The effects of the oral supplementation of L‐Cystine associated with reduced L‐Glutathione‐GSH on human skin pigmentation: a randomized, double‐blinded, benchmark‐ and placebo‐controlled clinical trial

Abstract

Background: Glutathione has become a potential skin-lightening ingredient after the discovery of its anti-melanogenic properties. Various mechanisms of action have been considered to explain this property, one of them being the skewing of the melanin synthesis pathway toward the production of lighter pheomelanin instead of darker eumelanin, consequently producing a lightening effect. Aims:To evaluate the skin lightening and anti-dark spot effects of oral supplementation with L-Cystine associated with L-Glutathione as compared to placebo and benchmark.Methods: Effects of this L-Cystine-L-Glutathione oral combination were investigated in a 12-week randomized, double-blind, parallel-group, benchmark-and placebocontrolled trial involving 124 Asian female subjects. Women were randomly allocated into 4 equal groups (500 mg L-Cystine and 250 mg L-Glutathione, 250 mg reduced L-Glutathione, 500 mg L-Cystine, or a placebo, daily). Skin color was measured at baseline, after 6 and 12 weeks by spectrophotometry. Size and color of facial dark spots were determined from digital photographs.Results: A significant skin lightening was observed after 12 weeks of oral supplementation with L-Cystine associated with L-Glutathione. This combination also induced a significant reduction in the size of facial dark spots after 6 and 12 weeks. It is noteworthy that the observed effects were not only significantly better than those obtained with placebo, but also with L-Cystine alone or L-Glutathione alone. Conclusion:The daily oral administration of 500 mg L-Cystine and 250 mg L-Glutathione during 12 weeks was a safe treatment to effectively lighten the skin and reduce the size of facial dark spots of Asian women.

Improved pharmacodynamics of epidermal growth factor via microneedles-based self-powered transcutaneous electrical stimulation

“…Reduced GSH (M w ≈ 307.33), a highly active antioxidant, is widely distributed in the skin tissue fluid with the concentration of 2~20 μM 49 , 50 . GSH could reduce EGF by opening the disulfide bond, rendering it inactive 51 , 52 .…”

Medical therapies for melasma

“…Wahab et al 128 in a double‐blind randomized controlled study involving 46 subjects found glutathione an effective skin‐lightening agent and a combination of topical and oral glutathione was superior than either route used alone. Another randomized, double‐blind, placebo‐controlled clinical trial comprising 124 Asian females demonstrated significant skin‐lightening and reduction in size of facial pigmentation after oral supplementation with combination of l‐cystine and l‐glutathione 129 . While benefits of skin lightening with 500 mg/d orally administered glutathione given for 4 weeks were limited to certain age groups and body areas in 60 healthy Asian subjects, no significant improvement occurred in 16 patients receiving glutathione and any improvement seen in two separate randomized controlled trials was short lasting 130–132 …”

“…The results of its efficacy to treat melasma remain variable 128–131 . Wahab et al 128 in a double‐blind randomized controlled study involving 46 subjects found glutathione an effective skin‐lightening agent and a combination of topical and oral glutathione was superior than either route used alone.…”

“…in a double-blind randomized controlled study involving 46 subjects found glutathione an effective skin-lightening agent and a combination of topical and oral glutathione was superior than either route used alone. Another randomized, doubleblind, placebo-controlled clinical trial comprising 124 Asian females demonstrated significant skin-lightening and reduction in size of facial pigmentation after oral supplementation with combination of l-cystine and l-glutathione 129. While benefits of skin lightening with 500 mg/d orally administered glutathione given for 4 weeks were limited to certain age groups and body areas in 60 healthy Asian subjects, no significant improvement occurred in 16 patients receiving glutathione and any improvement seen in two separate randomized controlled trials was short lasting.130-Cosmeceuticals and botanicalsTable 643,133-170 lists some naturally occurring depigmenting agents and flavonoids such as vitamin C, vitamin E, rucinol, glucosamine, niacinamide, extracts of soybean (soy), safflower (linoleic acid), licorice, mulberry and grapes (hydroxylstilbene compound resveratrol), coffee berry, orchid, green tea leaves (epigallocatechin-3-gallate), eucalyptus and strawberry (ellagic acid), Silybum marianum (sylimarin), Pinus pinaster (pycnogenol) Boswellia serrata (boswellic acids), citrus fruits (bioflavonoid hesperidin), grape seed, aloe (aloesin), sunflower seed (octadecenedioic acid), ginseng, and plants of Apiaceae family such as carrot and coriander (umbelliferone).…”

The effect of diet on melanin pigmentation in animals

“…Stress leads to high levels of haemolymph dopamine, an intermediate compound in the melanization pathway (Box 1). The antioxidant glutathione (GSH), can influence pigmentation by shifting production from eumelanin to pheomelanin (Box 1), which can change the colour and darkness of skin (Duperray et al, 2022).…”