But they cautioned that participants in the study lived in a Mediterranean country and were already at high risk for cardiovascular events, so it is not clear how well the results will apply to other people.
Nonetheless, the trial's data and safety monitoring board ruled late in 2011 that the benefits were sufficiently clear that the study should be stopped, Estruch and colleagues reported online in the New England Journal of Medicine.
The traditional Mediterranean diet, the researchers noted, is characterized by lots of olive oil, fruit, nuts, vegetables, legumes, and cereals, some fish and poultry, and limited amounts of dairy products, red meat, processed meats, and sweets. As well, the diet includes moderate amounts of wine with meals.
To test the idea that the diet protected against heart disease, the researchers randomly assigned 7,447 people, ages 55 to 80, to one of three diets -- a Mediterranean diet with additional unrefined (or extra-virgin) olive oil, a Mediterranean diet supplemented with mixed nuts (mainly walnuts), or a control diet, which consisted essentially of advice to reduce dietary fat.
The majority of the participants were women (57%) and were free of cardiovascular disease when they started, but either had diabetes or at least three important cardiovascular risk factors, such as smoking, hypertension, or obesity. They received quarterly educational sessions and, depending on group assignment, free extra-virgin olive oil, mixed nuts, or small nonfood gifts
The primary endpoint was a composite of strokes, heart attacks, and cardiovascular death.
After a median follow-up of 4.8 years, 288 participants had a primary endpoint event, including 96 (3.8%) in the olive-oil group, 83 (3.4%) in the mixed-nut group, and 109 (4.4%) in the control group.
In a multivariable analysis, the olive-oil diet led to a 28% reduction in risk, compared with the control diet (hazard ratio 0.72, 95% CI 0.54 to 0.92, P=0.01).
The mixed nut diet led to a similar risk reduction (HR 0.72, 95% CI 0.54 to 0.97, P=0.03).
Results were similar when the two Mediterranean diets were combined and compared with the control diet, they found.
The researchers cautioned that loss to follow-up might have affected the results, although those lost were mainly from the control group and had worse cardiovascular risk profiles than those who remained in the trial.
Although the study suggests benefits for unrefined olive oil and nuts, the key factor was change in the dietary pattern, argued senior author Miguel Angel Martínez-González, MD, PhD, of the University of Navarra in Pamplona, Spain, who presented the data at the International Congress on Vegetarian Nutrition being held in Loma Linda, Calif.
"Our aim was to modify the whole dietary pattern," he told a media conference at the meeting, adding there was good evidence that both the unrefined olive oil and the nuts reduced cardiovascular risk.
But it would be "overly optimistic to think that with a single food you can obtain a very large reduction in risk," he said, adding it's not just a matter of cooking meat and sausage in olive oil or adding walnuts to sweet desserts.
The study is important because it is one of the first to yield gold-standard evidence of the effect of a dietary intervention, commented David Jacobs, PhD, of the University of Minnesota in Rochester, who was not part of the study.
"What this study gives us is A-level evidence," Jacobs said during the media conference.
He added that regulators and agencies that establish dietary guidelines will likely take notice of the quality of the evidence.
Although the study was presented a meeting on vegetarian nutrition, the Mediterranean diet is "plant-based" rather than strictly vegetarian, commented conference chairman Joan Sabate, MD, of Loma Linda University.