Glutathione for Skin Whitening
Glutathione should not be used for skin whitening due to lack of efficacy evidence, absence of long-term safety data, and significant concerns about increased skin cancer risk from melanin switching. 1
Critical Safety Concerns
The most concerning issue is the complete absence of long-term cancer surveillance data for chronic glutathione use. 1 This is particularly problematic because:
- Glutathione switches melanin production from protective brown eumelanin to red phaeomelanin, which may increase sun-induced skin cancer risk in previously protected individuals with darker skin tones 1
- Patients using glutathione require counseling about dramatically increased photoprotection needs due to this melanin switching mechanism 1
- The British Journal of Dermatology guidelines do not support glutathione use for cosmetic purposes, highlighting the lack of high-quality evidence 1
Efficacy Evidence by Route of Administration
Intravenous Glutathione
Intravenous glutathione is contraindicated for skin lightening due to lack of efficacy and side effects. 2 The evidence base consists of only one placebo-controlled study showing minimal benefit [6/16 (37.5%) vs. 3 (18.7%), p=0.054] 2, and the FDA of Philippines has issued a public warning condemning its use for off-label indications like skin lightening 3
Oral Glutathione
- Five randomized controlled trials showed significant melanin index reduction at doses of 250 mg once daily, 250 mg twice daily, and 500 mg once daily compared to placebo 2
- However, effects are unsustainable and reversible after treatment cessation 4, 5
- The evidence comes from small trials with high risk of bias 2
Topical Glutathione
- Glutathione 0.5% was significantly more effective than 0.1% and placebo 2
- Combination of topical 2% glutathione plus oral glutathione was superior to monotherapy 2
- Effects are localized and reversible 2
Key Unanswered Questions
The current evidence fails to address critical clinical parameters 3, 5:
- Optimal duration of treatment
- Longevity of skin-lightening effect
- Maintenance protocols
- Long-term safety profile beyond melanoma risk
Clinical Recommendation
Do not prescribe glutathione for skin whitening. The combination of absent long-term safety data, cancer risk from melanin switching, lack of guideline support, and only modest, reversible efficacy makes this an inappropriate intervention 1, 2. If patients insist despite counseling, oral formulations have better safety profiles than intravenous, but the fundamental recommendation remains against use 4, 2.