BACKGROUND: Age- and disease-related muscle deterioration is driven by oxidative stress, chronic inflammation, mitochondrial dysfunction, and impaired regeneration. N-acetylcysteine (NAC), a glutathione precursor, may modulate these pathways, but evidence is mainly preclinical. METHODS: This systematic review followed PRISMA 2020 guidelines. PubMed, Scopus, Embase, Web of Science, and the Cochrane Library were searched (January 2000-January 2024) for in vivo or human studies evaluating NAC, alone or combined, on muscle-related outcomes. Eligible studies reported muscle mass, morphology, function, or biomarkers of oxidative, inflammatory, or apoptotic stress. Risk of bias was assessed using SYRCLE, RoB 2.0, or the Newcastle-Ottawa Scale. RESULTS AND DISCUSSION: Eight studies were included (seven in vivo, one with human data). Animal models received NAC dosages ranging from 500 mg/kg (i.p.) to 1-2% in drinking water, while the human trial utilized 1800 mg/day for 7 days. NAC significantly improved maximum force generation at 7 and 14 days post-injury, preserved tetanic force, and reduced oxidative stress markers (e.g., lipid peroxidation) and inflammatory cytokines like IL-1β and IL-6. Human data were limited to acute fatigue recovery. Evidence was limited by heterogeneity in dosing and study design. Human data were scarce and restricted to acute fatigue recovery. CONCLUSION: NAC shows potential in modulating mechanisms of muscle deterioration, but evidence remains largely preclinical. Well-designed randomized trials in older adults, particularly with sarcopenia or frailty, are needed.
Mazzola et al. (Fri,) studied this question.