Nutraceutical: Mediterranean Diet

Indication: Cardiovascular Disease Risk

Source: New England Journal of Medicine, Feb. 25, 2013, (E-pub ahead of print)

Research: The PREDIMED trial (Prevención con Dieta Mediterránea) was a parallel-group, multicenter, randomized trial conducted in Spain. Eligible were men (55 to 80 years of age) and women (60 to 80 years of age) with no cardiovascular disease at enrollment, who had either type 2 diabetes mellitus or at least three of the following major risk factors: smoking, hypertension, elevated low-density lipoprotein cholesterol levels, low high-density lipoprotein cholesterol levels, overweight or obesity or a family history of premature coronary heart disease.

Researchers randomly assigned participants 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 (advice to reduce dietary fat). Participants in the two Mediterranean-diet groups received either extra-virgin olive oil (approximately 1 liter per week) or 30 grams of mixed nuts per day (15 grams of walnuts, 7.5 grams of hazelnuts and 7.5 grams of almonds). A general medical questionnaire, a validated food-frequency questionnaire and the Minnesota Leisure-Time Physical Activity Questionnaire were administered on a yearly basis. Information from the food-frequency questionnaire was used to calculate intake of energy and nutrients. Weight, height and waist circumference were directly measured. Biomarkers of compliance, including urinary hydroxytyrosol levels (to confirm compliance in the group receiving extra-virgin olive oil) and plasma alpha-linolenic acid levels (to confirm compliance in the group receiving mixed nuts), were measured in random subsamples of participants at 1, 3 and 5 years. The primary end point was a composite of myocardial infarction, stroke and death from cardiovascular causes. Secondary end points were stroke, myocardial infarction, death from cardiovascular causes and death from any cause.

Results: The median follow-up period was 4.8 years. A total of 288 primary-outcome events occurred: 96 in the group assigned to a Mediterranean diet with extra-virgin olive oil (3.8%), 83 in the group assigned to a Mediterranean diet with nuts (3.4%) and 109 in the control group (4.4%). Taking into account the small differences in the accrual of person-years among the three groups, the respective rates of the primary end point were 8.1, 8.0 and 11.2 per 1,000 person-years. The unadjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.53 to 0.91) for a Mediterranean diet with extra-virgin olive oil and 0.70 (95% CI, 0.53 to 0.94) for a Mediterranean diet with nuts as compared with the control diet (P = 0.015, by the likelihood ratio test, for the overall effect of the intervention).

The results of multivariate analyses showed a similar protective effect of the two Mediterranean diets versus the control diet with respect to the primary end point. Regarding components of the primary end point, only the comparisons of stroke risk reached statistical significance. Researchers concluded that in this trial, an energy-unrestricted Mediterranean diet supplemented with either extra-virgin olive oil or nuts resulted in an absolute risk reduction of approximately three major cardiovascular events per 1,000 person-years, for a relative risk reduction of approximately 30%, among high-risk persons who were initially free of cardiovascular disease. These results support the benefits of the Mediterranean diet for cardiovascular risk reduction. They are particularly relevant given the challenges of achieving and maintaining weight loss.