Supplements
L-methylfolate decreases homocysteine
Part of: 🧪 Folate & L-methylfolate
📅 Last reviewed: 2026-07-15 ⓘ
Evidence ladder
How far up the ladder this claim has climbed. A high consensus on a low rung means "consistent so far," not "proven in people."
Top evidence so far: All trials, pooled (Meta-analysis)
How the studies fall
What the evidence shows
L-methylfolate is superior to folic acid for lowering homocysteine.
The evidence (8)
| Source | Grade | Stance | Quality | Finding |
|---|---|---|---|---|
| Xie M et al 2025 · study_type: meta-analysis | meta-analysis | contradicts | moderate | 11 RCTs, active folate vs equimolar folic acid: active form ↑plasma folate (P=.04), ↑RBC folate (P=.01), but NO significant difference in homocysteine, B12, or betaine. |
| Venn 2003 · Am J Clin Nutr | RCT | mixed | moderate | RCT: low-dose L-5-MTHF and folic acid lowered tHcy comparably (no superiority) |
| lamers-2004 2004 | RCT | tested-null | moderate | 5-MTHF and folic acid EQUAL for homocysteine lowering (no superiority). |
| Mazza 2016 2016 · Clin Nutr | RCT | supports | moderate | 5-MTHF nutraceutical lowered homocysteine in hypertensives |
| Willems FF, Boers GH, Blom HJ, Aengevaeren WR, Verheugt FW 2004 · Br J Pharmacol | RCT | mixed | moderate | Randomised two-way crossover PK study (CAD patients, single 5 mg dose): 5-MTHF bioavailability HIGHER than folic acid, peak ~7x, irrespective of MTHFR genotype. RELEVANCE GATE: the endpoint is folate PHARMACOKINETICS, not homocysteine - it does not test this claim's outcome. Superior bioavailability does not establish superior homocysteine lowering (cf. Lamers 2004, which found the two EQUAL on homocysteine). |
| Song J et al 2025 · study_type: RCT | RCT | mixed | low | Methylfolate vs synthetic folic acid in high-HCY/adverse-pregnancy-history cohort: methylfolate 'efficiently reduced' HCY and lower adverse-pregnancy incidence, but no comparative HCY statistic vs folic-acid arm reported. |
| Coppola 2005 · Br J Haematol | observational | supports | low | 5-MTHF supplementation lowered tHcy in 677TT early-thrombosis patients, durable effect |
| Bostom 2000 · Atherosclerosis | RCT | mixed | moderate | Controlled comparison in hemodialysis: L-5-MTHF vs folic acid both lowered tHcy, no clear superiority |
Disagree, or know a study we missed?
We grade by evidence, not opinions. The way to weigh in is to point us to a study we haven't cited (check the evidence table above first), or to flag a problem with one we have. Every submission is reviewed; if it holds up, the grade updates and shows in Science Changes Its Mind.
Opens a short form. You'll sign in with Google so submissions are tied to a real account — we don't display your identity, and we only accept a link we can verify (PubMed, DOI, ClinicalTrials.gov).
Educational only, not medical advice. Grades and scores reflect published evidence weighted by study design and quality; see the methodology.