Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Reviewer Report

The manuscript entitled “Mediterranean Diet and Multidimensional Healthy Ageing: A Narrative Review” addresses a relevant and timely topic. The attempt to examine Mediterranean diet adherence within a multidimensional healthy-ageing framework, rather than focusing exclusively on individual clinical outcomes, is valuable. I particularly appreciate the effort to distinguish between different levels of evidence across cognitive, physical, and cardiometabolic domains and the inclusion of socioeconomic, cultural, and age-specific determinants of dietary adherence.

The manuscript is generally well structured and covers a substantial body of recent literature. However, several methodological and interpretative issues should be addressed before the manuscript can be considered for publication. My main concern relates to the methodology of the narrative review and the extent to which some conclusions can be supported by the literature-selection process described by the authors.

Major comments

1. The literature-search methodology requires substantially greater transparency.

Although this is presented as a narrative rather than a systematic review, the manuscript includes a specific search period, databases, eligibility considerations, and statements concerning the relative strength and consistency of evidence. Therefore, the reader should be provided with enough methodological information to understand how the evidence included in the review was identified and selected.

Currently, the Methods section states that PubMed and Scopus were searched beginning with the terms “Mediterranean diet” and “older adults”, with additional terms added “as the review developed”. This approach is insufficiently reproducible and introduces a potentially important selection bias.

I recommend that the authors provide, at minimum:

• the complete search strategy or principal combinations of search terms used for each major domain;

• the date of the final search;

• clearer inclusion and exclusion criteria;

• information regarding how studies were selected;

• whether screening and study selection were performed by one or more authors;

• an explanation of how the authors prioritised individual studies, systematic reviews, meta-analyses, and RCTs when several sources addressed the same outcome.

The authors correctly acknowledge later that the review was not preregistered and did not employ formal selection or quality-assessment criteria. However, acknowledging this limitation does not fully compensate for the limited transparency of the search process.

2. The definition of the target population needs clarification.

The review is explicitly focused on healthy ageing and older adults, yet the authors state that no fixed age cut-off was applied and that studies involving younger and middle-aged adults were retained “when appropriate”. Several studies subsequently discussed include populations considerably younger than what would generally be considered an older population.

This creates some tension between the stated objective and the actual evidence base. The authors should establish a clearer operational definition of the population of interest and explain under what circumstances studies including younger populations were considered relevant. Where evidence is derived predominantly from middle-aged populations, this should also be made explicit in the corresponding sections rather than only acknowledged globally as a limitation.

3. The manuscript would benefit from a summary table of the evidence.

Considering the breadth of outcomes covered, it is currently difficult for the reader to obtain an overview of the evidence supporting each domain. A table summarising the main evidence would substantially strengthen the manuscript.

I suggest including columns such as: domain/outcome, main source(s) of evidence, study design, population, principal findings, and overall limitations/level of certainty. The table could cover cognition, frailty, sarcopenia/physical function, cardiometabolic outcomes, successful ageing/longevity, and potentially the proposed biological mechanisms.

This would also help support one of the central messages of the review: that the strength of evidence differs substantially between domains.

4. Some statements regarding the strength of evidence should be reconsidered.

The authors make a commendable effort to differentiate association from causation. Nevertheless, some passages still use language that appears stronger than warranted by the evidence discussed.

For example, the manuscript describes “high-certainty” evidence linking Mediterranean diet adherence with frailty based on observational cohort and cross-sectional evidence. Even if this terminology reflects the GRADE assessment reported in the cited meta-analysis, the manuscript should make clear that this is the certainty rating reported by that review rather than an independent assessment conducted by the present authors.

More generally, expressions such as “protective effect”, “benefits”, “improves”, or similar causal wording should be carefully reviewed throughout the manuscript when the underlying evidence is observational. Terms such as “was associated with”, “was related to”, or “was linked to” would be more appropriate unless supported by intervention evidence.

5. The distinction between the Mediterranean diet and other dietary patterns should be maintained consistently.

The Introduction appropriately notes that DASH and MIND are related but distinct dietary patterns and should not be treated as equivalent to Mediterranean-diet adherence. However, evidence concerning the MIND diet is subsequently used relatively extensively in the cognitive section.

This evidence can certainly provide useful context, but the authors should more clearly distinguish evidence directly concerning the Mediterranean diet from evidence concerning MIND or other related dietary patterns. Otherwise, the reader may interpret findings from different dietary constructs as part of a single evidence base.

6. The section on biological mechanisms should more clearly distinguish mechanistic plausibility from demonstrated mediation.

The mechanisms section is comprehensive and interesting, particularly the discussion of inflammation, oxidative stress, the microbiome, endothelial function, and biological ageing. However, evidence that Mediterranean-diet adherence is associated with biomarkers or physiological pathways does not necessarily establish that these mechanisms mediate the observed clinical outcomes.

This distinction is particularly relevant for the microbiome/gut-brain axis and epigenetic ageing sections, where the authors themselves acknowledge conflicting or predominantly cross-sectional evidence. I suggest making the distinction between “proposed mechanisms”, “biological plausibility”, and demonstrated causal mediation more explicit throughout this section.

7. The Public Health Implications section occasionally goes beyond the evidence synthesised in the review.

Statements such as “the MedDiet is an excellent candidate for promotion at the population level” appear somewhat stronger than the otherwise cautious interpretation adopted by the manuscript. This is particularly relevant because the authors themselves emphasise that most evidence is observational, generalisability is limited, and adherence is strongly influenced by socioeconomic and cultural conditions.

I recommend moderating some of this wording and distinguishing more clearly between evidence supporting health associations and evidence supporting the effectiveness, feasibility, cost-effectiveness, and equity of population-level implementation.

8. The HORUS project requires careful contextualisation.

The discussion of the HORUS programme is relevant to the sections concerning adaptation and disadvantaged populations. However, the manuscript is funded within the framework of the HORUS project, and several authors appear associated with this programme. The paragraph therefore risks appearing disproportionately detailed relative to other intervention examples.

I suggest either shortening this description or explicitly explaining why HORUS provides a particularly relevant example for the conceptual framework of the review. Since the cited publication is a protocol, it should also be made very clear that outcome data are not yet being presented as evidence of effectiveness.

9. The manuscript requires careful language editing.

There are several grammatical problems, awkward constructions, repetitions, and punctuation issues throughout the manuscript. These do not generally prevent comprehension, but they affect readability.

One clear example occurs in the cognitive ageing section, where the sentence “Beyond observational data, intervention evidence points in the same direction” is essentially repeated consecutively before the MedEx-UK trial is described.

There are also several expressions throughout the manuscript that would benefit from editing by a fluent English speaker. I recommend a comprehensive linguistic revision rather than correction of isolated sentences.

Minor comments

1. Please ensure consistent terminology for “Mediterranean diet”, “MedDiet”, and Mediterranean dietary pattern throughout the manuscript.

2. Abbreviations should generally be defined at first appearance and then used consistently. Some abbreviations are introduced even when they are used only a few times.

3. The description of “inflammageing” could be shortened. Some passages in the mechanisms section read more like a general textbook description of ageing biology than material directly necessary for the review question.

4. Please check numerical and typographical consistency throughout the manuscript, including decimal separators, spaces around confidence intervals, en dashes, and presentation of sample sizes.

5. In Section 4.1, the duplicated wording preceding the description of the MedEx-UK trial should be removed.

6. The discussion of alcohol within the traditional Mediterranean diet is useful and appropriately cautious. However, the authors may wish to state more explicitly that alcohol consumption should not be initiated for the purpose of increasing Mediterranean-diet adherence.

7. In Section 7.2, the description of the Mediterranean Diet Score and MEDAS is useful, but the statement that MEDAS scores below 10 “typically indicate low adherence” should be carefully referenced and terminology harmonised with the validation/source literature.

8. The manuscript would benefit from a figure presenting the proposed conceptual framework: Mediterranean-diet adherence → biological pathways → multidimensional healthy-ageing outcomes, with socioeconomic, cultural, behavioural, and age-related factors influencing adherence.

9. Please review the Conclusions to avoid repetition of material already discussed extensively in Sections 6 and 7. The conclusion could be more concise and focused on the principal take-home message.

 

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript presents a solid, up-to-date, and critically balanced discussion of the role of the Mediterranean diet in the context of functional decline and healthy aging, aligned with the World Health Organization (WHO) framework. While the text does not require a structural methodological overhaul, it does need the correction of certain typos (including a text duplication), an enhancement of the visual and tabular material, and greater transparency regarding the bibliographic search string.

Weaknesses
1. Absence of graphic elements and summary tables:
The text is entirely narrative and spans 20 pages. It lacks a conceptual summary figure (e.g., biological mechanisms → clinical domains → barriers) and a summary table outlining the levels of evidence for each outcome considered (cognition, frailty, sarcopenia, cardiometabolic profile, longevity).

2. Textual errors and duplications:
- Lines 258–260: There is an obvious duplication: "Beyond observational data, intervention evidence points in the same direction: a further RCT, was conducted, implementing MedDiet and/or physical activity over a 24-week period. Beyond observational data, intervention evidence points in the same direction. In the MedEx-UK...".
- Line 261: Typographical error in the sample size: "feasibility RCT (n – 104; 57–76 years)" (hyphen used instead of the equals sign "=").
- Lines 401 and 624: Missing final period at the end of the paragraph.
- Line 694: Missing space after the period in "funding acquisition: V.V., T.R.All authors have read...".
- Line 804 (Ref. 21): Character encoding error in the author's surname ("KÖ chl, C." instead of "Köchl, C.").

3. Research methodology details:
In Section 2 (Materials and Methods)—despite this being a narrative review—neither the combinations of Boolean operators (AND/OR) nor the specific exclusion criteria (beyond language-based ones) are specified.

Suggestions for Authors
1. Visual summary. It is recommended to include:
- A summary table listing: clinical domain, predominant study designs (RCT vs. cohort), strength of evidence/GRADE, key biological mechanisms, and main known limitations.
- An explanatory figure linking biological mechanisms (inflammation, microbiota, endothelium, epigenetics) to multidimensional outcomes and adherence barriers in the elderly.

2. Text revision:
- Remove the duplicate sentence at lines 258–260.
- Correct the numerical notation at line 261 to (n=104).
- Revise punctuation at lines 401 and 624, as well as the typographical formatting of the references.

3. Methods:
Briefly detail the search string used to query PubMed and Scopus.

We suggest a major revision for this manuscript. 

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

In this review article, the authors summarize and discuss the efficacy of the Mediterranean diet and the various limitations of past research, drawing on studies published between 2020 and 2026. The article is considered valuable from both research and clinical perspectives because it goes beyond merely highlighting efficacy; it also addresses the limitations of randomized controlled trials (RCTs) and observational studies, inconsistencies in assessment, factors hindering adherence, and potential solutions. Overall, the paper is well-structured and free of logical leaps. However, there are several instances where the cited references supporting the authors' claims are missing. Providing citations not only substantiates the authors' arguments but also helps other researchers gain knowledge from the referenced sources. Please review the specific instances listed below:

 

Line 164-165 “Greater adherence is … frailty in older adults.”

Line 165-167 “Frailty is connected with … in people at risk of sarcopenia.”

Line 178-180 “Nonetheless, other research has … beneficial dietary patterns.”

Line 194-196 “A meta-analysis suggests that…at increased risk of CVDs.”

Line 431-435 “A large feasibility…free food provision.”

Line 481-482 “The protective association was … the assessment method used.”

Line 483-485 “Some define it by…not usually the same.”

Line 485-486 “Some studies ask participants … it with tests.”

Line 510-511 “Some of the studies discussed … specifically to older populations.”

Line 581-583 “However, to assess whether … NMR- based biomarkers.”

 

Other notes:

Regarding the MD-score, it is first introduced in Line 278 and subsequently explained in detail from Line 563 onwards. A detailed explanation of MDS should be provided where it is first introduced.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have satisfactorily addressed all comments; therefore, the publication of their article can proceed.

Author Response

We thank the reviewer for the positive evaluation of our revised manuscript.

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have addressed my previous comments in a substantial and convincing manner. The new conceptual figure and the summary table significantly improve readability and the integration of the evidence; the requested textual corrections have been made, and the description of the literature search is now more transparent. However, a minor revision is required before final acceptance.

Remaining issues before acceptance
A. The statement regarding RCTs on cognition needs to be qualified
Lines 293–294 state:
"the evidence from RCTs in this domain is currently limited to a single small feasibility trial." The same point appears in Table 1.
As a statement concerning the entire body of literature, this is too absolute; there are previous randomized studies on the Mediterranean diet that include cognitive assessments, such as analyses conducted within the PREDIMED framework. While the specific time frame chosen by the authors may explain their selection, it does not justify a broad conclusion regarding the absence of other trials.
The authors should either qualify this statement by limiting it to the studies included in this review and the time period considered, or briefly acknowledge the existence of relevant prior randomized evidence.
It is important to ensure that a limitation inherent to a narrative selection process is not presented as a characteristic of the entire field.

B. The request regarding methodology has been only partially addressed
1. The primary PubMed search string is now provided: "(Mediterranean diet) AND (older adults)." However, two details remain:
- Scopus: The search string used is not specified, nor is it explicitly clarified whether this string was also not recorded.
- Search repeated on October 16, 2026: It is unclear whether the 2,964 results were obtained by applying the same temporal and linguistic filters used in the original selection.
For a narrative review, acknowledging that the exploratory search strings were not preserved is a transparent and acceptable response. The authors are asked to clarify what can actually be documented.
2. The fact that 44 of the 53 articles were retrieved via the repeated search confirms a correspondence with the selected bibliography, but it does not demonstrate the completeness of the search.

C. Some textual errors remain. The most obvious issue is in the Introduction:
- Lines 39–40: "has made healthy ageing the functional ability that allowsa global priority." This sentence is garbled and needs to be corrected—for example, to: "has made healthy ageing a global priority."

D. Other examples that need fixing:
- Line 252: "role of the MedDiet" should be "the role of the MedDiet."
- Line 275: "20-80 year" should be "20–80 years."
- Lines 390–391: "as by the two studies above illustrate" should be "as the two studies above illustrate."
- Line 600: "The quality ... depend" should be "The quality ... depends."
These are issues to be addressed during the final linguistic review. Additionally, the page numbering—which restarts after the insertion of the table—requires editorial adjustment.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf