Folinic acid (5-formyl-THF)
What it is
A reduced folate form (leucovorin) that bypasses the DHFR step required to activate folic acid, and is convertible to all active folate derivatives including 5-MTHF. Particularly important in individuals with cerebral folate deficiency (CFD) — including a subset of autism — where folate receptor autoantibodies block 5-MTHF transport into CNS; folinic acid uses an alternative (reduced folate carrier) pathway. RCTs in CFD-positive autism show language and behavioural improvements. More versatile than 5-MTHF in some contexts.
Dose
5–50 mg daily (autism/CFD at physician-directed doses up to 2 mg/kg)
Time of day & tips
Best evidence in folate receptor autoantibody-positive patients; rule out B12 deficiency first (masking risk); combines with methylcobalamin for comprehensive one-carbon support
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