Octacosanol improves lactic acid clearance during exhaustive exercise via gut microbiota remodeling and improved mitochondrial function

BACKGROUND: Endurance exercise-induced fatigue is closely associated with disordered lactic acid metabolism. As a natural long-chain alcohol, octacosanol (Octa) exhibits anti-fatigue effects, while its detailed mechanism remains unclear. This study investigated the effect of Octa on lactic acid metabolism in the gastrocnemius muscle of mice subjected to exhaustive exercise and explored the potential gut-muscle axis mechanisms involved. RESULTS: We found that Octa supplementation significantly enhanced endurance performance, reduced lactic acid accumulation in plasma and muscle, and upregulated the lactic acid transporter MCT1. Octa reshaped the gut microbiota structure, increasing the abundance of beneficial bacteria and the production of short-chain fatty acids. Consequently, it suppressed the LPS/TLR4/NF-κB inflammatory pathway and ameliorated oxidative stress by activating NRF2/ARE signaling. These changes were accompanied by enhanced mitochondrial biogenesis and function, as evidenced by increased PGC-1α expression, mtDNA copy number, and expression of key enzyme in the oxidative phosphorylation pathway. CONCLUSION: Our findings demonstrate that Octa improves lactic acid metabolism and attenuates exercise-induced fatigue through a gut microbiota-regulated mechanism involving the suppression of inflammation and oxidative stress, and the enhancement of mitochondrial function via the NRF2/PGC-1α pathway. © 2026 Society of Chemical Industry.