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A Plant-Based Diet and Cardiovascular Disease, Coronary Heart Disease, and Stroke: A Systematic Review and Meta-Analysis of Prospective Cohort Studies

Nutrients 2026, 18(17), 2779; https://doi.org/10.3390/nu18172779

by Youngyo Kim

and Yoona Kim^*

Reviewer 1:

Christos Fragoulis

Reviewer 2: Anonymous

Reviewer 3: Anonymous

Reviewer 4:

David Diamond

Nutrients 2026, 18(17), 2779; https://doi.org/10.3390/nu18172779

Submission received: 15 June 2026 / Revised: 19 August 2026 / Accepted: 21 August 2026 / Published: 25 August 2026

(This article belongs to the Special Issue Nutrient Intake and Dietary Therapy in Prevention of Cardiovascular Disease (CVD))

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript presents an updated systematic review and meta-analysis examining the association between plant-based dietary patterns and cardiovascular outcomes. The topic is timely and of public health relevance. The study includes a large number of participants and distinguishes between healthful and unhealthful plant-based diets, which is a notable strength. However, several issues should be addressed before publication:

1)The literature search appears limited to PubMed and Web of Science. The authors should justify the exclusion of other major databases (e.g., Embase, Scopus) and provide the complete search strategy in the Supplementary Materials.

2)The included studies used different definitions and scoring systems for PBD, hPBD, and uPBD. Greater discussion is needed regarding potential misclassification and its impact on pooled estimates.

3)Moderate-to-high heterogeneity was observed in several analyses. The manuscript would benefit from additional exploration of heterogeneity sources through meta-regression or more detailed subgroup analyses.

4)The analysis is restricted to highest versus lowest adherence categories. If data permit, a dose–response meta-analysis would provide more informative evidence regarding the relationship between plant-based diet adherence and cardiovascular risk.

5)The conclusion emphasizes cardioprotective effects of plant-based diets; however, no significant association was observed for stroke. This discrepancy should be discussed in greater depth, including potential biological and methodological explanations.

6)The authors should correct the apparent typographical error in the Results section: “Li et al. (2003)” should likely be “Li et al. (2023).”

7)The authors should revise fro mistypo.

8)Figure and table legends should be more self-explanatory and clearly define all abbreviations.

9)The PRISMA checklist and detailed quality assessment results should be included as supplementary material.

10)The statement that dietary modification may play “the most beneficial role” in CVD prevention is too strong and should be moderated.

Author Response

Response: Thank you for your suggestions. We have additionally performed a Scopus search and presented the search strategy in Supplementary Table 1. Thank you.

2)The included studies used different definitions and scoring systems for PBD, hPBD, and uPBD. Greater discussion is needed regarding potential misclassification and its impact on pooled estimates.

Response: We agree with your point. We have revised the discussion section to include a description regarding this matter (lines 331-337). Thank you.

Response: Thank you for your suggestions. We have performed additional subgroup analysis and added the results to Table 2. We did not find the cause of heterogeneity through subgroup analysis. As described in the results, heterogeneity disappeared when specific studies were excluded in the sensitivity analysis. Please see the lines 132-134, 158-159, 172-174. Thank you.

Response: We agree with you. However, we were unable to perform a dose-response analysis due to a lack of studies providing the necessary information. Thank you.

Response: Thank you for your comments. We have addressed in lines 305-308 as follows;

The present study observed no significant association between a PBD and stroke risk. High blood pressure is a major contributor to stroke risk [61 ,62]. PBDs included in the present meta-analysis might not be strong enough to lower blood pressure, which might lead to limited stroke risk reduction.

6)The authors should correct the apparent typographical error in the Results section: “Li et al. (2003)” should likely be “Li et al. (2023).”

Response: Thank you for your careful review and feedback. We have corrected that part. Thank you.

7)The authors should revise fro mistypo.

Response: We have thoroughly reviewed and corrected the typos in the manuscript. Thank you.

8)Figure and table legends should be more self-explanatory and clearly define all abbreviations.

Response: We have reorganized the abbreviations in the tables and figures. Thank you.

9)The PRISMA checklist and detailed quality assessment results should be included as supplementary material.

Response: Thank you for your suggestions. We have added the PRISMA Checklist and table of Newcastle-Ottawa Scale results (supplementary table 3) as supplementary materials. Thanks.

10)The statement that dietary modification may play “the most beneficial role” in CVD prevention is too strong and should be moderated.

Response: Thank you for your suggestions. It has been revised to “a beneficial role” by deleting “the most”.

Reviewer 2 Report

Comments and Suggestions for Authors

This systematic review and meta-analysis addresses an important and highly relevant topic. The manuscript is generally well organized, the methodology is appropriate, and the conclusions are supported by the reported findings.

The distinction between overall plant-based diets, healthful plant-based diets, and unhealthful plant-based diets represents a particular strength of this work and provides clinically meaningful information.

I have several minor comments that may help improve the manuscript:

1. Additional literature context

The Discussion could be enriched by referring to studies from research groups actively investigating cardiovascular risk across different plant-based dietary patterns. For example, Kwiatkowska et al. evaluated cardiovascular risk prediction among healthy vegans, vegetarians, pescatarians, and omnivores and identified associations between dietary patterns and selected cardiovascular biomarkers (Int. J. Environ. Res. Public Health 2023, 20, 2237). Although such studies were not eligible for inclusion in the present meta-analysis, they may provide useful context for interpreting cardiovascular risk differences associated with plant-based dietary patterns.

In addition, the authors may consider discussing the recent umbrella review by Capodici et al. (PLoS One, 2024), which reported favorable associations of plant-based dietary patterns with multiple cardiometabolic risk factors, ischemic heart disease risk, and cardiovascular mortality. Such evidence may further strengthen the biological and clinical interpretation of the present findings.

2. Emerging cardiovascular biomarkers

The Discussion focuses primarily on traditional cardiovascular risk factors, including blood pressure, lipid profiles, glucose metabolism, inflammation, endothelial function, and TMAO. A brief discussion of emerging cardiovascular biomarkers and multidimensional cardiovascular risk assessment approaches could further strengthen the mechanistic interpretation of the findings.

3. Literature search strategy

Although the overall methodology is appropriate, the literature search strategy could be described in greater detail. The manuscript would benefit from reporting the complete search strings (including MeSH terms where applicable), language restrictions, and the exact date of the final literature search. In addition, consideration could be given to explicitly presenting the research question within a PICO framework to further improve methodological transparency.

4. Minor inconsistency

In Section 3.2, the sensitivity analysis refers to “Li et al. (2003)”. This appears to be a typographical error, as the cited study was published in 2023. Please verify and correct this statement.

5. Summary of mechanisms

The educational value of the review could be enhanced by adding a concise summary table that illustrates the proposed mechanisms by which healthful and unhealthful plant-based diets may influence the risk of cardiovascular disease and coronary heart disease. Such a table would improve the readability of the Discussion and Conclusions sections.

Comments on the Quality of English Language

The manuscript would benefit from minor English-language editing. Examples include occasional grammatical inconsistencies, inappropriate tense usage (e.g., present instead of past tense when describing study results), and several sentences that could be streamlined for improved readability.

Author Response

Additional literature context

The Discussion could be enriched by referring to studies from research groups actively investigating cardiovascular risk across different plant-based dietary patterns. For example, Kwiatkowska et al. evaluated cardiovascular risk prediction among healthy vegans, vegetarians, pescatarians, and omnivores and identified associations between dietary patterns and selected cardiovascular biomarkers (Int. J. Environ. Res. Public Health 2023, 20, 2237). Although such studies were not eligible for inclusion in the present meta-analysis, they may provide useful context for interpreting cardiovascular risk differences associated with plant-based dietary patterns.

Response: Thank you for your comments. We have addressed on Kwiatkowska et al.2023 in lines 294-299 as follows:

In addition, the authors may consider discussing the recent umbrella review by Capodici et al. (PLoS One, 2024), which reported favorable associations of plant-based dietary patterns with multiple cardiometabolic risk factors, ischemic heart disease risk, and cardiovascular mortality. Such evidence may further strengthen the biological and clinical interpretation of the present findings.

Response: Thank you for your comments. We have addressed on Capodici et al. 2024 in lines 224-226

as follows:

The recent umbrella review by Capodici et al. 2024 [47] showed that vegetarian and vegan diets were associated with improved glucose, lipid, body weight/BMI, and inflammatory markers, and a lower risk of ischemic heart disease [47].

Emerging cardiovascular biomarkers

Response: Thank you for your comments. We have addressed in lines 294-304 as follows:

The interpretation of the present findings can be supported by emerging cardiovascular biomarkers and multidimensional cardiovascular risk assessment approaches. Kwiat-kowska et al. 2023 [59] estimated CVD risk using newly developed metrics based on as-sessments of biochemical parameters in healthy subjects aged 18-39 years who adhered to one of 4 dietary patterns: vegans, lacto- or ovo-vegetarians, pescatarians, and omnivores. The vegan group was likely to have the lowest CVD risk compared with other diet groups [59]. Very recently, Kim et al. 2025 [60] examined the association between a PBD and CVD risk in the ARIC study and Framingham Heart Study Offspring cohort using a proteomics approach to investigate the underlying mechanism. Thrombospondin-2 (THBS2) and N-terminal pro-BNP(NPPB) were negatively associated with a hPBD. Moreover, THBS2 and N-terminal pro-BNP were positively associated with CVD risk [60].

Literature search strategy

Response: Thank you for your comments. We have added search strategies and PICO elements as a supplementary table. Thank you.

Minor inconsistency

Response: Thank you for your careful review and feedback. We have corrected that part. Thank you.

Summary of mechanisms

Response: Thank you for your suggestions. Since our meta-analysis integrates the results of prospective cohort studies—observational research—we believe it is difficult to definitively identify the mechanisms by which healthful and unhealthful plant-based diets may influence the risk of cardiovascular and coronary heart disease. We have made every effort to adequately describe potential mechanisms in the discussion section. Thank you.

Comments on the Quality of English Language

Response: Thank you for your feedback. We have reviewed the manuscript thoroughly and corrected grammatical errors and incorrect tense usage. As a result, the manuscript has been improved. Thank you.

Reviewer 3 Report

Comments and Suggestions for Authors

The manuscript addresses an important topic. However, several issues require clarification. My detailed comments are listed below.

The authors should add supplementary materials with completed PRISMA Checklist, table with Newcastle-Ottawa Scale results, the results of Begg’s test and Egger’s regression asymmetry test.
The authors should explain what does it mean “an unhealthful plant-based diet”. How the uPBD was defined in different publications included in the meta-analysis.
Discussion lines 217-220. The appropriate references should be added to this part.
Discussion lines 237-240. This part is misleading. Achieving an intake of 2 g/day of phytosterols from a habitual diet alone is almost impossible, even in individuals consuming a plant-based diet. The authors should verify this part and provide a more precise statement, supported by appropriate references.
Discussion lines 241-244. The first sentence is that “A PBD is high in mono- and polyunsaturated fatty acids and low in saturated fats”. The second sentence is about the effect of soy nuts intake with diet. The information introduced in the first sentence is not further developed. The second sentence shifts to a different topic. Soy nuts are not the main source of fat in a diet. The authors should revise this part.
Discussion lines 264-265. The authors should verify the information given in this sentence. Was a high intake of refined grains associated with a decreased TG level?
Why the planetary health diet (EAT-Lancet diet) was not included in the analysis? The authors should discuss this issue.

Author Response

The manuscript addresses an important topic. However, several issues require clarification. My detailed comments are listed below.

The authors should add supplementary materials with completed PRISMA Checklist, table with Newcastle-Ottawa Scale results, the results of Begg’s test and Egger’s regression asymmetry test.

Response: Thank you for your suggestions. We have added the PRISMA Checklist and table of Newcastle-Ottawa Scale results (supplementary table 3) as supplementary materials. The results of Begg’s and Egger’s test are presented at the end of each result description. Thank you.

The authors should explain what does it mean “an unhealthful plant-based diet”. How the uPBD was defined in different publications included in the meta-analysis.

Response: Thank you for your suggestions. We have explained “an unhealthful plant-based diet” in introduction. Most studies included in the meta-analysis, for an uPBD, positive scores were given to less healthy plant food groups (fruit juices, sugar-sweetened beverages, refined grains, potatoes, and sweets/desserts), and reverse scores to healthy plant food groups (whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea/coffee) and animal food groups according to criteria proposed by Satija et al, 2016.

Discussion lines 217-220. The appropriate references should be added to this part.

Response: Thank you for your comments. We have revised sentences and cited references in lines 220-224 as follows;

The inverse association between a PBD and the incidence of CVD and CHD can be linked to the protection against CVD. This diet can reduce CVD risk factors by lowering blood pressure [37], lipids [38-40], inflammation [41], glucose [42], body weight [42], and trimethylamine-N-oxide (TMAO) [43], and by increasing gut microbiota diversity [41] and endothelial function [44-46]

Discussion lines 237-240. This part is misleading. Achieving an intake of 2 g/day of phytosterols from a habitual diet alone is almost impossible, even in individuals consuming a plant-based diet. The authors should verify this part and provide a more precise statement, supported by appropriate references.

Response: Thank you for your comments. We have addressed in lines 244-247 as follows;

In a meta-analysis of 124 RCTs, the average phytosterols intake of 0.6 - 3.3 g per day gradually decreased serum LDL-C levels by approximately 6-12% [40]. However, adherence to a PBD typically provides about 300-600 mg of phytosterol per day [49].

Discussion lines 241-244. The first sentence is that “A PBD is high in mono- and polyunsaturated fatty acids and low in saturated fats”. The second sentence is about the effect of soy nuts intake with diet. The information introduced in the first sentence is not further developed. The second sentence shifts to a different topic. Soy nuts are not the main source of fat in a diet. The authors should revise this part.

Response: We have revised in lines 248-258 as follows:

The main sources of fats in a PBD are plant-based oils, nuts, and seeds. Olive oil, as a plant-based oil, is high in monounsaturated fatty acids, containing 70% to 73% of its total fat. A meta-analysis of 8 RCTs showed that olive intake improved endothelial function by increasing flow-mediated dilation compared with controls [45]. Nuts are rich in mono- and polyunsaturated fatty acids, while they are low in saturated fats. A meta-analysis of 10 RCTs showed that nut consumption improved endothelial function [46]. Soy nuts can be a good option in fats derived from a PBD. Healthy subjects aged 60-70 years who con-sumed soy nuts for 16 weeks increased serum concentrations of isoflavones (daidzein and genistein) and cis-polyunsaturated fatty acids, and improved endothelial function in a RCT [44]

Discussion lines 264-265. The authors should verify the information given in this sentence. Was a high intake of refined grains associated with a decreased TG level?

Response: Thank you for your comments. We have revised in lines 281-284.

In line with our findings, the Framingham Offspring Cohort Study of 3,121 subjects with a baseline age of 55 years showed that the highest intake of refined grains was associated with increased waist circumference and decreased TG levels, compared with the lowest intake during the mean follow-up period of 13 years [54].

Why the planetary health diet (EAT-Lancet diet) was not included in the analysis? The authors should discuss this issue.

Response: The Planetary Health Diet is a “scientific dietary model to promote human and environmental health simultaneously,” and the Plant-based Diet is a “broad concept of a plant-based diet.” Although similar, the two differ in their purpose and scope, as well as in the methods used to derive diet scores; therefore, we believe it is unreasonable to group them together for analysis. Our meta-analysis was conducted specifically on the Plant-based Diet. Thank you.

Reviewer 4 Report

Comments and Suggestions for Authors

The authors studied the association between plant-based diets and outcomes in a systematic review and meta-analysis of prospective cohort studies. They concluded: “healthy plant-based diets exert much stronger cardio-protective effects, whereas unhealthy plant-based diets may have a negative impact on cardiovascular health.”

This perspective follows a tradition begun by Ancel Keys in the 1950’s and perpetuated by subsequent epidemiologists, such as Walter Willett, who promote the hypothesis that a plant-based diet has cardiovascular and overall metabolic benefits compared to animal-based diets. However, the flaw in this approach, which is not specific to this study but is a universal flaw, is that the authors ignored the powerful influence of sugar consumption on metabolic health. In the current study, the authors reported that healthy plant-based diets were associated with better CVD outcomes than unhealthy plant-based diets. According to the authors, the following components are in an unhealthy diet: “refined grains, fruit juices, sugary drinks, snacks, and desserts”. This is a problem because these are components of any unhealthy diet. Moreover, there is evidence that a reduction of sugar (carbohydrate) consumption alone can mimic most if not all of the markers reported in this work. The authors did not discuss any of this research, but they should be aware of the decades of research, including long-term (1-2 years) studies showing dramatic metabolic benefits of targeted carbohydrate reduction, without targeting animal or plant-based protein. Here are just a few studies showing benefits of carbohydrate reduction, in the absence of protein type, animal- or plant-based diets [1-17]. Thus, the authors cannot conclude that the plant-based diet “improved” CVD biomarkers when they didn’t take into account carbohydrate consumption.

Finally, the demonization of meat-based diets by the authors is just another example of how they promote a plant-based diet without taking into account the totality of the food in the western diet that has caused obesity and diabetes epidemics. The western diet is high in both sugar and fat, and ignoring that combination perpetuates the myth that meat, alone, causes diseases. The authors should reassess their promotion of the plant-based diet and reconsider that much if not all of the benefits of a plant-based diet are simply because adherents reduce their sugar intake, as well as to make positive lifestyle changes, e.g., smoking cessation, exercise, stress reduction. Numerous reviews have provided objective assessments of the metabolic value of meat consumption [8, 15, 18-21], which adherents of plant-based diets have chosen to ignore.

Thus, in the absence of a single RCT targeting the reduction of animal-based foods, the authors have not provided support for their view that a plant-based diet, alone, is superior to an omnivorous diet that limits refined grains, fruit juices, sugary drinks, snacks, and desserts.

Dynka, D., et al., Ketogenic Diets for Body Weight Loss: A Comparison with Other Diets. Nutrients, 2025. 17(6).
Buchanan, L., et al., TOWARD, a metabolic health intervention, demonstrates robust 1-year weight loss and cost-savings through deprescription. Frontiers in Nutrition, 2025. 12.
Volek, J.S., et al., Expert consensus on nutrition and lower-carbohydrate diets: An evidence- and equity-based approach to dietary guidance. Frontiers in Nutrition, 2024. 11.
McKenzie, A.L., et al., 5-Year effects of a novel continuous remote care model with carbohydrate-restricted nutrition therapy including nutritional ketosis in type 2 diabetes: An extension study. Diabetes Research and Clinical Practice, 2024. 217.
Brown, A., et al., Dietary strategies for remission of type 2 diabetes: A narrative review. Journal of Human Nutrition and Dietetics, 2022. 35(1): p. 165-178.
Westman, E.C. and W. Yancy, Using a low-carbohydrate diet to treat obesity and type 2 diabetes mellitus. Current Opinion in Endocrinology Diabetes and Obesity, 2020. 27(5): p. 255-260.
Unwin, D., et al., Insights from a general practice service evaluation supporting a lower carbohydrate diet in patients with type 2 diabetes mellitus and prediabetes: a secondary analysis of routine clinic data including HbA1c, weight and prescribing over 6 years. Bmj Nutrition, Prevention & Health, 2020. 3(2): p. 285-294.
Diamond, D.M., B.J. O'Neill, and J.S. Volek, Low carbohydrate diet: are concerns with saturated fat, lipids, and cardiovascular disease risk justified? Current Opinion in Endocrinology Diabetes and Obesity, 2020. 27(5): p. 291-300.
Athinarayanan, S.J., et al., Impact of a 2-year trial of nutritional ketosis on indices of cardiovascular disease risk in patients with type 2 diabetes. Cardiovascular Diabetology, 2020. 19(1).
Hyde, P.N., et al., Dietary carbohydrate restriction improves metabolic syndrome independent of weight loss. Jci Insight, 2019. 4(12).
Lennerz, B.S., et al., Management of Type 1 Diabetes With a Very Low-Carbohydrate Diet. Pediatrics, 2018. 141(6).
Feinman, R.D., et al., Dietary carbohydrate restriction as the first approach in diabetes management: Critical review and evidence base. Nutrition, 2015. 31(1): p. 1-13.
Unwin, D. and J. Unwin, Low carbohydrate diet to achieve weight loss and improve HbAic in type 2 diabetes and pre-diabetes: experience from one general practice. Practical Diabetes, 2014. 31(2): p. 76-79.
Paoli, A., et al., Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. European Journal of Clinical Nutrition, 2013. 67(8): p. 789-796.
Blesso, C.N., et al., Whole egg consumption improves lipoprotein profiles and insulin sensitivity to a greater extent than yolk-free egg substitute in individuals with metabolic syndrome. Metabolism-Clinical and Experimental, 2013. 62(3): p. 400-410.
Volek, J.S., E.E. Quann, and C.E. Forsythe, Low-Carbohydrate Diets Promote a More Favorable Body Composition Than Low-Fat Diets. Strength and Conditioning Journal, 2010. 32(1): p. 42-47.
Al-Sarraj, T., et al., Carbohydrate restriction favorably alters lipoprotein metabolism in Emirati subjects classified with the metabolic syndrome. Nutrition Metabolism and Cardiovascular Diseases, 2010. 20(10): p. 720-726.
Kavanaugh, M., et al., Considering the nutritional benefits and health implications of red meat in the era of meatless initiatives. Frontiers in Nutrition, 2025. 12.
Magkos, F., et al., Unprocessed red meat in the dietary treatment of obesity: a randomized controlled trial of beef supplementation during weight maintenance after successful weight loss. American Journal of Clinical Nutrition, 2022. 116(6): p. 1820-1830.
Astrup, A., et al., Saturated Fats and Health: A Reassessment and Proposal for Food-Based Recommendations State-of-the-Art Review. Jacc-Journal of the American College of Cardiology, 2020. 76(7): p. 844-857.
Thorning, T.K., et al., Diets with high-fat cheese, high-fat meat, or carbohydrate on cardiovascular risk markers in overweight postmenopausal women: a randomized crossover trial. American Journal of Clinical Nutrition, 2015. 102(3): p. 573-581.

Author Response

The authors studied the association between plant-based diets and outcomes in a systematic review and meta-analysis of prospective cohort studies. They concluded: “healthy plant-based diets exert much stronger cardio-protective effects, whereas unhealthy plant-based diets may have a negative impact on cardiovascular health.”

This perspective follows a tradition begun by Ancel Keys in the 1950’s and perpetuated by subsequent epidemiologists, such as Walter Willett, who promote the hypothesis that a plant-based diet has cardiovascular and overall metabolic benefits compared to animal-based diets. However, the flaw in this approach, which is not specific to this study but is a universal flaw, is that the authors ignored the powerful influence of sugar consumption on metabolic health. In the current study, the authors reported that healthy plant-based diets were associated with better CVD outcomes than unhealthy plant-based diets. According to the authors, the following components are in an unhealthy diet: “refined grains, fruit juices, sugary drinks, snacks, and desserts”. This is a problem because these are components of any unhealthy diet. Moreover, there is evidence that a reduction of sugar (carbohydrate) consumption alone can mimic most if not all of the markers reported in this work. The authors did not discuss any of this research, but they should be aware of the decades of research, including long-term (1-2 years) studies showing dramatic metabolic benefits of targeted carbohydrate reduction, without targeting animal or plant-based protein. Here are just a few studies showing the benefits of carbohydrate reduction, in the absence of protein type, animal- or plant-based diets [1-17]. Thus, the authors cannot conclude that the plant-based diet “improved” CVD biomarkers when they didn’t take into account carbohydrate consumption.

Finally, the demonization of meat-based diets by the authors is just another example of how they promote a plant-based diet without taking into account the totality of the food in the Western diet that has caused obesity and diabetes epidemics. The western diet is high in both sugar and fat, and ignoring that combination perpetuates the myth that meat, alone, causes diseases. The authors should reassess their promotion of the plant-based diet and reconsider that much if not all of the benefits of a plant-based diet are simply because adherents reduce their sugar intake, as well as to make positive lifestyle changes, e.g., smoking cessation, exercise, stress reduction.

Response:

Thank you for your valuable comments. We have addressed in lines 309-315 as follows;

The population-based Rotterdam Study indicated that a hPBD combined with positive lifestyle modifications (e.g., smoking cessation, adequate physical activity, moderate sleep duration) is vital for personalized CVD prevention [63]. Wang et al. 2026 [63] examined the association between the healthy plant-based diet-lifestyle score and CHD risk in the pop-ulation-based Rotterdam Study. They observed the association between a higher healthy plant-based diet-lifestyle score and lower CHD risk during a mean follow-up of 15.2 years among 7,764 subjects [63].

Numerous reviews have provided objective assessments of the metabolic value of meat consumption [8, 15, 18-21], which adherents of plant-based diets have chosen to ignore. Thus, in the absence of a single RCT targeting the reduction of animal-based foods, the authors have not provided support for their view that a plant-based diet, alone, is superior to an omnivorous diet that limits refined grains, fruit juices, sugary drinks, snacks, and desserts.

Response:

Thank you for your valuable comments. We had no intention to demonize meat-based diets. We definitely agree on the metabolic value of meat consumption. Therefore, we have addressed this in lines 275-280 by discussing our findings and studies of 18 and 19 recommended by you as follows;

Meanwhile, we observed no significant RR for CVD risk comparing meat eaters and vegetarians, with significant heterogeneity. Red meat is rich in high bioavailability protein, iron, zinc, and vitamin B12, which can be limited or absent in a PBD [51]. Recent RCTs have shown that unprocessed beef or lean beef added to healthy dietary patterns benefited body weight maintenance [52], gut microbiota diversity, and TMAO reduction [53]

Furthermore, we have revised the word “effects” to “association” throughout the texts, as this research is a meta-analysis of prospective studies.

Dynka, D., et al., Ketogenic Diets for Body Weight Loss: A Comparison with Other Diets.Nutrients, 2025. 17(6).
Buchanan, L., et al., TOWARD, a metabolic health intervention, demonstrates robust 1-year weight loss and cost-savings through deprescription.Frontiers in Nutrition, 2025. 12.
Volek, J.S., et al., Expert consensus on nutrition and lower-carbohydrate diets: An evidence- and equity-based approach to dietary guidance.Frontiers in Nutrition, 2024. 11.
McKenzie, A.L., et al., 5-Year effects of a novel continuous remote care model with carbohydrate-restricted nutrition therapy including nutritional ketosis in type 2 diabetes: An extension study.Diabetes Research and Clinical Practice, 2024. 217.
Brown, A., et al., Dietary strategies for remission of type 2 diabetes: A narrative review.Journal of Human Nutrition and Dietetics, 2022. 35(1): p. 165-178.
Westman, E.C. and W. Yancy, Using a low-carbohydrate diet to treat obesity and type 2 diabetes mellitus.Current Opinion in Endocrinology Diabetes and Obesity, 2020. 27(5): p. 255-260.
Unwin, D., et al., Insights from a general practice service evaluation supporting a lower carbohydrate diet in patients with type 2 diabetes mellitus and prediabetes: a secondary analysis of routine clinic data including HbA1c, weight and prescribing over 6 years.Bmj Nutrition, Prevention & Health, 2020. 3(2): p. 285-294.
Diamond, D.M., B.J. O'Neill, and J.S. Volek, Low carbohydrate diet: are concerns with saturated fat, lipids, and cardiovascular disease risk justified?Current Opinion in Endocrinology Diabetes and Obesity, 2020. 27(5): p. 291-300.
Athinarayanan, S.J., et al., Impact of a 2-year trial of nutritional ketosis on indices of cardiovascular disease risk in patients with type 2 diabetes.Cardiovascular Diabetology, 2020. 19(1).
Hyde, P.N., et al., Dietary carbohydrate restriction improves metabolic syndrome independent of weight loss.Jci Insight, 2019. 4(12).
Lennerz, B.S., et al., Management of Type 1 Diabetes With a Very Low-Carbohydrate Diet.Pediatrics, 2018. 141(6).
Feinman, R.D., et al., Dietary carbohydrate restriction as the first approach in diabetes management: Critical review and evidence base.Nutrition, 2015. 31(1): p. 1-13.
Unwin, D. and J. Unwin, Low carbohydrate diet to achieve weight loss and improve HbAic in type 2 diabetes and pre-diabetes: experience from one general practice.Practical Diabetes, 2014. 31(2): p. 76-79.
Paoli, A., et al., Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets.European Journal of Clinical Nutrition, 2013. 67(8): p. 789-796.
Blesso, C.N., et al., Whole egg consumption improves lipoprotein profiles and insulin sensitivity to a greater extent than yolk-free egg substitute in individuals with metabolic syndrome.Metabolism-Clinical and Experimental, 2013. 62(3): p. 400-410.
Volek, J.S., E.E. Quann, and C.E. Forsythe, Low-Carbohydrate Diets Promote a More Favorable Body Composition Than Low-Fat Diets.Strength and Conditioning Journal, 2010. 32(1): p. 42-47.
Al-Sarraj, T., et al., Carbohydrate restriction favorably alters lipoprotein metabolism in Emirati subjects classified with the metabolic syndrome.Nutrition Metabolism and Cardiovascular Diseases, 2010. 20(10): p. 720-726.
Kavanaugh, M., et al., Considering the nutritional benefits and health implications of red meat in the era of meatless initiatives.Frontiers in Nutrition, 2025. 12.
Magkos, F., et al., Unprocessed red meat in the dietary treatment of obesity: a randomized controlled trial of beef supplementation during weight maintenance after successful weight loss.American Journal of Clinical Nutrition, 2022. 116(6): p. 1820-1830.
Astrup, A., et al., Saturated Fats and Health: A Reassessment and Proposal for Food-Based Recommendations State-of-the-Art Review.Jacc-Journal of the American College of Cardiology, 2020. 76(7): p. 844-857.
Thorning, T.K., et al., Diets with high-fat cheese, high-fat meat, or carbohydrate on cardiovascular risk markers in overweight postmenopausal women: a randomized crossover trial.American Journal of Clinical Nutrition, 2015. 102(3): p. 573-581.

Round 2

Reviewer 3 Report

Comments and Suggestions for Authors

Line 254 - Soy nuts are not a main source of fat in a diet, even in a plant-based diet. The authors should rephrase this sentence to improve its clarity and correctness.

Please revise the citations throughout the text to ensure that a single referencing style is applied in accordance to the Journal rules.

Author Response

Line 254 - Soy nuts are not a main source of fat in a diet, even in a plant-based diet. The authors should rephrase this sentence to improve its clarity and correctness.

Response: Thank you. We have deleted sentences in 254 -258 to avoid misleading information.

Please revise the citations throughout the text to ensure that a single referencing style is applied in accordance to the Journal rules.

Response: Thank you. We have followed the referencing style of the Nutrients Journal.

Author Response File: Author Response.pdf

Reviewer 4 Report

Comments and Suggestions for Authors

The authors have made only one important point in their entire paper, which is in the introduction where they stated: "An unhealthful plant-based diet (uPBD) includes fruit juices, sugar-sweetened beverages, refined grains, potatoes, and sweets/desserts". If that is the standard with which a healthy diet of any kind is compared, then any diet, omnivorous or carnivorous, will fare better. Of course it is unhealthy to consume "fruit juices, sugar-sweetened beverages, refined grains, potatoes, and sweets/desserts" in excess. It is absurd to compare diets with foods that raise blood glucose with those that don't. It's a bit like saying that diets without smokers are healthier than diets with smokers. Therefore, it's simply a biased sample to focus on people who eat less sugar to those who eat more sugar and then promote the benefits of the low sugar, plant-based diet. In summary, the authors have simply taken an unhealthy high sugar diet and compared it to a low sugar diet and then call the plant-based diet without sugary foods = a healthier diet. The findings may have nothing to do with the plants and everything to do with the low sugar component. The repeated statements suggesting the plant-based diets are so beneficial ignores the fact that lower sugar is healthy, independent of the source of protein.

Author Response

Response

We appreciate your valuable comments. We think the raised issue relates to interpretation and wording regarding the cardiovascular benefits of plant-based diets. This research does not contain substantial methodological bias.

This study is a meta-analysis of prospective cohort studies, which are observational in nature. In the majority of the included studies, plant-based diets were defined according to the food classification and scoring system developed by Satija et al. (2016; PMID: 27299701).

We would like to clarify that our meta-analysis synthesized the results of studies that examined the association between plant-based diet adherence and cardiovascular disease using this established and widely accepted definition. Therefore, we believe that our analysis is not subject to the bias suggested by the reviewer.

According to the scoring system proposed by Satija et al. (2016), the overall plant-based diet index (PDI) assigns positive scores to all plant-derived foods, including fruit juices, sugar-sweetened beverages, refined grains, potatoes, and sweets/desserts. Therefore, we do not consider it appropriate to interpret the findings of this study by categorizing foods according to the presence or absence of sugar.

Furthermore, this meta-analysis compared the risk of cardiovascular disease between individuals with low and high adherence to each dietary pattern. Accordingly, the findings should be interpreted as indicating that greater adherence to a healthy plant-based diet is associated with a lower risk of cardiovascular disease compared with lower adherence. Conversely, greater adherence to an unhealthy plant-based diet is associated with a higher risk of cardiovascular disease compared with lower adherence.

Finally, because this meta-analysis is based on observational prospective cohort studies, we respectfully suggest that the findings should not be interpreted as a direct comparison between healthy and unhealthy plant-based diets. Rather, each dietary pattern was evaluated independently by comparing different levels of adherence within that specific pattern.

Therefore, we have addressed scoring system proposed by Satija et al. (2010) in limitation of lines 327-333, based on previous reviewers’ comments. In addition, this time, we attempted to moderately write conclusion acknowledging potential residual confounding from overall dietary quality and lifestyle factors in lines 339-344.

Round 3

Reviewer 4 Report

Comments and Suggestions for Authors

The authors have used generalized terms "healthy" vs "unhealthy" plant-based diets, but what may be crucial is the sugar content in the diets, which is higher in the unhealthy plant-based diet. It is crucial for the authors to include this statement in their discussion and conclusion. The authors have not included any of the research showing improvement in CVD measures with a low carb diet, independent of protein source, which is relevant because it can explain why healthy plant-based diets have positive outcomes.

Author Response

We appreciate your valuable comments. Comments have been addressed as follows;

In lines 312-317 of discussion,

“This study found an inverse association between a hPBD and CVD, whereas an uPBD was positively associated with CVD. When comparing food composition and scoring systems, the unhealthful plant-based diet's higher sugar content than the healthful plant-based diet may have influenced the differing associations with the risk of CVD development. In addition, studies have shown improvements in CVD measures with a low-carbohydrate diet, independent of protein source. This may explain why a hPBD is associated with CVD [64-67].”

In lines 348-350 of conclusion,

“In addition, it should be noted that unhealthy plant-based diets have a higher sugar content than healthful plant-based diets, which may have influenced the results.”

Round 4

Reviewer 4 Report

Comments and Suggestions for Authors

the authors have responded sufficiently to my comments

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A Plant-Based Diet and Cardiovascular Disease, Coronary Heart Disease, and Stroke: A Systematic Review and Meta-Analysis of Prospective Cohort Studies

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