<![CDATA[Melasma is a hyperpigmentation disorder characterized by increased melanin production, commonly affecting women. Chronic UV exposure increases reactive oxygen species (ROS), and when ROS exceed the body's antioxidant capacity, oxidative stress occurs and is mitigated by glutathione peroxidase (GPx). However, evidence linking oral glutathione supplementation to endogenous GPx activity in patients with melasma remains limited. This study aims to evaluate the effect of glutathione supplementation on GPx levels and melasma severity in patients with melasma. A quasi-experimental, single-blind, pre-post study with a placebo control group was conducted at CITO Laboratory in South Jakarta among 54 women aged 30–59 years with melasma between December 2023 and May 2024. The participants were randomly allocated into two groups: a treatment group receiving oral reduced L-glutathione 500 mg once daily for one month, and a control group receiving a matched placebo tablet. GPx levels were measured in serum by ELISA, and modified melasma area and severity index (mMASI) scores were assessed before and after treatment; data were analyzed using the Wilcoxon signed-rank test for within-group comparisons and the Mann-Whitney U test for between-group comparisons at baseline. In the glutathione group, the median GPx level increased from 11.70 to 16.67 (p<0.001) and the median mMASI score decreased from 4.1 to 2.0 (p<0.001), whereas the placebo group showed no significant change in either GPx level (11.81 to 12.26, p=0.279) or mMASI score (0.6 to 0.6, p=0.250). In conclusion, these findings indicate that oral glutathione supplementation increases GPx levels and reduces melasma severity, suggesting that its clinical benefit may be mediated by strengthening the endogenous enzymatic antioxidant defense. Oral glutathione may therefore be considered a potential adjunct therapy for melasma; however, larger multicentre, double-blind trials with longer follow-up and additional oxidative stress biomarkers are needed to confirm these findings.]]>
