Therapeutic Efficacy of a Modified Ketogenic Diet in Autism Spectrum Disorder: A Randomized Controlled Trial

<title>Abstract</title> <bold>Background</bold> Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social communication deficits, restricted interests, and repetitive behaviors, often accompanied by comorbidities such as epilepsy, sleep disturbances, and gastrointestinal disorders (GIDs). The global prevalence of ASD has been steadily increasing, resulting in significant lifelong treatment costs and substantial societal burdens, underscoring the urgent need for effective therapeutic intervention. Conventional rehabilitation therapies often exhibit limited efficacy and slow progress, particularly in the treatment of comorbid conditions. In recent years, the ketogenic diet (KD) has emerged as a promising intervention, demonstrating both safety and efficacy in managing ASD symptoms in children. This study aimed to evaluate the therapeutic potential of a modified ketogenic diet in children with ASD through a randomized, double-blind, controlled trial, thereby providing a clinical foundation for expanding treatment strategies. <bold>Methods</bold> A total of 62 children diagnosed with ASD and admitted to Hefei Maternal and Child Health Hospital between January 2024 and January 2025 were prospectively enrolled in this study. Participants were randomly assigned to either the treatment or control group using a randomized numerical table method, with 31 children in each group. The treatment group received a modified ketogenic diet (comprising ketogenic nutritional powder and an intervention diet) combined with standard rehabilitation training, while the control group received a normal diet alongside routine rehabilitation training. After a two-month intervention period, changes in autism-related symptoms were assessed using the Autism Behavior Checklist (ABC) and Childhood Autism Rating Scale (CARS). Pre- and post-treatment scores were compared between the two groups. <bold>Results</bold> Baseline characteristics, including sex, age, ABC scores, and CARS scores, showed no significant differences between the two groups (P &gt; 0.05). Following the two-month intervention, both groups exhibited significant improvements in ABC and CARS scores compared to their baseline values (P &lt; 0.05). However, the treatment group demonstrated significantly greater improvements in both ABC (U = 195.500, P &lt; 0.05) and CARS scores (U = 190.500, P &lt; 0.05) compared with the control group, indicating superior therapeutic efficacy. <bold>Conclusions</bold> The modified ketogenic diet, when combined with rehabilitation intervention training, significantly alleviated core symptoms in children with ASD. This approach represents a viable alternative to the classical ketogenic model, with the added advantage of high patient compliance. Further research is warranted to explore the long-term benefits and mechanisms underlying this dietary intervention. <bold>Trial registration</bold>: The Project was registered on MRCTS with the identifier MR-44-23-041122. Registered 06 November 2023, https://www.medicalresearch.org.cn/login/MR-44-23-041122