Effect of Cocoa Beverage and Dark Chocolate Intake on Lipid Profile in People Living with Normal and Elevated LDL Cholesterol: A Systematic Review and Meta-Analysis

Round 1

Reviewer 1 Report

In the presented systematic review and meta-analysis the authors have made a literature overview about the influence of the cocoa beverage and dark chocolate intake on lipid profiles in both healthy and individuals with elevated levels of LDL cholesterol. The results are well-presented. 

The abstract is clearly written and adequately structured. However, please rewrite the last sentence (Lines 27-30): ...but not for chocolate...?

Please, use comma before "such as" and "including".

Lines 47-48: please, use regular decimal point for decimal numbers.

Lines 54-57: please, correct English.

Line 61: ...Since bile acids ARE..

Lines 76-79: please, correct English.

In the discussion section the authors compared their results with the results of previous studies. However, after the lines 457-465 it is not clear what would be the actual conclusion, because the results are inconsistent. The authors should add what are the main drawbacks of these studies and what is the cause of the difference of the results obtained.

Author Response

Response to reviewer comments

The authors are grateful to you for making time to review this work and for the constructive comments made which we believe has led to further improvement in the content and intent of the manuscript. Kindly, find below our response to your comments for your perusal.

Reviewer 1

Comment: In the presented systematic review and meta-analysis the authors have made a literature overview about the influence of the cocoa beverage and dark chocolate intake on lipid profiles in both healthy and individuals with elevated levels of LDL cholesterol. The results are well-presented.

Response to comment: The authors are very grateful to the reviewer for making time to review the work. The constructive comments raised have been addressed below.

 

Comment: The abstract is clearly written and adequately structured. However, please rewrite the last sentence (Lines 27-30): ...but not for chocolate...?

Response to comment:

The authors have revised the sentence (now Lines 27 – 31) as suggested. The new sentence reads as “When considering food matrix, cocoa beverage intake significantly increased HDL cholesterol by 0.11 (95%CI [0.06, 0.17]) mmol/L (P<0.001), but the improvement in HDL cholesterol was not significant when chocolate (P=0.10) or a combination of cocoa beverage and chocolate (P=0.19) (subgroup differences, P=0.03) was administered”.

 

Comment: Please, use comma before "such as" and "including".

Response to comment: The authors have revised this in the manuscript and corrected as suggested.

 

Comment: Lines 47-48: please, use regular decimal point for decimal numbers.

Response to comment: Thank you for the comment. The decimal numbers were reported according to the decimal numbers in the original reports.

 

Comment: Lines 54-57: please, correct English.

Response to comment: The authors have corrected the English. The new sentence (Lines 56 – 58) reads as “Several systematic reviews and meta-analysis of prospective studies [6,7] have reported that increased intake of energy-dense and nutrient-poor foods is positively associated with increased risk of dyslipidaemia.”

 

Comment: Line 60-62: ...Since bile acids ARE..

Response to comment: The authors have changed the “is” to “are”. The new sentence reads as “Excretion of circulating cholesterol is known to be mediated by bile acids. Upon in-gesting dietary fiber, the soluble fiber chelates bile acids which are released during fat digestion, preventing bile acids from being re-absorbed……”.

 

Comment: Lines 84-87: please, correct English.

Response to comment: The authors have revised the sentence. The new sentence reads as “Another feature that distinguishes chocolate from cocoa powder is that chocolate contains cocoa butter, which is composed of mainly saturated fatty acids (25% palmitic acid and 35% stearic acid), some monosaturated fatty acids (35% oleic acid), and a small amount of polyunsaturated fatty acid (3% linoleic acid) [15]”.

 

Comment: In the discussion section, the authors compared their results with the results of previous studies. However, after the lines 457-465 it is not clear what would be the actual conclusion, because the results are inconsistent. The authors should add what are the main drawbacks of these studies and what is the cause of the difference of the results obtained.

Response to comment: Thank you for the comment. The authors have provided some clarification for that. These meta-analyses engaged the use of participants with co-morbidities including type 2 diabetes, obesity and hypertension. The physiological changes in the anthropometric parameters and requirements of these individuals living with the various chronic diseases compared to those included in the eligibility criteria (those without significant comorbidities) for the selection of studies for the meta-analysis of this current meta-analysis. This is probably why variations in outcomes of cocoa beverage and dark chocolate intake on lipid profile outcomes. No significant drawbacks were identified which would have led the inconsistencies in the outcomes.

Nevertheless, the authors have now added a sentence (Lines 474-479) to clarify the main conclusion despite the inconsistent results with the other meta-analyses. The sentence reads as “Despite the differences in the health condition of study populations may have contributed towards the inconsistencies in lipid profile outcome between meta-analyses, we are confident that daily cocoa beverage and chocolate consumption was at least beneficial in increasing HDL cholesterol in a relatively healthy population without increasing the atherogenic LDL cholesterol.”

To further clarify the conclusion, we have added a sentence “Cocoa consumption could be recommended as part of a healthy diet in a general population with normal and elevated LDL cholesterol.” to Lines 30 – 31 in the Abstract, and Lines 502 – 503 in the Conclusion.

 

Author Response File: Author Response.docx

Reviewer 2 Report

This manuscript needs complete rewriting. Construction of sentences is poor, and the meaning is very difficult to understand. The whole article reads as random collection of thoughts and sentences. 

Author Response

Response to reviewer comments

The authors are grateful to you for making time to review this work and for the constructive comments made which we believe has led to further improvement in the content and intent of the manuscript. Kindly, find below our response to your comments for your perusal.

Reviewer 2

Comment: This manuscript needs complete rewriting. Construction of sentences is poor, and the meaning is very difficult to understand. The whole article reads as random collection of thoughts and sentences.

Response to comment: The authors have revised the manuscript thoroughly. For example (Lines 53-68), in the second paragraph of the Introduction, the authors have re-written that section which now reads as “Improving dyslipidaemia through dietary intervention is considered as a sustain-able approach. In developing countries the higher cost of cholesterol-lowering drugs, further aggravated by poor drug adherence, are some of the common reasons for uncontrolled dyslipidaemias. Several systematic reviews and meta-analysis of prospective studies [6,7] have reported that increased intake of energy-dense and nutrient-poor foods is positively associated with increased risk of dyslipidaemia. Foods that are rich in dietary fibre [8] especially soluble fibre, and some bioactive compounds present in plants are important modulators of dyslipidaemia [8]. Excretion of circulating cholesterol is known to be mediated by bile acids. Upon ingesting dietary fiber, the soluble fiber chelates bile acids which are released during fat digestion, preventing bile acids from being re-absorbed from the intestinal lumen, resulting in bile acid excretion through faeces [9]. This inhibition of bile acid re-absorption stimulates liver to replenish the bile acids pool through endogenous synthesis of bile acids from cholesterol, consequently lowering the circulating concentration of total cholesterol. In the case of bioactives, especially polyphenols, some in-vitro and animal studies proposed that certain polyphenols may lower endogenous cholesterol and fatty acid synthesis by modulating gene expressions [10].”

In the Discussion section (Line 474-479) “Despite the differences in the health condition of study populations may have contributed towards the inconsistencies in lipid profile outcome between meta-analyses, we are confident that daily cocoa beverage and chocolate consumption was at least beneficial in increasing HDL cholesterol in a relatively healthy population without increasing the atherogenic LDL cholesterol.”

The authors have tweaked several sections of the manuscript including the Abstract and the Conclusion. We are hopeful that the Reviewer will be satisfied with the revisions we have undertaken. 

Reviewer 3 Report

The authors have tried hard to prepare this meta-analysis regarding cocoa product consumption and change in the level of different types of cholesterol. 

the author should include a table to clearly indicate how cocoa powder, butter, and chocolate differ in the ingredients.  

Small summary tables for the bigger tables would enhance the fast understanding of the viewer. 

Author Response

Please see the attachment

Author Response File: Author Response.docx

Reviewer 4 Report

The systematic review work done by Amoah I et al entitled ""Effect of Cocoa beverage and dark chocolate intake on lipid profile in people living with normal and elevated LDL cholesterol: a systematic review and meta-analysis" is very well writen. the article may be publishable as it is.  In general, the full perception was excellent.

I have only a minor concern that the author already took into account in the discussion section:

This is in relation to the exclusion criteria met for this systematic review. Particularly, the one regarding the exclusion of participants with significant comorbidities. The authors discussed the potential contribution of overweight/obese as a comorbidity being deserved for future studies. The study is fine as it is, but I wonder if it would have been possible to adjust for BMI data analysis shown in figures 3, 4 and Table 2?

Another possible limitation of the study may be related to the HDL-C increase, which may not necessarily mean that it would be linked to increased quality or function and thus improved cardiovascular health.

Other minor issues were:

Table 1, in certain cases it was  difficult to discern between the outcomes of two consecutive studies; maybe, some extra space between studies (rows) with a large number of outcomes could be added to clearly separate the outcomes of two different studies.

Author Response

Response to reviewer comments

The authors are grateful to you for making time to review this work and for the constructive comments made which we believe has led to further improvement in the content and intent of the manuscript. Kindly, find below our response to your comments for your perusal.

Reviewer 5

The systematic review work done by Amoah I et al entitled "Effect of Cocoa beverage and dark chocolate intake on lipid profile in people living with normal and elevated LDL cholesterol: a systematic review and meta-analysis" is very well writen. the article may be publishable as it is.  In general, the full perception was excellent.

I have only a minor concern that the author already took into account in the discussion section:

Comment: This is in relation to the exclusion criteria met for this systematic review. Particularly, the one regarding the exclusion of participants with significant comorbidities. The authors discussed the potential contribution of overweight/obese as a comorbidity being deserved for future studies. The study is fine as it is, but I wonder if it would have been possible to adjust for BMI data analysis shown in figures 3, 4 and Table 2?

Response to reviewer comment: The authors appreciate the reviewer for commending this systematic review. We had considered to include BMI into subgroup analysis. However, since many studies included a wide range of BMI, with huge standard deviations causing the BMI to span of participants to span from normal weight to overweight (see Table 2), categorising the BMI into subgroups may not result in a reliable outcome.

Comment: Another possible limitation of the study may be related to the HDL-C increase, which may not necessarily mean that it would be linked to increased quality or function and thus improved cardiovascular health.

Response to comment: Thank you for this comment. The authors agree with the reviewer’s comment and have subsequently mentioned that in the discussion section (Lines 452-455). The new sentence reads as, “It should however be noted that, even though improvement in HDL cholesterol is an essential outcome, the endothelial function was not reported, hence may not necessarily translate to improved cardiovascular health.”

Other minor issues were:

Comment: Table 1, in certain cases it was difficult to discern between the outcomes of two consecutive studies; maybe, some extra space between studies (rows) with a large number of outcomes could be added to clearly separate the outcomes of two different studies.

Response to comment: Thank you for this comment. The authors have added some extra spacing between studies in particular that had bulkier outcomes of presentation. This has now enhanced the spacing alignment.

Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

The revised review article incorporated some of suggestions. The conclusions of review are based on combining random studies which were done at various times and were analyzing different variables. The comparison of specific food group prepared in different ways is not ideal baseline for comparison. The review is not informative and conclusive.

Author Response

Dear Reviewer,

The authors thank you for your time in reviewing the manuscript and providing comments.

Reviewer Comment 1:

The conclusions of review are based on combining random studies which were done at various times and were analyzing different variables.

Author Response 1:

The authors would like to assure the Reviewer that this is a Systematic Review and Meta-Analysis which follow the standard PRISMA guidelines. Specifically in the Methods, we formulated search terms, inclusion and exclusion criteria to identify articles which can answer the aim "to investigate the effects of cocoa and chocolate consumption in individuals with normal and elevated LDL cholesterol concentrations, whether cocoa and chocolate differentially modify serum lipid profile (triglycerides, LDL, HDL and total cholesterol), and to verify the threshold concentration of flavanol and epicatechin required to improve lipid profile". All articles selected have to meet the inclusion and exclusion criteria, there is no randomness or bias in the selection of articles.

Reviewer Comment 2:

The comparison of specific food group prepared in different ways is not ideal baseline for comparison.

Author Response 2:

We absolutely agree that cocoa beverage and chocolate are different foods. It is also for this reason that we believe it is necessary to split cocoa intervention into two subgroups, one administered in the form of cocoa powder beverage, and another administered in the form of chocolate, as the effect of cocoa beverages and chocolate on lipid profile may be different. 

We hope that our comments can assure the reviewer of the quality of the Systematic Review and Meta-Analysis.

The authors have also carefully read through the manuscript again and have identified an error in Table 1, which we have now corrected in the latest revision.