Effects of early, late and self-selected time-restricted eating on visceral adipose tissue and cardiometabolic health in participants with overweight or obesity: a randomized controlled trial

Abstract

Key Aspects

• Study Objective: TRE and VAT: The primary objective of this study was to determine the optimal eating window for time-restricted eating (TRE) and its impact on visceral adipose tissue (VAT). VAT is a type of fat that accumulates around internal organs and is strongly linked to increased risk of cardiometabolic diseases and mortality. The researchers aimed to compare the effects of different TRE schedules on VAT reduction, a crucial factor in improving metabolic health.
• Study Design: Randomized Controlled Trial: The study employed a randomized controlled trial design, comparing three different TRE schedules (early, late, and self-selected 8-hour eating windows) combined with usual care (UC, based on education about the Mediterranean diet) against UC alone. The intervention lasted 12 weeks, and participants were adults with overweight or obesity. This rigorous design allows for the assessment of cause-and-effect relationships between TRE timing and VAT changes.
• Main Finding: No Significant Differences in VAT: The main finding of the study was that there were no significant differences in VAT changes between any of the TRE groups (early, late, or self-selected) and the UC group, nor were there significant differences among the TRE groups themselves. This suggests that the timing of the eating window within an 8-hour TRE protocol, when combined with a Mediterranean diet, does not significantly impact VAT reduction beyond the effects of the Mediterranean diet alone. This finding is crucial as it informs dietary recommendations and interventions for managing obesity and related health risks.
• Adherence and Safety: The study reported high adherence rates (85-88%) across all TRE groups, and no serious adverse events were observed. Five participants reported mild adverse events. These findings suggest that TRE is a generally safe and well-tolerated dietary approach for adults with overweight or obesity, making it a potentially feasible option for long-term weight management and cardiometabolic health improvement.

Strengths

• Clear Statement of Objective

  The abstract clearly states the study's objective, which is to investigate the effects of different TRE schedules on VAT and cardiometabolic health.

  "We investigated the effects of three TRE schedules (8 h windows in the early day, late day and participant-chosen times) combined with usual care (UC, based on education about the Mediterranean diet) versus UC alone over 12 weeks in adults with overweight or obesity." (Page 1)
• Concise Summary of Main Findings

  The abstract concisely summarizes the main findings, including the lack of significant differences in VAT changes between the TRE groups and the control group.

  "No significant differences were found in VAT changes between early TRE (mean difference (MD): −4%; 95% confidence interval (CI), −12 to 4; P = 0.87), late TRE (MD: −6%; 95% CI, −13 to 2; P = 0.31) and self-selected TRE (MD: −3%; 95% CI, −11 to 5; P ≥ 0.99) compared with UC, nor among the TRE groups (all P ≥ 0.99)." (Page 1)
• Inclusion of Practical Considerations

  The abstract mentions the high adherence rates and safety of TRE, which are important practical considerations for implementing this dietary approach.

  "Adherence was high (85–88%) across TRE groups. These findings suggest that adding TRE, irrespective of eating window timing, offers no additional benefit over a Mediterranean diet alone in reducing VAT. TRE appears to be a safe, well-tolerated and feasible dietary approach for adults with overweight or obesity." (Page 1)
• Key Methodological Details

  The abstract provides key methodological details, such as the study design, sample size, intervention duration, and primary outcome measure.

  "A total of 197 participants were randomized to UC (n = 49), early TRE (n = 49), late TRE (n = 52) or self-selected TRE (n = 47). The primary outcome was VAT changes measured by magnetic resonance imaging." (Page 1)

Suggestions for Improvement

• Clarify Effect of Control Intervention

  This high-impact improvement focuses on providing context for interpreting the main result. The Abstract section is crucial for framing the study's importance. Currently, the abstract states that TRE offered no *additional* benefit over the Mediterranean diet alone. It's important to briefly state whether the Mediterranean diet *itself* resulted in VAT reduction, to avoid potential misinterpretations. Without this, readers might incorrectly assume *neither* intervention was effective.

  "These findings suggest that adding TRE, irrespective of eating window timing, offers no additional benefit over a Mediterranean diet alone in reducing VAT." (Page 1)

  Implementation: Add a brief phrase indicating the effect of the Mediterranean diet (UC) on VAT. For example, after "...offers no additional benefit over a Mediterranean diet alone in reducing VAT," add "which also resulted in VAT reduction." The exact wording should reflect the study's findings.

• Summarize Other Cardiometabolic Outcomes

  This medium-impact improvement would enhance the abstract's completeness. While the abstract mentions "cardiometabolic health," it primarily focuses on VAT. Including a brief mention of the *direction* of any observed changes (even if non-significant) in other cardiometabolic outcomes would provide a more comprehensive overview. This is important for the Abstract, as it gives a quick, complete snapshot of the research.

  "The optimal eating window for time-restricted eating (TRE) remains unclear, particularly its impact on visceral adipose tissue (VAT), which is associated with cardiometabolic morbidity and mortality." (Page 1)

  Implementation: Add a short phrase summarizing the direction of changes in other cardiometabolic health markers. For example, "...with non-significant changes observed in other cardiometabolic markers." or "...with slight improvements/decreases observed in [mention specific markers]."

Introduction

Key Aspects

• Obesity as a Global Health Concern: Obesity is presented as a significant global health issue, associated with increased risk of chronic diseases like diabetes, cardiovascular disease, and cancer. This establishes the broader context and highlights the importance of finding effective interventions for weight management and improving cardiometabolic health. The increasing prevalence of obesity and its associated health and economic burdens underscore the urgency of this research area.
• Introduction of Time-Restricted Eating (TRE): Time-restricted eating (TRE) is introduced as a promising dietary intervention for obesity. TRE involves limiting daily energy intake to a specific eating window (≤10 hours) and fasting for the remaining time (≥14 hours). This approach is presented as an alternative to traditional energy-restricted diets, potentially offering better long-term adherence and modest improvements in body weight and cardiometabolic health.
• Knowledge Gap: VAT and TRE Timing: The introduction identifies a key knowledge gap in the existing TRE literature: the impact of TRE on visceral adipose tissue (VAT) and the optimal timing of the eating window. VAT, a type of ectopic fat, is a significant risk factor for cardiometabolic diseases. Determining the most effective TRE schedule for reducing VAT is crucial for maximizing its health benefits.
• Limitations of Previous TRE Studies: Previous studies comparing early versus late TRE schedules have limitations, including short durations, small sample sizes, and lack of randomization. These limitations make it difficult to draw definitive conclusions about the optimal timing of the eating window. The current study aims to address these shortcomings by employing a more rigorous research design.
• Novelty of Self-Selected TRE: The introduction highlights the novelty of comparing early and late TRE with a self-selected TRE schedule. Allowing participants to choose their eating window may improve adherence and acceptability, potentially enhancing the efficacy of the intervention. This aspect of the study addresses the growing interest in personalized nutrition approaches.
• Study Aim: Comparing TRE Schedules: The main aim of the study is clearly stated: to investigate the effects of three distinct TRE schedules (early, late, and self-selected 8-hour eating windows) combined with usual care (UC, based on education about the Mediterranean diet) versus UC alone, over 12 weeks. The primary focus is on VAT changes, measured by MRI, and cardiometabolic health in men and women with overweight or obesity.

Strengths

• Clear Rationale for the Study

  The introduction clearly establishes the global health concern of obesity and its association with chronic diseases, providing a strong rationale for the study.

  "Obesity is a global health concern1,2 and is associated with a higher risk of developing chronic conditions such as diabetes, cardiovascular disease and cancer1,3, imposing a substantial strain on healthcare systems1,4." (Page 1)
• Effective Introduction of TRE

  The introduction effectively introduces time-restricted eating (TRE) as a promising dietary intervention and highlights its potential benefits and current limitations in the literature.

  "Time-restricted eating (TRE) has emerged as an alternative and promising dietary intervention to address obesity6–8. TRE limits the daily energy intake to a predetermined eating window (≤10 h) and fasting for the rest of the day (≥14 h)6–8." (Page 1)
• Identification of Knowledge Gap

  The introduction identifies a specific knowledge gap regarding the impact of TRE on visceral adipose tissue (VAT) and the optimal timing of the eating window.

  "However, some important aspects related to the effects of TRE remain uncertain, such as its impact on specific ectopic fat deposition6, particularly on visceral adipose tissue (VAT)10–12, an important risk factor for cardiometabolic morbidity and mortality13. Another important question regarding TRE is whether the timing of the eating window" (Page 1)
• Clear Statement of Study Aim

  The introduction clearly states the main aim of the study, which is to investigate the effects of three distinct TRE schedules on VAT and cardiometabolic health.

  "The main aim of the present study was to investigate the effects of three distinct TRE schedules—an 8 h eating window in the early part of the day (early TRE), an 8 h window later in the day (late TRE) and a participant-selected eating window (self-selected TRE)—combined with usual care (UC, which included 2-monthly sessions of a group nutritional education program based on the Mediterranean diet) versus UC alone, over 12 weeks, focusing on VAT changes (measured by magnetic resonance imaging (MRI)) and cardiometabolic health among men and women with overweight or obesity." (Page 2)

Suggestions for Improvement

• Explicitly Address Limitations of Previous Studies

  This medium-impact improvement would enhance the introduction's logical flow and completeness. Currently, the Introduction jumps from discussing limitations of *previous* TRE studies (short duration, small sample size, lack of randomization) to the *current* study's aim. It would be stronger to explicitly state how the *current* study addresses those *previous* limitations. This is important for the Introduction, as it sets up the significance of the *current* work by contrasting it with what came before.

  "However, drawing definitive conclusions from existing studies comparing early with late TRE is challenging owing to shortcomings such as their relatively short duration (≤8 weeks), small sample sizes or lack of randomization16–19." (Page 2)

  Implementation: Add a sentence or short paragraph before stating the main aim, explicitly mentioning how the current study design overcomes the limitations of previous research. For example: "To address these limitations, the present study employed a randomized controlled design with a larger sample size and a longer intervention period of 12 weeks, comparing three distinct TRE schedules..."

• Strengthen Rationale for Self-Selected TRE Arm

  This high-impact improvement would strengthen the justification for including a *self-selected* TRE arm. While the Introduction mentions that this *may* improve adherence, it doesn't fully explain *why* this is a valuable research question. The Introduction needs to establish the importance of *all* aspects of the study design. Connecting this to the broader context of personalized nutrition and patient-centered care would make the rationale more compelling.

  "Furthermore, there is a notable gap in the literature regarding comparing early or late TRE with a self-selected TRE, which may be of great interest. Allowing participants to select the TRE window that aligns with their personal preferences and schedule may further improve adherence and acceptability and, thus, enhance efficacy." (Page 2)

  Implementation: Expand the discussion of the self-selected TRE arm. Include a sentence or two explaining the potential importance of patient preference in dietary interventions and how this relates to long-term adherence and success. For example, "Given the growing emphasis on personalized nutrition and patient-centered care, investigating a self-selected TRE arm is crucial for understanding the role of individual preferences in the effectiveness of dietary interventions."

• Clarify "Usual Care" (UC) Earlier

  This low-impact improvement would add clarity and context. While the Introduction mentions "usual care (UC)", it doesn't immediately define what this entails. Although the full details are in the Methods, briefly stating the *core* of UC in the Introduction would improve reader understanding. This is important for the Introduction because it's the first time UC is mentioned, and readers need to grasp the basic study design.

  "We investigated the effects of three TRE schedules (8 h windows in the early day, late day and participant-chosen times) combined with usual care (UC, based on education about the Mediterranean diet) versus UC alone over 12 weeks in adults with overweight or obesity." (Page 1)

  Implementation: Add a brief phrase clarifying what "usual care" involves when it's first mentioned. For example, change "...combined with usual care (UC)..." to "...combined with usual care (UC), which consisted of education about the Mediterranean diet,..."

Results

Key Aspects

• Participant Enrollment and Randomization: The study enrolled 197 adults with overweight or obesity, who were randomized into four groups: usual care (UC), early time-restricted eating (TRE), late TRE, and self-selected TRE. Fourteen participants were lost to follow-up, leaving 197 for the intention-to-treat analysis. This aspect describes the initial participant pool and the final number included in the primary analysis, providing context for the study's sample size and generalizability.
• Primary Outcome: VAT Changes: The primary outcome, changes in visceral adipose tissue (VAT), showed no statistically significant differences between any of the TRE groups (early, late, or self-selected) and the UC group. There were also no significant differences in VAT changes among the TRE groups themselves. This is the central finding of the study, indicating that the timing of the 8-hour eating window did not significantly impact VAT reduction beyond the effects of the Mediterranean diet (UC).
• Secondary Outcome: SAT Changes: The decrease in subcutaneous adipose tissue (SAT) was significantly greater in the early TRE group compared to the UC group. However, there were no significant differences between the late and self-selected TRE groups compared to the UC group, nor among the TRE groups. This suggests a potential specific benefit of early TRE on SAT reduction.
• Secondary Outcome: Body Weight Changes: Body weight decreased significantly in all three TRE groups (early, late, and self-selected) compared to the UC group. However, there were no significant differences in body weight loss among the TRE groups. This indicates that TRE, regardless of timing, led to greater weight loss than the control condition.
• Secondary Outcome: Glucose Homeostasis: Fasting glucose and nocturnal mean glucose levels decreased more in the early TRE group compared to the UC, late TRE, and self-selected TRE groups. This suggests a potential advantage of early TRE for improving glucose homeostasis.
• Secondary Outcomes: Other Cardiometabolic Risk Factors: There were no statistically significant differences in body composition (fat-free mass, appendicular lean mass, fat mass), blood pressure, insulin resistance (HOMA-IR), HbA1c, or blood lipid profiles across all groups. This indicates that the different TRE schedules did not differentially affect these cardiometabolic risk factors.
• Secondary Outcome: Dietary Energy Intake: Dietary energy intake decreased significantly more in the early TRE group compared to the UC group. No other significant group comparisons were observed. This suggests that early TRE may lead to a greater reduction in caloric intake.
• Secondary Outcomes: Physical Activity and Sleep: Physical activity and sleep patterns remained largely unchanged across all groups after the intervention. This suggests that the observed changes in other outcomes were not due to differences in physical activity or sleep.
• Eating Window and Adherence: The eating window was significantly shorter in all three TRE groups compared to the UC group. Adherence to the TRE protocol (defined as an eating window ≤9 hours) was comparable across the TRE groups (85.3% to 88.1%). This demonstrates the feasibility of implementing TRE and achieving high adherence.
• Adverse Events: No serious adverse events were observed during the trial. A few mild adverse events were reported, leading to study discontinuation in five participants. This suggests that TRE is a generally safe dietary approach.

Strengths

• Clear Participant Flow Diagram

  The Results section clearly presents the flow of participants through the study, from initial screening to final analysis, using a well-structured flow diagram (Fig. 1). This provides transparency regarding participant enrollment, allocation, follow-up, and analysis.

  "Fig. 1 | Study design and participant allocation overview. Study flow diagram. WC, waist circumference; CVD, cardiovascular. Figure created with BioRender.com." (Page 2)
• Detailed Baseline Characteristics

  The baseline characteristics of participants are presented in detail in Table 1, demonstrating the comparability of the groups at the start of the intervention. This is important for assessing the internal validity of the study.

  "Table 1 | Baseline characteristics of participants by intervention group" (Page 3)
• Clear Presentation of Outcomes

  The primary and secondary outcomes are presented clearly and concisely, using both figures (Fig. 2) and tables (Tables 2 and 3) to summarize the findings. The use of statistical significance testing (P-values) and confidence intervals allows for a proper interpretation of the results.

  "Primary outcome: VAT We could not detect statistically significant differences in VAT changes between the early TRE (mean difference: −4%; 95% confidence interval (CI), −12 to 4; P = 0.87), the late TRE (mean difference: −6%; 95% CI, −13 to 2; P = 0.31) and the self-selected TRE groups (mean difference: −3%; 95% CI, −11 to 5; P ≥ 0.99) compared with the UC group (Fig. 2 and Table 2)." (Page 3)
• Comprehensive Reporting of Outcomes

  The Results section reports on a wide range of outcomes, including not only VAT but also subcutaneous and intermuscular abdominal adipose tissue, body weight, body composition, blood pressure, glucose homeostasis, blood lipid profile, dietary intake, physical activity, sleep, eating window, adherence, and adverse events. This comprehensive approach provides a holistic view of the effects of TRE.

  "Table 2 | Changes in abdominal adipose tissue, body composition, BP, glucose homeostasis, blood lipid profile and dietary intake endpoints in the TRE groups compared with the UC group after the 12 week intervention" (Page 5)
• Reporting of Adherence and Adverse Events

  The Results section appropriately reports on adherence to the intervention and adverse events, which are important considerations for the feasibility and safety of TRE.

  "Adverse events. No serious adverse events were observed during the trial. Mild adverse events were reported, including hypoglycemia (n = 1) and thrombosis (n = 1) in the early TRE group, migraine (n = 1) in the late TRE group, and headache (n = 1) and colitis (n = 1) in the self-selected TRE group. Participants chose to discontinue the study after experiencing these adverse events." (Page 6)

Suggestions for Improvement

• Include Figure 3 (CGM Data)

  This medium-impact improvement would enhance the clarity and completeness of the Results section. While the text mentions Figure 3 and continuous glucose monitoring (CGM) data, the actual figure is not included within the provided section. This makes it difficult to fully understand the results related to glucose homeostasis. The Results section should present all key findings, and the CGM data is crucial for understanding the effects of TRE on glycemic control.

  "Figure 3 shows the interstitial glucose levels across 24 h, tracked by continuous glucose monitoring (CGM) for 14 days at baseline and during the final 2 weeks of the 12 week intervention." (Page 4)

  Implementation: Include Figure 3 within the Results section. Ensure the figure is properly labeled and referenced in the text. Provide a brief description of the figure's key features and findings within the main text.

• Reorder Text and Tables for Logical Flow

  This medium-impact improvement would improve the clarity and flow of information. While Table 2 is mentioned, it's placed *after* the description of some of its contents. This disrupts the logical flow, as readers encounter results *before* seeing the table that summarizes them. The Results section should follow a consistent structure, presenting tables and figures *before* or *simultaneously with* their detailed discussion.

  "Primary outcome: VAT We could not detect statistically significant differences in VAT changes between the early TRE (mean difference: −4%; 95% confidence interval (CI), −12 to 4; P = 0.87), the late TRE (mean difference: −6%; 95% CI, −13 to 2; P = 0.31) and the self-selected TRE groups (mean difference: −3%; 95% CI, −11 to 5; P ≥ 0.99) compared with the UC group (Fig. 2 and Table 2)." (Page 3)

  Implementation: Reorder the text and tables/figures so that Table 2 is introduced *before* its contents are discussed in detail. The same applies to Table 3. Ensure a smooth transition between the text and the tables.

• Include Extended Data Figures

  This low-impact improvement would enhance the completeness of the Results section. While the text mentions Extended Data Figs. 1 and 2, these figures are not included within the provided section. While not essential for the main findings, these figures likely provide additional details on physical activity, sleep, and eating window adherence, which are relevant to the study's overall context.

  "Physical activity and sleep. After the intervention, physical activity and sleep patterns were largely unchanged across all groups (P = 0.40; Extended Data Fig. 1)." (Page 6)

  Implementation: If possible, include Extended Data Figs. 1 and 2 within the Results section or as supplementary material. Ensure they are properly referenced in the text.

• Define Abbreviations Within the Results Section

  This high-impact improvement would enhance the clarity and interpretability of the Results. The section frequently uses abbreviations (e.g., VAT, SAT, TRE, UC, HOMA-IR, HbA1c, CGM, CV, HDL-C, LDL-C, APOA1, APOB) without defining them *within the Results section itself*. While these abbreviations *may* be defined elsewhere in the paper (Introduction, Methods), the Results section should be self-contained and understandable on its own. Readers shouldn't have to search other sections to understand the core findings.

  "Primary outcome: VAT" (Page 3)

  Implementation: Define all abbreviations the *first time* they are used within the Results section, even if they are defined elsewhere in the paper. For example: "...visceral adipose tissue (VAT)...", "...subcutaneous adipose tissue (SAT)...", "...time-restricted eating (TRE)...", etc.

Non-Text Elements

Fig. 1 | Study design and participant allocation overview. Study flow diagram....

Full Caption

Fig. 1 | Study design and participant allocation overview. Study flow diagram. WC, waist circumference; CVD, cardiovascular. Figure created with BioRender.com.

Figure/Table Image (Page 2)

First Reference in Text

Overall, 14 participants (3, 2, 4 and 5 participants from the UC and early, late and self-selected TRE groups, respectively) were lost to the intervention endpoint, owing to several reasons, including work incompatibility, lack of motivation or other health or personal issues not directly related to the intervention.

Description

• Initial Screening and Randomization: The study design is visually represented as a flow diagram, starting with an initial pool of 2,598 individuals who filled out a pre-screening questionnaire. This initial pool is then filtered down to 248 individuals who attended a screening visit, indicating that a large number of individuals did not meet the initial criteria or chose not to proceed after filling out the questionnaire. A key decision point is the 'Included in the screening visit' which leads to 'Did not meet eligibility criteria (n = 2,350)' and 'Randomized (n = 197)'. The 2,350 individuals not meeting the criteria are excluded, while the 197 that are eligible are then randomized into four groups: UC (Usual Care), early TRE (Time-Restricted Eating), late TRE, and self-selected TRE. The number of participants allocated to each group is approximately 49, 49, 52 and 47 respectively.
• Allocation, Follow-up and Analysis: After randomization, there's an 'Allocation' phase showing the number of participants allocated to each of the four groups, each with roughly equal numbers (UC: 49, early TRE: 49, late TRE: 52, self-selected TRE: 47). Subsequently, there is a 'Follow-up' phase where participants may drop out of the study. The number of participants lost to follow-up varies between the groups, with specific reasons listed, such as labor reasons, hypoglycemia, personal problems, or unknown reasons. The 'Analysis' phase indicates the number of participants analyzed in each group, reflecting those who completed the study (UC: 49, early TRE: 49, late TRE: 52, self-selected TRE: 47).
• Exclusion Criteria: The reasons for exclusion after screening are listed, including BMI (Body Mass Index), WC (Waist Circumference), not having CVD (Cardiovascular Disease) risk factors, eating window problems and specific diseases. This provides insight into the specific health and lifestyle factors that were considered important for the study population.

Scientific Validity

• Adherence to CONSORT Guidelines: The flow diagram accurately depicts the CONSORT guidelines for reporting randomized controlled trials, including the number of participants screened, excluded, randomized, lost to follow-up, and analyzed. This adherence to established reporting standards enhances the transparency and credibility of the study.
• Transparency in Reporting Exclusions and Drop-outs: The reasons for exclusion and loss to follow-up are clearly stated, providing valuable information about potential biases and limitations. For example, the exclusion of individuals with certain diseases and the reasons for drop-out (e.g., work incompatibility, lack of motivation) offer context for interpreting the results.
• Numerical Consistency: The numbers presented in the reference text ('Overall, 14 participants (3, 2, 4 and 5 participants from the UC and early, late and self-selected TRE groups, respectively) were lost to the intervention endpoint...') are consistent with the numbers displayed in the flow diagram.

Communication

• The study flow diagram is well-organized and easy to follow.: The figure provides a clear visual representation of the participant flow through the study, aiding in understanding the experimental design. The use of color-coding for different groups enhances clarity. The inclusion of drop-out numbers and reasons at each stage adds transparency.
• The caption is clear and informative.: The caption is concise and informative, accurately describing the figure's content. The abbreviations are defined, which is helpful for readers unfamiliar with those terms. Mentioning BioRender.com acknowledges the tool used for creating the figure.

Table 1 | Baseline characteristics of participants by intervention group

Figure/Table Image (Page 3)

First Reference in Text

A total of 197 participants (99 men and 98 women) were thus included in the intention-to-treat analysis. The participant baseline characteristics are shown in Table 1.

Description

• Overview of Baseline Characteristics: Table 1 presents the baseline characteristics of the 197 participants enrolled in the study, divided into four intervention groups: UC (Usual Care), Early TRE (Time-Restricted Eating), Late TRE, and Self-Selected TRE. Baseline characteristics are measurements taken at the start of the experiment before any intervention has taken place. These characteristics include age, sex (number of women), anthropometric measurements (weight, height, BMI (Body Mass Index)), abdominal adipose tissue (visceral, subcutaneous, and intermuscular), body composition (fat-free mass, appendicular lean mass, fat mass, fat mass percentage), blood pressure (systolic and diastolic), glucose homeostasis (fasting glucose, insulin, HOMA-IR (Homeostatic Model Assessment for Insulin Resistance), HbA1c (Glycated Hemoglobin)), blood lipid profile (total cholesterol, HDL-C (High-Density Lipoprotein Cholesterol), LDL-C (Low-Density Lipoprotein Cholesterol), triglycerides, APOA1 (Apolipoprotein A1), APOB (Apolipoprotein B)), and dietary intake (energy intake by 24HRs (24-hour dietary recalls)).
• Age, Sex and Anthropometry: The age of the participants is presented as the mean and standard deviation for each group (e.g., 46.7 (6.0) years for the UC group). The number of women in each group is also provided (e.g., 24 (49%) for the UC group). Anthropometric measures such as weight (e.g., 96.1 (14.4) kg for the UC group), height (e.g., 169.5 (9.1) cm for the UC group), and BMI (e.g., 33.4 (3.7) kg/m^2 for the UC group) are included. BMI, or Body Mass Index, is a simple calculation using a person's height and weight. The formula is BMI = kg/m^2 where kg is a person's weight in kilograms and m^2 is their height in metres squared.
• Adipose Tissue, Body Composition and Blood Pressure: Abdominal adipose tissue measurements are provided as median and interquartile range (e.g., 1,244 (862-1,771) cm^3 for visceral adipose tissue in the UC group). Body composition data, including fat-free mass (e.g., 55.5 (11.0) kg for the UC group), appendicular lean mass (e.g., 22.0 (5.2) kg for the UC group), fat mass (e.g., 39.7 (8.0) kg for the UC group), and fat mass percentage (e.g., 41.8 (6.7)% for the UC group), are also included. Blood pressure measurements, including systolic and diastolic BP, are presented as mean and standard deviation (e.g., 125 (13) mm Hg and 81 (11) mm Hg, respectively, for the UC group).
• Glucose Homeostasis and Blood Lipid Profile: Glucose homeostasis data includes fasting glucose (e.g., 93 (88-101) mg/dL for the UC group), insulin (e.g., 11.6 (8.7-13.5) mU/L for the UC group), HOMA-IR (e.g., 2.68 (2.20-3.40) for the UC group), HbA1c (e.g., 5.3 (5.2-5.6)% for the UC group), and 24-hour mean glucose (e.g., 107 (99-114) mg/dL for the UC group). HOMA-IR, or Homeostatic Model Assessment for Insulin Resistance, is a method used to quantify insulin resistance. It's calculated from fasting glucose and insulin levels. HbA1c, or Glycated Hemoglobin, is a blood test that reflects average blood sugar levels over the past 2-3 months. It's used to monitor diabetes control. Blood lipid profile includes total cholesterol (e.g., 211 (184-226) mg/dL for the UC group), HDL-C (e.g., 56 (45-64) mg/dL for the UC group), LDL-C (e.g., 128 (107-149) mg/dL for the UC group), triglycerides (e.g., 122 (84-158) mg/dL for the UC group), APOA1 (e.g., 164 (145-185) mg/dL for the UC group), and APOB (e.g., 101 (81-119) mg/dL for the UC group).
• Dietary Intake and Data Presentation: Dietary intake is assessed by energy intake from 24-hour dietary recalls (e.g., 2,012 (501) kcal/day for the UC group). The table also indicates whether data is presented as mean (standard deviation) or median (interquartile range) based on the distribution of the data.

Scientific Validity

• Importance of Baseline Characteristics: The table provides essential information for assessing the comparability of the intervention groups at baseline. The inclusion of a wide range of characteristics, including demographic, anthropometric, metabolic, and dietary variables, strengthens the rigor of the study.
• Appropriate Descriptive Statistics: The use of appropriate descriptive statistics (mean, standard deviation, median, interquartile range) based on the distribution of the data is commendable. However, a formal assessment of normality for each variable would further enhance the rigor of the analysis.
• Lack of Statistical Testing for Baseline Differences: While the table presents a comprehensive overview of baseline characteristics, a statistical test for significant differences between groups at baseline would enhance the scientific validity. This would confirm whether the randomization process was successful in creating comparable groups.

Communication

• Organization and Clarity: The table is well-organized, with clear headings and subheadings, facilitating easy comparison of baseline characteristics across the intervention groups. The use of appropriate statistical measures (mean, standard deviation, median, interquartile range) enhances the interpretability of the data.
• Comprehensiveness: The table provides comprehensive information about the baseline characteristics of the study participants, which is essential for assessing the comparability of the intervention groups at the start of the study. This allows readers to evaluate the potential for confounding factors.
• Use of Footnotes: The footnote provides necessary information about how data are presented (mean vs. median) and definitions of abbreviations (e.g., MRI).

Fig. 2 | Changes in VAT, body weight and composition after intervention. a-e,...

Full Caption

Fig. 2 | Changes in VAT, body weight and composition after intervention. a-e, Changes in VAT volume (a), VAT percentage (b), body weight (c), fat-free mass (d) and fat mass (e) among the UC, early TRE, late TRE and self-selected TRE groups after the 12 week intervention.

Figure/Table Image (Page 4)

First Reference in Text

The decrease in body weight was significantly greater in the early TRE group (mean difference: -2.9 kg; 95% CI, -4.7 to -1.1; P<0.001), late TRE group (mean difference: -2.4 kg; 95% CI, -4.2 to -0.6; P=0.004) and self-selected TRE group (mean difference: -3.1 kg; 95% CI, -4.9 to-1.2; P < 0.001) compared with the UC group (Fig. 2 and Table 2).

Description

• Overview of the Figure: Figure 2 presents the changes in visceral adipose tissue (VAT), body weight, and body composition after a 12-week intervention across four groups: UC (Usual Care), early TRE (Time-Restricted Eating), late TRE, and self-selected TRE. The figure is divided into five subplots (a-e), each representing a different outcome measure. These outcome measures are: change in VAT volume (a), change in VAT percentage (b), change in body weight (c), change in fat-free mass (d), and change in fat mass (e).
• Data Representation: Each subplot displays data points for individual participants in each group, along with the mean and 95% confidence interval (CI) for each group. The x-axis of each plot represents the intervention groups (UC, early TRE, late TRE, self-selected TRE), and the y-axis represents the change in the respective outcome measure after the intervention. Similar letters (a, b, c) above the data points indicate statistically significant differences between groups, determined by post hoc Bonferroni correction for multiple comparisons. The P values reported are two-sided and Bonferroni-adjusted.
• Significant Body Weight Changes: Body weight changes show that the early TRE group experienced a significant decrease in body weight. The mean difference in body weight change is -2.9 kg; the 95% confidence interval (CI) is -4.7 to -1.1; and the P value is less than 0.001. The late TRE group also experienced a statistically significant decrease in body weight, The mean difference in body weight change is -2.4 kg; the 95% confidence interval (CI) is -4.2 to -0.6; and the P value is 0.004. The self-selected TRE group also experienced a statistically significant decrease in body weight, The mean difference in body weight change is -3.1 kg; the 95% confidence interval (CI) is -4.9 to -1.2; and the P value is less than 0.001.
• Statistical Significance: The changes were calculated as the difference between post-intervention and pre-intervention values. The 95% confidence interval (CI) provides a range within which the true population mean is likely to fall, with a 95% certainty. The P-value indicates the probability of observing the results (or more extreme results) if there is no true effect. A P-value less than 0.05 is commonly considered statistically significant, indicating strong evidence against the null hypothesis.

Scientific Validity

• Accurate Representation of Statistical Results: The figure accurately reflects the results of the statistical analysis, with the significance indicators (a, b, c) corresponding to the reported P-values. The use of post hoc Bonferroni correction addresses the issue of multiple comparisons, enhancing the reliability of the findings.
• Inclusion of Confidence Intervals: The inclusion of 95% confidence intervals provides valuable information about the precision of the mean estimates. The absence of overlap between the confidence intervals of the TRE groups and the UC group for body weight changes supports the conclusion that the TRE interventions had a significant effect on body weight.
• Lack of Baseline Information: While the figure presents changes in VAT, body weight, and body composition, it would be beneficial to include information about the baseline values for these measures. This would allow the reader to assess the magnitude of the changes relative to the initial values.

Communication

• Effective Visualization of Data: The figure uses scatter plots with overlaid means and confidence intervals, which effectively visualize the distribution of data and the uncertainty around the mean estimates. This allows for a clear comparison of changes across the intervention groups.
• Clarity and Differentiation of Groups: The use of different symbols and colors for each intervention group enhances clarity and allows for easy differentiation between the groups. The inclusion of significance indicators (a, b, c) allows for a clear understanding of which groups differ significantly from each other.
• Informative Caption: The figure caption clearly describes what is being presented in each subplot (a-e), making it easy for the reader to understand the different outcomes being measured. The mention of '12 week intervention' provides context for the time frame of the changes.

Table 2 | Changes in abdominal adipose tissue, body composition, BP, glucose...

Full Caption

Table 2 | Changes in abdominal adipose tissue, body composition, BP, glucose homeostasis, blood lipid profile and dietary intake endpoints in the TRE groups compared with the UC group after the 12 week intervention

Figure/Table Image (Page 5)

First Reference in Text

We could not detect statistically significant differences in VAT changes between the early TRE (mean difference: -4%; 95% confidence interval (CI), -12 to 4; P = 0.87), the late TRE (mean difference: -6%; 95% CI, -13 to 2; P = 0.31) and the self-selected TRE groups (mean difference: -3%; 95% CI, -11 to 5; P≥ 0.99) compared with the UC group (Fig. 2 and Table 2).

Description

• Overview of Endpoints: Table 2 presents the changes in various endpoints after a 12-week intervention in TRE (Time-Restricted Eating) groups compared to a UC (Usual Care) group. The table displays the mean difference and 95% Confidence Interval (CI) for each endpoint, showing the impact of the intervention relative to the control group. The endpoints include abdominal adipose tissue (visceral cm³, visceral %, subcutaneous cm³, subcutaneous %, intermuscular cm³, intermuscular %), body composition (weight kg, weight %, fat-free mass kg, appendicular lean mass kg, fat mass kg, fat mass %), blood pressure (systolic BP mm Hg, diastolic BP mm Hg), glucose homeostasis (fasting glucose mg dl⁻¹, insulin mUl⁻¹, HOMA-IR, HbA1c %, 24h mean glucose mgdl⁻¹, Diurnal mean glucose mgdl⁻¹, Nocturnal mean glucose mgdl⁻¹, 24h CV glucose %, Diurnal CV glucose %, Nocturnal CV glucose %), blood lipid profile (Total cholesterol mg dl⁻¹, HDL-C mgdl⁻¹, LDL-C mgdl⁻¹, Triglycerides mgdl⁻¹, APOA1 mg dl⁻¹, APOB mgdl⁻¹), dietary intake (Energy intake by 24HRs kcald⁻¹).
• Abdominal Adipose Tissue: For abdominal adipose tissue, the table presents the mean difference and 95% CI for visceral adipose tissue in cm³ and as a percentage. For example, the early TRE group had a mean difference of -75 cm³ (95% CI: -198, 48) compared to the UC group. A confidence interval (CI) is a range of values that's likely to contain a population parameter (like the true mean difference). A 95% CI means that if the same population were sampled repeatedly, approximately 95% of the intervals calculated would contain the true population parameter.
• Body Composition, Blood Pressure and Glucose Homeostasis: For body composition, the table presents the mean difference and 95% CI for weight in kg and as a percentage, fat-free mass, appendicular lean mass, fat mass, and fat mass percentage. For blood pressure, the table presents the mean difference and 95% CI for systolic and diastolic blood pressure. For glucose homeostasis, the table includes mean difference and 95% CI for fasting glucose, insulin, HOMA-IR, HbA1c, 24h mean glucose, diurnal mean glucose, nocturnal mean glucose, 24h CV glucose, diurnal CV glucose, and nocturnal CV glucose. HOMA-IR, or Homeostatic Model Assessment for Insulin Resistance, is a method used to quantify insulin resistance. It's calculated from fasting glucose and insulin levels. HbA1c, or Glycated Hemoglobin, is a blood test that reflects average blood sugar levels over the past 2-3 months. It's used to monitor diabetes control. CV glucose is a measure of glucose variability.
• Blood Lipid Profile and Dietary Intake: For the blood lipid profile, the table presents the mean difference and 95% CI for total cholesterol, HDL-C (High-Density Lipoprotein Cholesterol), LDL-C (Low-Density Lipoprotein Cholesterol), triglycerides, APOA1, and APOB. For dietary intake, the table presents the mean difference and 95% CI for energy intake by 24HRs (24-hour dietary recalls). An asterisk (*) indicates a statistically significant difference between the TRE group and the UC group.

Scientific Validity

• Comprehensive Overview of Changes: The table provides a comprehensive overview of the changes in various endpoints, allowing for a thorough assessment of the effects of the interventions. The inclusion of mean differences, confidence intervals, and p-values allows for a clear understanding of the statistical significance and precision of the findings.
• Facilitates Comparison of Interventions: The table allows for easy comparison of the effects of different TRE interventions on various outcomes. The inclusion of data for multiple endpoints provides a more complete picture of the effects of the interventions on cardiometabolic health.
• Lack of Information on Statistical Methods: The table presents data on a wide range of variables, but it does not include information about the statistical methods used to calculate the mean differences and confidence intervals. Specifying the statistical methods (e.g., ANOVA, t-tests) would enhance the rigor of the analysis.

Communication

• Organization and Clarity: The table is well-organized, with clear headings and subheadings, facilitating easy comparison of changes in various endpoints across the intervention groups. The inclusion of mean differences and confidence intervals provides a clear indication of the magnitude and precision of the effects.
• Comprehensiveness: The table provides comprehensive information about the changes in a wide range of outcomes, including abdominal adipose tissue, body composition, blood pressure, glucose homeostasis, blood lipid profile, and dietary intake. This allows readers to assess the effects of the interventions on multiple aspects of cardiometabolic health.
• Clear Indication of Statistical Significance: The use of asterisks to indicate statistically significant differences is helpful for quickly identifying significant findings. The table also provides the mean difference and 95% CI, allowing readers to assess the clinical significance of the findings.

Fig. 3 24 h glucose profiles before and after the intervention. a-d, Glucose...

Full Caption

Fig. 3 24 h glucose profiles before and after the intervention. a-d, Glucose levels during 24 h as measured by CGM over 14 days in both the baseline and the last 2 weeks of the 12 week intervention for the UC (a), early TRE (b), late TRE (c) and self-selected TRE (d) groups.

Figure/Table Image (Page 8)

First Reference in Text

Figure 3 shows the interstitial glucose levels across 24 h, tracked by continuous glucose monitoring (CGM) for 14 days at baseline and during the final 2 weeks of the 12 week intervention.

Description

• Overview of Glucose Profiles: Figure 3 presents 24-hour glucose profiles, measured using Continuous Glucose Monitoring (CGM), for four groups: UC (Usual Care), early TRE (Time-Restricted Eating), late TRE, and self-selected TRE. Each group's glucose levels are tracked over 14 days, both at baseline (before the intervention) and during the last two weeks of the 12-week intervention. Continuous Glucose Monitoring (CGM) is a method used to track glucose levels in real-time throughout the day and night, using a small sensor inserted under the skin. Each of the four subplots (a-d) corresponds to one of the intervention groups.
• Data Representation: In each subplot, the x-axis represents the time of day (0-24 hours), and the y-axis represents the glucose level in mg/dL (milligrams per deciliter). Two lines are plotted on each graph: one representing the glucose levels at baseline and another representing the glucose levels during the last two weeks of the intervention. The solid lines represent mean glucose levels, and the shaded areas around the lines represent the 95% confidence interval (CI). A confidence interval (CI) is a range of values that's likely to contain a population parameter (like the true mean). A 95% CI means that if the same population were sampled repeatedly, approximately 95% of the intervals calculated would contain the true population parameter.
• Eating Window Representation: Each subplot also includes a colored bar indicating the eating window for the respective group. The color intensity of the eating window corresponds to the number of participants having their meals at that specific time of day. This provides a visual representation of when participants in each group were consuming their meals.

Scientific Validity

• Use of Continuous Glucose Monitoring: The use of CGM to track glucose levels provides a detailed and continuous assessment of glucose dynamics throughout the day. This is a strength of the study, as it captures more nuanced information than traditional fasting glucose measurements.
• Lack of Information on Statistical Methods: The figure presents mean glucose levels and confidence intervals, but it would be helpful to include information about the statistical methods used to compare the glucose profiles between groups. Specifying the statistical methods (e.g., repeated measures ANOVA) would enhance the rigor of the analysis.
• Lack of Statistical Significance Indicators: While the figure provides a visual representation of the glucose profiles, it would be beneficial to include information about the statistical significance of the differences between the baseline and intervention glucose levels. This could be done by including p-values or significance indicators on the plots.

Communication

• Effective Visualization of Glucose Profiles: The figure effectively visualizes the 24-hour glucose profiles for each intervention group, allowing for a comparison of glucose levels throughout the day. The use of shaded areas to represent confidence intervals provides a measure of the variability in the data.
• Inclusion of Eating Window: The inclusion of the eating window on each plot is helpful for understanding the relationship between meal timing and glucose levels. The color intensity of the eating window provides information about the number of participants having their meals at that specific time of day.
• Informative Caption: The caption is clear and informative, accurately describing what is being presented in each subplot (a-d). The mention of 'CGM over 14 days' provides context for the data collection period.

Table 3 | Changes in abdominal adipose tissue, body composition, BP, glucose...

Full Caption

Table 3 | Changes in abdominal adipose tissue, body composition, BP, glucose homeostasis, blood lipid profile and dietary intake endpoints in the TRE groups compared with each other after the 12 week intervention

Figure/Table Image (Page 7)

First Reference in Text

In addition, there were no statistically significant differences between the early TRE and the late TRE groups (mean difference: 1%; 95% CI, -6 to 9; P≥ 0.99), between the early TRE and self-selected TRE groups (mean difference: -1%; 95% CI, -9 to 7; P≥ 0.99) and between the late TRE and self-selected TRE groups (mean difference: -2%; 95% CI, -10 to 5; P≥ 0.99) (Table 3).

Description

• Overview of Endpoints: Table 3 presents the changes in various endpoints after a 12-week intervention in the TRE (Time-Restricted Eating) groups compared to each other. It shows how the early TRE, late TRE, and self-selected TRE groups compare. The table displays the mean difference and 95% Confidence Interval (CI) for each endpoint. It includes abdominal adipose tissue (visceral cm³, visceral %, subcutaneous cm³, subcutaneous %, intermuscular cm³, intermuscular %), body composition (weight kg, weight %, fat-free mass kg, appendicular lean mass kg, fat mass kg, fat mass %), blood pressure (systolic BP mm Hg, diastolic BP mm Hg), glucose homeostasis (fasting glucose mg dl⁻¹, insulin mUl⁻¹, HOMA-IR, HbA1c %, 24h mean glucose mgdl⁻¹, Diurnal mean glucose mgdl⁻¹, Nocturnal mean glucose mgdl⁻¹, 24h CV glucose %, Diurnal CV glucose %, Nocturnal CV glucose %), blood lipid profile (Total cholesterol mg dl⁻¹, HDL-C mgdl⁻¹, LDL-C mgdl⁻¹, Triglycerides mgdl⁻¹, APOA1 mg dl⁻¹, APOB mgdl⁻¹), dietary intake (Energy intake by 24HRs kcald⁻¹).
• Abdominal Adipose Tissue: For abdominal adipose tissue, the table presents the mean difference and 95% CI for visceral adipose tissue in cm³ and as a percentage, comparing the TRE groups to each other. A confidence interval (CI) is a range of values that's likely to contain a population parameter (like the true mean difference). A 95% CI means that if the same population were sampled repeatedly, approximately 95% of the intervals calculated would contain the true population parameter.
• Body Composition, Blood Pressure and Glucose Homeostasis: For body composition, the table presents the mean difference and 95% CI for weight in kg and as a percentage, fat-free mass, appendicular lean mass, fat mass, and fat mass percentage. For blood pressure, the table presents the mean difference and 95% CI for systolic and diastolic blood pressure. For glucose homeostasis, the table includes mean difference and 95% CI for fasting glucose, insulin, HOMA-IR, HbA1c, 24h mean glucose, diurnal mean glucose, nocturnal mean glucose, 24h CV glucose, diurnal CV glucose, and nocturnal CV glucose. HOMA-IR, or Homeostatic Model Assessment for Insulin Resistance, is a method used to quantify insulin resistance. It's calculated from fasting glucose and insulin levels. HbA1c, or Glycated Hemoglobin, is a blood test that reflects average blood sugar levels over the past 2-3 months. It's used to monitor diabetes control. CV glucose is a measure of glucose variability.
• Blood Lipid Profile and Dietary Intake: For the blood lipid profile, the table presents the mean difference and 95% CI for total cholesterol, HDL-C (High-Density Lipoprotein Cholesterol), LDL-C (Low-Density Lipoprotein Cholesterol), triglycerides, APOA1, and APOB. For dietary intake, the table presents the mean difference and 95% CI for energy intake by 24HRs (24-hour dietary recalls). An asterisk (*) indicates a statistically significant difference between the TRE groups compared to each other.

Scientific Validity

• Comprehensive Overview of Changes: The table provides a comprehensive overview of the changes in various endpoints, allowing for a thorough assessment of the relative effects of different TRE interventions. The inclusion of mean differences, confidence intervals, and p-values allows for a clear understanding of the statistical significance and precision of the findings.
• Focus on Relative Effectiveness of TRE Timings: The focus on comparing the different TRE groups to each other, rather than to the UC group, provides valuable information about the relative effectiveness of different TRE timings.
• Lack of Information on Statistical Methods: The table presents data on a wide range of variables, but it does not include information about the statistical methods used to calculate the mean differences and confidence intervals. Specifying the statistical methods (e.g., ANOVA, t-tests) would enhance the rigor of the analysis.

Communication

• Organization and Clarity: The table's organization, with clear headings and subheadings, facilitates easy comparison of changes in various endpoints across the different TRE groups. The inclusion of mean differences and confidence intervals provides a clear indication of the magnitude and precision of the effects.
• Comprehensiveness: The table provides comprehensive information about the changes in a wide range of outcomes, including abdominal adipose tissue, body composition, blood pressure, glucose homeostasis, blood lipid profile, and dietary intake. This allows readers to assess the effects of different TRE timings on multiple aspects of cardiometabolic health relative to each other.
• Clear Indication of Statistical Significance: The use of asterisks to indicate statistically significant differences is helpful for quickly identifying significant findings. The table also provides the mean difference and 95% CI, allowing readers to assess the clinical significance of the findings.

Discussion

Key Aspects

• No Significant Difference in VAT Reduction with TRE Timing: The study found that adding time-restricted eating (TRE), regardless of the timing of the 8-hour eating window (early, late, or self-selected), to a usual care (UC) intervention based on a Mediterranean diet did not significantly reduce visceral adipose tissue (VAT) compared to UC alone in adults with overweight or obesity. This is the primary finding and suggests that the timing of TRE, when combined with a healthy diet, does not provide additional benefits for VAT reduction.
• Greater SAT Reduction with Early TRE: The early TRE group showed a more pronounced reduction in subcutaneous adipose tissue (SAT) compared to the UC group. This finding suggests a potential specific benefit of early TRE for reducing SAT, although the clinical significance of this difference requires further investigation.
• Greater Body Weight Loss with TRE: All three TRE groups (early, late, and self-selected) experienced greater body weight loss compared to the UC group, with no significant differences among the TRE groups themselves. This indicates that TRE, regardless of timing, can lead to greater weight loss than the control condition (Mediterranean diet education alone).
• Improved Glucose Homeostasis with Early TRE: The early TRE group showed decreased fasting glucose and nocturnal mean glucose levels compared to the UC, late TRE, and self-selected TRE groups. This suggests a potential advantage of early TRE for improving glucose homeostasis, potentially due to alignment with circadian rhythms and diurnal variations in glucose tolerance.
• No Differences in Other Cardiometabolic Risk Factors: There were no significant differences in body composition (other than SAT) and other cardiometabolic risk factors (e.g., blood pressure, insulin resistance, HbA1c, blood lipids) across all groups. This suggests that the different TRE schedules did not differentially affect these parameters.
• TRE is Safe and Tolerable: TRE was found to be a safe and tolerable dietary approach for obesity management, with no major adverse events reported. Mild adverse events were reported by a small number of participants, leading to discontinuation in five cases. This supports the feasibility and safety of TRE as a dietary intervention.
• Comparison with Existing Literature: The study's findings are discussed in the context of existing literature, with comparisons to previous studies investigating the effects of TRE on VAT, body weight, and glucose homeostasis. The authors highlight similarities and discrepancies with previous findings and offer potential explanations for these differences.
• Discussion of Potential Mechanisms: The authors discuss potential mechanisms underlying the observed effects, including the roles of caloric restriction, weight loss, and meal timing. They suggest that caloric restriction and weight/fat loss are key factors in reducing VAT, while the effects of fasting and meal timing may play a secondary role.
• Study Limitations: The study acknowledges several limitations, including the sample size, study duration, blinding procedures (only personnel evaluating the primary outcome were blinded), the inclusion of a usual care intervention in all groups, potential heterogeneity due to adherence to the Mediterranean diet, and the absence of follow-up data.
• Adherence to TRE: The study highlights the high adherence across the TRE groups. It also notes that the self-selected group was included to potentially enhance adherence, acceptability, and effectiveness.

Strengths

• Clear Summary of Main Findings

  The Discussion section clearly summarizes the main findings of the study, highlighting the lack of significant differences in VAT reduction between the TRE groups and the control group, and the greater reduction in SAT in the early TRE group.

  "This multicenter randomized controlled trial found that adding TRE, irrespective of the timing of the eating window, into the UC intervention (Mediterranean diet nutritional education program) did not significantly reduce VAT compared with UC alone in adults with overweight or obesity. The early TRE group showed a more pronounced reduction in SAT than the UC group." (Page 6)
• Contextualization Within Existing Literature

  The Discussion section appropriately contextualizes the study's findings within the existing literature, comparing the results to those of previous studies and highlighting similarities and differences.

  "Our results align with those of Deng et al.12 who showed no statistically significant difference between 8 h early and late schedules in reducing VAT and SAT, both measured by MRI, as well as body weight and fat mass in individuals with metabolic dysfunction-associated steatotic liver disease over an 8 week trial." (Page 6)
• Discussion of Potential Mechanisms

  The Discussion section addresses the potential mechanisms underlying the observed effects, such as the role of caloric restriction, weight loss, and meal timing in VAT reduction.

  "Overall, previous studies and our findings suggest that caloric restriction and weight and fat loss are key in reducing VAT. By contrast, the effects of fasting and meal timing might play a secondary role7,13." (Page 6)
• Acknowledgement of Study Limitations

  The Discussion section acknowledges the limitations of the study, such as the sample size, study duration, blinding procedures, and lack of follow-up.

  "The study has several limitations that warrant mention. Firstly, the sample size and relatively short study duration may limit our ability to detect differences in VAT and other outcomes among the intervention groups." (Page 8)
• Clear Conclusion and Implications

  The Discussion section concludes by reiterating the main findings and their implications, suggesting that TRE, regardless of timing, offers no additional benefit over a Mediterranean diet alone in reducing VAT, but is a safe and tolerable dietary approach.

  "In this 12 week multicenter randomized controlled trial involving men and women with overweight or obesity, we found that incorporating TRE, regardless of the timing of the eating window, into the UC intervention (Mediterranean diet nutritional education program) does not offer any additional benefit over the UC alone for reducing VAT." (Page 8)

Suggestions for Improvement

• Discuss Within-Group VAT Changes

  This medium-impact improvement would enhance the Discussion section's depth and provide a more nuanced interpretation of the findings. While the Discussion mentions the *lack* of significant difference in VAT reduction between TRE and UC, it doesn't sufficiently discuss the *observed* reductions in VAT within *each* group. Even if not statistically different *between* groups, the magnitude and clinical relevance of the VAT changes *within* each group (including UC) deserve discussion. This is important for the Discussion, as it provides a more complete picture of the intervention's effects and helps readers understand the overall impact on VAT.

  "This multicenter randomized controlled trial found that adding TRE, irrespective of the timing of the eating window, into the UC intervention (Mediterranean diet nutritional education program) did not significantly reduce VAT compared with UC alone in adults with overweight or obesity." (Page 6)

  Implementation: Add a paragraph or sentences discussing the observed changes in VAT *within* each group (including the UC group). Mention the magnitude of these changes (using data from Fig. 2 and the Results section) and discuss whether these changes are clinically meaningful, even if not statistically different between groups. For example, "While no statistically significant differences were found between groups, it's important to note the magnitude of VAT reduction observed within each group. The UC group experienced a mean reduction of [X] cm3, while the TRE groups showed reductions ranging from [Y] to [Z] cm3. These changes may be clinically relevant, even if not statistically different, and warrant further investigation."

• Address Conflicting Evidence on Early TRE

  This high-impact improvement would strengthen the Discussion by providing a more balanced and critical appraisal of the existing literature. While the Discussion cites studies with *similar* findings, it doesn't adequately address studies with *conflicting* results, particularly regarding the potential benefits of *early* TRE on glucose homeostasis. The Discussion section should acknowledge and discuss *all* relevant evidence, not just supportive evidence. This is crucial for providing a comprehensive and unbiased overview of the research landscape.

  "The evidence regarding the timing of the eating window during TRE on glycemic traits is mixed. While some studies did not find significant differences in fasting glucose, insulin and HOMA-IR between early and late TRE12,17–19, Xie et al.16 reported a greater reduction in HOMA-IR, but not in fasting glucose, with early TRE compared with late TRE after 5 weeks of intervention." (Page 6)

  Implementation: Include a paragraph or sentences discussing studies that have shown *different* results, particularly those suggesting benefits of early TRE on glucose homeostasis. Acknowledge these conflicting findings and offer potential explanations for the discrepancies (e.g., differences in study populations, intervention durations, eating window lengths). For example: "While our findings suggest no significant difference between early and late TRE on most cardiometabolic outcomes, some studies have reported greater improvements in glucose homeostasis with early TRE [cite relevant studies]. These discrepancies may be due to differences in participant characteristics, such as baseline metabolic status, or variations in the intervention protocols, including the length of the eating window."

• Define "Eucaloric"

  This low-impact improvement would add clarity and context. The Discussion section mentions "eucaloric early TRE" in the context of a study by Sutton et al., but it doesn't fully explain what "eucaloric" means in this context. While some readers will understand this term, providing a brief definition within the Discussion would improve accessibility for a broader audience. This is important for the Discussion, as it ensures that all readers can fully understand the cited research and its relevance to the current study.

  "In addition, Sutton et al.14 showed that eucaloric (that is, energy intake equals energy needs, resulting in the absence of weight loss) early TRE led to an improvement in insulin sensitivity and β cell responsiveness in men with prediabetes compared with an" (Page 6)

  Implementation: Add a brief parenthetical explanation of "eucaloric" when it's first mentioned. For example, change "...Sutton et al.14 showed that eucaloric early TRE..." to "...Sutton et al.14 showed that eucaloric (that is, energy intake equals energy needs, resulting in the absence of weight loss) early TRE..."

• Discuss Clinical and Public Health Implications

  This medium-impact improvement would enhance the Discussion's practical implications. While the Discussion mentions that TRE is "safe and tolerable," it could be strengthened by more explicitly discussing the implications of the findings for clinical practice and public health recommendations. This is important for the Discussion, as it helps translate the research findings into actionable advice.

  "In this 12 week multicenter randomized controlled trial involving men and women with overweight or obesity, we found that incorporating TRE, regardless of the timing of the eating window, into the UC intervention (Mediterranean diet nutritional education program) does not offer any additional benefit over the UC alone for reducing VAT." (Page 8)

  Implementation: Add a paragraph or sentences specifically addressing the implications for clinical practice and/or public health. For example: "Given the lack of significant differences between TRE schedules and the high adherence rates observed, our findings suggest that clinicians may consider TRE as a flexible dietary option for individuals with overweight or obesity, allowing patients to choose an eating window that best suits their lifestyle. However, it's important to emphasize that TRE, in this context, was combined with education about the Mediterranean diet, and the benefits may not be solely attributable to TRE itself."

Methods

Key Aspects

• Study Design: This was an investigator-initiated, parallel-group, multicenter randomized clinical trial. This design is considered the gold standard for evaluating the efficacy of interventions, as it minimizes bias and allows for causal inferences.
• Participant Eligibility Criteria: The study included men and women aged 30 to 60 years with overweight or obesity (BMI ≥ 25.0 and < 40.0 kg/m²), abdominal obesity, weight stability, a sedentary lifestyle, a habitual eating window of at least 12 hours, and at least one cardiometabolic risk factor. These criteria ensured that the study population was relevant to the research question and had potential to benefit from the intervention.
• Recruitment and Enrollment: Participants were recruited through advertisements and from Endocrinology and Nutrition services at two hospitals in Spain. Potential participants underwent clinical and physical examinations to ensure eligibility before enrollment.
• Randomization: Enrolled participants were randomly assigned to one of four groups: usual care (UC), early time-restricted eating (TRE), late TRE, or self-selected TRE. Randomization was stratified by site and sex, and used permuted blocks with random block sizes of 4 and 8. This ensured balanced allocation to the intervention groups and minimized selection bias.
• Blinding: Personnel in charge of evaluating the primary outcome (VAT and other ectopic fat depots measured by MRI), fasting blood samples, and statistical analysis were blinded to group assignment. Personnel in charge of other measures and the intervention were not blinded (open-label). This blinding strategy aimed to minimize assessment bias for the primary outcome.
• Outcomes: The primary outcome was changes in VAT percentage measured by MRI. Secondary outcomes included changes in subcutaneous adipose tissue (SAT), intermuscular adipose tissue, body weight, body composition, blood pressure, glucose homeostasis, blood lipid profile, dietary intake, physical activity, and sleep. These outcomes were assessed at baseline and 12 weeks post-intervention.
• Intervention and Control Conditions: The UC group continued their usual eating window schedule and received an educational program for weight management and cardiovascular health promotion based on the Mediterranean diet and World Health Organization physical activity recommendations. The TRE groups received the same educational program and were instructed to follow an 8-hour eating window. Early TRE participants chose a window starting no later than 10:00, late TRE participants chose a window starting no earlier than 13:00, and self-selected TRE participants chose their preferred 8-hour window.
• Intervention Meetings: Intervention meetings for all groups were held every 2 weeks by experienced dietitians and covered topics such as healthy lifestyle, food intake organization, hunger and satiety control, nutritional labeling, nutritional myths, and healthy snacks. Participants discussed challenges and received tailored support.
• Meal Timing Recording: Participants recorded the exact time of their first and last meal over the 12-week intervention period using a custom mobile phone app. Calorie-containing food or beverage intake outside the eating window was not allowed for the TRE groups, but water, coffee, and tea without sugar or artificial sweeteners were permitted.
• Sample Size Calculation: The sample size was estimated based on previous studies, providing 90% statistical power at an alpha level of 0.008 (adjusted for multiple comparisons) to detect a minimum effect size of 10% in VAT. This indicates that the study was adequately powered to detect meaningful differences in the primary outcome.
• Statistical Analysis: Intervention effects were assessed using repeated-measures linear mixed-effects multilevel models, which included random cluster (site) effects. Individual measures of change were modeled as a function of randomly assigned group, site, assessment time, and their interaction terms. Sex was also considered as a covariate. Model-based estimations were performed with an intention-to-treat approach, and Bonferroni correction was applied to account for multiple comparisons.

Strengths

• Clear Statement of Study Design

  The Methods section clearly states that the study was an investigator-initiated, parallel-group, multicenter randomized clinical trial, providing a concise overview of the study design.

  "This study was an investigator-initiated, parallel-group, multicenter randomized clinical trial." (Page 11)
• Detailed Description of Eligibility Criteria

  The section provides a detailed description of the participant eligibility criteria, including age, BMI, waist circumference, weight stability, lifestyle, eating window, and cardiometabolic risk factors, ensuring transparency and replicability.

  "Eligible participants were men and women aged 30 to 60 years with overweight or obesity (body mass index (BMI) ≥ 25.0 and <40.0 kg m−2), abdominal obesity (waist circumference ≥95 cm in men and ≥82 cm in women), weight stability, a sedentary lifestyle, a habitual eating window ≥12 h and at least one cardiometabolic risk factor for metabolic syndrome25." (Page 11)
• Reference to Study Protocol

  The study protocol is referenced, allowing readers to access detailed information on the trial rationale, design, and methods, promoting transparency and reproducibility.

  "For detailed information on the trial rationale, design and methods, readers are referred to the study protocol25." (Page 11)
• Clear Description of Randomization Process

  The randomization process is clearly described, including stratification by site and sex, and the use of permuted blocks with random block sizes, ensuring balanced allocation to the intervention groups.

  "Subsequently, enrolled participants were randomly assigned to one of four groups (that is, UC, early TRE, late TRE or self-selected TRE) using both stratification for each site and sex, and permuted blocks with random block sizes of 4 and 8, one randomization list being generated for each site and strata." (Page 11)
• Clear Definition of Outcomes and Measurement Methods

  The primary and secondary outcomes are clearly defined, including the measurement methods (MRI for VAT, stadiometer and scale for body weight and height, etc.), providing a comprehensive overview of the assessed variables.

  "The primary outcome was VAT changes in percentage measured by MRI (Siemens 3 T Magnetom Vida)." (Page 11)
• Detailed Statistical Analysis Plan

  The statistical analysis plan is described in detail, including the use of repeated-measures linear mixed-effects multilevel models, intention-to-treat approach, Bonferroni correction, and software used, ensuring transparency and replicability.

  "Intervention effects on primary and secondary outcomes at 3 months after the intervention were assessed based on repeated-measures linear mixed-effects multilevel models, which included random cluster (site) effects34." (Page 12)

Suggestions for Improvement

• Specify Roles of Blinded Personnel

  This medium-impact improvement would enhance the clarity and completeness of the Methods section. While the section mentions blinding of personnel evaluating the primary outcome, it doesn't explicitly state *who* was blinded (e.g., radiologists, technicians, statisticians). The Methods section is where readers expect to find all details relevant to reducing bias. Specifying the roles of those blinded would strengthen the study's methodological rigor and transparency.

  "Personnel in charge of the evaluations of the primary outcome (that is, VAT and other ectopic MRI-derived fat depots), fasting blood samples and statistical analysis were blinded to the group assignment, whereas personnel in charge of the other measures as well as the intervention were not blinded to the group assignment (open label)." (Page 11)

  Implementation: Clarify the specific roles of the personnel who were blinded to group assignment. For example, instead of "Personnel in charge of the evaluations of the primary outcome...were blinded...", specify "Radiologists and technicians responsible for MRI acquisition and analysis, as well as statisticians performing the primary outcome analysis, were blinded to group assignment."

• Provide More Detail on Educational Program Content

  This high-impact improvement would significantly improve the reproducibility and transparency of the study. The Methods section describes the intervention and control conditions, but it doesn't provide sufficient detail about the *content* of the educational program on the Mediterranean diet and physical activity. The Methods section is where researchers expect to find all details needed to replicate the study. Providing a more detailed description (or referencing a readily accessible resource containing this information) is crucial for other researchers to implement the same intervention.

  "Intervention meetings for all groups separately were held every 2 weeks by experienced dietitians. These meetings covered six topics: (1) healthy lifestyle based on Mediterranean dietary patterns and physical activity recommendations, (2) organization and planning of food intake, (3) control of hunger and satiety, (4) nutritional labeling, (5) nutritional myths and (6) healthy snacks." (Page 11)

  Implementation: Provide a more detailed description of the educational program content. This could include: (1) Specific topics covered in each session (beyond the general list provided). (2) The format of the sessions (e.g., lectures, group discussions, handouts). (3) The qualifications of the dietitians delivering the program (beyond "experienced"). (4) The duration and frequency of each session. Alternatively, provide a reference to a publicly available resource (e.g., a website or supplementary material) that contains the full program details.

• Describe Mobile App Features

  This low-impact improvement would enhance the clarity and completeness of the Methods section. While the section mentions the use of a custom mobile phone app (EXTREME) for recording meal timing, it doesn't describe the app's features or how it was used to ensure accurate data collection. The Methods section should include all details relevant to data quality. Briefly describing the app's functionality would improve transparency and allow readers to assess the reliability of the meal timing data.

  "All participants recorded the exact time of the first and last meal over the 12-week intervention period using a custom mobile phone app (EXTREME: com.nnbi. app_extreme, NNBi2020 S L)." (Page 12)

  Implementation: Provide a brief description of the EXTREME app's features and how it was used to ensure accurate data collection. For example: "Participants used a custom mobile phone app (EXTREME) to record the exact time of their first and last meal each day. The app included features such as [list key features, e.g., reminders, photo uploads, timestamps]. Data were reviewed weekly by research staff to ensure completeness and accuracy."

• Specify Accelerometer Data Processing Procedures

  This medium-impact improvement would enhance the clarity and methodological rigor of the Methods section. While the section mentions the use of accelerometers to measure physical activity, it doesn't specify the *accelerometer data processing procedures*. The Methods section should provide all details needed to replicate the study. This is crucial for physical activity research, as different processing methods can lead to different results. Specifying these details is essential for transparency and reproducibility.

  "Concurrently, physical activity levels and sedentary behavior were objectively measured using accelerometers (ActiGraph GT3X in both Granada and Pamplona) worn on the nondominant wrist and the data processed in the GGIR R package (version 2.10-3)." (Page 11)

  Implementation: Provide details on the accelerometer data processing procedures, including: (1) The epoch length used (e.g., 60 seconds). (2) The criteria for defining non-wear time (e.g., 90 consecutive minutes of zero counts). (3) The cut-points used to define different intensity levels (e.g., sedentary, light, moderate, vigorous). (4) The minimum wear time required for a day to be considered valid (e.g., 10 hours). (5) The minimum number of valid days required for inclusion in the analysis.