The Mediterranean Diet: Is It Cardioprotective?

Marita C. Bautista, RN; Marguerite M. Engler, PhD, RN, MS


Prog Cardiovasc Nurs. 2005;20(2):70-76. 

In This Article

Evidence From Clinical Trials

The Lyon Diet Heart Study[3,38] was the first clinical trial to demonstrate the beneficial effects of the Mediterranean diet in reducing heart disease. The study was a prospective, randomized, single-blind, multi-clinic secondary prevention trial that compared the effectiveness of a Mediterranean diet enriched with ALA with a prudent Western-type diet (AHA Step I) typically prescribed for CV health. The purpose of the study was to determine whether a diet based on the Cretan Mediterranean diet reduces cardiac mortality and morbidity after MI.

The study consisted of a sample of 605 patients less than 70 years old who had an MI within the prior 6 months. Patients were recruited during their hospital stay from multiple centers in Lyon, France. Patients assigned to the experimental group (n=302) were advised to follow the Mediterranean dietary guidelines, whereas those assigned to the control group (n=303) received only usual dietary advice from their attending physicians. The participants in the experimental group were instructed by the research cardiologist and dietitian to consume the following: more bread, more root vegetables and green vegetables, fruit at least once daily, more fish, less red meat (replaced with poultry), and a margarine high in ALA (supplied by the study) to replace butter and cream.

An intermediate analysis was performed after a minimum follow-up of 1 year per patient because significant beneficial findings were noted in the experimental group. The major finding was that after a mean follow-up of 27 months, subjects following the Mediterranean diet had a significantly reduced rate of recurrence of MI, other cardiac events, and overall mortality. In 1999, de Lorgeril et al.[3] published the results of an extended follow-up (mean of 46 months per patient) which confirmed the findings of the intermediate analyses and supported the long-term effectiveness of the Mediterranean diet. The study showed that a modified Cretan diet enriched with ALA is more effective than the AHA Step I diet in the secondary prevention of CHD.

Limitations of the Lyon Diet Heart Study have been identified in an AHA Science Advisory.[4] For example, since dietary evaluation in the control group was done only at the conclusion of the study in an effort to avoid influencing dietary habits, changes in the control group's dietary patterns could not be monitored. Moreover, comparisons between the two groups at baseline and during the study could not be analyzed. Another limitation was that dietary data for the final analysis were reported for only 30% of subjects in the control group and less than 50% of subjects in the experimental group. Thus, complete evaluation of the effect of diet on the outcomes measured could not be determined. Other key issues to be addressed in future studies include definition and consideration of geographic and nonmeasured cultural and social differences in potential target populations, and an assessment of any changes in comorbid risk factors during the study.[5]

The Italian GISSI-Prevenzione study[39] tested the efficacy of omega-3 fatty acid supplements for the secondary prevention of cardiac events in patients with recent MIs. Independent and combined effects of dietary supplementation with omega-3 fatty acids and vitamin E (α-tocopherol) on morbidity and mortality after MI were investigated. The hypothesis of the study was that there may be a complementary role between vitamin E and omega-3 fatty acids in providing cardio-protective effects.

The study sample consisted of 11,324 patients (mean age 59.4 years, 85.3% men) who survived an MI within the prior 3 months. Patients were recruited from 172 centers across Italy. Less restrictive inclusion criteria allowed for the impressive sample size. Recent MI survivors were eligible if they did not have a poor short-term prognosis or any contraindications to vitamin E or omega-3 fatty acids. Age limits were not defined. The study design was a multicenter, open-label design. Patients were randomly assigned to receive either omega-3 fatty acids alone (1 capsule daily, containing 850-882 mg of EPA and DHA; n=2836), vitamin E alone (300 mg daily; n=2830), omega-3 fatty acids and vitamin E combined (n=2830), or no supplement (control; n=2828) for 3.5 years. A limitation was that there was no placebo. All subjects followed the Mediterranean dietary principles and were encouraged to follow standard pharmacological treatments (e.g., aspirin, β blockers, angiotensin-converting enzyme inhibitors).

The major findings were that after 3.5 years, treatment with omega-3 fatty acids (alone or in combination), but not vitamin E, significantly reduced the rate of death, nonfatal MI, and stroke. Benefit was attributable to a decrease in the risk of overall and CV death. The researchers addressed limitations of the study, such as the biases an open-label study design could introduce and the risk of patients adopting different dietary habits. The study findings support the concept that long-term supplementation with omega-3 fatty acids reduces the risk of death in recent MI survivors who follow the Mediterranean diet and current standard pharmacologic treatments.

The results from several studies suggest that the Mediterranean dietary pattern can be adapted in other cultures. The Lyon Diet Heart Study[3,38] showed that a modified Cretan diet could be successfully implemented in France. The Indo-Mediterranean Diet Heart Study[40] was a single-blind, randomized, controlled trial that examined the effect of an Indo-Mediterranean diet rich in ALA in patients with or at high risk for coronary artery disease (CAD). The study consisted of a convenience sample of subjects recruited through newspaper listings and local service clubs. Participants were included in the study if they were 25 years of age or older and if they had major risk factors for CAD. The sample represented a homogenous, predominantly vegetarian population of Indianslivingin urban communities. Participants(N=1000) were randomly assigned to receive either the intervention diet (n=499) or control diet (n=501). Patients in the control group were advised to consume a reduced fat diet according to the National Cholesterol Education Program (NCEP) Step I guidelines. The active intervention group received the same advice, but were instructed to increase their daily consumption of fruits, vegetables, nuts, whole grains, and mustard seed or soy bean oil. The intervention group diet was rich in cardioprotective elements such as phytochemicals, antioxidants, and ALA.

After 2 years, both groups had significant reductions in total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride levels, with greater reductions observed in those following the Mediterranean diet. Levels of high-density lipoprotein cholesterol (HDL-C) increased with the Mediterranean diet but decreased in the control group. The Mediterranean diet was associated with a substantial reduction in the risk of nonfatal MI, sudden cardiac death, and total cardiac end points in patients at high risk for CHD. The findings provide further evidence that an Indo-Mediterranean diet rich in ALA may provide better cardioprotection than traditional low fat diets. The results also suggest that the Mediterranean diet is safe and cost-effective, with widespread adaptability to other cultures.

Strategies to enhance the adaptability of the Mediterranean dietary pattern to other cultures continue to be explored. Recent investigations have focused on various food alternatives—including a clinical trial that found that substituting walnuts for monounsaturated fat in a Mediterranean diet enhances vascular health.[41] The purpose of the study was to test the hypothesis that walnut consumption could improve endothelial function in subjects with hypercholesterolemia. Epidemiologic studies and clinical trials have demonstrated that high nut consumption can significantly decrease the risk of CHD. The positive effects of nuts are attributed to their high content of dietary fiber, folic acid, antioxidants, and L-arginine (precursor of the vasodilator nitric oxide). Walnuts, in particular, also have a high content of ALA. The study was significant because unlike previous investigations, which focused on the effect of individual factors on vascular function, it encompassed the effects of whole foods rich in these components.

The study design was a randomized, crossover dietary trial that included 21 patients (ages 25-75) with moderate hypercholesterolemia, recruited from the Lipid Clinic in Barcelona, Spain. All subjects were instructed to follow the Mediterranean dietary guidelines. Participants were then randomly assigned in a crossover design between the two diets for 4-week periods: a control, Mediterranean-type diet and a walnut diet (similar energy and nutrient content) in which walnuts replaced 32% of monounsaturated fatty acid energy content. After each dietary phase, fasting blood measurements (primarily markers of endothelial activation) and ultrasound measurements of brachial artery vasomotor function were obtained.

In comparison to the Mediterranean diet, subjects on the walnut diet had improved endothelium-dependent vasodilation and reduced levels of vascular cell adhesion molecule-1. Endothelium-independent vasodilation and levels of intercellular adhesion molecule-1, high-sensitivity C-reactive protein, homocysteine, and oxidation biomarkers were similar between groups. Lipid levels were also affected by the walnut diet. Significant reductions were observed in total and LDL-C levels. Decreased cholesterol levels correlated with an increased dietary intake of ALA and LDL α-tocopherol. Changes in endothelium-dependent vasodilation were inversely correlated with changes of cholesterol-to-HDL ratios. Limitations of the study included the use of outpatient intervention diets rather than prepared meals and the evaluation of postprandial rather than fasting endothelial function. Although the study was also limited by the small sample size and short-term duration, it provided preliminary evidence that a walnut-enriched Mediterranean diet improves endothelial function and lowers cholesterol levels.

A recent study assessed the effect of a Mediterranean-style diet on endothelial function and vascular inflammation in patients with the metabolic syndrome.[12] The metabolic syndrome consists of several factors associated with an increased risk of CV disease and type 2 diabetes. The study was a randomized, single-blind trial that consisted of 180 adult subjects (99 men and 81 women) recruited from a metabolic disease clinic at a university hospital in Naples, Italy. Eligibility criteria required that patients have three or more components of the metabolic syndrome as defined by the ATP III guidelines. Participants were randomly assigned to the intervention group (n=90) or control group (n=90). Participants in the intervention group received individualized counseling to follow a Mediterranean-style diet rich in whole grains, fruits, vegetables, legumes, walnuts, and olive oil. They also regularly attended small-group sessions held by a nutritionist during the 2-year program. Participants in the control group attended monthly sessions with study staff, but received only general dietary instruction to follow a prudent diet.

After 2 years, patients following the Mediterranean diet had significant decreases in mean body weight, insulin resistance, blood pressure, levels of glucose, insulin, total cholesterol, and triglycerides, and a significant increase in levels of HDL-C. Those in the intervention group showed improvement in endothelial function and had significantly lower levels of vascular inflammatory markers compared with those in the control group. Only 40 of the 90 patients who followed the Mediterranean diet could still be classified as having the metabolic syndrome, compared with 78 of the 90 patients in the control group. This reduction corresponded to a 50% decrease in the prevalence of metabolic syndrome.

A limitation of the study noted by the authors was that individual components of the Mediterranean diet were not investigated; however, the findings provide further supportive evidence of the effectiveness of a "whole-diet approach."


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