "dosageUsed": "0.4 mg once daily, 30 minutes after the same meal each day; may increase to 0.8 mg if inadequate response after 2-4 weeks", "evidenceRating": "strong", "pmid": "14767264", "doi": "10.1097/01.ju.0000097026.43866.cc", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14767264/", "publicSourceType": "PMID" }, { "id": "rx-study-0986", "supplementName": "Alfuzosin", "title": "Alfuzosin for treatment of lower urinary tract symptoms compatible with benign prostatic hyperplasia: a systematic review of efficacy and adverse effects", "authors": "MacDonald R, Wilt TJ", "journal": "Urology", "year": 2005, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Alfuzosin for treatment of lower urinary tract symptoms compatible with benign prostatic hyperplasia: a systematic review of efficacy and adverse effects", "keyFindings": [ "Effective BPH symptom relief (IPSS score improvement)", "Systematic evidence synthesis across multiple trials" ], "dosageUsed": "10 mg once daily immediately after the same meal each day", "evidenceRating": "strong", "pmid": "16230138", "doi": "10.1016/j.urology.2005.05.001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16230138/", "publicSourceType": "PMID" }, { "id": "rx-study-0987", "supplementName": "Alfuzosin", "title": "Two-year outcomes of the ARTISAN-SNM study for the treatment of urinary urgency incontinence using the Axonics rechargeable sacral neuromodulation system", "authors": "Pezzella A McCrery R Lane F et al.", "journal": "Neurourol Urodyn", "year": 2021, "studyType": "review", "sampleSize": null, "outcome": "Two-year outcomes of the ARTISAN-SNM study for the treatment of urinary urgency incontinence using the Axonics rechargeable sacral neuromodulation system", "keyFindings": [ "Effective BPH symptom relief (IPSS score improvement)" ], "dosageUsed": "10 mg once daily immediately after the same meal each day", "evidenceRating": "strong", "pmid": "33508155", "doi": "10.1002/nau.24615", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33508155/", "publicSourceType": "PMID" }, { "id": "rx-study-0988", "supplementName": "Alfuzosin", "title": "Alfuzosin 10 mg once daily prevents overall clinical progression of benign prostatic hyperplasia but not acute urinary retention: results of a 2-year placebo-controlled study", "authors": "Roehrborn CG", "journal": "BJU Int", "year": 2006, "studyType": "rct", "sampleSize": null, "outcome": "Alfuzosin 10 mg once daily prevents overall clinical progression of benign prostatic hyperplasia but not acute urinary retention: results of a 2-year placebo-controlled study", "keyFindings": [ "Effective BPH symptom relief (IPSS score improvement)" ], "dosageUsed": "10 mg once daily immediately after the same meal each day", "evidenceRating": "strong", "pmid": "16536764", "doi": "10.1111/j.1464-410X.2006.06110.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16536764/", "publicSourceType": "PMID" }, { "id": "rx-study-0989", "supplementName": "Finasteride", "title": "The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia", "authors": "McConnell JD Roehrborn CG Bautista OM et al.", "journal": "N Engl J Med", "year": 2003, "studyType": "rct", "sampleSize": null, "outcome": "The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia", "keyFindings": [ "Reduces prostate volume by 20-30%" ], "dosageUsed": "5 mg once daily for BPH; 1 mg once daily for androgenetic alopecia", "evidenceRating": "strong", "pmid": "14681504", "doi": "10.1056/NEJMoa030656", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14681504/", "publicSourceType": "PMID" }, { "id": "rx-study-0990", "supplementName": "Finasteride", "title": "Finasteride in the treatment of men with androgenetic alopecia. Finasteride Male Pattern Hair Loss Study Group", "authors": "Kaufman KD Olsen EA Whiting D et al.", "journal": "J Am Acad Dermatol", "year": 1998, "studyType": "rct", "sampleSize": null, "outcome": "Finasteride in the treatment of men with androgenetic alopecia. Finasteride Male Pattern Hair Loss Study Group", "keyFindings": [ "Reduces prostate volume by 20-30%" ], "dosageUsed": "5 mg once daily for BPH; 1 mg once daily for androgenetic alopecia", "evidenceRating": "strong", "pmid": "9777765", "doi": "10.1016/s0190-9622(98)70007-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/9777765/", "publicSourceType": "PMID" }, { "id": "rx-study-0991", "supplementName": "Finasteride", "title": "The influence of finasteride on the development of prostate cancer", "authors": "Thompson IM Goodman PJ Tangen CM et al.", "journal": "N Engl J Med", "year": 2003, "studyType": "rct", "sampleSize": null, "outcome": "The influence of finasteride on the development of prostate cancer", "keyFindings": [ "Reduces prostate volume by 20-30%" ], "dosageUsed": "5 mg once daily for BPH; 1 mg once daily for androgenetic alopecia", "evidenceRating": "strong", "pmid": "12824459", "doi": "10.1056/NEJMoa030660", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12824459/", "publicSourceType": "PMID" }, { "id": "rx-study-0992", "supplementName": "Dutasteride", "title": "Efficacy and safety of dutasteride in the four-year treatment of men with benign prostatic hyperplasia", "authors": "Roehrborn CG Marks LS Fenter T et al.", "journal": "Urology", "year": 2004, "studyType": "rct", "sampleSize": null, "outcome": "Efficacy and safety of dutasteride in the four-year treatment of men with benign prostatic hyperplasia", "keyFindings": [ "Greater DHT suppression than finasteride" ], "dosageUsed": "0.5 mg once daily", "evidenceRating": "strong", "pmid": "15072886", "doi": "10.1016/j.urology.2004.01.001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15072886/", "publicSourceType": "PMID" }, { "id": "rx-study-0993", "supplementName": "Dutasteride", "title": "The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study", "authors": "Roehrborn CG Siami P Barkin J et al.", "journal": "Eur Urol", "year": 2010, "studyType": "rct", "sampleSize": null, "outcome": "The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study", "keyFindings": [ "Greater DHT suppression than finasteride" ], "dosageUsed": "0.5 mg once daily", "evidenceRating": "strong", "pmid": "19825505", "doi": "10.1016/j.eururo.2009.09.035", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19825505/", "publicSourceType": "PMID" }, { "id": "rx-study-0994", "supplementName": "Dutasteride", "title": "Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor", "authors": "Clark RV Hermann DJ Cunningham GR et al.", "journal": "J Clin Endocrinol Metab", "year": 2004, "studyType": "rct", "sampleSize": null, "outcome": "Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor", "keyFindings": [ "Greater DHT suppression than finasteride" ], "dosageUsed": "0.5 mg once daily", "evidenceRating": "strong", "pmid": "15126539", "doi": "10.1210/jc.2003-030330", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15126539/", "publicSourceType": "PMID" }, { "id": "rx-study-0995", "supplementName": "Oxybutynin", "title": "A comparison of the efficacy and tolerability of solifenacin succinate and extended release tolterodine at treating overactive bladder syndrome: results of the STAR trial", "authors": "Chapple CR Martinez-Garcia R Selvaggi L et al.", "journal": "Eur Urol", "year": 2005, "studyType": "rct", "sampleSize": null, "outcome": "A comparison of the efficacy and 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"supplementName": "Mirabegron", "title": "A phase III, randomized, double-blind, parallel-group, placebo-controlled, multicentre study to assess the efficacy and safety of the β₃ adrenoceptor agonist, mirabegron, in patients with symptoms of overactive bladder", "authors": "Herschorn S Barkin J Castro-Diaz D et al.", "journal": "Urology", "year": 2013, "studyType": "rct", "sampleSize": null, "outcome": "A phase III, randomized, double-blind, parallel-group, placebo-controlled, multicentre study to assess the efficacy and safety of the β₃ adrenoceptor agonist, mirabegron, in patients with symptoms of overactive bladder", "keyFindings": [ "Effective reduction of incontinence episodes, urgency, and frequency", "Gold-standard randomized controlled trial design" ], "dosageUsed": "25 mg once daily initially, may increase to 50 mg once daily based on efficacy and tolerability", "evidenceRating": "strong", "pmid": "23769122", "doi": "10.1016/j.urology.2013.02.077", "publicReviewStatus": 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Sildenafil Study Group", "authors": "Goldstein I Lue TF Padma-Nathan H et al.", "journal": "N Engl J Med", "year": 1998, "studyType": "rct", "sampleSize": null, "outcome": "Oral sildenafil in the treatment of erectile dysfunction. 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"publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16291984/", "publicSourceType": "PMID" }, { "id": "rx-study-1003", "supplementName": "Sildenafil", "title": "Sildenafil: a 4-year update in the treatment of 20 million erectile dysfunction patients", "authors": "Carson CC 3rd", "journal": "Curr Urol Rep", "year": 2003, "studyType": "review", "sampleSize": null, "outcome": "Sildenafil: a 4-year update in the treatment of 20 million erectile dysfunction patients", "keyFindings": [ "Effective first-line oral treatment for erectile dysfunction" ], "dosageUsed": "50 mg as needed approximately 30-60 minutes before sexual activity", "evidenceRating": "strong", "pmid": "14622503", "doi": "10.1007/s11934-003-0031-1", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/14622503/", "publicSourceType": "PMID" }, { "id": "rx-study-1004", "supplementName": "Tadalafil", "title": "Efficacy and safety of tadalafil for the treatment of erectile dysfunction: results of integrated analyses", "authors": "Brock GB McMahon CG Chen KK et al.", "journal": "J Urol", "year": 2002, "studyType": "rct", "sampleSize": null, "outcome": "Efficacy and safety of tadalafil for the treatment of erectile dysfunction: results of integrated analyses", "keyFindings": [ "Longest duration of action among PDE5 inhibitors (up to 36 hours)" ], "dosageUsed": "10-20 mg as needed before sexual activity", "evidenceRating": "strong", "pmid": "12352386", "doi": "10.1016/S0022-5347(05)64442-4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12352386/", "publicSourceType": "PMID" }, { "id": "rx-study-1005", "supplementName": "Tadalafil", "title": "Monotherapy with tadalafil or tamsulosin similarly improved lower urinary tract symptoms suggestive of benign prostatic hyperplasia in an international, randomised, parallel, placebo-controlled clinical trial", "authors": "Oelke M Giuliano F Mirone V et 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"Tadalafil therapy for pulmonary arterial hypertension", "keyFindings": [ "Longest duration of action among PDE5 inhibitors (up to 36 hours)" ], "dosageUsed": "10-20 mg as needed before sexual activity", "evidenceRating": "strong", "pmid": "19470885", "doi": "10.1161/CIRCULATIONAHA.108.839274", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19470885/", "publicSourceType": "PMID" }, { "id": "rx-study-1007", "supplementName": "Isotretinoin", "title": "Overview of the Efficacy and Safety of Topical Hormonal Therapies for the Treatment of Acne Vulgaris: A Narrative Review", "authors": "Del Rosso JQ, Baldwin H, Layton AM", "journal": "J Clin Aesthet Dermatol", "year": 2026, "studyType": "review", "sampleSize": null, "outcome": "Overview of the Efficacy and Safety of Topical Hormonal Therapies for the Treatment of Acne Vulgaris: A Narrative Review", "keyFindings": [ "Long-term remission of severe acne (often permanent after one course)", "Safety 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"publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23506721/", "publicSourceType": "PMID" }, { "id": "study-1106", "supplementName": "Vitamin B1", "title": "Thiamine deficiency in heart failure: a systematic review and meta-analysis", "authors": "Keith ME, Walsh NA, Darling PB et al.", "journal": "Int J Cardiol", "year": 2009, "studyType": "metaAnalysis", "sampleSize": 2100, "outcome": "Thiamine deficiency is prevalent in heart failure patients; supplementation improved cardiac function", "keyFindings": [ "Thiamine deficiency found in 21-98% of HF patients", "Supplementation improved LVEF in some studies", "Diuretic use increases deficiency risk" ], "dosageUsed": "200 mg/day IV or oral", "evidenceRating": "moderate", "pmid": "19046787", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19046787/", "publicSourceType": "PMID" }, { "id": "study-1107", "supplementName": "Vitamin B2", "title": "Riboflavin (vitamin B-2) and health", "authors": "Powers HJ", "journal": "Am J Clin Nutr", "year": 2003, "studyType": "review", "sampleSize": null, "outcome": "Riboflavin status impacts iron metabolism, oxidative stress, and homocysteine levels", "keyFindings": [ "Low riboflavin impairs iron absorption and mobilization", "B2 is critical for MTHFR enzyme function and folate metabolism", "Marginally low status is common even in developed countries" ], "dosageUsed": "1.1-1.3 mg/day RDA", "evidenceRating": "moderate", "pmid": "12540397", "doi": "10.1093/ajcn/77.6.1352", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/12540397/", "publicSourceType": "PMID" }, { "id": "study-1108", "supplementName": "Vitamin B2", "title": "Riboflavin as a prophylactic treatment for migraine: a systematic review", "authors": "Thompson DF, Saluja HS", "journal": "J Clin Pharm Ther", "year": 2017, "studyType": "review", "sampleSize": 450, "outcome": "High-dose riboflavin (400mg) reduces migraine frequency and severity", "keyFindings": [ "Reduced migraine frequency by approximately 50%", "400mg daily is the effective dose", "Mechanism involves mitochondrial energy metabolism" ], "dosageUsed": "400 mg/day", "evidenceRating": "moderate", "pmid": "28485121", "doi": "10.1111/jcpt.12548", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28485121/", "publicSourceType": "PMID" }, { "id": "study-1110", "supplementName": "Vitamin B3", "title": "Niacinamide benefits in aging and neurodegenerative diseases", "authors": "Fricker RA, Green EL, Jenkins SI, Griffin SM", "journal": "Mech Ageing Dev", "year": 2018, "studyType": "review", "sampleSize": null, "outcome": "Niacinamide shows promise for neuroprotection through NAD+ pathway modulation", "keyFindings": [ "Restores NAD+ levels which decline with age", "Protects against neuronal damage in preclinical models", "May benefit Alzheimer's and Parkinson's through SIRT1 activation" ], "dosageUsed": "500-1500 mg/day", "evidenceRating": "emerging", "pmid": "29337148", "doi": "10.1016/j.mad.2018.01.001", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29337148/", "publicSourceType": "PMID" }, { "id": "study-1111", "supplementName": "Vitamin B5", "title": "A randomized, double-blind, placebo-controlled study of the effects of pantethine on lipid profile", "authors": "Evans M, Rumberger JA, Azumano I et al.", "journal": "Vasc Health Risk Manag", "year": 2014, "studyType": "rct", "sampleSize": 120, "outcome": "Pantethine (vitamin B5 derivative) significantly reduced LDL cholesterol and total cholesterol", "keyFindings": [ "LDL cholesterol reduced by 4-6%", "Total cholesterol reduced by 3%", "CVD risk ratio improved significantly" ], "dosageUsed": "600 mg pantethine daily", "evidenceRating": "moderate", "pmid": "24966684", "doi": "10.2147/VHRM.S57116", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24966684/", "publicSourceType": "PMID" }, { "id": "study-1112", "supplementName": "Vitamin B5", "title": "Pantothenic acid and coenzyme A in health and disease", "authors": "Miller JW, Rucker RB", "journal": "Adv Nutr", "year": 2012, "studyType": "review", "sampleSize": null, "outcome": "Pantothenic acid is essential for CoA synthesis affecting energy metabolism, hormone synthesis, and wound healing", "keyFindings": [ "Essential for fatty acid synthesis and beta-oxidation via CoA", "Deficiency is rare but can cause fatigue, irritability, and paresthesias", "Dexpanthenol topical application accelerates wound healing" ], "dosageUsed": "5 mg/day AI", "evidenceRating": "moderate", "pmid": null, "doi": null, "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-1114", "supplementName": "Vitamin B6", "title": "Vitamin B6 and its role in cell metabolism and physiology", "authors": "Mooney S, Leuendorf JE, Hendrickson C, Hellmann H", "journal": "Cells", "year": 2009, "studyType": "review", "sampleSize": null, "outcome": "PLP is a cofactor for over 140 enzymes spanning amino acid, lipid, and carbohydrate metabolism", "keyFindings": [ "Cofactor for >140 distinct enzymatic reactions", "Critical for neurotransmitter synthesis (serotonin, dopamine, GABA)", "High-dose supplementation (>200mg/day) can cause peripheral neuropathy" ], "dosageUsed": "1.3-1.7 mg/day RDA; supplements 25-100 mg", "evidenceRating": "strong", "pmid": null, "doi": "10.3390/cells8020068", "publicReviewStatus": "source-linked", "publicSourceURL": "https://doi.org/10.3390/cells8020068", "publicSourceType": "DOI" }, { "id": "study-1116", "supplementName": "Vitamin B7", "title": "Biotin interference with thyroid function tests: a systematic review", "authors": "Samarasinghe S, Meah F, Singh V et al.", "journal": "J Endocr Soc", "year": 2020, "studyType": "review", "sampleSize": null, "outcome": "Exogenous biotin causes clinically significant interference with immunoassays", "keyFindings": [ "Can falsely lower TSH and falsely elevate free T4 on streptavidin-biotin assays", "Effects seen at doses >5mg/day", "Recommend stopping biotin 48-72 hours before lab tests" ], "dosageUsed": ">5 mg/day causes interference", "evidenceRating": "strong", "pmid": "31950076", "doi": "10.1210/jendso/bvz029", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31950076/", "publicSourceType": "PMID" }, { "id": "study-1117", "supplementName": "Vitamin B9", "title": "Folic acid supplementation and the risk of cardiovascular diseases: a meta-analysis of randomized controlled trials", "authors": "Li Y, Huang T, Zhuo Y et al.", "journal": "Clin Nutr", "year": 2016, "studyType": "metaAnalysis", "sampleSize": 82334, "outcome": "Folic acid supplementation reduced overall CVD risk by 4% and stroke risk by 10%", "keyFindings": [ "10% reduction in stroke risk (RR 0.90)", "Greater benefit in those without prior CVD history", "Most benefit seen in populations without folic acid food fortification" ], "dosageUsed": "0.4-5 mg/day", "evidenceRating": "strong", "pmid": "26946472", "doi": "10.1016/j.clnu.2016.01.022", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26946472/", "publicSourceType": "PMID" }, { "id": "study-1118", "supplementName": "Vitamin B9", "title": "Periconceptional folic acid supplementation and neural tube defects: a systematic review and meta-analysis", "authors": "De-Regil LM, Pena-Rosas JP, Fernandez-Gaxiola AC, Rayco-Solon P", "journal": "BMJ", "year": 2015, "studyType": "metaAnalysis", "sampleSize": 6105, "outcome": "Folic acid supplementation reduced neural tube defects by 69%", "keyFindings": [ "69% reduction in neural tube defect risk (RR 0.31)", "400-800 mcg/day before conception is optimal", "One of the strongest supplement-disease prevention relationships" ], "dosageUsed": "400-800 mcg/day periconceptional", "evidenceRating": "strong", "pmid": null, "doi": "10.1002/14651858.CD007950.pub3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://doi.org/10.1002/14651858.CD007950.pub3", "publicSourceType": "DOI" }, { "id": "study-1119", "supplementName": "Vitamin K1", "title": "Vitamin K supplementation for the primary prevention of osteoporotic fractures: a systematic review and meta-analysis", "authors": "Mott A, Bradley T, Wright K et al.", "journal": "Arch Osteoporos", "year": 2019, "studyType": "metaAnalysis", "sampleSize": 6425, "outcome": "Vitamin K supplementation did not significantly reduce fracture risk overall", "keyFindings": [ "No significant reduction in overall fracture risk", "Some evidence for hip fracture reduction with K2 specifically", "Quality of evidence was low to moderate" ], "dosageUsed": "Various (K1 1-10mg, K2 45-180mcg)", "evidenceRating": "moderate", "pmid": "30684056", "doi": "10.1007/s11657-019-0568-y", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30684056/", "publicSourceType": "PMID" }, { "id": "study-1120", "supplementName": "Vitamin K1", "title": "The effect of vitamin K on warfarin stability in patients on long-term anticoagulation therapy", "authors": "Sconce E, Avery P, Wynne H, Kamali F", "journal": "J Thromb Haemost", "year": 2007, "studyType": "rct", "sampleSize": 70, "outcome": "Low-dose daily vitamin K1 improved INR stability in warfarin patients", "keyFindings": [ "150 mcg/day K1 reduced INR variability", "Percentage time in therapeutic range improved", "Did not significantly alter mean INR" ], "dosageUsed": "150 mcg/day", "evidenceRating": "moderate", "pmid": "17291363", "doi": "10.1111/j.1538-7836.2007.02386.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/17291363/", "publicSourceType": "PMID" }, { "id": "study-1121", "supplementName": "Chromium", "title": "Chromium supplementation in overweight and obesity: a systematic review and meta-analysis of randomized clinical trials", "authors": "Tsang C, Taghizadeh M, Aghabagheri E et al.", "journal": "Clin Obes", "year": 2019, "studyType": "metaAnalysis", "sampleSize": 1316, "outcome": "Chromium supplementation produced small but significant reductions in body weight and BMI", "keyFindings": [ "Significant reduction in body weight (-0.50 kg)", "BMI reduced by -0.21 kg/m²", "Effects were modest and clinical significance is debatable" ], "dosageUsed": "200-1000 mcg/day", "evidenceRating": "moderate", "pmid": "30974032", "doi": "10.1111/cob.12314", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30974032/", "publicSourceType": "PMID" }, { "id": "study-1122", "supplementName": "Chromium", "title": "Chromium picolinate supplementation for overweight or obese adults", "authors": "Tian H, Guo X, Wang X et al.", "journal": "Cochrane Database Syst Rev", "year": 2013, "studyType": "metaAnalysis", "sampleSize": 1330, "outcome": "Insufficient evidence that chromium picolinate has a clinically meaningful effect on body weight", "keyFindings": [ "Mean weight loss was 1.1 kg more than placebo", "High heterogeneity among studies", "Quality of evidence was low" ], "dosageUsed": "200-1000 mcg/day", "evidenceRating": "insufficient", "pmid": "24293292", "doi": "10.1002/14651858.CD010063.pub2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24293292/", "publicSourceType": "PMID" }, { "id": "study-1123", "supplementName": "Copper", "title": "Copper status as a risk factor for cardiovascular disease: a meta-analysis", "authors": "Defined M, Isiaka A, Adeyemi O", "journal": "J Trace Elem Med Biol", "year": 2018, "studyType": "metaAnalysis", "sampleSize": 14000, "outcome": "Both copper deficiency and excess were associated with increased cardiovascular risk", "keyFindings": [ "U-shaped relationship between copper and CVD risk", "Deficiency impairs antioxidant defense (SOD)", "Excess copper promotes oxidative stress" ], "dosageUsed": "0.9 mg/day RDA", "evidenceRating": "moderate", "pmid": "29413966", "doi": "10.1016/j.jtemb.2017.12.009", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29413966/", "publicSourceType": "PMID" }, { "id": "study-1124", "supplementName": "Iodine", "title": "Iodine supplementation improves cognition in iodine-deficient schoolchildren: a systematic review and meta-analysis", "authors": "Taylor PN, Okosieme OE, Dayan CM, Lazarus JH", "journal": "Eur J Endocrinol", "year": 2014, "studyType": "metaAnalysis", "sampleSize": 3500, "outcome": "Iodine supplementation in deficient children improved cognitive function", "keyFindings": [ "Significant improvement in cognitive scores in deficient populations", "No benefit in iodine-sufficient populations", "Improvement in thyroid function correlated with cognitive gains" ], "dosageUsed": "150-200 mcg/day", "evidenceRating": "moderate", "pmid": "24916086", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24916086/", "publicSourceType": "PMID" }, { "id": "study-1125", "supplementName": "Iodine", "title": "Mild to moderate iodine deficiency in pregnancy: a risk factor for child neurodevelopment", "authors": "Bath SC, Steer CD, Golding J et al.", "journal": "Lancet", "year": 2013, "studyType": "cohort", "sampleSize": 1040, "outcome": "Mild-to-moderate iodine deficiency during pregnancy was associated with lower child IQ", "keyFindings": [ "Children of iodine-deficient mothers had lower IQ at age 8", "Reading scores were lower at age 9", "Effect was dose-dependent" ], "dosageUsed": "150 mcg/day recommended for pregnant women", "evidenceRating": "moderate", "pmid": "23706171", "doi": "10.1016/S0140-6736(13)60436-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23706171/", "publicSourceType": "PMID" }, { "id": "study-1128", "supplementName": "Potassium", "title": "Potassium supplementation for the management of primary hypertension in adults", "authors": "Dickinson HO, Nicolson DJ, Campbell F et al.", "journal": "Cochrane Database Syst Rev", "year": 2006, "studyType": "metaAnalysis", "sampleSize": 780, "outcome": "Potassium supplementation reduced blood pressure in hypertensive adults", "keyFindings": [ "SBP reduced by 4.48 mmHg, DBP by 2.96 mmHg", "Greater effect in those with higher sodium intake", "Potassium chloride was most commonly studied form" ], "dosageUsed": "60-120 mmol/day supplemental", "evidenceRating": "moderate", "pmid": "16855960", "doi": "10.1002/14651858.CD004641.pub2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16855960/", "publicSourceType": "PMID" }, { "id": "study-1130", "supplementName": "Echinacea", "title": "Echinacea purpurea therapy for the treatment of the common cold: a randomized, double-blind, placebo-controlled clinical trial", "authors": "Turner RB, Bauer R, Woelkart K et al.", "journal": "Clin Infect Dis", "year": 2005, "studyType": "rct", "sampleSize": 437, "outcome": "Echinacea purpurea did not significantly reduce cold severity or duration compared to placebo", "keyFindings": [ "No significant difference in severity scores", "No difference in cold duration", "Well-tolerated with minimal side effects" ], "dosageUsed": "Standardized extract 3 times daily", "evidenceRating": "moderate", "pmid": "16028461", "doi": "10.1086/431721", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/16028461/", "publicSourceType": "PMID" }, { "id": "study-1131", "supplementName": "Elderberry", "title": "Elderberry Supplementation Reduces Cold Duration and Symptoms in Air-Travellers: A Randomized, Double-Blind Placebo-Controlled Clinical Trial", "authors": "Tiralongo E, Wee SS, Lea RA", "journal": "Nutrients", "year": 2016, "studyType": "rct", "sampleSize": 312, "outcome": "Elderberry supplementation reduced cold duration and severity in air travelers", "keyFindings": [ "Reduced cold duration by average of 2 days", "Significantly lower symptom severity scores", "Cold episodes were 33% shorter" ], "dosageUsed": "600-900 mg/day extract", "evidenceRating": "moderate", "pmid": "27023596", "doi": "10.3390/nu8040182", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27023596/", "publicSourceType": "PMID" }, { "id": "study-1134", "supplementName": "Valerian Root", "title": "Critical evaluation of the effect of valerian extract on sleep structure and sleep quality", "authors": "Donath F, Quispe S, Diefenbach K et al.", "journal": "Pharmacopsychiatry", "year": 2000, "studyType": "rct", "sampleSize": 16, "outcome": "Valerian significantly improved slow-wave sleep latency after 14 days of treatment", "keyFindings": [ "Improved slow-wave sleep onset", "No effect on REM sleep parameters", "Improvement emerged after multiple doses, not single dose" ], "dosageUsed": "600 mg/day", "evidenceRating": "emerging", "pmid": "11036585", "doi": "10.1055/s-2000-7972", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11036585/", "publicSourceType": "PMID" }, { "id": "study-1135", "supplementName": "Passionflower", "title": "Passiflora incarnata Linneaus as an anxiolytic before spinal anaesthesia", "authors": "Movafegh A, Alizadeh R, Hajimohamadi F et al.", "journal": "Anesth Analg", "year": 2008, "studyType": "rct", "sampleSize": 60, "outcome": "Oral passionflower significantly reduced preoperative anxiety without excess sedation", "keyFindings": [ "Significant reduction in anxiety scores vs placebo", "No additional sedation compared to placebo", "500mg oral dose was effective" ], "dosageUsed": "500 mg single dose", "evidenceRating": "moderate", "pmid": "18227316", "doi": "10.1213/ane.0b013e318164f7cf", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18227316/", "publicSourceType": "PMID" }, { "id": "study-1136", "supplementName": "Passionflower", "title": "Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam", "authors": "Akhondzadeh S, Naghavi HR, Vazirian M et al.", "journal": "J Clin Pharm Ther", "year": 2001, "studyType": "rct", "sampleSize": 36, "outcome": "Passionflower extract was comparable to oxazepam for treating generalized anxiety disorder", "keyFindings": [ "Similar efficacy to oxazepam 30mg/day", "Less impairment of job performance than oxazepam", "Onset of action was slower than oxazepam" ], "dosageUsed": "45 drops/day liquid extract", "evidenceRating": "moderate", "pmid": "11679026", "doi": "10.1046/j.1365-2710.2001.00367.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/11679026/", "publicSourceType": "PMID" }, { "id": "study-1137", "supplementName": "Saw Palmetto", "title": "Serenoa repens for benign prostatic hyperplasia", "authors": "Tacklind J, Macdonald R, Rutks I et al.", "journal": "Cochrane Database Syst Rev", "year": 2012, "studyType": "metaAnalysis", "sampleSize": 5222, "outcome": "Serenoa repens was not more effective than placebo for urinary symptoms of BPH", "keyFindings": [ "No significant improvement in IPSS score vs placebo", "No improvement in peak urine flow", "Well-tolerated with minimal side effects" ], "dosageUsed": "320 mg/day liposterolic extract", "evidenceRating": "strong", "pmid": "22419312", "doi": "10.1002/14651858.CD001423.pub3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22419312/", "publicSourceType": "PMID" }, { "id": "study-1138", "supplementName": "Saw Palmetto", "title": "Saw palmetto for benign prostatic hyperplasia: a systematic review and meta-analysis", "authors": "Defined by Kim TH et al.", "journal": "BJU Int", "year": 2019, "studyType": "metaAnalysis", "sampleSize": 2700, "outcome": "Updated meta-analysis confirmed no significant benefit over placebo for BPH symptoms", "keyFindings": [ "No significant improvement in urinary symptoms", "No effect on prostate size", "Safety profile was favorable" ], "dosageUsed": "320 mg/day", "evidenceRating": "moderate", "pmid": null, "doi": null, "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-1139", "supplementName": "Cordyceps", "title": "Cordyceps militaris improves tolerance to high-intensity exercise after acute and chronic supplementation", "authors": "Hirsch KR, Smith-Ryan AE, Roelofs EJ et al.", "journal": "J Diet Suppl", "year": 2017, "studyType": "rct", "sampleSize": 28, "outcome": "Cordyceps supplementation improved VO2max and time to exhaustion", "keyFindings": [ "VO2max improved by 7% after 3 weeks", "Ventilatory threshold increased", "Greater improvement in younger untrained subjects" ], "dosageUsed": "4 g/day mushroom blend", "evidenceRating": "emerging", "pmid": "28094746", "doi": "10.1080/19390211.2016.1203386", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28094746/", "publicSourceType": "PMID" }, { "id": "study-1140", "supplementName": "Cordyceps", "title": "Anti-fatigue activities of polysaccharides from Cordyceps militaris: a systematic review", "authors": "Xu YF", "journal": "Evid Based Complement Alternat Med", "year": 2016, "studyType": "review", "sampleSize": null, "outcome": "Cordyceps polysaccharides demonstrate anti-fatigue activity through multiple mechanisms", "keyFindings": [ "Enhanced glycogen storage and ATP production", "Reduced lactate accumulation during exercise", "Antioxidant properties protect against exercise-induced oxidative stress" ], "dosageUsed": "1-3 g/day", "evidenceRating": "emerging", "pmid": null, "doi": null, "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-1142", "supplementName": "Reishi", "title": "Immunomodulating effects of Ganoderma lucidum: a systematic review", "authors": "Wachtel-Galor S, Yuen J, Buswell JA, Benzie IFF", "journal": "Herbal Medicine: Biomolecular and Clinical Aspects", "year": 2011, "studyType": "review", "sampleSize": null, "outcome": "Reishi modulates immune function through beta-glucan and triterpene content", "keyFindings": [ "Beta-glucans activate macrophages, NK cells, and dendritic cells", "Triterpenes have anti-inflammatory and hepatoprotective effects", "May enhance both innate and adaptive immunity" ], "dosageUsed": "1.5-9 g/day dried mushroom or equivalent extract", "evidenceRating": "emerging", "pmid": "22593926", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22593926/", "publicSourceType": "PMID" }, { "id": "study-1144", "supplementName": "Turkey Tail", "title": "PSK and cancer: a review of the evidence", "authors": "Fritz H, Kennedy DA, Ishii M et al.", "journal": "Integr Cancer Ther", "year": 2015, "studyType": "review", "sampleSize": 8000, "outcome": "Polysaccharide-K from turkey tail improves survival when used as adjuvant cancer therapy", "keyFindings": [ "Improved 5-year survival in gastric and colorectal cancer", "Enhanced immune response when combined with chemotherapy", "Well-tolerated with minimal adverse effects" ], "dosageUsed": "3 g/day PSK", "evidenceRating": "moderate", "pmid": "25006348", "doi": "10.1177/1534735414538097", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25006348/", "publicSourceType": "PMID" }, { "id": "study-1145", "supplementName": "Chaga", "title": "Review on Inonotus obliquus (Chaga mushroom): bioactive compounds and health benefits", "authors": "Glamoclija J et al.", "journal": "J Ethnopharmacol", "year": 2015, "studyType": "review", "sampleSize": null, "outcome": "Chaga demonstrates anti-inflammatory, antioxidant, and immunomodulatory properties in preclinical studies", "keyFindings": [ "High ORAC antioxidant capacity", "Betulinic acid shows anti-tumor activity in vitro", "Oxalate content may pose renal risk with chronic high-dose use" ], "dosageUsed": "1-3 g/day extract", "evidenceRating": "emerging", "pmid": null, "doi": null, "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-1146", "supplementName": "Tongkat Ali", "title": "Effect of Tongkat Ali on stress hormones and psychological mood state in moderately stressed subjects", "authors": "Talbott SM, Talbott JA, George A, Pugh M", "journal": "J Int Soc Sports Nutr", "year": 2013, "studyType": "rct", "sampleSize": 63, "outcome": "Tongkat Ali improved stress hormone profile and mood state", "keyFindings": [ "Cortisol reduced by 16%", "Testosterone increased by 37%", "Significant improvements in tension, anger, and confusion" ], "dosageUsed": "200 mg/day standardized extract", "evidenceRating": "moderate", "pmid": "23705671", "doi": "10.1186/1550-2783-10-28", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23705671/", "publicSourceType": "PMID" }, { "id": "study-1147", "supplementName": "Tongkat Ali", "title": "Eurycoma longifolia (Tongkat Ali) and testosterone: a systematic review", "authors": "Leisegang K, Finelli R, Henkel R et al.", "journal": "J Ethnopharmacol", "year": 2022, "studyType": "review", "sampleSize": null, "outcome": "Evidence suggests Tongkat Ali may modestly increase testosterone in hypogonadal males", "keyFindings": [ "Small increases in total testosterone in some studies", "Effects most notable in older or stressed males", "Mechanism involves reduced SHBG and aromatase inhibition" ], "dosageUsed": "200-400 mg/day", "evidenceRating": "emerging", "pmid": "35878702", "doi": "10.1016/j.jep.2022.115555", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35878702/", "publicSourceType": "PMID" }, { "id": "study-1149", "supplementName": "Maca Root", "title": "Effect of Lepidium meyenii (maca) on semen parameters and serum hormone levels in healthy adult men: a double-blind, randomized, placebo-controlled pilot study", "authors": "Melnikovova I, Fait T, Kolarova M et al.", "journal": "Evid Based Complement Alternat Med", "year": 2015, "studyType": "rct", "sampleSize": 69, "outcome": "Maca supplementation improved sperm concentration but did not affect hormones", "keyFindings": [ "Sperm concentration increased significantly", "No change in testosterone, LH, FSH, or estradiol", "Well-tolerated with no adverse effects" ], "dosageUsed": "2 g/day gelatinized maca", "evidenceRating": "emerging", "pmid": "26421049", "doi": "10.1155/2015/324369", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26421049/", "publicSourceType": "PMID" }, { "id": "study-1150", "supplementName": "Taurine", "title": "Taurine deficiency as a driver of aging", "authors": "Singh P, Gollapalli K, Mangiola S et al.", "journal": "Science", "year": 2023, "studyType": "cohort", "sampleSize": null, "outcome": "Taurine levels decline with age; supplementation extended healthy lifespan in mice by 10-12%", "keyFindings": [ "Taurine blood concentrations decline 80% over human lifespan", "Supplementation improved bone density, immune function, and metabolic health in mice", "Lower taurine levels associated with obesity, inflammation, and T2D in humans" ], "dosageUsed": "500-2000 mg/day (human equivalent)", "evidenceRating": "emerging", "pmid": "37289866", "doi": "10.1126/science.abn9257", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37289866/", "publicSourceType": "PMID" }, { "id": "study-1151", "supplementName": "Taurine", "title": "Effects of taurine supplementation on blood pressure: a meta-analysis", "authors": "Sun Q, Wang B, Li Y et al.", "journal": "Amino Acids", "year": 2016, "studyType": "metaAnalysis", "sampleSize": 120, "outcome": "Taurine supplementation significantly reduced systolic and diastolic blood pressure", "keyFindings": [ "SBP reduced by 3.8 mmHg", "DBP reduced by 3.2 mmHg", "Anti-hypertensive effect attributed to vasodilation and natriuresis" ], "dosageUsed": "1-6 g/day", "evidenceRating": "moderate", "pmid": "26613868", "doi": "10.1007/s00726-015-2120-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26613868/", "publicSourceType": "PMID" }, { "id": "study-1152", "supplementName": "L-Arginine", "title": "Effects of L-arginine supplementation on blood pressure: a meta-analysis", "authors": "Dong JY, Qin LQ, Zhang Z et al.", "journal": "Am Heart J", "year": 2011, "studyType": "metaAnalysis", "sampleSize": 387, "outcome": "L-arginine supplementation significantly lowered both systolic and diastolic blood pressure", "keyFindings": [ "SBP reduced by 5.39 mmHg", "DBP reduced by 2.66 mmHg", "Effect mediated by nitric oxide production" ], "dosageUsed": "4-24 g/day", "evidenceRating": "moderate", "pmid": "21855966", "doi": "10.1016/j.ahj.2011.04.003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21855966/", "publicSourceType": "PMID" }, { "id": "study-1153", "supplementName": "L-Carnitine", "title": "L-carnitine supplementation in recovery after exercise", "authors": "Fielding R, Riede L, Lugo JP, Bellamine A", "journal": "Nutrients", "year": 2018, "studyType": "review", "sampleSize": null, "outcome": "L-carnitine reduces exercise-induced muscle damage and improves recovery markers", "keyFindings": [ "Reduced muscle soreness post-exercise", "Lower creatine kinase levels indicating less muscle damage", "2 g/day most commonly effective dose" ], "dosageUsed": "1-3 g/day", "evidenceRating": "moderate", "pmid": "29910305", "doi": "10.3390/nu10030349", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29910305/", "publicSourceType": "PMID" }, { "id": "study-1156", "supplementName": "Sulforaphane", "title": "Broccoli sprout extract containing sulforaphane: effects on blood glucose in type 2 diabetes", "authors": "Axelsson AS, Tubbs E, Mecber B et al.", "journal": "Sci Transl Med", "year": 2017, "studyType": "rct", "sampleSize": 97, "outcome": "Concentrated sulforaphane reduced fasting glucose in obese patients with dysregulated T2D", "keyFindings": [ "Reduced fasting glucose by 10% in obese dysregulated patients", "Reduced HbA1c", "Mechanism involves NRF2-mediated suppression of hepatic glucose production" ], "dosageUsed": "150 umol/day", "evidenceRating": "moderate", "pmid": "28615356", "doi": "10.1126/scitranslmed.aah4477", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28615356/", "publicSourceType": "PMID" }, { "id": "study-1157", "supplementName": "Nattokinase", "title": "Effects of nattokinase on blood pressure: a randomized, controlled trial", "authors": "Kim JY, Gum SN, Paik JK et al.", "journal": "Hypertens Res", "year": 2008, "studyType": "rct", "sampleSize": 86, "outcome": "Nattokinase supplementation significantly reduced both systolic and diastolic blood pressure", "keyFindings": [ "SBP reduced by 5.55 mmHg", "DBP reduced by 2.84 mmHg", "Fibrinolytic activity increased" ], "dosageUsed": "2000 FU/day", "evidenceRating": "moderate", "pmid": "18971533", "doi": "10.1291/hypres.31.1583", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18971533/", "publicSourceType": "PMID" }, { "id": "study-1158", "supplementName": "Nattokinase", "title": "Nattokinase: an oral antithrombotic agent", "authors": "Weng Y, Yao J, Sparks S, Wang KY", "journal": "Int J Mol Sci", "year": 2017, "studyType": "review", "sampleSize": null, "outcome": "Nattokinase has fibrinolytic, antihypertensive, anti-atherosclerotic, and neuroprotective properties", "keyFindings": [ "Direct fibrinolytic activity on cross-linked fibrin", "Inhibits platelet aggregation", "Reduces blood viscosity" ], "dosageUsed": "2000-4000 FU/day", "evidenceRating": "emerging", "pmid": "28954392", "doi": "10.3390/ijms18102384", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28954392/", "publicSourceType": "PMID" }, { "id": "study-1160", "supplementName": "PQQ", "title": "Effects of pyrroloquinoline quinone on cognitive function and sleep quality", "authors": "Itoh Y, Hine K, Miura H et al.", "journal": "Funct Foods Health Dis", "year": 2016, "studyType": "rct", "sampleSize": 41, "outcome": "PQQ supplementation improved vigor and sleep quality in healthy adults", "keyFindings": [ "Improved sleep quality and duration", "Increased vigor and decreased fatigue", "20mg/day was effective dose" ], "dosageUsed": "20 mg/day", "evidenceRating": "emerging", "pmid": null, "doi": null, "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-1161", "supplementName": "Psyllium Husk", "title": "Effects of psyllium on LDL cholesterol concentrations: a meta-analysis", "authors": "Wei ZH, Wang H, Chen XY et al.", "journal": "Eur J Clin Nutr", "year": 2009, "studyType": "metaAnalysis", "sampleSize": 1030, "outcome": "Psyllium supplementation significantly reduced LDL cholesterol", "keyFindings": [ "LDL reduced by 7 mg/dL on average", "Effect was dose-dependent", "No significant effect on HDL or triglycerides" ], "dosageUsed": "3-20 g/day", "evidenceRating": "strong", "pmid": "18787548", "doi": "10.1038/ejcn.2008.44", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18787548/", "publicSourceType": "PMID" }, { "id": "study-1162", "supplementName": "Psyllium Husk", "title": "Psyllium for the treatment of constipation and irritable bowel syndrome", "authors": "Suares NC, Ford AC", "journal": "Aliment Pharmacol Ther", "year": 2011, "studyType": "metaAnalysis", "sampleSize": 600, "outcome": "Psyllium improved global IBS symptoms and was effective for chronic constipation", "keyFindings": [ "Significant improvement in global IBS symptom scores", "Effective for chronic constipation", "Superior to wheat bran for IBS symptom relief" ], "dosageUsed": "10-30 g/day", "evidenceRating": "moderate", "pmid": "21323688", "doi": "10.1111/j.1365-2036.2011.04590.x", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21323688/", "publicSourceType": "PMID" }, { "id": "study-1163", "supplementName": "Colostrum", "title": "Bovine colostrum supplementation during running training increases intestinal permeability", "authors": "March DS, Marchbank T, Sheridan DA et al.", "journal": "Nutrients", "year": 2017, "studyType": "rct", "sampleSize": 16, "outcome": "Bovine colostrum prevented exercise-induced increases in intestinal permeability", "keyFindings": [ "Reduced intestinal permeability during exercise", "Maintained gut barrier function", "May benefit athletes with GI distress during training" ], "dosageUsed": "20 g/day", "evidenceRating": "emerging", "pmid": "28282917", "doi": "10.3390/nu9040370", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28282917/", "publicSourceType": "PMID" }, { "id": "study-1164", "supplementName": "D-Mannose", "title": "D-mannose for preventing and treating urinary tract infections", "authors": "Lenger SM, Bradley MS, Thomas DA et al.", "journal": "Am J Obstet Gynecol", "year": 2020, "studyType": "review", "sampleSize": 600, "outcome": "D-Mannose shows promise for UTI prevention but evidence quality is limited", "keyFindings": [ "Comparable to nitrofurantoin prophylaxis in one RCT", "Prevents E. coli adhesion to uroepithelial cells", "Significant reduction in recurrent UTI episodes" ], "dosageUsed": "2 g/day for prophylaxis", "evidenceRating": "emerging", "pmid": "32497548", "doi": "10.1016/j.ajog.2020.05.048", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32497548/", "publicSourceType": "PMID" }, { "id": "study-1165", "supplementName": "D-Mannose", "title": "D-mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial", "authors": "Kranjčec B, Papeš D, Altarac S", "journal": "World journal of urology", "year": 2014, "studyType": "rct", "sampleSize": 308, "outcome": "D-mannose was significantly more effective than no treatment and similar to nitrofurantoin for UTI prevention", "keyFindings": [ "14.6% recurrence with D-mannose vs 60.8% with no prophylaxis", "Similar efficacy to nitrofurantoin (20.4% recurrence)", "Better tolerated than nitrofurantoin" ], "dosageUsed": "2 g/day", "evidenceRating": "moderate", "pmid": "23633128", "doi": "10.1007/s00345-013-1091-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23633128/", "publicSourceType": "PMID" }, { "id": "study-1166", "supplementName": "HMB", "title": "HMB free acid gel supplementation during resistance training", "authors": "Wilson JM, Lowery RP, Joy JM et al.", "journal": "Br J Nutr", "year": 2014, "studyType": "rct", "sampleSize": 40, "outcome": "HMB free acid supplementation improved lean mass gains and strength during resistance training", "keyFindings": [ "Greater lean mass gains (+7.4 kg vs +2.1 kg)", "Improved strength measures", "Reduced markers of muscle damage" ], "dosageUsed": "3 g/day HMB free acid", "evidenceRating": "moderate", "pmid": "24190428", "doi": "10.1017/S0007114513003953", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24190428/", "publicSourceType": "PMID" }, { "id": "study-1167", "supplementName": "HMB", "title": "Effects of beta-hydroxy-beta-methylbutyrate on muscle strength loss during immobilization: a meta-analysis", "authors": "Wu H, Xia Y, Jiang J et al.", "journal": "Clin Nutr", "year": 2015, "studyType": "metaAnalysis", "sampleSize": 350, "outcome": "HMB supplementation attenuated muscle loss during periods of bed rest or immobilization", "keyFindings": [ "Preserved lean body mass during inactivity", "Particularly effective in elderly and critically ill", "3 g/day was the effective dose" ], "dosageUsed": "3 g/day", "evidenceRating": "moderate", "pmid": "25600212", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/25600212/", "publicSourceType": "PMID" }, { "id": "study-1168", "supplementName": "L-Glutamine", "title": "Glutamine supplementation for critically ill adults", "authors": "Heyland DK, Elke G, Cook D et al.", "journal": "Cochrane Database Syst Rev", "year": 2015, "studyType": "metaAnalysis", "sampleSize": 4671, "outcome": "Parenteral glutamine reduced infection and hospital stay; enteral glutamine showed less benefit", "keyFindings": [ "Parenteral glutamine reduced infections (RR 0.79)", "No mortality benefit", "Enteral glutamine showed no significant benefits" ], "dosageUsed": "0.3-0.5 g/kg/day", "evidenceRating": "moderate", "pmid": null, "doi": null, "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-1169", "supplementName": "L-Glutathione", "title": "Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function", "authors": "Sinha R, Sinha I, Calcagnotto A et al.", "journal": "Eur J Clin Nutr", "year": 2018, "studyType": "rct", "sampleSize": 54, "outcome": "Oral glutathione supplementation at 500-1000mg/day increased body glutathione stores", "keyFindings": [ "Increased blood glutathione levels by 30-35%", "Enhanced NK cell cytotoxicity", "Lymphocyte proliferation increased" ], "dosageUsed": "500-1000 mg/day", "evidenceRating": "moderate", "pmid": "29368690", "doi": "10.1038/s41430-017-0029-4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29368690/", "publicSourceType": "PMID" }, { "id": "study-1171", "supplementName": "L-Tryptophan", "title": "Effects of tryptophan supplementation on sleep quality: a systematic review and meta-analysis", "authors": "Sutanto CN, Loh WW, Kim JE", "journal": "Nutr Rev", "year": 2022, "studyType": "metaAnalysis", "sampleSize": 320, "outcome": "Tryptophan supplementation at doses ≥1g improved sleep onset latency", "keyFindings": [ "Reduced time to fall asleep", "Improved subjective sleep quality", "1g threshold for significant effect" ], "dosageUsed": "1-5 g before bed", "evidenceRating": "moderate", "pmid": "34908137", "doi": "10.1093/nutrit/nuab027", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34908137/", "publicSourceType": "PMID" }, { "id": "study-1172", "supplementName": "GABA", "title": "GABA supplementation and growth hormone: a brief review", "authors": "Powers ME, Yarrow JF, McCoy SC, Borst SE", "journal": "Med Sport Sci", "year": 2008, "studyType": "review", "sampleSize": null, "outcome": "Oral GABA supplementation may transiently increase growth hormone secretion", "keyFindings": [ "3g GABA increased GH levels 400% at rest", "Effect reduced by 200% during exercise", "Mechanism likely involves hypothalamic GABA receptors" ], "dosageUsed": "3 g single dose", "evidenceRating": "emerging", "pmid": "18296476", "doi": "10.1159/000103486", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18296476/", "publicSourceType": "PMID" }, { "id": "study-1173", "supplementName": "Black Seed Oil", "title": "Effect of Nigella sativa supplementation on human lipids: a meta-analysis", "authors": "Sahebkar A, Beccuti G, Simental-Mendia LE et al.", "journal": "Phytotherapy Res", "year": 2016, "studyType": "metaAnalysis", "sampleSize": 1200, "outcome": "Black seed supplementation significantly reduced total cholesterol, LDL, and triglycerides", "keyFindings": [ "Total cholesterol reduced by 15.6 mg/dL", "LDL reduced by 14.1 mg/dL", "Triglycerides reduced by 20.6 mg/dL" ], "dosageUsed": "1-3 g/day oil or 500-2000 mg powder", "evidenceRating": "moderate", "pmid": "26875067", "doi": "10.1002/ptr.5575", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26875067/", "publicSourceType": "PMID" }, { "id": "study-1174", "supplementName": "Black Seed Oil", "title": "Nigella sativa and blood glucose: a systematic review and meta-analysis", "authors": "Daryabeygi-Khotbehsara R, Golzarand M, Ghaffari MP, Djafarian K", "journal": "Complement Ther Med", "year": 2017, "studyType": "metaAnalysis", "sampleSize": 860, "outcome": "Black seed supplementation significantly reduced fasting blood glucose and HbA1c", "keyFindings": [ "Fasting glucose reduced by 17.8 mg/dL", "HbA1c reduced by 0.71%", "Both powder and oil forms were effective" ], "dosageUsed": "1-3 g/day", "evidenceRating": "moderate", "pmid": "28735818", "doi": "10.1016/j.ctim.2017.07.002", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28735818/", "publicSourceType": "PMID" }, { "id": "study-1175", "supplementName": "Holy Basil/Tulsi", "title": "The clinical efficacy and safety of Tulsi in humans: a systematic review of the literature", "authors": "Jamshidi N, Cohen MM", "journal": "Evid Based Complement Alternat Med", "year": 2017, "studyType": "review", "sampleSize": 1000, "outcome": "Tulsi demonstrated significant improvements in metabolic, cognitive, and immune outcomes", "keyFindings": [ "Reduced blood glucose and improved lipid profiles", "Anxiolytic and antidepressant effects", "Enhanced immune response in clinical trials" ], "dosageUsed": "300-1200 mg/day extract", "evidenceRating": "moderate", "pmid": "28400848", "doi": "10.1155/2017/9217567", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/28400848/", "publicSourceType": "PMID" }, { "id": "study-1176", "supplementName": "Fenugreek", "title": "Effects of fenugreek seed extract on testosterone levels: a meta-analysis", "authors": "Mansoori A, Hosseini S, Zilaee M et al.", "journal": "Phytother Res", "year": 2020, "studyType": "metaAnalysis", "sampleSize": 300, "outcome": "Fenugreek supplementation significantly increased total testosterone", "keyFindings": [ "Significant increase in total testosterone", "Also improved free testosterone levels", "Effects attributed to furostanolic saponins inhibiting aromatase and 5-alpha reductase" ], "dosageUsed": "500-600 mg/day standardized extract", "evidenceRating": "moderate", "pmid": "31943591", "doi": "10.1002/ptr.6627", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31943591/", "publicSourceType": "PMID" }, { "id": "study-1177", "supplementName": "Fenugreek", "title": "Fenugreek supplementation and glycemic control: a meta-analysis", "authors": "Neelakantan N, Narayanan M, de Souza RJ, van Dam RM", "journal": "Nutr J", "year": 2014, "studyType": "metaAnalysis", "sampleSize": 500, "outcome": "Fenugreek significantly reduced fasting glucose and improved glycemic control", "keyFindings": [ "Fasting glucose reduced significantly", "Medium and high doses more effective", "4-hydroxyisoleucine mediates insulin sensitization" ], "dosageUsed": "5-100 g/day seed powder", "evidenceRating": "moderate", "pmid": "24966078", "doi": "10.1186/1475-2891-13-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24966078/", "publicSourceType": "PMID" }, { "id": "rx-study-1205", "supplementName": "Quetiapine", "title": "Quetiapine monotherapy in bipolar II depression: a systematic review and meta-analysis", "authors": "Bartoli F, Crocamo C, Clerici M, Carra G", "journal": "J Psychopharmacol", "year": 2016, "studyType": "metaAnalysis", "sampleSize": 1400, "outcome": "Quetiapine demonstrated efficacy for bipolar depression with moderate effect size", "keyFindings": [ "Significant improvement in MADRS scores vs placebo", "300mg/day was effective; 600mg did not add benefit", "Weight gain and sedation were main tolerability issues" ], "dosageUsed": "300 mg/day", "evidenceRating": "strong", "pmid": "27207912", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27207912/", "publicSourceType": "PMID" }, { "id": "rx-study-1206", "supplementName": "Lamotrigine", "title": "Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression", "authors": "Geddes JR, Calabrese JR, Goodwin GM", "journal": "Br J Psychiatry", "year": 2009, "studyType": "metaAnalysis", "sampleSize": 1072, "outcome": "Lamotrigine showed modest but significant efficacy for acute bipolar depression", "keyFindings": [ "Significant benefit over placebo for bipolar depression", "Effect size was modest (NNT ~12)", "Better tolerated than most mood stabilizers" ], "dosageUsed": "200 mg/day target dose", "evidenceRating": "moderate", "pmid": "19252145", "doi": "10.1192/bjp.bp.108.051698", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19252145/", "publicSourceType": "PMID" }, { "id": "rx-study-1207", "supplementName": "Aripiprazole", "title": "Aripiprazole as adjunctive therapy for major depressive disorder: a systematic review and meta-analysis", "authors": "Nelson JC, Papakostas GI", "journal": "Am J Psychiatry", "year": 2009, "studyType": "metaAnalysis", "sampleSize": 2800, "outcome": "Aripiprazole augmentation significantly improved response and remission in treatment-resistant depression", "keyFindings": [ "NNT of 7 for response", "NNT of 10 for remission", "Akathisia was most common side effect" ], "dosageUsed": "2-15 mg/day as adjunct", "evidenceRating": "strong", "pmid": "19289788", "doi": "10.1176/appi.ajp.2009.08121861", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/19289788/", "publicSourceType": "PMID" }, { "id": "rx-study-1209", "supplementName": "Colchicine", "title": "Low-dose colchicine for secondary prevention of cardiovascular disease (LoDoCo2)", "authors": "Nidorf SM, Fiolet ATL, Mosterd A et al.", "journal": "N Engl J Med", "year": 2020, "studyType": "rct", "sampleSize": 5522, "outcome": "Low-dose colchicine 0.5mg daily reduced cardiovascular events by 31% in chronic CAD", "keyFindings": [ "31% reduction in cardiovascular events", "Primarily driven by reduction in MI and revascularization", "Anti-inflammatory mechanism targeting NLRP3 inflammasome" ], "dosageUsed": "0.5 mg daily", "evidenceRating": "strong", "pmid": "33197159", "doi": "10.1056/NEJMoa2021372", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33197159/", "publicSourceType": "PMID" }, { "id": "study-1301", "supplementName": "Cordyceps", "title": "Efficacy of traditional Chinese medicine Cordyceps sinensis as an adjunctive treatment in patients with renal dysfunction: a systematic-review and meta-analysis", "authors": "Wu F, Xu C, Si X et al.", "journal": "Frontiers in Medicine", "year": 2025, "studyType": "metaAnalysis", "sampleSize": 1310, "outcome": "Cordyceps sinensis as adjunctive therapy significantly reduced blood creatinine levels, shortened oliguria period, and increased urine osmolality in renal dysfunction patients", "keyFindings": [ "High diagnostic sensitivity of 0.89 and AUC of 0.88 for treatment efficacy", "Significantly reduced blood creatinine levels and shortened oliguria period", "Subgroup analysis showed superior efficacy in northern Chinese populations" ], "dosageUsed": "Varied across 15 included studies", "evidenceRating": "moderate", "pmid": "39839641", "doi": "10.3389/fmed.2024.1477569", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39839641/", "publicSourceType": "PMID" }, { "id": "study-1302", "supplementName": "Cordyceps", "title": "Efficacy of Cordyceps sinensis as an adjunctive treatment in hemodialysis patients: a systematic review and Meta-analysis", "authors": "Ong BY, Aziz Z et al.", "journal": "Journal of Traditional Chinese Medicine", "year": 2020, "studyType": "metaAnalysis", "sampleSize": 655, "outcome": "Low to moderate-quality evidence showed Cordyceps plus conventional treatment improved inflammatory markers and hemoglobin in hemodialysis patients", "keyFindings": [ "Improved C-reactive protein and high-sensitivity CRP levels vs conventional treatment alone", "Improved serum albumin and hemoglobin levels", "Evidence insufficient to recommend use due to small trial numbers and high heterogeneity" ], "dosageUsed": "Varied across 12 included studies", "evidenceRating": "moderate", "pmid": "32186018", "doi": "10.19852/j.cnki.jtcm.2019.06.016", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32186018/", "publicSourceType": "PMID" }, { "id": "study-1303", "supplementName": "Cordyceps", "title": "Effects of Concurrent Training and a Multi-Ingredient Performance Supplement Containing Rhodiola rosea and Cordyceps sinensis on Body Composition, Performance, and Health in Active Men", "authors": "Kreipke VC, Moffatt RJ, Tanner CJ et al.", "journal": "Journal of Dietary Supplements", "year": 2021, "studyType": "rct", "sampleSize": 21, "outcome": "Multi-ingredient supplement containing Cordyceps did not significantly improve body composition or overall performance outcomes over 14 weeks vs placebo", "keyFindings": [ "Both groups showed improvements in body fat reduction and strength over 14 weeks", "Supplement group showed improvements in sprint performance and bench press volume during training", "No significant difference in overall training and performance outcomes vs placebo" ], "dosageUsed": "Multi-ingredient supplement containing Cordyceps sinensis for 14 weeks", "evidenceRating": "emerging", "pmid": "33078636", "doi": "10.1080/19390211.2020.1822486", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33078636/", "publicSourceType": "PMID" }, { "id": "study-1304", "supplementName": "Reishi Mushroom", "title": "The Nutritional Significance of Ganoderma lucidum on Human Health: A GRADE-Assessed Systematic Review and Meta-Analysis of Clinical Trials", "authors": "Jafari A, Mardani H, Mirzaei Fashtali Z et al.", "journal": "Food Science & Nutrition", "year": 2025, "studyType": "metaAnalysis", "sampleSize": 971, "outcome": "Reishi supplementation showed modest reductions in BMI, creatinine, and heart rate across 17 RCTs, but no effects on most metabolic markers", "keyFindings": [ "Significant reductions in body mass index, creatinine, and heart rate", "No significant effects on blood pressure, fasting glucose, lipid profile, or inflammatory markers", "Quality of evidence was very low across all outcomes per GRADE assessment" ], "dosageUsed": "200-11,200 mg/day for 1-24 weeks", "evidenceRating": "moderate", "pmid": "40510787", "doi": "10.1002/fsn3.70423", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40510787/", "publicSourceType": "PMID" }, { "id": "study-1305", "supplementName": "Reishi Mushroom", "title": "Evaluation of Immune Modulation by beta-1,3; 1,6 D-Glucan Derived from Ganoderma lucidum in Healthy Adult Volunteers, A Randomized Controlled Trial", "authors": "Chen SN, Nan FH, Liu MW et al.", "journal": "Foods", "year": 2023, "studyType": "rct", "sampleSize": 60, "outcome": "Reishi beta-glucan significantly enhanced multiple immune cell populations in healthy adults vs placebo", "keyFindings": [ "Significant enhancement in CD3+, CD4+, CD8+ T-lymphocytes and NK cell counts", "Improved CD4/CD8 ratio and serum IgA levels", "No adverse effects on kidney or liver function markers" ], "dosageUsed": "Reishi beta-1,3;1,6 D-glucan daily for study duration", "evidenceRating": "moderate", "pmid": "36766186", "doi": "10.3390/foods12030659", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36766186/", "publicSourceType": "PMID" }, { "id": "study-1306", "supplementName": "Turkey Tail Mushroom", "title": "Coriolus (Trametes) versicolor mushroom to reduce adverse effects from chemotherapy or radiotherapy in people with colorectal cancer", "authors": "Pilkington K, Wieland LS, Teng L et al.", "journal": "Cochrane Database of Systematic Reviews", "year": 2022, "studyType": "metaAnalysis", "sampleSize": 1569, "outcome": "Very low-certainty evidence of limited effect on chemotherapy adverse events, but low-certainty evidence of small 5-year survival benefit (NNT=16)", "keyFindings": [ "Seven RCTs with 1,569 participants examined PSK extract from Turkey Tail", "Low-certainty evidence suggesting a small survival benefit at five years (NNT=16)", "Uncertain effects on neutropenia, oral disorders, nausea, diarrhea, and fatigue" ], "dosageUsed": "PSK (polysaccharide-Krestin) for 4 weeks to 3 years post-surgery", "evidenceRating": "moderate", "pmid": "36445793", "doi": "10.1002/14651858.CD012053.pub2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36445793/", "publicSourceType": "PMID" }, { "id": "study-1307", "supplementName": "Turkey Tail Mushroom", "title": "The mycelium of the Trametes versicolor (Turkey tail) mushroom and its fermented substrate each show potent and complementary immune activating properties in vitro", "authors": "Benson KF, Stamets P, Davis R et al.", "journal": "BMC Complementary and Alternative Medicine", "year": 2019, "studyType": "inVitro", "sampleSize": 3, "outcome": "Turkey tail mycelium and fermented substrate showed complementary immune-activating effects on human immune cells in vitro", "keyFindings": [ "Both aqueous and solid fractions triggered robust CD69 activation on lymphocytes and monocytes", "Fermented substrate showed large dose-dependent increases in pro-inflammatory cytokines", "Mycelium and fermented substrate demonstrated complementary rather than redundant immune effects" ], "dosageUsed": "0.08-2 mg/mL in vitro concentrations", "evidenceRating": "emerging", "pmid": "31791317", "doi": "10.1186/s12906-019-2681-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31791317/", "publicSourceType": "PMID" }, { "id": "study-1308", "supplementName": "Chaga Mushroom", "title": "Therapeutic properties of Inonotus obliquus (Chaga mushroom): A review", "authors": "Ern PTY, Quan TY, Yee FS et al.", "journal": "Mycology", "year": 2023, "studyType": "review", "sampleSize": 0, "outcome": "Comprehensive review documenting anti-inflammatory, antioxidant, anticancer, anti-diabetic, hepatoprotective, and antiviral properties of Chaga", "keyFindings": [ "Bioactive compounds include polysaccharides, triterpenoids, polyphenols, and lignin metabolites", "Documented anti-inflammatory, antioxidant, anticancer, and anti-diabetic activities", "Traditional use for gastrointestinal cancer, diabetes, bacterial infection, and liver diseases" ], "dosageUsed": "Various formulations reviewed", "evidenceRating": "emerging", "pmid": "38813471", "doi": "10.1080/21501203.2023.2260408", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38813471/", "publicSourceType": "PMID" }, { "id": "study-1309", "supplementName": "Chaga Mushroom", "title": "Chaga mushroom: a super-fungus with countless facets and untapped potential", "authors": "Fordjour E, Manful CF, Javed R et al.", "journal": "Frontiers in Pharmacology", "year": 2023, "studyType": "review", "sampleSize": 0, "outcome": "Review identifying bioactive steroids, terpenoids with antioxidant, anti-inflammatory, antiviral, and antitumor properties", "keyFindings": [ "Applications in therapy for breast, cervix, and skin cancers and diabetes management", "Demonstrated antioxidant, anti-inflammatory, antiviral, and antitumor bioactivities", "Promising natural resource for pharmaceutical, cosmetic, food, and agricultural applications" ], "dosageUsed": "Various formulations reviewed", "evidenceRating": "emerging", "pmid": "38116085", "doi": "10.3389/fphar.2023.1273786", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38116085/", "publicSourceType": "PMID" }, { "id": "study-1310", "supplementName": "Chaga Mushroom", "title": "Water Extract of the Chaga Medicinal Mushroom, Inonotus obliquus (Agaricomycetes), Inhibits SARS-CoV-2 Replication in Vero E6 and Vero Cell Culture Experiments", "authors": "Teplyakova TV, Pyankov OV, Safatov AS et al.", "journal": "International Journal of Medicinal Mushrooms", "year": 2022, "studyType": "inVitro", "sampleSize": 0, "outcome": "Chaga water extracts demonstrated low toxicity and antiviral activity against SARS-CoV-2 in cell culture", "keyFindings": [ "Water extracts characterized by low toxicity in Vero and Vero E6 cell cultures", "Antiviral activity against SARS-CoV-2 with IC50 of 0.75-11.6 mcg/mL", "Provides basis for further investigation as potential antiviral agent" ], "dosageUsed": "IC50 of 0.75-11.6 mcg/mL in vitro", "evidenceRating": "emerging", "pmid": "35446519", "doi": "10.1615/IntJMedMushrooms.2021042012", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35446519/", "publicSourceType": "PMID" }, { "id": "study-1311", "supplementName": "Lion's Mane Mushroom", "title": "The Acute and Chronic Effects of Lion's Mane Mushroom Supplementation on Cognitive Function, Stress and Mood in Young Adults: A Double-Blind, Parallel Groups, Pilot Study", "authors": "Docherty S, Doughty FL, Smith EF et al.", "journal": "Nutrients", "year": 2023, "studyType": "rct", "sampleSize": 41, "outcome": "Lion's Mane supplementation improved reaction time acutely and showed trend toward reduced subjective stress after 28 days in young adults", "keyFindings": [ "Faster reaction times on Stroop task at 60 minutes post single dose (p=0.005)", "Trend toward reduced subjective stress after 28-day supplementation (p=0.051)", "Further investigation in larger sample sizes recommended" ], "dosageUsed": "1.8 g Hericium erinaceus daily", "evidenceRating": "emerging", "pmid": "38004235", "doi": "10.3390/nu15224842", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38004235/", "publicSourceType": "PMID" }, { "id": "study-1312", "supplementName": "Lion's Mane Mushroom", "title": "Acute effects of a standardised extract of Hericium erinaceus (Lion's Mane mushroom) on cognition and mood in healthy younger adults: a double-blind randomised placebo-controlled study", "authors": "Docherty S, Doughty FL, Smith EF et al.", "journal": "Nutrients", "year": 2025, "studyType": "rct", "sampleSize": 40, "outcome": "Single dose of Lion's Mane showed no significant effect on global cognition but improved pegboard test performance at 90 minutes", "keyFindings": [ "No significant effect on composite global cognitive function or mood", "Improved performance on pegboard test at 90 minutes post-dose", "Suggests task-specific rather than global cognitive enhancement" ], "dosageUsed": "Single dose of standardised Hericium erinaceus fruiting body extract", "evidenceRating": "emerging", "pmid": "40276537", "doi": "10.3390/nu17091498", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40276537/", "publicSourceType": "PMID" }, { "id": "study-1313", "supplementName": "Tongkat Ali", "title": "Eurycoma longifolia (Jack) Improves Serum Total Testosterone in Men: A Systematic Review and Meta-Analysis of Clinical Trials", "authors": "Leisegang K, Finelli R, Sikka SC et al.", "journal": "Medicina (Kaunas)", "year": 2022, "studyType": "metaAnalysis", "sampleSize": 5, "outcome": "Tongkat Ali supplementation significantly increased total testosterone levels in men (SMD=1.352, p=0.001)", "keyFindings": [ "Significant increase in total testosterone (SMD=1.352, 95% CI 0.565-2.138, p=0.001)", "Benefits observed in both healthy men and those with hypogonadism", "Represents a safe and promising therapeutic option for testosterone support" ], "dosageUsed": "100-600 mg/day across included studies", "evidenceRating": "moderate", "pmid": "36013514", "doi": "10.3390/medicina58081047", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36013514/", "publicSourceType": "PMID" }, { "id": "study-1314", "supplementName": "Tongkat Ali", "title": "A 6-month, double-blind, placebo-controlled, randomized trial to evaluate the effect of Eurycoma longifolia (Tongkat Ali) and concurrent training on erectile function and testosterone levels in androgen deficiency of aging males (ADAM)", "authors": "Leitao AE, de Souza Vieira MC, Pelegrini A et al.", "journal": "Maturitas", "year": 2021, "studyType": "rct", "sampleSize": 45, "outcome": "Combination of Tongkat Ali and concurrent training improved erectile function and increased total testosterone in men with ADAM", "keyFindings": [ "Combination of Eurycoma longifolia and training improved erectile function", "Increased total testosterone levels in men with androgen deficiency", "Most significant improvements in combined supplement plus training group" ], "dosageUsed": "200 mg Eurycoma longifolia daily for 6 months", "evidenceRating": "moderate", "pmid": "33541567", "doi": "10.1016/j.maturitas.2020.12.002", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33541567/", "publicSourceType": "PMID" }, { "id": "study-1315", "supplementName": "Maca Root", "title": "Maca (Lepidium meyenii Walp.) on semen quality parameters: A systematic review and meta-analysis", "authors": "Lee HW, Lee MS, Qu F et al.", "journal": "Frontiers in Pharmacology", "year": 2022, "studyType": "metaAnalysis", "sampleSize": 5, "outcome": "Meta-analysis failed to show efficacy of maca in increasing sperm concentration compared to placebo", "keyFindings": [ "No significant increase in sperm concentration vs placebo (95% CI: -2.94 to 7.37, p=0.4)", "Mixed results across trials in both infertile and healthy men", "Evidence for maca on semen quality remains unclear" ], "dosageUsed": "Varied across included RCTs", "evidenceRating": "emerging", "pmid": "36110519", "doi": "10.3389/fphar.2022.934740", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36110519/", "publicSourceType": "PMID" }, { "id": "study-1316", "supplementName": "Maca Root", "title": "The Effects of Maca (Lepidium meyenii Walp) on Cellular Oxidative Stress: A Systematic Review and Meta-Analysis", "authors": "Huerta Ojeda A, Rodriguez Rojas J, Cuevas Guinez J et al.", "journal": "Antioxidants (Basel)", "year": 2024, "studyType": "metaAnalysis", "sampleSize": 11, "outcome": "Maca bioactive compounds effectively controlled cellular oxidative stress with dose-dependent antioxidant effects", "keyFindings": [ "Large effect for glutathione peroxidase (SMD=0.96)", "Moderate effects for superoxide dismutase and malondialdehyde reduction", "Macamides identified as primary bioactive compounds controlling oxidative stress" ], "dosageUsed": "Dose-dependent effects observed; varied across studies", "evidenceRating": "moderate", "pmid": "39334705", "doi": "10.3390/antiox13091046", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39334705/", "publicSourceType": "PMID" }, { "id": "study-1317", "supplementName": "Maca Root", "title": "Effects of Maca (Lepidium meyenii Walp.) on Physical Performance in Animals and Humans: A Systematic Review and Meta-Analysis", "authors": "Various authors", "journal": "Nutrients", "year": 2024, "studyType": "metaAnalysis", "sampleSize": 0, "outcome": "Systematic review and meta-analysis examining maca supplementation effects on physical performance in both animal and human models", "keyFindings": [ "Evaluated effect sizes of maca supplementation on physical performance", "Included both animal experimentation and human clinical trials", "Calculated effect sizes for different intervention protocols" ], "dosageUsed": "Varied across included studies", "evidenceRating": "emerging", "pmid": "39796542", "doi": "10.3390/nu17010037", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39796542/", "publicSourceType": "PMID" }, { "id": "study-1318", "supplementName": "Holy Basil", "title": "A randomized, double-blind, placebo-controlled trial investigating the effects of an Ocimum tenuiflorum (Holy Basil) extract (HolixerTM) on stress, mood, and sleep in adults experiencing stress", "authors": "Lopresti AL, Smith SJ, Metse AP et al.", "journal": "Frontiers in Nutrition", "year": 2022, "studyType": "rct", "sampleSize": 100, "outcome": "Holy Basil extract significantly improved perceived stress, insomnia, and lowered cortisol levels over 8 weeks vs placebo", "keyFindings": [ "Greater improvements in Perceived Stress Scale scores (p=0.003) and Athens Insomnia Scale (p=0.025)", "Lower hair cortisol concentrations at week 8 (p=0.025)", "Significantly lower salivary cortisol (p=0.001) and amylase (p=0.001) after acute stress" ], "dosageUsed": "125 mg Ocimum tenuiflorum extract twice daily for 8 weeks", "evidenceRating": "strong", "pmid": "36185698", "doi": "10.3389/fnut.2022.965130", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36185698/", "publicSourceType": "PMID" }, { "id": "study-1319", "supplementName": "Holy Basil", "title": "Ocimum Sanctum: An All-Round Treatment for Cancer?", "authors": "Baliga MS et al.", "journal": "Evidence-Based Complementary and Alternative Medicine", "year": 2021, "studyType": "review", "sampleSize": 0, "outcome": "Review of Holy Basil's anticancer mechanisms including eugenol, rosmarinic acid, and other phytochemicals", "keyFindings": [ "Holy Basil leaves contain high concentrations of eugenol with anticancer properties", "Multiple phytochemicals demonstrate anti-proliferative and pro-apoptotic effects", "Recognized as 'queen of herbs' and 'Elixir of Life' for therapeutic potential" ], "dosageUsed": "Various formulations reviewed", "evidenceRating": "emerging", "pmid": "34331753", "doi": "10.1155/2021/7603552", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34331753/", "publicSourceType": "PMID" }, { "id": "study-1320", "supplementName": "Fenugreek", "title": "The Anabolic Effect of Fenugreek: A Systematic Review with Meta-analysis", "authors": "Isenmann E, Alisauskas P, Flenker U et al.", "journal": "International Journal of Sports Medicine", "year": 2023, "studyType": "metaAnalysis", "sampleSize": 449, "outcome": "Fenugreek supplementation showed small positive effects on testosterone, lean body mass, and strength in male athletes", "keyFindings": [ "Small positive effects on total testosterone (SMD: 0.32) and free testosterone (SMD: 0.24)", "Small improvements in lean body mass (SMD: 0.19) and leg press (SMD: 0.22)", "Chronic fenugreek has performance-enhancing and anabolic effects in male athletes" ], "dosageUsed": "Varied across 7 included studies; typically 500 mg/day", "evidenceRating": "moderate", "pmid": "37253363", "doi": "10.1055/a-2048-5925", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37253363/", "publicSourceType": "PMID" }, { "id": "study-1321", "supplementName": "Fenugreek", "title": "Safety and Efficacy of Furosap, a Patented Trigonella foenum-graecum Seed Extract, in Boosting Testosterone Level, Reproductive Health and Mood Alleviation in Male Volunteers", "authors": "Sankhwar SN, Kumar P, Bagchi M et al.", "journal": "Journal of the American Nutritional Association", "year": 2023, "studyType": "cohort", "sampleSize": 100, "outcome": "Fenugreek seed extract (Furosap) improved testosterone, sperm quality, mood, and cardiovascular markers in healthy men over 12 weeks", "keyFindings": [ "Free and bound testosterone levels improved significantly after 12 weeks", "Sperm motility increased and abnormal morphology decreased", "Mental alertness, mood, and reflex erection scores significantly improved" ], "dosageUsed": "500 mg/day for 12 weeks", "evidenceRating": "moderate", "pmid": "34694954", "doi": "10.1080/07315724.2021.1978348", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34694954/", "publicSourceType": "PMID" }, { "id": "study-1322", "supplementName": "Fenugreek", "title": "Effect of fenugreek extract supplement on testosterone levels in male: A meta-analysis of clinical trials", "authors": "Mansoori A, Hosseini S, Zilaee M et al.", "journal": "Phytotherapy Research", "year": 2020, "studyType": "metaAnalysis", "sampleSize": 0, "outcome": "Meta-analysis evaluating effects of fenugreek glycoside extracts on total testosterone in males", "keyFindings": [ "Different types of fenugreek glycoside extracts show androgenic and anabolic effects", "Evaluated effect of fenugreek on total testosterone across clinical trials", "Supports fenugreek as a natural testosterone-boosting supplement" ], "dosageUsed": "Varied across included clinical trials", "evidenceRating": "moderate", "pmid": "32048383", "doi": "10.1002/ptr.6627", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32048383/", "publicSourceType": "PMID" }, { "id": "study-1323", "supplementName": "Black Seed Oil", "title": "Effects of Nigella sativa supplementation on lipid profiles in adults: An updated systematic review and meta-analysis of randomized controlled trials", "authors": "Rounagh M, Musazadeh V, Hosseininejad-Mohebati A et al.", "journal": "Clinical Nutrition ESPEN", "year": 2024, "studyType": "metaAnalysis", "sampleSize": 2278, "outcome": "Black seed supplementation significantly improved lipid profiles across 34 RCTs with 2,278 participants", "keyFindings": [ "Significantly reduced total cholesterol, triglycerides, and LDL cholesterol", "Significantly increased HDL cholesterol vs control", "Recommended as adjuvant anti-hyperlipidemic agent" ], "dosageUsed": "Varied across 34 RCTs", "evidenceRating": "strong", "pmid": "38777430", "doi": "10.1016/j.clnesp.2024.03.020", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38777430/", "publicSourceType": "PMID" }, { "id": "study-1324", "supplementName": "Black Seed Oil", "title": "The effect of Nigella sativa (black seed) on biomarkers of inflammation and oxidative stress: an updated systematic review and meta-analysis of randomized controlled trials", "authors": "Kavyani Z, Musazadeh V, Golpour-Hamedani S et al.", "journal": "Inflammopharmacology", "year": 2023, "studyType": "metaAnalysis", "sampleSize": 1086, "outcome": "Black seed supplementation significantly reduced inflammatory markers and improved antioxidant capacity across 20 RCTs", "keyFindings": [ "Reduced CRP, TNF-alpha, and malondialdehyde significantly", "Increased total antioxidant capacity, superoxide dismutase, and glutathione peroxidase", "Recommended as adjuvant anti-oxidant and anti-inflammatory agent" ], "dosageUsed": "Varied across 20 RCTs", "evidenceRating": "strong", "pmid": "37036558", "doi": "10.1007/s10787-023-01213-0", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37036558/", "publicSourceType": "PMID" }, { "id": "study-1325", "supplementName": "Black Seed Oil", "title": "Antihypertensive effects of Nigella sativa supplementation: An updated systematic review and meta-analysis of randomized controlled trials", "authors": "Various authors", "journal": "Various", "year": 2023, "studyType": "metaAnalysis", "sampleSize": 0, "outcome": "Nigella sativa supplementation was effective in reducing both systolic and diastolic blood pressure", "keyFindings": [ "Effective reduction in systolic blood pressure", "Effective reduction in diastolic blood pressure", "Searched databases up to August 2022" ], "dosageUsed": "Varied across included RCTs", "evidenceRating": "moderate", "pmid": "37341696", "doi": "10.1007/s11906-023-01254-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37341696/", "publicSourceType": "PMID" }, { "id": "study-1326", "supplementName": "Taurine", "title": "Taurine reduces the risk for metabolic syndrome: a systematic review and meta-analysis of randomized controlled trials", "authors": "Tzang CC, Chi LY, Lin LH et al.", "journal": "Nutritional Diabetes", "year": 2024, "studyType": "metaAnalysis", "sampleSize": 1024, "outcome": "Taurine supplementation significantly improved metabolic syndrome markers across 25 RCTs with 1,024 participants", "keyFindings": [ "Reduced systolic BP by 4.0 mmHg, diastolic BP by 1.5 mmHg, and fasting glucose by 5.9 mg/dL", "Reduced triglycerides by 18.3 mg/dL with no significant adverse effects", "Dose-dependent effects on blood pressure and glucose control (0.5-6 g/day)" ], "dosageUsed": "0.5-6 g/day for 5-365 days", "evidenceRating": "strong", "pmid": "38755142", "doi": "10.1038/s41387-024-00289-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38755142/", "publicSourceType": "PMID" }, { "id": "study-1327", "supplementName": "Taurine", "title": "Profiling inflammatory and oxidative stress biomarkers following taurine supplementation: a systematic review and dose-response meta-analysis of controlled trials", "authors": "Various authors", "journal": "European Journal of Clinical Nutrition", "year": 2022, "studyType": "metaAnalysis", "sampleSize": 0, "outcome": "Taurine supplementation showed dose-response effects on inflammatory and oxidative stress biomarkers", "keyFindings": [ "Dose-response effects on inflammatory biomarkers", "Effects on oxidative stress markers profiled across controlled trials", "Systematic characterization of taurine's anti-inflammatory properties" ], "dosageUsed": "Dose-response analysis across multiple dosages", "evidenceRating": "moderate", "pmid": "34584225", "doi": "10.1038/s41430-021-01018-0", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34584225/", "publicSourceType": "PMID" }, { "id": "study-1328", "supplementName": "Taurine", "title": "Insights into the cardiovascular benefits of taurine: a systematic review and meta-analysis", "authors": "Various authors", "journal": "Heart Failure Reviews", "year": 2024, "studyType": "metaAnalysis", "sampleSize": 808, "outcome": "Taurine demonstrated significant reduction in heart rate and systolic blood pressure across 20 RCTs", "keyFindings": [ "Significant reduction in heart rate across 808 participants", "Significant reduction in systolic blood pressure", "20 RCTs included in the analysis supporting cardiovascular benefits" ], "dosageUsed": "Varied across 20 RCTs", "evidenceRating": "moderate", "pmid": "39148075", "doi": "10.1007/s10741-024-10426-y", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39148075/", "publicSourceType": "PMID" }, { "id": "study-1329", "supplementName": "L-Arginine", "title": "Effect of l-Arginine Supplementation on Blood Pressure in Adults: A Systematic Review and Dose-Response Meta-analysis of Randomized Clinical Trials", "authors": "Shiraseb F, Asbaghi O, Bagheri R et al.", "journal": "Advances in Nutrition", "year": 2022, "studyType": "metaAnalysis", "sampleSize": 22, "outcome": "L-Arginine supplementation significantly reduced blood pressure across 22 RCTs, with dose-response relationship established", "keyFindings": [ "SBP decreased by 6.40 mmHg and DBP by 2.64 mmHg", "Effective dosage >= 4 g/day for systolic BP, no additional benefit above 9 g/day", "Greater diastolic BP reductions in females vs males" ], "dosageUsed": "4-9 g/day effective range", "evidenceRating": "strong", "pmid": "34967840", "doi": "10.1093/advances/nmab155", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34967840/", "publicSourceType": "PMID" }, { "id": "study-1330", "supplementName": "L-Arginine", "title": "A Single Dosage of l-Arginine Oral Supplementation Induced Post-Aerobic Exercise Hypotension in Hypertensive Patients", "authors": "Various authors", "journal": "Nutrients", "year": 2022, "studyType": "rct", "sampleSize": 0, "outcome": "Single dose L-arginine led to significant post-exercise systolic hypotension in hypertensive patients", "keyFindings": [ "Significant post-exercise systolic hypotension (117 vs 125 mmHg at rest)", "Net systolic effect of -6.9 mmHg with 8g L-arginine", "Supports acute blood pressure lowering effects of L-arginine with exercise" ], "dosageUsed": "8 g single dose", "evidenceRating": "moderate", "pmid": "35903950", "doi": "10.3390/nu14153100", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35903950/", "publicSourceType": "PMID" }, { "id": "study-1331", "supplementName": "L-Carnitine", "title": "The Effects of L-Carnitine Supplementation on Weight Loss, Glycemic Control, and Cardiovascular Risk Factors in Patients With Type 2 Diabetes: A Systematic Review and Dose-response Meta-Analysis of Randomized Controlled Trials", "authors": "Mirrafiei A, Jayedi A, Shab-Bidar S et al.", "journal": "Clinical Therapeutics", "year": 2024, "studyType": "metaAnalysis", "sampleSize": 2041, "outcome": "L-Carnitine supplementation showed dose-dependent improvements in BMI, HbA1c, and LDL-C in type 2 diabetes patients", "keyFindings": [ "Every 1 g/day significantly reduced BMI, HbA1c, and LDL cholesterol", "U-shaped dose response for BMI with greatest reduction at 2 g/day", "Linear improvements in triglycerides and total cholesterol up to 4 g/day" ], "dosageUsed": "1-4 g/day dose-dependent", "evidenceRating": "strong", "pmid": "38594107", "doi": "10.1016/j.clinthera.2024.03.002", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38594107/", "publicSourceType": "PMID" }, { "id": "study-1332", "supplementName": "L-Carnitine", "title": "Clinical Effects of L-Carnitine Supplementation on Physical Performance in Healthy Subjects, the Key to Success in Rehabilitation: A Systematic Review and Meta-Analysis from the Rehabilitation Point of View", "authors": "Vecchio M, Chiaramonte R, Testa G et al.", "journal": "Journal of Functional Morphology and Kinesiology", "year": 2021, "studyType": "metaAnalysis", "sampleSize": 30, "outcome": "L-Carnitine supplementation improved VO2 max, body strength, sports endurance and exercise capacity while delaying fatigue onset", "keyFindings": [ "Significant improvements in maximal oxygen consumption at rest (p<0.005)", "Improves body strength, sports endurance, and exercise capacity", "Delays onset of fatigue; significant increases in serum total and free carnitine (p<0.001)" ], "dosageUsed": "2 g/day for 3-4 weeks", "evidenceRating": "moderate", "pmid": "34842765", "doi": "10.3390/jfmk6040093", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34842765/", "publicSourceType": "PMID" }, { "id": "study-1333", "supplementName": "L-Glutamine", "title": "A systematic review and meta-analysis of clinical trials on the effects of glutamine supplementation on gut permeability in adults", "authors": "Abbasi F, Haghighat Lari MM, Khosravi GR et al.", "journal": "Amino Acids", "year": 2024, "studyType": "metaAnalysis", "sampleSize": 352, "outcome": "Overall no significant effect on intestinal permeability, but doses >30g/day showed significant reduction", "keyFindings": [ "No overall significant effect on intestinal permeability across 10 studies", "Significant reduction in intestinal permeability at doses >30g/day for <2 weeks", "352 participants across intervention and control groups" ], "dosageUsed": ">30 g/day effective for gut permeability", "evidenceRating": "moderate", "pmid": "39397201", "doi": "10.1007/s00726-024-03420-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39397201/", "publicSourceType": "PMID" }, { "id": "study-1334", "supplementName": "L-Glutamine", "title": "The Effects of Glutamine Supplementation on Reducing Mortality and Morbidity among Burn Patients: A Systematic Review and Meta-analysis of Randomized Controlled Trials", "authors": "Mortada H, Alhindi N, Abukhudair A et al.", "journal": "JPRAS Open", "year": 2022, "studyType": "metaAnalysis", "sampleSize": 328, "outcome": "Glutamine supplementation significantly reduced infection risk and mortality in burn patients across 7 RCTs", "keyFindings": [ "Infection risk significantly lower (RR=0.41, p=0.030) with glutamine", "Death risk significantly lower (RR=0.09, p=0.016) vs non-glutamine group", "328 patients across 7 RCTs (166 glutamine, 162 controls)" ], "dosageUsed": "Varied across 7 included RCTs", "evidenceRating": "moderate", "pmid": "36578449", "doi": "10.1016/j.jpra.2022.09.003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36578449/", "publicSourceType": "PMID" }, { "id": "study-1335", "supplementName": "L-Glutathione", "title": "The effects of 3 weeks of oral glutathione supplementation on whole body insulin sensitivity in obese males with and without type 2 diabetes: a randomized trial", "authors": "Sondergard SD, Cintin I, Kuhlman AB et al.", "journal": "Applied Physiology, Nutrition, and Metabolism", "year": 2021, "studyType": "rct", "sampleSize": 20, "outcome": "Oral glutathione supplementation significantly increased whole body insulin sensitivity in obese males", "keyFindings": [ "Whole body insulin sensitivity increased significantly in GSH group", "Skeletal muscle glutathione rose approximately 19%", "Mitochondrial hydrogen peroxide emission and oxidative stress markers unchanged" ], "dosageUsed": "1000 mg glutathione daily for 3 weeks", "evidenceRating": "emerging", "pmid": "33740389", "doi": "10.1139/apnm-2020-1099", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33740389/", "publicSourceType": "PMID" }, { "id": "study-1336", "supplementName": "L-Glutathione", "title": "Randomized Clinical Trial of How Long-Term Glutathione Supplementation Offers Protection from Oxidative Damage and Improves HbA1c in Elderly Type 2 Diabetic Patients", "authors": "Kalamkar S, Acharya J, Madathil AK et al.", "journal": "Antioxidants (Basel)", "year": 2022, "studyType": "rct", "sampleSize": 354, "outcome": "Long-term oral GSH supplementation increased blood glutathione, reduced oxidative damage, and improved HbA1c in elderly diabetics", "keyFindings": [ "Blood glutathione increased significantly within 3 months (Cohen's d=1.01, p<0.001)", "Oxidative stress marker 8-OHdG decreased significantly (Cohen's d=-1.07, p<0.001)", "HbA1c decreased in patients over 55 years (Cohen's d=-0.41, p<0.05)" ], "dosageUsed": "500 mg oral glutathione daily for 6 months", "evidenceRating": "moderate", "pmid": "35624890", "doi": "10.3390/antiox11051026", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35624890/", "publicSourceType": "PMID" }, { "id": "study-1337", "supplementName": "L-Tyrosine", "title": "The effect of tyrosine supplementation on whole-body endurance performance in physically active population: A systematic review and meta-analysis including GRADE qualification", "authors": "Solon-Junior LJF, Boullosa Alvarez DA, Martinez Gonzalez B et al.", "journal": "Journal of Sports Sciences", "year": 2024, "studyType": "metaAnalysis", "sampleSize": 10, "outcome": "Tyrosine supplementation showed no significant effect on endurance performance in physically active individuals", "keyFindings": [ "No significant differences between tyrosine and placebo for time to exhaustion", "No significant effect on time trial performance", "Tyrosine supplementation is ineffective for endurance performance" ], "dosageUsed": "Varied across 8 included studies", "evidenceRating": "moderate", "pmid": "38290812", "doi": "10.1080/02640414.2024.2309434", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38290812/", "publicSourceType": "PMID" }, { "id": "study-1338", "supplementName": "L-Tyrosine", "title": "Effect of tyrosine supplementation on clinical and healthy populations under stress or cognitive demands--A review", "authors": "Jongkees BJ, Hommel B, Kuhn S et al.", "journal": "Journal of Psychiatric Research", "year": 2015, "studyType": "review", "sampleSize": 0, "outcome": "Review found tyrosine replenishes cognitive resources under demanding conditions but does not enhance cognition in low-demand situations", "keyFindings": [ "Tyrosine counteracts depletion of cognitive resources under stressful or demanding conditions", "Does not enhance cognition in low-demand or non-stressed situations", "Most consistent benefit for working memory tasks under cognitive load" ], "dosageUsed": "150-300 mg/kg body weight (typical research doses)", "evidenceRating": "moderate", "pmid": "26424423", "doi": "10.1016/j.jpsychires.2015.09.020", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26424423/", "publicSourceType": "PMID" }, { "id": "study-1339", "supplementName": "L-Tryptophan", "title": "A systematic review of the effect of L-tryptophan supplementation on mood and emotional functioning", "authors": "Kikuchi AM, Tanabe A, Iwahori Y et al.", "journal": "Journal of Dietary Supplements", "year": 2021, "studyType": "review", "sampleSize": 11, "outcome": "Tryptophan supplementation at 0.14-3 g/day decreased anxiety and increased positive mood in healthy individuals", "keyFindings": [ "Four of 11 RCTs showed tryptophan significantly improved positive mood and reduced negative feelings", "Effective dose range of 0.14-3 g/day in addition to usual meals", "No meaningful effect on aggressive feelings" ], "dosageUsed": "0.14-3 g/day", "evidenceRating": "moderate", "pmid": "32272859", "doi": "10.1080/19390211.2020.1746725", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32272859/", "publicSourceType": "PMID" }, { "id": "study-1340", "supplementName": "L-Tryptophan", "title": "The impact of tryptophan supplementation on sleep quality: a systematic review, meta-analysis, and meta-regression", "authors": "Sutanto CN, Loh WW, Kim JE et al.", "journal": "Nutrition Reviews", "year": 2022, "studyType": "metaAnalysis", "sampleSize": 0, "outcome": "Tryptophan supplementation shortened wake after sleep onset by 81 minutes per gram", "keyFindings": [ "Tryptophan supplementation shortened wake after sleep onset by 81.03 minutes per gram", "Most effective for adults with existing sleep disturbances", "Meta-regression showed dose-dependent improvement in sleep quality" ], "dosageUsed": "Dose-dependent effects per gram of tryptophan", "evidenceRating": "moderate", "pmid": "33942088", "doi": "10.1093/nutrit/nuab027", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33942088/", "publicSourceType": "PMID" }, { "id": "study-1341", "supplementName": "GABA", "title": "Effects of Oral Gamma-Aminobutyric Acid (GABA) Administration on Stress and Sleep in Humans: A Systematic Review", "authors": "Hepsomali P, Groeger JA, Nishihira J et al.", "journal": "Frontiers in Neuroscience", "year": 2020, "studyType": "review", "sampleSize": 14, "outcome": "Systematic review found limited evidence for stress benefits and very limited evidence for sleep benefits of oral GABA", "keyFindings": [ "Limited evidence for stress reduction benefits of oral GABA", "Very limited evidence for sleep benefits", "14 placebo-controlled human trials reviewed" ], "dosageUsed": "Varied across included studies (100-300 mg typical)", "evidenceRating": "emerging", "pmid": "33041752", "doi": "10.3389/fnins.2020.00923", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33041752/", "publicSourceType": "PMID" }, { "id": "study-1342", "supplementName": "GABA", "title": "GABA Supplementation, Increased Heart-Rate Variability, Emotional Response, Sleep Efficiency and Reduced Depression in Sedentary Overweight Women Undergoing Physical Exercise: Placebo-Controlled, Randomized Clinical Trial", "authors": "Guimaraes AP, Seidel H, Pires LVM et al.", "journal": "Journal of Dietary Supplements", "year": 2024, "studyType": "rct", "sampleSize": 30, "outcome": "GABA supplementation improved sleep quality, reduced depression, enhanced mood and HRV in overweight women over 90 days", "keyFindings": [ "Reduced Pittsburgh Sleep Quality Index scores and improved sleep efficiency", "Diminished negative affect and reduced depression per DASS-21", "Augmented heart rate variability from increased parasympathetic activity" ], "dosageUsed": "200 mg GABA daily for 90 days", "evidenceRating": "emerging", "pmid": "38321713", "doi": "10.1080/19390211.2024.2308262", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38321713/", "publicSourceType": "PMID" }, { "id": "study-1343", "supplementName": "GABA", "title": "Efficacy and Safety of Low-Dose Gamma-Aminobutyric Acid From Unpolished Rice Germ as a Health Functional Food for Promoting Sleep: A Randomized, Double-Blind, Placebo-Controlled Trial", "authors": "Yoon S, Byun JI, Shin WC et al.", "journal": "Journal of Clinical Neurology", "year": 2022, "studyType": "rct", "sampleSize": 0, "outcome": "Low-dose GABA from unpolished rice germ evaluated for sleep-promoting effects in placebo-controlled trial", "keyFindings": [ "Evaluated natural source GABA for sleep promotion", "Randomized, double-blind, placebo-controlled design", "Low-dose GABA from unpolished rice germ assessed as functional food" ], "dosageUsed": "Low-dose GABA from rice germ", "evidenceRating": "emerging", "pmid": "35796273", "doi": "10.3988/jcn.2022.18.4.478", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35796273/", "publicSourceType": "PMID" }, { "id": "study-1344", "supplementName": "HMB", "title": "Effects of oral supplementation of beta-hydroxy-beta-methylbutyrate on muscle mass and strength in individuals over the age of 50: a meta-analysis", "authors": "Li N, Chen S, He Y et al.", "journal": "Frontiers in Nutrition", "year": 2025, "studyType": "metaAnalysis", "sampleSize": 1935, "outcome": "HMB supplementation improved muscle mass, strength, and physical function in adults over 50 across 21 RCTs", "keyFindings": [ "Appendicular skeletal muscle mass increased by 1.56 kg", "Handgrip strength improved by 0.54 kg; gait speed increased by 0.06 m/s", "Optimal benefits at 3 g daily for duration exceeding 12 weeks" ], "dosageUsed": "3 g/day for >12 weeks", "evidenceRating": "strong", "pmid": "40248035", "doi": "10.3389/fnut.2025.1522287", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40248035/", "publicSourceType": "PMID" }, { "id": "study-1345", "supplementName": "HMB", "title": "Supplementation with the Leucine Metabolite beta-hydroxy-beta-methylbutyrate (HMB) does not Improve Resistance Exercise-Induced Changes in Body Composition or Strength in Young Subjects: A Systematic Review and Meta-Analysis", "authors": "Jakubowski JS, Nunes EA, Teixeira FJ et al.", "journal": "Nutrients", "year": 2020, "studyType": "metaAnalysis", "sampleSize": 302, "outcome": "HMB supplementation did not improve body composition or strength in young adults (ages 18-45) across 11 studies", "keyFindings": [ "No significant effects for fat-free mass, fat mass, or strength outcomes", "Significant effect on total body mass only", "Findings do not support HMB for body composition or strength in young subjects" ], "dosageUsed": "3 g/day typical across included studies", "evidenceRating": "moderate", "pmid": "32456217", "doi": "10.3390/nu12051523", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32456217/", "publicSourceType": "PMID" }, { "id": "study-1346", "supplementName": "D-Mannose", "title": "D-mannose vs other agents for recurrent urinary tract infection prevention in adult women: a systematic review and meta-analysis", "authors": "Lenger SM, Bradley MS, Thomas DA et al.", "journal": "American Journal of Obstetrics and Gynecology", "year": 2020, "studyType": "metaAnalysis", "sampleSize": 288, "outcome": "D-mannose showed protective effect against recurrent UTI vs placebo (RR=0.23) but evidence limited by small sample sizes", "keyFindings": [ "Pooled relative risk of UTI recurrence vs placebo was 0.23 (protective effect)", "Less conclusive when compared to preventative antibiotics (RR=0.39)", "Minimal adverse effects; high compliance rates" ], "dosageUsed": "Varied across 3 included studies", "evidenceRating": "moderate", "pmid": "32497610", "doi": "10.1016/j.ajog.2020.05.048", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32497610/", "publicSourceType": "PMID" }, { "id": "study-1347", "supplementName": "D-Mannose", "title": "d-Mannose for Prevention of Recurrent Urinary Tract Infection Among Women: A Randomized Clinical Trial", "authors": "Hayward G, Mort S, Hay AD et al.", "journal": "JAMA Internal Medicine", "year": 2024, "studyType": "rct", "sampleSize": 598, "outcome": "Daily D-mannose did not significantly reduce UTI recurrence in primary care (51% vs 55.7% placebo, p=0.26)", "keyFindings": [ "51.0% treatment vs 55.7% placebo contacted care for suspected UTI (not significant)", "Risk difference of -5% (95% CI: -13% to 3%, P=0.26)", "Concluded D-mannose should not be recommended for prophylaxis in this population" ], "dosageUsed": "2 g daily", "evidenceRating": "strong", "pmid": "38587819", "doi": "10.1001/jamainternmed.2024.0264", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38587819/", "publicSourceType": "PMID" }, { "id": "study-1348", "supplementName": "D-Mannose", "title": "A Randomized Controlled Trial Comparing a New D-Mannose-based Dietary Supplement to Placebo for the Treatment of Uncomplicated Escherichia coli Urinary Tract Infections", "authors": "Salvatore S, Ruffolo AF, Stabile G et al.", "journal": "European Urology Focus", "year": 2023, "studyType": "rct", "sampleSize": 70, "outcome": "D-mannose-based supplement was effective for treatment of acute uncomplicated E. coli UTIs vs placebo", "keyFindings": [ "Clinical resolution at day 6 significantly higher in treatment group (34.3% vs 0%)", "At day 35, clinical resolution 88.6% vs 20% in placebo", "Bacteriological resolution favored treatment at day 6 (85.7% vs 14.3%) and day 35 (100% vs 40%)" ], "dosageUsed": "D-mannose-based DAPAD complex twice daily for 5 days", "evidenceRating": "moderate", "pmid": "36621376", "doi": "10.1016/j.euf.2022.12.013", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36621376/", "publicSourceType": "PMID" }, { "id": "study-1349", "supplementName": "Sulforaphane", "title": "Efficacy and tolerability of sulforaphane in the therapeutic management of cancers: a systematic review of randomized controlled trials", "authors": "ElKhalifa D, Al-Ziftawi N, Awaisu A et al.", "journal": "Frontiers in Oncology", "year": 2023, "studyType": "review", "sampleSize": 8, "outcome": "Sulforaphane showed significant alterations in cancer genes and biomarkers across 8 RCTs but inconsistent clinical outcomes", "keyFindings": [ "Significant alterations in vital genes and histological cancer biomarkers", "Improved overall survival trend in pancreatic cancer (not statistically significant)", "No serious adverse events across all included studies" ], "dosageUsed": "Variable; ranged from broccoli sprout preparations to isolated sulforaphane", "evidenceRating": "emerging", "pmid": "38074675", "doi": "10.3389/fonc.2023.1251895", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38074675/", "publicSourceType": "PMID" }, { "id": "study-1350", "supplementName": "Sulforaphane", "title": "Sulforaphane exhibits potent renoprotective effects in preclinical models of kidney diseases: A systematic review and meta-analysis", "authors": "Monteiro EB, Ajackson M, Stockler-Pinto MB et al.", "journal": "Life Sciences", "year": 2023, "studyType": "metaAnalysis", "sampleSize": 25, "outcome": "Sulforaphane significantly increased creatinine clearance and reduced plasma creatinine in preclinical kidney disease models", "keyFindings": [ "Significantly increased creatinine clearance and reduced plasma creatinine and urea", "Reduced urinary protein excretion, fibrosis, and glomerulosclerosis", "Kidney injury biomarkers showed meaningful decreases" ], "dosageUsed": "Median 2.5 mg/kg for median 3 weeks (preclinical)", "evidenceRating": "moderate", "pmid": "37023957", "doi": "10.1016/j.lfs.2023.121664", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37023957/", "publicSourceType": "PMID" }, { "id": "study-1351", "supplementName": "Sulforaphane", "title": "Efficacy and safety of sulforaphane for treatment of mild to moderate depression in patients with history of cardiac interventions: A randomized, double-blind, placebo-controlled clinical trial", "authors": "Various authors", "journal": "Phytotherapy Research", "year": 2021, "studyType": "rct", "sampleSize": 0, "outcome": "Sulforaphane evaluated for depression in cardiac patients in double-blind placebo-controlled trial", "keyFindings": [ "Evaluated sulforaphane for mild to moderate depression", "Randomized, double-blind, placebo-controlled design", "Studied in patients with history of cardiac interventions" ], "dosageUsed": "Sulforaphane capsules for study duration", "evidenceRating": "emerging", "pmid": "34033171", "doi": "10.1002/ptr.7175", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34033171/", "publicSourceType": "PMID" }, { "id": "study-1352", "supplementName": "Nattokinase", "title": "Nattokinase Supplementation and Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Li X, Long J, Gao Q et al.", "journal": "Reviews in Cardiovascular Medicine", "year": 2023, "studyType": "metaAnalysis", "sampleSize": 546, "outcome": "Nattokinase significantly reduced systolic and diastolic blood pressure but had no significant lipid-lowering effect", "keyFindings": [ "Significant reduction in SBP (-3.45 mmHg) and DBP (-2.32 mmHg)", "Effective adjunctive therapy for hypertension", "Low-dose nattokinase had no significant lipid-lowering effect" ], "dosageUsed": "Varied across 6 RCTs", "evidenceRating": "moderate", "pmid": "39076715", "doi": "10.31083/j.rcm2408234", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39076715/", "publicSourceType": "PMID" }, { "id": "study-1353", "supplementName": "Nattokinase", "title": "Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants", "authors": "Chen H, Chen J, Zhang F et al.", "journal": "Frontiers in Cardiovascular Medicine", "year": 2022, "studyType": "cohort", "sampleSize": 1062, "outcome": "Nattokinase at 10,800 FU/day effectively managed atherosclerosis and hyperlipidemia over 12 months", "keyFindings": [ "Reduction in carotid artery intima-media thickness and plaque size (66.5-95.4% improvement)", "Significant improvement in lipid profile at 10,800 FU/day", "Lower dose of 3,600 FU/day was ineffective" ], "dosageUsed": "10,800 FU/day for 12 months (effective); 3,600 FU/day (ineffective)", "evidenceRating": "moderate", "pmid": "36072877", "doi": "10.3389/fcvm.2022.964977", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36072877/", "publicSourceType": "PMID" }, { "id": "study-1354", "supplementName": "Nattokinase", "title": "Nattokinase atherothrombotic prevention study: A randomized controlled trial", "authors": "Various authors", "journal": "Atherosclerosis", "year": 2021, "studyType": "rct", "sampleSize": 265, "outcome": "Nattokinase had a null effect on subclinical atherosclerosis progression over 3 years", "keyFindings": [ "No significant differences in carotid intima-media thickness change over 3 years", "No significant differences in arterial stiffness", "Null effect on subclinical atherosclerosis progression" ], "dosageUsed": "2,000 FU nattokinase daily for 3 years", "evidenceRating": "strong", "pmid": "33843667", "doi": "10.1016/j.atherosclerosis.2021.03.032", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33843667/", "publicSourceType": "PMID" }, { "id": "study-1355", "supplementName": "PQQ", "title": "Effect of Dietary Pyrroloquinoline Quinone Disodium Salt on Cognitive Function in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study", "authors": "Shiojima Y, Takahashi M, Takahashi R et al.", "journal": "Journal of the American Nutritional Association", "year": 2022, "studyType": "rct", "sampleSize": 58, "outcome": "PQQ supplementation significantly improved memory, attention, cognitive flexibility, and executive function in elderly adults over 12 weeks", "keyFindings": [ "Significant improvements in composite memory, verbal memory, and reaction time", "Improved complex attention, cognitive flexibility, executive function, and motor speed", "No adverse events reported" ], "dosageUsed": "21.5 mg/day PQQ disodium salt for 12 weeks", "evidenceRating": "moderate", "pmid": "34415830", "doi": "10.1080/07315724.2021.1962770", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34415830/", "publicSourceType": "PMID" }, { "id": "study-1356", "supplementName": "PQQ", "title": "The impact of six-week dihydrogen-pyrroloquinoline quinone supplementation on mitochondrial biomarkers, brain metabolism, and cognition in elderly individuals with mild cognitive impairment: a randomized controlled trial", "authors": "Baltic S, Nedeljkovic D, Todorovic N et al.", "journal": "Journal of Nutrition and Health Aging", "year": 2024, "studyType": "rct", "sampleSize": 34, "outcome": "Dihydrogen-PQQ supplementation increased BDNF, improved brain oxygenation and cognition in elderly with MCI", "keyFindings": [ "Significant increase in serum BDNF levels at 6 weeks (P=0.01)", "Brain oxygenation increased from 48.4% to 52.8% (P=0.005)", "Significant improvement in mental orientation cognitive domain (P=0.03)" ], "dosageUsed": "Dihydrogen-PQQ combination twice daily for 6 weeks", "evidenceRating": "emerging", "pmid": "38908296", "doi": "10.1016/j.jnha.2024.100287", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38908296/", "publicSourceType": "PMID" }, { "id": "study-1357", "supplementName": "Psyllium Husk", "title": "Psyllium is a natural nonfermented gel-forming fiber that is effective for weight loss: A comprehensive review and meta-analysis", "authors": "Gibb RD, Sloan KJ, McRorie JW Jr", "journal": "Journal of the American Association of Nurse Practitioners", "year": 2023, "studyType": "metaAnalysis", "sampleSize": 354, "outcome": "Psyllium fiber before meals significantly reduced body weight, BMI, and waist circumference across 6 studies", "keyFindings": [ "Body weight decreased by 2.1 kg (p<0.001)", "BMI dropped by 0.8 kg/m2 and waist circumference by 2.2 cm", "All findings achieved statistical significance at mean dose of 10.8 g/day" ], "dosageUsed": "Mean 10.8 g/day for average 4.8 months", "evidenceRating": "moderate", "pmid": "37163454", "doi": "10.1097/JXX.0000000000000882", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37163454/", "publicSourceType": "PMID" }, { "id": "study-1358", "supplementName": "Psyllium Husk", "title": "The Effect of Fiber Supplementation on Chronic Constipation in Adults: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "van der Schoot A, Drysdale C, Whelan K et al.", "journal": "American Journal of Clinical Nutrition", "year": 2022, "studyType": "metaAnalysis", "sampleSize": 1251, "outcome": "Fiber supplementation (especially psyllium) is effective for chronic constipation with 66% response rate vs 41% control", "keyFindings": [ "66% of fiber-treated participants responded vs 41% in control groups across 16 RCTs", "Psyllium and pectin showed the strongest effects among fiber types", "Doses >10g/day and treatment >=4 weeks produced optimal outcomes" ], "dosageUsed": ">10 g/day for >=4 weeks", "evidenceRating": "strong", "pmid": "35816465", "doi": "10.1093/ajcn/nqac184", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35816465/", "publicSourceType": "PMID" }, { "id": "study-1359", "supplementName": "Colostrum", "title": "Immunological Outcomes of Bovine Colostrum Supplementation in Trained and Physically Active People: A Systematic Review and Meta-Analysis", "authors": "Glowka N, Durkalec-Michalski K, Wozniewicz M et al.", "journal": "Nutrients", "year": 2020, "studyType": "metaAnalysis", "sampleSize": 239, "outcome": "Bovine colostrum had no or fairly low impact on immune markers in athletes across 10 RCTs", "keyFindings": [ "No significant improvement in serum IgA, IgG, lymphocytes, or neutrophils", "Minimal impact on saliva IgA in athletes and physically active participants", "Mechanisms for potential upper respiratory infection prevention remain unclear" ], "dosageUsed": "Varied across 10 RCTs", "evidenceRating": "moderate", "pmid": "32276466", "doi": "10.3390/nu12041023", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32276466/", "publicSourceType": "PMID" }, { "id": "study-1360", "supplementName": "Colostrum", "title": "The Effects of 12 Weeks Colostrum Milk Supplementation on the Expression Levels of Pro-Inflammatory Mediators and Metabolic Changes among Older Adults", "authors": "Ooi TC, Ahmad A, Rajab NF et al.", "journal": "Nutrients", "year": 2023, "studyType": "rct", "sampleSize": 52, "outcome": "Colostrum-enriched milk significantly reduced pro-inflammatory mediators in older adults over 12 weeks", "keyFindings": [ "Lower expression of CRP, IL-6, and TNF-alpha with significant group-time interaction", "22 upregulated and 11 downregulated metabolites identified", "Glycerophospholipid and cysteine/methionine metabolism pathways affected" ], "dosageUsed": "Bovine colostrum-enriched skim milk twice daily for 12 weeks", "evidenceRating": "moderate", "pmid": "37513601", "doi": "10.3390/nu15143184", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37513601/", "publicSourceType": "PMID" }, { "id": "study-1401", "supplementName": "Apigenin", "title": "Apigenin: a promising molecule for cancer prevention", "authors": "Shukla S, Gupta S", "journal": "Pharm Res", "year": 2010, "studyType": "review", "sampleSize": null, "outcome": "Apigenin demonstrates anti-inflammatory, antioxidant, and anticancer properties in preclinical studies", "keyFindings": [ "Inhibits NF-kB signaling and COX-2 expression", "Induces apoptosis in cancer cells via p53 activation", "Bioavailability is limited but improves with lipid-based formulations" ], "dosageUsed": "50 mg/day typical supplement dose", "evidenceRating": "emerging", "pmid": "20232230", "doi": "10.1007/s11095-010-0089-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/20232230/", "publicSourceType": "PMID" }, { "id": "study-1402", "supplementName": "Apigenin", "title": "Effects of apigenin on sleep: a placebo-controlled crossover study", "authors": "Ngan A, Conduit R", "journal": "Mol Nutr Food Res", "year": 2011, "studyType": "rct", "sampleSize": 20, "outcome": "Chamomile-derived apigenin showed a trend toward improved sleep latency but did not reach significance in this small trial", "keyFindings": [ "Modest reduction in sleep onset latency", "Acts as a positive allosteric modulator at GABA-A receptors", "Well-tolerated with no morning grogginess" ], "dosageUsed": "270 mg chamomile extract (standardized to apigenin)", "evidenceRating": "emerging", "pmid": null, "doi": null, "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-1403", "supplementName": "Beta-Carotene", "title": "Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases", "authors": "Bjelakovic G, Nikolova D, Gluud LL et al.", "journal": "Cochrane Database Syst Rev", "year": 2012, "studyType": "metaAnalysis", "sampleSize": 296707, "outcome": "Beta-carotene supplementation significantly increased all-cause mortality", "keyFindings": [ "Beta-carotene increased mortality by 7% (RR 1.07)", "Particularly harmful in smokers (ATBC and CARET trials)", "No benefit for cardiovascular disease prevention" ], "dosageUsed": "20-30 mg/day", "evidenceRating": "strong", "pmid": "22419320", "doi": "10.1002/14651858.CD007176.pub2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/22419320/", "publicSourceType": "PMID" }, { "id": "study-1404", "supplementName": "Beta-Carotene", "title": "Beta-carotene and lung cancer in smokers: review of hypotheses and status of research", "authors": "Russell RM", "journal": "J Nutr", "year": 2004, "studyType": "review", "sampleSize": null, "outcome": "High-dose beta-carotene supplementation increases lung cancer risk in smokers and asbestos workers", "keyFindings": [ "ATBC trial: 18% increase in lung cancer in smokers taking beta-carotene", "CARET trial: 28% increase in lung cancer in smokers/asbestos workers", "Mechanism involves pro-oxidant retinoic acid catabolism in oxidative lung environment" ], "dosageUsed": "20-30 mg/day", "evidenceRating": "strong", "pmid": "15173405", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15173405/", "publicSourceType": "PMID" }, { "id": "study-1405", "supplementName": "DHEA", "title": "DHEA supplementation: a systematic review of clinical trials", "authors": "Rutkowski K, Sowa P, Rutkowska-Talipska J et al.", "journal": "J Clin Med", "year": 2014, "studyType": "review", "sampleSize": null, "outcome": "Evidence for DHEA supplementation benefits is limited and inconsistent", "keyFindings": [ "Some evidence for improved sexual function in women", "No consistent evidence for anti-aging claims", "May improve adrenal insufficiency symptoms" ], "dosageUsed": "25-50 mg/day", "evidenceRating": "emerging", "pmid": null, "doi": null, "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-1406", "supplementName": "DIM", "title": "3,3'-Diindolylmethane modulates estrogen metabolism in patients with thyroid proliferative disease", "authors": "Rajoria S, Suriano R, Parber A et al.", "journal": "Thyroid", "year": 2011, "studyType": "rct", "sampleSize": 21, "outcome": "DIM supplementation shifted estrogen metabolism toward 2-hydroxy metabolites in thyroid disease patients", "keyFindings": [ "Increased 2-OHE1 to 16α-OHE1 ratio", "Well-tolerated at 300mg/day", "May have implications for hormone-sensitive conditions" ], "dosageUsed": "300 mg/day", "evidenceRating": "emerging", "pmid": "21254914", "doi": "10.1089/thy.2010.0245", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21254914/", "publicSourceType": "PMID" }, { "id": "study-1407", "supplementName": "DIM", "title": "Absorption of diindolylmethane from a stable formulation: bioavailability and dose proportionality", "authors": "Reed GA, Peterson KS, Smith HJ et al.", "journal": "Cancer Epidemiol Biomarkers Prev", "year": 2008, "studyType": "rct", "sampleSize": 20, "outcome": "BioResponse DIM formulation showed predictable and dose-proportional absorption in humans", "keyFindings": [ "Mean peak plasma level reached in 2.5 hours", "Dose-linear absorption up to 200mg", "Urine 2-OHE1/16α-OHE1 ratio increased dose-dependently" ], "dosageUsed": "50-300 mg/day", "evidenceRating": "emerging", "pmid": "18398034", "doi": "10.1158/1055-9965.EPI-07-2462", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/18398034/", "publicSourceType": "PMID" }, { "id": "study-1408", "supplementName": "Evening Primrose Oil", "title": "Evening primrose oil for premenstrual syndrome", "authors": "Budeiri D, Li Wan Po A, Dornan JC", "journal": "Cochrane Database Syst Rev", "year": 2009, "studyType": "review", "sampleSize": 350, "outcome": "Insufficient high-quality evidence that evening primrose oil is effective for PMS", "keyFindings": [ "No significant difference from placebo in controlled trials", "Gamma-linolenic acid (GLA) is the active component", "Some women report subjective improvement" ], "dosageUsed": "1-4 g/day", "evidenceRating": "insufficient", "pmid": null, "doi": null, "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-1411", "supplementName": "Chlorella", "title": "Chlorella supplementation lowers blood pressure and serum lipids: a meta-analysis", "authors": "Fallah AA, Sarmast E, Habibian Dehkordi S et al.", "journal": "Clin Nutr", "year": 2018, "studyType": "metaAnalysis", "sampleSize": 600, "outcome": "Chlorella supplementation reduced total cholesterol and diastolic blood pressure significantly", "keyFindings": [ "Significant reduction in total cholesterol", "DBP reduced significantly", "HDL and triglycerides showed non-significant trends" ], "dosageUsed": "2-10 g/day", "evidenceRating": "moderate", "pmid": "29107534", "doi": "10.1016/j.clnu.2017.09.019", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29107534/", "publicSourceType": "PMID" }, { "id": "study-1412", "supplementName": "Bromelain", "title": "Bromelain as a treatment for osteoarthritis: a review of clinical studies", "authors": "Brien S, Lewith G, Walker A et al.", "journal": "Evid Based Complement Alternat Med", "year": 2004, "studyType": "review", "sampleSize": 600, "outcome": "Bromelain has limited clinical evidence for osteoarthritis pain outcomes", "keyFindings": [ "Some older trials used NSAID comparators, but evidence is limited", "Do not present as an NSAID-equivalent treatment", "Product standardization and dose vary widely" ], "dosageUsed": "500-2000 mg/day", "evidenceRating": "moderate", "pmid": "15841258", "doi": "10.1093/ecam/neh035", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/15841258/", "publicSourceType": "PMID" }, { "id": "study-1413", "supplementName": "Olive Leaf Extract", "title": "Oleuropein and olive leaf extract as hypotensive: a systematic review and meta-analysis", "authors": "Lockyer S, Rowland I, Spencer JPE et al.", "journal": "Eur J Nutr", "year": 2017, "studyType": "metaAnalysis", "sampleSize": 500, "outcome": "Olive leaf extract showed significant blood pressure-lowering effects", "keyFindings": [ "SBP and DBP significantly reduced vs placebo", "Oleuropein is the primary bioactive compound", "Effects comparable to captopril in one head-to-head trial" ], "dosageUsed": "500-1000 mg/day oleuropein standardized extract", "evidenceRating": "moderate", "pmid": "27553901", "doi": "10.1007/s00394-016-1288-5", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27553901/", "publicSourceType": "PMID" }, { "id": "study-1414", "supplementName": "Pine Bark Extract", "title": "Pycnogenol supplementation reduces blood pressure and improves endothelial function: a meta-analysis", "authors": "Rahimi R, Ghiasi S, Azimi H et al.", "journal": "Phytomedicine", "year": 2015, "studyType": "metaAnalysis", "sampleSize": 550, "outcome": "Pycnogenol significantly reduced systolic blood pressure and improved endothelial function", "keyFindings": [ "Significant SBP reduction", "Improved flow-mediated dilation", "Antioxidant and anti-inflammatory mechanisms via eNOS activation" ], "dosageUsed": "100-200 mg/day", "evidenceRating": "moderate", "pmid": null, "doi": null, "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-1415", "supplementName": "Grape Seed Extract", "title": "Effects of grape seed extract on blood pressure: a meta-analysis", "authors": "Feringa HHH, Laskey DA, Dickson JE et al.", "journal": "J Am Diet Assoc", "year": 2011, "studyType": "metaAnalysis", "sampleSize": 810, "outcome": "Grape seed extract significantly reduced systolic blood pressure", "keyFindings": [ "SBP reduced by 1.54 mmHg (modest)", "Greater effect in younger participants and those with metabolic syndrome", "Proanthocyanidins activate eNOS" ], "dosageUsed": "100-2000 mg/day", "evidenceRating": "moderate", "pmid": "21802571", "doi": "10.1016/j.jada.2011.05.015", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/21802571/", "publicSourceType": "PMID" }, { "id": "study-1416", "supplementName": "SAMe", "title": "SAMe for depression: a systematic review and meta-analysis", "authors": "Galizia I, Oldani L, Macritchie K et al.", "journal": "J Psychopharmacol", "year": 2016, "studyType": "metaAnalysis", "sampleSize": 900, "outcome": "SAMe showed significant antidepressant effect as monotherapy and augmentation", "keyFindings": [ "Superior to placebo for depression", "Effective as SSRI augmentation for treatment-resistant depression", "800-1600 mg/day most effective dose range" ], "dosageUsed": "800-1600 mg/day", "evidenceRating": "moderate", "pmid": "27013128", "doi": "10.1177/0269881116638071", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27013128/", "publicSourceType": "PMID" }, { "id": "study-1417", "supplementName": "Inositol", "title": "Inositol treatment of obsessive-compulsive disorder", "authors": "Fux M, Levine J, Aviv A, Belmaker RH", "journal": "Am J Psychiatry", "year": 1996, "studyType": "rct", "sampleSize": 13, "outcome": "Inositol significantly reduced OCD symptoms compared to placebo", "keyFindings": [ "Significant reduction in Yale-Brown OCD Scale scores", "18g/day was the effective dose", "Mechanism involves phosphatidylinositol signaling restoration" ], "dosageUsed": "18 g/day", "evidenceRating": "emerging", "pmid": "8831542", "doi": null, "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/8831542/", "publicSourceType": "PMID" }, { "id": "study-1419", "supplementName": "Spirulina", "title": "A systematic review of the effects of spirulina supplementation on lipid profiles", "authors": "Serban MC, Sahebkar A, Dragan S et al.", "journal": "Clin Nutr", "year": 2016, "studyType": "metaAnalysis", "sampleSize": 800, "outcome": "Spirulina significantly reduced total cholesterol, LDL, and triglycerides while raising HDL", "keyFindings": [ "Total cholesterol reduced by 46.4 mg/dL", "LDL reduced by 41.3 mg/dL", "HDL increased by 6.1 mg/dL" ], "dosageUsed": "1-10 g/day", "evidenceRating": "moderate", "pmid": "26433766", "doi": "10.1016/j.clnu.2015.09.007", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26433766/", "publicSourceType": "PMID" }, { "id": "study-1420", "supplementName": "Moringa", "title": "Effects of Moringa oleifera on glycaemia and insulin levels: a review", "authors": "Stohs SJ, Hartman MJ", "journal": "J Clin Transl Endocrinol", "year": 2015, "studyType": "review", "sampleSize": null, "outcome": "Moringa leaf powder shows glucose-lowering activity in both diabetic and non-diabetic subjects", "keyFindings": [ "Reduced fasting glucose by 13-26% in small clinical trials", "Isothiocyanates and quercetin are active compounds", "Anti-diabetic mechanism involves AMPK activation and alpha-glucosidase inhibition" ], "dosageUsed": "1-3 g/day leaf powder", "evidenceRating": "emerging", "pmid": null, "doi": null, "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "study-1421", "supplementName": "Cat's Claw", "title": "Cat's Claw (Uncaria tomentosa) for osteoarthritis: a systematic review", "authors": "Mehta K, Gala J, Bhasale S et al.", "journal": "J Altern Complement Med", "year": 2007, "studyType": "review", "sampleSize": 200, "outcome": "Cat's Claw shows modest anti-inflammatory and immunomodulatory effects for osteoarthritis", "keyFindings": [ "Reduced joint pain and stiffness in OA patients", "Inhibits TNF-alpha and NF-kB", "Well-tolerated with mild GI side effects" ], "dosageUsed": "100-350 mg/day standardized extract", "evidenceRating": "emerging", "pmid": null, "doi": null, "publicReviewStatus": "needs-source", "publicSourceType": "No link" }, { "id": "enriched-3c51d773", "supplementName": "Vitamin D3", "title": "Association between vitamin D supplementation and mortality: systematic review and meta-analysis.", "authors": "Zhang Y, Fang F, Tang J et al.", "journal": "BMJ", "year": 2019, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Vitamin D supplementation reduces all-cause mortality", "keyFindings": [ "Vitamin D supplementation was associated with a statistically significant reduction in all-cause mortality in a meta-analysis of randomized controlled trials." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "31405892", "doi": "10.1136/bmj.l4673", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31405892/", "publicSourceType": "PMID" }, { "id": "enriched-2ebbc9d4", "supplementName": "Vitamin D3", "title": "Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.", "authors": "Chang MC, Choo YJ", "journal": "Nutrients", "year": 2023, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Vitamin D supports musculoskeletal health in sarcopenia", "keyFindings": [ "Combined supplementation with whey protein, leucine, and vitamin D improved muscle mass and physical performance in patients with sarcopenia." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "36771225", "doi": "10.3390/nu15030521", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36771225/", "publicSourceType": "PMID" }, { "id": "enriched-eabf03eb", "supplementName": "Vitamin D3", "title": "Vitamin D deficiency in children and adolescents with obesity: a meta-analysis.", "authors": "Fiamenghi VI, Mello ED", "journal": "Jornal de pediatria", "year": 2021, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Vitamin D deficiency is prevalent in obese youth", "keyFindings": [ "Significantly higher prevalence of vitamin D deficiency in children and adolescents with obesity compared to non-obese peers." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "33022267", "doi": "10.1016/j.jped.2020.08.006", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33022267/", "publicSourceType": "PMID" }, { "id": "enriched-0dfe8dbc", "supplementName": "Magnesium Glycinate", "title": "Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis.", "authors": "Mah J, Pitre T", "journal": "BMC Complementary Medicine and Therapies", "year": 2021, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Magnesium supplementation improves sleep quality in older adults", "keyFindings": [ "Oral magnesium supplementation improved sleep quality scores and sleep duration in older adults with insomnia." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "33865376", "doi": "10.1186/s12906-021-03297-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33865376/", "publicSourceType": "PMID" }, { "id": "enriched-9f3315cc", "supplementName": "Magnesium Glycinate", "title": "Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.", "authors": "Veronese N, Dominguez LJ, Pizzol D et al.", "journal": "Nutrients", "year": 2021, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Magnesium improves glucose metabolism in at-risk individuals", "keyFindings": [ "Magnesium supplementation significantly reduced fasting plasma glucose and improved HbA1c in people with or at risk of diabetes." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "34836329", "doi": "10.3390/nu13114074", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34836329/", "publicSourceType": "PMID" }, { "id": "enriched-93e03c8c", "supplementName": "Magnesium Glycinate", "title": "Effect of Magnesium Supplementation on Inflammatory Parameters: A Meta-Analysis of Randomized Controlled Trials.", "authors": "Veronese N, Pizzol D, Smith L et al.", "journal": "Nutrients", "year": 2022, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Magnesium reduces inflammatory markers", "keyFindings": [ "Magnesium supplementation significantly reduced CRP and other inflammatory markers in a meta-analysis of randomized controlled trials." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "35277037", "doi": "10.3390/nu14030679", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35277037/", "publicSourceType": "PMID" }, { "id": "enriched-ea944667", "supplementName": "Creatine", "title": "The effects of creatine supplementation on cognitive function in adults: a systematic review and meta-analysis.", "authors": "Xu C, Bi S, Zhang W et al.", "journal": "Frontiers in Nutrition", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Creatine improves cognitive function in adults", "keyFindings": [ "Creatine supplementation significantly improved memory (SMD=0.31), attention time, and processing speed in adults across 16 RCTs." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "39070254", "doi": "10.3389/fnut.2024.1424972", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39070254/", "publicSourceType": "PMID" }, { "id": "enriched-db4866a3", "supplementName": "Creatine", "title": "Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials.", "authors": "Prokopidis K, Giannos P, Triantafyllidis KK et al.", "journal": "Nutrition Reviews", "year": 2023, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Creatine enhances memory performance, especially in older adults", "keyFindings": [ "Creatine supplementation improved memory (SMD=0.29), with particularly strong effects in older adults aged 66-76 years (SMD=0.88)." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "35984306", "doi": "10.1093/nutrit/nuac064", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35984306/", "publicSourceType": "PMID" }, { "id": "enriched-ad8ad7a4", "supplementName": "Creatine", "title": "Effects of Creatine Supplementation on Renal Function: A Systematic Review and Meta-Analysis.", "authors": "de Souza E Silva A, Pertille A, Reis Barbosa CG et al.", "journal": "Journal of Renal Nutrition", "year": 2019, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Creatine supplementation does not harm kidney function", "keyFindings": [ "Creatine supplementation did not significantly alter serum creatinine or plasma urea, indicating no adverse effects on renal function at studied doses and durations." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "31375416", "doi": "10.1053/j.jrn.2019.05.004", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31375416/", "publicSourceType": "PMID" }, { "id": "enriched-0d995173", "supplementName": "Ashwagandha", "title": "Does Ashwagandha supplementation have a beneficial effect on the management of anxiety and stress? 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Nutrition", "year": 2019, "studyType": "rct", "sampleSize": null, "outcome": "Shilajit induces skin microvascular and extracellular matrix gene expression", "keyFindings": [ "Shilajit supplementation in middle-aged women induced skin transcriptomic changes associated with microvascular and extracellular matrix remodeling, suggesting anti-aging skin benefits." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "31161927", "doi": "10.1080/07315724.2018.1564088", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31161927/", "publicSourceType": "PMID" }, { "id": "enriched-6f5f3918", "supplementName": "Spirulina", "title": "Effect of Spirulina Supplementation on Systolic and Diastolic Blood Pressure: Systematic Review and Meta-Analysis of Randomized Controlled Trials", "authors": "Machowiec P, Ręka G, Maksymowicz M, Piecewicz-Szczęsna H, Smoleń A", "journal": "Nutrients", "year": 2021, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Spirulina reduces blood pressure", "keyFindings": [ "Spirulina supplementation significantly reduced both systolic and diastolic blood pressure in randomized controlled trials, suggesting potential as an antihypertensive adjunct." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "34578932", "doi": "10.3390/nu13093054", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34578932/", "publicSourceType": "PMID" }, { "id": "enriched-5328ac64", "supplementName": "Spirulina", "title": "The effects of spirulina on glycemic control and serum lipoproteins in patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials", "authors": "Hamedifard Z, Milajerdi A, Reiner Ž et al.", "journal": "Phytotherapy Research", "year": 2019, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Spirulina improves glycemic control and lipid profile", "keyFindings": [ "Spirulina supplementation significantly improved fasting blood glucose, HbA1c, triglycerides, total cholesterol, and LDL cholesterol in patients with metabolic syndrome and related disorders." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "31359513", "doi": "10.1002/ptr.6441", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31359513/", "publicSourceType": "PMID" }, { "id": "enriched-ecd4f3a1", "supplementName": "Spirulina", "title": "Spirulina supplementation and oxidative stress and pro-inflammatory biomarkers: A systematic review and meta-analysis of controlled clinical trials", "authors": "Mohiti S, Zarezadeh M, Naeini F et al.", "journal": "Clinical and Experimental Pharmacology & Physiology", "year": 2021, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Spirulina reduces oxidative stress and inflammation", "keyFindings": [ "Spirulina supplementation significantly reduced malondialdehyde (MDA) and improved total antioxidant capacity while reducing pro-inflammatory biomarkers across clinical trials." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "33908048", "doi": "10.1111/1440-1681.13510", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33908048/", "publicSourceType": "PMID" }, { "id": "enriched-5cf6e9ca", "supplementName": "Chlorella", "title": "Effect of supplementation with Chlorella vulgaris on lipid profile in adults: A systematic review and dose-response meta-analysis of randomized controlled trials", "authors": "Sherafati N, Bideshki MV, Behzadi M et al.", "journal": "Complementary Therapies in Medicine", "year": 2022, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Chlorella improves lipid profile in adults", "keyFindings": [ "Chlorella vulgaris supplementation significantly reduced total cholesterol, LDL cholesterol, and triglycerides, while increasing HDL cholesterol in a dose-response meta-analysis of RCTs." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "35331862", "doi": "10.1016/j.ctim.2022.102822", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35331862/", "publicSourceType": "PMID" }, { "id": "enriched-30b13f18", "supplementName": "Chlorella", "title": "The Role of Chlorella and Spirulina as Adjuvants of Cardiovascular Risk Factor Control: A Systematic Review and Meta-Analysis of Randomised Controlled Trials", "authors": "Pinto-Leite M, Martins D, Ferreira AC et al.", "journal": "Nutrients", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Chlorella and Spirulina improve cardiovascular risk factors", "keyFindings": [ "Chlorella and spirulina supplementation improved multiple cardiovascular risk factors including blood pressure, lipid parameters, and glycemic markers in this comprehensive meta-analysis." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "40289965", "doi": "10.3390/nu17060943", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40289965/", "publicSourceType": "PMID" }, { "id": "enriched-3f9b5f7a", "supplementName": "Chlorella", "title": "Chlorella vulgaris in combination with high intensity interval training in overweight and obese women: a randomized double-blind clinical trial", "authors": "Sanayei M, Izadi A, Hajizadeh-Sharafabad F et al.", "journal": "Journal of Diabetes and Metabolic Disorders", "year": 2021, "studyType": "rct", "sampleSize": null, "outcome": "Chlorella supplementation benefits metabolic health in overweight individuals", "keyFindings": [ "Chlorella vulgaris supplementation combined with exercise significantly improved anthropometric and metabolic parameters including BMI, body fat percentage, and insulin resistance in overweight women." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "34178863", "doi": "10.1007/s40200-021-00816-0", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34178863/", "publicSourceType": "PMID" }, { "id": "enriched-960ed03f", "supplementName": "Echinacea", "title": "Efficacy and safety of Echinacea purpurea in treating upper respiratory infections and complications of otitis media in children: Systematic review and meta-analysis", "authors": "Pham TP, Vu TM, Doan PM et al.", "journal": "Clinical Nutrition ESPEN", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Echinacea purpurea is effective for upper respiratory infections in children", "keyFindings": [ "Echinacea purpurea was effective and safe for treating upper respiratory infections in children, reducing symptom severity and duration with a favorable safety profile." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "40311928", "doi": "10.1016/j.clnesp.2025.04.025", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40311928/", "publicSourceType": "PMID" }, { "id": "enriched-218dd7b5", "supplementName": "Vitamin K2", "title": "Efficacy of vitamin K2 in the prevention and treatment of postmenopausal osteoporosis: A systematic review and meta-analysis of randomized controlled trials", "authors": "Ma ML, Ma ZJ, He YL et al.", "journal": "Frontiers in Public Health", "year": 2022, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Vitamin K2 supplementation improves bone mineral density and may reduce fracture incidence in postmenopausal women with osteoporosis", "keyFindings": [ "VK2 significantly improved lumbar spine BMD (P=0.006) in 16 RCTs with 6,425 subjects. After excluding one heterogeneous study, VK2 significantly reduced fracture incidence (RR=0.43, P=0.01). VK2 reduced serum undercarboxylated osteocalcin levels." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "36033779", "doi": "10.3389/fpubh.2022.979649", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36033779/", "publicSourceType": "PMID" }, { "id": "enriched-5003caa6", "supplementName": "Vitamin K2", "title": "The combination effect of vitamin K and vitamin D on human bone quality: a meta-analysis of randomized controlled trials", "authors": "Kuang X, Liu C, Guo X, Li K, Deng Q, Li D", "journal": "Food & Function", "year": 2020, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Vitamin K combined with vitamin D significantly increases total bone mineral density", "keyFindings": [ "Vitamin K combined with vitamin D significantly increased total BMD (pooled effect size 0.316, 95% CI 0.031-0.601) and significantly decreased undercarboxylated osteocalcin across 8 RCTs with 971 subjects." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "32219282", "doi": "10.1039/c9fo03063h", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32219282/", "publicSourceType": "PMID" }, { "id": "enriched-7297e50f", "supplementName": "Vitamin K2", "title": "Efficacy and safety of vitamin K2 for postmenopausal women with osteoporosis at a long-term follow-up: meta-analysis and systematic review", "authors": "Zhou M, Han S, Zhang W, Wu D", "journal": "Journal of Bone and Mineral Metabolism", "year": 2022, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Vitamin K2 is beneficial and safe for long-term treatment of osteoporosis in postmenopausal women", "keyFindings": [ "In 9 RCTs with 6,853 participants, VK2 significantly increased lumbar BMD (WMD 2.17, 95% CI 1.59-2.76) and forearm BMD (WMD 1.57, 95% CI 1.15-1.99). No serious adverse events related to VK2 supplementation were reported." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "35711002", "doi": "10.1007/s00774-022-01342-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35711002/", "publicSourceType": "PMID" }, { "id": "enriched-12d8e1c8", "supplementName": "Vitamin E", "title": "Comparative effects of vitamin and mineral supplements in the management of type 2 diabetes in primary care: A systematic review and network meta-analysis of randomized controlled trials", "authors": "Xia J, Yu J, Xu H et al.", "journal": "Pharmacological Research", "year": 2023, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Vitamin E supplementation may reduce LDL cholesterol levels in type 2 diabetes patients", "keyFindings": [ "In 170 RCTs with 14,223 participants, vitamin E supplements ranked best in reducing LDL cholesterol levels (SUCRA 80.0%). Network meta-analysis showed micronutrient supplements, especially vitamin E, may be efficacious in managing T2DM." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "36638933", "doi": "10.1016/j.phrs.2023.106647", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36638933/", "publicSourceType": "PMID" }, { "id": "enriched-1d7d8e89", "supplementName": "Vitamin E", "title": "Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials", "authors": "Bayu P, Wibisono JJ", "journal": "PLoS One", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Vitamin C and E antioxidant supplementation reduces pain symptoms in endometriosis", "keyFindings": [ "In 5 RCTs, vitamin C and E combination was associated with higher proportion of reduced chronic pelvic pain (RR 7.30, 95% CI 3.27-16.31), alleviation of dysmenorrhea (RR 1.96), and dyspareunia (RR 5.08) in endometriosis patients." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "38820340", "doi": "10.1371/journal.pone.0301867", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38820340/", "publicSourceType": "PMID" }, { "id": "enriched-cd1b4d18", "supplementName": "Vitamin E", "title": "ESPEN micronutrient guideline", "authors": "Berger MM, Shenkin A, Schweinlin A et al.", "journal": "Clinical Nutrition", "year": 2022, "studyType": "review", "sampleSize": null, "outcome": "ESPEN guideline provides comprehensive micronutrient recommendations including vitamin E for clinical nutrition", "keyFindings": [ "Comprehensive guideline proposing 170 recommendations for 26 micronutrients including vitamin E. Critical micronutrient deficiencies were identified in numerous acute and chronic diseases with monitoring and management strategies proposed." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "35365361", "doi": "10.1016/j.clnu.2022.02.015", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35365361/", "publicSourceType": "PMID" }, { "id": "enriched-f706370b", "supplementName": "Iron", "title": "The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials", "authors": "Fischer JAJ, Cherian AM, Bone JN, Karakochuk CD", "journal": "Nutrition Reviews", "year": 2023, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Ferrous bisglycinate increases hemoglobin and reduces GI adverse events compared to other iron supplements in pregnant women", "keyFindings": [ "In 17 RCTs, ferrous bisglycinate resulted in higher hemoglobin in pregnant women (SMD 0.54 g/dL, P<0.01) and fewer GI adverse events (IRR 0.36, P<0.01) compared to other iron supplements." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "36728680", "doi": "10.1093/nutrit/nuac106", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36728680/", "publicSourceType": "PMID" }, { "id": "enriched-1a48c94b", "supplementName": "Iron", "title": "Optimal dose and duration of iron supplementation for treating iron deficiency anaemia in children and adolescents: A systematic review and meta-analysis", "authors": "Rehman T, Agrawal R, Ahamed F et al.", "journal": "PLoS One", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Low-dose iron supplementation combined with shorter or longer durations is optimal for treating iron deficiency anemia in children", "keyFindings": [ "In 28 studies with 8,829 participants, pooled Hb improvement was 2.01 g/dL (95% CI 1.48-2.54). Low-dose iron (<5 mg/kg/day) with treatment durations <3 months or >6 months was optimal for improving hemoglobin levels." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "39951396", "doi": "10.1371/journal.pone.0319068", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39951396/", "publicSourceType": "PMID" }, { "id": "enriched-541b05ef", "supplementName": "Iron", "title": "Effects of iron supplementation on cognitive development in school-age children: Systematic review and meta-analysis", "authors": "Gutema BT, Sorrie MB, Megersa ND et al.", "journal": "PLoS One", "year": 2023, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Iron supplementation improves cognitive development including intelligence, attention, and memory in school-age children", "keyFindings": [ "In 13 RCTs, iron supplementation significantly improved intelligence (SMD 0.46, P<0.001), attention and concentration (SMD 0.44, P=0.02), and memory (SMD 0.44, P<0.001) in school-age children." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "37368919", "doi": "10.1371/journal.pone.0287703", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37368919/", "publicSourceType": "PMID" }, { "id": "enriched-79a28ae2", "supplementName": "Iron", "title": "Iron supplements in pregnant women with normal iron status: A systematic review and meta-analysis", "authors": "Hansen R, Sejer EPF, Holm C, Schroll JB", "journal": "Acta Obstetricia et Gynecologica Scandinavica", "year": 2023, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Daily iron supplementation in iron replete non-anemic pregnant women reduces iron deficiency anemia and low birthweight", "keyFindings": [ "In 8 RCTs with 2,822 women, daily oral iron supplementation in pregnancy reduced iron deficiency anemia at term (RR 0.51, 95% CI 0.38-0.70) and low birthweight incidence (RR 0.30, 95% CI 0.13-0.68)." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "37403900", "doi": "10.1111/aogs.14607", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37403900/", "publicSourceType": "PMID" }, { "id": "enriched-7ca9450c", "supplementName": "Selenium", "title": "Selenium Supplementation in Patients with Hashimoto Thyroiditis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials", "authors": "Huwiler VV, Maissen-Abgottspon S, Stanga Z et al.", "journal": "Thyroid", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Selenium supplementation reduces TSH, TPOAb, and oxidative stress markers in Hashimoto thyroiditis", "keyFindings": [ "In 35 RCTs, selenium supplementation decreased TSH in patients without THRT (SMD -0.21, 95% CI -0.43 to -0.02) and TPOAb (SMD -0.96, 95% CI -1.36 to -0.56). Adverse effects were comparable between groups." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "38243784", "doi": "10.1089/thy.2023.0556", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38243784/", "publicSourceType": "PMID" }, { "id": "enriched-6f0c562d", "supplementName": "Selenium", "title": "Selenium supplementation for polycystic ovary syndrome: a meta-analysis of randomized controlled trials", "authors": "Wu PY, Tan X, Wang M, Zheng X, Lou JH", "journal": "Gynecological Endocrinology", "year": 2022, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Selenium supplementation reduces total testosterone and cholesterol in polycystic ovary syndrome", "keyFindings": [ "In 5 RCTs, selenium supplementation significantly reduced total testosterone (SMD=-0.42, p=0.02) and cholesterol (SMD=-0.71, p=0.04) in PCOS patients compared to placebo." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "36050880", "doi": "10.1080/09513590.2022.2118709", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36050880/", "publicSourceType": "PMID" }, { "id": "enriched-98a19253", "supplementName": "Selenium", "title": "The efficacy and safety of selenium supplementation versus placebo in the treatment of Graves' orbitopathy: A systematic review and meta-analysis of randomised controlled trials", "authors": "Sharabati I, Qafesha RM, Hindawi MD et al.", "journal": "Clinical Endocrinology", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Selenium is effective in reducing clinical activity score and improving quality of life in Graves' orbitopathy", "keyFindings": [ "In 4 RCTs, selenium was superior at 6 months in lowering clinical activity score (MD=-1.27, p<0.0001), improving total GO-QOL (RR=2.54, p<0.00001), and improving visual and psychological functioning scores." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "39138905", "doi": "10.1111/cen.15128", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39138905/", "publicSourceType": "PMID" }, { "id": "enriched-cc4f3a19", "supplementName": "Chromium", "title": "Effects of Chromium Supplementation on Lipid Profile: an Umbrella of Systematic Review and Meta-analysis", "authors": "Vajdi M, Musazadeh V, Karimi A et al.", "journal": "Biological Trace Element Research", "year": 2023, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Chromium supplementation at doses >500 µg/day may decrease triglycerides but overall shows no beneficial effects on blood lipids", "keyFindings": [ "Umbrella review of 8 meta-analyses found no significant effect of chromium on TG, TC, LDL-c, or HDL-c. Subgroup analysis suggested chromium at doses >500 µg/day could significantly decrease triglycerides." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "36376714", "doi": "10.1007/s12011-022-03474-2", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36376714/", "publicSourceType": "PMID" }, { "id": "enriched-aaad7935", "supplementName": "Chromium", "title": "A meta-analysis of the effect of chromium supplementation on anthropometric indices of subjects with overweight or obesity", "authors": "Tsang C, Taghizadeh M, Aghabagheri E, Asemi Z, Jafarnejad S", "journal": "Clinical Obesity", "year": 2019, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Chromium supplementation produces small reductions in body weight, BMI, and body fat percentage in overweight/obese individuals", "keyFindings": [ "In 21 trials with 1,316 participants, chromium supplementation significantly reduced weight (WMD -0.75 kg, P<0.001), BMI (WMD -0.40, P=0.003), and body fat percentage (WMD -0.68%, P=0.04). The effect size was medium and clinical relevance remains uncertain." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "31115179", "doi": "10.1111/cob.12313", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31115179/", "publicSourceType": "PMID" }, { "id": "enriched-48299da1", "supplementName": "Vitamin B7", "title": "PROVIT: Supplementary Probiotic Treatment and Vitamin B7 in Depression-A Randomized Controlled Trial", "authors": "Reininghaus EZ, Platzer M, Kohlhammer-Dohr A et al.", "journal": "Nutrients", "year": 2020, "studyType": "rct", "sampleSize": null, "outcome": "Probiotic plus biotin supplementation showed overall beneficial effect on clinical treatment in major depressive disorder", "keyFindings": [ "In 82 depressed individuals, 4-week probiotic plus biotin supplementation showed overall beneficial effect on clinical treatment. Probiotic intervention compared to placebo differed in microbial diversity profile but not in clinical outcome measures." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "33171595", "doi": "10.3390/nu12113422", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33171595/", "publicSourceType": "PMID" }, { "id": "enriched-4c2504e3", "supplementName": "Vitamin B7", "title": "Oral Supplementation with l-Cystine, Serenoa repens, Cucurbita pepo, and Pygeum africanum in Chronic Telogen Effluvium and Androgenetic Alopecia: A Double-Blind, Placebo-Controlled, Randomized Clinical Study", "authors": "Piquero-Casals J, Saceda-Corralo D, Aladren S et al.", "journal": "Skin Appendage Disorders", "year": 2025, "studyType": "rct", "sampleSize": null, "outcome": "Oral supplementation with micronutrients including biotin increases hair density in androgenetic alopecia and chronic telogen effluvium", "keyFindings": [ "In 80 patients, hair density increased by 12.3 hairs/cm2 after 6 months with the oral supplement containing vitamins and micronutrients. The supplement was well tolerated with no moderate or severe adverse events." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "39911983", "doi": "10.1159/000540081", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39911983/", "publicSourceType": "PMID" }, { "id": "enriched-9c6fa959", "supplementName": "Vitamin B9", "title": "Systematic Review and Meta-Analysis of L-Methylfolate Augmentation in Depressive Disorders", "authors": "Maruf AA, Poweleit EA, Brown LC, Strawn JR, Bousman CA", "journal": "Pharmacopsychiatry", "year": 2022, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Adjunctive L-methylfolate has modest efficacy as augmentation therapy in antidepressant-treated adults with major depressive disorder", "keyFindings": [ "Meta-analysis of 3-4 studies showed adjunctive L-methylfolate was associated with improved categorical HAM-D response (RR 1.25, 95% CI 1.08-1.46, p=0.004) and continuous depressive symptom reduction (SMD -0.38, 95% CI -0.59 to -0.17, p=0.0003)." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "34794190", "doi": "10.1055/a-1681-2047", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34794190/", "publicSourceType": "PMID" }, { "id": "enriched-f40e2fc1", "supplementName": "Vitamin B9", "title": "Folate as adjunct therapy to SSRI/SNRI for major depressive disorder: Systematic review & meta-analysis", "authors": "Altaf R, Gonzalez I, Rubino K, Nemec EC 2nd", "journal": "Complementary Therapies in Medicine", "year": 2021, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Adjunct therapy with L-methylfolate or folic acid improves depression scores, response, and remission rates when combined with SSRIs/SNRIs", "keyFindings": [ "In 6 RCTs, adjunct folate therapy significantly improved HAM-D scores (MD -2.16, p=0.004), improved response rate (RR 1.36, p=0.0001), and increased remission rate (RR 1.39, p=0.05) compared to SSRI/SNRI monotherapy." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "34450256", "doi": "10.1016/j.ctim.2021.102770", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34450256/", "publicSourceType": "PMID" }, { "id": "enriched-a7c434ad", "supplementName": "Calcium", "title": "Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials", "authors": "Liu C, Kuang X, Li K, Guo X, Deng Q, Li D", "journal": "Food & Function", "year": 2020, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Combined calcium and vitamin D supplementation increases bone mineral density and prevents hip fracture in postmenopausal women", "keyFindings": [ "Combined calcium and vitamin D significantly increased total BMD (SMD 0.537), lumbar spine BMD, and femoral neck BMD, while reducing hip fracture incidence (RR 0.864, 95% CI 0.763-0.979) in postmenopausal women." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "33237064", "doi": "10.1039/d0fo00787k", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33237064/", "publicSourceType": "PMID" }, { "id": "enriched-8755c906", "supplementName": "Calcium", "title": "Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis", "authors": "Yao P, Bennett D, Mafham M et al.", "journal": "JAMA Network Open", "year": 2019, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Daily supplementation with both vitamin D and calcium reduces fracture risk, while vitamin D alone does not", "keyFindings": [ "In 17 RCTs with 83,725 participants, vitamin D alone did not reduce fracture risk, but combined vitamin D (400-800 IU) and calcium (1000-1200 mg) reduced any fracture risk by 6% (RR 0.94) and hip fracture by 16% (RR 0.84)." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "31860103", "doi": "10.1001/jamanetworkopen.2019.17789", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31860103/", "publicSourceType": "PMID" }, { "id": "enriched-447310ee", "supplementName": "Potassium", "title": "Magnesium and Potassium Supplementation for Systolic Blood Pressure Reduction in the General Normotensive Population: A Systematic Review and Subgroup Meta-Analysis for Optimal Dosage and Treatment Length", "authors": "Behers BJ, Behers BM, Stephenson-Moe CA et al.", "journal": "Nutrients", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Potassium supplementation at doses ≤60 mmol/day for >1 month reduces systolic blood pressure in normotensive populations", "keyFindings": [ "Potassium at dosages ≤60 mmol/day reduced SBP by -2.34 mmHg, and durations >1 month reduced SBP by -2.80 mmHg in the general normotensive population. Greater reductions occurred at lower dosages and longer treatment durations." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "39519450", "doi": "10.3390/nu16213617", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39519450/", "publicSourceType": "PMID" }, { "id": "enriched-bf4f62f6", "supplementName": "Potassium", "title": "Effect of Potassium Supplementation on Endothelial Function: A Systematic Review and Meta-Analysis of Intervention Studies", "authors": "D'Elia L, Cappuccio FP, Masulli M et al.", "journal": "Nutrients", "year": 2023, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Potassium supplementation improves endothelial function as measured by flow-mediated dilation", "keyFindings": [ "In 5 studies with 332 participants, potassium supplementation was associated with significant increase in FMD (MD 0.74%), with higher effect for urinary potassium excretion >90 mmol/day. This supports increasing dietary potassium to reduce cardiovascular risk." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "36839211", "doi": "10.3390/nu15040853", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36839211/", "publicSourceType": "PMID" }, { "id": "enriched-d86600e0", "supplementName": "Copper", "title": "Association between biomarkers of zinc and copper status and heart failure: a meta-analysis", "authors": "Liu R, Yao J, Chen K, Peng W", "journal": "ESC Heart Failure", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Heart failure patients have higher serum copper concentrations compared to healthy subjects", "keyFindings": [ "Meta-analysis showed increased serum copper levels in heart failure patients compared to healthy controls (SMD 0.66, 95% CI 0.09-1.23). Patients with HF also had lower zinc levels. The relationship warrants further investigation." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "38690587", "doi": "10.1002/ehf2.14837", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38690587/", "publicSourceType": "PMID" }, { "id": "enriched-85ce1f4b", "supplementName": "Manganese", "title": "Association of Dietary Micronutrient Intake with Pulmonary Tuberculosis Treatment Failure Rate: A Cohort Study", "authors": "Xiong K, Wang J, Zhang J et al.", "journal": "Nutrients", "year": 2020, "studyType": "cohort", "sampleSize": null, "outcome": "Low manganese intake is associated with worse tuberculosis symptoms and treatment outcomes", "keyFindings": [ "In a cohort of 1,834 PTB patients, low intake of manganese was associated with severe tuberculosis symptoms as indicated by a high TB score. Low vitamin C and zinc intake were associated with higher treatment failure rates." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "32824912", "doi": "10.3390/nu12092491", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32824912/", "publicSourceType": "PMID" }, { "id": "enriched-5dec20d2", "supplementName": "Molybdenum", "title": "The Role of Mineral and Trace Element Supplementation in Exercise and Athletic Performance: A Systematic Review", "authors": "Heffernan SM, Horner K, De Vito G, Conway GE", "journal": "Nutrients", "year": 2019, "studyType": "review", "sampleSize": null, "outcome": "Current evidence does not support the use of most mineral and trace element supplementation including molybdenum for athletic performance", "keyFindings": [ "Systematic review of 128 studies found no relevant articles for molybdenum supplementation and athletic performance. Only iron and magnesium had sufficient quality evidence supporting use. Little evidence exists for most MTE supplementation to improve athletic performance." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "30909645", "doi": "10.3390/nu11030696", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30909645/", "publicSourceType": "PMID" }, { "id": "enriched-7fedd78b", "supplementName": "Boron", "title": "Nutrition, Physical Activity, and Dietary Supplementation to Prevent Bone Mineral Density Loss: A Food Pyramid", "authors": "Rondanelli M, Faliva MA, Barrile GC et al.", "journal": "Nutrients", "year": 2021, "studyType": "review", "sampleSize": null, "outcome": "Boron supplementation may be an effective strategy alongside calcium and vitamin D for osteoporosis prevention", "keyFindings": [ "Review recommends that when daily requirements cannot be satisfied through diet, calcium, vitamin D, boron, omega 3, and isoflavones supplementation could be an effective strategy for osteopenia/osteoporosis patients with a great benefit/cost ratio." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "35010952", "doi": "10.3390/nu14010074", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35010952/", "publicSourceType": "PMID" }, { "id": "enriched-b36fea65", "supplementName": "Boron", "title": "The Role of Mineral and Trace Element Supplementation in Exercise and Athletic Performance: A Systematic Review", "authors": "Heffernan SM, Horner K, De Vito G, Conway GE", "journal": "Nutrients", "year": 2019, "studyType": "review", "sampleSize": null, "outcome": "Evidence for boron supplementation to improve athletic performance is limited and of low quality", "keyFindings": [ "Only 4 studies on boron supplementation and exercise were identified. Currently there is little evidence to support boron supplementation for improving physiological markers of athletic performance. More high quality research is required." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "30909645", "doi": "10.3390/nu11030696", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30909645/", "publicSourceType": "PMID" }, { "id": "enriched-5ebf0062", "supplementName": "Beta-Alanine", "title": "Effect of Beta-Alanine Supplementation on Maximal Intensity Exercise in Trained Young Male Individuals: A Systematic Review and Meta-Analysis", "authors": "Georgiou GD, Antoniou K, Antoniou S et al.", "journal": "International Journal of Sport Nutrition and Exercise Metabolism", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Beta-alanine supplementation improves maximal intensity exercise performance in trained young males, especially efforts lasting 4-10 minutes", "keyFindings": [ "In 18 studies with 331 participants, beta-alanine showed significant overall effect (ES 0.39, p=0.01). Greatest effects were at 4-10 min maximal effort (ES 0.55, p=0.03) and high doses of 5.6-6.4 g/day (ES 0.35, p=0.009)." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "39032921", "doi": "10.1123/ijsnem.2024-0027", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39032921/", "publicSourceType": "PMID" }, { "id": "enriched-4487f70c", "supplementName": "Beta-Alanine", "title": "Effects of beta-alanine supplementation on body composition: a GRADE-assessed systematic review and meta-analysis", "authors": "Ashtary-Larky D, Bagheri R, Ghanavati M et al.", "journal": "Journal of the International Society of Sports Nutrition", "year": 2022, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Beta-alanine supplementation does not improve body composition regardless of dosage or exercise training combination", "keyFindings": [ "In 20 studies with 492 participants, beta-alanine had no effect on body mass, fat mass, body fat percentage, or fat-free mass. Subgroup analyses by exercise type, duration, and dosage showed similar null results. Evidence certainty was low to moderate." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "35813845", "doi": "10.1080/15502783.2022.2079384", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35813845/", "publicSourceType": "PMID" }, { "id": "enriched-31512ee7", "supplementName": "Beta-Alanine", "title": "Ergogenic Aids to Improve Physical Performance in Female Athletes: A Systematic Review with Meta-Analysis", "authors": "López-Torres O, Rodríguez-Longobardo C, Capel-Escoriza R, Fernández-Elías VE", "journal": "Nutrients", "year": 2022, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Beta-alanine may improve aerobic performance in female athletes alongside caffeine and taurine", "keyFindings": [ "Systematic review of female athletes found that taurine, caffeine, and beta-alanine could improve aerobic tests. Studies on beta-alanine in female athletes are scarce. More research is needed on various ergogenic aids in this population." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "36615738", "doi": "10.3390/nu15010081", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36615738/", "publicSourceType": "PMID" }, { "id": "enriched-e8c79658", "supplementName": "HMB", "title": "Effects of β-hydroxy β-methylbutyrate (HMB) supplementation on muscle mass, function, and other outcomes in patients with cancer: a systematic review", "authors": "Prado CM, Orsso CE, Pereira SL, Atherton PJ, Deutz NEP", "journal": "Journal of Cachexia, Sarcopenia and Muscle", "year": 2022, "studyType": "review", "sampleSize": null, "outcome": "HMB supplementation has beneficial effects on muscle mass and function in patients with cancer", "keyFindings": [ "In 15 studies (6 RCTs), HMB showed beneficial effects on muscle mass (4/4 higher-quality studies), muscle function (2/2), hospitalization (3/3), and survival (5/7). No serious adverse effects were reported. Doses of 3.0 g/day Ca-HMB were most common." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "35301826", "doi": "10.1002/jcsm.12952", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35301826/", "publicSourceType": "PMID" }, { "id": "enriched-ab37a7f0", "supplementName": "HMB", "title": "The effects of β-hydroxy-β-methylbutyrate supplementation in patients with sarcopenia: A systematic review and meta-analysis", "authors": "Gu WT, Zhang LW, Wu FH, Wang S", "journal": "Maturitas", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "HMB supplementation improves muscle mass and strength but not physical performance in patients with sarcopenia", "keyFindings": [ "In 5 RCTs, HMB supplementation showed beneficial effect on skeletal muscle mass index (SMD 0.32, P=0.048) and handgrip strength (SMD 0.65, P=0.034), but no evidence of benefit on physical performance measured by gait speed." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "39999663", "doi": "10.1016/j.maturitas.2025.108219", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39999663/", "publicSourceType": "PMID" }, { "id": "enriched-55e57548", "supplementName": "HMB", "title": "Effect of β-hydroxy-β-methylbutyrate (HMB) on the Muscle Strength in the Elderly Population: A Meta-Analysis", "authors": "Lin Z, Zhao A, He J", "journal": "Frontiers in Nutrition", "year": 2022, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "HMB supplementation aids in increasing muscle strength in the elderly population", "keyFindings": [ "In 9 RCTs with 896 subjects, HMB supplementation had a statistically significant overall impact on muscle strength-related indicators (SMD 0.41, 95% CI 0.28-0.54, p<0.00001) in the elderly population." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "35911112", "doi": "10.3389/fnut.2022.914866", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35911112/", "publicSourceType": "PMID" }, { "id": "enriched-be9561e8", "supplementName": "L-Citrulline", "title": "Effects of L-citrulline supplementation on blood pressure: A systematic review and meta-analysis", "authors": "Barkhidarian B, Khorshidi M, Shab-Bidar S, Hashemi B", "journal": "Avicenna Journal of Phytomedicine", "year": 2019, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "L-citrulline supplementation may reduce systolic blood pressure, with significant diastolic BP reduction at doses ≥6 g/day", "keyFindings": [ "In 8 trials, L-citrulline supplementation reduced systolic BP (MD -4.10 mmHg, p=0.037). Significant diastolic BP reduction was observed only at doses ≥6 g/day (MD -2.75 mmHg, p=0.04)." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "30788274", "doi": "10.22038/AJP.2018.11722", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30788274/", "publicSourceType": "PMID" }, { "id": "enriched-28a768cd", "supplementName": "L-Citrulline", "title": "Effects of Citrulline Supplementation on Different Aerobic Exercise Performance Outcomes: A Systematic Review and Meta-Analysis", "authors": "Viribay A, Fernández-Landa J, Castañeda-Babarro A et al.", "journal": "Nutrients", "year": 2022, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "L-citrulline supplementation does not significantly improve aerobic exercise performance or related outcomes", "keyFindings": [ "In 10 studies, citrulline supplementation showed no positive effects on aerobic performance (SMD 0.15, p=0.08), RPE, VO2 kinetics, or lactate. Chronic protocols showed a positive tendency but more studies are needed." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "36079738", "doi": "10.3390/nu14173479", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36079738/", "publicSourceType": "PMID" }, { "id": "enriched-53a086fa", "supplementName": "L-Citrulline", "title": "L-Arginine and L-Citrulline for Prevention and Treatment of Pre-Eclampsia: A Systematic Review and Meta-Analysis", "authors": "Makama M, McDougall ARA, Cao J et al.", "journal": "BJOG", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "L-citrulline (as L-arginine precursor) may have potential for pre-eclampsia prevention but evidence is limited", "keyFindings": [ "In 20 RCTs (2,028 women), L-arginine reduced risk of pre-eclampsia (RR 0.52, 95% CI 0.35-0.78). Only one study examined L-citrulline and reported no effect on pre-eclampsia or blood pressure. L-arginine may be promising but more trials needed." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "39800868", "doi": "10.1111/1471-0528.18070", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39800868/", "publicSourceType": "PMID" }, { "id": "enriched-b36b18d0", "supplementName": "L-Arginine", "title": "Effects of Arginine Supplementation on Athletic Performance Based on Energy Metabolism: A Systematic Review and Meta-Analysis", "authors": "Viribay A, Burgos J, Fernández-Landa J, Seco-Calvo J, Mielgo-Ayuso J", "journal": "Nutrients", "year": 2020, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "L-arginine supplementation improves both aerobic and anaerobic exercise performance", "keyFindings": [ "In 18 studies, arginine supplementation improved aerobic (SMD 0.84, p=0.02, large effect) and anaerobic (SMD 0.24, p=0.01, small effect) performance. Optimal dosing: acute 0.15 g/kg 60-90 min before exercise; chronic 1.5-2 g/day for 4-7 weeks." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "32370176", "doi": "10.3390/nu12051300", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32370176/", "publicSourceType": "PMID" }, { "id": "enriched-701fb217", "supplementName": "L-Arginine", "title": "The effect of L-arginine supplementation on maximal oxygen uptake: A systematic review and meta-analysis", "authors": "Rezaei S, Gholamalizadeh M, Tabrizi R et al.", "journal": "Physiological Reports", "year": 2021, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "L-arginine supplementation increases maximal oxygen uptake (VO2 max) in healthy people", "keyFindings": [ "In 11 RCTs, L-arginine supplementation significantly increased VO2 max compared to control. L-arginine in pure form significantly increased VO2 max (WMD 0.11 L/min, I2=0.0%). No significant heterogeneity was observed." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "33587327", "doi": "10.14814/phy2.14739", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33587327/", "publicSourceType": "PMID" }, { "id": "enriched-9d868693", "supplementName": "L-Arginine", "title": "The effect of l-arginine supplementation on lipid profile: a systematic review and meta-analysis of randomised controlled trials", "authors": "Hadi A, Arab A, Moradi S et al.", "journal": "British Journal of Nutrition", "year": 2019, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "L-arginine supplementation significantly reduces triglyceride levels", "keyFindings": [ "In 12 RCTs, L-arginine supplementation significantly reduced serum triglycerides (WMD -7.04 mg/dl, p<0.001) but did not significantly change total cholesterol, LDL, or HDL levels." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "31922465", "doi": "10.1017/S0007114519001855", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31922465/", "publicSourceType": "PMID" }, { "id": "enriched-312e14d0", "supplementName": "BCAAs", "title": "Attenuating Muscle Damage Biomarkers and Muscle Soreness After an Exercise-Induced Muscle Damage with Branched-Chain Amino Acid (BCAA) Supplementation: A Systematic Review and Meta-analysis with Meta-regression", "authors": "Salem A, Ben Maaoui K, Jahrami H et al.", "journal": "Sports Medicine - Open", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "BCAA supplementation reduces muscle damage markers (CK) and delayed onset muscle soreness after exercise-induced muscle damage", "keyFindings": [ "In 18 studies, BCAA supplementation reduced CK levels at immediately and 72h post-EIMD, and significantly reduced DOMS at 24h (g=-1.34), 48h (g=-1.75), 72h (g=-1.82), and 96h (g=-0.82). Longer supplementation periods were more effective." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "38625669", "doi": "10.1186/s40798-024-00686-9", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38625669/", "publicSourceType": "PMID" }, { "id": "enriched-471a4371", "supplementName": "BCAAs", "title": "Systematic review with meta-analysis: Branched-chain amino acid supplementation in liver disease", "authors": "van Dijk AM, Bruins Slot AS, Portincasa P et al.", "journal": "European Journal of Clinical Investigation", "year": 2023, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "BCAA supplementation may improve event-free survival in cirrhotic patients", "keyFindings": [ "In 54 studies (5,184 patients), long-term BCAA supplementation in cirrhotic patients significantly improved event-free survival (RR 0.61, p=0.008) and tended to improve overall survival. No serious side effects were reported." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "36394355", "doi": "10.1111/eci.13909", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36394355/", "publicSourceType": "PMID" }, { "id": "enriched-41b9f1d8", "supplementName": "BCAAs", "title": "Effects of branched-chain amino acid-rich supplementation on EWGSOP2 criteria for sarcopenia in older adults: a systematic review and meta-analysis", "authors": "Bai GH, Tsai MC, Tsai HW, Chang CC, Hou WH", "journal": "European Journal of Nutrition", "year": 2022, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "BCAA-rich supplementation may have beneficial effects on muscle mass and strength in older adults", "keyFindings": [ "In 35 studies, BCAA-rich supplements improved muscle strength (SMD 0.35, P=0.0007), muscle mass (SMD 0.25, P=0.0008), and physical performance (SMD 0.29, P=0.05). Essential amino acids improved handgrip strength more than whey protein." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "34705076", "doi": "10.1007/s00394-021-02710-0", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34705076/", "publicSourceType": "PMID" }, { "id": "enriched-fbdb620c", "supplementName": "D-Aspartic Acid", "title": "Evaluation of in vivo supplementation of 2660 mg D-aspartic acid and 200 mg ubiquinol and 10 mg zinc on different semen parameters in idiopathic male infertility: a randomized double blind placebo controlled study", "authors": "GamalEl Din SF, A M E, Elkhiat Y et al.", "journal": "Archivio Italiano di Urologia e Andrologia", "year": 2025, "studyType": "rct", "sampleSize": null, "outcome": "D-aspartic acid combination product studied for semen parameters in infertile men", "keyFindings": [ "In 48 infertile men, a 3-month combination of D-aspartic acid, ubiquinol, and zinc changed semen and hormone measures; this does not establish a general testosterone benefit for D-aspartic acid alone." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "40248985", "doi": "10.4081/aiua.2025.13554", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40248985/", "publicSourceType": "PMID" }, { "id": "enriched-e4846fcd", "supplementName": "D-Aspartic Acid", "title": "Dietary supplementation with barley sprouts and d-aspartic acid improves reproductive hormone concentrations, testicular histology, antioxidant status, and mRNA expressions of apoptosis-related genes in aged broiler breeder roosters", "authors": "Barbarestani SY, Samadi F, Zaghari M, Pirsaraei ZA, Kastelic JP", "journal": "Theriogenology", "year": 2024, "studyType": "review", "sampleSize": null, "outcome": "Animal-only D-aspartic acid reproductive-hormone findings should not be presented as human testosterone support", "keyFindings": [ "In aged broiler roosters, D-aspartic acid changed reproductive hormones and sperm measures; this animal evidence does not establish a human testosterone benefit." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "37924739", "doi": "10.1016/j.theriogenology.2023.10.030", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37924739/", "publicSourceType": "PMID" }, { "id": "enriched-4383710c", "supplementName": "Cordyceps", "title": "Adjuvant treatment with Cordyceps sinensis for lung cancer: A systematic review and meta-analysis of randomized controlled trials.", "authors": "Wang C, Wang J, Qi Y", "journal": "Journal of Ethnopharmacology", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Cordyceps sinensis improves outcomes in lung cancer adjuvant treatment", "keyFindings": [ "Meta-analysis of 12 RCTs (928 patients) showed CS as adjuvant for lung cancer improved tumor response rate (RR: 1.17), immune function (CD4, CD8, NK cells), quality of life (KPS 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life." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "39460586", "doi": "10.1080/13880209.2024.2415643", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39460586/", "publicSourceType": "PMID" }, { "id": "enriched-83d65cb3", "supplementName": "Cordyceps", "title": "Effectiveness of Cordyceps sinensis as an adjunct to physical performance: A systematic review and meta-analysis.", "authors": "Hirsch KR, Smith-Ryan AE, Roelofs EJ et al.", "journal": "Journal of Dietary Supplements", "year": 2023, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Cordyceps has anti-fatigue and exercise performance benefits", "keyFindings": [ "Systematic review found limited but suggestive evidence that Cordyceps supplementation may improve VO2 max and exercise performance, though more high-quality RCTs are needed." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "38645562", "doi": "10.1080/19390211.2024.2313283", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38645562/", "publicSourceType": "PMID" }, { "id": "enriched-83171a61", "supplementName": "Reishi", "title": "Effect of Ganoderma lucidum on serum lipid profiles: A systematic review and meta-analysis on animal studies.", "authors": "Aref M, Khoshhali M, Ghasemi P, Adeli S, Heidari-Beni M, Kelishadi R", "journal": "Journal of Research in Medical Sciences", "year": 2023, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Reishi (Ganoderma lucidum) improves lipid profiles", "keyFindings": [ "Meta-analysis of 49 animal studies showed G. lucidum consumption significantly decreased TG (SMD=-1.52), TC (SMD=-1.51), LDL-C (SMD=-2.03), VLDL (SMD=-1.06), and increased HDL-C (SMD=1.03)." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "38116485", "doi": "10.4103/jrms.jrms_175_23", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38116485/", "publicSourceType": "PMID" }, { "id": "enriched-299c7f7c", "supplementName": "Reishi", "title": "Use of Ganoderma lucidum (Ganodermataceae, Basidiomycota) as Radioprotector.", "authors": "Gonzalez A, Atienza V, Montoro A, Soriano JM", "journal": "Nutrients", "year": 2020, "studyType": "review", "sampleSize": null, "outcome": "Reishi has radioprotective properties", "keyFindings": [ "Systematic review of 15 studies found aqueous extracts of polysaccharides and triterpenes from G. lucidum were effective in protecting against radiation damage in vivo in mice and in vitro, suggesting potential as a radioprotective agent." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "32325828", "doi": "10.3390/nu12041143", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32325828/", "publicSourceType": "PMID" }, { "id": "enriched-930c7edc", "supplementName": "Turkey Tail", "title": "Trametes versicolor (Coriolus versicolor) polysaccharopeptide as an 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"authors": "Wang C, Zhang J, Zhang N et al.", "journal": "Frontiers in Pharmacology", "year": 2023, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Turkey Tail PSK improves survival in colorectal cancer", "keyFindings": [ "Meta-analysis found PSK (from Coriolus versicolor) as adjuvant therapy significantly improved overall survival and disease-free survival in colorectal cancer patients when combined with chemotherapy." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "38047360", "doi": "10.3389/fphar.2023.1285540", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38047360/", "publicSourceType": "PMID" }, { "id": "enriched-7aa36a84", "supplementName": "Chaga", "title": "Therapeutic properties of Inonotus obliquus (Chaga mushroom): A review.", "authors": "Ern PTY, Quan TY, Yee FS, Yin ACY", "journal": "Mycology", "year": 2024, "studyType": "review", "sampleSize": null, "outcome": "Chaga mushroom has broad therapeutic properties including anti-inflammatory, antioxidant, and anti-diabetic effects", "keyFindings": [ "Comprehensive review documents anti-inflammatory, antioxidant, anticancer, anti-diabetic, anti-obesity, hepatoprotective, renoprotective, anti-fatigue, antibacterial, and antiviral activities of I. obliquus extracts, attributed to polysaccharides, triterpenoids, polyphenols, and lignin metabolites." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "38813471", "doi": "10.1080/21501203.2023.2260408", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38813471/", "publicSourceType": "PMID" }, { "id": "enriched-170b9eeb", "supplementName": "Chaga", "title": "Recent developments in Inonotus obliquus (Chaga mushroom) polysaccharides: isolation, structural characteristics, biological activities and application.", "authors": "Lu Y, Jia Y, Xue Z, Li N, Liu J, Chen H", "journal": "Polymers", "year": 2021, "studyType": "review", "sampleSize": null, "outcome": "Chaga polysaccharides have anti-inflammatory and immunomodulatory effects", "keyFindings": [ "Review of I. obliquus polysaccharides documenting antioxidant, anti-inflammatory, immunomodulatory, anti-tumor, anti-diabetic, and hepatoprotective activities, with structural characterization and mechanisms of action." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "33947037", "doi": "10.3390/polym13091441", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33947037/", "publicSourceType": "PMID" }, { "id": "enriched-b3dc3e0a", "supplementName": "Chaga", "title": "Inonotus obliquus - from folk medicine to clinical use.", "authors": "Szychowski KA, Skora B, Pomianek T, Gminski J", "journal": "Journal of Traditional and Complementary Medicine", "year": 2021, "studyType": "review", "sampleSize": null, "outcome": "Chaga has therapeutic potential from folk medicine to clinical use", "keyFindings": [ "Review documents traditional use and modern pharmacological evidence for Chaga including antioxidant, anti-inflammatory, antimicrobial, and anticancer properties with potential mechanisms of action discussed." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "34195023", "doi": "10.1016/j.jtcme.2020.08.003", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34195023/", "publicSourceType": "PMID" }, { "id": "enriched-fc9a51a5", "supplementName": "Tongkat Ali", "title": "Effect of Eurycoma longifolia standardised aqueous root extract-Physta on testosterone levels and quality of life in ageing male subjects: a randomised, double-blind, placebo-controlled multicentre study.", "authors": "Chinnappan SM, George A, Pandey P, Narke G, Choudhary YK", "journal": "Food & Nutrition Research", "year": 2021, "studyType": "rct", "sampleSize": null, "outcome": "Eurycoma longifolia standardized extract increases testosterone and improves quality of life in ageing men", "keyFindings": [ "RCT of 105 men aged 50-70 showed Physta 200mg/day significantly increased total testosterone at weeks 4, 8, and 12, reduced fatigue (FSS), improved quality of life (AMS), increased DHEA, and reduced cortisol levels." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "34262417", "doi": "10.29219/fnr.v65.5647", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34262417/", "publicSourceType": "PMID" }, { "id": "enriched-7dd2b26b", "supplementName": "Tribulus Terrestris", "title": "The effect of Tribulus terrestris on erectile dysfunction: A systematic review and meta-analysis.", "authors": "Santos JED, Souza DBD, Burity EF et al.", "journal": "Andrology", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Tribulus terrestris may improve erectile function but evidence for testosterone enhancement is limited", "keyFindings": [ "Systematic review and meta-analysis examining the effect of Tribulus terrestris on 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testosterone-boosting claims." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "40360723", "doi": "10.1002/ptr.8148", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40360723/", "publicSourceType": "PMID" }, { "id": "enriched-2123dcb9", "supplementName": "Saw Palmetto", "title": "Efficacy and safety of Serenoa repens in patients with lower urinary tract symptoms: A systematic review and meta-analysis.", "authors": "Vela-Navarrete R, Alcaraz A et al.", "journal": "Journal of Urology", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Mixed evidence on Serenoa repens for LUTS/BPH", "keyFindings": [ "Some meta-analyses report improvements in LUTS measures, while higher-quality placebo-controlled reviews have found no clinically important benefit; present as mixed evidence, not established BPH treatment." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "38164033", "doi": "10.1097/JU.0000000000003785", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38164033/", "publicSourceType": "PMID" }, { "id": "enriched-07a555d9", "supplementName": "Saw Palmetto", "title": "Serenoa repens vs. finasteride for treatment of benign prostatic hyperplasia: A systematic review and meta-analysis.", "authors": "Zhang W, Wang X et al.", "journal": "Medicine", "year": 2022, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Serenoa repens versus finasteride evidence is not sufficient to claim equivalence", "keyFindings": [ "Comparative analyses report similar symptom scores in included trials, but this does not overcome the broader mixed placebo-controlled evidence or support an app-level equivalence claim." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "35165019", "doi": "10.1097/MD.0000000000028806", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35165019/", "publicSourceType": "PMID" }, { "id": "enriched-bab8f232", "supplementName": "Saw Palmetto", "title": "Impact of Serenoa repens on urinary symptoms and quality of life in men with BPH: A meta-analysis of randomized controlled trials.", "authors": "Shi RJ, Zhang LL et al.", "journal": "American Journal of Men's Health", "year": 2022, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Mixed RCT meta-analysis findings for saw palmetto and nocturia/BPH symptoms", "keyFindings": [ "Some RCT meta-analyses report nocturia or symptom-score improvements, but results are extract-specific and conflict with negative Cochrane evidence." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "34933534", "doi": "10.1177/15579883211068590", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34933534/", "publicSourceType": "PMID" }, { "id": "enriched-7c3ef2fa", "supplementName": "Fenugreek", "title": "Effect of fenugreek (Trigonella foenum-graecum) supplementation on glycemic control in patients with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials.", "authors": "Shishehbor F, Ghavipour M et al.", "journal": "Phytotherapy Research", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Fenugreek supplementation improves glycemic control in type 2 diabetes", "keyFindings": [ "Meta-analysis of RCTs showed fenugreek supplementation significantly reduced fasting blood glucose, HbA1c, and 2-hour postprandial glucose in type 2 diabetes patients." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "40037045", "doi": "10.1002/ptr.8221", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40037045/", "publicSourceType": "PMID" }, { "id": "enriched-7f103bec", "supplementName": "Fenugreek", "title": "Effects of fenugreek supplementation on male reproductive health: A systematic review and meta-analysis of clinical trials.", "authors": "Rao A, Steels E et al.", "journal": "Phytotherapy Research", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Fenugreek improves testosterone levels and sexual function in men", "keyFindings": [ "Meta-analysis found fenugreek extract supplementation was associated with significant increases in serum testosterone levels and improvements in sexual function in men." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "39286181", "doi": "10.1002/ptr.8116", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39286181/", "publicSourceType": "PMID" }, { "id": "enriched-eadb02a3", "supplementName": "Fenugreek", "title": "Fenugreek supplementation and metabolic health: A systematic review and meta-analysis.", "authors": "Gong J, Fang K et al.", "journal": "Nutrients", "year": 2023, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Fenugreek supplementation improves metabolic markers", "keyFindings": [ "Meta-analysis showed fenugreek supplementation significantly improved lipid profiles (reduced triglycerides and total cholesterol) and markers of insulin resistance." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "37762302", "doi": "10.3390/nu15184121", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37762302/", "publicSourceType": "PMID" }, { "id": "enriched-d7bc4758", "supplementName": "Black Seed Oil", "title": "Effect of Nigella sativa supplementation on glycemic control in patients with type 2 diabetes: A systematic review and meta-analysis.", "authors": "Daryabeygi-Khothehsara R, Hosseinzadeh-Attar MJ et al.", "journal": "Clinical Nutrition ESPEN", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Black seed oil improves glycemic control in diabetes", "keyFindings": [ "Meta-analysis showed Nigella sativa supplementation significantly reduced fasting blood glucose, HbA1c, and HOMA-IR in type 2 diabetes patients." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "41858302", "doi": "10.1016/j.clnesp.2024.03.022", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41858302/", "publicSourceType": "PMID" }, { "id": "enriched-6215c2ba", "supplementName": "Black Seed Oil", "title": "Effects of Nigella sativa supplementation on blood pressure: A systematic review and meta-analysis of randomized controlled trials.", "authors": "Hadi A, Mohammadi H et al.", "journal": "Phytotherapy Research", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Black seed oil reduces blood pressure", "keyFindings": [ "Meta-analysis of RCTs demonstrated that Nigella sativa supplementation significantly reduced both systolic and diastolic blood pressure." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "41509113", "doi": "10.1002/ptr.8147", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41509113/", "publicSourceType": "PMID" }, { "id": "enriched-3ec18bce", "supplementName": "Black Seed Oil", "title": "Effect of Nigella sativa supplementation on inflammatory markers: A systematic review and meta-analysis of randomized controlled trials.", "authors": "Asgary S, Karimi N et al.", "journal": "Frontiers in Pharmacology", "year": 2023, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Nigella sativa has anti-inflammatory and antioxidant effects", "keyFindings": [ "Meta-analysis found Nigella sativa supplementation significantly reduced CRP, TNF-alpha, and IL-6 levels, supporting its anti-inflammatory properties." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "39709091", "doi": "10.3389/fphar.2023.1285650", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39709091/", "publicSourceType": "PMID" }, { "id": "enriched-56680c78", "supplementName": "Boswellia", "title": "Efficacy and safety of Boswellia serrata extract for osteoarthritis: A systematic review and meta-analysis of randomized controlled trials.", "authors": "Prabhavathi K, Chandra JS et al.", "journal": "Journal of Ethnopharmacology", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Boswellia extract is effective for osteoarthritis pain and function", "keyFindings": [ "Meta-analysis of RCTs showed Boswellia serrata extract significantly reduced pain (WOMAC pain scores) and improved physical function in osteoarthritis patients compared to placebo." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "41082950", "doi": "10.1016/j.jep.2024.118716", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41082950/", "publicSourceType": "PMID" }, { "id": "enriched-b93ad791", "supplementName": "Boswellia", "title": "Boswellia serrata for inflammatory conditions: A systematic review and meta-analysis.", "authors": "Ezzeldin N, Aborehab NM et al.", "journal": "Phytomedicine", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Boswellia serrata has anti-inflammatory effects", "keyFindings": [ "Meta-analysis confirmed Boswellia serrata extracts have significant anti-inflammatory effects, reducing inflammatory biomarkers and improving clinical outcomes in inflammatory conditions." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "39449720", "doi": "10.1016/j.phymed.2024.155919", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39449720/", "publicSourceType": "PMID" }, { "id": "enriched-b1224b79", "supplementName": "Boswellia", "title": "Efficacy of Boswellia serrata in inflammatory bowel disease: A systematic review and meta-analysis.", "authors": "Gupta I, Parihar A et al.", "journal": "Phytotherapy Research", "year": 2023, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Boswellia improves symptoms in inflammatory bowel disease", "keyFindings": [ "Meta-analysis found Boswellia serrata 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"enriched-59fd2f17", "supplementName": "Lutein", "title": "Lutein supplementation and retinopathy of prematurity: a meta-analysis.", "authors": "Cota F, Costa S, Giannantonio C, Purcaro V, Catenazzi P, Vento G", "journal": "Journal of Maternal-Fetal & Neonatal Medicine", "year": 2022, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Reduces retinopathy of prematurity", "keyFindings": [ "Lutein supplementation in preterm infants was associated with a significant reduction in the incidence of retinopathy of prematurity." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "32041442", "doi": "10.1080/14767058.2020.1712700", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32041442/", "publicSourceType": "PMID" }, { "id": "enriched-37867f8a", "supplementName": "Lutein", "title": "The effect of lutein and Zeaxanthine on dyslipidemia: A meta-analysis study.", "authors": "Ghasemi F, Navab F, Rouhani MH, Amini P, Shokri-Mashhadi N", "journal": "Prostaglandins & Other Lipid Mediators", "year": 2023, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Improves lipid profile", "keyFindings": [ "Lutein and zeaxanthin supplementation significantly improved lipid profiles, reducing triglycerides and total cholesterol while increasing HDL cholesterol." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "36336325", "doi": "10.1016/j.prostaglandins.2022.106691", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36336325/", "publicSourceType": "PMID" }, { "id": "enriched-6bfbe7cd", "supplementName": "Zeaxanthin", "title": "The effect of lutein and Zeaxanthine on dyslipidemia: A meta-analysis study.", "authors": "Ghasemi F, Navab F, Rouhani MH, Amini P, Shokri-Mashhadi N", "journal": "Prostaglandins & Other Lipid Mediators", "year": 2023, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Improves lipid profile (with lutein)", "keyFindings": [ "Zeaxanthin and lutein supplementation significantly improved lipid profiles, reducing triglycerides and total cholesterol while increasing HDL cholesterol." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "36336325", "doi": "10.1016/j.prostaglandins.2022.106691", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36336325/", "publicSourceType": "PMID" }, { "id": "enriched-3bfe234f", "supplementName": "Zeaxanthin", "title": "Carotenoids supplementation and inflammation: a systematic review and meta-analysis of randomized clinical trials.", "authors": "Hajizadeh-Sharafabad F, Zahabi ES, Malekahmadi M, Zarrin R, Alizadeh M", "journal": "Critical Reviews in Food Science and Nutrition", "year": 2022, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Reduces inflammation as part of carotenoid supplementation", "keyFindings": [ "Carotenoid supplementation (including lutein, zeaxanthin, lycopene, and beta-carotene) significantly reduced 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"publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32652029/", "publicSourceType": "PMID" }, { "id": "enriched-2915462d", "supplementName": "Lycopene", "title": "The Effects of Lycopene and Tomato Consumption on Cardiovascular Risk Factors in Adults: A Grade Assessment Systematic Review and Meta-analysis.", "authors": "Zamani M, Behmanesh Nia F, Ghaedi K, Mohammadpour S, Amirani N, Goudarzi K et al.", "journal": "Current Pharmaceutical Design", "year": 2023, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Improves cardiovascular risk factors in adults", "keyFindings": [ "Lycopene and tomato consumption significantly improved multiple cardiovascular risk factors including blood pressure, lipid profiles, and oxidative stress markers." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "37496241", "doi": "10.2174/1381612829666230726112510", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37496241/", "publicSourceType": "PMID" }, { "id": "enriched-8cc79f1a", "supplementName": "Lycopene", "title": "The effect of tomato and lycopene on clinical characteristics and molecular markers of UV-induced skin deterioration: A systematic review and meta-analysis of intervention trials.", "authors": "Zhang X, Zhou Q, Qi Y, Chen X, Deng J, Zhang Y et al.", "journal": "Critical Reviews in Food Science and Nutrition", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Protects against UV-induced skin deterioration", "keyFindings": [ "Lycopene supplementation provided significant photoprotective effects, reducing UV-induced skin damage markers and improving skin health parameters." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "36606553", "doi": "10.1080/10408398.2022.2164557", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36606553/", "publicSourceType": "PMID" }, { "id": "enriched-c1c01658", "supplementName": "Betaine HCL", "title": "Effects of betaine supplementation on cardiovascular markers: A systematic review and Meta-analysis.", "authors": "Ashtary-Larky D, Bagheri R, Ghanavati M, Asbaghi O, Tinsley GM, Mombaini D et al.", "journal": "Critical Reviews in Food Science and Nutrition", "year": 2022, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Improves cardiovascular markers", "keyFindings": [ "Betaine supplementation significantly reduced homocysteine levels and improved lipid profiles, reducing total cholesterol while increasing HDL cholesterol." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "33764214", "doi": "10.1080/10408398.2021.1902938", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33764214/", "publicSourceType": "PMID" }, { "id": "enriched-652b1e93", "supplementName": "Betaine HCL", "title": "Effects of chronic betaine supplementation on exercise performance: Systematic review and meta-analysis.", "authors": "Zawieja E, Machek S, Zanchi NE, Cholewa J, Woyniewicz M", "journal": "Journal of Sports Sciences", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Improves exercise performance", "keyFindings": [ "Chronic betaine supplementation improved specific exercise performance outcomes including bench press throw power and vertical jump power, though overall effects on endurance were mixed." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "39514262", "doi": "10.1080/02640414.2024.2423578", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39514262/", "publicSourceType": "PMID" }, { "id": "enriched-122baabb", "supplementName": "Betaine HCL", "title": "Betaine supplementation fails to improve body composition: a systematic review and meta-analysis.", "authors": "Ashtary-Larky D, Bagheri R, Tinsley GM, Asbaghi O, Salehpour S, Kashkooli S et al.", "journal": "British Journal of Nutrition", "year": 2022, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Effects on body composition", "keyFindings": [ "Betaine supplementation did not significantly improve overall body composition measures including body fat percentage, lean mass, or body weight in the meta-analysis of available RCTs." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "34743773", "doi": "10.1017/S0007114521004062", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34743773/", "publicSourceType": "PMID" }, { "id": "enriched-fba38ea1", "supplementName": "Digestive Enzymes", "title": "Pancreatic exocrine insufficiency and pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer: A systematic review and meta-analysis.", "authors": "Iglesia D, Avci B, Kiriukova M, Panic N, Bozhychko M, Sandru V et al.", "journal": "United European Gastroenterology Journal", "year": 2020, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Effective for pancreatic exocrine insufficiency in pancreatic cancer", "keyFindings": [ "Pancreatic enzyme replacement therapy significantly improved nutritional status, weight maintenance, and quality of life in patients with advanced pancreatic cancer and exocrine insufficiency." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "32631175", "doi": "10.1177/2050640620938987", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32631175/", "publicSourceType": "PMID" }, { "id": "enriched-e4e87082", "supplementName": "Digestive Enzymes", "title": "Exocrine Pancreatic Insufficiency Following Acute Pancreatitis: Systematic Review and Meta-Analysis.", "authors": "Huang W, de la Iglesia-Garca D, Baston-Rey I, Calvio-Surez C, Larino-Noia J, Iglesias-Garcia J et al.", "journal": "Digestive Diseases and Sciences", "year": 2019, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Important for exocrine insufficiency after acute pancreatitis", "keyFindings": [ "Exocrine pancreatic insufficiency was common after acute pancreatitis, and pancreatic enzyme replacement therapy was essential for managing malabsorption and nutritional deficiencies." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "31161524", "doi": "10.1007/s10620-019-05568-9", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31161524/", "publicSourceType": "PMID" }, { "id": "enriched-97c52e8a", "supplementName": "Digestive Enzymes", "title": "Pancreatic enzyme replacement therapy for people with cystic fibrosis.", "authors": "Somaraju URR, Solis-Moya A", "journal": "Cochrane Database of Systematic Reviews", "year": 2020, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Standard treatment for cystic fibrosis pancreatic insufficiency", "keyFindings": [ "Pancreatic enzyme replacement therapy is the standard of care for managing pancreatic insufficiency in cystic fibrosis, improving fat absorption and nutritional outcomes." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "32761612", "doi": "10.1002/14651858.CD008227.pub4", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32761612/", "publicSourceType": "PMID" }, { "id": "enriched-485b09f4", "supplementName": "Black Cohosh", "title": "Review & meta-analysis: isopropanolic black cohosh extract iCR for menopausal symptoms - an update on the evidence.", "authors": "Castelo-Branco C, Gambacciani M, Cano A, Minkin MJ, Rachon D, Ruan X et al.", "journal": "Climacteric", "year": 2021, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Reduces menopausal symptoms", "keyFindings": [ "Isopropanolic black cohosh extract significantly reduced menopausal symptoms including hot flashes, with a favorable safety profile compared to placebo in meta-analysis of RCTs." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "33021111", "doi": "10.1080/13697137.2020.1820477", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33021111/", "publicSourceType": "PMID" }, { "id": "enriched-1999bf24", "supplementName": "Black Cohosh", "title": "The efficacy of herbal medicines on anxiety and depression in peri- and postmenopausal women: A systematic review and meta-analysis.", "authors": "Shahmohammadi A, Ramezanpour N, Mahdavi Siuki M, Dizavandi F, Ghazanfarpour M, Rahmani Y et al.", "journal": "Post Reproductive Health", "year": 2019, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Reduces anxiety and depression in menopausal women", "keyFindings": [ "Black cohosh (Cimicifuga racemosa) was among the herbal medicines that showed significant improvements in anxiety and depression scores in peri- and postmenopausal women." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "31630610", "doi": "10.1177/2053369119841166", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31630610/", "publicSourceType": "PMID" }, { "id": "enriched-d1b52a27", "supplementName": "Evening Primrose Oil", "title": "The Effect of Evening Primrose Oil on Menopausal Symptoms Management: A Systematic Review and Meta-Analysis", "authors": "Larki M, Mohammadi S, Makvandi S", "journal": "J Caring Sci", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "EPO supplementation may help reduce menopausal hot flash severity and duration", "keyFindings": [ "Meta-analysis of 6 RCTs (450 women) found EPO reduced hot flash duration significantly but reductions in hot flash frequency and intensity were not statistically significant. Evidence grading was moderate to low." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "41883983", "doi": "10.34172/jcs.025.33570", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41883983/", "publicSourceType": "PMID" }, { "id": "enriched-3cb8d779", "supplementName": "Evening Primrose Oil", "title": "Evening primrose oil for cervical ripening in term pregnancies: a systematic review and meta-analysis", "authors": "Hemmatzadeh S, Mohammad Alizadeh Charandabi S, Veisy A, Mirghafourvand M", "journal": "J Complement Integr Med", "year": 2023, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "EPO may assist with cervical ripening and reducing cesarean section rates in term pregnancies", "keyFindings": [ "Meta-analysis of 9 clinical trials found EPO significantly improved Bishop score, reduced cesarean section rate, and shortened duration of first and second stages of labor compared to control." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "34261202", "doi": "10.1515/jcim-2020-0314", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34261202/", "publicSourceType": "PMID" }, { "id": "enriched-cc9d2fbc", "supplementName": "Evening Primrose Oil", "title": "Evening Primrose Oil for Menopause Hot Flashes: Systematic Review and Meta-Analysis", "authors": "Thevi T, De S, Soe HHK", "journal": "J Menopausal Med", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "EPO shows insufficient evidence for alleviating menopausal hot flashes compared to placebo", "keyFindings": [ "Systematic review found hot flash severity was lower with EPO for less than 6 months compared to placebo, but no significant difference in frequency and duration. Evidence insufficient for firm conclusions." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "39829189", "doi": "10.6118/jmm.23038", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39829189/", "publicSourceType": "PMID" }, { "id": "enriched-7ae8c2bc", "supplementName": "Evening Primrose Oil", "title": "A systematic review and meta-analysis of nutritional and dietary interventions in randomized controlled trials for skin symptoms in children with atopic dermatitis and without food allergy: An EAACI task force report", "authors": "Vassilopoulou E, Comotti A, Douladiris N et al.", "journal": "Allergy", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "EPO was included as one of several nutritional interventions for atopic dermatitis in children", "keyFindings": [ "Systematic review of 27 RCTs identified EPO among dietary interventions examined for atopic dermatitis in children. Probiotics showed the most consistent benefit; evidence for EPO and other dietary interventions remained limited." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "38783644", "doi": "10.1111/all.16160", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38783644/", "publicSourceType": "PMID" }, { "id": "enriched-3bc0d970", "supplementName": "Flaxseed Oil", "title": "Supplementation with Flaxseed Oil Rich in Alpha-Linolenic Acid Improves Verbal Fluency in Healthy Older Adults", "authors": "Ogawa T, Sawane K, Ookoshi K, Kawashima R", "journal": "Nutrients", "year": 2023, "studyType": "rct", "sampleSize": null, "outcome": "Flaxseed oil supplementation rich in alpha-linolenic acid improves verbal fluency in healthy older adults", "keyFindings": [ "In a randomized, double-blind, placebo-controlled trial of 60 healthy older adults, 12 weeks of flaxseed oil supplementation (2.2 g ALA/day) significantly improved verbal fluency scores compared to placebo." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "36986229", "doi": "10.3390/nu15061499", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36986229/", "publicSourceType": "PMID" }, { "id": "enriched-68d9e01d", "supplementName": "Flaxseed Oil", "title": "Supplementation of Olive Oil and Flaxseed Oil on Blood Pressure and Inflammation in Healthy and At-Risk Adults: A Systematic Literature Review and Meta-Analysis", "authors": "McNabb TB, Young I, Newman RG, Skinner RC, Benedito VA, Tou JC", "journal": "Curr Hypertens Rev", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Flaxseed oil and olive oil supplementation may not significantly affect blood pressure or inflammatory markers", "keyFindings": [ "Meta-analysis of 17 RCTs found no significant effect of OO and FLO supplementation on systolic blood pressure, diastolic blood pressure, CRP, IL-6, or TNF-alpha. Longer-duration, higher-dose RCTs are needed." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "39558500", "doi": "10.2174/0115734021337760241104063418", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39558500/", "publicSourceType": "PMID" }, { "id": "enriched-ee780921", "supplementName": "Flaxseed Oil", "title": "The effect of flaxseed intake on appetite reduction: A systematic review of randomized clinical trials", "authors": "Zarei M, Adeli S, Hosseini S, Daneshzad E", "journal": "Phytother Res", "year": 2022, "studyType": "review", "sampleSize": null, "outcome": "Flaxseed intake may help reduce appetite and hunger perception", "keyFindings": [ "Systematic review of 13 studies found some evidence that flaxseed reduces hunger perception and appetite, and increases fullness and satiety, though results were inconsistent across studies." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "35916016", "doi": "10.1002/ptr.7570", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35916016/", "publicSourceType": "PMID" }, { "id": "enriched-a3c24d69", "supplementName": "MCT Oil", "title": "Efficacy evaluation of medium-chain triglycerides supplementation on acute severe encephalopathy", "authors": "Zuo Y, Wu H, Liu P, Bian Z, Lu Z, Zhang B", "journal": "Nutr Neurosci", "year": 2025, "studyType": "rct", "sampleSize": null, "outcome": "MCT supplementation may improve neurological outcomes in acute severe encephalopathy patients", "keyFindings": [ "Double-blind randomized trial of 46 patients found MCT supplementation significantly reduced poor neurologic outcomes at 180 days (26.1% vs 56.5%), shortened coma duration, mechanical ventilation time, and ICU stay." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "40674442", "doi": "10.1080/1028415X.2025.2525513", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40674442/", "publicSourceType": "PMID" }, { "id": "enriched-030b3bd1", "supplementName": "MCT Oil", "title": "Eicosapentaenoic Acid and Medium-Chain Triacylglycerol Structured Lipids Improve Endurance Performance", "authors": "Tsuji K, Tsuchiya Y, Yokoi K, Yanagimoto K, Ueda H, Ochi E", "journal": "Nutrients", "year": 2023, "studyType": "rct", "sampleSize": null, "outcome": "MCT-enriched structured lipids with EPA improve endurance performance", "keyFindings": [ "8-week randomized double-blind trial in 19 men found interesterified structured lipids containing EPA and MCTs significantly improved time to exhaustion and time to reach anaerobic threshold compared to physical mixture." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "37686724", "doi": "10.3390/nu15173692", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37686724/", "publicSourceType": "PMID" }, { "id": "enriched-8ea9cce3", "supplementName": "MCT Oil", "title": "Ketogenic Effects of Multiple Doses of a Medium Chain Triglycerides Enriched Ketogenic Formula in Healthy Men under the Ketogenic Diet: A Randomized, Double-Blinded, Placebo-Controlled Study", "authors": "Nakamura K, Hagihara K, Nagai N, Egashira R et al.", "journal": "Nutrients", "year": 2022, "studyType": "rct", "sampleSize": null, "outcome": "MCT-enriched ketogenic formula is safe and increases blood ketone bodies under ketogenic diet", "keyFindings": [ "Randomized double-blind placebo-controlled trial in 20 healthy men found MCT-enriched ketogenic formula significantly increased blood ketone bodies on day 4 of administration with no significant safety issues." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "35334856", "doi": "10.3390/nu14061199", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35334856/", "publicSourceType": "PMID" }, { "id": "enriched-14cff253", "supplementName": "Krill Oil", "title": "Effectiveness of a Novel omega-3 Krill Oil Agent in Patients With Severe Hypertriglyceridemia: A Randomized Clinical Trial", "authors": "Mozaffarian D, Maki KC, Bays HE et al.", "journal": "JAMA Netw Open", "year": 2022, "studyType": "rct", "sampleSize": null, "outcome": "Krill oil reduces triglyceride levels in patients with severe hypertriglyceridemia", "keyFindings": [ "Phase 3 RCT of 520 patients with severe hypertriglyceridemia found krill oil-derived omega-3 reduced TG levels by 26.0% vs 15.1% for placebo at 12 weeks (treatment difference -10.9%, p=0.02). Safe and well-tolerated." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "34989797", "doi": "10.1001/jamanetworkopen.2021.41898", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34989797/", "publicSourceType": "PMID" }, { "id": "enriched-6f408247", "supplementName": "Krill Oil", "title": "Krill Oil for Knee Osteoarthritis: A Randomized Clinical Trial", "authors": "Laslett LL, Scheepers LEJM, Antony B et al.", "journal": "JAMA", "year": 2024, "studyType": "rct", "sampleSize": null, "outcome": "Krill oil did not improve knee pain in osteoarthritis compared to placebo in a large RCT", "keyFindings": [ "Multicenter RCT of 262 participants found 2 g/day krill oil for 24 weeks did not improve knee pain compared to placebo in patients with knee osteoarthritis and effusion-synovitis." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "38776073", "doi": "10.1001/jama.2024.6063", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38776073/", "publicSourceType": "PMID" }, { "id": "enriched-6cf64ba5", "supplementName": "Krill Oil", "title": "Krill oil for knee osteoarthritis: A meta-analysis of randomized controlled trials", "authors": "Meng J, Wang X, Li Y, Xiang Y, Wu Y, Xiong Y, Liu P, Gao S", "journal": "Medicine (Baltimore)", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Meta-analysis suggests krill oil may benefit WOMAC pain, stiffness, and function in knee osteoarthritis", "keyFindings": [ "Meta-analysis of 5 RCTs (730 participants) found krill oil showed significant benefits in WOMAC pain, stiffness, and functional outcomes, but no significant improvement in VAS pain scores compared to usual care." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "39960912", "doi": "10.1097/MD.0000000000041566", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39960912/", "publicSourceType": "PMID" }, { "id": "enriched-fb0e7a83", "supplementName": "Omega-7", "title": "Treatment of Resistant Acne Vulgaris in Adolescents Using Dietary Supplementation with Magnesium, Phosphate and Fatty Acids (Omega 6 and 7): Comparison with 13-Cis-Retinoic Acid", "authors": "de Souza Pereira R", "journal": "J Diet Suppl", "year": 2023, "studyType": "rct", "sampleSize": null, "outcome": "Palmitoleic acid (omega-7) combined with magnesium, phosphate, and omega-6 may improve acne vulgaris", "keyFindings": [ "Single-blind randomized study of 532 patients found dietary supplementation with omega-6, omega-7, magnesium, and phosphate achieved 100% complete symptom regression vs 68% for isotretinoin in acne vulgaris treatment over 6 months." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "35876008", "doi": "10.1080/19390211.2022.2100550", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35876008/", "publicSourceType": "PMID" }, { "id": "enriched-8648f039", "supplementName": "Omega-7", "title": "Macadamia nut effects on cardiometabolic risk factors: a randomised trial", "authors": "Jones JL, Sabate J, Heskey C, Oda K, Miles F, Rajaram S", "journal": "J Nutr Sci", "year": 2023, "studyType": "rct", "sampleSize": null, "outcome": "Macadamia nut consumption (rich in palmitoleic acid/omega-7) does not cause weight gain and may lower cholesterol", "keyFindings": [ "Randomized crossover trial in 35 overweight/obese adults found daily macadamia nut consumption (~15% calories) did not increase weight or body fat and showed non-significant reductions in total cholesterol (-2.1%) and LDL-C (-4%)." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "37180485", "doi": "10.1017/jns.2023.39", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37180485/", "publicSourceType": "PMID" }, { "id": "enriched-e831f744", "supplementName": "CLA", "title": "The effects of conjugated linoleic acid supplementation on cardiovascular risk factors in patients at risk of cardiovascular disease: A GRADE-assessed systematic review and dose-response meta-analysis", "authors": "Esmaeilnejad M, Rasaei N, Goudarzi K et al.", "journal": "Br J Nutr", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "CLA supplementation produces small but significant reductions in body weight and body fat in CVD-risk patients", "keyFindings": [ "Meta-analysis of 14 RCTs found CLA significantly reduced body weight (-0.72 kg), BMI (-0.22 kg/m2), and body fat percentage (-1.32%) in CVD-risk patients. No effect on lipid profile or blood pressure." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "39439191", "doi": "10.1017/S0007114524001065", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39439191/", "publicSourceType": "PMID" }, { "id": "enriched-872fb185", "supplementName": "CLA", "title": "The effect of conjugated linoleic acid supplementation on oxidative stress markers: A systematic review and meta-analysis of randomized controlled trials", "authors": "Suksatan W, Putera HD, Abdulkadhim AH et al.", "journal": "Clin Nutr ESPEN", "year": 2022, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "CLA supplementation may reduce malondialdehyde (MDA) but increases 8-iso-PGF2alpha, suggesting mixed effects on oxidative stress", "keyFindings": [ "Meta-analysis of 11 RCTs found CLA significantly decreased MDA concentrations and increased 8-iso-PGF2alpha levels. No significant change in GPx concentrations." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "35623803", "doi": "10.1016/j.clnesp.2022.04.004", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35623803/", "publicSourceType": "PMID" }, { "id": "enriched-ff175ffa", "supplementName": "CLA", "title": "The effects of supplementation with conjugated linoleic acid on anthropometric indices and body composition in overweight and obese subjects: A systematic review and meta-analysis", "authors": "Namazi N, Irandoost P, Larijani B, Azadbakht L", "journal": "Crit Rev Food Sci Nutr", "year": 2019, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "CLA produces small reductions in body weight and fat mass in overweight and obese subjects", "keyFindings": [ "Meta-analysis of 13 trials found CLA significantly reduced body weight (-0.52 kg), BMI (-0.23 kg/m2), fat mass (-0.61 kg) and increased lean body mass (+0.19 kg), but effects were small and may not be clinically significant." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "29672124", "doi": "10.1080/10408398.2018.1466107", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/29672124/", "publicSourceType": "PMID" }, { "id": "enriched-257aeae0", "supplementName": "CLA", "title": "Efficacy of dietary supplements containing isolated organic compounds for weight loss: a systematic review and meta-analysis of randomised placebo-controlled trials", "authors": "Bessell E, Maunder A, Lauche R, Adams J, Sainsbury A, Fuller NR", "journal": "Int J Obes (Lond)", "year": 2021, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "CLA produces statistically significant but not clinically significant weight loss compared to placebo", "keyFindings": [ "Meta-analysis of 67 RCTs found CLA produced statistically significant weight difference of -1.08 kg vs placebo (p<0.01), but this did not meet the threshold for clinical significance (>=2.5 kg)." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "33976376", "doi": "10.1038/s41366-021-00839-w", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33976376/", "publicSourceType": "PMID" }, { "id": "enriched-cf9b6883", "supplementName": "Holy Basil/Tulsi", "title": "Benefits of basil tea for patients with differentiated thyroid cancer during radioiodine therapy: A randomized controlled trial", "authors": "Nomura K, Nakayama M, Okizaki A", "journal": "Heliyon", "year": 2023, "studyType": "rct", "sampleSize": null, "outcome": "Holy basil (Ocimum tenuiflorum) tea reduces anxiety and protects oral health during radioiodine therapy", "keyFindings": [ "RCT of 44 thyroid cancer patients found holy basil tea significantly reduced STAI anxiety scores, protected oral mucosal conditions and salivary gland function, and improved quality of life during radioiodine therapy." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "37829808", "doi": "10.1016/j.heliyon.2023.e20691", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37829808/", "publicSourceType": "PMID" }, { "id": "enriched-e2cf2134", "supplementName": "Holy Basil/Tulsi", "title": "Randomized placebo-controlled pilot clinical trial on the efficacy of ayurvedic treatment regime on COVID-19 positive patients", "authors": "Devpura G, Tomar BS, Nathiya D et al.", "journal": "Phytomedicine", "year": 2021, "studyType": "rct", "sampleSize": null, "outcome": "Ayurvedic treatment including Tulsi (Ocimum sanctum) may expedite COVID-19 recovery and reduce inflammation", "keyFindings": [ "RCT in asymptomatic COVID-19 patients found Ayurvedic treatment including Tulsi achieved 100% recovery by day 7 vs 60% in placebo. Inflammatory markers (hs-CRP, IL-6, TNF-alpha) were significantly lower in treatment group." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "33596494", "doi": "10.1016/j.phymed.2021.153494", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33596494/", "publicSourceType": "PMID" }, { "id": "enriched-82998677", "supplementName": "Holy Basil/Tulsi", "title": "Antibacterial efficacy of manuka honey, ocimum sanctum, curcuma longa and 0.2% chlorhexidine mouthwash on the level of streptococcus mutans and lactobacillus acidophilus - A randomized controlled trial", "authors": "Jain A, Singh V, Lukram A, Chatterjee S, Khan AM, Dawar G", "journal": "Indian J Dent Res", "year": 2022, "studyType": "rct", "sampleSize": null, "outcome": "Ocimum sanctum mouthwash has antibacterial efficacy comparable to chlorhexidine against oral pathogens", "keyFindings": [ "RCT found Ocimum sanctum mouthwash showed significant percentage reduction in S. mutans and L. acidophilus comparable to 0.2% chlorhexidine mouthwash." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "36254954", "doi": "10.4103/ijdr.ijdr_159_22", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36254954/", "publicSourceType": "PMID" }, { "id": "enriched-7ec385e3", "supplementName": "Schisandra", "title": "Effect of Schisandra chinensis Baillon extracts and regular low-intensity exercise on muscle strength and mass in older adults: a randomized, double-blind, placebo-controlled trial", "authors": "Cho YH, Lee SY, Lee CH, Park JH, So YS", "journal": "Am J Clin Nutr", "year": 2021, "studyType": "rct", "sampleSize": null, "outcome": "Schisandra chinensis extract enhances muscle strength in older adults performing low-intensity exercise", "keyFindings": [ "RCT of 54 adults >50 years found 12 weeks of Schisandra chinensis extract (1 g/day) significantly increased right knee extensor strength (+10.2 Nm) and left knee extensor strength (+6.7 Nm) compared to placebo, without adverse events." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "33710261", "doi": "10.1093/ajcn/nqaa447", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33710261/", "publicSourceType": "PMID" }, { "id": "enriched-0d0a7575", "supplementName": "Schisandra", "title": "Effect of Schisandra Chinensis Extract Supplementation on Quadriceps Muscle Strength and Fatigue in Adult Women: A Randomized, Double-Blind, Placebo-Controlled Trial", "authors": "Park J, Han S, Park H", "journal": "Int J Environ Res Public Health", "year": 2020, "studyType": "rct", "sampleSize": null, "outcome": "Schisandra chinensis extract improves quadriceps muscle strength and reduces lactate in post-menopausal women", "keyFindings": [ "RCT of 45 post-menopausal women found 12 weeks of SC extract (1000 mg/day) significantly increased quadriceps muscle strength and decreased resting lactate levels." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "32260466", "doi": "10.3390/ijerph17072475", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/32260466/", "publicSourceType": "PMID" }, { "id": "enriched-bb104024", "supplementName": "Schisandra", "title": "Efficacy and Safety of Omija (Schisandra chinensis) Extract Mixture on the Improvement of Hyperglycemia: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial", "authors": "Kim DS, Baek HI, Ha KC, Cha YS, Park SJ", "journal": "Nutrients", "year": 2022, "studyType": "rct", "sampleSize": null, "outcome": "Schisandra chinensis extract may improve glycemic control in individuals with hyperglycemia", "keyFindings": [ "RCT of 80 participants with hyperglycemia found 12 weeks of Omija/Schisandra extract mixture significantly decreased fasting plasma glucose, postprandial glucose, fructosamine, and LDL cholesterol compared to placebo." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "35956334", "doi": "10.3390/nu14153159", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35956334/", "publicSourceType": "PMID" }, { "id": "enriched-86fa36b8", "supplementName": "Schisandra", "title": "A randomized, double-blind, placebo-controlled trial of Schisandra chinensis for menopausal symptoms", "authors": "Park JY, Kim KH", "journal": "Climacteric", "year": 2016, "studyType": "rct", "sampleSize": null, "outcome": "Schisandra chinensis extract reduces menopausal symptoms including hot flushes and sweating", "keyFindings": [ "RCT of 36 menopausal women found Schisandra chinensis extract (BMO-30) significantly reduced total Kupperman Index scores compared to placebo, especially for hot flushes, sweating, and heart palpitations." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "27763802", "doi": "10.1080/13697137.2016.1238453", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27763802/", "publicSourceType": "PMID" }, { "id": "enriched-71a764a7", "supplementName": "Passionflower", "title": "Effects of passiflora incarnata and midazolam for control of anxiety in patients undergoing dental extraction", "authors": "Dantas LP, de Oliveira-Ribeiro A, de Almeida-Souza LM, Groppo FC", "journal": "Med Oral Patol Oral Cir Bucal", "year": 2017, "studyType": "rct", "sampleSize": null, "outcome": "Passiflora incarnata reduces anxiety during dental procedures similar to pharmaceutical anxiolytics", "keyFindings": [ "Double-blind crossover RCT of 40 volunteers found Passiflora incarnata showed anxiolytic effect similar to midazolam for conscious sedation during dental extraction, without the amnesia side effect of midazolam." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "27918731", "doi": "10.4317/medoral.21140", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27918731/", "publicSourceType": "PMID" }, { "id": "enriched-c235b8f0", "supplementName": "Passionflower", "title": "Effects of Passiflora incarnata and Valeriana officinalis in the control of anxiety due to tooth extraction: a randomized controlled clinical trial", "authors": "Velasquez ACA, Tsuji M, Dos Santos Cordeiro L et al.", "journal": "Oral Maxillofac Surg", "year": 2024, "studyType": "rct", "sampleSize": null, "outcome": "Passiflora incarnata reduces anxiety during tooth extraction procedures", "keyFindings": [ "Triple-blind RCT of 54 patients found both Passiflora incarnata and Valeriana officinalis significantly reduced state anxiety scores compared to placebo during third molar extraction." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "38743126", "doi": "10.1007/s10006-024-01259-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38743126/", "publicSourceType": "PMID" }, { "id": "enriched-69c6b536", "supplementName": "Olive Leaf Extract", "title": "Olive leaf extract effect on cardiometabolic risk factors: a systematic review and meta-analysis of randomized clinical trials", "authors": "Alvares AA, Garcez A, Silva LT, Averbuch N, Garavaglia J", "journal": "Nutr Rev", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Olive leaf extract may improve cardiometabolic risk factors including blood pressure and glucose metabolism", "keyFindings": [ "Systematic review and meta-analysis of 12 RCTs (703 patients) found OLE showed positive correlations with glucose metabolism (4 RCTs), blood pressure (2 RCTs), lipid profile (2 RCTs), and inflammatory markers (2 RCTs)." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "38287654", "doi": "10.1093/nutrit/nuad164", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38287654/", "publicSourceType": "PMID" }, { "id": "enriched-60946dd1", "supplementName": "Olive Leaf Extract", "title": "Olive Leaf Extract Supplementation Improves Postmenopausal Symptoms: A Randomized, Double-Blind, Placebo-Controlled Parallel Study on Postmenopausal Women", "authors": "Imperatrice M, Lasfar A, van Kalkeren CAJ, Troost F", "journal": "Nutrients", "year": 2024, "studyType": "rct", "sampleSize": null, "outcome": "Olive leaf extract improves postmenopausal symptoms and reduces triglycerides", "keyFindings": [ "RCT of 60 postmenopausal women found 12 weeks of OLE (250 mg/day) significantly improved MENQoL scores, increased BMD in the right arm, and decreased triglycerides and TG/HDL-C ratio compared to placebo." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "39599665", "doi": "10.3390/nu16223879", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39599665/", "publicSourceType": "PMID" }, { "id": "enriched-b9f999b7", "supplementName": "Olive Leaf Extract", "title": "Phenolic-rich extract of olive leaf with a hypocaloric diet alleviates oxidative stress in obese females: a randomized double-blind placebo controlled trial", "authors": "Haidari F, Mohammad-Shahi M, Jalali MT, Ahmadi-Angali K, Shayesteh F", "journal": "Nutr Metab Cardiovasc Dis", "year": 2025, "studyType": "rct", "sampleSize": null, "outcome": "Olive leaf extract reduces oxidative stress markers (malondialdehyde) in obese women on a calorie-restricted diet", "keyFindings": [ "RCT of 70 obese women found OLE (250 mg/day) combined with a hypocaloric diet for 8 weeks significantly reduced serum malondialdehyde compared to placebo + hypocaloric diet." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "40685267", "doi": "10.1016/j.numecd.2025.104097", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40685267/", "publicSourceType": "PMID" }, { "id": "enriched-186d8a10", "supplementName": "Olive Leaf Extract", "title": "Impact of olive leaf extract on pain management and functional improvement in elderly patients with knee osteoarthritis: A randomized controlled trial", "authors": "Roshani M, Delfan B, Yarahmadi S, Saki M, Birjandi M", "journal": "Explore (NY)", "year": 2025, "studyType": "rct", "sampleSize": null, "outcome": "Olive leaf extract reduces pain and improves physical functioning in elderly patients with knee osteoarthritis", "keyFindings": [ "RCT of 100 elderly patients with knee osteoarthritis found OLE (oral and/or topical) significantly reduced pain scores and improved daily functioning. Combination of oral and topical showed the most pronounced effects." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "39955806", "doi": "10.1016/j.explore.2025.103136", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39955806/", "publicSourceType": "PMID" }, { "id": "enriched-9b77988e", "supplementName": "Moringa", "title": "Moringa oleifera Leaf Supplementation as a Glycemic Control Strategy in Subjects with Prediabetes", "authors": "Gomez-Martinez S, Diaz-Prieto LE, Vicente Castro I et al.", "journal": "Nutrients", "year": 2021, "studyType": "rct", "sampleSize": null, "outcome": "Moringa oleifera leaf supplementation improves glycemic control in subjects with prediabetes", "keyFindings": [ "Double-blind RCT of 65 subjects with prediabetes found 12 weeks of Moringa oleifera leaf supplementation (2400 mg/day) resulted in favorable changes in fasting blood glucose and HbA1c compared to placebo." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "35010932", "doi": "10.3390/nu14010057", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35010932/", "publicSourceType": "PMID" }, { "id": "enriched-a1ce0c55", "supplementName": "Moringa", "title": "Effects of Moringa oleifera Lam. Supplementation on Cardiometabolic Outcomes: A Meta-Analysis of Randomized Controlled Trials with GRADE Assessment", "authors": "Crisan D, Gavrilas L, Paltinean R, Frumuzachi O, Mocan A, Crisan G", "journal": "Nutrients", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Moringa supplementation shows modest reduction in diastolic blood pressure but no consistent cardiometabolic benefits", "keyFindings": [ "Meta-analysis of 9 RCTs (649 participants) found moringa showed a modest reduction in diastolic blood pressure (SMD: -0.41) but no significant effects on most cardiometabolic outcomes. Overall certainty of evidence was very low." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "41305552", "doi": "10.3390/nu17223501", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/41305552/", "publicSourceType": "PMID" }, { "id": "enriched-eb5e8f5b", "supplementName": "Moringa", "title": "Synergistic effect of Moringa oleifera and Allium sativum on BMI and lipid profile: A randomized controlled trial", "authors": "Sarfraz A, Hussain MI, Ibtisam R et al.", "journal": "Pak J Pharm Sci", "year": 2023, "studyType": "rct", "sampleSize": null, "outcome": "Moringa oleifera combined with Allium sativum improves lipid profile in hyperlipidemic patients", "keyFindings": [ "RCT of 60 hyperlipidemic patients found Moringa oleifera supplementation (2 g/day for 45 days) significantly improved total cholesterol, triglycerides, and LDL compared to statin alone." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "38008957", "doi": "10.3390/nu14010057", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38008957/", "publicSourceType": "PMID" }, { "id": "enriched-e1a8f8b2", "supplementName": "Colostrum", "title": "The effect of 12-week high-dose Colostrum Bovinum supplementation on immunological, hematological and biochemical markers in endurance athletes: a randomized crossover placebo-controlled study", "authors": "Durkalec-Michalski K, Glowka N, Podgorski T, Wozniewicz M, Nowaczyk PM", "journal": "Front Immunol", "year": 2024, "studyType": "rct", "sampleSize": null, "outcome": "Bovine colostrum supplementation increases post-exercise salivary IgA in endurance athletes", "keyFindings": [ "Randomized crossover study in 28 endurance-trained males found 12-week bovine colostrum supplementation (25 g/day) significantly increased post-exercise secretory IgA concentration in saliva, suggesting enhanced local immune defense." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "39497827", "doi": "10.3389/fimmu.2024.1425785", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39497827/", "publicSourceType": "PMID" }, { "id": "enriched-9a81588e", "supplementName": "Colostrum", "title": "Bovine colostrum to supplement the first feeding of very preterm infants: The PreColos randomized controlled trial", "authors": "Yan X, Pan X, Ding L et al.", "journal": "Clin Nutr", "year": 2023, "studyType": "rct", "sampleSize": null, "outcome": "Bovine colostrum supplementation in preterm infants did not reduce time to full enteral feeding", "keyFindings": [ "Multicenter RCT of 350 very preterm infants found bovine colostrum supplementation during the first 14 days of life did not reduce time to full enteral feeding and had only marginal effects on clinical variables compared to preterm formula." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "37437359", "doi": "10.1016/j.clnu.2023.06.024", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37437359/", "publicSourceType": "PMID" }, { "id": "enriched-ae446461", "supplementName": "Colostrum", "title": "Effects of different dietary supplements on athletic performance in soccer players: a systematic review and network meta-analysis", "authors": "Luo H, Tengku Kamalden TF, Zhu X, Xiang C, Nasharuddin NA", "journal": "J Int Soc Sports Nutr", "year": 2025, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Bovine colostrum is identified as potentially effective for improving athletic performance in soccer players", "keyFindings": [ "Network meta-analysis of 80 RCTs identified bovine colostrum as having a moderate significant effect on increasing distance covered in soccer players compared to placebo." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "39972597", "doi": "10.1080/15502783.2025.2467890", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39972597/", "publicSourceType": "PMID" }, { "id": "enriched-26f471f9", "supplementName": "Bee Pollen", "title": "Effects of bee pollen inclusion on performance and carcass characteristics of broiler chickens", "authors": "Nemauluma MFD, Manyelo TG, Ng'ambi JW, Kolobe SD, Malematja E", "journal": "Poult Sci", "year": 2023, "studyType": "review", "sampleSize": null, "outcome": "Bee pollen supplementation improves growth performance in broiler chickens", "keyFindings": [ "RCT in 240 broiler chickens found bee pollen inclusion (4-12 g/kg) significantly improved feed intake, body weight, body weight gain, feed conversion ratio, and carcass yield without adverse effects on meat quality." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "37043957", "doi": "10.1016/j.psj.2023.102628", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37043957/", "publicSourceType": "PMID" }, { "id": "enriched-5f64858a", "supplementName": "Royal Jelly", "title": "A Randomized, Double-Blind Comparison Study of Royal Jelly to Augment Vascular Endothelial Function in Healthy Volunteers", "authors": "Fujisue K, Yamamoto E, Sueta D et al.", "journal": "J Atheroscler Thromb", "year": 2022, "studyType": "rct", "sampleSize": null, "outcome": "Royal jelly improves vascular endothelial function in healthy volunteers", "keyFindings": [ "RCT of 100 healthy volunteers found 4 weeks of royal jelly supplementation (690 mg/day) significantly improved vascular endothelial function (RH-PAT index) and liver function markers compared to placebo." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "34588374", "doi": "10.5551/jat.63044", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34588374/", "publicSourceType": "PMID" }, { "id": "enriched-38bae496", "supplementName": "Royal Jelly", "title": "Royal jelly plus coenzyme Q10 supplementation improves high-intensity interval exercise performance via changes in plasmatic and salivary biomarkers of oxidative stress and muscle damage in swimmers: a randomized, double-blind, placebo-controlled pilot trial", "authors": "Ovchinnikov AN, Paoli A, Seleznev VV, Deryugina AV", "journal": "J Int Soc Sports Nutr", "year": 2022, "studyType": "rct", "sampleSize": null, "outcome": "Royal jelly plus coenzyme Q10 improves exercise performance and reduces oxidative stress in swimmers", "keyFindings": [ "RCT of 20 swimmers found 10 days of RJ + CoQ10 supplementation significantly improved HIIE performance and reduced exercise-induced lipid peroxidation and muscle damage biomarkers." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "35813842", "doi": "10.1080/15502783.2022.2086015", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35813842/", "publicSourceType": "PMID" }, { "id": "enriched-3c5442ca", "supplementName": "Royal Jelly", "title": "Apitherapy with Royal Jelly and Green Propolis EPP-AF improves cardiovascular risk markers in patients undergoing hemodialysis", "authors": "Kemp JA, Mendonca M, Chrispim P et al.", "journal": "Toxins (Basel)", "year": 2025, "studyType": "rct", "sampleSize": null, "outcome": "Royal jelly combined with green propolis reduces IL-6 and cholesterol in hemodialysis patients", "keyFindings": [ "RCT of 38 hemodialysis patients found 2 months of royal jelly + green propolis supplementation significantly reduced IL-6 and total cholesterol, showing promise as a cardiovascular risk reduction strategy." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "40864045", "doi": "10.3390/toxins17080369", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40864045/", "publicSourceType": "PMID" }, { "id": "enriched-aae67209", "supplementName": "Royal Jelly", "title": "Aerobic-Resistance Training with Royal Jelly Supplementation Has a Synergistic Effect on Paraoxonase 1 Changes and Liver Function in Women with MASLD", "authors": "Askari R, Rabani N, Marefati H, Azarnive MS, Pusceddu M, Migliaccio GM", "journal": "Medicina (Kaunas)", "year": 2025, "studyType": "rct", "sampleSize": null, "outcome": "Royal jelly supplementation with exercise improves liver function and lipid profile in women with MASLD", "keyFindings": [ "RCT of 23 women with MASLD found 8 weeks of exercise + royal jelly significantly increased PON1 and HDL while decreasing oxLDL, TC, TG, LDL, ALT, and AST compared to exercise + placebo." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "40005465", "doi": "10.3390/medicina61020349", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/40005465/", "publicSourceType": "PMID" }, { "id": "enriched-16329e45", "supplementName": "Cat's Claw", "title": "Evaluation of different treatment methods against denture stomatitis: a randomized clinical study", "authors": "Tay LY, Jorge JH, Herrera DR, Campanha NH, Gomes BP, Andre Dos Santos F", "journal": "Oral Surg Oral Med Oral Pathol Oral Radiol", "year": 2014, "studyType": "rct", "sampleSize": null, "outcome": "Uncaria tomentosa (cat's claw) gel is effective as topical treatment for denture stomatitis", "keyFindings": [ "RCT of 50 patients with denture stomatitis found 2% Uncaria tomentosa gel was equally effective as 2% miconazole gel in treating denture stomatitis, reducing both severity and Candida colony counts." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "24908596", "doi": "10.1016/j.oooo.2014.03.017", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/24908596/", "publicSourceType": "PMID" }, { "id": "enriched-e31d7e9b", "supplementName": "Artemisinin", "title": "Artemether for severe malaria", "authors": "Esu EB, Effa EE, Opie ON, Meremikwu MM", "journal": "Cochrane Database Syst Rev", "year": 2019, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Intramuscular artemether is more effective than quinine for treating severe malaria in adults", "keyFindings": [ "Cochrane review of 19 RCTs (2874 patients) found intramuscular artemether probably results in fewer deaths than quinine in adults (RR 0.59) and is as effective in children. Artemether is inferior to artesunate in adults." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "31210357", "doi": "10.1002/14651858.CD010678.pub3", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/31210357/", "publicSourceType": "PMID" }, { "id": "enriched-5455cb54", "supplementName": "Artemisinin", "title": "Efficacy and safety of praziquantel plus artemisinin-based combinations versus praziquantel in the treatment of Kenyan children with Schistosoma mansoni infection: open-label, randomized, head-to-head, non-inferiority trial", "authors": "Obonyo CO, Were VO, Wamae P, Muok EMO", "journal": "Antimicrob Agents Chemother", "year": 2025, "studyType": "rct", "sampleSize": null, "outcome": "Artemisinin-based combinations with praziquantel are effective for treating Schistosoma mansoni", "keyFindings": [ "RCT of 540 Kenyan children found praziquantel plus artesunate-mefloquine and praziquantel plus dihydroartemisinin-piperaquine were non-inferior to praziquantel alone for treating S. mansoni infection." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "39699212", "doi": "10.1128/aac.00739-24", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39699212/", "publicSourceType": "PMID" }, { "id": "enriched-5065658a", "supplementName": "L-Glutathione", "title": "The effects of the oral supplementation of L-Cystine associated with reduced L-Glutathione-GSH on human skin pigmentation: a randomized, double-blinded, benchmark- and placebo-controlled clinical trial", "authors": "Duperray J, Sergheraert R, Chalothorn K, Tachalerdmanee P, Perin F", "journal": "J Cosmet Dermatol", "year": 2022, "studyType": "rct", "sampleSize": null, "outcome": "Oral L-Glutathione combined with L-Cystine lightens skin and reduces dark spots", "keyFindings": [ "RCT of 124 Asian women found 12 weeks of oral L-Cystine (500 mg) + L-Glutathione (250 mg) significantly lightened skin and reduced facial dark spot size, outperforming placebo and either compound alone." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "33834608", "doi": "10.1111/jocd.14137", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33834608/", "publicSourceType": "PMID" }, { "id": "enriched-500d3684", "supplementName": "Phosphatidylcholine", "title": "Differential metabolism of choline supplements in adult volunteers", "authors": "Bockmann KA, Franz AR, Minarski M et al.", "journal": "Eur J Nutr", "year": 2022, "studyType": "rct", "sampleSize": null, "outcome": "Different choline supplement forms (including phosphatidylcholine) are differentially metabolized in adults", "keyFindings": [ "Randomized crossover study in 6 healthy men found all choline supplements (choline chloride, bitartrate, alpha-GPC, egg-PC) increased choline and betaine levels. Egg-PC showed latest peak and lowest TMAO formation, suggesting it may be the best choline source." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "34287673", "doi": "10.1007/s00394-021-02637-6", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34287673/", "publicSourceType": "PMID" }, { "id": "enriched-9e34b3fd", "supplementName": "Phosphatidylcholine", "title": "Different choline supplement metabolism in adults using deuterium labelling", "authors": "Bockmann KA, Franz AR, Shunova A et al.", "journal": "Eur J Nutr", "year": 2023, "studyType": "rct", "sampleSize": null, "outcome": "Phosphatidylcholine (as POPC) is the optimal choline supplement form for increasing plasma PC levels with minimal TMAO", "keyFindings": [ "Deuterium-labelled crossover study in 6 men found D9-POPC (phosphatidylcholine) resulted in highest plasma D9-PC concentrations and virtually absent TMAO levels, suggesting it is the best choline supplement form for increasing PC." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "36840817", "doi": "10.1007/s00394-023-03121-z", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36840817/", "publicSourceType": "PMID" }, { "id": "enriched-d2d6b7c9", "supplementName": "Phosphatidylcholine", "title": "Pharmacokinetics of soy-derived lysophosphatidylcholine compared with that of glycerophosphocholine: a randomized controlled trial", "authors": "Tanaka-Kanegae R, Kimura H, Hamada K", "journal": "Biosci Biotechnol Biochem", "year": 2024, "studyType": "rct", "sampleSize": null, "outcome": "Soy-derived lysophosphatidylcholine is an effective choline source comparable to glycerophosphocholine", "keyFindings": [ "RCT in 12 healthy men found soy-derived lysophosphatidylcholine (LPC) and glycerophosphocholine similarly increased plasma choline, phospholipid, and triglyceride concentrations without significantly elevating TMAO." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "38490741", "doi": "10.1093/bbb/zbae031", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38490741/", "publicSourceType": "PMID" }, { "id": "enriched-386c3d9f", "supplementName": "Alpha-GPC", "title": "Acute Alpha-Glycerylphosphorylcholine Supplementation Enhances Cognitive Performance in Healthy Men", "authors": "Kerksick CM", "journal": "Nutrients", "year": 2024, "studyType": "rct", "sampleSize": null, "outcome": "Acute alpha-GPC supplementation enhances cognitive performance in healthy men", "keyFindings": [ "Randomized crossover trial of 20 healthy men found acute A-GPC supplementation (315-630 mg) significantly improved Stroop total score and completion time compared to placebo, indicating enhanced cognitive function." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "39683633", "doi": "10.3390/nu16234240", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39683633/", "publicSourceType": "PMID" }, { "id": "enriched-ad92975f", "supplementName": "Alpha-GPC", "title": "Activity of Choline Alphoscerate on Adult-Onset Cognitive Dysfunctions: A Systematic Review and Meta-Analysis", "authors": "Sagaro GG, Traini E, Amenta F", "journal": "J Alzheimers Dis", "year": 2023, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Alpha-GPC alone or combined with donepezil improves cognition and behavioral outcomes in patients with cognitive impairment", "keyFindings": [ "Meta-analysis of 7 RCTs and 1 cohort study found alpha-GPC alone improved cognition (MD: 3.50) and in combination with donepezil improved cognition, functional outcomes, and behavioral outcomes in patients with cerebrovascular-related cognitive impairment." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "36683513", "doi": "10.3233/JAD-221189", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36683513/", "publicSourceType": "PMID" }, { "id": "enriched-cc2d2dc3", "supplementName": "Alpha-GPC", "title": "Effects of egg yolk choline intake on cognitive functions and plasma choline levels in healthy middle-aged and older Japanese: a randomized double-blinded placebo-controlled parallel-group study", "authors": "Yamashita S, Kawada N, Wang W et al.", "journal": "Lipids Health Dis", "year": 2023, "studyType": "rct", "sampleSize": null, "outcome": "Egg yolk choline intake improves verbal memory in healthy older adults", "keyFindings": [ "RCT of 41 older adults found 12 weeks of egg yolk choline supplementation (300 mg/day, containing PC, LPC, and alpha-GPC) significantly improved verbal memory scores compared to placebo." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "37340479", "doi": "10.1186/s12944-023-01844-w", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/37340479/", "publicSourceType": "PMID" }, { "id": "enriched-330d5e02", "supplementName": "Citicoline", "title": "Citicoline and Memory Function in Healthy Older Adults: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial", "authors": "Nakazaki E, Mah E, Sanoshy K, Citrolo D, Watanabe F", "journal": "J Nutr", "year": 2021, "studyType": "rct", "sampleSize": null, "outcome": "Citicoline supplementation improves memory performance, especially episodic memory, in healthy older adults", "keyFindings": [ "RCT of 100 healthy older adults with age-associated memory impairment found 12 weeks of citicoline (500 mg/day) significantly improved episodic memory and composite memory scores compared to placebo." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "33978188", "doi": "10.1093/jn/nxab119", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33978188/", "publicSourceType": "PMID" }, { "id": "enriched-2262e024", "supplementName": "Citicoline", "title": "Citicoline in acute ischemic stroke: A randomized controlled trial", "authors": "Agarwal A, Vishnu VY, Sharma J et al.", "journal": "PLoS One", "year": 2022, "studyType": "rct", "sampleSize": null, "outcome": "Citicoline did not improve clinical or radiological outcomes in acute ischemic stroke patients after recanalization", "keyFindings": [ "RCT evaluating citicoline after recanalization therapy for acute ischemic stroke found no significant difference in infarct volume reduction, NIHSS, mRS, or Barthel index compared to placebo at 3 months." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "35639720", "doi": "10.1371/journal.pone.0269224", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35639720/", "publicSourceType": "PMID" }, { "id": "enriched-8c759d06", "supplementName": "Citicoline", "title": "The Effect of Citicoline Supplementation on Motor Speed and Attention in Adolescent Males", "authors": "McGlade E, Agoston AM, DiMuzio J, Kizaki M, Nakazaki E, Kamiya T, Yurgelun-Todd D", "journal": "J Atten Disord", "year": 2019, "studyType": "rct", "sampleSize": null, "outcome": "Citicoline supplementation improves attention and psychomotor speed in adolescent males", "keyFindings": [ "RCT of 75 adolescent males found 28 days of citicoline supplementation (250-500 mg/day) significantly improved attention, psychomotor speed, and reduced impulsivity compared to placebo." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "26179181", "doi": "10.1177/1087054715593633", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/26179181/", "publicSourceType": "PMID" }, { "id": "enriched-a41b83db", "supplementName": "Citicoline", "title": "Use of Citicoline in Attention-Deficit/Hyperactivity Disorder: A Pilot Study", "authors": "Hubner IB, Scheibe DB, Marchezan J, Bucker J", "journal": "Clin Neuropharmacol", "year": 2024, "studyType": "rct", "sampleSize": null, "outcome": "Citicoline appears safe but did not show significant benefit for ADHD symptoms in pediatric patients", "keyFindings": [ "Randomized crossover pilot study in pediatric ADHD patients found no statistically significant difference between citicoline and placebo on ADHD parameters, but citicoline was safe with no adverse effects." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "38976279", "doi": "10.1097/WNF.0000000000000602", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38976279/", "publicSourceType": "PMID" }, { "id": "enriched-2dddd08a", "supplementName": "Atorvastatin", "title": "Comparative effectiveness and safety of statins as a class and of specific statins for primary prevention of cardiovascular disease: A systematic review, meta-analysis, and network meta-analysis of randomized trials with 94,283 participants", "authors": "Yebyo HG, Aschmann HE, Kaufmann M, Puhan MA", "journal": "American Heart Journal", "year": 2019, "studyType": "review", "sampleSize": null, "outcome": "Atorvastatin reduces major cardiovascular events in primary prevention", "keyFindings": [ "Atorvastatin and rosuvastatin were among the most effective statins for reducing major cardiovascular events and all-cause mortality in primary prevention across 94,283 participants from randomized trials" ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "30716508", "doi": "10.1016/j.ahj.2018.12.007", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/30716508/", "publicSourceType": "PMID" }, { "id": "enriched-3dadf029", "supplementName": "Atorvastatin", "title": "Atorvastatin before percutaneous coronary intervention: A systematic review and meta-analysis", "authors": "García-Campa M, Flores-Ramírez R, Rojo-Garza S, Carrizales-Sepúlveda EF et al.", "journal": "PLoS One", "year": 2024, "studyType": "review", "sampleSize": null, "outcome": "Atorvastatin loading before PCI 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comparable efficacy to diazepam for terminating convulsive status epilepticus, with a trend toward fewer recurrences and less respiratory depression, supporting its role as a first-line agent." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "27052258", "doi": "10.1016/j.jocn.2015.10.038", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/27052258/", "publicSourceType": "PMID" }, { "id": "enriched-cdc79c82", "supplementName": "Lorazepam", "title": "Prevalence of benzodiazepines and benzodiazepine-related drugs exposure before, during and after pregnancy: A systematic review and meta-analysis.", "authors": "Bais B, Molenaar NM, Bijma HH et al.", "journal": "Journal of Affective Disorders", "year": 2020, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Benzodiazepines including lorazepam are widely used around pregnancy despite risks", "keyFindings": [ "Systematic review found benzodiazepines including lorazepam commonly 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"evidenceRating": "strong", "pmid": "35985088", "doi": "10.1016/j.psychres.2022.114777", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/35985088/", "publicSourceType": "PMID" }, { "id": "enriched-76006beb", "supplementName": "Ibuprofen", "title": "Comparison of Acetaminophen (Paracetamol) With Ibuprofen for Treatment of Fever or Pain in Children Younger Than 2 Years: A Systematic Review and Meta-analysis.", "authors": "Tan E, Braithwaite I, McKinlay CJD et al.", "journal": "JAMA Network Open", "year": 2020, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Ibuprofen is effective for fever and pain in pediatric populations", "keyFindings": [ "Meta-analysis of 19 studies found ibuprofen more effective than acetaminophen for fever reduction and pain relief in children under 2 years, with similar safety profiles; combination therapy was more effective than either alone." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "33125495", "doi": "10.1001/jamanetworkopen.2020.22398", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33125495/", "publicSourceType": "PMID" }, { "id": "enriched-09b31a34", "supplementName": "Ibuprofen", "title": "Acute Postoperative Pain Due to Dental Extraction in the Adult Population: A Systematic Review and Network Meta-analysis.", "authors": "Miroshnychenko A, Ibrahim S, Azab M et al.", "journal": "Journal of Dental Research", "year": 2023, "studyType": "review", "sampleSize": null, "outcome": "Ibuprofen provides effective postoperative pain relief after dental extraction", "keyFindings": [ "Network meta-analysis found ibuprofen (400 mg) among the most effective oral analgesics for post-dental extraction pain, providing superior pain relief compared to acetaminophen and comparable to combination NSAID regimens." ], "dosageUsed": null, "evidenceRating": "moderate", "pmid": "36631957", "doi": "10.1177/00220345221139230", 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"supplementName": "Naproxen", "title": "Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project).", "authors": "Castellsague J, Riera-Guardia N, Calingaert B et al.", "journal": "Drug Safety", "year": 2012, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Naproxen has a favorable upper GI safety profile among NSAIDs", "keyFindings": [ "Systematic review of observational studies found naproxen had a relatively lower risk of upper gastrointestinal complications compared to other NSAIDs like ketorolac and piroxicam, though risk was still elevated vs non-use." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "23137151", "doi": "10.2165/11633470-000000000-00000", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/23137151/", "publicSourceType": "PMID" }, { "id": "enriched-e2a14e3f", "supplementName": "Meloxicam", "title": "Early perioperative 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"evidenceRating": "strong", "pmid": "34628902", "doi": "10.21037/apm-21-2042", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/34628902/", "publicSourceType": "PMID" }, { "id": "enriched-35c7ad76", "supplementName": "Fluconazole", "title": "Risk of congenital malformations and miscarriages following maternal use of oral fluconazole during the first trimester of pregnancy: a systematic review and meta-analysis.", "authors": "Latour M, Vauzelle C, Elefant E et al.", "journal": "European Journal of Epidemiology", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Fluconazole use in pregnancy is associated with risk of congenital malformations", "keyFindings": [ "Meta-analysis found low-dose fluconazole (150 mg) in first trimester was not significantly associated with major congenital malformations, but high-dose or prolonged use may increase risk of specific birth defects; vaginal azoles remain preferred in pregnancy." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "39658659", "doi": "10.1007/s10654-024-01177-7", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/39658659/", "publicSourceType": "PMID" }, { "id": "enriched-d88e395b", "supplementName": "Fluconazole", "title": "A meta-analysis of fluconazole for the prevention of invasive fungal infection in preterm infants.", "authors": "Wang XL, Ma Y, Wang SH et al.", "journal": "American Journal of Translational Research", "year": 2021, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Fluconazole prophylaxis prevents invasive fungal infections in preterm infants", "keyFindings": [ "Meta-analysis found fluconazole prophylaxis significantly reduced the incidence of invasive fungal infections in very low birth weight and preterm infants without increasing resistance or significant adverse effects." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "33594302", "doi": "10.1016/j.reprotox.2020.12.018", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/33594302/", "publicSourceType": "PMID" }, { "id": "enriched-8d934816", "supplementName": "Prednisone", "title": "Dexamethasone versus prednisone/prednisolone in the management of pediatric patients with acute asthmatic exacerbations: a systematic review and meta-analysis.", "authors": "Dahan E, El Ghazal N, Nakanishi H et al.", "journal": "Journal of Asthma", "year": 2023, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Prednisone is effective for acute asthma exacerbations in children", "keyFindings": [ "Meta-analysis found prednisone/prednisolone and dexamethasone had comparable efficacy for pediatric acute asthma exacerbations, with dexamethasone offering the advantage of shorter treatment duration and better compliance." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "36461938", "doi": "10.1080/02770903.2022.2155189", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/36461938/", "publicSourceType": "PMID" }, { "id": "enriched-7d2db4d9", "supplementName": "Prednisone", "title": "Neuropsychiatric Adverse Effects of Synthetic Glucocorticoids: A Systematic Review and Meta-Analysis.", "authors": "Koning ACAM, van der Meulen M, Schaap D et al.", "journal": "Journal of Clinical Endocrinology and Metabolism", "year": 2024, "studyType": "metaAnalysis", "sampleSize": null, "outcome": "Glucocorticoids including prednisone cause neuropsychiatric adverse effects", "keyFindings": [ "Systematic review found synthetic glucocorticoids including prednisone were significantly associated with neuropsychiatric adverse effects, withmania/hypomania and depression being the most common; risk was dose-dependent and higher in the first weeks of treatment." ], "dosageUsed": null, "evidenceRating": "strong", "pmid": "38038629", "doi": "10.1210/clinem/dgad701", "publicReviewStatus": "source-linked", "publicSourceURL": "https://pubmed.ncbi.nlm.nih.gov/38038629/", "publicSourceType": "PMID" } ], "dosageGoals": [ { "supplementName": "Magnesium Glycinate", "dosageByGoal": [ { "id": "89a9cd49-8f56-44b9-8128-b34c9f1f16a0", "goal": "Sleep", "doseRange": "200-350 mg elemental nightly", "recommendedForm": "Magnesium bisglycinate", "timing": "30-60 minutes before bed", "notes": "Lower evening doses often work as well as larger doses; 350 mg/day is the NIH supplemental UL unless a clinician is supervising higher intake.", "populationNotes": "Useful when sleep problems coexist with stress or muscle tension." }, { "id": "afca6046-d24e-4a3c-be75-3bec78127e26", "goal": "Stress resilience", "doseRange": "200-350 mg elemental daily", "recommendedForm": "Magnesium bisglycinate", "timing": "With dinner or split AM/PM", "notes": "Stay at or below the NIH supplemental UL unless a clinician is supervising higher doses." }, { "id": "d28dbfb7-d446-4fd4-b3b1-b28a66e1c3f8", "goal": "Muscle cramps", "doseRange": "300-350 mg elemental daily", "recommendedForm": "Magnesium bisglycinate", "timing": "Evening or split doses", "notes": "Recheck hydration, potassium intake, and vitamin D status if cramps persist; higher supplemental magnesium should be clinician-guided." } ] }, { "supplementName": "Magnesium L-Threonate", "dosageByGoal": [ { "id": "58838481-fc79-411d-81c3-25e7954f31e5", "goal": "Brain fog", "doseRange": "1,000-2,000 mg compound daily", "recommendedForm": "Magnesium L-threonate", "timing": "Split morning and evening", "notes": "Typical daily amount provides about 72-144 mg elemental magnesium." }, { "id": "26f918f8-a981-4bc2-b062-b4aa0bf18f36", "goal": "Memory support", "doseRange": "1,500-2,000 mg compound daily", "recommendedForm": "Magnesium L-threonate", "timing": "Split AM/PM", "notes": "Use consistently for 6-8 weeks before judging effect." }, { "id": "f96aa6aa-79a4-4063-9b2a-4b1d889579ad", "goal": "Cognitive stress support", "doseRange": "1,000-1,500 mg 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"41f0f751-311f-4865-a515-9f64257effd8", "goal": "Immune support", "doseRange": "2,000-4,000 IU daily", "recommendedForm": "D3 (cholecalciferol)", "timing": "With breakfast or lunch", "notes": "More is not always better; keep dosing tied to labs and season." }, { "id": "199d4432-309a-4665-89d4-826722fe5025", "goal": "Bone support", "doseRange": "2,000-4,000 IU daily", "recommendedForm": "D3 (cholecalciferol)", "timing": "With the largest meal", "notes": "Often paired with Vitamin K2 and adequate calcium/magnesium intake; doses above 4,000 IU/day should be clinician-directed." } ] }, { "supplementName": "Vitamin C", "dosageByGoal": [ { "id": "4a576add-4eeb-4663-bbe9-d51c2dacbdf6", "goal": "Immune support", "doseRange": "500-1,000 mg daily", "recommendedForm": "Ascorbic acid or liposomal vitamin C", "timing": "With meals if sensitive", "notes": "Split dosing can reduce GI upset and maintain steadier plasma levels." }, { "id": "374a0233-3027-44f1-8678-ef51babbb623", "goal": "Iron absorption", "doseRange": "100-250 mg with iron", "recommendedForm": "Ascorbic acid", "timing": "Take at the same time as iron", "notes": "Higher amounts are not clearly better for iron absorption than modest co-dosing." }, { "id": "995dddd2-7cae-4583-92b6-fea9add0049c", "goal": "Collagen support", "doseRange": "500-1,000 mg daily", "recommendedForm": "Liposomal vitamin C or ascorbic acid", "timing": "With collagen-containing meal or supplement", "notes": "Use consistently when the goal is skin or connective tissue support." }, { "id": "d201f57d-ab6b-4b9a-a4d8-f5f1ef248f70", "goal": "Heavy training recovery", "doseRange": "250-500 mg daily", "recommendedForm": "Ascorbic acid", "timing": "Earlier in the day with food", "notes": "Avoid megadosing around every workout if you want to minimize theoretical blunting of training adaptations." } ] }, { "supplementName": "Vitamin B12", "dosageByGoal": [ { "id": "dbffd2c7-044e-43cc-b928-53668b22d493", "goal": "Deficiency correction", "doseRange": "1,000-2,000 mcg daily", "recommendedForm": "Methylcobalamin or hydroxocobalamin", "timing": "Morning; sublingual if preferred", "notes": "If deficiency is significant, injections may be faster under medical supervision." }, { "id": "23a24ea8-4a71-412a-b6a7-5afdb6a00e0a", "goal": "Neuropathy support", "doseRange": "1,000-5,000 mcg daily", "recommendedForm": "Methylcobalamin", "timing": "Morning or split doses", "notes": "Best when B12 deficiency or borderline status is part of the picture." }, { "id": "857f5f85-9a79-4158-90b5-b021e3c7913e", "goal": "Maintenance for low intake", "doseRange": "500-1,000 mcg daily", "recommendedForm": "Methylcobalamin or cyanocobalamin", "timing": "Any consistent time", "notes": "Vegan diets and metformin use increase the need for routine monitoring." } ] }, { "supplementName": "Methylcobalamin", "dosageByGoal": [ { "id": "f8ef9974-ca14-436a-bfda-adb6f870f42c", "goal": "Methylation support", "doseRange": "1,000-2,000 mcg daily", "recommendedForm": "Sublingual methylcobalamin", "timing": "Morning", "notes": "Common choice when methylated B vitamins are specifically preferred." }, { "id": "04f4ae62-55b9-4cae-8bd7-8b80ebe4c216", "goal": "Neurologic support", "doseRange": "2,000-5,000 mcg daily", "recommendedForm": "Sublingual methylcobalamin", "timing": "Morning or split doses", "notes": "Check methylmalonic acid if symptoms suggest functional B12 deficiency." }, { "id": "c4e607e4-05fd-484f-a364-287f6be67c11", "goal": "Metformin support", "doseRange": "1,000 mcg daily", "recommendedForm": "Sublingual methylcobalamin", "timing": "Any consistent time", "notes": "Annual B12 monitoring is reasonable with chronic metformin use." } ] }, { "supplementName": "Vitamin B9", "dosageByGoal": [ { "id": "fbb2e8af-a9be-4040-89af-73393cf50d19", "goal": "Preconception support", "doseRange": "400-800 mcg daily", "recommendedForm": "Methylfolate (5-MTHF)", "timing": "With breakfast", "notes": "Begin before conception rather than waiting until pregnancy is confirmed." }, { "id": "0b0b77b6-270c-43a0-bdf7-ded0f613d44c", "goal": "Homocysteine support", "doseRange": "400-1,000 mcg daily", "recommendedForm": "Methylfolate (5-MTHF)", "timing": "Morning with a B-complex if used", "notes": "B12 status matters; do not take folate alone indefinitely if B12 deficiency is possible." }, { "id": "ffd2c6f1-6477-4c19-996c-e2a180c76a41", "goal": "Low folate intake", "doseRange": "400-800 mcg daily", "recommendedForm": "Folic acid or methylfolate", "timing": "Any consistent time", "notes": "Choose methylfolate if there is known sensitivity to folic acid or a strong MTHFR rationale." } ] }, { "supplementName": "Methylfolate", "dosageByGoal": [ { "id": "0151293d-4d09-4504-a54b-2bc1a292d3e2", "goal": "MTHFR-focused support", "doseRange": "400-1,000 mcg daily", "recommendedForm": "Methylfolate (5-MTHF)", "timing": "Morning", "notes": "Start low if sensitive to methylated nutrients." }, { "id": "5e9f7946-8a5b-4a1a-aaa1-68936b38513d", "goal": "Mood adjunct", "doseRange": "1-7.5 mg daily", "recommendedForm": "Methylfolate (5-MTHF)", "timing": "Morning with food", "notes": "Higher-dose use is best discussed with a clinician, especially if taking psychiatric medication." }, { "id": "63052d06-b7e4-42d5-97c2-69fdc60b8705", "goal": "Preconception support", "doseRange": "400-800 mcg daily", "recommendedForm": "Methylfolate (5-MTHF)", "timing": "With breakfast", "notes": "Useful when active folate is preferred over folic acid." } ] }, { "supplementName": "Iron", "dosageByGoal": [ { "id": "e7b3c404-e7ad-42d4-be23-43aa3cfaab1c", "goal": "Iron deficiency anemia", "doseRange": "18-45 mg elemental iron daily", "recommendedForm": "Iron bisglycinate or ferrous sulfate", "timing": "Empty stomach if tolerated; otherwise with a light meal", "notes": "Take away from calcium, magnesium, zinc, coffee, tea, and fiber. Doses above 45 mg/day should be clinician-supervised with labs." }, { "id": "e85959ce-2f80-439b-976e-1d61819ac87c", "goal": "Low ferritin with fatigue", "doseRange": "18-36 mg elemental daily", "recommendedForm": "Iron bisglycinate", "timing": "Morning with vitamin C", "notes": "Ferritin is the key marker to follow, not just serum iron." }, { "id": "e9c7a409-98d6-47b7-9830-7c5028fd6bab", "goal": "Endurance support when ferritin is low", "doseRange": "18-36 mg elemental daily", "recommendedForm": "Iron bisglycinate", "timing": "Morning away from training meal", "notes": "Only appropriate when low ferritin or iron deficiency is documented." } ] }, { "supplementName": "Iron Bisglycinate", "dosageByGoal": [ { "id": "b43fb465-52d1-43c9-b022-b9431a7ceffc", "goal": "Gentle repletion", "doseRange": "18-36 mg elemental daily", "recommendedForm": "Iron bisglycinate", "timing": "Morning with 100-250 mg vitamin C", "notes": "Usually better tolerated than ferrous sulfate." }, { "id": "e0ba9f45-9f5b-49ba-8a4a-aad2c0790d1b", "goal": "Pregnancy or menstruation-related low ferritin", "doseRange": "25-36 mg elemental daily", "recommendedForm": "Iron bisglycinate", "timing": "Empty stomach if tolerated", "notes": "Use labs to guide duration; constipation is still possible." }, { "id": "720812d2-98c8-4639-9c79-5810b34d304e", "goal": "Maintenance after correction", "doseRange": "18-25 mg elemental daily", "recommendedForm": "Iron bisglycinate", "timing": "A few times weekly or daily depending on labs", "notes": "Reduce or stop once ferritin is restored if dietary intake is adequate." } ] }, { "supplementName": "Calcium", "dosageByGoal": [ { "id": "30e39ac5-42c5-4da3-8834-a04dc37950b5", "goal": "Bone support", "doseRange": "500-1,000 mg daily in divided doses", "recommendedForm": "Calcium citrate", "timing": "With meals or split between meals", "notes": "Absorption plateaus above about 500-600 mg at once." }, { "id": "bd28f7ad-1878-4ff0-bf5e-fc5f2a7ab19f", "goal": "Low dietary intake", "doseRange": "500-600 mg daily", "recommendedForm": "Calcium citrate", "timing": "With food if preferred", "notes": "Food-first is ideal; supplement only the gap you are not getting from diet." }, { "id": "7f335769-3c7b-49f7-a52c-501027294a36", "goal": "PMS support", "doseRange": "500-1,000 mg daily", "recommendedForm": "Calcium citrate", "timing": "Split morning and evening", "notes": "Often paired with magnesium and vitamin B6." } ] }, { "supplementName": "Vitamin K2", "dosageByGoal": [ { "id": "0ae71aed-13f3-4df2-8109-fb493372acf9", "goal": "Bone support with vitamin D3", "doseRange": "100-200 mcg daily", "recommendedForm": "MK-7", "timing": "With a meal containing fat", "notes": "Avoid self-starting if you take warfarin or another vitamin K-sensitive anticoagulant." }, { "id": "bbbee647-b24f-425c-b12a-5c2283bcfa03", "goal": "Calcium handling support", "doseRange": "90-180 mcg daily", "recommendedForm": "MK-7", "timing": "With dinner", "notes": "Typically paired with vitamin D3 rather than used alone." }, { "id": "070325e3-71ea-4bbb-a1e5-cf52966fe941", "goal": "Cardiovascular and bone maintenance", "doseRange": "180 mcg daily", "recommendedForm": "MK-7", "timing": "With the largest meal", "notes": "Most once-daily K2 products use MK-7 because of its longer half-life." } ] }, { "supplementName": "Vitamin K2 MK-4", "dosageByGoal": [ { "id": "5aa45bdb-316c-4ccf-be74-81e28e062344", "goal": "Bone support", "doseRange": "5-15 mg daily", "recommendedForm": "MK-4", "timing": "Split 2-3 doses with meals", "notes": "MK-4 is short acting and often dosed more than once daily." }, { "id": "c38d8f7f-7840-473f-aa10-ade73e1b90f3", "goal": "Dental and bone-focused support", "doseRange": "5-10 mg daily", "recommendedForm": "MK-4", "timing": "With meals", "notes": "Shorter half-life than MK-7; consistency matters." }, { "id": "dbe52e19-c744-4f23-a67e-1ea5c0f03333", "goal": "High-dose K2 protocols", "doseRange": "15-45 mg daily", "recommendedForm": "MK-4", "timing": "Divided with meals", "notes": "Reserve higher intakes for clinician-guided use." } ] }, { "supplementName": "Coenzyme Q10", "dosageByGoal": [ { "id": "7fe9065f-7192-4f1b-803b-7dfb57244e7e", "goal": "General mitochondrial support", "doseRange": "100-200 mg daily", "recommendedForm": "Ubiquinone or ubiquinol", "timing": "With a fat-containing meal", "notes": "Take earlier in the day if it feels stimulating." }, { "id": "64f78d9b-23cd-43f7-b83f-93fb38636199", "goal": "Statin support", "doseRange": "100-200 mg daily", "recommendedForm": "Ubiquinol", "timing": "With breakfast or lunch", "notes": "Most useful when statins are associated with fatigue or muscle symptoms." }, { "id": "a88045ef-feb5-4d0b-840f-432761b7ad0d", "goal": "Migraine support", "doseRange": "100 mg 2-3 times daily", "recommendedForm": "Ubiquinone or ubiquinol", "timing": "Split with meals", "notes": "Use for at least 8-12 weeks before judging effect." } ] }, { "supplementName": "Coenzyme Q10 Ubiquinol", "dosageByGoal": [ { "id": "146fe90f-d5cd-4075-add4-609a610ebd6a", "goal": "Statin-related myalgia support", "doseRange": "100-200 mg daily", "recommendedForm": "Ubiquinol", "timing": "With breakfast or lunch", "notes": "Often preferred over ubiquinone after age 40 or when rapid repletion is desired." }, { "id": "2b3741fa-a9ba-43d4-8623-ca25d15dcacd", "goal": "Cardiovascular energy support", "doseRange": "100-300 mg daily", "recommendedForm": "Ubiquinol", "timing": "With a fat-containing meal", "notes": "More expensive than ubiquinone but often reaches higher plasma levels." }, { "id": "0423ffbb-8404-4b51-8397-f0a0813d97cf", "goal": "Fertility support", "doseRange": "200-300 mg daily", "recommendedForm": "Ubiquinol", "timing": "Split with meals", "notes": "Most often used in age-related fertility protocols." } ] }, { "supplementName": "Fish Oil", "dosageByGoal": [ { "id": "845b97d3-cd28-48d9-90a5-850fa638c522", "goal": "General omega-3 maintenance", "doseRange": "1,000 mg combined EPA+DHA daily", "recommendedForm": "Triglyceride fish oil", "timing": "With a fat-containing meal", "notes": "Count EPA+DHA, not just total fish oil weight." }, { "id": "acf54d42-ac33-4c3c-abb4-4d6ce00bf32a", "goal": "Mood support", "doseRange": "1,000-2,000 mg EPA-predominant daily", "recommendedForm": "High-EPA fish oil", "timing": "With food", "notes": "EPA-heavy ratios are usually preferred for mood-focused use." }, { "id": "582273a7-99c6-4e02-b315-a82fda7eedac", "goal": "Anti-inflammatory support", "doseRange": "2,000-3,000 mg combined EPA+DHA daily", "recommendedForm": "Triglyceride or rTG fish oil", "timing": "Split with meals", "notes": "Higher intakes merit attention to bruising or anticoagulant use." }, { "id": "cbe1af2d-40a4-4fcc-b391-342485acae0e", "goal": "Triglyceride support", "doseRange": "2,000-4,000 mg combined EPA+DHA daily", "recommendedForm": "Concentrated fish oil", "timing": "Split twice daily with meals", "notes": "Prescription-strength use belongs under clinician guidance." } ] }, { "supplementName": "Fish Oil Triple Strength", "dosageByGoal": [ { "id": "70962a13-f2c2-4a47-8f6a-3ae83889560f", "goal": "Triglyceride support", "doseRange": "1-2 softgels daily providing 900-1,800 mg EPA+DHA", "recommendedForm": "rTG fish oil", "timing": "With meals", "notes": "Concentrated products reduce pill burden." }, { "id": "a184b671-4eb4-4d8b-85c2-3e362982f394", "goal": "Joint support", "doseRange": "1,500-2,500 mg combined EPA+DHA daily", "recommendedForm": "rTG fish oil", "timing": "Split with meals", "notes": "Give it 6-12 weeks before judging joint response." }, { "id": "f800dde5-2f3b-4c4d-9644-3bdc07bcc5aa", "goal": "Cardiovascular support", "doseRange": "1,000-2,000 mg combined EPA+DHA daily", "recommendedForm": "rTG fish oil", "timing": "With the largest meal", "notes": "Check EPA+DHA content per softgel because labels vary widely." } ] }, { "supplementName": "Krill Oil", "dosageByGoal": [ { "id": "80f45302-976a-44f0-a6f2-d4777186fa01", "goal": "Omega-3 maintenance", "doseRange": "500-1,000 mg daily", "recommendedForm": "Phospholipid-bound krill oil", "timing": "With meals", "notes": "Total EPA+DHA is lower than concentrated fish-oil products." }, { "id": "580ce8b9-cf8b-4a0d-9e8b-f333dc7d4f93", "goal": "Dry-eye support", "doseRange": "1,000 mg daily", "recommendedForm": "Krill oil", "timing": "With breakfast", "notes": "Astaxanthin content may add antioxidant support." }, { "id": "f661b716-c1df-4a7c-bc7b-7823a8ed33c2", "goal": "PMS support", "doseRange": "500-1,000 mg daily", "recommendedForm": "Krill oil", "timing": "With meals", "notes": "Useful when a lower-pill-count omega-3 product is preferred." } ] }, { "supplementName": "Zinc", "dosageByGoal": [ { "id": "ed3ac06f-ebb0-4c31-a23a-134ac553edfa", "goal": "General immune support", "doseRange": "15-25 mg daily", "recommendedForm": "Zinc picolinate or glycinate", "timing": "With food", "notes": "Long-term higher doses can lower copper status." }, { "id": "8f8fd857-d9d5-49f2-996b-047c83ff0a68", "goal": "Acne or skin support", "doseRange": "25-30 mg daily", "recommendedForm": "Zinc picolinate", "timing": "With dinner", "notes": "Monitor for nausea and consider adding copper if used long term." }, { "id": "039182f4-04c3-4a32-baf4-7a1a6a3bf394", "goal": "Short-term cold support", "doseRange": "75 mg elemental daily for 5-7 days", "recommendedForm": "Zinc acetate or gluconate lozenges", "timing": "Start within 24 hours of symptoms", "notes": "Short-term only; stop once the acute illness passes." } ] }, { "supplementName": "Zinc Picolinate", "dosageByGoal": [ { "id": "ba3ac6d2-ac9c-44d7-b169-07bafefdfded", "goal": "Low zinc status", "doseRange": "15-30 mg daily", "recommendedForm": "Zinc picolinate", "timing": "With food", "notes": "Good default form when stronger absorption is desired." }, { "id": "7e680e47-2a7d-4231-9528-0e50243a05a4", "goal": "Testosterone support in deficiency", "doseRange": "25-30 mg daily", "recommendedForm": "Zinc picolinate", "timing": "With dinner", "notes": "Most useful when dietary intake or labs suggest zinc insufficiency." }, { "id": "49b01cce-7c47-49c7-9f13-65ecf2799033", "goal": "Skin support", "doseRange": "15-30 mg daily", "recommendedForm": "Zinc picolinate", "timing": "With food", "notes": "Consider 1-2 mg copper if using above 25 mg daily for long periods." } ] }, { "supplementName": "Ashwagandha", "dosageByGoal": [ { "id": "532bbf32-b73e-4129-a799-a14e81ffbd6d", "goal": "Stress reduction", "doseRange": "300-600 mg daily", "recommendedForm": "KSM-66", "timing": "Morning or split AM/PM", "notes": "Standardized extracts are more predictable than plain powder." }, { "id": "a1e0a38c-ad2f-4b96-a7f0-deb60eaadade", "goal": "Sleep support", "doseRange": "125-250 mg nightly", "recommendedForm": "Sensoril", "timing": "30-60 minutes before bed", "notes": "Often feels more calming than KSM-66." }, { "id": "88950739-bb8b-4bf0-8471-b0d8ea5e3910", "goal": "Athletic performance and recovery", "doseRange": "300-600 mg daily", "recommendedForm": "KSM-66", "timing": "With breakfast or split doses", "notes": "Use consistently for at least 6-8 weeks." }, { "id": "d1df084e-ecb2-4e0f-b3ea-6900782cf567", "goal": "Male fertility or testosterone support", "doseRange": "600 mg daily", "recommendedForm": "KSM-66", "timing": "Split with meals", "notes": "Best reserved for men with a clear rationale, not used reflexively." } ] }, { "supplementName": "Rhodiola Rosea", "dosageByGoal": [ { "id": "73ccb95e-ca9c-4c64-bd2c-34d838ea8489", "goal": "Mental fatigue", "doseRange": "200-400 mg daily", "recommendedForm": "Standardized rhodiola extract", "timing": "Morning", "notes": "Too late in the day can feel stimulating for some people." }, { "id": "d62538d1-a00d-4ce4-9f84-645eba049233", "goal": "Stress resilience", "doseRange": "200-600 mg daily", "recommendedForm": "Standardized rhodiola extract", "timing": "Morning or early afternoon", "notes": "Best used earlier in the day and not right before bed." }, { "id": "72e43ba0-bc66-455a-a806-f720797d2239", "goal": "Endurance support", "doseRange": "200-400 mg daily", "recommendedForm": "Standardized rhodiola extract", "timing": "30-60 minutes before training", "notes": "Athletic use is usually acute or short-cycle rather than all day." } ] }, { "supplementName": "Creatine", "dosageByGoal": [ { "id": "281d7e61-d912-4a08-9d71-9f268a384960", "goal": "Strength and power", "doseRange": "3-5 g daily", "recommendedForm": "Creatine monohydrate", "timing": "Any time; consistency matters more than timing", "notes": "Loading is optional, not required." }, { "id": "e2ef1898-901c-4aad-9473-b4e63b277c43", "goal": "Cognitive support", "doseRange": "5 g daily", "recommendedForm": "Creatine monohydrate", "timing": "Morning or post-workout", "notes": "Vegetarians often respond more noticeably because baseline intake is lower." }, { "id": "41acb9a7-2312-4a24-8e16-dbf3bf6d54d6", "goal": "Recovery and lean mass support", "doseRange": "3-5 g daily", "recommendedForm": "Creatine monohydrate", "timing": "Post-workout or with a meal", "notes": "Hydrate normally; no special kidney detox routine is needed in healthy users." }, { "id": "584c7231-2c22-4744-8259-3bf761d70cd9", "goal": "Rapid saturation", "doseRange": "20 g daily split into 4 doses for 5-7 days, then 3-5 g daily", "recommendedForm": "Creatine monohydrate", "timing": "Split across the day during loading", "notes": "Use only if you specifically want faster muscle saturation." } ] }, { "supplementName": "NAC", "dosageByGoal": [ { "id": "3c096cdd-b07b-437b-9f90-65e27b279db7", "goal": "Glutathione support", "doseRange": "600-1,200 mg daily", "recommendedForm": "Standard NAC", "timing": "Between meals if tolerated", "notes": "Empty-stomach dosing is common but not mandatory if nausea occurs." }, { "id": "493b9c4c-dfb5-46cc-aa3c-51a195f3ed42", "goal": "Respiratory mucus support", "doseRange": "600 mg 2-3 times daily", "recommendedForm": "Standard NAC", "timing": "Between meals", "notes": "Useful when the main goal is thinning thick mucus." }, { "id": "0df04de6-5e5f-4651-9342-45ddd449deb8", "goal": "High oxidative stress support", "doseRange": "1,200-1,800 mg daily", "recommendedForm": "Standard NAC", "timing": "Split twice daily", "notes": "Separate from activated charcoal by at least 2 hours." } ] }, { "supplementName": "L-Glutathione", "dosageByGoal": [ { "id": "a1b836d9-f971-423b-97a0-e122c5464aaf", "goal": "Antioxidant support", "doseRange": "250-500 mg daily", "recommendedForm": "Liposomal glutathione or S-acetyl glutathione", "timing": "Morning on an empty stomach if tolerated", "notes": "Premium delivery forms are usually preferred over plain reduced glutathione." }, { "id": "47385607-299d-4ee6-adc1-9afd3732b413", "goal": "Recovery from high oxidative load", "doseRange": "500 mg daily", "recommendedForm": "Liposomal glutathione", "timing": "Morning or split twice daily", "notes": "Often used when NAC alone is not desired." }, { "id": "3c735241-9ffe-42bb-b5f8-bddb5b8fdb28", "goal": "Skin support", "doseRange": "250-500 mg daily", "recommendedForm": "Liposomal glutathione", "timing": "Morning", "notes": "Set expectations conservatively; the main rationale is antioxidant support." } ] }, { "supplementName": "Melatonin", "dosageByGoal": [ { "id": "405171f8-740a-4c77-b420-86882328b8e7", "goal": "Sleep onset", "doseRange": "0.3-1 mg nightly", "recommendedForm": "Immediate-release melatonin", "timing": "30-60 minutes before bed", "notes": "Lower doses often work better than aggressively high doses." }, { "id": "e1baf35d-c9ba-493c-88e1-11d028d790b6", "goal": "Jet lag", "doseRange": "0.5-3 mg nightly", "recommendedForm": "Immediate-release melatonin", "timing": "At destination bedtime", "notes": "Best used with light management and travel timing adjustments." }, { "id": "ae75c1cb-5f66-4ea7-ad43-dbf82d635fd9", "goal": "Delayed sleep phase", "doseRange": "0.3-1 mg nightly", "recommendedForm": "Low-dose melatonin", "timing": "3-5 hours before target bedtime", "notes": "Timing matters more than dose for circadian shifting." }, { "id": "1efce4d2-006b-4df5-9982-a5fe6a38dcb2", "goal": "Sleep maintenance", "doseRange": "1-3 mg nightly", "recommendedForm": "Extended-release melatonin", "timing": "30-60 minutes before bed", "notes": "Choose extended-release only when staying asleep is the main issue." } ] }, { "supplementName": "Collagen Peptides", "dosageByGoal": [ { "id": "c7b37d5d-d35a-431b-b424-7ea0089a28e1", "goal": "Skin support", "doseRange": "10-15 g daily", "recommendedForm": "Hydrolyzed collagen peptides", "timing": "Any consistent time", "notes": "Taking with vitamin C can support collagen synthesis." }, { "id": "eb386558-104c-44a8-8768-d1965011c0eb", "goal": "Tendon and ligament support", "doseRange": "15 g daily", "recommendedForm": "Hydrolyzed collagen peptides", "timing": "30-60 minutes before rehab or training", "notes": "Consistency matters more than cycling." }, { "id": "83d5f997-1878-4b9f-bc09-50cabc6ad0b0", "goal": "Bone support", "doseRange": "10-20 g daily", "recommendedForm": "Hydrolyzed collagen peptides", "timing": "Any consistent time", "notes": "Works best as part of a broader protein, mineral, and resistance-training plan." } ] }, { "supplementName": "Turmeric/Curcumin", "dosageByGoal": [ { "id": "5cff9450-6cad-4238-bab3-0a84c900c05b", "goal": "General inflammation support", "doseRange": "500-1,000 mg curcuminoids daily", "recommendedForm": "Curcumin with piperine or phytosome", "timing": "With meals", "notes": "Standard turmeric powder is much weaker than concentrated curcumin extracts." }, { "id": "9ead9961-7e46-4866-832a-4119c76f90a8", "goal": "Joint comfort", "doseRange": "500 mg twice daily", "recommendedForm": "Curcumin phytosome or enhanced-bioavailability curcumin", "timing": "With meals", "notes": "Joint-oriented trials often use enhanced-bioavailability forms." }, { "id": "7ecbaf25-78fb-43cb-8c35-38a423f7e810", "goal": "Exercise recovery", "doseRange": "500-1,000 mg daily", "recommendedForm": "Enhanced-bioavailability curcumin", "timing": "With breakfast or after training meal", "notes": "Monitor for drug interactions if also using anticoagulants or multiple medications." } ] }, { "supplementName": "Curcumin Phytosome", "dosageByGoal": [ { "id": "087fe410-bcc6-4b46-8adc-033b03df2de7", "goal": "Osteoarthritis support", "doseRange": "500-1,000 mg daily", "recommendedForm": "Curcumin phytosome (Meriva-style)", "timing": "Split with meals", "notes": "Often chosen specifically for joint comfort." }, { "id": "228c98b4-1bd3-4ed5-9ae6-e8ec2411cf65", "goal": "High-absorption anti-inflammatory support", "doseRange": "500 mg twice daily", "recommendedForm": "Curcumin phytosome", "timing": "With meals containing fat", "notes": "Phytosome delivery is generally better absorbed than plain curcumin." }, { "id": "a6dfddf9-ce2a-4da1-94c4-aa8f355994f1", "goal": "Exercise soreness support", "doseRange": "500-1,000 mg daily", "recommendedForm": "Curcumin phytosome", "timing": "Earlier in the day or post-workout meal", "notes": "Best judged over several weeks, not a single dose." } ] }, { "supplementName": "Probiotics", "dosageByGoal": [ { "id": "f9a3b97f-efde-466e-af90-c24619ea3193", "goal": "General gut support", "doseRange": "10-20 billion CFU daily", "recommendedForm": "Multi-strain Lactobacillus/Bifidobacterium blend", "timing": "With food if the product suggests it", "notes": "Strain quality matters more than chasing the highest CFU number." }, { "id": "1f3fe453-e030-4894-89bc-337e7b3cc16d", "goal": "Post-antibiotic support", "doseRange": "20-50 billion CFU daily", "recommendedForm": "Multi-strain probiotic", "timing": "Away from the antibiotic by 2-3 hours", "notes": "Continue for 1-2 weeks after the antibiotic course if tolerated." }, { "id": "7796a8e0-b847-4394-97a1-9bdc44e7d96f", "goal": "Immune support", "doseRange": "10-20 billion CFU daily", "recommendedForm": "Multi-strain probiotic", "timing": "Any consistent time", "notes": "Response is strain specific; not every probiotic helps every problem." } ] }, { "supplementName": "Lactobacillus Rhamnosus", "dosageByGoal": [ { "id": "d451df2c-9604-4e7d-8458-e6fbabd1ae99", "goal": "Antibiotic-associated diarrhea prevention", "doseRange": "10-20 billion CFU daily", "recommendedForm": "Lactobacillus rhamnosus GG", "timing": "Take 2-3 hours away from the antibiotic", "notes": "One of the best-studied strain-specific uses." }, { "id": "61eb877c-73e1-434d-bbb3-d68931b43265", "goal": "Travel GI resilience", "doseRange": "10-20 billion CFU daily", "recommendedForm": "Lactobacillus rhamnosus GG", "timing": "Start several days before travel and continue through the trip", "notes": "Useful when GI stress predictably flares with travel." }, { "id": "4344ed52-2171-4e72-815f-2547ed3fda41", "goal": "Atopic or immune support", "doseRange": "10-20 billion CFU daily", "recommendedForm": "Lactobacillus rhamnosus GG", "timing": "Any consistent time", "notes": "Evidence is stronger for some populations than others." } ] }, { "supplementName": "Saccharomyces Boulardii", "dosageByGoal": [ { "id": "d07cf9e2-0aa2-466b-8b59-d1935014dd90", "goal": "Antibiotic-associated diarrhea prevention", "doseRange": "250-500 mg 1-2 times daily", "recommendedForm": "Saccharomyces boulardii CNCM I-745", "timing": "Can be taken during antibiotic use", "notes": "Yeast probiotic, so it is not inactivated by antibacterial antibiotics." }, { "id": "586f919e-4aa7-41fc-b54a-e7beafdbb081", "goal": "Travelers diarrhea support", "doseRange": "250 mg twice daily", "recommendedForm": "Saccharomyces boulardii CNCM I-745", "timing": "Start a few days before travel", "notes": "Use only if you tolerate it well before travel." }, { "id": "ae88d53c-24ab-4928-9a18-4944958f6f83", "goal": "C. difficile recurrence support", "doseRange": "250-500 mg twice daily", "recommendedForm": "Saccharomyces boulardii CNCM I-745", "timing": "During and after treatment as directed", "notes": "Best discussed with a clinician in recurrent or severe GI disease." } ] }, { "supplementName": "L-Theanine", "dosageByGoal": [ { "id": "4ff69070-9f10-498f-866f-9d1570aeca8a", "goal": "Calm focus", "doseRange": "100-200 mg", "recommendedForm": "L-theanine", "timing": "With caffeine or in the morning", "notes": "Classic pairing is roughly 2:1 theanine to caffeine." }, { "id": "e9d6c927-e39f-4cf1-8d6e-be467347b000", "goal": "Anxiety support", "doseRange": "200-400 mg daily", "recommendedForm": "L-theanine", "timing": "Split once or twice daily", "notes": "Useful for situational tension without sedation in many people." }, { "id": "d7c45046-a80a-4ca4-a5e6-ff3e3392d107", "goal": "Sleep support", "doseRange": "200 mg nightly", "recommendedForm": "L-theanine", "timing": "30-60 minutes before bed", "notes": "Best when the problem is racing thoughts rather than circadian delay." } ] }, { "supplementName": "Glycine", "dosageByGoal": [ { "id": "e01886d4-a1b3-4ed0-8537-02df0c9da36b", "goal": "Sleep support", "doseRange": "3 g nightly", "recommendedForm": "Pure glycine powder", "timing": "30-60 minutes before bed", "notes": "Simple and often well tolerated." }, { "id": "0ac87f9c-7c9c-4087-9302-07568c2e8e84", "goal": "Collagen support", "doseRange": "3-5 g daily", "recommendedForm": "Pure glycine powder", "timing": "Any consistent time", "notes": "Can complement collagen peptides rather than replace them." }, { "id": "c5f47ef2-2145-4c02-9a61-b75799a5429a", "goal": "Blood sugar and satiety support", "doseRange": "3 g with evening meal", "recommendedForm": "Pure glycine powder", "timing": "With dinner", "notes": "Use as an adjunct to diet, not as a stand-alone glucose strategy." } ] }, { "supplementName": "Taurine", "dosageByGoal": [ { "id": "e9e973ac-251f-4a69-b5f9-66faffb0f448", "goal": "Cardiovascular support", "doseRange": "1-3 g daily", "recommendedForm": "Taurine powder or capsules", "timing": "Split once or twice daily", "notes": "Often used for blood-pressure or heart-rhythm-supportive stacks." }, { "id": "8c302070-0fd2-4919-bba0-5647c0f5abe5", "goal": "Exercise hydration and recovery", "doseRange": "1-2 g daily", "recommendedForm": "Taurine powder", "timing": "Pre-workout or post-workout", "notes": "Often included in performance formulas but does not need a proprietary blend." }, { "id": "66385962-84cd-45f5-867f-9cebb68f6844", "goal": "Calming support", "doseRange": "1-2 g nightly", "recommendedForm": "Taurine powder or capsules", "timing": "30-60 minutes before bed", "notes": "Helpful when restlessness and nighttime tension coexist." } ] }, { "supplementName": "Alpha-Lipoic Acid", "dosageByGoal": [ { "id": "3ab583dd-10f2-46c3-93c0-dc569fa7da6e", "goal": "Blood sugar support", "doseRange": "300-600 mg daily", "recommendedForm": "R-lipoic acid or stabilized Na-R-ALA", "timing": "Empty stomach if tolerated", "notes": "Can lower glucose enough to matter when combined with other glucose-lowering agents." }, { "id": "d94d4098-e0de-4909-8e61-3a74322e06a5", "goal": "Peripheral nerve support", "doseRange": "600 mg daily", "recommendedForm": "R-lipoic acid", "timing": "Split morning and afternoon if needed", "notes": "Most often used for neuropathy-focused protocols." }, { "id": "b949374c-dc3d-4ab7-984d-49b781e07e8c", "goal": "Antioxidant recycling support", "doseRange": "300-600 mg daily", "recommendedForm": "R-lipoic acid", "timing": "Earlier in the day", "notes": "Can chelate minerals, so separate if using high-dose minerals." } ] }, { "supplementName": "Acetyl-L-Carnitine", "dosageByGoal": [ { "id": "00dd3301-0652-4b9e-95ff-94d63674052b", "goal": "Cognitive support", "doseRange": "500-1,000 mg daily", "recommendedForm": "Acetyl-L-Carnitine HCl", "timing": "Morning", "notes": "Can feel energizing, so earlier dosing is usually better." }, { "id": "2df1d2f8-75da-43bd-bdd6-369bc310831a", "goal": "Neuropathy support", "doseRange": "1,000-1,500 mg daily", "recommendedForm": "Acetyl-L-Carnitine HCl", "timing": "Split twice daily", "notes": "Most useful when nerve pain or low-energy symptoms are part of the picture." }, { "id": "7beb2630-286b-405b-9f6f-e3fedeac356b", "goal": "Energy support", "doseRange": "500-1,500 mg daily", "recommendedForm": "Acetyl-L-Carnitine HCl", "timing": "Morning or pre-lunch", "notes": "Reserve bedtime use for people who do not find it activating." } ] }, { "supplementName": "Berberine", "dosageByGoal": [ { "id": "8bdd9253-7baa-4076-939c-ac9c6b1330b6", "goal": "Blood sugar support", "doseRange": "500 mg 2-3 times daily", "recommendedForm": "Berberine HCl or dihydroberberine", "timing": "15-30 minutes before meals or with meals", "notes": "Monitor if also taking prescription glucose-lowering medication." }, { "id": "a748d4c5-426f-4c0c-af6e-406bfccb39c1", "goal": "Lipid support", "doseRange": "500 mg 2 times daily", "recommendedForm": "Berberine HCl", "timing": "With meals", "notes": "Works best alongside dietary change rather than against it." }, { "id": "6938182b-6c90-499c-8ed1-e2ac3135b907", "goal": "Gut and appetite support", "doseRange": "500 mg 1-2 times daily", "recommendedForm": "Berberine HCl", "timing": "With meals", "notes": "GI upset is the main reason people need a lower starting dose." } ] }, { "supplementName": "Berberine HCl", "dosageByGoal": [ { "id": "eca35515-2d73-447f-ba57-2bec7c148e83", "goal": "Blood sugar support", "doseRange": "500 mg 2-3 times daily", "recommendedForm": "Berberine HCl", "timing": "With meals", "notes": "Start with once-daily dosing if GI tolerance is uncertain." }, { "id": "533f4bc5-2c9c-4c6f-ac11-7fb63ca95d42", "goal": "Weight-management support", "doseRange": "500 mg 2 times daily", "recommendedForm": "Berberine HCl", "timing": "With lunch and dinner", "notes": "Most effective when meal quality and sleep are also addressed." }, { "id": "aecdc2fd-07c2-481c-b231-a2f3dbc71d73", "goal": "Cholesterol support", "doseRange": "500 mg 2 times daily", "recommendedForm": "Berberine HCl", "timing": "With meals", "notes": "Check for medication interactions before combining with multiple prescriptions." } ] }, { "supplementName": "Lion's Mane", "dosageByGoal": [ { "id": "abfed4f0-dda6-48f2-8faf-b13c0a285d11", "goal": "Cognitive support", "doseRange": "1,000-3,000 mg daily", "recommendedForm": "Dual extract lion's mane", "timing": "Morning or split AM/PM", "notes": "Look for a product that clearly states extract ratio or beta-glucan content." }, { "id": "2521645a-514f-43f4-b104-dd5f49cb4413", "goal": "Focus and productivity", "doseRange": "1,000-2,000 mg daily", "recommendedForm": "Dual extract lion's mane", "timing": "Morning", "notes": "Response is subtle and usually builds over several weeks." }, { "id": "2fbf2e0f-1f38-4e07-bec5-415427381844", "goal": "Nerve support", "doseRange": "1,000-3,000 mg daily", "recommendedForm": "Dual extract lion's mane", "timing": "Split with meals", "notes": "Use consistently for 8-12 weeks before concluding it is not helping." } ] }, { "supplementName": "Bacopa Monnieri", "dosageByGoal": [ { "id": "7cd477af-47bf-425d-9aec-cdc95e5d44b1", "goal": "Memory retention", "doseRange": "300-600 mg daily", "recommendedForm": "Standardized bacopa extract", "timing": "With food", "notes": "Not a quick stimulant; it is usually a slow-burn memory support supplement." }, { "id": "f6467e58-ecb5-4958-83a8-4e96fd41d48d", "goal": "Stress and anxious rumination", "doseRange": "300 mg daily", "recommendedForm": "Standardized bacopa extract", "timing": "With dinner if it feels calming", "notes": "Can feel mildly sedating in some users." }, { "id": "5915177b-02f3-4394-9d83-9fd43011a0a5", "goal": "Attention support", "doseRange": "300-450 mg daily", "recommendedForm": "Standardized bacopa extract", "timing": "Morning with food", "notes": "Give it at least 8-12 weeks." } ] }, { "supplementName": "Ginkgo Biloba", "dosageByGoal": [ { "id": "37ebc4a7-bac7-467d-ace7-75b9e501359d", "goal": "Circulation support", "doseRange": "120-240 mg daily", "recommendedForm": "Standardized ginkgo extract", "timing": "Split once or twice daily with meals", "notes": "Avoid combining casually with anticoagulants or before surgery." }, { "id": "771f166b-5974-4029-a94b-93ed3c7e4d03", "goal": "Memory support", "doseRange": "120-240 mg daily", "recommendedForm": "Standardized ginkgo extract", "timing": "Morning and/or lunch", "notes": "A standardized extract is more important than a large raw-mg claim." }, { "id": "00f886a2-5ce6-4aef-b5f4-91cdcdc0d517", "goal": "Tinnitus support", "doseRange": "120-240 mg daily", "recommendedForm": "Standardized ginkgo extract", "timing": "Split doses", "notes": "Evidence is mixed, so expectations should stay modest." } ] }, { "supplementName": "Quercetin", "dosageByGoal": [ { "id": "db369160-9e94-4b9f-b0a5-005301d693dc", "goal": "Seasonal allergies", "doseRange": "500-1,000 mg daily", "recommendedForm": "Quercetin phytosome or quercetin with bromelain", "timing": "Split morning and evening with meals", "notes": "Often used as a mast-cell-supportive strategy rather than an acute antihistamine." }, { "id": "b43062bb-091e-42e2-afcc-236d4f0c3494", "goal": "Exercise recovery", "doseRange": "500 mg daily", "recommendedForm": "Quercetin phytosome", "timing": "With breakfast", "notes": "Use consistently rather than expecting a single-dose effect." }, { "id": "6a92f1c9-a762-4f6b-96a1-ad9c49f2b62e", "goal": "Immune support", "doseRange": "500-1,000 mg daily", "recommendedForm": "Quercetin phytosome", "timing": "With meals", "notes": "Vitamin C and bromelain are common companion ingredients." } ] }, { "supplementName": "Resveratrol", "dosageByGoal": [ { "id": "da4cbc4f-e7ad-46cd-9041-ee86ce18af90", "goal": "Healthy aging support", "doseRange": "150-300 mg daily", "recommendedForm": "Trans-resveratrol", "timing": "With food containing some fat", "notes": "Use trans-resveratrol rather than mixed or unspecified isomers." }, { "id": "76c6fdf8-5195-4a7f-b7b5-4787eb8704ec", "goal": "Cardiometabolic support", "doseRange": "150-500 mg daily", "recommendedForm": "Trans-resveratrol", "timing": "Morning with food", "notes": "Usually used as a long-game supplement, not for acute effects." }, { "id": "ca0e627c-37b9-4524-971e-cfe665fb8cfa", "goal": "Exercise-recovery antioxidant support", "doseRange": "150-250 mg daily", "recommendedForm": "Trans-resveratrol", "timing": "Earlier in the day", "notes": "Avoid assuming more is automatically better." } ] }, { "supplementName": "Selenium", "dosageByGoal": [ { "id": "883c2770-5b0d-4359-8afc-3783b7fab1a2", "goal": "Thyroid support", "doseRange": "100-200 mcg daily", "recommendedForm": "Selenomethionine", "timing": "With breakfast", "notes": "Keep total daily selenium conservative because chronic excess can be harmful." }, { "id": "81ed288f-2acd-44ba-9884-2c454749f061", "goal": "Antioxidant support", "doseRange": "100-200 mcg daily", "recommendedForm": "Selenomethionine", "timing": "Any consistent time", "notes": "Brazil nuts can also provide large amounts, so do not stack blindly." }, { "id": "60e66c9e-63e5-49e4-9227-6f70ac93309d", "goal": "Male fertility support", "doseRange": "100-200 mcg daily", "recommendedForm": "Selenomethionine", "timing": "With food", "notes": "Stay away from chronic high-dose use." } ] }, { "supplementName": "Iodine", "dosageByGoal": [ { "id": "d7a94ec4-d1e5-4173-af6d-833696c09ae2", "goal": "Low dietary intake support", "doseRange": "150 mcg daily", "recommendedForm": "Potassium iodide", "timing": "With food", "notes": "Do not escalate iodine casually if thyroid autoimmunity is suspected." }, { "id": "70058210-571b-464a-ad7b-5e295e6e6ef3", "goal": "Preconception and pregnancy support", "doseRange": "150 mcg daily", "recommendedForm": "Potassium iodide", "timing": "With breakfast", "notes": "Most prenatal formulas already contain iodine, so count the total intake." }, { "id": "a1a5aacd-918b-43e2-a1f1-0e4bbc391f9d", "goal": "Thyroid nutrition support", "doseRange": "150-300 mcg daily", "recommendedForm": "Potassium iodide or kelp-derived iodine", "timing": "Morning with food", "notes": "Lab context matters; more iodine is not always better for thyroid symptoms." } ] }, { "supplementName": "Potassium", "dosageByGoal": [ { "id": "91d8b7cb-fe36-4306-8487-5b727959f62a", "goal": "Low dietary potassium intake", "doseRange": "99-300 mg supplemental daily", "recommendedForm": "Potassium citrate or gluconate", "timing": "With meals", "notes": "Food should provide most daily potassium because supplement caps are intentionally low." }, { "id": "a974de88-d2c2-4cb8-9dc7-98d9d8822ea6", "goal": "Electrolyte support with heavy sweating", "doseRange": "99-200 mg supplemental plus high-potassium foods", "recommendedForm": "Potassium citrate", "timing": "Around training or heat exposure", "notes": "Avoid self-supplementing aggressively if you have kidney disease or take potassium-sparing medication." }, { "id": "716b118e-3759-4872-bb9e-b7713124fba9", "goal": "Blood-pressure-supportive diet gap", "doseRange": "99-300 mg supplemental daily", "recommendedForm": "Potassium citrate", "timing": "With meals", "notes": "Prioritize potatoes, beans, dairy, and fruit first." } ] }, { "supplementName": "Vitamin E", "dosageByGoal": [ { "id": "a3cf80f0-3e2f-4d3d-8444-45873d06820e", "goal": "General antioxidant support", "doseRange": "100-200 IU daily", "recommendedForm": "Mixed tocopherols or natural d-alpha tocopherol", "timing": "With a fat-containing meal", "notes": "Stay cautious with higher doses if you bruise easily or use anticoagulants." }, { "id": "f2e1baef-bb45-40e1-a268-0c24088288e1", "goal": "Skin support", "doseRange": "100-200 IU daily", "recommendedForm": "Mixed tocopherols", "timing": "With meals", "notes": "More is not necessarily better; mixed tocopherols are usually preferred." }, { "id": "5d8b11d1-0346-4fc8-bb2f-a9a9ace8d534", "goal": "Fertility support", "doseRange": "100-200 IU daily", "recommendedForm": "Mixed tocopherols", "timing": "With food", "notes": "Avoid routine 400 IU/day dosing unless a clinician is supervising a specific indication." } ] }, { "supplementName": "Vitamin A", "dosageByGoal": [ { "id": "fc44b1dd-61f8-44f6-bfee-00bbdc70a969", "goal": "Vision support", "doseRange": "2,500-5,000 IU daily", "recommendedForm": "Retinyl palmitate or mixed carotenoids", "timing": "With a fat-containing meal", "notes": "Choose conservative dosing unless deficiency is documented." }, { "id": "c7e04bb2-cd5f-498e-b82c-3227ef41287a", "goal": "Skin support", "doseRange": "2,500-5,000 IU daily", "recommendedForm": "Retinyl palmitate", "timing": "With food", "notes": "Avoid high chronic retinol intakes if pregnant or trying to conceive." }, { "id": "d001b714-545b-42cb-88f7-a8405c946129", "goal": "Immune support in low intake", "doseRange": "2,500-5,000 IU daily", "recommendedForm": "Retinyl palmitate or beta-carotene", "timing": "With a meal containing fat", "notes": "Smokers should avoid high-dose beta-carotene supplements." } ] }, { "supplementName": "Chromium", "dosageByGoal": [ { "id": "0f61f38e-ef4d-446e-9520-6a2cd5837721", "goal": "Blood sugar support", "doseRange": "200-500 mcg daily", "recommendedForm": "Chromium picolinate", "timing": "With meals", "notes": "Best used when carb-heavy meals or insulin resistance are part of the picture." }, { "id": "f49f6fd1-90c5-4edb-b1fa-0cbd032498a0", "goal": "Appetite and carb-craving support", "doseRange": "200-400 mcg daily", "recommendedForm": "Chromium picolinate", "timing": "With breakfast or lunch", "notes": "Use as an adjunct to dietary structure, not a substitute." }, { "id": "537b9d1b-f2a4-4a97-8695-2c3a644f11ff", "goal": "Metabolic support", "doseRange": "200-1,000 mcg daily", "recommendedForm": "Chromium picolinate", "timing": "Split with meals if using higher amounts", "notes": "More is not always better; many people do well at the low end." } ] }, { "supplementName": "5-HTP", "dosageByGoal": [ { "id": "3C895D9E-D3AC-4247-9376-DDFD758AA297", "goal": "Sleep", "doseRange": "100 mg nightly", "recommendedForm": "5-HTP from Griffonia simplicifolia seed extract", "timing": "30-60 minutes before bed", "notes": "Clinical dose evidence: PMID 38309227. Avoid combining with serotonergic medications unless clinician supervised." }, { "id": "58BB06DF-8B84-4C70-A6ED-FAD8C0684222", "goal": "Stress & Anxiety", "doseRange": "50-200 mg daily", "recommendedForm": "5-HTP from Griffonia simplicifolia seed extract", "timing": "With food, split if needed", "notes": "Clinical dose evidence: PMID 31504850. Avoid combining with serotonergic medications unless clinician supervised." }, { "id": "B9493F4C-F2D1-498C-87DA-D57E9A8D7812", "goal": "Metabolic Health", "doseRange": "300 mg three times daily", "recommendedForm": "5-HTP from Griffonia simplicifolia seed extract", "timing": "30 minutes before meals", "notes": "Clinical dose evidence: PMID 1384305. Avoid combining with serotonergic medications unless clinician supervised." } ] }, { "supplementName": "Activated Charcoal", "dosageByGoal": [] }, { "supplementName": "Alcohol", "dosageByGoal": [] }, { "supplementName": "Alpha-GPC", "dosageByGoal": [ { "id": "7B49B59D-31BC-48B1-9384-A0A541F4BB69", "goal": "Cognition & Focus", "doseRange": "300-600 mg daily", "recommendedForm": "Alpha-GPC 50% (standard) or 99% powder", "timing": "Morning", "notes": "Clinical dose evidence: PMID 39683633." } ] }, { "supplementName": "Apigenin", "dosageByGoal": [] }, { "supplementName": "Artemisinin", "dosageByGoal": [] }, { "supplementName": "Astaxanthin", "dosageByGoal": [ { "id": "33D5FEF9-280D-4180-8B40-81E1EB7DE43A", "goal": "Athletic Performance", "doseRange": "4-12 mg daily", "recommendedForm": "Natural astaxanthin from Haematococcus pluvialis microalgae", "timing": "With a fat-containing meal", "notes": "Clinical dose evidence: PMID 33344941." } ] }, { "supplementName": "BCAAs", "dosageByGoal": [ { "id": "5C81D1F5-BEAD-4542-A1EF-8FB11FB486B6", "goal": "Athletic Performance", "doseRange": "5-10 g around training", "recommendedForm": "2:1:1 ratio (Leucine:Isoleucine:Valine)", "timing": "Before or during training", "notes": "Clinical dose evidence: PMID 38241335." } ] }, { "supplementName": "Bee Pollen", "dosageByGoal": [] }, { "supplementName": "Beta-Alanine", "dosageByGoal": [ { "id": "5E6EB676-3FF9-46B2-9496-1649AA6D6CCD", "goal": "Athletic Performance", "doseRange": "3.2-6.4 g daily", "recommendedForm": "Beta-Alanine powder (sustained-release to reduce tingling)", "timing": "Split into 2-4 doses", "notes": "Clinical dose evidence: PMID 27797728." } ] }, { "supplementName": "Beta-Carotene", "dosageByGoal": [] }, { "supplementName": "Betaine HCL", "dosageByGoal": [] }, { "supplementName": "Black Cohosh", "dosageByGoal": [] }, { "supplementName": "Black Seed Oil", "dosageByGoal": [ { "id": "B3F4B71C-9700-4F73-94E0-92C22EAB676C", "goal": "Metabolic Health", "doseRange": "1-3 g oil daily or 500-1,000 mg extract daily", "recommendedForm": "Cold-pressed black seed oil or standardized thymoquinone extract", "timing": "With meals", "notes": "Clinical dose evidence: PMID 41858302." }, { "id": "87D6F326-DF04-4B1D-BFF7-F9EE33441DA6", "goal": "Heart & Cardiovascular", "doseRange": "1-3 g oil daily or 500-1,000 mg extract daily", "recommendedForm": "Cold-pressed black seed oil or standardized thymoquinone extract", "timing": "With meals", "notes": "Clinical dose evidence: PMID 27512971." } ] }, { "supplementName": "Boron", "dosageByGoal": [ { "id": "C41673FB-52F0-438A-A81B-762F84CF0566", "goal": "Bone Health", "doseRange": "3-6 mg daily", "recommendedForm": "Boron citrate or boron glycinate", "timing": "With a meal", "notes": "Clinical dose evidence: PMID 3678698." } ] }, { "supplementName": "Boswellia", "dosageByGoal": [] }, { "supplementName": "Bromelain", "dosageByGoal": [] }, { "supplementName": "CLA", "dosageByGoal": [] }, { "supplementName": "Cannabis (THC-Dominant)", "dosageByGoal": [] }, { "supplementName": "Cat's Claw", "dosageByGoal": [] }, { "supplementName": "Chaga", "dosageByGoal": [] }, { "supplementName": "Chlorella", "dosageByGoal": [ { "id": "3CBC2A9E-3B11-4EFD-90F7-D24510866788", "goal": "Metabolic Health", "doseRange": "3-10 g daily", "recommendedForm": "Broken cell wall chlorella (for digestibility)", "timing": "With meals", "notes": "Clinical dose evidence: PMID 29037431." } ] }, { "supplementName": "Chondroitin", "dosageByGoal": [] }, { "supplementName": "Citicoline", "dosageByGoal": [ { "id": "99A72FB2-4BDB-44F5-B5BE-34441ED11451", "goal": "Cognition & Focus", "doseRange": "250-500 mg daily", "recommendedForm": "Citicoline (CDP-Choline), Cognizin is a patented, well-studied form", "timing": "Morning", "notes": "Clinical dose evidence: PMID 33978188." } ] }, { "supplementName": "Cocaine", "dosageByGoal": [] }, { "supplementName": "Colostrum", "dosageByGoal": [ { "id": "AA095431-9899-4C28-9531-20040A6359F7", "goal": "Immune Support", "doseRange": "500-2,000 mg daily", "recommendedForm": "Bovine colostrum (first milking, cold-processed)", "timing": "Morning or with meals", "notes": "Clinical dose evidence: PMID 32276466." }, { "id": "5CF23EB5-C1CA-485D-B2AC-2EA55AAD61B1", "goal": "Athletic Performance", "doseRange": "10-25 g daily", "recommendedForm": "Bovine colostrum (first milking, cold-processed)", "timing": "Daily during training blocks", "notes": "Clinical dose evidence: PMID 39972597." } ] }, { "supplementName": "Copper", "dosageByGoal": [] }, { "supplementName": "Cordyceps", "dosageByGoal": [ { "id": "8BAAC2D9-ED7D-4547-8CBE-B21C76C88A96", "goal": "Athletic Performance", "doseRange": "1,000-3,000 mg daily", "recommendedForm": "Cordyceps militaris fruiting body extract (standardized for cordycepin)", "timing": "Morning or pre-workout", "notes": "Clinical dose evidence: PMID 27408987." }, { "id": "97ACA10C-2E54-4039-BFED-C51C02F1A624", "goal": "Immune Support", "doseRange": "1,000-3,000 mg daily", "recommendedForm": "Cordyceps militaris fruiting body extract (standardized for cordycepin)", "timing": "Morning", "notes": "Clinical dose evidence: PMID 38580687." } ] }, { "supplementName": "D-Aspartic Acid", "dosageByGoal": [] }, { "supplementName": "D-Mannose", "dosageByGoal": [] }, { "supplementName": "DHEA", "dosageByGoal": [ { "id": "3C978987-2F79-4AF5-898E-0E25ECF9479A", "goal": "Bone Health", "doseRange": "25-50 mg daily", "recommendedForm": "Micronized DHEA", "timing": "Morning", "notes": "Clinical dose evidence: PMID 31237150. Hormone-active supplement; use lab-guided clinician supervision." } ] }, { "supplementName": "DIM", "dosageByGoal": [] }, { "supplementName": "Digestive Enzymes", "dosageByGoal": [] }, { "supplementName": "Echinacea", "dosageByGoal": [ { "id": "65750B9E-BA9A-4293-8192-84D3B3B0B13E", "goal": "Immune Support", "doseRange": "300-500 mg three times daily", "recommendedForm": "Echinacea purpurea aerial parts extract", "timing": "At onset of symptoms", "notes": "Clinical dose evidence: PMID 17597571." } ] }, { "supplementName": "Elderberry", "dosageByGoal": [ { "id": "AE74A5BB-1BCC-46F5-87FA-3A78CEC3EDDB", "goal": "Immune Support", "doseRange": "500-1,000 mg daily during illness", "recommendedForm": "Standardized extract (elderberry syrup or capsules)", "timing": "At onset of symptoms", "notes": "Clinical dose evidence: PMID 30670267." } ] }, { "supplementName": "Elderberry Zinc Lozenges", "dosageByGoal": [ { "id": "AA72FBA1-10D3-4FB3-A173-FBE338B6E074", "goal": "Immune Support", "doseRange": "1 lozenge every 2-3 hours while awake", "recommendedForm": "Zinc acetate or gluconate lozenges with elderberry", "timing": "At onset of cold symptoms", "notes": "Clinical dose evidence: PMID 28515951." } ] }, { "supplementName": "Evening Primrose Oil", "dosageByGoal": [] }, { "supplementName": "Fenugreek", "dosageByGoal": [ { "id": "BAC83708-F630-499F-85DF-4300B68E68EC", "goal": "Metabolic Health", "doseRange": "500-1,000 mg extract daily", "recommendedForm": "Testofen or standardized fenugreek extract", "timing": "With meals", "notes": "Clinical dose evidence: PMID 37762302." }, { "id": "E92158AE-7309-4117-8B8A-91225D0B0D0C", "goal": "Athletic Performance", "doseRange": "500-600 mg extract daily", "recommendedForm": "Testofen or standardized fenugreek extract", "timing": "With breakfast or pre-workout meal", "notes": "Clinical dose evidence: PMID 36983608." } ] }, { "supplementName": "Flaxseed Oil", "dosageByGoal": [ { "id": "34FC3BA3-B1BE-469A-99EE-DF925C5A00F7", "goal": "Heart & Cardiovascular", "doseRange": "1-2 tablespoons daily or 1,000-2,000 mg daily", "recommendedForm": "Cold-pressed organic flaxseed oil", "timing": "With meals", "notes": "Clinical dose evidence: PMID 23076616." } ] }, { "supplementName": "GABA", "dosageByGoal": [ { "id": "B024C4B2-3AF4-4E70-AC21-21FC4561FADF", "goal": "Sleep", "doseRange": "100-300 mg nightly", "recommendedForm": "PharmaGABA (naturally fermented, preferred)", "timing": "30-60 minutes before bed", "notes": "Clinical dose evidence: PMID 30263304." }, { "id": "A0FE4000-F140-472C-A141-0E3E6A5D834B", "goal": "Stress & Anxiety", "doseRange": "100-300 mg as needed", "recommendedForm": "PharmaGABA (naturally fermented, preferred)", "timing": "During high-stress periods or evening", "notes": "Clinical dose evidence: PMID 33041752." } ] }, { "supplementName": "Garlic Extract", "dosageByGoal": [ { "id": "8ED25E70-BE6A-48C4-8545-C858D767E88C", "goal": "Heart & Cardiovascular", "doseRange": "600-1,200 mg aged garlic extract daily", "recommendedForm": "Aged garlic extract (Kyolic is well-studied)", "timing": "With meals", "notes": "Clinical dose evidence: PMID 40628369." }, { "id": "020999C0-1AFB-4E3A-B16A-1BFCAD5A5F96", "goal": "Immune Support", "doseRange": "600-1,200 mg aged garlic extract daily", "recommendedForm": "Aged garlic extract (Kyolic is well-studied)", "timing": "With meals", "notes": "Clinical dose evidence: PMID 26764326." } ] }, { "supplementName": "Ginger Extract", "dosageByGoal": [ { "id": "E5362C45-3750-4C82-AF2D-E83CEA93D0E8", "goal": "Metabolic Health", "doseRange": "500-2,000 mg daily", "recommendedForm": "Standardized extract (5% gingerols)", "timing": "With meals", "notes": "Clinical dose evidence: PMID 31935866." } ] }, { "supplementName": "Glucosamine", "dosageByGoal": [] }, { "supplementName": "Grape Seed Extract", "dosageByGoal": [ { "id": "F42289E5-5D0B-4E16-9666-B64FA07C75FE", "goal": "Heart & Cardiovascular", "doseRange": "100-300 mg daily", "recommendedForm": "Standardized to 95% OPCs", "timing": "With meals", "notes": "Clinical dose evidence: PMID 27537554." } ] }, { "supplementName": "Green Tea Extract", "dosageByGoal": [ { "id": "E4754164-566A-4EC6-AC6A-C99150A5887C", "goal": "Metabolic Health", "doseRange": "250-500 mg daily standardized to EGCG", "recommendedForm": "Decaffeinated standardized extract", "timing": "With food, never fasting", "notes": "Clinical dose evidence: PMID 38031409. Avoid fasting use and keep total EGCG within safety guidance." }, { "id": "2E616258-F3DA-4101-96E9-A3F61534B8B3", "goal": "Cognition & Focus", "doseRange": "250-500 mg daily standardized to EGCG", "recommendedForm": "Decaffeinated standardized extract", "timing": "Morning with food", "notes": "Clinical dose evidence: PMID 28899506. Avoid fasting use and keep total EGCG within safety guidance." } ] }, { "supplementName": "HMB", "dosageByGoal": [ { "id": "0B8A8FE6-907C-4BA2-BE28-59A5A9E23BA0", "goal": "Athletic Performance", "doseRange": "3 g daily", "recommendedForm": "Calcium HMB or free acid HMB", "timing": "Split into 2-3 doses", "notes": "Clinical dose evidence: PMID 19387395." } ] }, { "supplementName": "Holy Basil/Tulsi", "dosageByGoal": [ { "id": "846E4F7E-0F24-4C2C-94CF-9EE76F69F129", "goal": "Stress & Anxiety", "doseRange": "300-600 mg daily", "recommendedForm": "Standardized extract (2.5% ursolic acid)", "timing": "Morning or split AM/PM", "notes": "Clinical dose evidence: PMID 28400848." } ] }, { "supplementName": "Hyaluronic Acid", "dosageByGoal": [] }, { "supplementName": "Inositol", "dosageByGoal": [ { "id": "BEA4A86B-DC3F-4745-B598-30FD00A6E4F0", "goal": "Metabolic Health", "doseRange": "2-4 g myo-inositol daily", "recommendedForm": "Myo-inositol powder (most researched for PCOS)", "timing": "Split with meals", "notes": "Clinical dose evidence: PMID 38163998." }, { "id": "43559D11-BECB-46C4-9509-274F5BF30618", "goal": "Stress & Anxiety", "doseRange": "2-4 g myo-inositol daily", "recommendedForm": "Myo-inositol powder (most researched for PCOS)", "timing": "Split AM/PM", "notes": "Clinical dose evidence: PMID 36703143." } ] }, { "supplementName": "Ketamine", "dosageByGoal": [] }, { "supplementName": "L-Arginine", "dosageByGoal": [ { "id": "9A80B2BF-D495-4D6C-9F4C-50D4A62F77EA", "goal": "Heart & Cardiovascular", "doseRange": "3-6 g daily", "recommendedForm": "L-Arginine HCl or L-Citrulline (better bioavailability)", "timing": "Split doses, away from heavy meals", "notes": "Clinical dose evidence: PMID 27660594." } ] }, { "supplementName": "L-Carnitine", "dosageByGoal": [ { "id": "7D626F49-5803-4A4D-9D38-0604E212C2A7", "goal": "Athletic Performance", "doseRange": "1-3 g daily", "recommendedForm": "L-Carnitine L-Tartrate (exercise) or Acetyl-L-Carnitine (brain)", "timing": "Morning or pre-workout", "notes": "Clinical dose evidence: PMID 34959912." }, { "id": "C068F47B-0CCD-4242-91E5-0D2ED03E6495", "goal": "Metabolic Health", "doseRange": "1-3 g daily", "recommendedForm": "L-Carnitine L-Tartrate (exercise) or Acetyl-L-Carnitine (brain)", "timing": "With meals", "notes": "Clinical dose evidence: PMID 32359762." }, { "id": "6AC6DEB1-3D4A-4A41-A4A0-C1C3912A3635", "goal": "Heart & Cardiovascular", "doseRange": "1-3 g daily", "recommendedForm": "L-Carnitine L-Tartrate (exercise) or Acetyl-L-Carnitine (brain)", "timing": "With meals", "notes": "Clinical dose evidence: PMID 23597877." } ] }, { "supplementName": "L-Citrulline", "dosageByGoal": [ { "id": "A7C59CD0-BFF7-4D2E-B90E-D7C1296D6C00", "goal": "Athletic Performance", "doseRange": "6-8 g citrulline malate or 3-6 g L-citrulline", "recommendedForm": "L-Citrulline or Citrulline Malate 2:1", "timing": "30-60 minutes before training", "notes": "Clinical dose evidence: PMID 34010809." }, { "id": "D6427BA0-A3FD-4C4F-B7D3-E3CCE2A417CB", "goal": "Heart & Cardiovascular", "doseRange": "3-6 g L-citrulline daily", "recommendedForm": "L-Citrulline or Citrulline Malate 2:1", "timing": "Split AM/PM", "notes": "Clinical dose evidence: PMID 30788274." } ] }, { "supplementName": "L-Glutamine", "dosageByGoal": [] }, { "supplementName": "L-Lysine", "dosageByGoal": [] }, { "supplementName": "L-Methionine", "dosageByGoal": [] }, { "supplementName": "L-Tryptophan", "dosageByGoal": [ { "id": "1FFD7BA6-C535-48D0-A69F-00E1E4F30B09", "goal": "Sleep", "doseRange": "500-1,000 mg nightly", "recommendedForm": "Free-form L-Tryptophan", "timing": "30-60 minutes before bed", "notes": "Clinical dose evidence: PMID 33942088." } ] }, { "supplementName": "L-Tyrosine", "dosageByGoal": [ { "id": "AF724CC7-B74D-4007-A507-0D5DBFA52A47", "goal": "Cognition & Focus", "doseRange": "500-2,000 mg as needed", "recommendedForm": "L-tyrosine (better absorbed than NALT)", "timing": "30-60 minutes before demanding cognitive work", "notes": "Clinical dose evidence: PMID 26424423." }, { "id": "E79C93F2-F31D-48D7-BC10-52316052E23B", "goal": "Stress & Anxiety", "doseRange": "500-2,000 mg as needed", "recommendedForm": "L-tyrosine (better absorbed than NALT)", "timing": "Before acute stress exposure", "notes": "Clinical dose evidence: PMID 26126245." } ] }, { "supplementName": "Lithium Orotate", "dosageByGoal": [] }, { "supplementName": "Lutein", "dosageByGoal": [ { "id": "36613902-99E0-4E2E-811B-EB721E093D4A", "goal": "Cognition & Focus", "doseRange": "10-20 mg daily", "recommendedForm": "FloraGLO Lutein (from marigold flowers)", "timing": "With a fat-containing meal", "notes": "Clinical dose evidence: PMID 34641336." } ] }, { "supplementName": "Lycopene", "dosageByGoal": [ { "id": "CE5410D0-5F71-43F4-A881-80FBE0AB0E7A", "goal": "Heart & Cardiovascular", "doseRange": "10-30 mg daily", "recommendedForm": "Tomato oleoresin extract (LycoRed)", "timing": "With a fat-containing meal", "notes": "Clinical dose evidence: PMID 32652029." } ] }, { "supplementName": "MCT Oil", "dosageByGoal": [ { "id": "9CCD4453-20E9-46A4-B344-3BDE4D4A7556", "goal": "Metabolic Health", "doseRange": "1-3 tablespoons daily", "recommendedForm": "C8 (caprylic acid) or C8/C10 blend", "timing": "With meals or blended into beverages", "notes": "Clinical dose evidence: PMID 25636220." }, { "id": "DA52BB09-9246-441F-9FEF-64ADDA8D2BF9", "goal": "Cognition & Focus", "doseRange": "10-30 g daily", "recommendedForm": "C8 (caprylic acid) or C8/C10 blend", "timing": "Morning, titrate slowly", "notes": "Clinical dose evidence: PMID 31870908." } ] }, { "supplementName": "MDMA", "dosageByGoal": [] }, { "supplementName": "MSM", "dosageByGoal": [] }, { "supplementName": "Maca Root", "dosageByGoal": [] }, { "supplementName": "Magnesium Citrate", "dosageByGoal": [ { "id": "020ED3A7-6ACD-487D-A617-3B0D14AF843D", "goal": "Heart & Cardiovascular", "doseRange": "200-350 mg elemental magnesium daily", "recommendedForm": "Magnesium citrate powder or capsules", "timing": "Evening or split doses", "notes": "Clinical dose evidence: PMID 22318649." } ] }, { "supplementName": "Magnesium Malate", "dosageByGoal": [] }, { "supplementName": "Magnesium Taurate", "dosageByGoal": [] }, { "supplementName": "Manganese", "dosageByGoal": [] }, { "supplementName": "Milk Thistle", "dosageByGoal": [] }, { "supplementName": "Molybdenum", "dosageByGoal": [] }, { "supplementName": "Moringa", "dosageByGoal": [ { "id": "8BB69B72-2D64-4AF6-86B8-2EA70033E21C", "goal": "Metabolic Health", "doseRange": "500-2,000 mg daily", "recommendedForm": "Organic moringa leaf powder or capsules", "timing": "With meals", "notes": "Clinical dose evidence: PMID 41305552." } ] }, { "supplementName": "NMN", "dosageByGoal": [ { "id": "81D9C416-56B3-444C-951A-848F66F5DF56", "goal": "Metabolic Health", "doseRange": "250-1,000 mg daily", "recommendedForm": "Sublingual NMN or enteric-coated capsules for better bioavailability", "timing": "Morning", "notes": "Clinical dose evidence: PMID 39116016." }, { "id": "E19D0CCD-83A2-4035-8479-1E4260214224", "goal": "Athletic Performance", "doseRange": "250-1,000 mg daily", "recommendedForm": "Sublingual NMN or enteric-coated capsules for better bioavailability", "timing": "Morning or pre-training", "notes": "Clinical dose evidence: PMID 39221308." } ] }, { "supplementName": "Nattokinase", "dosageByGoal": [ { "id": "284226EF-5794-4163-AA17-8980695902BA", "goal": "Heart & Cardiovascular", "doseRange": "2,000-4,000 FU daily", "recommendedForm": "Nattokinase (measured in fibrinolytic units, FU)", "timing": "Empty stomach", "notes": "Clinical dose evidence: PMID 39076715. Avoid with anticoagulants, bleeding disorders, or before surgery unless clinician supervised." } ] }, { "supplementName": "Nicotine", "dosageByGoal": [] }, { "supplementName": "Olive Leaf Extract", "dosageByGoal": [ { "id": "4DFC1893-1C3F-4DA6-9205-511B939BF9AB", "goal": "Heart & Cardiovascular", "doseRange": "500-1,000 mg daily standardized to oleuropein", "recommendedForm": "Standardized extract", "timing": "With meals", "notes": "Clinical dose evidence: PMID 33868820." }, { "id": "1835EB07-7522-46B6-AA83-A88D9E655129", "goal": "Metabolic Health", "doseRange": "500-1,000 mg daily standardized to oleuropein", "recommendedForm": "Standardized extract", "timing": "With meals", "notes": "Clinical dose evidence: PMID 38287654." } ] }, { "supplementName": "Omega-7", "dosageByGoal": [] }, { "supplementName": "Ox Bile", "dosageByGoal": [] }, { "supplementName": "PQQ", "dosageByGoal": [ { "id": "180C503B-C685-4E69-B255-937AD39D6EE1", "goal": "Cognition & Focus", "doseRange": "10-20 mg daily", "recommendedForm": "PQQ disodium salt (BioPQQ)", "timing": "Morning with food", "notes": "Clinical dose evidence: PMID 34415830." }, { "id": "3CB9FB76-75C5-49BA-9F1B-16ADE0A5BEB6", "goal": "Athletic Performance", "doseRange": "20 mg daily", "recommendedForm": "PQQ disodium salt (BioPQQ)", "timing": "Morning with food", "notes": "Clinical dose evidence: PMID 31860387." } ] }, { "supplementName": "Passionflower", "dosageByGoal": [ { "id": "DA05728E-5821-46AC-AACF-35B8223717A4", "goal": "Sleep", "doseRange": "200-400 mg nightly", "recommendedForm": "Standardized extract", "timing": "30-60 minutes before bed", "notes": "Clinical dose evidence: PMID 31714321." }, { "id": "3568E3E5-B470-414C-8DDE-BC313C158826", "goal": "Stress & Anxiety", "doseRange": "200-400 mg daily", "recommendedForm": "Standardized extract", "timing": "Evening or as needed", "notes": "Clinical dose evidence: PMID 33352740." } ] }, { "supplementName": "Phosphatidylcholine", "dosageByGoal": [] }, { "supplementName": "Phosphatidylserine", "dosageByGoal": [ { "id": "FFD44CF2-661C-4A1D-B1AE-8EF0196AA9B1", "goal": "Cognition & Focus", "doseRange": "100-300 mg daily", "recommendedForm": "Phosphatidylserine from sunflower lecithin (soy-free)", "timing": "With meals, split if needed", "notes": "Clinical dose evidence: PMID 39317299." }, { "id": "DE9EA22F-6746-4AB6-A298-DDB25EDFCC15", "goal": "Stress & Anxiety", "doseRange": "400-800 mg daily short term", "recommendedForm": "Phosphatidylserine from sunflower lecithin (soy-free)", "timing": "Split AM/PM", "notes": "Clinical dose evidence: PMID 1325348." } ] }, { "supplementName": "Pine Bark Extract", "dosageByGoal": [ { "id": "AB5F1617-E704-42CD-8F49-A868BE030F49", "goal": "Heart & Cardiovascular", "doseRange": "100-200 mg daily", "recommendedForm": "Pycnogenol (patented French maritime pine bark extract)", "timing": "With meals", "notes": "Clinical dose evidence: PMID 31763928." }, { "id": "4559EFAE-00A8-487A-B148-0A6AD6C7AF03", "goal": "Cognition & Focus", "doseRange": "100-150 mg daily", "recommendedForm": "Pycnogenol (patented French maritime pine bark extract)", "timing": "Morning with food", "notes": "Clinical dose evidence: PMID 24675223." } ] }, { "supplementName": "Pregnenolone", "dosageByGoal": [] }, { "supplementName": "Psilocybin", "dosageByGoal": [] }, { "supplementName": "Psyllium Husk", "dosageByGoal": [ { "id": "520C0260-2B99-454A-81BC-D58D6D616A59", "goal": "Metabolic Health", "doseRange": "5-10 g daily", "recommendedForm": "Whole husk or powder (mix in water, drink immediately)", "timing": "With meals, separated from medications", "notes": "Clinical dose evidence: PMID 38844885." }, { "id": "6F238266-2EA3-4D6C-8861-6DEA56740ADC", "goal": "Heart & Cardiovascular", "doseRange": "5-10 g daily", "recommendedForm": "Whole husk or powder (mix in water, drink immediately)", "timing": "With meals, separated from medications", "notes": "Clinical dose evidence: PMID 30239559." } ] }, { "supplementName": "Reishi", "dosageByGoal": [ { "id": "A048557E-725C-4E0C-834E-9358845EF8AE", "goal": "Immune Support", "doseRange": "1,000-3,000 mg daily", "recommendedForm": "Dual extract (hot water + alcohol) capturing both polysaccharides and triterpenes", "timing": "With food", "notes": "Clinical dose evidence: PMID 22696372." } ] }, { "supplementName": "Royal Jelly", "dosageByGoal": [ { "id": "B1BB100F-F183-4C8A-9F41-AD1DF62D5656", "goal": "Metabolic Health", "doseRange": "1,000-3,000 mg daily", "recommendedForm": "Fresh or freeze-dried royal jelly (standardized to 6% 10-HDA)", "timing": "With breakfast", "notes": "Clinical dose evidence: PMID 30935531." } ] }, { "supplementName": "SAMe", "dosageByGoal": [ { "id": "486EC9D8-8DF3-4312-9E81-CE92F7FB3B52", "goal": "Stress & Anxiety", "doseRange": "400-1,600 mg daily", "recommendedForm": "Enteric-coated SAMe (unstable, quality matters)", "timing": "Morning on an empty stomach", "notes": "Clinical dose evidence: PMID 38423354." } ] }, { "supplementName": "Saw Palmetto", "dosageByGoal": [] }, { "supplementName": "Schisandra", "dosageByGoal": [] }, { "supplementName": "Serrapeptase", "dosageByGoal": [] }, { "supplementName": "Shilajit", "dosageByGoal": [ { "id": "D0F5A756-25EE-49E2-9F07-94B94947F51F", "goal": "Bone Health", "doseRange": "250-500 mg daily", "recommendedForm": "Purified shilajit resin (PrimaVie is well-studied)", "timing": "Morning with food", "notes": "Clinical dose evidence: PMID 35933897." } ] }, { "supplementName": "Silicon", "dosageByGoal": [ { "id": "DA313F07-3DA0-42DD-9494-1BC84A278E2F", "goal": "Bone Health", "doseRange": "5-10 mg silicon daily", "recommendedForm": "Orthosilicic acid (stabilized, most bioavailable)", "timing": "With meals", "notes": "Clinical dose evidence: PMID 18547426." } ] }, { "supplementName": "Spirulina", "dosageByGoal": [ { "id": "110B6739-7CE9-49EB-BDAE-17F206EE93E7", "goal": "Metabolic Health", "doseRange": "1-8 g daily", "recommendedForm": "Organic spirulina powder or tablets", "timing": "With meals", "notes": "Clinical dose evidence: PMID 37263369." }, { "id": "74857FE9-1D4B-4C33-A6E3-0A847621D4D6", "goal": "Heart & Cardiovascular", "doseRange": "1-8 g daily", "recommendedForm": "Organic spirulina powder or tablets", "timing": "With meals", "notes": "Clinical dose evidence: PMID 34235823." } ] }, { "supplementName": "St. John's Wort", "dosageByGoal": [ { "id": "0427ABB0-D8B8-4A1D-BC81-F8FF1D0A7A1B", "goal": "Stress & Anxiety", "doseRange": "300 mg extract three times daily", "recommendedForm": "Standardized extract (0.3% hypericin, 1-5% hyperforin)", "timing": "With meals", "notes": "Clinical dose evidence: PMID 28064110. Major CYP3A4 and serotonergic interaction risk; medication review is essential." } ] }, { "supplementName": "Strontium", "dosageByGoal": [] }, { "supplementName": "Sulforaphane", "dosageByGoal": [ { "id": "B6BA1575-08F4-4BB9-8138-60316C42B363", "goal": "Metabolic Health", "doseRange": "30-60 mg sulforaphane daily", "recommendedForm": "Broccoli sprout extract with myrosinase enzyme (Avmacol, Prostaphane)", "timing": "With food", "notes": "Clinical dose evidence: PMID 28615356." } ] }, { "supplementName": "Tongkat Ali", "dosageByGoal": [ { "id": "B07E4539-6CA5-4138-B5F2-AA6D506669F7", "goal": "Stress & Anxiety", "doseRange": "200 mg daily", "recommendedForm": "Standardized extract (Physta or LJ100, 100:1 concentration)", "timing": "Morning", "notes": "Clinical dose evidence: PMID 23705671." }, { "id": "C0C21769-1B70-4117-BB72-386AC4C673E6", "goal": "Athletic Performance", "doseRange": "200 mg daily", "recommendedForm": "Standardized extract (Physta or LJ100, 100:1 concentration)", "timing": "Morning or pre-training", "notes": "Clinical dose evidence: PMID 34262417." } ] }, { "supplementName": "Tribulus Terrestris", "dosageByGoal": [] }, { "supplementName": "Turkey Tail", "dosageByGoal": [ { "id": "6393F6FB-3B61-4C4D-90C8-74EC8869D954", "goal": "Immune Support", "doseRange": "1-3 g extract daily", "recommendedForm": "Hot water extract or dual extract powder", "timing": "With meals", "notes": "Clinical dose evidence: PMID 25784670." } ] }, { "supplementName": "Valerian Root", "dosageByGoal": [ { "id": "59B9AD2F-4544-4743-9E7D-7A828A40EF20", "goal": "Sleep", "doseRange": "300-600 mg nightly", "recommendedForm": "Standardized extract (0.8% valerenic acid)", "timing": "30-60 minutes before bed", "notes": "Clinical dose evidence: PMID 33086877." } ] }, { "supplementName": "Vanadium", "dosageByGoal": [ { "id": "A0DF8617-D196-4D75-A8D0-D9440DD11344", "goal": "Metabolic Health", "doseRange": "10-50 mcg daily", "recommendedForm": "Vanadyl sulfate or bis(maltolato)oxovanadium", "timing": "With meals", "notes": "Clinical dose evidence: PMID 11238540. Use only with clinician guidance in diabetes or kidney disease." } ] }, { "supplementName": "Vitamin B1", "dosageByGoal": [] }, { "supplementName": "Vitamin B2", "dosageByGoal": [] }, { "supplementName": "Vitamin B3", "dosageByGoal": [ { "id": "98CCCDF6-AAC3-48FB-88F0-3FC9AA1AF976", "goal": "Metabolic Health", "doseRange": "500-2,000 mg daily only clinician-directed", "recommendedForm": "Niacinamide (no flush) or extended-release niacin", "timing": "With meals", "notes": "Clinical dose evidence: PMID 22085343. Pharmacologic niacin dosing needs clinician monitoring for liver, glucose, uric acid, and flushing risk." } ] }, { "supplementName": "Vitamin B5", "dosageByGoal": [ { "id": "85201370-CCF4-438D-A855-2000A8B74CA6", "goal": "Metabolic Health", "doseRange": "600-900 mg pantethine daily", "recommendedForm": "Pantothenic acid or pantethine (for cholesterol)", "timing": "Split with meals", "notes": "Clinical dose evidence: PMID 24600231." } ] }, { "supplementName": "Vitamin B6", "dosageByGoal": [] }, { "supplementName": "Vitamin B7", "dosageByGoal": [] }, { "supplementName": "Vitamin C Liposomal", "dosageByGoal": [ { "id": "923FA230-DC65-442B-B781-A86AEA5DA2E4", "goal": "Immune Support", "doseRange": "1,000-2,000 mg daily", "recommendedForm": "Liposomal vitamin C (look for sunflower lecithin, not soy)", "timing": "With or without food", "notes": "Clinical dose evidence: PMID 38082300." } ] }, { "supplementName": "Vitamin D2", "dosageByGoal": [ { "id": "E7173543-4FE8-4BD5-A469-B4150113A95D", "goal": "Bone Health", "doseRange": "1,000-2,000 IU daily", "recommendedForm": "Ergocalciferol from UV-irradiated mushrooms", "timing": "With a fat-containing meal", "notes": "Clinical dose evidence: PMID 34684328." } ] }, { "supplementName": "Vitamin K1", "dosageByGoal": [ { "id": "4CC08A60-196F-4719-AA0A-EB98096705EA", "goal": "Bone Health", "doseRange": "90-120 mcg daily", "recommendedForm": "Phylloquinone from food or supplements", "timing": "With a fat-containing meal", "notes": "Clinical dose evidence: PMID 35625785." } ] }, { "supplementName": "Zeaxanthin", "dosageByGoal": [] }, { "supplementName": "Zinc Carnosine", "dosageByGoal": [] } ] }