Intermittent Fasting and Its Association with Metabolic, Inflammatory, and Fibrosis-Related Outcomes in Adults with Non-alcoholic Fatty Liver Disease: Findings from a Randomized Clinical Trial

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver dysfunction worldwide and commonly coexists with obesity, insulin resistance, and other metabolic disturbances. Lifestyle-based strategies remain central to disease management, and intermittent fasting has recently emerged as a potentially beneficial nutritional intervention. Objectives: This study aimed to evaluate whether intermittent fasting affects anthropometric measures, inflammatory biomarkers, fibrosis-related indices, and ultrasonographic manifestations of hepatic steatosis in individuals with NAFLD. Methods: This randomized clinical trial included 102 adults with ultrasonography-confirmed NAFLD who were randomly assigned in a 1:1 ratio to either a 16:8 intermittent fasting intervention or a control group for 12 weeks. Clinical and laboratory evaluations were performed at baseline and after the intervention. Outcomes included anthropometric measures, inflammatory markers, liver-related laboratory parameters, noninvasive fibrosis-related indices (FIB-4, APRI, NAFLD Fibrosis Score, and BARD score), and an ultrasonographic assessment of hepatic steatosis. Results: Participants assigned to the intermittent fasting regimen showed significant reductions in body weight, body mass index (BMI), and waist circumference compared with controls (all P < 0.001). Marked reductions were also observed in inflammatory markers, particularly the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). In addition, significant improvements were observed across all evaluated non-invasive fibrosis indices, including FIB-4, APRI, NAFLD Fibrosis Score, and BARD score. Ultrasonographic evaluation demonstrated a greater reduction in hepatic steatosis severity among participants undergoing intermittent fasting than among controls. Conclusions: Intermittent fasting appears to be a feasible and potentially beneficial dietary strategy for patients with NAFLD, with favorable effects on noninvasive, fibrosis-related surrogate markers. Further long-term studies incorporating histological endpoints are needed to clarify its role in preventing or delaying fibrosis progression.