Ergothioneine as a functional nutraceutical: Mechanisms, bioavailability, and therapeutic implications

Ergothioneine (EGT), a naturally occurring sulfur-containing antioxidant, has gained significant attention owing to its potent cytoprotective, anti-inflammatory, and neuroprotective properties. As a dietary-derived compound predominantly found in mushrooms, EGT exhibits remarkable stability and bioavailability, facilitated by a specific ergothioneine transporter that is highly expressed in mammalian tissues. Its ability to scavenge reactive oxygen and nitrogen species effectively mitigates oxidative stress, which is a key factor in the pathogenesis of various chronic diseases, including cardiovascular disorders, neurodegenerative conditions, and cancer. Emerging evidence has highlighted the role of EGT in modulating key signaling pathways involved in inflammation, apoptosis, and cellular homeostasis, suggesting its potential as a therapeutic agent. Clinical and preclinical studies have indicated its involvement in metabolic regulation, endothelial protection, and attenuation of neurodegeneration, further reinforcing its significance as a functional nutraceutical agent. This review provides a comprehensive analysis of EGT, including its biosynthesis, dietary sources, absorption mechanisms, and metabolism, and elucidates its therapeutic potential and mechanistic underpinnings for disease prevention and management. By summarizing recent advances in EGT research, this review aims to guide future investigations and support its broader application in clinical and nutritional sciences.