SAMe
Other ·Exploratory record · not publication-reviewed ·Updated July 13, 2026
Universal methyl donor involved in over 100 methylation reactions in the body.
Exploratory record, not a reviewed medical publication.
See the editorial and medical-review policies for the publication gate.
This generated database record has not completed a claim-level review by a qualified human medical reviewer. Bibliography links and evidence labels are not approval. The page remains available for reference and is excluded from search indexing.
What the research says.
A quick, data-only summary. The full evidence, dosing, and sources are below.
SAMe is an other most often used for mood support, joint health, liver health. NutriStack rates the overall evidence as strong. A typical adult dose is 400-1,600 mg daily, commonly taken as enteric-coated same (unstable, quality matters). This profile indexes 20 sources.
The bottom line
Evidence rating strong. Most-documented uses: mood support, joint health, liver health. 20 sources indexed (1993–2024), with 0 interaction records on file.
How it works, mechanistically.
Core mechanism
Donates methyl groups for DNA methylation, neurotransmitter synthesis (dopamine, serotonin, norepinephrine), phospholipid metabolism, and glutathione production.17,5
Dosing & protocol.
Take on empty stomach; enteric coating essential; refrigerate
What it actually costs.
Real-world pricing across three quality tiers. Assumes Enteric-Coated SAMe.
Assumes 400-1,600 mg/day. Vendor basis: NOW/iHerb, Vitacost, Life Extension, and Amazon marketplace; higher-dose enteric tablets drive premium pricing. Updated 2026-05-28.
The same dose, as food.
How much you'd eat to match a supplemental dose.
SAMe is made in the body from methionine and ATP; methionine foods such as eggs, fish, meat, Brazil nuts, and sesame seeds do not provide SAMe directly.
Full safety detail.
Side effects
- GI upset
- Anxiety
- Insomnia
- Mania or hypomania, especially in bipolar disorder
- Serotonin syndrome risk when combined with serotonergic agents
Sources, by evidence tier.
Numbered references. Citations throughout the page link here.
Meta-analyses & systematic reviews
13- 1Efficacy and acceptability of S-adenosyl-L-methionine (SAMe) for depressed patients: A systematic review and meta-analysisPMIDLi Q et al. · J Affect Disord · 2024
23 trials (N=2183) assessed SAMe for depression as monotherapy, adjunctive, and comparator; evidence shows promising but mixed efficacy.
- 2S-Adenosylmethionine (SAMe) as an adjuvant therapy for patients with depression: An updated systematic review and meta-analysisPMIDLin YT et al. · J Psychiatr Res · 2024
14 trials (1,522 subjects): no significant difference in depression with SAMe vs comparison when used as monotherapy or adjunctive therapy.
- 3S-Adenosylmethionine (SAMe) for Central Nervous System Health: A Systematic ReviewPMIDBaden KER, McClain H, Craig E et al. · Nutrients · 2024
Baden KER, McClain H, Craig E et al.. S-Adenosylmethionine (SAMe) for Central Nervous System Health: A Systematic Review. Nutrients. 2024
- 4Pharmacological interventions for treating intrahepatic cholestasis of pregnancy.PMIDWalker KF, Chappell LC, Hague WM, Middleton P, Thornton JG · Cochrane Database of Systematic Reviews · 2020
SAMe was among the pharmacological interventions evaluated; it reduced pruritus and liver enzymes in intrahepatic cholestasis of pregnancy, though UDCA showed more consistent benefits.
- 5Influence of nutrients involved in one-carbon metabolism on DNA methylation in adults-a systematic review and meta-analysis.PMIDAmenyah SD, Hughes CF, Ward M, Rosborough S, Deane J, Thursby SJ et al. · Nutrition Reviews · 2020
Nutrients involved in one-carbon metabolism, including SAMe pathway components (folate, B12, betaine), significantly influenced global DNA methylation status in adults.
- 6S-Adenosylmethionine (SAMe) in major depressive disorder (MDD): a clinician-oriented systematic reviewPMIDCuomo A, Beccarini Crescenzi B, Bolognesi S et al. · Annals of general psychiatry · 2020
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
- 7S-adenosyl-L-methionine for the treatment of depression: a systematic review and meta-analysisSource linkedPMIDSharma A, Gerbarg P, Bottiglieri T et al. · J Clin Psychiatry · 2017
- 8Ursodeoxycholic Acid and S-adenosylmethionine for the Treatment of Intrahepatic Cholestasis of Pregnancy: A Meta-analysisPMIDZhang Y, Lu L, Victor DW et al. · Hepatitis monthly · 2016
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
- 9SAMe for depression: a systematic review and meta-analysisSource linkedPMIDGalizia I, Oldani L, Macritchie K et al. · J Psychopharmacol · 2016
- 10S-adenosyl-L-methionine for the treatment of chronic liver disease: a systematic review and meta-analysisPMIDGuo T et al. · PLoS One · 2015
SAMe significantly improved total bilirubin and AST levels in chronic liver disease with few adverse events (primarily mild GI complaints).
- 11S-Adenosylmethionine for osteoarthritis of the knee or hipPMIDRutjes AW et al. · Cochrane Database Syst Rev · 2009
Four trials (656 patients) showed small standardized mean difference of -0.17 for pain; inconclusive due to small trial size and quality issues.
- 12S-adenosylmethionine (SAMe) as treatment for depression: a systematic reviewPMIDWilliams AL, Girard C, Jui D et al. · Clinical and investigative medicine. Medecine clinique et experimentale · 2005
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
- 13[A meta-analysis of therapeutic trials with ademetionine in the treatment of intrahepatic cholestasis]PMIDFrezza M · Annali italiani di medicina interna : organo ufficiale della Societa italiana di medicina interna · 1993
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
Randomized controlled trials
2- 14[Efficacy and safety of ademetionine for treatment of drug-induced liver disease in children]PMIDZhu SS, Dong Y, Gan Y et al. · 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
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
- 15Dietary supplement S-adenosyl-L-methionine (AdoMet) effects on plasma homocysteine levels in healthy human subjects: a double-blind, placebo-controlled, randomized clinical trialPMIDThompson MA, Bauer BA, Loehrer LL et al. · Journal of alternative and complementary medicine (New York, N.Y.) · 2009
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
Reviews & position papers
3- 16S-Adenosylmethionine (SAMe) for Liver Health: A Systematic ReviewPMIDAhmed S et al. · Cureus · 2024
SAMe (commonly 1000-1200 mg/day) was effective for liver function improvement with favorable safety profile; no serious adverse events reported.
- 17S-Adenosylmethionine (SAMe) for Neuropsychiatric Disorders: A Clinician-Oriented Review of ResearchPMIDSharma A et al. · J Clin Psychiatry · 2017
SAMe shows promise for major depressive disorder with limited evidence as monotherapy and augmentation; involved in methylation for neurotransmitter synthesis.
- 18Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidenceSource linkedPMIDPapakostas GI · Am J Clin Nutr · 2002
Observational studies
2- 19Possible SAMe-induced maniaPMIDAbeysundera H, Gill R · BMJ Case Reports · 2018
Case report describes mania with psychotic features during concomitant SAMe and SSRI use.
- 20A Case Report of a Manic Episode Triggered by S-Adenosylmethionine (SAMe)PMIDBerigan TR · Primary Care Companion to the Journal of Clinical Psychiatry · 2002
Case report documents a manic episode temporally associated with SAMe use.
Common questions.
Quick answers about SAMe, drawn from the data on this page.
What is SAMe?
Universal methyl donor involved in over 100 methylation reactions in the body.
What is SAMe used for?
Commonly cited benefits of SAMe include: Mood support; Joint health; Liver health; Methylation support. NutriStack rates the overall evidence as strong.
What is a typical dose of SAMe?
A typical adult dose of SAMe is 400-1,600 mg daily. The commonly recommended form is Enteric-coated SAMe (unstable, quality matters). These are general ranges, not personalized advice; confirm the right dose with a clinician.
What are the side effects of SAMe?
Reported side effects include gi upset, anxiety, insomnia, mania or hypomania, especially in bipolar disorder, serotonin syndrome risk when combined with serotonergic agents. This is educational information; check with a healthcare professional before use.
How strong is the evidence for SAMe?
NutriStack rates this as Strong, meaning multiple high-quality meta-analyses or systematic reviews converge on the same finding. Full tier criteria are at https://nutristackapp.com/methodology/evidence-tiers.
Use this with your stack
SAMe in NutriStack.
Add it to your stack, see how it interacts with everything else you take, and get a Stack Score that updates the moment it does.