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.