Folate (Vitamin B9)
Also known as: folic acid, methylfolate, 5-mthf, l-methylfolate, b9
Recommended Dosage
400–1000 mcg DFE
Folate is an essential B vitamin required for DNA synthesis, cell division, and methylation reactions — most critically during pregnancy, where deficiency causes neural tube defects. The methylfolate (5-MTHF) form bypasses the MTHFR enzyme, which roughly 40% of the population has reduced function in due to genetic variants. Beyond prenatal health, folate has evidence for mood support and is often used adjunctively for treatment-resistant depression.
TL;DR: Essential for DNA synthesis, methylation, and mood regulation. ~40% of people have MTHFR variants reducing conversion — use methylfolate. Always pair with B12.
Quick Facts
Evidence
Grade A
Studies
3
Interactions
2
Forms
1
Evidence Rating: Grade A — Strong Evidence
Multiple high-quality RCTs, systematic reviews, or meta-analyses with consistent findings.
Interaction Warnings
Folate supplementation during methotrexate treatment can reduce efficacy. Discuss with doctor.
Anticonvulsants deplete folate; folate may also reduce anticonvulsant levels.
Important Notes
- Use methylfolate (5-MTHF) if you have MTHFR gene variant (~40% of population)
- Folic acid can mask B12 deficiency — always pair with B12 supplementation
- High doses may promote growth of existing cancers (theoretical)
Clinical Evidence (3 studies)
Folate and depression: meta-analysis of 11 studies
Gilbody S et al. (2007) — J Epidemiol Community Health
Low folate strongly associated with depression; supplementation may improve antidepressant response
View on PubMedMTHFR polymorphism and treatment response
Papakostas GI et al. (2012) — Am J Psychiatry
L-methylfolate augmentation significantly improved depression in MTHFR variant carriers
View on PubMedFolate and risk of neural tube defects
MRC Vitamin Study Research Group (1991) — Lancet
Folic acid supplementation reduced neural tube defect recurrence by 72%
View on PubMedAlternatives to Consider
These supplements target similar goals and may be worth considering alongside or instead of Folate (Vitamin B9).
Omega-3 Fish Oil
Grade AEssential fatty acids with strong evidence for cardiovascular and mental health. EPA-dominant for mood; triglyceride form for absorption.
Vitamin B12
Grade ACritical for nerve function, DNA synthesis, and red blood cell formation. Vegans, elderly, and metformin users are at high risk of deficiency. Methylcobalamin preferred for neurological benefit.
Choline
Grade BEssential nutrient for acetylcholine synthesis, liver health, and brain development. 90% of Americans are deficient. Critical during pregnancy. Alpha-GPC or citicoline preferred for cognitive enhancement.
Related Supplements
Vitamin B12
Grade A — Strong EvidenceCritical for nerve function, DNA synthesis, and red blood cell formation. Vegans, elderly, and metformin users are at high risk of deficiency. Methylcobalamin preferred for neurological benefit.
Omega-3 Fish Oil
Grade A — Strong EvidenceEssential fatty acids with strong evidence for cardiovascular and mental health. EPA-dominant for mood; triglyceride form for absorption.
Choline
Grade B — Moderate EvidenceEssential nutrient for acetylcholine synthesis, liver health, and brain development. 90% of Americans are deficient. Critical during pregnancy. Alpha-GPC or citicoline preferred for cognitive enhancement.
Vitamin D3
Grade A — Strong EvidenceEssential hormone precursor. Most people in northern latitudes are deficient. Strong evidence for immunity, bone health, and mood.
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⚕️ Important Disclaimer
This information is for educational purposes only. It is not medical advice. Always consult a healthcare provider before starting any supplement regimen, especially if you take medications or have health conditions.
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