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

Abstract

Abstract 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.