Sex-specific marathon-induced metabolome changes
Abstract
Abstract Background: Marathon running imposes substantial metabolic stress, with sex-specific responses driven by differences in substrate utilisation, hormonal regulation, and muscle phenotype. Despite this, sex-specific metabolomic data remain limited, due to historical underrepresentation of female athletes. The aim of the study was to better understand how marathon running affects metabolism in male and female endurance athletes. Methods: Serum samples from male (n = 19) and female (n = 12) endurance athletes were analysed pre- and post-marathon using a multi-platform untargeted metabolomics approach, combining nuclear magnetic resonance spectroscopy and two-dimensional gas chromatography coupled with time-of-flight mass spectrometry. Two-way ANOVA identified 21 metabolites that differed significantly ( p Results: Post-marathon, males exhibited higher concentrations of ketone bodies, tricarboxylic acid cycle intermediates, branched-chain amino acids, and α-keto acids, consistent with greater reliance on lipid and amino acid catabolism for energy production. Elevated creatinine further reflected increased muscle stress and damage. Females however, showed higher creatine concentrations than males at both pre- and post-marathon timepoints, suggesting sex differences in creatine synthesis and breakdown. Gut microbiome-associated metabolites, including arabitol, methanol, and 3-phenylpropionic acid, also differed between sexes across timepoints, highlighting interactions…
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