Plant Foods Rich in Antioxidants and Human Cognition: A Systematic Review

Round 1

Reviewer 1 Report

The present manuscript reviews the association between plant foods rich in antioxidants and human cognition. This manuscript presents important information in the topic. However, in my opinion there are some issues to be clarified before the manuscript could be considered for publication.

My general main concern is that both results and discussion sections are too long, and they should be significantly shortened. A more concise and systematic approach should be presented.

Abstract

Following instructions for authors, please remove headings within the abstract (background, methods, etc.)

Introduction

Lines 34-35. For non-familiarized readers I suggest including some more details regarding these risk factors. For example, stating that gender is associated with dementia is not very informative, it would be more useful if the authors indicate which gender is associated with higher dementia prevalence.

Lines 45-46 (and others). While the manuscript, from the title, seems to be focused on oxidative stress, an important role in given to inflammation. The authors should clarify the role of inflammation in the topic considered an whether inflammation issues will be considered in the review. Actually, having a look to Table 1 it seems that inflammation is as important as oxidation in this review.

Lines 63-64. The presence of lower antioxidants levels does not necessarily indicate that a diet high in antioxidants would prevent any disease.

Lines 69-70. In my opinion this question should be clearly clarified from the beginning. Which are the antioxidant rich plant foods? Which are the antioxidants considered?

Line 70. I understand the inclusion of the term “Mediterranean diet” but I suggest stating the positive characteristics of this diet rather than the general diet. A high adherence to the Mediterranean diet could suppose a high wine consumption, with lots of phenolic antioxidants. I don’t believe this is the pattern of diet to follow.

Line 76. I’m not sure vitamin D could be considered an antioxidant, at least at the same level as the others listed.

Lines 76-77. I suggest not considering and/or discussing together exogenous and endogenous antioxidants. Mechanisms leading to their increases and/or decreases could be quite different.

Lines 88-95. Consider as a possible reason the decreased bioavailability of most antioxidants when they are taken as supplements, out of their “natural food environment”.

Materials and Methods

Line 105 (and in the introduction and, in general, in whole manuscript). I don’t know whether it is appropriate to consider together veganism and “plant-based”. The Mediterranean diet allows, among others, fish, eggs, dairy products and some meat consumption, leading to a diet that could be quite different to the vegan one.

Line 110. Why was “oxidative stress” not considered?

Results

Table 1. Consider including the number of participants in the studies, as this could indicate the validity, or confidence, of evidence reported. In relation to the inclusion and exclusion criteria, was the number of participants considered to include or exclude studies

In my opinion results there is a general lack of clarity in the presentation of results. Why the authors present firstly studies by plant foods (table 1) and then other studies that are the ones included in the review (table 2)? While products considered are the same, this seems to be an unnecessary differentiation. This should be more clearly explained and justified.

Lines 168-559. This content should be clearly shortened.

Discussion

Lines 567-571. This seems to be contradictory with the initial aim of the review. May be a way to shorten the manuscript it to consider from the beginning only polyphenols.

In my opinion a review of all plant foods is not necessary as results in a too long listing of all plant-foods. There is a lot of repetitions of contents previously included in the results section and in the tables.

The discussion should be focused on the main mechanisms leading to the beneficious effects. Most of these mechanisms seem to be common to the main phenolic compounds.

Conclusions

In line with my previous comments, content of the conclusion section reinforces the idea of a review focused only on phenolic compounds from the initial aim.

Lines 852-853. Consider removing this content as this could be considered the reason to be included in the review.

Lines 860-861. Avoid speculations and include only concise conclusions form results presented.

Author Response

see attached file

Author Response File: Author Response.docx

Reviewer 2 Report

The study by Baroni and co-authors focuses on the very interesting topic of the link between the consumption of antioxidant-rich foods and the impact on human cognition.
The methodology used for this systematic review of the literature is well described and the introduction is clearly written.
The biases associated with this type of study are well known. In each study, different foods, administered in different ways for different lengths of time to a different population, are considered. Impacts on human cognition are also measured in different ways. It is also well known in this type of study that the evidence of a correlation between the consumption of a particular food product and a health effect may be due to another factor than the consumption of the food itself (e.g. lifestyle).
However, this study has the merit of bringing together in a single publication all the studies on the subject, describing the compounds present in each of these foods and the potential mode of action on cognitive capacity.
In this respect, the conclusion could emphasize the potential bias of the studies analyzed here.

Author Response

see attached file

Author Response File: Author Response.docx

Reviewer 3 Report

In the manuscript authored by Luciana Baroni et al. performed a systematic revision of the current literature on the beneficial effects on cognition of plant-derived antioxidants used in the diet.

Authors provided an accurate revision of the literature. Despite valuable in the attempt, the manuscript results approximative.  Especially in the introduction section authors provided a sort of summary of what is the contribution of oxidative stress and inflammation in Alzheimer's disease, considering the simplistic vision of ROS seen as harmful and not considering ROS can also act as second messengers (see PMID: 33129798). I suggest also revising the entire structure of the introduction since it is really a simplistic vision of the disease. 

There is a lower incidence of dementia or Alzheimer's disease in vegeterians? this information should be included in the manuscript. 

line 133-137: authors contribution should not be reported in the manuscript text but in the author contribution paragraph at the end of the manuscript.

Authors included in table 4 some concepts that were not better described in the text as the capability to reduce AGEs formation or MAO-B activity. The table instead should summarize and better focalize the most impactful concepts already described in the manuscript. In fact, table 4 is a sort of an additional chapter instead of a table. 

Clinical trials with Ginko Biloba are now ongoing in Alzheimer's disease fields, but this is not reported. 

Plant-derived foods are well-known as plenty of beneficial properties, among which also antioxidant and neuroprotective effects. These concepts have been already well-stressed in the literature thus the manuscript in this present form sounds not of impactfulness. 

Author Response

see attached file

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

All my previous comments have been properly addressed.

Author Response

Reviewer 3 Report

Authors performed the following revisions that still need to be modified:

Question: There is a lower incidence of dementia or Alzheimer's disease in vegetarians? this information should be included in the manuscript. 

Authos reply: they included the following sentence in the study: "The only study performed on vegetarians found that in a group of over 3,000 individuals, non-vegetarians had twice the risk of developing dementia compared to vegetarians (Giem, P et al. Neuroepidemiology 1993)"

New comment: Giem et al (1993) reported that there was a trend towards delay onset of dementia in vegetarians. Thus please modify accordingly in the revised version of the manuscript. 

New comments:

 1) what authors mean with "a reductionistic perspective"?

2) Is nuts a "plant species" or is a "Dietary Plant Foods"? please modify in table1

3) please check the correct use of trial, clinical recruitment, subjects recruitment, case control study and voluntiers recruitment in all the studies reported. 

4) table 2 : use the same format for gender distribution (count or %)

5) again table4 need to be revised. Too many information are included in the table. It is more like a new chapter rather than a table. summarize and reformat the table with also columns. 

Author Response

see attached file, please

Author Response File: Author Response.docx

Round 3

Reviewer 3 Report

The revised version of the manuscript has been highly improved from the original version, thus I suggest this revised version of the manuscript for a possible publication after Editor's approval.