Benefits of the Mediterranean diet beyond the Mediterranean Sea and beyond food patterns

The huge toll of death and disability caused each year by cardiovascular disease (CVD) continues to represent a great humiliation for public health. More people die annually from CVDs than from any other cause, and global projections are somber with a projected increase from 17 million to more than 24 million yearly CVD deaths in 2030 [1, 2]. Not a minor part of this humiliation comes from the knowledge that CVD can largely be prevented by timely population changes in metabolic risk factors including obesity, hypertension, dyslipidemia, and diabetes. This unambiguously indicates the need to address unhealthy lifestyles and replace unhealthy food patterns with their healthiest alternatives [3].

In this context, strong evidence supports the traditional Mediterranean diet (MedDiet) as the optimal choice for preventing CVD [3, 4]. Two decades ago, the Lyon diet-heart study, a randomized controlled clinical trial, was unique in showing that a dietary intervention brought about a dramatic reduction in cardiovascular events among survivors of a previous myocardial infarction [5]. The dietary intervention was based on the MedDiet. Subsequently, many prospective cohort studies have consistently confirmed the cardiovascular benefits of the traditional MedDiet. These cohort studies (pooled in different meta-analyses) constitute an impressive accrual of high-quality epidemiological evidence, currently not available for any other dietary pattern [6–11] and meet the classical criteria for causality in epidemiology [12]. However, for a long time, the only available evidence on cardiovascular prevention by the MedDiet was exclusively based on observational designs (with the single exception of the Lyon study). Observational studies can be affected by some biases, particularly measurement errors and residual confounding. But, this potential objection was only tenable until 2013, when the final results of the PREDIMED (“Prevencion con Dieta Mediterranea”) primary prevention trial were published [13]. This landmark trial included 7447 participants and showed a 30 % relative reduction in the risk of hard CVD events during 4.8 years of follow-up. Most hesitations about and criticisms of previous observational designs were removed by the almost perfect consistency between well-conducted observational cohort studies and trials. This consistency is of paramount importance for supporting the validity of well-conducted observational cohort studies in nutritional epidemiology as well as for evidence-based health promotion [8, 12, 14].

A review summarizing only the cohort studies published during 2015 and the first months of 2016 identified 19 new prospective studies on the traditional MedDiet [15]. Substantial benefits were observed with regards to myocardial infarction, stroke, heart failure, and total mortality.

The pending challenge was to test if the proven benefits of the MedDiet were restricted to populations living in Mediterranean areas or whether they were fully transferable far beyond the shores of the Mediterranean Sea. An excellent positive answer to this question is found in the new results from the EPIC-Norfolk cohort study [16]. In a UK general population setting, Tong et al. evaluated 23,902 participants followed-up for 12.2 years on average and observed several thousand new cases of CVD and 1714 CVD deaths. MedDiet adherence (repeatedly evaluated during follow-up) was inversely associated with hard clinical cardiovascular events (a composite end-point including ischemic heart disease [IHD], ischemic stroke, hemorrhagic stroke, heart failure, peripheral vascular disease, and other CVD events) [16]. The design, conduction, epidemiological/statistical analyses, and interpretation of findings in this study are superb. The authors are to be commended for their excellent work. Interestingly, they included absolute measures of risk reduction, potential impact (population attributable fractions [PAF]), and number needed to treat, under the assumption of a truly causal protective effect of the MedDiet on CVD. Approximately 8.5 % of incident IHD or stroke events in the UK were attributable to low adherence to the MedDiet (equivalent to 10.2 IHD or stroke cases preventable per 1000 population). They estimated that 19,375 cases of CVD death would be prevented each year by promoting the MedDiet in the UK.

Further strengths of the study by Tong et al. [16] include its long-term follow-up, optimal ascertainment of outcomes, careful adjustment for a wide array of potential confounders, considerations to potential competing risks, and, in particular, the diverse sensitivity analyses using different definitions of the MedDiet. It is reassuring that benefits were similar upon alternative categorizations of food groups in four scores of the MedDiet. However, the profile of a traditional MedDiet may be different in the UK than in Southern European countries and further questions about transferability still remain. This may explain why some magnitudes of effect were inferior to those from the PREDIMED trial [9].

It is a fact that culinary practices, average intakes (and consequently the cut-off points used for computing scores), serving sizes, and combinations of foods are likely to be different in studies conducted in Mediterranean settings than in those conducted beyond the shores of the Mediterranean Sea. Despite this, Tong et al. have presented an excellent study that has obtained salient results with practical consequences for nutrition policy after using food frequency questionnaires (FFQs) habitually applied in sound studies of nutritional epidemiology. Well-validated FFQs represent a valid and realistic tool for nutritional assessment in large longitudinal studies and randomized trials in nutrition [14].