Glutathione for skin lightening via intravenous, oral, and topical routes: a critical narrative review of current evidence, safety, and the evidence-practice gap.

Intravenous glutathione (IV GSH) has emerged as a prominent cosmetic skin-lightening treatment despite continuing uncertainty about its efficacy and safety. This narrative review critically appraises the available evidence on IV GSH, with special emphasis on its proposed mechanisms of action, clinical efficacy, safety profile, and knowledge gaps. We performed a structured literature search using PubMed/MEDLINE, Scopus, Embase, and Google Scholar from inception through March 2026. We screened and included mechanistic, preclinical, and clinical trials assessing GSH for skin lightening in the final narrative synthesis. The biological hypothesis for GSH is that it can block the tyrosinase pathway, influence oxidative stress regulation, and direct melanogenesis toward pheomelanin synthesis. However, translating these mechanisms into clinically meaningful outcomes remains uncertain. Available literature provides limited evidence of modest, varied skin pigmentation improvements and is generally limited by small sample sizes, methodological differences, the absence of standardized outcomes, and limited follow-up. In addition, the regular co-administration of vitamin C has made it difficult to know the independent effect of IV GSH in such individuals. New safety concerns, such as hepatotoxicity, hypersensitivity reactivity, and potential renal and endocrine effects, may further complicate the risk-benefit relationship during IV GSH. Current evidence is too limited to justify routine use for cosmetic skin lightening, highlighting the necessity for sufficiently powered RCTs and prolonged safety studies.