NSTK · 01.2026Independent supplement reference
NutriStack
Edition 1.0Updated August 1, 2026

Supplement × Supplement·Evidence index

L-Methionine and Methylfolate: what the published research says

PubMed indexes 5 records that name L-Methionine and Methylfolate together, either in the title or in an interaction, co-administration, or pharmacokinetic context. Each one is listed below with its study design and, where the abstract states one, the authors’ own conclusion, quoted and linked. This page reports that literature. It does not tell you whether to combine them.

Read this first

An evidence index, not guidance.

Every statement below is attributed to a named, dated, linked source.

This page lists published research relevant to L-Methionine and Methylfolate. It deliberately does not state whether the combination is safe, whether it interacts, in which direction, at what dose, or how far apart to take them.

The research

5 studies naming L-Methionine and Methylfolate.

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

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 L-Methionine and Methylfolate in its title.

5-MTHF enhances the portal pressure reduction achieved with propranolol in patients with cirrhosis: A randomized placebo-controlled trial.

Journal of hepatology · 2023 · PMID 37482222

Randomized Controlled Trial

“In patients with cirrhosis and portal hypertension, 5-MTHF administration significantly enhanced the HVPG reduction achieved with propranolol. This effect appears to be mediated by improved nitric oxide bioavailability in the hepatic microcirculation.”

Vukotic et al. · Authors' conclusion

Names L-Methionine and Methylfolate together in an interaction, co-administration, or pharmacokinetic context.

Bioavailability of S-adenosyl methionine and impact on response in a randomized, double-blind, placebo-controlled trial in major depressive disorder.

The Journal of clinical psychiatry · 2012 · PMID 22687580

Randomized Controlled TrialResearch Support, N.I.H., Extramural73 participants

“Despite concerns about the impact that SAMe therapy may have on homocysteine levels and risk of adverse cardiovascular effects, the lack of significant increase in tHCY levels after treatment suggests that no toxic effects from SAMe should be expected. Our findings, however, have some significant limitations and should be interpreted with caution.”

Mischoulon et al. · Authors' conclusion

Names L-Methionine and Methylfolate together in an interaction, co-administration, or pharmacokinetic context.

Pharmacokinetic study on the utilisation of 5-methyltetrahydrofolate and folic acid in patients with coronary artery disease.

British journal of pharmacology · 2004 · PMID 14769778

Clinical TrialComparative StudyRandomized Controlled Trial

“Our results demonstrate that oral 5-MTHF has a different pharmacokinetic profile with a higher bioavailability compared to folic acid, irrespective of the patient's genotype. Detrimental effects of the storage of high levels of the non-natural isomer 6[R] 5-MTHF cannot be excluded.”

Willems et al. · From the abstract

Names L-Methionine and Methylfolate together in an interaction, co-administration, or pharmacokinetic context.

Limitations

What this evidence cannot tell you.

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

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 L-Methionine, Methylfolate, and several hundred other substances.

The checker is a research and organisation tool, not a clinical decision aid, and its per-pair assessments are excluded from search until they pass claim-level review.

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.