Glutathione as an oral whitening agent: A randomized, double-blind, placebo-controlled study

Objective: To determine whether orally administered glutathione, 500 mg per day for 4 weeks, affects the skin melanin index, when compared with placebo. Methods: This randomized, double-blind, two-arm, placebo-controlled study was set in the King Chulalongkorn Memorial Hospital, Bangkok, Thailand, a teaching hospital affiliated with a medical school. Sixty otherwise healthy medical students were randomized to receive either glutathione capsules, 500 mg/day in two divided doses, or placebo for 4 weeks. The main outcome was mean reduction of melanin indices measured at six different sites. Several secondary outcomes, including UV spots, were recorded by VISIA™. Efficacies of glutathione and placebo were compared by ANCOVA with baseline values as co-variates. Results: Sixty participants enrolled and completed the study. At 4 weeks, the melanin indices decreased consistently at all six sites in subjects who received glutathione. The reductions were statistically significantly greater than those receiving placebo at two sites, namely the right side of the face and the sun-exposed left forearm (p-values = 0.021 and 0.036, respectively). This was similarly reflected in the changes in the number of UV spots, as measured by VISIA. Both glutathione and placebo were very well tolerated. Conclusion: Oral glutathione administration results in a lightening of skin color in a small number of subjects. However, long-term safety has not been established and warrants more extensive clinical trials.