Effects of different-intensity exercise and creatine supplementation on mitochondrial biogenesis and redox status in mice

Dietary supplementation combined with exercise may potentiate the beneficial effects of exercise by reducing exercise-induced oxidative stress and improving mitochondrial quality and capacity. In this study, the effects of creatine monohydrate (CrM) supplementation with low and high-intensity exercise on mitochondrial biogenesis regulators, Nrf2 anti-oxidant signaling pathway and muscle damage levels were investigated.  Balb/c male mice were divided into six experimental groups: control, control+CrM, high-intensity exercise, high-intensity exercise+CrM, low-intensity exercise, and low-intensity exercise+CrM. Mice were given CrM supplementation and at the same time, low and high-intensity exercise was applied to the groups on the treadmill at 30min/5day/8week. Then, mitochondrial biogenesis marker (PGC-1α, NRF-1, TFAM), Nrf2 and HO-1 protein expressions, total oxidant-anti-oxidant status level, and histopathological changes were investigated in serum and muscle tissue.  Exercise intensity and CrM supplementation were found to be effective factors in mitochondrial biogenesis induction via the PGC-1α signaling pathway. Nrf2 and HO-1 protein levels increased with exercise intensity, and this result was directly related to serum oxidative stress markers. In addition, CrM supplementation was effective in reducing exercise-induced muscle damage.  This combination induced skeletal muscle adaptations, including mitochondrial biogenesis and enhanced anti-oxidant reserves. This synergistic effect of dietary supplementation with low-intensity exercise may be valuable as a complement to treatment, especially in diseases caused by mitochondrial dysfunction.