The metabolic signature of excessive endurance exercise – a prospective study in Tour de France cyclists

Professional grand tour cycling represents an ecological model of excessive endurance exercise. We hypothesized that the extreme metabolic demands of a three-week Tour de France would induce widespread alterations in circulating metabolite concentrations, providing mechanistic insights into adverse health effects associated with excessive endurance exercise.

This dataset contains metabolomic analyses of fasted blood samples from 7 elite male cyclists (mean ± SD: age: 31 ± 6 years, height: 1.83 ± 0.07 m, body mass: 73.0 ± 6.7 kg, ethnicity: Caucasian) who completed the 2023 Tour de France (19 stages, 3,404 km, 56,482 m elevation). Fasted blood samples were each time collected just after waking up at four timepoints: (i) the first racing day (day 1, START), (ii) the first rest day (day 10, RD1), (iii) the second rest day (day 17, RD2), and (iv) the final racing day (day 23, FINISH). Combined targeted and untargeted metabolomics identified 274 metabolites. Furthermore, perceived fatigue was evaluated immediately following each blood sample collection using a 0-10 Likert visual analogue scale with the question: “Your general perception of fatigue in this Grand Tour is?”.

Key findings reveal that 43% of metabolites (118/274) were significantly altered (p<0.05, FDR-corrected), with the most pronounced changes occurring in the first 10 days. Unlike acute exercise, excessive endurance exercise predominantly depleted circulating metabolites. Amino acids, L-carnitine, specific acylcarnitines, and saturated fatty acids showed significant depletion. Pathway enrichment analysis identified β-oxidation and glutathione metabolism as the most affected pathways.