Editorial: Chrononutrition and MASLD—It is About Time (Restricted Feeding)! Authors' Reply

We sincerely appreciate the opportunity to respond to the editorial by Mohr and Stine discussing our study on the effects of a 12-week Mediterranean-type time-restricted feeding (TRF) protocol in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) [1, 2]. We are grateful for their insightful commentary and for highlighting the strengths of our randomised controlled trial (RCT). Their analysis underscores the emerging role of chrononutrition in managing MASLD while also highlighting key questions regarding the independent contribution of TRF and caloric restriction to metabolic improvements. There is indeed a great need for studies that directly compare ad libitum TRF protocols with caloric restriction to evaluate their differentiative impact on several metabolic parameters. Most of the studies in MASLD have compared either ad libitum TRF protocols with the usual dietary habits of the participants or hypocaloric diets in both TRF and control groups, as in our study.

Our study was the first RCT that used the Mediterranean Diet (MD) as a control group, the gold standard for patients with MASLD [3]. The MD has been extensively documented as an effective intervention for MASLD [4]. Our study adds to this body of evidence by demonstrating that a hypocaloric MD, even over a short-term period, yields significant improvements in body weight, body fat, blood pressure and liver fat content [1]. Regarding the comment on the generalizability of the results [2], it is true that Greece is a Mediterranean country, and as described in previous studies, Greeks' adherence to the MD is moderate [5]. Our results [1] agree with these studies [5] and this may have enhanced our participants' adherence.

The TRF interventions (early or late) did not seem to improve the metabolic parameters mentioned above further in this population [1]. However, insulin resistance and haemoglobin A_1c (HbA_1c) were only improved in the early but not in the late TRF group. The reduction in HbA_1c in the early TRF group (0.3% in total, 0.37% in those with T2DM under early TRF) in our study [1] was greater than in other similar studies, for example, 0.2% in the study by Wei et al. (early TRF + caloric restriction group) [6], whilst this grade of improvement has been associated with lower mortality in individuals with T2DM [7] and reduction in diabetic complications [8]. Prior studies suggest that aligning food intake with circadian rhythms and the light/dark cycle via TRF may enhance glucose metabolism independent of caloric restriction as humans are diurnal [9]. This is particularly relevant for MASLD patients, where insulin resistance is a pivotal driver of disease progression [10]. That means that the differences in glucose metabolism observed in our study were probably due to the early TRF intervention, as all groups had the same caloric restriction.

We would like to thank the authors for their thoughtful comments, which have allowed us to refine our interpretation and highlight the robustness of our findings. Future research will provide answers to all the raised concerns.

Sofia Tsitsou: writing – original draft, investigation, methodology, data curation. Magdalini Adamantou: writing – original draft, data curation, investigation. Triada Bali: investigation, data curation. Aristi Saridaki: data curation, investigation. Kalliopi-Anna Poulia: methodology. Dimitrios S. Karagiannakis: methodology. Emilia Papakonstantinou: methodology. Evangelos Cholongitas: conceptualization, investigation, methodology, writing – review and editing, project administration, supervision, visualization, writing – original draft.

The 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.70078.