Dr. Ron’s Research Review – March 9, 2016

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This week’s research review focuses on skin-whitening with glutathione.

Proposed mechanisms of action include on melanin synthesis include:  (Villarama and Maibach, 2005)
(a) direct inactivation of the enzyme tyrosinase by binding with the copper-containing active site of the enzyme;
(b) mediating the switch mechanism from eumelanin to phaeomelanin production;
(c) quenching of free radicals and peroxides that contribute to tyrosinase activation and melanin formation; and
d) modulation of depigmenting abilities of melanocytotoxic agents.

Oral glutathione (500 mg/day day in two divided doses for 4 weeks or placebo) was administered in a study of sixty participants. At 4 weeks, the melanin indices decreased consistently at all six sites in subjects who received glutathione. The reductions were statistically significantly greater than those receiving placebo at two sites, namely the right side of the face and the sun-exposed left forearm (p-values = 0.021 and 0.036, respectively). This was similarly reflected in the changes in the number of UV spots, as measured by VISIA. (Arjinpathana and Asawanonda, 2012)
Substances that are absorbed through the buccal route go directly into the systemic circulation, effectively bypassing the gastrointestinal tract. Thirty Filipino females with Fitzpatrick skin types IV or V received a glutathione-containing lozenge (500 mg) daily for eight weeks.  Findings showed a significant decrease in melanin indices from baseline to endpoint that became evident in as little as two weeks. (Handog et al., 2016)
A randomized, double-blind, matched-pair, placebo-controlled clinical trial included 30 healthy adult women aged 30 to 50 years. Subjects applied GSSG 2% (weight/weight [w/w]) lotion to one side of the face and a placebo lotion to the other side twice daily for 10 weeks. The skin melanin index was significantly lower with GSSG treatment than with placebo from the early weeks after the start of the trial through to the end of the study period (at 10 weeks, P<0.001). In addition, in the latter half of the study period GSSG-treated sites had significant increases in moisture content of the stratum corneum, suppression of wrinkle formation, and improvement in skin smoothness. There were no marked adverse effects from GSSG application. (Watanabe et al., 2014)

Dr. Ron


 

Articles

Glutathione as an oral whitening agent: a randomized, double-blind, placebo-controlled study.
            (Arjinpathana and Asawanonda, 2012) Download
OBJECTIVE:  To determine whether orally administered glutathione, 500 mg per day for 4 weeks, affects the skin melanin index, when compared with placebo. METHODS:  This randomized, double-blind, two-arm, placebo-controlled study was set in the King Chulalongkorn Memorial Hospital, Bangkok, Thailand, a teaching hospital affiliated with a medical school. Sixty otherwise healthy medical students were randomized to receive either glutathione capsules, 500 mg/day in two divided doses, or placebo for 4 weeks. The main outcome was mean reduction of melanin indices measured at six different sites. Several secondary outcomes, including UV spots, were recorded by VISIA™. Efficacies of glutathione and placebo were compared by ANCOVA with baseline values as co-variates. RESULTS:  Sixty participants enrolled and completed the study. At 4 weeks, the melanin indices decreased consistently at all six sites in subjects who received glutathione. The reductions were statistically significantly greater than those receiving placebo at two sites, namely the right side of the face and the sun-exposed left forearm (p-values = 0.021 and 0.036, respectively). This was similarly reflected in the changes in the number of UV spots, as measured by VISIA. Both glutathione and placebo were very well tolerated. CONCLUSION:  Oral glutathione administration results in a lightening of skin color in a small number of subjects. However, long-term safety has not been established and warrants more extensive clinical trials.

 

An open-label, single-arm trial of the safety and efficacy of a novel preparation of glutathione as a skin-lightening agent in Filipino women.
            (Handog et al., 2016) Download
BACKGROUND:  Glutathione (GSH) is a naturally occurring thiol that has been reported to cause skin lightening in a manner for which several mechanisms have been proposed. Highest plasma concentrations are achieved with IV administration but are accompanied by greater levels of risk. Oral administration has been less successful in elevating plasma GSH levels. OBJECTIVES:  The use of a lozenge containing GSH was investigated in order to evaluate the buccal mucosa as a route for GSH administration. Substances that are absorbed through the buccal route go directly into the systemic circulation, effectively bypassing the gastrointestinal tract. METHODS:  Thirty Filipino females with Fitzpatrick skin types IV or V received a glutathione-containing lozenge daily for eight weeks. RESULTS:  Findings showed a significant decrease in melanin indices from baseline to endpoint that became evident in as little as two weeks. There were no serious adverse events, and laboratory examination findings remained normal. CONCLUSIONS:  The authors conclude that the lozenge containing glutathione was safe and effective in lightening the skin of Filipino women.

Glutathione as a depigmenting agent: an overview.
            (Villarama and Maibach, 2005) Download
Glutathione is an ubiquitous compound found in our bodies. Aside from its many ascribed biologic functions, it has also been implicated in skin lightening. We review in vitro and in vivo studies that show evidence of its involvement in the melanogenic pathway and shed light on the its anti-melanogenic effect. Proposed mechanisms of action include: (a) direct inactivation of the enzyme tyrosinase by binding with the copper-containing active site of the enzyme; (b) mediating the switch mechanism from eumelanin to phaeomelanin production; (c) quenching of free radicals and peroxides that contribute to tyrosinase activation and melanin formation; and d) modulation of depigmenting abilities of melanocytotoxic agents. These concepts supported by the various experimental evidence presented form basis for future research in the use of glutathione in the treatment of pigmentary disorders.

 

Skin-whitening and skin-condition-improving effects of topical oxidized glutathione: a double-blind and placebo-controlled clinical trial in healthy women.
            (Watanabe et al., 2014) Download
PURPOSE:  Glutathione is a tripeptide consisting of cysteine, glycine, and glutamate and functions as a major antioxidant. It is synthesized endogenously in humans. Glutathione protects thiol protein groups from oxidation and is involved in cellular detoxification for maintenance of the cell environment. Reduced glutathione (GSH) has a skin-whitening effect in humans through its tyrosinase inhibitory activity, but in the case of oxidized glutathione (GSSG) this effect is unclear. We examined the skin-whitening and skin-condition effects of topical GSSG in healthy women. SUBJECTS AND METHODS:  The subjects were 30 healthy adult women aged 30 to 50 years. The study design was a randomized, double-blind, matched-pair, placebo-controlled clinical trial. Subjects applied GSSG 2% (weight/weight [w/w]) lotion to one side of the face and a placebo lotion to the other side twice daily for 10 weeks. We objectively measured changes in melanin index values, moisture content of the stratum corneum, smoothness, wrinkle formation, and elasticity of the skin. The principal investigator and each subject also used subjective scores to investigate skin whitening, wrinkle reduction, and smoothness. Analysis of variance was used to evaluate differences between groups. RESULTS:  The skin melanin index was significantly lower with GSSG treatment than with placebo from the early weeks after the start of the trial through to the end of the study period (at 10 weeks, P<0.001). In addition, in the latter half of the study period GSSG-treated sites had significant increases in moisture content of the stratum corneum, suppression of wrinkle formation, and improvement in skin smoothness. There were no marked adverse effects from GSSG application. CONCLUSION:  Topical GSSG is safe and effectively whitens the skin and improves skin condition in healthy women.

 

References

Arjinpathana, N and P Asawanonda (2012), ‘Glutathione as an oral whitening agent: a randomized, double-blind, placebo-controlled study.’, J Dermatolog Treat, 23 (2), 97-102. PubMed: 20524875
Handog, EB, MS Datuin, and IA Singzon (2016), ‘An open-label, single-arm trial of the safety and efficacy of a novel preparation of glutathione as a skin-lightening agent in Filipino women.’, Int J Dermatol, 55 (2), 153-57. PubMed: 26148180
Villarama, CD and HI Maibach (2005), ‘Glutathione as a depigmenting agent: an overview.’, Int J Cosmet Sci, 27 (3), 147-53. PubMed: 18492181
Watanabe, F, et al. (2014), ‘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, 7 267-74. PubMed: 25378941