Glutathione and N-acetylcysteine in athletes: redox regulation and performance

Abstract

Exercise-derived reactive oxygen species contribute to both cellular stress and training adaptation, creating uncertainty regarding the potential value of thiol-based antioxidant strategies in physically active populations. This structured narrative review critically evaluated human studies of glutathione (GSH)-containing interventions and N-acetylcysteine (NAC) in athletes and physically active adults. GSH and NAC were treated as related but distinct thiol-containing compounds, with NAC considered a cysteine donor rather than a surrogate for GSH. PubMed, Scopus, and Web of Science Core Collection were searched through 7 September 2026. For evidence synthesis, exercise/performance outcomes were prioritized as primary, whereas recovery, perceptual, physiological, biochemical, and molecular outcomes were treated as secondary or mechanistic. Direct exercise/performance evidence for GSH-containing interventions was sparse and inconsistent. One small elite-swimmer report favored GSH, whereas a GSH-L-citrulline trial found no significant improvement in time to exhaustion and several other studies did not include a direct performance endpoint. NAC evidence was broader but mixed across oral and intravenous routes. Secondary biochemical, physiological, and perceptual changes did not consistently align with functional benefit. Current evidence does not support routine use of oral GSH or NAC as a general ergogenic strategy. NAC findings are route- and context-dependent and cannot be considered surrogate evidence for oral GSH. Adequately powered, preregistered trials using clearly defined formulations, prespecified performance endpoints, and transparent safety reporting are needed.