An essential B vitamin critical for DNA synthesis, methylation, and neural tube development. L-methylfolate (5-MTHF) is the bioactive form, bypassing MTHFR polymorphisms that affect 40-60% of the population.
Prevents neural tube defects
Required for proper DNA synthesis during rapid cell division in embryogenesis; deficiency causes spina bifida and anencephaly
Reduces homocysteine levels
Methylfolate donates methyl group to convert homocysteine to methionine via methionine synthase (with B12)
May augment antidepressant therapy
L-methylfolate is required for synthesis of serotonin, dopamine, and norepinephrine via BH4 pathway
Supports healthy cell division
Essential cofactor for thymidylate synthase in DNA synthesis; deficiency leads to megaloblastic anemia
COMMON: 400-800 mcg DFE
TIMING: Any time, daily
L-methylfolate (5-MTHF) bypasses MTHFR C677T mutation. Folic acid is synthetic and requires enzymatic conversion. 1mg (1000mcg) UL for folic acid specifically (can mask B12 deficiency). Methylfolate does not have a defined UL.
Independently graded against 178,763 indexed supplements and 757 reviewed supplement and medication pairs, sourced from PubMed, FDA CAERS, openFDA, and NIH DSLD.
Safety
Methotrexate
Your prescriber may recommend this
This medicine can lower your folate. Ask your prescriber whether you need it.
Folic acid supplementation reduces the incidence of methotrexate-induced gastrointestinal and hepatic toxicity without significantly compromising its clinical efficacy in rheumatoid arthritis.
Methotrexate is a folate antagonist that inhibits dihydrofolate reductase, leading to depletion of intracellular folate and subsequent inhibition of purine and pyrimidine synthesis. Folic acid supplementation replenishes folate stores, counteracting the toxic effects of methotrexate on healthy rapidly dividing cells.
Folic acid is routinely prescribed alongside methotrexate. In a double-blind placebo-controlled trial it did not reduce methotrexate's efficacy and lowered toxicity scores. Take it as prescribed.
DUAL ROLE: For CANCER use, folic acid may reduce methotrexate efficacy and is generally avoided unless prescribed. For RA / autoimmune use, folic acid 1 mg/day is standard of care to reduce methotrexate toxicity. Context is critical, discuss with your prescriber.
Methotrexate inhibits dihydrofolate reductase. Folic acid bypasses this inhibition.
Phenytoin (Dilantin)
Ask your prescriber first
Enzyme-inducing anti-seizure medicines lower folate and supplementation is routinely advised, especially before and during pregnancy. High-dose folic acid can lower phenytoin levels and reduce seizure control, so doses above the usual supplement range need monitoring.
ALL women of childbearing potential on antiepileptic drugs MUST take folic acid 4-5mg/day (10x standard prenatal dose). Start BEFORE conception.
AEDs deplete folate via multiple mechanisms (CYP induction, gut absorption interference). Folate deficiency multiplies neural-tube-defect risk in pregnancy.
Your prescriber may recommend this
This medicine can lower your folate. Ask your prescriber whether you need it.
Enzyme-inducing anti-seizure medicines lower folate and supplementation is routinely advised, especially before and during pregnancy. Evidence is class-level for enzyme-inducing AEDs; the phenytoin-level-lowering caveat is phenytoin-specific and omitted here.
ALL women of childbearing potential on antiepileptic drugs MUST take folic acid 4-5mg/day (10x standard prenatal dose). Start BEFORE conception.
AEDs deplete folate via multiple mechanisms (CYP induction, gut absorption interference). Folate deficiency multiplies neural-tube-defect risk in pregnancy.
5-Fluorouracil (5-FU)
Educational information only. This is not medical advice. These statements have not been evaluated by the FDA. Talk to your prescriber before starting, stopping, or combining any supplement with prescription medication.