Written by: dr. Raheemiyya Noor Fajrani
Supervised by: dr. Fatima Aulia Khairani, Sp.DV
Skin color plays a significant role in daily life, particularly for women, as it can enhance their attractiveness. Its sociopsychological impact often outweighs its biological function, sometimes leading to cosmetic concerns that affect both quality of life and self-esteem.
As a result, today, skin-whitening agents—whether topical, oral, or intravenous—are widely accessible in the market. One such agent is glutathione, an antioxidant commonly present in the human body and used in the cosmetic industry for skin-lightening purposes.
What exactly is glutathione?
Reduced glutathione (GSH) is a low-molecular-weight, water-soluble tripeptide, composed of the amino acids cysteine, glutamic acid, and glycine. It is one of the most active antioxidant systems in the human body, playing a crucial role in maintaining overall health.
Glutathione is involved in various biological functions, with the most important ones listed in the box below:
Reduced glutathione (GSH) has a range of systemic benefits, including improving liver function, addressing diabetic complications, offering protection against viral infections, and exhibiting antitumor properties.
Additionally, glutathione is known to stimulate pheomelanin production, inhibit melanogenic enzymes within cells, and provide antioxidative and anti-aging effects.
How does glutathione work as a skin-lightening agent?
Melanin, the pigment responsible for skin color, is made up of two types: blackish-brown eumelanin and reddish-yellow pheomelanin. A higher proportion of pheomelanin tends to make the skin appear brighter. Hyperpigmentation occurs when the skin is exposed to ultraviolet radiation, leading to the production of reactive oxygen and nitrogen species in the cells. Oral antioxidants help reduce melanogenesis by neutralizing these free radicals.
The discovery of glutathione’s role as a skin-lightening agent was accidental, as it was observed that skin lightening occurred as a side effect of large doses of glutathione. Several mechanisms have been suggested to explain its hypopigmentary effect, with the inhibition of tyrosinase being the most significant.
Administration of Glutathione
Natural dietary sources
Natural dietary sources of glutathione include fresh fruits, vegetables, and nuts. Some of the most common foods that can help boost glutathione levels in the body are tomatoes, avocados, oranges, walnuts, and asparagus.
Pharmaceutical formulations
The three major routes of administration used for skin lightening are topical (creams, face washes), oral (capsules and sublingual/buccal tablets) and intravenous injections.
Topical glutathione
Topical glutathione is available in various forms, such as face washes, creams, and soaps. Studies have shown that using glutathione significantly reduces the melanin index compared to a placebo, with noticeable improvements in other skin parameters as well. No adverse drug effects have been reported. Recently, a glutathione-based chemical peel has also been introduced, although there is limited evidence supporting its effectiveness. The manufacturers claim that it helps improve conditions like melasma, hyperpigmentation, and signs of skin aging.
Oral glutathione
Oral glutathione is made from torula yeast (Candida utilis) and is sold as a dietary supplement, either alone or combined with vitamin C, alpha-lipoic acid, and other antioxidants. In a study, participants were given either 500 mg of glutathione daily in two doses or a placebo for four weeks. The main goal was to see if melanin levels decreased at six different spots on the skin. After four weeks, the glutathione group showed a consistent reduction in melanin levels across all six sites, while the placebo group only showed a significant decrease on the right side of the face and the left forearm. Glutathione was well-tolerated. The study had some limitations, but despite them, it was the first to show that oral glutathione can help lighten skin.
Oral glutathione supplements have been recognized as “Generally recognized as safe” by the U.S. Food and Drug Administration.
Intravenous glutathione
Intravenous (IV) glutathione is promoted as a more effective method for achieving therapeutic levels of glutathione in the blood and skin, offering faster skin-lightening results. While IV treatment provides a stronger dose, it also comes with a higher risk of overdose and toxicity. Furthermore, the use of IV glutathione is still controversial, as there is no safety profile and in existing studies with a limited number of subjects, side effects are known to range from mild to potentially life-threatening.
The Philippines Food and Drug Administration has issued a warning about the safety risks of using IV glutathione injections off-label for skin lightening, noting reported adverse reactions.
Glutathione mesotherapy
Glutathione mesotherapy, although lacking published research on its efficacy and methodology, is commonly practiced by dermatologists to treat melasma and other facial melanoses. It is used either as a standalone treatment or in combination with substances like ascorbic acid, vitamin E, and tranexamic acid. While the results are reported to be highly positive, more evidence and published data are needed to fully support the use of glutathione in mesotherapy.
In conclusion, there is currently insufficient strong evidence to support the use of glutathione for treating hyperpigmentation. While its mechanism of action suggests it could be effective as a skin-lightening agent, only three randomized controlled trials have been conducted, and these had short follow-up periods. These studies show some skin-lightening effects of both topical and oral glutathione, but it isn’t consistently effective, as it only worked in certain areas. Additionally, once glutathione use is stopped, skin color tends to return to its original state, meaning long-term effects are not sustainable. The safety of topical and oral glutathione appears to be reasonable, but there is no evidence to support the use of intravenous glutathione, which also carries potential risks and complications.
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