Exploring the potential association between dietary factors and autism spectrum disorder: A Mendelian randomization analysis and retrospective study

This study examines the complex interplay between dietary factors, ketones, food allergies, and the risk of autism spectrum disorder (ASD) through Mendelian randomization (MR) and clinical research methodologies. Utilizing two-sample MR, the research analyzed 199 dietary factors in relation to ASD risk, leveraging data from genome-wide association studies (GWAS). The findings revealed significant positive causal associations between the consumption of wholemeal pasta (Odds Ratio [OR]: 16.0, 95% Confidence Interval [CI]: 2.86–89.4, p = 0.002) and cheese spread (OR: 9.53, 95% CI: 1.64–55.4, p = 0.020) with increased ASD risk. Notably, these estimates reflect the lifetime effects of genetic predisposition to higher intake levels rather than short-term consumption risks. Conversely, banana consumption was associated with a protective effect against ASD (OR: 0.50, 95% CI: 0.30–0.83, p = 0.008). Mediation analysis indicated that cheese spread intake may elevate ASD risk by reducing HLA-DR + T cell CD45 levels (10.2% mediation) and increasing anti-Epstein–Barr virus IgG seropositivity (12.9% mediation).

Clinically, a retrospective study involving 78 participants aged 2–7 years assessed the impact of a gluten-free casein-free (GFCF) diet on ASD symptoms using the Childhood Autism Rating Scale (CARS) and the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2). Although the GFCF diet did not yield statistically significant improvements in ADOS-2 and CARS scores when compared to a normal diet, it did demonstrate greater symptom improvement and a significant reduction in milk- and wheat-specific IgG levels, suggesting its potential to modulate immune responses.

This research provides genetic evidence for causal relationships between specific dietary factors and ASD risk, while clinical data underscore the potential benefits of a GFCF diet in modulating immune responses and possibly improving ASD symptoms. These insights are pivotal for advancing the understanding of ASD etiology and refining nutritional treatment strategies. [NPID: Gluten, Autism Spectrum Disorder, ASD, genetic, diet, casein-free]

Year: 2026

Reference: Guo, Y. S., Wang, Y., Zhu, M. N., Che, C., Yu, X. X., Cai, Z. F., Leng, J., Chen, K. P., & Cao, A. H. (2026). Exploring the potential association between dietary factors and autism spectrum disorder: A Mendelian randomization analysis and retrospective study. Frontiers in Nutrition, 12, 1716044. https://doi.org/10.3389/fnut.2025.1716044