Topical glutathione amino acid precursors protect skin against environmental and oxidative stress

Abstract Background Although glutathione (GSH) has long been considered a master antioxidant, poor stability and bioavailability limit its application in skin protection. To overcome the challenges, Unilever R&D formulated a Glutathione Amino acid Precursors blend (named GAP) to boost GSH de novo synthesis. Objective Determine whether GAP can boost GSH levels and provide skin protection against stressors. Methods Normal human epidermal keratinocytes were treated with GAP, with or without stressors, namely, menadione, blue light or pollutants. Ascorbic acid was used as a benchmark. The levels of GSH, glutathione disulfide (GSSG), adenosine triphosphate (ATP) and reactive oxygen species (ROS) were quantified. A placebo‐controlled clinical study was conducted on 21 female subjects who received product applications and subsequent UV radiation. Tape strip samples were collected from the subjects for GSH and GSSG quantification using ultra‐performance liquid chromatography‐mass spectrometry/mass spectrometry (UPLC‐MS/MS). The UV‐protective effect of GAP was investigated using ex vivo skin. Biomarkers related to DNA damage and the skin barrier were analysed using immunohistochemistry. Results Glutathione amino acid precursors significantly increased the GSH levels and GSH/GSSG ratio in normal human epidermal keratinocytes. Menadione treatment resulted in excessive ROS production and a decline in ATP levels, which were effectively abrogated by GAP. The protective effects of GAP against menadione‐induced oxidative stress were superior to those of ascorbic acid. In addition, GAP effectively protected the cells against blue light‐induced ROS production and pollutant‐induced ATP depletion. Topical application of the GAP formulation significantly elevated the skin GSH/GSSG ratio in a clinical study. Ex vivo skin treated with the GAP formulation displayed a reduction in DNA damage and high levels of barrier proteins after UV exposure. Conclusions Glutathione amino acid precursors effectively increases cellular GSH levels to protect the skin from oxidative and environmental stresses.