Mediterranean diet

Highlights:

• Mediterranean diet is one of the most popular diets across the globe characterized by high consumption of fish, olive oil, fruits, vegetables, and nuts
• It has shown significant efficacy in cardiovascular disease prevention and may possess benefits in the prevention of type 2 diabetes and neurodegenerative disorders
• Mediterranean diet is part of a larger system, which includes the culture of food consumption and sharing 

What is the Mediterranean diet?

Nowadays, it is hard to find a person who never heard of the Mediterranean diet (MD). One of the most well-known diets globally, the Mediterranean diet, encompasses various food habits of the people who inhabit Cyprus, Croatia, Spain, Greece, Italy, Morocco, and Portugal. The meals vary, but the main cornerstones remain constant across different regions. MD is rich in fruits, vegetables, legumes, nuts, beans, cereals, grains, fish, and unsaturated fats, such as olive oil. The MD was extensively linked with health benefits including decreased risks of heart disease. This article will discuss how this diet emerged, its current formulation, its influence on various health aspects, and its pros and cons.

History and definition of the diet

The MD takes its roots in the eating habits of ancient Romans. American nutritionist Ancel Keys popularized the modern MD in the 1950s. An unusual fact caught his attention – poor inhabitants of small southern Italian towns were much healthier than much richer inhabitants of New York. Keys attributed this to the food and tried to connect eating habits, lifestyle, risk of cardiovascular diseases (CVD), and health in various populations. This led to a famous “Seven Countries Study”, which included Finland, Holland, Italy, USA, Japan, and former Yugoslavia. This study was able to show the impact of the MD on the health of the populations who adopted it – lowering cholesterol levels and subsequently the risk of CVD. Keys formulated the diet as follows: “... homemade minestrone, pasta of all varieties, with tomato sauce and a sprinkling of Parmesan, [...] served with a small fish ..., so much bread, never removed from the oven more than a few hours before being eaten, [...], lots of fresh vegetables sprinkled with olive oil, [...] and always fresh fruit for dessert” (1).

Modern definitions of MD generally look very similar to the description of Keys, emphasizing the same vital components. The definitions include guidelines for high intake of extra-virgin (cold pressed) olive oil, vegetables including leafy green vegetables, fruits, cereals, nuts and pulses/legumes, moderate intake of fish and other meat, moderate intake of dairy products and red wine, and low intake of eggs and sweets (2). The general intake of red meat, saturated fats, and processed food with high sugar content across all diet variations tend to be moderate or low. Thus, the main features of MD are its high content of omega-6 and omega-3 fatty acids, polyphenols, and fiber. Further, we will discuss in detail how this diet composition affects health.

Cardiovascular diseases

Cardiovascular diseases (CVD) include coronary artery disease, stroke, hypertension, rheumatic heart, and present one of the largest causes of death worldwide. The ability of MD to prevent CVD was extensively studied and is supported by a large array of observational data. The multicenter “Primary Prevention of Cardiovascular Disease with a Mediterranean Diet” (PREDIMED) trial included 7,447 participants with a high risk of CVD (though otherwise healthy and not yet diagnosed with CVD) and compared MD (with extra-virgin olive oil or with nuts) to control low-fat diet. The results (3) confirmed the lower risk of CVD among the MD cohort compared to a reduced-fat diet cohort. The subsequent meta-analysis on more than one million subjects (4) further confirmed the reverse dependence between MD and CVD occurrence.

Several factors may contribute to the CVD-prevention effect stemming from the large consumption of fish, seafood, nuts, and extra-virgin olive oil (5). In PREDIMED all the subjects adhering to MD had a relatively high fat intake (35-40%) but with high content of mono- and polyunsaturated fatty acids. There is evidence that consumption of unsaturated fatty acids reduces low-level density lipoprotein cholesterol and triglycerides while increasing the high-density lipoprotein (6). Moreover, the MD is very close to the “ideal ratio” of omega-6 and omega-3 unsaturated fatty acids. Another beneficial factor is the high content of various polyphenols in MD, particularly flavonoids and their metabolites, which demonstrate multiple health- and longevity-promoting effects. Polyphenols possess antithrombotic properties and improve vascular reactivity while decreasing tissue inflammation and reducing oxidative stress, thus promoting cardiovascular health (7). 

Type 2 diabetes

Some studies present evidence connecting MD with blood sugar regulation and prevention of type 2 diabetes and metabolic disorder (8). In the umbrella study, Dinu et al. (9) analyzed 29 observational and randomized clinical trial meta-analyses and concluded that reduced risk of diabetes was robustly observed across most studies, but the evidence for a protective effect against metabolic syndrome was weaker. Also, the analysis suggested better glycemic control and consequently reduced insulin resistance in subjects following MD. Many factors influencing CVD are also connected to type 2 diabetes and might explain the MD preventive effect, such as lipoprotein concentrations, blood pressure, glucose-insulin homeostasis, oxidative stress, and regulation of inflammation (10). The MD diet was also positively linked to a healthy weight loss, which is another risk factor for diabetes (11).

Neurodegenerative diseases

The variety of neurodegenerative diseases includes Alzheimer’s, Parkinson’s, and different forms of dementia (from mild cognitive decline to its vascular form) and is usually age-related. Lower rates of saturated fatty acids in MD and abundance of fish, fruits, and vegetables were connected with protective effects against Parkinson’s. Polyphenols in extra-virgin olive oil were linked to slower cognitive decline and reduced risk of Alzheimer’s in individuals (age 55-80) at high risk of CVD (11). A prospective study in Greece on subjects 65 years of age or older showed an inverse link between MD and cognitive decline (12). There are meta-analyses of case-control studies that confirm that link (13), but the cross-sectional studies fail to find significant dependency primarily due to the lack of standardization in determining cognitive function.

Aging

All the above-mentioned diseases are strongly correlated with aging and account for a significant fraction of health decline in older age. The protective effects of MD can be especially beneficial for older individuals showing improvement in lipid profiles and inflammatory markers. The studies showed that older individuals at high risk of CVD following a MD diet with increased olive oil content had a 40% lesser risk of developing diabetes, and older individuals following MD with with increased nuts content had an 18% lesser risk of diabetes compared to the low-fat diet (14).

Another age-related issues against which MD demonstrated its preventive effects are frailty and systemic inflammation. The frailty can be defined as an increased vulnerability to stress events, which increases the risk of negative outcomes such as falls, delirium, and disability. The meta-analysis by Kojima et al. (15) confirmed that greater adherence to MD is linked to a significantly lower incident frailty risk. The frailty onset is closely related to inflammation in aging people, and there is evidence that MD can also decrease inflammation.  The change in markers levels such as c-reactive protein, fibrinogen, homocysteine, and LDL, showed consistent improvement in individuals adherent to MD.

Gut microbiome

A recent study by Wang et al. linked the protective impact of MD to its influence on the gut microbiome (16). The researchers discovered the moderate but significant effect of MD on gut microbiome profiles and showed that long-term adherence to MD lowers the levels of biomarkers of CVD (namely, biomarkers of glucose homeostasis, lipid metabolism, and inflammation measured on blood samples). Another study (17) showed that the MD leads to increased  microbiome profiles positively associated with several markers of lower frailty and improved cognitive function, and negatevely associated with pro-inflammatory markers such as C-reactive protein and interleukin-17.

How to follow the MD

One of the supposed reasons for the success of MD is it being not only about food but about lifestyle in general. UNESCO, when declaring MD a part of intangible cultural heritage, described it in the following way: “The Mediterranean diet involves a set of skills, knowledge, [...] and traditions concerning crops, harvesting, fishing, animal husbandry, conservation, processing, cooking, and particularly the sharing and consumption of food”. Thus, MD includes much more than only food, it is also a whole system and culture of food consumption, sharing, and communication.

To follow the MD one can use several simple rules:

• Choose high-quality fresh food and avoid processed and fast foods; 
• Make emphasis on variety, traditional MD includes over 150 different fruits and vegetables;
• Make sure to use high-quality extra-virgin olive oil;
• Consume in moderation, especially when consuming more heavy meals;
• Cook and eat slowly;
• Make eating a social event;
• Include fasting, which is also a part of traditional MD

Conclusions

MD has numerous confirmed benefits and has been included in various recommendations on CVD prevention. However, the lack of strict formulation of the diet, various measurements of adherence to the diet, and different study designs sometimes lead to discrepancies in current studies. Due to the vague formulations, incorrect adherence to the diet can sometimes cause weight gain (from eating an excessive amount of food), low iron levels, or calcium loss (due to the limitations in dairy products). Lack of physical activity will also drastically decrease the benefits of this (or any other) diet.

​​References

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2.         Davis C, Bryan J, Hodgson J, Murphy K. Definition of the Mediterranean Diet; A Literature Review. Nutrients. 2015 Nov 5;7(11):9139–53.

3.         Estruch R, Ros E, Salas-Salvadó J, Covas M-I, Corella D, Arós F, et al. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. N Engl J Med. 2018 Jun 21;378(25):e34.

4.         Sofi F, Abbate R, Gensini GF, Casini A. Accruing evidence on benefits of adherence to the Mediterranean diet on health: an updated systematic review and meta-analysis. The American Journal of Clinical Nutrition. 2010 Nov 1;92(5):1189–96.

5.         Billingsley HE, Carbone S. The antioxidant potential of the Mediterranean diet in patients at high cardiovascular risk: an in-depth review of the PREDIMED. Nutr & Diabetes. 2018 Dec;8(1):13.

6.         Willett WC. The Mediterranean diet: science and practice. Public Health Nutr. 2006 Feb;9(1a):105–10.

7.         Del Rio D, Rodriguez-Mateos A, Spencer JPE, Tognolini M, Borges G, Crozier A. Dietary (Poly)phenolics in Human Health: Structures, Bioavailability, and Evidence of Protective Effects Against Chronic Diseases. Antioxidants & Redox Signaling. 2013 May 10;18(14):1818–92.

8.         Salas-Salvadó J, Bulló M, Estruch R, Ros E, Covas M-I, Ibarrola-Jurado N, et al. Prevention of Diabetes With Mediterranean Diets: A Subgroup Analysis of a Randomized Trial. Ann Intern Med. 2014 Jan 7;160(1):1–10.

9.         Dinu M, Pagliai G, Casini A, Sofi F. Mediterranean diet and multiple health outcomes: an umbrella review of meta-analyses of observational studies and randomised trials. Eur J Clin Nutr. 2018 Jan;72(1):30–43.

10.       Esposito K, Maiorino MI, Bellastella G, Panagiotakos DB, Giugliano D. Mediterranean diet for type 2 diabetes: cardiometabolic benefits. Endocrine. 2017 Apr;56(1):27–32.

11.       Valls-Pedret C, Lamuela-Raventós RM, Medina-Remón A, Quintana M, Corella D, Pintó X, et al. Polyphenol-rich foods in the Mediterranean diet are associated with better cognitive function in elderly subjects at high cardiovascular risk. J Alzheimers Dis. 2012;29(4):773–82.

12.       Trichopoulou A, Kyrozis A, Rossi M, Katsoulis M, Trichopoulos D, La Vecchia C, et al. Mediterranean diet and cognitive decline over time in an elderly Mediterranean population. Eur J Nutr. 2015 Dec;54(8):1311–21.

13.       Wu L, Sun D. Adherence to Mediterranean diet and risk of developing cognitive disorders: An updated systematic review and meta-analysis of prospective cohort studies. Sci Rep. 2017 Feb;7(1):41317.

14.       Serra Majem L. Effectiveness of the Mediterranean diet in the elderly. CIA. 2008 Mar;Volume 3:97–109.

15.       Capurso C, Bellanti F, Lo Buglio A, Vendemiale G. The Mediterranean Diet Slows Down the Progression of Aging and Helps to Prevent the Onset of Frailty: A Narrative Review. Nutrients. 2019 Dec 21;12(1):35.

16.       Wang DD, Nguyen LH, Li Y, Yan Y, Ma W, Rinott E, et al. The gut microbiome modulates the protective association between a Mediterranean diet and cardiometabolic disease risk. Nat Med. 2021 Feb;27(2):333–43.

17.       Ghosh TS, Rampelli S, Jeffery IB, Santoro A, Neto M, Capri M, et al. Mediterranean diet intervention alters the gut microbiome in older people reducing frailty and improving health status: the NU-AGE 1-year dietary intervention across five European countries. Gut. 2020 Jul;69(7):1218–28.