Folinic acid (5-formyl-THF)

Tier 2 — promising · Folate · Autism · Methylation

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)