Olive Oil Phenolic Compounds’ Activity against Age-Associated Cognitive Decline: Clinical and Experimental Evidence

Round 1

Reviewer 1 Report

Comments for author File: Comments.pdf

Author Response

We appreciate Reviewer #1's insightful comment regarding the focus on hydroxytyrosol in our pre-clinical studies and the omission of other relevant EVOO phenolic compounds. To clarify our rationale, we wish to provide two observations that guided our decision.

Firstly, while tyrosol and oleuropein are indeed important phenolic compounds found in EVOO, we have previously reported that in vivo, tyrosol is bioconverted into hydroxytyrosol through CYP450 isoforms, and oleuropein is extensively hydrolyzed into hydroxytyrosol upon ingestion. Hence, we believe that hydroxytyrosol (HT) is the phenolic compound that plays a pivotal role in triggering a significant portion of the beneficial effects attributed to EVOO consumption in an in vivo setting.

Secondly, one of the reasons we chose to focus solely on hydroxytyrosol in this revision was to limit its length. The literature contains a substantial number of pre-clinical studies investigating the effects of various olive oil phenolic compounds. By concentrating on hydroxytyrosol, we aimed to streamline our research while still addressing an essential component of EVOO's bioactivity.

In response to reviewer #1 feedback, we have revised the introduction section to incorporate a statement that elucidates the rationale behind this revision.

“In this article, we review the scientific evidence of the neuroprotective role of olive oil phenolic compounds in the prevention of age-associated cognitive decline. Our aim in the first part of the article was to review the mechanisms described in pre-clinical studies that could explain the results observed in epidemiological studies. We focused our revision around HT, which we considered to be the most relevant among the EVOO phenolic compounds. Acknowledging the presence of other relevant phenolic compounds like Tyr or oleuropein, it is important to note that they undergo conversion/metabolism into HT after its ingestion in vivo. Thus, HT plays a central role in the biological effects attributed to EVOO consumption. We focus our interest on those studies using doses compatible with those achieved in the diet and put special emphasis on the role of the metabolites of the phenolic compounds. In the second part, we critically review the main existing evidence from clinical trials assessing cognitive performance and the intake of olive oil phenolic compounds, either in the form of EVOO or in nutraceutical formulations.”

Reviewer 2 Report

The manuscript by Boronat A et al reviewed the effects of olive oil phenolic compounds on age-associated cognitive decline. Although I have a feeling that this review is too wide and too long, the manuscript is written very well. In my opinion, this manuscript is not recommended for publication in its present form, but can be accepted as the paper after minor revision.

 

1. Paragraphs: Unfortunately, I feel that this manuscript consists of too many paragraphs. Especially, Introduction section. I strongly recommend you to describe in appropriate paragraphs.

 

2.  Abbreviations: Abbreviations used should be defined once the first time they appear in the text. Once a word is abbreviated, by contrast, the abbreviation should be used throughout the manuscript.

(Aβ, NF-ĸB, APP/PS1, SOD, GPX, CAT, IL-18, IL-6, TNF-α, iNOS, COX-2, MAPK, SIRT1/AMPK/PGC1 axis, MPP+, MCI)

 

3 minor point

MAO (monoamine oxidase) →Monoamine oxidase (MAO)

 

Ca2+→Ca²⁺

Abbreviations used should be defined once the first time they appear in the text. Once a word is abbreviated, by contrast, the abbreviation should be used throughout the manuscript.

Author Response

Following the advice of reviewer #2, we have diligently revised the entire manuscript, eliminating unnecessary information and summarizing the main ideas as much as possible. We have successfully reduced the final manuscript from 29 to 27 pages, representing a reduction of approximately 1000 words. However, we believe that further reduction in length would compromise the quality of the summarized information and make it more cumbersome to read.

Reviewer comment 1:

Paragraphs: Unfortunately, I feel that this manuscript consists of too many paragraphs. Especially, Introduction section. I strongly recommend you to describe in appropriate paragraphs.

We thank Reviewer #2 for pointing this out. We have reduced the total length and the number of paragraphs from the introduction section.

Reviewer comment 2:

Abbreviations: Abbreviations used should be defined once the first time they appear in the text. Once a word is abbreviated, by contrast, the abbreviation should be used throughout the manuscript.

(Aβ, NF-ĸB, APP/PS1, SOD, GPX, CAT, IL-18, IL-6, TNF-α, iNOS, COX-2, MAPK, SIRT1/AMPK/PGC1 axis, MPP+, MCI)

We appreciate the comment and we have properly modified throughout the manuscript.

Reviewer comment 3:

3 minor point

MAO (monoamine oxidase) →Monoamine oxidase (MAO)

Ca2+→Ca2+

Thanks, we have accordingly modified.

 

Reviewer 3 Report

In this study, the authors summarized the neuroprotective effects of olive oil phenolic compounds in vitro and in vivo. Further, they summarized clinical evidence regarding nutritional interventions supplemented with olive oil on cognition. The manuscript is well-written and interesting. I have minor comments.

 

1. In the section 3.2.2. and Table 3, the authors describe the effects of HT on depression. Since depression is not age-related neurodegenerative disorder, I think it is better to remove the statement regarding depression or make a new section about depression.

Author Response

Reviewer 3

In this study, the authors summarized the neuroprotective effects of olive oil phenolic compounds in vitro and in vivo. Further, they summarized clinical evidence regarding nutritional interventions supplemented with olive oil on cognition. The manuscript is well-written and interesting. I have minor comments.

1. In the section 3.2.2. and Table 3, the authors describe the effects of HT on depression. Since depression is not age-related neurodegenerative disorder, I think it is better to remove the statement regarding depression or make a new section about depression.

 

We appreciate reviewer #3 comments and following his/her suggestion we have accordingly modified section 3.2.2 and table 3.