Home
Scan
Ask
Protocols
Profile
HomeIngredientsMethylfolate
Reviewed by the Scan Dose Research Team and Clinical Advisory Board

Methylfolate

MODERATE EVIDENCEVitaminLast updated

SCAN DOSE SUMMARY

Methylfolate is the biologically active form of folate (vitamin B9) — the form your body actually uses. This matters because approximately 40% of the population has at least one copy of the MTHFR C677T polymorphism, reducing their ability to convert folic acid to methylfolate by 30-70%. Our research shows methylfolate supplementation bypasses this genetic bottleneck entirely. L-methylfolate (Deplin®) is also FDA-approved as a medical food for depression (15mg/day as SSRI adjunct), making it one of the very few supplements that has crossed into prescription territory. For pregnancy, adequate folate prevents 70% of neural tube defects — and methylfolate ensures those with MTHFR variants are protected.

WHAT IT DOES

Methylfolate (5-MTHF) is the final active form of folate that donates methyl groups in one-carbon metabolism. Its primary function: (1) remethylating homocysteine to methionine (via methionine synthase + B12), reducing cardiovascular-toxic homocysteine; (2) methionine → S-adenosylmethionine (SAMe) → methyl donor for DNA methylation, neurotransmitter synthesis (serotonin, dopamine, norepinephrine), and 200+ methylation reactions; (3) thymidylate synthesis for DNA replication (critical in pregnancy). The MTHFR enzyme converts folic acid → dihydrofolate → tetrahydrofolate → 5-MTHF. Variants (C677T, A1298C) reduce this enzyme's efficiency, creating a bottleneck that supplemental 5-MTHF bypasses entirely.

OPTIMAL DOSAGE

  • Look for: L-5-MTHF (the L isomer specifically); Quatrefolic® (most stable, best bioavailability); Metafolin® (calcium L-5-MTHF); dose in mcg or mg clearly stated
  • Avoid: Folic acid (for known MTHFR carriers); DL-5-MTHF (contains inactive D-isomer — 50% wasted); "folate" without specifying form; products relying solely on folic acid labeled as "methylfolate"
  • Minimum effective dose: 400mcg/day (RDA); 1-5mg for depression adjunct; 15mg for treatment-resistant depression (Deplin)
  • Third-party tested brands: Thorne (5-MTHF), Seeking Health (Optimal Methylate), Life Extension, Pure Encapsulations
Scan a supplement containing Methylfolate

SAFETY PROFILE

Critical Interactions (Do Not Combine Without Medical Supervision)

Moderate Interactions (Monitor Closely)

Theoretical/Low-Risk Interactions

RELATED RESEARCH

Acerola Cherry
Amla
BiotinBiotin is a cofactor for five carboxylase enzymes critical to metabolism: pyruva
Amla

Quality Testing Intelligence

Based on independent third-party laboratory analysis

Category pass rate: ~75%. Dose accuracy and dissolution are the main issues.

Scan Your Methylfolate SupplementBrowse all ingredients

Reviewed by the Scan Dose Research Team and Clinical Advisory Board | Last updated:

Not medical advice. Based on published clinical research and systematic reviews.

Discover More

Explore
Browse All 538 IngredientsBrowse All 20 Conditions