Effect of high dose N-acetyl cysteine supplementation on markers of oxidative stress and insulin resistance in non-diabetic patients with metabolic dysfunction associated steatotic liver disease: a randomized controlled trial.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cause of chronic liver disease. N-acetylcysteine (NAC) has demonstrated antioxidant and hepatoprotective effects in non-alcoholic steatohepatitis. This study evaluated the impact of high-dose NAC on oxidative stress, insulin resistance, and liver-related outcomes in non-diabetic MASLD patients. METHODS: This prospective, randomized, open-label controlled trial included 60 non-diabetic adults with MASLD. Participants were randomly assigned to receive either oral NAC (2400 mg/day) combined with lifestyle intervention (n = 30) or lifestyle intervention alone (n = 30) for 12 weeks. The primary outcome was change in serum malondialdehyde (MDA). Secondary outcomes included markers of insulin resistance (leptin, fasting insulin, and HOMA-IR), lipid profile, liver steatosis and fibrosis assessed by FibroScan® and non-invasive scores, and quality of life (QOL). RESULTS: No significant differences in serum MDA, leptin, fasting insulin, or HOMA-IR (all p > 0.05) between groups. Similarly, FibroScan® parameters, non-invasive steatosis and fibrosis scores did not differ significantly between groups. A significant reduction in liver steatosis scores in the control group (p = 0.004) while the Hepatic steatosis index improved in both groups (p = 0.008).Triglyceride levels decreased significantly in the control group, whereas HDL-cholesterol increased significantly in the NAC group. QOL scores remained unchanged overall, except for a significant increase in the emotional domain scores in the NAC group. CONCLUSIONS: High-dose NAC for three months did not significantly improve oxidative stress, insulin resistance, or hepatic steatosis or fibrosis in non-diabetic MASLD patients. NAC was safe and well tolerated during the study period. TRIAL REGISTRATION: This study was registered on clinicaltrials.gov under the identifier number NCT05589584 in October 2022.