Why do we need Glutathione for skin?

The recent hype surrounding glutathione’s anti-melanogenic properties has led to it being often prescribed by doctors as a “miracle” drug for skin lightening and treating hyperpigmentation, especially in darker-skinned ethnic groups. This phenomenon has recently seen an increase due to aggressive marketing and capitalization by pharmaceutical and cosmetic companies. However, its unrestricted and indiscriminate use, especially as a parenteral formulation, does not seem to be justified due to our lack of knowledge on antimelanogenic potential, limited clinical evidence favoring its role in skin reduction, and legal prohibition/recommendation issued by some federal. agencies. Although parenteral glutathione is approved only for severe liver disease and for the prevention of chemotherapy-related neurotoxicity, the lack of laws regulating the use of systemic glutathione in most countries contributes to its uncontrolled use for skin lightening. Current clinical evidence for intravenous glutathione for skin lightening is limited to one study with questionable study design and apparently flawed analysis of the results, which questioned the effectiveness of the drug and reported no good effects. Two studies evaluating oral/sublingual administration and one study using topical glutathione reported a good safety profile and significant but reversible results in skin tone. In this article, we will review and discuss the current status of glutathione as a skin lightening agent and address several unanswered questions regarding dosage, duration of use, and longevity of cumulative effects based on clinical evidence and new insights into its antimelanogenic mechanism.

The preoccupation with exploration of treatment options that may help attain a lighter skin tone or fairer complexion has been an ongoing phenomenon in people with skin of color (SOC). The direct implication of this craze is the exploitation of topical agents originally developed for treatment of hyperpigmentation, such as skin lightening therapies. Topicals containing hydroquinone, alpha and beta hydroxy acids, tretinoin, mequinol, arbutin, vitamin C, soy extracts and concoctions of multiple ingredients, including newer cosmeceuticals, are now in vogue for treatment of facial melanoses especially melasma and for general skin lightening, at least of the face, neck and other exposed parts. The local adverse effects of these agents and the quantity required for large surface area application constitute major limitations of this approach. Understandably, the effect of such locally applied topicals remains limited to the application site alone without any notable systemic skin lightening effect. The quest for a systemic skin-whitening agent ensues. Oral antioxidants, such as vitamin C, vitamin E, tranexamic acid, flavonoids, and various botanical extracts have been tried in melasma and disorders of hyperpigmentation, but none has proven to provide an overall skin lightening effect .

Glutathione, being a strong antioxidant with additional anti-melanogenic properties, has recently become the most popular “systemic skin lightening molecule.” The most “popular” and controversial route of administration of glutathione for skin lightening has been intravenous (IV).