N-acetylcysteine increases total glutathione levels in experimental models of heart diseases: a systematic review and meta-analysis

Background : Cardiovascular diseases (CVD) are the leading cause of death globally. Oxidative stress plays a significant role in cell damage, inflammation, and progression of CVD. The use of N-acetylcysteine (NAC), a well-known antioxidant and a precursor to glutathione (GSH), has shown potential in preventing different types of CVD. Yet, there is limited data assessing NAC’s impact on GSH levels in animal models of CVD. Objective : To evaluate reduced glutathione (GSH) and total glutathione levels in cardiac tissue or serum/plasma from animals with established heart disease treated with NAC. Method: The literature search included PubMed, Embase, WoS, Scielo, Lilacs/BINACIS, and rXiv databases. The search in the databases was completed in December 2022. Results : We identified 619 articles, fully reviewed 35, and included 7 in the meta-analysis. The included studies varied in cardiovascular disease models, NAC doses, and outcomes. Meta-analysis revealed that NAC supplementation significantly increased total glutathione levels (SMD = 1.23, 95% CI = 0.56–1.89; p = 0.0003) with low heterogeneity ( I² = 37%). GSH levels showed a marginal increase (SMD = 2.49, 95% CI = -0.20–5.18; p = 0.07), with high heterogeneity ( I² = 93%). Conclusion : NAC supplementation effectively increases total glutathione in animal models of heart disease. The impact on GSH levels was less clear, possibly due to dose variability and limited study numbers. Standardization of NAC dosing and improved methodological reporting are needed for more consistent and clinically relevant findings.