People mainly take Methylfolate for mood, energy, anxiety. Based on 73 first-hand reports and 9 meta-analyses & systematic reviews in the medical literature. Ranked #62 of 1,974 overall.
Of reports that state an outcome, 67% are positive.
Of the people who reported each effect, the share who said it got better.
Systematic reviews and meta-analyses from PubMed, with their published conclusions.
3+ meta-analyses or systematic reviews and 10+ randomized controlled trials in humans. The grade measures how much human research exists — read the conclusions below for what it found.
Conclusion: Adjunctive L-methylfolate may have modest efficacy in antidepressant-treated adults with MDD.
PubMed 34794190 ↗Conclusion: Based on the current data and clinician input, a range of nutraceuticals and phytoceuticals were given either a supportive recommendation or a provisional recommendation across a range of various psychiatric disorders. However several had only a weak endorsement for potential use; for a few it was not possible to reach a clear recommendation direction, largely due to mixed study findings; while some other agents showed no obvious therapeutic benefit and were clearly not recommended for use. It is the intention of these guidelines to inform psychiatric/medical, and health professional practice
PubMed 35311615 ↗Conclusion: Current evidence supports adjunctive use of SAMe, methylfolate, omega-3, and vitamin D with antidepressants to reduce depressive symptoms.
PubMed 27113121 ↗Conclusion: Whilst previous guidelines on the treatment of unipolar depression have either avoided this topic entirely, or made recommendations on the basis of cherry-picked evidence, this review is the first to attempt to provide clinically useful recommendations based on comprehensive, current randomised placebo-controlled data. We invite discussion of the review and its recommendations, which are based on the limited evidence regarding folate formulation delivered and appropriate dosage.
PubMed 29442609 ↗As stated by users — not a recommendation. Follow the label or your doctor.
How often each side effect came up across all reports.
Verbatim quotes, shortened only — each links to the original discussion.
“When I get wired up with mania, anxiety, insomnia. I usually take methylfolate and NAC.”
“Because folate is a reputable prompter. It wrecks undermethylators”
“All of the NAD+ precursors are methyl absorbers so it's recommended to also take Methylfolate and B12”
“Replace folic acid with methyl folate for MTHFR”
“methyl folate multivitamin”
User data from public discussions; research from PubMed. Information only, not medical advice — talk to a doctor before starting, stopping or combining anything. Data updated October 2, 2026. How we rate