Summary
Vitamin B9 — folate — is a water-soluble B vitamin required for one-carbon metabolism: the synthesis of DNA and RNA, the division of new cells, the maturation of red blood cells, and (with vitamin B12) the conversion of homocysteine to methionine. Adequate folate before conception and in early pregnancy sharply reduces the risk of neural-tube defects, which is why it is the most widely fortified and supplemented B vitamin.
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Where Does It Come From?
Folate is concentrated in dark leafy greens (spinach, kale), legumes, asparagus, broccoli, citrus fruit and liver. Many grain products are fortified with folic acid, the stable synthetic form. Supplements supply either folic acid or the active form, L-methylfolate (5-MTHF).
General Actions
- One-carbon transfers in DNA and RNA synthesis
- Red-blood-cell formation
- Cell division and tissue growth
- Homocysteine remethylation (with B12)
- Neural-tube-defect prevention in early pregnancy
Specific Actions
In its active form, tetrahydrofolate (THF), folate shuttles single-carbon units used to build the purine and thymidine bases of DNA, and donates a methyl group (as 5-MTHF) so that vitamin B12 can remethylate homocysteine to methionine. Rapidly dividing tissues — bone marrow and the developing embryo — are the most sensitive to a shortfall.
Indications
- Preconception and pregnancy (neural-tube-defect prevention)
- Folate-deficiency (megaloblastic) anaemia
- Elevated homocysteine (with B6 and B12)
- Malabsorption states and certain medications that deplete folate
Chemical Description
Folate is the umbrella term for pteroylglutamic acid and its many derivatives. The synthetic form, folic acid, is fully oxidised and very stable; the body reduces it to the active coenzymes tetrahydrofolate and 5-methyltetrahydrofolate. Recommendations are expressed in dietary folate equivalents (DFE) because folic acid is far more bioavailable than food folate.
Extractions/Synthesis
Folic acid is manufactured by chemical synthesis; methylfolate (5-MTHF) supplements are made as a stabilised salt of the naturally active form.
Pharmacology/Medical Research
Folate’s role in DNA synthesis and neural-tube-defect prevention is firmly established, and mandatory folic-acid fortification has measurably lowered birth-defect rates. Ongoing research examines folate’s interaction with B12, its place in homocysteine lowering, and the relevance of the MTHFR gene variants to methylfolate use.
Toxicity
Folate has low toxicity. The upper limit of 1,000 mcg/day is set for synthetic folic acid specifically: high folic-acid intake can correct the anaemia of B12 deficiency while allowing the underlying neurological damage to progress undetected.
Synergy
Works with vitamin B12 (which it depends on for homocysteine remethylation) and vitamin B6 across the one-carbon and transsulfuration pathways.
References
- National Institutes of Health, Office of Dietary Supplements. Folate — Health Professional Fact Sheet. ods.od.nih.gov/factsheets/Folate-HealthProfessional