MetaExtreme: Years of aerobic, resistance and sprint training differentially shape the human serum metabolome

Introduction. Human metabolism is highly ariable. At the pathological end, inborn or acquired defects cause metabolic disease and systematically alter blood metabolites. Physiologically, genetic predisposition and years of training result in a highly anabolic, glycolytic or oxidative metabolism. We aimed to investigate whether years of aerobic, resistance or sprint training, resulting in physiological extremes of human metabolism systematically change blood metabolites.Methods. We recruited 35 healthy male subjects, 9 natural bodybuilders, 8 sprinters, 11 endurance athletes and 7 untrained controls. We phenotyped participants according to endurance performance, strength, and anthropometry. We drew blood at fasted rest and 5 minutes after a cycle ergometry to exhaustion and profiled 857 metabolites by untargeted metabolomics.Results. Multivariate analysis revealed that endurance athletes and natural bodybuilders years of training differentially shapes their blood metabolome at rest and after exercise, whereas sprinters and controls shared similarities. Endurance athletes and natural bodybuilders have lower levels of sulfated steroids compared to sprinters and controls and higher levels of sphingomyelins and long-chain polyunsaturated fatty acids. Endurance athletes showed higher concentrations of long-chain saturated acylcarnitines than bodybuilders, suggesting acutely higher oxidation rates during exercise or a higher capacity to mobilize. Natural bodybuilders have higher levels of amino acids mainly such involved in histidine metabolism. While we observed changes of known exercise metabolitessuch as lactate, pyruvate and hypoxanthine in all groups, we found significant differences in the responsiveness to exercise between each athlete group versus controls (e.g. acylcarnitines, dopamine metabolites).Discussion. We confirmed findings of our targeted metabolomics that highly anabolic and oxidative athletes have sysematically changed blood metabolite concentrations, c