That Huge Mediterranean Diet Study Was Flawed. But Was It Wrong?

A highly publicized trial in Spain found that the Mediterranean diet protects against heart disease. Now the original work has been retracted and re-analyzed, with the same result.

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An olive farm in Tuscany. Participants in a study of the Mediterranean diet were not always assigned at random to test various diets, the investigators conceded.CreditGiulio Piscitelli for The New York Times

The study was a landmark, one of the few attempts to rigorously evaluate a particular diet. And the results were striking: A Mediterranean diet, with abundant vegetables and fruit, can slash the risk of heart attacks and strokes.

But now that trial, published in the New England Journal of Medicine in 2013, has come under fire. The authors retracted their original paper on Wednesday and published an unusual “re-analysis” of their data in the same journal.

Despite serious problems in the way the study was conducted, their conclusions are the same: A Mediterranean diet can cut the risk of heart attacks and strokes by about 30 percent in those at high risk.

Not everyone is convinced. “Nothing they have done in this re-analyzed paper makes me more confident,” said Dr. Barnett Kramer, director of the division of cancer prevention at the National Cancer Institute.

For decades, researchers have noted that people living in some Mediterranean countries have lower rates of heart disease and cancer. Scientists have long suspected that the regional diet — rich in fruits, vegetables, nuts and olive oil, with moderate levels of fat — played a protective role.

But the idea has been hard to prove. It is very difficult to test any diet in a clinical trial. Participants may be reluctant to stick to the prescribed meal plan, for instance, and it can be difficult to monitor them over months or years.

The original study was conducted in Spain by Dr. Miguel A. Martínez-González of the University of Navarra and his colleagues. The trial enrolled 7,447 participants aged 55 to 80 who were assigned one of three diets: a Mediterranean diet with at least four tablespoons a day of extra virgin olive oil; the same diet with an ounce of mixed nuts; or a traditional low-fat diet.

The participants were followed for a median of nearly five years. Dr. Martínez-González and his colleagues reported that there were fewer cardiovascular events in the groups consuming olive oil and nuts.

But last year Dr. Martínez-González found his study on a list of clinical trials whose data seemed suspect, compiled by Dr. John Carlisle of Torbay Hospital in England.

“We realized we had never reported that,” Dr. Martínez-González said.

Dr. Miguel A. Martínez-GonzálezCreditvia Wikimedia Commons

An omission like that erodes the randomized nature of the trial. Family members are likely to share more than just a diet: If a husband and wife both dodge heart disease, it’s difficult to say that their diet is the only reason.

In their re-analysis, the investigators statistically adjusted data on 390 people who happened to be household members but whose diets were not randomly assigned.

Then the investigators discovered another problem.

A researcher at one of the 11 clinical centers in the trial worked in small villages. Participants there complained that some neighbors were receiving free olive oil, while they got only nuts or inexpensive gifts.

So the investigator decided to give everyone in each village the same diet. He never told the leaders of the study what he had done.

“He did not think it was important,” Dr. Martínez-González said.

But the decision meant that participants were not truly randomized and forced Dr. Martínez-González and his colleagues to make another statistical adjustment to data on 652 people in the trial.

The investigators spent a year working on the re-analysis in collaboration with Dr. Miguel Hernan of the Harvard T.H. Chan School of Public Health.

In the end, they concluded that the original findings were still accurate.

“You cannot imagine what it has been like,” Dr. Martínez-González said, adding that he and his team worked through vacations and weekends — and swallowed considerable professional embarrassment.

A version of this article appears in print on , on Page A17 of the New York edition with the headline: Mediterranean-Diet Study Is Retracted, Then Reissued With Same Findings. Order Reprints | Today’s Paper | Subscribe



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