Synopsis

Source of validity: Scientific
Rating (out of 5): 2

Vitamin B9, specifically in its active form as methylfolate (L-methylfolate), has a modest but growing body of scientific research exploring its use in autism spectrum disorder (ASD). The rationale stems from findings that a subset of children with autism exhibit abnormalities in folate metabolism, particularly cerebral folate deficiency (CFD). CFD is characterized by low levels of folate in the cerebrospinal fluid despite normal blood levels. Some individuals with autism have tested positive for folate receptor alpha autoantibodies, which can block folate transport into the brain. Studies, including small open-label trials and case reports, have suggested that supplementation with high-dose folinic acid (a form of folate similar to methylfolate) may lead to improvements in verbal communication, social interaction, and other core autism symptoms in this subgroup. However, the overall quality and quantity of evidence remain limited. Most studies are small, non-randomized, or open-label, and there is a lack of large-scale, placebo-controlled trials specifically investigating methylfolate. Current clinical guidelines do not recommend routine use of methylfolate or folinic acid for all individuals with autism, but testing for CFD or folate receptor autoantibodies may be considered in select cases. The evidence is stronger for folinic acid than methylfolate, but both are sometimes used interchangeably in practice. In summary, there is preliminary scientific rationale and limited evidence for the use of methylfolate/folinic acid in a subset of autistic individuals, but more robust research is needed.

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