Characterizing the plasma metabolome during and following a maximal exercise cycling test.

While complex in nature, a number of metabolites have been implicated in the onset of exercise-induced fatigue. The purpose of this study was to identify changes in the plasma-metabolome and specifically, identify candidate-metabolites associated with the onset of fatigue during prolonged cycling. Eighteen healthy and recreationally active men (mean{plus minus}SD age: 24.7{plus minus}4.8 years; mass 67.1{plus minus}6.1 kg; BMI: 22.8{plus minus}2.2; VO2peak: 40.9{plus minus}6.1 ml.kg.min-1) were recruited to this study. Participants performed a prolonged cycling Time-To-Exhaustion (TTE) test at an intensity corresponding to a fixed blood lactate concentration (3 mmol.L-1). Plasma samples collected at 10 min of exercise, prior to fatigue (last sample prior to fatigue; <10 min prior to fatigue), immediately post-fatigue (point of exhaustion) and 20 min post-fatigue were assessed using a liquid chromatography-mass spectrometry based metabolomic approach. Eighty metabolites were putatively identified, with 68 metabolites demonstrating a significant change during the cycling task (duration: ~80.9{plus minus}13.6 min). A clear multivariate structure in the data was revealed, with the first principal component (36% total variance) describing a continuous increase in metabolite concentration throughout the TTE trial and recovery; while the second principal component (14% total variance) showed an increase in metabolite concentration followed by a recovery trajectory, peaking at the point of fatigue. Six clusters of correlated metabolites demonstrating unique metabolite trajectories were identified, including significant separation in the metabolome between pre-fatigue and post-fatigue time-points. In accordance with our hypothesis, free-fatty acids and tryptophan contributed to differences in the plasma metabolome at fatigue.