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Multiple mechanisms are involved in exercise-induced fatigue, including energy depletion, metabolite accumulation, and oxidative stress, etc. The mechanistic findings provide a rationale for a multi-targeted approach to exercise-induced fatigue management. This study created a multi-ingredient formula mixed with valine, isoleucine, leucine, β-alanine, creatine, l-carnitine, quercetin, and betaine, based on the functional characteristics of these agents, and evaluated the preventive effect of this mechanism-based formula on exercise-induced fatigue. Results showed that the 7-d formula supplement significantly increased the running duration time of mice by 14% and the distance by 20% in an exhaustive treadmill test, indicating that the formula could delay fatigue appearance and improve exercise performance. Mechanistically, the formula enhanced fatty acid oxidation and spared liver glycogen by regulating the fat/glucose metabolism-related signaling pathways, including phospho-adenosine monophosphate-activated protein kinase α (p-AMPKα), phospho-acetyl CoA carboxylase (p-ACC), carnitine palmitoyl-transferase 1B (CPT1B), fatty acid translocase (CD36), and glucose transporter type 4 (GLUT4), and increased antioxidant capacity. The findings suggested that the formula tested in this study effectively ameliorated exercise-induced fatigue by targeting multi-signaling pathways, showing promise as a regimen to fight exercise-induced fatigue.

A Multi-Ingredient Formula Ameliorates Exercise-Induced Fatigue by Changing Metabolic Pathways and Increasing Antioxidant Capacity in Mice