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. 2008 Mar;3(1):97–109. doi: 10.2147/cia.s1349

Table 1.

Characteristics of selected studies about the effectiveness of the Mediterranean diet in the elderly

Author/year publication Country Type study Population Methodology Outcome Results
CVD
Panagiotakos et al 2002 Greece multicenter restrospective case-control study (CARDIO2000) 848 hospitalized patients (695 M, 58 ± 10 y; 153 F, 65 ± 9 y) a with first event of CHD; 1,078 controls (830 M, 58 ± 10 y; 248 F, 64.8 ± 9 y) FFQ; 526 patients and 765 controls adopted the Mediterranean-type of diet BP, TC, blood glucose, BMI > adherence to the MD = reduction of the coronary risk factors (in hypertensive patients)
Scali et al 2001 France cross-sectional 989 subjects (473 M, 491 F; 3 age groups: 20–34 y, 35–54 y, 55–76 y) FFQ, MDQI BMI in subjects aged 55–75y, > adherence MDQI associated to < % obesity
Martinez-Gonzalez et al 2002 Spain case-control study 342 subjects (171 first acute myocardial infarction: 81 M, 90 F; mean age 61.7; controls: 171) FFQ, MDscore BP, TC, blood glucose, BMI > adherence to the MD = reduction of myocardial infarction risk factors
Singh et al 2002 UK RCT, single blind 56 subjects (26 M, 30 F; range 57–80 y, mean age 67 ± 1) with average sitting BP: 134/78 ± 3/1 mmHg 6 w healthy “M-type”diet, 6 w vitamin C supplements, or 6w placebo plasma vitamin C, % dilatation by BK, % dilatation by GTN Increase in plasma vitamin C similar with supplements compared with a “healthy diet”. Healthy diet: significant increase in BK-dependent vasodilatation vs placebo (p < 0.011). Healthy diet: significant differences between the 3 study groups in GTN-dependent relaxation (p < 0.011). MD improved vasodilatator function in the forearm of healthy older subjects whereas supplementation of vitamin C as tablets had no major effect. Acute intra-arterial vitamin C did not alter dilatation to BK or GTN. Treatment with healthy diet (but not oral vitamin C) improved endothelium-dependent (p = 0.043) and endtothelium-independent dilatation (p = 0.011)
Barzi et al 2003 Italy clinical trial (GISSI-Prevenzione trial) 11,323 subjects with MI (M and F; aged 19–90 y, mean age 59 ± 10) advice to adhere to the MD; visit and dietary assessment 6th, 18th and 42nd months, clinical visit; dietary questionnaire; diet-score Association of food intakes (fish, fruit, raw and cooked vegetables and olive oil), a combined dietary score and risk of death Compared with people in the worst dietary score quartile, odds ratio for people in best score was 0.51.↑ consumption of each food was associated with ↓ risk of death. MI patients can respond positively to simple dietary advice, and this can be expected to lead to a substantial reduction in the risk of early death. Regardless of any drug treatment prescribed, clinicians should routinely advise patients with myocardial infarction to increase their frequency of consumption of Mediterranean foods
Ciccarone et al 2003 Italy case-control study T2DM patients: 144 with PAD (103 M, 41 F; <60 y n:36, 60–69 y n:60, >70 y n:48); 288 without PAD (206 M, 82 F; <60 y n:72, 60–69 y n:120, >70 y n:96) FFQ, diet-score BMI, glycated hemoglobin (HbA1c) > adherence to the MD = significant reduction in PAD risk, independently of diabetes duration and hypertension
Pitsavos et al 2003 Greece multicenter case-control study (CARDIO2000) 848 hospitalized patients (695 M, 58 ± 10 y; 153 F, 65 ± 9 y) with a first event of ACS FFQ, NCEP ATPIII blood pressure, cholesterol level, blood glucose, BMI > adherence to the MD = reduction of the coronary risk factors (in metabolic syndrome patients)
Sondergaard et al 2003 Denmark intervention study (unblinded 1-to-1) 131 patients (70 M, 61 F; 18 to 80 y; mean age 62.5 ± 9.9) with documented IHD n: 68 intervention group (received MD advice), n: 63 control group (no specific dietary advice); all patients started statin treatment with Fluvastatin at baseline; 24-hour recall FMD, serum lipids, liver transaminases, blood glucose, TSH-samples every third month at regular clinical control session improvement in FMD (p < 0.01) in the intervention group vs control (after 12 months); no differences in the arterial diameter or in the nitroglycerin response (NMD); LDL cholesterol levels p < 0.001 for the reduction in both of groups; triglyceride level p < 0.05 only in intervention group; unchanged in both of groups HDL-cholesterol
Fung et al 2005 USA Nurse’s Health Study 690 F, 43–69 y, without cardiovascular disease, diabetes or cancer at the time blood was drawn FFQ, HEI, AHEI, DQI-R, RFS, aMED, blood sample BMI; CRP, IL-6, E-selectin, sICAM-1, sVCAM-1 > scores of HEI, AHEI, DQI-R = lower BMI. > AHEI and aMED scores = reduction in biomarker concentrations (CRP, IL-6, E-selectin)
Panagiotakos, Pitsavos, Matalas et al 2005 Greece multicenter case-control study (CARDIO2000) 848 individuals (700 M, 59 ± 10 y; 148 F; 65 ± 9 y); 1078 controls FFQ BP, TC, blood glucose, BMI inverse association between adherence to the MD and prevalence of hypertension, hypercholesterolemia (in both patients and controls)
Panagiotakos, Pitsavos, Chrysohoou et al 2005 Greece cross-sectional study 3,042 subjects (1514 M, 1528 F; 18–89 y). Diabetes Mellitus: 118 M (7,8%), 92 F (6,0%); >65 y M 32 (25,4%), F40 (31,0%) FFQ, MD score fasting glucose, TC, LDL-C, HDL-C, TG, waist circumf. > adherence to the MD = significantly lower odds of having diabetes. Age was associated to > diabetes; participants with diabetes: ↑obesity, ↑BMI, ↑WHR, ↑BP, ↑TC, ↑LDL-C, ↑TG, ↑hypercholesterolemia. A 10-unit increase in the diet score was associated with 21% lower odds of diabetes
Polychronopoulos et al 2005 Greece cohort study 150 subjects, 65–100 y (53 M, 79 ± 8 y; 97 F, 75 ± 7 y) FFQ, MD score TCl, LDL, HDL, TG inverse association between hypercholesterolemia, alcohol drinking and the adherence to MD
Serrano-Martinez M49, 2005 Spain case-control study 24 patients (14 M, 10 F; 61.4 ± 12.6 y) with unstable angina FFQ, MD score, blood sample TNF-alpha, VCAM-1 MED-diet score was inversely associated with the TNF-alpha and VCAM-1. MD may protect against coronary artery wall production of inflammatory mediators
Trichopoulou, Orfanos et al 2005 Greece Cohort study (EPIC-Greece) 23,597 adults (M, F), aged 20–86 y FFQ, MD score BMI adherence to MD was unrelated to BMI in both sexes and was weakly related to WHR only in women
Estruch et al 2006 Spain Substudy of a multicenter, randomized, clinical trial of CVD (PREDIMED study) 772 asymptomatic subj. (M and F; 55–80 y) 3 groups: low-fat diet – group; 1 MD + 1 liter/week of olive oil; 2 MD + 30 g/d nuts + nutritional education BP, CRP, IL–6, ICAM-1, VCAM-1 1MD and 2MD vs Low fat diet = < CRP (only 1MD), IL–6, ICAM-1, VCAM-1. MD have beneficial effects on cardiovascular risk factors
Alvarez Leon et al 2006 Spain cross-sectional study 578 subjects (249 M, 329 F; aged >18 y) NCEP ATPIII definition of MS, FFQ, anthropometric variables, BP HOMA index, MD score MD adherence was not related to MS prevalence, but subjects in the third tertile of adherence presented 70% lower prevalence of the blood pressure criteria and 2.5 times more prevalence of the glycaemia criteria with respect to the first tertile
Michaelsen et al 2006 Germany clinical trial 101 patients (59.4 ± 8.6 y, 23% F) with established and treated CAD (80% statins) 48 subjects MD (1y programme of 100h of education); 53 subjects diet rich in ALA, PUFA, MUFA and low in SFA (written advice-only) hs-CRP, fibrinogen, homocysteine, fasting insuline, HDL-C, LDL-C, TC, TG MD has no effect on markers of inflammation and metabolic risk factors (hs-CRP, fibrinogen, homocysteine, fasting insulin, HDL-C, LDL-C, TC, TG)
Panagiotakos, Chrysohoou et al 2006 Greece Greek Study of ACS (the GREECS) 2172 patients (1,649 M, 65 ± 13y; 523 F, 72 ± 11 y) with a discharge diagnosis of ACS FFQ, MD score, blood sample troponin I, creatine phosphokinase, creatine phosphokinase-MB, BP, TC, blood glucose, BMI inverse correlation between Med-diet score with troponin I, creatine phosphokinase, creatine phosphokinase-MB. MD habits seems to be associated with lower severity of coronary heart disease
Fitó et al 2007 Spain randomized controlled trial (cross-sectional analysis Substudy of PREDIMED Study) 372 subjects (162 M, 210 F; 55–80 y) with high cardiovascular risk low fat diet (n: 121) or one of 2 TMDs (TMD + virgin olive oil, 1L/wk or TMD + nuts, 30 g/d) oxidative stress markers (oxidized LDL levels), MDA, serum glutathione peroxidase activity decreased oxidized LDL levels in TMD with olive oil and in TMD with nuts, no change in Low-Fat diet; malondialdehyde changes in mononuclear cells paralleled those of oxidized LDL. No changes in serum glutathione peroxidase activity were observed
Salas-Salvadó et al 2007 Spain cross-sectional analysis (Substudy of PREDIMED Study) 772 subjects, 55–80 y (339 M, 67.6 ± 6.5; 433 F, 69.8 ± 6.2) with T2DM and 3 or more CHD risk factors FFQ, blood sample CRP, IL-6, ICAM-1, VCAM-1 > adherence to the MD = did not show significantly lower concentrations of inflammatory markers (p < 0.1 for VCAM-1 and ICAM-1). > consumption of fruits and cereals = lower concentrations of IL-6. > consumption of nuts and virgin olive oil = lowest concentrations of VCAM-1, ICAM-1, IL-6 and CRP; albeit only for ICAM-1 was this difference statistically significant in the case of nuts (for trend 0.003) and for VCAM-1 in the case of virgin olive oil (P for trend 0.02)
Cancer
Bosetti et al 2003 Italy case-control studies (3) 1 = 598 patients with cancer of the oral cavity and pharynx, aged <78 y (512 M, 86 F),1,491 hospital controls (1,008 M, 483 F); 2 = 304 patients with squamous cell carcinoma of the esophagus, aged <77 y (275 M, 29 F), 743 hospital controls (593 M, 150 F); 3 = 460 patients with squamous cell carcinoma of the larynx, aged < 79 y(415 M, 45 F) 1,088 hospital controls (863 M, 225 F) FFQ, MD score OR for all cancers considered: a reduced risk was found for increasing level of the MD score; > risk for cancers of the upper aerodigestive tract for no or high consumption of alcohol, high meat and. meat products intake; < risk (estimates were not always significant) for high intake of monounsaturated/saturated fat ratio, vegetables
Nkondjock and Ghadirian 2007 Canada case-control studies 280 subjects (30 M, 250 F; 56.2 ± 11.5 y) from 80 French-Canadian families. Each family had at least 3 cases of BC (diagnosed at <65 y), epithelial ovarian cancer or male BC. 100 subjects control, never had BC (F, 51 carriers, 49 non-carriers of a deleterious mutation in the BRCA gene) FFQ, DQI-R, AHEI, aMED, CHEI OR no detected any association between the AHEI or aMED and BC. Strong and significant inverse relationship between DQI-R and CHEI and BRCA-associated risk
Mental Health
Scarmeas, Stern, Tang et al 2006 USA Cohort study (participants of 2 related cohorts recruited in 1992 and 1999 WHICAP) 2,258 community-based nondemented individuals, (nondemented n = 1,964, 77.2 ± 6.6 y; during 4 y of follow-up incident AD n = 262) FFQ, 7-day food records, MD score DSM-III-R for the diagnosis of dementia; criteria of the NINCDS-ADRDA for diagnosis of probable or possible AD > adherence to the MD = lower risk for AD (each additional unit of the MD score was associated with 9 to 10% less risk for development of AD)
Scarmeas, Stern, Mayeux et al 2006 USA Cohort study (participants of 2 related cohorts recruited in 1992 and 1999 WHICAP) 1,984 subjects (nondemented n = 1,790, prevalent AD n = 194), 76.3 ± 6.6 y FFQ, 7-day food records, MD score, BP, history hypertension, TC, HDL-C, TG, LDL-C DSM-III-R for the diagnosis of dementia; criteria of the NINCDS-ADRDA for diagnosis of probable or possible AD > adherence to the MD = lower risk for AD, this association does not seem to be mediated by vascular comorbidity
Solfrizzi et al 2006 Italy Prospective study Italian Longitudinal Study on Aging (ILSA) (5,632 subjects 65–84 y, free-living or institutionalized) 278 free-living elderly subjects (154 M, 124 F; 65–84 y, 73.01 ± 5.52 y) FFQ intake MUFA, PUFA; MMSE adherence to the MD (high MUFA and PUFA intakes) appeared to be protective against ARCD
Longevity
Trichopoulou et al 1995 Greece Cohort study 2 y follow-up 182 subjects, (91 M, 91 F; >70 y, 53 died, survivors, mean age 75.4 y) FFQ, 24h diet recall, MD score overall mortality > adherence to the MD: 17% reduction in overall mortality
Osler and Schroll 1997 Denmark cohort study longitudinal study (part of the Euronut SENECA study) 202 subjects, (101 M and 101 F) (52 died); survivors 150 subjects (73 M, 53 F), mean age 72 y 3-day estimated record and a frequency checklist of foods; MD score; blood sample TC, LDL-C, HDL-C > adherence to the MD = reduction in overall mortality; > adherence to the MD = significally higher plasma carotene levels. Low score and plasma carotene was negatively associated with mortality
Kouris-Blazos et al 1999 Australia prospective cohort study 330 subjects (M, F), 189 greek-australians, 141 anglo-celts; >70 y, 70–85 + y FFQ, MD score Mortality rate ratio A one unit increase in a diet score was associated with a 17% reduction in overall mortality. Mortality reduction with increasing diet score was evident in both greek-australians and anglo-celts
Lasheras et al 2000 Spain Cohort study 161 volunteers (49 M, 112 F), 65–95 y FFQ, MD score BMI adherence to the MD in elderly subjects aged <80 y: reduction in overall mortality (31%); but not in subjects aged >80 y (not have any available evidence)
Trichopoulou et al 2003 Greece population-based, prospective investigation (EPIC, Greece (1994–1999) 22,043 participants, 20–86 y, (5028, 55–64 y; 4369, >65 y) FFQ, MD score overall mortality > adherence to the MD = significant reduction in total mortality among participants 55 y of age or older but not among participants younger than 55 y
Knoops et al 2004 multicenter study (11 European Countries) Healthy Aging: a Longitudinal study in Europe population (HALE); SENECA and FINE 1,507 M, 832 F, 70–90 y; SENECA (M 781. 73 ± 2.0 y; F 832. 73 ± 1.8 y); FINE (M 726, 77 ± 4 y); (935 died) FFQ, MD score ten-year mortality from all causes, coronary heart disease, cardiovardiovascular diseases, and cancer In individuals aged 70–90 y, > adherence to the MD and healthful lifestyle = 50% lower rate of all-causes and cause-specific mortality
Trichopoulou et al 2005 multicenter, prospective cohort study (9 European Countries) European Prospective Investigation into Cancer and Nutrition-elderly subjects 74,607 (M, F), > 60 y FFQ, records of intake over 7 or 14 days, MD score modified (relying on plant foods and unsaturated lipids) death from any cause > adherence to the modified MD = reduced overall mortality
Waijers et al 2006 Netherlands Cohort study, European Prospective Investigation into Cancer and Nutrition-elderly 5,427 F, 60–69 y FFQ, 24 h diet recall 3 major principal components: a Mediterranean-like dietary pattern, traditional dutch dinner dietary pattern, healthy traditional dietary pattern the healthy traditional dutch diet rather than a MD appears beneficial for longevity and feasible for health promotion in older Dutch women
Quality of life
Haveman-Nies et al 2001 multicenter-study (USA and Europe) Framingham Heart Study (USA) and European SENECA study 828 subjects (Framingham study) + 1,282 subjects (SENECA) 70–77 y FFQ, MD score, HDI Albumin, Haemoglobin, Waist circum., BMI no association between HDI and Med diet score and albumin and haemoglobin. < score of HDI and MD score = > Waist circum, BMI
Haveman-Nies et al 2003 multicenter-study (Europe) SENECA study (Survey in Europe on Nutrition and the Elderly: a Concerted Action) 1,091 M, 1,190 F; 70–75 y FFQ, MD score health staus measures and lifestyle indicators high-quality diet (MD), physical activity, non-smoking were related to survival in elderly Europeans
Stathakos et al 2005 Greece Nationwide study 489 individuals (113 M, 376 F, 101.0 ± 2.0 y) questionnaire for health disorders, anthropometric characteristics, activity of daily living, degree of autonomy, nutritional habits health and functional assessment most of greek centenarians adhere to the TMD. 19% dementia, 6% T2DM, 4% medical record of cancer

Abbtreviation: ACS, acute coronary syndrome; AD, Alzheimer Disease; AHEI, Alternate Healthy Eating Index; aMED, alternate Mediterranean Diet Index; ApoB, Apo lipoprotein B; ARCD, Age-Related Cognitive Decline; BC, Breast Cancer; BK, Bradykinin; BMI, Body Mass Index; BP, Blood Pressure; CAD, Coronary artery Disease; CHD, Coronary Heart Disease; CHEI, Canadian Healthy Eating Index; CRP, C-reactive protein; CVD, Cardiovascular Disease; DAS28, Disease Activity Score; DQI-R, Diet Quality Index-Revised; DSM-III-R, Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition; EC50, 50% Effective Concentration; FFQ, Food Frequency Questionnaire; FMD, Flow Mediated Vasodilatation; GTN, Glyceryl-trinitrate; HAQ, Health Assessment Questionnaire; HbA1c, glycated haemoglobin; HDI, Healthy Diet Indicator; HDL-C, HDL Cholesterol, HEI, Healthy Eating Index; HOMA index, Homeostasis Model Assessment index; ICAM-1, Intracellular Adhesion Molecule-1; IHD, Ischemic Heart Disease; IL-6, Interleukin-6; LDL-C, LDL Cholesterol; MD, Mediterranean Diet; MDA, Malondialdehyde; MDQI, Mediterranean Diet Quality Index; MDscore, Mediterranean Diet score; MI, Myocardial Infarction; MMSE, Mini-Mental State Examination; MS, Metabolic Syndrome; MUFA, Monounsaturated Fatty Acids; NCEP ATPIII, National Cholesterol Education Program’s Adult Treatment Panel III; NINCDS-ADRDA, National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer’s Disease and Related Disorders Association; NMD, Nitroglycerin-Mediated Dilatation; NSAID, Non-Steroidal Anti-Inflammatory Drugs; OR, Odds ratio; ORP, Outpatient based Rehabilitation Programme; PAD, Peripheral Arterial Disease; PUFA, Polyunsaturated Fatty Acids; RCT, Randomized Clinical Trial; RFS, Recommended Food Score; SFA, Saturated Fatty Acids; SF36, Short Form-36 Health Survey; sICAM-1, soluble Intercellular Cell Adhesion Molecule; sVCAM-1, soluble Vascular Cell Adhesion Molecule; TC, Total Cholesterol, TG, Tryglicerides, TNF-alpha, Tumor Necrosis Factor; TMD, Traditional Mediterranean Diet; T2DM, Type 2 Diabetes Mellitus; VCAM-1, Vascular Cell Adhesion Molecule-1; VLDL-C, VLDL Cholesterol.