Molecular modeling of azo-food dye metabolites in the brain and their effects on attention deficit and hyperactivity disorder (ADHD) using ArgusLab software

Abstract

This study hypothesizes that the attention deficit and hyperactivity disorder (ADHD) effect of azo food dyes could arise from their hydroxylated amine metabolites. These metabolites are generated either by the action of body’s enzymes or by the intestinal microbiome. The blood-brain barrier (BBB) penetration and competitive binding abilities of metabolites with dopamine receptors in the brain are investigated. Geometries of metabolites were optimized using quantum chemical Austin Model 1 (AM1). Lipophilicity, diffusion coefficient, topological polar surface area, and hydrogen bonding atom distances were calculated for the metabolites in the optimized geometries. Based on BBB penetrability as well as the competitive binding abilities of metabolites with dopamine receptors, it is concluded that the metabolites of Amaranth dye are likely to cause the strongest ADHD effect, followed by Ponceau 4R and Allura Red. Dyes Sunset yellow, Azorubine and Tartrazine could cause milder ADHD effects in that order. Besides relative grading of water-soluble food dyes for their ADHD potential, the study provides an alternative model for molecular basis of origin of ADHD and provides plausible reasons for its differential manifestation in different children.