Synthetic fully-oxidised form. Reduced in vivo by DHFR to tetrahydrofolate (see folate one carbon) (THF), then to 5,10-methylene-THF and 5-methyl-THF (5-MTHF). DHFR capacity is finite — unmetabolised folic acid (UMFA) appears in plasma at doses >400 mcg, with uncertain long-term significance. MTHFR C677T homozygotes convert folic acid to 5-MTHF less efficiently (rationale for methylfolate supplementation).
Half-Life (t½)
PO: 5h
Dosing Guidelines
PO: Typical 400 mcg (Range: 400–400 mcg)
Target Organ Systems
immune-hematologic
nervous
Interactions
Methylfolate (5-MTHF) (synergistic): Same family — folic acid requires DHFR reduction, 5-MTHF is pre-reduced. Pick one; methylfolate preferred in MTHFR variants.
Methotrexate (caution): Antagonises MTX cytotoxicity: folic acid 1 mg/d is standard adjunct in rheumatologic MTX for side-effect reduction, but in oncology folic acid can blunt efficacy and leucovorin (folinic acid, 5-formyl-THF) is the dedicated rescue agent after high-dose MTX because it bypasses the inhibited DHFR step. [Howard 2016]