Impact of weight loss and reduction of ultra-processed foods on liver fat content in MASLD: a randomized controlled trial.

BACKGROUND & AIMS: Dietary interventions are a cornerstone of management for metabolic dysfunction-associated steatotic liver disease (MASLD). However, it remains unclear whether specific dietary patterns confer benefits beyond weight loss. We aimed to compare the effects of different dietary strategies on liver fat and metabolic health in patients with MASLD. METHODS: We conducted a 6-month, three-arm, parallel-group randomized controlled trial including patients with MASLD and overweight or obesity who were naïve to structured nutritional counselling. Participants were randomized to Mediterranean diet (MeD), low-carbohydrate, high-protein diet (LCHO), or standard nutritional recommendations. Liver fat content was assessed by controlled attenuation parameter (CAP). Secondary outcomes included changes in anthropometric and metabolic parameters, body composition, and ultra-processed food (UPF) consumption. Structural equation modelling (SEM) was used to investigate pathways linking dietary allocation, weight loss, and UPF intake with changes in CAP. RESULTS: Of 173 enrolled participants, 148 (85.5%) completed the study. CAP decreased significantly within the LCHO and control groups (Δ -19.5 [-48.8 to 8.0], p=0.004 and -11.0 [-32.0 to 12.0], p<0.001), with no significant between-group differences. All study arms achieved significant improvements in body weight, body mass index (BMI), adiposity measures, metabolic profile, and dietary quality, including reductions in UPF intake. SEM analyses showed no direct or total effect of dietary pattern on changes in CAP. In contrast, reductions in BMI and UPF consumption independently and significantly predicted CAP improvements: β=14.34 (95% CI 10.55-18.13), and β=0.64 (95% CI 0.25-1.03). CONCLUSIONS: In patients with MASLD, weight loss and reductions in UPF intake, rather than diet type, were the main drivers of improvements in liver fat and metabolic health. These findings support a patient-centered dietary approach in MASLD management. CLINICAL TRIAL NUMBER: NCT073043336 IMPACT AND IMPLICATIONS: This randomized controlled trial shows that weight loss and reductions in ultra-processed food intake, rather than the specific dietary pattern, are the primary factors associated with improvements in liver fat and metabolic health in MASLD. These findings challenge the emphasis on prescriptive dietary models and support a more flexible, patient-centered approach focused on sustainable weight reduction and improved dietary quality. Prioritizing reduction of ultra-processed foods may represent a practical and scalable strategy to enhance adherence and maximize long-term clinical benefit in routine care.