Vitamin B9 in the form of folinic acid (not to be confused with folic acid) has been investigated as a potential treatment for Autism Spectrum Disorder (ASD), particularly in children who have cerebral folate deficiency (CFD) or autoantibodies to the folate receptor alpha (FRAA). Several studies, including randomized controlled trials, have shown that high-dose folinic acid supplementation (typically 2 mg/kg/day up to 50 mg/day) can improve some core and associated symptoms of ASD—especially language and communication—in a subset of children with these biomarkers.

The scientific rationale is based on findings that some individuals with ASD exhibit impaired transport of folate across the blood-brain barrier, often due to FRAA, leading to low levels of folate in the cerebrospinal fluid despite normal blood levels. Folinic acid, unlike folic acid, can cross into the brain via alternative pathways and bypass this blockage. Notably, a 2016 double-blind, placebo-controlled study (Frye et al., Molecular Psychiatry) found significant improvements in verbal communication and other domains in children with ASD and FRAA who received folinic acid compared to placebo.

The evidence is promising but not universal: benefits seem restricted to subgroups of ASD patients with specific folate pathway abnormalities. Guidelines do not universally recommend folinic acid for all individuals with ASD, and more research is needed to determine long-term efficacy and safety. Overall, the use of folinic acid in ASD is supported by moderate quality scientific evidence, particularly for those with documented folate pathway dysfunction.