The PREDIMED Study

Original Study / Revised Analysis

Estruch R, Ros E, Salas-Salvadó J, et al. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. New England Journal of Medicine. 2018;378(25):e34.

Links to This Study

• PubMed record
  The U.S. National Library of Medicine’s record for the revised 2018 analysis, including the abstract, citation information, and links to the earlier 2013 report and retraction notice.
• DOI — permanent study identifier
  The DOI is the revised study’s permanent digital identifier and should continue to direct readers to the official journal page even if the journal’s web address changes.
• Official journal page — New England Journal of Medicine
  The revised analysis on the official journal website.

What Did the Researchers Study?

PREDIMED was a large multicenter dietary intervention trial conducted in Spain. Researchers enrolled 7,447 adults who were at high risk for cardiovascular disease but did not have cardiovascular disease when the study began.

Participants were assigned to one of three dietary groups and followed for a median of about 4.8 years.

What Were the Three Diets?

• Mediterranean diet plus extra-virgin olive oil
• Mediterranean diet plus mixed nuts
• Control diet with advice to reduce dietary fat

The Mediterranean-diet groups were encouraged to emphasize foods such as vegetables, fruits, legumes, fish, nuts, and olive oil while reducing some less-healthful foods.

What Outcome Did the Researchers Measure?

The primary outcome was a major cardiovascular event: heart attack, stroke, or death from cardiovascular causes.

This makes PREDIMED especially important because researchers were not only measuring intermediate risk factors such as cholesterol or blood pressure. They were tracking serious cardiovascular events themselves.

What Did They Find?

Both Mediterranean-diet groups had a lower risk of the combined cardiovascular outcome than the control group. The relative reduction was roughly 30%.

The overall difference was driven largely by fewer strokes in the Mediterranean-diet groups.

Why Is This Study Included Under “Can Diet Prevent Disease?”

The participants were at high cardiovascular risk but had not yet experienced cardiovascular disease when the trial began. The study therefore addressed primary prevention: whether a dietary pattern could reduce the risk of serious cardiovascular events before disease had already occurred.

What Happened in 2013 and 2018?

The original PREDIMED report was published in 2013 and became one of the most influential Mediterranean-diet studies in the world.

Later, researchers reviewing the trial discovered irregularities in how participants had been assigned to groups at some study sites. Some participants had not been randomized according to the original protocol.

Because of these problems, the authors withdrew the original 2013 report and published a revised analysis in 2018. The revised analysis used statistical methods designed to account for the protocol deviations. The overall conclusion remained similar: the Mediterranean-diet groups experienced fewer major cardiovascular events than the control group.

Why Does the Correction Matter?

The PREDIMED story is a useful example of how science corrects itself. Even very famous studies can contain methodological problems that are discovered after publication.

Retraction and republication do not automatically mean that every finding was wrong. In this case, the researchers disclosed the randomization problems, reanalyzed the data, and published a corrected report. Readers should therefore use the revised 2018 analysis rather than relying only on the original 2013 paper.

What Is a Multicenter Trial?

PREDIMED was conducted at multiple research sites in Spain. Multicenter studies are explained in Chapter 7 of Super Baby Food.

An Important Limitation

The irregularities in random assignment at some sites are an important limitation and are the reason the original report was withdrawn and replaced.

In addition, PREDIMED tested whole dietary patterns rather than one isolated food or nutrient, so the study cannot tell us exactly which part of the Mediterranean diet produced the observed benefits.

Why This Study Matters Alongside DASH and the Diabetes Prevention Program

DASH showed that diet could lower an important cardiovascular risk factor—blood pressure. The Diabetes Prevention Program showed that intensive lifestyle change could reduce the development of type 2 diabetes.

PREDIMED adds another level of evidence by examining actual major cardiovascular events. Together, these studies show several different ways that diet and lifestyle can contribute to disease prevention.