Folinic acid as a treatment for autism in children: A within-subjects open-label study on safety and efficacy.

The folate cycle has been implicated in the pathophysiology of autism due to its role in the glutathione oxidative stress pathway, amino acid and DNA methylation reactions, and neurotransmitter synthesis pathway. Previous research on folinic acid supplementation in autistic children has suggested potential benefits. The primary aim of this pilot study was to determine the safety, feasibility and efficacy of oral folinic acid in improving communication and behaviour in autistic children. Ten autistic children were recruited into an open-label pre-post treatment within-subjects design study. At T = 0, 12 and 24 weeks, participants underwent safety evaluations, standardized assessments of language, autism symptoms, adaptive skills and global illness severity, and eye-gaze tracking. During the control period (0-12 weeks), participants continued with standard care. In the treatment period (12-24 weeks), participants took oral folinic acid at 2 mg/kg/day. All 10 children (nine boys, one girl; aged 4-8 years), successfully consumed oral folinic acid supplements with no adverse events. There was a reduction in Pervasive Developmental Disorder Behavior Inventory (PDDBI) Autism Composite T-score with treatment (mean [SD] T-score 49.2 [8.89] pre-treatment, 44.6 [6.19] post-treatment, p = 0.103). Although this difference was not statistically significant due to the small sample size, the effect size was medium-large, indicating that, as a group, there were clinically meaningful changes in PDDBI T-scores. There were also trends towards gains in communication scores and overall Clinical Global Impression scores. Folinic acid is a safe and feasible potential treatment for autism, and results from this pilot justify the need for a larger placebo-controlled trial.