Evidence supporting the use of: Folinic acid
For the health condition: Autism

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Synopsis

Source of validity: Scientific
Rating (out of 5): 3

Folinic acid (also known as leucovorin) has been studied as a potential treatment in children with autism spectrum disorder (ASD), particularly in those who exhibit folate metabolism abnormalities. Research has identified a subset of children with ASD who possess autoantibodies against the folate receptor alpha (FRAA), which can impair the transport of folate into the brain. This condition, known as cerebral folate deficiency, may contribute to the neurological and behavioral symptoms seen in ASD. Several clinical studies, including randomized controlled trials, have explored the effects of high-dose folinic acid supplementation in these children. For example, a 2016 double-blind, placebo-controlled study (Frye et al., Molecular Psychiatry) reported significant improvements in verbal communication and other core symptoms of autism in children with FRAA who received folinic acid compared to placebo. However, the evidence base is still limited by small sample sizes and the need for further replication. The most promising results are observed in children with documented folate receptor autoantibodies rather than the broader ASD population. Therefore, the use of folinic acid in autism is supported by emerging but not definitive scientific evidence, with most benefit likely in a specific subgroup of patients. Current guidelines suggest considering folinic acid supplementation in ASD only for those with laboratory evidence of folate pathway abnormalities.

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