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

Abstract

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.

Keywords: Dkeletal muscle; Glutathione; Lipid metabolism; PGC-1α; Running exercise.

Figure 1

The effect of glutathione on blood glucose (A), NEFA (B), and intermuscular pH (C) in sedentary and exercised mice. Values are provided as mean ± SE. *p < 0.05, **p < 0.01, ***p < 0.001.

Figure 2

The effect of glutathione on PGC-1α (A), AMPK (B) and mtDNA (C) levels in skeletal muscle in sedentary mice. Values are provided as mean ± SE. *p < 0.05.

Figure 3

The effect of glutathione on blood glucose (A) and lactate (B) level in humans. Values are provided as the mean ± SE. *p < 0.05, **p < 0.01 vs. Rest.

Figure 4

The effect of glutathione on plasma ethanol-soluble (A) and protein-bound (B) glutathione level in humans. Values are provided as the mean ± SE. *p < 0.05.

Figure 5

The effect of glutathione on heart rate (A) and the rating of perceived exertion (B) level in in humans. Values are provided as the mean ± SE. *p < 0.05 vs. placebo.