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
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
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
Folic acid is a synthetic form of vitamin B9. It is prescribed for prevention of neural tube defects in fetuses (for all women planning pregnancy), folate deficiency, and treatment of megaloblastic anemia. In anti-aging communities, folic acid is sold to slow aging and lower homocysteine for CV prevention. Meta-analyses (Lonn 2006, NEJM and later work) show that lowering homocysteine with folic acid does not reduce cardiovascular events or all-cause mortality in healthy adults. International anti-aging guidelines do not include folic acid. High doses (above 1 mg/day) can mask vitamin B12 deficiency with risk of progressive neurological symptoms. If folic acid is being taken in high doses for anti-aging, consider seeking a second opinion.
1 pair found. Sorted from critical to minor.
Mechanism
Metformin on long-term use (over 5 years) moderately reduces blood B12 (by 10–30%). Effect on folate is minimal. Folate deficiency on metformin has not been described.
Symptoms
The combination usually causes no specific symptoms. Each drug's individual side effects remain.
Management
No folate dose adjustment needed. On long-term metformin, check B12 yearly. For pregnancy planning in women with diabetes, folic acid 400–800 mcg/day is standard regardless of metformin.
Sources
Opens the checker prefilled with this drug. Pick the second one from your regimen.
Direct links to regulator labels. Open in a new tab.
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: Methotrexate-related adverse event prevention (evidence tier A), Neural tube defect 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.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
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.