Vitamin D in Autism Spectrum Disorder: A Critical Systematic Review of Evidence and Methodological Limitations

BACKGROUND: Vitamin D is discussed in neurodevelopmental and immune pathways relevant to autism spectrum disorder (ASD). This systematic review synthesizes evidence on serum vitamin D status and vitamin D supplementation outcomes in children and adolescents with ASD, with descriptive reporting of one combined vitamin D plus omega-3 arm for context only. METHODS: PubMed was searched on 16 August 2024 for observational studies reporting serum 25-hydroxyvitamin D [25(OH)D] and for randomized controlled trials (RCTs) of vitamin D supplementation; the primary narrative synthesis of trial evidence was restricted to double-blind, placebo-controlled studies with the maximum Jadad score (5/5). RESULTS: Eight observational studies met inclusion criteria. Most reported lower 25(OH)D in children with ASD compared with comparator groups, while neonatal findings were mixed across cohorts. Among three placebo-controlled RCTs, one high-dose study reported statistically significant improvements on symptom scales, whereas trials using 2,000 IU/day reported marginal or no effects on ASD-related outcomes. One combined vitamin D plus omega-3 trial arm is summarized descriptively for context. CONCLUSION: Current evidence does not support vitamin D supplementation as a general ASD-targeted intervention. Larger, well-controlled trials with prespecified baseline status, standardized outcomes, and safety-focused follow-up are needed to clarify potential subgroup effects and clinical relevance.