Effects of Intermittent Calorie Restriction in Nondiabetic Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease

Background & Aims: We compared the effects of a 12-week intermittent calorie restriction (ICR) and standard-of-care (SOC) diet on liver fat content (LFC) in metabolic dysfunction–associated steatotic liver disease patients. Methods: This randomized controlled trial included patients with magnetic resonance imaging–proton density fat fraction ≥8%. Patients were randomly assigned to the ICR (5:2 diet) or SOC (80% of the recommended calorie intake) groups and stratified according to the body mass index (≥25 or <25 kg/m²). The primary outcome was the proportion of patients who achieved a relative LFC reduction as measured by magnetic resonance imaging–proton density fat fraction ≥30%. Results: Seventy-two participants underwent randomization (36 patients with and 36 without obesity), and 63 (34 patients with and 29 without obesity) completed the trial. At week 12, a higher proportion of patients in the ICR arm achieved a relative LFC reduction of ≥30% compared with the SOC arm (72.2% vs 44.4%; P = .033), which was more prominent in the group with obesity (61.1% vs 27.7%; P = .033) than in the group without obesity (83.3% vs 61.1%; P = .352). The relative weight reduction was insignificant between the ICR and SOC arms (–5.3% vs –4.2%; P = .273); however, it was higher in the ICR arm compared with the SOC arm (–5.5% vs –2.9%; P = .039) in the group with obesity. Changes in fibrosis, muscle and fat mass, and liver enzyme levels were similar between the 2 groups (all P > .05). Conclusions: The ICR diet reduced LFC more effectively than SOC in patients with metabolic dysfunction–associated steatotic liver disease, particularly in patients with obesity. Additional studies are warranted in larger and more diverse cohorts. ClinicalTrials.gov, Number: NCT05309642.