Systemic glutathione for skin lightening – A scoping review of current evidence

Systemic glutathione, administered orally or intravenously, has gained popularity in aesthetic dermatology for its purported skin-lightening effects.1 Its use is rising in parts of Asia and Africa, as well as among darker-skinned populations in Europe and the Americas.2 Systemic glutathione has established medical indications due to its antioxidant properties such as in hepatic failure management and as a chemotherapy adjuvant to reduce cisplatin-associated neurotoxicity.3 However, its observed skin-lightening effects have led to its off-label cosmetic use.4, 5 Given its growing demand in aesthetic practice, the proliferation of unregulated online markets, conflicting efficacy data, safety concerns and unclear regulatory positions, we conducted a scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. PubMed and Cochrane Library were searched for English-language available articles published between January 2000 and May 2025. Eligible sources included reviews, clinical trials, observational studies, case reports and regulatory documents evaluating the use, efficacy, safety, adverse effects and regulatory stance of oral and IV glutathione for skin lightening. Animal or in vitro studies and non-systemic routes of glutathione administration were excluded. Reference list screening identified additional studies. In total, 35 eligible articles were included comprising 3 systematic reviews, 12 narrative reviews, 9 trials, 2 cross-sectional studies, 3 case reports, 1 book chapter, 1 commentary and 4 advisories (Figure 1). The literature showed, at best modest, transient and variable reductions in pigmentation with oral and buccal glutathione and minimal efficacy but significant risks with intravenous use (Table 1). Oral administration was mostly tolerable, with reported adverse effects being predominantly transient gastrointestinal adverse effects, though one case of toxic epidermal necrolysis was reported (Table 1). However, both high-quality evidence and long-term safety data were insufficient. Oral GSH resulted in modest skin lightening in sun-exposed areas (reduced melanin index) compared to placebo. Oral GSH 250–500 mg daily IV GSH 1200 mg twice weekly Reported safety concerns with IV GSH Oral GSH 250–500 mg, topical 2% GSH; IV GSH 600 mg Safety in short-term demonstrable. Long-term safety uncertain. Major safety concerns with IV GSH Thailand/ France JCCP Advisory (2024) Advice againts use for aesthetic purposes Sterile compounded GSH IV GSH cosmetic use Intravenousglutathione for skin lightening lacks convincing evidence of efficacy and has serious documented adverse effects. The only placebo-controlled trial showed no sustained benefit, while reports document serious adverse effects including liver dysfunction, anaphylaxis, pulmonary embolism, Stevens–Johnson syndrome and toxic epidermal necrolysis following use.6, 7 Contaminants have been identified in unlicensed injectable products, compounding safety concerns.8 Although prevalence data of systemic glutathione use are largely anecdotal, use spans Asia, Africa, the UK and USA, often administered by non-dermatologists. Several countries such as the Phillippines, the United States and the United Kingdom have issued warnings or outright bans on IV glutathione for aesthetic use.9 Despite this, access and use persists through informal markets highlighting enforcement gaps and the need for public risk awareness. Major research gaps were identified, including a lack of prevalence data and adequately powered long-term randomized clinical trials evaluating efficacy, dosing and safety. Data is particularly limited in individuals of darker skin phototypes, pregnancy or with comorbidities such as diabetes. Psychosocial drivers and perspectives among patients and aesthetic providers are also underexplored. Study limitations include restriction to English-language publications and heterogeneous data with small sample sizes, variable methodology and short follow-up periods, which may limit generalizability. In summary, current evidence indicates that systemic glutathione offers very limited dermatological benefit. Intravenous use is associated with significant safety risks and should not be recommended, while oral formulations, although relatively safer, lack robust efficacy and long-term safety data. Importantly, their effects are non-selective and are not confined to hyperpigmented areas, thereby negating their appropriateness for managing hyperpigmentation. Accordingly, the authors do not support the use of systemic glutathione for this indication and discourage the cosmetic depigmentation of healthy skin. Clinicians should prioritize safer, evidence-based alternatives for managing hyperpigmentation, such as targeted topical therapies and counsel patients on the limited safety and efficacy data supporting systemic glutathione use in this context.10 There is an urgent need for well-designed, adequately powered randomized controlled trials inclusive of all skin phototypes and stronger regulatory oversight to ensure. Studies on the psychosocial motivations for systemic glutathione use, the promotion of evidence-based dermatological care for hyperpigmentation and public health strategies addressing the sociocultural influences of cosmetic skin lightening among affected populations are also crucial. The authors have nothing to report. The authors declare no conflicts of interest. Not applicable. Not applicable. The data that support the findings of this study are available from the corresponding author upon reasonable request.