Comparative analysis of circulating metabolomic profiles identifies shared metabolic alterations across distinct multistressor military training exercises.

Military training provides insight into metabolic responses under unique physiological demands that can be comprehensively characterized by global metabolomic profiling to identify potential strategies for improving performance. This study identified shared changes in metabolomic profiles across three distinct military training exercises, varying in magnitude and type of stress. Blood samples collected before and after three real or simulated military training exercises were analyzed using the same untargeted metabolomic profiling platform. Exercises included a 2-wk survival training course (ST, n = 36), a 4-day cross-country ski march arctic training (AT, n = 24), and a 28-day controlled diet- and exercise-induced energy deficit (CED, n = 26). Log₂-fold changes of greater than ±1 in 191, 121, and 64 metabolites were identified in the ST, AT, and CED datasets, respectively. Most metabolite changes were within the lipid (57-63%) and amino acid metabolism (18-19%) pathways and changes in 87 were shared across studies. The largest and most consistent increases in shared metabolites were found in the acylcarnitine, fatty acid, ketone, and glutathione metabolism pathways, whereas the largest decreases were in the diacylglycerol and urea cycle metabolism pathways. Multiple shared metabolites were consistently correlated with biomarkers of inflammation, tissue damage, and anabolic hormones across studies. These three studies of real and simulated military training revealed overlapping alterations in metabolomic profiles despite differences in environment and the stressors involved. Consistent changes in metabolites related to lipid metabolism, ketogenesis, and oxidative stress suggest a potential common metabolomic signature associated with inflammation, tissue damage, and suppression of anabolic signaling that may characterize the unique physiological demands of military training.NEW & NOTEWORTHY The extent to which metabolomic responses are shared across diverse military training environments is unknown. Global metabolomic profiling across three distinct military training exercises identified shared metabolic responses with the largest changes observed for metabolites related to fatty acids, acylcarnitines, ketone metabolism, and oxidative stress. These changes also correlated with alterations in markers of tissue damage, inflammation, and anabolic signaling and comprise a potential common metabolomic signature underlying the unique physiological demands of military training.