Aerobic Exercise andWeight Loss in Adults A Systematic Review and Dose-Response Meta-Analysis

Abstract

Key Aspects

• Dose-Response Association of Aerobic Exercise and Adiposity: This meta-analysis investigates the dose-response relationship between aerobic exercise and adiposity measures, including body weight, waist circumference, and body fat, in adults with overweight or obesity. It addresses a gap in existing literature, which primarily relies on individual trials rather than comprehensive meta-analyses to establish this relationship.
• Methodology: Systematic Review and Meta-Analysis: The study employs a rigorous systematic review and dose-response meta-analysis methodology. It adheres to PRISMA guidelines and includes data from PubMed, Scopus, the Cochrane Central Register of Controlled Trials, and gray literature sources. The analysis incorporates 116 randomized clinical trials involving 6880 participants, enhancing the robustness and generalizability of the findings.
• Primary Findings: Linear and Monotonic Reductions in Adiposity: The results indicate that body weight, waist circumference, and body fat measures decrease linearly or monotonically with increasing duration of aerobic exercise up to 300 minutes per week at moderate to vigorous intensities. Each 30-minute increment of aerobic exercise per week is associated with significant reductions in these adiposity measures.
• Clinical Significance Threshold: 150 Minutes per Week: A key finding is that aerobic exercise of at least 150 minutes per week at moderate intensity or higher is associated with clinically important reductions in waist circumference and measures of body fat. This aligns with existing guidelines but provides more specific quantitative evidence for the dose-response relationship.
• Impact on Quality of Life and Adverse Events: The study also examines the impact of aerobic exercise on quality of life and adverse events. It finds that aerobic exercise is associated with modest improvements in physical and mental aspects of quality of life, albeit with low certainty. Additionally, it notes a modest increase in mild to moderate adverse events, primarily musculoskeletal symptoms.
• Certainty of Evidence: GRADE Assessment: The certainty of the evidence is assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. The certainty ranges from very low to high, with moderate certainty for the association between aerobic exercise and body weight reduction, and high certainty for the association with waist circumference reduction.

Strengths

• Comprehensive Data Synthesis

  The abstract effectively synthesizes data from a large number of randomized clinical trials, providing a robust overview of the dose-response association between aerobic exercise and adiposity measures.

  "This meta-analyses of 116 randomized clinical trials involving 6880 adults with overweight or obesity" (Page 1)
• Clear Presentation of Key Findings

  The abstract clearly presents the main findings, including the linear or monotonic reductions in body weight, waist circumference, and body fat with increasing aerobic exercise duration.

  "levels of body weight, waist circumference, and body fat decreased linearly or monotonically with increasing duration of aerobic exercise" (Page 1)
• Use of GRADE for Evidence Assessment

  The inclusion of the GRADE assessment adds a layer of rigor by providing an evaluation of the certainty of the evidence for each outcome.

  "The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool" (Page 1)

Suggestions for Improvement

• Clarify Clinical Importance Threshold

  This medium-impact improvement would enhance the practical applicability of the study's findings. The Abstract section is the entry point for readers to grasp the study's significance, and therefore, a more precise definition of "clinically important reductions" would be valuable here. Elaborating on this point would strengthen the paper by providing a clearer benchmark for clinicians and researchers to interpret the magnitude of the observed effects. This would also facilitate the translation of these findings into actionable recommendations for exercise prescription. Ultimately, providing a more specific definition of the clinical importance threshold would improve the study's impact by making its findings more readily interpretable and applicable in real-world settings.

  "Aerobic exercise at least 150 minutes per week was associated with clinically important reductions in waist circumference" (Page 1)

  Implementation: Specify the threshold used to define "clinically important reductions" in waist circumference and body fat measures. For example, "Aerobic exercise at least 150 minutes per week was associated with clinically important reductions in waist circumference (e.g., >2 cm) and measures of body fat (e.g., >2% reduction)."

• Elaborate on Study Selection Criteria

  This medium-impact improvement would bolster the study's methodological transparency. While the Methods section will contain the full details, the Abstract section should provide a more comprehensive overview of the study selection criteria, as it sets the stage for understanding the scope and limitations of the included studies. Expanding on the selection criteria would strengthen the paper by providing readers with a clearer understanding of the population to which these findings apply. This would also enhance the study's reproducibility by providing more specific information about the types of trials included. In conclusion, providing a more detailed description of the study selection criteria in the Abstract would improve the study's transparency and allow readers to better assess the applicability of the findings.

  "Randomized clinical trials with intervention durations of at least 8 weeks evaluating the effects of supervised aerobic training on adults with overweight or obesity." (Page 1)

  Implementation: Expand the description of the study selection criteria to include more specific details about the types of aerobic training, participant characteristics, and any specific inclusion/exclusion criteria related to comorbidities or other factors. For example, "Randomized clinical trials with intervention durations of at least 8 weeks evaluating the effects of supervised aerobic training (e.g., walking, running, cycling) on adults with overweight or obesity (BMI > 25 kg/m2 or >23 kg/m2 in Asian populations). Trials involving participants with specific comorbidities were included if they met the primary inclusion criteria."

• Provide More Context on Adverse Events

  This medium-impact improvement would provide a more balanced perspective on the risks and benefits of aerobic exercise. While the full details will be in the Results section, providing more context on the adverse events in the Abstract is crucial for a comprehensive initial understanding of the study's findings. Adding more detail about the nature and severity of the adverse events would strengthen the paper by allowing readers to weigh the potential benefits of aerobic exercise against its risks. This would also help to inform clinical decision-making regarding exercise prescription for individuals with overweight or obesity. In summary, providing a more nuanced description of the adverse events in the Abstract would enhance the study's clinical relevance and provide a more complete picture of the overall impact of aerobic exercise.

  "It was associated with modestly increased mild to moderate adverse events, which were mostly musculoskeletal symptoms" (Page 1)

  Implementation: Expand the description of adverse events to include more specific information about the types of musculoskeletal symptoms observed and their frequency. For example, "It was associated with modestly increased mild to moderate adverse events, which were mostly musculoskeletal symptoms (e.g., knee pain, back pain) with a risk difference of 2 more events per 100 participants."

Introduction

Key Aspects

• Global Prevalence of Overweight and Obesity: The Introduction establishes the global health concern of overweight and obesity, highlighting a tripling in prevalence over the past 45 years, resulting in approximately 50% of adults having excess body weight. This sets the stage for the importance of addressing this issue through lifestyle interventions.
• Exercise as a Key Element in Obesity Management: Current guidelines recommend aerobic exercise, alone or combined with resistance training, as a key component of lifestyle modification programs for managing obesity. This emphasizes the established role of exercise in addressing overweight and obesity.
• Guideline Recommendations for Aerobic Exercise: The Introduction outlines the general recommendation from existing guidelines that at least 150 minutes per week of moderate-intensity aerobic exercise is necessary to achieve clinically important weight loss. It also mentions the American College of Sports Medicine's suggestion that exercise programs shorter than 150 minutes per week promote minimal weight loss, while 225 to 420 minutes per week are recommended for more substantial weight loss (5.0 to 7.5 kg).
• Limitations of Existing Evidence: The authors point out that the current guidance on the duration of aerobic exercise primarily comes from individual trials and older data, rather than comprehensive meta-analyses. This identifies a gap in the existing literature and highlights the need for a more robust evaluation of the dose-response relationship between aerobic exercise and adiposity measures.
• Gap in Dose-Response Meta-Analyses: The Introduction specifically identifies the lack of systematic reviews and meta-analyses examining the dose-response association between aerobic exercise and body weight, waist size, and fat. This establishes the primary research gap that the current study aims to address.
• Clinical and Public Health Importance: Evaluating the dose-response association is presented as having clinical and public health importance because it can help determine how body weight, waist size, and fat change with increasing aerobic training dose. This information is crucial for making informed decisions about exercise prescription.
• Study Aim: Dose-Response Association: The Introduction clearly states the study's aim: to perform a systematic review and meta-analysis of randomized clinical trials investigating the dose-response association of aerobic exercise of varying intensity with measures of body weight, waist size, and fat in adults with overweight or obesity.

Strengths

• Clear Identification of Research Gap

  The Introduction effectively highlights the gap in existing literature regarding the dose-response relationship between aerobic exercise and adiposity measures, justifying the need for this study.

  "systematic reviews and meta-analyses are lacking to examine the possible dose-response association of aerobic exercise" (Page 2)
• Well-Defined Study Aim

  The authors clearly state the study's aim to investigate the dose-response association of aerobic exercise with body weight, waist size, and fat in adults with overweight or obesity.

  "to investigate the possible dose-response association of aerobic exercise of varying intensity with measures of body weight, waist size, and fat" (Page 2)
• Contextualization within Existing Guidelines

  The Introduction effectively places the study within the context of current guidelines for obesity management, highlighting the role of aerobic exercise and the limitations of existing recommendations.

  "It is generally recommended in the guidelines that at least 150 minutes per week of aerobic exercise at moderate intensity is required" (Page 2)

Suggestions for Improvement

• Expand on the Limitations of Pairwise Comparisons

  This medium-impact improvement would provide a more nuanced understanding of the limitations of previous meta-analyses. While the Introduction mentions that previous meta-analyses relied on pairwise comparisons, it could elaborate on why this approach is insufficient for establishing a dose-response relationship. This section is the ideal place to explain this methodological limitation, as it sets the stage for the study's approach. Expanding on this point would strengthen the paper by providing a clearer rationale for the current study's methodology. It would also highlight the importance of dose-response meta-analyses in providing more precise and informative evidence for clinical practice. Ultimately, providing a more detailed explanation of the limitations of pairwise comparisons would enhance the study's justification and highlight the novelty of its approach.

  "the results of these meta-analyses are mainly based on pairwise comparisons between intervention and control groups" (Page 2)

  Implementation: Add a sentence or two explaining why pairwise comparisons are insufficient for establishing a dose-response relationship. For example: "However, these pairwise comparisons do not fully capture the nuanced relationship between varying durations of aerobic exercise and changes in adiposity. Dose-response meta-analyses, which can model the effect of different exercise durations, are needed to provide a more comprehensive understanding of this relationship."

• Strengthen the Link to Public Health Importance

  This medium-impact improvement would further emphasize the broader relevance of the study. While the Introduction mentions the clinical and public health importance of evaluating the dose-response association, it could more explicitly link this to the potential for developing more targeted and effective exercise guidelines. This section is crucial for establishing the study's significance, and a stronger connection to public health would enhance its impact. Strengthening this link would enhance the paper by highlighting the potential for the study's findings to inform public health policies and interventions aimed at combating obesity. It would also underscore the importance of optimizing exercise prescription for maximizing health benefits. In conclusion, a more explicit connection between the dose-response evaluation and its public health implications would significantly enhance the study's overall impact and relevance.

  "Evaluating the potential dose-response association is of clinical and public health importance" (Page 2)

  Implementation: Add a sentence or two that explicitly links the dose-response evaluation to the potential for developing more targeted and effective exercise guidelines. For example: "By elucidating the dose-response relationship, this study can contribute to the development of more precise and effective exercise guidelines, ultimately improving public health strategies for obesity prevention and management."

• Briefly Mention the Health Consequences of Obesity

  This low-impact improvement would provide additional context for the study's importance. While the Introduction mentions the high prevalence of overweight and obesity, briefly mentioning the associated health consequences would further underscore the need for effective interventions. This section sets the stage for the study, and adding this information would strengthen the rationale. Including this information would strengthen the paper by providing a more complete picture of the problem being addressed. It would also reinforce the importance of finding effective strategies for managing obesity and its associated health risks. In summary, briefly mentioning the health consequences of obesity would provide valuable context and further emphasize the study's relevance.

  "Overweight and obesity are among the most important health problems worldwide" (Page 2)

  Implementation: Add a sentence briefly mentioning the health consequences of obesity. For example: "Overweight and obesity are associated with an increased risk of numerous health problems, including cardiovascular disease, type 2 diabetes, and certain cancers, highlighting the urgent need for effective management strategies."

Methods

Key Aspects

• Study Design and Registration: This study is a systematic review and meta-analysis of randomized clinical trials. The study protocol was registered with PROSPERO (CRD42023460474), indicating a pre-planned and transparent approach to the research. The authors adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement, ensuring comprehensive and standardized reporting of the methodology.
• Search Strategy and Data Sources: A comprehensive search was conducted in multiple databases, including PubMed, Scopus, the Cochrane Central Register of Controlled Trials, and gray literature sources (ProQuest and ClinicalTrials.gov), from inception until April 30, 2024. This broad search strategy aimed to identify all relevant studies, minimizing the risk of publication bias.
• Study Selection Criteria: The study included randomized clinical trials that met specific criteria: (1) intervention duration of at least 8 weeks; (2) inclusion of adults older than 18 years with overweight or obesity (BMI >25 in Western countries and >23 in Asian countries) or central obesity; (3) supervised continuous aerobic training program as the intervention; (4) reported efficacy of aerobic exercise on study outcomes; and (5) reported frequency, duration, and intensity of aerobic exercise. These criteria ensure that the included studies are relevant to the research question and of sufficient quality.
• Outcome Measures: The primary outcomes were body weight change (in kg) and adverse events. Secondary outcomes included changes in waist circumference (in cm), body fat percentage, fat mass (in kg), area of visceral and subcutaneous adipose tissue (in cm2), health-related quality of life score, and medication reduction. This comprehensive set of outcomes allows for a thorough assessment of the effects of aerobic exercise on various aspects of adiposity and health.
• Data Extraction and Risk of Bias Assessment: Data extraction was performed independently and in duplicate by two teams of two reviewers, ensuring accuracy and reliability. The risk of bias was assessed using version 2 of the Cochrane risk of bias tool, a standardized method for evaluating the quality of randomized clinical trials.
• Classification of Aerobic Exercise Intensity: The intensity of aerobic exercise programs was classified as light, moderate, vigorous, or moderate to vigorous based on metabolic equivalents (METs), maximum heart rate, or maximum oxygen consumption (V˙O2max). This classification allows for a detailed analysis of the dose-response relationship between exercise intensity and outcomes.
• Statistical Analysis: A random-effects model was used to calculate summary effect estimates for primary and secondary outcomes. Mean differences and 95% confidence intervals were calculated for each 30-minute per week increment in aerobic exercise. Nonlinear dose-response meta-analysis was conducted to investigate the association between exercise duration and continuous outcomes. These statistical methods are appropriate for meta-analyzing data from randomized clinical trials and exploring dose-response relationships.
• Subgroup and Sensitivity Analyses: Predefined subgroup analyses were performed based on exercise intensity, participant health status, and study risk of bias. Post hoc subgroup analyses were conducted based on various factors, including geographical location, intervention duration, and sex. These analyses help to explore potential sources of heterogeneity and identify factors that may modify the effects of aerobic exercise.
• Assessment of Evidence Certainty: The certainty of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool, providing a transparent and standardized assessment of the confidence in the effect estimates.

Strengths

• Comprehensive Search Strategy

  The authors conducted a thorough search across multiple databases, including gray literature, maximizing the likelihood of identifying all relevant studies and reducing potential publication bias.

  "PubMed, Scopus, the Cochrane Central Register of Controlled Trials, and gray literature sources" (Page 3)
• Rigorous Study Selection

  The clearly defined inclusion and exclusion criteria ensured that only high-quality, relevant randomized clinical trials were included, enhancing the validity of the findings.

  "randomized clinical trials that (1) had an intervention duration of at least 8 weeks" (Page 3)
• Independent Data Extraction

  Data extraction was performed independently and in duplicate by two teams, minimizing errors and increasing the reliability of the data.

  "Data extraction was conducted by 2 teams of 2 reviewers" (Page 3)
• Robust Risk of Bias Assessment

  The use of the Cochrane risk of bias tool provides a standardized and transparent assessment of the methodological quality of the included trials.

  "We assessed risk of bias of the trials using version 2 of the Cochrane risk of bias tool" (Page 3)
• Appropriate Statistical Analysis

  The use of a random-effects model and dose-response meta-analysis is appropriate for synthesizing data from heterogeneous studies and exploring the relationship between exercise duration and outcomes.

  "to assess mean differences and their corresponding 95% Cls for each 30-minute per week increment in aerobic exercise" (Page 3)

Suggestions for Improvement

• Clarify Handling of Missing Data

  This medium-impact improvement would enhance the transparency of the data analysis process. While the Methods section mentions calculating the mean and SD of changes for trials that did not report this information, it could be more explicit about how missing data for other variables were handled. This is particularly important for the Methods section as it provides the foundation for understanding how the data were analyzed. Providing more detail on the handling of missing data would strengthen the paper by allowing readers to better assess the potential impact of missing data on the results. This would also improve the reproducibility of the study by providing a clearer description of the data analysis procedures. Ultimately, clarifying the approach to missing data would enhance the study's methodological rigor and transparency.

  "We computed the mean and SD of changes for the trials that did not report this information" (Page 3)

  Implementation: Add a subsection or a few sentences that explicitly describe how missing data for variables other than the mean and SD of changes were handled. For example: "For trials that did not report data on specific outcomes or covariates, we contacted the study authors to request the missing information. If the data were still unavailable, we excluded the trial from the analysis of that specific outcome or covariate. If a substantial proportion of trials were missing data for a particular variable, we conducted sensitivity analyses to assess the potential impact of the missing data on the results."

• Provide More Detail on Data Transformation

  This low-impact improvement would provide greater clarity regarding the data analysis process. While the Methods section mentions the method used to assess mean differences for each 30-minute increment in aerobic exercise, it could provide more detail on any data transformations that were performed prior to analysis. This is relevant to the Methods section as it describes the specific steps taken to analyze the data. Providing more detail on data transformations would strengthen the paper by allowing readers to better understand how the data were prepared for analysis. This would also improve the reproducibility of the study by providing a more complete description of the data analysis procedures. In conclusion, providing more detail on data transformations would enhance the transparency and reproducibility of the data analysis.

  "we followed the method introduced by Crippa and Orsini19 to assess mean differences" (Page 3)

  Implementation: Add a sentence or two describing any data transformations that were performed. For example: "Prior to analysis, we log-transformed the data on exercise duration to improve normality. We also standardized the scores for health-related quality of life to ensure comparability across different scales."

• Justify the Choice of Random-Effects Model

  This low-impact improvement would provide a stronger rationale for the chosen statistical approach. While the Methods section states that a random-effects model was used, it could briefly justify this choice over a fixed-effect model. This is relevant to the Methods section as it explains the statistical methods used to analyze the data. Justifying the choice of a random-effects model would strengthen the paper by providing a clearer rationale for the statistical approach. This would also help readers understand the assumptions underlying the analysis and the implications for the interpretation of the results. In summary, providing a brief justification for the use of a random-effects model would enhance the methodological rigor and transparency of the statistical analysis.

  "We used a random-effects model (DerSimonian and Laird method)17 to calculate summary effect estimates" (Page 3)

  Implementation: Add a sentence or two explaining why a random-effects model was chosen. For example: "We anticipated heterogeneity across the included trials due to variations in study populations, interventions, and outcome measures. Therefore, we used a random-effects model, which assumes that the true effect size varies across studies, to account for this heterogeneity."

Results

Key Aspects

• Study Inclusion and Participant Characteristics: The Results section begins by detailing the literature search and study selection process, ultimately including 116 trials with 6880 participants. The participants were primarily adults with overweight or obesity (mean age 46 years, 61% female), providing a clear demographic context for the findings. This establishes the scope and population to which the results apply.
• Primary Outcome: Body Weight Reduction: A key finding is that each 30 minutes per week of aerobic exercise was associated with a body weight reduction of 0.52 kg (95% CI, -0.61 to -0.44 kg). This result, based on 109 trials and graded as moderate certainty, establishes a quantifiable relationship between aerobic exercise duration and weight loss. It suggests that even modest increases in exercise can lead to measurable weight reduction.
• Primary Outcome: Adverse Events: The analysis found that aerobic exercise was associated with an increase in mild to moderate adverse events, primarily musculoskeletal symptoms, by 2 more events per 100 patients (95% CI, 1 to 2 more). This finding, based on 9 trials and graded as low certainty, highlights the potential risks associated with aerobic exercise, although these risks appear to be relatively minor.
• Secondary Outcomes: Waist Circumference and Body Fat: Each 30 minutes per week of aerobic exercise was associated with lower waist circumference (mean difference, -0.56 cm), lower body fat percentage (mean difference, -0.37%), and lower body fat mass (mean difference, -0.20 kg). These findings, based on a substantial number of trials and graded as high to moderate certainty, demonstrate the positive impact of aerobic exercise on key indicators of adiposity beyond just body weight.
• Secondary Outcomes: Visceral and Subcutaneous Adipose Tissue: Aerobic exercise was associated with lower visceral and subcutaneous adipose tissue areas. This is particularly important as visceral fat is strongly linked to metabolic health risks. The certainty of evidence for these outcomes was graded as high to moderate, further supporting the beneficial effects of aerobic exercise on body composition.
• Secondary Outcomes: Quality of Life and Medication Use: The study found that aerobic exercise was associated with modest improvements in physical and mental aspects of quality of life, although the certainty of evidence was low. There was no significant association between aerobic exercise and a reduction in antidiabetic or antihypertensive medication use, possibly due to the limited number of trials examining this outcome.
• Subgroup Analyses: Subgroup analyses were conducted to explore potential effect modifiers. While some differences were observed, further evaluation using the ICEMAN criteria suggested that there were no credible subgroup differences, except for a smaller effect on body fat mass in trials with a low risk of bias compared to those with a higher risk of bias. This highlights the importance of considering study quality when interpreting the results.
• Nonlinear Dose-Response Meta-Analyses: Nonlinear dose-response meta-analyses were performed to examine the relationship between aerobic exercise duration and outcomes. These analyses indicated a linear reduction in body weight with increasing exercise duration up to 300 minutes per week. For waist circumference, a nonlinear relationship was observed in the main analysis, but a linear relationship was found in trials with moderate to vigorous intensity. These findings provide a more nuanced understanding of the dose-response relationship between aerobic exercise and adiposity measures.

Strengths

• Comprehensive Reporting of Outcomes

  The Results section provides a thorough and detailed report of the findings for both primary and secondary outcomes, including effect sizes, confidence intervals, and certainty of evidence ratings.

  "Each 30 minutes per week of aerobic exercise was associated with body weight reduced by 0.52 kg" (Page 5)
• Clear Presentation of Dose-Response Relationship

  The authors effectively present the dose-response relationship between aerobic exercise and various outcomes using both linear and nonlinear meta-analysis, providing a nuanced understanding of this association.

  "our dose-response meta-analysis suggested a linear reduction in body weight associated with increasing duration of aerobic exercise to 300 minutes per week" (Page 6)
• Inclusion of Subgroup Analyses

  The inclusion of subgroup analyses, along with the use of the ICEMAN criteria to assess their credibility, adds depth to the analysis and helps to identify potential sources of heterogeneity.

  "we conducted a series of post hoc subgroup analyses to identify potential sources of heterogeneity" (Page 6)
• Use of GRADE for Evidence Assessment

  The use of the GRADE tool to assess the certainty of evidence provides a transparent and standardized evaluation of the confidence in the findings.

  "Certainty of the evidence (GRADE)" (Page 5)

Suggestions for Improvement

• Provide More Context for Adverse Events

  This medium-impact improvement would provide a more complete picture of the safety profile of aerobic exercise. While the Results section mentions an increase in mild to moderate adverse events, it could elaborate on the specific types of musculoskeletal symptoms observed and their frequency. This is particularly important for the Results section as it presents the study's primary findings, and a balanced presentation of benefits and risks is crucial. Expanding on the nature and frequency of adverse events would strengthen the paper by allowing readers to better assess the potential risks associated with aerobic exercise. This would also inform clinical decision-making regarding exercise prescription for individuals with overweight or obesity. Ultimately, providing a more detailed description of adverse events would enhance the study's clinical relevance and provide a more comprehensive understanding of the overall impact of aerobic exercise.

  "Adverse events were mostly mild to moderate musculoskeletal symptoms" (Page 5)

  Implementation: Include a more detailed description of the adverse events, specifying the types of musculoskeletal symptoms (e.g., knee pain, back pain, arthritis) and their frequency. For example: "The most common adverse events were musculoskeletal symptoms, including knee pain (reported in X trials), back pain (reported in Y trials), and arthritis (reported in Z trials). The overall frequency of these events was low, with an average of X events per 100 participants."

• Clarify the Clinical Significance Threshold

  This medium-impact improvement would enhance the practical applicability of the study's findings. While the Results section mentions the concept of a "minimum clinically important difference," it could explicitly state the thresholds used for each outcome. This is crucial for the Results section as it provides the basis for interpreting the magnitude of the observed effects. Clearly defining the clinical significance thresholds would strengthen the paper by providing a benchmark for clinicians and researchers to interpret the findings. This would also facilitate the translation of these results into actionable recommendations for exercise prescription. In conclusion, explicitly stating the clinical significance thresholds would improve the study's impact by making its findings more readily interpretable and applicable in real-world settings.

  "surpassed the threshold set as the minimum clinically important difference" (Page 6)

  Implementation: Clearly state the thresholds used to define clinically important differences for each outcome. For example: "A reduction of 2 cm in waist circumference and a 2% reduction in body fat percentage were considered clinically important, based on previous research (reference). For body weight, a reduction of 5% was considered clinically important."

• Elaborate on the Lack of Association with Medication Reduction

  This low-impact improvement would provide more context for the findings related to medication use. While the Results section states that there was no significant association between aerobic exercise and medication reduction, it could briefly discuss potential reasons for this finding, such as the limited number of studies examining this outcome or the relatively short follow-up periods. This is relevant to the Results section as it presents the study's findings, and providing context for null results is important. Expanding on this point would strengthen the paper by providing a more nuanced interpretation of the findings related to medication use. This would also help to guide future research in this area. In summary, providing more context for the lack of association with medication reduction would enhance the completeness of the Results section and provide a more thorough discussion of the study's findings.

  "exercise was not associated with lower antidiabetic34,119 and antihypertensive34 medication use" (Page 6)

  Implementation: Add a sentence or two discussing potential reasons for the lack of association with medication reduction. For example: "The lack of association between aerobic exercise and medication reduction may be due to the limited number of trials (only 2) that examined this outcome. Additionally, the relatively short follow-up periods (12-16 weeks) in these trials may have been insufficient to observe significant changes in medication use."

Non-Text Elements

Table. Association of Supervised Aerobic Exercise With Body Weight, Waist...

Full Caption

Table. Association of Supervised Aerobic Exercise With Body Weight, Waist Circumference, and Body Fat Among Participants With Overweight or Obesity

Figure/Table Image (Page 5)

First Reference in Text

A summary of the association of aerobic exercise with body waist circumference and measures of fat is given in the Table.

Description

• Overview: This table summarizes the results of a meta-analysis, which is a statistical method that combines the findings from multiple scientific studies to get a more robust estimate of an effect. In this case, it's looking at how supervised aerobic exercise is related to changes in body weight, waist circumference, and various measures of body fat in people who are overweight or obese.
• Outcomes Measured: The table presents data on several different outcomes, which are the things being measured. These include: body weight (how much someone weighs), waist circumference (the measurement around a person's waist), body fat percentage (the proportion of a person's weight that is fat), body fat mass (the total weight of fat in the body), visceral adipose tissue area (the area of fat around internal organs, which is linked to health risks), subcutaneous adipose tissue area (the area of fat just under the skin), adverse events (unwanted medical occurrences), hypoglycemia (low blood sugar), medication use reduction, and health-related quality of life scores (both mental and physical).
• Risk and Relative Risk: The table shows "anticipated absolute effect," which includes the "risk with control group" and the "risk with intervention." "Risk" here refers to the likelihood or magnitude of an outcome in each group. For continuous variables like body weight or waist circumference, risk is shown as an average value. For binary variables like adverse events, it's shown as the number of events per 1000 participants. "Relative effect" is presented as "relative risk (RR)," which is a ratio comparing the risk in the intervention group (those doing the exercise) to the risk in the control group (those not doing the exercise). A relative risk greater than 1 means the intervention increased the risk of the outcome, while less than 1 means it decreased the risk. The 95% CI (confidence interval) provides a range of values within which the true relative risk is likely to fall.
• Certainty of Evidence: The table includes a column for "certainty of the evidence," which is graded using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) system. GRADE is a standardized way of assessing the quality of evidence in research. The certainty is categorized as high, moderate, low, or very low, indicating how confident we can be that the true effect is close to what the study found.

Scientific Validity

• Comprehensive Outcome Measures: The table presents a wide range of outcome measures, encompassing anthropometric measurements, body composition parameters, adverse events, and health-related quality of life scores. This comprehensive approach provides a holistic view of the effects of aerobic exercise. However, the scientific validity hinges on the quality of the included studies in the meta-analysis and the consistency of measurement methods across these studies.
• GRADE Certainty Assessment: The inclusion of the GRADE certainty assessment enhances the scientific rigor of the table. This system provides a standardized method for evaluating the quality of evidence and allows readers to assess the reliability of the reported associations. However, the validity of the GRADE assessments depends on the accuracy of the underlying data and the judgment calls made during the assessment process. Any limitations or inconsistencies in the included studies could affect the GRADE ratings.
• Statistical Reporting: The table provides both absolute and relative effect measures, along with 95% confidence intervals. This detailed statistical reporting allows for a nuanced interpretation of the findings. The use of relative risk ratios facilitates the comparison of outcomes between the intervention and control groups. However, the validity of these measures depends on the appropriateness of the statistical methods used in the meta-analysis, such as the choice of a random-effects model and the handling of heterogeneity between studies.
• Selection of Included Studies: The scientific validity of the table's findings is contingent upon the appropriate selection of studies for inclusion in the meta-analysis. The authors should have employed rigorous and transparent criteria for study selection to minimize bias. The validity also depends on the quality of the individual studies included in the analysis.

Communication

• Clarity of Column Headers: The column headers are generally clear and informative, using standard abbreviations where appropriate (e.g., RR for relative risk, NA for not applicable). However, the header "Anticipated absolute effect (95% CI)" could be made clearer by explicitly stating that it refers to the expected outcomes in both the control and intervention groups.
• Use of Footnotes: The table employs a footnote to clarify the meaning of the GRADE certainty levels and to highlight a specific finding related to study risk of bias. This use of footnotes enhances the clarity and transparency of the table. However, the footnote could be expanded to provide a brief explanation of the random-effects model used in the meta-analysis, or to define any abbreviations that might be unfamiliar to some readers.
• Overall Organization: The table is logically organized, grouping related outcomes together (e.g., body weight, waist circumference, body fat measures). This organization facilitates the comparison of different outcomes and allows readers to quickly grasp the main findings of the meta-analysis. However, the table could be made even more effective by visually separating the different outcome categories with horizontal lines or shading, further improving readability.
• Conciseness and Readability: The table presents a large amount of information in a relatively compact format. While this is efficient, it can also make the table appear dense and potentially overwhelming to some readers. The use of boldface type or different font colors could help to highlight key findings and improve readability.

Figure 1. Dose-Response Association of Aerobic Exercise With Body Weight Among...

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Figure 1. Dose-Response Association of Aerobic Exercise With Body Weight Among Adults With Overweight or Obesity

Figure/Table Image (Page 7)

First Reference in Text

In the main analysis, our dose-response meta-analysis suggested a linear reduction in body weight associated with increasing duration of aerobic exercise to 300 minutes per week (P = .17 for nonlinearity; P < .001 for dose response; n = 109 trials) (Figure 1).

Description

• Overall Purpose: This figure uses graphs to show how the amount of aerobic exercise people do each week relates to changes in their body weight. It focuses on adults who are considered overweight or obese. The term "dose-response" means that the figure explores how different "doses" or amounts of exercise might lead to different "responses" or changes in body weight. Essentially, it's asking: "Does more exercise lead to more weight loss?"
• Graph Components: Each graph in the figure is made up of circles, each representing a different study. The size of each circle corresponds to the precision of that study's results - larger circles mean more precise results. The position of the circles shows what each study found regarding exercise duration and weight change. A solid line running through the circles represents the overall trend found when combining the results of all the studies. The shaded area around this line is called the "95% confidence interval." Think of it as a range that likely contains the true relationship between exercise and weight change.
• X-axis (Horizontal): The x-axis, or the horizontal axis, represents the duration of aerobic exercise, measured in minutes per week. This ranges from 0 to 300 minutes. Aerobic exercise is any activity that gets your heart pumping faster, like brisk walking, running, or cycling.
• Y-axis (Vertical): The y-axis, or the vertical axis, represents the change in body weight, measured in kilograms. A negative value on this axis means a reduction in weight. So, the further down a circle or the trend line is, the greater the weight loss associated with that amount of exercise.
• Sub-Figures and Exercise Intensity: The figure is divided into four parts, called sub-figures (A, B, C, and D). Each sub-figure shows a different scenario. Figure A shows the overall relationship, combining all types of aerobic exercise. Figures B, C, and D show the relationship for different intensities of exercise: moderate, moderate to vigorous, and vigorous, respectively. Exercise intensity refers to how hard the exercise is. For example, a brisk walk might be moderate intensity, while running could be vigorous intensity.
• Statistical Significance: The figure includes information about statistical significance, indicated by "P" values. A P-value helps determine if an observed effect (like weight loss) is likely due to chance or if it's a real effect. A P-value less than .05 is often considered statistically significant, meaning it's unlikely the observed effect is due to chance. The figure mentions "P < .001 for dose response," suggesting a very low probability that the observed relationship between exercise duration and weight loss is due to chance.

Scientific Validity

• Dose-Response Meta-Analysis: The figure presents a dose-response meta-analysis, which is a robust method for synthesizing data from multiple studies to assess the relationship between an exposure (exercise duration) and an outcome (body weight). The validity of this approach depends on the quality of the included studies and the appropriateness of the statistical methods used to combine their results. The reference text mentions a linear reduction in body weight, which should be supported by appropriate statistical tests for linearity, and the reported P-value of .17 for nonlinearity suggests that a linear model is appropriate.
• Heterogeneity Assessment: The scientific validity of the findings is strengthened by assessing and reporting heterogeneity, which refers to the variability in results across the included studies. The reference text does not mention heterogeneity statistics (e.g., I-squared), but the dispersion of the circles around the trend line in the figure provides a visual indication of heterogeneity. High heterogeneity would warrant further investigation and potentially limit the generalizability of the findings. The authors should report and discuss heterogeneity in the main text.
• Control for Confounding Factors: The validity of the dose-response relationship depends on adequately controlling for potential confounding factors, such as differences in diet, baseline physical activity levels, and participant characteristics across the included studies. The figure and reference text do not provide information on how these factors were addressed, which is a limitation. The authors should discuss how potential confounders were handled in the main text.
• Sample Size and Generalizability: The reference text mentions that 109 trials were included in the analysis, suggesting a large sample size, which enhances the statistical power and generalizability of the findings. However, the specific characteristics of the included populations (e.g., age, sex, health status) should be considered when interpreting the results and assessing their applicability to specific populations.

Communication

• Clarity of Axis Labels: The axis labels are clear and informative, specifying the units of measurement (minutes per week for exercise duration and kilograms for weight change). The use of negative values to indicate weight loss is intuitive and consistent with standard practice in this field.
• Visual Representation of Uncertainty: The shaded 95% confidence intervals effectively communicate the uncertainty associated with the estimated dose-response relationship. This visual representation allows readers to quickly grasp the range of plausible effects.
• Differentiation of Exercise Intensities: The division of the figure into sub-figures based on exercise intensity is a strength, as it allows for a more nuanced understanding of the dose-response relationship. However, the specific criteria used to define each intensity category should be clearly stated, either in the figure caption or the main text.
• Visual Clutter: In some of the sub-figures, particularly Figure A, the large number of overlapping circles creates visual clutter, making it somewhat difficult to discern the overall trend. This could be improved by using different symbols or colors for different studies or by increasing the transparency of the circles, allowing for a clearer visualization of the data distribution and the trend line.

Figure 2. Dose-Response Association of Aerobic Exercise With Waist...

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Figure 2. Dose-Response Association of Aerobic Exercise With Waist Circumference Among Adults With Overweight or Obesity

Figure/Table Image (Page 8)

First Reference in Text

For waist circumference, there was a nonlinear reduction associated with dose of aerobic exercise in the main analysis (P = .04 for nonlinearity; P < .001 for dose response; n = 62 trials) (Figure 2); however, the analysis of trials with moderate to vigorous intensity showed a linear reduction in waist circumference associated with the dose of aerobic exercise.

Description

• Overall Purpose: This figure illustrates how the amount of aerobic exercise people do each week relates to changes in their waist size. It focuses on adults who are considered overweight or obese. Like the previous figure, this is a "dose-response" analysis. It's exploring how different "doses" or amounts of exercise might lead to different "responses" or changes in waist circumference. In simpler terms, it's asking: "How does the amount of exercise affect waist size?"
• Graph Structure: Similar to Figure 1, each graph in Figure 2 represents individual studies as circles. The size of each circle indicates the precision of that study's results - larger circles mean more precise results. The horizontal position of each circle shows the duration of exercise in that study, while the vertical position shows the change in waist circumference. A solid line connects the circles, representing the overall trend found by combining all the studies. The shaded area around this line is the 95% confidence interval, which represents a range within which the true relationship likely falls.
• X-axis (Horizontal): The x-axis, or the horizontal axis, represents the duration of aerobic exercise in minutes per week, ranging from 0 to 300. This is the "dose" of exercise being looked at.
• Y-axis (Vertical): The y-axis, or the vertical axis, shows the change in waist circumference, measured in centimeters (cm). A negative value means a reduction in waist size. So, the lower a circle or the trend line, the greater the reduction in waist circumference associated with that amount of exercise.
• Sub-Figures and Exercise Intensity: Figure 2 is divided into three sub-figures (A, B, and C). Figure A shows the overall relationship between exercise and waist circumference, combining all exercise intensities. Figures B and C focus on specific exercise intensities: moderate and moderate to vigorous, respectively. Moderate intensity exercise might be something like a brisk walk, while moderate to vigorous could involve activities like jogging or cycling at a faster pace.
• Nonlinear Relationship: The reference text mentions a "nonlinear reduction" in waist circumference in the main analysis. This means that the relationship between exercise and waist size isn't a straight line. Instead, it might curve, suggesting that the effect of exercise on waist circumference changes at different exercise durations. For example, it's possible that the benefit of exercise on waist size increases quickly at first but then levels off at higher exercise durations. The P-value of .04 for nonlinearity suggests that this curved relationship is statistically significant, meaning it's unlikely to be due to chance.

Scientific Validity

• Assessment of Nonlinearity: The figure explores a nonlinear dose-response relationship, which is appropriate given that physiological responses to exercise may not always be linear. The reported P-value for nonlinearity (P = .04) supports the statistical significance of this nonlinear relationship. However, the specific method used to model and test for nonlinearity should be clearly stated (e.g., fractional polynomial, spline regression). Providing the equation or parameters of the nonlinear model would enhance transparency and allow for a more thorough evaluation of the model's fit.
• Comparison of Exercise Intensities: The figure appropriately differentiates between different exercise intensities, allowing for a more nuanced understanding of the dose-response relationship. However, the validity of these comparisons depends on the consistency of how exercise intensity was defined and measured across the included studies. The reference text mentions a linear relationship for moderate-to-vigorous intensity, contrasting with the overall nonlinear trend. This difference should be explored further, considering potential effect modifiers or factors that might explain this discrepancy.
• Heterogeneity and Confounding: Similar to Figure 1, the scientific validity would be strengthened by explicitly reporting heterogeneity statistics (e.g., I-squared) and discussing how potential confounding factors were addressed. The visual spread of the data points suggests some degree of heterogeneity, which warrants further investigation. Potential confounding factors, such as dietary changes or baseline activity levels, should be considered and discussed in the main text.
• Sample Size and Generalizability: The reference text mentions that 62 trials were included in the analysis, suggesting a reasonable sample size. However, the specific characteristics of the included populations (e.g., age, sex, health status) should be considered when interpreting the results and assessing their generalizability to different populations.

Communication

• Axis Labels and Units: The axis labels are clear and informative, including the units of measurement (minutes per week for exercise duration and centimeters for waist circumference). The use of negative values to indicate reductions in waist circumference is consistent with standard practice.
• Visualization of Uncertainty: The shaded 95% confidence intervals effectively convey the uncertainty associated with the estimated dose-response relationship. This allows readers to visually assess the precision of the findings.
• Clarity of Nonlinear Trend: While the figure presents a nonlinear trend, the specific shape of the curve and its implications could be made clearer. For example, the authors could discuss whether there is a threshold effect or a plateau in the dose-response relationship. Additionally, providing the equation or parameters of the nonlinear model would enhance transparency.
• Visual Clutter in Sub-figure A: Similar to Figure 1, sub-figure A suffers from some visual clutter due to the large number of overlapping circles. Using different symbols, colors, or transparency could improve the clarity of the visualization, making it easier to discern the overall trend and the distribution of the data points.

Figure 3. Dose-Response Association of Aerobic Exercise With Body Fat...

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Figure 3. Dose-Response Association of Aerobic Exercise With Body Fat Percentage Among Adults With Overweight or Obesity

Figure/Table Image (Page 9)

First Reference in Text

For body fat percentage associated with dose of aerobic exercise, the greatest reduction was observed at 150 minutes per week (mean difference, -2.08% [95% CI, -2.47% to -1.69%]) (Figure 3; eTable 19 in Supplement 1), surpassing the threshold (2%) as the minimum clinically important difference for body fat percentage.

Description

• Overall Purpose: This figure examines how different amounts of aerobic exercise relate to changes in body fat percentage among adults who are overweight or obese. It's a type of analysis called a dose-response analysis, which means it looks at how the "dose" or amount of exercise affects the "response" or change in body fat percentage. In simple terms, it's asking: "How does the amount of exercise affect the percentage of body fat a person has?"
• Graph Structure: Like the previous figures, each graph in Figure 3 presents individual studies as circles. The size of a circle reflects the precision of that study's results, with larger circles indicating greater precision. The horizontal position of each circle represents the duration of exercise in that study, while the vertical position shows the change in body fat percentage. A solid line connects the circles, indicating the overall trend, and the shaded area around the line is the 95% confidence interval, which provides a range where the true relationship likely falls. It's like a margin of error for the trend line.
• X-axis (Horizontal): The x-axis, or the horizontal axis, represents the duration of aerobic exercise in minutes per week, ranging from 0 to 300. This is the "dose" of exercise being considered.
• Y-axis (Vertical): The y-axis, or the vertical axis, shows the change in body fat percentage. A negative value means a reduction in body fat percentage. The lower a circle or the trend line, the greater the reduction in body fat percentage associated with that amount of exercise.
• Sub-Figures and Exercise Intensity: Figure 3 is divided into four sub-figures (A, B, C, and D). Figure A displays the overall relationship between exercise and body fat percentage, combining all exercise intensities. Figures B, C, and D focus on specific exercise intensities: moderate, moderate to vigorous, and vigorous, respectively. Moderate intensity exercise could be a brisk walk, moderate to vigorous might be jogging or cycling faster, and vigorous could be running.
• Clinical Significance: The reference text mentions a "minimum clinically important difference" of 2% for body fat percentage. This means that a change of 2% or more is considered meaningful in a practical or clinical sense. It's not just a statistical difference; it's a difference that could actually make a noticeable impact on a person's health. The text also states that the greatest reduction in body fat percentage was observed at 150 minutes of exercise per week, surpassing this 2% threshold.

Scientific Validity

• Dose-Response Analysis and Linearity Testing: The figure presents a dose-response meta-analysis, which is an appropriate method for evaluating the relationship between exercise duration and body fat percentage. The reference text does not specify whether a test for nonlinearity was conducted, which would be important to determine the shape of the dose-response relationship. If a nonlinear model was used, the authors should provide the model specifications and report the results of the nonlinearity test. The P-values for the dose-response relationship are provided, indicating statistical significance.
• Clinical Significance Threshold: The reference text mentions a 2% threshold for the minimum clinically important difference in body fat percentage. The origin and justification for this specific threshold should be provided and supported by relevant literature. The validity of using this threshold depends on its acceptance and applicability in the field of obesity and exercise research. The authors should cite studies that establish this threshold as clinically meaningful.
• Heterogeneity and Confounding Factors: As with the previous figures, the scientific validity would be improved by reporting heterogeneity statistics (e.g., I-squared) and discussing how potential confounding factors (e.g., dietary changes, baseline activity levels) were addressed in the analysis. The spread of the data points suggests some degree of heterogeneity, which should be investigated and discussed. The authors should explain how they accounted for potential confounding factors in their analysis.
• Assessment of Different Exercise Intensities: The division of the figure into sub-figures based on exercise intensity is appropriate and allows for a more nuanced understanding of the dose-response relationship. However, the validity of the comparisons between intensities depends on the consistency of how exercise intensity was defined and measured across the included studies. The authors should provide clear definitions of each intensity category and discuss any potential variability in measurement methods.

Communication

• Axis Labels and Units: The axis labels are clear and informative, specifying the units of measurement (minutes per week for exercise duration and percentage points for body fat percentage). The use of negative values to indicate reductions in body fat percentage is consistent with standard practice.
• Visualization of Uncertainty: The shaded 95% confidence intervals effectively communicate the uncertainty associated with the estimated dose-response relationship. This allows readers to visually assess the precision of the findings.
• Emphasis on Clinically Significant Reduction: The reference text highlights the finding that the greatest reduction in body fat percentage was observed at 150 minutes per week and that this reduction surpassed the 2% threshold for clinical significance. This emphasis on a clinically meaningful finding is valuable for readers interested in the practical implications of the results. However, it would be beneficial to also visually indicate the 2% threshold on the graphs themselves, perhaps with a horizontal dashed line.
• Visual Clutter: Similar to the previous figures, some of the sub-figures, particularly Figure A, suffer from visual clutter due to the large number of overlapping circles. This could be improved by using different symbols, colors, or transparency levels for different studies. Reducing the size of the circles or increasing the spacing between them could also enhance clarity.

Figure 4. Dose-Response Association of Aerobic Exercise With Fat Mass Among...

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Figure 4. Dose-Response Association of Aerobic Exercise With Fat Mass Among Adults With Overweight or Obesity

Figure/Table Image (Page 10)

First Reference in Text

Similar findings were observed for body fat mass associated with dose of aerobic exercise, in which the size of the effect was larger than the minimum clinically important difference threshold (2 kg) at 100 minutes per week in the main analysis (mean difference, -2.03 kg [95% CI, -2.77 to -1.29 kg]) and in the analysis of trials with moderate to vigorous exercise intensity (mean difference, -2.23 kg [95% CI, -3.36 to -1.10 kg]) (Figure 4; eTable 19 in Supplement 1).

Description

• Overall Purpose: This figure explores the relationship between the amount of aerobic exercise done each week and changes in fat mass among adults who are overweight or obese. Fat mass is the total weight of fat in the body. This is a dose-response analysis, meaning it looks at how different amounts or "doses" of exercise might lead to different changes or "responses" in fat mass. In simpler terms, it's asking: "How does the amount of exercise affect the amount of fat a person has?"
• Graph Structure: Each graph in Figure 4 presents individual studies as circles, where the size of each circle reflects the precision of that study's results (larger circles mean more precise results). The horizontal position of a circle shows the duration of exercise in that study, while the vertical position indicates the change in fat mass. A solid line connects the circles, representing the overall trend, and the shaded area around the line is the 95% confidence interval, which is like a margin of error, showing the range where the true relationship most likely falls.
• X-axis (Horizontal): The x-axis represents the duration of aerobic exercise in minutes per week, ranging from 0 to 300. This is the "dose" of exercise.
• Y-axis (Vertical): The y-axis displays the change in fat mass, measured in kilograms (kg). A negative value indicates a reduction in fat mass. The lower a circle or the trend line, the greater the reduction in fat mass associated with that amount of exercise.
• Sub-Figures and Exercise Intensity: Figure 4 is divided into three sub-figures (A, B, and C). Figure A shows the overall relationship between exercise and fat mass, combining all exercise intensities. Figures B and C focus on specific exercise intensities: moderate and moderate to vigorous, respectively. Moderate intensity exercise might be a brisk walk, while moderate to vigorous could involve activities like jogging or cycling at a faster pace.
• Clinical Significance: The reference text mentions a "minimum clinically important difference" threshold of 2 kg for fat mass. This means that a change of 2 kg or more in fat mass is considered meaningful in a practical or clinical sense. It's not just a statistical difference; it's a difference that could actually make a noticeable impact on a person's health. The text highlights that the effect of exercise on fat mass was larger than this threshold at 100 minutes per week in the main analysis and in trials with moderate to vigorous exercise intensity.

Scientific Validity

• Dose-Response Meta-Analysis: The figure presents a dose-response meta-analysis, an appropriate method for investigating the relationship between exercise duration and fat mass. The reference text reports the mean differences and 95% confidence intervals for fat mass reduction at specific exercise durations, indicating statistical significance. However, it does not mention whether a test for nonlinearity was conducted, which would be important to determine the shape of the dose-response relationship. The authors should clarify whether a nonlinear model was considered and, if so, provide the results of the nonlinearity test.
• Clinical Significance Threshold Justification: The reference text uses a 2 kg threshold for the minimum clinically important difference in fat mass. The scientific validity depends on the justification for this threshold. The authors should provide a clear rationale and cite relevant literature supporting the use of this specific value in the context of obesity and exercise research. It is important to establish that this threshold is widely accepted and applicable in this field.
• Heterogeneity and Confounding Factors: As with the previous figures, the scientific validity would be enhanced by reporting heterogeneity statistics (e.g., I-squared) and discussing how potential confounding factors (e.g., dietary changes, baseline activity levels, participant characteristics) were addressed in the analysis. The spread of the data points suggests some degree of heterogeneity, which warrants further investigation. The authors should discuss the potential impact of heterogeneity on the results and explain how they accounted for confounding factors.
• Comparison of Exercise Intensities: The division of the figure into sub-figures based on exercise intensity is appropriate and allows for a more nuanced understanding of the dose-response relationship. However, the validity of the comparisons between intensities depends on the consistency of how exercise intensity was defined and measured across the included studies. The authors should provide clear definitions of each intensity category and discuss any potential variability in measurement methods among the studies.

Communication

• Axis Labels and Units: The axis labels are clear and informative, specifying the units of measurement (minutes per week for exercise duration and kilograms for fat mass). The use of negative values to indicate reductions in fat mass is consistent with standard practice and intuitive for readers.
• Visualization of Uncertainty: The shaded 95% confidence intervals effectively communicate the uncertainty associated with the estimated dose-response relationship, allowing readers to visually assess the precision of the findings.
• Emphasis on Clinically Significant Effect: The reference text highlights that the reduction in fat mass surpassed the 2 kg clinically important difference threshold at specific exercise durations. This emphasis on a clinically meaningful finding is valuable for readers. However, it would be beneficial to also visually indicate the 2 kg threshold on the graphs themselves, perhaps with a horizontal dashed line, to further enhance clarity.
• Visual Clutter: Some of the sub-figures, particularly Figure A, suffer from visual clutter due to the large number of overlapping circles. This could be improved by using different symbols, colors, or transparency levels for different studies, making it easier to discern the overall trend. Reducing the size of the circles or increasing the spacing between them could also enhance clarity.

Discussion

Key Aspects

• Summary of Findings: The Discussion section begins by summarizing the main findings of the meta-analysis, emphasizing that each 30 minutes of aerobic exercise per week is associated with modest reductions in body weight, waist circumference, and body fat measures in adults with overweight or obesity. This provides a concise overview of the study's primary results and sets the stage for further interpretation.
• Dose-Response Relationship: The authors highlight the linear or monotonic relationship between aerobic exercise duration and improvements in body weight and waist circumference, up to 300 minutes per week. For body fat percentage, the greatest improvement was associated with 150 minutes per week. This dose-response relationship is a key aspect of the study, providing valuable information for exercise prescription.
• Comparison with Previous Research: The Discussion compares the current findings with those of previous meta-analyses and individual trials. The authors note that their study is more comprehensive, including a larger number of trials and providing a more detailed analysis of the dose-response relationship. This comparison helps to contextualize the current findings within the existing literature and highlights the study's novel contributions.
• Subgroup Analyses and Clinical Importance: The authors discuss the results of subgroup analyses, noting that progressive exercise showed greater association with weight reduction, although the credibility of this finding was rated low. They also highlight that vigorous exercise was associated with larger effect sizes for some outcomes. The concept of "minimum clinically important difference" is discussed in relation to exercise duration and intensity, suggesting that at least 150 minutes per week may be needed for clinically meaningful changes. These analyses provide further insights into the factors that may influence the effectiveness of aerobic exercise.
• Health-Related Quality of Life: The Discussion briefly addresses the finding of a low-certainty association between aerobic exercise and increased health-related quality of life. This acknowledges the potential broader benefits of aerobic exercise beyond just changes in adiposity measures.
• Limitations: The authors acknowledge several limitations of the study, including high heterogeneity in the data, the inability to perform dose-response meta-analyses based on health status due to a low number of studies, the use of study-level data, and potential publication bias for subcutaneous adipose tissue. These limitations provide a balanced perspective on the study's findings and suggest areas for future research.
• Conclusions: The Discussion concludes by reiterating that aerobic exercise may be associated with clinically important reductions in waist circumference and measures of body fat, particularly with longer durations of exercise. The authors emphasize that they did not find any credible subgroup differences based on exercise intensity but suggest that aerobic training exceeding 150 minutes per week at moderate intensity or greater may be needed for clinically important reductions. These conclusions summarize the study's main takeaways and their implications for clinical practice.

Strengths

• Comprehensive Comparison with Existing Literature

  The Discussion effectively compares the study's findings with those of previous meta-analyses and individual trials, highlighting the larger number of trials included and the more detailed dose-response analysis. This contextualizes the current findings within the broader research landscape.

  "We included 109 trials assessing body weight and 62 trials assessing waist circumference" (Page 9)
• Clear Presentation of Dose-Response Relationship

  The authors clearly explain the linear or monotonic relationship between aerobic exercise duration and improvements in body weight and waist circumference, providing valuable information for exercise prescription.

  "body weight decreased linearly in association with increasing duration of aerobic exercise up to 300 minutes per week" (Page 8)
• Thorough Discussion of Limitations

  The Discussion section provides a comprehensive and transparent discussion of the study's limitations, including heterogeneity, potential aggregation bias, and publication bias. This adds credibility to the study by acknowledging its shortcomings.

  "There were several shortcomings of this study that need further evaluation in future research" (Page 11)

Suggestions for Improvement

• Expand on the Implications of Heterogeneity

  This medium-impact improvement would provide a more nuanced understanding of the study's findings in light of the observed heterogeneity. While the Discussion section mentions the high heterogeneity as a limitation, it could further elaborate on how this heterogeneity might affect the interpretation of the results and the generalizability of the findings. This is crucial for the Discussion section as it provides the final interpretation of the results and their implications. Expanding on the implications of heterogeneity would strengthen the paper by providing a more cautious and realistic assessment of the study's findings. It would also help readers understand the potential variability in individual responses to aerobic exercise and the need for personalized exercise prescription. Ultimately, a more thorough discussion of heterogeneity would enhance the study's scientific rigor and provide a more balanced perspective on the overall impact of aerobic exercise.

  "there was high heterogeneity in the data, which may limit the generalizability of the findings" (Page 11)

  Implementation: Add a paragraph discussing the implications of heterogeneity, including potential reasons for the observed variability (e.g., differences in study populations, exercise protocols, adherence) and how this might affect the interpretation of the results. For example: "The high heterogeneity observed in our analyses suggests that the effects of aerobic exercise may vary considerably across individuals and contexts. This variability could be due to differences in participant characteristics, such as age, sex, baseline fitness levels, and comorbidities, as well as variations in exercise protocols, intensity, and adherence rates. While our findings provide valuable insights into the average effects of aerobic exercise, clinicians should consider this heterogeneity when prescribing exercise and tailor their recommendations to individual needs and circumstances."

• Further Elaborate on Clinical Implications

  This medium-impact improvement would enhance the practical applicability of the study's findings. While the Discussion section mentions the concept of "minimum clinically important difference," it could provide a more detailed discussion of how the study's results can inform clinical practice and public health recommendations. This is particularly important for the Discussion section as it bridges the gap between research findings and their real-world application. Elaborating on the clinical implications would strengthen the paper by providing more specific guidance for clinicians and policymakers on how to use the study's findings to optimize exercise prescription and promote healthy weight management. This would also help to translate the research into actionable strategies for improving public health. In conclusion, a more detailed discussion of clinical implications would significantly enhance the study's impact and relevance to real-world practice.

  "Point-specific estimates for different aerobic exercise duration and intensity can help patients and health care professionals select the optimal aerobic exercise" (Page 10)

  Implementation: Add a paragraph that specifically addresses the clinical implications of the findings, including how they can inform exercise prescription guidelines, patient counseling, and public health interventions. For example: "Our findings have important implications for clinical practice and public health. The dose-response relationship observed in our study suggests that clinicians can use this information to tailor exercise prescriptions to individual patient goals and preferences. For example, patients aiming for modest weight loss may be advised to start with 150 minutes of moderate-intensity aerobic exercise per week, while those seeking more substantial weight loss or improvements in body composition may be encouraged to gradually increase their exercise duration up to 300 minutes per week. Public health campaigns promoting aerobic exercise should emphasize the importance of both duration and intensity for achieving optimal health benefits."

• Discuss the Lack of Credible Subgroup Differences by Intensity

  This low-impact improvement would provide a more complete picture of the findings related to exercise intensity. While the Discussion mentions the lack of credible subgroup differences based on intensity, it could elaborate on the potential reasons for this finding and its implications. This is relevant to the Discussion section as it provides an opportunity to interpret the findings in a broader context. Expanding on this point would strengthen the paper by providing a more nuanced understanding of the role of exercise intensity in modifying the effects of aerobic exercise on adiposity. It would also help to guide future research in this area. In summary, a more detailed discussion of the lack of credible subgroup differences by intensity would enhance the completeness of the Discussion section and provide a more thorough interpretation of the study's findings.

  "By contrast, we did not find any credible subgroup differences based on the intensity of aerobic exercise" (Page 11)

  Implementation: Add a few sentences discussing the potential reasons for the lack of credible subgroup differences by intensity, such as the possibility that the intensity classifications were too broad or that the effects of intensity are more pronounced at higher durations of exercise. For example: "The lack of credible subgroup differences based on exercise intensity may be due to several factors. It is possible that the intensity classifications used in our analysis were too broad to capture subtle differences in the effects of different exercise intensities. Additionally, the effects of intensity may be more pronounced at higher durations of exercise, and future studies could explore the interaction between exercise duration and intensity in more detail."

Conclusions

Key Aspects

• Main Findings: Dose-Response Relationship: The Conclusions section reiterates the primary finding of the meta-analysis: aerobic exercise demonstrates a dose-response relationship with reductions in body weight, waist circumference, and body fat measures in adults with overweight or obesity. Specifically, each additional 30 minutes of aerobic exercise per week is associated with modest improvements in these adiposity measures. This reinforces the importance of exercise duration in achieving desired outcomes.
• Linearity and Intensity: The study concludes that the relationship between aerobic exercise duration and reductions in body weight, waist circumference, and fat is linear or monotonic. This implies that increasing exercise duration, up to 300 minutes per week, may lead to progressively greater benefits. While no credible subgroup differences were found based on exercise intensity, the authors suggest that aerobic training exceeding 150 minutes per week at moderate intensity or higher may be necessary to achieve clinically important reductions.
• Clinical Importance of Waist Circumference and Body Fat: A key conclusion drawn is that aerobic exercise may be associated with clinically important reductions in waist circumference and measures of body fat. This highlights the potential of aerobic exercise to positively impact not just overall weight but also body composition, which is crucial for metabolic health. Waist circumference, in particular, is a strong indicator of visceral fat, which is linked to increased risk of cardiovascular disease and other health problems.
• Limitations and Considerations: The Conclusions section acknowledges the limitations of the study, including the presence of high heterogeneity in the data, which may affect the generalizability of the findings. Other limitations mentioned are the inability to perform dose-response meta-analyses based on health status due to a limited number of studies, the use of study-level data (which is subject to aggregation bias), and potential publication bias for subcutaneous adipose tissue. These limitations are important to consider when interpreting the results and highlight areas for future research.
• Implication for Future Research and Practice: The study concludes by emphasizing the need for future research to address the identified limitations, such as the influence of dietary habits and smoking status, which could not be accounted for in this meta-analysis. The findings suggest that aerobic exercise, particularly longer durations exceeding 150 minutes per week at moderate intensity or greater, may be an effective strategy for achieving clinically important reductions in waist circumference and body fat measures. This has implications for exercise prescription in clinical practice and public health recommendations.

Strengths

• Clear Summary of Main Findings

  The Conclusions section effectively summarizes the key findings of the meta-analysis, emphasizing the dose-response relationship between aerobic exercise and improvements in adiposity measures.

  "The results indicated that levels of body weight, waist circumference, and fat decreased linearly or monotonically" (Page 11)
• Emphasis on Clinical Relevance

  The authors highlight the clinical importance of the findings, particularly regarding reductions in waist circumference and body fat, which are key indicators of metabolic health.

  "aerobic exercise may be associated with clinically important reductions in waist circumference and measures of body fat" (Page 11)
• Acknowledgment of Limitations

  The Conclusions section transparently acknowledges the study's limitations, including heterogeneity, potential aggregation bias, and the inability to account for certain confounding factors.

  "There were several shortcomings of this study that need further evaluation in future research" (Page 11)

Suggestions for Improvement

• Strengthen the Connection to Previous Sections

  This medium-impact improvement would enhance the coherence and flow of the paper. While the Conclusions section summarizes the findings, it could more explicitly connect these conclusions to the specific evidence and arguments presented in the Results and Discussion sections. This is crucial for the Conclusions section as it serves to synthesize the entire study and provide a cohesive narrative. Explicitly linking the conclusions to the preceding sections would strengthen the paper by reinforcing the logical flow of the argument and demonstrating how the conclusions are directly supported by the study's findings. This would also improve the reader's understanding of the study's overall contribution to the field. Ultimately, strengthening the connection between the Conclusions and the previous sections would enhance the paper's cohesiveness and provide a more satisfying and impactful conclusion.

  "This dose-response meta-analysis of 116 randomized clinical trials presented evidence of moderate to high certainty" (Page 11)

  Implementation: Incorporate specific references to the Results and Discussion sections when summarizing the findings. For example: "As detailed in the Results section (page 5), each 30-minute increase in aerobic exercise was associated with a 0.52 kg reduction in body weight. This finding, further discussed in the context of previous research on page 9, supports our conclusion that aerobic exercise has a dose-dependent relationship with weight loss."

• Provide More Specific Recommendations for Future Research

  This medium-impact improvement would enhance the study's contribution to the field by providing a clearer roadmap for future investigations. While the Conclusions section mentions the need for further research to address the study's limitations, it could provide more specific recommendations regarding the types of studies needed, the populations to be targeted, and the variables that should be investigated. This is particularly important for the Conclusions section as it often guides the direction of future research in the field. Providing more specific recommendations would strengthen the paper by highlighting the most pressing research gaps and suggesting concrete avenues for advancing the understanding of the relationship between aerobic exercise and adiposity. This would also increase the study's impact by providing a more actionable framework for future research. In conclusion, offering more specific guidance for future research would significantly enhance the study's contribution to the field and provide a more valuable resource for researchers.

  "There were several shortcomings of this study that need further evaluation in future research" (Page 11)

  Implementation: Expand the discussion of future research directions by providing specific examples of studies that could address the limitations. For example: "Future research should focus on conducting individual patient data meta-analyses to overcome the limitations of using study-level data and to explore the effects of aerobic exercise in specific subgroups, such as individuals with type 2 diabetes. Additionally, studies with longer follow-up periods are needed to assess the long-term effects of aerobic exercise on adiposity and to investigate the influence of potential confounders, such as dietary habits and smoking status."

• Reiterate the Novelty and Significance of the Findings

  This low-impact improvement would further emphasize the study's contribution to the existing literature. While the Discussion section compares the findings to previous research, the Conclusions section could briefly reiterate the novel aspects of this study, such as the comprehensive dose-response analysis and the large number of included trials. This is relevant to the Conclusions section as it provides a final opportunity to highlight the study's unique contribution. Reiterating the novelty and significance of the findings would strengthen the paper by providing a more impactful conclusion that clearly positions the study within the broader research landscape. This would also help readers appreciate the study's unique value and its potential to advance the field. In summary, briefly reiterating the study's novel contributions in the Conclusions section would enhance its overall impact and provide a more memorable takeaway for the reader.

  "The results indicated that levels of body weight, waist circumference, and fat decreased linearly or monotonically" (Page 11)

  Implementation: Add a sentence or two that briefly summarizes the study's unique contributions. For example: "This study provides the most comprehensive dose-response meta-analysis to date on the relationship between aerobic exercise and adiposity, including a larger number of trials than previous reviews. Our findings offer novel insights into the linear or monotonic relationship between exercise duration and improvements in body weight, waist circumference, and body fat measures."