Multinutrient Supplementation in Children With ADHD Reduced Pro- and Anti-Inflammatory Immune Factors in the MADDY Randomized Controlled Trial

Objective: While individual nutrients have shown effects on inflammatory mechanisms, the effects of multinutrients (vitamins + minerals, antioxidants, and amino acids) on inflammation are unknown. We investigated whether 8 weeks of multinutrient supplementation, in a randomized controlled trial of 83 children with ADHD, would alter immune factors compared to placebo. Methods: Multiplex technology was used to measure 25 immune factors in blood samples collected at baseline and week 8. Immune factors were compared between multinutrient and placebo groups using the Mann-Whitney test. Linear mixed effects models evaluated immune factor change over time. To understand the functional relevance of the immune factors affected by multinutrient supplementation, pathway analysis was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) v6.7 Bioinformatics Resources. Results: Interleukin (IL)-5 and IL-13 levels differed following multinutrient supplementation versus placebo ( p = .005 and .03, respectively). IL-5 decreased by 1.3% in the multinutrient group (95% CI [−8.6%, 6.7%]) and increased by 17.5% in the placebo group (95% CI [6.9%, 29.2%]). IL-13 decreased by 11.4% in the multinutrient group (95% CI [−18.2%, −4.0%]), compared to a 2.4% increase in the placebo group (95% CI [−7.2%, 13.1%]). When comparing immune factors between treatment responders versus non-responders in the multinutrient group, there was a 4.3% increase in IL-15 in multinutrient responders (95% CI [−6.8%, 16.8%]) and a 14.3% decrease in non-responders ( p = .03, 95% CI [−24.9%, −2.4%]). Pathway analysis identified T helper type 2 (Th2) signaling pathways affected by multinutrient supplementation, including IL-17 and cytokine-cytokine receptor interaction pathways. Conclusion: Th2 immune factors may be influenced by multinutrient supplementation and associated with behavioral improvements in ADHD.