Topical Oxidized Glutathione for Skin-Whitening: Efficacy and Safety

Glutathione is an endogenous tripeptide antioxidant composed of cysteine, glycine and glutamic acid. It exists in two forms: reduced glutathione (GSH) and oxidized glutathione (GSSG). Although GSH is a proven skin-lightening agent, its poor stability in aqueous media makes topical formulation difficult. GSSG, in contrast, is markedly more stable and therefore better suited for cutaneous application, positioning it as an ideal candidate for localized skin whitening.

Randomized controlled trial

Thirty healthy women aged 30–50 years were enrolled in a split-face, randomized, placebo-controlled study. One side of each subject’s face received a 2 % (w/w) GSSG emulsion, while the contralateral side received an identical vehicle without GSSG. Applications were performed twice daily for 10 weeks. Efficacy was evaluated with objective instrumental measurements and subjective assessments.

Significant whitening effect

GSSG produced a rapid and sustained reduction in cutaneous melanin. Melanin index fell from a baseline of 272.77 to 243.47 after 10 weeks (P < 0.001 versus placebo). This objective lightening was corroborated by subjective ratings: 76.7 % of participants and 66.7 % of investigators reported visible whitening on the GSSG-treated side at week 10.

Global skin-quality improvement

Beyond depigmentation, GSSG enhanced overall skin condition. Stratum-corneum hydration rose significantly during the second half of the study, with moisture indices on weeks 8–9 exceeding those of the placebo side. Periorbital wrinkle formation was inhibited and skin smoothness improved; corneocyte desquamation indices remained lower on the GSSG side from week 6 onward, demonstrating a dual “whitening + skin-care” benefit.

Safety profile

No clinically relevant adverse reactions attributable to GSSG were observed.

One subject developed mild erythema that resolved spontaneously within 4 days, confirming good cutaneous tolerance in healthy female volunteers.Mechanistically, GSSG is thought to be reduced to GSH by cutaneous glutathione reductase;

the regenerated GSH then inhibits tyrosinase activity and modulates melanogenesis.

Because GSSG is an endogenous metabolite, its biocompatibility exceeds that of many traditional whitening agents, while its superior chemical stability facilitates reliable topical delivery.

This trial establishes that a 2 % GSSG emulsion is a safe and effective topical regimen that significantly lowers melanin content while simultaneously improving hydration and smoothness.

For consumers seeking gentle yet measurable lightening, oxidized glutathione offers a novel, physiologically based approach to topical skin-brightening and opens new avenues for cosmetic ingredient development.

Reference

Watanabe F, Hashizume E, Chan G P, et al. Skin-whitening and skin-condition-improving effects of topical oxidized glutathione: a double-blind and placebo-controlled clinical trial in healthy women. Clin Cosmet Investig Dermatol. 2014;7:267-274.

*Special note - This article is for informational purposes only and cannot replace a doctor's treatment diagnosis and advice. It should not be regarded as a recommendation or proof of efficacy of the medical products involved. If it involves disease diagnosis, treatment, and rehabilitation, please be sure to go to a professional medical institution to seek professional advice.

by GSHWORLD

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