The ergothioneine enigma: Navigating the chasm between anti-aging hype and clinical validation

Ergothioneine (EGT) has garnered widespread attention due to its purported antioxidant and anti-aging effects, even sparking considerable debate. However, its clinical translation remains hindered by insufficient and fragmented evidence. This article focuses on EGT’s newly identified molecular targets—MPST and CSE—and the indirect regulatory mechanisms mediated by hydrogen sulfide (H₂S), thereby exploring key challenges in its clinical application. We highlight major issues in pharmacokinetics, formulation development, and long-term safety, and advocate for interdisciplinary efforts and target-driven clinical evaluation strategies to advance EGT from a cosmetic additive and dietary supplement to a mechanism-based therapeutic agent with a solid scientific foundation.