Enhancing Exercise Performance Under Hypoxia: A Network Meta-Analysis and Animal Experimental Validation of Plant Bioactive Compounds

Background: Hypoxic environments significantly impair exercise performance, whilst existing interventions are often limited by adverse effects or insufficient efficacy. Objectives and Methods: This study employed network meta-analysis to screen plant bioactive compounds that effectively enhance exercise performance under hypoxic conditions, with subsequent validation of the efficacy and underlying mechanisms of their combined formulations through animal experiments. Results: Results from hypoxic mouse experiments demonstrated that supplementation with the plant bioactive compound combination significantly improved exercise performance, as evidenced by increased weight-loaded swimming time and limb grip strength. Differential metabolite analysis revealed that the intervention altered key metabolic pathways, including the biosynthesis of unsaturated fatty acids and the metabolism of arginine and proline. Supplementation with the plant bioactive compound combination modulated short-chain fatty acid (SCFA) production by gut microbiota, decreased levels of lactic acid (LA), lactate dehydrogenase (LDH), and creatine kinase (CK), maintained blood glucose levels before and after exercise, and increased muscle and hepatic glycogen reserves. These effects collectively improved exercise endurance and performance in mice under hypoxic conditions. Conclusions: The findings provide novel insights into developing functional interventions to enhance exercise performance in hypoxic environments.