Vats P, Singh VK, Singh SN, Singh SB. Glutathione metabolism under high-altitude stress and effect of antioxidant supplementation. Aviat Space Environ Med 2008; 79:1106–11.Introduction: Humans have a number of mechanisms for protection against reactive oxygen species, but under stressful conditions these defenses are not completely successful. Glutathione plays an important role in protection against free radicals and reactive oxygen species induced damages. The present study was undertaken to understand the effect of high-altitude (HA) exposure on glutathione metabolism and antioxidant status along with the effects of N-acetyl cysteine (NAC) and vitamin E supplementation in humans. Methods: The study was conducted on 30 healthy male volunteers (age 22.9 ± 2.6, mean ± SD) divided into three groups. Group 1 was placebo control and 2 and 3 were supplemented with 400 mg of NAC or vitamin E, respectively, per day. The study was conducted initially at sea level (Phase I, 320 m); then the subjects were taken to high altitude (Phase II, 3600 m) by air. After a week at this altitude, subjects ascended on foot to an altitude of 4580 m (Phase III). Results: Significant decreases in reduced glutathione and increases in oxidized glutathione levels were observed on HA exposure. Increase in glutathione peroxidase and glutathione reductase levels were also observed on HA exposure. Lower levels of plasma vitamin C and total antioxidant status were observed during HA exposure. The changes observed were less in the supplemented groups as compared to placebo control. Discussion: Results indicate that HA exposure adversely affects glutathione metabolism and antioxidant defense mechanisms and these changes can be ameliorated through supplementation of NAC and vitamin E.