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Multinutrients Decrease Oxidative Stress in Children With ADHD: Mediation/Moderation Analysis of Randomized Controlled Trial Data

Robinette LM, Hatsu IE, Adetona O, Wu CM, Johnstone JM, Bruton AM, Ast HK, Odei JB et al.

Journal of attention disorders, 2025

77 participants · 2 citations

Abstract

Background: ADHD is associated with oxidative stress (OS), possibly stemming from deficiencies in essential nutrients. Previous randomized controlled trials (RCTs), including Micronutrients for ADHD in Youth (MADDY), demonstrated improved symptoms in response to treatment with multinutrients compared to placebo. It remains unknown whether multinutrient supplementation influences antioxidant status and OS, and if these factors contributed to improvements observed in children with ADHD in the MADDY RCT.

Objectives: Utilizing samples from the MADDY RCT, (1) compare the change in antioxidant (AO) and OS biomarkers after 8 weeks of multinutrient supplementation vs placebo, and (2) evaluate these biomarkers at baseline, and their change after 8 weeks, as moderators/mediators of treatment response.

Methods: Activity of glutathione peroxidase (GPx) and glutathione reductase (GR) enzymes, plus oxidative stress index (OSI) based on ratio of reactive oxygen metabolites (ROM) to biological antioxidant potential (BAP), were measured in plasma at baseline and week 8. Differences between groups were determined using two-sample t-test or Mann-Whitney U-test. Logistic regression models assessed AO/OS biomarkers for mediation/moderation of treatment response.

Results: Plasma from 77 children (aged 9.9 ± 1.7 years; 71% male) treated with multinutrients (n = 45) or placebo (n = 32) was analyzed. After 8 weeks, ROM decreased with multinutrients and increased with placebo (-14.3 vs. +26.8…

How strong is the evidence?

Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 77 participants or records.

How the five levels of evidence work. The level is assigned automatically from the abstract and can be wrong, so check the paper.

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