Glutathione as a skin-lightening agent and in melasma: a systematic review

This review of ten years of PubMed, Embase and Cochrane literature found topical glutathione 0.5% significantly more effective than 0.1% and than placebo, with further improvement when combined with microneedling. Five randomised trials and one open-arm study of oral glutathione at 250 mg once or twice daily or 500 mg daily showed a significant reduction in melanin index versus placebo, and topical 2% plus oral glutathione outperformed either alone. Only one placebo-controlled study examined intravenous glutathione (37.5% vs 18.7% response, p = 0.054, not significant). Risk of bias was low in roughly half the studies and high in the rest, and the authors conclude intravenous glutathione is contraindicated for lack of efficacy and side effects, while topical and oral forms give moderate but unsustained lightening.