Evidence supporting the use of: Vitamin B9 (methyltetrahydrofolate)
For the health condition: Autism

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Synopsis

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

Vitamin B9, particularly in the form of L-methyltetrahydrofolate (L-MTHF), has been studied in relation to autism spectrum disorder (ASD) due to findings of altered folate metabolism and transport in some individuals with ASD. Some children with ASD have been found to have autoantibodies against the folate receptor alpha (FRA), which can lead to cerebral folate deficiency. Supplementation with folinic acid or L-methyltetrahydrofolate has been hypothesized to bypass these issues and improve neurological function.

A few open-label studies and small randomized controlled trials have suggested that high-dose folinic acid supplementation may result in improvements in language and communication in a subset of children with ASD, particularly those with FRA autoantibodies. For example, a 2016 double-blind, placebo-controlled trial (Frye et al.) found that folinic acid improved verbal communication in children with ASD and FRA autoantibodies. However, these studies are limited by small sample sizes, heterogeneity of ASD, and lack of long-term follow-up.

Despite promising early findings, the overall quality and quantity of evidence remains limited. Larger, well-designed clinical trials are needed to confirm efficacy, establish optimal dosing, and determine which subgroups of ASD may benefit most. Thus, while there is a scientific rationale and some preliminary evidence supporting the use of L-methyltetrahydrofolate in autism, it should not be considered a standard treatment at this time.

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