February 25th, 2013

Large Trial Shows Cardiovascular Benefits of Mediterranean Diet

A large new trial offers powerful evidence that a Mediterranean diet can reduce the risk for cardiovascular disease. Results of the PREDIMED (Prevención con Dieta Mediterránea) study were published online in the New England Journal of Medicine.

Investigators in Spain randomized 7447 people at high risk for cardiovascular disease to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with nuts, or a control diet for which people were advised to lower their intake of dietary fat. The diets were designed not to restrict calories but to change the composition of the diet.

The trial was stopped early in July 2011 by the data and safety monitoring board when the benefits in the Mediterranean diet groups crossed a predetermined boundary. After 4.8 years of follow-up a primary endpoint event (the composite of MI, stroke, and death from CV causes) occurred in 3.8% of patients in the Mediterranean diet extra-virgin olive oil group, 3.4% in the Mediterranean diet with nuts group, and 4.4% of patients in the control group. After adjusting for small differences among the groups, the hazard ratios for the two Mediterranean diet groups were 0.70 (95% CI, 0.54-0.92) and 0.72 (95% CI, 0.54-0.96). The benefit in favor of the Mediterranean diet groups occurred early in the trial and continued throughout the follow-up period. The results were consistent across a broad range of subgroups.

Given that the results appear consistent with those from previous smaller trials and observational studies, the authors said that “a causal role of the Mediterranean diet in cardiovascular prevention has high biologic plausibility. The results of our trial might explain, in part, the lower cardiovascular mortality in Mediterranean countries than in northern European countries of the United States.”

The authors said the benefits of the Mediterranean diet may be explained by several different factors, including moderate alcohol consumption, low consumption of meat, and high consumption of vegetables, fruits, nuts, legumes, fish, and olive oil.

“Perhaps there is a synergy among the nutrient-rich foods included in the Mediterranean diet that fosters favorable changes in intermediate pathways of cardiometabolic risk, such as blood lipids, insulin sensitivity, resistance to oxidation, inflammation, and vasoreactivity.”

One limitation, acknowledged by the authors, is that the reduction in total fat intake in the control group was small. In addition, although people in the Mediterranean diet groups ate more fish and legumes, they did not substantially alter other aspects of their diet. The authors speculated that the consumption of the recommended olive oil and nuts, which were distributed for free to patients in the Mediterranean diet groups, may have been “responsible for most of the observed benefits of the Mediterranean diets.”

One PREDIMED investigator, Emilio Ros, told CardioExchange that he believes the results of the trial mean that current recommendations regarding dietary fat should be changed to reflect that a “high fat, high vegetable fat diet is optimal for cardiovascular health.” Another study investigator, Ramón Estruch, said that “a major problem with low-fat diets is their low potential for long-term sustainability.” He said that the results clearly demonstrate “the superiority of the Mediterranean diets.”

7 Responses to “Large Trial Shows Cardiovascular Benefits of Mediterranean Diet”

  1. Why don’t we have more large trials of dietary strategies? We need evidence here. I was very interested in this result and blogged about it on the Forbes site (http://www.forbes.com/sites/harlankrumholz/2013/02/25/ole-how-the-new-spanish-study-should-change-your-diet/).

    Here is an excerpt:

    “How does this result compare with other strategies to lower risk? Well, we spend billions of dollars on medications such as ezetimibe, fenofibrate, and niacin that have no recent clinical trial evidence of benefit – so this diet far exceeds those popular medications. Statins, one of our best agents to reduce cardiovascular risk, is in the same ballpark – with most studies showing that this class of drugs reduces risk by about 25%. I suppose of these Mediterranean diets were drugs, they might be considered blockbuster drugs.”

  2. Antonio Reis, Ph.D says:

    Good point Dr Krumholz: “How does this result compare with other strategies to lower risk? Well, we spend billions of dollars on medications such as ezetimibe, fenofibrate, and niacin that have no recent clinical trial evidence of benefit – so this diet far exceeds those popular medications.”
    However, many other studies have shown that Mediterranean diet is well-balanced and healthy in my view this study only shows that Med diet is far more healthy than the “low-fat diet” that was used as control and that is the current paradigm of a cardiovascular friendly diet.
    Med diet against statins? Well, Mediterranean diet as is not a business that could be of interest to Big Pharma!

  3. Antonio Reis, Ph.D says:

    Only one additional observation:
    In the paper cited and with the values ​​shown in “Figure 2. Results of Subgroup Analyses” it appears that adding the end-point events of the participants in the Med diet and the control diet they result as negative aspects: being male, age, diabetes, hypertension, smoking, family history of premature CHD, waist, waist-to-height ratio.
    However, dyslipidemia appears to be a positive aspect. In fact considering the totality of the partipants, dyslipidemic ones had fewer end-point events (175/5383) = 3.2% than non dyslipidaemic (113/2064) = 5.4%!
    Does anyone have an explanation for this?

  4. I wonder if they are the ones on statins.

    • Antonio Reis, Ph.D says:

      Dr Krumholz,
      In this study 6447 participants were dyslipidaemic, and 2986 were on statins. Assume that only dyslipidaemic were on statins. Assume further that the sub-group of dyslipidaemic that were on statins has had zero end-points, and that all end-points (175) of the dyslipidaemic group occurred in the sub-group of those who are not on statins (3461). Yet this sub-group had a better score (175/3461=5%) than the group of non-dyslipidaemic (113/2064 = 5.4%)!
      The mystery of lower end-points of the dyslipidaemic group with respect to non-dyslipidaemic one remains unexplained!!!

  5. Arthur Agatston, MD says:

    An answer to the dyslipidemia paradox may be that type 2 diabetics with dyslipidemia (mainly low HDL, high TG, small LDL) are responders to diet and lifestyle changes more than those at risk for CAD from other familial causes. This is in fact why those who “yo yo diet have been found to be at higher risk for CAD than those who don’t. It is not the yo yoing but the selection of those who are likely to yo yo (dyslipidemic, insulin resistant, metabolic syndrome types) that confers the bad prognosis. In the PREDIMED study, those without dyslipidemia may have been more likely to be smokers, have a family history of premature CAD not associated or less associated with lifestyle than the dyslipidemics and may have had hypertension also less responsive to diet. In addition, type 2 diabetics without dyslipidemia may be less insulin resistant and also less responsive to the Mediterranean Diet.

  6. Mark Perlroth Mark, md says:

    The “low fat” diet was not really low fat (i.e. not 10% fat)

    The only significant end point was fewer strokes, not MI’s or mortality.

    The people who benefited from the intervention were those who are traditionally at risk (ie family history, overweight, etc).

    The absolute magnitude of the differences was minuscule during the period of the study.