(P25-032-24) Oxidative Stress Changes in Response to Multinutrient Supplementation for Children With ADHD: The MADDY RCT

Objectives: Children with attention-deficit/hyperactivity disorder (ADHD) have increased oxidative stress leading to oxidative damage. An 8-wk double-blind RCT [Micronutrients for ADHD in Youth (“MADDY”)] examined use of broad-spectrum multinutrients (BSM) containing all essential vitamins and minerals (dosed above RDA) in children aged 6-12 with ADHD and emotional dysregulation. Results showed 3 times as many children had significant behavioral improvements with BSM compared to placebo. Micronutrients serve critical roles in the body’s antioxidant protection systems, therefore these secondary analyses examined changes in biomarkers of oxidative stress after the 8-wk RCT.

Methods: Glutathione peroxidase (GPx) and glutathione reductase (GR) enzyme activity, along with Diacron reactive oxygen metabolites (dROM) and biological antioxidant potential (BAP) were measured in plasma using spectrophotometric methods. Oxidative stress index (OSI) was calculated as the ratio of BAP/dROM. Differences in 8-wk change between BSM and placebo groups were determined using two-sample t-test or Mann-Whitney U-test.

Results: Plasma from 77 children (45 BSM, 32 placebo; aged 9.9 +/- 1.7 yrs; 71% male) were analyzed. At baseline, GR mean (SD) was 17.7 (6.7) nmol/min/mL, GPx median (IQR) was 147.8 (134.3-158.0) nmol/min/mL, and dROM was 30.04 (27.02-34.03) mgH₂O₂/dL. After 8-wk RCT, dROM decreased in BSM vs. increased in placebo group (-1.14 vs. +2.14 mgH₂O₂/dL, p=0.017), but difference in group change was not significant for either GPx (-0.4 vs. +0.98 nmol/min/mL, p=0.726) or GR (-2.06 vs. 0.89 nmol/min/mL, p=0.297). BAP and OSI results are being finalized.

Conclusions: Although glutathione enzyme activities did not change, 8 wks of BSM supplementation in children with ADHD led to oxidative stress decrease per dROM measure, potentially through action of antioxidants (e.g., Vit E and C) in the supplement.

Funding Sources: Foundation for Excellence in Mental Health Care, Gratis Foundation, and CTSA award #s UL1TR002733, UL1TR002369.