Synopsis

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

Calcium methylfolate, a bioavailable form of Vitamin B9 (folate), has been investigated for its potential role in supporting/treating autism spectrum disorder (ASD), primarily based on links between folate metabolism and neurodevelopment. Some children with autism have been found to have abnormalities in folate metabolism, including the presence of folate receptor autoantibodies, which can impair folate transport to the brain (cerebral folate deficiency). Several small studies and case reports have suggested that supplementation with folinic acid (a related form of folate) or methylfolate may improve some core symptoms of autism, particularly in individuals with documented folate pathway abnormalities. For instance, a randomized controlled trial published in 2016 (Frye et al.) showed that high-dose folinic acid improved verbal communication in children with ASD who had folate receptor autoantibodies. However, the overall quality and size of the evidence remain limited, with most studies being small, open-label, or lacking replication. There is currently insufficient robust, large-scale evidence to recommend calcium methylfolate supplementation for all individuals with autism, but its use may be considered in specific subgroups with confirmed folate-related abnormalities. Major clinical guidelines do not yet endorse methylfolate as a standard treatment for ASD. Thus, while there is a scientific rationale and some preliminary data, the strength of evidence is modest.

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