Accruing evidence on benefits of adherence to the Mediterranean diet on health: an updated systematic review and meta-analysis1,2
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Accruing evidence on benefits of adherence to the Mediterranean diet on health: an updated systematic review and meta-analysis1,2 Francesco Sofi, Rosanna Abbate, Gian Franco Gensini, and Alessandro Casini ABSTRACT great deal of attention has been given to tools that estimate the Background: The Mediterranean diet has long been reported to adherence of individuals to the Mediterranean diet because of the be protective against the occurrence of several different health usefulness of these tools to identify the whole dietary pattern outcomes. instead of single foods or nutrients (4). Hence, computational Objective: We aimed to update our previous meta-analysis of pub- scores have been created and used in several large epidemiologic lished cohort prospective studies that investigated the effects of studies to seek whether they could be useful to estimate the risk of adherence to the Mediterranean diet on health status. disease in the general population (5). Some large epidemiologic Downloaded from ajcn.nutrition.org by guest on February 10, 2015 Design: We conducted a comprehensive literature search through studies conducted in different cohorts evidenced an association electronic databases up to June 2010. between a greater adherence to Mediterranean diet, a reduced risk Results: The updated review process showed 7 prospective studies of mortality, and the incidence of major chronic diseases (6–9). In published in the past 2 y that were not included in the previous 2008, we performed a meta-analysis that included all cohort meta-analysis (1 study for overall mortality, 3 studies for cardiovas- prospective studies that investigated this issue, and we observed cular incidence or mortality, 1 study for cancer incidence or mor- that a 2-point increase of adherence to Mediterranean diet tality, and 2 studies for neurodegenerative diseases). These recent conferred a significant protection against mortality, the occur- studies included 2 health outcomes not previously investigated (ie, rence of cardiovascular diseases, and major chronic degenerative mild cognitive impairment and stroke). The meta-analysis for all diseases (3). However, the previous meta-analysis is 3 y old, and studies with a random-effects model that was conducted after the more prospective cohort studies have since been published. inclusion of these recent studies showed that a 2-point increase in Therefore, the aim of this study was to update our previous adherence to the Mediterranean diet was associated with a signifi- systematic review and meta-analysis conducted in cohort pro- cant reduction of overall mortality [relative risk (RR) = 0.92; 95% spective studies that investigated the effects of adherence to CI: 0.90, 0.94], cardiovascular incidence or mortality (RR = 0.90; Mediterranean diet on several health outcomes and to use these 95% CI: 0.87, 0.93), cancer incidence or mortality (RR = 0.94; data to conduct a meta-regression analysis to explore a potential 95% CI: 0.92, 0.96), and neurodegenerative diseases (RR = 0.87; source of heterogeneity in studies. 95% CI: 0.81, 0.94). The meta-regression analysis showed that sam- ple size was the most significant contributor to the model because it significantly influenced the estimate of the association for overall METHODS mortality. Conclusion: This updated meta-analysis confirms, in a larger num- Literature search ber of subjects and studies, the significant and consistent protection According to the statement of the Preferred Reporting Items for provided by adherence to the Mediterranean diet in relation to the Systematic Reviews and Meta-Analyses (10), we systematically occurrence of major chronic degenerative diseases. Am J Clin searched published cohort prospective studies that investigated Nutr 2010;92:1189–96. the association between adherence to the Mediterranean diet and health outcomes in electronic databases: MEDLINE (source: PubMed, 1966 to June 2010; www.pubmed.com), EMBASE (1980 INTRODUCTION to June 2010; www.embase.com), Web of Science (isiweb The Mediterranean diet has long been reported to be the ofknowledge.com), The Cochrane Library (source: The Cochrane optimal diet for preventing noncommunicable diseases and 1 preserving good health (1–3). The Mediterranean-style diet is not From the Department of Medical and Surgical Critical Care, Thrombo- a specific diet, but rather a collection of eating habits traditionally sis Centre, University of Florence, Florence, Italy (FS, RA, and GFG); the followed by people in the different countries bordering the Agency of Nutrition, Azienda Ospedaliero-Universitaria Careggi, Florence, Mediterranean Sea. The diet refers to a dietary profile commonly Italy (FS and AC); and the Don Carlo Gnocchi Foundation, Centro Santa Maria agli Ulivi, Onlus IRCCS, Florence, Italy (FS and GFG). available in the early 1960s in the Mediterranean regions and 2 Address correspondence to F Sofi, Department of Medical and Surgical characterized by a high consumption of fruit, vegetables, le- Critical Care, Thrombosis Centre, University of Florence, Viale Morgagni gumes, and complex carbohydrates, with a moderate consump- 85, 50134 Florence, Italy. E-mail: firstname.lastname@example.org. tion of fish, and the consumption of olive oil as the main source of Received April 14, 2010. Accepted for publication July 27, 2010. fats and a low-to-moderate amount of red wine during meals. A First published online September 1, 2010; doi: 10.3945/ajcn.2010.29673. Am J Clin Nutr 2010;92:1189–96. Printed in USA. Ó 2010 American Society for Nutrition 1189
1190 SOFI ET AL Central Register of Controlled Trials, 2010, issue 2; www.the ment for confounders that include demographic, anthropometric, cochranelibrary.com/), clinicaltrials.org, and Google Scholar and traditional risk factors were considered of high quality. (scholar.google.com). Relevant keywords relating to the Medi- terranean diet in combination as MeSH terms and text words (“Mediterranean diet,” or “diet” or “dietary pattern” “Mediterra- Statistical analyses nean,” or “adherence” or “score” and their variants) were used in We used the Review Manager program (RevMan, version combination with words relating to health status (“health,” or 5.0.18 for Macintosh, 2008; The Cochrane Collaboration, “mortality” or “morbidity,” or “cardiovascular diseases,” or Copenhagen, Denmark) and the Statistical Package for Social “neoplastic diseases,” or “cancer,” or “neoplasm,” or “de- Sciences software (SPSS, version 18.0 for Macintosh; SPSS, generative diseases,” or “Alzheimer’s disease,” or “Parkinson’s Chicago, IL) to pool and analyze results from the individual disease,” or “cerebrovascular disease,” or “dementia,” or “cog- studies. The methods and results of all recently identified cohort nition disorder,” or “stroke,” or “outcome,” or “prospective,” or prospective studies were added to the previous table, and data “follow-up,” or “cohort” and their variants). The search strategy were formally combined. Pooled results were reported as relative had no language restrictions. References from the extracted articles risks (RRs) and presented with 95% CIs with 2-sided P values by and reviews were also consulted to complete the data bank. When using a random-effects model (DerSimonian and Laird method) multiple articles for a single study were present, we used the latest and the general variance-based method. P , 0.05 was consid- publication and supplemented it, if necessary, with data from the ered statistically significant. When available, we used the results most complete or updated publication. of the original studies from multivariate models with the most complete adjustment for potential confounders; the confounding variables included in the analyses are shown in Table 1. Downloaded from ajcn.nutrition.org by guest on February 10, 2015 Study selection Statistical heterogeneity was evaluated by using the I2 statistic, We identified studies that prospectively evaluated the asso- which assessed the appropriateness of pooling the individual ciation of an a priori score used for assessing adherence to study results. The I2 value provided an estimate of the amount of Mediterranean diet and adverse clinical outcomes. We excluded variance across studies because of heterogeneity rather than studies if they had a cross-sectional or case-control design, if they chance. Where I2 was .50%, the heterogeneity was considered analyzed adherence to a nonspecific dietary pattern or to a rec- substantial. A small study bias or publication bias was appraised ommended dietary guideline and not to Mediterranean diet, if by visual inspection of the funnel plot of effect size against the they evaluated cohort of patients who suffered from a prior SE and, analytically, by the Egger’s test. Moreover, to in- clinical event (ie, in a secondary prevention), if they did not adjust vestigate possible sources of heterogeneity across studies, we for potential confounders, and if they did not report an adequate performed a meta-regression analysis to investigate the effects statistical analysis. of various characteristics of studies on the study estimates of RRs. Data extraction Two investigators (FS and AC) assessed potentially relevant RESULTS articles for eligibility. The decision to include or exclude studies The updated search from recent years resulted in the identi- was hierarchical and initially made on the basis of the study title, fication of 7 additional prospective studies (11–17) published up then of the study abstract, and finally of the complete study to June 2010 that were not identified and included previously. manuscript. Two researchers independently completed searches, Characteristics of these recent studies are displayed in Table 1. Of identification of studies, data abstraction, and tabulation, and these, 1 study presented the overall mortality as a clinical out- discordances were resolved by discussions. The following base- come (14), 3 studies presented the incidence and/or mortality line characteristics were extracted from the original articles by from cardiovascular diseases (13, 15, 16), 1 study presented the using a standardized data extraction form and included in the incidence and/or mortality from neoplastic diseases (17), and 2 meta-analysis: lead author, year of publication, cohort name, studies presented the incidence of neurodegenerative diseases country of origin of the cohort, sample size of the cohort, number (11, 12). Notably, 2 of the 7 studies reported clinical outcomes not of outcomes, duration of follow-up, age at entry, sex, outcomes, previously investigated, such as mild cognitive impairment and components of the Mediterranean diet adherence score, and stroke (12, 13). On the other hand, one study was an updated variables that entered into the multivariable model as potential analysis of a study already reported in the previous meta-analysis confounders (Table 1). for the overall mortality outcome; therefore, only the most Outcomes of interests were overall mortality, mortality and/or updated study was added to this updated final analysis (14). Taken incidence from cardio- and cerebrovascular diseases, mortality altogether, a total of 18 cohort prospective studies were included and/or incidence from cancer, and incidence of neurodegenera- and entered into the final analysis. As a whole, the updated tive diseases. analysis determined a study population that reached a total of 2,190,627 subjects analyzed. Included samples ranged in size from 161 to 485,044, with a follow-up time that ranged from 4 to Quality assessment 20 y. Study quality was assessed according to the following criteria: Considerable variations among studies were observed in the 1) number of study participants, 2) duration of follow-up, and 3) number of participants, sex and age of participants, length of adjustment for potential confounders. Studies with a high follow-up, and dietary components used to measure the adher- number of participants, long duration of follow-up, and adjust- ence score to the Mediterranean diet. Studies conducted in
TABLE 1 Study characteristics of the recent prospective studies investigating adherence to the Mediterranean diet and health outcomes1 Author, year (cohort) Country Sample size/total cohort Outcome Follow-up Age Sex Components of the adherence score Adjustment n/total n y y Feàrt et al, France 50/1410 Alzheimer 5 68–952 M/F 1) High legume intake Age, sex, BMI, hypertension, 2009 (11) disease 2) High whole-grain products intake hypercholesterolemia, (Three-City 3) High fruit intake smoking habit, education, Study) 4) High vegetable intake marital status, total energy, 5) High fish intake physical activity, medications, 6) High MUFA:SFA ratio depression, apoE genotype, 7) Moderate alcohol consumption and stroke 8) Low red and processed meat intake 9) Low dairy product intake Scarmeas et al, United States 241/1199 Mild 4.5 76.73 M/F 1) High legume intake Age, sex, ethnicity, education, 2009 (12) (only in those cognitive 2) High cereal intake apoE genotype, total energy, (Washington who were impairment 3) High fruit intake and BMI Heights- cognitively 4) High vegetable intake Inwood normal at 5) High fish intake Columbia baseline) 6) High MUFA:SFA ratio Aging 7) Moderate alcohol consumption Project) 8) Low meat intake 9) Low dairy product intake Fung et al, United States 2391/74,886 CHD 20 38–63 F 1) High legume intake Age, smoking habit, BMI, 2009 1763/74,886 Stroke 2) High whole-grain products intake menopausal status, hormone (13) (Nurses’ 3) High fruit intake use, total energy, multivitamin Health 4) High vegetable intake intake, alcohol, family history, Study) 5) High fish intake physical activity, and 6) High nuts intake aspirin use 7) High MUFA:SFA ratio 8) Moderate alcohol consumption 9) Low red and processed meat intake UPDATED META-ANALYSIS ON MEDITERRANEAN DIET Trichopoulou Greece 1075/23,349 Overall 8.5 20–86 M/F 1) High legume intake Age, sex, education, smoking et al, 2009 mortality 2) High cereal intake habit, waist:hip ratio, MET (14) (EPIC- 3) High fruit/nuts intake score, total energy, and BMI Greece) 4) High vegetable intake 5) High fish intake 6) High MUFA:SFA ratio 7) Moderate alcohol consumption 8) Low meat and poultry intake 9) Low dairy product intake (Continued) 1191 Downloaded from ajcn.nutrition.org by guest on February 10, 2015
1192 TABLE 1 (Continued ) Author, year (cohort) Country Sample size/total cohort Outcome Follow-up Age Sex Components of the adherence score Adjustment n/total n y y Buckland et al, Spain 606/40,151 CHD 10.4 29–69 M/F 1) High legume intake Age, education, BMI, physical 2009 (15) 2) High cereal intake activity, smoking habit, (EPIC Spain) 3) High fruit/nuts intake diabetes, hypertension, 4) High vegetable intake hyperlipidemia, and total 5) High fish intake energy 6) High MUFA:SFA ratio 7) Moderate alcohol consumption 8) Low meat and poultry intake 9) Low dairy product intake Martı́nez-González Spain 100/13,609 CVD 4.9 383 M/F 1) High legume intake Age, sex, family history of CVD, et al, 2010 (16) 2) High cereal intake total energy, physical activity, (SUN Study) 3) High fruit/nuts intake smoking habit, BMI, diabetes, 4) High vegetable intake aspirin, hypertension, and 5) High fish intake hypercholesterolemia 6) High MUFA:SFA ratio SOFI ET AL 7) Moderate alcohol consumption 8) Low meat and poultry intake 9) Low dairy product intake Buckland et al, United Kingdom, 449/485,044 Gastric 8.9 35–70 M/F 1) High legume intake Age, sex, BMI, education, 2010 (17) France, Denmark, adenocarcinoma 2) High cereal intake smoking habit, and total (Spanish cohort Sweden, Germany, 3) High fruit/nuts intake energy of the EPIC-Heart Italy, Spain, 4) High vegetable intake Study) Netherlands, 5) High fish intake Norway, and 6) High olive oil intake Greece 7) Moderate alcohol consumption 8) Low meat and poultry intake 9) Low dairy product intake 1 MUFA, monounsaturated fatty acid; SFA, saturated fatty acid; CHD, coronary heart disease; EPIC, European Prospective Investigation into Cancer and Nutrition; MET, metabolic equivalent tasks; SUN, Seguimiento Universidad de Navarra; CVD, cardiovascular disease. 2 Range (all such values). 3 Mean. Downloaded from ajcn.nutrition.org by guest on February 10, 2015
UPDATED META-ANALYSIS ON MEDITERRANEAN DIET 1193 European countries increased to 9 studies (50% of the total from and incidence of neoplastic diseases (Figure 3), a greater number of studies included). adherence to the Mediterranean diet still determined a signifi- By grouping the studies according to the different clinical cant amount of protection, with a similar extent than that of outcomes, the overall mortality did not change for the number previous meta-analysis (RR = 0.94; 95% CI: 0.92, 0.96; P , of studies evaluated (ie, 9 studies that included an updated 0.00001) and again no significant heterogeneity (I2 = 6%; P = analysis of the Greek cohort of the EPIC (European Prospective 0.38). The results of the previous meta-analysis were also Investigation into Cancer and Nutrition) with a total of 514,118 confirmed for the occurrence of neurodegenerative diseases subjects and 34,322 deaths, whereas a consistent increase of (Figure 4), which extended to mild cognitive impairment, with studies and subjects analyzed for the other clinical outcomes a 13% reduced risk of individuals who most adhered to the has been reported. Indeed, cardiovascular mortality and in- Mediterranean diet (RR = 0.87; 95% CI: 0.81, 0.94; P , cidence were consistently augmented by the number of studies 0.00001) and no significant heterogeneity across studies (I2 = and subjects analyzed, with a total of 7 cohorts, 534,064 0%; P = 0.73). subjects, and 8739 deaths or incident cases. Similarly, the mortality from and incidence of neoplastic diseases reached 1,006,410 subjects and 11,378 events, whereas the number of Publication bias studies that evaluated the association between adherence to the Mediterranean diet and neurodegenerative diseases increased The funnel plots of effect sizes compared with SEs that were from 3 to 5 cohorts, with a total of 136,235 subjects and 1074 performed to investigate possible publication biases were sym- cases, including an additional clinical outcome such as mild metric for all different clinical outcomes, which suggested the cognitive impairment. absence of possible publication biases. Downloaded from ajcn.nutrition.org by guest on February 10, 2015 Meta-analysis Meta-regression analysis Meta-analytic pooling under a random-effects model con- Finally, to investigate the effects of various study character- firmed the already reported significant association between a 2- istics on the study estimates of the RRs, we conducted a meta- point increased adherence to the Mediterranean diet and a reduced regression analysis by grouping studies according to some risk of mortality from all causes (RR = 0.92; 95% CI: 0.90, 0.94; characteristics, such as the number of subjects studied, number of P , 0.00001) (Figure 1) with no evidence of statistical cases observed, country of origin of the patients, age of the heterogeneity across studies (I2 = 33%; P = 0.15). When studies patients, and length of follow-up. The sample size of the included that evaluated different clinical outcomes were grouped, we studies was the only contributor to the protection compared with observed that a 2-point increase of adherence to the Mediter- the overall mortality (b = 0.059 6 0.018; P = 0.013) in the ranean diet still remained associated with a reduced risk of present model. By plotting the estimates of associations for mortality from and incidence of cardiovascular diseases (RR = overall mortality with the number of subjects analyzed for each 0.90; 95% CI: 0.87, 0.93; P , 0.00001) (Figure 2), which study, it was shown that the average protection compared with showed no significant heterogeneity across studies (I2 = 35%; the overall mortality was reached with studies that investigated P = 0.15). Likewise, in studies that investigated the mortality .2000 subjects (Figure 5). FIGURE 1. Forest plot of the association between a 2-point increase of adherence score to the Mediterranean diet and the risk of all-cause mortality. The center of each square indicates the relative risk of the study, and the horizontal lines indicate 95% CIs. The area of the square is proportional to the amount of information from the study. The diamond indicates pooled estimates.
1194 SOFI ET AL FIGURE 2. Forest plot of the association between a 2-point increase of adherence score to the Mediterranean diet and the risk of mortality from or incidence of cardiovascular diseases. The center of each square indicates the relative risk of the study, and the horizontal lines indicate 95% CIs. The area of Downloaded from ajcn.nutrition.org by guest on February 10, 2015 the square is proportional to the amount of information from the study. The diamond indicates pooled estimates. CHD, coronary heart disease. DISCUSSION neurodegenerative diseases. Furthermore, in this updated meta- In this updated meta-analysis of prospective studies that in- analysis, which included 7 articles published in the past 3 y that vestigated the association between adherence to the Mediterranean could not be considered in the previous meta-analysis, some other diet and health status, findings were pooled from .2 million clinical outcomes, such as stroke and mild cognitive impairment, subjects and 50,000 deaths or incident cases from any causes and/ were included, and a meta-regression analysis to investigate the or from any cardiovascular, neoplastic, and neurodegenerative possible role of confounding factors was also conducted. diseases. We confirmed the results of our previously published Several studies over the past decades showed the Mediterra- meta-analysis, which suggested a significant protection against nean diet to be significantly associated with different health major chronic degenerative diseases for subjects who reported outcomes, such as a favorable health status, better biochemical a greater adherence to the Mediterranean diet (3). Indeed, a 2- profile, and quality of life (1–3, 26, 27). Accordingly, over- point increase of adherence to the Mediterranean diet significantly whelming evidence on the health effects of such a dietary profile determined a 8% reduction of death from any causes, a 10% re- has been reported in many different study cohorts by stimulating duction from death and/or incidence of cardio- and cerebrovas- both scientific and lay communities to promote this dietary cular diseases, a 6% reduction from death and/or the incidence pattern as the ideal dietary pattern for preventing non- of neoplastic diseases, and a 13% reduction of the incidence of communicable diseases (3, 27). FIGURE 3. Forest plot of the association between a 2-point increase of adherence score to the Mediterranean diet and the risk of mortality from or incidence of neoplastic diseases The center of each square indicates the relative risk of the study, and the horizontal lines indicate 95% CIs. The area of the square is proportional to the amount of the information from the study. The diamond indicates pooled estimates.
UPDATED META-ANALYSIS ON MEDITERRANEAN DIET 1195 FIGURE 4. Forest plot of the association between a 2-point increase of adherence score to the Mediterranean diet and the risk of incidence of neurodegenerative diseases. The center of each square indicates the relative risk of the study, and the horizontal lines indicate 95% CIs. The area of the square is proportional to the amount of the information from the study. The diamond indicates pooled estimates. In this context, with the aim of identifying a practical tool to the interest of researchers on this issue rose, and a total of 7 new estimate how populations follow the guidelines of Mediterranean cohort prospective studies were added to the literature (11–17). Downloaded from ajcn.nutrition.org by guest on February 10, 2015 diet, adherence scores were computed (4). Many different scores On the other hand, the issue has been shown to be of extreme were created and tested in different study cohorts, but the most interest for the general population as well as for health admin- important was definitely that created in 1995 and developed in istrators and governments for better tailoring their prevention its final form in 2003 by Trichopoulou et al (6, 18). In their strategies and policies. studies, which investigated the Greek cohort of the EPIC study, The present updated meta-analysis has some advantages with Trichopoulou et al showed, for the first time to our knowledge, respect to the previous one: first, it present, to out knowledge, the a significant association between an increase of such an adher- most comprehensive and updated assessment on this issue, with ence score and the reduction of overall mortality. Subsequently, inclusion of new studies and an update of previously reported many studies that used this kind of epidemiologic approach have studies; second, the association between the Mediterranean diet been released by extending the evidence to many different health and health outcomes was extended to other relevant disease states outcomes (3). that were not previously investigated, such as stroke and mild The results of the first meta-analysis published in 2008, which cognitive impairment. These clinical outcomes are of clinical comprised a total of 12 studies and .1.5 million subjects, were relevance for the ever-increasing age of the general population. that a 2-point increase of score that estimated adherence to the Third, it reinforces the findings that a slight increase of the Mediterranean diet significantly determined protection com- adherence score to the Mediterranean diet, as was observed by an pared with premature death and various diseases. In the past 3 y, increase of 2 points of the adherence score, is significantly FIGURE 5. Meta-regression analysis of the relation between sample sizes of the studies and all-cause mortality. The area of the circle is proportional to the number of subjects studied in the study; the dashed line indicates the overall estimate of the association for studies that investigated all-cause mortality.
1196 SOFI ET AL associated with a reduced risk of mortality and the incidence of 2. Serra-Majem L, Roman B, Estruch R. Scientific evidence of inter- main chronic degenerative diseases. Moreover, in the present ventions using the Mediterranean diet: a systematic review. Nutr Rev 2006;64:S27–47. updated meta-analysis, we performed a meta-regression analysis 3. Sofi F, Cesari F, Abbate R, Gensini GF, Casini A. Adherence to Medi- to give deeper insight into the nature of the association between terranean diet and health status: meta-analysis. BMJ 2008;337:a1344. the adherence score and health status. The meta-regression 4. Bach A, Serra-Majem L, Carrasco JL, et al. The use of indexes evalu- analysis showed that studies with larger study populations were ating the adherence to the Mediterranean diet in epidemiological studies: a review. Public Health Nutr 2006;9:132–46. more significantly associated with a lesser degree of heterogeneity 5. Kourlaba G, Panagiotakos DB. Dietary quality indices and human and a higher estimate of association. In particular, studies with health: a review. Maturitas 2009;62:1–8. populations of .2000 subjects seemed to be more significantly 6. Trichopoulou A, Costacou T, Bamia C, Tricopoulou D. Adherence to related to the mean outcome observed in the meta-analysis. This a Mediterranean diet and survival in a Greek population. N Engl J Med 2003;348:2599–608. finding could be easily explained by the increased power of the 7. Knoops KTB, de Groot LCPGM, Kromhout D, et al. Mediterranean diet, studies related to the higher number of subjects analyzed. lifestyle factors, and 10-year mortality in elderly European men and In contrast, although we believe that this updated meta- women. JAMA 2004;292:1433–9. analysis provides useful information, the findings must be 8. Lagiou P, Trichopoulos D, Sandin S, et al. Mediterranean dietary pattern and mortality among young women: a cohort study in Sweden. 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Adherence to a Mediterranean currence of several and different diseases can lead to an over- diet, cognitive decline, and risk of dementia. JAMA 2009;302:638–48. 12. Scarmeas N, Stern Y, Mayeux R, Manly JJ, Schupf N, Luchsinger JA. estimation of the results. Third, the transferability of such an Mediterranean diet and mild cognitive impairment. Arch Neurol 2009; adherence score to the general population and the day-to-day 66:216–25. clinical practice is not free of practical problems. The adherence 13. Fung TT, Rexrode KM, Mantzoros CS, Manson JE, Willett WC, Hu FB. score’s ease of use is low because the method of calculation Mediterranean diet and incidence of and mortality from coronary heart disease and stroke in women. Circulation 2009;119:1093–100. implies the analysis of raw data that comes from a cohort study, 14. Trichopoulou A, Bamia C, Trichopoulos D. Anatomy of health effects of and the real amount of each food category to consume is not Mediterranean diet: Greek EPIC prospective cohort study. BMJ 2009; established. Some relevant differences among the studies are 338:b2337. present, and the transferability to the clinical practice is difficult 15. Buckland G, González CA, Agudo A, et al. Adherence to the Medi- terranean diet and risk of coronary heart disease in the Spanish EPIC to understand. However, with the use of such meta-analyses, we Cohort Study. Am J Epidemiol 2009;170:1518–29. are able to understand the real estimate of the association between 16. Martı́nez-González MA, Garcı́a-López M, Bes-Rastrollo M, et al. Medi- the adherence score to the Mediterranean diet and health status terranean diet and the incidence of cardiovascular disease: a Spanish co- and to stimulate the interest of researchers to make uniform and hort. Nutr Metab Cardiovasc Dis (Epub ahead of print 20 January 2010). 17. 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