Time to Eat - A Personalized Circadian Eating Schedule Leads to Weight Loss Without Calorie Restriction: A Randomized Controlled Trial

Reviewer #1 (Public Review):

The authors Wilming and colleagues set out to determine the impact of regularity of feeding per se on the efficiency of weight loss. The idea was to determine if individuals who consume 2-3 meals within individualized time frames, as opposed to those who exhibit stochastic feeding patterns throughout the circadian period, will cause weight loss.

The methods are rigorous, and the research is conducted using a two-group, single-center, randomized-controlled, single-blinded study design. The participants were aged between 18 and 65 years old, and a smartphone application was used to determine preferred feeding times, which were then used as defined feeding times for the experimental group. This adds strength to the study since restricting feeding within preferred/personalized feeding windows will improve compliance and study completion. Following a 14-day exploration phase and a 6-week intervention period in a cohort of 100 participants (inclusive of both the controls and the experimental group that completed the study), the authors conclude that when meals are restricted to 45min or less durations (MTVS of 3 or less), this leads to efficient weight loss. Surprisingly, the study excludes the impact of self-reported meal composition on the efficiency of weight loss in the experimental group. In light of this, it is important to follow up on this observation and develop rigorous study designs that will comprehensively assess the impact of changes (sustained) in dietary composition on weight loss. The study also reports interesting effects of regularity of feeding on eating behavior, which appears to be independent of weight loss. Perhaps the most important observation is that personalized interventions that cater to individual circadian needs will likely result in more significant weight loss than when interventions are mismatched with personal circadian structures. One are of concern for the study is its two-group design; however, single-group cross-over designs are tedious to develop, and an adequate 'wash-out' period may be difficult to predict. A second weakness is not considering the different biological variables and racial and ethnic diversity and how that might impact outcomes. In sum, the authors have achieved the aims of the study, which will likely help move the field forward.

Reviewer #2 (Public Review):

Summary:

The authors investigated the effects of the timing of dietary occasions on weight loss and well-being with the aim of explaining if a consistent, timely alignment of dietary occasions throughout the days of the week could improve weight management and overall well-being. The authors attributed these outcomes to a timely alignment of dietary occasions with the body's own circadian rhythms. However, the only evidence the authors provided for this hypothesis is the assumption that the individual timing of dietary occasions of the study participants identified before the intervention reflects the body's own circadian rhythms. This concept is rooted in understanding of dietary cues as a zeitgeber for the circadian system, potentially leading to more efficient energy use and weight management. Furthermore, the primary outcome, body weight loss, was self-reported by the study participants.

Strengths:

The innovative focus of the study on the timing of dietary occasions rather than daily energy intake or diet composition presents a fresh perspective in dietary intervention research. The feasibility of the diet plan, developed based on individual profiles of the timing of dietary occasions identified before the intervention, marks a significant step towards personalised nutrition.

Weaknesses:

Several methodological issues detract from the study's credibility, including unclear definitions not widely recognized in nutrition or dietetics (e.g., "caloric event"), lack of comprehensive data on body composition, and potential confounders not accounted for (e.g., age range, menstrual cycle, shift work, unmatched cohorts, inclusion of individuals with normal weight, overweight, and obesity). The primary outcome's reliance on self-reported body weight and subsequent measurement biases further undermines the reliability of the findings. Additionally, the absence of registration in clinical trial registries, such as the EU Clinical Trials Register or clinicaltrials.gov, and the multiple testing of hypotheses which were not listed a priori in the research protocol published on the German Register of Clinical Trials impede the study's transparency and reproducibility.

Achievement of Objectives and Support for Conclusions:

The study's objectives were partially met; however, the interpretation of the effects of meal timing on weight loss is compromised by the weaknesses mentioned above. The evidence only partially supports some of the claims due to methodological flaws and unstructured data analysis.

Impact and Utility:

Despite its innovative approach, significant methodological and analytical shortcomings limit the study's utility. If these issues were addressed, the research could have meaningful implications for dietary interventions and metabolic research. The concept of timing of dietary occasions in sync with circadian rhythms holds promise but requires further rigorous investigation.

Reviewer #3 (Public Review):

The authors tested a dietary intervention focused on improving meal regularity in this interesting paper. The study, a two-group, single-center, randomized, controlled, single-blind trial, utilized a smartphone application to track participants' meal frequencies and instructed the experimental group to confine their eating to these times for six weeks. The authors concluded that improving meal regularity reduced excess body weight despite food intake not being altered and contributed to overall improvements in well-being.

The concept is interesting, but the need for more rigor is of concern.

A notable limitation is the reliance on self-reported food intake, with the primary outcome being self-reported body weight/BMI, indicating an average weight loss of 2.62 kg. Despite no observed change in caloric intake, the authors assert weight loss among participants.

The trial's reliance on self-reported caloric intake is problematic, as participants tend to underreport intake; for example, in the NEJM paper (DOI: 10.1056/NEJM199212313272701), some participants underreported caloric intake by approximately 50%, rendering such data unreliable and hence misleading. More rigorous methods for assessing food intake are available and should have been utilized. Merely acknowledging the unreliability of self-reported caloric intake is insufficient as it would still leave the reader with the impression that there is no change in food intake when we actually have no idea if food intake was altered. A more robust approach to assessing food intake is imperative. Even if a decrease in caloric intake is observed through rigorous measurement, as I am convinced a more rigorous study would unveil testing this paradigm, this intervention may merely represent another short-term diet among countless others that show that one may lose weight by going on a diet, principally due to heightened dietary awareness.

Furthermore, the assessment of circadian rhythm using the MCTQ, a self-reported measure of chronotype, may not be as reliable as more objective methods like actigraphy.

Given the potential limitations associated with self-reported data in both dietary intake and circadian rhythm assessment, the overall impact of this manuscript is low. Increasing rigor by incorporating more objective and reliable measurement techniques in future studies could strengthen the validity and impact of the findings.