Modified Mediterranean diet and survival: EPIC-elderly prospective cohort study
1 Department of Hygiene and Epidemiology, University of Athens Medical School, Athens 11527, Greece,2 Nutrition and Hormones Group, International Agency for Research on Cancer, Lyon, France,3 Centre for Nutrition and Health, National Institute for Public Health and the Environment, Bilthoven, Netherlands,4 Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, Netherlands,5 Department of Epidemiology, German Institute of Human Nutrition, Potsdam, Germany,6 Division of Clinical Epidemiology, German Cancer Research Centre, Heidelberg, Germany,7 Molecular and Nutritional Epidemiology Unit, CSPO-Scientific Institute of Tuscany, Florence, Italy,8 Epidemiology Unit, National Cancer Institute, Milan, Italy,9 Dipartimento di Medicina Clinica e Sperimentale Università Federico II, Naples, Italy, 10 Cancer Registry Azienda Ospedaliera "Civile M P Arezzo," Ragusa, Italy, 11 Environmental Epidemiology, Imperial College London, 12 Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain, 13 Andalusian School of Public Health, Granada, Spain, 14 Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain, 15 Department of Public Health of Guipuzcoa, San Sebastian, Spain, 16 Cancer Research UK Epidemiology Unit, University of Oxford, 17 Medical Research Council Dunn Nutrition Unit, Cambridge, 18 Clinical Gerontology, University of Cambridge, 19 Equipe E3N-EPIC, Institut National de la Sante et de la Recherche Medicale, Institut Gustave Roussy, France, 20 Malmo Diet and Cancer Study, Department of Medicine, Lund University, Sweden, 21 Department of Public Health and Clinical Medicine, Umea University, Umea, Sweden, 22 Department of Odontology, Umea University, 23 Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark, 24 Department of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark, 25 Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
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Abstract
Design Multicentre, prospective cohort study.
Setting Nine European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Spain, Sweden, United Kingdom).
Participants 74 607 men and women, aged 60 or more, without coronary heart disease, stroke, or cancer at enrolment and with complete information about dietary intake and potentially confounding variables.
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Main outcome measures Extent of adherence to a modified Mediterranean diet using a scoring system on a 10 point scale, and death from any cause by time of occurrence, modelled through Cox regression.
Results An increase in the modified Mediterranean diet score was associated with lower overall mortality, a two unit increment corresponding to a statistically significant reduction of 8% (95% confidence interval 3% to 12%). No statistically significant evidence of heterogeneity was found among countries in the association of the score with overall mortality even though the association was stronger in Greece and Spain. When dietary exposures were calibrated across countries, the reduction in mortality was 7% (1% to 12%).
, http://www.100md.com
Conclusion The Mediterranean diet, modified so as to apply across Europe, was associated with increased survival among older people.
Introduction
The Mediterranean diet has been used in many studies because several of its components have been related to common chronic diseases,2 10 ecological evidence suggests that such a diet may be beneficial to health,11 and variants of this diet have improved the prognosis of patients with coronary heart disease.12 13 The Mediterranean diet is characterised by a high intake of vegetables, legumes, fruits, and cereals (in the past largely unrefined); a moderate to high intake of fish; a low intake of saturated lipids but high intake of unsaturated lipids, particularly olive oil; a low to moderate intake of dairy products, mostly cheese and yogurt; a low intake of meat; and a modest intake of ethanol, mostly as wine.14 Adherence to a Mediterranean diet was operationalised through a 10 unit dietary score by Trichopoulou et al.4 15 Several studies have used variants of this score and have reported inverse associations with overall mortality.4 6 8 9 15 These studies, however, relied on small samples of mostly elderly participants or on the Greek population only.15
, 百拇医药
We calculated a score reflecting the Mediterranean diet.15 To allow the score to be applied to non-Mediterranean populations, in which intake of monounsaturates from olive oil is minimal, we substituted monounsaturated lipids with the sum of monounsaturated and polyunsaturated lipids in the numerator of the lipid ratio. We investigated the relation of this modified score with overall mortality in a large sample of elderly Europeans participating in EPIC (the European prospective investigation into cancer and nutrition study).16
, 百拇医药
Participants and methods
Data for participants aged 60 or over at recruitment were included in the EPIC-elderly study. This study aims to identify dietary patterns among elderly Europeans and to investigate the associations of diet with survival.
Dietary intakes
Usual dietary intakes were assessed through compatible instruments (food frequency questionnaires and, in some centres, records of intake over seven or 14 days) that had been developed and validated within each centre.17-19 In addition, a computerised instrument for recall of dietary intake over 24 hours was developed to collect information from a stratified random sample of the aggregate cohort. The aim was to calibrate the measurements across countries.17
, http://www.100md.com
Nutrient intakes were calculated using food composition tables specific to the country.20 In the present study, 14 food groups and nutrients were considered: potatoes, vegetables, legumes, fruits, dairy products, cereals, meat and meat products, fish and seafood, eggs, monounsaturated lipids, polyunsaturated lipids, saturated lipids, sugar and confectionery, and non-alcoholic beverages. For each participant, daily intake (grams) of each of the groups and total energy intake (megajoules) were estimated.
, http://www.100md.com
Lifestyle, anthropometric, and medical variables
A precoded questionnaire was used to record data on lifestyle and health,16 which included educational achievement, history of illnesses, history of smoking, and physical activity. For participants still in work, the physical demand of their job was recorded. For leisure, time spent on each of several activities was multiplied by an energy cost coefficient; the products were then summed to produce a score of daily physical activity.21 Sex and centre specific thirds of the estimated physical activity score at leisure were used.
, http://www.100md.com
Anthropometric measurements were taken in all EPIC centres using similar, standardised procedures, except for France, Oxford (United Kingdom), and Norway. In these centres self reported values were recorded, but actual measurements were obtained for only a fraction of the participants.
Mediterranean diet scale
A scale indicating the degree of adherence to the traditional Mediterranean diet has been constructed by Trichopoulou et al.4 15 Values of zero or one were assigned to each of nine indicated components, using as cut-off values the sex specific medians among the participants. People whose consumption of presumed beneficial components (vegetables, legumes, fruits, cereals, fish) was below the median consumption were assigned a value of zero, and a value of one otherwise. People whose consumption of presumed detrimental components (meat and dairy products) was below the median consumption were assigned a value of one, and a value of zero otherwise. A value of one was given to men consuming from 10 g to less than 50 g of ethanol per day and to women consuming from 5 g to 25 g. For lipid intake, the ratio of the sum of monounsaturates and polyunsaturates to saturates was calculated. This modified Mediterranean diet score, as both monounsaturates and polyunsaturates are included in the numerator of the lipid ratio, can take a value from zero (minimal adherence) to nine (maximal adherence).
, 百拇医药
Follow-up
Information on the vital status of participants was obtained from mortality registries and by active follow-up. Earliest and latest years of follow-up were 1999 (some participants in the Netherlands) and December 2003 (most centres). Participants were classified as alive at last follow-up, dead, emigrated, refused to participate further, and unknown.
Overall, 100 442 participants of the EPIC cohort were aged 60 years or more at recruitment and had acceptable records of energy intakes (those in the top and bottom 1% of the ratio of energy intake to estimated energy requirement were excluded).22 Vital status has been ascertained for 100 309 (99.9%) of these participants; however, 15 362 were excluded from the EPIC-elderly study database because coronary heart disease, stroke, cancer, or a combination of these had been diagnosed at enrolment. Of the remaining 84 947 participants, 10 340 had missing information for one or more of the dietary, anthropometric, or lifestyle variables, or had died within the year after enrolment. Thus 74 607 individuals were included in the study.
, 百拇医药
Statistical analysis
Analyses were carried out with Stata 7.0 and SAS 8.2. Descriptive presentation relied on cross tabulations. Survival data were modelled through Cox's proportional hazards regression,23 with length of follow-up as the primary time variable. Adjustment was made for sex, age, self reported diabetes mellitus at enrolment, educational achievement, smoking status, physical activity, waist to hip ratio, body mass index, and total energy intake. In analyses that investigated the relation of the score with mortality, consumption of eggs, potatoes, and sugar and confectionery (which are not part of the score) were also controlled for continuously. Both fixed effects and random effects models were used. Separate proportional hazard models were used for all participants and for participants in each country. Models were stratified by country or by centre (for the country specific analyses).
, 百拇医药
Dietary exposures across centres were equilibrated using an additive calibration.18 Briefly, the differences between the sex and centre specific means of the values from the food frequency questionnaire and the means of the 24 hour recall values were calculated and added to the questionnaire values. The calibrated score was computed and its association to mortality was investigated using similar models.
Results
Table 1 Distribution of 74 607 participants in EPIC-elderly cohort, by country, sex, and age at enrolment. Values are numbers (percentages)
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The patterns for deaths and accumulated person years by non-nutritional variables were generally as expected (table 2). Table 3 shows the cross classifications of broad categories of the score by non-nutritional variables. The score is higher among older people ( 70 years) and lower among current smokers.
Table 2 Number of deaths and accumulated person years among 74 607 participants in EPIC-elderly cohort by age, sex, sociodemographic, anthropometric, and lifestyle variables
, 百拇医药
Table 3 Baseline characteristics by categories of modified Mediterranean diet score among 74 607 participants in EPIC-elderly study and 4047 deaths
Table 4 Median and mean (standard deviation) daily intake of selected food groups and associated mortality ratio (95% confidence intervals) for chosen increment in EPIC-elderly study
Table 5 Mortality ratios (95% confidence intervals) for all countries (stratified by country) by category of modified Mediterranean diet score in 74 607 participants in EPIC-elderly study
, 百拇医药
Table 6 Mortality ratios (95% confidence intervals) by country (stratified by centre within country) by category of modified Mediterranean diet score in EPIC-elderly study
Discussion
We slightly modified the definition of the score by including polyunsaturates in the numerator of the lipid ratio.4 6 8 9 15 This was necessary because polyunsaturates are the principal unsaturated added lipids in diets in non-Mediterranean countries and have established beneficial effects on coronary heart disease.12 Moreover, the definition of lipid ratio with monounsaturates alone in the numerator would strongly depend on meat consumption in northern European countries in which a principal source of monounsaturates is meat.
, http://www.100md.com
We focused on a variant of the Mediterranean diet with potentially wide applicability, because of the strong evidence that the traditional Mediterranean diet is beneficial to health. The principal characteristic of the modified Mediterranean diet score is that it relies on plant foods and unsaturated lipids. Reduction of total lipids, however, is not a prerequisite for a healthy diet provided the lipids are not saturated or trans and are not mainly derived from meat.15 24 The question whether monounsaturates from olive oil, or specific categories of polyunsaturates, are particularly beneficial cannot be answered from this investigation, because the distributions of the intake of the particular lipids are so different in the participating countries as to introduce a strong ecological element into the study. The important point is that a diet that can be operationalised does have a relation with mortality, and that realistically achievable changes in diet—for example, 3 or 4 point increments—are associated with a reduction of total mortality by 11% or 14%, respectively.
, 百拇医药
The calibration used in this study deals with much of the concern about the comparability of results across different populations. No significant heterogeneity was found among the country specific results with or without calibration for dietary exposures. The results were generally more evident in Greece and Spain, probably because in these countries the modified Mediterranean diet is genuinely a Mediterranean diet (in Italy most of the deaths occurred in northern Italy, where the diet cannot be considered as Mediterranean). It is possible that the association of the score with mortality may vary among populations because of different distribution patterns for food and conceivably non-linear underlying relations of the components of the score with mortality. The parsimonious interpretation of the findings, however, supported by the non-significant heterogeneity in the analyses, is that the modified Mediterranean diet is beneficial to health across populations.
, http://www.100md.com
Advantages of this study include its prospective nature, its large size, its reliance on a European population sample, and the calibration of dietary exposures across countries. The study also exploited the availability of information on several non-dietary variables and was able to control for them as potential confounders. Socioeconomic status was controlled for by adjusting for educational achievement, the only factor that is both objectively ascertainable and internationally applicable. Control for physical activity took into account participants still working. Because the study is observational, it is possible for residual confounding from suboptimally measured factors. The association of the score with non-nutritional variables was, however, generally weak (see table 3), reducing the potential for such confounding. Exceptions were the clear associations of the score with sex, age, country, and tobacco consumption, but these variables were validly measured allowing little room for residual confounding.
, 百拇医药
In conclusion, adherence to a diet relying on plant foods and unsaturated lipids and that resembles the Mediterranean diet, may be particularly appropriate for elderly people, who represent a rapidly increasing group in Europe.
What is already known on this topic
Small cohort studies have shown that Mediterranean type diets increase longevity
No international study with assured comparability of dietary information through calibration has been undertaken
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What this study adds
Qualitative aspects of diet predict overall death rate and hence survival
A dietary pattern that resembles that of the Mediterranean is associated with a lower overall death rate
Polyunsaturated lipids are an acceptable substitute when monounsaturated lipids are not readily available
--------------------------------------------------------------------------------
, 百拇医药
Contributors: AT is the principal investigator of the EPIC-elderly project. She is guarantor for the paper. PO is the principal biostatistician in this project. Contributors from the participating centres provided the original data, information on the respective populations, and advice on study design and analysis. Participants from the International Agency for Research on Cancer were responsible for coordination of the overall EPIC project and also contributed advice on study design and analysis.
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Funding: This study was supported by the quality of life and management of living resources programme of the European Commission (contract No QLK6-CT-2001-00241), coordinated by the Department of Hygiene and Epidemiology, University of Athens Medical School; the Europe against cancer programme of the European Commission coordinated by the International Agency for Research on Cancer; the Greek Ministry of Health and the Greek Ministry of Education; the fellowship "Vasilios and Nafsika Tricha"; Danish Cancer Society; Ligue contre le Cancer (France); Société 3M (France); Mutuelle Générale de l'Education Nationale (France); Institut National de la Santé et de la Recherche Médicale (France); Gustave Roussy Institute and several general councils in France; German Cancer Aid; German Cancer Research Centre; German Federal Ministry of Education and Research; Associazione Italiana per la Ricerca contro il Cancro; Compagnia di San Paolo (Italy); Regione Sicilia, Provincia Regionale Sicilia, Comune di Ragusa, AIRE-ONLUS and AVIS-Ragusa (Italy); national cancer registry and comprehensive cancer centres east Amsterdam and Limburg (Netherlands); Dutch Ministry of Public Health, Welfare and Sports; health research fund (FIS) of the Spanish Ministry of Health (Spain); the Spanish Regional governments of Andalucia, Asturias, Basque country, Murcia, and Navarra (Spain); ISCIII Network RCESP (Spain); Swedish Cancer Society; Swedish Scientific Council, Malm; regional government of Skne (Sweden); Cancer Research UK; Medical Research Council (United Kingdom). The researchers were financed independently from the funding organisations.
, 百拇医药
Competing interests: None declared.
Ethical approval: This study was approved by the ethical committees at the International Agency for Research on Cancer and at participating centres.
References
De Groot LC, van Staveren WA, Burema J. Survival beyond age 70 in relation to diet. Nutr Rev 1996;54: 211-2.
World Cancer Research Fund and American Institute for Cancer Research. Food, nutrition and the prevention of cancer: a global perspective. Washington DC: WCRF and AICR, 1997.
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Jacques PF, Tucker KL. Are dietary patterns useful for understanding the role of diet in chronic disease Am J Clin Nutr 2001;73: 1-2.
Trichopoulou A, Kouris-Blazos A, Wahlqvist ML, Gnardellis C, Lagiou P, Polychronopoulos E, et al. Diet and overall survival in elderly people. BMJ 1995;311: 1457-60.
Huijbregts P, Feskens E, Rasanen L, Fidanza F, Nissinen A, Menotti A, et al. Dietary pattern and 20 year mortality in elderly men in Finland, Italy, and the Netherlands: longitudinal cohort study. BMJ 1997;315: 13-7.
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Osler M, Schroll M. Diet and mortality in a cohort of elderly people in a north European community. Int J Epidemiol 1997;26: 155-9.
Kumagai S, Shibata H, Watanabe S, Suzuki T, Haga H. Effect of food intake pattern on all-cause mortality in the community elderly: a 7-year longitudinal study. J Nutr Health Aging 1999;3: 29-33.
Lasheras C, Fernandez S, Patterson AM. Mediterranean diet and age with respect to overall survival in institutionalised, nonsmoking elderly people. Am J Clin Nutr 2000;71(4): 987-92.
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Knoops KT, de Groot LC, Kromhout D, Perrin AE, Moreiras-Varela O, Menotti A, et al. Mediterranean diet, lifestyle factors, and 10-year mortality in elderly European men and women: the HALE project. JAMA 2004;292: 1433-9.
Willett WC, ed. Diet and coronary heart disease. Nutritional epidemiology, 2nd ed. New York: Oxford University Press, 1998: 414-66.
Keys A. Seven countries. A multivariate analysis of death and coronary heart disease. Cambridge, MA: Harvard University Press, 1980.
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De Lorgeril M, Renaud S, Mamelle N, Salen P, Martin JL, Monjaud I, et al. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet 1994;343: 1454-9.
Singh RB, Dubnov G, Niaz MA, Ghosh S, Singh R, Rastogi SS, et al. Effect of an IndoMediterranean diet on progression of coronary artery disease in high risk patients (Indo-Mediterranean diet heart study): a randomised single-blind trial. Lancet 2002;360: 1455-61.
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Willett WC, Sacks F, Trichopoulou A, Drescher G, Ferro-Luzzi A, Helsing E, et al. Mediterranean diet pyramid: a cultural model for healthy eating. Am J Clin Nutr 1995;61(suppl 6): S1402-6.
Trichopoulou A, Costacou T, Bamia C, Trichopoulos D. Adherence to Mediterranean diet and survival in a Greek population. N Engl J Med 2003;348: 2599-608.
Riboli E, Hunt KJ, Slimani N, Ferrari P, Norat T, Fahey M, et al. European prospective investigation into cancer and nutrition (EPIC): study populations and data collection. Public Health Nutr 2002;5: 1113-24.
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Slimani N, Kaaks R, Ferrari P, Casagrande C, Clavel-Chapelon F, Lotze G, et al. European prospective investigation into cancer and nutrition (EPIC) calibration study: rationale, design and population characteristics. Public Health Nutr 2002;5: 1125-45.
Kaaks R, Riboli E. Validation and calibration of dietary intake measurements in the EPIC project: methodological considerations. European prospective investigation into cancer and nutrition. Int J Epidemiol 1997;26(suppl 1): S15-25.
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Margetts BM, Pietinen P. European prospective investigation into cancer and nutrition: validity studies on dietary assessment methods. Int J Epidemiol 1997;26(Suppl 1): S1-5.
Deharveng G, Charrondiere UR, Slimani N, Southgate DA, Riboli E. Comparison of nutrients in the food composition tables available in the nine European countries participating in EPIC. European prospective investigation into cancer and nutrition. Eur J Clin Nutr 1999;53: 60-79.
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James WPT, Schofield EC. Human energy requirements: a manual for planners and nutritionists. Oxford: Oxford University Press, 1990.
Department of Health. Dietary reference values for food energy and nutrients for the United Kingdom. UK Department of Health report on health and social subjects No 41. London: Stationery Office, 1991.
Breslow NE, Day NE. Statistical methods in cancer research. Vol II. The design and analysis of cohort studies. Lyons: International Agency for Research on Cancer, 1987. (IARC scientific publication No 82)
Willett WC, Stampfer MJ, Manson JE, Colditz GA, Speizer FE, Rosner BA, et al. Intake of trans fatty acids and risk of coronary heart disease among women. Lancet 1993;341: 581-5., 百拇医药(Antonia Trichopoulou, Phi)
, http://www.100md.com
Abstract
Design Multicentre, prospective cohort study.
Setting Nine European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Spain, Sweden, United Kingdom).
Participants 74 607 men and women, aged 60 or more, without coronary heart disease, stroke, or cancer at enrolment and with complete information about dietary intake and potentially confounding variables.
, http://www.100md.com
Main outcome measures Extent of adherence to a modified Mediterranean diet using a scoring system on a 10 point scale, and death from any cause by time of occurrence, modelled through Cox regression.
Results An increase in the modified Mediterranean diet score was associated with lower overall mortality, a two unit increment corresponding to a statistically significant reduction of 8% (95% confidence interval 3% to 12%). No statistically significant evidence of heterogeneity was found among countries in the association of the score with overall mortality even though the association was stronger in Greece and Spain. When dietary exposures were calibrated across countries, the reduction in mortality was 7% (1% to 12%).
, http://www.100md.com
Conclusion The Mediterranean diet, modified so as to apply across Europe, was associated with increased survival among older people.
Introduction
The Mediterranean diet has been used in many studies because several of its components have been related to common chronic diseases,2 10 ecological evidence suggests that such a diet may be beneficial to health,11 and variants of this diet have improved the prognosis of patients with coronary heart disease.12 13 The Mediterranean diet is characterised by a high intake of vegetables, legumes, fruits, and cereals (in the past largely unrefined); a moderate to high intake of fish; a low intake of saturated lipids but high intake of unsaturated lipids, particularly olive oil; a low to moderate intake of dairy products, mostly cheese and yogurt; a low intake of meat; and a modest intake of ethanol, mostly as wine.14 Adherence to a Mediterranean diet was operationalised through a 10 unit dietary score by Trichopoulou et al.4 15 Several studies have used variants of this score and have reported inverse associations with overall mortality.4 6 8 9 15 These studies, however, relied on small samples of mostly elderly participants or on the Greek population only.15
, 百拇医药
We calculated a score reflecting the Mediterranean diet.15 To allow the score to be applied to non-Mediterranean populations, in which intake of monounsaturates from olive oil is minimal, we substituted monounsaturated lipids with the sum of monounsaturated and polyunsaturated lipids in the numerator of the lipid ratio. We investigated the relation of this modified score with overall mortality in a large sample of elderly Europeans participating in EPIC (the European prospective investigation into cancer and nutrition study).16
, 百拇医药
Participants and methods
Data for participants aged 60 or over at recruitment were included in the EPIC-elderly study. This study aims to identify dietary patterns among elderly Europeans and to investigate the associations of diet with survival.
Dietary intakes
Usual dietary intakes were assessed through compatible instruments (food frequency questionnaires and, in some centres, records of intake over seven or 14 days) that had been developed and validated within each centre.17-19 In addition, a computerised instrument for recall of dietary intake over 24 hours was developed to collect information from a stratified random sample of the aggregate cohort. The aim was to calibrate the measurements across countries.17
, http://www.100md.com
Nutrient intakes were calculated using food composition tables specific to the country.20 In the present study, 14 food groups and nutrients were considered: potatoes, vegetables, legumes, fruits, dairy products, cereals, meat and meat products, fish and seafood, eggs, monounsaturated lipids, polyunsaturated lipids, saturated lipids, sugar and confectionery, and non-alcoholic beverages. For each participant, daily intake (grams) of each of the groups and total energy intake (megajoules) were estimated.
, http://www.100md.com
Lifestyle, anthropometric, and medical variables
A precoded questionnaire was used to record data on lifestyle and health,16 which included educational achievement, history of illnesses, history of smoking, and physical activity. For participants still in work, the physical demand of their job was recorded. For leisure, time spent on each of several activities was multiplied by an energy cost coefficient; the products were then summed to produce a score of daily physical activity.21 Sex and centre specific thirds of the estimated physical activity score at leisure were used.
, http://www.100md.com
Anthropometric measurements were taken in all EPIC centres using similar, standardised procedures, except for France, Oxford (United Kingdom), and Norway. In these centres self reported values were recorded, but actual measurements were obtained for only a fraction of the participants.
Mediterranean diet scale
A scale indicating the degree of adherence to the traditional Mediterranean diet has been constructed by Trichopoulou et al.4 15 Values of zero or one were assigned to each of nine indicated components, using as cut-off values the sex specific medians among the participants. People whose consumption of presumed beneficial components (vegetables, legumes, fruits, cereals, fish) was below the median consumption were assigned a value of zero, and a value of one otherwise. People whose consumption of presumed detrimental components (meat and dairy products) was below the median consumption were assigned a value of one, and a value of zero otherwise. A value of one was given to men consuming from 10 g to less than 50 g of ethanol per day and to women consuming from 5 g to 25 g. For lipid intake, the ratio of the sum of monounsaturates and polyunsaturates to saturates was calculated. This modified Mediterranean diet score, as both monounsaturates and polyunsaturates are included in the numerator of the lipid ratio, can take a value from zero (minimal adherence) to nine (maximal adherence).
, 百拇医药
Follow-up
Information on the vital status of participants was obtained from mortality registries and by active follow-up. Earliest and latest years of follow-up were 1999 (some participants in the Netherlands) and December 2003 (most centres). Participants were classified as alive at last follow-up, dead, emigrated, refused to participate further, and unknown.
Overall, 100 442 participants of the EPIC cohort were aged 60 years or more at recruitment and had acceptable records of energy intakes (those in the top and bottom 1% of the ratio of energy intake to estimated energy requirement were excluded).22 Vital status has been ascertained for 100 309 (99.9%) of these participants; however, 15 362 were excluded from the EPIC-elderly study database because coronary heart disease, stroke, cancer, or a combination of these had been diagnosed at enrolment. Of the remaining 84 947 participants, 10 340 had missing information for one or more of the dietary, anthropometric, or lifestyle variables, or had died within the year after enrolment. Thus 74 607 individuals were included in the study.
, 百拇医药
Statistical analysis
Analyses were carried out with Stata 7.0 and SAS 8.2. Descriptive presentation relied on cross tabulations. Survival data were modelled through Cox's proportional hazards regression,23 with length of follow-up as the primary time variable. Adjustment was made for sex, age, self reported diabetes mellitus at enrolment, educational achievement, smoking status, physical activity, waist to hip ratio, body mass index, and total energy intake. In analyses that investigated the relation of the score with mortality, consumption of eggs, potatoes, and sugar and confectionery (which are not part of the score) were also controlled for continuously. Both fixed effects and random effects models were used. Separate proportional hazard models were used for all participants and for participants in each country. Models were stratified by country or by centre (for the country specific analyses).
, 百拇医药
Dietary exposures across centres were equilibrated using an additive calibration.18 Briefly, the differences between the sex and centre specific means of the values from the food frequency questionnaire and the means of the 24 hour recall values were calculated and added to the questionnaire values. The calibrated score was computed and its association to mortality was investigated using similar models.
Results
Table 1 Distribution of 74 607 participants in EPIC-elderly cohort, by country, sex, and age at enrolment. Values are numbers (percentages)
, http://www.100md.com
The patterns for deaths and accumulated person years by non-nutritional variables were generally as expected (table 2). Table 3 shows the cross classifications of broad categories of the score by non-nutritional variables. The score is higher among older people ( 70 years) and lower among current smokers.
Table 2 Number of deaths and accumulated person years among 74 607 participants in EPIC-elderly cohort by age, sex, sociodemographic, anthropometric, and lifestyle variables
, 百拇医药
Table 3 Baseline characteristics by categories of modified Mediterranean diet score among 74 607 participants in EPIC-elderly study and 4047 deaths
Table 4 Median and mean (standard deviation) daily intake of selected food groups and associated mortality ratio (95% confidence intervals) for chosen increment in EPIC-elderly study
Table 5 Mortality ratios (95% confidence intervals) for all countries (stratified by country) by category of modified Mediterranean diet score in 74 607 participants in EPIC-elderly study
, 百拇医药
Table 6 Mortality ratios (95% confidence intervals) by country (stratified by centre within country) by category of modified Mediterranean diet score in EPIC-elderly study
Discussion
We slightly modified the definition of the score by including polyunsaturates in the numerator of the lipid ratio.4 6 8 9 15 This was necessary because polyunsaturates are the principal unsaturated added lipids in diets in non-Mediterranean countries and have established beneficial effects on coronary heart disease.12 Moreover, the definition of lipid ratio with monounsaturates alone in the numerator would strongly depend on meat consumption in northern European countries in which a principal source of monounsaturates is meat.
, http://www.100md.com
We focused on a variant of the Mediterranean diet with potentially wide applicability, because of the strong evidence that the traditional Mediterranean diet is beneficial to health. The principal characteristic of the modified Mediterranean diet score is that it relies on plant foods and unsaturated lipids. Reduction of total lipids, however, is not a prerequisite for a healthy diet provided the lipids are not saturated or trans and are not mainly derived from meat.15 24 The question whether monounsaturates from olive oil, or specific categories of polyunsaturates, are particularly beneficial cannot be answered from this investigation, because the distributions of the intake of the particular lipids are so different in the participating countries as to introduce a strong ecological element into the study. The important point is that a diet that can be operationalised does have a relation with mortality, and that realistically achievable changes in diet—for example, 3 or 4 point increments—are associated with a reduction of total mortality by 11% or 14%, respectively.
, 百拇医药
The calibration used in this study deals with much of the concern about the comparability of results across different populations. No significant heterogeneity was found among the country specific results with or without calibration for dietary exposures. The results were generally more evident in Greece and Spain, probably because in these countries the modified Mediterranean diet is genuinely a Mediterranean diet (in Italy most of the deaths occurred in northern Italy, where the diet cannot be considered as Mediterranean). It is possible that the association of the score with mortality may vary among populations because of different distribution patterns for food and conceivably non-linear underlying relations of the components of the score with mortality. The parsimonious interpretation of the findings, however, supported by the non-significant heterogeneity in the analyses, is that the modified Mediterranean diet is beneficial to health across populations.
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Advantages of this study include its prospective nature, its large size, its reliance on a European population sample, and the calibration of dietary exposures across countries. The study also exploited the availability of information on several non-dietary variables and was able to control for them as potential confounders. Socioeconomic status was controlled for by adjusting for educational achievement, the only factor that is both objectively ascertainable and internationally applicable. Control for physical activity took into account participants still working. Because the study is observational, it is possible for residual confounding from suboptimally measured factors. The association of the score with non-nutritional variables was, however, generally weak (see table 3), reducing the potential for such confounding. Exceptions were the clear associations of the score with sex, age, country, and tobacco consumption, but these variables were validly measured allowing little room for residual confounding.
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In conclusion, adherence to a diet relying on plant foods and unsaturated lipids and that resembles the Mediterranean diet, may be particularly appropriate for elderly people, who represent a rapidly increasing group in Europe.
What is already known on this topic
Small cohort studies have shown that Mediterranean type diets increase longevity
No international study with assured comparability of dietary information through calibration has been undertaken
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What this study adds
Qualitative aspects of diet predict overall death rate and hence survival
A dietary pattern that resembles that of the Mediterranean is associated with a lower overall death rate
Polyunsaturated lipids are an acceptable substitute when monounsaturated lipids are not readily available
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Contributors: AT is the principal investigator of the EPIC-elderly project. She is guarantor for the paper. PO is the principal biostatistician in this project. Contributors from the participating centres provided the original data, information on the respective populations, and advice on study design and analysis. Participants from the International Agency for Research on Cancer were responsible for coordination of the overall EPIC project and also contributed advice on study design and analysis.
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Funding: This study was supported by the quality of life and management of living resources programme of the European Commission (contract No QLK6-CT-2001-00241), coordinated by the Department of Hygiene and Epidemiology, University of Athens Medical School; the Europe against cancer programme of the European Commission coordinated by the International Agency for Research on Cancer; the Greek Ministry of Health and the Greek Ministry of Education; the fellowship "Vasilios and Nafsika Tricha"; Danish Cancer Society; Ligue contre le Cancer (France); Société 3M (France); Mutuelle Générale de l'Education Nationale (France); Institut National de la Santé et de la Recherche Médicale (France); Gustave Roussy Institute and several general councils in France; German Cancer Aid; German Cancer Research Centre; German Federal Ministry of Education and Research; Associazione Italiana per la Ricerca contro il Cancro; Compagnia di San Paolo (Italy); Regione Sicilia, Provincia Regionale Sicilia, Comune di Ragusa, AIRE-ONLUS and AVIS-Ragusa (Italy); national cancer registry and comprehensive cancer centres east Amsterdam and Limburg (Netherlands); Dutch Ministry of Public Health, Welfare and Sports; health research fund (FIS) of the Spanish Ministry of Health (Spain); the Spanish Regional governments of Andalucia, Asturias, Basque country, Murcia, and Navarra (Spain); ISCIII Network RCESP (Spain); Swedish Cancer Society; Swedish Scientific Council, Malm; regional government of Skne (Sweden); Cancer Research UK; Medical Research Council (United Kingdom). The researchers were financed independently from the funding organisations.
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Competing interests: None declared.
Ethical approval: This study was approved by the ethical committees at the International Agency for Research on Cancer and at participating centres.
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