Inflammatory Cytokines as Biologic Signatures of the Effect of Dietary Supplementation With Omega Fatty Acids on Autism-Related Behaviors and Features Among Young Children: A Randomized Controlled Trial.

PURPOSE: Evidence for the efficacy of dietary omega fatty acid supplementation as a supportive intervention for autism is mixed. Mechanisms by which supplementation may offer benefit are unclear. Inflammation may contribute to autism-related behaviors and features. This double-blind, randomized controlled trial evaluated inflammatory cytokines as biologic signatures of the effect of daily dietary supplementation with omega-3 and omega-6-rich fish and borage oil ("omega 3-6") versus placebo in children ages 2 - < 7 years recently diagnosed with autism. METHODS: Children were randomized to omega 3-6 or placebo for 90 days. Cytokines were measured in plasma, and autism-related behaviors and features were assessed by caregiver report and direct assessment. Linear mixed models followed intent-to-treat and evaluated the effect of omega 3-6 supplementation on the change in cytokines. Pearson correlation coefficients estimated associations between change in cytokines and change in autism-related behaviors and features. Exploratory analyses examined moderation by sex, age, gastrointestinal symptoms, and overweight. RESULTS: Of 98 children randomized, 96 were included in this analysis. Omega 3-6 had no overall effect on cytokines or autism-related behaviors and features (e.g., group difference in change for PDDBI autism composite = 0.1, 95% CI= -10.9, 11.1). Changes in cytokines were generally uncorrelated with changes in autism-related behaviors and features. Some sex-specific effects were observed. CONCLUSION: This study offered little support for inflammation serving as a mechanism for the effect of omega 3-6 fatty acids on autism-related behaviors and features among young children. Suggestive sex-specific effects should be replicated in a larger trial. CLINICAL TRIAL REGISTRY: Clinicaltrials.gov NCT04312932 registered March 16, 2020.