Using Metabolomics to Classify the Underlying Effects of Multi-Nutrient Supplementation in ADHD Youth

Attention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric disorder with increasing global prevalence and high heritability commonly diagnosed in childhood. Current pharmaceutical treatment options provide a poor long-term risk:benefit ratio with little knowledge of the long-term effects. A broad-spectrum multi-nutrient formula for ADHD has shown promise in children, but its effects on nutrient status and the underlying nutrient-metabolome interactions have not been characterized. 
Blood samples from medication-free children (n = 74) with ADHD enrolled in a double–blind randomized placebo-controlled multinutrient trial (RCT) were collected at baseline and 8 weeks post-intervention. Targeted LC-MS/MS analyses will be performed to assess the blood nutrient status of nutrients whose levels are predicted to negatively correlate with ADHD symptom severity (i.e. tyrosine, phenylalanine, tryptophan, magnesium, zinc, and iron). An untargeted LC-MS metabolomics screening approach will be used to assess polar analytes in blood plasma extracts using an Agilent 1290 UHPLC interfaced with an Agilent QTof 6545. Metabolite levels will be compared pre-and post- supplement intervention and correlated with symptom severity. Preliminary findings of the open label phase show a significant improvement in inattention (p=0.0435), hyperactivity (p=0.0068), ODD (p=0.0108) and DMDD (p=0.0119). We hypothesize that these improvements in ADHD symptoms will be correlated with increased circulating concentrations of tyrosine, phenylalanine, tryptophan, magnesium, zinc, and metabolites involved in neurotransmitter synthesis and/or branched chain amino acid metabolism. These proposed results will address a significant gap in the nutritional psychiatry literature and provide new hypotheses as to how multi-nutrients may benefit a pediatric ADHD population.