Intermittent compared with continuous calorie restriction for treatment of metabolic dysfunction-associated steatotic liver disease: a randomized clinical trial

Calorie restriction has been demonstrated to be effective in treating metabolic dysfunction-associated steatotic liver disease (MASLD). However, it has been limited by poor long-term adherence. This study aimed to compare intermittent calorie restriction (ICR) with traditional continuous calorie restriction (CCR) for the treatment of MASLD. We conducted a 12-wk, parallel-arm, randomized controlled trial that included 60 adults with MASLD and abnormal glucose metabolism. The participants were randomly assigned to either the ICR group (2 successive days of fasting [∼500 kcal/d] and 5 d of recovery per week) or the CCR group. The primary outcome was liver fat content (LFC) measured by 1H-proton magnetic resonance spectroscopy. The secondary and exploratory outcomes included weight, body composition, glucose, insulin, lipids, and liver stiffness. The mean reduction in LFC was −20.5% [95% confidence interval (CI): −25.0, −15.9%] in the ICR group and −15.5% (95% CI: −20.3, −10.8%) in the CCR group. Changes in LFC were not significantly different between the 2 groups (P = 0.15), and were homogeneous among different liver segments. The analysis of exploratory endpoints provided clues that the ICR was associated with greater reductions in fat mass and glycosylated hemoglobin. There were no significant differences in changes of weight, lean mass, insulin resistance, triglyceride, and liver stiffness between the 2 groups. Participants showed high adherence to both the ICR and CCR schemes. The ICR and CCR schemes had similar effects on reducing LFC, suggesting that the ICR 5:2 diet can be an effective alternative for treating MASLD with high adherence. This trial was registered at clinicaltrials.gov as NCT04283942.