ImportanceDiscretionary fortified beverages contain several ingredients such as vitamins and minerals in excess amounts, yet their consumption and sales have been burgeoning. Marketed as providing a unique health benefits to consumers, concerns have been raised about the overconsumption of some nutrients, especially in children and adolescents.ObjectiveTo evaluate the impact of discretionary fortified beverage consumption on energy metabolism, gut hormones and metabolic profiles of adolescents.DesignA double blind, randomized, placebo‐controlled crossover trial examined the metabolic effects of a concentrated, small format B‐vitamin fortified beverage. Healthy adolescents (10 males, 10 females, 13–19y) completed two trials separated by at least 1 week, consuming either water as placebo (PL) or an artificially sweetened discretionary fortified beverage (FB, 1.5ml/kg), which were given 40min prior to an oral glucose tolerance test (OGTT).MethodBlood samples were collected at baseline and at different time‐points throughout the OGTT for insulin, gut hormones and 1H‐NMR spectroscopy‐based metabolomics analyses. To evaluate gene‐metabolic interactions, a group of the most common single nucleotide polymorphisms (SNPs) linked to B‐vitamin metabolism was also assessed.ResultsPlasma glucose was not different between the treatment groups (p=0.111). However, plasma insulin was significantly higher in the FB group (p=0.003) and accompanied by a 28% decrease in insulin sensitivity in FB compared to PL as indicated by the composite Insulin Sensitivity Index (ISI). Gut hormone secretion was also differentially modulated by the consumption of FB. We found a significant increase in AUC of GLP‐1 (p<0.001), glucagon (p=0.015), PYY (p=0.001) and C‐peptide (p=0.017) in FB compared to the PL group. Employing 1H‐NMR metabolomics, we also show perturbations to one carbon, B‐vitamin linked sulfur amino acid metabolism with FB consumption. This metabolic response was dependent on genotypic variance at rs651852 (Betaine Homocysteine methyltransferase, BHMT, p<0.05).ConclusionCurrent data provide evidence that FB are not inert, but may promote insulin resistance, perturb one carbon, B‐vitamin‐linked metabolism and differentially modulate gut hormone secretion in adolescent consumers. Results may warrant reconsideration of regular, artificially sweetened FB consumption for adolescents at risk for obesity and metabolic disease.Support or Funding InformationThe research was funded by the Alberta Children's Hospital Research Institute and the National Science and Engineering Council of Canada (JS). SM is funded through an Eyes High Postdoctoral Fellowship and an Alberta Innovates Health Solutions Postdoctoral Fellowship.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.