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Backgrounds  Glutathione is an endogenous redox couple in animal cells and plays important roles in antioxidant defense and detoxification, although it is unknown if oral glutathione supplementation affects exercise-induced physiological changes. The present study investigated the effect of glutathione intake on exercise-induced muscle metabolism and fatigue in mice and humans.    Methods  ICR mice were divided into 4 groups: sedentary control, sedentary supplemented with glutathione (2.0%, 5 μL/g body weight), exercise control, and exercise supplemented with glutathione. After 2 weeks, the exercise groups ran on a treadmill at 25 m/min for 30 min. Immediately post-exercise, intermuscular pH was measured, and hind limb muscle and blood samples were collected to measure biochemical parameters. In a double-blind, cross-over study, 8 healthy men (35.9 ± 2.0 y) were administered either glutathione (1 g/d) or placebo for 2 weeks. Then, they exercised on a cycle ergometer at 40% maximal heart rate for 60 min. Psychological state and blood biochemical parameters were examined after exercise.    Results  In the mouse experiment, post-exercise plasma non-esterified fatty acids were significantly lower in the exercise supplemented with glutathione group (820 ± 44 mEq/L) compared with the exercise control group (1152 ± 61 mEq/L). Intermuscular pH decreased with exercise (7.17 ± 0.01); however, this reduction was prevented by glutathione supplementation (7.23 ± 0.02). The peroxisome proliferator-activated receptor-γ coactivator-1α protein and mitochondrial DNA levels were significantly higher in the sedentary supplemented with glutathione group compared with the sedentary control group (25% and 53% higher, respectively). In the human study, the elevation of blood lactate was suppressed by glutathione intake (placebo, 3.4 ± 1.1 mM; glutathione, 2.9 ± 0.6 mM). Fatigue-related psychological factors were significantly decreased in the glutathione trial compared with the placebo trial.    Conclusions  These results suggest that glutathione supplementation improved lipid metabolism and acidification in skeletal muscles during exercise, leading to less muscle fatigue.    Electronic supplementary material  The online version of this article (doi:10.1186/s12970-015-0067-x) contains supplementary material, which is available to authorized users.

Glutathione supplementation suppresses muscle fatigue induced by prolonged exercise via improved aerobic metabolism