Association Between Trace Mineral Concentrations and Oxidative Stress in Children with ADHD Supplemented with Multinutrients

Oxidative stress (OS) arises from an imbalance between antioxidant defenses and the generation of reactive oxygen species (ROS), both of which are influenced by the levels and composition of trace elements. The Micronutrients for ADHD in Youth randomized controlled trial demonstrated behavioral improvements following 8 weeks of multinutrient supplementation in 54% of children compared to 18% on placebo. This secondary analysis examined the relationship between plasma minerals and OS-related parameters [biological antioxidant potential (BAP), glutathione peroxidase (GPx), glutathione reductase (GR), and reactive oxygen metabolites (ROM)] in 71 children (44 multinutrient, 27 placebo; median age 10.4 years). Correlation analysis revealed that selenium and zinc improved antioxidant response measured as GPx change in both treatment groups (r = 0.26, p = 0.03) and BAP in multinutrient group (r = 0.37, p = 0.01), respectively, while chromium change was inversely related to BAP (r=-0.41, p = 0.005) in the multinutrient group. BAP change was moderated by baseline selenium (β=-9.45, p = 0.006), zinc (β=-2.13, p < 0.001), and chromium (β = 68.9, p = 0.02), where children in the multinutrient group with low selenium, low zinc, and high chromium at baseline experienced BAP increases. Selenium also exhibited pro-oxidant effects: ROM change correlated positively with change in selenium in multinutrient group only (r = 0.34, p = 0.03). Baseline copper predicted ROM change (β = 0.213, p < 0.001), and ROM change correlated positively with changes in copper in both groups (r = 0.51, p < 0.001) and negatively with Mn (r=-0.24, p = 0.05), while iron did not moderate OS. Multinutrient supplementation may enhance antioxidant defenses in children who had low plasma zinc and selenium, while potential pro-oxidant effects in those with higher selenium and chromium warrant further investigation. Clinical Trial Registry number for MADDY RCT: NCT03252522.