BACKGROUND: The Mediterranean diet has been hypothesized to reduce fatality among patients with coronary heart disease.

METHODS: We examined the association between the degree of adherence to the traditional Mediterranean diet and survival of persons with diagnosed coronary heart disease at enrollment, in a population-based prospective investigation of 1302 Greek men and women, who were followed up for an average of 3.78 years (the European Prospective Investigation Into Cancer and Nutrition cohort). Information on usual dietary intakes during the year preceding enrollment was recorded through a validated food frequency questionnaire. Adherence to the Mediterranean diet was assessed by a 10-unit Mediterranean diet score that incorporates the salient characteristics of this diet. Proportional hazards regression was used to assess the relation of overall degree of adherence to the Mediterranean diet with mortality overall or by cause (cardiac vs noncardiac).

RESULTS: Higher adherence to the Mediterranean diet by 2 units was associated with a 27% lower mortality rate among persons with prevalent coronary heart disease at enrollment (total deaths, 131; adjusted mortality ratio, 0.73; 95% confidence interval, 0.58-0.93). The reduced mortality was more evident and amounted to 31% (total deaths, 85; adjusted mortality ratio, 0.69; 95% confidence interval, 0.52-0.93) when only cardiac deaths were considered as the relevant outcome. Associations between individual food groups contributing to the Mediterranean diet score and mortality were generally not significant.

CONCLUSION: Greater adherence to the traditional Mediterranean diet is associated with a significant reduction in mortality among individuals diagnosed as having coronary heart disease.

BACKGROUND & AIMS:A healthy lifestyle has been associated with longer telomeres, but whether Mediterranean Diet (MeDiet) affect telomere length (TL) has not been fully elucidated yet. Our aim was to assess the relationship between MeDiet and TL in high cardiovascular risk subjects in the context of a randomized nutritional intervention trial.

METHODS:We assessed 520 participants (55-80 years, 55% women) from the PREDIMED-NAVARRA trial. Leukocyte TL was measured by qPCR at baseline and after 5 years of a dietary intervention program where subjects were randomly assigned to a low-fat control diet or to two MeDiets, one supplemented with extra virgin olive oil (MeDiet-EVOO) and the other with mixed nuts (MeDiet-nuts). A validated 14-item questionnaire was used to appraise baseline adherence of participants to the MeDiet.

RESULTS:Better adherence to MeDiet (as appraised by the 14-item score) was associated with longer basal telomeres in women in the baseline cross-sectional analysis, whereas the opposite was observed in men (P interaction = 0.036). Female subjects who scored 10 points had longer basal telomeres (0.27, 95% CI: 0.03-0.52) than women scoring ≤6 points at the beginning of the study (-0.46, 95% CI: -0.85 to -0.7) (P = 0.003). However, allocation to the MeDiet-nuts group (-0.24, 95% CI: -0.38 to -0.01) was associated with a higher risk of telomere shortening after 5 years of intervention, whereas no differences were found for the MeDiet-EVOO group (0.14, 95% CI: 0.02-0.27), in comparison with the Control group (0.07, 95% CI: -0.08 to 0.23) (P = 0.003 and P = 0.537, respectively).

CONCLUSION:A greater baseline adherence to a Mediterranean dietary pattern was associated with longer telomeres only in women. No beneficial effect of the intervention with the MeDiet for the prevention of telomere shortening in comparison with a low-fat diet was observed.

The Mediterranean Diet, characterized by higher intakes of plant foods including plant proteins, monounsaturated fat, fish, and lower consumption of animal products and saturated fat, has long been associated with reduced cardiovascular risk, but the molecular mechanisms underlying these associations have not been fully elucidated. We conducted a pilot study to evaluate associations of an Alternate Mediterranean Diet Score, reflective of adherence to this diet pattern and adapted for US populations, and its components, with markers of endothelial inflammation directly measured in endothelial cells harvested from a diverse sample of women (n = 25, mean ± SD age 33 ± 10.5y, 68% racial/ethnic minorities). Cardiovascular risk markers including nuclear factor kappa B (NF-κB)-a marker of inflammation, as well as oxidative stress and endothelial nitric oxide synthase (eNOS) gene expression-markers of endothelial function, wereevaluated in harvested endothelial cells. We hypothesized that the Mediterranean diet pattern would be associated with lower inflammation and oxidative stress and higher eNOS expression in endothelial cells. Results showed that lower oxidative stress was associated with higher plant-based protein (Exp(β) = 0.96; P = .007), overall protein (Exp(β) = 0.99; P = .007), and red and processed meat intake (Exp(β) = 0.93; P = .012). Lower NF-κB was associated with higher legume (Exp(β) = 0.79; P = .045) intake, and higher eNOS was associated with higher red and processed meat intake (Exp(β) = 1.13; P = .005). Our findings suggest potential novel mechanisms through which certain Mediterranean dietary components may influence pre-clinical vascular alterations that may be associated with cardiovascular risk through lower endothelial oxidative stress, lower inflammation, and greater endothelial functioning. These findings warrant confirmation, prospectively in a larger sample.

BACKGROUND AND AIMS:Endothelial dysfunction (ED) plays a key role in the development of atherosclerotic cardiovascular disease (ASCVD). Likewise, type 2 diabetes (T2D) is a major CVD risk factor. Therefore, our objective was to explore whether long-term consumption of a Mediterranean diet (MedDiet) rich in olive oil or a low-fat diet (LF diet) was associated with an improvement in ED and whether the potential benefits were similar in patients with or without T2D in the CORDIOPREV clinical trial (NCT00924937).

METHODS:Endothelial function was measured in 805 participants who had completed follow-up ultrasound image studies, using ultrasonography of brachial artery to calculate flow mediated vasodilatation (FMD) before and after 1.5 years of intervention with a MedDiet [35% of calories from fat (22% monounsaturated) and 50% from carbohydrates] and LF diet [28% fat (12% monounsaturated) and 55% of calories from carbohydrates]. We categorized participants as patients with T2D, prediabetes, and without T2D according to the American Diabetes Association (ADA) criteria.

RESULTS:MedDiet increased FMD in patients with T2D [5.2 ± 0.4 at 1.5 years vs. 3.8 ± 0.4 at baseline; p=0.04] and prediabetes [4.9 ± 0.4 vs. 3.8 ± 0.4; p=0.04] and induced an improvement in FMD compared to LF diet in patients with diabetes [5.2 ± 0.4 (MedDiet) vs.3.7 ± 0.4 (LF diet); p=0.01]; whereas both diets maintained FMD stablein patients without diabetes.

CONCLUSIONS:Habitual consumption of a MedDiet rich in extra virgin olive oil improves endothelial function in patients with prediabetes and diabetes. This takes great importance given that diet must be the cornerstone of treatment of patients with diabetes at high cardiovascular risk.

Men with the metabolic syndrome demonstrate an increased prevalence of erectile dysfunction (ED). In the present study, we tested the effect of a Mediterranean-style diet on ED in men with the metabolic syndrome. Men were identified in our database of subjects participating in controlled trials evaluating the effect of lifestyle changes and were included if they had a diagnosis of ED associated with a diagnosis of metabolic syndrome, complete follow-up in the study trial, and intervention focused mainly on dietary changes. Sixty-five men with the metabolic syndrome met the inclusion/exclusion criteria; 35 out of them were assigned to the Mediterranean-style diet and 30 to the control diet. After 2 years, men on the Mediterranean diet consumed more fruits, vegetables, nuts, whole grain, and olive oil as compared with men on the control diet. Endothelial function score and inflammatory markers (C-reactive protein) improved in the intervention group, but remained stable in the control group. There were 13 men in the intervention group and two in the control group (P=0.015) that reported an IIEF score of 22 or higher. Mediterranean-style diet rich in whole grain, fruits, vegetables, legumes, walnut, and olive oil might be effective per se in reducing the prevalence of ED in men with the metabolic syndrome.

In the present study, we tested the effect of a Mediterranean-style diet on sexual function in women with the metabolic syndrome. Women were identified in our database of subjects participating in controlled trials evaluating the effect of lifestyle changes and were included if they had a diagnosis of female sexual dysfunction (FSD) associated with a diagnosis of metabolic syndrome, a complete follow-up in the study trial and an intervention focused mainly on dietary changes. Fifty-nine women met the inclusion/exclusion criteria; 31 out of them were assigned to the Mediterranean-style diet and 28 to the control diet. After 2 years, women on the Mediterranean diet consumed more fruits, vegetables, nuts, whole grain and olive oil as compared with the women on the control diet. Female sexual function index (FSFI) improved in the intervention group, from a mean basal value of 19.7+/-3.1 to a mean post-treatment value of 26.1+/-4.1 (P=0.01), and remained stable in the control group. C-reactive protein (CRP) levels were significantly reduced in the intervention group (P<0.02). No single sexual domain (desire, arousal, lubrication, orgasm, satisfaction, pain) was significantly ameliorated by the dietary treatment, suggesting that the whole female sexuality may find benefit from lifestyle changes. A Mediterranean-style diet might be effective in ameliorating sexual function in women with metabolic syndrome.

BACKGROUND:The endothelium plays a key role in the maintenance of vascular health and represents a potential physiological target for dietary and other lifestyle interventions designed to reduce the risk of cardiovascular diseases (CVD) including stroke or coronary heart disease.

OBJECTIVE:To conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating the effects of the Mediterranean dietary pattern (MedDiet) on endothelial function.

METHODS:Medline, Embase, and Scopus databases were searched from inception until January 2019 for studies that met the following criteria: 1) RCTs including adult participants, 2) interventions promoting the MedDiet, 3) inclusion of a control group, and 4) measurements of endothelial function. A random-effects meta-analysis was conducted. Metaregression and subgroup analyses were performed to identify whether effects were modified by health status (i.e., healthy participants versus participants with existing comorbidities), type of intervention (i.e., MedDiet alone or with a cointervention), study duration, study design (i.e., parallel or crossover), BMI, and age of participants.

RESULTS:Fourteen articles reporting data for 1930 participants were included in the meta-analysis. Study duration ranged from 4 wk to 2.3 y. We observed a beneficial effect of the MedDiet on endothelial function [standardized mean difference (SMD): 0.35; 95% CI: 0.17, 0.53; P <0.001; I2 = 73.68%]. MedDiet interventions improved flow-mediated dilation (FMD)-the reference method for noninvasive, clinical measurement of endothelial function-by 1.66% (absolute change; 95% CI: 1.15, 2.17; P <0.001; I2 = 0%). Effects of the MedDiet on endothelial function were not modified by health status, type of intervention, study duration, study design, BMI, or age of participants (P >0.05).

CONCLUSIONS:MedDiet interventions improve endothelial function in adults, suggesting that the protective effects of the MedDiet are evident at early stages of the atherosclerotic process with important implications for the early prevention of CVD. This study has the PROSPERO registration number: CRD42018106188.

Sleep duration and sleep quality are important predictors of risk for cardiovascular disease (CVD). One potential link between sleep health and CVD is through lifestyle factors such as diet. To clarify the association between diet and sleep, we assessed the associations of sleep duration and insomnia symptoms with current Mediterranean-style diet (aMed), and with historical changes in aMed score.Actigraphy-measured sleep duration and self-reported insomnia symptoms categorized as insomnia with short sleep (<6 h/night), insomnia without short sleep, no insomnia with short sleep and no insomnia or short sleep, were obtained from 2068 individuals who also had dietary intake data. A 10-point aMed score, derived from a self-report food frequency questionnaire, was collected concurrently with the sleep assessment, and 10 y before.Compared to individuals who currently reported a low aMed score, those with a moderate-high aMed score were more likely to sleep 6-7 h/night vs.<6 h/night (p<0.01) and less likely to report insomnia symptoms occurring with short sleep (vs. no insomnia or short sleep alone) (p<0.05). An increase in aMed score over the preceding 10 y was not associated with sleep duration or insomnia symptoms. However, compared to those with decreasing aMed score, individuals with an unchanging score reported fewer insomnia symptoms (p≤0.01).These results suggest that a Mediterranean-style diet is associated with adequate sleep duration, less insomnia symptoms, and less likely to have insomnia accompanied by short sleep. Further research should identify possible mediators through which diet may promote adequate sleep duration and reduce the risk of insomnia.

BACKGROUND:Endothelial dysfunction is a fundamental step in the atherosclerotic disease process. Activation or injury of the endothelium leads to a variety of inflammatory disorders, including the release of microparticles. Endothelial progenitor cells may contribute to the maintenance of the endothelium by replacing injured mature endothelial cells.

OBJECTIVE:We studied the influence of dietary fat on the release of endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs) in elderly subjects.

DESIGN:Twenty healthy, elderly subjects (10 men and 10 women) consumed 3 diets following a randomized crossover design, each for 4 wk: a saturated fatty acid diet; a low-fat, high-carbohydrate diet; and a Mediterranean diet (MedDiet) enriched in monounsaturated fatty acids. We investigated total microparticles, EMPs from activated endothelial cells (activated EMPs), EMPs from apoptotic endothelial cells (apoptotic EMPs), EPCs, oxidative stress variables, and ischemic reactive hyperemia (IRH).

RESULTS:The MedDiet led to lower total microparticle, activated EMP, and apoptotic EMP concentrations and higher EPC numbers than did the other diets (P<0.001). We detected lower superoxide dismutase activity (P<0.001), a higher plasmaβ-carotene concentration (P<0.001), and lower urinary isoprostane and plasma nitrotyrosine concentrations after consumption of the MedDiet than after consumption of the other 2 diets (P<0.05). Furthermore, the occurrence of IRH was higher after consumption of the MedDiet than after consumption of the other 2 diets (P<0.05).

CONCLUSION:Consumption of the MedDiet induces a reduction in endothelial damage and dysfunction, which is associated with an improvement in the regenerative capacity of the endothelium, in comparison with 2 other diets.

PURPOSE:To examine associations between adherence to a Mediterranean diet and prevalence of age-related macular degeneration (AMD) in countries ranging from Southern to Northern Europe.

DESIGN:Cross-sectional, population-based epidemiologic study.

PARTICIPANTS:Of 5060 randomly sampled people aged 65 years or older from 7 study centers across Europe (Norway, Estonia, United Kingdom, France, Italy, Greece, and Spain), full dietary data were available in 4753. The mean age of participants was 73.2 years (standard deviation, 5.6), and 55% were women.

METHODS:Participants underwent an eye examination and digital retinal color photography. The images were graded at a single center. Dietary intake during the previous 12 months was assessed by using a semiquantitative food-frequency questionnaire (FFQ). A previously published Mediterranean Diet Score (MDS) was used to classify participants according to their responses on the FFQ. Multivariable logistic regression was used to investigate the association of the MDS score and AMD, taking account of potential confounders and the multicenter study design.

MAIN OUTCOME MEASURES:Images were graded according to the International Classification System for age-related maculopathy and stratified using the Rotterdam staging system into 5 exclusive stages (AMD 0-4) and a separate category of large drusen (≥125 μm). Age-related macular degeneration 4 included neovascular AMD (nvAMD) and geographic atrophy (GA).

RESULTS:Increasing MDS was associated with reduced odds of nvAMD in unadjusted and confounder-adjusted analysis. Compared with the lowest MDS adherence (≤4 score), those in the highest category MDS adherence (>6 score) showed lower odds of nvAMD (odds ratio, 0.53; 0.27-1.04; P trend = 0.01). The association with MDS did not differ by Y204H risk allele (P = 0.89). For all early AMD (grade 1-3), there was no relationship with MDS (P trend = 0.9). There was a weak trend (P = 0.1) between MDS and large drusen; those in the highest category of MDS had 20% reduced odds comparedwith those in the lowest (P = 0.05).

CONCLUSIONS:This study adds to the limited evidence of the protective effect of adherence to a Mediterranean dietary pattern in those with late AMD, although it does not support previous reports of a relationship with genetic susceptibility. Interventions to encourage the adoption of the Mediterranean diet should be developed, and methods by which such behavior change can be achieved and maintained investigated.

To update the clinical practice guidelines for nutrition therapy of the European Association for the Study of Diabetes, we conducted a systematic review and meta-analysis of prospective cohort studies and randomized clinical trials (RCTs) to evaluate the effect of the Mediterranean diet (MedDiet) on the prevention of cardiovascular disease (CVD) incidence and mortality. We searched Medline, EMBASE (through April 20, 2018) and Cochrane (through May 7, 2018) databases. Pooled relative risks (RRs) and 95% confidence interval (CI) were calculated by the generic inverse variance method. A total of 41 reports (3 RCTs and 38 cohorts) were included. Meta-analyses of RCTs revealed a beneficial effect of the MedDiet on total CVD incidence (RR: 0.62; 95% CI: 0.50, 0.78) and total myocardial infarction (MI) incidence (RR: 0.65; 95% CI: 0.49, 0.88). Meta-analyses of prospective cohort studies, which compared the highest versus lowest categories of MedDiet adherence, revealed an inverse association with total CVD mortality (RR: 0.79; 95% CI: 0.77, 0.82), coronary heart disease (CHD) incidence (RR: 0.73; 95% CI: 0.62, 0.86), CHD mortality (RR: 0.83; 95% CI: 0.75, 0.92), stroke incidence (RR: 0.80; 95% CI: 0.71, 0.90), stroke mortality (RR: 0.87; 95% CI: 0.80, 0.96) and MI incidence (RR: 0.73; 95% CI: 0.61, 0.88). The present study suggests that MedDiet has a beneficial role on CVD prevention in populations inclusive of individuals with diabetes.

A growing body of evidence suggests that adherence to the Mediterranean diet (MD) may protect against cognitive decline and dementia. Many epidemiologic studies and several randomized controlled trials (RCTs) have found positive effects of the MD on cognitive function, but findings remain inconsistent. The aim of this systematic review was to provide an update on the current knowledge of the effects of the MD on cognitive function, cognitive impairment, Alzheimer disease (AD), and all-type dementia. Five databases were searched-PubMed, Embase, CINAHL, CENTRAL, and PsycINFO (1806 to 25 May 2015)-with the use of prespecified criteria. Human studies that were published in English without any restriction on study type, population assessed, intervention period, follow-up time, or publication date, and that examined the association between adherence to the MD and cognitive function or dementia symptoms (as measured by cognitive function tests), were included. Only primary publication types were included. Thirty-two studies from 25 unique cohorts, including 5 RCTs and 27 observational studies, met the inclusion criteria. The majority of studies showed that the MD was associated with improved cognitive function, a decreased risk of cognitive impairment or decreased risk of dementia, or AD. Three studies found no correlation between the MD and AD, 3 further studies found no association between the MD and cognitive impairment, and 5 studies found no association between the MD and cognitive function. There was large heterogeneity, and studies differed with regard to quality. Based on the findings and the limitations in study design, we conclude that adherence to the MD is associated with better cognitive performance. However, it should be noted that the majority of findings come from epidemiologic studies that provide evidence for a correlation between the MD and cognition but not for a cause-and-effect relation. More controlled trials are required to establish a causational relation.

OBJECTIVES:To investigate eating habits and adherence to Mediterranean Diet (MD) in relation to the risk of depression in a cohort of nonagenarians enrolled within the Mugello Study, an epidemiological study aimed at investigating both clinically relevant geriatric items and various health issues, including those related to nutritional status.

DESIGN:Cross-sectional study.

SETTING:Homes and nursing homes in the Mugello area, Florence, Italy.

PARTICIPANTS:Subjects aged 90-99 years [N=388 (271F; 117M) mean age: 92.7±3.1].

MEASUREMENTS:All subjects were evaluated through questionnaires and instrumental examinations. Adherence to MD was assessed through the Mediterranean Diet Score. A shorter version of the Geriatric Depression Scale (GDS) was used to detect the possible presence of depressive symptoms. In addition, cognitive and functional status was assessed using the Mini-Mental State Examination, the Clock Drawing Test, as well as the Basic and Instrumental Activities of Daily Living test.

RESULTS:Depressed subjects (DS) (GDS score≥5, 43.8%) were older, females and widows, than non-depressed subjects (NDS). DS reported a slightly but not statistically significant lower MD score than NDS (33.9±3.9 vs. 34.6±3.3, p=0.149). Subjects who reported to consume a greater amount of olive oil and fruit were associated with a lower risk of depression (OR=0.35, 95%CI=0.20-0.59, p<0.001 and OR=0.46, 95%CI=0.26-0.84, p=0.011, respectively) after adjustment for many possible confounders. Similar results were obtained for women, while no statistically significant differences emerged for men.

CONCLUSION:Our results support the hypothesis that a diet rich in olive oil and fruit, characteristics of MD, may protect against the development of depressive symptoms in older age.

CONTEXT:Dietary patterns and lifestyle factors are associated with mortality from all causes, coronary heart disease, cardiovascular diseases, and cancer, but few studies have investigated these factors in combination.

OBJECTIVE:To investigate the single and combined effect of Mediterranean diet, being physically active, moderate alcohol use, and nonsmoking on all-cause and cause-specific mortality in European elderly individuals.

DESIGN, SETTING, AND PARTICIPANTS:The Healthy Ageing: a Longitudinal study in Europe (HALE) population, comprising individuals enrolled in the Survey in Europe on Nutrition and the Elderly: a Concerned Action (SENECA) and the Finland, Italy, the Netherlands, Elderly (FINE) studies, includes 1507 apparently healthy men and 832 women, aged 70 to 90 years in 11 European countries. This cohort study was conducted between 1988 and 2000.

MAIN OUTCOME MEASURES:Ten-year mortality from all causes, coronary heart disease, cardiovascular diseases, and cancer.

RESULTS:During follow-up, 935 participants died: 371 from cardiovascular diseases, 233 from cancer, and 145 from other causes; for 186, the cause of death was unknown. Adhering to a Mediterranean diet (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.68-0.88), moderate alcohol use (HR, 0.78; 95% CI, 0.67-0.91), physical activity (HR, 0.63; 95% CI, 0.55-0.72), and nonsmoking (HR, 0.65; 95% CI, 0.57-0.75) were associated with a lower risk of all-cause mortality (HRs controlled for age, sex, years of education, body mass index, study, and other factors). Similar results were observed for mortality from coronary heart disease, cardiovascular diseases, and cancer. The combination of 4 low risk factors lowered the all-cause mortality rate to 0.35 (95% CI, 0.28-0.44). In total, lack of adherence to this low-risk pattern was associated with a population attributable risk of 60% of all deaths, 64% of deaths from coronary heart disease, 61% from cardiovascular diseases, and 60% from cancer.

CONCLUSION:Among individuals aged 70 to 90 years, adherence to a Mediterranean diet and healthful lifestyle is associated with a more than 50% lower rate of all-causes and cause-specific mortality.

AIM:To evaluate the association between the Mediterranean diet (MD) pattern and its components, and advanced colorectal polyps (adenoma and serrated adenoma).

METHODS:A case-control study among patients undergoing screening, diagnostic or surveillance colonoscopies during 2010-2015 at the Tel-Aviv Medical Center, Gastroenterology Department. Cases with advanced polyps were defined as: Advanced adenoma [>10 mm, with features of high grade dysplasia (HGD) or villous histology], advanced serrated adenoma (>10 mm or with dysplasia) or multiple (≥ 3) non-advanced adenomas or serrated adenomas. Cases of non-advanced adenomas were defined as adenomas<10 mm, without features of HGD or villous histology. Controls were defined as those without polyps at the current colonoscopy and without a history of colorectal polyps. Data collection included: anthropometrics measured according to a standardized protocol, fasting blood tests performed at the same lab, medical history recorded by a structured interview and dietary intake evaluated by a 116-item food frequency questionnaire. Adherence to the MD components was evaluated according to intake above/below the sample median, for potentially beneficial/detrimental components respectively, as accepted.

RESULTS:We recruited 206 cases with advanced polyps, 192 cases with non-advanced adenoma and 385 controls. The number of adhered MD components was inversely associated with a diagnosis of advanced polyps in a dose-response manner (OR = 0.34, 95%CI: 0.17-0.65; OR = 0.22, 95%CI: 0.11-0.43; and OR = 0.18, 95%CI: 0.07-0.47 for 3-4, 5-7 and 8-10 components, respectively), but not with non-advanced adenomas (OR = 0.54, 95%CI: 0.25-1.13; OR = 0.48, 95%CI: 0.23-0.99; and OR = 0.43, 95%CI: 0.16-1.12 for 3-4, 5-7 and 8-10 components, respectively). Low intake of sugar-sweetened beverages and red meat, as well as high intake of fish, were inversely associated with advanced polyps (OR = 0.56, 95%CI: 0.36-0.87; OR = 0.63, 95%CI: 0.42-0.95; and OR = 0.66, 95%CI: 0.44-0.99, respectively), while only low intake of red meat was inversely associated with non-advanced adenomas (OR = 0.71, 95%CI: 0.49-0.97).

CONCLUSION:A better adherence to the MD, specifically low intake of sugar-sweetened beverages and red meat as well as high intake of fish, is related to lower odds for advanced polyps.

BACKGROUND: The Mediterranean diet has been suggested to play a beneficial role for health and longevity. However, to our knowledge, no prospective US study has investigated the Mediterranean dietary pattern in relation to mortality.

METHODS: Study participants included 214,284 men and 166,012 women in the National Institutes of Health (NIH)-AARP (formerly known as the American Association of Retired Persons) Diet and Health Study. During follow-up for all-cause mortality (1995-2005), 27,799 deaths were documented. In the first 5 years of follow-up, 5,985 cancer deaths and 3,451 cardiovascular disease (CVD) deaths were reported. We used a 9-point score to assess conformity with the Mediterranean dietary pattern (components included vegetables, legumes, fruits, nuts, whole grains, fish, monounsaturated fat-saturated fat ratio, alcohol, and meat). We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) using age- and multivariate-adjusted Cox models.

RESULTS: The Mediterranean diet was associated with reduced all-cause and cause-specific mortality. In men, the multivariate HRs comparing high to low conformity for all-cause, CVD, and cancer mortality were 0.79 (95% CI, 0.76-0.83), 0.78 (95% CI, 0.69-0.87), and 0.83 (95% CI, 0.76-0.91), respectively. In women, an inverse association was seen with high conformity with this pattern: decreased risks that ranged from 12% for cancer mortality to 20% for all-cause mortality (P = .04 and P<.001, respectively, for the trend). When we restricted our analyses to never smokers, associations were virtually unchanged.

CONCLUSION: These results provide strong evidence for a beneficial effect of higher conformity with the Mediterranean dietary pattern on risk of death from all causes, including deaths due to CVD and cancer, in a US population.

BACKGROUND:The Mediterranean diet (MD) has been reported to be associated with lower cancer risk. However, while previous studies explored major single components of the MD, only 1 previous study has investigated adherence to the MD in relation to melanoma risk.

OBJECTIVE:The aim of this study was to explore the relations between adherence to the MD and the risk of skin cancer, including melanomas, basal cell carcinomas (BCCs), and squamous cell carcinomas (SCCs).

DESIGN:Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale (E3N) is a prospective cohort of 98,995 French women aged 40-65 y in 1990. Dietary data were collected via a validated food questionnaire in 1993. Adherence to the MD was assessed using a 9-unit dietary score that incorporates intakes of fruit, vegetables, legumes, cereal products, olive oil, fish, dairy products, meat products, and alcohol. We used Cox proportional hazards regression models to compute HRs and 95% CIs adjusted for age and main known skin cancer risk factors.

RESULTS:From 1993 to 2008, a total of 2003 skin cancer cases were ascertained among 67,332 women, including 404 melanomas, 1367 BCCs, and 232 SCCs. Score of adherence to the MD was associated with lower risk of skin cancer (HR: 0.83; 95% CI: 0.73, 0.93 for high compared with low score, Ptrend = 0.001). MD score was also inversely and linearly associated with risks of melanoma (HR: 0.72; 95% CI: 0.54, 0.96; Ptrend = 0.02) and BCC (HR: 0.77; 95% CI: 0.66, 0.90; Ptrend = 0.0006) but not SCC (HR: 1.08; 95% CI: 0.75, 1.55; Ptrend = 0.68), although with no heterogeneity across skin cancer types (Pheterogeneity = 0.23).

CONCLUSION:These findings suggest that adherence to the MD is associated with a lower skin cancer risk in women, particularly melanoma and BCC. If confirmed in future research, these findings may have important implications in skin cancer prevention.

PURPOSE:To explore the association of the previously described Western, Prudent and Mediterranean dietary patterns with prostate cancer risk by tumor aggressiveness and extension.

METHODS:MCC-Spain is a population-based multicase-control study, carried out in 7 Spanish provinces between September 2008 and December 2013. It collected anthropometric, epidemiologic and dietary information on 754 histologically confirmed incident cases of prostate cancer and 1277 controls aged 38 to 85 years. Three previously identified dietary patterns -Western, Prudent and Mediterranean- were reconstructed using MCC-Spain data. The association between each pattern and prostate cancer risk was assessed using logistic regression models with random province-specific intercepts. Risk according to tumor aggressiveness (Gleason score grade =6 vs>6) and extension (cT1-cT2a vs cT2b-cT4) was evaluated with multinomial regression models.

RESULTS:High adherence to Mediterranean dietary pattern -rich in fruits and vegetables, but also in fish, legumes and olive oil- was specifically associated to lower risk of prostate cancer with Gleason score>6: RRRQuartile3(Q3)vsQuartile1(Q1)=0.66; 95%CI:0.46-0.96 and RRRQuartile4(Q4)vsQuartile1=0.68;95%CI:0.46-1.01;p-trend=0.023) or with higher clinical stage (cT2b-T4: RRRQuartile4vsQuartile1=0.49; 95%CI:0.25-0.96; p-trend=0.024). This association was not observed with Prudent pattern, which combines vegetables and fruits with low fat dairy products, whole grains and juices. Western pattern did not show any association with prostate cancer risk.

CONCLUSIONS:Nutritional recommendations for prostate cancer prevention should consider whole dietary patterns instead of individual foods. We found important differences between Mediterranean dietary pattern, which was associated to lower risk of aggressive prostate cancer, and Western and Prudent dietary patterns, that had no relationship with prostate cancer risk.

The final proof about the specific mechanisms by which the different components of olive oil, the principal source of fat in a typical "Mediterranean diet", exert their potential protective effects on the promotion and progression of several human cancers requires further investigations. A recent discovery that dietary fatty acids can interact with the human genome by regulating the amount and/or activity of transcription factors has opened a whole new line of research aimed to molecularly corroborate the ant-cancer benefits of the olive oil-based Mediterranean diet and the underlying mechanisms. Our most recent findings reveal that oleic acid (OA; 18:1n-9), the main olive oil's monounsaturated fatty acid, can suppress the overexpression of HER2 (erbB-2), a well-characterized oncogene playing a key role in the etiology, invasive progression and metastasis in several human cancers. First, exogenous supplementation with physiological concentrations of OA significantly down-regulates HER2-coded p185(Her-2/neu) oncoprotein in human cancer cells naturally harboring amplification of the HER gene. Second, OA exposure specifically represses the transcriptional activity of the human HER2 gene promoter in tumor-derived cell lines naturally exhibiting HER2 gene amplification and p185(Her-2/neu) protein overexpression but not in cancer cells expressing physiological levels of HER2. Third, OA treatment induces the up-regulation of the Ets protein PEA3 (a transcriptional repressor of the HER2 gene promoter) solely in cancer cells naturally displaying HER2 gene amplification. Fourth, HER2 gene promoter bearing a PEA3 site-mutated sequence cannot be negatively regulated by OA, while treatment with OA fails to repress the expression of a human full-length HER2 cDNA controlled by a SV40 viral promoter. Fifth, OA-induced inhibition of HER2 promoter activity does not occur if HER2 gene-amplified cancer cells do no concomitantly exhibit high levels of Fatty Acid Synthase (FASN; Oncogenic antigen-519) as specific depletion of FASN, which itself similarly suppresses HER2 overexpression by inducing PEA3-dependent repression of HER2 gene promoter, strongly antagonizes the inhibitory effects of OA on HER2 gene promoter activity. Considering that OA treatment efficiently blocks FASN activity and down-regulates FASN protein expression, it is reasonable to suggest that an accumulation of supra-physiological concentrations of the FASN substrate malonyl-CoA, due to its reduced utilization by FASN in the presence of exogenous OA, appears to act as an indicator of "cell fuel" availability capable to suppress HER2 expression via formation of inhibitory "PEA3 protein-PEA3 DNA binding site" complexes on the endogenous HER2 promoter. Indeed, malonyl-CoA on its own dramatically decreases HER2 promoter activity, while OA or malonyl-CoA similarly up-regulates PEA3 gene promoter activity. This previously unrecognized ability of OA to directly affect the expression of a cluster of interrelated human cancer genes (i.e., HER2, FASN and PEA3) should open a new line of research aimed to explore the anti-cancer effects of OA. Certainly, an appropriate dietary intervention reproducing this prominent anti-oncogenic feature of the "Mediterranean diet" must be carried out in animal models and human pilot studies in the future. Only then we will know whether the old "Mediterranean dietary traditions" will become a new molecular approach in the management of cancer disease.

Considering the high prevalence of metabolic syndrome and its association with cardiovascular mortality, we prospectively evaluated the role of diet in the incidence of metabolic syndrome in renal transplant recipients. Our prospective cohort of 160 adult renal allograft recipients was followed for 1 year and had no existing metabolic syndrome or diabetes mellitus. Routine dietary intakes were assessed with food-frequency questionnaires, and metabolic syndrome was defined according to the Adult Treatment Panel III guidelines. We identified 3 major patterns by factor analysis, consisting of those recipients predominantly consuming fats and sugars, those predominantly consuming whole grain, and the Mediterranean diet. When analyzed by multivariable logistic regression and after controlling for potential confounders, subjects in the highest tertile of scores for the Mediterranean diet had a significantly lower odds of metabolic syndrome than those in the lowest tertile. Subjects in the highest tertile of scores for consuming fats and sugars had significantly greater odds of metabolic syndrome compared with those in the lowest tertile. Our study shows that the Mediterranean dietary pattern is associated with a reduced risk of metabolic syndrome in renal transplant recipients.