N-Acetylcysteine for NAFLD / MASLD

Finding: Over 8 weeks NAC (600 mg TID) showed NO significant effect vs placebo on steatosis grade (P=0.215), AST (P=0.21) or ALT (P=0.28), with benefit only on surrogate metabolic markers (HOMA-IR and CRP both P<0.001, glutathione P=0.003).

Finding: NAC produced a significant decrease in serum ALT after 3 months versus vitamin C (active comparator) and significantly reduced spleen span, but the trial was tiny (n=30), un-blinded and reported no exact effect sizes.

Finding: In a 3-arm trial with NO placebo (NAC 1200 mg BID vs rosuvastatin vs vitamin E), NAC was the only agent showing significant antifibrotic effect on liver stiffness and fibrosis scores (p<0.05), but all comparisons are versus active drugs rather than placebo.

Finding: Across the three arms there were NO significant between-group differences in biochemistry or histology at 48 weeks; only the intragroup intention-to-treat analysis of NAC+metformin showed improved steatosis (P=0.014), ballooning (P=0.027), NAS (P=0.005) and ALT, with no change in fibrosis in any group.

Finding: In a 16-week pilot of 13 children with biopsy-confirmed MASLD, NAC (600 or 1200 mg/day) significantly improved inflammation (IL-6, hs-CRP), oxidative stress (GSH), HOMA-IR, and reduced liver enzymes, liver fat fraction and liver stiffness (baseline-adjusted between-group P<0.05 for all), though n=13 is far too small for definitive conclusions.

Finding: This is a PRECLINICAL (animal-only) meta-analysis of 13 studies finding NAC significantly improved hepatic lipid metabolism (p<0.01), liver injury (p<0.01), steatosis (p<0.01) and glucose intolerance (p<0.05) by restoring glutathione; it explicitly concludes NAC 'should be considered for future clinical trials' and provides no human efficacy estimate.