Synopsis

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

L-5-methyltetrahydrofolate (5-MTHF) glucosamine salt is used in some clinical and research settings to support or treat autism spectrum disorder (ASD), primarily based on emerging scientific evidence rather than tradition. The rationale stems from findings that a subset of children with autism may have cerebral folate deficiency (CFD), characterized by low levels of folate in the cerebrospinal fluid despite normal peripheral blood folate. In several studies, including open-label trials and small controlled cohorts, supplementation with folinic acid or 5-MTHF has been associated with improvements in core and associated ASD symptoms, particularly in children who test positive for folate receptor alpha autoantibodies (FRAA). These autoantibodies can block folate transport into the central nervous system. A few randomized controlled trials (RCTs) have shown moderate improvements in verbal communication and behavior, though the sample sizes are small and results are not universally replicated. The evidence is not strong enough to recommend universal use in all individuals with ASD, but screening for CFD and FRAA may be justified in select cases. Major guidelines, such as those from the American Academy of Pediatrics, do not currently endorse 5-MTHF for all children with autism. Thus, while the scientific rationale exists and some clinical evidence supports its use in specific subgroups, overall evidence quality remains limited (rated 2/5).

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