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Original research
How fragile are Mediterranean diet interventions? A research-on-research study of randomised controlled trials
  1. Maria G Grammatikopoulou1,2,3,
  2. Meletios P Nigdelis1,
  3. Xenophon Theodoridis2,4,
  4. Konstantinos Gkiouras2,4,
  5. Antigoni Tranidou4,5,
  6. Theodora Papamitsou6,
  7. Dimitrios P Bogdanos2,7 and
  8. Dimitrios G Goulis1
  1. 1 Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Central Macedonia, Greece
  2. 2 Rheumatology and Clinical Immunology, Faculty of Health Sciences, University of Thessaly, Larissa, Greece
  3. 3 Nutritional Sciences & Dietetics, Faculty of Health Sciences, International Hellenic University, Thessaloniki, Greece
  4. 4 Medical School, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Central Macedonia, Greece
  5. 5 Department of Endocrinology, Diabetes and Metabolism, Hippokration General Hospital of Thessaloniki, Thessaloniki, Central Macedonia, Greece
  6. 6 Laboratory of Histology and Embryology, Medical School, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Central Macedonia, Greece
  7. 7 Division of Transplantation, Immunology and Mucosal Biology, MRC Centre for Transplantation, School of Medical Education, King's College London, London, UK
  1. Correspondence to Dr Maria G Grammatikopoulou, Nutritional Sciences & Dieteticss, International Hellenic University Faculty of Health Sciences, Alexander Campus, Thessaloniki, Greece; mariagram{at}auth.gr; Professor Dimitrios G Goulis, Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki Faculty of Health Sciences, Thessaloniki, Greece; dgg{at}auth.gr

Abstract

Introduction The Mediterranean diet (MD) is a traditional regional dietary pattern and a healthy diet recommended for the primary and secondary prevention of various diseases and health conditions. Results from the higher level of primary evidence, namely randomised controlled trials (RCTs), are often used to produce dietary recommendations; however, the robustness of RCTs with MD interventions is unknown.

Methods A systematic search was conducted and all MD RCTs with dichotomous primary outcomes were extracted from PubMed. The fragility (FI) and the reverse fragility index (RFI) were calculated for the trials with significant and non-significant comparisons, respectively.

Results Out of 27 RCTs of parallel design, the majority failed to present a significant primary outcome, exhibiting an FI equal to 0. The median FI of the significant comparisons was 5, ranging between 1 and 39. More than half of the comparisons had an FI <5, indicating that the addition of 1–4 events to the treatment arm eliminated the statistical significance. For the comparisons with an FI=0, the RFI ranged between 1 and 29 (Median RFI: 7). When the included RCTs were stratified according to masking, the use of a composite primary endpoint, sample size, outcome category, or dietary adherence assessment method, no differences were exhibited in the FI and RFI between groups, except for the RFI among different compliance assessment methods.

Conclusions In essence, the present study shows that even in the top tiers of evidence hierarchy, research on the MD may lack robustness, setting concerns for the formulation of nutrition recommendations.

  • nutritional treatment

Data availability statement

Although most of the data are already presented in the manuscript text, they are also available upon reasonable request. For expression of interest, please contact Prof. Dimitrios G. Goulis.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjnph-2020-000188

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    Data availability statement

    Although most of the data are already presented in the manuscript text, they are also available upon reasonable request. For expression of interest, please contact Prof. Dimitrios G. Goulis.

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    Footnotes

    • Twitter @melnigdelis, @x_theodoridis, @dbogdanos

    • MPN and XT contributed equally.

    • Contributors MGG and DGG developed the research question and finalised the paper inclusion. MPN, MGG, KG and XT performed the search and extracted the data. AT and TP participated in the search. KG designed the protocol. XT, MGG and DPB calculated the FI and the RFI. MPN and KG assessed the risk of bias of the included trials, with some help from MGG and supervision from DGG and DPB. MPN and MGG performed the statistical analyses. KG, MPN, XT, TP and MGG prepared tables and figures. DGG, DPB and MGG interpreted results, drafted and finalised the manuscript. All authors read the manuscript, contributed comments to its revision, and have approved and agreed to the final version. MGG submitted the manuscript, and DGG is responsible for the overall content as guarantor.

    • Funding The present research was funded by the “MSc in Health and Environmental factors”, Medical School, Aristotle University of Thessaloniki.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.