Efficacy and safety of time-restricted eating in metabolic dysfunction-associated steatotic liver disease

What is the significance of time-restricted eating in the treatment of metabolic dysfunction-associated steatohepatitis (MASLD)?

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects between 30% and 40% of the adult population worldwide, with a continuing rise in incidence. Obesity is one of the most important risk factors. Accordingly, irrespective of the pharmacological treatment options now available for patients with MASLD-associated liver fibrosis, weight loss through lifestyle modification is the first-line and central therapeutic approach for MASLD patients. A reduction in body weight of at least 5% leads to improvement in steatosis, while greater weight loss may result in improvements in inflammatory activity and even fibrosis. To date, however, no large randomized clinical trials have directly compared different diets head-to-head regarding their effectiveness in the treatment of MASLD. Available individual studies and meta-analyses suggest that magnitude and durability of weight loss, rather than the specific type of diet (e.g., low-carbohydrate, low-fat, ketogenic) are the key determinants of therapeutic benefit.
This assessment is supported by the study by Oh JH et al. published in the Journal of Hepatology. In this randomized controlled trial, 337 overweight or obese patients with MASLD received dietary guidance for 16 weeks and were assigned to 3 study groups: “standard of care” (SoC), “calorie reduction” (CR), and “time-restricted eating” (TRE). At baseline, all patients were advised to reduce daily calorie intake by 500 kcal relative to individually calculated daily energy requirements and received personalized nutritional counselling. Patients in the SoC group (n = 114) additionally received monthly feedback on their diet via text messaging. Participants in the CR (n = 112) and TRE (n = 111) groups received the same dietary recommendations but underwent more intensive monitoring. Using a special mobile application, these patients were encouraged to closely track meals and body weight and received feedback on calorie intake and nutritional quality from nutritionists twice a week. Patients in the TRE group also followed a 16:8 intermittent fasting regimen, consisting of 16 hours of fasting and an 8-hour eating window. 
Intensive monitoring and counselling resulted in significantly greater reductions in calorie intake in the TRE and CR groups compared with the SoC group (mean calorie reduction from baseline: -851.2 kcal for TRE, -878.7 kcal for CR, and -434.0 kcal for SoC). After 16 weeks, patients who received intensive dietary support demonstrated significant improvements in the primary end point, liver fat content measured by MRI-proton density fat fraction (MRI-PDFF) (-23.7% for TRE, -24.7 for CR, and -0.7% for SoC). However, the timing of calorie restriction did not result in significant differences between the CR and TRE groups. The other cardiometabolic parameters recorded, including body weight and body fat percentage, also improved significantly with close dietary supervision, without evidence of benefit or harm associated with time-restricted eating. In all groups, nearly two-thirds of participants regained at least 80% of the weight lost or exceeded 95% of baseline body weight within 6 months after completion of the intervention. In line with previous studies, loss of skeletal muscle mass during the intervention was a particular risk factor for subsequent weight regain.
In summary, this trial confirms the effectiveness of a calorie-restricted diet for reducing hepatic steatosis in patients with MASLD but demonstrates no additional benefit of implementing calorie restriction through time-restricted eating. The data also highlight the potential value of close and sustained nutritional counselling for weight loss. Important limitations include the predominant implementation of intermittent fasting as “late” food intake in the afternoon and evening. The beneficial effects of “early” TRE on insulin sensitivity and glycemic control described in other studies are not captured. In addition, the relevance of the findings to specific hepatological end points is also limited, as the study largely consisted of patients with only slightly elevated aminotransferase levels (mean alanine aminotransferase [ALT] levels: 44.3 IU/L for TRE, 44.0 IU/L for CR, and 41.4 IU/L for SoC) and normal liver stiffness, indicating the absence of liver fibrosis. The study period was also too short to expect meaningful results on prognostically relevant outcomes. As expected, the hepatological parameters mentioned were unaffected at the end of the intervention. The study likewise provides no new insights into the potential benefits of a specific diet. Based on the strongest long-term evidence for reducing cardiometabolic risk and mortality, both European and US guidelines recommend a Mediterranean diet for MASLD patients. Overall, however, the optimal diet should be individualized to align with patients’ daily routine and long-term adherence, which may explain why this study conducted in Korea deviated from guideline-based recommendations for cultural reasons.