Introduction: d-Glucosamine (GlcN) is one of the most widely consumed dietary supplements and complementary medicines in the world and has been traditionally used to attenuate osteoarthritis in humans. GlcN extends life span in different animal models. In humans, its supplementation has been strongly associated with decreased total mortality and improved vascular endothelial function. GlcN acts as a suppressor of inflammation, and by inhibiting glycolysis, it can activate the metabolism of stored fat and mitochondrial respiration.

Methods: The conventional human GlcN dose is 1500 mg·d-1, but extensive evidence indicates that much higher doses are well tolerated. GlcN is one of the supplements that has experienced a greater use in the last years in elite athletes mainly because of its potential chondroprotective effects that may promote cartilage health. However, the possibility of it being an ergogenic aid has not been explored. We aimed to study the potential beneficial effects of GlcN on mitochondrial content, physical performance, and oxidative stress in mice that were aerobically trained and supplemented with three different doses of glucosamine (250, 500, and 1000 mg·kg-1) for 6 wk. We measured exercise performance (grip strength, motor coordination, and running capacity) before and after the training period. Proteins involved in mitochondrial biogenesis (AMPK, PGC-1, NRF-1, SIRT-1, cytochrome c, citrate synthase), markers of oxidative stress (GSSG/GSH) or damage (malondialdehyde, carbonylated proteins), antioxidant enzymes (NRF-2, SOD1, SOD2, catalase, and PRDX6), and MAPKs (p38 and ERK1/2 were also determined in skeletal muscle.

Results and conclusions: Our results show that GlcN supplementation in aerobically trained mice, at doses equivalent to those conventionally used in humans, increases the protein levels of mitochondrial biogenesis markers, improves motor coordination, and may have a synergistic effect with exercise training on running distance.