Language

English

Publication Date

5-1-2026

Journal

Journal of the Endocrine Society

DOI

10.1210/jendso/bvag097

PMID

42094865

PMCID

PMC13142796

PubMedCentral® Posted Date

4-27-2026

PubMedCentral® Full Text Version

Post-print

Abstract

To identify metabolites as potential biomarkers of fructose vs 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 between the 2 intervention groups. Changes in 16 metabolites (5 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 < .2, unadjusted P-value ≤ .08) differences in response to the 2 interventions. We observed a 2.19 µM (or 13%) and a 10.17 µM (or 25%) increase in ketomethylvaleric acid (PFDR = 0.04, P = .001) and 2-hydroxybutyrate (PFDR = 0.11, P = .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 beverages high in glucose vs 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.

Published Open-Access

yes

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