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Review
Peer-Review Record

Effect of Cocoa and Cocoa Products on Cognitive Performance in Young Adults

Nutrients 2020, 12(12), 3691; https://doi.org/10.3390/nu12123691
Reviewer 1: Anonymous
Reviewer 2: Anonymous
Reviewer 3: Anonymous
Nutrients 2020, 12(12), 3691; https://doi.org/10.3390/nu12123691
Received: 22 October 2020 / Revised: 18 November 2020 / Accepted: 28 November 2020 / Published: 30 November 2020
(This article belongs to the Special Issue Cocoa and Chocolate in Human Health)

Round 1

Reviewer 1 Report

This review is an interesting and useful contribution, which I think is entirely suitable for publication of this journal.
Please revise the following minor points:

The selection criteria for articles excludes cases where there is “no control group”. However, #44 article do not have a control group, why did you choose? (Figure 1 and Table 1)

In the Screening of Figure 1, the Number is 124, but it is 123 in the text.

Author Response

The authors thank the reviewer for his/her compliments on the general idea of the manuscript. The specific comment regarding the absence of control group on reference Calderon-Garciduenas et al (2013) has been corrected in the revised version. Actually, in the mentioned work, children were followed up during 2 years, as this study was part of a bigger cohort study. Participants served as their own control as they were asked not to consume any cocoa product or flavanol-rich food for 15 days before their first assessment for inflammation, cardiovascular and cognitive function.

Besides, discrepancy between numbers in figure 1 and text has also been corrected.

Author Response File: Author Response.docx

Reviewer 2 Report

The manuscript entitled “ Effect of Cocoa and Cocoa Products on Cognitive Performance in Children and Young Adults.” presents an interesting issue, and may be interesting for readers, however it requires major amendments.

ABSTRACT:

According to the Nutrients journal rules, abstract should not be longer than 200 words. It is recommended to shorten the abstract (especially results) by following strictly the structure suggested by the journal (background, method, results and conclusion).

Methodology section should be clarified. There are inconsistencies between databases mentioned in the abstract section and in figure 1 (Web of Science, Pubmed, Medline).

Since the authors conducted a systematic review according to the PRISMA rules, the proper information must be mentioned in abstract.

The contribution of this research should be better emphasized.

KEYWORDS:

It is suggested to add "literature review" in the keywords.

INTRODUCTION:

The introduction should be rewritten to get reader's attention, to introduce the topic, explain its relevance, state the thesis or purpose, and outline the structure of the paper (e.g. results sections should be mentioned).

The definition of “acute” and “chronic” should be reported.

References should be reinforced to support the concepts expressed from line 41 to line 51.

MATHERIAL AND METHODS:

The methodological section requires improvements and clarifications.

In the abstract Web of Science and Medline databases are mentioned, however, in Figure 1 Pubmed is mentioned as other database used. Please clarify in the text.

It would be useful to insert a table indicating for each database, the FINAL string used, the search field (e.g. TITLE;ABS; KEYWORDS, etc.) in order to make the search replicable, and the number of results for each database.

Since the final number of papers selected is particularly limited, it is advisable to explain in detail the exclusion criteria that led to the selection of the 11 final papers.

It would be useful to go deeper into the criteria with which the string has been defined. This would strengthen the methodological basis on which the research was built. Moreover, specify how the papers were analyzed (based on e.g. applied methodology, sample analyzed, etc.), and consequently how the results were organized. Furthermore, the paper (see line 172) should specify why the 25 years is the age threshold for young adults.

Please check the number of " records screened". There are inconsistencies between the figure and the text.

Figure 1 should appear at the end of this section, not within the results.

RESULTS AND DISCUSSION:

This is a key aspect for the validity of the paper. The paper should better explain why the results of other papers than those indicated in Table 1 (11 papers) are analyzed. The suggestion is to restructure the results section by, for example, explain what the current literature review on young adults says, versus what other literature says. Or it may be worth focusing only on the 11 papers. Please clarify this aspect in abstract and methodology section.

Please explain the implications of including both chocolate (dark and other types) and cocoa studies. How much cocoa is there in the different types of chocolate? Does this have implications in assessing and reviewing the results?

Line 141: check the references. The should be in numerical order          

Line 201: Please insert references. The text says “a number of studies….” but only one is specified.

Line 207: Remove brackets

CONCLUSION:

Line 299 - Remove brackets

It is suggested to add a limitations section of the review paper carried out.

Author Response

The manuscript entitled “Effect of Cocoa and Cocoa Products on Cognitive Performance in Children and Young Adults.” presents an interesting issue, and may be interesting for readers, however it requires major amendments.

Reply:The authors thank the reviewer for the compliments on the review and interesting suggestions and specific comments on the text.

ABSTRACT:

According to the Nutrients journal rules, abstract should not be longer than 200 words. It is recommended to shorten the abstract (especially results) by following strictly the structure suggested by the journal (background, method, results and conclusion).

Reply: as required by the journals rules and pointed by the reviewer the abstract has been shortened to around 200 words.

Methodology section should be clarified. There are inconsistencies between databases mentioned in the abstract section and in figure 1 (Web of Science, Pubmed, Medline).

Reply: methods section has been revised and inconsistencies have been mended or clarified.

Since the authors conducted a systematic review according to the PRISMA rules, the proper information must be mentioned in abstract.

Reply: proper information regarding PRISMA rules has been included in abstract.

The contribution of this research should be better emphasized.

Reply: since discussion and conclusions have been thoroughly revised we expect that contribution of this review to the field is now more emphasized. A new conclusion of the study has now been included in the abstract. 

KEYWORDS:

It is suggested to add "literature review" in the keywords.

Reply: keyword has been added.

 INTRODUCTION:

The introduction should be rewritten to get reader's attention, to introduce the topic, explain its relevance, state the thesis or purpose, and outline the structure of the paper (e.g. results sections should be mentioned).

As suggested by the reviewer, the introduction has been rewritten and all changes suggested have been considered in the revised version

The definition of “acute” and “chronic” should be reported.

Both definition have now included in the revised version

References should be reinforced to support the concepts expressed from line 41 to line 51.

Reply: all changes suggested by the reviewer have been considered in the revised version.

The main objective of the study was to revise and update results from recent studies reporting beneficial effects of cocoa flavanols on brain function and cognitive function that might confirm in young humans most of the findings previously observed in adults and aged people. As most authors involved in this topic, we also believe that cognitive function in young adults has great potential for intervention since brain tissue is less damaged and shows greater plasticity to response to new challenges. Additionally, we think that working from the first steps in life would most probably prevent ulterior damages at the neurological level.

The main objective of the study has now been emphasized in the introduction.

MATHERIAL AND METHODS:

The methodological section requires improvements and clarifications.

In the abstract Web of Science and Medline databases are mentioned, however, in Figure 1 Pubmed is mentioned as other database used. Please clarify in the text.

Reply: methods section has been revised and inconsistencies have been mended or clarified

It would be useful to insert a table indicating for each database, the FINAL string used, the search field (e.g. TITLE;ABS; KEYWORDS, etc.) in order to make the search replicable, and the number of results for each database.

Reply: methods section has been revised and the search field used indicated accordingly

Since the final number of papers selected is particularly limited, it is advisable to explain in detail the exclusion criteria that led to the selection of the 11 final papers.

It would be useful to go deeper into the criteria with which the string has been defined. This would strengthen the methodological basis on which the research was built. Moreover, specify how the papers were analyzed (based on e.g. applied methodology, sample analyzed, etc.), and consequently how the results were organized. Furthermore, the paper (see line 172) should specify why the 25 years is the age threshold for young adults.

Reply: all changes suggested by the reviewer have been considered in the revised version.

Please check the number of " records screened". There are inconsistencies between the figure and the text.

Figure 1 should appear at the end of this section, not within the results.

Reply: all changes suggested by the reviewer have been considered in the revised version.

RESULTS AND DISCUSSION:

This is a key aspect for the validity of the paper. The paper should better explain why the results of other papers than those indicated in Table 1 (11 papers) are analyzed. The suggestion is to restructure the results section by, for example, explain what the current literature review on young adults says, versus what other literature says. Or it may be worth focusing only on the 11 papers. Please clarify this aspect in abstract and methodology section.

Reply: we understand the concern of the reviewer regarding the inclusion of analysis of data from some other articles that are not focused on the objective of the review; however, we would like to point out that one of our main goals was to try to extrapolate the beneficial effects of cocoa/chocolate in brain cardiovascular and cognitive function observed in adults to young adults, thus, an overall view of the most interesting findings in adults was entirely necessary to set the physiological basis of our approach and make possible the further comparison to the scarce data from young adults. In line with this we would like to point out that the first paragraph of Results and Discussion deals with the potential mechanisms of action and second paragraph with brain bioavailability of flavanols, all in adult studies, in order to support the physiological possibility for flavanol action. After the methodological aspects, the crucial role of NO in adult vascular flow is fully developed to end up the sub-section with some considerations on visual function, exercise and angiogenesis. Then, the last part specifically deals with the cognitive endpoints focusing on the cell signaling pathways and specific neurothrophic factors and NO involved in the cognitive process.

Perhaps this idea was not clearly exposed or explained in the text, and some sentences have been added to the revised version in order to clarify this point.

Please explain the implications of including both chocolate (dark and other types) and cocoa studies. How much cocoa is there in the different types of chocolate? Does this have implications in assessing and reviewing the results?

Reply: due to the limited number of manuscripts on this current topic all studies dealing with cocoa or chocolate were considered for this review and the specific concentration of cocoa was indicated when available.  This is included in table 1. In fact, some of the non-included papers initially selected were in fact eliminated due to the lack of data related to flavanol or polyphenol or even pure cocoa contents in chocolate products.

Line 141: check the references. The should be in numerical order

Reply: reference list has been checked for errors.          

Line 201: Please insert references. The text says “a number of studies….” but only one is specified.

Reply: we would like to point out that reference 16 is a comprehensive review including a fair number of references dealing with the effect of epicatechin and other flavanols on cardiovascular function and its correlation to cognitive response. In any case, to further support the idea as suggested by the reviewer references 12, 15 and 19 have been added in the revised version.

Line 207: Remove brackets

Reply: Some references were missing here by error. Thank you to reviewer for noticing this error.

CONCLUSION:

Line 299 - Remove brackets

Reply: brackets have been removed.

It is suggested to add a limitations section of the review paper carried out.

Reply: some limitations of the review have now been added at the end of the section. The main limitation is the scarce number of studies on the subject, although we feel that the number will rapidly increase due to the great potential for research and the high applicability of the results to improve dietary and nutritional patterns.

Reviewer 3 Report

As a popular food product consumed all over the world, a favourite especially among children, cocoa may attract interest of scientists in terms of its impact on health.

However, the paper submitted for review raises serious doubts as to its content.

In light of the conducted research review, the very title of the paper is incorrect, because out of 11 analysed studies only one (Calderon-Garciduenas L. et al.) concerned children (average age: 10.55 years). Therefore, in a literature review paper, one cannot draw conclusions as regards children on the basis of one study only, especially since it covered merely 18 children. This is not very objective from the scientific point of view.

In the paper, the authors specify that the analysis covered 11 intervention studies. However, Table 1 mentions publication no. 57 twice, which could mean that in the end there were 10 studies???

The statement that research covered young people aged 25 and younger (lines: 19, 130) is unclear because Table 1 specifies the age of people in individual studies as being in the range of 18-31 years in the Francis S.T. et al. study and 20-31 years in the Sumiyoshi E. et al. study.

In my opinion, the following conclusion is far-fetched: “cocoa supplementation may be a realistic and reasonable preventive approach on neurodegenerative diseases and cognitive decline.” The research was short-term (from several to 30 days), conducted on young and healthy people, and results pointing out to improvements in cognitive functions (e.g. memory tasks, reaction time, mental fatigue) cannot be applied to such distant health effects. What is more, in one place the authors write that “Interestingly, better beneficial effects of polyphenols on brain plasticity biomarkers and on different cognitive functions have been found in young and middle-aged adults than in elderly” (lines 63-65) but then mention that „Evidences from human clinical studies suggest that cocoa and cocoa-derived products consumption can be effective to improve general cognition and working memory, particularly among older population at risk or with cognitive decline” (lines 76-78). In general, it seems to me that the whole paper is written with the aim to prove beneficial effects of consuming cocoa and/or cocoa polyphenols. One of disputable sentences is as follows: “Cell renovation and neuronal plasticity are higher in young people and their brain is not yet damaged, thus intervention affecting children and young populations will better prevent age-related cognitive decline.”

The ‘Materials and Methods’ chapter specifies that “After merging the two data lists from Web of Science and Medline and reviewing only the title of the papers we ended up with 123 papers (Figure 1)”, whereas Figure 1 gives n = 124???

Item 3.1. ‘Methodological aspects’ mentions study no. 26 (number in references) but such study is missing from Table 1.

In ‘Conclusions’, the authors state that “The immediate effects can be attained with a single acute or sub chronic (for several weeks) administration of CF in appropriate dosages” (lines 288-289) but one question remains: what are exact dosages of cocoa flavanols that should be used to produce such effect and to be safe?

The final argument in the ‘Conclusions’ is also unclear: “Overall, most findings support the beneficial effect of cocoa flavonoids on cognitive function and neuroplasticity in young adults, suggesting that cocoa supplementation may be a realistic and reasonable preventive approach on neurodegenerative diseases and cognitive decline. Furthermore, short and middle-term effects of daily cocoa intake may provide children and young adults with a better cognitive performance in verbal learning, memory and attention favoring academic achievement.” What is meant here? Using cocoa in the form of some dietary supplements or consuming cocoa as a standard food product? When producing such recommendations it has to be remembered that cocoa for children currently produced in Western countries is usually heavily sweetened, hence children will at the same time have a high sugar intake. Moreover, this may be interpreted as an invitation to consume large amounts of other products based on cocoa, such as milk chocolate which children are already eager to eat.

Lines 90-96 and 135-143 repeat information about cocoa’s potential mechanism of action.

Minor technical errors: there is an opening bracket in line 207 but no literature; there is an unnecessary bracket in line 299 before “Consequently”.

 

Author Response

As a popular food product consumed all over the world, a favourite especially among children, cocoa may attract interest of scientists in terms of its impact on health.

However, the paper submitted for review raises serious doubts as to its content.

The authors thank the reviewer for the through reading of the review and all interesting suggestions and specific comments on the text.

In light of the conducted research review, the very title of the paper is incorrect, because out of 11 analysed studies only one (Calderon-Garciduenas L. et al.) concerned children (average age: 10.55 years). Therefore, in a literature review paper, one cannot draw conclusions as regards children on the basis of one study only, especially since it covered merely 18 children. This is not very objective from the scientific point of view.

Reply: as suggested by the reviewer title has been changed accordingly to only mention young adults in the revised version.

In the paper, the authors specify that the analysis covered 11 intervention studies. However, Table 1 mentions publication no. 57 twice, which could mean that in the end there were 10 studies???

Reply: a mistake in the numeration of references within the table has been corrected in the revised version.

The statement that research covered young people aged 25 and younger (lines: 19, 130) is unclear because Table 1 specifies the age of people in individual studies as being in the range of 18-31 years in the Francis S.T. et al. study and 20-31 years in the Sumiyoshi E. et al. study.

Reply: the mistake in the top age for studies included in the review has now been corrected.

In my opinion, the following conclusion is far-fetched: “cocoa supplementation may be a realistic and reasonable preventive approach on neurodegenerative diseases and cognitive decline.” The research was short-term (from several to 30 days), conducted on young and healthy people, and results pointing out to improvements in cognitive functions (e.g. memory tasks, reaction time, mental fatigue) cannot be applied to such distant health effects. What is more, in one place the authors write that “Interestingly, better beneficial effects of polyphenols on brain plasticity biomarkers and on different cognitive functions have been found in young and middle-aged adults than in elderly” (lines 63-65) but then mention that „Evidences from human clinical studies suggest that cocoa and cocoa-derived products consumption can be effective to improve general cognition and working memory, particularly among older population at risk or with cognitive decline” (lines 76-78). In general, it seems to me that the whole paper is written with the aim to prove beneficial effects of consuming cocoa and/or cocoa polyphenols. One of disputable sentences is as follows: “Cell renovation and neuronal plasticity are higher in young people and their brain is not yet damaged, thus intervention affecting children and young populations will better prevent age-related cognitive decline.”

Reply: we agree that some conclusions might be too optimistic or far-fetched, but please note that those related to adults and aged people are based on extensive literature and are more solidly supported; in any case we emphasize expressions such as may be, might, suggest and others in order not to show opinionated on the subject.

On the other hand, since all three authors have previously and currently conducted research on the bioactive effects of cocoa flavanols, we agree on the fact that we might be biased to stress the beneficial effects of consuming cocoa or cocoa polyphenols however the target of research. To amend this potential bias or limitation, the main objective of this revision regarding the potential extrapolation of significant changes evoked by cocoa flavonoids in adult brain and cognitive function to young humans has now been emphasized in the introduction.

The ‘Materials and Methods’ chapter specifies that “After merging the two data lists from Web of Science and Medline and reviewing only the title of the papers we ended up with 123 papers (Figure 1)”, whereas Figure 1 gives n = 124???

Reply: discrepancy between numbers in figure 1 and text has also been corrected.

Item 3.1. ‘Methodological aspects’ mentions study no. 26 (number in references) but such study is missing from Table 1.

Reply: Thank you for the correction. Table 1 and in general all the manuscript has been corrected for reference numbers.

In ‘Conclusions’, the authors state that “The immediate effects can be attained with a single acute or sub chronic (for several weeks) administration of CF in appropriate dosages” (lines 288-289) but one question remains: what are exact dosages of cocoa flavanols that should be used to produce such effect and to be safe?

Reply: due to the limited number of clinical assays published on the subject we cannot foresee and would not dare to state a range of effective doses of cocoa flavanols to obtain the beneficial results on cognitive function as it has been established by EFTA for their cardiovascular effects.  Regarding doses of flavanols, the authors, however have noticed that there are a number of inconsistences between studies or even in the same study. Some authors do not make the difference between total polyphenols and flavanols.

The final argument in the ‘Conclusions’ is also unclear: “Overall, most findings support the beneficial effect of cocoa flavonoids on cognitive function and neuroplasticity in young adults, suggesting that cocoa supplementation may be a realistic and reasonable preventive approach on neurodegenerative diseases and cognitive decline. Furthermore, short and middle-term effects of daily cocoa intake may provide children and young adults with a better cognitive performance in verbal learning, memory and attention favoring academic achievement.” What is meant here? Using cocoa in the form of some dietary supplements or consuming cocoa as a standard food product? When producing such recommendations it has to be remembered that cocoa for children currently produced in Western countries is usually heavily sweetened, hence children will at the same time have a high sugar intake. Moreover, this may be interpreted as an invitation to consume large amounts of other products based on cocoa, such as milk chocolate which children are already eager to eat.

Reply: we absolutely agree with the reviewer that suggesting an overall higher cocoa intake during childhood might be misleading since most cocoa-derived products in the market are supplemented with sugar and fat in a variable proportion that might interfere with their proposed beneficial effects on health. In concert, a full marketing campaign to increase the ratio of cocoa in all cocoa products should be launched simultaneously to reduce the harmful effects of the rest of components. In fact, this movement to acknowledge and publicize the beneficial effects of cocoa to the population based on scientific criteria has been running for a few years already in some countries like Spain (see Observatorio del Cacao webpage), and it has been fairly successful since.  in 2019 sells of chocolate with or over 70 % of cocoa in Spain were higher than those of chocolate with lower cocoa concentration.

Lines 90-96 and 135-143 repeat information about cocoa’s potential mechanism of action.

Reply: thank you for the comment. This has now been corrected.

Minor technical errors: there is an opening bracket in line 207 but no literature; there is an unnecessary bracket in line 299 before “Consequently”.

Reply: Thank you for the comment, Line 207 was an error and references were in fact missing.

Round 2

Reviewer 2 Report

The paper has been improved. However, further developments are suggested.

Line 20-22: Does this sentence describe a useful finding to be included in the abstract? Please elaborate or delete.

Please clarify what is meant by young adults since sometimes we talk about people under 25, sometimes under 35

Line 100: Is 25 years an average or the maximum age to define young adults? Please clarify thorough the text.

Line 87-89: Please add references.

Methodology

The methodology description needs to be improved. We recommend to add a table indicating for each database, the string used, and how many papers it selected.  Since 268 and 96 are indicated in the PRISMA flow diagram as the selected papers, please align the description in the methodology paragraph. Other information generates some confusion (e.g.: 654, 518,136,83, etc.).

Results and discussion:

We would like to stress that presenting the results in this way, including conclusions from other papers, leads to a methodological discrepancy. It would be more appropriate to include findings from other studies in the introduction section. This would further justify the contribution of your research. From a methodological point of view, it is highly recommended to focus on the results the elaboration of the data provided in the 11 papers selected.

Author Response

The paper has been improved. However, further developments are suggested.

We deeply appreciate the interest and highly interesting comments from reviewer 2. We understand that this has allowed us to continue the improvement of our manuscript. We really hope that now it would be considered suitable for publication, even if we do understand that the fact that the literature in this subject being really limited and in some cases with limited description of the product or the population group has had made it difficult for us to stick to only the eleven papers selected by using the Prima method.

We understand that some aspects were not clear enough. For instance, the age of the participants. We hope that know it would be clear for the reader that even if our initial aim was to study the effect of cocoa and cocoa products in children and adolescents, this proved to be impossible due to the scarce literature in this group of age (1 out of 11). This was the reason why we compromised to include only studies in which the average age was 25 years old or less. We really think that in some of them there are some kind of discrepancies in the definition of age group and also in the description of the product used for the intervention that makes it really difficult to improve our manuscript farther. We hope that now we have made this clear by including several changes that we will detail bellow.

Line 20-22: Does this sentence describe a useful finding to be included in the abstract? Please elaborate or delete.

We have improved the text in lines 20-22 that now reads: “Findings from individual studies confirm that acute and chronic cocoa intake have a positive effect on several cognitive outcomes. After acute consumption, these beneficial effects seem to be accompanied with an increase in cerebral blood flow or cerebral blood oxygenation. After chronic intake of cocoa flavanols in young adults a better cognitive performance was go together with increased levels of neurotrophins.” We hope that now it is considered useful as it is.

Please clarify what is meant by young adults since sometimes we talk about people under 25, sometimes under 35

We have now corrected and clarified this throughout the manuscript, 35 was indeed an error.

Line 100: Is 25 years an average or the maximum age to define young adults? Please clarify thorough the text.

We consider that we have now clarified this throughout the whole text. The initial idea was to carry on a thorough review on the effect of cocoa and cocoa products in children and adolescents, however this was impossible due to the total lack of studies in this group of age. This is why we decided to include a reasonable number of studies that include young adults, adolescents and children, all of them in a group of age where many are still studding-learning and in most cases they do not have their neurocognitive capacities compromised.

Line 87-89: Please add references.

I think that we have now corrected and included all the references needed. We really hope that we have now make it clear to the reader the way this study was done.

Methodology

The methodology description needs to be improved. We recommend to add a table indicating for each database, the string used, and how many papers it selected.  Since 268 and 96 are indicated in the PRISMA flow diagram as the selected papers, please align the description in the methodology paragraph. Other information generates some confusion (e.g.: 654, 518,136,83, etc.).

We have now, we hope, improved the methodology section. We consider that there is no use of a table, because all the information is included in methodology section and figure 1. We have double checked and there is no error in the number of papers included at the different steps of this study. The reason why 273 papers were obtained after melting PubMed and Web of science data bases results is because, most of the Web of science papers were included already in the 268 that we got from Med Line. The search in Med Line is much more unspecific and for some reason it gets papers that, as we have already stated, were included at first because their author surname or a study acronym was Cocoa

Results and discussion:

We would like to stress that presenting the results in this way, including conclusions from other papers, leads to a methodological discrepancy. It would be more appropriate to include findings from other studies in the introduction section. This would further justify the contribution of your research. From a methodological point of view, it is highly recommended to focus on the results the elaboration of the data provided in the 11 papers selected.

We have improved and changed different parts of the results section in order to better full fill the reviewer’s impression on our manuscript. We consider, as mentioned before, that because we want the reader to get a broad idea of the implications of cocoa and cocoa products consumption by young healthy adults we need to talk about the general mechanism of actions involved, and for this we need to mention some studies, other than the eleven initially selected.

We really hope that now the reviewer will find our paper suitable for its publication in Nutrients as it is, considering all the limitations encountered in this specific area.

Reviewer 3 Report

Although the authors claim that it has been corrected, the following study (reference 34) is still cited in 'Methodological aspects', which is not included in table 1: “On the other hand, the only study in which the statistical treatment of the data had into consideration the effect of sex on different parameters related to the cognitive functions in sleep deprivation conditions showed a beneficial effect of CF on working memory accuracy only in women [34]”. Previously, this study had reference number 26. Whether this study was included in your analysis or not. This is not understandable ???

The same applies to the conclusions of the study: “Overall, most findings support the beneficial effect of cocoa flavonoids on cognitive function and neuroplasticity in young adults, suggesting that cocoa supplementation may be a realistic and  reasonable preventive approach on neurodegenerative diseases and cognitive decline. Furthermore, short and middle-term effects of daily cocoa intake may provide children and young adults with a better cognitive performance in verbal learning, memory and attention favoring academic achievement”.  What does cocoa supplementation mean. Dietary supplements are products in the form of tablets or capsules. Cocoa, on the other hand, is an ordinary food product. Do the authors consider taking cocoa polyphenols in the form of supplements? With regard to daily cocoa intake, it should be stated that it concerns products with a high proportion of cocoa beans and with little sugar added

Author Response

Although the authors claim that it has been corrected, the following study (reference 34) is still cited in 'Methodological aspects', which is not included in table 1: “On the other hand, the only study in which the statistical treatment of the data had into consideration the effect of sex on different parameters related to the cognitive functions in sleep deprivation conditions showed a beneficial effect of CF on working memory accuracy only in women [34]”. Previously, this study had reference number 26. Whether this study was included in your analysis or not. This is not understandable ???

Again we thank reviewer 3 comments and suggestions that have helped us to farther improbe our manuscript. We really thank you for the comment on reference 34. Sorry about that, we really missed the error and it has now been corrected. All references have been double checked and the mentioned reference placed in its appropriate place as reference 21. In accordance a number of consecutive reference numbers have been now changed.

The same applies to the conclusions of the study: “Overall, most findings support the beneficial effect of cocoa flavonoids on cognitive function and neuroplasticity in young adults, suggesting that cocoa supplementation may be a realistic and  reasonable preventive approach on neurodegenerative diseases and cognitive decline. Furthermore, short and middle-term effects of daily cocoa intake may provide children and young adults with a better cognitive performance in verbal learning, memory and attention favoring academic achievement”.  What does cocoa supplementation mean. Dietary supplements are products in the form of tablets or capsules. Cocoa, on the other hand, is an ordinary food product. Do the authors consider taking cocoa polyphenols in the form of supplements? With regard to daily cocoa intake, it should be stated that it concerns products with a high proportion of cocoa beans and with little sugar added.

We thank reviewer 3 for the comment and the suggestion. In fact, we agree that this way of concluding was uncertain and lacked clarity. We have now, instead, use the name food or product instead of supplement to avoid misunderstandings. Accordingly, it now reads “Overall, most findings support the beneficial effect of cocoa flavanols on cognitive function and neuroplasticity in young adults, suggesting that the inclusion of cocoa powder or high-cocoa flavanols products may be a realistic and reasonable preventive approach on neurodegenerative diseases and cognitive decline. Furthermore, short and middle-term effects of daily cocoa intake may provide young adults with a better cognitive performance in verbal learning, memory and attention favoring academic achievement. Nevertheless, the available evidence is very scarce and future studies are needed to increase the robustness of the results.”

We hope that by including the changes suggested in this and the previous revision of our manuscript we have improved it as to be accepted for its publication as it is.

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