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Evidence-Based Supplement Research
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L-Methylfolate and Reduced Depression Symptoms

Research synthesisLow evidenceMixed effect size3 studies · 3 beneficial · 0 neutral · 0 harmful

All 3 studies (3 of 3) reported beneficial effects for L-methylfolate on reducing depressive symptoms, with effect sizes varying from small to large. The strongest evidence, a meta-analysis of 4 studies (N=507) in adults with major depressive disorder, found a moderate beneficial effect (standardized mean difference = -0.38, 95% CI -0.59 to -0.17, p=0.0003). One clinical trial used 15 mg/day for 42 days, and the median study duration among those reporting was 42 days.

  • Studied populations: adults with major depressive disorder

Caveats: Available evidence is overwhelmingly positive — clinical literature in this area is subject to publication bias (null-result studies are less likely to be published or indexed). Evidence base is small (only 3 studies) — conclusions should be considered preliminary. One included study was a small open-label trial (n=10) with a large effect size, and another was a narrative review; the meta-analysis included only 4 studies.

Generated Jun 12, 2026
Doses used in studies
  • mg/day: 15 (median 15, IQR 15–15) — 1 study
Time to effect
Median: 6 weeks · IQR 6 weeks–6 weeks · Range 6 weeks–6 weeks — Reported in 1 of 3 studies
Safety in these studies
3 of 3 papers
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