Abstract
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously referred to as non-alcoholic fatty liver disease (NAFLD), is a common liver disorder associated with metabolic abnormalities. This study aimed to evaluate the effectiveness of N-acetylcysteine (NAC) in improving liver function and metabolic profile in patients with MASLD. METHODS: In this randomized controlled trial (RCT), 69 patients with MASLD were randomly assigned to either the NAC group (600 mg, administered three times daily, n=34) or the placebo group (n=35) for eight weeks. The severity of hepatic steatosis, liver enzymes, and metabolic profile were measured at baseline and the final trial. Data were analyzed using SPSS. FINDINGS: Following eight weeks of NAC administration in patients with MASLD, no significant changes were observed compared to the placebo in hepatic steatosis grade (P=0.215), serum aspartate aminotransferase (AST) (P=0.21), alanine transaminase (ALT) (P=0.28), malondialdehyde (MDA) (P=0.79), total antioxidant capacity (TAC) (P=0.56), triglycerides (P=0.15), total cholesterol (P=0.28), low-density lipoprotein cholesterol (P=0.32), and high-density lipoprotein cholesterol (P=0.16). However, NAC administration resulted in significant reductions in fasting blood glucose (FBG) (P=0.01), fasting insulin levels (P<0.001), homeostatic model assessment for insulin resistance (HOMA-IR) (P<0.001), and C-reactive protein (CRP) (P<0.001), along with a significant increase in total glutathione levels (P=0.003), compared to the placebo group. CONCLUSION: NAC administration in patients with MASLD does not significantly impact hepatic steatosis, liver enzymes, or lipid profiles; however, it improves oxidative, glycemic, and inflammatory markers. Therefore, NAC may be a beneficial adjunct therapy for managing metabolic parameters and reducing inflammation and oxidative stress in MASLD patients. TRIAL REGISTRATION: The trial was registered with the Iranian Registry of Clinical Trials (IRCT20201220049772N1) on February 20, 2021.