Repurposing landscape of N-acetylcysteine: A scoping review of reviews toward clinical translation

Background: Growing interest in drug repurposing and oxidative stress has heightened attention on N‑acetylcysteine (NAC). Despite the abundance of reviews across diverse clinical domains, clinical translation remains limited. This review seeks to map the existing evidence, identify critical gaps, and outline priorities for future research. Methods: Five databases were systematically searched to identify relevant reviews based on predetermined inclusion and exclusion criteria. Comprehensive data extraction enabled meaningful evidence mapping. To enhance rigor, critical appraisal was conducted using two validated tools assessing methodological quality and risk of bias, thereby allowing stratification of evidence. Additionally, the corrected covered area (CCA) was calculated to detect potential evidence inflation or redundancy. Results: Among the 140 retrieved reviews spanning 17 clinical domains, only 63 were systematic reviews with meta‑analysis, representing the highest level of evidence included in this study. Approximately half of these supported NAC repurposing. Beyond its antioxidant, anti‑inflammatory, and glutamatergic modulatory roles, which were most frequently reported, several additional mechanisms have been proposed. The number of NAC reviews has increased over time, with most originating from China and the United States. Appraisals revealed a high prevalence of critically low‑quality systematic reviews, alongside a notable proportion of reviews with low risk of bias. Finally, CCA analysis demonstrated substantial overlap and redundancy across domains, particularly within subdomains. Conclusion: This novel overview mapped the extensive NAC evidence landscape, highlighting its pleiotropic roles and repurposing potential while revealing possible research waste and critical gaps across domains and evidence levels. Psychiatry, reproductive medicine, nephrology, pulmonology, and toxicology emerged as priority clinical domains for future exploration. However, the overall inconsistency in review certainty remains a barrier to the integration of NAC into clinical guidelines. By delineating research priorities and highlighting new avenues, this review underscores the need for precision medicine approaches to guide future NAC clinical implementation and research.