Systematic review on the effectiveness of the gluten- and casein-free diet as a non-pharmacological therapy in children and adolescents with Autism Spectrum Disorder

Abstract

Introduction: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition with high prevalence, frequently associated with gastrointestinal and behavioral symptoms. The gluten- and casein-free (GFCF) diet has been proposed as a non-pharmacological intervention to improve these symptoms, although scientific evidence remains heterogeneous. Methods: A systematic review of literature published between 2020 and 2025 was conducted using PubMed, Google Scholar, and Cochrane databases. Inclusion criteria comprised studies in English and Spanish, involving participants aged 2–18 years, that implemented a GFCF diet. Systematic reviews, meta-analyses, and narrative reviews were included, while case reports and adult studies were excluded. A total of 30 articles were identified, with 15 meeting the final inclusion criteria. Results: Among the 15 studies analyzed, 7 reported improvements in behavioral symptoms, 5 described benefits in gastrointestinal outcomes, and 3 found no significant changes. Systematic reviews and meta-analyses highlighted inconsistent findings, with methodological limitations, heterogeneous samples, short intervention periods, and variable adherence. Evidence suggests greater a possible benefit in ASD patients with significant gastrointestinal symptoms. Conclusion: The GFCF diet cannot be universally recommended for children and adolescents with ASD due to the heterogeneity of outcomes. Further experimental studies with larger samples and standardized protocols are needed to confirm its efficacy.