Benefits of the Mediterranean diet on cardiovascular disease

Abstract

Future CardiologyVol. 3, No. 6 EditorialFree AccessBenefits of the Mediterranean diet on cardiovascular diseaseMaría-Isabel CovasMaría-Isabel CovasLipids & Cardiovascular Epidemiology Unit, Institut Municipal d’Investigació Mèdica (IMIM-Hospital del Mar), CIBER de Fisiopatología de la Obesidad y Nutrición (CB06/03/0028), Parc de Recerca Biomèdica de Barcelona (PRBB), Carrer Dr, Aiguader 88, 08003-Barcelona, Spain. Search for more papers by this authorEmail the corresponding author at mcovas@imim.esPublished Online:30 Nov 2007https://doi.org/10.2217/14796678.3.6.575AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail The term Mediterranean diet (Med-diet) refers to the traditional dietary patterns found in areas of the Mediterranean approximately 50 years ago [1,2]. There are several variants of the Med-diet, but some common components can be identified; high consumption of grains, vegetables, fruits, dry fruits and legumes; olive oil as a main source of fat; moderate consumption of fish, poultry, milk and dairy products (specially in the form of cheese or yoghurt); low consumption of meat and meat products. Associated habits are a moderate-to-high level of physical activity and a daily, moderate consumption of wine [1,2]. In recent years, a large body of basic, clinical and epidemiological studies have been developed to provide evidence of the benefits of the Med-diet, or of its components on health. Evidence of the benefits of the Med-diet in terms of cancer prevention and promotion of longevity is increasing [2–4].Cardiovascular disease is the main cause of mortality in industrialized countries [5]. The Med-diet may explain, in part, the low coronary heart disease (CHD) mortality observed in southern European countries in comparison with northern European countries or the USA [5]. Considering this, the key question is: could the Med-diet pattern be considered as a useful tool in the management of diseases, and could it be recommended as a public health preventive intervention? The evidence concerning the relationship between the Med-diet and CHD has recently been classified as ecological (independent association), analytical (cohort and case-control studies) and interventional (nutritional intervention trials) [2]. However, on the basis of the precepts of the evidence-based medicine, a high level of scientific evidence is required before nutritional recommendations for the general public can be formulated. The required scientific evidence is only provided by randomized, controlled, double-blind, clinical intervention trials (level I of evidence) and, to some extent, by large cohort studies (level II of evidence) [6]. Here, we analyze the state-of-the-art of the body of knowledge and the extent to which we possess evidence of the health benefits of the Med-diet on primary (disease development or mortality) and secondary (risk factors, such as lipids, hypertension, etc.) end points for cardiovascular disease.Mediterranean diet & primary end points for cardiovascular diseaseFew level I or II studies have tested a Med-diet – as a whole dietary intervention – on the development of diseases such as cardiovascular disease. A key work is the Lyon Diet Heart Study [7], a randomized, controlled, parallel clinical trial with 605 CHD patients and a follow-up period of 46 months. In this study, a Med-diet was shown not only to reduce CHD events in secondary prevention [7], but was also associated with possible benefits on cancer prevention [4]. A large cohort study with 22,043 participants of the Greek component of the European Prospective Investigation into Cancer and Nutrition (EPIC), followed during 44 months, demonstrated that adherence to the Med-diet was associated with low overall, cardiovascular and cancer mortality [3]. Similar results were obtained in the Health Ageing: a Longitudinal Study in Europe (HALE), a cohort study performed in 2339 Europeans aged from 70 to 90 years and with a follow-up period of 6 months [8]. The Melbourne Study [9], a cohort study that replicated the design of a previous Greek study [10], demonstrated the transferability of the benefits of the Med-diet, to other elderly population groups, Anglo–Celts and Greek–Australians, on overall mortality. The Prevention with Mediterranean Diet (PREDIMED) study [11], a parallel-group, multicenter, controlled, randomized 5-year clinical trial aimed at assessing the effects of the Med-diet on the primary prevention of cardiovascular disease, is ongoing with an expected number of 9000 high-CHD-risk participants [11].Mediterranean diet & secondary end points for cardiovascular diseaseThe Med-diet was first considered to be a low-saturated fat diet that conveyed protection against CHD by lowering plasma total cholesterol levels, but was later less appreciated for being a high-fat diet, as a result of the high consumption of olive oil associated with this type of diet [2]. However, the benefits of olive oil consumption are becoming increasingly recognized. In November 2004, the US FDA permitted a claim on olive oil bottle labels concerning ‘the benefits on the risk of CHD of eating about two tablespoons (23 g) of olive oil daily, due to the monounsaturated fat (MUFA) in olive oil’. Besides the MUFA content of the olive oil, its minor components, predominantly the phenolic compounds, have been shown to have beneficial effects on cardiovascular risk factors [12]. Recent results from The Effect of Olive Oil Consumption on Oxidative Damage in European Populations (EUROLIVE) study, a randomized crossover intervention trial investigating three similar olive oils with differences in their phenolic content and performed in 200 Europeans, demonstrated that olive oil consumption increased HDL-cholesterol levels in a dose-dependent manner with the phenolic content of the olive oil administered [13]. As a general rule, an improvement in the lipid cardiovascular-risk profile has been observed in the intervention studies performed with the Med-diet [11,14,15].One of the factors that may contribute to the protective effects of the Med-diet is the high antioxidant content that could prevent the oxidation of LDL and DNA. Current evidence indicates oxidative damage as a promoter of pathophysiological changes occurring in oxidative stress-associated diseases, such as CHD, cancer and neurodegenerative disorders, as well as in ageing [16]. It is currently thought that oxidized LDL is more damaging to the arterial wall than native LDL [17]. Adherence to a Mediterranean-type diet has been shown to be inversely associated with the degree of in vivo LDL oxidation in a cross-sectional study [18], and reduced lipoprotein oxidation in healthy women in a linear intervention study [19]. Recent results from the PREDIMED study [20] provide first-level evidence of the efficacy of the Med-diet on in vivo LDL oxidation. In this sense, in the Med-diet, besides the richness of antioxidant vitamins and polyphenols present in vegetables, fruits and wine, a key role must be attributed to olive oil. In most of the studies performed comparing the effects of MUFA- and ω-6 polyunsaturated fatty acid-rich diets on the susceptibility of LDL to oxidation, oleate-rich LDL has been shown to be less susceptible to oxidation than linoleate-rich LDL [12]. Results from the EUROLIVE study demonstrated a reduction in DNA oxidation after olive oil consumption [21], and a dose-dependent reduction in the oxidative damage to LDL with the phenolic content of the olive oil administered [13].Besides the lipid profile, in randomized, controlled, intervention studies, the Med-diet has been shown to provide benefits on other cardiovascular risk factors, such as blood pressure [11], inflammatory status [11,14], endothelial dysfunction [14,15] and prothrombotic profile [22,23]. Whether all these benefits are related to the antioxidant capacity of the Med-diet, or exerted through other biological mechanisms, specifically, nutrigenomic effects, merits further investigation.Mediterranean diet as a tool for cardiovascular-disease preventionFrom all the available data we have only some evidence of the benefits of the Med-diet on primary end points for cardiovascular disease. However, more evidence is available concerning secondary points for cardiovascular disease. Intervention studies on this issue have been performed mainly in CHD-risk individuals, such as those who have suffered a myocardial infarction [7] or have diabetes [11], metabolic syndrome [14], hypercholesterolemia [11,15,23], hypertension [12] or a combination of several risk factors [12,14]. Results from the Greek EPIC cohort demonstrated the benefits of a high adherence to the Med-diet, both in primary and secondary end points, such as blood pressure [24], for cardiovascular disease. Thus, we have enough evidence for recommending the Med-diet for controlling cardiovascular risk factors, particularly for individuals at high risk for CHD.Future perspectiveDespite their consistency and quality, there are few level I studies on the benefits of the Med-diet on primary end points for cardiovascular disease. More studies of this type are needed, and the results of the PREDIMED study will eventually provide more evidence. In addition, the traditional Med-diet is a high-fat diet in which olive oil is taken ad libitum. In spite of this, there was no weight gain reported in the long-term intervention studies with the Med-diet [7,14], nor was there any association in cohort studies [3,8]. However, in the case of obese subjects in which a weight reduction is desired, a caloric reduction incorporated into the Med-diet pattern would be advisable. Classical dietary patterns for reducing weight are generally of low palatability. Although some attempts have been made to modify the Med-diet for obesity control [25], the degree of caloric reduction that can be incorporated within the Med-diet pattern, without compromising its palatability, and thus, the adherence to it, deserves further investigation. The high interindividual variability in the response to dietary changes, mainly to dietary fat, on cardiovascular risk factors indicates the importance of the gene–environment interaction. It has been proposed that the Med-diet may be closely linked to ancestral foods and, as a result, our metabolism may have evolved to work optimally on such a diet rather than with the current diets that are richer in saturated fat and contain highly refined and processed foods [26]. 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This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download