Advances in Understanding the Molecular Basis of the Mediterranean Diet Effect

Posted with permission from the Annual Review of Food Science and Technology, Volume 9 by Annual Reviews, http://www.annualreviews.org.Increasingly, studies showing the protective effects of the Mediterranean diet (MedDiet) on different diseases (cardiovascular, diabetes, some cancers, and even total mortality and aging indicators) are being published. The scientific evidence level for each outcome is variable, and new studies are needed to better understand the molecular mechanisms whereby the MedDiet may exercise its effects. Here, we present recent advances in understanding the molecular basis of MedDiet effects, mainly focusing on cardiovascular diseases but also discussing other related diseases. There is heterogeneity in defining the MedDiet, and it can, owing to its complexity, be considered as an exposome with thousands of nutrients and phytochemicals. We review MedDiet composition and assessment as well as the latest advances in the genomic, epigenomic (DNA methylation, histone modifications, microRNAs, and other emerging regulators), transcriptomic (selected genes and whole transcriptome), and metabolomic and metagenomic aspects of the MedDiet effects (as a whole and for its most typical food components). We also present a critical review of the limitations of the studies undertaken and propose new analyses and greater bioinformatic integration to better understand the most important molecular mechanisms whereby the MedDiet as a whole, or its main food components, may exercise their protective effects

Influence of lipids and obesity on haemorheological parameters in patients with deep vein thrombosis

It is not well established whether haemorheological alterations constitute independent risk factors for deep vein thrombosis (DVT).We have determined in 149 DVT patients and in 185 control subjects the body mass index (BMI), the haemorheological profile: blood viscosity (BV), plasma viscosity (PV), fibrinogen (Fg), erythrocyte aggregation (EA), erythrocyte deformability (ED) and plasma lipids. In the crude analysis BMI, Fg, PV, EA, triglycerides (TG) and ApoB were statistically higher and HDL cholesterol (HDL-Chol) statistically lower in DVT patients than in controls. No differences in BV and ED were observed.After BMI adjustment, Fg, PV and EA remained statistically higher in DVT cases than in controls (P=0.013; P=0.012; P=0.013; P=0.028, respectively). When the risk of DVT associated with these variables (using cut-offs that corresponded to the mean plus one SD of the control group) was estimated, EA>8.2 and PV>1.28 mPa.s were significantly associated with DVT even further adjustment for lipids and obesity (OR=2.78, P=0.004; OR=1.91, P=0.024, respectively). However, PV did not remain statistically significant after additional adjustment for Fg.When we consider together all the analyzed variables in order to control every variable for each other,TG>175 mg/dl (OR=3,2,P=0.004) and BMI>30 kg/m2 (OR=3.5, P=0.003), were also independently associated with a greater risk of DVT. Our results suggest that increased EA constitute an independent risk factor for DVT. However, when associated to hyperlipidaemia and obesity it further increases thrombotic [email protected]

Empirically-derived food pattern and total ortality in the PREDIMED study

[Background]: There has been growing interest in the last years in assessing the relationship between diet and disease through the study of whole dietary patterris and not only focusing on single nutrients or foods. Though several studies have assessed the relationship between a posteriori dietary patterns and different health outcomes, there is little evidence on post hoc dietary patterns and all cause mortality in Southern European populations.[Objective]: To identify the association between a posteriori defined major dietary patterns and total mortality in the PREDIMED study. Methods We followed-up 7,340 participants (57.5 percent women, mean age: 67 years) during a median follow-up time of 4.8 years. To assess dietary exposures, a validated 137-item semi-quantitative food- frequency questionnaire was administered. Dietary patterns were ascertained through a factor analysis based on 30 predefined food groups. Participants were classified according to tertiles of adherence to dietary pattern scores at baseline. Cox regression models were used to estimate multivariable-adjusted hazard ratios (HR) for mortality. Deaths were confirmed by review of medical records and consultation of the National Death Index.[Results]: We identified two major dietary patterns: the “Western” dietary pattern and “Mediterranean” dietary pattern. During follow- up, 337 participants died. Among deceased participants, the median age of death was 70 (6.5). After controlling for potential confounders including the intervention group, higher baseline adherence to a “Mediterranean” dietary pattern was associated with lower risk of all- cause mortality (adjusted HR for third tertile vs. first textile: 0.68; 95 la CI: 0.49—0.95) (p for trend 0.028). [Conclusion]: Higher adherence to a Mediterranean-type diet may reduce the risk of all-cause mortality in elderly people at high cardiovascular risk

Mediterranean diet supplemented with nuts reduces waist circumference and shifts lipoprotein subfractions to a less atherogenic pattern in subjects at high cardiovascular risk

[Objective]: The PREDIMED trial showed that Mediterranean diets supplemented with either extra-virgin olive oil or nuts reduced incident cardiovascular events compared to a control diet. Consumption of both supplemental foods has been associated with reduced LDL-cholesterol, but it is unknown whether they can shift lipoprotein subfractions to a less atherogenic pattern. We investigated changes in adiposity and lipoprotein subfractions after consumption of the PREDIMED diets.[Methods]: In a PREDIMED sub-cohort (n = 169), lipoprotein subclasses (particle concentrations and size) were determined by nuclear magnetic resonance spectroscopy at baseline and after intervention for 1 year.[Results]: Participants allocated to the Mediterranean diet supplemented with nuts showed significant reductions from baseline of waist circumference (mean [95% CI]; −5 cm [−7; −3]) and concentrations of medium-small (−27 nmol/l [−46; −8]) and very small LDL (−111 nmol/l [−180; −42]); decreased LDL particle number (a nuclear magnetic resonance-specific measurement) (−98 nmol/l [−184; −11]); and an increase of large LDL concentrations (54 nmol/l [18; 90]), with a net increase (0.2 nmol/l [0.1; 0.4]) of LDL size. The Mediterranean diets with olive oil and nuts increased large HDL concentrations (0.6 μM [0.0; 1.1] and 1.0 μM [0.4; 1.5], respectively). Compared to the other two intervention groups, participants in the nut-enriched diet showed significantly reduced waist circumference (p ≤ 0.006, both) and increased LDL size (p < 0.05, both).[Conclusion]: Lipoprotein subfractions are shifted to a less atherogenic pattern by consumption of Mediterranean diets enriched with nuts. The results contribute mechanistic evidence for the reduction of cardiovascular events observed in the PREDIMED trial.This study was funded in part by ISCIII (Spanish Ministry of Economy) through grants RTIC G03/140, RTIC RD 06/0045, and FIS PS09/01292 and grant CNIC 06/2007 from Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain. AS-V was supported by post-doctoral contract FIS CD07/0083. MF was supported by a joint contract of ISCIII and the Health Department of the Catalan Government (Generalitat de Catalunya), CP 06/00100

Human transcriptome response after Mediterranean diet consumption

Trabajo presentado en el IV Congress of International Society of Nutrigenetics/Nutrigenomics ISNN, celebrado en Pamplona (España) del 18 al 20 de noviembre de 2010.[Introduction]: Despite the benefits associated with healthy diets, data on the mechanisms by which these benefits are promoted are scarce. Our aim was to explore the global transcriptomic response of biological pathways related to cardiovascular disease associated with traditional Mediterranean diet (TMD) intervention.[Methods]: The PREDIMED study is a large on-going, parallel, multicentre, randomized, controlled trial aimed at assessing the TMD effect on primary cardiovascular prevention. High cardiovascular risk participants were recruited and assigned to one of the following interventions: 1) TMD plus virgin olive oil (VOO); 2) TMD plus mixed nuts; or 3) low-fat diet (control group). In a sub sample of 30 volunteers of the PREDIMED-Barcelona Sur Centre, gene expression changes in peripheral mononuclear cells, after 3 months of intervention, were assessed by microarray analysis (Affymetrix) in which about 30,000 individual human genes were included. Crude and adjusted models for data analyses were performed separately in two different centres. Pearson´s correlation coefficients for log2ratio (post-intervention/pre-intervention value) and T-statistics were greater than 0.97. Gene ontology analyses were performed by Bioingenuity Software on genes with T-statistics ≥1.5 or ≥-1.5 after interventions.[Results]: Analyses of canonical pathways related with cardiovascular risk highlighted that: 1) MUFA versus PUFA rich diets (MUFA/PUFA ratio >3.5; TMD plus VOO and Low-fat) promoted changes in clusters of genes associated with cytokine and nuclear receptor signaling; and 2) TMD plus VOO promoted changes in blood pressure related pathways. In agreement with this, the greatest decrease in systolic and diastolic blood pressure levels were observed after TMD plus VOO diet.[Conclusions]: One of the mechanisms by which MUFA rich diets, and particularly a TMD rich in virgin olive oil, can exert their health benefits is through an enhancement of the global transcriptomic response in pathways related with cardiovascular risk

Metabolomic pattern analysis after Mediterranean diet intervention in non-diabetic population: a 1- and 3-year follow-up in the PREDIMED study

The Mediterranean diet (MD) is considered a dietary pattern with beneficial effects on human health. The aim of this study was to assess the effect of an MD on urinary metabolome by comparing subjects at 1 and 3 years of follow-up, after an MD supplemented with either extra-virgin olive oil (MD + EVOO) or nuts (MD + Nuts), to those on advice to follow a control low-fat diet (LFD). Ninety-eight nondiabetic volunteers were evaluated, using metabolomic approaches, corresponding to MD + EVOO (n = 41), MD + Nuts (n = 27), or LFD (n = 30) groups. The 1H NMR urinary profiles were examined at baseline and after 1 and 3 years of follow-up. Multivariate data analysis (OSC-PLS-DA and HCA) methods were used to identify the potential biomarker discriminating groups, exhibiting a urinary metabolome separation between MD groups against baseline and LFD. Results revealed that the most prominent hallmarks concerning MD groups were related to the metabolism of carbohydrates (3-hydroxybutyrate, citrate, and cis-aconitate), creatine, creatinine, amino acids (proline, N-acetylglutamine, glycine, branched-chain amino acids, and derived metabolites), lipids (oleic and suberic acids), and microbial cometabolites (phenylacetylglutamine and p-cresol). Otherwise, hippurate, trimethylamine-N-oxide, histidine and derivates (methylhistidines, carnosine, and anserine), and xanthosine were predominant after LFD. The application of NMR-based metabolomics enabled the classification of individuals regarding their dietary pattern and highlights the potential of this approach for evaluating changes in the urinary metabolome at different time points of follow-up in response to specific dietary interventions

Primary prevention of cardiovascular disease with a Mediterranean diet

© 2013 Massachusetts Medical Society[Background]: Observational cohort studies and a secondary prevention trial have shown an inverse association between adherence to the Mediterranean diet and cardiovascular risk. We conducted a randomized trial of this diet pattern for the primary prevention of cardiovascular events.[Methods]: In a multicenter trial in Spain, we randomly assigned participants who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly individual and group educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes). On the basis of the results of an interim analysis, the trial was stopped after a median follow-up of 4.8 years.[Results]: A total of 7447 persons were enrolled (age range, 55 to 80 years); 57% were women. The two Mediterranean-diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses. A primary end-point event occurred in 288 participants. The multivariable-adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54 to 0.92) and 0.72 (95% CI, 0.54 to 0.96) for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events). No diet-related adverse effects were reported.[Conclusions]: Among persons at high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events.Supported by the official funding agency for biomedical research of the Spanish government, Instituto de Salud Carlos III (ISCIII), through grants provided to research networks specifically developed for the trial (RTIC G03/140, to Dr. Estruch; RTIC RD 06/0045, to Dr. Martínez-González and through Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición [CIBERobn]), and by grants from Centro Nacional de Investigaciones Cardiovasculares (CNIC 06/2007), Fondo de Investigación Sanitaria–Fondo Europeo de Desarrollo Regional (PI04-2239, PI 05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407, PI10/02658, PI11/01647, and P11/02505), Ministerio de Ciencia e Innovación (AGL-2009-13906-C02 and AGL2010-22319-C03), Fundación Mapfre 2010, Consejería de Salud de la Junta de Andalucía (PI0105/2007), Public Health Division of the Department of Health of the Autonomous Government of Catalonia, Generalitat Valenciana (ACOMP06109, GVACOMP2010-181, GVACOMP2011-151, CS2010-AP-111, and CS2011-AP-042), and Regional Government of Navarra (P27/2011)

Association between adherence to the Mediterranean diet and waist-to-height ratio among high-risk subjects: the PREDIMED trial.

Trabajo presentado en European Congress of Epidemiology EUROEPI2012, celebrado en Oporto (Portugal) del 05 al 08 de septiembre de 2012.Association between adherence to the Mediterranean diet and waist-to-height ratio among high-risk subjects: the PREDIMED trial

Waist-to-Height Ratio and Cardiovascular Risk Factors in Elderly Individuals at High Cardiovascular Risk

IntroductionSeveral anthropometric measurements have been associated with cardiovascular disease, type-2 diabetes mellitus and other cardiovascular risk conditions, such as hypertension or metabolic syndrome. Waist-to-height-ratio has been proposed as a useful tool for assessing abdominal obesity, correcting other measurements for the height of the individual. We compared the ability of several anthropometric measurements to predict the presence of type-2 diabetes, hyperglycemia, hypertension, atherogenic dyslipidemia or metabolic syndrome.Materials and MethodsIn our cross-sectional analyses we included 7447 Spanish individuals at high cardiovascular risk, men aged 55–80 years and women aged 60–80 years, from the PREDIMED study. Logistic regression models were fitted to evaluate the odds ratio of presenting each cardiovascular risk factor according to various anthropometric measures. The areas under the receiver-operating characteristic curve (AUC) were used to compare the predictive ability of these measurements.ResultsIn this relatively homogeneous cohort with 48.6% of type-2 diabetic individuals, the great majority of the studied anthropometric parameters were significantly and positively associated with the cardiovascular risk factors. No association was found between BMI and body weight and diabetes mellitus. The AUCs for the waist-to-height ratio and waist circumference were significantly higher than the AUCs for BMI or weight for type-2 diabetes, hyperglycemia, atherogenic dyslipidemia and metabolic syndrome. Conversely, BMI was the strongest predictor of hypertension.ConclusionsWe concluded that measures of abdominal obesity showed higher discriminative ability for diabetes mellitus, high fasting plasma glucose, atherogenic dyslipidemia and metabolic syndrome than BMI or weight in a large cohort of elderly Mediterranean individuals at high cardiovascular risk. No significant differences were found between the predictive abilities of waist-to-height ratio and waist circumference on the metabolic disease

A provegetarian food pattern and reduction in total mortality in the Prevención con Dieta Mediterránea

[Background]: Vegetarian diets have been associated with reduced mortality. Because a pure vegetarian diet might not easily be embraced by many individuals, consuming preferentially plant-derived foods would be a more easily understood message. A provegetarian food pattern (FP) emphasizing preference for plant-derived foods might reduce all-cause mortality.[Objective]: The objective was to identify the association between an a priori–defined provegetarian FP and all-cause mortality.[Design]: We followed 7216 participants (57% women; mean age: 67 y) at high cardiovascular risk for a median of 4.8 y. A validated 137-item semiquantitative food-frequency questionnaire was administered at baseline and yearly thereafter. Fruit, vegetables, nuts, cereals, legumes, olive oil, and potatoes were positively weighted. Added animal fats, eggs, fish, dairy products, and meats or meat products were negatively weighted. Energy-adjusted quintiles were used to assign points to build the provegetarian FP (range: 12–60 points). Deaths were confirmed by review of medical records and the National Death Index.[Results]: There were 323 deaths during the follow-up period (76 from cardiovascular causes, 130 from cancer, 117 for noncancer, noncardiovascular causes). Higher baseline conformity with the provegetarian FP was associated with lower mortality (multivariable-adjusted HR for ≥40 compared with <30 points: 0.59; 95% CI: 0.40, 0.88). Similar results were found with the use of updated information on diet (RR: 0.59; 95% CI: 0.39, 0.89).[Conclusions]: Among omnivorous subjects at high cardiovascular risk, better conformity with an FP that emphasized plant-derived foods was associated with a reduced risk of all-cause mortality. This trial was registered at www.controlled-trials.com as ISRCTN35739639