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evidence · mechanism · dose
Supplements/Vitamin

Folate (Vitamin B9)

aka Folic acid · 5-MTHF · L-methylfolate

One-carbon donor essential for DNA synthesis and neural tube development.

Women's HealthFertilityMood & AnxietyGeneral Wellness

Overview

One-carbon donor essential for DNA synthesis and neural tube development.

Natural sources
  • Leafy greens
  • Legumes
  • Liver
Common forms
  • Folic acid (synthetic)
  • 5-MTHF (active)
  • Folinic acid

Forms & variants of Folate (Vitamin B9)

Different chemical forms of Folate (Vitamin B9) behave differently. Browse each form's mechanism, bioavailability, and best-use context.

L-5-MTHF (Methylfolate)
Methylfolate (L-5-MTHF)

Bioactive folate that bypasses the MTHFR enzyme — preferred in MTHFR variants and pregnancy.

Mechanism of action

Provides methyl groups for DNA synthesis, homocysteine remethylation, and monoamine synthesis.

Pathways
  • · One-carbon metabolism
  • · Methylation cycle

Effects on the body

Decreases
Homocysteine
Supports
Erythropoiesis

Organ system effects

Brain & CNS

Adjunct in depression, especially with MTHFR variants.

Evidence-based benefits

Prevents neural tube defects (preconception)

Strong evidence

Augments SSRIs in depression (L-methylfolate)

Moderate evidence

Potential side effects

Common
    Rare
      Serious
      • · Masks B12 deficiency

      Drug interactions

      Methotrexate
      Folic acid mitigates toxicity but reduces efficacy in cancer.
      moderate
      Antiseizure drugs
      Lower folate.
      moderate

      Supplement interactions

      Pairs well with

      None listed.

      Avoid combining with

      No specific avoidances listed.

      Dosing & bioavailability

      Typical dose
      400–800 mcg DFE
      Upper safe limit
      1,000 mcg synthetic
      Best form
      5-MTHF if MTHFR variant

      Where to buy

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      Scientific evidence (9)

      Systematic reviewExamine.com Supplement Database · 2023

      Folate (Vitamin B9): pharmacology, clinical evidence, and safety — narrative review

      Examine.com Research Team

      Curated narrative review of human and preclinical evidence for Folate (Vitamin B9), including mechanism, typical dosing, and safety considerations.

      Key findings

      Best-supported outcome: Prevents neural tube defects (preconception) (evidence: strong). Additional outcomes and limitations summarized in the full profile.

      Open study
      Systematic reviewPubMed (NLM) · 1970

      PubMed: Folate (Vitamin B9) — Prevents neural tube defects

      Live PubMed search

      Live results for "Folate (Vitamin B9) Prevents neural tube defects" across the PubMed/MEDLINE peer-reviewed index.

      Key findings

      Opens current human and preclinical literature matching Folate (Vitamin B9) and "Prevents neural tube defects". Filter by RCT, meta-analysis, or year on the results page.

      Open study
      Systematic reviewPubMed (NLM) · 1970

      PubMed: Folate (Vitamin B9) — Augments SSRIs in depression

      Live PubMed search

      Live results for "Folate (Vitamin B9) Augments SSRIs in depression" across the PubMed/MEDLINE peer-reviewed index.

      Key findings

      Opens current human and preclinical literature matching Folate (Vitamin B9) and "Augments SSRIs in depression". Filter by RCT, meta-analysis, or year on the results page.

      Open study
      Systematic reviewPubMed (NLM) · 1970

      PubMed: Folate (Vitamin B9) — randomized controlled trial

      Live PubMed search

      Live results for "Folate (Vitamin B9) randomized controlled trial" across the PubMed/MEDLINE peer-reviewed index.

      Key findings

      Opens current human and preclinical literature matching Folate (Vitamin B9) and "randomized controlled trial". Filter by RCT, meta-analysis, or year on the results page.

      Open study
      Systematic reviewPubMed (NLM) · 1970

      PubMed: Folate (Vitamin B9) — meta-analysis

      Live PubMed search

      Live results for "Folate (Vitamin B9) meta-analysis" across the PubMed/MEDLINE peer-reviewed index.

      Key findings

      Opens current human and preclinical literature matching Folate (Vitamin B9) and "meta-analysis". Filter by RCT, meta-analysis, or year on the results page.

      Open study
      Systematic reviewPubMed (NLM) · 1970

      PubMed: Folate (Vitamin B9) — pharmacokinetics

      Live PubMed search

      Live results for "Folate (Vitamin B9) pharmacokinetics" across the PubMed/MEDLINE peer-reviewed index.

      Key findings

      Opens current human and preclinical literature matching Folate (Vitamin B9) and "pharmacokinetics". Filter by RCT, meta-analysis, or year on the results page.

      Open study
      Systematic reviewPubMed (NLM) · 1970

      PubMed: Folate (Vitamin B9) — safety adverse events

      Live PubMed search

      Live results for "Folate (Vitamin B9) safety adverse events" across the PubMed/MEDLINE peer-reviewed index.

      Key findings

      Opens current human and preclinical literature matching Folate (Vitamin B9) and "safety adverse events". Filter by RCT, meta-analysis, or year on the results page.

      Open study
      Systematic reviewPubMed (NLM) · 1970

      PubMed: Folate (Vitamin B9) — dose response

      Live PubMed search

      Live results for "Folate (Vitamin B9) dose response" across the PubMed/MEDLINE peer-reviewed index.

      Key findings

      Opens current human and preclinical literature matching Folate (Vitamin B9) and "dose response". Filter by RCT, meta-analysis, or year on the results page.

      Open study
      Systematic reviewGoogle Scholar · 1970

      Google Scholar: Folate (Vitamin B9) — clinical evidence

      Live Scholar search

      Cross-database citation index for Folate (Vitamin B9) as it relates to "clinical evidence".

      Key findings

      Includes preprints, theses, and journal articles. Useful for tracking citation counts and follow-on work.

      Open study
      Educational use only. This profile is not medical advice. Consult a qualified healthcare professional before starting any supplement, especially if you take prescription medication or have a chronic condition.