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Purpose: High cardiorespiratory capacity is a key determinant of human performance and life expectancy; however, the underlying mechanisms are not fully understood. The objective of this pilot study was to investigate biochemical signatures of endurance-performance athletes using high-resolution nontargeted metabolomics. Methods: Elite long-distance runners with similar training and anthropometrical records were studied. After athletes’ maximal oxygen consumption (V˙O2max) was measured, they were divided into 2 groups: low V˙O2max (<65 mL·kg−1·min−1, n = 7) and high V˙O2max (>75 mL·kg−1·min−1, n = 7). Plasma was collected under basal conditions after 12 hours of fasting and after a maximal exercise test (nonfasted) and analyzed by high-resolution LC–MS. Multivariate and univariate statistics were applied. Results: A total of 167 compounds were putatively identified with an LC–MS-based metabolomics pipeline. Partial least-squares discriminant analysis showed a clear separation between groups. Significant variations in metabolites highlighted group differences in diverse metabolic pathways, including lipids, vitamins, amino acids, purine, histidine, xenobiotics, and others, either under basal condition or after the maximal exercise test. Conclusions: Taken together, the metabolic alterations revealed in the study affect cellular energy use and availability, oxidative stress management, muscle damage, central nervous system signaling metabolites, nutrients, and compound bioavailability, providing new insights into metabolic alterations associated with exercise and cardiorespiratory fitness levels in trained athletes.

Monnerat and Campos de Carvalho are with the Inst of Biophysics Carlos Chagas Filho; Sánchez, Paulucio, Velasque, and Pompeu, the School of Physical Education and Sports; G. Evaristo, J. Evaristo, and Nogueira, LADETEC, Inst of Chemistry; and Nogueira and Domont, Proteomic Unit, Inst of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. Santos is with the Brazilian Army Inst of Biology, Rio de Janeiro, Brazil. Serrato is with the Dept of Internal Medicine and Dept of Exercise Physiology, National University of Colombia, Bogotá, Colombia. Lima is with the Military Inst of Engineering (IME), Rio de Janeiro, Brazil. Bishop is with the Inst for Health and Sport, Victoria University, Melbourne, VIC, Australia. Monnerat is also with the National Inst of Cardiology, Rio de Janeiro, RJ, Brazil.

Santos ( is corresponding author.

Supplementary Materials

    • Supplementary Figure S1 (pdf 210 KB)
    • Supplementary Figure S2 (pdf 278 KB)
    • Supplementary Material (pdf 84 KB)
    • Supplementary Table S1 (pdf 1 MB)
    • Supplementary Table S2 (pdf 192 KB)
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    • Supplementary Table S5 (pdf 94 KB)