Plasma metabolites after a 10-weeks of glucose vs fructose-sweetened beverages in subjects with overweight/obesity

To identify metabolites as potential biomarkers of fructose versus glucose consumption and related metabolic changes, we conducted exploratory metabolomic profiling of fasting blood samples from participants in a double-blind, parallel-arm trial involving 31 male and female adults with overweight or obesity, both before and after supplementation with glucose- or fructose-sweetened beverages. Orthogonal Partial Least Square Discriminatory Analysis (OPLS-DA) was used to identify metabolites that could discriminate the two intervention groups. Changes in sixteen metabolites (five of which are branched-chain amino acid catabolic pathway metabolites) and the branched chain keto acid (BCKA) composite score showed nominal (FDR adjusted p-value < 0.2, unadjusted p-value ≤ 0.08) differences in response to the two interventions. We observed a 2.19 µM (or 13%) and a 10.17 µM (or 25%) increase in ketomethylvaleric acid (PFDR =0.04, P = 0.001) and 2-hydroxybutyrate (PFDR = 0.11, P = 0.008), respectively, after glucose supplementation compared to a null change after fructose supplementation. Notable trends after fructose supplementation included increased long- and median-chain acylcarnitines (ACs); decreased short-chain ACs; and increased homocysteine compared to the glucose supplementation. These data suggest that in people with overweight/obesity, consumption of bevarages high in glucose versus fructose may differentially affect the metabolism of branched-chain amino acids and acylcarnitine species reflective of changes in fatty acid oxidation and de novo lipogenesis.