Vitamins. Haemopoietic stimulants
ATC code: B03BB01 (Folic acid)
Brand names – drugs
Folvite, Deplin
Brand names – supplements
Thorne 5-MTHF, Solgar Folate
Supplements are not tested in clinical trials and are not registered as medications.
Folic acid (vitamin B9) is reduced in the body to tetrahydrofolate – a one-carbon group carrier in purine, thymidine, and amino acid (methionine, serine, glycine) synthesis. Required for DNA synthesis and division of rapidly proliferating cells (bone marrow, GI epithelium, foetus). Deficiency causes megaloblastic anaemia and, in early embryogenesis, neural tube defects.
First line
Folic acid 1–5 mg daily for 1–4 months is first-line for folate deficiency anaemia. Clinical response: reticulocyte crisis at 5–10 days, haemoglobin normalisation over 1–2 months. Co-existing B12 deficiency must be excluded before starting therapy – isolated folate use in unrecognised B12 deficiency masks anaemia but does not prevent neurological degeneration.
First line
Concurrent folic acid 5 mg once weekly (day after methotrexate) is a required component of low-dose methotrexate therapy in rheumatoid arthritis, psoriatic arthritis, and psoriasis. 2023 includes folic acid in the standard protocol. Reduces hepatotoxicity, nausea, stomatitis, and cytopenias without compromising methotrexate's anti-inflammatory effect.
First line
Folic acid 400 µg daily in all women planning pregnancy and through the first 12 weeks of pregnancy is foundational neural tube defect prevention. 2023 reaffirmed recommendation A. In women with a prior NTD pregnancy, diabetes, epilepsy, obesity, or on antiepileptics, the dose is increased to 4–5 mg daily. The Cochrane review confirmed a 70% reduction in open neural tube defects.
Supplementation starts 1–3 months before conception. Most NTDs form by day 28 of embryogenesis, before the woman may be aware of pregnancy.
Sources
Not recommended
The 2019 Cochrane review (3 RCTs, 247 participants) did not find a clinically meaningful effect of folic acid or L-methylfolate as monotherapy or adjunct in major depression. Small positive RCTs in patients with folate deficiency or MTHFR polymorphism have not been reproduced. and mental health do not include folate in depression treatment standards.
Not recommended
— Anti-aging and longevity: Folic acid for slowing ageing or extending lifespan is not mentioned in international guidelines. Homocysteine-lowering therapy (folate, B6, B12) in patients without inherited homocystinuria has not shown an effect on cardiovascular outcomes or all-cause mortality in several large RCTs. High-dose folic acid in older adults is discussed as a possible risk factor for progression of early cancers – data are mixed.
FDA category A at neural tube defect prevention doses. High-dose therapy (4–5 mg) in pregnant women with epilepsy, diabetes, or obesity is safe and is encouraged by international obstetric societies.
Transfers into breast milk. Supplementation at the RDA of 500 µg is safe and encouraged.
folic acid is evaluated for the following indications with varying evidence strength: Neural tube defect prevention (evidence tier A), Methotrexate-related adverse event prevention (evidence tier A), Folate deficiency anaemia (evidence tier A). See the full indication matrix with dosing and citations above on this page.
Common side effects of folic acid (≥ 1 in 100): Epigastric discomfort at high doses, Altered taste. See the Safety section for uncommon and serious reactions.
FDA category A. FDA category A at neural tube defect prevention doses. High-dose therapy (4–5 mg) in pregnant women with epilepsy, diabetes, or obesity is safe and is encouraged by international obstetric societies.
Transfers into breast milk. Supplementation at the RDA of 500 µg is safe and encouraged.
folic acid is contraindicated in: Hypersensitivity to folic acid; Untreated B12 deficiency anaemia (risk of masking and neurological progression); Pernicious anaemia without B12 (same reason); Malignancy (relative contraindication for high doses). Full list in the Safety section.
supplementation is recommended for all women of reproductive age who may become pregnant – most unintended pregnancies are unplanned, and the critical neural tube window is the first 28 days.
for most women, folic acid 400 µg is fully effective. Methylfolate costs 5–10 times more without proven advantage in general populations. There may be benefit in women with homozygous MTHFR polymorphism and high homocysteine – but this is a narrow group.
there are observational data linking high doses with progression of pre-existing tumours in older adults – clinically significant effect not confirmed. In reproductive-age women at prophylactic doses, cancer risk is not increased.