Vitamins. Haemopoietic stimulants
Brand names – drugs: Folvite, Deplin
Brand names – supplements: Thorne 5-MTHF, Solgar FolateSupplements are not tested in clinical trials and are not registered as medications.
Updated · Methodology
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.
ICD-10: D52 · ICD-11: 3A02
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
ICD-10: Q05 · ICD-11: LA02
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
Folic acid is a B vitamin needed for cell division and blood formation. For anti-aging and longevity it gets marketed as a supplement that supposedly slows aging and extends lifespan. No convincing benefit has been shown for this use: there is no evidence base supporting an anti-aging effect in people without a deficiency. Folic acid makes sense for a confirmed deficiency and when planning a pregnancy; for slowing aging, other approaches help – sleep, diet, physical activity, not smoking, and protecting skin from the sun.
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.
ICD-10: F32.9 · ICD-11: 6A70.Z
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.
AEMPS summary of product characteristics (section 4.6): based on human experience, no risks of folic acid use in pregnancy are known, and folic acid supplements are usually beneficial. Folate deficiency not caused by drugs and abnormal folate metabolism are linked to birth defects, including some neural tube defects, and drug-induced interference with folic acid metabolism or folate deficiency early in pregnancy (anticonvulsants, some antineoplastics) leads to congenital anomalies. A lack of this vitamin or its metabolites may also be responsible for some cases of miscarriage and intrauterine growth restriction.
Transfers into breast milk. Supplementation at the RDA of 500 µg is safe and encouraged.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
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
Verbatim lines from the interaction sections, in the language of the label
«Medicamentos afectados por la administración concomitante de ácido fólico: La toxicidad del fluorouracilo y de los profármacos de fluorouracilo puede producirse en pacientes que toman ácido fólico…»AEMPS, section 4.5 · Open on CIMA
«Fármacos que influyen en los niveles de ácido fólico: Los anticonceptivos orales, anticonvulsivos, fármacos antituberculosos, el alcohol, la glucarpidasa y los antagonistas del ácido fólico como el…»AEMPS, section 4.5 · Open on CIMA
«Medicamentos afectados por la administración concomitante de ácido fólico: Los niveles séricos de los medicamentos anticonvulsivos (fenitoína, fenobarbital, primidona y posiblemente carbamazepina)…»AEMPS, section 4.5 · Open on CIMA
«Drug Interactions: There is evidence that the anticonvulsant action of phenytoin is antagonized by folic acid. A patient whose epilepsy is completely controlled by phenytoin may require increased…»FDA, section 7 · Open on DailyMed
«Drug Interactions: Folate deficiency may result from increased loss of folate, as in renal dialysis and/FDA, section 7 · Open on DailyMed
«Medicamentos afectados por la administración concomitante de ácido fólico: El ácido fólico puede potenciar la toxicidad de la capecitabina.»AEMPS, section 4.5 · Open on CIMA
«Medicamentos afectados por la administración concomitante de ácido fólico: Los niveles séricos de los medicamentos anticonvulsivos (fenitoína, fenobarbital, primidona y posiblemente carbamazepina)…»AEMPS, section 4.5 · Open on CIMA
«Fármacos que influyen en los niveles de ácido fólico: Los anticonceptivos orales, anticonvulsivos, fármacos antituberculosos, el alcohol, la glucarpidasa y los antagonistas del ácido fólico como el…»AEMPS, section 4.5 · Open on CIMA
«Drug Interactions: Folate deficiency may result from increased loss of folate, as in renal dialysis and/FDA, section 7 · Open on DailyMed
«Medicamentos afectados por la administración concomitante de ácido fólico: Los niveles séricos de los medicamentos anticonvulsivos (fenitoína, fenobarbital, primidona y posiblemente carbamazepina)…»AEMPS, section 4.5 · Open on CIMA
«Medicamentos afectados por la administración concomitante de ácido fólico: Los niveles séricos de los medicamentos anticonvulsivos (fenitoína, fenobarbital, primidona y posiblemente carbamazepina)…»AEMPS, section 4.5 · Open on CIMA
«Drug Interactions: There is evidence that the anticonvulsant action of phenytoin is antagonized by folic acid. A patient whose epilepsy is completely controlled by phenytoin may require increased…»FDA, section 7 · Open on DailyMed
«Medicamentos afectados por la administración concomitante de ácido fólico: Agentes antibacterianos del subgrupo terapéutico sulfonamidas y sulfasalazina.»AEMPS, section 4.5 · Open on CIMA
«Drug Interactions: False low serum and red cell folate levels may occur if the patient has been taking antibiotics, such as tetracycline, which suppress the growth of Lactobacillus casei.»FDA, section 7 · Open on DailyMed
«Fármacos que influyen en los niveles de ácido fólico: Los anticonceptivos orales, anticonvulsivos, fármacos antituberculosos, el alcohol, la glucarpidasa y los antagonistas del ácido fólico como el…»AEMPS, section 4.5 · Open on CIMA
«Fármacos que influyen en los niveles de ácido fólico: Los anticonceptivos orales, anticonvulsivos, fármacos antituberculosos, el alcohol, la glucarpidasa y los antagonistas del ácido fólico como el…»AEMPS, section 4.5 · Open on CIMA
Opens the checker prefilled with this drug. Pick the second one from your regimen.
Summary of a multi-drug list →
Medicine list: everything you take in one place →
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.
AEMPS summary of product characteristics (section 4.6): based on human experience, no risks of folic acid use in pregnancy are known, and folic acid supplements are usually beneficial. Folate deficiency not caused by drugs and abnormal folate metabolism are linked to birth defects, including some neural tube defects, and drug-induced interference with folic acid metabolism or folate deficiency early in pregnancy (anticonvulsants, some antineoplastics) leads to congenital anomalies. A lack of this vitamin or its metabolites may also be responsible for some cases of miscarriage and intrauterine growth restriction.
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.
Direct links to regulator labels. Open in a new tab.
Cyanocobalamin, Hydroxocobalamin, Iron oral (salts: sulfate, bisglycinate, fumarate, gluconate, polymaltose; heme iron polypeptide, lactoferrin), Methylcobalamin, Levomefolate (L-methylfolate, 5-MTHF), Vitamin B12 (cobalamin)