Folate (Vitamin B9)

Also known as: folic acid, methylfolate, 5-mthf, l-methylfolate, b9

Grade A — Strong Evidencevitaminfoundational
400–1000 mcg DFEMorning with food

Essential for DNA synthesis, methylation, and mood regulation. ~40% of people have MTHFR variants reducing conversion — use methylfolate. Always pair with B12.

😊Mood🧠Cognitive Performance🧬Longevity
Last reviewed: 2026-03-11

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

MethotrexateHigh Risk

Folate supplementation during methotrexate treatment can reduce efficacy. Discuss with doctor.

Anticonvulsants (phenytoin, carbamazepine)Moderate

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 PubMed

MTHFR polymorphism and treatment response

Papakostas GI et al. (2012) — Am J Psychiatry

L-methylfolate augmentation significantly improved depression in MTHFR variant carriers

View on PubMed

Folate 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 PubMed

Alternatives to Consider

These supplements target similar goals and may be worth considering alongside or instead of Folate (Vitamin B9).

Omega-3 Fish Oil

Grade A

Essential fatty acids with strong evidence for cardiovascular and mental health. EPA-dominant for mood; triglyceride form for absorption.

😊 Mood🧠 Cognitive Performance🧬 Longevity

Vitamin B12

Grade A

Critical 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.

🧠 Cognitive Performance😊 Mood🧬 Longevity

Choline

Grade B

Essential 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.

🧠 Cognitive Performance😊 Mood🧬 Longevity

Related Supplements

Vitamin B12

Grade A — Strong Evidence

Critical 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 Evidence

Essential fatty acids with strong evidence for cardiovascular and mental health. EPA-dominant for mood; triglyceride form for absorption.

Choline

Grade B — Moderate Evidence

Essential 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 Evidence

Essential 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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