Metabolomics reveals that fittest trail runners show a better adaptation of bioenergetic pathways

Objectives: To analyze the effect in the blood metabolome of trail running, a demanding sport that takes place in the natural environment, places considerable strain on both muscles and joints. While metabolic responses to aerobic exercise have been analyzed in-depth, few studies have focused on trail running. Design: Observational study to analyze changes in 35 different metabolites - representative of aerobic exercise- induced by a simulated 21-km trail race with an uphill gradient of 1400 m. Methods: We performed a semiquantitative metabolomics study consisting of capillary blood microsampling and targeted screening with liquid chromatography and mass spectrometry to analyze, in 33 licensed athletes, changes concerning 35 metabolites. Results: We observed significant changes in many metabolites, including increased acetyl-carnitine and taurine concentrations (false discovery rate–corrected paired t-test P value 1.63 × 10–13, and P value 5.021 × 10-12, re- spectively) and decreased carnitine and proline concentrations (P value 6.33 × 10–10, and P value 1.21 × 10–9, re- spectively). Metabolic responses to trail running were largely independent of sex but were influenced by the level of training, with runners with a higher level showing resistance to exercise-induced changes in taurine, 1-methyl histidine, acetyl-carnitine, and hypoxanthine concentrations. Performance (measured as race time) was inversely correlated with changes in specific metabolites (including taurine, serotonin, and hypoxanthine) and directly correlated with increases in glutathione. Conclusions: Our findings demonstrate the usefulness of metabolomics studies for analyzing exercise-induced physiological changes and show individual differences associated with the level of training and performance.This work was supported by the Generalitat de Catalunya, Agency for Management of University and Research Grants [2017SGR696]; by the Spanish Ministry of Economy and Competitiveness, Institute of Health Carlos III [PI17-00134 and PI20-00155]; and by the Spanish Ministry of Science, Innovation and Universities [RTI2018-099200-B-I00]. MJ is a Serra-Hunter program fellow. AF is a fellow of Banco de Santander-UdL predoctoral program. We are also grateful for the support of; the National Institute of Physical Education of Catalonia (INEFC); and the Spanish government subproject Integration ways between qualitative and quantitative data, multiple case development, and synthesis review as main axis for an innovative future in physical activity and sports research [PGC2018-098742-B-C31] (2019–2021) (Ministry of Science, Innovation and Universities/Spanish State Research Agency/European Regional Development Fund), that is part of the coordinated project New approach of research in physical activity and sport from mixed methods perspective (NARPAS_MM) [SPGC201800X098742CV0]; and the Generalitat de Catalunya Research Group [Research group and innovation in designs] (GRID). Technology and multimedia and digital application to observational designs [Grant number 2017 SGR 1405]. FEDER funds are acknowledged [“A way to build Europe”]