RT Journal Article SR Electronic T1 How fragile are Mediterranean diet interventions? A research-on-research study of randomised controlled trials JF BMJ Nutrition, Prevention & Health JO BMJ Nutrition FD BMJ Publishing Group Ltd SP 115 OP 131 DO 10.1136/bmjnph-2020-000188 VO 4 IS 1 A1 Maria G Grammatikopoulou A1 Meletios P Nigdelis A1 Xenophon Theodoridis A1 Konstantinos Gkiouras A1 Antigoni Tranidou A1 Theodora Papamitsou A1 Dimitrios P Bogdanos A1 Dimitrios G Goulis YR 2021 UL http://nutrition.bmj.com/content/4/1/115.abstract AB 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.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.