TABLE 1.

Evidence of Glutathione as a Skin Lightening Agent: Current Summary of Studies Conducted to Date

Glutathione Formulation	Topical (GSSG cream)	Oral (Capsules)	Oral / Buccal Lozenges	Intravenous
Authors	Watanabe et al. [12]	Arjinpathana & Asawanonda [10]	Handog et al. [11]	Zubair et al. [15]
Study subjects	30 healthy Filipino women Ages: 30–50 years	60 healthy medical students Ages: 19–22 years	30 healthy women Ages: 22–42 years Fitzpatrick skin types IV or V	50 healthy Pakistani women Ages: 25–47 years Skin type not mentioned
Study design	Randomized, double-blind, placebo-controlled, Split-face study	Randomized, double-blind, placebo-controlled study	Open-label, single-arm, pilot study	Open-label, placebo-controlled study
Methodology	Split-face study; application of 2% (w/w) GSSG lotion and placebo lotion, twice daily for 10 weeks	Oral glutathione (500 mg) or placebo capsules daily, in 2 divided doses on an empty stomach for 4 weeks	One buccal lozenge (500 mg) per day, for 8 weeks.	Injection glutathione 1200 mg or normal saline (placebo) injected over 30 minutes
Frequency of evaluation	Baseline; weekly for 10 weeks	Baseline; and at 4 weeks	Baseline, twice weekly for 8 weeks	Baseline, twice weekly for 8 weeks
Primary outcome	Melanin index—by Mexameter MX18	Melanin index—by Mexameter	Melanin index—by Mexameter	Visual Taylor hyperpigmentation scale
Subjective parameters	Global evaluation on a 7-point rating scale	Global evaluation s on a 4-point rating scale	Global evaluation on a 5-point rating scale	None
Results	Melanin index Melanin index reduction significant in GSSG group vs. placebo Other parameters such as skin moisture, curvature index, keratin index also improved in the GSSG group	Melanin index Melanin index reduction significant at all six sites in oral GSH group vs. placebo	Melanin index Melanin index reduction significant at all sites in buccal GSH group vs. placebo Global Assessment: 27 subjects (90%) noted moderate skin lightening	Taylor scale Improvement (IV GSH vs placebo): Completion of 12 injections—37.5% vs. 18.7% After 2 months: 18.7% vs. 12.5% After 4 months: 18.7% vs, 0% After 6 months: 6.2% vs. 0%
Tolerance & Safety	Very well tolerated No significant adverse effects in either group	Very well tolerated No significant adverse effects in either group	Very well tolerated No significant adverse effects in either group	Adverse effects in all GSH treated patients Serious—Liver dysfunction in 32% (8) patients and anaphylactic shock in 1 patient.
Follow-up After Completion of Study	None	None	None	Done on 3 occasions—2nd, 4th, 6th month after treatment completion
Study Limitations	Small sample size Short duration of study Subjects: Healthy Filipino women No post-study follow up	Small sample size Short duration of study Subjects: Healthy young adults No post-study follow up Serum GSH levels not measured	Small sample size Short duration of study Subjects: Healthy women No post-study follow up Serum GSH levels not measured.	Small sample size Poor study design No mention of statistical analysis Only two sites evaluated Unreliable method of efficacy evaluation No information on baseline bio-chemical parameters No details on hepatic adverse effects, nature, severity and recovery Serum GSH levels not measured

^*Modified from Table 1 published in: Sonthalia S, Daulatabad D, Sarkar R. Glutathione as a skin whitening agent: facts, myths, evidence and controversies. Indian J Dermatol Venereol Leprol. 2016;82:262.