The Nutrition Source

PREDIMED Study Retraction and Republication

What Changed, What Didn’t, and the Big Picture

On June 13, 2018, the New England Journal of Medicine (NEJM) retracted the 2013 study, “Primary Prevention of Cardiovascular Diseases with a Mediterranean Diet,” [1] as a result of error in randomization procedures affecting a portion of participants in the PREDIMED (Prevención con Dieta Mediterránea) trial. Concurrently, NEJM published a corrected version of the study with reanalyzed data, “Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts.” [2]

What Changed?

  • The number of participants included in the analysis:
    • The original study included 7447 participants at high cardiovascular risk 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 (advice to reduce dietary fat). [1]
    • The republished study disclosed several issues related to the randomization process: enrollment of household members without randomization; allocation of several clinics instead of individual patients at 1 of 11 study sites; and apparent inconsistent use of randomization tables at another study site.
    • The authors re-ran the analyses by statistically correcting for correlations within families or clinics. They also re-ran the analyses omitting 1588 participants whose trial-group assignments were known or suspected to have departed from proper randomization protocol. [2]

What Didn’t Change?

  • Despite these revelations, there was no significant change in the results of the trial when researchers reanalyzed the data:
    • In both the original and republished study, the incidence of cardiovascular disease in the Mediterranean diet groups was lowered by approximately 30% when compared to the control diet. [1,2]
    • The overall conclusion remains largely unchanged: “In this study involving persons at high cardiovascular risk, the incidence of major cardiovascular events was lower among those assigned to a Mediterranean diet supplemented with extra-virgin olive oil or nuts than among those assigned to a reduced-fat diet.” [2]
  • To date, PREDIMED remains the largest dietary intervention trial to assess the effects of the Mediterranean diet on cardiovascular disease prevention.

The Big Picture

As a randomized clinical trial, results from PREDIMED remain a significant contribution to the scientific literature on a traditional Mediterranean diet. That said, it is only a portion of the large body of evidence indicating the healthfulness of this dietary pattern. The bottom line remains that strong evidence supports the use of the traditional Mediterranean diet as a healthy eating pattern for the prevention of cardiovascular diseases, increasing lifespan, and healthy aging.

Furthermore, the discussion surrounding the retraction and republication of this landmark research study is an important reminder that solid science is not based on any single study, but the result of sustained and critically evaluated research by multiple investigators through many studies, over many years.

Related

Diet Review: Mediterranean Diet
What should I Eat?
Preventing Heart Disease

References

  1. Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, Gómez-Gracia E, Ruiz-Gutiérrez V, Fiol M, Lapetra J, Lamuela-Raventos RM. Primary prevention of cardiovascular disease with a Mediterranean diet. New England Journal of Medicine. 2013 Apr 4;368(14):1279-90.
  2. Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, Gómez-Gracia E, Ruiz-Gutiérrez V, Fiol M, Lapetra J, Lamuela-Raventos RM. Primary prevention of cardiovascular disease with a mediterranean diet supplemented with extra-virgin olive oil or nuts. New England Journal of Medicine. 2018 Jun 13.