The Mediterranean Diet: History
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Paula Silva
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María Rodríguez-Pérez
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Emma Burgos-Ramos

A cornerstone of any healthy lifestyle program is the inclusion of a balanced diet that can prevent various diseases, including cardiovascular conditions. The Mediterranean diet (MD) has become one of the most studied and widely reported diets and has received a lot of attention. The MD is a dietary plan based on Crete’s traditional eating habits. 

  • Mediterranean diet (MD)
  • cardiovascular disease

1. Mediterranean Diet Definition

The MD is a dietary plan based on Crete’s traditional eating habits. The term “Mediterranean Diet” was coined by Ancel Keys, an American physiologist, in 1960, during the publication of his book How to Eat Well and Stay Well [1]. The scientific evidence for its existence before 1960 is controversial, but it is reasonable to consider a broader temporal context, reaching back to biblical times or even earlier [2]. Interestingly, the strength of the MD is closely linked to ancient biblical culture. In fact, when researchers look for the seven key components of the traditional biblical diet, namely, wheat, barley, grapes, figs, pomegranates, olives, and honey, researchers recognize some MD components [2]. The evolution of the MD is intertwined with the development of Western civilization. Initially, people in the region adapted their food consumption to the seasons, which was determined by climate and agriculture [3].
The origins of the MD reflect the cultural, societal, and economic growth of the region. The Latin term “Mediterranean” means “the sea in the middle of the earth”, highlighting its historical role as a meeting point between southern Europe, northern Africa, and western Asia. The word “diet” itself is derived from the Greek word “diaeta”, which encompasses not only food but also one’s overall lifestyle. The Mediterranean region spans numerous countries, including Italy, Greece, Spain, southern France, Turkey, parts of North Africa, and the Middle East, resulting in a rich diversity of ingredients and culinary traditions within the MD.
Although the MD has often been associated with the “eternal trinity” of wheat, olive oil, and wine, it also embodies the essence of traditional agricultural practices and dietary habits, which are marked by a culture of sharing and reciprocity [4]. For instance, wealthy urban Greeks favored a diet rich in vegetables, grains, legumes, olive oil, and wine. Barley and wheat were used for oatmeal and bread, whereas various legumes such as fava beans, chickpeas, lentils, lupines, and peas were either prepared in specific dishes or incorporated into flour for bread and oatmeal [5]. A typical MD is characterized by several key features: substantial consumption of vegetables, fruits, legumes, and grains (including complex carbohydrates and dietary fiber), limited total fat intake (<30%), low saturated fat intake (<10%), emphasis on monounsaturated fats, and moderate alcohol consumption (primarily wine) [6]. Over time, the introduction of new ingredients and influences from regions such as Asia and the Americas, including tomatoes, potatoes, maize, beans, and cane sugar, have resulted in changes in Mediterranean cuisine, expanding its culinary horizons beyond indigenous roots. Throughout different historical eras, cultures, religions, agricultural practices, and economic circumstances, the emphasis on food elements within the MD has varied. Additionally, factors such as climate, economic challenges, and scarcity have played a significant role in shaping this diet rather than relying on intellectual foresight or deliberate dietary planning, which is often the approach adopted in modern times to create popular diets. This might explain why it has been challenging to precisely characterize this dietary regimen, as it exhibits unexpected complexity and variations across different countries and historical periods. In 2010, the MD gained recognition as an Intangible Cultural Heritage by the United Nations Educational, Scientific, and Cultural Organization (UNESCO). The official submission made to UNESCO characterizes the MD as “a social tradition rooted in a collection of competencies, wisdom, customs, and traditions that encompass everything from the natural environment to culinary practices. These encompass activities such as cultivation, harvesting, fishing, preservation, processing, cooking, and, most notably, consumption, particularly within the Mediterranean region” [7]. In 2011, the Mediterranean Diet Foundation in Spain, in collaboration with experts in the field, revised the “classic” MD pyramid to accommodate changes brought about by modernization and to integrate cultural and lifestyle aspects [8]. A literature review by Davis et al. (2015) attempted to establish an integrated definition of the MD. In conducting their analysis, the authors considered a variety of criteria, including general descriptive terms, recommended serving sizes of key food groups, and nutrient content [9]. Based on this comprehensive review, the authors defined daily dietary intake as follows: vegetables, 3–9 servings; fruits, 0.5–2 servings; cereals, 1–13 servings; and olive oil, up to 8 servings. In terms of energy content and macronutrient composition, the MD typically consists of approximately 2220 kcal/day, with fat accounting for 37% of the total calories [9]. Regardless of the definition adopted, there is a consensus regarding the health benefits of the MD. Since Ancel Keys’ pioneering research revealed that the dietary practices of Mediterranean countries are associated with longer lifespans and reduced incidences of coronary heart disease (CHD), many more studies have been published [1].

2. Mediterranean Diet Health Benefits

2.1. Mediterranean Diet and Longevity

After the Seven Countries Study, which strongly suggested that low levels of mortality from CHD are strongly associated with the MD [10], scientists began to study the effects of the MD on aging. Aging is defined as a progressive decline in physiological function over time [11]. This natural process is associated with a higher risk of various chronic diseases such as cognitive decline, neurodegenerative diseases, CVD, cancer, diabetes, sarcopenia, and osteoporosis [12]. The aging mechanism is intricate, and nine distinct cellular and molecular characteristics (genomic instability, telomere decline, changes in epigenetic patterns, disruptions in proteostasis, dysregulated nutrient detection, issues with mitochondrial function, cellular senescence, stem cell depletion, and modified intercellular communication) collectively influence the aging trajectory [11][13]. The aging process is not fixed and can be altered by diet and lifestyle factors [13].
It is not surprising that initial studies investigating the impact of the MD on longevity were conducted in Mediterranean countries. Trichopoulou et al. (1995) studied the diets of elderly individuals in three rural Greek villages. They conducted a 5-year follow-up study of 182 elderly Greek participants and showed that those whose diets were different from the traditional MD had a higher risk of all-cause mortality than those who faithfully followed the traditional MD [14]. Trichopoulou also examined how traditional MD affects the survival rate of a large group of elderly men and women aged >60 years at baseline. The results indicated that adherence to the MD was associated with improved longevity in this older population [15]. In Italy, as part of the Italian Longitudinal Study on Aging, 278 participants without dementia were tracked, with an average age of 73.4, for a duration of 8.5 years. Those with a higher intake of monounsaturated fatty acids (MUFA) demonstrated improved longevity. This MUFA-increased intake was significantly associated with a reduction in overall mortality risk [16]. In a Spanish study involving 161 non-smoking men and women aged 65 years, an increase of one unit in the eight-unit MD score was associated with a significant reduction in mortality of 31% among elderly individuals [17]. The “Healthy Aging: A Longitudinal Study in Europe” project was a large-scale cohort study that included healthy men and women aged between 70 and 90 years from 11 European countries. Over the course of a decade, individuals who maintained a healthy lifestyle, characterized by four low-risk behaviors, such as adherence to the medical doctor’s guidelines, moderate alcohol consumption, nonsmoking, and a minimum of 30 min of daily physical activity, have demonstrated a significant reduction in mortality. The lack of adherence to this low-risk pattern was the reason for the 60–64% mortality rate. The authors concluded that pursuing a Mediterranean lifestyle among individuals aged 70–90 years was associated with a 50% decrease in the rates of all-cause and cause-specific mortality [18].
The effects of the MD on longevity were examined in regions outside the Mediterranean, where the consumption of monounsaturated fat from olive oil is restricted. In 1988, a European-wide, multicenter study on nutrition and health in the elderly (SENECA: Survey Europe on Nutrition in the Elderly: A Concerted Action) was started to examine dietary patterns in the elderly in relation to lifestyle, social and economic conditions, health, and performance. Nine years later, a paper reporting the results of a study aiming to examine the impact of the MD on life expectancy in a Danish cohort was published. Over a period of six years, a dietary assessment based on seven MD characteristics revealed that a one-unit increase in diet score was associated with a remarkable 21% reduction in mortality [19]. Another important study was the European Prospective Investigation into Cancer and Nutrition (EPIC), which involved 74,607 participants from Denmark, France, Germany, Greece, Italy, the Netherlands, Spain, Sweden, and the UK. The researchers used a modified MD score to assess the degree of MD adhesion among individuals in Europe. In such cases, the monounsaturated fats were replaced with a combination of monounsaturated and polyunsaturated fats to calculate the lipid ratio. Among individuals aged ≥60 years, a higher modified MD score was associated with a lower overall mortality rate. Specifically, a two-unit increase in the score was associated with a statistically significant 8% reduction (with a confidence interval of 3% to 12%). Although this association was more pronounced in Greece and Spain, there was no significant variation in the impact of the score on the overall mortality among different countries. When dietary exposure was adjusted across countries, the reduction in mortality was 7% (with a confidence interval of 1–12%) [20]. In a study involving 818 individuals aged ≥70 years from different European nations, the MD was found to play a significant role in promoting longevity. It did so independently and in conjunction with other factors, displaying a noteworthy impact on survival that was equal to or greater than the influence of all other factors examined in the study [21]. The NIH-AARP Diet and Health Study provided convincing evidence that, among older Americans, following a Mediterranean-style diet regimen significantly reduced all-cause and cause-specific mortality [22]. Reedy et al. (2014) discovered identical outcomes in a study that examined the correlations between four indices, namely, the Healthy Eating Index–2010, the Alternative Healthy Eating Index–2010, the alternate Mediterranean Diet, and Dietary Approaches to Stop Hypertension, and mortality rates from all causes, CVD, and cancer. A decreased risk of all-cause, CVD, and cancer mortality was associated with higher index scores [23].
The MD may also have a positive effect on longevity in younger individuals. Data from Swedish research have shown that the MD can reduce mortality in young individuals. An inverse association was found between closer adherence to the MD, reduced cancer deaths, and decreased all-cause mortality in a cohort of 42,237 young women (aged 30–49 years). There was a 13% reduction in all-cause mortality and a 16% reduction in cancer-related deaths associated with a 2-point increase in diet score [24].
A meta-analysis of 12 studies found that over 1.5 million people followed the MD over a period of 3–18 years. A scoring system was set up to determine how closely participants followed the MD. The findings showed that adherence to the MD reduced the likelihood of premature death from any cause by 9%, lowered cardiovascular mortality by 9%, decreased cancer-related mortality by 6%, and diminished the risk of Alzheimer’s and Parkinson’s disease by 13% [25]. A meta-analysis of observational studies, encompassing twenty-nine prospective studies with 1,676,901 participants, found a 10% reduction in all-cause mortality for every 2-point increase in adherence to the MD. The inverse association was stronger in participants residing in the Mediterranean region than in those residing in non-Mediterranean areas according to the subgroup analyses. A nonlinear dose–response analysis also revealed a linear decrease in the risk of all-cause mortality with a greater commitment to the MD [26]. Telomere length, a widely accepted biomarker of the aging process, is longer in those who closely adhere to the MD, as shown in a recent meta-analysis. An analysis of eight original cross-sectional studies and 13,733 participants from five countries found a positive association between adherence to the MD and telomere length [27]. When the MD was followed in 4676 healthy middle-aged women, longer telomeres were observed [28].
Observational studies have successfully demonstrated a correlation between adherence to the MD and a reduced risk of overall mortality. However, as assessed by Guasch-Ferré and Willett in 2021, RCTs do not seem to show a substantial effect of the MD on total mortality [29]. Preclinical animal studies may play a pivotal role in bridging this discrepancy in the results. Studies on animals can provide a controlled environment for investigating the precise impact of the MD components on various health outcomes, including longevity. Through animal experiments, researchers can isolate and manipulate specific dietary factors, and closely monitor their effects on mortality. This controlled approach allows for a more nuanced understanding of how the MD influences longevity, potentially shedding light on why RCTs may not consistently reflect the findings of observational studies in human populations.

2.2. Mediterranean Diet and Cardiovascular Diseases

Heart and blood vessel disorders are often referred to as CVDs. These include hypertension, CHD, stroke, heart failure (HF), and several other heart-related diseases [30]. CVD is a life-threatening condition and a leading cause of death worldwide [31]. The burden of CVD can be greatly reduced by adopting a healthy lifestyle that includes a healthy dietary pattern [32].
When discussing studies that investigated the association between the MD and CVD, it is mandatory to mention The Seven Countries Study. After a 25-year follow-up period, researchers demonstrated a strong correlation between variations in CHD mortality rates across 16 study cohorts and differences in adherence to the MD within those populations [10]. The EPIC study also played a crucial role in expanding researchers' understanding of how the MD affects CVD. Despite geographic differences, similar outcomes have been observed in various cohorts. In a large prospective survey of 22,043 middle-aged and older adults in Greece, Trichopoulou et al. [15] reported a negative association between adherence to the MD and death due to CHD. An increase of approximately 2/9 in the MD score was associated with a 25% reduction in total mortality and a 33% reduction in mortality due to CHD. These associations were evident regardless of sex, smoking status, education level, body mass index, or physical activity level. It is noteworthy that the correlation between MD scores and mortality was significant among participants aged ≥55 years, whereas it was not observed among younger participants. Increased exposure to a healthier diet, such as the MD, may be the reason for this association [15]. Moreover, in a cohort study conducted on a larger sample of 23,929 apparently healthy women and men in Greece, adherence to the MD was associated with a lower incidence and mortality from CHD [33]. A substantial EPIC cohort of healthy individuals from a Spanish population was followed for >10 years. After adjusting for significant confounders, adherence to a relative MD score was associated with a 40% reduction in the likelihood of a first CHD event [34]. In a Dutch cohort, higher adherence to the MD was associated with a lower risk of a combined CVD endpoint (fatal CVD, nonfatal myocardial infarction (MI), and nonfatal stroke) [35].
In addition to the EPIC study, other studies have shown positive effects of the MD on cardiovascular health in non-Mediterranean countries. The MONICA (Multinational MONItoring of Trends and Determinants in CArdiovascular Disease (MONICA)) study examined 1849 Danish men and women and found that each 1-unit increase in adherence to an 8-point scale reduced the risk of CVD by 8% [36]. The Northern Manhattan Study, a cohort study conducted on a large population (n = 2568), also revealed that a higher level of adherence to an MD was associated with a decreased risk of MI, stroke, or vascular mortality [37].
The ATTICA Epidemiological Cohort Study (2002–2022) included a sample of approximately 3000 individuals aged 18–89 years from the Attica region of Greece. Within the scope of this study, Panagiotakos et al. (2008) [38] explored the association between the MD and CVD events. This study evaluated the 5-year incidence of CVD in a population-based sample of men and women. In both men and women, the 5-year incidence of CVD was 11.0%, and the case fatality rate was 1.6%. Panagiotakos et al. 2008, observed that greater adherence to the MD was associated with a lower 5-year CVD incidence, especially among middle-aged people [38]. Similar findings were obtained in a prospective cohort study involving university graduates from all regions of Spain, in which an inverse correlation was observed between adherence to the MD and the incidence of fatal and non-fatal CVD in initially healthy middle-aged adults. Interestingly, only vegetables, olive oil, and alcohol were significantly associated with CHD risk in a Spanish study, although the inverse association between the MD score and CHD was highly significant [39].
Several observational studies have examined the effects of the MD on women. In a prospective study involving 64,000 postmenopausal women, a higher level of adherence to the MD was associated with a reduction in CVD mortality risk of 18–26% [40]. Furthermore, the MD pattern may be associated with a lower likelihood of sudden cardiac death in women [41]. Recently, a prospective cohort study conducted over 10 years involving 32,921 Swedish women revealed that adherence to the MD was associated with a lower likelihood of MI, HF, and ischemic stroke [42].
In a four-year observational study, individuals from the Health Professionals Follow-up Study and the Nurses’ Health Study were found to be significantly less likely to develop CVD if they improved their adherence to the MD quality scores over time. In the long-term follow-up, the increase in CVD with reduction in diet quality was more pronounced. These findings provide further evidence that modest enhancements in diet quality over time confer benefits for CVD prevention [43].
Researchers have also examined the effects of the MD in patients with a clinical cardiovascular history. Scientists from the CARDIO2000 study examined 661 middle-aged individuals from various regions in Greece who had experienced their first MI or unstable angina episode, along with 661 controls of the same age and sex. The results revealed that adopting an MD resulted in a 7–10% reduction in coronary risk among individuals with hypertension, regardless of whether they were treated, untreated, or had uncontrolled hypertension [44]. Furthermore, in individuals with high cholesterol levels, CARDIO2000 investigators observed that following an MD resulted in a 12% decrease in coronary risk independent of cholesterol levels and other cardiovascular variables [45]. The same researchers also reported that following this dietary regimen resulted in a 35% decrease in coronary risk within a subgroup of individuals with metabolic syndrome, after accounting for sex, education, financial status, and conventional cardiovascular risk factors [46]. The ATTICA study uncovered data from 1188 individuals, unaffected by CVD but exhibiting defined high blood pressure levels (prehypertension) at the time of baseline examination (2001–2002). The five-year follow-up of the study was conducted in 2006, and 798 participants with prehypertension were enrolled. The findings revealed that a substantial proportion of individuals with prehypertension progressed to hypertension over a 5-year period. A multi-adjusted analysis revealed that low adherence to the MD was one of the elements of the profile of prehypertensive individuals who were prone to developing hypertension within a 5-year period [47]. Furthermore, the MD decreased the 10-year CVD risk among smokers and sedentary and obese subjects. Adherence to the MD resulted in a significant reduction in CVD risk irrespective of various factors. Therefore, even subjects with unhealthy lifestyle behaviors may benefit from adherence to this diet, suggesting another dimension of prevention strategy [48].
Several case-control studies have contributed to the growing body of evidence supporting the health benefits of the MD. In a case-control study conducted in Greece (CARDIO2000), investigators discovered protective associations for the primary prevention of acute coronary syndrome. Each 10-unit increase in the MD score was associated with 27% lower odds of acute coronary syndrome (95% CI: 0.66–0.89) [49]. Applying the same score to a Spanish case-control study involving 171 patients and 171 matched controls, researchers discovered that the probability of sustaining MI decreased as the MD score increased. Moreover, even after adjusting for primary cardiovascular risk factors, a significant linear correlation was observed between the diet score and the risk of MI. These findings support the idea that the MD can effectively reduce the risk of MI [50]. In a hospital-based case-control study, researchers assessed adherence to the traditional MD using the MD scores. This score was based on nine dietary components, including high consumption of vegetables, legumes, fruits, nuts, cereals, fish, and seafood, as well as a high ratio of monounsaturated to saturated lipids. In contrast, low consumption of dairy and meat, along with moderate alcohol intake, were considered. The association between the MD score and its individual components and the risk of acute MI was investigated using multiple logistic regression models, while controlling for potential confounding variables. This study was conducted in Italy, between 1995 and 2003. This study demonstrated that adherence to the MD was associated with a reduced risk of acute MI [51]. Another case-control study that investigated cardiovascular events highlighted the influence of anxiety and depressive symptoms on cardiovascular events. The participants with low anxiety levels exhibited stronger adherence to the MD, which emerged as a significant protective factor. The study included 1000 individuals from Greece, half of whom had previously experienced an episode of acute coronary syndrome or stroke. Therefore, the authors propose including assessments for anxiety and depressive symptoms as part of the baseline evaluation for primary cardiovascular prevention in apparently healthy individuals. To achieve synergistic effects, they recommended combining dietary interventions with psychological treatments [52]. These results were consistent with those of another cohort study of 30,000 participants in the United States, where high adherence to the MD was associated with a lower risk of incident stroke, independent of potential confounders [53].
The PREDIMED (Prevention with Mediterranean Diet) study was designed to assess the long-term effects of the MD on incident CVD in men and women at high cardiovascular risk in Spain from 2003 to 2011. They recruited 7216 participants, aged 55–80 years, who had no CVD at enrollment but were at high cardiovascular risk because of the presence of type 2 diabetes or at least three of the following risk factors: current smokers, hypertension, high low-density lipoprotein (LDL)-cholesterol, low high-density lipoprotein (HDL)-cholesterol, overweight or obesity, and family history of premature CVD. The median follow-up was 4.8 years. For the first time, the findings demonstrated that an MD supplemented with either extra virgin olive oil (EVOO) or nuts reduced the risk of developing CVD by 30% and by 50% in the case of peripheral arterial disease [54].
While observational studies have shed light on the cardiovascular benefits of adhering to the MD, there are several critical questions that require further investigation. These inquiries extend beyond the epidemiological context and explore into the specifics of the diet itself, including the relative impact of individual food components, and the need to eliminate or replace items to enhance its benefits. Addressing these questions necessitates a focused approach involving the investigation of individual food components, formulation of informed dietary recommendations, and conduct of thorough animal trials. Furthermore, a profound connection between the MD and gut health emerges, highlighting the importance of maintaining a harmonious gut, characterized by diverse microbial profiles and regular bowel habits, in promoting overall physical well-being and serving as a shield against chronic diseases including CVDs. Several factors, including dietary changes and stress, can disrupt this balance. The MD plays a significant role in restoring and maintaining this equilibrium. Although the current understanding is promising, it is important to have caution when extrapolating these findings to human health and to continue further research in this area [55].

This entry is adapted from the peer-reviewed paper 10.3390/antiox12101843

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