Abstract

Methods

Results

Updated systematic review and meta-analysis

The updated search from recent years resulted in the identification of eighteen additional prospective studies published up to June 2013⁽ 7 ^– 24 ⁾. Characteristics of these recent studies are displayed in Table 3. Of these, seven cohorts presented overall mortality as clinical outcome⁽ 7 ^, 8 ^, 10 ^, 11 ^, 14 ^– 16 ⁾, eight incidence and/or mortality from cardio- and cerebrovascular diseases⁽ 7 ^, 9 ^, 10 ^, 12 ^, 16 ^– 19 ⁾, and eight incidence and/or mortality from neoplastic diseases⁽ 10 ^, 13 ^, 16 ^, 20 ^– 24 ⁾. No updated studies for the incidence of neurodegenerative diseases have been found. On the other hand, one study resulted to be an updated analysis of a study already reported in the previous meta-analyses for the overall mortality outcome, so only the most updated study was added to this updated final analysis⁽ 13 ⁾. Altogether with the studies previously investigated, a total of thirty-five cohort prospective studies were included and entered into the final analysis. This updated analysis determined an increase of the study population up to a total of 4 172 412 subjects analysed.

Meta-analytic pooling under a random-effects model showed the already reported significant association between 2-point increased adherence to the Mediterranean diet and reduced risk of mortality from all causes (RR = 0·92; 95 % CI 0·91, 0·93; P < 0·00001; Fig. 1), with little evidence of statistical heterogeneity across the studies (I ² = 47 %; P = 0·01). This heterogeneity seems to be determined mainly by the study of van den Brandt⁽ 11 ⁾. After exclusion of this latter study, the statistical heterogeneity disappeared (I ² = 35 %; P = 0·08), with no modification of the association between adherence to the Mediterranean diet and overall mortality (RR = 0·92; 95 % CI 0·91, 0·93; P < 0·00001).

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Fig. 1

Forest plot for updated meta-analysis on greater adherence score to the Mediterranean diet (2-point increase) and overall mortality risk. Plotted are the relative risk (RR; represented by , with the symbol size proportional to the weight in meta-analysis) and the 95 % confidence interval (represented by horizontal bars), with the summary measure (represented by - - - - - and , with the associated 95 % confidence interval indicated by the symbol width) and the line of no effect (——)

Moreover, we found that a 2-point increase of adherence to the Mediterranean diet still remained associated with a reduced risk of mortality from and incidence of CVD (RR = 0·90; 95 % CI 0·87, 0·92; P < 0·00001; Fig. 2), showing no significant heterogeneity across the studies (I ² = 38 %; P = 0·07). Likewise, among studies investigating mortality and incidence of neoplastic diseases (Fig. 3), a greater adherence to the Mediterranean diet still determined a significant protection, to a similar extent as the previous meta-analysis (RR = 0·96; 95 % CI 0·95, 0·97; P < 0·00001), with evidence of significant heterogeneity across the studies (I ² = 65 %; P < 0·0 0 1). The heterogeneity seems to be determined by the recent studies investigating breast and colorectal cancer⁽ 21 ^– 23 ⁾. After exclusion of these three studies, the statistical heterogeneity disappeared (I ² = 36 %; P = 0·10), with no modification on the protection of the Mediterranean diet v. neoplastic disease (RR = 0·96; 95 % CI 0·95, 0·97; P < 0·00001).

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Fig. 2

Forest plot for updated meta-analysis on greater adherence score to the Mediterranean diet (2-point increase) and cardiovascular incidence and/or mortality risk. Plotted are the relative risk (RR; represented by , with the symbol size proportional to the weight in meta-analysis) and the 95 % confidence interval (represented by horizontal bars), with the summary measure (represented by - - - - - and , with the associated 95 % confidence interval indicated by the symbol width) and the line of no effect (——)

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Fig. 3

Forest plot for updated meta-analysis on greater adherence score to the Mediterranean diet (2-point increase) and cancer incidence and/or mortality risk. Plotted are the relative risk (RR; represented by , with the symbol size proportional to the weight in meta-analysis) and the 95 % confidence interval (represented by horizontal bars), with the summary measure (represented by - - - - - and , with the associated 95 % confidence interval indicated by the symbol width) and the line of no effect (——)

Literature-based adherence score to the Mediterranean diet

Characteristics of the studies included for this analysis are reported in Tables 1 and ​and22 for men and women, respectively. For the purpose of this analysis some studies previously included in the updated meta-analytic analysis were excluded, due to the lack of information on amount of consumption for the different food groups composing the adherence score.

We were able to collect data from twenty-four cohort studies for men⁽ 7 ^– 13 ^, 15 ^– 20 ^, 25 ^– 35 ⁾ and twenty-six for women⁽ 8 ^– 13 ^, 15 ^– 22 ^, 25 ^– 36 ⁾. It is interesting to note that values of consumption for food groups composing adherence score to the Mediterranean diet resulted to be, in some cases, different across the studies. For instance, between two cohorts of subjects coming from the same continent (e.g. Spain and Greece) the median consumption of some food groups varied from 90 to 187 g/d (e.g. cereals for men between Martinez-Gonzalez et al.⁽ 35 ⁾ and Buckland et al.⁽ 10 ⁾). More interestingly, vegetable consumption showed a wide variability even between two cohorts of subjects coming from the same country (e.g. vegetables: 75 g/d v. 239 g/d for Sjorgen et al.⁽ 7 ⁾ and Tognon et al.⁽ 8 ⁾, respectively).

We utilized such data for proposing an adherence score based on literature data. To this aim, we weighted all the median (or mean) values for the sample size of each study population and then we calculated the mean value of all the weighted medians. Hence, we calculated the 2 sd value and we rounded the number close to the ±2 sd, determining three different categories of consumption for each food group (e.g. for cereals: weighted mean = 162·7 (sd 34·6) g/d that determined three different categories <130 g; 131–200 g; >200 g). For food groups typical of the Mediterranean diet (fruit, vegetables, cereals, legumes and fish) we gave 2 points to the highest category of consumption, 1 point for the middle category and 0 point for the lowest category. Conversely, for food groups not typical of the Mediterranean diet (meat and meat products, dairy products) we gave 2 points for the lowest category, 1 point for the middle category and 0 point for the highest category of consumption. For alcohol, we used the categories related to the alcohol unit (1 alcohol unit = 12 g of alcohol), by giving 2 points to the middle category (1–2 alcohol units/d), 1 point to the lowest category (<1 alcohol unit/d) and 0 point to the highest category of consumption (>2 alcohol units/d). Finally, we introduced olive oil as part of the proposed score due to its importance in the typical Mediterranean diet and the beneficial effect of its consumption on health and longevity (2 points = regular use; 1 point = frequent use; 0 point = occasional use). The final adherence score comprised nine food categories with a score ranging from 0 point (lowest adherence) to 18 points (highest adherence). Since no relevant differences for proposed food categories across men and women were obtained, a single score was computed for both sexes (Fig. 4).

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Fig. 4

Literature-based adherence score to the Mediterranean diet (range: 0–18 points). Portion sizes derive from the calculation of mean value of weighted medians (or means) ±2 sd coming from all the cohort studies reported in Tables 1 and ​and22

Discussion

In the present study we conducted an updated meta-analysis on the association between adherence to the Mediterranean diet and health outcomes, with the additional purpose of proposing an adherence score, based on data from the literature, that can be used also at an individual level and not only in an epidemiological setting.

Greater adherence to the Mediterranean diet has long been reported to be protective against the occurrence of chronic degenerative disease⁽ 1 ⁾. Two previous meta-analyses conducted by our group reported the Mediterranean diet to be the optimal diet for preserving a good health status⁽ 2 ^, 3 ⁾. Moreover, recently, the protective role of the Mediterranean diet has been also demonstrated in a dietary intervention study conducted in Spanish middle-aged subjects. Over a follow-up period of 4·8 years, subjects following the Mediterranean diet reported to have a protection of 30 % v. the occurrence of CVD in a primary prevention setting⁽ 37 ⁾.

We decided to update the meta-analysis previously published by our group because many studies have been released in the last 3 years. This updated analysis was conducted with the same methods used for the previous meta-analysis⁽ 3 ⁾ and allowed us to add eighteen prospective studies to the final analysis⁽ 7 ^– 24 ⁾. Hence, we were able to extend the evidence to an overall study population of more than 4 000 000 subjects and to other countries such as Italy and Scandinavian countries⁽ 7 ^– 9 ^, 16 ^, 22 ^, 23 ⁾. From this updated analysis we could report that a 2-point increase in adherence score to the Mediterranean diet is actually protective v. the occurrence of overall mortality, incidence and/or mortality from cardiovascular and neoplastic causes, with again similar results compared with the previous analyses (−8 % for overall mortality, −10 % for CVD and −4 % for cancer).

An additional purpose of the present article was to obtain, from the most updated prospective cohort studies, data regarding the amount of consumption for food groups composing the adherence score to the Mediterranean diet in order to propose a literature-based adherence score that can be used to assess adherence to the Mediterranean diet also at an individual level.

Over the last years, research on nutritional science and on its relationship with disease has shifted from the study of single nutrients to the evaluation of food patterns, since subjects do not eat isolated nutrients and because the complex interactions among different nutrients have been reported to be extremely relevant for the healthy aspects of diet. Some attempts for estimating the adherence to the whole diet, and particularly to the Mediterranean diet, have been conducted⁽ 4 ^, 5 ⁾. The first and most widely used tool to assess adherence to the Mediterranean diet, created by Trichopoulou et al.⁽ 6 ⁾, has been extremely widely used for epidemiological research and is based on the sex-based median amount of consumption of food groups that are characteristic of the traditional Mediterranean diet in the sample investigated. On one hand, this score has many advantages because it helped to introduce the concept of an adherence score to a specific diet and allowed to estimate the association between the adherence score and risk of disease in an epidemiological setting. On the other hand, however, it has the main disadvantage of being widely related to the availability of data coming from a sample population, differing substantially from one cohort to another, even within the same country, and more importantly because it does not give an amount of consumption for food groups composing the score that can be used in everyday clinical practice, at an individual level. This is the reason why other indices have been created. One example is that of Panagiotakos et al.⁽ 38 ⁾ who created a simple questionnaire based on recommendations of the guidelines for a healthy diet and characterized by a few questions used for estimating the frequency of consumption (monthly or daily) of food groups more or less characteristic of the Mediterranean diet. Another example is the questionnaire developed in the PREDIMED study and recently assessed in the SUN (Seguimiento Universidad de Navarra) cohort⁽ 39 ⁾. Both these questionnaires have the advantage of being feasible for assessing adherence to the Mediterranean diet at an individual level but they are not based on data from the literature.

That is why we decided to utilize all the available data coming from the most relevant cohort studies for proposing a new evidence-based score for assessing adherence to the Mediterranean diet.

The approach we used, despite able to obtain all the literature data available in this context, may present some limitations. Different cohorts coming from the same country reported to have different cut-offs of consumption for the adherence to the Mediterranean diet, and even among the same countries the range of consumption within the same food group varied. Moreover, by analysing data it became apparent that the median of consumption was extremely related to the sample size of the population investigated. To date, smaller cohorts had, at the same time, higher consumption and vice versa. Hence, we decided to calculate the mean value of all the food groups by taking into account the sample size of the population, i.e. estimating the weighted medians for consumption of all of the food groups.

Despite all these efforts, some limitations that are intrinsic to the single studies still remain. One of these is the lack of uniformity in data regarding the same food group. Some studies report potatoes together with vegetables, while others include them as a single food group, whereas some others include legumes with nuts and not by themselves, and so on.

Nevertheless, the strength of this proposed adherence score is that food group data come from the most updated and comprehensive review of the literature in this context. If confirmed and validated in other studies, the evidence-based search strategy used for obtaining data from the available studies will hopefully help the transferability of such an adherence score into clinical practice.

Conclusion

We updated the results of our previous meta-analyses by including eighteen cohort prospective studies published in the last 3 years and we were able to show the beneficial effects of a greater adherence to the Mediterranean diet in terms of protection v. overall mortality and occurrence of the most important chronic diseases. In addition, by using data coming from the systematic review we proposed an adherence score based on literature data that can be also feasible for assessment of the adherence to the Mediterranean diet at an individual level.

Acknowledgements

References