Editorial: Chrononutrition and MASLD—Its About Time (Restricted Feeding)!

The global obesity epidemic and the widespread adoption of a Westernised diet high in sugar and processed foods, alongside a sedentary lifestyle, have fueled the rise of metabolic dysfunction-associated steatotic liver disease (MASLD) [1]. Since an unhealthy lifestyle is central to MASLD development, effective lifestyle interventions remain essential for improving patient outcomes [2]. The Mediterranean diet (MD), rich in produce, whole grains and healthy fats like olive oil, while limiting red meat and processed foods, is widely recognized as a key dietary intervention [3, 4]. Adherence to MD has shown reduction in hepatic fat, improved insulin sensitivity, and slowed MASLD progression [5, 6]. However, barriers such as cost, accessibility, and cultural preferences hinder widespread adoption. As a result, alternative dietary strategies, such as time-restricted feeding (TRF), have gained attention. TRF limits food intake to a set daily window, typically 6 to 10 h, followed by fasting. Although TRF has demonstrated metabolic health benefits, particularly when paired with caloric restriction [7], its optimal implementation and impact on MASLD remain unclear, and it is not yet considered standard of care.

In the CHRONO-NAFLD study, Tsitsou et al. [8] explored the efficacy of a TRF + MD combination. The 12-week trial randomized 71 adults with MASLD and overweight/obesity into three groups: hypocaloric MD (control), hypocaloric MD + early TRF (8 AM–6 PM), and hypocaloric MD + late TRF (12 PM–10 PM). Dietary adherence was rigorously measured using self-reports verified by study personnel and reinforced via phone calls, with > 90% adherence in each group. The study boasted a high completion rate of 83%. All groups experienced significant reductions in body weight, body fat, and blood pressure, along with improvements in VCTE-measured liver fat and a modest trend toward reduced liver stiffness. Notably, the only between-group differences emerged in glycemic control, with improvements in insulin resistance and hemoglobin A1c observed in both TRF groups. However, these changes, while statistically significant, did not reach clinically meaningful thresholds (Figure 1).

Importantly, this study has several strengths, including a well-characterized population, rigorous methodology, and validated dietary adherence measures assessing multiple clinically relevant outcomes. However, limitations include selection bias (84% of participants had moderate MD adherence at baseline) and most were physically active (> 600 MET-min/week). This limits generalisability, as the cohort was relatively homogenous and inclined toward MD consumption. Key confounders, such as meal composition and physical activity changes, were also not fully controlled. The study design also precluded distinguishing whether observed benefits stemmed from TRF itself or from caloric restriction.

In summary, TRF shows promise in improving insulin resistance and glycemic control. However, further studies are needed to determine if TRF independently improves liver histology and long-term patient outcomes. Key questions remain whether the metabolic benefits of TRF are due to fasting or simply reduced caloric intake, and whether TRF is sustainable over time. While TRF appears safe and feasible, it remains unclear whether it offers advantages over other structured dietary interventions when calorically matched.

Hannah Mohr: writing – original draft, writing – review and editing. Jonathan G. Stine: conceptualization, writing – review and editing.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. AI-based software was used for grammatical and stylistic editing at various parts of this manuscript.

Dr. Stine receives or has received research support from Astra Zeneca, Galectin, Kowa Inc., Novo Nordisk, Regeneron and Zydus Therapeutics. Dr. Stine consults Novo Nordisk and is on an Advisory Board for Madrigal. The other authors declare no conflicts of interest.

This article is linked to Tsitsou et al papers. To view these articles, visit https://doi.org/10.1111/apt.70044 and https://doi.org/10.1111/apt.70107.