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Summary Background & aims There is compelling evidence showing that moderate alcohol consumption reduces cardiovascular risk factors related to atherosclerosis. The aim of this study was to evaluate the effects of aged white wine (AWW) and gin on circulating endothelial progenitor cells (EPC) and the expression of cell adhesion molecules, inflammatory cytokines and chemokines related to atherosclerosis in high cardiovascular risk subjects. Methods This was an open, randomized, controlled, crossover study in 38 high-risk male volunteers between 55 and 80 years of age randomized to receive 30 g of ethanol/day as AWW or gin during 3 weeks. We used the paired two-tailed t-test to compare differences in outcome variables in response to each intervention. Carryover effects for the two periods were evaluated comparing the outcome variables before the AWW and gin interventions. Results Compared to gin, AWW intake was associated with a significant 39.6% increase in EPCs. Expression of CD31 and CD40 in T-lymphocytes and of CCR2 and CD36 in monocytes also decreased significantly after AWW intake. In addition, compared to gin, AWW was associated with a significant decrease of plasma pro-inflammatory biomarkers interleukin-8 and interleukin-18 and vascular and intercellular adhesion molecules-1. Lfa-1, Mac-1, VLA4, CD40 and CD31 expression in monocytes and interferon gamma (IFN-γ) concentrations significantly decreased after intake of both alcoholic beverages. Conclusions AWW shows a greater ability to repair and maintain endothelial integrity compared to gin. This effect is probably due to grape-derived minor components in AWW, which are absent in gin.

[Background]: Inflammation is known to be related to the leading causes of death including cardiovascular disease, several types of cancer, obesity, type 2 diabetes, depression-suicide and other chronic diseases. In the context of whole dietary patterns, the Dietary Inflammatory Index (DII®) was developed to appraise the inflammatory potential of the diet. [Objective]: We prospectively assessed the association between DII scores and all-cause mortality in two large Spanish cohorts and valuated the consistency of findings across these two cohorts and results published based on other cohorts., [Design]: We assessed 18,566 participants in the “Seguimiento Universidad de Navarra” (SUN) cohort followed-up during 188,891 person-years and 6790 participants in the “PREvencion con DIeta MEDiterránea” (PREDIMED) randomized trial representing 30,233 person-years of follow-up. DII scores were calculated in both cohorts from validated FFQs. Higher DII scores corresponded to more proinflammatory diets. A total of 230 and 302 deaths occurred in SUN and PREDIMED, respectively. In a random-effect meta-analysis we included 12 prospective studies (SUN, PREDIMED and 10 additional studies) that assessed the association between DII scores and all-cause mortality., [Results]: After adjusting for a wide array of potential confounders, the comparison between extreme quartiles of the DII showed a positive and significant association with all-cause mortality in both the SUN (hazard ratio [HR] = 1.85; 95% CI: 1.15, 2.98; P-trend = 0.004) and the PREDIMED cohort (HR = 1.42; 95% CI: 1.00, 2.02; P-trend = 0.009). In the meta-analysis of 12 cohorts, the DII was significantly associated with an increase of 23% in all-cause mortality (95% CI: 16%–32%, for the highest vs lowest category of DII)., [Conclusion]: Our results provide strong and consistent support for the hypothesis that a pro-inflammatory diet is associated with increased all-cause mortality. The SUN cohort and PREDIMED trial were registered at clinicaltrials.gov as NCT02669602 and at isrctn.com as ISRCTN35739639, respectively., 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 R.E.; RTIC RD 06/0045, to Miguel A. 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 (Proyecto de Investigación (PI) 04-2239, PI 05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407, PI10/02658, PI11/01647, P11/02505, PI13/00462, PI13/00615, PI13/01090, PI14/01668, PI14/01798, PI14/01764), Ministerio de Ciencia e Innovación (Recursos y teconologia agroalimentarias(AGL)-2009-13906-C02 and AGL2010-22319-C03 and AGL2013-49083-C3-1- R), Fundación Mapfre 2010, the Consejería de Salud de la Junta de Andalucía (PI0105/2007), the Public Health Division of the Department of Health of the Autonomous Government of Catalonia, Generalitat Valenciana (Generalitat Valenciana Ayuda Complementaria (GVACOMP) 06109, GVACOMP2010-181, GVACOMP2011-151), Conselleria de Sanitat y, PI14/01764 AP; Atención Primaria (CS) 2010-AP-111, and CS2011-AP-042), and Regional Government of Navarra (P27/2011).). Drs. Shivappa and Hébert were supported by grant number R44DK103377 from the United States National Institute of Diabetes and Digestive and Kidney Diseases.

High dietary polyphenol intake is associated with reduced all-cause mortality and a lower incidence of cardiovascular events. However, the mechanisms involved are not fully understood. The aim of the present substudy of the PREvencion con DIetaMEDiterranea (Prevention with Mediterranean diet; PREDIMED) trial was to analyse the relationship between polyphenol intake measured by total urinary polyphenol excretion (TPE), and circulating inflammatory biomarkers and cardiovascular risk factors in elderly individuals. A substudy of 1139 high-risk participants was carried out within the PREDIMED trial. The subjects were randomly assigned to a low-fat control diet or to two Mediterranean diets, supplemented with either extra-virgin olive oil or nuts. Dietary intake, anthropometric data, clinical and laboratory assessments, including inflammatory biomarkers, and urinary TPE were measured at baseline and after the one-year intervention. Participants in the highest tertile of changes in urinary TPE (T3) showed significantly lower plasma levels of inflammatory biomarkers [vascular cell adhesion molecule 1 (VCAM-1) (-9.47 ng ml-1 ), intercellular adhesion molecule 1 (-14.71 ng ml-1 ), interleukin 6 (-1.21 pg ml-1 ), tumour necrosis factor alpha (-7.05 pg ml-1 ) and monocyte chemotactic protein 1 (-3.36 pg ml-1 )] than those inthe lowest tertile (T1, P < 0.02; all). A significant inverse correlation existed between urinary TPE and the plasma concentration of\VCAM-1 (r = -0.301; P < 0.001). In addition, systolic and diastolic blood pressure (BP) decreased and plasma high-density lipoprotein cholesterol increased in parallel with increasing urinary TPE (T3 vs. T1) (P < 0.005 and P = 0.004, respectively). Increases in polyphenol intake measured as urinary TPE are associated with decreased inflammatory biomarkers, suggesting a dose-dependent anti-inflammatory effect of polyphenols. In addition, high polyphenol intake improves cardiovascular risk factors- mainly BP and the lipid profile.

Previous studies on the association between alcohol intake and the development of the metabolic syndrome (MetS) have yielded inconsistent results. Besides, few studies have analysed the effects of red wine (RW) consumption on the prevalence of the MetS and its components. As moderate RW drinkers have a better lipid profile and lower incidence rates of diabetes, hypertension and abdominal obesity, all components of the MetS, it was hypothesised that moderate RW consumption could be associated with a lower prevalence of the MetS. In the present cross-sectional study of 5801 elderly participants at a high cardiovascular risk included in the PREDIMED (Prevención con Dieta Mediterránea) study, 3897 fulfilled the criteria of the MetS at baseline. RW intake was recorded using a validated 137-item FFQ. Multiple logistic regression analysis was carried out to estimate the association between RW intake and the prevalence of the MetS. Compared with non-drinkers, moderate RW drinkers (≥ 1 drink/d) were found to have a reduced risk of prevalent MetS (OR 0.56, 95 % CI 0.45, 0.68; P < 0.001), a lower risk of having an abnormal waist circumference (OR 0.59, 95 % CI 0.46, 0.77; P < 0.001), low HDL-cholesterol concentrations (OR 0.42, 95 % CI 0.32, 0.53; P < 0.001), high blood pressure (OR 0.28, 95 % CI 0.17, 0.45; P < 0.001) and high fasting plasma glucose concentrations (OR 0.67, 95 % CI 0.54, 0.82; P < 0.001) after adjusting for several confounders. This association was found to be stronger in female participants, in participants aged < 70 years and in participants who were former or current smokers. No significant association was found between RW intake (≥ 1 drink/d) and TAG concentrations. In conclusion, moderate RW consumption is associated with a lower prevalence of the MetS in an elderly Mediterranean population at a high cardiovascular risk. Publication of these papers was supported by unrestricted educational grants from Federación Española de Sociedades de Nutrición, Alimentación y Dietética (FESNAD), International Nut and Dried Fruit Council (INC), International Union of Nutritional Sciences (IUNS), Fundación Iberoamericana de Nutrición (FINUT), Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBERobn) and Centro Interuniversitario di Ricerca sulle Culture Alimentari Mediterranee (Ciiscam)

Overweight and obesity have been steadily increasing in recent years and currently represent a serious threat to public health. Few human studies have investigated the relationship between polyphenol intake and body weight. Our aim was to assess the relationship between urinary polyphenol levels and body weight. A cross-sectional study was performed with 573 participants from the PREDIMED (Prevención con Dieta Mediterránea) trial (ISRCTN35739639). Total polyphenol levels were measured by a reliable biomarker, total urinary polyphenol excretion (TPE), determined by the Folin-Ciocalteu method in urine samples. Participants were categorized into five groups according to their TPE at the fifth year. Multiple linear regression models were used to assess the relationships between TPE and obesity parameters; body weight (BW), body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR). After a five years follow up, significant inverse correlations were observed between TPE at the 5th year and BW (β = -1.004; 95% CI: -1.634 to -0.375, p = 0.002), BMI (β = -0.320; 95% CI: -0.541 to -0.098, p = 0.005), WC (β = -0.742; 95% CI: -1.326 to -0.158, p = 0.013), and WHtR (β = -0.408; 95% CI: -0.788 to -0.028, p = 0.036) after adjustments for potential confounders. To conclude, a greater polyphenol intake may thus contribute to reducing body weight in elderly people at high cardiovascular risk. We thank all the participants of the PREDIMED study. This work was supported in part by CICYT (AGL2016-79113-R), the Instituto de Salud Carlos III, ISCIII (CIBEROBN) from the Spanish Ministry of Economy and Competivity (MEC), and Generalitat de Catalunya (GC) 2014 SGR 773. X.G. received support from China Scholarship Council (CSC). Alexander Medina-Remón thanks the ‘Juan de la Cierva’ postdoctoral program (JCI-2012-13463) from MEC.

5 Tablas, Background: Potatoes have a high glycemic load but also antioxidants, vitamins, and minerals. It is unclear what mechanisms are involved in relation to their effect on blood pressure (BP) and hypertension. Objectives: This study aimed to assess the association between potato consumption, BP changes, and the risk of hypertension in 2 Spanish populations. Methods: Separate analyses were performed in PREDIMED (PREvención con DIeta MEDiterránea), a multicenter nutrition intervention trial of adults aged 55-80 y, and the SUN (Seguimiento Universidad de Navarra) project, a prospective cohort made up of university graduates and educated adults with ages (means±SDs) of 42.7±13.3 y for men and 35.1± 10.7 y for women. In PREDIMED, generalized estimating equations adjusted for lifestyle and dietary characteristics were used to assess changes in BP across quintiles of total potato consumption during a 4-y follow-up. Controlled BP values (systolic BP < 140 mm Hg and diastolic BP < 90 mm Hg) during follow-up were also assessed. For SUN, multivariateadjusted HRs for incident hypertension during a mean 6.7-y follow-up were calculated. Results: In PREDIMED, the total potato intake was 81.9 ± 40.6 g/d. No overall differences in systolic or diastolic BP changes were detected based on consumption of potatoes. For total potatoes, the mean difference in change between quintile 5 (highest intake) and quintile 1 (lowest intake) in systolic BP after multivariate adjustment was 20.90 mm Hg (95% CI: -2.56, 0.76 mm Hg; P-trend = 0.1) and for diastolic BP was 20.02 mm Hg (95% CI: -0.93, 0.89 mm Hg; P-trend = 0.8). In SUN, the total potato consumption was 52.7 ± 33.6 g/d, and no significant association between potato consumption and hypertension incidence was observed in the fully adjusted HR for total potato consumption (quintile 5 compared with quintile 1: 0.98; 95% CI: 0.80, 1.19; P-trend = 0.8). Conclusions: Potato consumption is not associated with changes over 4 y in blood pressure among older adults in Spain or with the risk of hypertension among Spanish adults., Supported by the official funding agency for biomedical research of the Spanish Government, Instituto de Salud Carlos III through grants provided to research networks specifically developed for the trial (RTIC G03/140, to RE; RTIC RD 06/0045, to MAM-G) 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 [Proyecto de Investigación (PI) 04-2239, PI 05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407, PI10/02658, PI11/01647, P11/02505 and PI13/00462], Ministerio de Ciencia e Innovación [Recursos y teconologia agroalimentarias (AGL)-2009-13906-C02 and AGL2010-22319-C03 and AGL2013-49083-C3-1-R], Fundación Mapfre 2010, the Consejería de Salud de la Junta de Andalucía (PI0105/2007), the Public Health Division of the Department of Health of the Autonomous Government of Catalonia, Generalitat Valenciana [Generalitat Valenciana Ayuda Complementaria (GVACOMP) 06109, GVACOMP2010-181, GVACOMP2011-151], Conselleria de Sanitat y AP; Atención Primaria (CS) 2010-AP-111 and CS2011-AP-042, and Regional Government of Navarra (P27/2011).

Background and aims: Epidemiologic and biological evidence supports an inverse association between polyphenol consumption and the risk of cardiovascular disease (CVD). However, no previous studies have prospectively evaluated the relationship between polyphenol intake and the incidence of CVD in such a comprehensive way. The aim was to evaluate the association between intakes of total polyphenol and polyphenol subgroups, and the risk of major cardiovascular events (myocardial infarction, stroke or death from cardiovascular causes) in the PREDIMED study. Methods and results: The present work is an observational study within the PREDIMED trial. Over an average of 4.3 years of follow-up, there were 273 confirmed cases of CVD among the 7172 participants (96.3%) who completed a validated 137-item food frequency questionnaire (FFQ) at baseline. Polyphenol consumption was calculated by matching food consumption data from the FFQ with the Phenol-Explorer database on polyphenol content of each reported food. After multivariate adjustment, a 46% reduction in risk of CVD risk was observed comparing Q5 vs. Q1 of total polyphenol intake (HR=0.54; 95% confidence interval [CI]=0.33-0.91; P-trend=0.04). The polyphenols with the strongest inverse associations were flavanols (HR=0.40; CI 0.23-0.72; P-trend=0.003), lignans (HR=0.51; CI 0.30-0.86; P-trend=0.007), and hydroxybenzoic acids (HR=0.47; CI 0.26-0.86; P-trend 0.02). Conclusion: Greater intake of polyphenols, especially from lignans, flavanols, and hydroxybenzoic acids, was associated with decreased CVD risk. Clinical trials are needed to confirm this effect and establish accurate dietary recommendations. Clinical trial registry: International Standard Randomized Controlled Trial Number (ISRCTN of London, England) 35739639. © 2014 Elsevier B.V., We would like to thank all the volunteers involved in the PREDIMED study for their valuable cooperation. This study was supported by CICYT (AGL2010-22319-C03) from the Spanish Ministry of Science and Innovation (MICINN), and the Instituto de Salud Carlos III, ISCIII (CIBERobn-CB06/03, PI1002658, and PI1001407). CIBERobn is an initiative of ISCIII, Spain. AT-R received support from ISCIII (FI10/00265).

Several epidemiological studies have shown an inverse association between the consumption of polyphenol-rich foods and risk of cardiovascular diseases. However, accuracy and reliability of these studies may be increased using urinary total polyphenol excretion (TPE) as a biomarker for total polyphenol intake. Our aim was to assess if antioxidant activity, measured by a Folin-Ciocalteu assay in urine, is correlated with an improvement in cardiovascular risk factors (blood pressure and serum glucose, cholesterol, HDL-cholesterol, LDL-cholesterol, and triglyceride concentrations) in an elderly population at high risk. A longitudinal study was performed with 573 participants (aged 67.3 ± 5.9) from the PREDIMED study (ISRCTN35739639). We used Folin-Ciocalteu method to determine TPE in urine samples, assisting with solid phase extraction. Participants were categorized into three groups according to changes in TPE. Multiple linear regression models were used to assess relationships between TPE and clinical cardiovascular risk factors, adjusting for potential confounders. After a 5-year follow-up, significant inverse correlations were observed between changes in TPE and plasma triglyceride concentration (β=-8.563;P=0.007), glucose concentration (β=-4.164;P=0.036), and diastolic blood pressure (β=-1.316;P=0.013). Our results suggest that the consumption of more polyphenols, measured as TPE in urine, could exert a protective effect against some cardiovascular risk factors.

Scope Polyphenols (ingested via food items) can decrease DNA, and oxidative damage of proteins and lipids. However, polyphenol effects in healthy populations have not been well defined. The aim of this study was to assess the relationship between urinary total polyphenol excretion (TPE), a biomarker of total polyphenol intake (TPI), polyphenol-rich foods, and oxidative stress biomarkers in healthy adults of different ages participating in the cross-sectional PAScual MEDicina study. Methods and results Urinary TPE was determined by Folin–Ciocalteau method in spot urine samples of 81 participants (46 women), classified into three age groups: 18 to 39, 40 to 54, and 55 to 72 years of age. TPI was quantified from 3-day dietary records using the Phenol-Explorer database. Urinary TPE increased with age (p < 0.001). Urinary TPE was inversely associated with urinary 8-hydroxydeoxyguanosine (8-OHdG; p

Previous epidemiological and feeding studies have observed that adherence to Mediterranean diet (Med-Diet) is associated with reduced cardiovascular risk. However, the molecular mechanisms involved are not fully understood. Since atherosclerosis is nowadays considered a low-grade inflammatory disease, recent studies have explored the anti-inflammatory effects of a Med-Diet intervention on serum and cellular biomarkers related to atherosclerosis. In two sub-studies of the PREDIMED (PREvencion con DIeta MEDiterranea) trial, we analyzed the effects at 3 months of two Med-Diet interventions supplemented with either virgin olive oil (VOO) or nuts compared with a control low-fat diet (LFD). Both Med-Diets showed an anti-inflammatory effect reducing serum C-reactive protein, interleukin-6 (IL6) and endothelial and monocytary adhesion molecules and chemokines (P

Industrial processing of tomatoes involves juice addition and heat treatment that may affect (increase or decrease) the levels of phenolic compounds. In this work, we evaluated the effect of each processing step in the paste-making process. Four technological processes were investigated on an industrial scale: Hot Break 28/30, Hot Break 22/24, Cold Break 28/30 and Passata 10/12; and four stages were monitored in each process: (1) fresh tomatoes; (2) juice after scalders and cream addition; (3) tomato paste from evaporators and (4) final paste. The effect of each processing stage was evaluated by different analyses: first, hydrophilic antioxidant capacity was evaluated using ABTS+ and DPPH assays and total phenolics using Folin–Ciocalteau method; then, individual polyphenols were quantified using HPLC-ESI-MS/MS. This multifaceted approach has revealed that each processing stage induces different changes in the antioxidant and phenolic profile. The results of this study indicated that cream addition increases the hydrophilic antioxidant capacity and the amount of phenolic compounds positively, while heat treatment and, to a lesser extent, the sterilization stage during the paste-making process affect these compounds negatively.

The present study aims to compare the phenolic and hydrophilic antioxidant profiles of organically and conventionally produced tomato juices. Comparisons of analyses of archived samples from conventional and organic production systems demonstrated statistically higher levels (P < 0.05) of phenolic compounds in organic tomato juices. This increase corresponds not only with increasing amounts of soil organic matter accumulating in organic plots but also with reduced manure application rates once soils in the organic systems had reached equilibrium levels of organic matter. Using principal component analysis, results show that phenolic compounds and hydrophilic antioxidant capacity were responsible for the differentiation between organic and conventional tomato juices. Thus, there appear to be genuine differences in the bioactive components of organic and conventional tomato juices not previously reported.

Tomatoes and tomato-based products are rich in antioxidants such as carotenoids, vitamin C and polyphenols. The industrial processing of diced tomatoes involves heat treatments in which these antioxidant compounds may be potentially affected. In this study, we evaluate the effect of each separate step in the dice-making process. Three technological processes were investigated: Hot, Cold and Cold treated with calcium salt (CaCl2). Four stages were monitored in each process: (1) fresh tomatoes; (2) peeled tomatoes; (3) diced tomatoes; and (4) final product after sauce addition. The main tool for minimising or counteracting the eventual processing damage was the strategy of 'reconstitution', achieved by adding a sauce rich in seeds and peels with high levels of antioxidants and phenolics to the diced tomatoes. Different analyses were carried out in order to evaluate the effect of each processing step. First, total polyphenols (TP) were evaluated using Folin-Ciocalteau (F-C) assay and antioxidant activity using ABTS(+) and DPPH assays. Flavonols, flavanones, hydroxycinnamic and phenolic acids were then quantified using liquid chromatography/electrospray ionisation tandem mass spectrometry (HPLC-ESI-MS/MS). The combination of principal component analysis (PCA) and analysis of variance (ANOVA) revealed that each processing step induces alterations in the antioxidant and phenolic profile, and in particular sauce addition and calcium treatment significantly affected the levels of antioxidants and phenolics during the dice-making process.

© 2014 Elsevier B.V. Background and aim: Hypertension is one of the main cardiovascular risk factors in the elderly. The aims of this work were to evaluate if a one-year intervention with two Mediterranean diets (Med-diet) could decrease blood pressure (BP) due to a high polyphenol consumption, and if the decrease in BP was mediated by plasma nitric oxide (NO) production. Methods and results: An intervention substudy of 200 participants at high cardiovascular risk was carried out within the PREDIMED trial. They were randomly assigned to a low-fat control diet or to two Med-diets, one supplemented with extra virgin olive oil (Med-EVOO) and the other with nuts (Med-nuts). Anthropometrics and clinical parameters were measured at baseline and after one year of intervention, as well as BP, plasma NO and total polyphenol excretion (TPE) in urine samples. Systolic and diastolic BP decreased significantly after a one-year dietary intervention with Med-EVOO and Med-nuts. These changes were associated with a significant increase in TPE and plasma NO. Additionally, a significant positive correlation was observed between changes in urinary TPE, a biomarker of TP intake, and in plasma NO (Beta=4.84; 95% CI: 0.57-9.10). Conclusions: TPE in spot urine sample was positively correlated with plasma NO in Med-diets supplemented with either EVOO or nuts. The statistically significant increases in plasma NO were associated with a reduction in systolic and diastolic BP levels, adding to the growing evidence that polyphenols might protect the cardiovascular system by improving the endothelial function and enhancing endothelial synthesis of NO., We would like to thank all the volunteers involved in the PREDIMED study for their valuable cooperation. This study was supported in part by CICYT (AGL2010-22319-C03 and AGL2013-49083-C3-1-R), RD06/0045 and CIBEROBN from the ISCIII (Spanish Ministry of Science and Innovation, MICINN), Quality Group from Generalitat de Catalunya 2009-SGR-724 and 2014-SGR-773, and Grant of support to research groups no.35/2011 (Balearic Islands Gov. and EU FEDER funds). A.M.-R. thanks the “Juan de la Cierva” postdoctoral program (JCI-2012-13463) from MEC. A.T.-R. would like to thank the ISCIII for granting her a predoctoral fellowship (FI10/00265).

[Background] Polyphenols may lower the risk of cardiovascular disease (CVD) and other chronic diseases due to their antioxidant and anti-inflammatory properties, as well as their beneficial effects on blood pressure, lipids and insulin resistance. However, no previous epidemiological studies have evaluated the relationship between the intake of total polyphenols intake and polyphenol subclasses with overall mortality. Our aim was to evaluate whether polyphenol intake is associated with all-cause mortality in subjects at high cardiovascular risk., [Methods] We used data from the PREDIMED study, a 7,447-participant, parallel-group, randomized, multicenter, controlled five-year feeding trial aimed at assessing the effects of the Mediterranean Diet in primary prevention of cardiovascular disease. Polyphenol intake was calculated by matching food consumption data from repeated food frequency questionnaires (FFQ) with the Phenol-Explorer database on the polyphenol content of each reported food. Hazard ratios (HR) and 95% confidence intervals (CI) between polyphenol intake and mortality were estimated using time-dependent Cox proportional hazard models., [Results] Over an average of 4.8 years of follow-up, we observed 327 deaths. After multivariate adjustment, we found a 37% relative reduction in all-cause mortality comparing the highest versus the lowest quintiles of total polyphenol intake (hazard ratio (HR) = 0.63; 95% CI 0.41 to 0.97; P for trend = 0.12). Among the polyphenol subclasses, stilbenes and lignans were significantly associated with reduced all-cause mortality (HR =0.48; 95% CI 0.25 to 0.91; P for trend = 0.04 and HR = 0.60; 95% CI 0.37 to 0.97; P for trend = 0.03, respectively), with no significant associations apparent in the rest (flavonoids or phenolic acids)., [Conclusions] Among high-risk subjects, those who reported a high polyphenol intake, especially of stilbenes and lignans, showed a reduced risk of overall mortality compared to those with lower intakes. These results may be useful to determine optimal polyphenol intake or specific food sources of polyphenols that may reduce the risk of all-cause mortality., [Clinical trial registration] ISRCTN35739639., This study was supported in part by CICYT (AGL2010-22319-C03) from the Spanish Ministry of Science and Innovation (MICINN), and the Instituto de Salud Carlos III, ISCIII (CIBERobn-CB06/03, RD 06/0045, PI1002658 and PI1001407). The CIBERobn is an initiative of the ISCIII, Spain. ATR received support from ISCIII (FI10/00265).

Hypertension is a major public health problem, and a leading cause of premature death and disability in both developed and developing countries, affecting one-quarter of the world’s adult population. It is also one of the main cardiovascular risk factors in the elderly. The first steps for the management of hypertension involve following a healthy diet, and modifying lifestyle, including smoking cessation, moderate alcohol consumption, sodium intake restriction, weight reduction, and regular physical activity. Several observational and intervention studies have found an inverse association between the risk of cardiovascular disease and the consumption of polyphenol-rich foods and beverages such as cocoa, fruit and vegetables, tea, virgin olive oil, and wine. This paper reviews the recent clinical and epidemiological studies on the relationship between polyphenol intake and blood pressure, as well as the plausible mechanisms of action for a cardioprotective role of polyphenols. We describe how the vasoprotective effect of dietary polyphenols has been related to their ability to increase endothelial synthesis of nitric oxide and endothelium-derived hyperpolarizing factor-mediated responses.

© 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).

[Background and aims]: Epidemiological data have shown an inverse association between the consumption of polyphenol-rich foods and the risk of cardiovascular disease or overall mortality. A comprehensive estimation of individual polyphenol intake in nutritional cohorts is needed to gain a better understanding of this association. The aim of this study was to estimate the quantitative intake of polyphenols and the major dietary sources in the PREDIMED (PREvención con DIeta MEDiterránea) cohort using individual food consumption records. [Methods and results]: The PREDIMED study is a large, parallel-group, multicentre, randomised, controlled 5-year feeding trial aimed at assessing the effects of the Mediterranean diet on the primary prevention of cardiovascular disease. A total of 7200 participants, aged 55–80 years, completed a validated 1-year food frequency questionnaire (FFQ) at baseline. Polyphenol consumption was calculated by matching food consumption data from the FFQ with the recently developed Phenol-Explorer database on polyphenol content in foods. The mean total polyphenol intake was 820 ± 323 mg day−1 (443 ± 218 mg day−1 of flavonoids and 304 ± 156 mg day−1 of phenolic acids). Hydroxycinnamic acids were the phenolic group with the highest consumption and 5-caffeoylquinic acid was the most abundantly ingested individual polyphenol. The consumption of olives and olive oil was a differentiating factor in the phenolic profile of this Spanish population compared with other countries. [Conclusion]: In Mediterranean countries, such as Spain, the main dietary source of polyphenols is coffee and fruits, but the most important differentiating factor with respect to other countries is the consumption of polyphenols from olives and olive oil., The authors would like to express their gratitude for financial support from CICYT (AGL2009-13906-C02-02 and AGL2010-22319-C03), RETICS-RD06/0045, and PI11/02505 from the Spanish Ministry of Economy and Competitiveness (MEC) and ACOMP/2012/190 from the Generalitat Valenciana. The CIBERobn-CB06/03 is an initiative of the Instituto de Salud Carlos III, Spain. A.T-R would like to thank the ISCIII for granting her a predoctoral fellowship (FI10/00265) and J.P-J would like to thank the ISCIII for a Sara Borrell postdoctoral contract (CD09/00068).

[Background and aim]: Hypertension is a major public health problem and a leading cause of death and disability in both developed and developing countries, affecting one-quarter of the world's adult population. Our aim was to evaluate whether the consumption of gazpacho, a Mediterranean vegetable-based cold soup rich in phytochemicals, is associated with lower blood pressure (BP) and/or reduced prevalence of hypertension in individuals at high cardiovascular risk., [Methods and results]: We selected 3995 individuals (58% women, mean age 67 y) at high cardiovascular risk (81% hypertensive) recruited into the PREDIMED study. BP, weight, and dietary and physical activity data were collected. In multivariate linear regression analyses, after adjustment, moderate and high gazpacho consumption categories were associated with reduced mean systolic BP of −1.9 mm Hg [95% confidence interval (CI): −3.4; −0.6] and −2.6 mm Hg (CI: −4.2; −1.0), respectively, and reduced diastolic BP of −1.5 mm Hg (CI: −2.3; −0.6) and −1.9 mm Hg (CI: −2.8; −1.1). By multiple-adjusted logistic regression analysis, gazpacho consumption was associated with a lower prevalence of hypertension, with OR = 0.85 (CI: 0.73; 0.99) for each 250 g/week increase and OR = 0.73 (CI: 0.55; 0.98) for high gazpacho consumption groups compared to the no-consumption group., [Conclusions]: Gazpacho consumption was inversely associated with systolic and diastolic BP and prevalence of hypertension in a cross-sectional Mediterranean population at high cardiovascular risk. The association between gazpacho intake and reduction of BP is probably due to synergy among several bioactive compounds present in the vegetable ingredients used to make the recipe., This work was supported by CICYT[AGL2010-22319-C03] and RETICS[RD06/0045] from MICINN.

Coumarins and flavonoids are heterocyclic molecules that have been associated with beneficial effects on human health, such as reducing the risk of cancer, diabetes, cardiovascular and brain diseases. These effects are thought to be related to the radical scavenging effect, due to their antioxidant activities, along with other possible mechanisms, such as anti-inflammatory properties and interaction with several enzymes. Over the past two decades, there have been an increasing number of publications on coumarins and flavonoids, which demonstrate the importance of understanding the chemistry behind the antioxidant activities of both natural and synthesized compounds, considering the benefits from their dietary ingestion as well as pharmacological use. This work aims to review the antioxidant effects of coumarin and flavonoid molecules in humans and the structural aspects that contribute to these effects.

Since ancient times, people have attributed a variety of health benefits to moderate consumption of fermented beverages such as wine and beer, often without any scientific basis. There is evidence that excessive or binge alcohol consumption is associated with increased morbidity and mortality, as well as with work related and traffic accidents. On the contrary, at the moment, several epidemiological studies have suggested that moderate consumption of alcohol reduces overall mortality, mainly from coronary diseases. However, there are discrepancies regarding the specific effects of different types of beverages (wine, beer and spirits) on the cardiovascular system and cancer, and also whether the possible protective effects of alcoholic beverages are due to their alcoholic content (ethanol) or to their non-alcoholic components (mainly polyphenols). Epidemiological and clinical studies have pointed out that regular and moderate wine consumption (one to two glasses a day) is associated with decreased incidence of cardiovascular disease (CVD), hypertension, diabetes, and certain types of cancer, including colon, basal cell, ovarian, and prostate carcinoma. Moderate beer consumption has also been associated with these effects, but to a lesser degree, probably because of beer"s lower phenolic content. These health benefits have mainly been attributed to an increase in antioxidant capacity, changes in lipid profiles, and the anti-inflammatory effects produced by these alcoholic beverages. This review summarizes the main protective effects on the cardiovascular system and cancer resulting from moderate wine and beer intake due mainly to their common components, alcohol and polyphenols.

The agronomic environments in which tomatoes are cultivated potentially affect the levels of antioxidants and other metabolites in commercial products. In this study, biochemical and metabolomic techniques were used to assess the differences between ketchups produced by organic and conventional systems. An untargeted metabolomic approach using QToF-MS was used to identify those nutrients that have the greatest impact on the overall metabolomic profile of organic ketchups as compared to conventional ones. Individual polyphenols were quantified using LC-ESI-QqQ. This multifaceted approach revealed that the agronomic environment in which tomatoes are grown induces alterations in the content of antioxidant capacity, phenolics, and other metabolites in ketchups. Organic cultivation was found to provide tomatoes and tomato-derived products with a significantly higher content of antioxidant microconstituents, whereas glutamylphenylalanine and N-malonyltryptophan were detected only in conventional ketchups.

Tomatoes (Solanum lycopersicum L.), the second most important vegetable crop worldwide, are a key component in the so-called "Mediterranean diet", which is strongly associated with a reduced risk of chronic degenerative diseases. In this work, we evaluate the differences in the total and individual polyphenol content and hydrophilic antioxidant capacity of seven varieties of tomato cultivated in Vegas Bajas del Guadiana, Badajoz (Spain), which were collected from two consecutive harvests (2008-2009). Hydrophilic antioxidant capacity was evaluated using the TEAC assay, while the Folin-Ciocalteau assay with a previous cleanup was used to establish total polyphenol content. The method was optimized and validated. Individual polyphenols were quantified using liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) on a triple quadrupole. All compounds were found to be significantly different when analysis of variance was performed. Results from the principal component analysis show that phenolic compounds and hydrophilic antioxidant capacity were responsible for the differences among tomato samples according to variety.

Background and aims Dietary factors are critical for the prevention and treatment of hypertension, but data on the effects of specific nutrients on blood pressure (BP) are scarce. The aim of this study was to assess the relationship between total polyphenol excretion (TPE) in urine, as an objective measurement of total polyphenol intake and BP in an elderly population at high cardiovascular risk. Methods and results Cross-sectional substudy of 589 high-risk participants entering in the PREDIMED trial. BP was measured and TPE was determined in urine by Folin–Ciocalteu assay. A significant positive association was observed between TPE in urine and daily intake of fruit and vegetables (F&V), coffee or wine after adjusting for potential confounders. The intake of 100 g of F&V (Beta = 0.150;P < 0.001) had a greater contribution to TPE than 100 mL of coffee (Beta = 0.141;P = 0.001), and the latter two foods contributed more than the consumption of 100 mL of wine (Beta = 0.120;P = 0.019). An inverse association was observed between urinary TPE and the prevalence of hypertension. Participants in the highest quartile of urinary TPE had a reduced prevalence of hypertension compared to those in the lowest quartile (Odds Ratio = 0.64; 95% confidence interval 0.45 to 0.92; P = 0.015). Systolic and diastolic BP were inversely associated with urinary TPE after adjustment for potential confounders (P = 0.024 and P = 0.003, respectively). Conclusions Polyphenol intake, assessed via TPE in urine, was negatively associated with BP levels and prevalence of hypertension in an elderly Mediterranean population at high cardiovascular risk. Participants with the highest intake of polyphenol-rich foods showed the lowest BP measurements., This work has received financial support from AGL2005-05597; AGL2006-14228-C03-02, AGL2007-66638-C02-01, RETICS RD06/0045/0003, and in part by the CONSOLIDER INGENIO 2010 Programme, FUN-C-FOOD CSD2007-063 all from the Spanish Ministry of Science and Innovation (MICINN) and grant PI070240 from Instituto de Salud Carlos III, Spain.

12 Páginas.-- 6 Tablas.-- 1 Figura, Background-Epidemiological evidence suggests a cardioprotective role of α-linolenic acid (ALA), a plant-derived ω-3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω-3 fatty acids (long-chain n-3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all-cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long-chain n-3 polyunsaturated fatty acids (≥500 mg/day). Methods and Results-We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable-adjusted Cox regressionmodels were fitted to estimate hazard ratios. ALA intake correlated towalnut consumption (r=0.94). During a 5.9-y follow-up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios formeeting ALArecommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56-0.92) for all-causemortality and 0.95 (95% CI 0.58-1.57) for fatal cardiovascular disease. The hazard ratios formeeting the recommendation for long-chain n-3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67-1.05) for all-causemortality, 0.61 (95% CI 0.39-0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29-0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22-1.01) for sudden cardiac death. The highest reduction in all-cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45-0.87]). Conclusions-In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all-cause mortality, whereas protection from cardiac mortality is limited to fish-derived long-chain n-3 polyunsaturated fatty acids., This study was funded in part by Instituto de Salud Carlos III (ISCIII) (Spanish Ministry of Economy) through grants RTIC G03/140, RTIC RD 06/0045, Centro Nacional de Investigaciones Cardiovasculares CNIC 06/2007, ISCIII FIS PS09/01292, the Spanish Ministry of Science and Innovation (MICINN) AGL2010‐22319‐C03‐02 and AGL2009‐13906‐C02‐02, and an unrestricted grant from the California Walnut Commission. Sala‐Vila holds a Miguel Servet I fellowship from the Ministry of Economy and Competitiveness through the ISCIII.

Diet and lifestyle play a significant role in the development chronic diseases; however the full complexity of this relationship is not yet understood. Dietary pattern investigation, which reflects the complexity of dietary intake, has emerged as an alternative and complementary approach for examining the association between diet and chronic diseases. Literature on this association has largely focused on individual nutrients, with conflicting outcomes, but individuals consume a combination of foods from many groups that form dietary patterns. Our objective was to systematically review the current findings on the effects of dietary patterns on chronic diseases. In this review, we describe and discuss the relationships between dietary patterns, such as the Mediterranean, the Dietary Approach to Stop Hypertension, Prudent, Seventh-day Adventists, and Western, with risk of obesity, type-2 diabetes mellitus, cardiovascular diseases, asthma, and neurodegenearive diseases. Evidence is increasing from both observational and clinical studies that plant-based dietary patterns, which are rich in fruits, vegetables, and whole grains, are valuable in preventing various chronic diseases, whereas a diet high in red and processed meat, refined grains and added sugar seems to increase said risk. Dietary pattern analysis might be especially valuable to the development and evaluation of food-based dietary guidelines.