February 2010 Issue

The Mediterranean Diet: A Proven CVD Preventive
By Ellen Coleman, MA, MPH, RD
Today’s Dietitian
Vol. 12 No. 2 P. 48

Suggested CDR Learning Codes: 3010, 3020, 5160, 5190, 5260; Level 2

Cardiovascular disease (CVD), the leading cause of mortality and disability worldwide, is inexorably linked to diet, and many dietitians recommend dietary strategies to help prevent CVD.

The Mediterranean diet, named for the traditional dietary pattern found in the olive-growing areas of the Mediterranean region (Crete, Greece, and southern Italy), has been credited since the early 1960s with high life expectancy and low rates of CVD among inhabitants of that region. Studying the actual dietary patterns of this highly diverse population while controlling for genetics and lifestyle factors is difficult. Over time, people have touted many diet regimens, and the Mediterranean diet was one in a crowd. Dietitians could say they knew it was beneficial but couldn’t necessarily prove it.

But that has changed. In recent years, a number of rigorous, carefully designed research projects have confirmed the protective and preventive effects of a Mediterranean dietary pattern, characterized by a high intake of olive oil, vegetables, legumes, fruits, nuts, and unrefined cereals; a moderately high intake of fish; a low-to-moderate intake of dairy products (mostly in the form of cheese or yogurt); a low intake of meat, poultry, and saturated fats; and a moderate intake of alcohol (primarily in the form of wine and consumed with meals).1

This article will summarize and briefly discuss the major studies and their findings and provide full references for further reading.

Mediterranean Diet Scale
The key to population research is a valid standard of measurement. Trichopoulou and colleagues introduced the Mediterranean diet scale in 1995 to assess adherence. This scale, or variations of it, has been used to evaluate the relationship of the diet to total mortality, CVD, and other chronic diseases in numerous studies. The scale relies on nine dietary components that capture the essence of the traditional Mediterranean diet.1

Vegetables, legumes, fruits and nuts, fish and seafood, and cereals are presumed to be beneficial for health, whereas meat and meat products and dairy products are presumed not to be beneficial. A higher ratio of monounsaturated to saturated fat is considered beneficial and reflects the high olive oil consumption of the traditional Mediterranean diet. Ethanol is used as a measure of alcoholic beverage consumption, which in Mediterranean countries is mainly in the form of wine consumed during meals.

Values of 0 or 1 are assigned to each of the previously indicated components (except for ethanol intake), using the sex-specific medians in the studied population as cut-offs. A value of 0 is assigned to people whose consumption of components with a presumably beneficial effect is below the median values; a value of 1 is assigned to those equal to or above the median. Conversely, a value of 1 is assigned to people with below-the-median consumption of components without a beneficial effect, and a value of 0 is assigned to those above the corresponding median. A value of 1 is given to men who consume from 10 g (or one unit) of ethanol per day to less than 50 g (or six units) per day and a value of 0 otherwise; for women, the values are from 5 g (or half a unit) of ethanol per day to 25 g (or three units) per day.

Thus, the total Mediterranean diet score can take values from 0 to 9—minimal or maximal conformity to the traditional Mediterranean diet. This simple scale has given researchers a uniform value system to conduct population studies and a means to compare them. Many studies were conducted during the early 2000s, with most reporting at least preliminary conclusions during the past five years. The paragraphs that follow summarize these studies by topic. The body of research now available to dietitians to understand just how valuable the Mediterranean dietary regime can be is overwhelming.

Primary CVD Prevention
Trichopoulou and associates conducted a population-based, prospective investigation involving 22,043 adults in the Greek cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC) study who completed a validated food-frequency questionnaire at baseline. The authors used proportional hazards regression to assess the association between adherence to the Mediterranean diet and total mortality, as well as mortality due to coronary heart disease and cancer. The statistical analysis adjusted for age, sex, body mass index (BMI), physical activity level, and other potential confounders.2

Greater adherence to the Mediterranean diet (as indicated by a two-point increase in the Mediterranean diet score) was significantly associated with a 25% reduction in total mortality and a 33% lower mortality from coronary heart disease after 3.7 years of follow-up.2

The longevity and cardiovascular benefits of following a Mediterranean dietary pattern are not limited to European citizens. Mitrou and associates evaluated the relationship of the Mediterranean dietary pattern to all-cause and cause-specific mortality in 214,284 men and 166,012 women in the National Institutes of Health (NIH)-AARP Diet and Health Study. Greater conformity to the Mediterranean diet was associated with a statistically significant reduction in total mortality (21% for men, 20% for women) and cardiovascular mortality (22% for men, 19% for women) after 10 years of follow-up.3

Sofi and colleagues conducted a systematic review of prospective studies that analyzed the relationship between adherence to a Mediterranean diet, mortality, and the incidence of chronic diseases.4 Overall mortality was evaluated in eight cohorts (nine studies) for a total of 514,816 subjects and cardiovascular mortality was assessed in three cohorts (four studies) for a total of 404,491 subjects. The analysis found that greater adherence to the Mediterranean diet (as shown by a two-point increase in the Mediterranean diet score) was significantly associated with a 9% reduced risk of total mortality and a 9% lower mortality from CVD.

Secondary CVD Prevention
Since atherosclerosis is a progressive disease, researchers have proposed that the Mediterranean diet can favorably influence the clinical outcome of individuals with CVD. Trichopoulou and associates examined the association between adherence to the Mediterranean diet and the survival of 1,302 men and women diagnosed with coronary heart disease upon enrollment in the Greek cohort of the EPIC study. Greater adherence to the Mediterranean diet (as indicated by a two-point increase in the Mediterranean diet score) was associated with a significant 27% lower mortality rate and 31% fewer deaths from coronary heart disease among individuals with preexisting heart disease after 3.7 years of follow-up.5

Cardiovascular Risk Factors
The Prevención con Dieta Mediterránea (or PREDIMED study, for Prevention with Mediterranean Diet) is an ongoing multicenter, primary prevention trial designed to assess the effects of three healthy diets on cardiovascular outcomes (eg, cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) in a high-risk population. The diets are a Mediterranean diet supplemented with 1 L of virgin olive oil per week, a Mediterranean diet supplemented with 30 g of mixed nuts per day, and a low-fat diet. The anticipated completion date of the trial is December.6

The pilot PREDIMED study conducted by Estruch and associates with 772 male subjects found that the two Mediterranean diets reduced blood pressure, improved lipid profiles, decreased insulin resistance, and reduced concentrations of inflammatory molecules after three months of follow-up compared with the low-fat diet.6

Sánchez-Taínta and colleagues found that following a Mediterranean diet was inversely associated with the clustering of hypertension, diabetes, obesity, and hypercholesterolemia in a cross-sectional survey of high-risk patients in the PREDIMED study.7

A Mediterranean-style diet may also be effective for reducing the prevalence of the metabolic syndrome and associated cardiovascular risk. Esposito and associates found that a Mediterranean diet significantly reduced C-reactive protein (CRP), interleukin-6 and -18, and insulin resistance in individuals with the metabolic syndrome compared with a low-fat diet.8 At two years of follow-up, only 40 of 90 patients in the Mediterranean diet group had features of the metabolic syndrome compared with 78 of 90 patients in the low-fat diet group.

Chrysohoou and colleagues found that subjects with the highest adherence to the Mediterranean diet had 20% lower CRP levels, 17% lower interleukin-6 levels, 15% lower homocysteine levels, 14% lower white blood cell counts, and 6% lower fibrinogen levels compared with those with the lowest adherence in the Greek ATTICA study.9

The Mediterranean Diet, Cardiovascular Risks and Gene Polymorphisms (Medi-RIVAGE) study evaluated the effect of a Mediterranean diet compared with a low-fat diet on cardiovascular risk factors in 212 male and female subjects at moderate risk for CVD. Although the dietary goals were only partly achieved, both diets significantly reduced CVD risk factors to the same extent after three months of dietary intervention. Based on the decrease in total cholesterol, the authors estimated that the Mediterranean diet reduced cardiovascular risk by 15% compared with a 9% reduction with the low-fat diet.10

The Seguimiento University of Navarra (SUN) study is an ongoing cohort of Spanish university graduates that began in 1999 and has included more than 17,000 participants since September 2007. Tortosa and colleagues assessed the relationship between adherence to the Mediterranean diet and the subsequent development of the metabolic syndrome in 5,360 initially healthy subjects in the SUN dynamic cohort. Subjects with the highest adherence to the Mediterranean diet had lower cumulative incidence of the metabolic syndrome than those with the lowest adherence after six years of follow-up.11

Martínez-González and associates evaluated the relationship between adherence to a Mediterranean diet and the incidence of diabetes among 13,380 initially healthy participants in the SUN dynamic cohort.12 Greater adherence to the Mediterranean diet (as indicated by a two-point increase in the Mediterranean diet score) was associated with a 35% relative reduction in the risk of type 2 diabetes after 4.4 years of follow-up.

Panagiotakos and colleagues found that the consumption of a Mediterranean diet was associated with a 26% lower risk of being hypertensive and a 36% greater probability of having  blood pressure controlled in the Greek ATTICA study.13

Núñez-Córdoba and associates found that greater adherence to the Mediterranean diet was associated with reduced changes in systolic and diastolic blood pressure in 9,408 men and women after 4.2 years in the SUN study. These results suggest that following a Mediterranean diet could help prevent age-related increases in blood pressure.14

Psaltopoulou and colleagues found that the Mediterranean diet score was significantly inversely associated with both systolic and diastolic blood pressure in the Greek cohort of the EPIC study.15

The Mediterranean dietary pattern may be more appropriate than a low-fat diet for individuals with the metabolic syndrome, type 2 diabetes, and insulin resistance. The Mediterranean diet has a positive effect on serum insulin, glucose, and lipid levels, as well as other metabolic factors that increase the risk of CVD.16

Weight Gain
Some health professionals are concerned that the high fat content of the Mediterranean dietary pattern may lead to obesity. However, a high olive oil consumption (within the context of the Mediterranean diet) was not associated with greater weight gain or a significantly greater risk of developing obesity in 7,368 male and female subjects in the SUN study during 2.3 years of follow-up.17

Mendez and colleagues found that high adherence to the Mediterranean diet was associated with a significantly lower likelihood of becoming obese among overweight subjects in the Spanish EPIC cohort after 3.3 years of follow-up.18 Schroder and associates found that the traditional Mediterranean dietary pattern was inversely associated with BMI and obesity in a cross-sectional survey.19

Another cross-sectional survey found that greater adherence to the Mediterranean diet was associated with a 51% lower risk of being obese and a 59% lower risk of having central obesity compared with a non-Mediterranean diet after controlling for potential confounders.20

Importance of Mediterranean Diet Components
Possible mechanisms for the cardiovascular protection offered by a Mediterranean dietary pattern include the improvement of lipid profiles and the reductions in blood pressure, insulin resistance, and inflammatory markers.1

Investigations regarding the dietary components responsible for the cardiovascular benefits of the Mediterranean diet have focused primarily on olive oil and red wine. Olive oil contains a high amount of monounsaturated fat from oleic acid and has well-documented favorable effects on blood lipids.21 However, the phenolic compounds in olive oil have antioxidant properties and may also affect serum lipid levels. Virgin olive oils have a higher phenolic content than refined olive oils. Covas and colleagues found that HDL cholesterol increased linearly with the phenolic content of olive oil and oxidative stress markers decreased linearly with increasing phenolic content.22

Numerous epidemiological studies indicate that drinking small-to-moderate amounts of alcohol can reduce the risk of CVD.23 Alcohol may protect against CVD by increasing HDL cholesterol, decreasing LDL cholesterol oxidation, and reducing blood fibrinogen and by other antithrombotic actions. Wine consumption has been associated with a lower risk of CVD compared with other types of alcohol. However, wine drinkers are also more likely to lead a healthier lifestyle, drink temperately, and drink with meals compared with individuals who prefer other alcoholic beverages.24

Trichopoulou and colleagues evaluated the contribution of the nine widely accepted components of the Mediterranean diet to the reduced total mortality associated with greater adherence to this diet among 23,349 subjects in the Greek EPIC cohort. Greater adherence to the Mediterranean diet (as indicated by a two-point increase in the Mediterranean diet score) was significantly associated with a 14% reduction in total mortality after 8.5 years of follow-up.25

The contributions of the Mediterranean diet’s individual components to this association were moderate alcohol consumption, 23.5%; low consumption of meat and meat products,16.6%; high vegetable consumption, 16.2%; high fruit and nut consumption, 11.2%; high monounsaturated to saturated fat ratio, 10.6%; and high legume consumption, 9.7%. The contributions of high cereal consumption (6.1%) and low dairy consumption (4.5%) were minimal, whereas high fish and seafood consumption was associated with a nonsignificant increase in mortality ratio.25

The authors concluded that the dominant components of the Mediterranean diet score that predict lower mortality are moderate alcohol consumption, low consumption of meat and meat products, and high consumption of vegetables, fruits, nuts, olive oil, and legumes. Minimal contributions were found for cereals and dairy products, possibly because they are heterogeneous categories of foods with differing health effects (eg, whole vs. refined grain, low-fat vs. high-fat dairy), and for fish and seafood, which were minimally consumed by this population.25

Trichopoulou and colleagues emphasized that their results do not refute the possibility of synergistic effects among foods and nutrients in the Mediterranean diet.25 Overall, research suggests that the health benefits associated with the Mediterranean diet are due to biological interactions between different components of the Mediterranean dietary pattern (food synergy) rather than an effect of only one nutrient, food, or food group. More research is required to understand these complex interactions.1

Summary
The numbers don’t lie. The Mediterranean eating pattern has been associated with a high life expectancy and low rates of CVD. Even better than that, it has no downside. There is no risk of side effects, as with many CVD-management drugs, and no known association with chronic conditions or allergies. It is versatile, palatable, and familiar, with no exotic grains or expensive vegetables required. With a little bit of attention to menu choices and careful shopping, people can realize dramatic improvements while enjoying a convivial dining experience.

Making the case for the Mediterranean diet and singling it out among the clamor of competing diet fads has been difficult for dietitians. Now, the methodology has emerged and studies have confirmed what anecdotal reports first announced: Greater adherence to the Mediterranean dietary pattern is associated with lower total and cardiovascular mortality in primary and secondary prevention studies. There are few concerns about recommending it. There is insufficient evidence that the high-fat content of the Mediterranean dietary pattern may lead to the development of obesity. Studies have shown an inverse relationship between adherence to the Mediterranean dietary pattern and weight gain.

Possible mechanisms for the cardiovascular protection offered by a Mediterranean dietary pattern include the improvement of lipid profiles and the reductions in blood pressure, insulin resistance, and inflammatory markers. It is likely that many components characteristic of the Mediterranean dietary pattern interact in a synergistic way to reduce the risk of CVD. Since we now have a simple, nine-point scale to assess compliance with the regimen, we can expect more intricate and sophisticated studies about the synergistic aspects in the future.

— Ellen Coleman, MA, MPH, RD, is a nutrition consultant at The SPORT Clinic in Riverside, Calif.

Mediterranean Dietary Pattern
• An abundance of food from plant sources, including fruits, vegetables, potatoes, breads and grains, beans, nuts, and seeds.
• Emphasis on a variety of minimally processed, seasonally fresh, and locally grown foods.
• Olive oil as the principal fat, replacing other fats and oils.
• Total fat ranging from less than 25% to more than 35% of energy, with saturated fat comprising no more than 7% to 8% of energy.
• Daily consumption of low to moderate amounts of cheese and yogurt.
• Twice-weekly consumption of low to moderate amounts of fish and poultry.
• Zero to four eggs per week.
• Fresh fruit as the typical daily dessert; sweets with a significant amount of sugar (often as honey) and saturated fat consumed no more than a few times per week.
• Red meat consumed a few times per month.
• Moderate consumption of wine, normally with meals, about one to two glasses per day for men and one glass per day for women.

Learning Objectives
After completing this continuing education exercise, the student should be able to:
1. Describe key characteristics of the Mediterranean dietary pattern.
2. Discuss the effect of the Mediterranean dietary pattern on risk factors for cardiovascular disease (CVD).
3. Explain why the Mediterranean dietary pattern may be more appropriate than a low-fat diet for individuals with the metabolic syndrome, type 2 diabetes, and insulin resistance.
4. Identify which components of the Mediterranean diet are presumed to be beneficial for preventing CVD.
5. Identify possible mechanisms for the cardiovascular protection offered by a Mediterranean dietary pattern.

Examination
1. In the Mediterranean diet scale, the following dietary components are assumed to be beneficial:
a. A higher ratio of monounsaturated to saturated fat
b. Meat and meat products and dairy products
c. Vegetables, legumes, fruits, nuts, fish, and seafood
d. a and c
e. a and b

2. The systematic review of prospective studies by Sofi and colleagues found that greater adherence to the Mediterranean diet was significantly associated with:
a. a 9% reduction in cardiovascular mortality.
b. a 14% reduction in total mortality.
c. a 25% reduction in total mortality.
d. a 33% reduction in cardiovascular mortality.
e. None of the above

3. A Mediterranean diet is associated with:
a. a lower risk of developing the metabolic syndrome.
b. a lower risk of developing type 2 diabetes.
c. a higher risk of weight gain.
d. a and c
e. a and b

4. The Mediterranean dietary pattern may be more appropriate than a low-fat diet for individuals with the metabolic syndrome, type 2 diabetes, and insulin resistance.
a. True 
b. False

5. Possible mechanisms for the cardiovascular protection offered by a Mediterranean dietary pattern include:
a. improvement of lipid profiles.
b. reductions in blood pressure.
c. decreased insulin resistance.
d. reduction of inflammatory markers.
e. All of the above

6. The following statement about olive oil is not substantiated:
a. It has a favorable effect on blood lipids.
b. Olive oils with higher phenolic content may increase HDL cholesterol.
c. A high consumption within the context of the Mediterranean diet is associated with a greater risk of developing obesity.
d. Olive oils with higher phenolic content may reduce oxidative stress.
e. Virgin olive oils have a higher phenolic content than refined olive oils.

7. Compared with individuals who prefer other alcoholic beverages, wine drinkers:
a. lead a healthier lifestyle.
b. drink temperately.
c. drink with meals.
d. have a lower risk of developing cardiovascular disease.
e. All of the above

8. Trichopoulou and colleagues (2005) found that greater adherence to the Mediterranean diet was significantly associated with this percentage of fewer deaths from coronary heart disease:
a. 27%
b. 31%
c. 25%
d. 33%
e. None of the above

9. Of the nine components of the Mediterranean diet, which component reduced mortality the most in the study conducted by Trichopoulou and colleagues?
a. High monounsaturated to saturated fat ratio
b. Low consumption of meat and meat products
c. Moderate alcohol consumption
d. High vegetable consumption
e. High fruit and nut consumption

10. Research suggests that the health benefits associated with the Mediterranean diet are due to:
a. the effect of individual dietary components in the Mediterranean diet.
b. synergistic interactions between different components in the Mediterranean diet.
c. high monounsaturated to saturated fat ratio.
d. moderate alcohol consumption.
e. residing in the Mediterranean region.

References
1. Martinez-Gonzales M, Bes-Rastrollo M, Serra-Majem L, et al. Mediterranean food pattern and the primary prevention of chronic disease: Recent developments. Nutr Rev. 2009;67 Suppl 1:S111-S116.

2. Trichopoulou A, Costacou T, Bamia C, Trichopoulos D. Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med. 2003;348(26):2599-2608.

3. Mitrou PN, Kipnis V, Thiébaut AC, et al. Mediterranean dietary pattern and prediction of all-cause mortality in a US population: Results from the NIH-AARP Diet and Health Study. Arch Intern Med. 2007;167(22):2461-2468.

4. Sofi F, Cesari F, Abbate R, Gensini, Casini A. Adherence to Mediterranean diet and health status: Meta-analysis. BMJ. 2008;337:a1344.

5. Trichopoulou A, Bamia C, Trichopoulos D. Mediterranean diet and survival among patients with coronary heart disease in Greece. Arch Intern Med. 2005;165(8):929-935.

6. Estruch R, Martinez-Gonzalez MA, Corella D, et al. Effects of a Mediterranean-style diet on cardiovascular risk factors: A randomized trial. Ann Intern Med. 2006;145(1):1-11.

7. Sánchez-Taínta A, Estruch R, Bulló M, et al. Adherence to a Mediterranean-type diet and reduced prevalence of clustered cardiovascular risk factors in a cohort of 3,204 high-risk patients. Eur J Cardiovasc Prev Rehabil. 2008;15(5):589-593.

8. Esposito K, Marfella R, Ciotola M, et al. Effect of a Mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: A randomized trial. JAMA. 2004;292(12):1440-1446.

9. Chrysohoou C, Panagiotakos DB, Pitsavos C, et al. Adherence to the Mediterranean diet attenuates inflammation and coagulation process in healthy adults: The ATTICA Study. J Am Coll Cardiol. 2004;44(1):152-158.

10. Vincent-Baudry S, Defoort C, Gerber M, et al. The Medi-RIVAGE study: Reduction of cardiovascular disease risk factors after a 3-mo intervention with a Mediterranean-type diet or a low-fat diet. Am J Clin Nutr. 2005;82(5):964-971.

11. Tortosa A, Bes-Rastrollo M, Sanchez-Villegas A, et al. Mediterranean diet inversely associated with the incidence of metabolic syndrome: The SUN prospective cohort. Diabetes Care. 2007;30(11):2957-2959.

12. Martínez-González MA, de la Fuente-Arrillaga C, Nunez-Cordoba JM, et al. Adherence to Mediterranean diet and risk of developing diabetes: Prospective cohort study. BMJ. 2008;336(7657):1348-1351.

13. Panagiotakos DB, Pitsavos CH, Chrysohoou C, et al. Status and management of hypertension in Greece: Role of the adoption of a Mediterranean diet: The ATTICA study. J Hypertens. 2003;21(8):1483-1489.

14. Núñez-Córdoba JM, Valencia-Serrano F, Toledo E, Alonso A, Martinez-Gonzalez MA. The Mediterranean diet and incidence of hypertension: The Seguimiento Universidad de Navarra (SUN) Study. Am J Epidemiol. 2009;169(3):339-346.

15. Psaltopoulou T, Naska A, Orfanos P, et al. Olive oil, the Mediterranean diet, and arterial blood pressure: the Greek European Prospective Investigation into Cancer and Nutrition (EPIC) study. Am J Clin Nutr. 2004;80(4):1012-1018.

16. Champagne CM. The usefulness of a Mediterranean-based diet in individuals with type 2 diabetes. Curr Diab Rep. 2009;9(5):389-395.

17. Bes-Rastrollo M, Sánchez-Villegas A, de la Fuente C, et al. Olive oil consumption and weight change: The SUN prospective cohort study. Lipids. 2006;41(3):249-256.

18. Mendez MA, Popkin BM, Jakszyn P, et al. Adherence to a Mediterranean diet is associated with reduced 3-year incidence of obesity. J Nutr. 2006;136(11):2934-2938.

19. Schroder H, Marrugat J, Vila J, Covas MI, Elosua R. Adherence to the traditional Mediterranean diet is inversely associated with body mass index and obesity in a spanish population. J Nutr. 2004;134(12):3355-3361.

20. Panagiotakos DB, Chrysohoou C, Pitsavos C, Stefanadis C. Association between the prevalence of obesity and adherence to the Mediterranean diet: The ATTICA study. Nutrition. 2006;22(5):449-456.

21. Kris-Etherton PM. AHA science advisory. Monounsaturated fatty acids and risk of cardiovascular disease. American Heart Association. Nutrition committee. Circulation. 1999;100(11):1253-1258.

22. Covas MI, Nyyssönen K, Poulsen HE, et al. The effect of polyphenols in olive oil on heart disease risk factors: A randomized trial. Ann Intern Med. 2006;145(5):333-341.

23. Goldberg IJ, Mosca L, Piano MR, et al. AHA science advisory: Wine and your heart: A science advisory for healthcare professionals from the Nutrition Committee, Council on Epidemiology and Prevention, and Council on Cardiovascular Nursing of the American Heart Association. Circulation. 2001;103(3):472-475.

24. Klatsky AL. Alcohol and cardiovascular diseases. Expert Rev Cardiovasc Ther. 2009;7(5):499-506.

25. Trichopoulou A, Bamia C, Trichopoulos D. Anatomy of health effects of Mediterranean diet: Greek EPIC prospective cohort study. BMJ. 2009;338:b2337.