A randomized controlled trial, originally published in 2013 which demonstrated a beneficial effect of Mediterranean diet on cardiovascular outcomes, was retracted because of randomization errors and republished in the June issue of NEJM 2018, with the correct data but the results were not changed substantially.
It is known that the Mediterranean diet may have a protective effect against coronary heart disease. Some small studies have shown certain biologic mechanisms to explain the benefits of this dietary model in the past literature.
The authors designed a randomized trial PREDIMED (Prevención con Dieta Mediterránea), led by Ramón Estruch, M.D., to evaluate the efficacy of two different Mediterranean diets, in comparison to a control diet, on primary cardiovascular prevention. In this multicenter trial, 7447 subjects with high cardiovascular risk, but with no cardiovascular disease at enrollment were assigned, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (low-fat diet). The follow-up duration was a median of 4.8 years. The primary end point was a composite of myocardial infarction, stroke, and death from cardiovascular causes.
After publishing in 2013, the authors noticed some inconsistencies in the randomization as some patients had not been randomized correctly when they checked the data again. Although this was not a cluster randomized trial, approximately 20% of the subjects (1588 of 7447) were randomized according to blocks (household, clinic) instead of individual randomization. Subsequently, the data has been reanalyzed and adjusted for potential clustering effects.
The primary end-point event was noted in 288 subjects. There were 96 events in the group on a Mediterranean diet with extra-virgin olive oil (3.8%), 83 in the group on a Mediterranean diet with nuts (3.4%), and 109 in the control group (4.4%). According to the 2013 unadjusted and the new 2018 adjusted results for the group assigned to a Mediterranean diet with extra-virgin olive oil, the hazard ratios for the cardiovascular outcomes were found to be 0.70 (95% CI, 0.53–0.91) and 0.69 (95% CI, 0.53 to 0.91) respectively, vs the control group. For the group on a Mediterranean diet with nuts, 2013 unadjusted results indicated a hazard ratio of 0.70 (95% CI, 0.53–0.94) and 2018 publication showed a hazard ratio of 0.72 (95% CI, 0.54 to 0.95), as compared with the control diet. Consequently, the results did not differ considerably. Furthermore, the results were also consistent when they ran another analysis after excluding 1588 subjects whose randomization were suspected.
The investigators concluded that these results are consistent with previously reported benefits of the mediterranean dietary model in terms of cardiovascular risk reduction. These findings also support prior observational studies in the field.
This study included people at high cardiovascular risk and highlighted the reduction in major cardiovascular events with these two different kinds of Mediterranean diet compared to a low-fat diet.
Additional trials are required to confirm the potential benefits of a Mediterranean diet.