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

Abstract

Abstract Objectives Attention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric disorder 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 has shown promise in children, but its effects on nutrient status and the underlying metabolome interactions have not been characterized. Methods 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. Following RCT is an 8-week open label phase during which all participants took the active supplement. Symptoms were assessed using the Child and Adolescent Symptom Inventory 5. Double-blinded plasma samples will be analyzed for tyrosine, phenylalanine, tryptophan, magnesium, and zinc. Untargeted LC-MS metabolomics using HILIC chromatography and a high resolution QTof will assess very polar analytes in plasma extracts. Linear modeling will elucidate the influence of treatment, sampling time, and ADHD symptom score on plasma nutrient and plasma metabolite concentration. Results 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. Conclusions Preliminary findings indicate improvements of ADHD symptoms of inattention, hyperactivity, ODD and DMDD following 8 weeks of open label multi-nutrient supplementation. Results of the double-blinded phase are expected to mirror those observed in the open label phase, with increases in nutrients in those receiving the multinutrient. Funding Sources The sample analyses were supported by NIH Award Number Grant P30 CA016058, OSU, and OSUCCC. Foundation for the Center of Excellence in Mental Health, Canada; The Ohio State University Department of Human Sciences, College of Education and Human Ecology; The Ohio State University Wexner Medical Center, Clinical Research Center.