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Study summary · research use only

Glutathione in Skin Aging and Tissue Regeneration: A Systematic Review of Molecular Mechanisms, Redox Modulation, and Biomedical Implications

Systematic review · human · Molecules (Basel, Switzerland) · 2026 · DOI 10.3390/molecules31060981 · PMID 41900080

Plain-language summary

Paraphrased from the published abstract below — not a verdict on whether anything works.

This systematic review, following PRISMA guidelines, evaluated 194 studies published between 2000 and 2025 on glutathione's molecular, clinical, and translational role in skin pigmentation, brightening, and tissue regeneration. The abstract reports that topical and oral glutathione showed associations with pigmentation, skin brightness, hydration, and oxidative stress markers, while injectable glutathione raised systemic levels rapidly but was linked to short-lasting effects and potential safety concerns. It describes glutathione's biochemical roles, including conjugation to electrophilic xenobiotics via glutathione S-transferases, reduction of hydrogen peroxide and lipid hydroperoxides by glutathione peroxidase, regeneration of vitamins C and E through redox cycling, and associations between reduced glutathione levels and neuronal dysfunction. The authors call for randomized controlled trials, standardized formulations, and long-term safety assessments.

Abstract

Glutathione (GSH) is a central regulator of redox homeostasis, melanogenesis, and cellular repair, and has gained increasing attention in dermatology for its potential roles in skin brightening, anti-aging, and tissue regeneration. This systematic review evaluated molecular, clinical, and translational evidence of glutathione's applications and safety across different delivery modalities. The review followed PRISMA guidelines and included studies published between 2000 and 2025. A total of 194 studies met the inclusion criteria, evaluating the effectiveness of glutathione in esthetic dermatology and regenerative medicine. Topical and oral glutathione demonstrated favorable effects on pigmentation, skin brightness, hydration, and oxidative stress markers. Injectable glutathione increases systemic levels rapidly, but is associated with short-lasting effects and potential safety concerns. Glutathione S-transferases facilitate the conjugation of glutathione to electrophilic xenobiotics, thereby protecting proteins and nucleic acids from electrophile-induced damage. Glutathione Peroxidase employs GSH as an electron donor to reduce hydrogen peroxide and lipid hydroperoxides, thus protecting membrane lipids, mitochondrial membranes, and DNA from oxidative damage. Glutathione facilitates the regeneration of other antioxidants, such as vitamin C and vitamin E, through redox cycling. A consistent correlation exists between reduced GSH levels and neuronal dysfunction. Elevated GSH levels enhance cellular resistance to oxidative stress and reduce apoptotic signaling. GSH plays a pivotal role in cutaneous aging and tissue repair through redox regulation, mitochondrial protection, and the modulation of inflammatory and extracellular matrix pathways. To elucidate the clinical significance of glutathione, future research should focus on conducting randomized controlled trials, developing standardized formulations, and performing long-term safety assessments.

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