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Supplement × Supplement·Evidence index

Methylfolate and Vitamin B12: what the research found

PubMed indexes 8 records that name Methylfolate and Vitamin B12 together, either in the title or in an interaction, co-administration, or pharmacokinetic context. The key findings come first, in the authors’ own words, followed by every study with its design and PubMed link.

A summary of published research, not medical advice. A pharmacist can check any combination against your full list of medicines and supplements.

Key findings

What the studies concluded.

Reviews and human studies first. Each quote is the authors’ own conclusion about their study, not a NutriStack assessment, and a single study is not a consensus.

“A three-month supplementation with a combination of 800 mcg methylfolate and 1000 mcg methylcobalamin showed promise in lowering blood pressure and serum homocysteine levels in ESRD patients with resistant hypertension. These findings require additional exploration in larger studies.”

Salem et al. · 2026 · Human study · details

“LDL-C levels decreased by 11.8% in homozygous carriers (95% CI: -15.8% to -7.8%, p < 0.01) and 4.8% in mixed allele carriers (95% CI: -6.8% to -2.8%, p < 0.01), with a significant between-group difference (7.0%, 95% CI: -13.0% to -1.0%, p < 0.01). Methylfolate, P5P, and methylcobalamin supplementation tailored to genetic profiles effectively reduced homocysteine and LDL-C levels in patients with specific MTHFR,…”

Pokushalov et al. · 2024 · Human study · details

“In a real-world clinical setting, patients with diabetic peripheral neuropathy treated with LMF-MC-PP achieved significant improvements in total symptom score (NTSS-6) and in quality of life and functioning, together with greater medication satisfaction. A limitation of this study was the use of a survey instrument to collect data on patient outcomes.”

The research

8 studies naming Methylfolate and Vitamin B12.

Strongest relevance first: papers naming both substances in the title, then human trials and systematic reviews.

Efficacy of L-methylfolate and methylcobalamin in treating resistant hypertension associated with elevated serum homocysteine in hemodialysis patients.

BMC nephrology · 2026 · PMID 41580678

Clinical Trial, Phase IVRandomized Controlled Trial

“A three-month supplementation with a combination of 800 mcg methylfolate and 1000 mcg methylcobalamin showed promise in lowering blood pressure and serum homocysteine levels in ESRD patients with resistant hypertension. These findings require additional exploration in larger studies.”

Salem et al. · Authors' conclusion

Names both Methylfolate and Vitamin B12 in its 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.

Nutrients · 2024 · PMID 38892484

Randomized Controlled Trial

“LDL-C levels decreased by 11.8% in homozygous carriers (95% CI: -15.8% to -7.8%, p < 0.01) and 4.8% in mixed allele carriers (95% CI: -6.8% to -2.8%, p < 0.01), with a significant between-group difference (7.0%, 95% CI: -13.0% to -1.0%, p < 0.01). Methylfolate, P5P, and methylcobalamin supplementation tailored to genetic profiles effectively reduced homocysteine and LDL-C levels in patients with specific MTHFR, MTR, and MTRR polymorphisms, particularly with homozygous minor…”

Pokushalov et al. · From the abstract

Names both Methylfolate and Vitamin B12 in its title.

Cellular folate vitamer distribution during and after correction of vitamin B12 deficiency: a case for the methylfolate trap.

British journal of haematology · 2006 · PMID 16445837

Case ReportsHuman subjects

“67.4%), polyglutamate chain length was shorter (more tetra- and pentaglutamates), and global DNA methylation was 22% lower. This is the first time that virtually all features of the methylfolate trap hypothesis have been demonstrated in a human with vitamin B12 deficiency.”

Smulders et al. · From the abstract

Names both Methylfolate and Vitamin B12 in its title.

The impact of vitamin B12 deficiency on urinary profile of de novo purine synthesis intermediates: consequences of the methylfolate trap.

Nucleosides, nucleotides & nucleic acids · 2026 · PMID 42343592

28 participants

“In linear correlation analyses, urinary FIGLU correlated with serum MMA, and GAr, SAICAr, and AICAr correlated with FIGLU, a marker of THF deficiency (p < 0.05). These findings are consistent with methylfolate trapping, linking B12 deficiency to reduced availability of folate cofactors for histidine catabolism and DNPS.”

Krijt et al. · From the abstract

Names both Methylfolate and Vitamin B12 in its title.

Nutritional management of patients with diabetic peripheral neuropathy with L-methylfolate-methylcobalamin-pyridoxal-5-phosphate: results of a real-world patient experience trial.

Current medical research and opinion · 2016 · PMID 26439233

Human subjects544 participants

“In a real-world clinical setting, patients with diabetic peripheral neuropathy treated with LMF-MC-PP achieved significant improvements in total symptom score (NTSS-6) and in quality of life and functioning, together with greater medication satisfaction. A limitation of this study was the use of a survey instrument to collect data on patient outcomes.”

Trippe et al. · Authors' conclusion

Names both Methylfolate and Vitamin B12 in its title.

Limitations

What this evidence cannot tell you.

Search-based evidence indexes have real limits, and it is worth being explicit about them:

How to read this page

A literature summary, not guidance.

NutriStack

Track what you actually take.

NutriStack is a free iPhone app for organising a supplement routine: what you take, when, and what the published record says about it. Its exploratory interaction checker covers Methylfolate, Vitamin B12, and several hundred other substances.

Log your routine, get reminders at the times you choose, and scan a label to add a product. The checker is a research and organisation tool, not a clinical decision aid.

NutriStack is an informational and organizational tool, not a medical service, and not a substitute for professional advice. Always consult a qualified healthcare professional before starting, stopping, or changing any supplement or medication.