Very low energy ketogenic diet vs. Mediterranean diet for MASLD: Superior steatosis reduction in a randomised pilot study.

BACKGROUND & AIMS: Weight loss is the cornerstone of treatment for metabolic dysfunction-associated steatotic liver disease (MASLD). This pilot study compared the efficacy and safety of a ketogenic very low energy diet (VLED) vs. a Mediterranean diet (MD) in improving hepatic steatosis and liver histology in individuals with overweight or obesity and MASLD. METHODS: We conducted a pilot randomised controlled trial in adults with histologically confirmed MASLD and a BMI of 27-35 kg/m. Participants were assigned to either a 12-week VLED (3,151 kJ/day) or MD program (8,950 kJ/day) and monitored for 24 weeks. The VLED group received low-dose semaglutide (0.5 mg/weekly) from week 13 for weight maintenance. The primary outcome was change in hepatic steatosis by MRI liver-fat-fraction at 12 weeks. Secondary outcomes included total body weight loss (TBWL) and change in liver histology over 24 weeks. RESULTS: The VLED group (n = 14) achieved significantly greater reduction in MRI-liver-fat-fraction (-77% relative reduction [IQR 51-88]) compared to the MD group (n = 11, -14% [IQR 0-30], p <0.01). The VLED also produced greater TBWL at week 12 (-13% [IQR -17 to -9] vs. -4% [-4.4 to -0.2], p <0.01). At 24 weeks, the VLED/semaglutide group maintained a -14% TBWL (IQR -17 to -10) from baseline vs. -3% TBWL (IQR -4 to 0) in the MD group. Liver histology improved in both groups, with greater improvements in the VLED group (NAFLD activity score reduction VLED: -2 [IQR -3.5 to -2] vs. MD: -1 [IQR -1 to -1], p <0.01). CONCLUSIONS: The ketogenic VLED resulted in significantly greater reduction in hepatic steatosis and weight loss compared to a MD. The very low energy diet is widely available, easily accessible and should be more commonly considered for patients with MASLD and overweight or obesity. IMPACT AND IMPLICATIONS: This pilot randomised controlled trial provides the first direct comparison between a ketogenic very low energy diet (VLED) and a Mediterranean diet (MD) for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD), demonstrating greater reductions in hepatic steatosis (77% vs. 14%) and body weight (13% vs. 4%) with the VLED. The growing burden of people who are overweight and obese with early-stage MASLD means that effective dietary weight loss interventions with proven hepatic and metabolic benefits are urgently required. The accessibility, effectiveness, and feasibility of the VLED in clinical settings suggest that it may represent a valuable therapeutic option for selected patients with MASLD and overweight or obesity. CLINICAL TRIAL REGISTRATION: www.anzctr.org.au trial ID: ACTRN12623000756628.