Examining the Impact of the Mediterranean Diet on CVD

Studies included in the review investigated the impact of the Mediterranean diet on primary prevention, progression, and mortality related to cardiovascular disease, hypertension, and rheumatoid arthritis.

Randomized controlled trials provided some limited evidence that a Mediterranean diet without fat restriction may reduce the incidence of cardiovascular disease (CVD), cancer, and diabetes, according to a new systematic review. However, there was no observed effect on all-cause mortality.1

The Mediterranean diet first appeared in the medical literature in 1970 with the publication of the initial results of the Seven Countries Study by biologist Ancel Keys, PhD.  Dr Keys’ report suggested that there was a lower incidence of CVD and coronary artery disease (CAD) in populations near the shores of the Mediterranean Sea. The diet was described as high in fruits, vegetables, whole grains, and fat primarily from nuts and olive oil, and low in meat.2 

Studies that have investigated the Mediterranean diet have also included fatty fish with ω-3 polyunsaturated fatty acids and lower-fat dairy products.2  In contrast, the standard Western diet tends to be higher in refined grains, saturated fats, and sugar. Diabetes, cancer, and CVD are major causes of mortality and morbidity in the United States with a suspected causal link to the suboptimal Western diet.1

Hanna E. Bloomfield, MD, MPH, of the Center for Chronic Disease Outcomes Research, the Minneapolis VA Health Care System, and professor of medicine at the University of Minnesota in Minneapolis, and colleagues conducted a systematic review and meta-analysis of studies assessing the outcomes of the Mediterranean diet with unrestricted fat content. Studies included in the review investigated the impact of the Mediterranean diet on primary prevention, progression, and mortality related to diabetes, CVD, hypertension, cancer, rheumatoid arthritis, kidney disease, and cognitive impairment. 

Of 10,349 abstracts, only 56 studies met their inclusion criteria. Of those included, 44 assessed primary prevention, 12 assessed secondary prevention, and no studies addressed adherence.

The analysis included 2 randomized control trials on primary prevention, which demonstrated no difference in all-cause mortality. The PREDIMED study had 7447 participants and compared the Mediterranean diet with olive oil, the Mediterranean diet with nuts, and a low-fat diet. Results indicated a lower incidence of diabetes (hazard ratio [HR], 0.70; 95% CI, 0.54-0.92), breast cancer (HR, 0.43; 95% CI, 0.21-0.88), and major CV events (HR, 0.71; 95% CI, 0.56-0.90) with the combined data from the 2 Mediterranean diets.1

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Pooled analysis of 28 cohort studies with more than 2 million participants suggested that participants in the highest quantile of Mediterranean diet adherence had a 14% lower cancer mortality (risk ratio [RR], 0.86; 95% CI, 0.82-0.91) and a 4% decrease in cancer incidence (RR, 0.96; 95% CI, 0.95-0.97).1 Likewise, there was a 9% reduction in colorectal cancer incidence in the pooled data (RR, 0.91; 95% CI, 0.84-0.98) and a lower risk for breast cancer (RR, 0.96; 95% CI, 0.90-1.03) for the highest quantile of adherence.1 

For secondary prevention, only 1 of 3 randomized control trials showed a reduction in recurrent myocardial infarction risk (RR, 0.32; 95% CI, 0.15-0.70) and CV death risk (RR, 0.32, 95% CI: 0.13-0.78) with a Mediterranean diet.Cohort studies found similar cancer-related mortality and cancer recurrence between the lowest and highest quantile of adherence to the Mediterranean diet.1

Proposed mechanisms of the positive clinical outcomes include decreases in inflammatory markers, glucose, LDL cholesterol, and body weight associated with a Mediterranean diet.Further, 2 large-scale prospective cohort studies seem to also support the mortality benefits of a primarily whole-foods, plant-based diet. For instance, the Adventist Health Study 2 included 73,308 participants followed for nearly 6 years. The all-cause mortality was lower in vegetarians than non-vegetarians (adjusted HR, 0.88; 95% CI, 0.80-0.97).3

The Greek segment of the European Prospective Investigation into Cancer and Nutrition (EPIC) study included 23,349 participants followed for 8.5 years. The investigators found that the higher the adherence to a Mediterranean, the greater the reduction in total mortality observed (14% reduction per 2-unit improvement in diet score).4 When the data were analyzed further, most of the benefit from the Mediterranean diet was attributed to moderate ethanol consumption (23.5%), decreased meat intake (16.6%), increased vegetable intake (16.2%), increased nut and fruit intake (11.2%), and increased legume intake (9.7%).4

Interestingly, only 10.6% of the benefit was thought to be from a high-monounsaturated-to-saturated-lipid ratio in the Greek Mediterranean diet, which the authors noted may be a reflection of higher consumption of olive oil.4

 “These results are somewhat disappointing, and yet not surprising. Since the Mediterranean diet contains both animal products and a significant fat content, it is not as likely to result in plaque regression in patients with CAD as one might obtain with a very low-fat, completely plant-based diet, such as the results obtained by Dr Caldwell Esselstyn. Repeating this kind of analysis with a purely plant-based diet, if mortality follows risk factor reduction, should result in a reduction in mortality as suggested in the Adventist Health Studies. Having our patients die at the same rate but with less cardiac events is not exactly the results we were hoping for,” noted Kim Allan Williams Sr, MD, MACC, immediate-past president of the American College of Cardiology and professor of cardiovascular disease at Rush University, Chicago, Illinois.

Despite the findings, this question remains: Are the benefits of a Mediterranean diet attributable to the high consumption of both whole-, plant-based foods with the high content of monounsaturated lipid or is the benefit more of a reflection of the overall whole-food, plant-based diet?

Dr Bloomfield and colleagues conclude that future studies should include more randomized controlled trials that assess not only the benefits of this diet but factor in adherence and if particular components provide more benefits than others .1

The researchers report no conflicts of interest. Dr Williams reports no conflicts of interest.


  1. Bloomfield HE, Koeller E, Greer N, MacDonald R, Kane R, Wilt TJ. Effects on Health Outcomes of a Mediterranean Diet With No Restriction on Fat Intake: A Systematic Review and Meta-analysis. Ann Intern Med. 2016. doi:10.7326/M16-0361.
  2. Ravera A, Carubelli V, Sciatti E, et al. Nutrition and Cardiovascular Disease: Finding the Perfect Recipe for Cardiovascular Health. Nutrients. 2016. doi:10.3390/nu8060363.
  3. Orlich MJ, Singh PN, Sabaté J, et al. Vegetarian dietary patterns and mortality in Adventist Health Study 2. JAMA Intern Med. 2013;173(13):1230-1238. doi:10.1001/jamainternmed.2013.6473.
  4. Trichopoulou A, Bamia C, Trichopoulos D. Anatomy of health effects of Mediterranean diet: Greek EPIC prospective cohort study. BMJ. 2009. doi:10.1136/bmj.b2337.

This article originally appeared on Endocrinology Advisor