Metabolite Shifts Induced by Marathon Race Competition Differ between Athletes Based on Level of Fitness and Performance: A Substudy of the Enzy-MagIC Study

Abstract

This study compared metabolite shifts induced by training for, participation in, and recovery from a marathon race competition among athletes divided into three groups based on fitness (relative maximum oxygen uptake (VO2max)) and performance levels (net running time). Plasma samples from 76 male runners participating in the Munich Marathon were analyzed for metabolite shifts using a targeted metabolomics panel. For the entire cohort of runners, pronounced increases were measured immediately after the race for plasma concentrations of acylcarnitines (AC), the ratio (palmitoylcarnitine + stearoylcarnitine)/free carnitine that is used as a proxy for the activity of the mitochondrial enzyme carnitine palmitoyltransferase, and arginine-related metabolites, with decreases in most amino acids (AA) and phospholipids. Plasma levels of AA and phospholipids were strongly increased 24 and 72 h post-race. Post-race plasma concentrations of AC and arginine-related metabolites were higher in the low compared to top performers, indicating an accumulation of fatty acids and a reliance on protein catabolism to provide energy after the marathon event. This study showed that marathon race competition is associated with an extensive and prolonged perturbation in plasma metabolite concentrations with a strong AC signature that is greater in the slower, less aerobically fit runners. Furthermore, changes in the arginine-related metabolites were observed.

Metabolomics and Lipidomics: Expanding the Molecular Landscape of Exercise Biology

“…The data from this study overall showed enhanced FA and BCAA utilization capacities in high- versus low-performance rats. While the increased FA oxidation capacities in high-performance rats are in line with findings from human marathon runners [ 73 ] described above, the amino acid results between these studies seem contradictory. However, the absence of significant changes in both plasma and muscle amino acids in low-performance rats may be due to the relatively short exercise bout (10 min) that may have been insufficient to induce protein breakdown as opposed to the 45-min run in high-performance rats.…”

“…Metabolomic responses to exercise in blood have also been shown to be influenced by an individual’s level of fitness. For instance, in a study by Schader and colleagues [ 73 ], male amateur marathon runners were divided into top ( n = 18), average ( n = 40) and low ( n = 18) performers, based on VO 2 max (~63, 50 and 42 mL × min −1 × kg −1 , respectively) and race completion time (~175, 225 and 277 min, respectively). Blood samples from these three groups were examined for potential differences in metabolomic responses to marathon running.…”

“…One possible explanation for these differences in acylcarnitine levels between top/average and low performers is that low performers may have a reduced capacity to oxidize lipids, which may in turn lead to an accumulation of acylcarnitines. Differences in arginine metabolism and urea cycle related-metabolites between low and top performers have also been reported [ 73 ]. Arginine is an amino acid central to the urea cycle, which is activated during protein breakdown when nitrogen is liberated from amino acids.…”

“…Another possible reason for reduced levels in citrulline observed in the low performers group may be the potential decrease in asymmetric dimethylarginine—a substrate for citrulline synthesis—that occurs during strenuous and prolonged exercise [ 76 ]. These overall differences in the urea cycle and arginine related-metabolites indicate a higher reliance on protein catabolism in low compared to top marathon performers [ 73 ]. However, given the complexity and multiple possible reactions leading to the production of arginine and urea cycle related-metabolites, further investigations are required to confirm the potential underlying mechanisms suggested above.…”

Physiological extremes of the human blood metabolome: A metabolomics analysis of highly glycolytic, oxidative, and anabolic athletes

“…4.4 | Endurance athletes have higher lysoPC a C18:1 and C18:2 concentrations, which may be linked to cardiovascular fitness Endurance athletes had higher concentration of lysoPC a C18:1 than bodybuilders and controls. Earlier studies have already associated lysoPCs containing 18 carbons with endurance traits (Felder et al, 2017;Schader et al, 2020). Specifically, lysoPC a C18:1 was, among other lysoPCs, reported to increase after several weeks of endurance training (Felder et al, 2017).…”