Vitamin B9 (Folate)
water-soluble
Key Takeaways
- Essential for DNA synthesis, repair, and methylation through one-carbon metabolism
- FDA daily value is 400 mcg DFE (dietary folate equivalents)
- Periconceptional supplementation reduces neural tube defect risk by an estimated 50-70%
- Available as folic acid (synthetic, requires MTHFR conversion) and L-methylfolate (active, bypasses MTHFR)
- Note: No PubMed studies in research data; content based on established biochemistry and FDA daily value
Evidence Spectrum
0 studies reviewed →Neural tube defect prevention
Periconceptional folic acid is one of the most well-established preventive interventions, reducing NTD risk by 50-70%. Led to mandatory food fortification. No PubMed citations in research data.
Megaloblastic anemia prevention
Folate deficiency impairs DNA synthesis in RBC precursors, causing megaloblastic anemia. Adequate intake prevents this. No PubMed citations in research data.
Homocysteine reduction
Folate (with B12 and B6) participates in homocysteine remethylation. Elevated homocysteine is a cardiovascular risk marker, though whether B-vitamin supplementation reduces CV events remains debated. No PubMed citations in research data.
400 mcg DFE
RDA (Adults (FDA Daily Value))
1000 mcg
Upper Limit
water-soluble
Solubility
Role in the Body
Vitamin B9 (folate) is essential for one-carbon metabolism: nucleotide synthesis for DNA/RNA, amino acid metabolism, and homocysteine remethylation to methionine (with B12). Critical for rapidly dividing cells, especially during pregnancy. MTHFR enzyme converts folic acid to active 5-MTHF. Common MTHFR polymorphisms (C677T, A1298C) can reduce conversion efficiency. No PubMed studies were available in the research data.
- DNA and RNA synthesis (nucleotide production)
- DNA repair and methylation
- Homocysteine-to-methionine remethylation (with vitamin B12)
- Red blood cell production (erythropoiesis)
- Neural tube closure during embryonic development
Supplement Forms
Folic acid (pteroylglutamic acid)
RecommendedBioavailability: 0.85%
Synthetic form in supplements and fortified foods. Requires MTHFR conversion to active 5-MTHF. ~85% bioavailable on empty stomach.
L-Methylfolate (5-MTHF, levomefolate)
RecommendedBioavailability: 0.85%
Active form bypassing MTHFR. May be preferred for MTHFR polymorphism carriers.
Food folate (polyglutamyl forms)
RecommendedBioavailability: 0.5%
~50% bioavailability of folic acid. DFE units account for this (1 mcg DFE = 0.6 mcg supplement folic acid).
Food Sources
Dark leafy greens (spinach, kale)
Legumes (lentils, black beans)
Asparagus
Broccoli and Brussels sprouts
Citrus fruits
Fortified cereals, bread, pasta
Liver and organ meats
Avocado
Deficiency
Prevalence: Decreased with mandatory fortification. Common in unfortified populations, pregnancy, and impaired absorption.
Symptoms:
- Megaloblastic (macrocytic) anemia
- Neural tube defects (spina bifida, anencephaly)
- Elevated plasma homocysteine
- Glossitis
- Fatigue and weakness
- Irritability and poor concentration
Risk Factors:
- Pregnancy and lactation
- Chronic alcoholism
- Malabsorption (celiac, IBD)
- MTHFR polymorphisms
- Antifolate drugs (methotrexate, trimethoprim)
- Phenytoin and anticonvulsants
Safety & Interactions
Possible Side Effects:
- • High-dose folic acid may mask B12 deficiency
- • Generally well tolerated at recommended doses
Drug Interactions:
- • Methotrexate: inhibits folate metabolism
- • Phenytoin: bidirectional interaction
- • Sulfasalazine: impairs folate absorption
Contraindications:
- • High-dose folic acid without ruling out B12 deficiency
- • Caution with antifolate chemotherapy
Frequently Asked Questions
Folate vs folic acid?
Folate is natural (foods). Folic acid is synthetic (supplements/fortification). Folic acid requires MTHFR conversion to active 5-MTHF.
Should I take methylfolate instead?
L-methylfolate bypasses MTHFR and may be preferred with MTHFR polymorphisms. For most people, folic acid is effective.
How much during pregnancy?
600 mcg DFE recommended. Begin at least one month before conception through first trimester.
Can you take too much?
UL for synthetic folic acid is 1,000 mcg. Excess may mask B12 deficiency. No UL for food folate.
Research Sources
15 peer-reviewed studies analyzed from PubMed. 0 directly cited in this review.