The Mediterranean diet's landmark trial was retracted, then republished

The Mediterranean diet has the strongest randomised evidence of any named dietary pattern for preventing cardiovascular disease — but the trial that anchors that claim, Spain's PREDIMED, was retracted in 2018 and republished the same month with corrected analyses [s1]. The reissued results still found fewer heart attacks, strokes and cardiovascular deaths among people assigned to a Mediterranean diet than among those told simply to cut fat, though the correction changed how firmly cause can be claimed [s1].

What PREDIMED tested

PREDIMED enrolled 7,447 participants aged 55 to 80, of whom 57% were women, all at high cardiovascular risk but with no cardiovascular disease at enrollment [s1]. They 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 consisting of advice to reduce dietary fat [s1]. The intervention groups received quarterly educational sessions and free provision of olive oil or nuts; the control group received small non-food gifts [s1].

The primary end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes [s1]. After a median follow-up of 4.8 years, the trial was stopped early on the basis of a prespecified interim analysis [s1].

The result, and what changed

In the corrected analysis, a primary end-point event occurred in 288 participants overall: 96 events in the olive-oil group (3.8%), 83 in the nut group (3.4%), and 109 in the control group (4.4%) [s1]. Adjusting for baseline characteristics and propensity scores, the hazard ratio was 0.69 (95% CI, 0.53 to 0.91) for the Mediterranean diet with olive oil and 0.72 (95% CI, 0.54 to 0.95) for the Mediterranean diet with nuts, each compared with the control diet [s1].

Those figures are close to the ones first reported in 2013 [s2]. What forced the correction was not the effect size but the randomisation. After publication, the authors identified protocol deviations: at one of the 11 study sites, some participants were assigned to a study group without randomisation; at another, randomisation tables appear to have been used inconsistently; and household members were enrolled together without being separately randomised [s1]. They withdrew the 2013 report and re-ran the analysis without relying on the assumption that every participant had been randomly assigned [s1].

The reassuring detail is that the conclusion held. When the authors omitted the 1,588 participants whose group assignments were known or suspected to have departed from the protocol, the results were similar [s1].

Why a correction of this size matters

Randomisation is the feature that separates a trial from an observational study. Done properly, it balances the two groups on everything — measured and unmeasured — so that a later difference in outcomes can be attributed to the intervention. Where it breaks down, some of that protection is lost, and the analysis has to lean on statistical adjustment instead, which can only correct for things that were measured.

That is why the republished PREDIMED is worded more cautiously than the original. It reports that the incidence of major cardiovascular events was lower in the Mediterranean-diet groups [s1] — an association within a large, mostly randomised trial — rather than presenting itself as a clean causal result untouched by the flaw. The honest reading is that PREDIMED remains the best randomised evidence available for the Mediterranean pattern and cardiovascular outcomes, and that "best available" is not the same as "definitive."

It is also a trial in a specific population. Participants were older Spanish adults already at high cardiovascular risk [s1]. The absolute gap between arms was modest — 4.4% of controls versus 3.4% to 3.8% of the intervention groups had an event over roughly five years [s1] — and in a younger or lower-risk group, the same relative reduction would prevent far fewer events, because there are fewer to prevent.

Where it sits among the diets

No other whole-diet pattern has a primary-prevention cardiovascular trial of this scale behind it, which is why the Mediterranean diet is routinely described as the strongest-evidenced. That standing rests heavily on this single trial and the large body of observational work around it, so the caveats travel with the claim rather than cancelling it.

The pattern has been tested for other endpoints too. A separate Spanish trial, PREDIMED-Plus, later examined whether adding calorie restriction and exercise to a Mediterranean diet reduced diabetes risk further, and a randomised trial has tested the Mediterranean diet against irritable bowel symptoms. Each answers a narrower question than "is this the healthiest way to eat," which no trial has been built to settle.

Nothing here is dietary advice for any individual. What to eat, and how it interacts with a person's own cardiovascular risk, is a question for a clinician who knows their history.

Sources

• Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts — New England Journal of Medicine, 2018-06-13
• RETRACTED: Primary Prevention of Cardiovascular Disease with a Mediterranean Diet — New England Journal of Medicine, 2013-04-04